Enhanced recovery after surgery, current, and future considerations in head and neck cancer.

Objectives: Review of the current and relevant literature to develop a list of evidence-based recommendations that can be implemented in head and neck surgical practices. To provide rationale for the multiple aspects of comprehensive care for head and neck surgical patients. To improve postsurgical outcomes for head and neck surgical patients. Methods: Extensive review of the medical literature was performed and relevant studies in both the head and neck surgery and other surgical specialties were considered for inclusion. Results: A total of 18 aspects of perioperative care were included in this review. The literature search included 276 publications considered to be the most relevant and up to date evidence. Each topic is concluded with recommendation grade and quality of evidence for the recommendation. Conclusion: Since it's conception, enhanced recovery after surgery (ERAS) protocols have continued to push for comprehensive and evidence based postsurgical care to improve patient outcomes. Head and neck oncology is one of the newest fields to develop a protocol. Due to the complexity of this patient population and their postsurgical needs, a multidisciplinary approach is needed to facilitate recovery while minimizing complications. Current and future advances in head and neck cancer research will serve to strengthen and add new principles to a comprehensive ERAS protocol. Level of Evidence: 2a.

Comparison of Survival Estimates Following Recurrence, Persistence, or Second Primary Malignancy in Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: This study investigated survival among patients with oropharyngeal squamous cell carcinoma (OPSCC) after recurrence, persistence, and second primary malignancies (SPMs). STUDY DESIGN: Retrospective cohort study. SETTING: Patients were treated at a tertiary cancer center. SUBJECTS AND METHODS: Patients with OPSCC who had completed treatment between 2001 and 2017 were included. Survival estimates of 4 groups of patients were calculated: (1) patients who were disease free after initial treatment, (2) patients who had persistent disease, (3) those with recurrent disease, and (4) patients with SPMs. Cox proportional hazard models and parametric survival analyses (using Weibull distributions) were used to obtain hazard ratios (HRs) and time ratios (TRs). RESULTS: The cohort included 364 patients. The crude overall SPM prevalence was 8.2%. Mean overall survival (OS) time in years for patients who remained disease free after treatment was 4.02 years. Among patients who experienced recurrence, the recurrence-free survival (RFS) was 2.58 years while their mean (SD) OS was 3.67 (2.7) years. Participants who experienced persistence had a mean (SD) OS of 1.67 (1.68) years. Patients with observed SPMs had a mean (SD) OS of 6.39 (4.06) years since their primary cancer but shortened survivals of 1.75 (2.34) years since the secondary diagnosis. Differences were present even after accounting for human papillomavirus (HPV) and smoking status. CONCLUSIONS: Our findings stress the importance of active surveillance as per current National Comprehensive Cancer Network guidelines, irrespective of the HPV status or smoking status. Prospective studies with a larger number of SPM cases and longer follow-up are needed to validate survival trends even beyond 5 years.

Perioperative Management of Total Laryngectomy Patients: A Survey of American Head and Neck Society Surgeons.

OBJECTIVES: Standards of care for total laryngectomy (TL) patients in the postoperative period have not been established. Perioperative care remains highly variable and perhaps primarily anecdotally based. The aim of this study was to survey members of the American Head and Neck Society to capture management practices in the perioperative care of TL patients. METHODS: In this survey study, an electronic survey was distributed to the international attending physician body of the American Head and Neck Society. Forty-five-question electronic surveys were distributed. A total of 777 members were invited to respond, of whom 177 (22.8%) fully completed the survey. The survey elicited information on management preferences in the perioperative care of TL patients. Differences in management on the basis of irradiation status and pharyngeal repair (primary closure vs regional or free flap reconstruction) were ascertained. Main outcomes and measures were time to initiate oral feeding, perioperative antibiotic selection and duration, and estimated pharyngocutaneous fistula rates. These measures were stratified by patient type. RESULTS: Most respondents completed head and neck fellowships (77.0%) and practice at academic tertiary centers (72.3%). Ampicillin/sulbactam was the most preferred perioperative antibiotic (43.2%-49.1% depending on patient type), followed by cefazolin and metronidazole in combination (32.0%-33.7%) and then clindamycin (10.8%-12.6%). Compared with nonirradiated patients, irradiated patients were significantly more likely to have longer durations of antibiotics ( P < .05), longer postoperative times to initiate oral feeding ( P < .05), and higher estimated fistula rates ( P < .05). Additionally, in nonirradiated patients, flap-repaired patients (vs primary repair) were significantly more likely to have longer durations of antibiotics (odds ratio, 1.29; 95% confidence interval, 1.13-1.48) and postoperative times to initiate oral feeding (odds ratio, 2.24; 95% confidence interval, 1.76-2.84). CONCLUSIONS: Perioperative management of TL patients is highly variable. Management of antibiotics and oral feeding are significantly affected by irradiation status and scope of pharyngeal repair. Further studies are needed to standardize perioperative care for this unique patient population.

Comparison of Survival Outcomes Following Postsurgical Radioactive Iodine Versus External Beam Radiation in Stage IV Differentiated Thyroid Carcinoma.

BACKGROUND: There is a lack of well-powered data regarding outcomes in stage IV differentiated thyroid carcinoma (DTC) treated with postsurgical radiation. The objective of this study was to examine survival in patients with stage IV papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) who received radioactive iodine (RAI), external beam radiation therapy (EBRT), or neither following surgery. METHODS: In this retrospective cohort study, data collected from the National Cancer Data Base (NCDB) yielded 11,832 patients with stage IV DTC who underwent primary surgical treatment between 2002 and 2012. Patients were stratified by histology and sub-stage. Fully parametric, multilevel survival-time models were used to evaluate survival outcomes in three adjuvant treatment groups: RAI, EBRT, or no adjuvant radiation. Hazard ratios (HR) and time ratios (TR) were calculated against patients who did not receive radiation. All models were adjusted for demographic and clinical factors. RESULTS: The mean age of all patients was 61.6 years (SD = 11.6), and 57.5% were female. Patients who received EBRT had significantly higher 5- and 10-year hazards of death in several PTC sub-stages (10-year HRPTC Stage IV-A = 2.12 [confidence interval (CI) 1.79-2.52]; HRPTC Stage IV-B = 2.03 [CI 1.33-3.10]). For stage IV-B PTC requiring EBRT, lifespan after diagnosis was shortened by a factor of 3 when compared to patients who did not receive radiation (TRPTC Stage IV-B = 0.32 [CI 0.16-0.62]). In contrast, RAI was significantly associated with improved 5- and 10-year survival in both PTC and FTC patients regardless of pathological sub-stage. Large reductions in mortality were observed in patients with FTC who were treated with RAI (HRFTC Stage IV-C = 0.19 [CI 0.06-0.65]). When patients with stage IV-C FTC were treated with RAI, life-span after diagnosis doubled (TRFTC Stage IV-C = 1.98 [CI 1.31-3.00]). CONCLUSIONS: Through the NCDB, this study sought to describe prognosis and survival for adjuvant radiation in stage IV DTC. RAI was associated with improved survival for stage IV DTC. Despite treatment benefits conferred by adjuvant EBRT, indications to treat with EBRT were associated with poorer survival outcomes in patients with advanced-stage DTC, particularly PTC.

Electrical stimulation of post-irradiated head and neck squamous cell carcinoma to improve xerostomia.

OBJECTIVE: We observed a significant improvement in the complaints of dysphagia in patients with head and neck cancer who had received noninvasive neuromuscular electrical stimulation (E-stim) of their pharyngeal muscles. We wanted to determine if the improvement in dysphagia was a result of decreased complaints of xerostomia and increased saliva production, since one of our first patients being treated with E-stim noticed a significant improvement in xerostomia. STUDY DESIGN: Prospective trial to determine the effects of E-stim by evaluating saliva production and dysphagia questionnaires instituted by our speech pathologists on head and neck cancer patients that had received radiotherapy (XRT) and were to undergo E-stim for dysphagia. METHODS: Prior to the initiation of E-stim and one to two months after E-stim, saliva samples were collected and patients were asked to answer a Dysphagia and Xerostomia Index Questionnaire. All patients received E-stim two to four months after completing XRT. Patients received three E-stim treatments per week for a total of one to two months. Four electrodes were placed along anterior neck over pharyngeal muscles. E-stim was initiated using four to 30mA at 80-100 pulse-widths. RESULTS: Five patients that received either postoperative radiation therapy or concomitant chemoradiotherapy had been treated with E-stim. All five patients noticed a significant improvement in dysphagia. Five out of five patients noticed a definite increase in saliva production with symptoms of decreased intake of water with meals, sleeping longer hours at night, and increased moistness of lips. CONCLUSION: E-stim therapy appears to be an effective and approved treatment for dysphagia. Our study shows that it may also be beneficial for xerostomia in the post-irradiated head and neck cancer patients. SIGNIFICANCE: To determine if E-stim will benefit the previously irradiated patient with dysphagia and xerostomia.

Mammalian target of rapamycin inhibitors as possible adjuvant therapy for microscopic residual disease in head and neck squamous cell cancer.

Molecular therapeutics identifies an aberration in tumors to select patients that benefit from molecular targeted therapy. Overexpression of eIF4E in histologically "tumor-free" surgical margins of head and neck squamous cell cancer (HNSCC) patients is an independent predictor of recurrence and is functionally activated through the Akt/mammalian target of rapamycin (mTOR) pathway. Although mTOR inhibitors are cytostatic agents, best used in combination therapy, we hypothesize that they can be used as long-term single agents in an HNSCC model of minimal residual disease (MRD). CCI-779, an mTOR inhibitor, arrested growth of a phosphatase and tensin homologue deleted on chromosome 10 (PTEN) abnormal HNSCC cell line FaDu, inhibiting phosphorylation of 4E-binding protein 1, resulting in increased association with eIF4E and inhibition of basic fibroblast growth factor and vascular endothelial growth factor. Fluorescence in situ hybridization detected PTEN abnormalities in 68% of patient tumors and 35% of tumor-free margins. CCI-779 inhibited growth of established tumors in nude mice. However, in the MRD model, there were significant differences in the tumor-free rate between the control (4%) and the treatment group (50%), and the median tumor-free time was 7 versus 18 days, respectively (P < 0.0001). In those animals that formed tumors, CCI-779 caused a significant decrease in the tumor volume. The Kaplan-Meier curve showed that CCI-779 significantly increased survival (P < 0.0001). The mTOR pathway was inhibited in peripheral blood mononuclear cells potential surrogate markers of response to therapy. Stable transfection of FaDu with luciferase allowed us to monitor the effects of CCI-779 with bioluminescence imaging in the MRD model. These results pave the way for a clinical trial using targeted molecular therapy with CCI-779 as a single agent for mTOR-activated residual cells.