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Comparing Image Guidance Based Adaptive IMRT Planning for Head and Neck Cancers With Standard IMRT: A Safety and Efficacy Analysis
Volume 93 Number 3S Supplement 2015 ultimately demonstrated a partial response as best overall response. Improvement in response (after first assessment) was noted in 3 of 9 patients (33%) treated with RT during immunotherapy and in 11 of 47 patients (23%) not receiving RT. Median survival was 27 months, with 1 and 2-year overall survival rates of 89% and 78%. Peripheral blood immune biomarker analyses are ongoing. Conclusion: In this small cohort of patients treated with concurrent RT, ipi and/or nivo on a phase 1 trial, grade 3-4 adverse events were consistent with those previously observed. All irradiated metastases demonstrated stability or response. Patients that underwent RT exhibited improvements in overall response after first assessment more often than those not irradiated, and survival was favorable. Further studies of RT, ipi and nivo are warranted. Author Disclosure: C.A. Barker: Research Grant; Elekta. Honoraria; MASCC. Consultant; Elekta, RP Pharmaceuticals. Advisory Board; Novartis. Travel Expenses; MASCC. Radiation and Cancer Biology Teaching and Curriculum/Radiobiology Practice Exam and Study Guide Subcommittee Vice-Chair; ASTRO. M.A. Postow: Research Grant; Bristol-Myers Squibb. Consultant; Bristol-Myers Squibb. S.A. Kronenberg: None. J. Ma: None. Y. Yamada: None. K. Beal: None. T.A. Chan: None. M.K. Callahan: Research Grant; Bristol-Myers Squibb. Consultant; Bristol-Myers Squibb. J.D. Wolchok: Research Grant; Bristol-Myers Squibb. Consultant; Bristol-Myers Squibb.
1134 Tumor Immunologic Heterogeneity Influences Response to Radiation and Anti-PD-1 Immunotherapy T.A. Aguilera,1 M. Rafat,2 M.S. Kariolis,1 E.E. Graves,2 and A.J. Giaccia2; 1 Stanford University, Stanford, CA, 2Stanford University, Stanford, CA Purpose/Objective(s): Clinical trials of CTLA-4 and PD-1/PD-L1 antibodies (Ab) have shown responses limited to 10-30% of patients. Increasing evidence suggests radiation (RT) can enhance responses to checkpoint therapies; however, understanding of tumor-derived factors that influence response is limited, and many preclinical models are manipulated to expressing specific antigens. We sought to develop a model of immunologic heterogeneity to study factors that influence responses to RT and immunotherapy. Materials/Methods: Tumor clones PyA1 and PyB2 exhibiting efficient orthotopic engraftment were derived from the PyMT mammary mouse carcinoma model. Cells were assayed by flow cytometry for MHCI and PD-L1 expression to evaluate antigen presentation and responses after interferon-g (IFNg) and 10 or 20 Gy RT treatment. Tumors were then grafted into naı¨ve mice and radiated to 12 or 20 Gy. Immune infiltrates were evaluated by flow cytometry after tumor dissociation. With evidence of immunologic responses, mice were treated with 12 Gy and PD-1 Ab in addition to a single pretreatment dose of CTLA-4 Ab to evaluate combination therapy. To elucidate factors influencing responsiveness of combination treatment in PyA1 but not PyB2 tumors, we inoculated mixed tumor cell populations at 80/20, 50/50, and 20/80 ratios. Results: PD-L1 and MHCI expression increased significantly after INFg and RT to a greater extent in PyA1 than PyB2 cells. Upon orthotopic implantation and RT, PyA1 but not PyB2 tumors regressed significantly. Dissociated tumors 10 days after 12 Gy treatment revealed a significant increase in CD45 leukocytes, CD8 effector T cells, and decreased CD4 T cells, myeloid derived suppressor cells, and macrophages in PyA1 tumors but minimal changes in PyB2 tumors. Secondly, there was elevated MHCI and induced PD-L1 expression in the responsive PyA1 compared to PyB2 tumors suggesting a greater antitumor response may be obtained with immunotherapy. Mice were treated with 12 Gy, 12 Gy + PD-1 Ab, and a single dose of CTLA-4 Ab 3 days prior to RT and PD1 therapy. There was prolonged tumor suppression in the combination RT + PD-1 and RT + PD-1 + CTLA-4 groups with repeated measures P values of .0003 and .0039, respectively. Notably 2/8 tumors treated with RT + PD-1 and 6/8 mice treated with RT + PD-1 +CTLA-4 were undetectable at day 81. Mixing tumors with different ratios of PyA1 and
ePoster Sessions S211 PyB2 revealed that 50% inoculation of PyA1 is sufficient for an immune response against both tumor clones. This suggests a mechanism where responsive tumors can induce antitumor activity against unresponsive tumors. Conclusion: These results support that tumor immunologic heterogeneity can influence immune responses after radiation. This is an excellent model to study tumor-derived factors that enhance or suppress the immune response after RT and could inform clinical approaches to radiation and immunotherapy combinations. Author Disclosure: T.A. Aguilera: Stock; Avelas Biosciences. Patent/License Fees/Copyright; UCSD. M. Rafat: None. M.S. Kariolis: None. E.E. Graves: None. A.J. Giaccia: Stock; Ruga Corp.
1135 Comparing Image Guidance Based Adaptive IMRT Planning for Head and Neck Cancers With Standard IMRT: A Safety and Efficacy Analysis N.P. Joshi,1 M.C. Ward,1 J.F. Greskovich, Jr,1 Q. Shang,1 A. Noble,2 B. Harr,1 C.A. Reddy,1 P. Xia,1 and S. Koyfman1; 1Cleveland Clinic, Cleveland, OH, 2Case Western Reserve University School of Medicine, Cleveland, OH Purpose/Objective(s): This study explores the comparative safety and efficacy of adaptive replanning for head and neck cancer intensity modulated radiotherapy (aIMRT) with standard IMRT (sIMRT) as measured by clinical rather than dosimetric outcomes. Materials/Methods: We identified all patients with stage III-IVB head and neck cancer treated with definitive chemoradiation using IMRT at a single institution over a 5-year period (2009-2014). Patients who exhibited either rapid disease regression and/or significant weight loss that resulted in substantial geometric changes with target volumes excessively encompassing skin or other uninvolved organs on daily cone beam computed tomography (CT) images by weeks 3 to 4 were adaptively replanned. Patient characteristics, disease parameters, locoregional control, overall survival, and acute and late toxicity (Common Terminology Criteria for Adverse Events version 4) were analyzed. Toxicity outcomes were compared by X2 tests; survival and control rates were determined from Kaplan-Meier estimates. Results: Two hundred three patients (42.9% aIMRT, 57.1% sIMRT) were identified from our institutional review boardeapproved registry. Median follow-up was 20 months (range, 0.5-58.6 months), median age 58 years, median KPS 90. The median radiation dose was 70 Gy for both groups (range, 63e78 Gy), and all patients received chemotherapy. The majority of tumors were oropharyngeal (84%) with larynx (11%) as the second most common site. Patients in the aIMRT and sIMRT groups were well balanced for baseline patient, tumor, and treatment characteristics with the notable exception that patients undergoing aIMRT had significantly higher rates of N2b-3 disease (83% vs. 62%; P Z .001) as well as group stage IVB disease (17.2% vs. 3.4%; P Z .0002). Despite more unfavorable disease characteristics in the aIMRT group, no significant differences were observed in locoregional failure rates for sIMRT versus aIMRT (5.2% vs. 9.2%; P Z .24) or in 2-year overall survival (87.3% vs. 86.8%; P Z .79), and only 1 locoregional failure in the aIMRT group was marginal. Acute toxicity was comparable for aIMRT versus sIMRT, respectively, including feeding tube use (39% vs. 37%; P Z .77), G2 mucositis (64% vs. 57%; P Z .28), G2 dermatitis (44% vs. 43%; P Z .93). Late swallowing dysfunction (aspiration, stricture, dysphagia) was higher in the aIMRT group (17.2% vs. 7.8%; P Z .04), as expected given the increased volume of pharyngeal constrictors receiving prescription dose in N2b-3 disease, while late fibrosis and pain was lower in the aIMRT group (4.6% vs. 12.1; P Z .05). Conclusion: Adaptive IMRT yields excellent control and survival rates comparable to standard IMRT without increasing the risk of marginal failures. Despite more adverse disease characteristics in the aIMRT patient group, similar acute and late toxicity profiles suggest that image guided aIMRT may help offset the expected increases in toxicity in patients with more locoregionally advanced disease.
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International Journal of Radiation Oncology Biology Physics
Author Disclosure: N.P. Joshi: None. M.C. Ward: None. J.F. Greskovich: None. Q. Shang: None. A. Noble: None. B. Harr: Stock; Johnson & Johnson. C.A. Reddy: None. P. Xia: Research Grant; Siemens medical solutions, Philips Medical Systems. S. Koyfman: None.
Materials/Methods: We used an integrated analytic relational database that systematically captures patient outcomes and all aspects of radiation therapy treatment plans. From a total of 642 head and neck cancer patients prospectively added to this knowledge base, 230 patients treated from 2008 to 2013 (Group A) and 50 patients treated in 2014 (Group B) were identified having Common Terminology Criteria for Adverse Events version 4.0 xerostomia assessed 3 months posttreatment. Baseline xerostomia scores were subtracted. The following dose features were also queried: minimum, mean, and maximum dose (Dmin, Dmean, Dmax), and dose to 20%, 50%, and 80% of the combined parotid volume (D20, D50, D80). Significant reductions in each dose point were assessed using the Welch 2sample t test. Xerostomia severity was modeled by logistic regression using stepwise selection from significant dose points (including interaction terms). Results: Mean baseline-adjusted xerostomia scores were significantly lower (P < .001) for Group B compared to Group A, with mean and standard deviations of 0.46 0.79 and 0.89 0.82, respectively. Group B also demonstrated significantly lower doses (P < .005) to the combined parotid glands for Dmean (-14.6%), D50 (-21.9%), and D80 (-21.3%). Of the logistic models incorporating these doses, backward stepwise selection revealed that Dmean was most predictive of xerostomia. Conclusion: Low doses to the parotid glands did not serve as a superior predictor of acute xerostomia. However, constraining the low-dose exposure to parotid tissue may reduce the mean dose, which may exert an indirect influence on xerostomia severity. Further prospective, multivariate evaluation is needed to assess the impact of low-dose objectives on xerostomia scores, target coverage, and sparing of adjacent normal structures. Author Disclosure: S.P. Robertson: Research Grant; Philips Radiation Oncology Systems. Z. Cheng: Research Grant; Toshiba Medical Research. M. Allen: None. S. Afonso: None. A. Choflet: None. A.P. Kiess: None. T.R. McNutt: Research Grant; Philips Radiation Oncology Systems, Elekta. H. Quon: None.
1136 Multicenter Phase 2 Study of Proton Beam Therapy as a Nonsurgical Approach for Mucosal Melanoma of the Nasal Cavity or Paranasal Sinuses S. Zenda,1 T. Akimoto,1 M. Mizumoto,2 R. Hayashi,1 S. Arahira,1 T. Okumura,2 and H. Sakurai2; 1National Cancer Center Hospital East, Kashiwa, Japan, 2University of Tsukuba, Tsukuba, Japan Purpose/Objective(s): The aim of this multicenter phase 2 study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the nasal cavity and paranasal sinuses. Materials/Methods: Patients with mucosal melanoma of the nasal cavity and paranasal sinuses with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered 3 times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. The primary endpoint was the local control rate at 1 year after treatment. Based on out pilot study result, the local control rate was estimated at 75%. When the local control rate is below 50%, the study treatment is regarded as having no advantage over other alternatives, and thus the local control rate and its threshold are set at 75% and 50%, respectively. On the assumption of a Z 0.05 and b Z 0.9, the study will need 32 patients. Results: Thirty-two patients were enrolled from June 2008 through October 2012. Patient characteristics were as follows: median age 73 years (range, 36 to 89 years); male/female ratio, 12/20; and T stage 3/4, 11/21. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 3%) and dermatitis (grade 3, 13%). Local control rate at 1 year as a primary endpoint was 75.8% (95% CI: 63.8%-92.4%). With a median follow-up period of 32.1 months, 2-year overall survival rate was 55.9%. There were 10 patients with no recurrence on follow-up. Of the remaining 17 patients, the most frequent pattern of first failure was distant metastases (10 patients), followed by regional failure in 4 patients. The main cause of death was also cancer death due to distant metastases (93.3%). Conclusion: Proton beam therapy showed promising local control benefits for mucosal melanoma of the nasal cavity and paranasal sinuses. Because controlling distant metastases is the next step, combining proton beam therapy with other modalities such as immunotherapy may be necessary in the near future. Author Disclosure: S. Zenda: None. T. Akimoto: None. M. Mizumoto: None. R. Hayashi: None. S. Arahira: None. T. Okumura: None. H. Sakurai: None.
1137 Impact of Low-Dose Parotid Gland Planning Objectives in Head and Neck Cancer Radiation Therapy S.P. Robertson,1 Z. Cheng,1 M. Allen,2 S. Afonso,2 A. Choflet,2 A.P. Kiess,1 T.R. McNutt,1 and H. Quon1; 1Johns Hopkins University, Baltimore, MD, 2Johns Hopkins Hospital, Baltimore, MD Purpose/Objective(s): Low-dose planning constraints for the combined parotid glands may help to reduce the severity of xerostomia in irradiated head and neck cancer patients when used in addition to mean dose constraints. A low-dose objective for the combined parotid glands has been included at our institution since the beginning of 2014, being utilized only in cases in which standard objectives were not compromised. This pragmatic controlled study examines prospectively acquired dose and toxicity data from the Oncospace Learning Health System to determine the role of low-dose parotid exposure in acute xerostomia outcomes.
1138 Double-Blind Randomized Phase 3 Study Comparing a Mixture of Natural Ingredients Versus Placebo in the Prevention of Acute Mucositis During Chemoradiation Therapy for Head and Neck Cancer A. Farneti, G. Sanguineti, L. Marucci, P. Di Ridolfi, P. Pinnaro, M. Mondati, L. Caramadre, P. Petitti, L. Bigiarini, B. Giardina, G. Giovinazzo, D. Giannarelli, and V. Landoni; Regina Elena National Cancer Institute, Rome, Italy Purpose/Objective(s): The effectiveness of a mixture of 7 natural ingredients (sodium alginate, sodium carbonate, propolis, aloe vera, calendula, honey, and chamomile) in preventing acute mucositis during chemoradiation therapy for head and neck cancer was tested within a double-blind phase 3 study. Materials/Methods: Patients undergoing definitive (70 Gy) or postoperative (60 Gy) intensity modulated radiation therapy (IMRT) concomitant to chemotherapy (cisplatin, 100 mg/m2, dd 1, 21, 42) for head and neck carcinoma were considered eligible. None of the patients had prophylactic placement of feeding tube. In addition to usual supportive care, starting day 1 of treatment, patients were given 7 mL of the Experimental (E) or the matched Placebo (P) compound, 4 times per day (before meals and radiation therapy, only 3 times per day during weekend) until treatment end. Patients were evaluated for acute toxicity weekly. Primary endpoint is the development of grade 3 (GR3) mucositis on physical exam according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Secondary endpoints included GR3 functional (CTCAEv3.0) mucositis, feeding tube placement (yes vs no), pain control (VDS), and relative weight loss (%). The study was sized to detect a reduction in the primary endpoint from 45% to 25%, setting the significance level at 5% with a power of 80%. Various covariates were tested at logistic regression. Of treatment-related ones, the amount of mucosa receiving at least 9.5 Gy per week (V9.5w) was
1134 Tumor Immunologic Heterogeneity Influences Response to Radiation and Anti-PD-1 Immunotherapy T.A. Aguilera,1 M. Rafat,2 M.S. Kariolis,1 E.E. Graves,2 and A.J. Giaccia2; 1 Stanford University, Stanford, CA, 2Stanford University, Stanford, CA Purpose/Objective(s): Clinical trials of CTLA-4 and PD-1/PD-L1 antibodies (Ab) have shown responses limited to 10-30% of patients. Increasing evidence suggests radiation (RT) can enhance responses to checkpoint therapies; however, understanding of tumor-derived factors that influence response is limited, and many preclinical models are manipulated to expressing specific antigens. We sought to develop a model of immunologic heterogeneity to study factors that influence responses to RT and immunotherapy. Materials/Methods: Tumor clones PyA1 and PyB2 exhibiting efficient orthotopic engraftment were derived from the PyMT mammary mouse carcinoma model. Cells were assayed by flow cytometry for MHCI and PD-L1 expression to evaluate antigen presentation and responses after interferon-g (IFNg) and 10 or 20 Gy RT treatment. Tumors were then grafted into naı¨ve mice and radiated to 12 or 20 Gy. Immune infiltrates were evaluated by flow cytometry after tumor dissociation. With evidence of immunologic responses, mice were treated with 12 Gy and PD-1 Ab in addition to a single pretreatment dose of CTLA-4 Ab to evaluate combination therapy. To elucidate factors influencing responsiveness of combination treatment in PyA1 but not PyB2 tumors, we inoculated mixed tumor cell populations at 80/20, 50/50, and 20/80 ratios. Results: PD-L1 and MHCI expression increased significantly after INFg and RT to a greater extent in PyA1 than PyB2 cells. Upon orthotopic implantation and RT, PyA1 but not PyB2 tumors regressed significantly. Dissociated tumors 10 days after 12 Gy treatment revealed a significant increase in CD45 leukocytes, CD8 effector T cells, and decreased CD4 T cells, myeloid derived suppressor cells, and macrophages in PyA1 tumors but minimal changes in PyB2 tumors. Secondly, there was elevated MHCI and induced PD-L1 expression in the responsive PyA1 compared to PyB2 tumors suggesting a greater antitumor response may be obtained with immunotherapy. Mice were treated with 12 Gy, 12 Gy + PD-1 Ab, and a single dose of CTLA-4 Ab 3 days prior to RT and PD1 therapy. There was prolonged tumor suppression in the combination RT + PD-1 and RT + PD-1 + CTLA-4 groups with repeated measures P values of .0003 and .0039, respectively. Notably 2/8 tumors treated with RT + PD-1 and 6/8 mice treated with RT + PD-1 +CTLA-4 were undetectable at day 81. Mixing tumors with different ratios of PyA1 and
ePoster Sessions S211 PyB2 revealed that 50% inoculation of PyA1 is sufficient for an immune response against both tumor clones. This suggests a mechanism where responsive tumors can induce antitumor activity against unresponsive tumors. Conclusion: These results support that tumor immunologic heterogeneity can influence immune responses after radiation. This is an excellent model to study tumor-derived factors that enhance or suppress the immune response after RT and could inform clinical approaches to radiation and immunotherapy combinations. Author Disclosure: T.A. Aguilera: Stock; Avelas Biosciences. Patent/License Fees/Copyright; UCSD. M. Rafat: None. M.S. Kariolis: None. E.E. Graves: None. A.J. Giaccia: Stock; Ruga Corp.
1135 Comparing Image Guidance Based Adaptive IMRT Planning for Head and Neck Cancers With Standard IMRT: A Safety and Efficacy Analysis N.P. Joshi,1 M.C. Ward,1 J.F. Greskovich, Jr,1 Q. Shang,1 A. Noble,2 B. Harr,1 C.A. Reddy,1 P. Xia,1 and S. Koyfman1; 1Cleveland Clinic, Cleveland, OH, 2Case Western Reserve University School of Medicine, Cleveland, OH Purpose/Objective(s): This study explores the comparative safety and efficacy of adaptive replanning for head and neck cancer intensity modulated radiotherapy (aIMRT) with standard IMRT (sIMRT) as measured by clinical rather than dosimetric outcomes. Materials/Methods: We identified all patients with stage III-IVB head and neck cancer treated with definitive chemoradiation using IMRT at a single institution over a 5-year period (2009-2014). Patients who exhibited either rapid disease regression and/or significant weight loss that resulted in substantial geometric changes with target volumes excessively encompassing skin or other uninvolved organs on daily cone beam computed tomography (CT) images by weeks 3 to 4 were adaptively replanned. Patient characteristics, disease parameters, locoregional control, overall survival, and acute and late toxicity (Common Terminology Criteria for Adverse Events version 4) were analyzed. Toxicity outcomes were compared by X2 tests; survival and control rates were determined from Kaplan-Meier estimates. Results: Two hundred three patients (42.9% aIMRT, 57.1% sIMRT) were identified from our institutional review boardeapproved registry. Median follow-up was 20 months (range, 0.5-58.6 months), median age 58 years, median KPS 90. The median radiation dose was 70 Gy for both groups (range, 63e78 Gy), and all patients received chemotherapy. The majority of tumors were oropharyngeal (84%) with larynx (11%) as the second most common site. Patients in the aIMRT and sIMRT groups were well balanced for baseline patient, tumor, and treatment characteristics with the notable exception that patients undergoing aIMRT had significantly higher rates of N2b-3 disease (83% vs. 62%; P Z .001) as well as group stage IVB disease (17.2% vs. 3.4%; P Z .0002). Despite more unfavorable disease characteristics in the aIMRT group, no significant differences were observed in locoregional failure rates for sIMRT versus aIMRT (5.2% vs. 9.2%; P Z .24) or in 2-year overall survival (87.3% vs. 86.8%; P Z .79), and only 1 locoregional failure in the aIMRT group was marginal. Acute toxicity was comparable for aIMRT versus sIMRT, respectively, including feeding tube use (39% vs. 37%; P Z .77), G2 mucositis (64% vs. 57%; P Z .28), G2 dermatitis (44% vs. 43%; P Z .93). Late swallowing dysfunction (aspiration, stricture, dysphagia) was higher in the aIMRT group (17.2% vs. 7.8%; P Z .04), as expected given the increased volume of pharyngeal constrictors receiving prescription dose in N2b-3 disease, while late fibrosis and pain was lower in the aIMRT group (4.6% vs. 12.1; P Z .05). Conclusion: Adaptive IMRT yields excellent control and survival rates comparable to standard IMRT without increasing the risk of marginal failures. Despite more adverse disease characteristics in the aIMRT patient group, similar acute and late toxicity profiles suggest that image guided aIMRT may help offset the expected increases in toxicity in patients with more locoregionally advanced disease.
S212
International Journal of Radiation Oncology Biology Physics
Author Disclosure: N.P. Joshi: None. M.C. Ward: None. J.F. Greskovich: None. Q. Shang: None. A. Noble: None. B. Harr: Stock; Johnson & Johnson. C.A. Reddy: None. P. Xia: Research Grant; Siemens medical solutions, Philips Medical Systems. S. Koyfman: None.
Materials/Methods: We used an integrated analytic relational database that systematically captures patient outcomes and all aspects of radiation therapy treatment plans. From a total of 642 head and neck cancer patients prospectively added to this knowledge base, 230 patients treated from 2008 to 2013 (Group A) and 50 patients treated in 2014 (Group B) were identified having Common Terminology Criteria for Adverse Events version 4.0 xerostomia assessed 3 months posttreatment. Baseline xerostomia scores were subtracted. The following dose features were also queried: minimum, mean, and maximum dose (Dmin, Dmean, Dmax), and dose to 20%, 50%, and 80% of the combined parotid volume (D20, D50, D80). Significant reductions in each dose point were assessed using the Welch 2sample t test. Xerostomia severity was modeled by logistic regression using stepwise selection from significant dose points (including interaction terms). Results: Mean baseline-adjusted xerostomia scores were significantly lower (P < .001) for Group B compared to Group A, with mean and standard deviations of 0.46 0.79 and 0.89 0.82, respectively. Group B also demonstrated significantly lower doses (P < .005) to the combined parotid glands for Dmean (-14.6%), D50 (-21.9%), and D80 (-21.3%). Of the logistic models incorporating these doses, backward stepwise selection revealed that Dmean was most predictive of xerostomia. Conclusion: Low doses to the parotid glands did not serve as a superior predictor of acute xerostomia. However, constraining the low-dose exposure to parotid tissue may reduce the mean dose, which may exert an indirect influence on xerostomia severity. Further prospective, multivariate evaluation is needed to assess the impact of low-dose objectives on xerostomia scores, target coverage, and sparing of adjacent normal structures. Author Disclosure: S.P. Robertson: Research Grant; Philips Radiation Oncology Systems. Z. Cheng: Research Grant; Toshiba Medical Research. M. Allen: None. S. Afonso: None. A. Choflet: None. A.P. Kiess: None. T.R. McNutt: Research Grant; Philips Radiation Oncology Systems, Elekta. H. Quon: None.
1136 Multicenter Phase 2 Study of Proton Beam Therapy as a Nonsurgical Approach for Mucosal Melanoma of the Nasal Cavity or Paranasal Sinuses S. Zenda,1 T. Akimoto,1 M. Mizumoto,2 R. Hayashi,1 S. Arahira,1 T. Okumura,2 and H. Sakurai2; 1National Cancer Center Hospital East, Kashiwa, Japan, 2University of Tsukuba, Tsukuba, Japan Purpose/Objective(s): The aim of this multicenter phase 2 study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the nasal cavity and paranasal sinuses. Materials/Methods: Patients with mucosal melanoma of the nasal cavity and paranasal sinuses with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered 3 times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. The primary endpoint was the local control rate at 1 year after treatment. Based on out pilot study result, the local control rate was estimated at 75%. When the local control rate is below 50%, the study treatment is regarded as having no advantage over other alternatives, and thus the local control rate and its threshold are set at 75% and 50%, respectively. On the assumption of a Z 0.05 and b Z 0.9, the study will need 32 patients. Results: Thirty-two patients were enrolled from June 2008 through October 2012. Patient characteristics were as follows: median age 73 years (range, 36 to 89 years); male/female ratio, 12/20; and T stage 3/4, 11/21. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 3%) and dermatitis (grade 3, 13%). Local control rate at 1 year as a primary endpoint was 75.8% (95% CI: 63.8%-92.4%). With a median follow-up period of 32.1 months, 2-year overall survival rate was 55.9%. There were 10 patients with no recurrence on follow-up. Of the remaining 17 patients, the most frequent pattern of first failure was distant metastases (10 patients), followed by regional failure in 4 patients. The main cause of death was also cancer death due to distant metastases (93.3%). Conclusion: Proton beam therapy showed promising local control benefits for mucosal melanoma of the nasal cavity and paranasal sinuses. Because controlling distant metastases is the next step, combining proton beam therapy with other modalities such as immunotherapy may be necessary in the near future. Author Disclosure: S. Zenda: None. T. Akimoto: None. M. Mizumoto: None. R. Hayashi: None. S. Arahira: None. T. Okumura: None. H. Sakurai: None.
1137 Impact of Low-Dose Parotid Gland Planning Objectives in Head and Neck Cancer Radiation Therapy S.P. Robertson,1 Z. Cheng,1 M. Allen,2 S. Afonso,2 A. Choflet,2 A.P. Kiess,1 T.R. McNutt,1 and H. Quon1; 1Johns Hopkins University, Baltimore, MD, 2Johns Hopkins Hospital, Baltimore, MD Purpose/Objective(s): Low-dose planning constraints for the combined parotid glands may help to reduce the severity of xerostomia in irradiated head and neck cancer patients when used in addition to mean dose constraints. A low-dose objective for the combined parotid glands has been included at our institution since the beginning of 2014, being utilized only in cases in which standard objectives were not compromised. This pragmatic controlled study examines prospectively acquired dose and toxicity data from the Oncospace Learning Health System to determine the role of low-dose parotid exposure in acute xerostomia outcomes.
1138 Double-Blind Randomized Phase 3 Study Comparing a Mixture of Natural Ingredients Versus Placebo in the Prevention of Acute Mucositis During Chemoradiation Therapy for Head and Neck Cancer A. Farneti, G. Sanguineti, L. Marucci, P. Di Ridolfi, P. Pinnaro, M. Mondati, L. Caramadre, P. Petitti, L. Bigiarini, B. Giardina, G. Giovinazzo, D. Giannarelli, and V. Landoni; Regina Elena National Cancer Institute, Rome, Italy Purpose/Objective(s): The effectiveness of a mixture of 7 natural ingredients (sodium alginate, sodium carbonate, propolis, aloe vera, calendula, honey, and chamomile) in preventing acute mucositis during chemoradiation therapy for head and neck cancer was tested within a double-blind phase 3 study. Materials/Methods: Patients undergoing definitive (70 Gy) or postoperative (60 Gy) intensity modulated radiation therapy (IMRT) concomitant to chemotherapy (cisplatin, 100 mg/m2, dd 1, 21, 42) for head and neck carcinoma were considered eligible. None of the patients had prophylactic placement of feeding tube. In addition to usual supportive care, starting day 1 of treatment, patients were given 7 mL of the Experimental (E) or the matched Placebo (P) compound, 4 times per day (before meals and radiation therapy, only 3 times per day during weekend) until treatment end. Patients were evaluated for acute toxicity weekly. Primary endpoint is the development of grade 3 (GR3) mucositis on physical exam according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Secondary endpoints included GR3 functional (CTCAEv3.0) mucositis, feeding tube placement (yes vs no), pain control (VDS), and relative weight loss (%). The study was sized to detect a reduction in the primary endpoint from 45% to 25%, setting the significance level at 5% with a power of 80%. Various covariates were tested at logistic regression. Of treatment-related ones, the amount of mucosa receiving at least 9.5 Gy per week (V9.5w) was