Anatomic Region of Cutaneous Melanoma Impacts Survival and Clinical Outcomes: A Population-Based Analysis.

PURPOSE: The objective was to determine the effects of the anatomic site of a cutaneous melanoma on the survival outcomes of diagnosed individuals. METHODS: We conducted a cross-sectional study using data from the Surveillance, Epidemiology, and End Results Program (SEER) Database from 2004-2014 and included 178,892 cases of individuals diagnosed with cutaneous melanoma. Overall survival (OS) for each anatomic site as well as associated demographics, primary site, stage, and pathologic prognostic factors (Breslow's depth of invasion (DOI), level of mitoses, and ulceration), were analyzed. RESULTS: Lower extremity melanoma (LEM) was the most likely to have locoregional nodal spread, yet head and neck melanoma (HNM) was the most likely to present at the most advanced stage of disease (IV). Independent of other factors, HNM was associated with the greatest risk of death (HR 1.90 [95% CI, 1.85-1.96]) compared to other sites, and males experienced worse overall survival (OS) (HR 1.74 [95% CI, 1.70-1.78]) compared to females. The last and greatest risk of death is associated with LEM and HNM, respectively. CONCLUSION: Given these survival differences, consideration should be given to incorporating the primary site of melanoma into staging to ensure treatment is efficacious as possible.

Trismus intra-operative release and expansion (TIRE): A novel operative treatment for trismus.

BACKGROUND: Trismus is a common symptom for patients with head and neck cancer. This study aimed to evaluate outcomes using the novel Trismus Intra-operative Release and Expansion (TIRE). METHODS: All patients from 2012 to 2022 with histories of head and neck cancers and trismus treated with TIRE were included. Data examined included measured interincisal distance (IID) before and after treatment, and improvement or worsening of trismus. RESULTS: Thirty-eight patients with trismus were identified, and fourteen underwent TIRE. All had undergone surgery, and 13 had completed radiation therapy prior to TIRE. Mean improvement of IID immediately after TIRE was 18.44 ± 6.02 mm (p < 0.0001). At first follow-up (2.51 ± 3.23 months, n = 8), mean improvement from pre-operational measurements was 11.14 ± 9.17 mm (p = 0.018). CONCLUSION: TIRE was initially successful in increasing IID in some patients, but sustained improvements were not consistently seen past 1 year follow-up. TIRE could help resolve trismus enough to proceed with options for trismus therapy using devices and/or mouth opening exercises.

Mucosal Melanoma In Situ of the Oral Cavity: A Case Report and Systematic Review of the Literature.

Objective: Malignant mucosal melanomas of the head and neck comprise a very small portion of all melanomas, particularly in the oral cavity. These lesions are associated with high rates of local recurrence, distant metastasis, and a very poor 5-year survival rate; however, the clinical outcomes of mucosal melanoma in situ of the oral cavity are unclear. Therefore, we present a case report of mucosal melanoma in situ and a systematic review of the literature to shed light on this rare but important disease. Methods: PubMed, Scopus, and CINAHL were searched per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were only considered for inclusion if they described oral cavity melanoma in situ and documented specific data pertaining to treatment including modality, lesion size, or outcomes. Results: A total of 28 reported cases from the literature fulfilled the inclusion criteria, as well as one case from our own institution. Men comprised the majority (64.3%) of the cases, and the average age at presentation was 57.4 years. The hard palate was the most common location, and most cases were treated with surgical excision. Eight had no evidence of disease after a minimum of six months of follow-up, one reported spread to the cervical lymph nodes, and only one reported progression with distant metastasis. Conclusion: Oral mucosal melanoma in situ is a rare entity and most commonly treated with surgical excision. High rates of recurrence necessitate long term follow-up. Further studies may be useful to determine whether adjuvant therapy may play a role in reducing recurrence.

A Randomized Multi-institutional Phase II Trial of Everolimus as Adjuvant Therapy in Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck.

PURPOSE: Investigate whether adjuvant everolimus, an mTOR inhibitor, improves progression-free survival (PFS) in advanced-stage head and neck squamous cell carcinoma (HNSCC) and provide outcomes related to correlative biological factors associated with disease control. PATIENTS AND METHODS: This was a prospective, randomized, double-blind phase II trial of patients with advanced-stage HNSCC from 13 institutions who were confirmed disease-free post-definitive therapy and enrolled between December 2010 and March 2015. Patients received adjuvant everolimus or placebo daily (10 mg, oral) for a maximum of 1 year. p16 IHC as a surrogate marker for human papillomavirus infection and whole-exome sequencing were performed. Cox proportional hazard models estimated hazard rates. Log-rank tests evaluated differences in survival. The primary endpoint was PFS. Secondary endpoints and objectives included overall survival (OS) and toxicity assessment. RESULTS: 52 patients [median (range) age, 58 (37-76) years; 43 men (83%), 9 women (17%)] were randomized to placebo (n = 24) or everolimus (n = 28). PFS favored everolimus, but was not significant [log-rank P = 0.093; HR = 0.44; 95% confidence interval (CI), 0.17-1.17]. There was no difference in OS (P = 0.29; HR = 0.57; 95% CI, 0.20-16.2). Everolimus resulted in significant improvement in PFS for p16-negative patients (n = 31; P = 0.031; HR = 0.26; 95% CI, 0.07-0.97), although subgroup analysis showed no difference for p16-positive patients (n = 21; P = 0.93). Further, PFS was significantly higher in TP53-mutated (TP53mut) patients treated with everolimus compared with placebo (log-rank P = 0.027; HR = 0.24; 95% CI, 0.06-0.95). No treatment difference was seen in patients with TP53 wild-type tumors (P = 0.79). CONCLUSIONS: p16-negative and TP53mut patients may benefit from adjuvant treatment with everolimus.

Programmed death 1 (PD-1) and ligand (PD-L1) inhibitors in head and neck squamous cell carcinoma: A meta-analysis.

Background: PD-1 and PD-L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC). Methods: Systematic review and meta-analysis of PD-1 and PD-L1 inhibitors in HNSCC. Outcomes: median overall survival (mOS), median progression-free survival (mPFS), Response Evaluation Criteria in Solid Tumors (RECIST) and treatment-related adverse events (TRAEs). Results: Eleven trials reported data on 1088 patients (mean age: 59.9 years, range: 18-90). The total mOS was 7.97 months (range: 6.0-16.5). Mean mPFS for all studies was 2.84 months (range: 1.9-6.5). PD-1 inhibitors had a lower rate of RECIST Progressive Disease than PD-L1 inhibitors (42.61%, 95% confidence interval [CI]: 36.29-49.06 vs. 56.79%, 95% CI: 49.18-64.19, P < 0.001). The rate of TRAEs of any grade (62.7%, 95% CI: 59.8-65.6) did not differ. Conclusions: Meta-analysis shows the efficacy of PD-1 and PD-L1 inhibitors in HNSCC and suggests a possible difference in certain RECIST criterion between PD-1 and PD-L1 inhibitors. Future work to investigate the clinical significance of these findings is warranted.

A pilot randomized controlled trial to evaluate a survivorship care planning intervention for head and neck cancer survivor-caregiver dyads.

PURPOSE: Head and neck cancer (HNC) survivors and caregivers face significant challenges after treatment. This study's objective was to evaluate the effects of a dyadic survivorship care planning (SCP) intervention on survivor and caregiver outcomes. METHODS: This randomized controlled trial enrolled HNC survivors and caregivers within 18 months post-treatment, randomized dyads to SCP (one-session with written SCP and follow-up telephone call) or usual care and administered baseline and 6-month surveys. Multivariable linear regression examined intervention effects on depression and unmet needs in dyads and burden on caregiverss and a set of secondary outcomes. Rating scales and open-ended questions assessed acceptability. RESULTS: We randomized 89 survivor-caregiver dyads (42 usual care, 47 SCP dyads). Fidelity to SCP was high for most survivorship domains except discussing care barriers (13%). The most commonly discussed referrals included nutrition (83%) and behavioral medicine (38%), but referral uptake was low. The SCP intervention did not improve depression or unmet needs among dyads or burden among caregivers at 6 months relative to usual care (p's > .05). Nurses and dyads rated SCP favorably with > 80% positive ratings for session length and care plan content. Qualitative findings highlighted that SCP helped consolidate complex clinical information and strengthened survivor-caregiver-clinician relationships. CONCLUSIONS: An HNC SCP intervention was acceptable but ineffective in improving dyads' outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Post-treatment SCP in HNC dyads was ineffective in improving outcomes in survivors and caregivers as delivered in this study. More research is needed to understand how to capitalize on the acceptability of the SCP approach and enhance its effectiveness to support dyads.

Systematic review of neuroendocrine carcinomas of the oropharynx.

Data describing features and management of oropharyngeal neuroendocrine carcinomas (NEC) remain sparse. A systematic review was performed. Patients were stratified by treatment modality and examined for disease progression and survival outcomes. Ninety-four patients from 50 publications were included. Average age at diagnosis was 59.7 years (range 14-83). 73.4% were male. Most studies did not document HPV status. Forty patients (85.1%) were p16 positive, and 34 (85.0%) were HPV-ISH positive. Overall survival was 75.4% at 1 year, and 40.0% at 2 years. Of patients with locoregional disease, 33.8% developed distant metastasis. 12.5% of patients developed locoregional recurrence. Patients who developed distant metastases had worse overall survival (p = 0.0004). No significant difference was found between treatment modalities. Human papilloma virus may be associated with oropharyngeal NEC. Current treatments provide locoregional control, but distant metastases are common and confer low overall survival.

Safety of microvascular free tissue transfer reconstruction of the head and neck in the setting of chronic pharmacologic immunosuppression.

BACKGROUND: Patients on chronic pharmacologic immunosuppressive therapy are at increased risk of wound infection and complications after surgery. There is a paucity of data examining perioperative complications after microvascular free tissue transfer (MVFTT) reconstruction of the head and neck in this patient population. METHODS: Retrospective cohort study performed at two tertiary referral centers between August 2016 and May 2020. RESULTS: Nine hundred and seventy-nine patients underwent MVFTT during the study period; of these 47 (5%) patients were taking chronic immunosuppressive medications. The most common indications for immunosuppression were solid organ transplant and autoimmune disease. Fourteen (30%) patients had surgical complications within 30 days of surgery: 8 (17%) wound dehiscences, 6 (12%) hematomas, and 2 (4%) surgical site infections. There was one total and one partial flap failure with a 30-day reoperation rate of 4%. CONCLUSIONS: MVFTT of the head and neck appears to be safe in patients on chronic pharmacologic immunosuppression.