- Email: [email protected]
Phase 2 Trial of Deintensified Chemoradiation Therapy for Low-Risk Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma
866
International Journal of Radiation Oncology Biology Physics
Late-Breaking (LB) Abstract
Purpose/Objective(s): We performed a prospective multi-institutional phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Materials/Methods: The major inclusion criteria were (1) T0-T3, N0N2c, M0; (2) HPV or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy (IMRT) with concurrent weekly intravenous cisplatinum (30 mg/m2). The primary study endpoint was pathologic complete response rate (pCR) based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless of radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and nZ40, resulting in a type I error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Terminology Criteria for Adverse Events [CTCAE]), patient-reported symptoms (Patient-Reported Outcomes [PRO]CTCAE), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaires for cancer [EORTC QLQ-C30] and head and neck patients [H&N35]), and penetration aspiration scale (PAS) scores for modified barium swallow studies. Results: The study population is 43 patients. The pCR rate was 86% (37/43). All 6 non-pCR cases were limited to microscopic foci of residual cancer: 1 primary site and 5 nodal. All patients are alive with no evidence of disease (median follow-up 21.3 months, range 4-41 months). Thirty-eight patients had a follow-up of at least 1 year. The incidence of acute CTCAE grade 3/4 toxicity and PRO-CTCAE severe/ very severe symptoms were mucositis 34%/45%, pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematological toxicities were 11%. Mean pre- and 6-months-post-CRT EORTC QOL scores were as follows: Global 80/71 (lower worse), Pain (mouth, jaw, throat) 19/21 (higher worse), Swallowing 11/16, Coughing 17/26, Dry Mouth 16/68, and Sticky Saliva 6/ 49. Six-months-post CRT mean PRO-CTCAE severity scores for swallowing and dry mouth were mild and moderate, respectively. Thirty-nine percent of patients required a feeding tube (none permanently) for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in PAS scores for thin, pureed, and solid foods before and after CRT. Conclusion: In conclusion, pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk OPSCC with evidence of decreased toxicity compared to standard therapies. (ClinicalTrials.gov, NCT01530997) Author Disclosure: B.S. Chera: None. R.J. Amdur: None. J.E. Tepper: None. B. Qaqish: None. R. Green: None. N.N. Hayes: None. J. Weiss: None. J. Grilley-Olson: None. A. Zanation: None. T. Hackman: None. W. Funkhouser: None. N.C. Sheets: None. M. Weissler: None. W.M. Mendenhall: None.
LB1 Determinants of Cost in the Treatment of T1-T3 Oropharynx Cancer A.D. Pinheiro1 and R.W. Kramar2; 1Mercy Clinic - Head and Neck Surgery Springfield, MO, 2Mercy Clinic - Springfield, Springfield, MO Purpose/Objective(s): Current treatment guidelines for T1-T3 oropharynx squamous cell carcinoma (OPC) offer surgical (Surg) or nonsurgical (NSurg) treatments as equivalent alternatives. In order to make value decisions, we must understand cost of care. Our goal was to identify the primary determinants of cost and we hypothesized that surgical treatment did not increase cost of care in OPC. To this end, we examined the relationship of cost to tumor stage, AJCC cancer stage, Charlson agecomorbidity index (CACI), and treatment strategy (Surg vs NSurg). Materials/Methods: Retrospective review of patient records in EPIC identified 299 patients with a diagnosis of oropharynx cancer between July 12, 2011, and May 15, 2015. We excluded patients with tumors that extended to the oral cavity, those with second primaries or distant metastases, and those whose histology was other than squamous cell carcinoma (SCC). We identified 71 patients staged T1-T3 who received all their treatment (S, RT, and/or CRT) at our facility. Cost was defined as revenue collected by the hospital and clinic for a 6-month episode of care that started with a biopsy positive for OPC. Results: A total of 72 patients were available for evaluation. Forty-two were treated with Surg and 29 were treated with NSurg. Among the Surg patients, 22 received adjuvant treatment. Of those tested for p16, 92.5% (62/67) were positive and 4 had unknown p16 status. All 5 p16 negative patients were treated with Surg. Among the 4 patients with unknown p16 status, 1 was treated with Surg and 3 with NSurg. Median age was 61 and 62 for the Surg and NSurg groups (tZ-0.16, PZ.8747). There were no differences between the Surg and NSurg groups in distribution of T stage (c2Z4.83, PZ.0893) or AJCC Stage (c2Z6.06, PZ.1946). Comorbidity was higher for the Surg group (CACIZ8.07) relative to the NSurg group (CACIZ7.34) but this did not reach significance (tZ-1.36, PZ.1792). Cost was lowest for those treated with surgery only relative to the NSurg group ($38,462 vs $83,222; tZ2.26, PZ.0298). Surgery followed by adjuvant CRT had similar cost to primary CRT (respectively, $84,598 and $83,222; tZ 0.06, PZ.9528) Conclusion: Surgically treated patients with higher CACI, similar age, and greater proportion of p16-negative tumors had more favorable cost relative to those treated with primary CRT. Surgical patients who require adjuvant CRT had similar cost to those treated with primary CRT. The highest opportunity for cost savings is in those patients who do not require adjuvant CRT. Starting with a surgical approach does not increase cost even for those who require adjuvant treatment. Future research should determine which treatment strategy yields the best value. Author Disclosure: A.D. Pinheiro: None. R.W. Kramer: None.
Oral Abstract Session 5 Phase 2 Trial of Deintensified Chemoradiation Therapy for LowRisk Human PapillomaviruseAssociated Oropharyngeal Squamous Cell Carcinoma B.S. Chera,1 R.J. Amdur,2 J.E. Tepper,3 B. Qaqish,4 R. Green,5 N.N. Hayes,5 J. Weiss,6 J. Grilley-Olson,5 A. Zanation,1 T. Hackman,1 W. Funkhouser,5 N.C. Sheets,7 M. Weissler,1 and W.M. Mendenhall8; 1 University of North Carolina Hospitals, Chapel Hill, NC, 2University of Florida Hospitals, Gainesville, FL, 3University of North Carolina Hospitals, Chapel Hill, NC, United States, 4University of North Carolina, Chapel Hill, NC, 5University of North Carolina School of Medicine, Chapel Hill, NC, 6University of North Carolina, Chapel Hill, NC, 7 Rex/UNC, Raliegh, NC, 8University of Florida Health Proton Therapy Institute, Jacksonville, FL
6 Detection of Recurrence in Human PapillomaviruseAssociated Oropharynx Squamous Cell Carcinoma J.M. Frakes, A.O. Naghavi, T. Strom, A.R. Giuliano, L.B. Harrison, A. Trotti, and J.J. Caudell; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL Purpose/Objective(s): Human papillomavirus (HPV)-associated squamous cell carcinomas of the oropharynx are on the rise with a much higher likelihood of cure. We reviewed our institutional experience to determine time to recurrence as well as mode of detection of recurrence to further help guide optimal follow-up. Materials/Methods: After institutional review board approval, we queried an institutional database for patients with HPV- or p16-positive nonmetastatic oropharyngeal cancers treated with definitive radiation therapy (RT) between 2006 and 2014, and 246 cases were identified. Charts were reviewed and patient, tumor, and treatment factors as well as mode of
International Journal of Radiation Oncology Biology Physics
Late-Breaking (LB) Abstract
Purpose/Objective(s): We performed a prospective multi-institutional phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Materials/Methods: The major inclusion criteria were (1) T0-T3, N0N2c, M0; (2) HPV or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy (IMRT) with concurrent weekly intravenous cisplatinum (30 mg/m2). The primary study endpoint was pathologic complete response rate (pCR) based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless of radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and nZ40, resulting in a type I error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Terminology Criteria for Adverse Events [CTCAE]), patient-reported symptoms (Patient-Reported Outcomes [PRO]CTCAE), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaires for cancer [EORTC QLQ-C30] and head and neck patients [H&N35]), and penetration aspiration scale (PAS) scores for modified barium swallow studies. Results: The study population is 43 patients. The pCR rate was 86% (37/43). All 6 non-pCR cases were limited to microscopic foci of residual cancer: 1 primary site and 5 nodal. All patients are alive with no evidence of disease (median follow-up 21.3 months, range 4-41 months). Thirty-eight patients had a follow-up of at least 1 year. The incidence of acute CTCAE grade 3/4 toxicity and PRO-CTCAE severe/ very severe symptoms were mucositis 34%/45%, pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematological toxicities were 11%. Mean pre- and 6-months-post-CRT EORTC QOL scores were as follows: Global 80/71 (lower worse), Pain (mouth, jaw, throat) 19/21 (higher worse), Swallowing 11/16, Coughing 17/26, Dry Mouth 16/68, and Sticky Saliva 6/ 49. Six-months-post CRT mean PRO-CTCAE severity scores for swallowing and dry mouth were mild and moderate, respectively. Thirty-nine percent of patients required a feeding tube (none permanently) for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in PAS scores for thin, pureed, and solid foods before and after CRT. Conclusion: In conclusion, pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk OPSCC with evidence of decreased toxicity compared to standard therapies. (ClinicalTrials.gov, NCT01530997) Author Disclosure: B.S. Chera: None. R.J. Amdur: None. J.E. Tepper: None. B. Qaqish: None. R. Green: None. N.N. Hayes: None. J. Weiss: None. J. Grilley-Olson: None. A. Zanation: None. T. Hackman: None. W. Funkhouser: None. N.C. Sheets: None. M. Weissler: None. W.M. Mendenhall: None.
LB1 Determinants of Cost in the Treatment of T1-T3 Oropharynx Cancer A.D. Pinheiro1 and R.W. Kramar2; 1Mercy Clinic - Head and Neck Surgery Springfield, MO, 2Mercy Clinic - Springfield, Springfield, MO Purpose/Objective(s): Current treatment guidelines for T1-T3 oropharynx squamous cell carcinoma (OPC) offer surgical (Surg) or nonsurgical (NSurg) treatments as equivalent alternatives. In order to make value decisions, we must understand cost of care. Our goal was to identify the primary determinants of cost and we hypothesized that surgical treatment did not increase cost of care in OPC. To this end, we examined the relationship of cost to tumor stage, AJCC cancer stage, Charlson agecomorbidity index (CACI), and treatment strategy (Surg vs NSurg). Materials/Methods: Retrospective review of patient records in EPIC identified 299 patients with a diagnosis of oropharynx cancer between July 12, 2011, and May 15, 2015. We excluded patients with tumors that extended to the oral cavity, those with second primaries or distant metastases, and those whose histology was other than squamous cell carcinoma (SCC). We identified 71 patients staged T1-T3 who received all their treatment (S, RT, and/or CRT) at our facility. Cost was defined as revenue collected by the hospital and clinic for a 6-month episode of care that started with a biopsy positive for OPC. Results: A total of 72 patients were available for evaluation. Forty-two were treated with Surg and 29 were treated with NSurg. Among the Surg patients, 22 received adjuvant treatment. Of those tested for p16, 92.5% (62/67) were positive and 4 had unknown p16 status. All 5 p16 negative patients were treated with Surg. Among the 4 patients with unknown p16 status, 1 was treated with Surg and 3 with NSurg. Median age was 61 and 62 for the Surg and NSurg groups (tZ-0.16, PZ.8747). There were no differences between the Surg and NSurg groups in distribution of T stage (c2Z4.83, PZ.0893) or AJCC Stage (c2Z6.06, PZ.1946). Comorbidity was higher for the Surg group (CACIZ8.07) relative to the NSurg group (CACIZ7.34) but this did not reach significance (tZ-1.36, PZ.1792). Cost was lowest for those treated with surgery only relative to the NSurg group ($38,462 vs $83,222; tZ2.26, PZ.0298). Surgery followed by adjuvant CRT had similar cost to primary CRT (respectively, $84,598 and $83,222; tZ 0.06, PZ.9528) Conclusion: Surgically treated patients with higher CACI, similar age, and greater proportion of p16-negative tumors had more favorable cost relative to those treated with primary CRT. Surgical patients who require adjuvant CRT had similar cost to those treated with primary CRT. The highest opportunity for cost savings is in those patients who do not require adjuvant CRT. Starting with a surgical approach does not increase cost even for those who require adjuvant treatment. Future research should determine which treatment strategy yields the best value. Author Disclosure: A.D. Pinheiro: None. R.W. Kramer: None.
Oral Abstract Session 5 Phase 2 Trial of Deintensified Chemoradiation Therapy for LowRisk Human PapillomaviruseAssociated Oropharyngeal Squamous Cell Carcinoma B.S. Chera,1 R.J. Amdur,2 J.E. Tepper,3 B. Qaqish,4 R. Green,5 N.N. Hayes,5 J. Weiss,6 J. Grilley-Olson,5 A. Zanation,1 T. Hackman,1 W. Funkhouser,5 N.C. Sheets,7 M. Weissler,1 and W.M. Mendenhall8; 1 University of North Carolina Hospitals, Chapel Hill, NC, 2University of Florida Hospitals, Gainesville, FL, 3University of North Carolina Hospitals, Chapel Hill, NC, United States, 4University of North Carolina, Chapel Hill, NC, 5University of North Carolina School of Medicine, Chapel Hill, NC, 6University of North Carolina, Chapel Hill, NC, 7 Rex/UNC, Raliegh, NC, 8University of Florida Health Proton Therapy Institute, Jacksonville, FL
6 Detection of Recurrence in Human PapillomaviruseAssociated Oropharynx Squamous Cell Carcinoma J.M. Frakes, A.O. Naghavi, T. Strom, A.R. Giuliano, L.B. Harrison, A. Trotti, and J.J. Caudell; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL Purpose/Objective(s): Human papillomavirus (HPV)-associated squamous cell carcinomas of the oropharynx are on the rise with a much higher likelihood of cure. We reviewed our institutional experience to determine time to recurrence as well as mode of detection of recurrence to further help guide optimal follow-up. Materials/Methods: After institutional review board approval, we queried an institutional database for patients with HPV- or p16-positive nonmetastatic oropharyngeal cancers treated with definitive radiation therapy (RT) between 2006 and 2014, and 246 cases were identified. Charts were reviewed and patient, tumor, and treatment factors as well as mode of