Metastatic HNSCC: Treatment Outcome in a Single Institution Cohort

4th ICHNO instruments help surgeons in improving surgical accuracy and post-operative parametres in conservative surgery, however we suggest to use cold instruments for the resection of the glottic plane and the crico-thyroid memebrane in order to avoid possible surgical artifacts liked to thermal damage. PO-073 LOW DOSE FRACTIONATED RADIOTHERAPY IN ASSOCIATION TO INDUCTION CHEMOTHERAPY IN LOCALLY ADVANCED H&N CANCER N. Dinapoli1, R. Autorino1, G.C. Mattiucci1, M. Balducci1, M. Rigante2, J. Galli2, F. Bussu2, V. Valentini1, G. Paludetti2, F. Miccichè1 1 Università Cattolica del Sacro Cuore, Radiation Oncology Department, Rome, Italy 2 Università Cattolica del Sacro Cuore, Otorhinolaryngoiatry, Rome, Italy Purpose/Objective: To analyze the efficacy and the feasibility of induction chemotherapy (ICT) with low-dose fractionated radiotherapy (LDR) compared to ICT alone prior to chemoradiation (CRT) in locally advanced head and neck squamous cell carcinoma. Materials and Methods: Between September 2008 and November 2011, 59 patients, with locally advanced stage III and IV squamous cell carcinoma of head & neck cancer, received three courses of induction chemotherapy with docetaxel (75 mg/mq), cisplatin (75 mg/mq) and 5fluoruracil (750 mg/mq/day on days 1-5) followed by radiotherapy plus two or three cycles of concurrent cisplatin 100 mg/mq (Group A). Twenty-nine of this patients received low dose fractionated radiotherapy concomitantly to induction chemotherapy (Group B). Treatment courses, hematological data and other parameters were also investigated. Results: Three cycles of ICT were administered in all patients: only one (Group B) received two cycle because of high hematological toxicity. After neoadjuvant therapy completation, clinical tumor response was observed in 49 patients (83%); patients undergone low dose radiotherapy showed better complete remission (p=0.08). Grade > 3 toxicity with dose reduction occurred in 5 patients (8%). Median time from the final cycle of TPF to starting radiotherapy was 21 days. All patients received radical radiotherapy; one, two and three cycles of concurrent cisplatin was delivered in 0 (0.0%), 17 (58.6%), 10 (41.4%) patients of Group A and 1 (3.5%), 28 (96.5%), 0 (0.0%) patients of Group B, respectively. With a median follow-up of 23.5 months (range 2-47), one-year local control was 62% and 82% for Group A and Group B, respectively (p=0.05). No difference was observed in terms of overall survival and disease free-survival between the two groups (p=0.9 and 0.8). Toxicity during chemo-radiation was acceptable in both groups without difference, specially, in terms of hematological toxicity (p=0.76). We found a correlation between hematological toxicity > G3 and local control (p=0.03). Conclusions: Low dose fractionated radiotherapy in association with ICT prior to CRT is tolerable, with encouraging efficacy in terms of response and local control, in locally advanced head and neck squamous cell carcinoma. Further investigation is warrented to confirm these data. PO-074 UTILISATION OF TC99M-TILMANOCEPT TO ASSESS SENTINEL LYMPH NODE STATUS IN HNSCC PATIENTS S.Y. Lai1, A. Agrawal2, F.J. Civantos3 1 University of Texas MD Anderson Cancer Center, Head and Neck Surgery, Houston TX, USA 2 Ohio State University, Head and Neck Surgery, Columbus OH, USA 3 University of Miami, Head and Neck Surgery, Miami FL, USA

S31 Purpose/Objective: A phase 3, prospective, multiinstitutional, open-label, single arm trial is ongoing to assess the utility and accuracy of Tc99m-tilmanocept (TCPT) for the intraoperative identification of sentinel lymph nodes (SLNs) in patients (pts) with confirmed cutaneous and intraoral head and neck squamous cell carcinoma (HNSCC). The results from three clinical sites were pooled for preliminary evaluation. Materials and Methods: Pts were enrolled with a diagnosis of cutaneous or intraoral HNSCC (T1-T4, N0, and M0). The primary objective was to determine the false negative rate (FNR) associated with TCPT-identified SLNs relative to the pathological status of non-SLNs (NSLNSs) in the elective neck dissection (END). Secondary measures of efficacy included diagnostic performance and rates of SLN detection. Pt safety was evaluated through observation of adverse events, clinical laboratory tests, vital signs, electrocardiograms and physical examinations. Results: A total of 46 pts (76% male, 24% female) have been injected with TCPT and completed surgery at three clinical sites. 43 pts had an intraoral primary tumor and 3 pts had a cutaneous tumor. There were 16 T1 lesions (35%), 25 T2 (54%), 3 T3 (7%), and 2 T4 (4%); with 41% (19/46) of pts being positive for pathology after central processing. TCPT localized in 96% (44/46) of pts. 4.7 SLNs and 27.1 NSLNs for pathology positive pts vs. 3.3 SLNs and 36.2 NSLNs for pathology negative pts with TCPT. A total of 182 SLNs (38 level I, 74 level II, 45 level III, 17 level IV, 7 level V, and 3 parotid) were identified intraoperatively and excised (0-11 SLNs /pt, median 4, average 5.0). A total of 1492 END nodes were excised (7-72 NSLNs /pt, median 30, average 32.4). All intraoperative TCPT findings were predictive of the END findings and led to correct pt staging. The overall negative predictive value (NPV) for TCPT was 1.00. TCPT demonstrated that SLN status was highly predictive and consistent with the status of the neck for clinical stage (T1T4) and tumor location (tongue: 58%, floor of mouth: 18%, and other: 26%). There was no difference between same (22/46, 48%) and next day (24/46, 52%) surgery relative to timing of TCPT injection. TCPT had a 0% FNR overall (zero false negatives of 19 known positives). Conclusions: This preliminary evaluation at three clinical study centers demonstrates the utility, predictive value, and safety of Tc99m-tilmanocept. In 46 patients, SLNs were predictive of NSLN pathology status. With a 0% FNR and a NPV of 1.00, Tc99m-tilmanocept accurately identifies SLNs and is likely to be predictive of occult pathological status. These findings demonstrate the ability of Tc99m-tilmanocept to identify those lymph nodes, which have the highest probability of containing tumor metastases, while potentially decreasing surgical morbidity.

POSTER: MOLECULAR TARGETED THERAPIES PO-075 THE EXTREME REGIMEN FOR RECURRENT/METASTATIC HNSCC: TREATMENT OUTCOME IN A SINGLE INSTITUTION COHORT C.D. Lynggaard1, C.A. Kristensen1, M.H. Therkildsen2, L. Specht1 1 The Finsen Center - Rigshospitalet, Department of Oncology, Copenhagen, Denmark 2 Rigshospitalet, Department of Pathology, Copenhagen, Denmark Purpose/Objective: The results of the phase III EXTREME trial showed that the combination of 5– Fluorouacil (5- FU), cisplatin and cetuximab significantly prolonged median progression free survival from 3.3 months to 5.6 and overall median survival from 7.4 months to 10.1 months of patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). The efficacy and toxicity of the

S32 EXTREME regimen were evaluated in a cohort of unselected patients outside clinical trial. Materials and Methods: 22 patients with recurrent and/or metastatic HNSCC were treated with 5-FU, cisplatin and cetuximab from October 2009 to Marts 2012. Biopsies from all patients histologically tested for HPV-status by p16 immunostaining. The patients received a maximum of six cycles of 5-FU (1000 mg/m2 per day for 4 days), cisplatin (100 mg/m2), and cetuximab (400 mg/m2, as a loading dose, followed by 250 mg/m2 per week), followed by cetuximab maintenance with 250mg/m2 every week until disease progression, unacceptable toxicity or death. Endpoints were overall response rate (ORR), disease control rate (DCR) (= complete and partial response or stable disease), progression-free survival (PFS), overall survival (OS), and the toxicity of the treatment. One patient received two cycles of the treatment as induction prior to brachytherapy and is therefore only included in the toxicity evaluation and not in ORR, DCR, PFS or OS. Results: In the analysed population of 21 patients ORR was 29 % (0 CR, 6 PR) and DCR was 48% (0 CR, 6 PR, 4 SD). Median PFS was 5.8 months (95 % confidence interval (CI) 4.3 – 7.3) and median OS was 7.3 months (95 % CI 5.0 – 9.7). Among adverse events grade 3 or 4 were hypokalemia (46 %), neutropenia (36 %), febrile neutropenia (23 %), thrombosis (23 %), and anaphylactic reaction (9 %). Two patients died of febrile neutropenia after one cycle of treatment. None of two deaths were considered to be related to cetuximab. 11 patients were HPV-negative and 9 patients were HPVpositive. The HPV-positive patients had a better survival than the HPV-negative. Conclusions: This study indicates that the combination of 5FU, cisplatin and cetuximab in patients with recurrent and/or metastatic HNSCC may be more toxic when used in an unselected population than the results published from the EXTREME trial. Two patients died from direct side effects from treatment, and 23% had grade 3 thrombosis complications. Regimens of cetuximab and chemotherapy with less toxicity for the palliative treatment of these patients should be investigated.

4th ICHNO Results: One patient died of anaphylactic shock, two discontinued study-participation on their own request. One patient died immediately after end of Re-RT, one was lost to follow–up. Median follow-up time for patients alive is 18.2 months (range: 11-35). Thus, 20 patients were evaluable for toxicity while 18 patients received follow-up imaging with MRI, CT or PET/CT scans and were completely evaluable for treatment response. Grade 3 side effects are documented for dermatitis (35%), dysphagia (30%), acneiform rash (23.8%), mucositis (15%), voice change (15%) and pain (9.5%). 4 patients attained a complete response (CR), 3 a partial response (PR), 2 stable disease (SD) and 9 progressive disease (PD). The median overall survival time is 12.2 months; the 1year OS rate 30.4%. Multivariate analysis does not demonstrate any influence of acne form rash, PET based planning or number of unresectable recurrences on survival. All patients with SCC histology progressed; 2 are still alive. One patient with recurrent high grade MEC is in complete response and still alive 42 months after finishing treatment. Conclusions: Re-RT with concurrent cetuximab is feasible at acceptable toxicity for previously irradiated patients with HNC. Given a comparable survival for patients reirradiated only or for patients administered systemic treatment (cisplatin, 5-FU, cetuximab) we suggest to sequentially treat relapsed HNC with single modalities.

PO-076 COMBINED REIRRADIATION AND CETUXIMAB FOR LOCALLY RECURRENT HEAD AND NECK CANCER Ñ MATURE OVERAL SURVIVAL RESULTS D. Milanovic1, A.L. Grosu1, G. Rücker2, M. Henke1 1 Universitätsklinik Freiburg, Department of Radiation Oncology, Freiburg, Germany 2 Universitätsklinik Freiburg, Institute of Medical Biometry and Medical Informatics, Freiburg, Germany

PO-077 CETUXIMAB PLUS RADIOTHERAPY FOR CHINESE PATIENTS WITH LOCALLY ADVANCED HEAD AND NECK CANCER L. Gao1, J. Pan2, S. Wu3, C. Xie4, M. Zhong5, X. Chen6, Y. Jin7, G. Wu8, J. Cai9, G. Xu1 1 Chinese Academy of Medical Science, Cancer Institute and Hospital, Beijing, China 2 Fujian Tumor Hospital, Radiation Oncology Department, Fuzhou, China 3 Sun Yat-sen University Cancer Center, Radiation Oncology Department, Guangzhou, China 4 Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei, China 5 Xiangya Hospital of Central South University, Department of Oncology, Hunan, China 6 Zhejiang Cancer Hospital, Radiation Oncology Department, Zhejiang, China 7 Ruijin Hospital, Radiotherapy and Chemotherapy Department, Shanghai, China 8 Huazhong University of Science and Technology, Cancer Centre Union Hospital of Tongji Medical College, Hubei, China 9 Merck Serono (Beijing) Pharmaceutical R&D Co. Ltd, Global Clinical Development Center Oncology, Shanghai, China

Purpose/Objective: Patients with recurrent, unresectableand previously irradiated head and neck cancer (HNC) may expect 5-year survival rates of approximately 15% following reirradiation (Re-RT). Chemotherapy with or without epidermal growth factor receptor (EGFR) inhibition is established as efficient palliative management. This phase I/II retrospective monocentric study investigates feasibility, toxicity and outcome of Re-RT combined with EGFR blockade for these patients. Materials and Methods: Between June 2008 and June 2011, we reirradiated (50.4-66.6 Gy, 5X 1.8 Gy/Week) 23 patients (20 male and 3 female) with histologically proven locally recurrent unresectable HNC, who had been previously treated with external beam radiotherapy. 22 patients had a squamous cell carcinoma (SCC), one patient high grade mucoepidermoid carcinoma (MEC). RT-planning was based to FDG-PET findings in 14 patients and on CT or MRI findings in the remaining. Concommittant EGFR blockade with Cetuximab was given initially at 400 mg/m2 two days before Re-RT and weekly (250 mg/m2) thereafter. Patients were seen weekly during the radiation course and at 3 months intervals in follow-up thereafter.

Purpose/Objective: The addition of cetuximab to radiotherapy (RT) significantly improved locoregional control, survival and progression-free survival (PFS) compared with RT alone in a phase III trial in Western patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) (Bonner et al, NEJM 2006). This trial investigated the safety and anti-tumor activity of cetuximab+RT in a similar population of Chinese patients with LASCCHN. Materials and Methods: This was an open-label, single-arm, multicenter trial. Chinese patients with previously untreated stage III/IV non-metastatic SCC of the oropharynx, hypopharynx or larynx received cetuximab from weeks -1 to 6 (400 mg/m2 initial infusion then 250 mg/m2/week) with concomitant boost RT from weeks 1 to 6 (total dose of 72.0 Gy in 42 fractions).The primary endpoint was best overall response assessed by the investigator according to modified WHO criteria. Results: From February 2009 to April 2010, 70 patients were screened and 66 were treated (intention-to-treat [ITT] population). Demographics and disease characteristics at baseline were: male (89.4%); median age 55.0 years (range 49.0–63.0 years); Karnofsky performance status ≥90% (68.2%),