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De-Escalation Strategies for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma-Where Are We Now?

ABSTRACT: The prevalence of oropharyngeal squamous cell carcinoma has been increasing in North America due to human papillomavirus-associated disease. It is molecularly distinct and differs from other head and neck cancers due to the young population and high survival rate. The treatment regimens currently in place cause significant long-term toxicities. Studies have transitioned from mortality-based outcomes to patient-reported outcomes assessing quality of life. There are many completed and ongoing trials investigating alternative therapy regimens or de-escalation strategies to minimize the negative secondary effects while maintaining overall survival and disease-free survival. The goal of this review is to discuss the most recent advancements within the field while summarizing and reviewing the available evidence.

SUBMITTER: Silver JA

PROVIDER: S-EPMC9139371 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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De-Escalation Strategies for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma-Where Are We Now?

Silver Jennifer A JA Turkdogan Sena S Roy Catherine F CF Subramaniam Thavakumar T Henry Melissa M Sadeghi Nader N

Current oncology (Toronto, Ont.) 20220518 5

The prevalence of oropharyngeal squamous cell carcinoma has been increasing in North America due to human papillomavirus-associated disease. It is molecularly distinct and differs from other head and neck cancers due to the young population and high survival rate. The treatment regimens currently in place cause significant long-term toxicities. Studies have transitioned from mortality-based outcomes to patient-reported outcomes assessing quality of life. There are many completed and ongoing tria ...[more]

PMID: 35621685

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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:ImportanceExtranodal extension (ENE) is an adverse feature in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and is an indication for adjuvant treatment escalation. Preoperative core needle biopsy (CNB) may cause lymph node capsule disruption related to ENE development; however, evidence regarding this association in OPSCC is lacking.ObjectiveTo assess whether preoperative nodal CNB is associated with presence of ENE in final pathology findings among patients with HPV-associated OPSCC targeted for primary surgical resection.Design, setting, and participantsThis retrospective cohort study was conducted at a single academic tertiary care center from 2012 to 2022. All patients with OPSCC treated with transoral robotic surgery were assessed for eligibility, and primary surgical patients with HPV-associated OPSCC and node-positive disease confirmed on neck dissection were included in analyses. Data were analyzed from November 28, 2022, to May 21, 2023.ExposurePreoperative nodal CNB.Main outcomes and measuresThe primary outcome was presence of ENE in final pathology findings. Secondary outcomes included adjuvant chemotherapy and recurrence rates. Outcomes of interest were investigated against patient demographic, clinical, and pathologic features.ResultsOf 106 patients (mean [SD] age, 60.2 [10.9] years; 99 [93.4%] men) included in analyses, 23 patients (21.7%) underwent CNB. Mean (range) preoperative node size was 3.0 (0.9-6.0) cm. Pathologic node class was pN1 in 97 patients (91.5%) and pN2 in 9 patients (8.5%). A total of 49 patients (46.2%) had ENE identified in final pathology analysis. Of 94 patients who received adjuvant therapy, 58 (61.7%) underwent radiation therapy and 36 (38.3%) underwent chemoradiation therapy. There were 9 recurrences (8.5%). In univariate analysis, CNB was associated with ENE (odds ratio [OR], 2.70; 95% CI, 1.03-7.08), but there was no association in a multivariable model including pN class and preoperative node size (OR, 2.56; 95% CI, 0.97-7.27). Compared with pN1 class, pN2 class was associated with ENE (OR, 10.93; 95% CI, 1.32-90.80). There were no associations of ENE with preoperative node size, presence of cystic or necrotic nodes, fine needle aspiration, tobacco or alcohol exposure, pathologic T class, prior radiation, or age. Furthermore, use of CNB was not associated with macroscopic ENE, adjuvant chemotherapy, or recurrence.Conclusions and relevanceThis cohort study of patients with HPV-associated OPSCC found that preoperative nodal CNB was strongly associated with ENE in final pathology, supporting the possibility of an artifactual ENE component in this population.

Dataset Information

De-Escalation Strategies for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma-Where Are We Now?

Publications

De-Escalation Strategies for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma-Where Are We Now?

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