27^th Hellenic Conference of Clinical Oncology

Amanda Psyrri, Myrto Moutafi, Georgia-Angeliki Koliou, George Papaxoinis, Niki Gavrielatou, Panagiota Economopoulou, Ioannis Kotsantis, Maria Gkotzamanidou, Maria Anastasiou, Dimitrios G. Pectasides, Aileen Fernandez, Vesal Yaghoobi, Saba Shafi, Ioannis Vathiotis, Thazin Nwe Aung, Stavros Gkolfinopoulos, Periklis Foukas, David L. Rimm, George Fountzilas

National Kapodistrian University of Athens, Attikon Hospital, Athens, Greece; Yale School of Medicine, New Haven, CT; Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Second Department of Medical Oncology, Agios Savvas Anticancer Hospital, Athens, Greece; Attikon University Hospital, Athens, Greece; Yale University, New Haven, CT; Yale University School of Medicine, New Haven, CT; National and Kapodistrian University of Athens School of Medicine, Athens, Greece; Yale, New Haven, CT; Hellenic Cooperative Oncology Group, Thessaloniki, Greece

Background: Preclinical and clinical models suggest that PARP inhibitor-induced DNA damage regulates immune response and can lead to and effective antitumour response. A range of mechanisms, including STING pathway activation, alter the tumour microenvironment and increase tumour susceptibility. In addition, adaptive upregulation of PD-L1 expression has been reported after PARP blockade. Gene expression profiling and immunohistochemistry (IHC)/fluorescent assessments of PD-L1 expression, CD8 T-cell infiltration and broad immune infiltrate were used to identify immune-related biomarker groups and understand the effects of PARP inhibition-related therapy on HNC tumour immunity.

Aim: To identify the biomarkers of response to olaparib-based treatment in patients with head and neck squamous cell carcinoma (HNSCC).

Methods: Pre- and post-treatment samples were collected form 39 patients enrolled in OPHELIA Phase II trial. In this open-label, non-comparative trial, patients were randomised 3:3:3:1 to cisplatin and olaparib, olaparib alone, no treatment or durvalumab and olaparib. Quantitative immunofluorescence (QIF) assessed PD-L1, STING, Ki67 and γ-H2AX expression. The GeneXpert (GX) closed system real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) quantified CD274 (PD-L1), PDCD1LG2 (PD-L2), CD8A and IRF1 mRNA expression in pre- and post-treatment samples.

Results: Ki67 was decreased after olaparib-based treatment in 23 of 29 (79.3%) available samples when assessed by QIF; 13/23 had a decrease of at least 25%. PD-L1 levels were significantly increased post-durvalumab/olaparib treatment (p = 0.023). An increase in post-treatment CD8A mRNA levels was observed in a majority of samples in the three treatment arms. There were no statistically significant changes in the expression levels of STING and γ-H2AX.

Conclusion: To conclude, in the present study, we showed that brief treatment with olaparib significantly decreased proliferation in HNSCC. We also observed an increase in PD-L1 mRNA levels that could suggest an activated adaptive immunity. Larger cohorts of patients are needed in order to assess the effect of PARP inhibitors on HNSCC immune regulation.

ClinicalTrials.gov Identifier: NCT02882308

Balgkouranidou I¹, Xenidis N¹, Amarantidis K¹, Koukaki T¹, Karamitrousis E¹, Chatzaki E², Lianidou E³, Kakolyris S¹, Biziota Ei¹

¹Department of Oncology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.

²Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.

³Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Greece

Background: Non-invasive blood-based molecular markers have been investigated for cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA) variables such as ctDNA concentration and ctDNA integrity (cfDI) are two special characteristics of cfDNA. DNA integrity is calculated as the ratio of the concentration of longer DNA fragments to shorter fragments in the plasma.

Aim: In the present study, we aim to correlate important features of ctDNA, such as concentration and integrity, with the clinical outcome of the disease and the potential prognostic ability.

Methods: Two groups of breast cancer patients were examined: group A (n = 65) who received adjuvant treatment and group B (n = 40) patients with metastatic disease who received first-line treatment, and also a control group of healthy blood donors (n = 20). ctDNA quantification and integrity were determined by real-time quantitative polymerase chain reaction (PCR) for the repeating sequences ALU 115 and 247. Integrity was defined as the ratio of ALU247-qPCR to ALU115-qPCR.

Results: ctDNA concentration was significantly higher in the metastatic group of patients compared to the adjuvant group (comparison of mean: 20.8 ng/mL vs. 7.2 ng/mL, respectively), while in the control group, the concentration was extremely low. The mean value of the integrity of DNA (cfDI) in group A was 0.54, while in group B, it was 0.78. In 22.5% of group A patients who relapsed in the first 3 years, a strong statistical correlation was observed between relapse and elevated cfDI (p = 0.001).

Conclusion: Based on these early results, ctDNA concentration and integrity could be innovative prognostic biomarker candidates. This result should be confirmed in a larger number of patients.

Dimitrakopoulos F.-I.^1,2, Mountzios G.³, Christopoulos P.^4,5, Papastergiou T.⁶, Elshiaty M.^4,5, Daniello L.^4,5, Zervas E.⁷, Agelaki S.⁸, Samantas E.⁹, Nikolaidi A.¹⁰, Athanasiadis I.¹⁰, Baka S.¹¹, Syrigos K.¹², Christopoulou A.¹³, Lianos E.¹⁴, Samitas K.⁷, Tsoukalas N.¹⁵, Perdikouri E. I.¹⁶, Oikonomopoulos G.¹⁷, Kottorou A.^1,2, Kalofonou F.¹⁸, Makatsoris T.^1,2, Koutras A.^1,2, Megalooikonomou V.⁶, Kalofonos H.^1,2

¹Division of Oncology, Department of Medicine, University Hospital of Patras, Greece

² Molecular Oncology Laboratory, Medical School, University of Patras, Greece

³ Second Department of Medical Oncology and Clinical trials Unit, Henry Dunant Hospital Center, Athens, Greece

⁴ Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany

⁵ Translational Lung Research Center Heidelberg, member of the German Center for Lung Research (DZL)

⁶ Computer Engineering and Informatics Department, University of Patras, Greece

⁷ 7th Respiratory Medicine Dept and Asthma Center, Athens Chest Hospital Sotiria, Athens, Greece

⁸ Department of Medical Oncology, University General Hospital, 71110 Heraklion, Greece

⁹ Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece

¹⁰ Department of Medical Oncology, Mitera Hospital, Athens, Greece

¹¹ Oncology Department, Interbalkan European Medical Center, Thessaloniki, Greece

¹² Oncology Unit, The Third Department of Medicine, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece

¹³ Medical Oncology Unit, S. Andrew Hospital, 26335 Patras, Greece

¹⁴ Department of Medicine, Division of Medical Oncology-Hematopoietic Cell Transplant Unit, ‘Metaxa’ Cancer Hospital, Piraeus, Greece

¹⁵ Medical Oncology Unit, NIMITS Hospital, Athens, Greece

¹⁶ Oncology Department, General Hospital of Volos, Volos, Greece

¹⁷ Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece

¹⁸ Department of Oncology, Imperial NHS Healthcare Trust, Charing Cross Hospital, London, UK

Background: Daily clinical management of advanced non-small-cell lung cancer (aNSCLC) has tremendously been reformed with the use of immune checkpoint inhibitors (ICIs). Recently, Patras Immunotherapy Score (PIOS) was suggested for this group of patients. PIOS is a baseline formula calculated by a combination of the non-interventional parameters performance status (PS), body mass index (BMI), age and line of treatment (LOT) following the formula PIOS = (PS × BMI)/(LOT × AGE).

Aim: The objective of this study was to validate the clinical value of PIOS in an external cohort of patients with aNSCLC treated with nivolumab or pembrolizumab as monotherapy.

Methods: In the current multicenter study, 626 patients with aNSCLC (stages 3 and 4) who were treated with nivolumab or pembrolizumab as monotherapy in Greek and German cancer centres were retrospectively enrolled. For the patients of the study, clinicopathological and molecular characteristics as well as data regarding response and clinical outcome were collected. Predictive and prognostic value of PIOS, in terms of progression-free survival (PFS) and overall survival (OS), as well as its association with best overall response (BOR) were investigated in the current study.

Results: Patients with PIOS score over median had statistically significant longer PFS compared to patients with lower PIOS score, not only in univariate (hazard ratio [γR] 0.621, 95% confidence interval [CI] 0.470–0.821, p = 0.001), but also in multivariate analysis, adjusted for clinical stage and PD-L1, (HR 0.651, 95% CI 0.492–0.863, p = 0.003). Similarly to PFS, PIOS score was also associated with OS (p < 0.001), with median OS for the favourable group being 778 days compared to 341 days for the patients with low PIOS score (HR = 0.608, 95% CI 0.482–0.766, p < 0.001). This association remained statistically significant (HR 0.620, 95% CI 0.492–0.783, p < 0.001) after adjusting for cofactor (PD-L1). In addition, PIOS was related to response to immunotherapy with patients presenting disease progression (PD) having lower scores compared to those with stable disease (SD), partial response (PR) or complete response (CR) (p < 0.001). Predictive significance of PIOS score was also proved using a binary logistic regression analysis, adjusted for disease stage and PD-L1 status (p = 0.002, OR 0.578, 95% CI 0.408–0.821).

Conclusions: The results from the current study confirm further the clinical value of PIOS biomarker in patients with aNSCLC treated with nivolumab or pembrolizumab.

Andreadis Ch., Douganiotis G., Andreadou A., Fotarelli A., Molyva D., Loulias N., Bleka E., Kamargianni M., Laspa Ch., Lalla E.

3^rd Department of Medical Oncology, Theagenio Cancer Hospital, Thessaloniki, Greece

Introduction: The recent Covid-19 pandemic created major problems in Cancer Centers.

Purpose: To assess the impact of the pandemic on the access of cancer patients to healthcare, diagnostic examinations and cancer treatments in the largest Cancer Center of Northern Greece.

Methods: Parameters relevant to the function of Theagenio Cancer Hospital were analyzed for the year 2020 and compared with 2019 and 2018.

Results: The most significant results are summarized in the following table

Conclusions: The Covid-19 pandemic caused a reduction in the entirety of services offered in the only Cancer Hospital in Northern Greece. The greatest reductions were observed in the number of new patients, outpatients examined, screening examinations and some diagnostic examinations. Medium reductions were observed in the number of hospital admissions, surgeries performed, and cancer treatments.

Paraskeva M., Agelaki S., Tsoukalas N., Konstantis A., Kiagia M., Arvanitou E., Rovithi M., Alexaki M., Ardavanis A., Boukovinas I.

On behalf of the Hellenic Society of Medical Oncologists (HeSMO, http://www.hesmo.gr), Athens, Greece

Background: Palliative care (PC) improves the quality of life, the levels of satisfaction and survival of cancer patients. The interest of medical oncologists (MO) in Greece in PC is constantly increasing.

Aim: To record the opinions and concerns of Greek MO regarding PC in Greece.

Methods: From 10 February to 1 March 2021, the Hellenic Society of Medical Oncologists (HeSMO) conducted an electronic survey with the registered members of HeSMO and the Greek young oncologists group (ONEO) regarding the delivery of PC to patients with advanced cancer in Greece.

Results: We received 69 answers (89.6% trained, 17.4% in training, 47.8% women) from those working in public (44.1%), university hospitals (25%) and in private practice (27.9%). Among the trained MO, 51.6% have a working experience ≥10 years. MO always/usually assess (42.7%/41.2%) and always/usually (57.1%/31.2%) reassess the PC needs of their patients. Although nearly all MO agree that PC is essential in cancer management, the majority believe that PC needs are met neither on time (89.9%) nor effectively (95.7%) in Greece. Only 36.3% consider themselves efficient to manage common PC needs of their patients, and 82.6% express interest in attending educational programmes in PC. Moreover, 52.2% and 36.2% consider that ≤20% and 20%–50% of cancer patients, respectively, require specialist PC and 95.7% consider that the organisation of multidisciplinary PC teams at cancer centres is a necessity.

Conclusions: MO consider that PC has a fundamental role in the treatment of patients suffering from advanced cancer, and that PC is not effectively provided in Greece. Promoting training and education of MO and organisation of multidisciplinary PC teams in cancer centres could improve the provided services.

Tsoukalas N., Christopoulou A., Papandreou Ch., Athanasiadis I., Koumarianou A., Peroukidis S., Samelis G., Psyrri A., Kapodistrias N., Kalofonos Ch., Andreadis Ch., Tripodaki E-S., Samantas E., Kentepozidis N., Barbounis V., Mavroudis D., Anastopoulou G., Arvanitou E., Timotheadou E., Papadopoulou P., Nikolaidi A., Kampoli A., Katsouli E., Dimitriadou A., Golfinopoulos S., Mouzakiti A., Nikolakopoulos A., Tzimou M., Perdikari K-X., Giannakou M., Bokas A., Litos I., Sofatzis I., Mala A., Thalassinou P., Assi A., Loulias N., Ardavanis-Loukeris G., Volakakis N., Athanasiadis A., Ardavanis A., Papakotoulas P., Boukovinas I.

On behalf of the Hellenic Society of Medical Oncology (HeSMO, http://www.hesmo.gr/en), Athens, Greece

Background: Cancer Associated Thrombosis (CAT) is an increasing challenge for oncology patients since oncologists sometimes are reluctant to mitigate the risk with thromboprophylaxis. Active cancer patients while receiving chemotherapy have a 7fold risk of thrombosis compared with no cancer patients. Anticoagulation holds a prominent place in prevention of CAT usually with Low Molecular Weight Heparins (LMWHs).

Methods: ACT4CAT is prospective observational study conducted by HeSMO across Greece, aiming to record the clinical practice of CAT prophylaxis in patients with solid tumors. Ambulatory, high thrombotic risk, active cancer patients who received thromboprophylaxis enrolled after signing informed consent.

Results: Preliminary results collected from 18 oncology departments. From 431 enrolled patients 322 (65.4%) had completed the study. Tumor types included: lung 28.8%, gastrointestinal 39.8%, gynecological 7.0%, breast 4.4%, urological 7.0% and others 20%. Majority of patients (88.2%) received High-Risk for Thrombosis Chemotherapy Agents (HRTCAs) such as platinum agents (55.9%), antimetabolites (44.7%) and immunotherapy (12.6%). In 1^st line were 62.1%, 2nd line 18.4%, adjuvant 8.9% and neoadjuvant 2.4%. The following table depicts: age, gender, metastatic disease, Khorana score ≥2 and HRTCAs.

All patients received thromboprophylaxis for 5.3±3.6 months with: tinzaparin 90.8%, fondaparinux 5.5%, bemiparin 1.5%, enoxaparin 1.2%, apixaban 0.5% and rivaroxaban 0.5%. Intermediate doses received 70.9% of patients regardless clinical setting (1^st, 2^nd, adjuvant & neoadjuvant: 70.2%, 79.2%, 51.3% and 70.0% respectively, p=0.0254), although intermediate doses were used more in metastatic stages (OR:2.4 95%CI: 1.4–4.2, p=0.0028). Nine thrombotic events reported (2.1%, 95%CI: 1.1–3.9%), irrespective of clinical setting but with a trend towards prophylactic doses. Eleven grade 1 bleedings reported (2.6%, 95%CI: 1.4–4.5%), despite clinical setting or dose used.

Conclusions: Thromboprophylaxis in ambulatory active cancer patients with high thrombotic risk is safe and effective. Oncologists are alerted about CAT negative influences in cancer patients’ prognosis. Apart from Khorana score, factors such as metastases, use of HRTCAs and drug-drug interactions influence the clinical decision of thromboprophylaxis in active cancer patients mainly with LMWHs and quite often with intermediate doses regardless clinical setting.

Karteri S.¹, Argyriou A.², Velissaris D.³, Bravou V.⁴, Kalofonos H.¹

¹Oncology Unit-Department of Internal Medicine, University Hospital of Patras

²Neurology Department, Saint Andrew’s General Hospital of Patras

³Department of Internal Medicine, University Hospital of Patras

⁴Department of Anatomy-Histology-Embryology, Medical School, University of Patras

Background: Serum neurofilament light chain (sNF-L) is a neuron-specific cytoskeletal protein important for cell structural stability. There is compelling experimental evidence that neurofilament light chain (NF-L) could sensitively be detected in serum as a biomarker of neuro-axonal damage induced by chemotherapy.

Aim: We sought to assess the significance of measuring sNF-L in the clinical setting of paclitaxel-induced peripheral neurotoxicity (PIPN).

Methods: We longitudinally measured sNF-L in breast cancer patients, scheduled to receive the 12-weekly paclitaxel-based regimen. Patients were clinically examined by means of the Total Neuropathy Score clinical version (TNSc), while sNF-L was quantified using the highly sensitive Simoa technique before the onset of chemotherapy (T0), after commencing two courses (T1), three courses (T2), at the end of chemotherapy (T3) and 3 months post-treatment (T4).

Results: A total of 24 female patients, having a mean age of 56.6 ± 12.6 (33–78) years, were included. Among them, 10 (41.7%) developed grade 0–1 and 14 (58.3%) developed grade 2–3 PIPN at T3. Analysis of variance (ANOVA) of repeated measures disclosed a significant longitudinal increase in sNF-L levels (pg/mL) from T0 to T3 (T0: 15.3 ± 11.9; T1: 30.1 ± 38.5; T2: 51.5 ± 82.1; T3: 134.9 ± 118.6; p < 0.001) and a drop from T3 to T4 (4 ± 11.3). Patients with grade 2–3 PIPN had significantly increased sNF-L levels at T3, compared to those with grade 0–1 (p < 0.001). Mean levels of sNF-L significantly correlated with TNSc scoring. Logistic binary regression analysis revealed that the difference of sNF-L levels between T1 and T0 independently predicted the manifestation of severe grade 3 PIPN at T3. ROC analysis defined that a discriminative increase of >21.5 in sNF-L levels at T1 versus T0 predicted with a sensitivity of 71% and a specificity of 100% the development of grade 3 PIPN at T3.

Conclusion: sNF-L seems to be a strong biomarker of neuro-axonal injury, while its early increase after two chemotherapy courses (T1) possesses a predictive value of final PIPN severity. Our findings could be relevant for future neuroprotection trials.

Monastirioti A.¹, Papadaki C.¹, Rounis K.², Kalapanida D.², Papakosta V.¹, Georgiadou M.², Vardakis N.², Mavroudis D.^1,2, Agelaki S.^1,2

¹Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece

²Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece

Background: MicroRNAs (miRNAs) have been reported to modulate the crosstalk between tumour cells and the immune system. Circulating miRNAs may conclude the systemic response to the tumour, providing in parallel the opportunity for repeated monitoring. Let-7c, miR-26a, miR-30d, mir-98, miR-195 and miR-202 are reported to be involved in the polarisation of macrophages.

Aim: To investigate the expression of miRNAs in the plasma of non-small cell lung cancer (NSCLC) patients treated with first-line platinum-based chemotherapy and their association with patients’ outcome.

Methods: Blood samples were obtained from NSCLC patients (N = 125), prior to the initiation of chemotherapy. Plasma miRNA expression levels were analysed by RT-qPCR and classified as high/low based on the median values.

Results: The median age was 65 years (range: 37–88), 86.4% of the patients were male, 68% of the patients had non-squamous (non-SqCC) histological type, and 26.4% of the patients experienced PR, 39.2% SD and 34.4% PD. High miR-202 expression was associated with disease progression (hazard ratio [HR]: 2.335; p = 0.040) and was revealed as an independent prognostic factor for shorter progression-free survival (PFS; HR: 1.564; p = 0.021) and overall survival (OS; HR: 1.558; p = 0.024) in the whole group of patients. In the non-SqCC subgroup, high miR-202 was also revealed as an independent predictor for shorter OS (HR: 1.989; p = 0.008), while in the SqCC subgroup, only high miR-26a expression was correlated with shorter OS (10.07 vs. 13.53 months, p = 0.033).

Conclusions: The present study is the first to demonstrate the potential role of circulating miR-202 in the prediction of outcome in NSCLC patients treated with platinum-based chemotherapy. Additionally, this study further supports the hypothesis that circulating miRNAs involved in the regulation of the immune response may represent promising biomarkers.

Kottorou A.¹, ^*, Dimitrakopoulos F.-I.^1,2,*, Antonacopoulou A.¹, Makatsoris T.^1,2, Stavropoulos M.³, Koutras A.^1,2, Kalofonos H.^1,2

¹Molecular Oncology Laboratory, Department of Medicine, University of Patras, Greece

²Division of Oncology, University Hospital of Patras, University of Patras, Greece

³Department of Surgery, University Hospital of Patras, University of Patras, Greece

^*Equal contribution

Background: In the last decade, a growing number of studies have shed light on the role of extracellular vesicles, mainly of exosomes, in cancer generally as well as in colorectal cancer (CRC) more specifically. The available published data mostly focus on exosome cargo, while data regarding the pathway of exosome biogenesis in CRC are limited.

Aim: The current study aims to investigate the clinical significance of the exosome biogenesis pathway in CRC, evaluating the expression of the most important molecules, which are implicated in the pathway, and associating them with the clinicopathological parameters and the clinical outcome of the patients.

Methods: Based on the data analysis of publicly available datasets, we selected the most promising molecules of the pathway with potential for clinical impact. Totally, 100 cancerous and 60 adjacent non-neoplastic fresh-frozen tissue specimens were used, which were prospectively collected from CRC patients (stages I–IV), who were surgically managed in the University Hospital of Patras, Greece. mRNA expression of RAB27A (Ras-Related Protein Rab-27A), RAB27B (Ras-Related Protein Rab-27γ), RAB2B (Ras-Related Protein Rab-2B), RAB3B (Ras-Related Protein Rab-3B), RAB9A (Ras-Related Protein Rab-9A), RAB11B (Ras-Related Protein Rab-11B), STX1A (syntaxin 1A) and VAMP7 (vesicle-associated membrane protein 7) genes was assessed in the these samples using real-time qPCR and specific primers and probes and was associated with the clinicopathological parameters as well as with the clinical outcome of patients.

Results: Gene expression of the studied molecules differed significantly between cancerous and non-cancerous tissues, with cancer tissues having lower levels of RAB27A (p = 0.003), RAB27B (p = 0.014), VAMP7 (p = 0.017) and RAB3B (p < 0.001) and higher levels of STX1A (p < 0.001), compared to non-neoplastic, tumour-adjacent tissues. In addition, patients with distant metastases at diagnosis had lower mRNA levels of RAB27A (p = 0.049), RAB27B (p = 0.033) and RAB9A (p = 0.034), compared to patients without distant metastases. Furthermore, patients with increased RAB27A (p = 0.008), RAB9A (p = 0.015), RAB11B (p = 0.011) and STX1A (p = 0.011) expression had favourable 3-year survival, while patients with increased VAMP7 expression had unfavourable 5-year survival (p = 0.022).

Conclusions: The results of this study suggest that biogenesis of exosomes is deregulated in CRC and is possibly implicated in metastasis development.

Glentis S., Katsibardi K., Andritsou A., Roka K., Filippidou M., Kattamis A.

Pediatric Hematology Oncology Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece

Background: The genetic variants of intermediate/high risk, as well as genetic counselling and prevention of cancer in other family members are crucial for the diagnosis, treatment and surveillance of paediatric cancer patients.

Aim/Methods: We aimed to investigate the genetic aetiology of cancer in children and teenagers. Our cohort was composed of 81 patients (31 with haematologic cancer and 50 with solid tumours). Inclusion criteria were family history, rare tumour type or site, relapse or refractory disease. Germline genomic DNA was isolated from the peripheral blood of each patient. Two next-generation sequencing (NGS) panels, covering genes associated with solid or haematologic malignancies and consisting of 155 and 160 genes, respectively, were developed. In-solution hybridisation-based probes were designed using appropriate software (Agilent SureDesing, custom-made panel), and they targeted all the exons of the genes of interest. Sequencing was performed with NGS technology in an Illumina Miseq platform. Raw data processing and analysis was performed with standard bioinformatic tools (BWA-MEM, GATK, VCFtools, VEP). Confirmation and family segregation analysis was performed via Sanger sequencing in the identified Pathogenic (P) and Likely Pathogenic (LP) genetic variants.

Results: We captured 859 (range: 750–950) genetic variants per patient. P/LP variants with a direct link to the phenotype were identified in 6/81 (7.4%) patients. Additionally, in 4/81 (4.9%) patients, we identified heterozygous P/LP variants in genes related to cancer predisposition. but not directly linked to their phenotype. Furthermore, five P/LP variants were detected in five patients, but were not linked to the phenotype and were considered incidental findings. Finally, seven variants of unknown significance (VUS) were detected, for which more investigation to assess a possible pathogenic role is required.

Conclusions: NGS contributes to the investigation of germline pathogenicity in paediatric cancer. A significant number of patients carry genetic variants in genes linked to cancer predisposition. VUS investigation is of great importance and requires further research to determine the possible pathogenic role of the variants.

Argyriou A.¹, Karteri S.², Velissaris D.³, Kalofonos H.²

¹¹Neurology Department, Saint Andrew’s General Hospital of Patras

²Oncology Unit-Department of Internal Medicine, University Hospital of Patras

³Department of Internal Medicine, University Hospital of Patras

Background: Chemotherapy-induced cognitive impairment (CICI), also called ‘chemobrain’, is a well-established clinical syndrome consisting of moderate to subtle cognitive impairment across various domains of gnosia. This syndrome occurs during and after discontinuation of chemotherapy, but its underlying mechanisms remain largely unknown.

Aim: To assess the utility of serum neurofilament light chain (sNfL) levels in identifying the risk to develop CICI in cancer patients. We also examined if sNfL can be identified as an early biomarker of CICI development.

Methods: We longitudinally measured sNfL levels in 20 female patients with breast cancer, scheduled to receive the 12-weekly paclitaxel-based regimen. An equal number of age-matched female heathy subjects were incuded as the control group. CICI was graded by means of the Montreal Cognitive Assessment scale (MOCA); peripheral neurotoxicity (PN) was graded using the neurosensory Common Criteria for Adverse Events (CTCAE) v5.0, while the sNfL levels were quantified using a high-sensitive technique (Quanterix, Simoa) before the administration of chemotherapy (T0), after three courses (T1) and at the end of chemotherapy (T2).

Results: Pre-treatment sNfL levels were comparable in patients and controls (p = 0.103). At T2, 5/20 patients (mean age 61.4 ± 5.0 years) developed CICI. These five patients also had clinically significant PN. Patients with and without CICI had comparable sNfL values at T2 (p = 0.1). In addition, at T2, the sNfL levels did not correlate significantly with MOCA score in CICI patients (p = 0.604). The difference in sNfL levels between T1 and T0 failed to predict independently the occurrence of CICI at T2.

Conclusion: Our findings do not support the utility of measuring sNfL levels as a biomarker of CICI. Grade 2–3 PN most strongly confounded the outcomes of our study.

Gkoumas G.,^1,2 Vlachothanassi E.,³ Simou E⁴

¹¹Medical Oncologist, MSc, Agios Savvas Anticancer Hospital, Athens, Greece

²Department of Public Health Policy, School of Public Health, University of West Attica

³RN MSc, Laiko General Hospital, Athens, Greece

⁴Associate Professor, Mass Media and Health Communication, Department of Public Health Policy, School of Public Health, University of West Attica

Background: Communication between doctor and patient and, in particular, breaking bad news in oncology is a key issue in the doctor–patient relationship. Bad news is any information that can negatively affect a person’s expectations for their present, future and, consequently, their quality of life.

Aim: The purpose of this study was to search the available literature regarding the main protocols used in breaking bad news to oncology patients.

Methods: We performed a systematic review of the literature from 1 to 12 April 2019 in search for related articles, studies, reviews of technical manuals and dissertations related to the topic using an appropriate algorithm in PubMed, regardless of the date, based on the following key words: communication, oncology, delivering bad news.

Results: Four main communication protocols for delivering bad news in oncology patients (SPIKES, ABCDE, BREAKES, PEWTER) and their adaptations in different countries according to the culture of each country’s people were identified. The use of an appropriate communication protocol for breaking bad news helps doctors to inform patients, reducing the stress and psychological burden of patients and doctors. Communication becomes more effective, anthropocentric and leads to the development of trust and a strong therapeutic bond between patient and physician, resulting in better treatment plan design and increased patient satisfaction with the medical services provided and respect for its individuality.

Conclusion: Breaking bad news in cancer patients must be done in a specific and structured way based on specific steps that are described in detail in the international protocols for the communication of bad news. There are differences and discrepancies in each protocol of announcing bad news. Most authors emphasise the importance of these protocols as well as the need to integrate them into daily clinical practice.

Keywords: communication, oncology, delivering bad news.

Levva S.^1,2, Sogka H.³, Skolariki A.³, Gkoura S.⁴, Tripodaki H.S.⁵, Stafylas P.⁶, Assi A.⁷, Goumas G.⁸, Dimitriadis I.^7,9, Stoupis I.¹⁰, Loga K.³, Kyriazoglou A.¹¹, Tsironis G.¹², Gavriatopoulou M.¹³, Boukovinas I.^1,2

¹Department of Medical Oncology, Bioclinic, Thessaloniki

²Department of Medical Oncology, Interbalkan Medical Center, Thessaloniki

³Medical Oncology University Clinic, AUTH, “Papageorgiou” Hospital, Thessaloniki

⁴Medical Oncology University Clinic, UoI, Ioannina

⁵“Agios Savvas” Hospital, Athens

⁶Scientific Director, HealThink, Thessaloniki

⁷Department of Medical Oncology, Errikos Dynan Hospital, Athens

⁸2nd Internal Medicine Clinic, “Agios Savvas” Hospital, Athens

⁹Department of Medical Oncology, Hospital Athens

¹¹Department of chemotherapy, General Hospital of Rethymno

¹²2nd Internal Medicine Clinic, Attikon University Hospital, National and Kapodistrian University of Athens

¹³Department of Medical Oncology, Nicosia General Hospital, Cyprus

¹⁴Therapeutic Unit, Hematology / Oncology University Clinic, Alexandra General Hospital, National and Kapodistrian University of Athens

Introduction: The importance of gender as a determinant of disease biology and treatment effectiveness is well known in some fields of medicine, but remains a poorly studied factor in oncology.

Aim: HeGYO created a questionnaire, in order to record whether the patient’s gender is a differentiating factor of Medical Oncologists’ therapeutic approach.

Method: The questionnaire was distributed to the members of HeSMO and HeGYO through an electronic platform and consisted of 22 questions, which concerned physicians’ demographic data and their practices regarding the management of their patients by gender. Statistical analysis was performed using Chi-Square and Fischer’s exact test, using the R programming language.

Results: 105 physicians answered the questionnaire, 79% of whom where specialized and 56% men. The majority of oncologists in a typical week see an equal number of female and male patients (67.9%), do not take gender as a factor in differentiating their therapeutic approach (73%), devote the same time to each patient in the first (83.8%) and in a standard visit for treatment (82.8%), do not modify the medication according to gender (84%) and consider that the occurrence of side effects is gender independent (67%). However, older doctors consider side effects to be more common in women (P = 0.05). 58% consider women patients more anxious, while 50% administer more frequent anxiolytics to them. Oncologists <45 years old discuss fertility and reproduction issues more often with women (P = 0.01). Finally, adherence to medical recommendations (52%) and consistency in follow-up appointments (59%) are gender independent.

Conclusions: Gender as a differentiating factor of cancer patients’ therapeutic approach is a new field of study, promoting personalized medicine and highlighting the peculiarities that arise from the different biology and psychology that accompanies each patient.

Stamatopoulou E.¹, Tsilias D.², Valassi L.³, Valassi S.⁴, Antonakou A.⁵, Stamatopoulou A.⁶

¹PhD(c), M.Sc-MPH National School of Public Health, M. Sc. in Management of Health and Social Welfare Services University of West Attica and European University Cyprus, Public Health Officer, R. N. General Hospital of Attica KAT, Teacher, Member Hellenic Society of Internal Medicine, Member PCRS UK.

²RN, MSc Clinical Pediatrics & Nursing-Research General Children’s Hospital of Athens P. & A. Kyriakou. Cross-sectoral Department of Pediatric Clinics: Pathology, Maxillofacial Surgery, Otolaryngology and Ophthalmology.

³Graduate of the University of Macedonia School of Social Humanities and Arts, Master of Special Pedagogy, University ‘Neofit Rilski’, MSc in music therapy Diploma in Byzantine Music, Academic Scholar.

⁴Graduate of E.K.Π.A. Diploma in Byzantine Music, MSc Special Education, MS (c) Management of Cultural Units.

⁵‘Senior Nurse Manager’, MSc General Hospital of Nikaia ‘Agios Panteleimon’.

⁶PhD(c), Economist, M. Sc. International Business Administration, M. Sc. in Management of Health and Social Welfare Services University of West Attica and European University Cyprus, Teacher, Academic fellow in University of West Attica

Background: Research on the effectiveness of artistic therapy has been studied in recent years.

Purpose: To investigate the effect of art therapy on oncology patients.

Methods: The method followed is secondary, as it draws on research and studies by experts. A bibliographic search was performed in the electronic database PubMed with the following keywords: art therapy oncology patient from 2011 onwards.

Results: Art therapy includes dance, movement, music therapy and art therapy that involves visual art materials and paintings. The creative process of art, as a path of non-verbal expression, enhances life and provides relief. Studies in cancer patients have shown that artistic therapy leads to increased self-awareness, improved ability to cope with symptoms such as stress and traumatic experiences, personal development, social interaction, improvement in mental health and quality of life. Art painting therapy reduces the fatigue levels during radiotherapy in cancer patients. In patients undergoing radiation therapy, participating in art therapy interventions supports the emotional, psychological and spiritual needs of patients. In addition, patients receiving chemotherapy are reported to have reduced anxiety, depression, stress and pain. Existing studies show that art therapy has benefited, and improved, quality of life by reducing stress, depression and anxiety in women with genital cancer. Further qualitative studies should be conducted to investigate the results of art therapy in oncology patients with adequate samples, various art forms and patient biomarker assessment to draw safe conclusions and application.

Conclusions: Art therapy is used as a psychosocial intervention to relieve patients’ symptoms, which can improve the physical, mental and emotional well-being of cancer patients.

Stamatopoulou E. ¹, Tsilias D.², Valassi L.³, Valassi S.⁴, Antonakou A.⁵, Stamatopoulou A.⁶

¹PhD(c), M.Sc-MPH National School of Public Health, M.Sc. in Management of Health and Social Welfare Services University of West Attica and European University Cyprus, Public Health Officer, R. N. General Hospital of Attica KAT, Teacher, Member Hellenic Society of Internal Medicine, Member PCRS UK.

²RN, MSc Clinical Pediatrics & Nursing-Research General Children’s Hospital of Athens P. & A. Kyriakou. Cross-sectoral Department of Pediatric Clinics: Pathology, Maxillofacial Surgery, Otolaryngology and Ophthalmology.

Background: Clinical trials recommend music therapy as a complementary, psychosocial intervention to both paediatric oncology patients and caregivers during treatment.

Aim: To investigate the effect of music therapy on paediatric oncology patients.

Methods: The method followed is secondary, as it draws on research and studies by experts. A bibliographic search was performed in the online PubMed database with the following keywords: oncology pediatric patients effect music therapy from 2008 onwards.

Results: According to the literature review, caregivers of children and adolescents hospitalised in the marrow transplant unit considered music therapy as a positive, beneficial, effective, complementary intervention. The song lyrics, melody listening and music video with preferred photos resulted in a courageous treatment of the disease and increased resilience of hospitalised children and adolescents/young adults with cancer undergoing haematopoietic stem cell transplantation. Rehabilitation in the unit enhanced the understanding of parents’ feelings, social interaction and cooperation of children, helped to minimise the effects of isolation, negative mood, reduced activity and reinforcement and helped in normalisation of negative experiences that the disease imposed in early childhood. Music therapy also supported the improvement of the health-related quality of life of children undergoing allogeneic haematopoietic stem cell transplants in the marrow transplant unit, according to the rating scale. HRQoL and PedsQL pilot study for children aged 3.5–4.5 years, expand the results of music therapy and report the reception of salivary and blood cortisol levels as a biomarker of stress by hospitalised children undergoing haematopoietic cell transplantation and their accompanying parents supported by music therapy for the objective assessment of its results.

Conclusions: The results of the music intervention in paediatric oncology patients show that the documented application proves to enhance their well-being.

Rigatou E., Tourkantoni N., Tsipou Ch., Roka K., Kattamis A.

University Oncology and Hematology Unit, National and Kapodistrian University of Athens, 1^st Department of Pediatrics, ‘Agia Sofia’ Children’s Hospital, Athens

Background: Ewing’s sarcoma (ES) is the second most common bone malignancy in both children and adolescents. Upon diagnosis, 30% of patients already have metastases. In the last three decades, the use of local therapy (surgery ± radiotherapy) and systemic chemotherapy has significantly increased survival.

Aim: In this study, we present the unit’s recent experience in treating children and adolescents with ES.

Methods: Patients with ES treated at the University Oncology Hematology Unit during the years 2012–2020 were retrospectively analysed. A total of 25 patients (M = 16, F = 9) with a mean age at diagnosis of 11 years (1–16) were treated. Three (12%) had multifocal disease, three (12%) had pulmonary metastases and 19 (76%) had localised disease.

Results: All patients (100%) received systemic chemotherapy according to the following protocol: AEWS0031, EUROEWING 99, EUROEWING 2012. Local control of the disease was achieved with surgery (100%) and radiation (80%). Three patients (12%) received megatherapy and autologous stem cell transplantation. With an average follow-up of 4 years, 18 patients are alive (overall survival 72%). Among survivors, 16/18 patients (64%) are in complete remission, 1/18 (4%) has stable disease and 2/18 (8%) have relapse/disease progression. Patients with relapse or disease progression are those with multifocal/metastatic disease at diagnosis. A key survival factor was the presence of metastases at diagnosis, with a survival rate of 33.3% (2/6 patients) versus 84% (16/19 patients). All patients completed treatment without irreversible toxicity.

Conclusions: ES is an aggressive tumour with a high recurrence rate and metastatic potential. Survival ranges from 60% to 80% for patients with localised disease treated with combination therapy. Patients with metastatic disease have a 4-year survival of0 30%. The survival rates in the present study are according to the current literature. This indicates the need for further improved therapeutic approach for patients with metastatic/multifocal disease.

Stefanou D., Mitsogianni M., Kotteas E., Charpidou A., Gkiozos I., Ntalakou E., Syrigos K.

Oncology Unit, 3^rd University Clinic for Internal Medicine, ‘Sotiria’ Hospital, Medical School of the University of Athens

Background: Immunotherapy is an established treatment in the second and later line for patients with non-small cell lung cancer (NSCLC) who did not receive it in the first line. Despite its high efficacy, there are patients who do not respond or achieve only short-term responses. Various efforts have been made to establish the predictive factors of efficacy of immunotherapy.

Aim: Aim of the study is to examine whether there is a connection between immune-related toxicity and efficacy of immunotherapy.

Methods: Patients with NSCLC receiving immunotherapy beyond first line in our clinic over a period of 3 years were included in the analysis. Besides demographics, we collected data concerning efficacy and toxicity of immunotherapy.

Results: One hundred and ninety-six patients were included in the study. Immune-related adverse events occurred in 32.1% of the patients, with skin toxicity (29%) and hypothyroidism (27.4%) occurring more often. Toxicity was grade ≥3 in 9.5% of immune-related adverse events. Treatment with corticosteroids was administered in 31.7% of the patients presenting with toxicity, while discontinuation of immunotherapy was necessary in 14.3% of them. Toxicity of any grade led to longer progression-free survival (13 vs. 3 months, p < 0.001) and duration of response (not reached vs. 8 months, p = 0.003). On the other hand, there was no connection between type and grade of toxicity, hold or discontinuation of immunotherapy or corticosteroid treatment and efficacy of immunotherapy (p > 0.05).

Conclusions: Our study suggests that immune-related toxicity leads to prolongation of progression-free survival and duration of response, while toxicity type and grade, treatment hold or discontinuation and corticosteroids do not have an impact on the therapeutic outcome.

Chatzinikolaou A.¹, Lavdaniti M.²

¹Postgraduate student, Nursing Department, International Hellenic University, Thessaloniki

²Associate Professor, Nursing Department, International Hellenic University, Thessaloniki

Background: Cancer is a genetic disease in which the characteristics and functions of normal cells have been altered and is considered as one of the leading causes of death worldwide. COVID-19 causes severe acute respiratory syndrome and has emerged as a new infection that has spread rapidly around the world. It poses a serious threat to the health of vulnerable populations, such as patients with malignancies and immunosuppression.

Methods: A literature review was conducted using the electronic databases PubMed and Google Scholar with the keywords ‘cancer’, ‘COVID-19’, ‘patients’, ‘severe implications’ and a combination thereof. Non-English articles were excluded. Twenty-five articles on the subject were used. The review concerned the last 5 years.

Aim: The aim of this review was to investigate the association between cancer and the complications caused by the COVID-19 virus.

Results: Cancer patients are at high risk for SARS-COVID-19 virus disease, as studies have shown that they are more prone and more susceptible. The patient’s age, treatment history and possible underlying diseases play an important role as they are crucial factors in the prognosis of infection in cancer patients. Also, their weakened immune system significantly increases the risk of developing an infection, which may be caused either by the community or by the hospital environment. Finally, the infection of cancer patients with the SARS-COVID-19 virus has been associated with a rapid worsening of symptoms, the occurrence of serious complications, an increase in admissions to intensive care units and a possible deterioration of their condition, which may even lead to death.

Conclusions: COVID-19 virus is a dangerous infection for patients with chronic and serious underlying diseases, such as cancer. Proper information, protection, safety and care of cancer patients during the pandemic should be a priority and the main concern of health professionals.

Danilatou V.¹, Mavroidis D.², Tzagarakis C.², Antonakaki D.², Kanterakis A.², Kostoulas T.³

¹Sphynx Technology Solutions

²Foundation for Research and Technology-Hellas (FORTH)

³University of the Aegean

Background: Patients with cancer hospitalised in Intensive Care Units (ICUs) suffer from high mortality rates. Current prognostic models predict only in-hospital mortality based on first day information, whereas late mortality is hardly predicted. Modern medical databases contain a huge amount of time series data that remain unexploited since classic statistical methods are unable to manage them.

Aim: Exploring the use of automated machine learning algorithms (auto-ML) to predict early and late mortality (months m0, m1, m3, m6, m12, m > 12) in ICU patients with cancer.

Methods: Exactly 5,691 ICU patients (>15 years old) with cancer from MIMIC-III database (median age 67 years old) were studied. Exclusion criteria: do not resuscitate (DNR) code = 358 and pregnancy = 15. Patients were grouped according to their outcome; 902 died early in hospital, 2,659 died later (median time 1.19 years) and 1,757 recorded as survivors in the database. Overall, 1,752 features were collected (including demographic, clinical, laboratory, medications, procedures, known medical scores and free-text medical notes with natural language processing). Prediction models were built based on the web-based platform JADBio. Several different algorithms such as Random Forests, Support Vector Machine and Logistic Regression have been applied with a new protocol called bootstrap bias-corrected cross-validation and hyper-parameter tuning, which is relatively conservative during performance estimation.

Results: Random Forests was the best performing model for mortality prediction (overall area under the curve [γUC] = 0.83). In detail, the AUC for months m0–m > 12 were 0.94, 0.88, 0.84, 0.78, 0.76 and 0.74, respectively. γest-budgeted Statistically Equivalent Signature algorithm revealed the following features with predictive significance: GCS scale, γPSIII score, sepsis, systolic arterial blood pressure, RDW, first day respiratory rate, SpO₂, coexistence of metastatic cancer and red cell transfusions.

Conclusion: Prediction of late mortality in ICU patients with cancer is difficult. The use of ‘big-data’ and auto-ML outperforms classic prognostic models. Identification of explainable, clinically meaningful features will help clinicians in decision-making process. RDW could be a rediscovered, easily applied biomarker, since it has been previously shown that it correlates with ICU mortality and cancer stage. Further external validation in other databases is necessary.

G. Douganiotis¹, L. Kontovinis², A. Pouptsis², A. Ainali², I. Natsiopoulos³, K. Papazisis^2,3

¹3rd Department of Medical Oncology, Theagenio Cancer Hospital, Thessaloniki, Greece

²Medical Oncology Department, Euromedica General Clinic, Thessaloniki, Greece

³Breast Cancer Unit, Interbalkan Medical Center, Thessaloniki, Greece

Introduction: Chemotherapy remains the only treatment option for patients with early triple negative breast cancer. One of the combinations that has been suggested in order to improve efficacy is the addition of carboplatin to the standard of care chemotherapy regimen of an anthracycline plus a taxane.

Methods: Data from the medical records of Oncomedicare were retrospectively collected. The analysis included all patients with early triple negative breast cancer who received neoadjuvant chemotherapy in the time period between 2010 and 2020. Pathologic responses following neoadjuvant treatment and patient survival data (disease-free survival, overall survival) were also recorded.

Results: A total of 70 patients were included in the analysis. All patients were included who received neoadjuvant chemotherapy, with or without the addition or carboplatin, for whom histology reports from the final surgery were available. The median age of the patients was 44 years, and the median follow-up was 2.3 years. Testing for the presence of germline mutations was performed in 47 patients, 11 of which had a mutation in BRCA1, BRCA2 and other three genes (PALB2, CHEK2, CDKN2A). A complete pathologic response (pCR) following neoadjuvant chemotherapy was recorded in 39 patients (55.7%). Of the 70 patients, 31 received carboplatin in addition to the standard neoadjuvant chemotherapy regimen, and 39 did not. The rate of pCR was higher in the patients who received carboplatin (21/33 patients, 67.7%) compared to those who did not (17/39 patients, 43.6%). Of the 11 patients with mutations in BRCA1/2, 9 recorded a pCR, one had a micrometastasis in one lymph node, and one had residual disease. The achievement of a pCR was an important favorable prognostic factor of disease-free survival (DFS: HR 0.086, 95% CI 0.025–0.301, p=0.0029) as well as overall survival (OS: HR 0.125, 95% CI 0.028–0.559, p=0.0209).

Conclusions: The addition of carboplatin significantly increased the rate of pathologic complete response following neoadjuvant chemotherapy and constitutes a potential treatment option in patients with early triple negative breast cancer.

There was a greater benefit in patients over 40 years of age (p=0.056) and patients with high Ki-67 (p=0.046)

Katsibardi K.¹, Vlacou A.¹, Nitsa E.¹, Avgerinou A.¹, Roka K.¹, Tourkantoni N.¹, Rigatou E.¹, Filippidou M.¹, Tsipou H¹, Bacopoulou F.², Kanaka-Gantenbein C.³, Kattamis A.¹

¹¹Pediatric Hematology-Oncology Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, “Aghia Sofia” Children’s Hospital, Athens, Greece.

²Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, National and Kapodistrian University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece.

³Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens, “Aghia Sofia” Children’s Hospital, Athens, Greece.

Introduction: Thyroid complications in pediatric cancer survivors are common and may present as thyroid dysfunction or thyroid carcinoma.

Aim/Methods: Thyroid function of children treated for pediatric cancer were evaluated retrospectively, within a 6-year period. Therapy was calculated as a category variable; chemotherapy, and or radiation. Hypothyroidism was considered as category value; TSH >5 μIU/mL and TSH<5 μIU/mL. Univariable logistic regression analysis performed to investigate association between hypothyroidism and therapy. Statistical analysis performed with RStudio version 3.6.2. P value <0 .05 was considered statistically significant.

Results: A total of 61 long-term adolescent survivors, 59.0% (N=36) males and 41.0% (N=25) females were longitudinally followed. The follow-up duration was 3.7 years (range 1.7–6.7 years). The median age of treatment was 11.6 years (range 6.6 to 19.2 years). Among them, 28/61 (45.9%) had leukemia, 17/61 (27.8%) lymphoma, 7/61 (11.7%) brain tumor and 9/61 (14.6%) other tumors. Median value of TSH and FT4 was 2.5 μIU/mL (range 0.05–8.2) and 13.4 pmol/L (range 0.35–17.4), respectively. One patient that presented TSH value from 125–147 μIU/mL under relapse treatment for lymphoma was excluded from the present study. Nine patients (15.0%) had hypothyroidism. Minimum/maximum observed time for hypothyroidism was 0.38/5.2 years after treatment completion. Radiation treatment was significantly associated with hypothyroidism (O.R=5.8;95%, C.I (1.3–26.1); p=0.02, 35.71% vs 8.7%). Thyroid lesions, such as cysts-nodules had 6 (10.0%) adolescent survivors. Ten (16.7%) and 4 (6.7%) patients had one and two thyroid parenchymal abnormalities, respectively, while 46 (76.7%) patients had normal thyroid parenchyma. Substitution treatment with levothyroxine was necessary in 10/61 (16.6%) survivors. Most of the patients 60/61 had negative antithyroid antibodies.

Conclusion: Thyroid sequelae resulting from radiation therapy may manifest only after years to decades of follow-up, and their resultant clinical symptoms may be indolent. Life-long monitoring of pediatric cancer survivors for thyroid function is paramount.

Galiti D.¹, Agelaki S.², Karampeazis A.², Linardou H.², Tsoukalas N.², Bamias A.², Psyrri A.², Karamouzis M.², Syrigos K.², Ardavanis A.², Athanasiadis I.², Arvanitou E.², Sgourou S.², Kouloulias V.², Zygogianni A.², Georgopoulou E.², Mala A.², Vallilas C.², Evangelou G.², Kokkali S.², Nikolaidi A.², Papadopoulou P.², Nicolatou-Galitis O.¹, Boukovinas I.²

¹CureCancer, Athens, Greece

²Hellenic Society of Medical Oncology, Athens, Greece

Aim: We assessed CureCancer’s feasibility and patients’ and HCPs’ satisfaction. CureCancer is a patient-centric/driven platform, which enables patients to self-create their profile, report symptoms and communicate with physicians.

Methods: Patients from 18 centres were asked to register at CureCancer, upload their data and complete a questionnaire on demographics, disease and treatment characteristics and their satisfaction.

Results: One hundred and fifty-nine patients were enrolled and 144 (90.6%) registered; 114 of 144 (79.1%), 63 males and 51 females, with a median age 54.5 years, completed the questionnaire. Sixty-four patients were university graduates and 35 were high school graduates. Forty-six patients had metastatic disease, 87 were on active treatment and 51 received supportive care. All patients also visited non-oncology HCPs. Nineteen patients changed their work status and 49 had children below 24 years.

Registration was ‘very/very much’ easy for 98 (86.0%) patients. File uploading was ‘very/very much’ easy for 47 (41.2%) patients. Over 80% of patients and physicians preferred the digital way. Ninety-nine patients and all HCPs will recommend CureCancer to others. Easy data access, improved communication, feeling safe, treatment adherence, interventions from distance, particularly during COVID-19 pandemic, and saving time and money were highly commented by patients and HCPs.

Conclusion: CureCancer was feasible, and patients and HCPs were satisfied. File uploading changed to become more user friendly. Integration of CureCancer in the routine practice is expected to improve cancer care and reduce cancer costs. Patients’ self-reporting, with CureCancer, can increase the accuracy of clinical trial results and map social/work/economic issues following cancer diagnosis to assist healthcare policy.

Stamatopoulou E.¹, Tsilias D.², Valassi L.³, Valassi S.⁴, Antonakou A.⁵, Stamatopoulou A.⁶

¹PhD(c), M.Sc-MPH National School of Public Health, M.Sc. in Management of Health and Social Welfare Services University of West Attica and European University Cyprus, Public Health Officer, R. N. General Hospital of Attica KAT, Teacher, Member Hellenic Society of Internal Medicine, Member PCRS UK.

²RN, MSc Clinical Pediatrics & Nursing-Research General Children’s Hospital of Athens P. & A. Kyriakou. Cross-sectoral Department of Pediatric Clinics: Pathology, Maxillofacial Surgery, Otolaryngology and Ophthalmology.

³Graduate of the University of Macedonia School of Social Humanities and Arts, Master of Special Pedagogy, University ‘Neofit Rilski’, MSc in music therapy Diploma in Byzantine Music, Academic Scholar.

⁴Graduate of E.K.Π.A. Diploma in Byzantine Music, MSc Special Education, MS (c) Management of Cultural Units.

⁵‘Senior Nurse Manager’, MSc General Hospital of Nikaia ‘Agios Panteleimon’.

⁶PhD(c), Economist, M.Sc. International Business Administration, M.Sc. in Management of Health and Social Welfare Services University of West Attica and European University Cyprus, Teacher, Academic fellow in University of West Attica.

Background: Childhood cancer involves long periods of hospitalisation that cause feelings of fear and sadness, where they have a significant impact on the well-being and quality of life of paediatric oncology patients.

Purpose: To investigate the effect of art therapy on paediatric oncology patients.

Methods: The method followed is secondary as it draws on research and studies by experts. A literature search was performed in the online database PubMed with the following keywords: art therapies effect oncology pediatric cancer patients.

Results: Art therapy includes a set of activities like dance, movement, music, art, laughter therapy, theatre, play and poetry, and studies report a positive effect on the well-being of oncology paediatric patients. Studies on artistic therapeutic intervention with dance/movement, music and graphic arts report positive results in children’s pain, taste and food intake during chemotherapy. Study of oncological children who underwent diagnostic procedures such as bone marrow aspiration, lumbar puncture and treatment participated in art therapies with medical play, free drawing and theatre to reconcile with the change of body image. Children who received a session from the very first hospitalisation showed cooperative behaviour. The parents expressed their ability to better manage the painful processes of caring for their children with art therapy. In paediatric oncology, interactive music therapy reduced stress, anxiety and pain by increasing communication, cooperation, participation in play activities during hospitalisation with a beneficial effect on the well-being of children with cancer. Gaming therapy promotes mental, emotional and social development. A recent study reports that the use of new gaming technologies such as HabitApp increases the levels of affection, love, physical activity and social interaction in the paediatric oncology unit.

Conclusions: In paediatric oncology, art therapy has a significant positive effect on pain, facial expression, nervousness and stress.

G. Douganiotis¹, S. Grigoriadis², E. Markopoulou², L. Kontovinis², A. Pouptsis², K. Papazisis²

¹3rd Department of Medical Oncology, Theagenio Cancer Hospital, Thessaloniki, Greece

²Medical Oncology Department, Euromedica General Clinic, Thessaloniki, Greece

Introduction: Dual HER2 targeting (trastuzumab+pertuzumab) has become the standard of care in the neoadjuvant treatment of patients with HER2-positive breast cancer. Given the potential cardiotoxicity of both the chemotherapy used (anthracyclines) and the anti-HER2 monoclonal antibodies, concerns exist regarding the cardiac safety of this combination regimen.

Methods: Data from the medical records of Oncomedicare were retrospectively collected. The analysis included all patients with early HER2-positive breast cancer who received neoajuvant chemotherapy with 4 cycles of epirubicin / cyclophosphamide (90 / 600 mg/m²) and 4 cycles of docetaxel (90mg/m²), trastuzumab and pertuzumab in the time period between 2014 and 2020. Patients additionally received adjuvant anti-HER2 treatment for one year where indicated. Following the regulatory approval of TDM-1, patients with residual disease received TDM-1 as adjuvant anti-HER2 treatment. The evaluation of cardiac function was performed with serial transthoracic ECHO and measurement of the Left Ventricle Ejection Fraction (LVEF). Pathologic responses following neoadjuvant treatment were also recorded.

Results: A total of 55 patients were included in the analysis, with a median age of 50 years at diagnosis and a median cardiological follow-up of 2.61 years following treatment. A total of 283 echocardiograms were performed. There was a consistent drop in LVEF values during treatment, which was not significant enough to necessitate treatment interruption. The values then consistently improved during follow-up. There were no cases of symptomatic heart failure, and there was only one recorded case of asymptomatic LVEF drop > 10%. A complete pathologic response was recorded in 64.8% of patients, with a higher rate for ER-negative patients (90%) than ER-positive ones (50%), a difference which was statistically significant and is consistent with the results from the relevant randomized clinical trials.

Conclusions: This data shows the long-term cardiac safety of this combination regimen in clinical practice and confirms both its safety and efficacy in patients with early HER2-positive breast cancer.

Mitsogianni M., Stefanou D., Charpidou A., Mani M., Gkiozos I., Syrigos N., Kotteas E.

Oncology Unit, 3^rd University Clinic for Internal Medicine, ‘Sotiria’ Hospital, Medical School of the University of Athens

Background: Immune checkpoint inhibitors are standard treatment options of patients with non-small cell lung cancer (NSCLC) who did not receive first-line immunotherapy, often leading to long-term responses. Nevertheless, the efficacy of various immunotherapeutic agents has not been directly compared in a randomised clinical trial, while retrospective studies are also limited.

Aim: The aim of the study is to determine possible superiority in the efficacy of pembrolizumab and nivolumab in patients with NSCLC beyond first-line treatment.

Methods: Pretreated patients with NSCLC receiving immunotherapy with pembrolizumab or nivolumab in our clinic in a period of 3 years were retrospectively analysed. We collected demographic data, disease control rate, progression-free survival and duration of response.

Results: One hundred and ninety-six patients were included in the analysis; 46 (23.5%) received pembrolizumab and 150 (76.5%) received nivolumab. Baseline demographic and clinical characteristics did not differ significantly between the two groups (p > 0.05). It has to be noted that there were no patients without PD-L1 expression in the pembrolizumab group. There were no differences in disease control rate (54.3% vs. 49.4%, p = 0.252), progression-free survival (5.0 vs. 4.0 months, p = 0.520) and duration of response (not reached vs. 11.0 months, p = 0.662) between the two groups.

Conclusions: According to our findings, the efficacy of pembrolizumab and nivolumab does not differ significantly in pretreated patients with NSCLC.

Fotopoulou E., Plohorou M., Gkirlemis K., Soulimioti G., Maravelis I., Tzorakakis S., Athanasiou E.

“Agioi Anargiroi” General Oncology Hospital, Department of Radiotherapy Oncology

Background: Prostate cancer with adverse pathological features (i.e. pT3 and/or positive margins) after prostatectomy may be treated either with adjuvant radiotherapy (ART) or surveillance followed by early salvage radiotherapy (ESRT) for biochemical recurrence.

Aim: To study the impact of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features after radical prostatectomy.

Methods: Forty-seven patients received ART within a year after radical prostatectomy. Three of them with lymph nodes metastasis who received hormone deprivation therapy were excluded. Four patients presented pT2N0M0/R1 disease, 23 patients pT3N0M0/R1 and 17 patients pT3N0M0/R0 excision. All patients, except four at the time of referral for radiotherapy (RT), were already under androgen deprivation therapy. According to postoperative PSA, patients were divided into two groups: a) patients with undetectable postoperative PSA (<0.2 ng/ml) who received adjuvant RT and b) patients who received ESRT and PSA (>0.2 ng/ml). For all patients, RT was performed using three-dimensional conformal RT (3D-CRT) at a dose of 60–64 Gy and a fractional dose of 2 Gy. Surveillance to biochemical recurrence was started from the date of surgery.

Results: From 44 followed patients, 20 had undetectable PSA (median value 0.04 ng/ml) and undergone γRT within 24 weeks from surgery. PSA for 24 of them was between 0.16 and 0.81 ng/ml (median value 0.38 ng/ml) and they were managed with ESRT, with the median time from surgery being 32 weeks (range 28–48 weeks). Median age was 65 years (53–77 years). Median time of follow-up was 48 months (24–84 months). From the ART group, all patients presented no biochemical recurrence until the time of submission. From the ESRT group, three patients (12.5%) presented with progressive increase of PSA.

Conclusions: Results regarding postoperative RT in our department are in agreement with international data. Concerning the second group of patients, the addition of ESRT was also beneficial as in the first group. More clinical data from randomised controlled studies are necessary in order to clarify the optimal postoperative RT approach, ART versus ESRT.

Christofyllakis K¹, Pföhler C², Bewarder M¹, Müller C S.L.², Thurner L¹, Rixecker T¹, Vogt T², Stilgenbauer S¹, Yordanova K² and Kaddu-Mulindwa D¹

¹Department of Hematology, Oncology, Clinical Immunology and Rheumatology Medical School, University of Saarland, Germany

²Department of Dermatology, Venerology and Allergology Medical School, University of Saarland, Germany

Background: Several agents are approved in the adjuvant setting of completely resected high-risk (stage IIC–IV) cutaneous melanoma. Subgroups may benefit differently depending on the agent used. Meta-analyses addressing this question are lacking.

Aim: To evaluate the efficiency and tolerability of available treatment agents in modern adjuvant therapy of cutaneous melanoma in the total population and across the following subgroups: patient age, stage, ulceration status, lymph node involvement, BRAF status.

Methods: We performed a systematic review and meta-analysis of the currently available data. The PubMed and Cochrane Library databases were searched without restriction in year of publication in June and September 2020. Data were extracted according to the PRISMA guidelines from two authors independently and were pooled according to the random-effects model. The predefined primary outcome was recurrence-free survival (RFS).

Results: After quality control, five prospective, randomised, placebo-controlled trials were included in the meta-analysis. The drug regimens included ipilimumab, pembrolizumab, nivolumab, nivolumab/ipilimumab, vemurafenib and dabrafenib/trametinib. Adjuvant treatment was associated with a higher RFS than placebo (hazard ratio [HR] 0.57; 95% confidence interval [CI] = 0.45–0.71). Nivolumab/ipilimumab in stage IV completely resected cutaneous melanoma was associated with the highest RFS benefit (HR 0.23; 97.5% CI = 0.12–0.45), followed by dabrafenib/trametinib in stage III BRAF-mutant melanoma (HR 0.49; 95% CI = 0.40–0.59). The presence of a BRAF mutation was associated with higher RFS rates (HR 0.30; 95% CI = 0.11–0.78), compared to the wildtype group (HR 0.60; 95% CI = 0.44–0.81). Patient age did not influence outcomes (≥65: HR 0.50; 95% CI = 0.36–0.70, <65: HR 0.58; 95% CI = 0.46–0.75). Immune checkpoint inhibitor monotherapy was associated with lower RFS in non-ulcerated melanoma. Patients with stage IIIA benefited equally from adjuvant treatment as those with stage IIIB/C. Nivolumab/ipilimumab and ipilimumab monotherapy were associated with higher toxicity.

Conclusion: Adjuvant therapy should not be withheld on account of advanced age or stage IIIA alone, as treatment benefit is maintained in these subgroups. The presence of a BRAF mutation is prognostically favourable. BRAF/MEK inhibitors should be preferred in the adjuvant treatment of BRAF-mutant non-ulcerated melanoma.

Andreadou A.¹, Moliva D.², Bleka Ev.², Panagiotidis Em³, Andreadis Ch.⁴

¹Consultant, medical Oncologist, 3rd department oncology clinic, Theagenio hospital

²Intern of medical oncology, 3rd department oncology clinic, Theagenio hospital

³Consultant, nuclear medicine, Theagenio hospital

⁴Chair of the 3rd department oncology clinic, Theagenio

Introduction: Novel targeted treatments have various side effects, some of which are autoimmune. Sarcoidosis is a disease that can be attributed to immunotherapy and there are a few case reports attributed to trastuzumab and none to pertuzumab.

Case: A 45-year-old woman was diagnosed with breast cancer. In Feb 2015, she was diagnosed with locally advanced triple-negative breast cancer. She received neoadjuvant chemotherapy (four cycles EC, four cycles docetaxel) and she had mastectomy ypT1N2/3 and radiotherapy.

In Sept 2017, a metastasis to the liver was present that was confirmed with a PET-CT (SUV: 6.9), which was biopsied. The histology report was different: ER: −, Pr: −, cerbb2: +3, FISH+. She was started on chemotherapy with docetaxel–pertuzumab–trastuzumab. She received six cycles, and then she was continued on maintenance (pertuzumab–trastuzumab) till Sept 2020. The CTs were stable and in Sept 2020, she had a PET-CT that did not show any metastasis, but there were multiple lymph nodes in the mediastinum (SUV: 8.4). The radiologist believed that the diagnosis was immunotherapy-like induced reaction. An EBUS biopsy was conducted. The histopathology report revealed findings of granulomatous reaction pattern, possibly sarcoidosis. The ACE blood exam was normal, although the normal findings did not exclude the diagnosis of sarcoidosis.

Is it a sarcoid-like reaction attributed to the treatment? Or a disease that was already there? Last year, the patient had tingling, palsy in the facial nerves and swelling in joints, but all these symptoms were transient. After a thorough discussion with the patient, we decided to continue only subcutaneous trastuzumab. The stage of the sarcoidosis based on the PET-CT findings was I, which means that the patient should remain on surveillance.

Literature: Trastuzumab has been used since 1998 for treatment of HER2-positive breast cancer. Although adverse effects are not common, some of the pulmonary complications associated with trastuzumab are acute lung injury, acute pneumonitis, organising pneumonia and bronchospasm. There are a few cases worldwide that correlate the use of trastuzumab with sarcoidosis.

Sarcoidosis is considered an adverse effect, but since there are not many cases, there is no guideline for further management. The patient received trastuzumab with pertuzumab; so, it is not certain which drug caused sarcoidosis, if not both. There are no cases reported of sarcoid-like reaction due to pertuzumab.

This young patient was informed about her choices of either stopping the treatment or continuing trastuzumab. She felt uncomfortable of stopping the treatment and decided to continue treatment with trastuzumab.

Conclusions: This is the case of a woman with HER2 metastatic breast cancer, who had complete resolution of her metastasis and was recently diagnosed with sarcoidosis that is likely attributed to anti-HER2 treatment. Each of such rare cases should be discussed individually and the decision should be taken according to the extent of cancer, the stage of sarcoidosis and patient’s wishes.

Chrysoglou S.I., Veniou E., Fioretzaki R., Georgiadou A., Logothetis M., Charalampakis N., Ntokou A., Kosmas C., Ziras N.

Department of Medical Oncology, ‘Metaxa’ Cancer Hospital, Piraeus, Greece

Background: Neuroendocrine neoplasms (NENs) are heterogenous, rare tumours arising from neuroendocrine cells, which are scattered all over the body. They occur more often in the lungs, gastrointestinal tract or pancreas. Their biological behaviour depends on the histopathological characteristics of the tumour (tumour grade, differentiation, number of mitoses, Ki-67) and their localisation.

Aim: To describe the special clinical and histological characteristics of NEN of rare primary site.

Methods: We collected and reviewed all NENs (neuroendocrine tumours [NETs] and neuroendocrine carcinomas [NECs]) of rare primary sites treated in Metaxa Cancer Hospital of Piraeus from 2016 to 2020 and summarised their clinicopathological features.

Results: One hundred and forty-three primary NENs were diagnosed. Among them, we identified 24 (16.8%) of rare primary sites: breast: five (three NECs and two NETs), skin (Merkel): four, thymus: three NETs, larynx: two NECs, bladder: two NECs, prostate: two NECs, liver (paraganglioma): one NET, adrenal gland (pheochromocytoma): one NEC, inguinal area: one NEC, oesophagus: one NEC, kidney: one NEC and ovary: one NEC. The population of the study consisted of 15 men and nine women. Out of the 24 tumours reviewed, 18 were NECs and six were NETs. All NETs were non-functional and their clinical presentation was non-specific. Primary treatment was surgical. Treatment with somatostatin analogues resulted in long-term stabilisation in the case of paraganglioma. The majority of NECs had an aggressive clinical behaviour. Except for breast NECs, which were treated as adenocarcinomas, relapsed or metastatic NECs were treated with first-line cisplatin–etoposide. Immunotherapy was administered in two cases of Merkel carcinoma. Despite their poor clinical outcomes, their prognosis does not seem to differ from other NETs of the same stage.

Conclusions: NENs in rare locations, most frequently NECs, have special characteristics and their management requires multidisciplinary approach offered in highly qualified reference centres. Creation of a national NEN registry and a hospital cooperation network are recommended.

Arvanitou E.¹, Parpa E.², Tsilika E.², Elmasian T-F², Hatzigeorgiou E.², Tsitsimpis A.¹, Gkiaouraki M.¹, Mpallasis K.¹ Chrystofyllakis Ch.¹, Panagou E.¹, Tsoukalas N.¹, Mystakidou K.²

¹Oncology Department, 401 General Military Hospital of Athens, Greece

²Palliative Care Unit, Department of Radiology, University Areteion Hospital School of Medicine, Athens, Greece

Background: Cancer diagnosis is related to fear and is a source of great distress for patients. Anxiety and depression are common in cancer patients and seem to affect quality of life, treatment compliance and even survival. Demoralisation that encompasses feelings of despair, loss of meaning and spiritual distress can occur in patients with cancer. The aim of this study is to investigate the relationship between demoralisation, anxiety and depression and to examine the demographic and clinical factors associated with anxiety and depression.

Methods: A convenience sample of 150 cancer inpatients and outpatients from two oncology centres, with various types of solid tumours, receiving oncology treatment, participated in a prospective cross-sectional observational study. The psychometric tools used were the Greek version of the Hospital Anxiety and Depression Scale (HAD) and the Demoralisation Scale II (DS-II). The study was approved by the ethical committee or related boards of each hospital. Each patient was informed about the aims of the study, and the patient gave his/her written consent to participate.

Results: Patients’ mean age was 62 years (20–85 years) and 89 patients (59.3%) were women. Among patients, 33% had breast, 24% had gastrointestinal and 15% had lung cancer. Eighty-two patients (54.7%) had metastatic disease. Women showed higher rates of anxiety (p = 0.054). Anxiety was inversely related to age (p = 0.043) and positively correlated with time since diagnosis (p = 0.076). Unmarried patients presented higher rates of depression (p = 0.026). Multiple linear regression showed a statistically significant impact of demoralisation on anxiety (p < 0.001, R² = 36.3%) and depression (p < 0.001, R² = 49%).

Conclusions: The results highlight the significant impact of demoralisation on anxiety and depression in cancer patients. This emphasises the need for empathy and understanding of patients’ feelings by healthcare providers to recognise the feelings of despair and distress in a timely manner.

Tsapakidis K., Papadopoulos V., Markou A., Kokkalis A., Chantzara E., Aidarinis C., Saloustros E., Koinis F., Samaras I., Kotsakis A.

Department of Medical Oncology, University General Hospital of Larissa, Larissa, Greece

Background: With the use of prostate-specific antigen (PSA), more and more prostate cancer patients are diagnosed at early stages (1). Almost all patients with metastatic prostate cancer have elevated PSA and only a small percentage of patients with metastatic prostate cancer have normal PSA levels (2–3).

Aim: A clinical case of prostate cancer with normal PSA that has been treated successfully with chemotherapy is presented.

Case report: We report a case of an 81-year-old man who presented with haematuria and underwent CT imaging that revealed lymphadenopathy, multiple bones and prostate heterogeneity. He underwent transurethral biopsy, and the histological examination of the specimen showed low-grade invasive carcinoma with the nuclei showing focal neuroendocrine differentiation, synaptophysin 5%–10% and also PSA focally positive, PSAP strongly positive. Laboratory test showed that he had increased NSE (50) and normal PSA (1,2). The patient was started on chemotherapy with carboplatin and docetaxel and has been disease free for 3 years.

Conclusions: In the prostate gland, a number of neuropeptides, such as GRP, chromogranin A and NSE, are found to be present not only in autonomic and sensory nerve terminals, but also in prostatic neuroendocrine cells (4). Their biological role is not fully understood, but their levels in patients who do not express PSA are elevated (5).

It is now accepted that besides prostate adenocarcinoma, there are cases that display clinical features associated with small-cell carcinoma and are very sensitive to the combination of carboplatin chemotherapy with docetaxel (6). These patients should receive chemotherapy, but the prognosis remains extremely poor (3).

Kouvela M., Stefanou D., Evangelou G., Tourkantonis G., Nasi D., Papafili A., Kotteas H., Syrigos KN

3^rd Department of Internal Medicine, Oncology Unit, ‘Sotiria’ Hospital, Medical School, University of Athens, Athens, Greece

Background: Venus thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE) and is a very common complication in lung cancer patients. Even though VTE is the second cause of death in cancer patients, there are no guidelines concerning which patients need to receive thromboprophylaxis and in what dosage.

Aim: To assess the efficacy and safety of thromboprophylaxis with low-molecular weight heparin (LMWH) in lung cancer patients.

Methods: This study is a single-centre, prospective, observational study. Lung cancer patients of any histology type were evaluated in the first cycle of treatment for the risk of thrombosis. High-thrombotic risk patients were started on thromboprophylaxis with tinzaparin 0.5 ml, 10.0 Anti-Xa IU, OD, used in current clinical practice, and patients with an indication for therapeutic dosage (atrial fibrillation or pre-existing thrombosis) were started on tinzaparin 175 Anti-Xa IU/kgr, OD.

Results: Preliminary results of 60 patients, five of which were set on therapeutic dosage. The median age was 65 years, and the most common histology was adenocarcinoma (50%). During follow-up (6 months), the compliance of the patients was sufficient. Nine patients died due to disease progression (15%), 10 patients discontinued treatment because of lack of sufficient thrombotic risk factors (17%) and six patients discontinued due to adverse events (10%). The adverse events were mild, without the need for medical intervention or hospitalisation of the patients, and they concerned mainly minor bleeding events (haemoptysis). One case of a minor allergic reaction was recorded. One patient experienced thrombotic event (efficacy 98.3%).

Conclusion: LMWH thromboprophylaxis in active lung cancer patients reduces the risk of potentially deadly thrombotic events and is safe and well tolerated by the patients.

Chatzinikolaou A.¹, Lavdaniti M.²

¹Postgraduate student, Nursing Department, International Hellenic University, Thessaloniki

²Associate Professor, Nursing Department, International Hellenic University, Thessaloniki

Introduction: People with cancer belong to the high-risk groups, both for infection with the Sars-Covid-19 virus and for psychological transitions due to their state of health.

Methods: A literature review was conducted using the electronic databases PubMed and Google Scholar with the keywords “psychological distress”, “cancer”, “patients”, “Covid-19 pandemic”, and a combination thereof. Exclusion criteria of articles was the language, except English. 15 articles were used on the subject. The review concerned the years 2020–2021.

Aim: The aim of this study was to investigate the psychological effects of a pandemic on cancer patients.

Results: Cancer patients experience high levels of stress. Cancer is a threat to a person’s life and can significantly change their social, emotional and relational world. According to research, women and young people with cancer appeared to be more prone to stress and post-traumatic stress during the pandemic. In addition, the new condition created by the Sars-Covid-19 virus resulted in additional psychological burden during the treatment period due to treatment delays and prohibition on the presence of a caregiver on the hospital premises. Finally, immunosuppression and the treatment given to them make cancer patients more vulnerable due to the weakening of their immune system, which raises additional concerns about the possibility of infection with the Covid-19 virus even in the non-Covid hospital.

Conclusions: The interdisciplinary care team of cancer patients should have a holistic approach to the patient and deal with both his physical-organic rehabilitation and the mental empowerment of the person during the pandemic.

Tsitsimpis A.¹, Tsoukalas N.¹, Katsouda A.², Mpagkos P.³

¹Oncology Department of 401GMHA

²5^th Surgical Department of GH ‘Ippokrateio’

³Computational Medicine and Bioinformatics University of Thessaly

Background: Immunotherapy has created a revolution in oncology in the last decade. Moreover, the combination of immunotherapy takes a great position in the therapy of solid tumours. Many adverse effects (AEs) have been reported, in connection with the stimulation of immune system, and some of them concern the endocrine system.

Methods: We made a systematic review and searched in PubMed, Medline and Clinical trials for the period from 01/2015 to 12/2020, following which we conducted a meta-analysis. Our search was about adult patients with solid tumours who were treated with EMA- or FDA-approved combination immunotherapy treatments and endocrine AEs were observed through phase 2 and 3. Twenty-six randomised clinical trials were included.

Results: We included 21 clinical trials with 3269 patients who were treated with ipilimumab + nivolumab. The percentage of hypophysitis was 6% (95% Cl: 4%–10%) with mild symptoms. The adrenal insufficiency was 2% (95% CI: 1–3). Although the heterogeneity was great, the percentage of hypothyroidism was 15% (95% CI: 13%–18%) and of hyperthyroidism was 14% (95% CI: 11%–18%). We included five clinical trials with 862 patients who were treated with durvalumab + tremelimumab. Hypophysitis was very rare (1%; 95% CI: 0–2%), but was almost always grade III/IV. The same observation was made for adrenal insufficiency, which concerned 2% (95% CI: 1%–5%) of the patients. The most common endocrine AE was hypothyroidism (10%; 95% CI: 8%–13%). The percentage of hyperthyroidism was 4% (95% CI: 1%–17%), but only two clinical trials had data on this AE.

Conclusion: Combination immunotherapy is a promising treatment in oncology. This study provides more accurate data on endocrine AE in patients who were treated with combination immunotherapy. The most common AE was thyroid dysfunction or hypophysitis instead of adrenal insufficiency. Oncologists need to be up-to-date and alerted on these endocrine AEs of immunotherapy in order to diagnose and treat them.

Chrysanthidis M., Molfeta A., Chatzichristou E., Bousboukea A., Leon O., Samonis G., Bafaloukos D.

1^st Medical Oncology Department, Metropolitan Hospital – N. Faliro, Pireas, Greece

Background: The potential role of elevated peripheral eosinophils in the response of solid tumours receiving systemic treatments remains ambiguous. The effects of hypereosinophilia in long-term survivors with non-small cell lung cancer (NSCLC) have not been investigated.

Aim: To evaluate whether any associations between hypereosinophilia and response to immunotherapy for NSCLC exist and to review the relevant literature.

Methods: Two cases with high levels of blood eosinophils in patients with NSCLC, showing long-term progression-free survival while in excellent clinical status under treatment with PD-1 and PD-L1 inhibitors, respectively, are presented. The relevant literature has been reviewed.

Results: The first patient, a 61-year-old male, who was a smoker without history of allergies, was diagnosed with NSCLC in October 2018 and initially received six cycles of therapy with paclitaxel and carboplatin. Due to disease progression, his treatment was changed to immunotherapy with nivolumab, and he had already received 43 consecutive doses every 2 weeks. As of June 2020, the mean value of eosinophils in peripheral blood was constantly above 200/μL (217.19/μL).

The second patient, a 67-year-old male, who was a smoker with allergy to eggplants, was diagnosed with lung adenocarcinoma in 2014. He then underwent a right bilobectomy followed by two adjuvant cycles of carboplatin and vinorelbine. Due to hydropneumothorax, he was consequently treated with six cycles of pemetrexed. Since September 2019, he has been receiving immunotherapy with pembrolizumab; he has already completed 26 consecutive infusions and is in an excellent condition. As of September 2020, the mean value of blood eosinophils was constantly above 1/μL (1.1125/μL – hypereosinophilic syndrome).

Conclusions: Potential associations between elevated blood eosinophil levels and response to immunotherapy in long–term survivors suffering from NSCLC are worth investigating further.

Stamatopoulou E.¹, Tsilias D.², Valassi L.³, Valassi S.⁴, Antonakou A.⁵, Stamatopoulou A. ⁶

¹PhD(c), M.Sc-MPH National School of Public Health, M.Sc. in Management of Health and Social Welfare Services University of West Attica and European University Cyprus, Public Health Officer, R. N. General Hospital of Attica KAT, Teacher, Member Hellenic Society of Internal Medicine, Member PCRS UK.

²RN, MSc Clinical Pediatrics and Nursing-Research General Children’s Hospital of Athens P. & A. Kyriakou, Cross-sectoral Department of Pediatric Clinics: Pathology, Maxillofacial Surgery, Otolaryngology and Ophthalmology.

³Graduate of the University of Macedonia School of Social Humanities and Arts, Master of Special Pedagogy, University ‘Neofit Rilski’, MSc in music therapy Diploma in Byzantine Music, Academic Scholar.

⁴Graduate of E.K.Π.A. Diploma in Byzantine Music, MSc Special Education, MS (c) Management of Cultural Units.

⁵‘Senior Nurse Manager’, MSc General Hospital of Nikaia ‘Agios Panteleimon’.

⁶PhD(c), Economist, M.Sc. International Business Administration, M.Sc. in Management of Health and Social Welfare Services University of West Attica and European University Cyprus, Teacher, Academic fellow in University of West Attica.

Background: Music therapy was introduced in the field of palliative care in 1978 by Munro and Mount to relax and encourage the expression of difficult emotions.

Purpose: To determine the effect of music therapy on oncology patients.

Methods: The method followed is secondary, as it draws on research and studies by experts. A bibliographic search was performed on the online PubMed database with the following keywords: oncology patients effect music therapy from 1978 onwards.

Results: The original 1978 study on music therapy in palliative care reported an improvement in patients’ quality of life. Subsequent meta-analyses, reviews and recent systematic reviews have shown that it plays an important role with short-term positive results such as promoting well-being, elevating mood, causing relaxation and reduction of stress, depression, fatigue and pain, with beneficial effects on heart rate, respiratory rate, arterial pressure, facilitating communication to oncology patients and caregivers, thus improving their quality of life. In women with head and neck cancer or with breast cancer undergoing radiation therapy, chemotherapy significantly reduced stress, anxiety, fatigue, depression and the frequency of vomiting and improved their quality of life. The quality of sleep also improved in patients with osteosarcoma. In patients with gastrointestinal tract cancer who underwent chemotherapy, nausea and vomiting significantly reduced. In women undergoing breast augmentation and cancer surgery, music therapy has helped manage preoperative stress and anaesthesia requirements.

Conclusions: Music therapy is associated with a favourable mood in oncology patients and caregivers. It is used as a psychosocial therapy with the aim of improving psychological, physical well-being, addressing the spiritual needs and relieving stress and existential fears as a way of non-verbal expression and communication to cancer patients and caregivers.

Kokkali S.¹, Boukovinas I.², Samantas E.³, Papakotoulas P.⁴, Athanasiadis I.⁵, Andreadis C.⁶, Makrantonakis P.⁷, Samelis G.⁸, Timotheadou E.⁹, Vassilopoulos G.¹⁰, Papadimitriou C.¹¹, Tzanninis D.¹², Ardavanis A.¹, Kotsantis I.¹³, Karvounis-Marolachakis K.¹⁴, Theodoropoulou T.¹⁴, Psyrri A.¹³

¹First Department of Medical Oncology, Agios Savvas Athens General Hospital, Athens

²Medical Oncology, Bioclinic of Thessaloniki

³Third Oncology Clinic, AgioiAnargiroi Athens General Hospital, Athens

⁴First Chemotherapeutic Oncology Department, Theagenion Anti-Cancer Hospital of Thessaloniki, Thessaloniki

⁵Oncology Department, Hygeia Athens Private Hospital, Maroussi, Athens

⁶Third Department of Clinical Oncology and Chemotherapy, Theagenion Anti-Cancer Hospital of Thessaloniki, Thessaloniki

⁷Second Department of Clinical Oncology and Chemotherapy, Theagenion Anti-Cancer Hospital of Thessaloniki, Thessaloniki

⁸Oncology Department at Hippocration General Hospital of Athens

⁹Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki

¹⁰Department of Hematology, Larissa University Hospital

¹¹Oncology Unit, Aretaieion University Hospital, National and Kapodistrian University of Athens

¹²Medical Oncology Unit of Athens Medical Center, Maroussi, Athens

¹³Division Medical Oncology, Attikon University General Hospital of Athens, Haidari

¹⁴Medical Department, Genesis Pharma SA, Athens

Background: Advanced soft tissue sarcomas (aSTS) represent a heterogeneous group of neoplasms with limited treatment options. Trabectedin is indicated in the European Union (EU) for the treatment of aSTS patients who have failed or are unfit to receive anthracycline/ifosfamide.

Aim: The study aims to generate real-world evidence on trabectedin effectiveness in aSTS and its impact on symptom burden and quality of life in routine clinical practice in Greece.

Methods: This prospective study consecutively enrolled patients with histologically confirmed aSTS and initiated on trabectedin per local label, who consented to participate in the study. Data were collected through routine assessments and patient-reported outcomes (MD Anderson Symptom Inventory [MDASI] and EuroQol-5 Dimensions-3-Levels [EQ-5D-3L] instrument) at 6-week intervals during the first 24 weeks and every 12 weeks thereafter for a maximum of 182 weeks.

Results: Between 21 Dec 2015 and 06 June 2018, 64 eligible patients (median age: 58.3 years; 62.5% females; median disease duration: 15.3 months; 67.2% metastatic) were enrolled by 13 hospital sites in Greece. At baseline, 93.8% had ECOG performance status ≤1 and 53.1% had ≥1 comorbidity. Disease histological subtypes included leiomyosarcoma (32.8%), pleomorphic undifferentiated sarcoma (15.6%) and liposarcoma (10.9%). Of the patients, 17.2%, 53.1% and 29.7% had received none, 1 and ≥2 prior treatment lines, respectively. A median of 3.0 (interquartile range: 2.0–6.0) trabectedin cycles were received. The median progression-free survival (PFS) and overall survival were 6.6 and 13.1 months, respectively. The 3- and 6-month PFS rates were 67.9% and 51.2%, respectively; the disease control rate was 21.9%. Baseline MDASI and EQ-5D index scores did not significantly change at post-baseline visits. The treatment discontinuation rate due to toxicity was 9.4%. The adverse drug reaction rate was 46.9% (serious: 17.2%; grade 3/4: 31.3%).

Conclusions: In a real-world setting, trabectedin demonstrated clinically meaningful benefits in aSTS patients who had failed or were unfit to receive anthracycline/ifosfamide, with no new emerging safety signals and without imposing additional burden on patients’ quality of life.

Acknowledgements: The authors acknowledge financial support for this study from Genesis pharma SA. The authors acknowledge abstract preparation support from Qualitis Ltd., Athens, Greece.

Disclosures: SK: GENESIS Pharma SA: honoraria, research funding; IB: GENESIS Pharma SA: honoraria, investigator fees, advisory board; ES: GENESIS Pharma SA: honoraria, investigator fees, advisory board; PP: GENESIS Pharma SA: honoraria, investigator fees; IA: GENESIS Pharma SA: advisory board, investigator fees, research funding; ChA: GENESIS Pharma SA: honoraria, investigator fees, advisory board; PM: GENESIS Pharma SA: investigator fees; GS: nothing to disclose; ET: GENESIS Pharma SA: honoraria, research funding, advisory board; GV: GENESIS Pharma SA: honoraria, investigator fees, advisory board, research funding; ChP: NOVARTIS/ASTRA ZENECA, GENESIS, MSD, AMGEN, MERCK AND ROCHE: speaker honoraria and honoraria for consultancy in advisory boards, BMS/ROCHE: research grants; DT: GENESIS Pharma SA: investigator fees; AA: GENESIS Pharma SA: honoraria, investigator fees, advisory board; IK: GENESIS Pharma SA: honoraria; KK-M: GENESIS Pharma SA employee; TT: GENESIS Pharma SA employee; AP: GENESIS Pharma SA: honoraria, investigator fees, advisory board

Rovithi Maria¹, Alexaki Maria², Patentalaki Krystali², Liodakis George¹

¹General Hospital of Agios Nikolaos, Lasithi, Crete

²General Hospital-Rural Health Center Dialynakeio, Neapoli, Lasithi, Crete

Quality in oncological care is a multidimensional concept. Palliative care constitutes a pillar of cancer care, unquestionably contributing to life prolongation and improvement of quality of life indexes. The development of the Chemotherapy Unit in Agios Nikolaos General Hospital offered the opportunity, by the cooperation of two integrated hospitals, to simultaneously develop the Cancer Homecare Unit.

Agios Nikolaos Cancer Homecare Unit operates once weekly, serving patients with cancer, in the prefecture of Agios Nikolaos, covering a geographically particular area of 511 km². It constitutes the only, to our knowledge, public unit in Greece that includes a general practitioner as a permanent member. This, alongside the nurse care provided by a specialised homecare nurse, allows the upgrade of homecare services to include, indicatively, physical examination and administration of monoclonal antibodies. We present here the cumulative data of the first 2 years of operation.

In total, 47 patients have been included thus far (57% women, data cutoff December 2020). Mean age is 68 years (range: 44–90 years). More frequent underlying malignancies were breast, colorectal and lung cancer (24%, 21% and 8%, respectively). In 2019, the team realised in total 56 at-home visits, resulting in 580 healthcare interventions, while in 2020 and amidst the extraordinary, restricted circumstances created in the covid era, the Homecare Unit exponentially increased the actions delivered, totalling 103 visits and 1803 interventions. Average duration of patient inclusion in the unit services is 151 days (range: 7–445 days), and average visits per patient is six (range: 1–14). Also, 44% of the included patients were under active oncological treatment, while the rest were included for end-of-life care.

Delivering of palliative care in Greece remains sadly inadequate. There is undoubtedly significant room for improvement, as furthermore highlighted by the Hellenic Society of Medical Oncology, which has included palliative care as a strategic endpoint. Administration of palliative care results in a humane, holistic approach of the cancer patient, while ensuing simultaneously decrease in hospitalisation duration, ultimately leading to relief of hospital workload. Especially in the current pandemic situation, Homecare has the potential to repurpose its role by the inclusion of patients in earlier disease state. We strongly feel that the development of Cancer Homecare should be realised within an extrovert, interdisciplinary context of cooperation of medical oncologists with other specialties, especially with the healthcare professionals of primary care, to maximise its potential.

Mitsogianni M, Bala VM, Laschos K, Pliakou E, Lazaridi E, Lampropoulou DI, Aravantinos G

2^nd Department of Medical Oncology, General Oncology Hospital of Kifissia ‘Agioi Anargyroi’

Background: BRAF/MEK inhibitors are widely used for the treatment of metastatic melanoma. While granulomatous sarcoidosis-like reactions have been reported in numerous cases of melanoma patients receiving immunotherapy, they are extremely uncommon under BRAF/MEK inhibition.

Aim: The aim of this report is to present a case of clinical interest regarding a granulomatous reaction in a patient under treatment with BRAF/MEK inhibitors for metastatic melanoma.

Method: Review of the clinical case.

Case report: A 55-year-old woman was submitted to wide excision due to melanoma of the left scapula (pT2b [1.5 mm], N0 [SLNB], cM0, Clark level 3). Fifteen months later, she presented with metastatic lymphadenopathy of the left axilla and mediastinum. Due to the presence of BRAF V600E mutation, she was treated with dabrafenib and trametinib and she achieved complete response. CT staging 16 months later showed enlarged mediastinal lymph nodes as possible manifestations of progressive disease. EBUS-TBNA was carried out and histopathology revealed the existence of sarcoidosis-like granulomatous lymphadenopathy. The patient was asymptomatic and received no treatment for sarcoidosis, while targeted therapy was continued. The lymphadenopathy regressed spontaneously in the next 5 months.

Conclusion: Mediastinal sarcoidosis-like lymphadenopathy is possible under treatment with BRAF/MEK inhibitors and should be included in differential diagnosis from disease progression.

Oikonomopoulos G, Galani E, Klouvas G, Agrogianni A, Rapti A, Nikolakopoulou A, Maria, Batziou A, Tsakalos G, Christodoulou C

2nd Oncology Department, Metropolitan Hospital, Pireus, Greece

Background: Trastuzumab is the cornerstone of treatment of Her-2 (+) breast cancer, turning a highly lethal disease into a chronic one. In the metastatic setting, after combination with chemotherapy, there is evidence proving that continuation of trastuzumab monotherapy as maintenance offers a significant benefit.

Aim: We present the experience of our centre with patients achieving complete response on trastuzumab-based treatment.

Methods: We evaluated retrospectively eight patients with Her-2 (+) metastatic breast cancer, who achieved complete response on treatment with trastuzumab-containing regimen and continued with monotherapy. Concurrent hormonal therapy was applied accordingly. We included patients with complete remission of visceral disease and at least stable bone disease.

Results: Median time on trastuzumab-based treatment was 93 months (54–111 months). Six patients had discontinued trastuzumab, whereas two still received it until December 2016. Only one patient had stopped treatment due to decrease in cardiac ejection fraction. After discontinuation of trastuzumab, five out of the six patients showed progression of disease (84%) with a mean time to progression of 20.2 months. Of the two patients on trastuzumab, one had recurrence of disease (50%). All patients with recurrence received trastuzumab-based treatment.

Conclusions: There is little evidence to define the duration of trastuzumab after complete response. Our study revealed that discontinuation of trastuzumab increases the risk of recurrence. There is definite need for larger trials to establish the optimal duration of trastuzumab after complete response.

G. Soulimioti, A. Fotopoulou, M. Ploxorou, I. Maravelis, S. Tzorakakis, K. Girlemis, E. Athanasiou

Radiotherapy Department of G.O.N.K <<Oi Agioi Anargiroi>>

Background: The standard of therapy for locally advanced rectum tumour is neoadjuvant chemo-radiotherapy followed by surgery.

Aim: The aim of our study is to determine the tumour response to surgery after neoadjuvant chemo-radiotherapy.

Methods: Thirty-three patients with locally advanced rectum tumours received neoadjuvant chemo-radiotherapy in our department from 2013 to 2020. Of these, 21 were males (68%) and 12 were females (32%). The median age was 67 years (range 35–89). Of these, seven had stage II tumour (35%) and 26 had stage IIγ tumour (65%). The clinical stage of the tumour was identified with colonoscopy and magnetic resonance imaging (MRI). The histology of all tumours was adenocarcinoma. Thirteen patients had tumours in the upper part of rectum (38%) and 20 patients had them in the lower part of rectum (62%). All the patients received 3D conformal RT with 45 Gy/1.8 Gy/day. Thirty-one patients (93%) received concomitant chemotherapy with capecitabine (850 mg/m² twice a day for 25 days). The surgery was done 4–8 weeks after the end of neoadjuvant chemo-radiotherapy.

Results: The results after the surgery were as follows: eight patients (24.4%) had complete response (ypT0) and 23 patients (72.6%) had partial response. Also, two patients died before the surgery due to other medical reasons (4%). In our study, it seems that of the eight patients who had complete response, six had tumours in the upper segments of rectum and two had them in the lower part of rectum (75% vs. 25%). So, it seems that the patients with tumours in the upper segments of rectum had better response to surgery after neoadjuvant chemo-radiotherapy.

Conclusions: Neoadjuvant chemo-radiotherapy shows very good results in tumour response of the locally advanced rectums tumours. Our results are similar of those of international studies.

¹Michas Athanasios MD MSc, ²Akrivos Thomas MD, ²Giannakas Panagiotis MD, ¹Arvanitou Eleni MD MSc, ¹Gkikas Konstantinos MD, ¹Kolomitrousi Andria MD, ¹Kagkaras Christos MD, ¹Gkiaouraki Marina MD, ¹Mpalasis Konstantinos MD, ¹Christofilakis Charalampos MD, ¹Tsoukalas Nikolaos MD MSc PhD

¹Oncology department of 401General Military Hospital of Athens (401GMHA)

²Gynecologic department of 401General Military Hospital of Athens (401GMHA)

Background: Mesonephric-like Mullerian adenocarcinomas of the ovaries are extremely rare gynaecological malignancies. Their embryological and histological origin remains debatable. The more prevalent tumorigenic theories support either development from mesonephric duct remnants of the female genital tract or development from Mullerian lesions that undergo mesonephric differentiation.

Case Report: This report concerns a 64-year-old female patient with medical history of hypothyroidism and dyslipidaemia. During annual gynaecological US screening examination, a solid formation (approximately 4 cm diameter) was found on the left ovary. An ensuing abdominal MRI tomography revealed a solid ovarian mass. Further staging with CTs and PET-CT scan excluded distant neoplasmatic dissemination. Subsequently, a surgical total hysterectomy was performed. After histological evaluation, the analysis concluded low-grade mesonephric-like Mullerian adenocarcinoma of the left ovary, adjacent to multiple foci of endometriosis. Due to the tumour rarity, the histological results were rechecked and verified by multiple histology experts. The patient received adjuvant chemotherapy with six cycles of carboplatin/paclitaxel. Treatment was completed without significant side effects, except for mild nausea and hand–foot syndrome. Follow-up examinations showed complete disease remission. Currently, the patient is regularly monitored with scheduled periodic assessments, without any sign of recurrence. Moreover, molecular analysis revealed heterozygous somatic KRAS mutation NM_033360.4:c.35G>A:p.(Gly12Asp) and heterozygous genomic PMS2 mutation NM_000535.7:c.2559C>G p.(Ile853Met).

Conclusion: Mesonephric-like Mullerian adenocarcinomas of ovaries are extremely rare tumours (<15 literature reports in PubMed, Scopus). The most prevalent theory of tumorigenesis involves cancer development from Mullerian lesions (e.g. foci of endometriosis) that undergo mesonephric differentiation. Further research is necessary for a deep understanding of the neoplastic nature of these lesions.

Gkikas K.¹, Malliopoulos D.², Pappas D.³, Kolomitrousi A.¹, Arvanitou E.¹, Tsitsibis A.¹, Michas A.¹, Chatzelis E.⁴, Gkiaouraki M.¹, Ballasis K.¹, Christofyllakis Ch.¹, Tsoukalas N.¹

¹Oncology Department, 401 General Military Hospital of Athens

²Endocrinology Department, 401 General Military Hospital of Athens

³Pathological Laboratory, 401 General Military Hospital of Athens

⁴Endocrinology Department, 251 Air Force General Hospital of Athens

Background: Multiple endocrine neoplasia (MEN) syndromes are rare endocrine cancer syndromes, inherited as an autosomal dominant disorder. The most common tumours seen in MEN1 involve the parathyroid gland, islet cells of the pancreas and the pituitary gland.

Aim: To present a case of MEN type 1 in an adult patient.

Case report: In March 2020, a 37-year-old male was diagnosed with MEN type 1 syndrome after his family members’ (mother/brother) positive diagnosis as well, through molecular genetic testing. Several diagnostic imaging and laboratory tests subsequently performed revealed the following disorders: 1) primary hyperparathyroidism with hypercalcaemia and hypophosphataemia, combined with two hypoechoic solid masses on the thyroid, and 2) abdominal magnetic resonance imaging (MRI) findings including two abnormal masses of tissue placed on the pancreas (1.7 and 2 cm), as well as two suspicious-appearing masses (1.3 and 1.9 cm) within the liver. Molecular testing on MEN1 gene showed an NM_000244.3:c.1126dup p.(Val376Glyfs^*38) heterozygous mutation. Further diagnostic imaging tests depicted nodular swelling on both the adrenal glands, such as a tiny pituitary lesion, which looked like a microadenoma. The 68-Ga-DOTATATE PET-CT scan showed an increased radiopharmaceutical uptake in the region of pancreas head, pancreas neck and liver part II. After finishing all necessary tests, the patient underwent an EUS-guided pancreas biopsy. Both cytological and histological examination results showed the existence of a high-grade neuroendocrine neoplasm. Therefore, after multidisciplinary oncology approach, the patient was suggested to perform a total parathyroidectomy to restore the insisting primary hyperparathyroidism. Furthermore, he was asked to perform a repetition of certain imaging tests 3 months later as a means to determinate the most suitable treatment option.

Conclusion: Clinical suspicion of MEN syndromes often results from family medical history, while molecular testing confirms the final diagnosis. Undoubtedly, treatment requires multidisciplinary oncology approach among many different medical specialties, not to mention the ultimate need for patients’ psychological support.

Kolomitrousi A¹, Gikas K.¹, Chrystofyllakis Ch.¹, Mpallasis K.¹, Gkiaouraki M.¹, Psarogiorgou S.², Zarogiannos A.³, Tsitsimpis A.⁴, Arvanitou E.⁴, Tsoukalas N.¹

¹Oncology Department, 401 General Military Hospital of Athens

²Pathology Department, 401 General Military Hospital of Athens

³Urology Department, 401 General Military Hospital of Athens

⁴1^st Internal Medicine Department, 401 General Military Hospital of Athens

Introduction: Hemangioblastoma is a benign tumor of the central nervus system (CNS). Occurrence of hemangioblastoma in other sites, outside the CNS, is extremely rare and is worth mentioned.

Case report: A 49-year-old female with a past medical history of breast cancer (pT2N(sn)γi invasive lobular breast carcinoma, which was diagnosed 2 years ago and treated with lumpectomy, sentinel lymph node biopsy and resection of two lymph nodes, adjuvant chemotherapy, radiotherapy, and hormonal therapy) presented with a 2,3cm solid mass in the lower pole of the right kidney, as detected in the imaging exams. No other pathological features were found. Patient denied further work up and a close follow-up performed. The next imaging assessment, 6 months later, showed an increase of the mass size and subsequently a mass resection was planned. Due to perioperative complications a total nephrectomy was performed, and histological examination of the specimen showed a tumor mass within the renal parenchyma, composed of a rich capillary vessels and stromal cells with foamy clear or eosinophilic cytoplasm, with PAS positivity in cytoplasmic vacuoles. Moreover, several peripheral deformed, irregular, thick-walled vessels were found, Congo red stain was negative, and no necrosis or mitosis was seen. Furthermore, was observed hemosiderin deposits and mild inflammatory infiltration, while mast cells were easily observed. Tumor cells were negative for AE1/3, PAX8, HMB45, Melan A, HHV-8, CD10, GFPA and CD117. CD31 and CD34 included vessels and a small number of stromal cells was positive for CD34. Finally, was observed positivity for S100, NSE and inhibin. These results were compatible with the diagnosis of hemangioblastoma.

Conclusion: Hemangioblastoma is a benign tumor of the central nervus system (CNS) and less often could be observed elsewhere. They can also rarely be associated with other conditions such as polyarthritis and pancreatic cysts and may occur in the context of Von Hippel-Lindau syndrome, which is why molecular testing is considered appropriate. Our case is presented due to the rarity of the presence of renal hemangioblastoma as an extensive review in the medical literature has so far highlighted 14 cases of renal hemangioblastoma.

Arvanitou E.¹, Plakas S.², Giannakouras G.³, Rigakos G.⁴, Pappas D.⁵, Tsitsimpis A.¹, Gikas K.¹, Kolomitrousi A.¹, Michas A.¹, Gkiaouraki M.¹, Mpallasis K.¹, Chrystofyllakis Ch.¹, Tsoukalas N.¹

¹Oncology Department, 401 General Military Hospital of Athens

²Neurosurgery Department, 401 General Military Hospital of Athens

³Radiotherapy Department, 401 General Military Hospital of Athens

⁴3rd Medical Oncology Department, Hygeia Hospital Athens

⁵Pathological Laboratory, 401 General Military Hospital of Athens

Background: Medulloblastoma is an embryonic type of tumour, mainly located in the cerebellum, which unlike children rarely occurs in adults, with an annual incidence of 0.05–0.1 cases per 100,000. Medulloblastoma shows heterogeneity and is distinguished according to the World Health Organisation (WHO) into four subtypes, based on histological and molecular characteristics: a) WNT activated, b) SHH activated and TP53 wildtype, c) SHH activated and TP53 mutant and d) non-WNT/non-SHH. The prognosis of each subtype depends on age and differs in adults and children. Treatment includes gross total resection, adjuvant chemotherapy and craniospinal irradiation.

Aim: To present a case of posterior fossa medulloblastoma in an adult patient.

Case report: In January 2020, a 39-year-old male presented with persistent headache and progressively increasing vomiting. Brain magnetic resonance imaging (MRI) depicted a space-occupying lesion of 37 × 39 × 44 mm in the right cerebellum, without contrast enhancement, causing intense pressing phenomena, displacement of structures and increased dimensions of the ventricles. Due to the oedema, corticosteroids were started, and the patient showed clinical improvement. At the same time, due to manifestations from the psychic sphere, he was evaluated by a psychiatrist. The initial staging with craniospinal MRI, chest and abdominal computed tomography (CT) was normal. A surgical removal of more than 50% of the tumour mass was performed. The histological examination showed a grade IV cerebellum medulloblastoma of nodular/desmoplastic type. Further examination revealed tumour with ki-67 = 40%, without pathological IDH 1,2, without MYC amplification, and with YAP1 overexpression, most likely of the SHH-activated molecular subtype (group 2). Postoperative MRI showed a large reduction in the size of the lesion. Subsequently, an assessment from a specialised central nervous system (CNS) tumour treatment centre was requested. Patient underwent craniospinal irradiation, and at present, receives chemotherapy with the lomustine/cisplatin/vincristine regimen, with adequate response according to the first follow-up. The molecular test that was performed revealed a TP53 heterozygous mutation of unknown clinical significance.

Conclusions: The management of rare tumours such as cerebellum medulloblastoma requires collaboration with specialised cancer treatment centres. The importance of an interdisciplinary team for the optimal management of patient care is also highlighted.

Arvanitou E.¹, Papandropoulos I.², Giannakouras G.³, Psarogiwrgou S.⁴, Tsitsimpis A.¹, Gikas K.¹, Kolomitrousi A.¹, Michas A.¹, Gkiaouraki M.¹, Mpallasis K.¹, Chrystofyllakis Ch.¹, Tsoukalas N.¹

¹Oncology Department, 401 General Military Hospital of Athens

²Urology Department, 401 General Military Hospital of Athens

³Radiotherapy Department, 401 General Military Hospital of Athens

⁴Pathological Laboratory, 401 General Military Hospital of Athens

Background: Rhabdomyosarcoma represents an aggressive tumour which originates from the embryonal mesenchyme. It is the most common soft tissue sarcoma in children. But it is extremely rare in adults, as it accounts for 2%–5% of the soft tissue sarcomas. Prostate rhabdomyosarcoma is an aggressive tumour characterised by rapid tissue infiltration and poor prognosis. Immunohistochemistry and molecular testing are useful for diagnosis and classification. Treatment involves surgery, irradiation and chemotherapy.

Aim: To present a case of prostate embryonal rhabdomyosarcoma in a young adult patient.

Case report: In June 2019, a 24-year-old male presented with acute urinary retention and was diagnosed with a locally extended prostate mass and secondary pulmonary and bone lesions. The histological examination showed sheets of spindle or round cells with moderate pleomorphism and plenty of mitoses. The tumour cells demonstrated immunohistochemical positivity for vimentin, desmin and myogenin. Proliferation index, Ki-67, was rather high (70%). These findings were referable to embryonal rhabdomyosarcoma. An assessment from a centre specialising in paediatric and adolescent oncology was requested, and first-line treatment with IVADo regimen (d-actinomycin, doxorubicin, ifofosfamide, vincristine) with mesna administration was initiated. After chemotherapy completion, restaging computed tomography (CTs) and magnetic resonance imaging (MRIs) showed significant response of the prostate mass and bone disease and partial response of the pulmonary lesions. Subsequently, patient underwent a course of radiotherapy with volumetric modulated arc therapy (VMAT)/image-guided radiation therapy (IGRT) technique to the primary and metastatic bone lesions. Due to disease progression, second-line treatment with irinotecan/vincristine/temozolamide was selected. Despite the initial response, patient developed clinical deterioration with local recurrence and new metastatic bone lesions. Palliative radiotherapy (RT) followed, and third-line chemotherapy with cisplatin/adriblastina was initiated. Molecular testing showed no findings compatible with hereditary cancer syndrome.

Conclusion: Rhabdomyosarcoma is rare in adults and its treatment requires cooperation with specialised cancer centres. The importance of palliative care for the optimal patient care is also highlighted.

Papadopoulos V., Tsapakidis K., Xantzara E., Markou A., Kokkalis A., Aidarinis X., Saloustros E., Koinis F., Samaras I., Kotsakis A.

Department of Clinical Oncology, University Hospital of Larissa, Greece

Background: About half of the patients diagnosed with non-small cell lung cancer have distant metastases. The liver, bones, brain and adrenal glands are the most common anatomical sites of metastasis. Multiple metastatic lesions in the gastrointestinal tract from primary lung carcinoma are very rare.

Aim: To describe a case of extremely rare synchronous metastases in the gastrointestinal tract from squamous non-small cell lung carcinoma, although their incidence in autopsies is described to be about 14%.

Case report: A 71-year-old patient was diagnosed with squamous cell carcinoma of the lung due to cough and shortness of breath (IHC: p40+, TTF1−, synaptophysin−). During the initial staging of the disease with positron emission tomography/computed tomography (PET/CT) 18F-FDG, a hypermetabolic lesion was found in the left pulmonary portal (SUVmax: 11.2) and increased intake of 18F-FDG was observed in thickening of the stomach wall (SUVmax: 15.6) and in caecum (SUVmax: 12.9). The patient underwent gastroscopy and colonoscopy, which showed squamous cell carcinoma immunohistochemically similar to the primary lung. The patient received first-line chemotherapy with gemcitabine and carboplatin. The treatment failed after three cycles of chemotherapy as a result of tumour progression to the liver, and the patient was switched to second-line treatment with nivolumab. In the third cycle of treatment, melena occurred and a new gastroscopy was performed that revealed bleeding from the known metastatic lesion of the stomach. The patient underwent gastric haemostatic radiotherapy and while initially he was stabilised haemodynamically, he relapsed with haemorrhagic brain metastases and eventually passed away.

Conclusions: Gastrointestinal metastases from lung cancers are very rare and occur more frequently in older smokers with squamous cell carcinoma. The sputum seeding metastasis hypothesis is referred as a possible explanation, but needs investigation. However, the small number of patients in the literature makes it difficult to interpret this rare disease entity.

References: 1. Xinyu Li, Songhe Li, Zhiming Ma, Shutao Zhao, Xudong Wang, Dacheng Wen. Multiple gastrointestinal metastases of squamous-cell lung cancer. A case report. Medicine (Baltimore).2018 Jun; 97(24): e11027

2. Ibrahim Azar, Efstratios Koutroumpakis, Raina Patel, Syed Mehdi. Squamous cell lung carcinoma presenting as melena: a case report and review of the literature. Rare Tumors. 2017 Oct 4;9(3):7164

3. Ying He, Yong Cui, Xinchun Duan, Chunquan Liu, and Xianqi Cai. Primary lung squamous cell carcinoma with gastric metastasis: A case report. Thorac Cancer.2019 Feb; 10(2): 373–377.

4. Mariko Nemoto, Pankaj Prasoon, Hiroshi Ichikawa, Takaaki Hanyu, Yosuke Kano, Yusuke Muneoka, Kenji Usui, Yuki Hirose, Kohei Miura, Yoshifumi Shimada, Masayuki Nagahashi, Jun Sakata, Takashi Ishikawa, Masanori Tsuchida, Toshifumi Wakai. Primary lung squamous cell carcinoma and its association with gastric metastasis: A case report and literature review. Thorac Cancer. 2020 Jun;11(6):1708–1711

E. Chrysoulidou, E. Panori

Blood donation Dep. G. H. KAVALA

Background: During the last years, there have been great leaps regarding the diagnosis and treatment of cancer. This is attributed to the development of technology which allows scientists to isolate and observe the activities of specific genes that have undergone mutations and are responsible for tumour growth. Genes with specific mutations are observed in different neoplacies, regardless of their origin. This means that the same medication can be used in different kinds of cancer.

The term myelodysplastic syndrome (MDS) refers to a heterogenic group of acquired clonal neoplasmatic disorders of the bone marrow at the level of a polyvalent haematopoietic cell. It is characterised by a non-effective hematopoiesis cytarropenia, morphological disorders of haematopoietic cells and could evolve into an acute myelogenic leukaemia. It usually affects people over 60 years old. Pulmonary adenocarcinoma constitutes the most common type of cancer. It belongs to the category of the non-microcellular lung cancer. It is asymptomatic and in most cases, before it is clinically perceived, it would have already become metastatic. It affects mostly middle-aged men aged 60–70.

Aim: Description of a case diagnosed with two different types of neoplacies simultaneously in the same biopathological material.

Methods: A male, 69 years old, presented with weakness, fatigue and shortness of breath in the course of 3 days and he had free individual background. During his clinical evaluation, a pulmonary murmur reduction was established, SpO₂- 85%. He was haemodynamically stable without fever. According to his lab results, he presented with respiratory acidosis, pancytopenia, elevated CRP, LDH, ALP and cancer indicators. His chest X-ray showed ozomorphic shading bilaterally, left semi-diaphragm fuzzification and atypical bone imaging. In his CT scan, leukoencephalopathy was observed. Image of a blurred glass in the lung parenchyma was seen bilaterally. Image of a lower left lung lobe percolation with a positive aerobronchgramme. Swollen lymph nodes were found in the mesothorax. Pleural effusion collection bilaterally. Multiple liver metastatic focus. At least one metastatic focus on the splene. Multiple bone metastases. During the examination, both on osteomyelic biopsy and a myelogram were conducted which present: elevated cytarobrithia with hyperplacia of granulomatous and red line cell, dysplastic lesions of all 3 hemopoitic series. CD34 and CD 117 coloring showed positive blast-cells at a >10% and <20%. Accumulation of neoplasmatic cells s obserued which exhibit immunohistochemically the phenotype of a pulmonary andenocarcinoma : AE1/AE3(+),CK7(+),NapsinA(+),TTF1(+),CK20(-),CK5/6(-), synaptophysyne(-), chromogranine().

Result: The patient was diagnosed with two different malignancies simultaneously: pulmonary adenocarcinoma with multiple metastatic focuses and myelodysplastic syndrome with excess blasts (EB-2).

Conclusions: The investigation of pancytopenia contributed to the diagnosis of pulmonary adenocarcinoma in conjunction with blood neoplasia. Similar cases of adenocarcinoma co-existing with other haemopoietic system malignancies have been reported. This co-existence is rare and is probably due to a common pathophysiological mechanism. Further study could help in its treatment.

Mutations in isocitrate dehydrogenase genes IDH1 and IDH2 were found in acute myelogenic leukaemia and the selective inhibitors IDH1 and IDH2 have been approved for the targeted treatment of acute myelogenic leukaemia. Studies have revealed IDH1 mutations in many malignancies, with the most frequent being IDH1 R132H. It has been proved that the expression IDH1/2 in non-small cell lung cancer (NSCLC) appears in pulmonary adenocarcinomas as an indication of sub-clonal evolution.

Papastergiou K.¹, Karantsiri M.², Lavdaniti M.³

¹RN, MSc, ‘Theageneio’ Hospital, Thessaloniki

²RN, School Nurse, Thessaloniki

³Associate Professor, Department of Nursing, International University of Greece, Thessaloniki

Background: Acute respiratory failure is a pathological condition in which the body is unable to perform gas exchange satisfactorily. Thoracic surgeries have a high risk of postoperative respiratory complications, especially in patients with risk factors (such as COPD) associated with anaesthesia. Non-invasive mechanical ventilation is a method of intervening in a patient’s breathing by supporting it mechanically, without the act of intubation.

Aim: The aim of the study was to describe an incident with the occurrence of acute postoperative respiratory failure in a patient undergoing thoracotomy and the use of non-invasive mechanical ventilation.

Method: This is a case study of a 77-year-old male patient who underwent right rear thoracotomy in a large hospital in Northern Greece.

Results: A 77-year-old male patient with right upper lung adenocarcinoma arrived in November 2020 for surgery. The patient underwent right posterior thoracotomy, wedge resection of the right upper lobe and mediastinal lymph node biopsies. He had chronic respiratory pulmonary disease, arterial hypertension, hepatitis C as special problems, along with being a former smoker 30 years ago. Forced vital capacity (FCV) was 2.02%–65% and forced expiratory volume (FEV1) was 1.90%–81%. There were no intraoperative complications, and the intubation was performed in the resuscitation room, while later, he was transferred to the ICU. During the first 6 h of hospitalisation in the ICU, there were symptoms of respiratory distress with SpO2 >85% and shortness of breath, while he had a good level of consciousness and communication. The difficulty was addressed with the placement of a NIV mask and regular monitoring of SpO2 and reduction of speed. Nursing care consisted of the timely recognition of shortness of breath, dyspnoea, sweating and decreased SpO2, in order to apply the NIV mask in a timely manner and to regularly monitor the vital signs hourly.

Conclusions: Acute respiratory failure is life-threatening to the patient. Non-invasive mechanical ventilation improves the efficiency of the lung in gas exchange in a short time and should be applied for the best outcome of the patient.