ESTRO 36 Abstract Book

S170 ESTRO 36 _______________________________________________________________________________________________

Scienza, Department of Medical Sciences, Torino, Italy 6 A.O.U. Citta' della Salute e della Scienza- Turin, Department of Oncology- Medical Oncology, Torino, Italy 7 University of Turin A.O.U. Citta' della Salute e della Scienza, Department of Medical Imaging, Torino, Italy 8 A.O.U. Citta' della Salute e della Scienza- Turin, Department of Oncology- Radiation Oncology, Torino, Italy Purpose or Objective To test the proof of principle that irradiated volume of pelvic active bone marrow ( ACT BM), as detected by 18 FDG- PET, may be a predictor of decreased blood cell nadirs in anal cancer patients undergoing concurrent chemo- radiation and to identify subregions within the pelvis potentially more involved in the occurrence of acute Forty four patients submitted to IMRT and concurrent chemotherapy were analyzed. Several bony structures were defined: pelvic and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. ACT BM was characterized employing 18 FDG-PET and defined as all subregions within pelvic bone marrow having Standard Uptake Values (SUVs) higher than SUV mean . All other regions were defined as inactive BM ( INACT BM) (Figure 1). On dose- volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet (Plt) nadirs. Acute toxicity was scored according to RTOG scoring scale. Generalized linear and logistic regression models were used to find correlations between dosimetric variables and blood cell toxicity. hematologic toxicity. Material and Methods Results act BM mean dose had a statistically significant correlation with WBC (β=-1.338; 95%CI: -2.455/-0.221; p=0.020), ANC (β=-1.651; 95%CI: -3.284/-0.183; p=0.048) and Plt (β=- 0.031; 95%CI: -0.057/-0.004; p=0.024) nadirs. On the contrary, no correlation was found between inact BM mean dose and any blood cell nadir (Table 1). act BM V 10 had a significant correlation with WBC (β=-0.062; 95%CI: - 0.104/-0.021; p=0.004) and ANC (β=-0.038; 95%CI: - 0.067/-0.007; p=0.015) nadirs. act BM V 20 was significantly correlated to WBC (β=-0.044; 95%CI: -0.080/-0.008; p=0.017), ANC (β=-0.027; 95%CI: -0.052/-0.001; p=0.039) and Plt (β=-1.570; 95%CI: -3.140/-0.002; p=0.050) nadirs. act BM V 30 had a significant correlation with WBC (β=-0.033; 95%CI: -0.064/-0.002; p=0.036) and Plt (β=- 1.720; 95%CI: -2.990/-0.450; p=0.010) nadirs. act BM V 40 was significantly correlated to WBC (β=-1.490; 95%CI: -2.900/- 0.072; p=0.040) nadir. With respect to subregions within the pelvis, WBC nadir was significantly correlated to act LSBM mean dose (β=-1.852; 95%CI: -3.205/-0.500; p=0.009), V 10 (β=-2.153; 95%CI: -4.263/-0.721; p=0.002), V 20 (β=-2.081; 95%CI: -4.880/-0.112; p=0.003), V 30 (β=- 1.971; 95%CI: -4.748/-0.090; p=0.023) and to act IBM V 10 (β=-0.073; 95%CI: -0.106/-0.023; p=0.016). ANC nadir found to be significantly associated to act LSBM V 10 (β=- 1.878; 95%CI: -4.799/-0.643; p=0.025), V 20 (β=-1.765; 95%CI: -4.050/-0.613; p=0.030). No significant correlation were found between dosimetric parameters and > G3 hematologic toxicity, even if borderline significance was found for act LSBM mean dose and WBC nadir.

Conclusion 18 FDG-PET is able to define active bone marrow within pelvic osseous structures. ACT BM is a predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemo-radiation. Lumbar-sacral bone marrow dose seems to be the strongest predictor. PV-0325 Tumor Regression Grading in the CAO/ARO/AIO-04 phase 3 trial in locally advanced rectal carcinoma E. Fokas 1 , M. Ghadimi 2 , R. Fietkau 3 , P. Ströbel 4 , A. Hartmann 5 , R. Sauer 6 , T. Liersch 2 , T. Hothorn 7 , C. Wittekind 8 , C. Rödel 1 1 Goethe University Frankfurt, Department of Radiotherapy and Oncology, Frankfurt, Germany 2 University of Göttingen, Department of General- Visceral and Pediatric Surgery, Göttingen, Germany 3 University of Erlangen, Department of Radiation Oncology, Erlangen, Germany 4 University of Göttingen, Deparment of Pathology, Göttingen, Germany 5 University of Erlangen, Deparment of Pathology, Erlangen, Germany 6 University of Erlangen, Deparment of Radiation Oncology, Erlangen, Germany 7 University of Zurich, Epidemiology- Biostatistics and Prevention Institute, Zurich, Switzerland 8 University of Leipzig, Institute of Pathology, Leipzig, Germany Purpose or Objective We examined the prognostic value of tumor regression grading (TRG) in 1208 patients with locally advanced rectal carcinoma treated within the CAO/ARO/AIO-04 trial after a median follow-up of 50 months. Material and Methods TRG and clinicopathologic parameters were correlated to clinical outcome. Statistical differences between groups were calculated by the Log-rank test, and incidence curves were plotted using the Kaplan-Meier method. The Cox regression and the Fine-Gray models were used for the multivariate analysis. We used the four Prentice criteria (PC1-4) to assess the surrogacy of TRG for disease-free survival (DFS). Results The 3-year cumulative incidence of DFS, distant metastases, local recurrence and overall survival (OS) were 64.6%, 25.4%, 6.9% and 76.8% for patients with TRG 0+1 (poor regression), 77.6%, 18.3%, 3.3% and 89.2% for TRG 2 + 3 (intermediate regression), and 92.3%, 4.1%, 0% and 96.2% for TRG 4 (complete regression), respectively (P < .001, for all four endpoints). Due to multicollinearity, TRG 4 and pathologic stage was not assessed within the same model. TRG 2+3 vs TRG 0+1 after preoperative CRT remained an independent prognostic factor for DFS (HR, 0.677; P = .007), the cumulative incidence of local recurrence (HR, 0.504; P = .028) and OS (HR, 0.582; P < .001). Notably, TRG satisfied PC1-3 for individual-level surrogacy (P = .037, P < .001 and P < .001, respectively). The treatment effect on DFS was captured by TRG and therefore PC4 satisfaction is plausible. Conclusion TRG following preoperative chemoradiotherapy predicted for a favorable long-term outcome in multivariate analysis. In the era of personalized medicine. TRG might constitute an attractive option to validate molecular biomarkers, facilitate successful clinical testing of new