ESTRO 38 Abstract book

S468 ESTRO 38

P. Shaikh 1 , F. Alite 2 , V. Bakalov 3 , B. Emami 4 , J. Vargo 5 , M. Wu 6 , G. Jacobson 5 , W. Small 4 , M. Harkenrider 4 1 West Virginia University, Radiation Oncology, Kentwood, USA ; 2 Geisinger Medical Center, Radiation Oncology, Danville- PA, USA ; 3 Allegany General Hospital, Internal Medicine, Pittsburgh- PA, USA ; 4 Loyola University Chicago, Radiation Oncology, Maywood- IL, USA ; 5 West Virginia University, Radiation Oncology, Morgantown- WV, USA ; 6 Loyola University Chicago, Radiation Oncology, Chicago- IL, USA Purpose or Objective Several retrospective matched-pair series have reported on late effects of radiotherapy(RT) in patients with collagen vascular disease(CVD). Results have been conflicting and concern remains that patients are at greater risk for late toxicity. Material and Methods A comprehensive EMBASE and Medline search was performed to identify case-control series reporting RT toxicity in patients with CVDs. Results were synthesized from studies reporting at least grade 2 or 3 (G2/3+) acute and/or late toxicities in patients with rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), scleroderma (SSc), Dermatomyositis/Polymyositis (DM/PM), Raynaud’s, Mixed connective tissue disease(MCTD)/Sjogren’s. Results were analyzed on the random-effects(RE) model if there was evidence of between-study heterogeneity, otherwise the fixed-effects model(FE) was used. Hazard ratio(HR) was used for overall late toxicity for all CVDs and survival endpoints and odds ratio(OR) for subgroup toxicity analysis. Results 10 studies were identified with 4112 patients (CVD=380, control=3732). Grade 2/3+late toxicity was seen in 18.4% (68/370) RT courses in CVD patients vs. 10.1% (262/2588) in control patients (Fig). Pooled data showed significantly worse grade 2/3+ late toxicity in patients with CVD vs. control (HR=2.37; 95% CI 1.71–3.28, p<0.00001, FE). Subgroup analysis showed RA patients had 16/137 (11.7%) RT courses complicated by grade 2/3+ late toxicities vs. 63/804 (7.8%) in control patients (OR=2.56; 95% CI 1.27–5.16, p=0.008). SLE patients had 14/67 (20.9%) RT courses complicated by grade 2/3+ late toxicities vs. 19/206 (9.2%) in control patients (OR=2.54; 95% CI 1.11–5.81, p=0.03, FE). SSc patients had 7/22 (31.8%) RT courses complicated by grade 2/3+ late toxicities vs. 12/138 (8.7%) in control patients(OR=3.85; 95% CI 1.14–12.98, p=0.03, FE). No significant differences were found in late grade 2/3+ toxicity for subgroups of DM/PM or Raynaud’s. Late grade 4 and 5 toxicity was significantly higher in CVD patients, 6.2% vs. 0.64% (HR=8.44, p=0.0002) for Grade 4 and 3.2 vs. 0.55% (HR=6.87, p=0.02) for Grade 5. Abdomen/Pelvis had the highest probability of late grade 2/3+ toxicity (32.2%, bowel toxicity) followed by head & neck (27.9%, likely reflecting higher dose) compared to breast, thorax and skin (<15%) anatomic sites. Overall acute G2/3+ was also significantly worse in CVD group(OR 2.0, p<0.0001) and in the subgroups of patients with SLE(OR=2.25, p=0.05) and DM/PM(OR=3.39, p<0.0001). There was statistically significant worse disease-free-survival in CVD patients vs. controls(HR=1.46, p<0.01) but no difference in overall, loco-regional or distant metastases free survival. Conclusion Metanalysis demonstrated significantly higher RT induced late toxicity, including risk of death in irradiated CVD patients, especially in RA, SLE and SSc subgroups and in abdomen/pelvis and head/neck anatomic sites. These findings support further validation in prospective manner.

hypovascularized-hypometabolic junctional zone between the central necrotic and peripheral hypervascularized- hypermetabolic tumor segment. Based on tumor site and volume, BTV was irradiated with 1-3 fractions of 10 or 12 Gy prescribed to 70% isodose, avoiding the tumor microenvironment (Fig.1, 2). No patient received systemic therapy. Immunohistochemistry was performed on the available tissue samples after neoadjuvant PTI and surgery to explore for the modifications within the tumor microenvironment.

Results On an average, the BTV corresponded to 30% of the bulky tumors. With median follow-up of 11 months (range: 2-22) OS and DSS were 71% and 84%, respectively. BE response rate was 95%. Average bulky shrinkage was 60%, with 20% complete responses. AE response rate was 47% with mean reduction of unirradiated metastases of 50% (range: 30- 100%). No patient experienced acute or late toxicity of any grade. The immunohistochemical findings after neoadjuvant PTI showed that apoptosis-inducing factor was massively upregulated in the partially irradiated bulky and also at unirradiated-abscopal tumor sites, whereas a dense immune reaction was observed only at the border of the partially irradiated tumor but not at the abscopal site indicating an important role for the tumor-abscopal signaling. Conclusion PTI for bulky tumors was feasible, effective and safe, showing high potential for induction of BE and AE, that could be translated in improved therapeutic ratio. Relevance : PTI showed high neoadjuvant potential to convert unresectable into resectable lesions; very convenient palliative 1-3 days treatment for patients in poor general conditions, offering an improved cost- effectiveness profile ; safe salvage re-irradiation option in case of relapses. PO-0887 Radiation toxicity in patients with collagen vascular disease: Meta-analysis of case-control studies