Dataset Information

Preservation of swallowing function with de-intensified chemoradiation therapy for HPV-associated oropharyngeal squamous cell carcinoma.

ABSTRACT: Purpose:This study aimed to compare the swallowing function in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma treated with de-intensified chemoradiation therapy (6 weeks, 60?Gy) versus those receiving standard-of-care chemoradiation therapy (7 weeks, 70?Gy). Methods and materials:A retrospective review was conducted of 78 patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma with modified barium swallow studies pretreatment and 6 to 8 weeks posttreatment. The swallowing function was objectively scored for penetration, aspiration, and pharyngeal residue. Forty patients received de-intensified chemoradiation therapy (60?Gy image guided radiation therapy with weekly cisplatin 30?mg/m2) and 38 patients received standard-of-care chemoradiation therapy (70?Gy image guided radiation therapy with chemotherapy of the medical oncologist's choosing). Univariate and multivariate analyses were performed to detect differences between the cohorts with regard to laryngeal penetration, aspiration, and pharyngeal residue. A multivariate logistic regression was used to determine the overall effect of treatment on the swallowing function. Patient-reported swallowing outcomes in de-intensified cohort were assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Module for Head and Neck Cancer and the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events questionnaires. Results:Patients treated with de-intensified chemoradiation therapy were associated with a suggestion of lower risk of developing overall swallowing dysfunction (odds ratio [OR], 0.62; P?=?.07), laryngeal penetration (OR, 0.63; P?=?.12), and pharyngeal residue (OR, 0.61; P?=?.08). The mean pre- and 2-year post-European Organisation for Research and Treatment of Cancer Quality of Life scores pertaining to swallowing (1-4 scale, higher worse) in the de-intensified cohort were 1.4 and 1.2 for liquids; 1.2 and 1.1 for purees; 1.5 and 1.7 for solids, 1.0 and 1.3 for choked when swallowing; and 9.0 and 10.8 for composite score, respectively. The mean pre- and 2-year post-Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events swallowing difficulty scores (1-5 scale, with higher scores being worse) were 1.5 and 1.8, respectively. Conclusions:Compared with 7 weeks of 70?Gy, 6 weeks of 60?Gy de-intensified chemoradiation therapy appears to better preserve the baseline swallowing function (per objective modified barium swallow assessment). Patients treated with de-intensified chemoradiation therapy reported minimal changes in swallowing function.

SUBMITTER: Judy GD

PROVIDER: S-EPMC6127973 | biostudies-literature | 2018 Jul-Sep

REPOSITORIES: biostudies-literature

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Preservation of swallowing function with de-intensified chemoradiation therapy for HPV-associated oropharyngeal squamous cell carcinoma.

Judy Greg D GD Green Rebecca R Aumer Shannon L SL Amdur Robert J RJ Tan Xianming X Sheets Nathan N Weissler Mark M Zanation Adam A Patel Samip S Hackman Trevor T Mendenhall William M WM Chera Bhishamjit S BS

Advances in radiation oncology 20180314 3

<h4>Purpose</h4>This study aimed to compare the swallowing function in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma treated with de-intensified chemoradiation therapy (6 weeks, 60 Gy) versus those receiving standard-of-care chemoradiation therapy (7 weeks, 70 Gy).<h4>Methods and materials</h4>A retrospective review was conducted of 78 patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma with modified barium swallow studies pre ...[more]

PMID: 30197941

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Project description:IntroductionMost patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) have an excellent response to chemoradiation, and trials are now investigating de-escalated treatment. However, up to 25% of patients with HPV-positive OPSCC will experience recurrence, and up to 5% will even progress through primary treatment. Currently, there are no molecular markers to identify patients with poor prognosis who would be harmed by de-escalation. Herein we report the clinical and genomic characteristics of persistent HPV-positive OPSCC after definitive platinum-based chemoradiation therapy.MethodsPatients with HPV-positive OPSCC treated with curative intent platinum-based chemoradiation between 2007 and 2017 at two institutions and with a persistent locoregional disease were included. We evaluated clinical characteristics, including smoking status, age, stage, treatment, and overall survival. A subset of five patients had tissue available for targeted exome DNA sequencing and RNA sequencing. Genomic analysis was compared to a previously published cohort of 47 treatment-responsive HPV+ OPSCC tumors after batch correction. Mutational landscape, pathway activation, and OncoGPS tumor states were employed to characterize these tumors.ResultsTen patients met the inclusion criteria. The tumor and nodal stages ranged from T1 to T4 and N1 to N2 by AJCC 8th edition staging. All patients were p16-positive by immunohistochemistry, and eight with available in situ hybridization were confirmed to be HPV-positive. The 1-year overall survival from the time of diagnosis was 57%, and the 2-year overall survival was 17%. TP53 mutations were present in three of five (60%) persistent tumors compared to 2% (one of 47) of treatment-responsive HPV-positive tumors (p = 0.008). Other genes with recurrent mutations in persistent HPV-positive OPSCC tumors were NF1, KMT2D, PIK3C2B, and TFGBR2. Compared to treatment-responsive HPV-positive tumors, persistent tumors demonstrated activation of DNA Repair and p53, EMT, MYC, SRC, and TGF-beta signaling pathways, with post-treatment samples demonstrating significant activation of the PI3K-EMT-Stem pathways compared to pretreatment samples.ConclusionChemoradiation-resistant HPV-positive OPSCC occurs infrequently but portends a poor prognosis. These tumors demonstrate higher rates of p53 mutation and activation of MYC, SRC, and TGF-beta pathways. A comparison of tumors before and after treatment demonstrates PI3K-EMT-Stem pathways post-treatment in HPV-positive tumors with persistent disease after platinum-based chemoradiation.

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:The global rise of HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) has generated considerable interest underlying its etiology and management. Despite an overall decline in head and neck malignancies, the incidence in OPSCC has by contrast sharply risen, with HPV(+) subtypes now comprising 80% of all OPSCC.1,2 Relative to HPV(-) OPSCC, HPV(+) patients are more responsive to chemoradiation and harbor a 52% risk-of-death reduction.3 Despite this distinct outcome, treatment regimens remain the same for all OPSCC subtypes (smoking-driven and virus-driven), rather than an adaptive approach to what most consider distinct diseases. The short-term effects (e.g., mucositis, odynophagia) and long-term toxicities (e.g., xerostomia, dysphagia, ototoxicity) from treatment substantially affect quality of life, and rival the impact of the cancer itself. Recently published as well as ongoing trials are actively examining deintensification approaches2,4-9, with the goal of diminishing treatment sequelae for HPV(+) subtypes. While deintensification may decrease chemoradiation-related toxicities, it nonetheless may also undertreat a meaningful percentage of HPV(+) patients who may then recur. In examining national trials, 19% of HPV(+) patients had disease progression after therapy, with a two-year survival rate of 60%.10 Current methods to ascertain HPV status involve p16 staining. However, on comparison with gold standard E6/E7 expression by qPCR, p16 harbored a 15% false positivity rate11, suggesting limited utility as a sole biomarker for deintensification. Improved molecular stratification would greatly enhance the clinician’s ability to precisely tailor treatment while minimizing the risk of jeopardizing outcomes. One approach encompasses in-depth proteomic profiling of HPV(+) OPSCC to reveal distinct protein expression profiles and delineate clinically relevant upstream pathways. In turn, these proteomic differences may distinguish higher-risk disease (cases predisposed to recurrence that may benefit from treatment intensification) from lower-risk phenotypes (cases whose treatment response is sufficiently robust to warrant deintensification). Here, two HPV(+) OPSCC cohorts stratified by treatment response are compared via a hybrid data dependent acquisition/data independent acquisition (DDA/DIA) approach via mass spectrometry. We focused on detection of low-abundance proteins to highlight proteomic signatures that can be potentially exploited for treatment stratification.

Dataset Information

Preservation of swallowing function with de-intensified chemoradiation therapy for HPV-associated oropharyngeal squamous cell carcinoma.

Publications

Preservation of swallowing function with de-intensified chemoradiation therapy for HPV-associated oropharyngeal squamous cell carcinoma.

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