Immune Checkpoint Inhibitor Therapy for Periocular Merkel Cell Carcinoma.

We herein report four patients with periocular Merkel cell carcinoma treated with immune checkpoint inhibitors who experienced a dramatic response and, therefore, had less morbid surgery and/or avoided radiation therapy with its inherent ocular toxicity.

Survival Outcomes of Temporal Bone Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: Temporal bone squamous cell carcinoma (TBSCC) is a rare malignancy with poor prognosis, and optimal treatment for advanced cases is uncertain. Our systematic literature review aimed to assess 5-year survival outcomes for advanced TBSCC across different treatment modalities. DATA SOURCES: EMBASE, Medline, PubMed, and Web of Science. REVIEW METHODS: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for articles published between January 1989 and June 2023. RESULTS: The review yielded 1229 citations of which 31 provided 5-year survival data for TBSCC. The final analysis included 1289 patients. T classification data was available for 1269 patients and overall stage for 1033 patients. Data for 5-year overall survival (OS) was 59.6%. Five-year OS was 81.9% for T1/2 and 47.5% for T3/4 (P < .0001). OS for T1/T2 cancers did not significantly differ between surgery and radiation (100% vs 81.3%, P = .103). For advanced-stage disease (T3/T4), there was no statistical difference in OS when comparing surgery with postoperative chemoradiotherapy (CRT) (OS 50.0%) versus surgery with postoperative radiotherapy (XRT) (OS 53.3%) versus definitive CRT (OS 58.1%, P = .767-1.000). There was not enough data to assess the role of neoadjuvant CRT. CONCLUSION: Most patients will present with advanced-stage disease, and nodal metastasis is seen in nearly 22% of patients. This study confirms the prognostic correlation of the current T classification system. Our results suggest that OS did not differ significantly between surgery and XRT for early stage disease, and combined treatment modalities yield similar 5-year OS for advanced cancers.

Checkpoint Inhibition in Addition to Dabrafenib/Trametinib for BRAFV600E-Mutated Anaplastic Thyroid Carcinoma.

Background: The dabrafenib plus trametinib combination (DT) has revolutionized the treatment of BRAFV600E-mutated anaplastic thyroid carcinoma (BRAFm-ATC). However, patients eventually develop resistance and progress. Single-agent anti-PD-1 inhibitor spartalizumab has shown a median overall survival (mOS) of 5.9 months. Combination of immunotherapy with BRAF/MEK inhibitors (BRAF/MEKi) seems to improve outcomes compared with BRAF/MEKi alone, although no direct comparison is available. BRAF-targeted therapy before surgery (neoadjuvant approach) has also shown improvement in survival. We studied the efficacy and safety of DT plus pembrolizumab (DTP) compared with current standard-of-care DT alone as an initial treatment, as well as in the neoadjuvant setting. Methods: Retrospective single-center study of patients with BRAFm-ATC treated with first-line BRAF-directed therapy between January 2014 and March 2023. Three groups were evaluated: DT, DTP (pembrolizumab added upfront or at progression), and neoadjuvant (DT before surgery, and pembrolizumab added before or after surgery). The primary endpoint was mOS between DT and DTP. Secondary endpoints included median progression-free survival (mPFS) and response rate with DT versus DTP as initial treatments, and the exploratory endpoint was mOS in the neoadjuvant group. Results: Seventy-one patients were included in the primary analysis: n = 23 in DT and n = 48 in DTP. Baseline demographics were similar between groups, including the presence of metastatic disease at start of treatment (p = 0.427) and prior treatments with surgery (p = 0.864) and radiation (p = 0.678). mOS was significantly longer with DTP (17.0 months [confidence interval CI, 11.9-22.1]) compared with DT alone (9.0 months [CI, 4.5-13.5]), p = 0.037. mPFS was also significantly improved with DTP as the initial treatment (11.0 months [CI, 7.0-15.0]) compared with DT alone (4.0 months [CI, 0.7-7.3]), p = 0.049. Twenty-three patients were in the exploratory neoadjuvant group, where mOS was the longest (63.0 months [CI, 15.5-110.5]). No grade 5 adverse events (AEs) occurred in all three cohorts, and 32.4% had immune-related AEs, most frequently hepatitis and colitis. Conclusions: Our results show that in BRAFm-ATC, addition of pembrolizumab to dabrafenib/trametinib may significantly prolong survival. Surgical resection of the primary tumor after initial BRAF-targeted therapy in selected patients may provide further survival benefit. However, conclusions are limited by the retrospective nature of the study. Additional prospective data are needed to confirm this observation.

Canadian French Translation and Validation of the Neck Dissection Impairment Index: A Quality of Life Measure for the Surgical Oncology Population.

BACKGROUND: Neck dissections (ND) are a routine procedure in head and neck oncology. Given the postoperative functional impact that some patients experience, it is imperative to identify and track quality of life (QoL) symptomatology to tailor each patient's therapeutic needs. To date, there is no validated French-Canadian questionnaire for this patient-population. We therefore sought to translate and validate the Neck Dissection Impairment Index (NDII) in Canadian French. METHODS: A 3-phased approach was used. Phase 1: The NDII was translated from English to Canadian French using a "forward and backward" translational technique following international guidelines. Phase 2: A cognitive debriefing session was held with 10 Canadian French-speaking otolaryngology patients to evaluate understandability and acceptability. Phase 3: The final version was administered prospectively to 30 patients with prior history of ND and 30 control patients. These patients were asked to complete the questionnaire 2 weeks after their first response. Test-retest reliability was calculated with Spearman's correlation. Internal consistency was elicited using Cronbach's alpha. RESULTS: NDII was successfully translated and validated to Canadian French. Cronbach's alpha revealed high internal consistency (0.92, lower 95% confidence limit 0.89). The correlation for test-retest validity were strong or very strong (0.61-0.91). CONCLUSION: NDII is an internationally recognized QoL tool for the identification of ND-related impairments. This validated Canadian French version will allow clinicians to adequately assess the surgery-related QoL effect of neck surgery in the French-speaking population, while allowing French institutions to conduct and/or participate in multisite clinical trials requiring the NDII as an outcome measure.

Initial Management of BRAF V600E-Variant Anaplastic Thyroid Cancer: The FAST Multidisciplinary Group Consensus Statement.

Importance: BRAF/MEK inhibitors revolutionized the treatment of BRAF V600E-variant anaplastic thyroid carcinoma (BRAFv-ATC), offering improved outcomes for patients with this previously incurable disease. Observations: Anaplastic thyroid carcinoma (ATC) accounts for approximately half of thyroid cancer-related deaths. It presents as a rapidly growing tumor that often invades locoregional structures and spreads to distant sites early; therefore, prompt diagnosis, staging, and treatment initiation are of the essence in the treatment of ATC. Although most oncologists will encounter a patient with ATC in their practice, the rarity of this disease makes treatment challenging, particularly because those with BRAFv-ATC no longer have a dismal prognosis. BRAF/MEK kinase inhibitors have transformed the outlook and treatment of BRAFv-ATC. Therefore, molecular profiling to identify these patients is critical. More recently, the addition of immunotherapy to BRAF/MEK inhibitors as well as the use of the neoadjuvant approach were shown to further improve survival outcomes in BRAFv-ATC. Many of these recent advances have not yet been incorporated in the currently available guidelines, allowing for disparities in the treatment of patients with BRAFv-ATC across the US. With the increasing complexity in the management of BRAFv-ATC, this Consensus Statement aims to formulate guiding recommendations from a group of experts to facilitate therapeutic decision-making. Conclusions and Relevance: This Consensus Statement from the FAST (Facilitating Anaplastic Thyroid Cancer Specialized Treatment) group at MD Anderson Cancer Center emphasizes that rapid identification of a BRAF V600E pathogenic variant and timely initiation of sequential therapy are critical to avoid excess morbidity and mortality in patients with BRAFv-ATC. In the past decade, remarkable progress has been made in the treatment of patients with BRAFv-ATC, justifying these new evidence-based recommendations reached through a consensus of experts from a high-volume center.