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interval between fibrosis diagnosis and pravastatin initiation was 17.1 months. At baseline, patients had gd 2 (n=37), gd 3 (n=22) and gd 4 (n=1) fibrosis. Pravastatin was disrupted before 11.6 months in 19 patients: due to toxicity related to statin use (n=9), patient withdrawal (n=4), social problem (n=1), cancer relapse (n=3), death independent to statin use (n=2). A total of 42 patients received daily pravastatin at least 11 months who are representative of population eligible for pravastatin efficacy evaluation. Among them, pravastatin efficacy was assessed by HF-US in 40 patients at 12 months, and a reduction of fibrosis thickness ≥30% was observed in 35.7% (15/42) patients (95% confidence interval (CI): 22% - 52%). The two patients without 12-month HF-US were considered as failure. According to 12-month clinical evaluation, pravastatin decreased fibrosis severity in 50% (21/42) patients (95%CI: 34% - 66%). Patients’ self- perception, mood state and social functioning were significantly improved at 12 months. Among the 60 patients, 6 (10%) had grade 3 adverse event (gd 3 myalgia and arthralgia in 3 (5%) patients). Conclusion This phase II prospective study is a prototypic example of a biology-driven trial in radiation oncology displaying the concept of fibrosis reversibility. It supports that Pravastatin (40mg/d during 12 months) can be an efficient anti-fibrotic agent in patients with early and grade≥2 cutaneous and subcutaneous fibrosis after HN cancer RT. OC-0487 EMT signatures as a prognostic marker for metastasis in HPV-negative HNSCC M. Van der Heijden 1 , P. Essers 1 , M. Verheij 2 , M. Van den Brekel 3 , C. Vens 4 1 Netherlands Cancer Institute, Cell Biology I, Amsterdam, The Netherlands 2 Netherlands Cancer Institute, Department of Radiation Oncology, Amsterdam, The Netherlands 3 Netherlands Cancer Institute, Department of Head and Neck Oncology and Surgery, Amsterdam, The Netherlands 4 Netherlands Cancer Institute, Cell Biology I and Department of Radiation Oncology, Amsterdam, The Netherlands Purpose or Objective The development of distant metastases largely influences the prognosis for head and neck squamous cell carcinoma (HNSCC) patients. Epithelial to mesenchymal transition (EMT) has been shown to be an important factor in metastasis formation. However, no biomarkers for EMT are currently used in clinical practice. EMT transcription signatures have been developed and tested in other cancer types. Our aim is to evaluate the prognostic value of such published gene-expression based markers for EMT in HNSCC. Material and Methods Fresh frozen biopsy specimens were collected from 95 patients with HPV-negative oropharyngeal, laryngeal or hypopharyngeal squamous cell carcinoma, treated with concurrent cisplatin based chemo-radiation. Follow up data were retrospectively collected and analyzed. Samples were processed for whole transcriptome sequencing. Applying six published EMT signatures, expression values were calculated and samples were divided into high and low expression groups, according to the instructions of the respective authors. Cox’s proportional hazard model was used to assess their prognostic value. In multivariate analysis, additional covariates used were tumor site and pathological T-stage and N-stage. Results For four out of six EMT signatures, high expression values were significantly associated with reduced distant metastasis-free survival (Figure 1), as well as progression- free and overall survival in multivariate analysis. The

Conclusion Our study identified SNPs at two loci significantly associated with acute endpoints after RT for head- and neck cancer. Larger sample sizes are needed to obtain additional power. Collaborative efforts with this objective are warranted. OC-0486 Pravastatin reverses fibrosis in head and neck cancer patients: phase II clinical trial results C. Bourgier 1 , S. Rivera 2 , M.C. Vozenin 3 , P. Boisselier 1 , D. Azria 1 , N. Lassau 4 , P. Taourel 5 , J. Bourhis 6 , E. Deutsch 2 , A. Aupérin 7 1 ICM-Val d'Aurelle, Radiation Oncology, Montpellier, France 2 institut gustave roussy, radiation oncology, Villejuif, France 3 CHUV, radiobiology, Lausanne, Switzerland 4 institut gustave roussy, radiology, Villejuif, France 5 CHU Arnaud de Villeneuve, Radiology, Montpelllier, France 6 CHUV, Radiation Oncology, Lausanne, Switzerland 7 institut gustave roussy, Biostatistic Unit, Villejuif, France Purpose or Objective Previous preclinical investigations brought the biological rational for PRAVACUR phase II trial (NCT01268202) that aimed at assessing efficacy of 12-month daily pravastatin delivered in patients suffering from established cutaneous and subcutaneous fibrosis after head and neck Main inclusion criteria were: patients with HN carcinoma in remission, with grade (gd) ≥2 cutaneous and subcutaneous radio-induced fibrosis (NCI-CTCAE v4.0); no current treatment by statin or fibrate. Patients should receive daily pravastatin (40mg) during 12 months. The primary endpoint was the reduction of fibrosis thickness more than 30% at 12 months measured by cutaneous high- frequency ultra-sound (HF-US). This one-stage bicentric phase II trial tested the null hypothesis that success rate was less than 10% versus the alternative that it was greater than 30%. If there were ≥8 successes among 40 evaluable patients, pravastatin would be considered interesting. Secondary endpoints included reduction of fibrosis severity; pravastatin compliance and tolerance; and of patients’ quality of life (VQ-dermato questionnaire). Results 60 eligible patients were enrolled from 02/2011 to 04/2016. Mean age was 59 years, tumor locations were oropharynx (n=25), oral cavity (n=12), hypopharynx (n=12), larynx (n=6) and nasopharynx (n=1). 95% of patients had concomitant chemoradiotherapy and 53% underwent surgery. Mean RT dose was 67.4Gy. Mean (HN) radiotherapy (RT). Material and Methods