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Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma.

ABSTRACT: PURPOSE:The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL). PATIENTS AND METHODS:MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL. RESULTS:Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement. CONCLUSION:Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

SUBMITTER: Ma DJ

PROVIDER: S-EPMC7098832 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma.

Ma Daniel J DJ Price Katharine A KA Moore Eric J EJ Patel Samir H SH Hinni Michael L ML Garcia Joaquin J JJ Graner Darlene E DE Foster Nathan R NR Ginos Brenda B Neben-Wittich Michelle M Garces Yolanda I YI Chintakuntlawar Ashish V AV Price Daniel L DL Olsen Kerry D KD Van Abel Kathryn M KM Kasperbauer Jan L JL Janus Jeffrey R JR Waddle Mark M Miller Robert R Shiraishi Satomi S Foote Robert L RL

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20190604 22

<h4>Purpose</h4>The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL).<h4>Patients and methods</h4>MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after sur ...[more]

PMID: 31163012

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Project description:PurposeTo report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.Materials and methodsMajor inclusion criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) being p16 positive, and (3) reporting minimal or remote smoking history. Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m2 once per week. Patients with T0-T2 N0-1 (AJCC 7th edition) did not receive chemotherapy. All patients had a 10- to 12-week post-treatment positron emission tomography/computed tomography to assess for neck dissection. The primary end point was 2-year progression-free survival. Secondary end points included 2-year local-regional control, distant metastasis-free survival and overall survival, and patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events).ResultsOne hundred fourteen patients were enrolled (median follow-up of 31.8 months), with 81% having a minimum follow-up of 2 years. Eighty percent of patients had 10 or fewer tobacco pack-years. Two-year local-regional control, distant metastasis-free survival, progression-free survival, and overall survival were as follows: 95%, 91%, 86%, and 95%, respectively. Mean pre- and 2-year post-treatment European Organisation for Research and Treatment of Cancer quality of life scores were as follows: global, 79/84 (lower worse); swallowing, 8/9 (higher worse); and dry mouth, 14/45 (higher worse). Mean pre- and 2-year post-treatment patient-reported outcomes version of the Common Terminology Criteria for Adverse Events scores (0 to 4 scale, higher worse) were as follows: swallowing, 0.5/0.7, and dry mouth, 0.4/1.3. Thirty-four percent of patients required a feeding tube (median, 10.5 weeks; none permanent). There were no grade 3 or higher late adverse events.ConclusionClinical outcomes with a de-intensified chemoradiotherapy regimen of 60 Gy intensity-modulated radiotherapy with concurrent low-dose cisplatin are favorable in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. Neither neoadjuvant chemotherapy nor routine surgery is needed to obtain favorable results with de-escalation.

Project description:BackgroundHead and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma.MethodsWe did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195.FindingsBetween Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment.InterpretationChemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients.FundingUniversity of California.

Project description:This study aims to identify the temporal kinetics of intravoxel incoherent motion (IVIM) MRI in patients with human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma. Patients were enrolled under an Institutional Review Board (IRB)-approved protocol as part of an ongoing prospective clinical trial. All patients underwent two MRI studies: a baseline scan before chemoradiotherapy and a mid-treatment scan 3-4 weeks after treatment initiation. Parametric maps representing pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) were generated. The Mann-Whitney U-test was used to assess the temporal variation of IVIM metrics. Bayesian quadratic discriminant analysis (QDA) was used to evaluate the extent to which mid-treatment changes in IVIM metrics could be combined to predict sites that would achieve complete response (CR) in multivariate analysis. Thirty-one patients were included in the final analysis with 59 lesions. Pretreatment ADC and D values of the CR lesions (n = 19) were significantly lower than those of non-CR lesions (n = 33). Mid-treatment ADC, D and f values were significantly higher (p < 0.0001) than pretreatment values for all lesions. Each increase in normalized ΔADC of size 0.1 yielded a 1.45-fold increase in the odds of CR (p < 0.0003), each increase in normalized ΔD of size 0.1 yielded a 1.53-fold increase in the odds of CR (p < 0.0002), and each unit increase in Δf yielded a 2.29-fold increase in the odds of CR (p < 0.02). Combined ΔD and ΔADC were integrated into a multivariate prediction model and attained an AUC of 0.87 (95% confidence interval: 0.79, 0.96), as well as a sensitivity of 0.63, specificity of 0.85 and accuracy of 0.78, under leave-one-out cross-validation. In conclusion, IVIM is feasible and potentially useful in the prediction and assessment of the early response of HPV+ oropharyngeal squamous cell carcinoma to chemoradiotherapy.

Dataset Information

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma.

Publications

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma.

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