Risk-stratified Treatment for Patients with Locally Advanced Oropharyngeal Carcinoma (OPC)

Proceedings of the 52nd Annual ASTRO Meeting Materials/Methods: From 3/2008 to 9/2009 we investigated 25 patients (pts.) with a carcinoma of the oropharynx, hypopharynx, or larynx that were not eligible for function-preserving surgical intervention. The patients received 75 mg/m2 docetaxel on day 1, and 30 mg/ m2 cisplatin on days 1 to 3 (n = 23), or carboplatin AUC 1 on days 1 to 3 (n = 2). Responders (more than 30% of tumor shrinking evaluated by endoscopy and a SUV decrease of more than 20% in FDG-PET) received a CRT with a dose of 2.0 Gy OD up to 30 Gy and 1.4 Gy BID up to 69.2 Gy or 72.0 Gy together with paclitaxel 20 mg/m2 on days 1, 5, 8, 11, 25, 29, 33, 36 with cisplatin 20 mg/m2 or carboplatin AUC1 on days 1 to 4 and 29 to 32. Results: Induction chemotherapy was feasible in all 25 pts with acceptable toxicity (leucopenia grade IV in one patient). Remission was observed in 88% of the pts. (n = 22). The 22 pts and one non-responder (refusal of surgical treatment) received a CRT without any delay due to toxicity of iCT. The two non-responders had partial laryngectomy and pharyngectomy. Radiotherapy in all others could be performed completely and 56% of the pts received more than 80% of the scheduled chemotherapy. There was no grade IV and V toxicity. Grade III toxicity was observed in some pts, i.e., infection: 9/23 (39%); dermatitis: 3/23 (13%); leucopenia: 7/23 (30%); thrombopenia: 1/23 (4%). Oral feeding was unproblematic in 52% of the pts (11 of 21 pts. with available data) at least 6 weeks after CRT, and feeding tube was still necessary in the remaining pts (48%, 10 of 21 pts). The iCT and CRT resulted in complete remission (ycT0) in 22/23 pts (95%). One pt had salvage-laryngectomy after CRT (4%) due to local tumor persistence. Lymph node clearance (yc/pN0) was observed in 15 of 17 pts (88%) with initial suspicious lymph nodes. After a median follow-up of 11 mo (5-24 mo) one local and one distant recurrence had been observed. Three pts died during the follow-up, two of them due to tumor related causes and one patient due to other causes. Local tumor control at 12 mo. was 84.6 ± 8.5%, overall survival was 89.6 ± 7.2%. Conclusions: Short-term iCT and subsequent CRT with a taxane and a platinum compound is feasible with little toxicity and effective concerning initial tumor remission. It should be investigated with respect to response-prediction and long term tumor control. Author Disclosure: S. Semrau, None; F. Waldfahrer, None; R. Linke, None; M. Lell, None; G. Klautke, None; T. Kuwert, None; H. Iro, None; R. Fietkau, None.

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Risk-stratified Treatment for Patients with Locally Advanced Oropharyngeal Carcinoma (OPC)

R. R. Boutrus, J. Wang, L. Wirth, J. McIntyre, J. R. Clark, A. W. Chan Massachusetts General Hospital, Boston, MA Purpose/Objective(s): To compare the treatment outcomes for patients with locally advanced OPC treated with different chemotherapy regimens based on risk factors. Materials/Methods: Between 1998 and 2009, 111 patients with Stage III and IVA/B squamous cell carcinoma were treated with definitive radiation therapy at the Massachusetts General Hospital. Sixty nine percent of the patients had positive smoking history. Patients were treated with either intensity modulated radiation therapy (n = 63) or conformal radiation therapy (n = 48). The median dose to the gross tumor volume was 70 Gy. The median overall radiation treatment time was 47 days. Systemic treatment was given to 94% of patients. Our general treatment policy was to tailor the type of systemic agents according to the individual patient’s risk if feasible. Patients with minimal disease (Group A, n = 32) were treated with radiation alone, weekly carboplatin, or weekly cetuximab. Patients with intermediate risk (Group B, n = 68) were treated with concurrent cisplatin-based or carboplatin/paclitaxel-based agents. Patients with advanced T- and N-stage (Group C, n = 11) were treated with cisplatin/paclitaxel/5-fluorouracil-based sequential chemotherapy if feasible. The T4- and N3-stage distribution was: 3% and 3% in Group A, 16% and 13% in Group B, and 36% and 27% in Group C, respectively. Results: At a median follow-up of 41 months, a total of 3 local, 3 regional, and 9 distant failures were observed. The actuarial local control, regional control, and freedom from distant metastasis (FDM) rates at 2 years were 97%, 97%, and 91%, respectively. The locoregional control rates at 2 years were 96%, 94%, and 100% for Group A, B, and C, respectively (p = 0.61). The FDM at 2 years were 96%, 90%, and 89% for Group A, B, and C, respectively (p = 0.5). Eighty percent of patients who failed locoregionally received Group B chemotherapy, and the majority had T4 disease. In univariate analysis, only T4 disease was predictive for decreased local control (p\0.001), regional control (p = 0.007), and FDM rates (p = 0.04). The rates of locoregional control at 2 years were 99% and 75% for patients with T1-3 and T4 disease, respectively (p\0.001). The rates of FDM at 2 years were 94% and 80% for patients with T1-3 and T4 disease, respectively (p = 0.04). In multivariate analysis, only T4 disease was predictive for decreased overall survival rate (p = 0.002). N-stage was not predictive of locoregional recurrences, distant metastasis, and overall survival. For patients with available HPV status, HPV status did not predict for overall survival. Conclusions: Our data suggests that risk-stratified treatment results in excellent outcome in patients with locally advanced OPC. This should be investigated in prospective settings, particularly patients with T4 disease should be considered for sequential chemotherapy. Author Disclosure: R.R. Boutrus, None; J. Wang, None; L. Wirth, None; J. McIntyre, None; J.R. Clark, None; A.W. Chan, None.

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Phase I/II Study of SMART-IMRT Plus Chemotherapy in Locoregionally Advanced Nasopharyngeal Cancer

T. Fan, J. Li, T. Liu Shandong Tumor Hospital, Jinan, China Purpose/Objective(s): To evaluate the efficacy, toxicity, and tolerability of simultaneous modulated accelerated radiation therapy (SMART) intensity modulated radiotherapy (IMRT) plus cisplatin and 5-FU chemotherapy for patients with advanced nasopharyngeal cancer. Materials/Methods: From 2006 Mar through 2009 Jan, 45 patients with American Joint Committee on Cancer stage II-IV nasopharyngeal carcinoma were treated with prescribed doses of 72 Gy (2.2 Gy/day*30fractions, 2 Gy/day*3 fractions) to the gross tumor volume, 60 Gy (2 Gy/day*30 fractions) to the clinical target volume and metastatic nodal station, and 54 Gy (1.8Gy/day*30 fractions) to the clinically negative neck region. Before radiotherapy two cycles of concurrent cisplatin (30 mg/m2 day on days

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