Predictors of distant metastasis in human papillomavirus-associated oropharyngeal cancer.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer is associated with favorable outcomes, prompting investigations into treatment deintensification. The purpose of this study was for us to present the predictors of distant metastases in patients with HPV-positive oropharyngeal cancer treated with cisplatin-based chemoradiotherapy (CRT) or cetuximab-based bioradiotherapy (bio-RT). METHODS: In patients with stage III to IVb HPV-positive oropharyngeal cancer, the Kaplan-Meier analysis was used to calculate distant metastases rates. Univariate analysis (UVA) and multivariate analysis (MVA) were used to identify factors associated with distant metastases. RESULTS: Increased distant metastases rates were noted in active smokers versus never/former smokers (22% vs 5%), T4 vs T1 to T3 (15% vs 6%), and cetuximab-based bio-RT versus CRT (23% vs 5%). All remained significant on MVA. CONCLUSION: T4 tumors and active smokers have substantial rates of distant metastases, and trials investigating intensified systemic therapies may be considered. Higher rates of distant metastases observed with concurrent cetuximab are hypothesis generating, but further data are needed. © 2017 Wiley Periodicals, Inc. Head Neck 39: 940-946, 2017.

Impaired vocal cord mobility in T2N0 glottic carcinoma: Suboptimal local control with Radiation alone.

BACKGROUND: T2 glottic cancer with impaired vocal cord mobility (T2b) is known to have higher local failure rates when compared with T2 cancers without impaired cord mobility (T2a) treated with radiotherapy (RT) alone. METHODS: In this retrospective review, we identified and compared the local control rates of 3 groups: T2aN0 treated with RT; T2bN0 treated with RT; and T2b-3N0-2 treated with chemoradiotherapy (CRT). RESULTS: The 3-year local control rate was 95.1% for T2aN0, 73.2% for T2bN0 treated with RT, and 91.5% for the CRT group (p = .01). On univariate analysis, T2bN0 disease versus T2aN0 treated with RT alone (p = .03) was significantly associated with inferior local control. CONCLUSION: Patients with glottic cancer with impaired vocal cord mobility (T2b) have a high rate of local failure with RT alone. The addition of concurrent chemotherapy should be considered for patients highly motivated toward larynx preservation and willing to accept the potential toxicity. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1832-1836, 2016.

Risk Factors Associated with Disease Recurrence in Patients with Stage III/IV Squamous Cell Carcinoma of the Oral Cavity Treated with Surgery and Postoperative Radiotherapy.

AIM: The purpose of the present study was to identify variables associated with high risk of failure in patients with locally advanced squamous cell carcinoma of the oral cavity (SCC-OC). PATIENTS AND METHODS: This retrospective study included 191 patients with stage III-IVb SCC-OC treated with post-operative radiotherapy (RT) or chemoradiotherapy (CRT) between 1995 and 2013. Disease-free (DFS) and overall survival (OS) were analyzed; variables associated with inferior DFS were identified. RESULTS: Seventy-five patients (39%) recurred. DFS and five-year OS were 52% and 54%, respectively. Poorly differentiated tumors (p=0.03), recurrent tumors (p=0.02) and high nodal ratio (p=0.02) were associated with an increased risk of recurrence. CRT was associated with improved DFS in patients with positive margins and/or extracapsular extension (p=0.021). CONCLUSION: Tumors that are recurrent, high grade, or have high nodal ratio are at risk of recurrence. Presence of these disease features should be taken into consideration for better risk stratification.

Severe late dysphagia and cause of death after concurrent chemoradiation for larynx cancer in patients eligible for RTOG 91-11.

PURPOSE: The long-term results of RTOG 91-11 suggested increased deaths not attributed to larynx cancer after concomitant chemoradiotherapy (CRT) despite no apparent increase in late effects. Because the timing of events was not reported by RTOG 91-11, one possibility is that severe late dysphagia (SLD) develops beyond five years and leads to unreported treatment-related deaths. Here we explore the timing of SLD after CRT. METHODS: Patients who would have met eligibility criteria for RTOG 91-11 and were treated with CRT between 1993 and 2013 were identified. Events occurring beyond 3months after treatment and suggestive of SLD were recorded including esophageal stricture dilations, hospital admissions for aspiration pneumonia or feeding-tube insertion. Feeding-tube dependence beyond one year was also considered SLD. The cumulative incidence of SLD and its components was quantified using Gray's competing risk analysis with recurrence or death considered competing risks. RESULTS: Eighty-four patients were included with a median follow-up of 43months. The 5-year overall survival was 70% (95% CI 58-80%). No death was directly a result of treatment-induced late dysphagia. The 5-year incidence of SLD was 26.5%. While 15 of 18 (83%) first stricture dilations occurred within 5years after CRT, 3 of 5 (60%) aspiration admissions and 5 of 8 late feeding tube insertions occurred beyond five years from CRT. CONCLUSIONS: SLD is common after CRT for larynx cancer and can occur beyond 5years from the end of treatment, emphasizing the importance of survivorship follow-up. Despite the incidence of SLD, death related to dysphagia is uncommon.

Early and Severe Radiation Toxicity Associated with Concurrent Sirolimus in an Organ Transplant Recipient with Head and Neck Cutaneous Squamous Cell Carcinoma: A Case Report.

We present a case of a 71-year-old man with a history of liver transplantation who was treated with adjuvant radiotherapy with concurrent cisplatin for recurrent cutaneous squamous cell carcinoma of the head and neck. The patient was transitioned from tacrolimus to sirolimus for immunosuppression immediately prior to the start of radiation therapy, with the goal of reducing the risk for further skin cancer recurrence. The patient developed severe normal tissue toxicity, disproportionate to the dose delivered. He was diagnosed with Grade 4 esophagitis and mucositis after just 2,400 cGy in 12 fractions (planned 6,400 cGy in 32 fractions), requiring cessation of therapy. Six months later, the patient was diagnosed with local recurrence and distant metastases in the lung, and unfortunately passed away one month later. Randomized data have demonstrated the anti-neoplastic benefit of sirolimus. Pre-clinical studies and animal models have suggested that sirolimus may be a radiation sensitizer; however, the literature is limited regarding the clinical translation of these biologic findings. The case we presented reflects that concurrent radiation therapy with sirolimus may enhance the cytotoxic effects of radiation therapy and contribute to dose-limiting toxicity. Certainly, further study is necessary to explore this observation.