Boron neutron capture therapy: moving towards targeted therapy for locally recurrent head and neck squamous cell carcinoma

Locally recurrent head and neck squamous cell carcinoma(HNSCC)is often unresectable,and a repeat course of radiotherapy is associated with incremental toxicities.Boron neutron capture therapy(BNCT)is a novel targeted radiotherapy modality that can achieve a high dose gradient between cancerous and adjacent normal tissues.However,the relationships among the dose resulting from BNCT,tumor response to BNCT,and survival are not completely understood.Recently,a study published in Radiotherapy and Oncology investigated the efficacy of BNCT in the treatment of patients with locally recurrent HNSCC and the factors associated with favorable treatment response and survival.In this article,the findings,strengths and limitations of this study are discussed in depth,and the significance of the study and motivations for future research are highlighted.

First-line cisplatin,docetaxel,and cetuximab for patients with recurrent or metastatic head and neck cancer:A multicenter cohort study

BACKGROUND The targeted therapy cetuximab[directed at the epidermal growth factor receptor(EGFR)]in combination with 5-fluorouracil and platinum-based chemotherapy(the EXTREME regimen)has shown substantial efficacy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck(R/M SCCHN).Thus,this scheme has been established as the preferred first-line option for these patients.However,more recently,a new strategy combining platinum,taxanes,and cetuximab(the TPEx regimen)has demonstrated similar efficacy with a more favorable toxicity profile in clinical trials.AIM To evaluate the safety and efficacy of the TPEx scheme as first-line therapy in advanced SCCHN in a multicenter cohort study.METHODS This retrospective multicenter cohort study included patients with histologically confirmed recurrent or metastatic SCCHN treated with first-line TPEx at five medical centers in Argentina between January 1,2017 and April 31,2020.Chemotherapy consisted of four cycles of docetaxel,cisplatin,and cetuximab followed by cetuximab maintenance therapy.Clinical outcomes and toxicity profiles were collected from medical charts.Treatment response was assessed by the investigator in accordance with Response Evaluation Criteria in Solid Tumors(version 1.1).Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 4.0).RESULTS Twenty-four patients were included.The median age at diagnosis was 58 years(range:36-77 years).The majority of patients(83.3%)received at least four chemotherapy cycles in the initial phase.In the included group,the overall response rate was 62.5%,and 3 patients achieved a complete response(12.5%).The median time to response was 2.4 mo[95% confidence interval(CI):1.3-3.5].With a median follow-up of 12.7 mo(95%CI:8.8-16.6),the median progression-free survival(PFS)was 6.9 mo(95%CI:6.5-7.3),and the overall survival rate at 12 mo was 82.4%.Patients with documented tumor response showed a better PFS than those with disease stabilization or progression[8.5 mo(95%CI:5.5-11.5)and 4.5 mo(95%CI:2.5-6.6),respectively;P=0.042].Regarding the safety analysis,two-thirds of patients reported at least one treatment-related adverse event,and 25% presented grade 3 toxicities.Of note,no patient experienced grade 4 adverse events.CONCLUSION TPEx was an adequately tolerated regimen in our population,with low incidence of grade 3-4 adverse events.The median PFS were consistent with those in recent reports of clinical trials evaluating this treatment combination.This regimen may be considered an attractive therapeutic strategy due to its simplified administration,decreased total number of chemotherapy cycles,and treatment tolerability.

Immune checkpoint inhibitors in head and neck squamous cell carcinoma:A systematic review of phase-3 clinical trials

BACKGROUND The outcomes of patients diagnosed with head and neck squamous cell carcinoma(HNSCC)who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal.A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors(ICIs).The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIM To evaluate the evidence on the effectiveness of ICIs in HNSCC,based on published phase-3 clinical trials.METHODS We searched PubMed,Cochrane Library,Embase,and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC(R/M HNSCC)and locally advanced head and neck squamous cell carcinoma(LAHNSCC).We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma,recurrent,metastatic,locally advanced,immunotherapy,immune checkpoint inhibitors,monoclonal antibodies,programmed cell death protein-1(PD-1),programmed death-ligand 1(PD-L1),cytotoxic T-lymphocyte associated protein-4(CTLA-4),and phase-3 clinical trial.A sensitive search filter was used to limit our results to randomized controlled trials.RESULTS Five phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far:Four in R/M HNSCC and one in LAHNSCC.In patients with R/M HNSCC,anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care(standard singleagent systemic therapy).While the net gain in overall survival(OS)with nivolumab was 2.4 mo[hazard ratio(HR)=0.69,P=0.01],that with pembrolizumab was 1.5 mo(HR=0.80 nominal P=0.0161).The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T-lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes.In the first-line setting,in R/M HNSCC,pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo(HR=0.77,P=0.0034)in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive(combined positive score>20)population compared to standard of care(EXTREME regime).In patients with PD-L1 positive R/M HNSCC,monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME.In LAHNSCC,immunotherapy using avelumab(an anti-PD-L1 agent)along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSION Anti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings,with acceptable toxicity profiles compared to standard therapy.There is no proven efficacy in the curative setting to date.