Accès libre

Quantifying the changes in the tumour vascular micro-environment in spinal metastases treated with stereotactic body radiotherapy - a single arm prospective study

Balamurugan Vellayappan

Balamurugan Vellayappan

Department of Radiation Oncology, National University Cancer Institute Singapore, National University HospitalSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Vellayappan, Balamurugan
, 
Dennis Cheong

Dennis Cheong

Clinical Imaging Research Centre, National University of SingaporeSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Cheong, Dennis
, 
Salil Singbal

Salil Singbal

Department of Diagnostic Imaging, National University HospitalSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Singbal, Salil
, 
Jeremy Tey

Jeremy Tey

Department of Radiation Oncology, National University Cancer Institute Singapore, National University HospitalSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Tey, Jeremy
, 
Yu Yang Soon

Yu Yang Soon

Department of Radiation Oncology, National University Cancer Institute Singapore, National University HospitalSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Yang Soon, Yu
, 
Cheng Nang Leong

Cheng Nang Leong

Department of Radiation Oncology, National University Cancer Institute Singapore, National University HospitalSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Nang Leong, Cheng
, 
Alvin Wong

Alvin Wong

Department of Haematology-Oncology, National University Cancer Institute Singapore, National University HospitalSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Wong, Alvin
, 
Sein Lwin

Sein Lwin

Division of Neurosurgery, Department of Surgery, National University HospitalSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Lwin, Sein
, 
Chau Hung Lee

Chau Hung Lee

Department of Radiology, Tan Tock Seng HospitalSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Hung Lee, Chau
, 
Pravin Periasamy

Pravin Periasamy

Centre for Life Sciences (CeLS), National University of SingaporeSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Periasamy, Pravin
, 
Simon Lo

Simon Lo

Department of Radiation Oncology, University of WashingtonSeattle, WA, USA
Recherchez cet auteur sur
Sciendo|Google Scholar
Lo, Simon
 et 
Naresh Kumar

Naresh Kumar

Department of Orthopaedic Surgery, National University HospitalSingapore, Singapore
Recherchez cet auteur sur
Sciendo|Google Scholar
Kumar, Naresh
  
13 déc. 2022
Quantifying the changes in the tumour vascular micro-environment in spinal metastases treated with stereotactic body radiotherapy - a single arm prospective study's Cover Image
À propos de cet article
Article précédent
Article suivant
Citez
Télécharger la couverture
Catégorie d'article: Research Article
Publié en ligne: 13 déc. 2022
Pages: 525 - 534
Reçu: 24 août 2022
Accepté: 29 sept. 2022
DOI: https://doi.org/10.2478/raon-2022-0046
Mots clés
© 2022 Balamurugan Vellayappan, Dennis Cheong, Salil Singbal, Jeremy Tey, Yu Yang Soon, Cheng Nang Leong, Alvin Wong, Sein Lwin, Chau Hung Lee, Pravin Periasamy, Simon Lo, Naresh Kumar, published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Schematic illustration of the DP model. Contrast agent (CA) concentration within the vessel decreases with position (x) along the vessel length (L), producing concentration gradients between the arterial (x = 0) and venous (x = L) capillary ends. During the CA passage, a portion of the CA molecules diffuses between the plasma and extracellular, extravascular space (EES) at a controlled permeability surface area product (PS) rate, so that the plasma, Cp(x, t), and EES, Ce(x, t), concentrations show both spatial and temporal dependence.
Schematic illustration of the DP model. Contrast agent (CA) concentration within the vessel decreases with position (x) along the vessel length (L), producing concentration gradients between the arterial (x = 0) and venous (x = L) capillary ends. During the CA passage, a portion of the CA molecules diffuses between the plasma and extracellular, extravascular space (EES) at a controlled permeability surface area product (PS) rate, so that the plasma, Cp(x, t), and EES, Ce(x, t), concentrations show both spatial and temporal dependence.

Figure 2

Normalized values of dynamic contrast enhanced (DCE) parameters (A) time-dependent leakage (Ktrans); (B) permeability surface product (PS); (C) fractional plasma volume (Vp); (D) extracellular volume (Ve); and (E) perfusion.
Normalized values of dynamic contrast enhanced (DCE) parameters (A) time-dependent leakage (Ktrans); (B) permeability surface product (PS); (C) fractional plasma volume (Vp); (D) extracellular volume (Ve); and (E) perfusion.

Figure 3

(A) Representative images for Patient 7a showing at L1 with reduction in dynamic contrast enhanced (DCE) parameters [i] time-dependent leakage (Ktrans); [ii] permeability surface product (PS); [iii] fractional plasma volume (Vp); [iv] extracellular volume (Ve); and [v] perfusion (F) across the 3 time points.
(A) Representative images for Patient 7a showing at L1 with reduction in dynamic contrast enhanced (DCE) parameters [i] time-dependent leakage (Ktrans); [ii] permeability surface product (PS); [iii] fractional plasma volume (Vp); [iv] extracellular volume (Ve); and [v] perfusion (F) across the 3 time points.

Figure 3

(B) [i] Metastatic deposit in L1 vertebral body (yellow arrow), as shown on T1 Axial MR (with gadolinium contrast); [ii] stereotactic body radiotherapy (SBRT) planning image (CT, MRI fused). SBRT 27 Gy in 3 fractions, delivered using volumetric modulated arc therapy. Clinical target volume (CTV) (blue outline), planning organ at risk volume (PRV)_cord (red outline), 95% isodose (orange colourwash).
(B) [i] Metastatic deposit in L1 vertebral body (yellow arrow), as shown on T1 Axial MR (with gadolinium contrast); [ii] stereotactic body radiotherapy (SBRT) planning image (CT, MRI fused). SBRT 27 Gy in 3 fractions, delivered using volumetric modulated arc therapy. Clinical target volume (CTV) (blue outline), planning organ at risk volume (PRV)_cord (red outline), 95% isodose (orange colourwash).

Figure 4

Correlative plasma markers (A) acid sphingomyelinase (ASM); and (B) sphingosine-1-phosphate (S1P).
Correlative plasma markers (A) acid sphingomyelinase (ASM); and (B) sphingosine-1-phosphate (S1P).

Inclusion and exclusion criteria

Inclusion criteria Exclusion criteria
1. Age ≥ 21 years 1. Metastatic haematological and germ cell neoplasms
2. Proven metastatic disease 2. Inability to undergo MRI or receive gadolinium contrast
3. Life expectancy > 3 months 3. Prior radiotherapy to region of interest
4. Eastern Cooperative Oncology group (ECOG) 0–2 4. Recent immediate surgery surgical to affected intervention spinal levels, or patients requiring
5. ≤ 3 contiguous vertebral body segments, including para-spinal disease 5. Spinal instability score (SINS) > 12
6. Able to lie supine for ≥ 60 minutes 6. Symptomatic cord compression (Bilksy grade 2 or 3), or worsening neurological deficits

Clinical outcomes

Patient ID (Change Post-SBRT from VAS pre- SBRT baseline) Acute toxicity Late toxicity Response at 3 months assessment (MD Anderson criteria) Follow-up duration (months) Local recurrence at last follow-up Status of patient at last follow-up
1 0 (-8) G1 esophagitis Nil PR 39 No Dead
2 0 (-3) Nil Nil PR 54 Yes Alive
3 0 (-5) Nil G1 compression fracture PR 50 No Alive
4 0 (-8) G1 esophagitis Nil SD 15 No Dead
5 3 (-3) G1 esophagitis Nil PR 22 No Dead
6 0 (-3) Nil Nil SD 13 No Dead
7a 2 (-5) Nil G1 compression fracture PR 42 No Alive
7b 2 (-5) Nil Nil PR 42 No Alive
8a - Nil N/A - N/A N/A Dead
8b - Nil N/A - N/A N/A Dead
8c - Nil N/A - N/A N/A Dead
9 0 Nil G3 compression fracture SD 37 No Alive
10 0 (-3) Nil Nil PR 22 No Alive

Patient characteristics

Patient ID Age Gender Primary histology Level of spinal metastases Extraspinal disease site Baseline analgesia requirement: opioid/non- opioid/nil Prior chemotherapy anti-Prior VEGF therapy Prior immunotherapy ECOG treatment Pre- VAS SINS Indication SBRT
Dose (Gy) Fractions
1 69 M RCC C1 Lung Non-opioid No No Yes 1 8 6 Radioresistant histology, pain control 24 3
2 60 M RCC S1 Nil Nil No No No 0 3 3 Oligometatasis 27 3
3 60 M NSCLC-EGFR - T5 Brain, lung bone. Nil Yes No No 1 5 6 Oligometastasis 24 3
4 62 F NSCLC-EGFR - C5 Brain, bone nodal, Opioid No No No 1 8 7 Oligometastasis, pain control 24 2
5 75 M adenocarcinoma Prostate T1 Bone Nil No No No 1 6 5 Oligometastasis 24 3
6 62 M adenocarcinoma Colon L1 LN, lung Nil Yes No No 1 3 9 Oligometastasis 27 3
7a 52 M RCC L1 Bone Opioid No No Yes 1 7 7 Radioresistant histology, pain control 27* 3*
7b 52 M RCC L2 Bone Opioid No No Yes 1 7 7 Radioresistant histology, pain control 27* 3*
8a 69 F NSCLC-EGFR + T1 Brain, lung bone. Non-Opioid No No Yes 1 3 5 Oligometastasis 24 3
8b 69 F NSCLC-EGFR + T10 Brain, lung bone. Non-Opioid No No Yes 1 3 4 Oligometastasis 27* 3*
8c 69 F NSCLC-EGFR + T12 Brain, lung bone. Non-Opioid No No Yes 1 3 6 Oligometastasis 27 3
9 51 F ductal Breast carcinoma Invasive T4 Nil Nil Yes No No 1 0 2 Oligometastasis 27 3
10 72 M adenocarcinoma Prostate L3 Nil Nil No No No 2 3 2 Oligometastasis 24 2
Langue:
Anglais
Périodicité:
4 fois par an
Sujets de la revue:
Médecine, Médecine clinique, Médecine interne, Hématologie, oncologie, Radiologie
RSS Feed de la revue