Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma.

OBJECTIVES: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. MATERIALS AND METHODS: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression-free and overall survival. Progression-free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression-free and overall survival were identified using multivariate analysis. RESULTS: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1- and 2-year progression-free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression-free survival were performance status and immune-related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune-related adverse events. CONCLUSION: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.

Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study).

INTRODUCTION: In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC. METHODS AND ANALYSIS: This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoints are 3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias. ETHICS AND DISSEMINATION: This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: UMIN000027875.

Multicenter Retrospective Study of Weekly Cetuximab Plus Paclitaxel for Recurrent or Metastatic Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: This study was conducted to compare the efficacy and safety of the weekly cetuximab plus paclitaxel (wCmab-PTX) regimen with those of the EXTREME regimen in patients with recurrent or metastatic oral squamous cell carcinoma (R/M OSCC). PATIENTS AND METHODS: This multicenter retrospective study involved a chart review of the clinical records of R/M OSCC patients treated with wCmab-PTX in each institution between January 2013 and December 2017. Data were collected, and the efficacy, safety, and treatment outcomes were analyzed. RESULTS: The best overall response and disease control rates were 48.4% and 61.3%, respectively. The median PFS and OS were 6 and 13 months, respectively. There was no significant difference in prognosis with or without previous platinum administration. The grade 3-4 adverse events were leukopenia (16.1%), followed by acne-like rash (12.9%), and neutropenia (9.7%). All adverse events, excluding more than grade 3 infusion reactions, were tolerable and manageable. CONCLUSION: wCmab-PTX may be considered as a treatment option for R/M patients with OSCC that is refractory to platinum-based chemotherapy, or progressive disease after receiving chemotherapy.

Change in allodynia of patients with post-lingual nerve repair iatrogenic lingual nerve disorder.

PURPOSE: Mandibular third molar extractions are common treatment in oral maxillofacial surgery, but risk disturbance of the lingual nerves causing anesthesia, eating difficulty and allodynia, which can seriously reduce patient quality of life. This study investigates the change in allodynia before and after repair in patients with lingual nerve disorder. SUBJECTS AND METHODS: This retrospective cohort study comprises the 52 patients with affected lingual nerve after third molar extraction at our hospital over a 7-year period. Pre- and postoperative (6 months and 12 months) neurosensory records were analyzed. RESULTS: Fifty-two patients underwent lingual nerve repair and returned for at least 1 year of follow-up. Mean age was 36.8 ± 11.9. Median interval between injury and surgery was 5 (4, 8) months. In 92.9% of those with pain before surgery, allodynia disappeared postoperatively. CONCLUSIONS: This study shows that microsurgical lingual reconstructions are effective in patients with preoperative allodynia, but a small number of patients may have remaining allodynia after surgery. Large-scale, more detailed analysis of such cases is required.

PD-L1 expression correlated with p53 expression in oral squamous cell carcinoma.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. METHODS: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. RESULTS: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. CONCLUSION: The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

Risk of lingual nerve injuries in removal of mandibular third molars: a retrospective case-control study.

BACKGROUND: Through the analysis of clinical data, we attempted to investigate the etiology and determine the risk of severe iatrogenic lingual nerve injuries in the removal of the mandibular third molar. METHODS: A retrospective chart review was performed for patients who had undergone microsurgical repair of lingual nerve injuries. The following data were collected and analyzed: patient sex, age, nerve injury side, type of impaction (Winter's classification, Pell and Gregory's classification). Ratios for the respective lingual nerve injury group data were compared with the ratios of the respective data for the control group, which consisted of data collected from the literature. The data for the control group included previous patients that encountered various complications during the removal of the mandibular third molar. RESULTS: The lingual nerve injury group consisted of 24 males and 58 females. The rate of female patients with iatrogenic lingual nerve injuries was significantly higher than the control groups. Ages ranged from 15 to 67 years, with a mean age of 36.5 years old. Lingual nerve injury was significantly higher in the patient versus the control groups in age. The lingual nerve injury was on the right side in 46 and on the left side in 36 patients. There was no significant difference for the injury side. The distoangular and horizontal ratios were the highest in our lingual nerve injury group. The distoangular impaction rate in our lingual nerve injury group was significantly higher than the rate for the control groups. CONCLUSION: Distoangular impaction of the mandibular third molar in female patients in their 30s, 40s, and 50s may be a higher risk factor of severe lingual nerve injury in the removal of mandibular third molars.

Comparison of Subjective and Objective Assessments of Neurosensory Function after Lingual Nerve Repair.

OBJECTIVE: Mandibular third molar extractions are important in oral maxillofacial surgery. Damage to the lingual nerves, although rare, is a possible complication. There are reports of postoperative recovery after lingual nerve repair, but few reports have compared subjective and objective assessments of neurosensory function. Therefore, this study aims to compare subjective and objective assessments of neurosensory function after lingual nerve repair. SUBJECTS AND METHODS: This retrospective cohort study comprised 52 patients with lingual nerve anesthesia after third molar extraction at the Department of Oral and Maxillofacial Surgery, Wakayama Medical University Hospital, Wakayama, Japan, between December 2008 and December 2015. We recorded pre- and postoperative (6 months and 12 months) neurosensory examinations. RESULTS: Patient's subjective assessments of neurosensory function suggested improvement between the preoperative period and 12 months postoperation, although this difference was not significant. Objective assessment based on examination and testing, on the other hand, showed a significant difference in improvement (p < 0.05). CONCLUSIONS: There was no evidence that improvement of subjective preoperative and postoperative assessments was significantly associated with improvement of objective neurosensory assessments after lingual nerve repair. Overall physical condition and background were thought to affect subjective evaluation. Subjective assessment is important in conjunction with objective evaluation because it may reveal dysesthesia that would otherwise be missed. In the future, we will examine those cases in whom subjective assessments showed no improvement although objective assessments showed improvement.

Effect of duration from lingual nerve injury to undergoing microneurosurgery on improving sensory and taste functions: retrospective study.

BACKGROUND: The prognosis of recovery following microneurosurgery for injured lingual nerves varies among individual cases. This study aimed to investigate if recovery ratios of sensory and taste functions are improved by the microneurosurgery within 6 months after lingual nerve injury. METHODS: We retrospectively assessed 70 patients who underwent microneurosurgery at the Wakayama Medical University Hospital for lingual nerve injuries between July 2004 and December 2016. Sensory and taste functions in lingual nerves were preoperatively evaluated using a static two-point discrimination test, an intact superficial pain/tactile sensation test, and a taste discrimination test. They were evaluated again at 12 and at 24 months postoperatively. The abundance ratio of Schwann cells in the excised traumatic neuromas was analyzed with ImageJ software following immunohistochemistry with anti S-100ß antibody. RESULTS: In early cases (microneurosurgery within 6 months after the injury), recovery ratios of sensory and taste functions were not significantly different at 24 months after microneurosurgery compared with later cases (microneurosurgery more than 6 months after the injury). Meanwhile, the ratio of patients with taste recovery within 12 months after microneurosurgery was significantly decreased in late cases compared with early cases. The abundance ratio of Schwann cells in traumatic neuroma was also significantly lower in later cases. CONCLUSION: Microneurosurgery more than 6 months after lingual nerve injury did not lead to decreased recovery ratio of sensory and taste functions, but it did lead to prolonged recovery of taste. This delay may be associated with a decrease in the abundance ratio of Schwann cells in traumatic neuromas.