PURPOSE Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven. PATIENTS AND METHODS In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI). RESULTS Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( P = .04). For IMRT, 2-year PFS was 87.6% ( P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( P = .56). CONCLUSION The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.

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IMPORTANCEThe optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown.OBJECTIVE To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. DESIGN, SETTING, AND PARTICIPANTSThis international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up.INTERVENTIONS Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). MAIN OUTCOMES AND MEASURESThe primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. RESULTSOverall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes.

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Dramatic advances have been made in brachytherapy for cervical cancer. Radiation treatment planning has evolved from two-dimensional to three-dimensional, incorporating magnetic resonance imaging and/or computed tomography into the treatment paradigm. This allows for better delineation and coverage of the tumor, as well as improved avoidance of surrounding organs. Consequently, advanced brachytherapy can achieve very high rates of local control with a reduction in morbidity, compared with historic approaches. This review provides an overview of state-of-the-art gynecologic brachytherapy, with a focus on recent advances and their implications for women with cervical cancer.