Recurrent Squamous Cell Carcinoma Research Articles

Correction: Effectiveness and safety of weekly paclitaxel and cetuximab as a salvage chemotherapy following immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: a multicenter clinical study

Correction: Effectiveness and safety of weekly paclitaxel and cetuximab as a salvage chemotherapy following immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: a multicenter clinical study

Network meta-analysis of pembrolizumab as monotherapy and in combination with chemotherapy for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma

Pembrolizumab monotherapy or in combination with chemotherapy is approved as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on improved overall survival (OS) versus EXTREME regimen in the KEYNOTE-048 trial. The clinical outcomes of pembrolizumab were compared with other recommended first-line treatments in R/M HNSCC in this study through a Bayesian network meta-analysis. A systematic literature review was conducted in July 2022, from which six trials that matched the KEYNOTE-048 patient eligibility criteria were included in the network. The OS and progression-free survival (PFS) outcomes were compared in the approved pembrolizumab indication (i.e., total population for pembrolizumab in combination with chemotherapy and combined positive score [CPS] ≥ 1 population for pembrolizumab monotherapy). A significant OS improvement was observed for pembrolizumab in combination with chemotherapy and pembrolizumab monotherapy versus EXTREME regimen (hazard ratio, 95% credible interval: 0.72, 0.60-0.86; 0.73, 0.60-0.88), platinum+5- FU (0.58, 0.43-0.76; 0.58, 0.44-0.78), and platinum+paclitaxel (0.53, 0.35-0.79; 0.53, 0.35-0.81), respectively. A non-significant numeric trend in OS improvement was observed versus the TPEx regimen. PFS was comparable with most first-line treatments and was improved versus platinum+5-FU (0.48, 0.36-0.64; 0.59, 0.45-0.79). Additional analyses in higher CPS subgroups also showed consistent results. Overall, our study results showed an improvement in OS outcomes versus alternative first-line treatments, consistent with the findings of the KEYNOTE-048 trial. These data support using pembrolizumab as a suitable firstline treatment option in R/M HNSCC.

Immunotherapy for Head and Neck Squamous Cell Carcinoma: Present and Future Approaches and Challenges.

Despite significant progress and improving outcomes in the management of head and neck squamous cell carcinoma (HNSCC), there are few effective treatment options for patients with recurrent or metastatic head and neck squamous cell carcinoma. The advent of immune checkpoint inhibitors has changed the treatment algorithm of head and neck squamous cell carcinoma and are approved in the frontline setting for recurrent and metastatic (R/M) head and neck squamous cell carcinomas. Although promising for some patients, most patients with R/M HNSCC do not derive clinical benefit from currently approved checkpoint inhibitors. Many studies are underway to identify the patient population that would benefit the most from immunotherapy as well as postimmunotherapy treatment failures, including novel combinations of immunomodulatory therapies. In this review, we summarize the clinical development of all major clinical trials of immunotherapy in HNSCC.

Phase II Study to Determine the Antitumor Activity and Safety of Simlukafusp Alfa (FAP-IL2v) Combined with Atezolizumab in Esophageal Cancer.

In this study, we report the results from the esophageal squamous cell carcinoma (SCC) cohort of a phase II, noncomparative, basket study evaluating the antitumor activity and safety of fibroblast activation protein-IL2 variant (FAP-IL2v) plus atezolizumab in patients with advanced/metastatic solid tumors (NCT03386721). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 to 1; measurable metastatic, persistent, or recurrent esophageal SCC; progression on ≥1 prior therapy; and were checkpoint inhibitor-naïve. Patients received FAP-IL2v 10 mg plus atezolizumab 1,200 mg intravenously every 3 weeks, or FAP-IL2v weekly for 4 weeks and then every 2 weeks plus atezolizumab 840 mg intravenously every 2 weeks. The primary endpoint was investigator-assessed objective response rate (ORR). In the response-evaluable population (N = 34), the best confirmed ORR was 20.6% [95% confidence interval (CI), 10.4-36.8], with a complete response seen in 1 patient and partial responses in 6 patients. The disease control rate was 44.1% (complete response = 2.9%; partial response = 17.6%; stable disease = 23.5%), and the median duration of response was 10.1 mon/ths (95% CI, 5.6-26.7). The median progression-free survival was 1.9 months (95% CI, 1.8-3.7). Analysis of response by PDL1 expression (Ventana SP263) resulted in an ORR of 26.7% for patients with PDL1-positive tumors (tumor area positivity cutoff ≥1%; n = 15) and 7.1% for patients with PDL1-negative tumors (tumor area positivity cutoff <1%; n = 14). Overall, the treatment combination was tolerable, and adverse events were consistent with the known safety profiles of each drug. FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.

Increased prevalence of recurrence in squamous cell carcinoma arising from buccal mucosa: A pervasive threat requiring multidimensional perspectives

Perspective goalSquamous cell carcinoma (SCC) of the buccal mucosa is at a higher risk of local recurrence. Surgery in this area is complex and frequently results in close or positive margins, which increases the risk of recurrence. A margin distance of less than 1 mm from the tumour is linked to a higher rate of recurrence. DiscussionAnatomic, genetic, environmental, and lifestyle factors contribute to its resurgence. Effective prevention strategies, early detection, and treatment require a multidimensional approach. Understanding genetic, environmental, and socio-cultural factors can help develop effective prevention strategies, improve early detection, and enhance treatment outcomes. ConclusionDespite advancements in medical technology and awareness campaigns, the aggressive nature of SCC and its adverse impact on patient's quality of life necessitates a comprehensive understanding of its factors. A comprehensive and multidimensional approach is crucial for combating this pervasive public health threat. By integrating this knowledge into prevention strategies, healthcare professionals can work towards reducing the burden of SCC and enhancing patients' quality of life.

Correlation of Prognostic Nutritional Index and Systemic Immune-Inflammation Index with the Recurrence and Prognosis in Oral Squamous Cell Carcinoma with the Stage of III/IV.

This study aimed to explore the correlation of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) with the recurrence and prognosis in patients with advanced oral squamous cell carcinoma (OSCC). A total of 298 OSCC patients with the stage of III/IV were finally included in the study. SII = neutrophil count (109/L) × platelet count (109/L)/lymphocyte count (109/L). PNI = serum albumin (g/L) + 5 × total lymphocyte count (109/L). High preoperative SII and low preoperative PNI were independent risk factors for tumor recurrence in OSCC patients of the stage of III/IV. The area under the curves (AUC) for SII was 0.69 (0.63 to 0.76), for PNI was 0.72 (0.67 to 0.78), and for joint model was 0.81 (0.76 to 0.85). Patients with low level of joint model had significantly higher overall survival rate for 5 years follow-up than those with high level. Both preoperative SII and PNI are valuable independent tumor recurrence prediction index in patients with advanced OSCC. Meanwhile, the combination of preoperative SII and PNI is also valuable on OSCC recurrence and prognosis prediction.

Programmed Death Ligand-1 and Tumor Burden Score Dictate Treatment Responses in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC. R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan-Meier curves were plotted for outcomes estimation. A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB (p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB (p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS. Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment.

Combined approach for predicting the efficacy of nivolumab in head and neck carcinoma by tissue and soluble expressions of PD-L1 and PD-L2.

Predictive biomarkers for nivolumab in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) have not yet been established. The tumor proportion score (TPS), combined positive score (CPS), and soluble forms of programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2) were retrospectively analyzed in patients with RMHNSCC treated with nivolumab. The positivity rates for TPS (PD-L1), CPS (PD-L1), TPS (PD-L2), and CPS (PD-L2) were 73.8%, 78.2%, 56.4%, and 78.2%, respectively. Patients with high TPS (PD-L1), CPS (PD-L1), or CPS (PD-L1 and PD-L2) showed significantly prolonged progression-free survival. Favorable overall survival was associated with high CPS (PD-L1 and PD-L2) and low soluble PD-L1 and PD-L2 levels. The expressions of tissue and soluble PD-L1/2 were not correlated. Our study revealed that compared to PD-L1 expression alone, dual expression of PD-L1 and PD-L2 in tissue or soluble form could be feasible biomarkers in patients with RMHNSCC who received nivolumab.

Occult neck metastasis in salvage laryngectomy: a road map for super-selective neck dissection.

This study aimed to solve the debate over the role and extent of neck dissection to treat any occult nodal metastasis in patients undergoing salvage laryngectomy for recurrent and/or residual squamous cell carcinoma of larynx. This was a retrospective study over a time frame of 6 years (2016-2022) of 74 patients who underwent bilateral neck dissection and salvage laryngectomy for recurrent or persistent disease with N0 neck. We calculated the incidence of occult nodal metastasis in ipsilateral and contralateral neck. Incidence of ipsilateral neck disease was calculated as 8.11 per cent and it was 0 per cent in contralateral neck. Regarding ipsilateral nodal level distribution, level II was the highest at 6.76 per cent, followed by level III at 5.41 per cent. There was 0 per cent metastasis in levels IV and IIb. In patients undergoing salvage laryngectomy with N0 neck, ipsilateral super selective neck dissection is considered a convenient and oncologically safe option to treat the neck.

Serum Albumin as an Independent Predictor of Long-Term Survival in Patients with Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab.

Background: Nivolumab has been shown to improve the overall survival (OS) of patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, there is a need to identify factors associated with long-term survival (beyond 2 years) in these patients. This study investigated the relationship between pretreatment factors and long-term survival in patients with R/M HNSCC treated with nivolumab. Methods: Forty-nine patients with R/M HNSCC who were treated with nivolumab were retrospectively reviewed. Baseline characteristics, clinical data, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify factors associated with long-term survival (OS ≥ 2 years). Results: The median OS in the overall cohort was 11.0 months, and the 2-year survival rate was 34.7%. Long-term survivors (OS ≥ 2 years) had significantly higher proportions of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of 0 or 1, serum albumin levels ≥ 3.5 g/dL, and neutrophil-to-eosinophil ratio (NER) < 32.0 compared to non-long-term survivors. On multivariate analysis, serum albumin levels ≥ 3.5 g/dL, in addition to ECOG-PS score of 0 or 1, were independent predictors of long-term survival. Conclusions: Pretreatment serum albumin levels may be useful for predicting long-term survival in R/M HNSCC patients treated with nivolumab.

Radiomic biomarkers of locoregional recurrence: prognostic insights from oral cavity squamous cell carcinoma preoperative CT scans.

This study aimed to identify CT-based imaging biomarkers for locoregional recurrence (LR) in Oral Cavity Squamous Cell Carcinoma (OSCC) patients. Computed tomography scans were collected from 78 patients with OSCC who underwent surgical treatment at a single medical center. We extracted 1,092 radiomic features from gross tumor volume in each patient's pre-treatment CT. Clinical characteristics were also obtained, including race, sex, age, tobacco and alcohol use, tumor staging, and treatment modality. A feature selection algorithm was used to eliminate the most redundant features, followed by a selection of the best subset of the Logistic regression model (LRM). The best LRM model was determined based on the best prediction accuracy in terms of the area under Receiver operating characteristic curve. Finally, significant radiomic features in the final LRM model were identified as imaging biomarkers. Two radiomics biomarkers, Large Dependence Emphasis (LDE) of the Gray Level Dependence Matrix (GLDM) and Long Run Emphasis (LRE) of the Gray Level Run Length Matrix (GLRLM) of the 3D Laplacian of Gaussian (LoG σ=3), have demonstrated the capability to preoperatively distinguish patients with and without LR, exhibiting exceptional testing specificity (1.00) and sensitivity (0.82). The group with LRE > 2.99 showed a 3-year recurrence-free survival rate of 0.81, in contrast to 0.49 for the group with LRE ≤ 2.99. Similarly, the group with LDE > 120 showed a rate of 0.82, compared to 0.49 for the group with LDE ≤ 120. These biomarkers broaden our understanding of using radiomics to predict OSCC progression, enabling personalized treatment plans to enhance patient survival.

The Genomic, Transcriptomic, and Immunologic Landscape of HRAS Mutations in Solid Tumors.

Tipifarnib is the only targeted therapy breakthrough for HRAS-mutant (HRASmt) recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The molecular profiles of HRASmt cancers are difficult to explore given the low frequency of HRASmt. This study aims to understand the molecular co-alterations, immune profiles, and clinical outcomes of 524 HRASmt solid tumors including urothelial carcinoma (UC), breast cancer (BC), non-small-cell lung cancer (NSCLC), melanoma, and HNSCC. HRASmt was most common in UC (3.0%), followed by HNSCC (2.82%), melanoma (1.05%), BC (0.45%), and NSCLC (0.44%). HRASmt was absent in Her2+ BC regardless of hormone receptor status. HRASmt was more frequently associated with squamous compared to non-squamous NSCLC (60% vs. 40% in HRASwt, p = 0.002). The tumor microenvironment (TME) of HRASmt demonstrated increased M1 macrophages in triple-negative BC (TNBC), HNSCC, squamous NSCLC, and UC; increased M2 macrophages in TNBC; and increased CD8+ T-cells in HNSCC (all p < 0.05). Finally, HRASmt was associated with shorter overall survival in HNSCC (HR: 1.564, CI: 1.16-2.11, p = 0.003) but not in the other cancer types examined. In conclusion, this study provides new insights into the unique molecular profiles of HRASmt tumors that may help to identify new targets and guide future clinical trial design.

Fragile hands: targeting nonmelanoma skin cancer on older hands using 595nm pulsed dye laser.

The mainstay of treatment for nonmelanoma skin cancer (NMSC) on thin skin remains surgical, but procedures on older hands may be complicated by skin fragility and dermal atrophy. Used without cooling, 595nm (nm) pulsed dye laser (PDL) has the capability of destroying NMSC through nonspecific thermal necrosis. The purpose of this study was to understand recurrence of NMSC on dorsal hands of older patients after one or two treatments using 595nm PDL. A retrospective chart review identified 147 cases of NMSC located on the dorsal hands treated with 595nm PDL. Cases of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) were included. All patients received one to two treatments with PDL. The primary outcome was the recurrence of carcinoma. Among NMSC cases treated with PDL, recurrence occurred in 12 patients (8.2%). No cases of BCC recurred during the study period. Recurrence of SCC was 4.7% for SCC in situ and 10.4% recurrence for invasive SCC (p = 0.34). Among 71 patients treated once, recurrence occurred in 10 patients (14.1%), and among 76 cases treated twice, recurrence occurred in 2 patients (2.6%, p = 0.01). Two treatments of PDL for NMSC on the dorsal hands of older patients was well tolerated, had low recurrence, and seemed more effective than one treatment.

Oncologic Outcomes of Salvage Surgery in Recurrent Oral Tongue Squamous Cell Carcinoma.

This study aimed to determine the oncologic outcomes and identify prognostic factors in patients undergoing salvage glossectomy for recurrent oral tongue squamous cell carcinoma (OTSCC). A retrospective chart review was conducted encompassing all patients who underwent salvage oral glossectomy out of 259 individuals undergoing oral glossectomy at a tertiary academic center. Inclusion criteria comprised patients who met the following conditions: 1) biopsy-proven oral tongue recurrence, 2) salvage glossectomy performed with curative intent, 3) availability of imaging records, and 4) comprehensive documentation. Cases involving base of tongue tumors and second primaries were excluded from the analysis. Categorical data were expressed as proportions, and continuous data as medians/quartiles. Univariate analysis used Fisher's exact test for categorical variables and Student's t-test for continuous ones. Survival analysis employed Kaplan-Meier estimates and the log-rank test. High-risk histopathological risk factors were significantly more common with recurrence compared to initial presentation. The mean locoregional disease-free interval was 35 months.Kaplan-Meier estimates for one- and three-year disease-free survival (DFS) were 62.7% and 33.4%, while disease-specific survival (DSS) rates were 73% and 38.9%, respectively.Recurrent T-stage was a predictor for DFS, while margin status was a strong predictor for both LR control (p = 0.024) and DSS (p = 0.030), as was perineural invasion (p = 0.001 and p = 0.030). Alcohol use was associated with worse overall survival (p = 0.024).In contrast to other reports, nodal status was not a predictor in this series. Upon recurrence, histopathological analysis unveils detrimental changes in tumor biology, which significantly influence disease control. Notably, consistent with findings from other studies, factors, such as recurrent T-stage, presence of perineural invasion, and, most importantly, margin status, play pivotal roles in determining oncologic outcomes. Consequently, the imperative for aggressive salvage surgery becomes evident in achieving sufficient disease control. This underscores the necessity for proactive management strategies aimed at addressing these factors to enhance patient outcomes.

Re-irradiation versus systemic therapy for the management of local-regionally recurrent head and neck cancer

PurposeThe optimal management of local-regionally recurrent head and neck cancer that is not amenable to surgical resection is uncertain. We sought to compare outcomes among patients treated with and without re-irradiation in this setting. Methods and MaterialsA review of institutional registries identified 65 patients with local-regionally recurrent squamous cell carcinoma of the head and neck who were ineligible for surgery. Forty patients (62 %) opted for re-irradiation with the remaining 25 patients (38 %) undergoing initial systemic therapy alone. All patients had measurable disease. Forty-three patients (66 %) were male and twenty-two (33 %) were female. The median age at the time of recurrence was 59 years (range, 39–84 years). The most common primary sites of disease were the oropharynx, (n = 25), oral cavity (N = 19), and nasopharynx (n = 11). The median interval from completion of prior radiation to the diagnosis of recurrent disease was 35 months (range, 2–102 months). ResultsRe-irradiation improved 2-year overall survival, (32 % versus 11 %), progression-free survival (31 % versus 7 %), and local–regional control (39 % versus 3 %) compared to systemic therapy alone (p < 0.05, for both). The likelihood of developing any new grade 3+ toxicity was significantly higher among patients treated by re-irradiation compared to those treated by systemic therapy (53 % vs. 28 %, p < 0.001). There were 3 treatment-related fatalities, all of which occurred in the re-irradiation group. The incidence of grade 3+ late toxicity was 48 % and 12 % for patients in the re-irradiation and systemic therapy cohorts, respectively (p < 0.001). ConclusionAlthough re-irradiation improved overall survival compared to systemic therapy for appropriately selected patients with local-regionally recurrent head and neck cancer, the relatively high risk of toxicity must be considered.

Considerable interlaboratory variation in PD-L1 positivity forhead and neck squamous cell carcinoma in the Netherlands- A nationwide evaluation study.

Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are eligible for first-line immune checkpoint inhibition if their tumour is positive for programmed death ligand 1 (PD-L1) determined by the combined positive score (CPS). This nationwide study, using real-world data, investigated the developing PD-L1 testing landscape in the first 3 years after introduction of the test in HNSCC and examined interlaboratory variation in PD-L1 positivity rates. Pathology reports of HNSCC patients mentioning PD-L1 were extracted from the Dutch Pathology Registry (Palga). Tumour and PD-L1 testing characteristics were analysed per year and interlaboratory variation in PD-L1 positivity rates was assessed using funnel plots with 95% confidence limits around the overall mean. A total of 817 PD-L1 tests were reported in 702 patients among 19 laboratories; 85.2% of the tests on histological material were stated to be positive. The national PD-L1 positivity rate differed significantly per year during the study period (79.7-89.9%). The use of the recommended 22C3 antibody increased from 59.9 to 74.3%. A total of 673 PD-L1 tests on histological material from 12 laboratories were analysed to investigate interlaboratory variation. Four (33%) deviated significantly from the national mean of PD-L1-positive cases using CPS ≥ 1 cut-off, while two (17%) deviated significantly for CPS ≥ 20 cut-off. In the first 3 years of PD-L1 assessment in HNSCC, the testing landscape became more uniform. However, interlaboratory variation in PD-L1 positivity rates between Dutch laboratories was substantial. This implies that there is a need for further test standardisation to reduce this variation.

Is Perineural Invasion an Independent Prognostic Factor for Local Recurrence in Oral Squamous Cell Carcinoma?

The purpose of this study was to analyse the independent prognostic significance of perineural invasion (PNI) on local recurrence (LR) in patients with oral squamous cell carcinoma (OSCC) managed primarily with surgery. Clinical and histopathological data of 195 patients with OSCC were analysed retrospectively to identify risk factors associated with PNI and to evaluate its significant correlation with local recurrence, overall survival (OS) and recurrence free survival (RFS). Patients were followed for a mean period of 39.5 ± 1.376months and median 35months. PNI was found in 57 patients (29.2%). PNI correlated with tongue subsite (p = 0.001), nodal metastasis (p < 0.000), depth of invasion (DOI) (p = 0.002), stage (p = 0.013) and adjuvant therapy (p < 0.001). Mean time to recurrence with PNI was significantly shorter (p = 0.002).Multivariate analysis did not establish significant relationship between PNI and LR. Kaplan-Meier curve did not show statistical significance with OS (p = 0.085) or RFS (p = 0.110). PNI remains an aggressive factor for nodal metastasis mandating neck management for regional control. Though PNI showed no statistical significance with LR, time to recurrence in PNI positive patients were significantly shorter. Hence, close follow-up regimen becomes necessary.

Diabetes Mellitus Induced by Nivolumab plus Regorafenib in a Patient with Esophageal Cancer

Abstract Nivolumab is now preferred as first-line and second-line treatment for advanced esophageal cancer, while regorafenib improves survival in refractory gastroesophageal cancer. The combined use of nivolumab and regorafenib has shown promising results. Nivolumab-induced thyroid dysfunction is a common immune-related adverse event (irAE), while type 1 diabetes mellitus induced by immune checkpoint inhibitors is rare and usually permanent. It is unclear whether the combination of regorafenib and nivolumab increases the risk of irAEs. We report a patient with recurrent esophageal squamous cell carcinoma who was treated with nivolumab plus regorafenib and developed thyroiditis and diabetic ketoacidosis. The rechallenge was successful, and the patient achieved a good treatment response.

Clinical Results and Prognostic Factors in Boron Neutron Capture Therapy for Recurrent Squamous Cell Carcinoma of the Head and Neck Under the Japan National Health Insurance System: A Retrospective Study of the Initial 47 Patients

PurposeRecurrent head and neck cancer presents a therapeutic challenge due to cumulative toxicity from initial radiation therapy, limiting re-irradiation options. Boron neutron capture therapy (BNCT) offers a promising alternative, selectively delivering a radical dose to tumors while sparing adjacent normal tissue. This study investigates the initial clinical outcomes and prognostic factors associated with BNCT for recurrent squamous cell carcinoma of the head and neck. Materials and MethodsThis retrospective analysis investigated the initial 47 patients treated with BNCT between May 2020 and February 2021 in Japan. All patients had received radiotherapy with a median dose of 70 Gy (range, 44–176) prior to BNCT. Median tumor size was 11 cm3 (range, 1–117 cm3), with 23% of tumors larger than 30 cm3, and 87% of patients had prior systemic therapy. The most common prescribed dose to the pharyngeal mucosa was 15 Gy-Eq (36%), followed by 18 Gy-Eq (34%). The minimum dose given to tumor was 27.4 Gy-Eq (range, 13.3–45.2). In 23 patients, 18F-FBPA-PET was performed within 1 week before BNCT, tumor to blood 10B ratio was 3.5 (range, 2.0–8.7). ResultsEfficacy analysis revealed a 51% complete response rate and a 74% overall response rate. Disease-free survival rates at 1 and 2 years were 34.6% and 26.6%, respectively. Overall survival rates at 1 and 2 years were 86.1% and 66.5%, respectively. Multivariate analysis revealed that, among the patient characteristics, whether the lesion was mucosal had a significant impact on achieving complete response. ConclusionsThis study provided valuable insights into the early integration of BNCT into routine clinical practice, highlighting its efficacy and safety. Technical improvements are needed to ensure precise dose administration. Ongoing prospective studies, such as the phase II REBIVAL study, will further elucidate the role of BNCT in recurrent head and neck cancer.

Toxicity profiles of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) are widely used in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC); however, the toxicity profiles are inconclusive. Clinical trials evaluating ICIs for R/M HNSCC were searched from online databases. The characteristics of the studies and the results of incidences of any grade treatment-related adverse events (trAEs), grade three or more trAEs, treatment-related deaths, trAEs leading to discontinuation of treatment, and specific trAEs were extracted. Twenty studies with 3756 patients were included. The pooled incidences of any grade trAEs, grade three or more trAEs, treatment-related deaths, trAEs leading to discontinuation of treatment for overall population were 62.07% (95% CI, 59.07%-65.02%), 13.82% (95% CI, 11.23%-16.62%), 0.39% (95% CI, 0.15%-0.71%), 3.99% (95% CI, 2.36%-5.95%), respectively. Programmed cell death protein 1 (PD-1) inhibitors monotherapy and ICIs combination therapy had significantly higher incidences of any grade trAEs (odds ratio [OR], 1.25, 95% CI, 1.05-1.49 and 1.36, 95% CI, 1.15-1.60, respectively), grade three or more trAEs (OR, 1.41, 95% CI, 1.08-1.84 and 1.79, 95% CI, 1.39-2.30, respectively), trAEs leading to discontinuation of treatment (OR, 3.98, 95% CI, 2.06-7.70 and 10.14, 95% CI, 5.49-18.70, respectively) compared with programmed death-ligand 1 (PD-L1) inhibitors monotherapy. ICIs combination therapy had a significantly higher incidence of grade three or more trAEs compared with PD-1 inhibitors monotherapy (OR, 1.27, 95% CI, 1.03-1.55); however, the incidences of any grade trAEs and trAEs leading to discontinuation of treatment were not significant different. Our study suggests that the incidences of grade three or more trAEs, treatment-related deaths, and trAEs leading to discontinuation of treatment are low in R/M HNSCC patients treated with ICIs. PD-L1 inhibitors monotherapy may be safer compared with PD-1 inhibitors monotherapy and ICIs combination therapy.