ESTRO 38 Abstract book

S281 ESTRO 38

Development, Milan, Italy; 2 Fondazione CNAO- Centro Nazionale di Adroterapia Oncologica, Clinical Department, Pavia, Italy; 3 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Department of Radiation Oncology 1, Milan, Italy Purpose or Objective Considering the relative radioresistance of prostate cancer (PCa) to conventional photon therapy, a novel form of external radiation therapy, hadrontherapy, has been recently proposed. Hadrontherapy uses high-linear energy transfer (LET) particle beams, such as carbon ions, and exhibits favorable results for several malignancies that poorly respond to conventional radiotherapy, including PCa. However, from a radiobiological perspective, the molecular basis underlying carbon ions is not yet fully understood. In this regard, among the various molecular determinants of response to radiotherapy are microRNAs (miRNAs). Material and Methods We explored changes in the miRNome and gene expression profile of PCa cell lines (LNCaP and DU145) upon carbon ion beam and photon irradiation –a study never pursued in the available literature– to search for commonalities and differences between the two irradiation sources. Considering the higher relative biological effectiveness (RBE) of carbon ions, PCa cells were exposed to different doses of photons (10 Gy) and high-LET carbon ion beams (5 Gy) delivered by a 137 Cs irradiator and a synchrotron (at CNAO, Pavia), respectively. miRNA and gene differential expression following irradiation was assessed by microarray analyses at different time points and then validated by qRT-PCR. Results We found that, among the 102 miRNAs modulated by photons and the 186 miRNAs affected by carbon ions, only 6 (2%) were shared by the two irradiation sources in both LNCaP and DU145 cell lines. Accordingly, the analysis of miRNA targets, selected from the intersection of targets predicted by in silico tools and genes found anticorrelated among those modulated upon irradiation, revealed that there was only a partial overlap (4%) between photons and carbon ions. These findings suggest that, unexpectedly, the two irradiation sources act by affecting different miRNAs and genes, still producing the same biological effect. Paradoxically, GSEA analyses revealed that genes significantly modulated by photons and/or carbon ions were prevalently enriched for common biological processes, including mitotic spindle and UV response, known to be strictly related to radiation response. This provides the first evidence that photons and carbon ion beams modulate different factors still converging on common cell processes, thus determining a comparable final biological effect.

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PV-0533 HPV16 viral load may explain gender differences in treatment outcome of anal squamous cell carcinoma D. Martin 1 , P. Balermpas 1 , R. Winkelmann 2 , U. Wieland 3 , M. Rave-Fränk 4 , J. Kitz 5 , C. Rödel 1 , E. Fokas 1 , F. Rödel 1 1 Klinikum der Johann Wolfgang Goethe Univ, Department of Radiotherapy and Oncology, Frankfurt, Germany ; 2 Klinikum der Johann Wolfgang Goethe Univ, Senckenberg Institute for Pathology, Frankfurt, Germany ; 3 University of Cologne, Institute of Virology- National Reference Centre for Papilloma- and Polyomaviruses, Cologne, Germany ; 4 University Medical Center Göttingen, Department of Radiotherapy and Radiation Oncology, Göttingen, Germany ; 5 University Medical Center Göttingen, Department of Pathology, Göttingen, Germany Purpose or Objective Female gender is a well-established favorable prognostic factor after definitive chemoradiotherapy (CRT) for patients with anal squamous cell carcinoma (ASCC), however, no clear explanation for this gender difference has been elucidated so far. ASCC is associated with high- risk strains of human papilloma virus (HPV) infection and HPV-positive patients have improved treatment outcomes. We hypothesized that the differences in outcome according to gender are due to differences in HPV We examined pretreatment tumor samples of 141 patients (64 male/77 female) with ASCC treated with standard chemoradiotherapy. Expression of p16 INK4a was measured semiquantitavely by a immunohistochemical score.. The HPV16 viral load was assessed via a quantitative PCR approach. Clinical outcomes of these patients were correlated with clinicopathological factors and p16 expression/HPV16 viral load. Results After a median follow-up of 46 months, the 5-year locoregional control rate (LRC) and disease-free survival (DFS) was 80.4% and 75.3%, respectively. There were no significant differences in age, cT/N-categories, pretreatment white blood cell and platelet count according to gender, but female patients had significantly lower hemoglobin levels at baseline. A high HPV16 viral load (using maximally selected rank statistics) was associated with a favorable LCR (p< 0.01), DFS (p<0.01), and overall survival (p<0.01). A high expression of p16 INK4a (score >6) was associated with a favorable LRC (p < 0.01) and DFS (p < 0.05). Female patients showed a significantly higher HPV16 viral load (p=0.012) at baseline. In a multivariate cox regression model, including gender and HPV16 viral load, only the viral load was significantly associated with LRC (HR 0.3, p<0.01) and DFS (HR 0.39, p<0.05). Conclusion A high HPV16 viral load in pretreatment tissue was associated with better treatment outcome and significantly higher in female patients. Multivariate analyses revealed that HPV16 viral load remained as a significant predictor of treatment outcome when combined with gender. These data suggest a possible biological background for gender differences after CRT in ASCC. PV-0534 Carbon ions and microRNAs: new insights into hadrontherapy biology in prostate cancer I. Salido 1 , R. El Bezawy 1 , M. Ciocca 2 , F. Valvo 2 , A. Facoetti 2 , P. Gandellini 1 , R. Valdagni 3 , N. Zaffaroni 1 1 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Applied Research and Technological infection parameters. Material and Methods