Survival impact of sequential chemotherapy following pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma.

BACKGROUND: Pembrolizumab alone or combined with chemotherapy is the standard of care for first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with positive programmed death-ligand 1 combined positive scores. However, data on second-line chemotherapy following pembrolizumab are scarce. METHODS: A single-center, retrospective study was conducted to determine the efficacies of pembrolizumab and pembrolizumab plus chemotherapy as first-line treatments and the efficacy of second-line chemotherapy for patients with R/M HNSCC who were refractory or intolerant to first-line treatment. RESULTS: Fifty-four patients were treated with pembrolizumab, and 29 received second-line therapy, with 27 opting for cetuximab-containing regimens. The median progression-free survival (PFS), overall survival (OS), and PFS on next-line therapy for first-line treatment were 4.7 (95% confidence interval [CI], 2.1-8.7), 22.1 (95% CI, 12.6-not reached), and 15.6 months (95% CI, 9.7-not reached) in the pembrolizumab group and 5.4 (95% CI, 3.3-6.8), 15.8 (95% CI, 8.6-not reached), and 13.7 months (95% CI, 8.1-not reached) in the pembrolizumab plus chemotherapy group, respectively. The overall response rate and median PFS for second-line treatment were 48.3% (95% CI, 30.4-67.0) and 6.1 months (95% CI, 2.30-8.84). The median OS for patients who received second-line treatment was 18.4 months, which was superior to the median OS of 6.0 months for patients who received the best supportive care (log-rank p = 0.10). CONCLUSION: This study indicates that cetuximab-containing second-line chemotherapy can improve outcomes in R/M HNSCC, even after first-line therapy failure or intolerance.

Should the Supraclavicular Lymph Nodes be Considered Regional Lymph Nodes in Cervical Esophageal Cancer?

BACKGROUND: The importance of supraclavicular lymph node (SCLN) metastases in esophageal cancer (EC) remains unknown. Few studies have reported on the prognostic impact of SCLN metastases on patients with cervical EC (CEC). This study aimed to investigate whether SCLNs should be considered regional lymph nodes and be dissected in patients with CEC. METHODS: This retrospective study enrolled 835 consecutive patients who underwent radical esophagectomy. Of these patients, 67 underwent radical surgery for CEC. These 67 patients were divided into three groups based on the presence of lymph node metastases with or without metastatic SCLNs or the absence of lymph node metastases. RESULTS: Of the 67 patients, 23 (34.3%) did not have metastatic lymph nodes (pN-negative group), 27 (40.3%) had metastatic lymph nodes except for metastatic SCLNs (pN-positive group without metastatic SCLN), and 17 (25.4%) had metastatic lymph nodes including metastatic SCLNs (pN-positive group with metastatic SCLNs). The 5-year overall survival rate was 58.4% for the pN-negative group, 46.2% for the pN-positive group without metastatic SCLNs, and 7.8% for the pN-positive group with metastatic SCLNs. The pN-positive group with metastatic SCLNs tended to show residual tumor cells and complications after surgery. The presence of metastatic SCLNs was a significantly poor prognostic factor (p = 0.004). The efficacy index was lowest for the lymph nodes in the supraclavicular region. CONCLUSIONS: The prognosis of the CEC patients with metastatic SCLNs was dismal. Although the cervical esophagus is located adjacent to the SCLNs, the SCLNs may be considered extra-regional lymph nodes in patients with CEC.

Role of Human Papilloma Virus and Lifestyle Factors in Overall Survival of Patients with Oropharyngeal Squamous Cell Carcinoma.

Background: Patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) have a significantly better treatment response and overall survival (OS) rates than non-HPV-associated OPSCC. Objectives: We conducted the present study to further characterize the interplay between lifestyle risk factors, which are not only HPV status, but also smoking history and alcohol consumption, and the OS to optimize the treatment of patients with OPSCC. Materials and Methods: Between January 2006 and December 2013, 94 patients newly diagnosed with OPSCC were treated with curative intent at Aichi Cancer Center Hospital (Nagoya, Japan). To determine negative prognostic factors associated with the OS, univariate and multivariable Cox regression analyses were performed. Results: Of the 94 OPSCC patients, 53 (56.4%) were positive for HPV. The univariate analysis revealed that T classification, smoking history, alcohol consumption, and HPV status were significant determinants of the OS. In the multivariate analysis, adjusted for the clinical stage, smoking history, alcohol consumption, HPV status, and a smoking history of >10 pack-years was an independent negative prognostic factor for the OS among patients with OPSCC (HR: 10.4, 95 %CI: 1.34−80.6, p < 0.05). Conclusions: Smoking is a very important negative prognostic factor even in cases of HPV-associated OPSCC. The impact of smoking needs to be reaffirmed when deciding on treatment plans and de-escalation trials in OPSCC, even in cases of HPV-associated OPSCC.

Eosinophil prognostic scores for patients with head and neck squamous cell carcinoma treated with nivolumab.

Although nivolumab, a programmed cell death 1 (PD-1) inhibitor, is a standard therapy for platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), no definitive biomarkers have been reported thus far. This study aimed to select promising prognostic markers in nivolumab therapy and to create a novel prognostic scoring system. In this retrospective cohort study, we reviewed patients with R/M HNSCC who were treated with nivolumab from April 2017 to April 2019. We developed a prognostic score for immune checkpoint inhibitor (ICI) therapy that was weighed using hazard ratio-based scoring algorithms. Significant variables were selected from the multivariate Cox proportional hazard analyses on overall survival (OS). A total of 85 patients with HNSCC were analyzed in the present study. The relative eosinophil count (REC), the ratio of eosinophil increase (REI), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) were selected as variables affecting the prognostic score. The patients were divided into four groups: very good (score = 0), good (score = 1), intermediate (score = 2), and poor (score = 3). The OS hazard ratios were 2.77, 10.18, and 33.21 for the good, intermediate, and poor risk groups compared with the very good risk group, respectively. The Eosinophil Prognostic Score is a novel prognostic score that is effective for predicting the prognosis of HNSCC patients treated with nivolumab. This score is more precise as it includes changes in biomarkers before and after the treatment.

Lymph node ratio as a predictor for minor salivary gland cancer in head and neck.

BACKGROUND: We investigate whether pathological continuous variables of lymph nodes were related with survival results of carcinomas of minor salivary gland carcinoma in head and neck. METHODS: Forty-four cases with minor salivary gland carcinoma who underwent both primary resection and neck dissection were retrospectively enrolled. The pathological continuous variables were evaluated by the number of positive lymph nodes, lymph node ratio, and log odds of positive lymph nodes. Receiver operating curve analysis was used for the cut-off values of the carcinoma-specific death. Log-rank test and Cox's proportional hazards model were used for uni-/multi-variate survival analyses adjusting for pathological stage, respectively. RESULTS: Lymph node ratio = 0.05 as well as log odds of positive lymph nodes = - 2.73 predicted the carcinoma-specific death. Both lymph node ratio and log odds of positive lymph nodes were significantly related with survival outcomes by the univariate analysis. Lymph node ratio ≥ 0.05 was associated with shorter disease-specific (hazard ratio = 7.90, 95% confidence interval = 1.54-57.1), disease-free (hazard ratio = 4.15, 95% confidence interval = 1.48-11.2) and overall (hazard ratio = 4.84, 95% confidence interval = 1.05-24.8) survival in the multivariate analysis. CONCLUSION: A higher lymph node ratio of minor salivary gland carcinoma is a predictor of shorter survival results.

Clinical impact of weekly paclitaxel plus cetuximab is comparable to the EXTREME regimen for recurrent/metastatic head and neck squamous cell carcinoma.

BACKGROUND: Until the emergence of immune checkpoint inhibitors, the EXTREME regimen comprising platinum-based chemotherapy plus cetuximab was the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Recent reports suggest the usefulness of regimens including taxanes in combination with cetuximab as treatment options for R/M HNSCC patients with contraindications for platinum. However, comparisons of weekly paclitaxel plus cetuximab (wPTX-Cmab) to the EXTREME regimen are limited. MATERIALS AND METHODS: We compared the clinical impact of wPTX-Cmab to EXTREME as first line treatment for R/M HNSCC in Aichi Cancer Center Hospital. The primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). Propensity score-adjusted Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: From 2012 to 2018, 77 patients, including 55 treated with EXTREME and 22 refractory or intolerant to platinum treated with wPTX-Cmab, were analyzed. wPTX-Cmab was comparable to EXTREME on OS [adjusted HR 0.82 (95% CI 0.39-1.48)], PFS [adjusted HR 0.90 (95% CI 0.49-1.65)], ORR [wPTX-Cmab 34.7% (12-43), EXTREME 30.9% (18-43), p = 0.877] and DCR [wPTX-Cmab 72.7% (52-92), EXTREME 65.4% (52-78), p = 0.337]. Survival trends remained similar after stratification by platinum-refractory or intolerance status. Disease control with wPTX-Cmab was significantly associated with better OS [adjusted HR 0.18 (0.05-0.57)]. CONCLUSION: wPTX-Cmab may be a suitable treatment option for R/M HNSCC patients with contraindications for platinum.

Prognostic value of lymph node density for major salivary gland carcinoma without clinical lymph node metastasis.

BACKGROUND AND OBJECTIVE: This study aimed to investigate whether lymph node density (LND) was correlated with overall survival (OS) in major salivary gland carcinoma without clinical lymph node metastasis. METHODS: Sixty patients who were diagnosed with major salivary gland carcinoma without clinical lymph node metastasis were enrolled. Of these, 50 patients underwent neck dissection. LND was defined as the ratio of the number of positive lymph nodes to the total number of resected lymph nodes. RESULTS: An LND of ≥0.1 was significantly associated with a short OS (p < 0.05). Multivariate analysis with adjustment for pathological N classification and positive surgical margin showed that an LND of ≥0.1 is a predictor of OS. CONCLUSION: Results demonstrated that lymph node density functions as a predictor of outcomes for major salivary gland carcinoma without clinical lymph node metastasis.

Sinonasal squamous cell carcinoma and EGFR mutations: a molecular footprint of a benign lesion.

AIMS: Molecular targeted therapy against EGFR kinase domain mutations has been successfully established for lung cancer. These mutations have now also been reported in head and neck tumours, particularly in inverted sinonasal papillomas (ISPs). The aim of this study was to clarify the spectrum of EGFR mutations in head and neck squamous cell carcinomas and papillomas. METHODS AND RESULTS: We examined EGFR mutations in 288 head and neck squamous cell carcinomas and 58 head and neck papillomas or polyps. EGFR mutations were detected in 24 (30%) of 80 sinonasal squamous cell carcinomas (SNSCCs) and in 19 (90%) of 21 ISPs. Notably, 15 (88%) of 17 SNSCCs that developed along with ISPs harboured EGFR mutations in both components, whereas EGFR mutations were detected in nine (14%) of 63 SNSCCs without any papilloma component. Analysis to detect other known driver oncogene mutations - KRAS, BRAF and HER2 - was also performed; none of these mutations was detected in SNSCCs. The other 208 non-sinonasal carcinomas and 37 non-ISP head and neck papillomas or polyps did not harbour EGFR mutations. CONCLUSIONS: Taken together with the specific involvement of EGFR mutations in ISP, a molecular benign lesion trail suggests that 26 (33%) of 80 SNSCCs developed in association with an ISP. SNSCCs with EGFR mutations may be biologically distinct among head and neck cancers.

Prospective randomized investigation implementing immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids during the perioperative period for head and neck carcinomas.

OBJECTIVES: The purpose of this study is to evaluate whether a nutritional supplement with a high blend ratio of ω-3 fatty acids can minimize weight loss and attenuate increases in inflammatory marker levels during the perioperative period in patients undergoing surgery for head and neck carcinoma. METHODS: Patients with ≥5% weight loss within 6 months were considered as targets for aggressive nutritional intervention. Among these patients, those with head and neck squamous cell carcinoma, who underwent major invasive surgery with free flap reconstruction were included in the present study. The patients were randomized into two groups: the 'nutritional supplementation group' and the 'non-intervention group'. The nutritional supplementation group received two packs of Prosure® (an eicosapentaenoic acid [EPA]-enriched oral nutritional supplement) per day for 28 days during the perioperative period. RESULTS: Compliance with the Prosure® dosage was very good at 6277/6720 ml (average) before surgery (93%) and 5229/6720 ml after surgery (78%), and a significant increase in EPA concentration was shown in the group that received Prosure® (P < 0.0001: Welch's t-test). However, 28 days of nutritional supplementation did not lead to further weight change or changes in the inflammatory marker levels of patients were already showing cachexia (based on weight loss). Interestingly, no further change in the mean weight was noted in these patients. The incidence of postoperative complications did not differ between the two groups. CONCLUSION: In this trial, immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids from 2 weeks before surgery until 2 weeks after surgery was not effective for maintaining the nutritional status of head and neck carcinoma patients.

Gross tumor volume in sinonasal tract cancer as a predictor of local recurrence after chemoradiotherapy.

OBJECTIVE: This study investigated whether gross tumor volume of the primary tumor before treatment was a predictor for local recurrence in patients with resectable sinonasal tract squamous cell carcinoma who were treated by chemoradiotherapy. METHODS: A total of 24 patients were enrolled. Pretreatment gross tumor volume of primary tumor was assessed by palpitation, perception and imaging. The cut-off value of the gross tumor volume for local recurrence was determined by receiver-operating curve analysis. A log-rank test and Cox's proportional hazards model were used for univariate and multivariate analyses with adjustment for the clinical T category (cT1-T4a/cT4b), respectively. RESULTS: In the univariate analysis, patients with the gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.0023) and disease-free survival (P = 0.0064) than those with gross tumor volume <83.7 ml. In the multivariate analysis, gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.041). CONCLUSIONS: Pretreatment gross tumor volume of primary tumor ≥83.7 ml was significantly associated with local recurrence-free rate in resectable sinonasal tract squamous cell carcinoma.

The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Skeletal muscle depletion and sarcopenia have been reported as poor prognostic factors for several types of cancer. The aim of this study was to investigate the prognostic impact of skeletal muscle depletion and sarcopenia on the outcomes in head and neck cancer patients. METHODS: Patients with head and neck squamous cell carcinoma (HNSCC) treated from January 2013 to June 2014 were included in this study. The pretreatment cross-sectional area of skeletal muscle at the third lumbar vertebra (L3) was measured by computed tomography image analysis using the ImageJ software. L3 skeletal muscle index (SMI) and fat-free mass (FFM) were calculated. RESULTS: Eighty-five patients with HNSCC were included. The cut-off value of sarcopenia was set at SMI <46.7 cm2/m2 (males) and 30.3 cm2/m2 (females). The cut-off value of FFM was set at 42.3 kg (males) and 30.6 kg (females). Patients with a low SMI (sarcopenia) and low FFM had a significantly poorer prognosis than others, especially those who received definitive radiotherapy. Sarcopenia and low FFM are independent factors for poor prognosis in patients with HNSCC. CONCLUSION: The skeletal muscle area at L3 should be calculated when considering treatment options for head and neck cancer.

Prognostic importance of pathological response to neoadjuvant chemotherapy followed by definitive surgery in advanced oral squamous cell carcinoma.

OBJECTIVE: The clinical importance of neoadjuvant chemotherapy (NAC) followed by definitive surgery was retrospectively investigated in clinical Stage III/IV oral squamous cell carcinoma (OSCC). METHODS: Surgery was performed for OSCC in 164 patients, including 72 patients who had received NAC (two cycles of cisplatin and fluorouracil) prior to surgery from January 2004 to December 2014. The clinical characteristics and survival parameters of the groups that received and did not receive NAC were evaluated. The pathological response was classified as Grade 0 (no effect), 1a (very slight effect), 1b (slight effect), 2 (moderate effect) or 3 (marked effect), and its correlation with prognosis was investigated. RESULTS: There were no statistical differences in survival indicators between patients who received NAC and those who did not (overall survival, P = 0.75). The proportion of patients who received NAC in the effective NAC group (Grades 1b, 2, and 3) was 52.8%. After a median follow-up of 35 months, overall survival (P = 0.01), disease-free survival (P = 0.002), locoregional disease-free survival (P = 0.003), and distant disease-free survival (P = 0.01) were significantly better in the effective NAC group than in the less effective NAC group (Grades 0 and 1a). CONCLUSION: Although NAC had a limited effect on disease prognosis in OSCC, the pathological response to NAC could be an important prognostic indicator for advanced OSCC.

Comparisons of the clinical outcomes of different postoperative radiation strategies for treatment of head and neck squamous cell carcinoma.

PURPOSE: We previously reported unfavorable locoregional control with limited field postoperative radiotherapy for head and neck squamous cell carcinoma patients and thus revised the strategy to cover the whole neck. Head and neck squamous cell carcinoma Patients' outcomes were retrospectively analyzed to compare the efficacy of two treatments. MATERIAL AND METHODS: Before 2010, the clinical target volume covered the tumor bed and/or involved the neck region. Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate analysis, and propensity score matching were performed. The study included 275 patients: 186 received limited field postoperative radiotherapy and 89 received whole-neck postoperative radiotherapy. The median follow-up time for the entire cohort was 40.8 months. RESULTS: In univariate analysis, the radiation strategy had no significant effect on overall survival and progression-free survival. In multivariate analysis, whole-neck postoperative radiotherapy was a favorable factor for overall survival, progression-free survival, and locoregional control. Propensity score matching resulted in a cohort comprising 118 well-matched patients evenly divided between the limited field postoperative radiotherapy and whole-neck postoperative radiotherapy groups. Whole-neck postoperative radiotherapy group achieved a significantly better 2-year overall survival (56.4% vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P = 0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited field postoperative radiotherapy group developed significantly more locoregional recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0% vs. 0%, P < 0.001) in the matched-pair cohort. CONCLUSION: Whole-neck postoperative radiotherapy is a more appropriate choice than limited field postoperative radiotherapy to improve overall survival, progression-free survival and locoregional control.

Comparison between chemoselection and definitive radiotherapy in patients with cervical esophageal squamous cell carcinoma.

BACKGROUD: Laryngeal preservation is an important consideration when treating cervical esophageal cancers (CECs) such as laryngeal cancer. The standard treatment for CEC allowing laryngeal preservation is chemoradiotherapy. However, in cases of laryngeal cancer, chemoselection has also been applied as a treatment strategy that promotes larynx preservation. This strategy involves assigning the appropriate radical treatment according to the primary tumor's response to induction chemotherapy. Since there have been no studies of the application of chemoselection in CEC cases, the present study compared the results, including laryngeal preservation rates, obtained upon applying chemoselection and chemoradiotherapy to CEC. STUDY DESIGN: This was a retrospective cohort study of cervical esophageal squamous cell carcinoma patients treated using chemoselection or chemoradiotherapy at Aichi Cancer Center Hospital between January 2000 and March 2013. A total of 42 patients were enrolled. RESULTS: The 2-year overall survival and laryngeal preservation rates for the chemoselection group versus the primary radiotherapy group were 65.1 and 57.3 versus 40 and 83.3%, respectively (P = 0.017 and P = 0.122, respectively). The 2-year locoregional control rates for the chemoselection and primary radiotherapy groups were 68 and 25%, respectively (P = 0.045). CONCLUSION: The chemoselection group achieved favorable results. Therefore, chemoselection can be applied as a treatment strategy for CEC.

Clinical results of definitive intensity-modulated radiation therapy for oropharyngeal cancer: retrospective analysis of treatment efficacy and safety.

OBJECTIVE: To evaluate the clinical outcomes of intensity-modulated radiotherapy for patients with oropharyngeal carcinoma. METHODS: Ninety-three oropharyngeal carcinoma patients histopathologically diagnosed with squamous cell carcinoma and treated with definitive intensity-modulated radiotherapy using helical tomotherapy between January 2006 and December 2013 were analyzed. Planning target volume primary and involved nodes was delivered 66-70 Gy at 2 Gy per fraction, while planning target volume prophylactic was delivered 54 Gy using the simultaneous integrated boost technique. RESULTS: The median follow-up period among the surviving patients was 40 months (range, 13-96). There were 76 males and 17 females with a median age of 60 years (range, 34-80). The disease was Stage II in 13%, Stage III in 10% and Stage IV in 77% of patients. Ninety-two patients received chemotherapy (99%); 68 patients received induction chemotherapy (73%), while 21 received concurrent chemotherapy (23%). The 3-year overall survival, progression-free survival and locoregional control rates were 80, 68 and 79%, respectively. Multivariate analysis identified an advanced T-category (T3-4), having double cancer, and smoking habit as significantly unfavorable factors for overall survival, progression-free survival and both progression-free survival and locoregional control, respectively. Only two patients who achieved disease control required percutaneous endoscopic gastrostomy tubes in the last follow-up. The rate of Grade 2 xerostomia at 2 years was 23%. CONCLUSIONS: Intensity-modulated radiotherapy using helical tomotherapy for patients with oropharyngeal carcinoma provided not only sufficient efficacy, but also preserved parotid function.

Retrospective analysis of the clinical efficacy of definitive chemoradiotherapy for patients with hypopharyngeal cancer.

OBJECTIVE: A retrospective analysis was performed to evaluate the clinical efficacy of definitive chemoradiotherapy including intensity-modulated radiotherapy for patients with hypopharyngeal cancer. METHODS: Previously untreated 204 patients with hypopharyngeal cancer were treated with definitive chemoradiotherapy. Of note, 66-70 Gy was delivered to the primary and involved nodes and 36-54 Gy was delivered to the prophylactic lymph node using standard fractionated radiotherapy. One hundred and forty-six patients received induction chemotherapy as a larynx preservation strategy, followed by definitive radiotherapy with or without concurrent chemotherapy. Intensity-modulated radiotherapy was also performed after 2006. RESULTS: The median follow-up time of this cohort was 43.4 months (range; 6.9-151.0). The 3-year overall survival, progression-free survival and larynx preservation survival rates were 78.8% (95% confidence interval; 73.0-85.0), 58.4% (95% confidence interval; 51.8-65.9) and 67.5% (95% confidence interval; 61.0-74.7), respectively. Multivariate analyses identified the following significant prognostic factors: an advanced age, the T category and N category for overall survival, the T category and N category for progression-free survival and the T category for larynx preservation survival. Acute toxicities of Grade 3 or higher were observed in 47 patients (23.0%). Two patients (1.0%) had Grade 4 pharyngeal edema. Suspicious treatment-related death due to lethal pharyngeal hemorrhage occurred in 1 (0.4%) patient. The rates of Grade 2 xerostomia in patients treated with intensity-modulated radiotherapy were 28.1, 17.4 and 9.5% at 6 months, 1 and 2 years after the completion of radiotherapy, respectively. CONCLUSIONS: The efficacy and safety of definitive chemoradiotherapy are considered feasible with sufficient laryngeal preservation.

The Charlson comorbidity index is a prognostic factor in sinonasal tract squamous cell carcinoma.

OBJECTIVE: High Charlson comorbidity index values have been reported to be associated with shorter overall survival in various types of cancer. We investigated whether Charlson comorbidity index values were correlated with overall survival in patients with resectable sinonasal tract squamous cell carcinoma. METHODS: Seventy-nine patients with resectable sinonasal tract squamous cell carcinoma were treated with curative intent. The Charlson comorbidity index values were calculated by the summation of the weight scores of 19 medical conditions (other than sinonasal tract squamous cell carcinoma) before treatment. The survival rate was analyzed according to the Kaplan-Meier method. Univariate and multivariate survival analyses were performed using the Wilcoxon test and the Cox proportional hazards model, respectively. RESULTS: According to a univariate analysis, a Charlson comorbidity index value ≥6 was found to be significantly correlated with shorter overall survival (P < 0.02). In the multivariate survival analysis with adjustment for the clinical T and N classification, age, sex, anatomical location, treatment group (radiotherapy/surgery) and chemotherapy (presence/absence), a Charlson comorbidity index value ≥6 was found to be associated with the significantly shorter overall survival. CONCLUSIONS: These results suggest that the Charlson comorbidity index functions as a prognostic factor in cases of resectable sinonasal tract squamous cell carcinoma.

Lymph node ratio predicts survival in hypopharyngeal cancer with positive lymph node metastasis.

The lymph node density (LND) has been reported to be a significant prognostic factor in various types of carcinoma. This study investigated whether the LND is associated with survival in patients with hypopharyngeal squamous cell carcinoma (HPSCC) who have positive lymph nodes without distant metastasis. Forty-six patients who were pathologically diagnosed with HPSCC with positive lymph nodes and without distant metastasis were enrolled in this study. The LND was defined as the ratio of positive lymph nodes to the total number of lymph nodes. An LND of ≥0.09 was found to be significantly correlated with a shorter overall (p = 0.044) and disease-specific (p = 0.019) survival according to a log-rank test. In a multivariate survival analysis using a Cox proportional hazards model adjusted for the pathological T category (pT3-4/pT1-2), pathological N category (pN2/pN1) and positive surgical margin and/or extracapsular spread (presence/absence), both an LND of ≥0.09 and pT3-4 category were associated with significantly shorter overall survival (p < 0.01) and disease-specific survival (p < 0.01). These results suggest that the LND functions as a prognostic factor for HPSCC patients with positive lymph nodes who do not have distant metastasis.

Safety and Efficacy of Gemcitabine Plus Cisplatin Against Recurrent/Metastatic Nasopharyngeal Carcinoma: A Retrospective Study.

BACKGROUND/AIM: Although gemcitabine plus cisplatin (GC) prolongs survival in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) compared with fluorouracil plus cisplatin, no study has evaluated the efficacy and safety of GC in nonendemic regions, including Japan, yet. Therefore, we assessed the safety and efficacy of GC in Japanese patients with R/M NPC. PATIENTS AND METHODS: We retrospectively reviewed patients with R/M NPC who received GC treatment at the Aichi Cancer Center Hospital from January 2017 to March 2020. The main eligibility criteria were histologically confirmed NPC, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2, and locally recurrent disease unsuitable for local treatment or metastatic disease. The regimen was administered every 3 weeks (gemcitabine, 1,000 mg/m2 on days 1 and 8; cisplatin, 80 mg/m2 on day 1). RESULTS: Fourteen patients (median age, 58 years) were included in the study. Two patients had an ECOG PS of 2 and 11 exhibited nonkeratinizing histology. Of the eight patients with measurable lesions, one exhibited complete response and seven exhibited partial response, with an objective response rate of 75%. Median progression-free survival and overall survival were 7.7 and 24.2 months, respectively. Common grade 3 or 4 adverse events included neutropenia (64%), thrombocytopenia (14%), and febrile neutropenia (14%). The median relative dose intensity of gemcitabine and cisplatin was 62% and 60%, respectively. No treatment-related deaths occurred. CONCLUSION: The GC regimen demonstrates promising activity and is tolerable in Japanese patients with R/M NPC.

Extent of thyroidectomy and paratracheal lymph node dissection in total pharyngolaryngectomy for pyriform sinus cancer, and recurrence, survival, and postoperative hypoparathyroidism: A multicenter retrospective study.

BACKGROUND: Total pharyngolaryngectomy (TPL) is standard treatment for hypopharyngeal cancer. However, extensive thyroidectomy and paratracheal nodal dissection (PTND) can cause hypoparathyroidism. We sought to determine the optimum extent of resection. METHODS: We analyzed the clinicopathological information of 161 pyriform sinus cancer patients undergoing TPL from 25 Japanese institutions. Rates of recurrence and risk factors for hypoparathyroidism, as well as incidence of pathological contralateral level VI nodal metastasis and stomal recurrence, were investigated. RESULTS: The extent of thyroidectomy and nodal dissection were not independent risk factors for recurrence. Incidences of contralateral level VI nodal involvement and stomal recurrence were 1.8% and 1.2%, respectively. Patients undergoing hemithyroidectomy/ipsilateral PTND did not develop stomal recurrence and had the lowest incidence of hypoparathyroidism. Prognosis in patients without tracheostomy prior to hemithyroidectomy/ipsilateral PTND was comparable to that with more extensive resections. CONCLUSIONS: Hemithyroidectomy/ipsilateral PTND may be sufficient for pyriform sinus cancer cases without tracheostomy.