Brandon Prendes

Modern Image-Guided Intensity-Modulated Radiotherapy for Oropharynx Cancer and Severe Late Toxic Effects: Implications for Clinical Trial Design

Importance Late toxic effects are common after definitive radiotherapy and chemoradiotherapy for oropharynx cancer and are considered a significant contributor to decreased quality of life for survivors. The incidence of severe late toxic effects may be reduced by modern narrow-margin image-guided intensity-modulated radiotherapy (IG-IMRT), current supportive care improvements, and the changing epidemiology of oropharynx cancer. Objective Assess the incidence of severe late toxic effects after modern definitive non-operative treatment for oropharynx cancer. Design, Setting, and Participants For this single-institution retrospective review, 156 patients with stage I-IVB squamous cell carcinoma of the oropharynx treated between April 2009 and February 2015 at a tertiary-referral academic multidisciplinary head and neck practice were recruited. Interventions Definitive narrow-margin IG-IMRT to a dose of 66 Gy (to convert milligray to rad, multiply by 0.1) or higher with or without concurrent cisplatin. Main Outcomes and Measures The primary outcome was the prospectively collected 2-year cumulative incidence of severe late toxic effects (Common Terminology Criteria for Adverse Events grade 3 or higher) occurring 3 months or more after radiotherapy. Toxic effect end points investigated included esophageal stricture requiring dilation, aspiration pneumonia hospitalization, vocal dysfunction, delayed feeding tube insertions, and osteoradionecrosis. Feeding tube dependence at 1 year was also considered a severe late toxic effect. Secondary outcomes collected include physician-reported grade 2 or higher neck fibrosis and xerostomia. The competing risks of recurrence and death were accounted for using the Gray method. Results One-hundred fifty-six patients (median [range] age, 58 [37-96] years) were identified; 130 patients (83%) were HPV positive. Concurrent cisplatin was delivered in 131 patients (84%) and 5 patients (3%) underwent an adjuvant neck dissection. The median (range) follow-up for survivors was 22 (4-73) months from diagnosis. The projected 2-year locoregional control was 93% (95% CI, 88.4%-97.6%) and overall survival was 88% (95% CI, 82.2%-94.0%). Thirty-eight patients (23%) required a feeding tube during treatment. The cumulative incidence of severe late toxic effects adjusted for competing risks at 2-year posttreatment was 2.3% (95% CI, 0%-5.6%). One patient required free-flap reconstruction for grade 3 osteoradionecrosis at 47 months. At 1 year, 2 patients (1%) experienced grade 2 neck fibrosis and 38 patients (23%) experienced grade 2 xerostomia. Conclusions and Relevance These results suggest that severe late toxic effects after modern definitive IG-IMRT, with or without cisplatin, for oropharynx cancer is likely uncommon. The importance of late toxic effect reduction in current and future investigational strategies, including clinical trials, should be considered.

The contemporary utility of intraoperative frozen sections in thyroid surgery

PURPOSE To determine the accuracy of intraoperative frozen section analysis on thyroidectomy specimens stratified by the Bethesda classification scheme and its utility for intraoperative decision-making. STUDY DESIGN Retrospective chart review. METHODS A retrospective review was performed on all patients who underwent thyroidectomy or thyroid lobectomy with intraoperative frozen sections at a tertiary care academic center from 2009 to 2015. RESULTS There were 74 total patients who underwent partial or total thyroidectomy with intraoperative frozen section analysis of a thyroid nodule whom had previously undergone a thyroid fine needle aspiration of the nodule. The sensitivity, specificity, positive predictive value, and negative predictive value for a thyroid frozen section with respect to its prediction for malignancy was 81%, 95%, 98%, and 66%, respectively, with a diagnostic accuracy of 85%. For 37 patients with an indeterminate cytologic diagnosis on fine needle aspiration (Bethesda categories III-V), the sensitivity, specificity, positive predictive value, and negative predictive value for a thyroid frozen section was 81%, 91%, 95%, and 67%, respectively, with a diagnostic accuracy of 84%. False positives and false negatives resulted in 1 completion thyroidectomy for benign pathology and 3 reoperations for malignancy not discovered on frozen section. CONCLUSION While intraoperative frozen sections on thyroid specimens may be helpful if positive, the false negative rate remains high. There appears to be limited value in routine frozen sections to guide clinical management and decision-making in the era of the Bethesda system.

A matched comparison of human papillomavirus–induced squamous cancer of unknown primary with early oropharynx cancer

Patients with human papillomavirus (HPV)–induced cancer of unknown primary (CUP) are generally excluded from clinical trials, despite surgical series reporting detection rates of occult oropharynx primaries of >80%. We performed a matched‐pair analysis to compare outcomes between T0N1‐3M0 HPV+ CUP and T1‐2N1‐3M0 HPV+ oropharynx known primary (OPX).

Increased pathologic upstaging with rising time to treatment initiation for head and neck cancer: A mechanism for increased mortality: Pathologic Upstaging and Time to Treatment

Time to treatment initiation (TTI) is increasing and is associated with worsening survival. In the current study, the authors sought to identify a mechanism for this relationship by assessing the effect of TTI on clinical‐to‐pathologic upstaging in patients with head and neck squamous cell carcinoma (HNSCC).

Definitive chemoradiation in locally advanced squamous cell carcinoma of the hypopharynx: Long-term outcomes and toxicity

Background/Aim: Definitive chemoradiation (CRT) is a common approach for locally advanced hypopharyngeal squamous cell carcinoma (SCC) with the goal of organ preservation. Reports on long-term oncologic and functional outcomes have been limited. This study reports on outcomes utilizing this approach at a single institution over 30 years. Materials and Methods: Medical records for patients with stage III-IVB SCC of the hypopharynx were retrospectively reviewed. Patient and disease-related factors were identified and analyzed for impact on overall survival (OS), cancer-specific survival (CSS), disease-free survival, distant failure, and locoregional failure. Results: A total of 54 patients were identified who were treated with definitive CRT to a mean dose of 72 Gy. With a median follow-up period of 49.8 months, 5- and 10-year OS was 62% and 43% respectively. Five and 10-year CSS were 74% and 72% respectively. Ten-year local control was 78%. Of the 37 patients with no treatment failure, 29% experienced a grade 3 or higher late toxicity, with the majority resolving during continued long-term follow-up. Conclusion: This study demonstrates good outcomes with long-term follow-up with acceptable rates of late toxicities. The findings here represent the longest published median follow-up in this population and validate the strategy of organ preservation.

Comprehensive approach to reestablishing form and function after radical parotidectomy

INTRODUCTION The reconstructive goals following radical parotidectomy include restoration of symmetry, reanimation of the face, and reestablishment of oral competence. We present our experience utilizing the anterolateral thigh (ALT) free flap, orthodromic temporalis tendon transfer (OTTT), and facial nerve cable grafting to reestablish form and function. MATERIAL AND METHODS From 2010 to 2016, 17 patients underwent radical parotidectomy followed by immediate reconstruction. An ALT was harvested to accommodate the volume and skin defect. Additional fascia lata and motor nerve to vastus lateralis (MNVL) were obtained. Anastomosis of the ALT to recipient vessels was performed, most commonly using the facial artery and internal jugular vein. OTTT was performed by securing the medial tendon of the temporalis to orbicularis oris through a nasolabial incision. Fascia lata was tunneled through the lower lip, then secured laterally to the temporalis tendon. The MNVL was cable grafted from either the proximal facial nerve or masseteric nerve to the distal facial nerve branches. ALT fascia was suspended to the superficial muscular aponeurotic system. RESULTS Average follow up was 19 months. Only one patient failed to achieve symmetry attributed to dehiscence of OTTT. All patients achieved oral competence and dynamic smile with OTTT activation. Facial nerve recovery was seen in 8 patients. 5 reached a House Brackman Score of 3. Two donor site seromas and two wound infections occurred. CONCLUSION Simultaneous ALT, OTTT, and facial nerve cable grafting provides early reestablishment of facial symmetry, facial reanimation, and oral competence with minimal morbidity.