Radiotherapy Plus Cisplatin With or Without Lapatinib for Non-Human Papillomavirus Head and Neck Carcinoma: A Phase 2 Randomized Clinical Trial.

Importance: Patients with locally advanced non-human papillomavirus (HPV) head and neck cancer (HNC) carry an unfavorable prognosis. Chemoradiotherapy (CRT) with cisplatin or anti-epidermal growth factor receptor (EGFR) antibody improves overall survival (OS) of patients with stage III to IV HNC, and preclinical data suggest that a small-molecule tyrosine kinase inhibitor dual EGFR and ERBB2 (formerly HER2 or HER2/neu) inhibitor may be more effective than anti-EGFR antibody therapy in HNC. Objective: To examine whether adding lapatinib, a dual EGFR and HER2 inhibitor, to radiation plus cisplatin for frontline therapy of stage III to IV non-HPV HNC improves progression-free survival (PFS). Design, Setting, and Participants: This multicenter, phase 2, double-blind, placebo-controlled randomized clinical trial enrolled 142 patients with stage III to IV carcinoma of the oropharynx (p16 negative), larynx, and hypopharynx with a Zubrod performance status of 0 to 1 who met predefined blood chemistry criteria from October 18, 2012, to April 18, 2017 (median follow-up, 4.1 years). Data analysis was performed from December 1, 2020, to December 4, 2020. Intervention: Patients were randomized (1:1) to 70 Gy (6 weeks) plus 2 cycles of cisplatin (every 3 weeks) plus either 1500 mg per day of lapatinib (CRT plus lapatinib) or placebo (CRT plus placebo). Main Outcomes and Measures: The primary end point was PFS, with 69 events required. Progression-free survival rates between arms for all randomized patients were compared by 1-sided log-rank test. Secondary end points included OS. Results: Of the 142 patients enrolled, 127 (median [IQR] age, 58 [53-63] years; 98 [77.2%] male) were randomized; 63 to CRT plus lapatinib and 64 to CRT plus placebo. Final analysis did not suggest improvement in PFS (hazard ratio, 0.91; 95% CI, 0.56-1.46; P = .34) or OS (hazard ratio, 1.06; 95% CI, 0.61-1.86; P = .58) with the addition of lapatinib. There were no significant differences in grade 3 to 4 acute adverse event rates (83.3% [95% CI, 73.9%-92.8%] with CRT plus lapatinib vs 79.7% [95% CI, 69.4%-89.9%] with CRT plus placebo; P = .64) or late adverse event rates (44.4% [95% CI, 30.2%-57.8%] with CRT plus lapatinib vs 40.8% [95% CI, 27.1%-54.6%] with CRT plus placebo; P = .84). Conclusion and Relevance: In this randomized clinical trial, dual EGFR-ERBB2 inhibition with lapatinib did not appear to enhance the benefit of CRT. Although the results of this trial indicate that accrual to a non-HPV HNC-specific trial is feasible, new strategies must be investigated to improve the outcome for this population with a poor prognosis. Trial Registration: ClinicalTrials.gov Identifier: NCT01711658.

Surface mould brachytherapy in oral and oropharyngeal cancers.

INTRODUCTION: There are insufficient data on surface mold brachytherapy (SMB) in treating oral cancers. We reviewed our institutional experience to investigate the efficacy and toxicity of this treatment modality. MATERIAL AND METHODS: We retrospectively reviewed all the patients treated between 1989 and 2018 with high-dose-rate iridium-192 SMB for oral and oropharyngeal squamous cell carcinomas at our institution. Surface mold brachytherapy was delivered via an acrylic surface mold with 1-5 inserted catheters spaced 1 cm apart fabricated by our dental oncologist. The Kaplan-Meier product estimator was used to assess local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS). Cox proportional hazards regression analysis was used to assess the relationship of various variables and patient outcomes. RESULTS: Eighteen patients met the inclusion criteria and were evaluated. Indications for treatment were primary tumor (n = 13), local recurrence (2), locoregional recurrence (1), and oligometastatic disease (1). Ten patients received SMB alone and 8 received external beam radiotherapy with an SMB boost. The acute toxicity outcomes were as follows: no toxicity (n = 1), grade 1 (7), grade 2 (9), and grade 3 (1). Late effects were rare, only occurring in 3 patients. The one- and two-year LC were 81% and 68%, LRC 77% and 64%, DMFS 81% and 81%, and OS 77% and 46%. CONCLUSIONS: Surface mold brachytherapy is a viable modality as either primary or boost treatment for superficial oral cancers. In our patients, this treatment method has a low toxicity profile and resulted in reasonable LC.

Prognostic factors and selection criteria in the retreatment of head and neck cancers.

OBJECTIVES: To determine predictors of treatment selection, outcome, and survival, we examined a cohort of previously irradiated head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: We retrospectively analyzed 100 patients at our institution who were treated for recurrent or second primary (RSP) HNSCC, focusing on subgroups receiving reirradiation (ReRT) alone and those undergoing surgical salvage (SS) with or without post-operative reirradiation therapy (POReRT). Logistic regression modeling was performed to identify factors predictive of retreatment modality. Cox regression modeling was used to determine prognostic factors for progression free survival (PFS) and overall survival (OS). RESULTS: ReRT alone was less likely in current smokers and neck recurrences, with reirradiation more likely in primary site recurrences. POReRT was significantly more likely in patients with positive surgical margins (PSM), neck dissection, or organ dysfunction. POReRT omission negatively impacted PFS when PSM (HR: 8.894, 95% CI: 1.742-45.403) and perineural invasion (PNI) (HR: 3.391, 95% CI: 1.140-10.089) were present. Tracheostomy was associated with worse OS, but ReRT alone and POReRT improved OS. PSM correlated with worse OS, regardless of whether POReRT was given (HR: 14.260, 95% CI: 2.064-98.547). CONCLUSION: This analysis confirms known factors for predicting outcome and shows nonsmoking status and primary site recurrence as predictors for ReRT alone. POReRT for PSM and PNI improves PFS. Tracheostomy patients are more likely to have ReRT due to acute toxicity not limiting treatment and POReRT improves OS compared to surgery alone. The presence of PSM negatively impacts survival which cannot be overcome by POReRT.

Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.

Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration.

Intraoperative goal-directed hemodynamic management in free tissue transfer for head and neck cancer.

BACKGROUND: The purpose of this study was to determine the effect of algorithmic physiologic management on patients undergoing head and neck free tissue transfer and reconstruction. METHODS: Ninety-four adult patients were randomized to treatment and control groups. The blood pressure of the control group was managed consistent with contemporary standards. The treatment group was managed using an algorithm based on blood pressure and calculated physiologic values derived from arterial waveform analysis. Primary outcome was intensive care unit (ICU) length of stay. RESULTS: ICU length of stay was decreased in the treatment group (33.7 vs 58.3 hours; p = .026). The complication rate was not increased in the treatment group. CONCLUSION: The goal-directed hemodynamic management algorithm decreased the ICU length of stay. Judicious use of vasoactive drugs and goal-directed fluid administration has a role in improving perioperative outcomes for patients undergoing head and neck free tissue transfer. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1974-E1980, 2016.

Surgical Management of Recurrent Tracheocarotid Fistula following Endovascular Stent Placement.

We report the case of a 25-year-old woman who developed a tracheocarotid fistula secondary to an infected endovascular stent placed in the right carotid artery after the patient experienced hemorrhage on her first tracheostomy change. The patient originally had the tracheostomy placed at an outside hospital in September 2014, due to prolonged intubation after a motor vehicle accident. The patient presented to the otolaryngology service with an acute tracheal hemorrhage. This necessitated a neck exploration, median sternotomy, right carotid stent removal with subclavian to carotid bypass, and sternocleidomastoid flap reconstruction. This paper addresses the epidemiology and anatomy of a tracheocarotid fistula and discusses methods to treat such a complication.

Persistent tracheostomy after primary chemoradiation for advanced laryngeal or hypopharyngeal cancer.

BACKGROUND: Despite the demonstrated survival equivalence between chemoradiation and ablative surgery as primary treatment for advanced laryngeal and hypopharyngeal cancers, a subset of patients who undergo organ-preservation therapy have persistent tracheostomy requirement after completion of treatment. METHODS: Patients who received primary chemoradiation for advanced laryngeal or hypopharyngeal cancer in a 3-year interval were identified. Rate of persistent posttreatment tracheostomy requirement was evaluated. The 12-month overall mortality rate was compared between patients who did and did not receive a tracheostomy before treatment. RESULTS: In 60 patients identified for this study, T3/T4 status and hemilarynx fixation at the time of presentation were associated with persistent tracheostomy requirement 6 and 12 months posttreatment (p = .022; p < .001; and p = .032; p = .0495, respectively). Twelve-month mortality was higher in T3/T4 patients who received pretreatment tracheostomy (p = .034). CONCLUSION: Patients with advanced laryngeal or hypopharyngeal cancer who require tracheostomy before treatment have low rates of decannulation and higher short-term mortality than those who do not require tracheostomy before organ-preservation therapy.