- Email: [email protected]
Phase 1b Trial of TLR8 Agonist VTX-2337 in Combination With Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinomas of the Head and Neck (SCCHN)
Volume 88 Number 2 Supplement 2014 Conclusions: By PET/CT simulation, changes in TNM classification or clinical stages occurred frequently for NPC. Although no significant improvement in overall survival rate and loco-regional control rate was noted by PET/CT simulation compared with a historical control, PET/CT simulation may contribute to reduce marginal recurrences in IMRT. Author Disclosure: T. Matsuura: None. Y. Nishimura: None. K. Ishikawa: None.
258 Outcomes Following Primary Chemoradiation Therapy for N3 Head and Neck Squamous Cell Carcinoma With PET-Directed Neck Management Policy: A Diminishing Role for Planned Neck Dissection Imaging S. Porceddu,1,2 G. Adams,3 D. Pryor,3,2 B. Panizza,3,2 M. Foote,3,2 and B. Burmeister3,2; 1Princess Alexandra Hospital, Brisbane, Australia, 2 University of Queensland, Brisbane, Australia, 3Princess Alexandra Hospital, Brisbane, Australia Purpose/Objective(s): The purpose of this study was to assess prospectively the utility of a positron emission tomography (PET)-directed policy for N3 disease following definitive chemoradiation therapy in head and neck squamous cell carcinoma. Materials/Methods: All patients with N3 disease treated with chemoradiation therapy treated between 2005 and 2012 at our institution who achieved a complete response at the primary site were included. A staging PET, and a re-staging PET at 12 weeks post-therapy, were performed. Only patients with a residual nodal PET abnormality, regardless of CT response, underwent a neck dissection. The primary endpoint was isolated nodal failure. Results: Median follow up from diagnosis for 33 patients was 36 (6-82) months. Oropharynx was the predominant primary site 25 (76%), with 18 of these patients p16 positive. The most common T-staging was T4 (46%). All patients received concurrent chemoradiation therapy with 30% of patients also receiving induction therapy. Four (12%) patients underwent a neck dissection, with 2 isolated nodal failures (6%). First failure was predominantly distant metastatic disease (10; 30%). Conclusions: PET-directed policy for the N3 disease following definitive chemoradiation therapy in patients who achieve a complete response at the primary site results in a low rate of isolated nodal failure. Author Disclosure: S. Porceddu: None. G. Adams: None. D. Pryor: None. B. Panizza: None. M. Foote: None. B. Burmeister: None.
259 WITHDRAWN
269 Deformable Image Registration-Based Automatic CT-to-CT Contour Propagation for Head-and-Neck Cancer Radiation Therapy Imaging F. Siddiqui, A. Kumarasiri, J. Kim, C. Liu, and I. Chetty; Henry Ford Health System, Detroit, MI Purpose/Objective(s): Reducing the manual workload associated with contouring organs and target volumes at each replanning session is critical for efficient H&N ART implementation in a routine clinical setting. The aim of this study is to evaluate the potential of using commercially available deformable image registration (DIR) algorithms in VelocityAI and Varian SmartAdapt systems for automatic propagation of physician contours from planning CT to subsequent CT images for head and neck (H&N) adaptive radiation therapy. Materials/Methods: Ten H&N patients who have undergone significant weight loss during the first few weeks of treatment were considered for this retrospective study. Each patient had a planning CT (CT1) and a second CT (CT2) taken approximately 3 weeks into treatment. Clinically relevant normal organs and treatment volumes were manually delineated by a physician on both sets of CT scans. B-spline based VelocityAI and
Poster Presentations
503
Demons based SmartAdapt DIR algorithms were used to deform CT1 including the structure sets onto corresponding CT2 images. Agreement between automatically propagated contours and physician’s manual contours were evaluated visually by a physician, and evaluated quantitatively using the DICE coefficients, 2x(V1XV2)/(V1+V2), for overlap quantification. The results of the two commercial systems were compared with elastix DIR algorithm, a B-spline based independent verification tool, using in-house developed visualization and quantification tools. Results: Both VelocityAI and SmartAdapt attained good results and were quantitatively similar to elastix results for well differentiated and relatively large organs like brainstem, eyes and spinal cord, showing a high degree of correlation (DICE>0.8). Smaller organs with unclear boundaries on CT images like the pituitary gland and optic nerves showed less correlation (DICEw0.5). B-spline based VelocityAI and elastix generally achieved better results for the smaller organs. GTVs and PTVs generally showed a significant amount of overlap, with DICE indices w0.7-0.8 for GTVs and w0.8-0.9 for PTVs respectively, even with the expected shrinkage. Conclusions: Retrospective volume analysis by DICE indices and physician review of propagated contours suggests organs with sizable volumes propagate well between CT images. Use of VelocityAI and SmartAdapt for automatic CT-to-CT contour propagation is expected to save significant manual delineation time for physicians in H&N adaptive radiation therapy. Currently, VelocityAI based DIR is used on a trial basis on our clinic for contour propagation under physician supervision. We estimate a time savings of approximately 30 minutes per each re-plan using this methodology. Author Disclosure: F. Siddiqui: None. A. Kumarasiri: None. J. Kim: None. C. Liu: None. I. Chetty: None.
100 Phase 1b Trial of TLR8 Agonist VTX-2337 in Combination With Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinomas of the Head and Neck (SCCHN) Immunology and Immunotherapy L.Q.M. Chow,1 K.D. Eaton,1 C. Baik,1 B. Goulart,1 C. Morishima,1 M.L. Disis,1 K. Manjarrez,2 G. Dietsch,2 R. Hershberg,2 and R.G. Martins1; 1University of Washington, Seattle, WA, 2VentiRx Pharmaceuticals, Seattle, WA Purpose/Objective(s): Cetuximab, an EGFR-specific monoclonal antibody, is an approved therapy for SCCHN alone or combined with radiation or chemotherapy. Beyond blocking the EFGR signaling pathway, natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is important for cetuximab-mediated tumor killing; hence, NK cell activation may enhance the anti-tumoral effect. VTX-2337, a novel Toll-like receptor 8 (TLR8) agonist, stimulates NK cells, myeloid-derived dendritic cells, and monocytes. Preclinical data demonstrated synergistic NK cell activation and enhancement of ADCC with combination cetuximab and VTX-2337, forming the rationale to assess the safety, tolerability, immunological correlates, and efficacy of this combination in SCCHN patients. Materials/Methods: This open label phase 1b study in platinum-refractory or -intolerant recurrent or metastatic SCCHN patients (NCT01836029; NZ12) included cetuximab-naı¨ve patients who received a 400 mg/m2 loading dose followed by 250 mg/m2 weekly for a lead-in assessment for cetuximab toxicity and previously cetuximab-treated patients who received 250 mg/m2 weekly, prior to VTX-2337 combination. Using a 3+3 design, patients were enrolled into cohorts of escalating VTX-2337 doses (2.5, 3.0, 3.5 mg/m2) given SC days 1, 8, 15 q 28 day cycle. Correlative pharmacokinetic and pharmacodynamic immunologic assessments of response and activity were performed. Response was evaluated using RECIST 1.1. Results: This combination was well-tolerated with no dose-limiting toxicities, no serious, unexpected or synergistic drug-related toxicities between cetuximab and VTX-2337 in 10 patients. Toxicities were similar in scope and severity to those observed with cetuximab (fatigue, skin rash, cough, malaise) or VTX-2337 alone (Gr 1/2 injection site reaction, flu-like symptoms and fatigue). Commonly observed flu-like symptoms, injection
504
International Journal of Radiation Oncology Biology Physics
site reactions and fatigue established the 3.0 mg/m2 dose as most tolerable. Serum biomarkers were consistent with TLR8 activation. Ex vivo analysis of NK cells collected pre- and post-dose demonstrated enhanced NK cell mobilization and activation. In 8 response-evaluable patients, one partial response, 4 stable disease and 3 disease progression were observed. Results of this ongoing study will be updated. Conclusions: Cetuximab and VTX-2337 in combination is tolerable and active in SCCHN patients. Clinical data and serum biomarkers demonstrating immunostimulation with marked NK cell activation provide rationale for further study in SCCHN. A randomized, placebo-controlled, phase 2 trial comparing cetuximab + platinum + 5-FU +/- VTX-2337 has been initiated. Author Disclosure: L.Q.M. Chow: E. Research Grant; VentiRx Pharmaceuticals. K.D. Eaton: None. C. Baik: None. B. Goulart: None. C. Morishima: E. Research Grant; Merck. M.L. Disis: E. Research Grant; VentiRx Pharmaceuticals. G. Consultant; VentiRx Pharmaceuticals. K. Manjarrez: A. Employee; VentiRx Pharmaceuticals. L. Stock Options; VentiRx Pharmaceuticals. G. Dietsch: A. Employee; VentiRx Pharmaceuticals. L. Stock Options; VentiRx Pharmaceuticals. R. Hershberg: A. Employee; VentiRx Pharmaceuticals. L. Stock Options; VentiRx Pharmaceuticals. Q. Leadership; VentiRx Pharmaceuticals. R.G. Martins: None.
Conclusions: This research documents immune changes during treatment for OPC and provides evidence that although there is chemoradiation induced lymphopenia, the functional capability of T cells is maintained. This information has implications for the development and timing of immunotherapy strategies that depend on functional immune T cells. Author Disclosure: W.T. Lee: None. R. Medinas: None. J.H. Lee: None. S. Sparks: None. D.M. Brizel: None. R.M. Esclamado: None. N. Ready: None. K.J. Weinhold: None.
147 WITHDRAWN
149 Impact of Concurrent Chemoradiation on T Cell Populations in Patients With Advanced-Stage Oropharyngeal Squamous Cell Carcinoma Immunology and Immunotherapy W.T. Lee,1,2 R. Medinas,1 J.H. Lee,3 S. Sparks,1 D.M. Brizel,1 R.M. Esclamado,1 N. Ready,1 and K.J. Weinhold1; 1Duke University Medical Center, Durham, NC, 2Durham VA Medical Center, Durham, NC, 3 Sanford Health, Sioux Falls, SD Purpose/Objective(s): Concurrent chemoradiation (CRT) is commonly used to treat advanced stage oropharyngeal cancer (OPC). CRT affects the immune system, but the specific effects on immune cell populations and function during and after treatment are poorly defined. This study was performed to assess the impact of CRT on T cell populations and their function during and after treatment in patients with advanced stage OPC. Materials/Methods: Peripheral blood mononuclear cells were obtained from six patients undergoing CRT at four time points. Treatment consisted of once daily 2 Gy per fraction intensity modulated radiation therapy (IMRT) and 2 cycles of concurrent cisplatin (20 mg/m2/day x 5 days per cycle) given during weeks one and five of IMRT. Total dose was 70 Gy/7 weeks. Defined time points were: A) pre-treatment, B) early treatment (10 Gy and cycle 1 of cisplatin), C) late treatment (50 Gy and cycle 2 of cisplatin), and D) post-treatment (end of week 12). Multi-parameter flow cytometry was used to measure CD8+ and CD4+ T cell population alterations at the defined time points. A cytomegalovirus (CMV) peptide pool stimulation (pp65) was also performed to assay for a non-specific viral specific immune response in two of the six patients. Paired T test was used for analysis of T cell populations compared with time point A with significance defined as pZ<0.05. Results: Three patients had human papilloma virus (HPV) induced disease. Significant decreases from baseline were observed in total T cell numbers compared to baseline at every time point. Despite this lymphopenia, both CD4 and CD8 populations were proportionally similar to baseline at every time point expect for time point D, which showed a significant decrease in CD4 percentage (pZ<0.01) and significant increase in CD8 percentage (pZ0.01). CMV-specific responses were tested on one HPV+ and one HPV- tumor. CMV reactivity persisted, even in the face of therapy-induced lymphopenia. T cell reactivity was mostly polyfunctional (ie, interferon-gamma and tumor necrosis factor-alpha) and was independent of HPV status.
203 WITHDRAWN
254 Advanced Cutaneous Squamous Cell Carcinoma: Outcomes of Concurrent Cetuximab and Radiation Therapy Immunology and Immunotherapy R.M. Samstein, N.Y. Lee, and C.A. Barker; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): Cetuximab (Erbitux, Genentech) is a chimeric IgG1 antibody that blocks the epidermal growth factor receptor. Concurrent cetuximab and radiation therapy (CRT) improves the outcome of radiation therapy (RT) for advanced mucosal squamous cell carcinoma (SCC) of the head and neck. Advanced cutaneous SCC (cSCC) is treated with radiation therapy (RT) and often occurs in patients with immune dysfunction or comorbidities making them ineligible for surgery or myelotoxic chemotherapy. We retrospectively analyzed the outcome of patients treated with CRT for advanced cSCC. Materials/Methods: With approval from the IRB, medical records of patients treated with concurrent cetuximab and RT for cSCC were reviewed. Demographic, adult comorbidity evaluation-27 (ACE-27), cancer, treatment and toxicity parameters were recorded. Cause-specific and overall survival was determined. Results: Between 2007 - 2013, 13 patients underwent CRT for advanced cSCC at our institution. All but one was male, and median age was 77 years (range 47-85 years). Median performance status was 1 (range 1-3). Median ACE-27 score was 2 (moderate, range 1-3). Six patients had coexistent immune dysfunction (hemopoietic malignancy, autoimmune disease, on immunosuppressants). At start of CRT, all but 2 patients presented with recurrent cSCC; stage was III (nZ2) or IV (nZ11, 8 without distant metastases); all but one patient harbored gross disease. Two patients received induction cetuximab prior to CRT. Four patients received taxane and/or platinum chemotherapy as part of CRT. Median radiation dose was 60 Gy (range 12-79.6 Gy) in 30 fractions (3-38 fractions). Seven patients completed treatment as planned, without delay. Nine patients required hospitalization during or shortly after treatment. Two-year causespecific and overall survival was 50.4% and 33.6%, respectively. Conclusions: To our knowledge, this is the largest series of CRT of advanced cSCC. Patients with advanced cSCC selected for CRT often had advanced comorbidities or immune dysfunction. These factors likely limit the tolerance of CRT, as well as outcome of treatment. Controlled trials in this challenging group of patients are needed to improve outcomes. Author Disclosure: R.M. Samstein: None. N.Y. Lee: G. Consultant; Bristol Meyers Squibb. C.A. Barker: None.
132 A Retrospective CaseeControl Cohort Evaluation of the Effectiveness of Hyperbaric Oxygen Therapy (HBOT) for the Prevention of Postoperative Complications in Patients Undergoing Salvage or Reconstructive Head-and-Neck Surgery Following Radiation or Chemoradiation Management of Recurrent Head-and-Neck Squamous Cell Carcinoma A. Marcinow, T. Teknos, A. Agrawal, E. Ozer, R. Carrau, D. Schuller, and M. Old; Ohio State University, Columbus, OH Purpose/Objective(s): Head and neck cancers are increasingly being treated with organ-preserving therapy (radiation or chemoradiation).
258 Outcomes Following Primary Chemoradiation Therapy for N3 Head and Neck Squamous Cell Carcinoma With PET-Directed Neck Management Policy: A Diminishing Role for Planned Neck Dissection Imaging S. Porceddu,1,2 G. Adams,3 D. Pryor,3,2 B. Panizza,3,2 M. Foote,3,2 and B. Burmeister3,2; 1Princess Alexandra Hospital, Brisbane, Australia, 2 University of Queensland, Brisbane, Australia, 3Princess Alexandra Hospital, Brisbane, Australia Purpose/Objective(s): The purpose of this study was to assess prospectively the utility of a positron emission tomography (PET)-directed policy for N3 disease following definitive chemoradiation therapy in head and neck squamous cell carcinoma. Materials/Methods: All patients with N3 disease treated with chemoradiation therapy treated between 2005 and 2012 at our institution who achieved a complete response at the primary site were included. A staging PET, and a re-staging PET at 12 weeks post-therapy, were performed. Only patients with a residual nodal PET abnormality, regardless of CT response, underwent a neck dissection. The primary endpoint was isolated nodal failure. Results: Median follow up from diagnosis for 33 patients was 36 (6-82) months. Oropharynx was the predominant primary site 25 (76%), with 18 of these patients p16 positive. The most common T-staging was T4 (46%). All patients received concurrent chemoradiation therapy with 30% of patients also receiving induction therapy. Four (12%) patients underwent a neck dissection, with 2 isolated nodal failures (6%). First failure was predominantly distant metastatic disease (10; 30%). Conclusions: PET-directed policy for the N3 disease following definitive chemoradiation therapy in patients who achieve a complete response at the primary site results in a low rate of isolated nodal failure. Author Disclosure: S. Porceddu: None. G. Adams: None. D. Pryor: None. B. Panizza: None. M. Foote: None. B. Burmeister: None.
259 WITHDRAWN
269 Deformable Image Registration-Based Automatic CT-to-CT Contour Propagation for Head-and-Neck Cancer Radiation Therapy Imaging F. Siddiqui, A. Kumarasiri, J. Kim, C. Liu, and I. Chetty; Henry Ford Health System, Detroit, MI Purpose/Objective(s): Reducing the manual workload associated with contouring organs and target volumes at each replanning session is critical for efficient H&N ART implementation in a routine clinical setting. The aim of this study is to evaluate the potential of using commercially available deformable image registration (DIR) algorithms in VelocityAI and Varian SmartAdapt systems for automatic propagation of physician contours from planning CT to subsequent CT images for head and neck (H&N) adaptive radiation therapy. Materials/Methods: Ten H&N patients who have undergone significant weight loss during the first few weeks of treatment were considered for this retrospective study. Each patient had a planning CT (CT1) and a second CT (CT2) taken approximately 3 weeks into treatment. Clinically relevant normal organs and treatment volumes were manually delineated by a physician on both sets of CT scans. B-spline based VelocityAI and
Poster Presentations
503
Demons based SmartAdapt DIR algorithms were used to deform CT1 including the structure sets onto corresponding CT2 images. Agreement between automatically propagated contours and physician’s manual contours were evaluated visually by a physician, and evaluated quantitatively using the DICE coefficients, 2x(V1XV2)/(V1+V2), for overlap quantification. The results of the two commercial systems were compared with elastix DIR algorithm, a B-spline based independent verification tool, using in-house developed visualization and quantification tools. Results: Both VelocityAI and SmartAdapt attained good results and were quantitatively similar to elastix results for well differentiated and relatively large organs like brainstem, eyes and spinal cord, showing a high degree of correlation (DICE>0.8). Smaller organs with unclear boundaries on CT images like the pituitary gland and optic nerves showed less correlation (DICEw0.5). B-spline based VelocityAI and elastix generally achieved better results for the smaller organs. GTVs and PTVs generally showed a significant amount of overlap, with DICE indices w0.7-0.8 for GTVs and w0.8-0.9 for PTVs respectively, even with the expected shrinkage. Conclusions: Retrospective volume analysis by DICE indices and physician review of propagated contours suggests organs with sizable volumes propagate well between CT images. Use of VelocityAI and SmartAdapt for automatic CT-to-CT contour propagation is expected to save significant manual delineation time for physicians in H&N adaptive radiation therapy. Currently, VelocityAI based DIR is used on a trial basis on our clinic for contour propagation under physician supervision. We estimate a time savings of approximately 30 minutes per each re-plan using this methodology. Author Disclosure: F. Siddiqui: None. A. Kumarasiri: None. J. Kim: None. C. Liu: None. I. Chetty: None.
100 Phase 1b Trial of TLR8 Agonist VTX-2337 in Combination With Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinomas of the Head and Neck (SCCHN) Immunology and Immunotherapy L.Q.M. Chow,1 K.D. Eaton,1 C. Baik,1 B. Goulart,1 C. Morishima,1 M.L. Disis,1 K. Manjarrez,2 G. Dietsch,2 R. Hershberg,2 and R.G. Martins1; 1University of Washington, Seattle, WA, 2VentiRx Pharmaceuticals, Seattle, WA Purpose/Objective(s): Cetuximab, an EGFR-specific monoclonal antibody, is an approved therapy for SCCHN alone or combined with radiation or chemotherapy. Beyond blocking the EFGR signaling pathway, natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is important for cetuximab-mediated tumor killing; hence, NK cell activation may enhance the anti-tumoral effect. VTX-2337, a novel Toll-like receptor 8 (TLR8) agonist, stimulates NK cells, myeloid-derived dendritic cells, and monocytes. Preclinical data demonstrated synergistic NK cell activation and enhancement of ADCC with combination cetuximab and VTX-2337, forming the rationale to assess the safety, tolerability, immunological correlates, and efficacy of this combination in SCCHN patients. Materials/Methods: This open label phase 1b study in platinum-refractory or -intolerant recurrent or metastatic SCCHN patients (NCT01836029; NZ12) included cetuximab-naı¨ve patients who received a 400 mg/m2 loading dose followed by 250 mg/m2 weekly for a lead-in assessment for cetuximab toxicity and previously cetuximab-treated patients who received 250 mg/m2 weekly, prior to VTX-2337 combination. Using a 3+3 design, patients were enrolled into cohorts of escalating VTX-2337 doses (2.5, 3.0, 3.5 mg/m2) given SC days 1, 8, 15 q 28 day cycle. Correlative pharmacokinetic and pharmacodynamic immunologic assessments of response and activity were performed. Response was evaluated using RECIST 1.1. Results: This combination was well-tolerated with no dose-limiting toxicities, no serious, unexpected or synergistic drug-related toxicities between cetuximab and VTX-2337 in 10 patients. Toxicities were similar in scope and severity to those observed with cetuximab (fatigue, skin rash, cough, malaise) or VTX-2337 alone (Gr 1/2 injection site reaction, flu-like symptoms and fatigue). Commonly observed flu-like symptoms, injection
504
International Journal of Radiation Oncology Biology Physics
site reactions and fatigue established the 3.0 mg/m2 dose as most tolerable. Serum biomarkers were consistent with TLR8 activation. Ex vivo analysis of NK cells collected pre- and post-dose demonstrated enhanced NK cell mobilization and activation. In 8 response-evaluable patients, one partial response, 4 stable disease and 3 disease progression were observed. Results of this ongoing study will be updated. Conclusions: Cetuximab and VTX-2337 in combination is tolerable and active in SCCHN patients. Clinical data and serum biomarkers demonstrating immunostimulation with marked NK cell activation provide rationale for further study in SCCHN. A randomized, placebo-controlled, phase 2 trial comparing cetuximab + platinum + 5-FU +/- VTX-2337 has been initiated. Author Disclosure: L.Q.M. Chow: E. Research Grant; VentiRx Pharmaceuticals. K.D. Eaton: None. C. Baik: None. B. Goulart: None. C. Morishima: E. Research Grant; Merck. M.L. Disis: E. Research Grant; VentiRx Pharmaceuticals. G. Consultant; VentiRx Pharmaceuticals. K. Manjarrez: A. Employee; VentiRx Pharmaceuticals. L. Stock Options; VentiRx Pharmaceuticals. G. Dietsch: A. Employee; VentiRx Pharmaceuticals. L. Stock Options; VentiRx Pharmaceuticals. R. Hershberg: A. Employee; VentiRx Pharmaceuticals. L. Stock Options; VentiRx Pharmaceuticals. Q. Leadership; VentiRx Pharmaceuticals. R.G. Martins: None.
Conclusions: This research documents immune changes during treatment for OPC and provides evidence that although there is chemoradiation induced lymphopenia, the functional capability of T cells is maintained. This information has implications for the development and timing of immunotherapy strategies that depend on functional immune T cells. Author Disclosure: W.T. Lee: None. R. Medinas: None. J.H. Lee: None. S. Sparks: None. D.M. Brizel: None. R.M. Esclamado: None. N. Ready: None. K.J. Weinhold: None.
147 WITHDRAWN
149 Impact of Concurrent Chemoradiation on T Cell Populations in Patients With Advanced-Stage Oropharyngeal Squamous Cell Carcinoma Immunology and Immunotherapy W.T. Lee,1,2 R. Medinas,1 J.H. Lee,3 S. Sparks,1 D.M. Brizel,1 R.M. Esclamado,1 N. Ready,1 and K.J. Weinhold1; 1Duke University Medical Center, Durham, NC, 2Durham VA Medical Center, Durham, NC, 3 Sanford Health, Sioux Falls, SD Purpose/Objective(s): Concurrent chemoradiation (CRT) is commonly used to treat advanced stage oropharyngeal cancer (OPC). CRT affects the immune system, but the specific effects on immune cell populations and function during and after treatment are poorly defined. This study was performed to assess the impact of CRT on T cell populations and their function during and after treatment in patients with advanced stage OPC. Materials/Methods: Peripheral blood mononuclear cells were obtained from six patients undergoing CRT at four time points. Treatment consisted of once daily 2 Gy per fraction intensity modulated radiation therapy (IMRT) and 2 cycles of concurrent cisplatin (20 mg/m2/day x 5 days per cycle) given during weeks one and five of IMRT. Total dose was 70 Gy/7 weeks. Defined time points were: A) pre-treatment, B) early treatment (10 Gy and cycle 1 of cisplatin), C) late treatment (50 Gy and cycle 2 of cisplatin), and D) post-treatment (end of week 12). Multi-parameter flow cytometry was used to measure CD8+ and CD4+ T cell population alterations at the defined time points. A cytomegalovirus (CMV) peptide pool stimulation (pp65) was also performed to assay for a non-specific viral specific immune response in two of the six patients. Paired T test was used for analysis of T cell populations compared with time point A with significance defined as pZ<0.05. Results: Three patients had human papilloma virus (HPV) induced disease. Significant decreases from baseline were observed in total T cell numbers compared to baseline at every time point. Despite this lymphopenia, both CD4 and CD8 populations were proportionally similar to baseline at every time point expect for time point D, which showed a significant decrease in CD4 percentage (pZ<0.01) and significant increase in CD8 percentage (pZ0.01). CMV-specific responses were tested on one HPV+ and one HPV- tumor. CMV reactivity persisted, even in the face of therapy-induced lymphopenia. T cell reactivity was mostly polyfunctional (ie, interferon-gamma and tumor necrosis factor-alpha) and was independent of HPV status.
203 WITHDRAWN
254 Advanced Cutaneous Squamous Cell Carcinoma: Outcomes of Concurrent Cetuximab and Radiation Therapy Immunology and Immunotherapy R.M. Samstein, N.Y. Lee, and C.A. Barker; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): Cetuximab (Erbitux, Genentech) is a chimeric IgG1 antibody that blocks the epidermal growth factor receptor. Concurrent cetuximab and radiation therapy (CRT) improves the outcome of radiation therapy (RT) for advanced mucosal squamous cell carcinoma (SCC) of the head and neck. Advanced cutaneous SCC (cSCC) is treated with radiation therapy (RT) and often occurs in patients with immune dysfunction or comorbidities making them ineligible for surgery or myelotoxic chemotherapy. We retrospectively analyzed the outcome of patients treated with CRT for advanced cSCC. Materials/Methods: With approval from the IRB, medical records of patients treated with concurrent cetuximab and RT for cSCC were reviewed. Demographic, adult comorbidity evaluation-27 (ACE-27), cancer, treatment and toxicity parameters were recorded. Cause-specific and overall survival was determined. Results: Between 2007 - 2013, 13 patients underwent CRT for advanced cSCC at our institution. All but one was male, and median age was 77 years (range 47-85 years). Median performance status was 1 (range 1-3). Median ACE-27 score was 2 (moderate, range 1-3). Six patients had coexistent immune dysfunction (hemopoietic malignancy, autoimmune disease, on immunosuppressants). At start of CRT, all but 2 patients presented with recurrent cSCC; stage was III (nZ2) or IV (nZ11, 8 without distant metastases); all but one patient harbored gross disease. Two patients received induction cetuximab prior to CRT. Four patients received taxane and/or platinum chemotherapy as part of CRT. Median radiation dose was 60 Gy (range 12-79.6 Gy) in 30 fractions (3-38 fractions). Seven patients completed treatment as planned, without delay. Nine patients required hospitalization during or shortly after treatment. Two-year causespecific and overall survival was 50.4% and 33.6%, respectively. Conclusions: To our knowledge, this is the largest series of CRT of advanced cSCC. Patients with advanced cSCC selected for CRT often had advanced comorbidities or immune dysfunction. These factors likely limit the tolerance of CRT, as well as outcome of treatment. Controlled trials in this challenging group of patients are needed to improve outcomes. Author Disclosure: R.M. Samstein: None. N.Y. Lee: G. Consultant; Bristol Meyers Squibb. C.A. Barker: None.
132 A Retrospective CaseeControl Cohort Evaluation of the Effectiveness of Hyperbaric Oxygen Therapy (HBOT) for the Prevention of Postoperative Complications in Patients Undergoing Salvage or Reconstructive Head-and-Neck Surgery Following Radiation or Chemoradiation Management of Recurrent Head-and-Neck Squamous Cell Carcinoma A. Marcinow, T. Teknos, A. Agrawal, E. Ozer, R. Carrau, D. Schuller, and M. Old; Ohio State University, Columbus, OH Purpose/Objective(s): Head and neck cancers are increasingly being treated with organ-preserving therapy (radiation or chemoradiation).