Treatment of Metastatic Salivary Duct Carcinoma With Combined Androgen Blockade (CAB) With Leuprolide Acetate and Bicalutamide

Volume 88  Number 2  Supplement 2014 Purpose/Objective(s): Paranasal sinus cancers account for 3% of all head and neck cancers (HNC). Of these cases, only 15% of HNC are ethmoid sinus cancers (ESC). The purpose of this study was to examine oncological outcomes in patients presenting with ESC and evaluate factors influencing local/regional control (LC/RC) and overall survival (OS). Materials/Methods: The medical records for 68 patients diagnosed with ESC between 7/98 and 3/12 were reviewed. Patients included in the study were treated either with definitive radiation therapy (RT) or with a multiple modality approachdRT with surgery and/or chemotherapy. Patients who did not receive RT or who received RT at an outside institution were excluded from the analysis. We analyzed population characteristics (eg, histology, tumor stage at presentation), LC/RC, distant metastasis (DM), and OS (Kaplan-Meier analysis). Results: 49 of the original 68 patients met criteria for inclusion in the study: 65.3% were male and 34.7% female (median age: 54.9 years). The median length of follow up for surviving patients was 92 months (range 15-214 months). At time of diagnosis, 79.5% of patients’ primary tumor had significant invasion into adjacent structures (Stage T4a or T4b) and only 6.2% had nodal involvement. Patients most commonly presented with nasal congestion and epistaxis. The most common histological presentations were squamous cell carcinoma (SCC) (35%), adenocarcinoma (18%) and sarcoma (14%). Patients underwent heterogeneous primary treatments: 65% underwent surgical resection, 41% underwent chemotherapy, and 53% received IMRT. 30.6% of patients had tumors that were unresectable. Approximately 63% of patients had visual complaints throughout treatment. The 5-year LC/RC, incidence of DM, and OS for the entire cohort was 51%, 28.5%, and 47%, respectively. Surgical resection with adjuvant (chemo)RT yielded better 5-year LC/RC and OS compared to definitive RT: 56% vs 41% and 59% vs 29%, respectively. SCC histology negatively impacted local recurrence and survival, while IMRT vs conventional RT had no impact on LC/RC or OS. Patients treated with surgery and adjuvant (chemo)RT experienced better disease control and OS. However, confounding factors such as age, stage, and intracranial tumor extension likely contributed to the poorer OS in the unresectable group. Conclusions: In ESC most patients present with tumors invading local structures but without lymph node involvement. Patients treated with a combined modality approach experienced significantly better LC/RC and OS, likely due to selection bias. High recurrence rates underlie the substantial challenge of ESC and indicate the need for earlier detection and enhanced treatment approaches to improve LC/RC and OS. Author Disclosure: J.H. Harari: None. S. Rosenberg: None. N. Riaz: None. L. Mitrani: None. M. Thompson: None. S. Rao: None. S. Wolden: None. N. Lee: None.

193 Single Agent Panitumumab in Patients With Incurable Cutaneous Squamous Cell Carcinoma: A Single-Center Phase 2 Study Non-Squamous Cell Malignancies of the Head and Neck (thyroid, skin cancers, salivary gland and sinus cancers) S. Porceddu,1,2 M. Foote,1,2 M. McGrath,1 A. Guminski,3 B. Hughes,4 J. Meakin,1 D. Thomson,1 D. Thomson,1,2 and F. Simpson5; 1Princess Alexandra Hospital, Brisbane, Australia, 2University of Queensland, Brisbane, Australia, 3Royal North Shore Hospital, Sydney, Australia, 4 Royal Brisbane Hospital, Brisbane, Australia, 5University of Queensland, Diamantina Institute, Brisbane, Australia Purpose/Objective(s): The systemic options for incurable cutaneous squamous cell carcinoma (CSCC) remains limited. The emergence of targeted therapy in other malignancies has provided promising results. The objective of this study was to prospectively investigate the efficacy of single agent panitumumab in the treatment of incurable CSCC. Materials/Methods: Eligibility included patients deemed to have incurable CSCC, not suitable for local therapy or chemotherapy. Prior chemotherapy or radiation therapy was permitted. Patients received panitumumab at a dose of 6 mg/kg every 14 days for a maximum of nine cycles, with response assessed after every third cycle prior to proceeding to the next 3 cycles. The

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primary endpoint was the best overall response rate (ORR) as assessed by RECIST version 1.1. Tissue was obtained for cellular signaling pathway studies. Results: Between May 2010 and May 2012, 16 patients were recruited. Fourteen patients were male and the median age was 69. Fourteen patients had locoregionally recurrent disease with 15 patients receiving previous radiation therapy and 4 patients receiving previous cytotoxic chemotherapy. The best overall response rate (partial or complete response, PR or CR) was 37.5% (4/16 PR, 2/16 CR) with a further 5 of 16 patients achieving stable disease. The duration of overall response was a median of 8 months. Grade 3 or 4 events were observed in 5 patients (all skin toxicity) with 1 patient ceasing due to skin toxicity. With a median follow up of 11 months, 9 patients died due to progressive disease, 7 are alive, 1 patient with no evidence of disease at the time of analysis. Conclusions: Single agent panitumumab is safe, but only resulted in modest response rates for incurable CSCC. Author Disclosure: S. Porceddu: E. Research Grant; Amgen Grant. M. Foote: None. M. McGrath: None. A. Guminski: None. B. Hughes: None. J. Meakin: None. D. Thomson: None. D. Thomson: None. F. Simpson: None.

200 Treatment of Metastatic Salivary Duct Carcinoma With Combined Androgen Blockade (CAB) With Leuprolide Acetate and Bicalutamide Non-Squamous Cell Malignancies of the Head and Neck (thyroid, skin cancers, salivary gland and sinus cancers) K.A.R. Price, S.H. Okuno, J.R. Molina, and J.J. Garcia; Mayo Clinic, Rochester, MN Purpose/Objective(s): Salivary duct carcinoma (SDC) is a rare, aggressive malignancy for which no standard therapy exists in the metastatic setting. The majority of SDCs express androgen receptor and various forms of androgen deprivation therapy have been reported. The efficacy of the combination of leuprolide acetate and bicalutamide has not been reported to date. Materials/Methods: Patients (pts) with metastatic SDC treated with CAB with adequate follow-up were identified. Demographic, pathologic, and clinical data were abstracted from the medical record. Results: Five pts with metastatic SDC were identified. The median age was 81 (range 74-87, all male). The primary site of disease was the parotid gland in 4 pts and unknown in one (presented as a neck mass). T- and Nstage at diagnosis included T2 (2), T3 (2), and TX (1); all pts had N2b disease. Two pts were metastatic at diagnosis. Definitive therapy for the non-metastatic pts included surgery followed by adjuvant radiation therapy (RT) in 2 pts and chemoRT in 1 pt. An immunohistochemical stain for androgen receptor immunostain was strongly and diffusely positive in tumor cells of all pts. Two of 5 pts (40%) were positive for HER2 (3+). Sites of metastatic disease included: bone (3), lung (3), lymph nodes (LN) in the chest (2), axillary LNs (2), brain (1), liver (1), and skin (1). Three pts had local-regional recurrence as well as distant metastases. Two pts received 1-2 chemotherapeutic regimens prior to initiation of CAB. All pts were treated with leuprolide acetate given intramuscularly as 1- or 3-month depot injections and oral bicalutamide 50 mg daily. CAB was well tolerated with 3 pts reporting increased fatigue and 2 pts with mild hot flashes. Three out of 5 pts (60%) had marked clinical and radiographic responses to CAB. One pt had a mixed response on PET/CT with improvement in biopsy-proven disease in an axillary LN but progression of disease in a supraclavicular LN. One pt had disease progression on therapy. The median time from initiation of CAB to disease progression was 91 days (range 78-229). Two pts remained on CAB beyond radiographic progression due to low disease burden and lack of development of other metastatic sites suggesting ongoing systemic benefit. One pt (HER 2 3+) with progressive brain metastases on CAB was subsequently treated with lapatinib with response in the brain. Four of 5 pts have died, with 1 pt alive 29 months with metastatic disease. The median time from diagnosis of metastatic disease to death was 20 months (range 15-29). The 1- and 2- year

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overall survival of pts after diagnosis of metastatic disease was 100% and 40%, respectively. Conclusions: CAB was well tolerated and resulted in a partial response rate of 60%. CAB represents a valuable therapeutic option, particularly given the advanced age of the patient population. Author Disclosure: K.A.R. Price: None. S.H. Okuno: None. J.R. Molina: None. J.J. Garcia: None.

Results: Thirteen patients underwent an open resection (OR) while twelve had endoscopic resection (ER) of their tumors. The OR and ER groups did not differ significantly with regard to demographics and tumor characteristics. Mean age (67.8 vs 65.5 years; pZ.63), the proportion of patients who received adjuvant radiation therapy (84.6% vs 91.6; p>.99) and those that achieved negative surgical margins on resection (53.8% vs 58.3%; pZ.82) were similar between the OR and ER groups, respectively. Rates of postoperative bleeding (7.7% vs 16.7%; pZ.59), cerebrospinal fluid leak (15.4% vs 25%; pZ.64) and length of hospital stay (3.6 vs 3.8 days; pZ.87) were also comparable between the OR and ER groups, respectively. Both the OR and ER groups, respectively, had high rates of local failure (38.5% vs 25%; pZ.67) and distant metastases (30.8% vs 50%; pZ.43), as well as modest median DFS (1.9 vs 1.2 yrs; pZ.72) and median OS (2.7 vs 1.9 yrs; pZ.87). Conclusions: Endoscopic resection of sinonasal melanoma offers an attractive, minimally invasive surgical option which yields comparable survival and morbidity outcomes to an open approach. Author Disclosure: W. Swegal: None. S. Koyfman: None. B. Burkey: None.

204 The Influence of Tumor Stage, Grade, and Treatment Modality on Survival in Acinic Cell Carcinoma: A Retrospective Analysis of 2061 Patients Non-Squamous Cell Malignancies of the Head and Neck (thyroid, skin cancers, salivary gland and sinus cancers) V.L. Biron,1 D. Gerry,2 E. Lentsch,2 and A. Bewley1; 1University of California Davis, Davis, CA, 2Medical University of South Carolina, Charleston, SC Purpose/Objective(s): To perform a retrospective analysis of variables influencing survival in a cohort of patients with acinic cell carcinoma (AciCC). Materials/Methods: A retrospective database analysis was performed using the United States National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) registry. We obtained demographic, staging, pathologic and treatment data pertaining to patients diagnosed with AciCC between 1973-2009. Univariate and multivariate analyses of overall and disease specific survival (DSS) were performed to compare survival trends associated with various clinical and pathological parameters. Results: We identified 2,061 patients from the SEER registry who were diagnosed with AciCC between 1973-2009, with demographics similar to recently published cohorts. Tumor size, nodal status, distant metastases and histologic grade were all significant predictors of survival up to 20 years post-treatment. Patients who received surgery alone for treatment had the highest 20-year DSS (92.4 %), with significantly lower DSS for patients treated with surgery and radiation (71.9%) or radiation alone (62.3 %). These survival differences remained significant when stratifying patients for age, gender, nodal status, stage and histologic grade. In addition, hazard ratios showed significantly improved prognosis with surgery only compared with surgery and radiation or radiation alone. Conclusions: To our knowledge, this study represents the largest cohort of AciCC survival according to treatment modality. Our results suggest the addition of radiation to surgical resection does not provide significant benefit to survival in patients with salivary AciCC. Author Disclosure: V.L. Biron: None. D. Gerry: None. E. Lentsch: None. A. Bewley: None.

215 Endoscopic and Open Surgical Approaches to Locally Advanced Sinonasal Melanoma: Comparing the Therapeutic Benefits Non-Squamous Cell Malignancies of the Head and Neck (thyroid, skin cancers, salivary gland and sinus cancers) W. Swegal,1 S. Koyfman,2 and B. Burkey2; 1Henry Ford Health System, Detroit, MI, 2The Cleveland Clinic, Cleveland, OH Purpose/Objective(s): Our objective was to compare the therapeutic benefits and treatment related outcomes of endoscopic and open surgical approaches to sinonasal melanoma. Materials/Methods: We retrospectively reviewed the medical charts of patients at a tertiary care medical center who had undergone surgical resection of sinonasal melanoma between the years of 1998 and 2012. Twenty five patients were identified and grouped based on surgical approach. Overall survival (OS) was the primary outcome measured, with postoperative complications, patterns of failure, and disease-free survival (DFS) as secondary outcomes.

224 Salivary Gland Tumors Treated With Adjuvant Radiation Therapy With or Without Concurrent Chemotherapy Non-Squamous Cell Malignancies of the Head and Neck (thyroid, skin cancers, salivary gland and sinus cancers) P. Vempati, V. Gupta, B. Miles, M. Teng, E. Genden, J. Glick, E. Demicco, K. Misiukiewicz, M. Posner, and R. Bakst; Mount Sinai School of Medicine, New York, NY Purpose/Objective(s): Major salivary gland tumors are rare head and neck malignancies. The standard initial therapy is surgical resection often followed by adjuvant radiation therapy. The use of adjuvant chemoradiation therapy (CRT) has significantly increased local control and overall survival for squamous cell cancers of the head and neck; however there is very limited data supporting its use in salivary gland malignancies. Here we aim to analyze a recent single-institution experience of patients with major salivary gland tumors who had undergone adjuvant intensitymodulated radiation therapy (IMRT), with or without concurrent chemotherapy (CC). Materials/Methods: We performed a retrospective analysis of 25 salivary gland carcinoma patients treated at our institution between 2006 and 2012 with surgery and adjuvant IMRT with or without CC. The primary endpoints were locoregional control (LRC), overall survival (OS), and acute toxicity. Kaplan-Meier method was used to calculate OS and recurrencefree survival (RFS). Results: Histologic subtypes included adenoid cystic carcinoma in 5 (20%), mucoepidermoid carcinoma in 7 (28%), squamous cell carcinoma in 8 (32%), and other in 5 (20%). The mean age of the cohort was 63 (range 29 to 84) years. The primary sites included the parotid gland in 22 (88%), and the submandibular gland in 3 (12%). The mean radiation dose was 62 Gy, and 10 patients (40%) received CRT. Cetuximab was the most common systemic agent used. Adverse prognostic factors were seen in both surgery + RT and surgery + CRT groups: perineural invasion was present in 27% in the RT group and 70% in the CRT group. Positive or close margins (<0.5 mm) were present in 53% in the RT group and 80% in the CRT group. In the RT group 54% were stage T3/4 vs 46% in the CRT group. Two patients developed distant metastasis (both in the CRT group) and one patient developed a local recurrence (in the CRT group). OS was 100% with Surgery + RT and 87.5% for Surgery + CRT with a mean follow-up of 30 months. RFS was 100% for surgery + RT and 75% for Surgery + CRT. Only one acute grade 3 toxicity (dermatitis) was observed in a patient receiving surgery + CRT. No acute Grade 4 or 5 toxicity occurred. Conclusions: Treatment of salivary gland malignancies with post-operative IMRT resulted in excellent LRC. CRT was well tolerated and also results in excellent local control despite the presence of adverse prognostic