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Long-Term Quality of Life (QOL) After Chemo-IMRT for Locally Advanced Oropharyngeal Cancer (OPC): A Prospective Longitudinal Study
Oral Scientific Sessions S101
Volume 90 Number 1S Supplement 2014
217 Prognostic Nomograms for Toxicity and Survival After Head and Neck Cancer Reirradiation and Chemotherapy: A Secondary Analysis of RTOG 9610 and 9911 C.E. Grossman,1 R. Mick,2 C.J. Langer,2 A. Lin,2 F. Wan,2 Q. Zhang,3 K. Ang,4 S.A. Spencer,5 E.M. Horwitz,6 S. Wong,7 Q. Le,8 and P.A. Kanetsky9; 1University of Rochester Medical Center, Rochester, NY, 2University of Pennsylvania, Philadelphia, PA, 3Radiation Therapy Oncology Group, Philadelphia, PA, 4University of Texas MD Anderson Cancer Center, Houston, TX, 5University of Alabama, Birmingham, AL, 6 Fox Chase Cancer Center, Philadelphia, PA, 7Medical College of Wisconsin, Milwaukee, WI, 8Stanford University, Stanford, CA, 9H. Lee Moffitt Cancer Center, Tampa, FL Purpose/Objective(s): Concurrent chemo-reirradiation (chemo-reRT) for recurrent head and neck cancers (HNCs) is a relatively novel concept, hampered by frequent and significant toxicity. Pretreatment models to predict overall survival (OS) and morbidity are lacking. Materials/Methods: Risk of severe [Grade 4 (life-threatening/disabling) and 5 (death)] acute toxicity and predictors of OS among patients with locoregionally recurrent or secondary HNC enrolled in the RTOG 9610 or 9911 Phase 2 chemo-reRT trials were evaluated. Reirradiation (reRT) was administered every-other-week in 1.5-Gy BID fractions to 60 Gy. Nomograms were generated from multivariable logistic and Cox regression models fitted to baseline host, tumor, and treatment predictors of severe acute toxicity and separately for OS, respectively. Results: Of 178 patients accrued, 162 and 123 had complete data for the modeled toxicity and OS predictors, respectively. Body surface area (BSA x 10) prior to chemo-reRT [OR Z 0.84 (95% CI Z 0.70, 1.00)], oral nutrition supplementation prior to chemo-reRT [OR Z (yes vs no) 0.35 (95% CI Z 0.15, 0.81)], AJCC stage of recurrent disease [ORs referent to IV; I: 0.24 (95% CI Z 0.03, 2.07); II: 0.62 (95% CI Z 0.19, 1.98); III: 0.33 (95% CI Z 0.11, 0.97)], and largest recurrent tumor diameter (cm) [OR Z 1.13 (95% CI Z 0.99, 1.30)] were statistically significant independent predictors of acute toxicity. Using this model, patients were stratified based on high (n Z 36) or low (n Z 87) probability of experiencing a severe acute toxicity. Predictors of OS were derived for each toxicity group. There was no difference in OS between high and low risk groups (median 310 vs 370 days, p Z 0.19). Among those with a high risk of developing a severe acute toxicity, age [HR Z 1.07 (95% CI Z 1.01, 1.14)], months between first recurrence diagnosis and reRT initiation [HR Z 0.98 (95% CI Z 0.97, 1.00)], and prior radiation dose to the index tumor [HR Z 1.05 (95% CI Z 0.98, 1.13)] independently predicted OS. Site of recurrence [HRs referent to oropharynx; oral cavity: 1.11 (95% CI Z 0.59, 2.07); hypopharynx: 1.33 (95% CI Z 0.52, 3.39); larynx: 0.32 (95% CI Z 0.12, 0.86)], AJCC stage of recurrent disease [HRs referent to IV; I: 0.85 (95% CI Z 0.35, 2.09); II: 0.70 (95% CI Z 0.31, 1.59); III: 0.33 (95% CI Z 0.17, 0.62)], and largest recurrent tumor diameter (cm) [HR Z 1.14 (95% CI Z 1.00, 1.30)] predicted OS in those with low risk of severe acute toxicity. Nomograms for OS had good discrimination (cindices of 0.61 and 0.68 for high and low acute toxicity) and calibration. Conclusions: Measurable baseline factors for independently predicting severe acute toxicity and OS after chemo-reRT of HNC have been identified. These nomograms can be implemented in discussions between physicians and patients when considering chemo-reRT and to direct future clinical trial design. Author Disclosure: C.E. Grossman: None. R. Mick: None. C.J. Langer: None. A. Lin: None. F. Wan: None. Q. Zhang: None. K. Ang: None. S.A. Spencer: None. E.M. Horwitz: None. S. Wong: None. Q. Le: None. P.A. Kanetsky: None.
218 Long-Term Quality of Life (QOL) After Chemo-IMRT for Locally Advanced Oropharyngeal Cancer (OPC): A Prospective Longitudinal Study D.H. Moon, J.M. Vainshtein, J. DeYoung, F.Y. Feng, D.B. Chepeha, M.H. Stenmark, and A. Eisbruch; University of Michigan, Ann Arbor, MI
Purpose/Objective(s): While organ-sparing IMRT has improved the toxicity profile of chemoradiation therapy (CRT) for head and neck cancer (HNC), prospective long-term patient-reported QOL (PRQOL) outcomes remain scarcely reported. Amidst concerns of delayed-onset dysphagia and other toxicities, we evaluated long-term PRQOL in two prospective studies of chemo-IMRT for OPC. Materials/Methods: Sixty-nine of 91 patients enrolled on two consecutive prospective single-institution studies of organ-sparing IMRT with concurrent carboplatin and paclitaxel for stage III/IV OPC between 2003 and 2011, who remained alive and HNC-free > 3 years after CRT, were eligible. All patients received protocol IMRT intended to minimize dose to the swallowing and salivary structures. QOL was collected for all patients pre-treatment and throughout the initial 2 year study period using three validated instruments (HNQOL questionnaire, University of Washington [UW] QOL questionnaire, and xerostomia questionnaire [XQ]). Eligible patients were mailed the three QOL instruments and a qualitative followup questionnaire. Long-term PRQOL was compared with prior patient responses during the initial 2-year study period using paired samples ttests. Results: Forty patients (58%) responded to the mailed questionnaires. Median follow-up was 6.5 years with follow-up of > 5 years for 30 patients (75%) and > 7 years for 16 patients (40%). Primary tumors were HPV+ in all respondents. PRQOL at 2 years did not differ between respondents and non-respondents (p > 0.5 for all assessments). Compared to 2 years post-CRT, no significant change in any PRQOL measure was detected with long-term follow-up, including all HNQOL domains (eating [p Z 0.33], communication [p Z 0.51], pain [p Z 0.085], emotion [p Z 0.49], overall bother [p Z 0.13]), swallowing (UWQOL swallowing question: p Z 0.48), and xerostomia (XQ summary score: p Z 0.65). Late dysphagia and HN-related complications > 2 years postCRT were uncommon. No patient reported late PEG tube placement; four patients (10%) reported new onset dysphagia of whom two required stricture dilation (all > 5 years post-CRT). Compared to pre-treatment, long-term PRQOL mean summary scores for eating, swallowing, and pain increased by < 10 points (out of 100), indicating minimal clinical change, while long-term emotional and overall bother domains decreased by > 10 points, indicating clinically meaningful improvements from pretreatment. Conclusions: At long-term follow-up of two prospective studies of chemo-IMRT for OPC, PRQOL remained excellent and unchanged compared to earlier 2-year follow-up, with rare self-reported de novo late toxicity. To our knowledge, these are the longest prospective PRQOL outcomes with comparisons to pre-treatment baseline after chemo-IMRT in HNC. Author Disclosure: D.H. Moon: None. J.M. Vainshtein: None. J. DeYoung: None. F.Y. Feng: None. D.B. Chepeha: None. M.H. Stenmark: None. A. Eisbruch: None.
219 Integrative Radiogenomic Profiling Identifies BRAF Mutations as Novel Radiotherapeutic Targets in Adenocarcinomas of the Lung J.W. Hearn,1 B.D. Yard,2 D.J. Adams,3 P. Tamayo,3 S.L. Schreiber,4 M.L. Meyerson,5 P.S. Hammerman,6 and M.E. Abazeed7; 1Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, 2Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, 3 Broad Institute of MIT and Harvard, Cambridge, MA, 4Broad Institute of MIT and Harvard; Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 5Broad Institute of MIT and Harvard; Dana-Farber Cancer Institute; Brigham and Women’s Hospital, Cambridge; Boston, MA, 6Broad Institute of MIT and Harvard; Dana-Farber Cancer Institute, Cambridge; Boston, MA, 7Departments of Radiation Oncology and Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH Purpose/Objective(s): Patients with non-small cell lung cancer (NSCLC) display a wide spectrum of oncologic outcomes, suggesting significant underlying biologic diversity. Despite two notable exceptions in cases of
Volume 90 Number 1S Supplement 2014
217 Prognostic Nomograms for Toxicity and Survival After Head and Neck Cancer Reirradiation and Chemotherapy: A Secondary Analysis of RTOG 9610 and 9911 C.E. Grossman,1 R. Mick,2 C.J. Langer,2 A. Lin,2 F. Wan,2 Q. Zhang,3 K. Ang,4 S.A. Spencer,5 E.M. Horwitz,6 S. Wong,7 Q. Le,8 and P.A. Kanetsky9; 1University of Rochester Medical Center, Rochester, NY, 2University of Pennsylvania, Philadelphia, PA, 3Radiation Therapy Oncology Group, Philadelphia, PA, 4University of Texas MD Anderson Cancer Center, Houston, TX, 5University of Alabama, Birmingham, AL, 6 Fox Chase Cancer Center, Philadelphia, PA, 7Medical College of Wisconsin, Milwaukee, WI, 8Stanford University, Stanford, CA, 9H. Lee Moffitt Cancer Center, Tampa, FL Purpose/Objective(s): Concurrent chemo-reirradiation (chemo-reRT) for recurrent head and neck cancers (HNCs) is a relatively novel concept, hampered by frequent and significant toxicity. Pretreatment models to predict overall survival (OS) and morbidity are lacking. Materials/Methods: Risk of severe [Grade 4 (life-threatening/disabling) and 5 (death)] acute toxicity and predictors of OS among patients with locoregionally recurrent or secondary HNC enrolled in the RTOG 9610 or 9911 Phase 2 chemo-reRT trials were evaluated. Reirradiation (reRT) was administered every-other-week in 1.5-Gy BID fractions to 60 Gy. Nomograms were generated from multivariable logistic and Cox regression models fitted to baseline host, tumor, and treatment predictors of severe acute toxicity and separately for OS, respectively. Results: Of 178 patients accrued, 162 and 123 had complete data for the modeled toxicity and OS predictors, respectively. Body surface area (BSA x 10) prior to chemo-reRT [OR Z 0.84 (95% CI Z 0.70, 1.00)], oral nutrition supplementation prior to chemo-reRT [OR Z (yes vs no) 0.35 (95% CI Z 0.15, 0.81)], AJCC stage of recurrent disease [ORs referent to IV; I: 0.24 (95% CI Z 0.03, 2.07); II: 0.62 (95% CI Z 0.19, 1.98); III: 0.33 (95% CI Z 0.11, 0.97)], and largest recurrent tumor diameter (cm) [OR Z 1.13 (95% CI Z 0.99, 1.30)] were statistically significant independent predictors of acute toxicity. Using this model, patients were stratified based on high (n Z 36) or low (n Z 87) probability of experiencing a severe acute toxicity. Predictors of OS were derived for each toxicity group. There was no difference in OS between high and low risk groups (median 310 vs 370 days, p Z 0.19). Among those with a high risk of developing a severe acute toxicity, age [HR Z 1.07 (95% CI Z 1.01, 1.14)], months between first recurrence diagnosis and reRT initiation [HR Z 0.98 (95% CI Z 0.97, 1.00)], and prior radiation dose to the index tumor [HR Z 1.05 (95% CI Z 0.98, 1.13)] independently predicted OS. Site of recurrence [HRs referent to oropharynx; oral cavity: 1.11 (95% CI Z 0.59, 2.07); hypopharynx: 1.33 (95% CI Z 0.52, 3.39); larynx: 0.32 (95% CI Z 0.12, 0.86)], AJCC stage of recurrent disease [HRs referent to IV; I: 0.85 (95% CI Z 0.35, 2.09); II: 0.70 (95% CI Z 0.31, 1.59); III: 0.33 (95% CI Z 0.17, 0.62)], and largest recurrent tumor diameter (cm) [HR Z 1.14 (95% CI Z 1.00, 1.30)] predicted OS in those with low risk of severe acute toxicity. Nomograms for OS had good discrimination (cindices of 0.61 and 0.68 for high and low acute toxicity) and calibration. Conclusions: Measurable baseline factors for independently predicting severe acute toxicity and OS after chemo-reRT of HNC have been identified. These nomograms can be implemented in discussions between physicians and patients when considering chemo-reRT and to direct future clinical trial design. Author Disclosure: C.E. Grossman: None. R. Mick: None. C.J. Langer: None. A. Lin: None. F. Wan: None. Q. Zhang: None. K. Ang: None. S.A. Spencer: None. E.M. Horwitz: None. S. Wong: None. Q. Le: None. P.A. Kanetsky: None.
218 Long-Term Quality of Life (QOL) After Chemo-IMRT for Locally Advanced Oropharyngeal Cancer (OPC): A Prospective Longitudinal Study D.H. Moon, J.M. Vainshtein, J. DeYoung, F.Y. Feng, D.B. Chepeha, M.H. Stenmark, and A. Eisbruch; University of Michigan, Ann Arbor, MI
Purpose/Objective(s): While organ-sparing IMRT has improved the toxicity profile of chemoradiation therapy (CRT) for head and neck cancer (HNC), prospective long-term patient-reported QOL (PRQOL) outcomes remain scarcely reported. Amidst concerns of delayed-onset dysphagia and other toxicities, we evaluated long-term PRQOL in two prospective studies of chemo-IMRT for OPC. Materials/Methods: Sixty-nine of 91 patients enrolled on two consecutive prospective single-institution studies of organ-sparing IMRT with concurrent carboplatin and paclitaxel for stage III/IV OPC between 2003 and 2011, who remained alive and HNC-free > 3 years after CRT, were eligible. All patients received protocol IMRT intended to minimize dose to the swallowing and salivary structures. QOL was collected for all patients pre-treatment and throughout the initial 2 year study period using three validated instruments (HNQOL questionnaire, University of Washington [UW] QOL questionnaire, and xerostomia questionnaire [XQ]). Eligible patients were mailed the three QOL instruments and a qualitative followup questionnaire. Long-term PRQOL was compared with prior patient responses during the initial 2-year study period using paired samples ttests. Results: Forty patients (58%) responded to the mailed questionnaires. Median follow-up was 6.5 years with follow-up of > 5 years for 30 patients (75%) and > 7 years for 16 patients (40%). Primary tumors were HPV+ in all respondents. PRQOL at 2 years did not differ between respondents and non-respondents (p > 0.5 for all assessments). Compared to 2 years post-CRT, no significant change in any PRQOL measure was detected with long-term follow-up, including all HNQOL domains (eating [p Z 0.33], communication [p Z 0.51], pain [p Z 0.085], emotion [p Z 0.49], overall bother [p Z 0.13]), swallowing (UWQOL swallowing question: p Z 0.48), and xerostomia (XQ summary score: p Z 0.65). Late dysphagia and HN-related complications > 2 years postCRT were uncommon. No patient reported late PEG tube placement; four patients (10%) reported new onset dysphagia of whom two required stricture dilation (all > 5 years post-CRT). Compared to pre-treatment, long-term PRQOL mean summary scores for eating, swallowing, and pain increased by < 10 points (out of 100), indicating minimal clinical change, while long-term emotional and overall bother domains decreased by > 10 points, indicating clinically meaningful improvements from pretreatment. Conclusions: At long-term follow-up of two prospective studies of chemo-IMRT for OPC, PRQOL remained excellent and unchanged compared to earlier 2-year follow-up, with rare self-reported de novo late toxicity. To our knowledge, these are the longest prospective PRQOL outcomes with comparisons to pre-treatment baseline after chemo-IMRT in HNC. Author Disclosure: D.H. Moon: None. J.M. Vainshtein: None. J. DeYoung: None. F.Y. Feng: None. D.B. Chepeha: None. M.H. Stenmark: None. A. Eisbruch: None.
219 Integrative Radiogenomic Profiling Identifies BRAF Mutations as Novel Radiotherapeutic Targets in Adenocarcinomas of the Lung J.W. Hearn,1 B.D. Yard,2 D.J. Adams,3 P. Tamayo,3 S.L. Schreiber,4 M.L. Meyerson,5 P.S. Hammerman,6 and M.E. Abazeed7; 1Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, 2Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, 3 Broad Institute of MIT and Harvard, Cambridge, MA, 4Broad Institute of MIT and Harvard; Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 5Broad Institute of MIT and Harvard; Dana-Farber Cancer Institute; Brigham and Women’s Hospital, Cambridge; Boston, MA, 6Broad Institute of MIT and Harvard; Dana-Farber Cancer Institute, Cambridge; Boston, MA, 7Departments of Radiation Oncology and Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH Purpose/Objective(s): Patients with non-small cell lung cancer (NSCLC) display a wide spectrum of oncologic outcomes, suggesting significant underlying biologic diversity. Despite two notable exceptions in cases of