ESTRO 37 Abstract book

S743

ESTRO 37

19 Complexo Hospitalario Universitario Santiago de Compostela, Radiation Oncology, A Coruña, Spain

receiving pCRT experienced fewer locoregional recurrences without higher severe treatment-related toxicity compared with the pCHT group. Although there were not significant differences in terms of OS and PFS in our series, it can not be ruled out significant differences with a longer follow-up. EP-1360 Heat shock Protein 70 serum levels as a predictor of clinical response in non-small-cell lung cancer C. Ostheimer 1 , S. Gunther 2 , M. Bache 1 , D. Vordermark 1 , G. Multhoff 2 1 Universitaetsklinikum HalleSaale, Radiation Oncology, Halle, Germany 2 Ludwigs-Maximilian-Universitaet Muenchen, Radiation Oncology, Munich, Germany Purpose or Objective Hypoxia mediates resistance to radio(chemo)therapy (RT) by stimulating the synthesis of hypoxia-related genes, such as osteopontin (OPN) and stress proteins, including the major stress-inducible heat shock protein 70 (Hsp70). Apart from its intracellular localization, Hsp70 is also present on the plasma membrane of viable tumor cells that actively release it in lipid vesicles with biophysical characteristics of exosomes. Exosomal Hsp70 contributes to radioresistance while Hsp70 derived from dying tumor cells can serve as a stimulator of immune cells. Material and Methods We investigated the prognostic and predictive role of Hsp70 in the plasma in n=44 patients with advanced, non- metastasized (M0) non-small-cell lung cancer (NSCLC) before (T1) and 4–6 weeks after RT (T2) in relation to OPN as potential biomarkers for clinical response and compared plasma levels with a control group of n=114 healthy individuals. Plasma biomarker concentration was determined with commercially available ELISA. Results Plasma levels of Hsp70 correlated with those of OPN at T1 (r = 0.422, p = 0.005) and high OPN levels were significantly associated with a decreased overall survival (high OPN: 13 vs. low OPN: 23 months; p < 0.05). Hsp70 plasma levels dropped significantly after RT, i.e. from 10.35 ng/ml before RT to 6.05 ng/ml after RT (p = 0.016). A significant positive correlation was determined between HSP70 levels before and after RT (r = 0.659, p < 0.0001). Compared to the cohort of 114 healthy donors (7.8 ng/ml), mean Hsp70 values in NSCLC patients remained to be significantly upregulated before (T1) and after (T2) RT (p < 0.05). Patients who responded to radiotherapy had significantly higher median Hsp70 plasma levels after RT (8.6 ng/ml) compared to those who showed no response after therapy (2.8 ng/ml, p = 0.013) and responding patients had a superior OS compared to non-responding patients (23 vs. 9 months, p = 0.026) who had an increased risk of death (rr = 2.11). The related ROC curve analysis showed a significant predictive function (p = 0.014) of plasma Hsp70 levels after RT for therapy response with an area under the curve (AUC) of 0.82 and an optimal cutoff value determining a positive therapy response at ≤4.35 ng/ml (sensitivity = 0.895; false positive rate = 0.143). Conclusion In summary, high OPN plasma levels at before RT are indicative for poor OS, whereas elevated post- therapeutic Hsp70 plasma levels together with a drop of Hsp70 between T1 and T2, successfully predict favorable responses to RT. Monitoring the dynamics of Hsp70 in NSCLC patients during and after RT can provide additional predictive information for clinical outcome and therefore might support the therapeutic decision-making process and allow a more rapid therapy adaptation after radiotherapy.

Purpose or Objective We conducted a multi-institutional retrospective study comparing preoperative high doses chemoradiotherapy (pCRT) and preoperative chemotherapy (pCHT) in operable stage IIIA-N2 non-small-cell lung cancer (NSCLC). Material and Methods 99 patients with stage T1-T3N2M0 NSCLC treated with either high doses (60-66 Gy, 1.8-2 Gy/fraction) pCRT or pCHT (three cycles, mostly platinum-doublet) followed by surgery were identified between January 2005 and December 2014 at 14 hospitals in Spain. The study was supported by the Radiation Oncology Clinical Research Group (GICOR) and the GOECP-SEOR (Oncologic Group for the Study of Lung Cancer-Spanish Society of Radiation Oncology. Patient and tumor characteristics (age; gender; clinical T stage; number and size of involved nodal stations; histology) were similar (p >0.05) in both groups. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was also performed. Results

47 patients were treated with pCRT and 52 with pCHT. Median follow-up was 41 months in the pCRT arm and 41.5 months in the pCHT arm. Surgery consisted of either lobectomy (87.2% in pCRT vs. 82.7% in pCHT) or pneumonectomy (12.8% in pCRT vs. 17.3% in pCHT). Postoperative radiotherapy was given to 57.6% of patients receiving pCHT. Adjuvant CHT was given to 14.9% of patients undergoing pCRT vs. 30.8% of patients undergoing pCHT (p=0.062). Nodal downstaging (to N1 or N0; 89.4% vs. 57.7%) and pathologic complete response (pT0pN0; 46.8% vs. 7.7%) were significantly higher in pCRT vs. pCHT group. Patients in the pCRT group experience fewer locoregional recurrences vs the pCHT group (8.5% vs. 13.5%, p = 0.047) and similar distant recurrences (31.9% vs. 34.6%, p=0.776). 4-year PFS (55.5% vs. 42.6%, log-rank p=0.505) and 4-year OS (61.8% vs. 58.1%, log-rank p=0.516) were similar for pCRT vs. pCHT group. Median PFS was 45 months in the pCHT group and not yet reached in pCRT group. Median OS was similar in both groups (61 months in pCRT vs. 56 months in pCHT, log-rank p=0.803). No differences were found in the overall grade ≥3 toxicity between the groups. One patient died from treatment-related causes in the pCRT group compared to none in the pCHT. Univariate analysis showed that the only factor associated with worse OS was an advanced pT stage (p<0.001). A higher pT stage (p<0.001) and persistent N2 (p=0.002) were independent prognostic factors associated with poorer PFS on multivariate analysis. Conclusion pCRT yields better nodal downstaging and pathologic complete response than pCHT . Moreover, patients