PO-0611: Long-term prognostic impacts of pretreatment plasma EBV DNA status in nasopharyngeal carcinoma

S318 ESTRO 36 _______________________________________________________________________________________________



than men (p< 0.001) and patients presenting nasal cavity tumors scored higher that all other tumoral sites (p=0.08). Conclusion HNC patients undergoing radiation therapy have high levels of emotional distress, anxiety and claustrophobia. Given the high percentage of psychological distress, awareness and management of these issues are primordial as they may have significant impact on treatment acceptance and tolerability as well QOL during and after treatment. PO-0609 18F-FDG-PET in Guiding Dose-painting with IMRT in Oropharyngeal Tumours (FiGaRO) – Early Results A. Michaelidou1, L. Pike2, C. Thomas3, L. Penketh4, Y. Suh5, S. Barrington2, M. Evans4, M. Lei1, T. Guerrero Urbano1 1 Guy's and St Thomas' NHS Foundation Trust, Clinical Oncology, London, United Kingdom 2 The PET Centre at St Thomas' Hospital, Nuclear Medicine, London, United Kingdom 3 Guy's and St Thomas' NHS Foundation Trust, Radiotherapy Physics, London, United Kingdom 4 Velindre Cancer Centre, Clinical Oncology, Cardiff, United Kingdom 5 Royal Marsden NHS Foundation Trust, Clinical Oncology, London, United Kingdom Purpose or Objective IMRT ± chemotherapy is an effective treatment for stage III/IVa oropharyngeal squamous cell carcinoma (SCC). Treatment failures occur mostly at the primary site and are difficult to salvage. Dose escalation strategies are being explored, with target volume definition and toxicity considered the main challenges. IMRT can boost doses to selected areas (dose painting) without exceeding normal tissue tolerances. 18F-FDG-PET/CT can mediate this, by defining areas of metabolic activity for dose escalation. This Phase 1 multicentre study aims to test the feasibility and safety of 18F-FDG-PET/CT dose-painted IMRT in locally advanced oropharyngeal SCC. We present toxicity results in the first 15 patients. Material and Methods Patients with ≥T2, HPV-negative or high-risk HPV-positive disease, suitable for radical treatment with neo-adjuvant chemotherapy and chemo-IMRT, are eligible. PET/CT is acquired after one chemotherapy cycle, in the radiotherapy position, in the immobilization shell. The FDG-avid gross tumour volume (GTV-T18F-FDG-PET) is manually delineated by a nuclear medicine physician then copied onto the fused CT for direct planning. Thirty daily fractions are delivered in 6 weeks, at 3 dose levels. The radical volume (PTV1) receives 65Gy, the prophylactic volume (PTV2) 54Gy and the GTV-T18F-FDG-PET receives 71.5Gy. Results Fifteen patients (14 male, 1 female; mean age-61, range 49-71) were treated April’14-March’16, at two centres (median follow-up 10 months, range 4-26 months. Eight (53.3%) are HPV-negative, 7(46.7%) are HPV-positive. Average GTV-T18F-FDG-PET volume was 11.9cc (range 1.667.7cc). Target volume objectives were met in all (median D9598.1%, range 96.1-98.9%; Median D5102.9%, range 101.1-103.6%), whilst respecting normal tissue tolerances and PTV1 hotspot constraints. On the CTCAEv.4.0 scale, end of treatment toxicities were: Grade 4–none; Grade 3 - dysphagia-46.7%(n=7), mucositis-26.7%(n=4), pain-13.3%(n=2), salivary gland6.7% (n=1); Grade 2- dysphagia-53.3%(n=8), mucositis73.3%(n=11), pain-73.3%(n=11), salivary gland86.7%(n=13), dermatitis-73.3%(n=11), xerostomia66.7%(n=10), fatigue-46.7%(n=7). Three month posttreatment toxicities were: Grade 4–none; Grade 3 dysphagia-20.0%(n=3); Grade 2- dysphagia-20.0%(n=3), mucositis-13.3%(n=2), pain-20.0%(n=3), xerostomia53.3%(n=8).

On the RTOG/EORTC scale 3-month post treatment toxicities were: Grade 4-none; Grade 3-salivary gland6.7%(n=1), oesophagus-6.7%(n=1); Grade 2–salivary gland46.7%(n=7), oesophagus-13.3%(n=2), mucosa-13.3%(n=2), joint(TMJ)-6.7%(n=1). On LENTSOMA categories one patient had a grade 4 toxicity - oropharyngeal dysphagia (gastrostomy dependent). Six (40.0%) had grade 3 toxicities and 13 (86.7%) had grade 2 toxicities. There were 2 local recurrences within 1 year, both underwent salvage surgery with clear margins. Conclusion 18 F-FDG-PET-guided selective dose escalation is feasible, with acceptable acute toxicity. Late toxicity assessment (3, 6 and 12-months post-treatment) is ongoing. PO-0610 Effects of an oral health promotion program in head and neck cancer patients receiving radiotherapy E. Kim1, H.G. Wu1, J.H. Kim1, K.S. Kim1, T. Yu1, C.W. Wee1, N. Choi1, B.S. Jang1, S.H. Jeon1, H.J. Lee2, D.H. Han2 1 Seoul National University College of Medicine, Radiation Oncology, Seoul, Korea Republic of 2 Seoul National University College of Dentistry, Preventive and Social Dentistry, Seoul, Korea Republic of Purpose or Objective To develop oral health promotion program and evaluate its effectiveness in head and neck cancer (HNC) patients receiving radiotherapy (RT). Material and Methods This was an open-label, non-randomized, prospective study in 84 HNC patients treated with RT. Dental health promotion program consisted of oral exam, oral health education, fluoride varnish and mouthwash. Forty-seven patients were assigned to an experimental group with the dental health care program and 37 to a control group. Clinical benefit was measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire head and neck module (QLQ-H&N35) and the oral examination before and up to 6 months after RT. Results Compared with the control group, the experimental group showed significant improvement in sexuality, use of pain killers, and worried about future (p = 0.045, p = 0.049, and p < 0.001, respectively). Oral health promotion program did not affect the development of xerostomia. Subgroups of patients with old age (≥ 60 years), stage IV HNC, and radical RT reported significant improvement in quality of life by oral health promotion protocol. Although caries experience significantly increased in a control group (p = 0.002), there was no significant change in an experimental group. The experimental group showed significantly decreased plaque score and bleeding on probe (p < 0.001 and p = 0.004). Conclusion Administration of our oral health promotion program decreased dental problems and slightly improved patients’ quality of life. We recommend the dental care program for HNC patients receiving RT to reduce treatment related oral toxicities. PO-0611 Long-term prognostic impacts of pretreatment plasma EBV DNA status in nasopharyngeal carcinoma J.C. Lin1, W.Y. Wang2, J.W. Huang1 1 Taichung Veterans General Hospital, Department of Radiation Oncology, Taichung, Taiwan 2 Hung Kuang University, Department of Nursing, Taichung, Taiwan Purpose or Objective To investigate the prognostic impacts of pretreatment plasma EBV (pEBV) DNA in patients with nasopharyngeal carcinoma.

S319 ESTRO 36 _______________________________________________________________________________________________



Material and Methods The study population consisted of 931 previously untreated, biopsy-proven, and no distant metastasis NPC patients who finished curative radiotherapy with/without chemotherapy at our department. The pre-treatment pEBV DNA level was measured by the real-time quantitative polymerase chain reaction. We analyzed the relationship between the pEBV DNA status and clinical characteristics. Various survival curves were compared between the patients with detectable and undetectable pEBV DNA by the Kaplan-Meier method. Results EBV DNA signal (> 0 copies/mL) was detected in 90.8% (845/931) NPC patients’ plasma before treatment. The percentages in patents with undetectable EBV DNA were inversely associated with presenting stages (24.6% for stage I/II, 8.5% for stage III and 2.8% for stage IV, P<0.001). The pEBV DNA levels were positively correlated with clinical stage (P<0.001). The age, gender, and pathological type between the patients with detectable and undetectable pre-treatment pEBV DNA were similar. However, patients with detectable pre-treatment pEBV DNA had relatively poor performance status, advanced Tclassification, advanced N-classification, and advanced overall stage than those with undetectable pEBV DNA. The overall survival (HR=0.4413, 95% CI = 0.29-0.67, P=0.0004, 10-year rate = 62.2% vs. 90.3%), neck failure-free survival (HR=0.3285, 95% CI = 0.12-0.93, P=0.0397, 10-year rate = 94.4% vs. 100%), and distant metastasis-free survival (HR=0.3751, 95% CI = 0.23-0.62, P=0.0002, 10-year rate = 79.9% vs. 97.7%) were significantly lower in patients with detectable pEBV DNA than in those with undetectable pEBV DNA. The local failure-free survival was similar between both subgroups (HR=0.8740, 95% CI = 0.46-1.67, P=0.9362, 10-year rate = 85.6% vs. 89.2%). Conclusion NPC patients presented with detectable pEBV DNA before treatment were associated with higher clinical stages and significant worse survivals. PO-0612 Significance of co-expression of mutant p53 protein and Ki67 in locally advanced HNSCC post chemoRT P. Baskaran Shanmuga1, K. Periasamy1, S. Sharma2, G.K. Singh1, V. Yadav1, A. Gupta1, J. Kaur1, A.K. Mandal2, K.T. Bhowmik1 1 Safdarjung Hospital, Radiotherapy, New Delhi, India 2 Safdarjung Hospital, Pathology, New Delhi, India Purpose or Objective To know the significance of the co-expression of mutant p53 protein and Ki67 in locally advanced HNSCC with respect to response to chemoradiation (CRT) and locoregional failure (LRF), distant metastasis (DM) and overall survival (OS) at 1 year. Material and Methods This prospective observational study included 62 patients with stage III-IV non nasopharyngeal HNSCC of which 58 patients completed CRT. Immunohistochemistry was done on the pre-treatment biopsy specimens and the expression of p53 and Ki67 in the tumor were graded based on the degree of nuclear staining. During statistical analysis, patients having co-expression (p53+/Ki67+) were categorised in one group and the rest in the non-coexpressed group (p53-/Ki67-, p53+/Ki67-, p53-/Ki67+). The patients were followed up for a minimum period of 1 year and the association between the co-expression of the markers and the tumor response to CRT and LRF, DM and OS at 1 year were analysed. Results 57% (33) patients showed co-expression of mutant p53 and Ki67 while 43% (25) patients fell in the non-co-expressed group. There was a statistically significant association between the co-expression of the markers and the parameters such as age <50 years, N2 stage, TNM stage IVA

and partial response(PR) to CRT at 8 weeks. Similarly, at 1 year, the absence of co-expression was associated significantly with the locoregional control of the disease while the presence was associated with LRF. Even though 8/9 patients with DM showed co-expression, a statistically significant association was not reached on analysis (p-value 0.064). The relative risk of PR and LRF were 4.16 and 3.59 respectively with p53 and Ki67 coexpression. On multivariate analysis, the co-expression of the markers was found to be a statistically significant independent predicting factor for PR at 8 weeks post CRT and LRF at 1 year with odds ratio 10.50 and 7.12 respectively, however, the N2 stage was a statistically significant independent factor of DM and mortality at 1 year with odds ratio of 6.16 and 11.14 respectively.

Conclusion These results signify that the co-expression of mutant p53 and Ki67 has specific role in the clinical course of locally advanced HNSCC, significant in predicting PR response to CRT and LRF at 1 year. Advanced Nodal stage (N2) has emerged as an independent predictor for DM and mortality at 1 year. PO-0613 Effect of geometric GTV-CTV margins in national contouring guidelines C.R. Hansen1,2, J. Johansen3, E. Samsøe4, E. Andersen5, J.B. Petersen6, K. Jensen7, H.M.B. Sand8, L.J. Andersen8, C. Grau7 1 Odense University Hospital, Laboratory of Radiation Physics, Odense, Denmark 2 University of Southern Denmark, Faculty of Health Sciences, Odense, Denmark 3 Odense University Hospital, Department of Oncology, Odense, Denmark 4 University Hospital Herlev, Radiotherapy Research UnitDepartment of Oncology, Herlev, Denmark 5 University Hospital Herlev, Department of Oncology, Herlev, Denmark 6 Aarhus University Hospital, Department of Medical Physics, Aarhus, Denmark 7 Aarhus University Hospital, Department of Oncology, Aarhus, Denmark