<abstract xml:lang="en"><title style='display:none'>Titanium dioxide in our everyday life; is it safe?</title><bold>Background.</bold> Titanium dioxide (TiO2) is considered as an inert and safe material and has been used in many applications for decades. However, with the development of nanotechnologies TiO2 nanoparticles, with numerous novel and useful properties, are increasingly manufactured and used. Therefore increased human and environmental exposure can be expected, which has put TiO2 nanoparticles under toxicological scrutiny. Mechanistic toxicological studies show that TiO2 nanoparticles predominantly cause adverse effects via induction of oxidative stress resulting in cell damage, genotoxicity, inflammation, immune response etc. The extent and type of damage strongly depends on physical and chemical characteristics of TiO2 nanoparticles, which govern their bioavailability and reactivity. Based on the experimental evidence from animal inhalation studies TiO2 nanoparticles are classified as "possible carcinogenic to humans" by the International Agency for Research on Cancer and as occupational carcinogen by the National Institute for Occupational Safety and Health. The studies on dermal exposure to TiO2 nanoparticles, which is in humans substantial through the use of sunscreens, generally indicate negligible transdermal penetration; however data are needed on long-term exposure and potential adverse effects of photo-oxidation products. Although TiO2 is permitted as an additive (E171) in food and pharmaceutical products we do not have reliable data on its absorption, distribution, excretion and toxicity on oral exposure. TiO2 may also enter environment, and while it exerts low acute toxicity to aquatic organisms, upon long-term exposure it induces a range of sub-lethal effects.<bold>Conclusions.</bold> Until relevant toxicological and human exposure data that would enable reliable risk assessment are obtained, TiO2 nanoparticles should be used with great care.</abstract>

Department for Nanostructured Materials, Jožef Stefan Institute, Ljubljana, Slovenia

Department for Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia

Titanium dioxide in our everyday life; is it safe?

<abstract xml:lang="en"><title style='display:none'>Effect of response quality and line of treatment with rituximab on overall and disease-free survival of patients with B-cell lymphoma</title><bold>Background.</bold> The introduction of rituximab into the treatment of patients with non-Hodgkin's lymphomas has improved the overall response rate, as well as the response duration and the overall survival of patients with B-cell lymphomas. But only a few studies have addressed the question whether the better response (complete response) and the early introduction of rituximab into the treatment translate into the better survival. The aim of this retrospective study was to assess the potential relationship between either the quality of the response or the line of the rituximab treatment and the overall survival (OS) as well as the disease-free survival (DFS) of patients with B-cell lymphomas.<bold>Patients and methods.</bold> In the study, we analysed treatment outcomes in patients with different histological types of B-cell lymphomas who were treated at the Institute of Oncology between 2003 and 2007 with rituximab and chemotherapy. We included only patients who had the level of CD20 expression assessed prior to the introduction of the treatment with quantitative flow-cytometric measurements. The OS and DFS were evaluated by Kaplan-Meier survival curves.<bold>Results.</bold> One hundred and fourteen patients were enrolled in the study. Patients who achieved a complete response after the rituximab containing treatment had a significantly longer OS than those reaching a partial response (hazard ratio [HR], 0.34; 95% CI, 0.05 to 0.91, P = 0.0375) and than patients with stable (hazard ratio [HR], 0.11; 95% CI, 0.0002 to 0.033, P &lt; 0.0001) or progressive disease (hazard ratio [HR], 0.09; 95% CI, 0.003 to 0.03, P &lt; 0.0001). Patients who achieved a complete response (CR; n = 70; 61.4%) had also a significantly longer DFS (hazard ratio [HR], 0.26; 95% CI, 0.021 to 0.538, P = 0.0068) than those reaching only a partial response (PR; n = 17; 14.9%). Patients treated with rituximab as the first-line treatment (n = 50; 43.9%) had a significantly longer OS than those treated with rituximab for the first (hazard ratio [HR], 0.27; 95% CI, 0.106 to 0.645, P = 0.0036) or second relapse (hazard ratio [HR], 0.22; 95% CI, 0.078 to 0.5, P = 0.0006). Also the DFS of patients treated with rituximab as the first-line treatment (n = 46; 52.9%) was significantly longer (hazard ratio [HR], 0.32; 95% CI, 0.088 to 0.9, P = 0.0325) than in patients treated with rituximab for their first relapse (n = 25; 28.7%).<bold>Conclusions.</bold> These data indicate that a better response to rituximab therapy presumably translates into an improved OS and DFS for patients with B-cell lymphomas. The early introduction of rituximab into the treatment (i.e. first-line treatment) might improve OS. Therefore, the response adapted first-line therapy with rituximab should be considered when the treatment decision is taken in B-cell lymphoma patients.</abstract>

Effect of response quality and line of treatment with rituximab on overall and disease-free survival of patients with B-cell lymphoma

<abstract><title style='display:none'>Abstract</title><sec id="j_raon-2019-0057_s_008_w2aab3b8c55b1b7b1aab1c16b1Aa"><title style='display:none'>Background</title>Glioblastoma is the most frequent and aggressive brain tumour in humans with median survival from 12 to 15 months after the diagnosis. This is mostly due to therapy resistant glioblastoma stem cells in addition to intertumour heterogeneity that is due to infiltration of a plethora of host cells. Besides endothelial cells, mesenchymal stem cells and their differentiated progenies, immune cells of various differentiation states, including monocytes, comprise resident, brain tumour microenvironment. There are compelling evidence for CCL5/CCR5 in the invasive and metastatic behaviour of many cancer types. CCR5, a G-protein coupled receptor, known to function as an essential co-receptor for HIV entry, is now known to participate in driving tumour heterogeneity, the formation of cancer stem cells and the promotion of cancer invasion and metastasis. Clinical trials have recently opened targeting CCR5 using a humanized monoclonal antibody (leronlimab) for metastatic triple negative breast cancer (TNBC) or a small molecule inhibitor (maraviroc) for metastatic colon cancer. There are important CCL5 and CCR5 structure and signalling mechanisms in glioblastoma. In addition, the CCL5/CCR5 axis directs infiltration and interactions with monocytes/macrophages and mesenchymal stem cells, comprising glioblastoma stem cell niches.</sec><sec id="j_raon-2019-0057_s_009_w2aab3b8c55b1b7b1aab1c16b2Aa"><title style='display:none'>Conclusions</title>CCR5 is highly expressed in glioblastoma and is associated with poor prognosis of patients. CCL5/CCR5 is suggested to be an excellent new target for glioblastoma therapy. The molecular mechanisms, by which chemoattractant and receptor respond within the complex tissue microenvironment to promote cancer stem cells and tumour heterogeneity, should be considered in forthcoming studies.</sec></abstract>

Cytokine CCL5 and receptor CCR5 axis in glioblastoma multiforme

<abstract><title style='display:none'>Abstract</title><sec id="j_raon-2020-0008_s_004_w2aab3b8c76b1b7b1aab1c18b1Aa"><title style='display:none'>Background</title>Since the end of the previous century, there has not been a comprehensive review of European studies on socioeconomic inequality in cancer incidence. In view of recent advances in data source linkage and analytical methods, we aimed to update the knowledge base on associations between location-specific cancer incidence and individual or area-level measures of socio-economic status (SES) among European adults.</sec><sec id="j_raon-2020-0008_s_005_w2aab3b8c76b1b7b1aab1c18b2Aa"><title style='display:none'>Materials and methods</title>We systematically searched three databases (<italic>PubMed, Scopus</italic> and <italic>Web of Science</italic>) for articles on cancer incidence and SES. Qualitative synthesis was performed on the 91 included English language studies, published between 2000 and 2019 in Europe, which focused on adults, relied on cancer registry data and reported on relative risk (RR) estimates.</sec><sec id="j_raon-2020-0008_s_006_w2aab3b8c76b1b7b1aab1c18b3Aa"><title style='display:none'>Results</title>Adults with low SES have increased risk of head and neck, oesophagogastric, liver and gallbladder, pancreatic, lung, kidney, bladder, penile and cervical cancers (highest RRs for lung, head and neck, stomach and cervix). Conversely, high SES is linked with increased risk of thyroid, breast, prostate and skin cancers. Central nervous system and haematological cancers are not associated with SES. The positive gap in testicular cancer has narrowed, while colorectal cancer shows a varying pattern in different countries. Negative associations are generally stronger for men compared to women.</sec><sec id="j_raon-2020-0008_s_007_w2aab3b8c76b1b7b1aab1c18b4Aa"><title style='display:none'>Conclusions</title>In Europe, cancers in almost all common locations are associated with SES and the inequalities can be explained to a varying degree by known life-style related factors, most notably smoking. Independent effects of many individual and area SES measures which capture different aspects of SES can also be observed.</sec></abstract>

Socioeconomic inequalities in cancer incidence in Europe: a comprehensive review of population-based epidemiological studies

<abstract xml:lang="en"><title style='display:none'>Lymphedema following cancer therapy in Slovenia: a frequently overlooked condition?</title><bold>Introduction.</bold> Secondary lymphedema following cancer therapy is a frequent, often painful, quality of life disturbing condition, reducing the patients' mobility and predisposing them to complications, e.g. infections and malignancies. The critical aspect of lymphedema therapy is to start as soon as possible to prevent the irreversible tissue damage.<bold>Patients and methods.</bold> We performed a retrospective study of patients with lymphedema, treated at the Department of Dermatovenereology, University Medical Center Ljubljana, from January 2002 to June 2010. The patients' demographic and medical data were collected, including type of cancer, type and stage of lymphedema, and time to first therapy of lymphedema. The number of referred patients with lymphedema following the therapy of melanoma, breast cancer, and uterine/cervical cancer, was compared to the number of patients expected to experience lymphedema following cancer therapy, calculated from the incidence reported in the literature.<bold>Results.</bold> In the period of 8.5 years, 543 patients (432 females, 112 males) with lymphedema were treated. The results show that probably many Slovenian patients with secondary lymphedema following cancer therapy remain unrecognized and untreated or undertreated. In the majority of our patients, the management of lymphedema was delayed; on average, the patients first received therapy for lymphedema 3.6 years after the first signs of lymphedema.<bold>Conclusions.</bold> To avoid a delay in diagnosis and therapy, and the complications of lymphedema following cancer therapy, the physician should actively look for signs or symptoms of lymphedema during the follow-up period, and promptly manage or refer the patients developing problems.</abstract>

Lymphedema following cancer therapy in Slovenia: a frequently overlooked condition?

<abstract><title style='display:none'>Abstract</title><sec id="j_raon-2018-0037_s_006_w2aab3b7b4b1b6b1aab1c18b1Aa"><title style='display:none' id="d2367800e7087_w2aab3b7b4b1b6b1aab1c18b1aAa">Background</title>Uncommon response during immunotherapy is a new challenging issue in oncology practice. Recently, new criteria for evaluation of response to immunotherapy <italic>immune response evaluation criteria in solid tumors</italic> (iRECIST) were accepted. According to iRECIST, worsening of performance status (PS) accompanied to pseudoprogression reflects most probably the true progression of the malignant disease.</sec><sec id="j_raon-2018-0037_s_007_w2aab3b7b4b1b6b1aab1c18b2Aa"><title style='display:none' id="d2367800e7098_w2aab3b7b4b1b6b1aab1c18b2aAa">Methods</title>A systematic review of the literature was made by using several electronic database with the following search criteria: symptomatic pseudoprogression, atypical response, immunotherapy and lung cancer.</sec><sec id="j_raon-2018-0037_s_008_w2aab3b7b4b1b6b1aab1c18b3Aa"><title style='display:none' id="d2367800e7106_w2aab3b7b4b1b6b1aab1c18b3aAa">Results</title>In the literature, we identified five reports of seven patients treated with immunotherapy that met the inclusion criteria. We also report our experience of patient with pseudoprogression and almost complete response after one dose of immunotherapy.</sec><sec id="j_raon-2018-0037_s_009_w2aab3b7b4b1b6b1aab1c18b4Aa"><title style='display:none' id="d2367800e7114_w2aab3b7b4b1b6b1aab1c18b4aAa">Conclusions</title>As seen from our review, iRECIST criteria might be insufficient in distinguishing true progression from pseudoprogression in some patients with advanced NSCLC treated with immunotherapy. More precise assessment methods are urgently needed.</sec></abstract>

Immune RECIST criteria and symptomatic pseudoprogression in non-small cell lung cancer patients treated with immunotherapy

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Background</title>
Non-cardia gastric cancer remains a major cause of cancer-related mortality worldwide, despite declining incidence rates in many industrialized countries. The development of intestinal-type gastric cancer occurs through a multistep process in which normal mucosa is sequentially transformed into hyperproliferative epithelium, followed by metaplastic processes leading to carcinogenesis. Chronic infection with <italic>Helicobacter pylori</italic> is the primary etiological agent that causes chronic inflammation of the gastric mucosa, induces atrophic gastritis, and can lead to intestinal metaplasia and dysplasia. Both intestinal metaplasia and dysplasia are precancerous lesions, in which gastric cancer is more likely to occur. Atrophic gastritis often improves after eradication of <italic>Helicobacter pylori</italic>; however, the occurrence of intestinal metaplasia has been traditionally regarded as “the point of no return” in the carcinogenesis sequence. <italic>Helicobacter pylori</italic> eradication heals non-atrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions. In this article, we discuss the pathogenesis, epigenomics, and reversibility of intestinal metaplasia and briefly touch upon potential treatment strategy.
</sec>
<sec><title style='display:none'>Conclusions</title>
Gastric intestinal metaplasia no longer appears to be an irreversible precancerous lesion. However, there are still many controversies regarding the improvement of intestinal metaplasia after <italic>Helicobacter pylori</italic> eradication.
</sec>
</abstract>

Pathogenesis and potential reversibility of intestinal metaplasia − a milestone in gastric carcinogenesis

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Background</title>
This retrospective study investigated the efficacy of endovascular treatment with multilayer flow modulators (MFMs) for treating aortic aneurysms in high-risk patients unsuitable for conventional treatments.
</sec>
<sec><title style='display:none'>Patients and methods</title>
Conducted from 2011 to 2019 at a single center, this retrospective observational study included 17 patients who underwent endovascular treatment with MFMs. These patients were selected based on their unsuitability for traditional surgical or endovascular procedures. The study involved meticulous pre-procedural planning, precise implantation of MFMs, and follow-up using CT angiography. The primary focus was on volumetric and flow volume changes in aneurysms, along with traditional diameter measurements. Moreover, the technical success and post-procedural complications were also registered.
</sec>
<sec><title style='display:none'>Results</title>
The technical success rate was 100%, and 30-day procedural complication rate was 17.6%. Post-treatment assessments revealed that 11 out of 17 patients showed a decrease in flow volume within the aneurysm sac, indicative of a favorable hemodynamic response. The median decrease in flow volume was 12 ml, with a median relative decrease of 8%. However, there was no consistent reduction in aneurysm size; most aneurysms demonstrated a median increase in volume for 46 ml and median increase in diameter for 18 mm.
</sec>
<sec><title style='display:none'>Conclusions</title>
While MFMs offer a potential alternative for high-risk aortic aneurysm patients, their effectiveness in preventing aneurysm expansion is limited. The results suggest that MFMs can provide a stable hemodynamic environment but do not reliably reduce aneurysm size. This underscores the need for ongoing vigilance and long-term monitoring in patients treated with this technology.
</sec>
</abstract>

Long-term outcome of multilayer flow modulator in aortic aneurysms

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Background</title>
This study explores the predictive and monitoring capabilities of clinical and multiparametric MR parameters in assessing capecitabine and temozolomide (CAPTEM) therapy response in patients with neuroendocrine tumors (NET).
</sec>
<sec><title style='display:none'>Patients and methods</title>
This retrospective study (n = 44) assessed CAPTEM therapy response in neuroendocrine liver metastases (NELM) patients. Among 33 monitored patients, as a subgroup of the overall study cohort, pretherapeutic and follow-up MRI data (size, apparent diffusion coefficient [ADC] values, and signal intensities), along with clinical parameters (chromogranin A [CgA] and Ki-67%), were analyzed. Progression-free survival (PFS) served as the reference. Responders were defined as those with PFS ≥ 6 months.
</sec>
<sec><title style='display:none'>Results</title>
Most patients were male (75%) and had G2 tumors (76%) with a pancreatic origin (84%). Median PFS was 5.7 months; Overall Survival (OS) was 25 months. Non-responders (NR) had higher Ki-67 in primary tumors (16.5 <italic>vs</italic>. 10%, p = 0.01) and increased hepatic burden (20% <italic>vs</italic>. 5%, p = 0.007). NR showed elevated CgA post-treatment, while responders (R) exhibited a mild decrease. ADC changes differed significantly between groups, with NR having decreased ADCmin (−23%) and liver-adjusted ADCmean/ADCmean liver (−16%), compared to R’s increases of ADCmin (50%) and ADCmean/ADCmean liver (30%). Receiver operating characteristic (ROC) analysis identified the highest area under the curve (AUC) (0.76) for a single parameter for ∆ ADC mean/liver ADCmean, with a cut-off of &lt; 6.9 (76% sensitivity, 75% specificity). Combining ∆ Size NELM and ∆ ADCmin achieved the best balance (88% sensitivity, 60% specificity) outperforming ∆ Size NELM alone (69% sensitivity, 65% specificity). Kaplan-Meier analysis indicated significantly longer PFS for ∆ ADCmean/ADCmean liver &lt; 6.9 (p = 0.024) and ∆ Size NELM &gt; 0% + ∆ ADCmin &lt; −2.9% (p = 0.021).
</sec>
<sec><title style='display:none'>Conclusions</title>
Survival analysis emphasizes the need for adapted response criteria, involving combined evaluation of CgA, ADC values, and tumor size for monitoring CAPTEM response in hepatic metastasized NETs.
</sec>
</abstract>

Christine.schmid-tannwald@med.uni-muenchen.de

ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM), University Hospital of Munich

Utility of clinical and MR imaging parameters for prediction and monitoring of response to capecitabine and temozolomide (CAPTEM) therapy in patients with liver metastases of neuroendocrine tumors

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Background</title>
Various types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment.
</sec>
<sec><title style='display:none'>Results</title>
Clinical presentation of toxicities of new anticancer therapies may be unpredictable and nonspecific. They can mimic other more common medical conditions such as infection or stroke. If not recognized and properly treated these toxicities can progress rapidly into life-threatening conditions. ICIs can cause immune-related inflammatory disorders of various organ systems (e.g. pneumonitis or colitis), and a cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may develop after treatment with CAR T-cells or BiTEs. The cornerstones of management of these hyper-inflammatory disorders are supportive care and systemic immunosuppressive therapy. The latter should start as soon as symptoms are mild-moderate. Similarly, some severe toxicities of ADCs also require immunosuppressive therapy. A multidisciplinary team including an oncologist/haematologist and a corresponding organ-site specialist (e.g. gastroenterologist in the case of colitis) should be involved in the diagnosis and treatment of these toxicities.
</sec>
<sec><title style='display:none'>Conclusions</title>
Health professionals should be aware of potential serious complications of new systemic anticancer therapies. Early diagnosis and treatment with adequate supportive care and immunosuppressive therapy are crucial for the optimal outcome of patients with these complications.
</sec>
</abstract>

Potentially fatal complications of new systemic anticancer therapies: pearls and pitfalls in their initial management

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Background</title>
A fast and well-organized complex diagnostic process is important for better success in the treatment of lung cancer patients. The aim of our study was to reveal the gaps and inefficiencies in the diagnostic process and to suggest improvement strategies in a single tertiary centre in Slovenia.
</sec>
<sec><title style='display:none'>Patients and methods</title>
We employed a comprehensive approach to carefully dissect all the steps in the diagnostic journey for individuals suspected of having lung cancer. We gathered and analysed information from employees and patients involved in the process by dedicated questionnaires. Further, we analysed the patients’ data and calculated the diagnostic intervals for patients in two different periods.
</sec>
<sec><title style='display:none'>Results</title>
The major concerns among employees were stress and excessive administrative work. The important result of the visual journey and staff reports was the design of electronic diagnostic clinical pathway (eDCP), which could substantially increase safety and efficacy by diminishing the administrative burden of the employees. The patients were generally highly satisfied with diagnostic journey, but reported too long waiting times. By analysing two time periods, we revealed that diagnostic intervals exceeded the recommended timelines and got importantly shorter after two interventions - strengthening the diagnostic team and specially by purchase of additional PET-CT machine (the average time from general practitioner (GP) referral to the multidisciplinary treatment board (MDTB) decision was 50.8 [± 3.0] prior and 37.1 [± 2.3] days after the interventions).
</sec>
<sec><title style='display:none'>Conclusions</title>
The study illuminated opportunities for refining the diagnostic journey for lung cancer patients, underscoring the importance of both administrative and capacity-related enhancements.
</sec>
</abstract>

University Clinic for Respiratory and Allergic Diseases Golnik

Unravelling the lung cancer diagnostic pathway: identifying gaps and opportunities for improvement

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Background</title>
Transarterial chemoembolisation with irinotecan-loaded drug-eluting beads (DEBIRI TACE) can be considered in patients with unresectable colorectal cancer liver metastases (CRLM) who progress after all approved standard therapies or in patients unsuitable for systemic therapy.
</sec>
<sec><title style='display:none'>Patients and methods</title>
Between September 2010 and March 2020, thirty patients (22 men and 8 women; mean age 66.8 ± 13.2) were included in this retrospective study. DEBIRI TACE was conducted in 43% of patients unsuitable for systemic therapy as a first-line treatment and 57% as salvage therapy after the progression of systemic therapy. All the patients had liver-limited disease. In the case of unilobar disease, two treatments were performed at four-week intervals, and in the case of bilobar disease, four treatments were performed at two-week intervals. All patients were premedicated and monitored after the procedure. Adverse events were graded according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification system for complications.
</sec>
<sec><title style='display:none'>Results</title>
The median overall survival (OS) from the beginning of DEBIRI TACE in the salvage group was 17.4 months; in the group without prior systemic therapy, it was 21.6 months. The median overall survival of all patients was 17.4 months (95% confidence interval [CI]: 10.0–24.7 months), and progression-free survival (PFS) was 4.2 months (95% CI: 0.9–7.4 months). The one-year survival rate after the procedure was 61%, and the two-year rate was 25%. Univariate analysis showed better survival of patients with four or fewer liver metastases (<italic>p = 0.002</italic>). There were no treatment-related deaths or grade 4 and 5 adverse events. Nonserious adverse events (Grades 1 and 2) were present in 53% of patients, and Grade 3 adverse events were present in 6% of the patients.
</sec>
<sec><title style='display:none'>Conclusions</title>
DEBIRI TACE is a well-tolerated treatment option for patients with liver metastases of colorectal cancer. Patients with four or fewer liver metastases correlated with better survival.
</sec>
</abstract>

Prognostic factors for overall survival and safety of trans-arterial chemoembolization (TACE) with irinotecan-loaded drug-eluting beads (DEBIRI) in patients with colorectal liver metastases

<abstract><title style='display:none'>Abstract</title><sec id="j_raon-2019-0018_s_008_w2aab3b7b5b1b6b1aab1c18b1Aa"><title style='display:none' id="d2965566e197_w2aab3b7b5b1b6b1aab1c18b1aAa">Background</title>Platinum-based anticancer drugs are widely used in the chemotherapy of human neoplasms. The major obstacle for the clinical use of this class of drugs is the development of resistance and toxicity. It is therefore very important to understand the chemical properties, transport and metabolic pathways and mechanism of actions of these compounds. There is a large body of evidence that therapeutic and toxic effects of platinum drugs on cells are not only a consequence of covalent adducts formation between platinum complexes and DNA but also with RNA and many proteins. These processes determine molecular mechanisms that underlie resistance to platinum drugs as well as their toxicity. Increased expression levels of various transporters and increased repair of platinum-DNA adducts are both considered as the most significant processes in the development of drug resistance. Functional genomics has an increasing role in predicting patients’ responses to platinum drugs. Genetic polymorphisms affecting these processes may play an important role and constitute the basis for individualized approach to cancer therapy. Similar processes may also influence therapeutic potential of nonplatinum metal compounds with anticancer activity.</sec><sec id="j_raon-2019-0018_s_009_w2aab3b7b5b1b6b1aab1c18b2Aa"><title style='display:none' id="d2965566e205_w2aab3b7b5b1b6b1aab1c18b2aAa">Conclusions</title>Cisplatin is the most frequently used platinum based chemotherapeutic agent that is clinically proven to combat different types of cancers and sarcomas.</sec></abstract>

Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy

<abstract xml:lang="en"><title style='display:none'>Magnetic nanoparticles as targeted delivery systems in oncology</title><bold>Background.</bold> Many different types of nanoparticles, magnetic nanoparticles being just a category among them, offer exciting opportunities for technologies at the interfaces between chemistry, physics and biology. Some magnetic nanoparticles have already been utilized in clinical practice as contrast enhancing agents for magnetic resonance imaging (MRI). However, their physicochemical properties are constantly being improved upon also for other biological applications, such as magnetically-guided delivery systems for different therapeutics. By exposure of magnetic nanoparticles with attached therapeutics to an external magnetic field with appropriate characteristics, they are concentrated and retained at the preferred site which enables the targeted delivery of therapeutics to the desired spot.<bold>Conclusions.</bold> The idea of binding chemotherapeutics to magnetic nanoparticles has been around for 30 years, however, no magnetic nanoparticles as delivery systems have yet been approved for clinical practice. Recently, binding of nucleic acids to magnetic nanoparticles has been demonstrated as a successful non-viral transfection method of different cell lines in vitro. With the optimization of this method called magnetofection, it will hopefully become another form of gene delivery for the treatment of cancer.</abstract>

Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

Magnetic nanoparticles as targeted delivery systems in oncology

<abstract xml:lang="en"><title style='display:none'>Triple negative breast cancer - prognostic factors and survival</title><bold>Background.</bold> Triple negative breast cancer (TNBC) is defined by a lack of expression of both estrogen (ER) and progesteron (PgR) receptors as well as human epidermal growth factor receptor 2 (HER2). Our retrospective analysis addressed prognostic factors for short- and long-term outcomes of patients (pts) with TNBC pts treated in routine clinical practice.<bold>Patient and methods.</bold> Our retrospective study included 269 TNBC treated at Institute of Oncology Ljubljana between March 2000 and December 2006. The collected data included patients', tumours' and treatments' characteristics. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model was used in the multivariate analysis.<bold>Results.</bold> The median age of our patients was 55.3 yrs (23-88.5) and the median follow-up was 5.9 yrs (0.3-9.6). Six (2%) pts experienced local only, 79 (92%) pts distal recurrence and 66 (24%) died. The predominant localisation of the first relapse was in visceral organs (70.4%). The 5-year disease-free survival (DFS) for the entire group was 68.2% and the 5-year overall survival (OS) was 74.5%. We found a pattern of high recurrence rate in the first 3 years following the diagnosis and a clear decline in recurrence rate over the next 3 years. In the univariate analysis age, nodal status, size and lymphovascular invasion (LVI) were found to have a significant impact on DFS as well as on OS. In the multivariate analysis only age (HR=1.79; 95%CI=1.14-2.82; p=0.012) and nodal status (HR=2.71; 95%CI=1.64-4.46; p&lt;0.001) retained their independent prognostic value for DFS and for OS only the nodal status (HR=2.96; 95%CI=1.51-5.82; p=0.002).<bold>Conclusions.</bold> In our series of TNBC pts nodal status and age (older than 65 yrs) were found to be independent prognostic factors for DFS, whereas for OS only the nodal status. We found a pattern of a high recurrence rate in the first 3 years following the diagnosis and a decline in the recurrence rate over the next 3 yrs with higher rate of distal versus local recurrence and a predominant localization of distal metastases in visceral organs.</abstract>

Triple negative breast cancer - prognostic factors and survival

<abstract><title style='display:none'>Abstract</title><sec><title style='display:none'>Background</title>Modern radiotherapy techniques enable delivery of high doses to the target volume without escalating dose to organs at risk, offering the possibility of better local control while preserving good quality of life. Uncertainties in target volume delineation have been demonstrated for most tumour sites, and various studies indicate that inconsistencies in target volume delineation may be larger than errors in all other steps of the treatment planning and delivery process. The aim of this paper is to summarize the degree of delineation uncertainties for different tumour sites reported in the literature and review the effect of strategies to minimize them.</sec><sec><title style='display:none'>Conclusions</title>Our review confirmed that interobserver variability in target volume contouring represents the largest uncertainty in the process for most tumour sites, potentially resulting in a systematic error in dose delivery, which could influence local control in individual patients. For most tumour sites the optimal combination of imaging modalities for target delineation still needs to be determined. Strict use of delineation guidelines and protocols is advisable both in every day clinical practice and in clinical studies to diminish interobserver variability. Continuing medical education of radiation oncologists cannot be overemphasized, intensive formal training on interpretation of sectional imaging should be included in the program for radiation oncology residents.</sec></abstract>

Department of Radiation Oncology, Institute of Oncology Ljubljana, Slovenia

Department of Radation Oncology, National Centre for Cancer Care and Research, Doha, Qatar

Uncertainties in target volume delineation in radiotherapy – are they relevant and what can we do about them?

<abstract><title style='display:none'>Abstract</title><sec><title style='display:none'>Background</title>Electrochemotherapy is becoming a well-established treatment for malignancies of skin and non-skin origin and its use is widening across Europe. The technique was developed and optimized from solid experimental and clinical evidence. A consensus document is now warranted to formalize reporting results, which should strengthen evidence-based practice recommendations. This consensus should be derived from high quality clinical data collection, clinical expertise and summarizing patient feedback. The first step, which is addressed in this paper, aims to critically analyze the quality of published studies and to provide the recommendations for reporting clinical trials on electrochemotherapy.</sec><sec><title style='display:none'>Methods</title>The quality of reporting in published studies on electrochemotherapy was analyzed in order to produce procedure specific reporting recommendations. A comprehensive literature search of studies published from 2006 to 2015 was performed followed by qualitative analysis of manuscripts assessing for 47 quality criteria grouped into four major clusters: (1) trial design, (2) description of patient population, (3) description of treatment delivery and patient outcome, (4) analysis of results and their interpretation. The summary measure during literature assessment was the proportion of studies fulfilling each manuscript quality criteria.</sec><sec><title style='display:none'>Results</title>A total of 56 studies were screened, from the period 2006 to 2015, of which 33 were included in the qualitative analysis, with a total of 1215 patients. Overall, the quality of reporting was highly variable. Twenty-four reports (73%) were single-center, non-comparative studies, and only 15 (45%) were prospective in nature (only 2 of them were entered into a clinical trials registry). Electrochemotherapy technique was consistently reported, with most studies (31/33) adhering closely to published standard operating procedures. The quality of reporting the patient population was variable among the analyzed studies, with only between 45% and 100% achieving dedicated quality criteria. Reporting of treatment delivery and patient outcome was also highly variable with studies only fulfilling between 3% and 100%. Finally, reporting study results critically varied, fulfilling from 27% to 100% of the quality criteria. Based on the critical issues emerging from this analysis, recommendations and minimal requirements for reporting clinical data on electrochemotherapy were prepared and summarized into a checklist.</sec><sec><title style='display:none'>Conclusions</title>There is an increasing body of published clinical data on electrochemotherapy, but more high quality clinical data are needed. Published papers often lack accurate description of study population, treatment delivery as well as patient outcome. Our recommendations, provided in the form of a summary checklist, are intended to ameliorate data reporting in future studies on electrochemotherapy and help researchers to provide a solid evidence basis for clinical practice.</sec></abstract>

Recommendations for improving the quality of reporting clinical electrochemotherapy studies based on qualitative systematic review

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Radiology and Oncology

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Radiology and Oncology is a multidisciplinary journal devoted to the publishing original and high-quality scientific papers and review articles, pertinent to oncologic...

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Radiology and Oncology is a multidisciplinary journal devoted to the publishing original and high-quality scientific papers and...