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.

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.

Changes in serum DAMPs and cytokines/chemokines during near-infrared photoimmunotherapy for patients with head and neck cancer.

BACKGROUND: Near-infrared photoimmunotherapy (NIR-PIT) for head and neck cancer is a recently developed therapy. However, there is limited data on patients receiving NIR-PIT in real clinical settings. METHODS: Seven NIR-PIT sessions were administered to five patients with head and neck squamous cell carcinoma (HNSCC). Serum damage-associated molecular patterns (DAMPs) (HMGB1 and Hsp70 levels), and cytokine and chemokine production, were compared before and after NIR-PIT. RESULTS: The serum concentration of HMGB1 increased after NIR-PIT (p = 0.031, Wilcoxon test) in all patients except one who did not achieve a clinical response. Chemokines MIP-1α (CCL3) and MIP-1ß (CCL4) increased significantly 1-3 days after treatment (CCL3, p = 0.0036; CCL4, p = 0.0016, Wilcoxon test). A low pre-treatment neutrophil-to-lymphocyte ratio (NLR) was associated with a better response to therapy and survival. CONCLUSIONS: The release of DAMPs, and cytokine/chemokine production, were detected in the patients' peripheral blood. The baseline NLR may predict patient outcomes in response to NIR-PIT.

Expression of CD5 in salivary gland tumors: an ancillary marker for carcinoma showing thymus-like differentiation (CASTLE) of the major salivary gland.

Recently, cases of carcinoma showing thymus-like differentiation (CASTLE) occurring in major salivary glands have been identified. To assess the diagnostic value of CD5 immunohistochemistry in distinguishing salivary CASTLE from other types of salivary gland tumors, we evaluated CD5 expression in 109 salivary gland tumors, encompassing 23 different histological types, including salivary CASTLE. In addition, we reviewed 10 previously reported cases of salivary CASTLE. Most salivary CASTLE cases (10/11, 91%) showed strong CD5 expression. In contrast, 104 of 108 (96%) non-salivary CASTLE tumors were negative for CD5, while the remaining four tumors (3.7%), all of which were histologically Warthin tumors, showed focal positivity for CD5 with weak to moderate intensity. In conclusion, the findings in this study support the potential use of CD5 immunohistochemistry for distinguishing salivary CASTLE from other histological types of salivary gland tumors. Aberrant CD5 expression in this tumor may be linked to the tumor microenvironment.

Indications for sentinel lymph node biopsy in node-negative oral cancers.

BACKGROUND: We aimed to define the indications for sentinel lymph node biopsy (SLNB), the third option for cervical treatment in oral cancer with negative cervical lymph nodes. METHODS: The greatest depth of invasion (DOI) and long diameter (LD) of the primary site were used as exposures. SLN metastasis was considered the outcome. RESULTS: In three trials conducted between 2009 and 2016, 158 patients were eligible and reassigned to this study group. The scatterplot based on the respective values of DOI and LD would eventually be divided into three sections. In cases of sections T1, T2, and T3, the proportions of SLN metastasis positivity were 21.3%, 35.3%, and 51.2%, respectively. In certain cases of T1 with 2 mm < DOI ≤ 5 mm and 8 mm < LD ≤ 20 mm, the proportion of SLN metastasis positivity was 40.9%. CONCLUSIONS: SLNB-navigated or assisted neck dissection can be added as an effective procedure for N0 neck control.

Association Between 18F-Fluorodeoxyglucose Uptake and Mutation Status of Epidermal Growth Factor Receptor in Sinonasal Tract Cancer.

BACKGROUND/AIM: The Warburg effect of cancer has been applied to detect various carcinomas though the 18F-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography with computed tomography (PET/CT). 18F-FDG-PET/CT in lung cancer predicted the mutation status of epidermoid growth factor receptor (EGFR). This study aimed to investigate whether 18F-FDG uptake parameters were significantly related to EGFR mutation status in patients with sinonasal tract squamous cell carcinoma (STSCC). PATIENTS AND METHODS: Twenty-nine tumor specimens of primary STSCC from patients with definitive treatment were collected. RESULTS: The 18F-FDG uptake from primary tumors was not different between mutant- and wild-status of EGFR on either Mann-Whitney U-test or the receiver operating curve. A metabolic tumor volume of ≥25 with the minimum p-value from the log-rank test for STSCC-specific survival was associated with a significantly shorter STSCC-specific, disease-free, local recurrence-free survival on the univariate and multivariate analyses adjusted for the clinical stage, treatment, and EGFR status. CONCLUSION: 18F-FDG-PET/CT did not predict mutation of the EGFR status in STSCC.

A novel technique in transoral robotic surgery: A case report of rotating and switching technique.

BACKGROUND: Transoral robotic surgery (TORS) for tongue base lesions located above the operative field is predominantly an upward procedure, which makes surgery difficult. METHODS: To illustrate our technique for this procedure, we report the case of an 82-year-old male with a p16-negative oropharyngeal carcinoma of the tongue base who underwent TORS. The field of view was turned upside down, and the operation switched the typical left- and right-arm functions. The daVinci Xi was docked, the 0° endoscope was rotated 180°, and the first arm was switched to the right hand and the third arm to the left hand. RESULTS: Although the lesion extended from the tongue base to the soft palate and mobile tongue, the planned resection line was followed. CONCLUSIONS: This technique improves operability by allowing downward manipulation and preventing the left and right arms from crossing. Further validation of the technique's effectiveness and safety is needed.

Utilization of ultrasound in photoimmunotherapy for head and neck cancer: a case report.

BACKGROUND: Photoimmunotherapy (PIT) is a new cancer treatment based on a different mechanism from conventional treatments that combines the administration of a photoabsorber and laser illumination. PIT has two characteristics: a high selectivity of target cells and the possibility of effects beyond the illuminated area. It is thus a potentially effective treatment for a wide variety of cancers. CASE PRESENTATION: We herein report a patient with oropharyngeal squamous cell carcinoma with superficial cervical lymph node recurrence. Intraoperative ultrasound confirmed the localization of the lesion and major vessels near the tumor. We punctured the tumor with catheters of laser illumination under ultrasound guidance. Laser illumination was able to be performed safely without causing serious adverse events, and the effect on the illuminated site was fully exhibited. CONCLUSIONS: Ultrasound allows for the intraoperative monitoring of each localized area and the puncture status easily in real-time. Accurate utilization of ultrasound is extremely important in PIT.

Lymph Node Ratio in Head and Neck Cancer with Submental Flap Reconstruction.

This study aimed to investigate the relationship between the lymph node ratio (LNR) and survival results of patients with head and neck squamous cell carcinoma (HNSCC) reconstructed by a submental artery flap (SMAF) to limit tumor size. This study retrospectively recruited 49 patients with HNSCC who underwent both primary resection and neck dissection with SMAF reconstruction. The LNR was the ratio of the number of metastatic lymph nodes to the sum number of examined lymph nodes. A LNR of 0.04 was the best cut-off value for HNSCC-specific death on receiver operating curve analysis. Patients with LNRs > 0.04 were univariately related to cancer-specific, disease-free, distant metastasis-free, and locoregional recurrence-free survival than those with LNRs ≤ 0.04 by log-rank test. In a Cox's proportional hazards model with hazard ratio (HR) and 95% confidence interval (CI) adjusting for pathological stage, extranodal extension and or surgical margins, the LNR (>0.04/≤0.04) predicted multivariate shorter cancer-specific (HR = 9.24, 95% CI = 1.49−176), disease-free (HR = 3.44, 95% CI = 1.23−10.3), and distant metastasis-free (HR = 9.76, 95% CI = 1.57−187) survival. In conclusion, LNR for patients of HNSCC with SMAF reconstruction for limited tumor size was a prognostic factor for survival outcomes.

Near-Infrared Photoimmunotherapy for Oropharyngeal Cancer.

Human papillomavirus (HPV)-associated oropharyngeal cancer has a better prognosis than other head and neck cancers. However, rates of recurrence and metastasis are similar and the prognosis of recurrent or metastatic HPV-associated oropharyngeal cancer is poor. Near-infrared photoimmunotherapy (NIR-PIT) is a treatment involving administration of a photosensitizer (IRDye®700DX) conjugated to a monoclonal antibody followed by activation with near-infrared light illumination. It is a highly tumor-specific therapy with minimal toxicity in normal tissues. Moreover, NIR-PIT is expected to have not only direct effects on a treated lesion but also immune responses on untreated distant lesions. NIR-PIT with cetuximab-IR700 (AlluminoxTM) has been in routine clinical use since January 2021 for unresectable locally advanced or locally recurrent head and neck cancer in patients that have previously undergone radiotherapy in Japan. NIR-PIT for head and neck cancer (HN-PIT) is expected to provide a curative treatment option for the locoregional recurrent or metastatic disease after radiotherapy and surgery. This article reviews the mechanism underlying the effect of NIR-PIT and recent clinical trials of NIR-PIT for head and neck cancers, treatment-specific adverse events, combination treatment with immune checkpoint inhibitors, illumination approach and posttreatment quality of life, and provides a case of series of two patients who receive NIR-PIT for oropharyngeal cancer at our institution.

A Case of Salvage Maxillectomy for Recurrent Oral Cancer After Boron Neutron Capture Therapy During the COVID-19 Pandemic.

BACKGROUND: During the COVID-19 pandemic, pedicle flaps instead of free flap transfer were recommended for head and neck reconstruction to reduce infection risk. Boron neutron-capture therapy in Japan was clinically approved in 2020 as a salvage radiotherapy for recurrent head and neck cancer following chemoradiotherapy. The efficacy and safety of salvage surgery following boron neutron-capture therapy remain unclear. CASE REPORT: We describe a 57-year-old male with crT4aN0M0 oral cancer after three different forms of radiotherapy including boron neutron-capture therapy, treated by salvage partial maxillectomy with both buccal fat pad and nasoseptal flaps. His postsurgical course was successful, without tracheostomy, and he had no Clavien- Dindo grade 3 or 4 complications. The pathological diagnosis was T4a squamous cell carcinoma with a negative surgical margin. No recurrence or metastasis had occurred at 113 days postoperatively. No opioid consumption was needed postoperatively. CONCLUSION: Pathological negative margins were achieved in this case and there were no severe complications. Further accrual of cases salvage surgery following boron neutron-capture therapy is required to clarify treatment strategies for recurrent head and neck cancer.

Metabolic Tumour Volume as a Predictor of Survival for Sinonasal Tract Squamous Cell Carcinoma.

BACKGROUND: High uptake of F18-fluorodeoxyglucose parameters for glucose metabolism is related to shorter survival in sinonasal tract cancer with various histological classifications. We investigated whether F18-fluorodeoxyglucose uptake parameters are associated with survival outcomes for patients with only squamous cell carcinoma (SCC) in the sinonasal tract that are treated either with surgery or nonsurgery. METHODS: We retrospectively observed F18-fluorodeoxyglucose uptake parameters on positron emission tomography with computed tomography for the primary tumour of SCC in 39 patients. Log-rank test or a Cox regression model with 95% confidence interval (95%CI) and hazard ratio (HR) were used for monovariable or multivariable analysis, respectively. We determined cut-off values of the F18-fluorodeoxyglucose uptake parameters using the lowest p value for monovariable sinonasal tract cancer-specific survival analysis. RESULTS: Monovariable analysis showed that patients with metabolic tumour volume (MTV) ≥ 21.8 had a shorter cancer-specific, disease-free and local recurrence-free survival than those with MTV < 21.8. After adjusting for age, gender, clinical stage and treatment group in the multivariable analysis, MTV (≥21.8/<21.8) was related to shorter cancer-specific (HR: 3.69, 95%CI: 1.17-12.0), disease-free (HR: 3.38, 95%CI: 1.19-9.71) and local recurrence-free (HR: 5.42, 95%CI: 1.59-20.3) survivals. CONCLUSIONS: MTV as advances in diagnostics of sinonasal tract SCC is a predictor.

A novel procedure of secondary voice prosthesis insertion from the inside out: The modified Fukuhara method.

OBJECTIVE: To present a new procedure for inserting a secondary voice prosthesis from the inside to the outside, which improves on the method previously reported by Fukuhara et al. METHODS: A flexible nasopharyngoscope was used to puncture pharynx (or transplanted jejunum) from the inside to the outside. In this method, it was possible to use the PROVOX® VegaTM Puncture Set as it is used for the placement of the voice prosthesis. RESULTS: We were able to place the PROVOX® VegaTM in all cases we experienced. Most of the cases had a history of radiation therapy. The time required for surgery ranged from 11-59 minutes (mean: 29 minutes) and there was no measurable amount of bleeding. CONCLUSION: This new method using the PROVOX® VegaTM Puncture Set, which is designed for the original purpose of voice prosthesis implantation, was therefore found to be safe and effective.

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.

Total lesion glycolysis as a predictor of clinical T3-4a laryngeal cancer with laryngectomy or nonlaryngectomy.

ABSTRACT: The purpose of the present study is to investigate whether the 18F-fluorodeoxyglucose (18F-FDG) uptake parameter is related to survival outcomes for patients with clinical T3-T4a laryngeal cancer with various definitive treatments including total laryngectomy (TL). Parameters of 18F-FDG uptake in the primary tumors of 46 cases which were assessed by positron emission tomography with computed tomography were enrolled in the present observation study. Monovariate or multivariate survival analyses were performed with log-rank test or Cox regression model, with the hazard ratio (HR) and 95% confidence interval (CI), respectively. Cutoff values of the 18F-FDG uptake parameters were determined by the lowest P-value for monovariate overall survival. In the monovariate analysis, both metabolic tumor volume ≥13.1 and total lesion glycolysis (TLG) ≥46.5 were significantly associated with shorter overall survival, and TLG ≥46.5 was also related to a reduction in distant metastasis-free survival. In the multivariate analysis adjusting for clinical T classification (cT4/cT3) and treatment group (TL/non-TL), TLG (≥46.5/<46.5) was associated with both poorer overall (HR: 3.16, 95% CI: 1.10-9.49) and distant metastasis-free (HR: 8.91, 95% CI: 1.93-62.6) survival. In conclusion, TLG is a predictor for survival in laryngeal cancer.

Supraclavicular Artery Flap for Oral Reconstruction Prior to Esophagectomy During the COVID-19 Pandemic: A Case Report.

BACKGROUND: During the coronavirus disease 2019 (COVID19) pandemic, pedicle flaps (instead of free flaps) were recommended for reconstruction following wide resection for patients with head and neck cancer, in order to reduce the use of medical resources. Currently, there are no established treatment guidelines for patients with head and neck cancer with synchronous esophageal cancer. CASE REPORT: We present a 68-year-old male with cT4aN2cM0 oral floor and synchronous cT1bN1M0 esophageal cancers who had defective reconstruction following oral tumor resection before esophagectomy during the pandemic. At the initial surgery, the oral resected defect was reconstructed using supraclavicular artery flap. The subsequent esophagectomy was reconstructed by gastric tube reconstruction. Both postoperative courses were successful, without the need for postoperative ventilator use. The days from initial or second surgery to discharge were 14 or 16 days, respectively. CONCLUSION: This case had achieved negative surgical margins and recovered oral intake with tracheostomy decannulation. Further case accruement using supraclavicular artery flap is required for patients with head and neck cancer and synchronous esophageal cancer.

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.

The Utility of Ultrasonography in the Diagnosis of Cervical Lymph Nodes after Chemoradiotherapy for Head and Neck Squamous Cell Carcinoma.

Background and Objectives: There is evidence or consensus on the use of 18F-2-fluorodeoxyglucose-positron emission tomography with computed tomography (PET-CT) in evaluating the effects of treatment at 12 weeks after chemoradiotherapy for head and neck squamous cell carcinoma with cervical lymph node metastasis. However, the use of imaging to evaluate the effects of treatment within 12 weeks after chemoradiotherapy is controversial. The aim of this study was to evaluate the usefulness of ultrasonography in the diagnosis of lymph nodes metastasis after chemoradiotherapy according to the criteria of the "Evaluation of the effects of treatment on metastatic cervical lymph nodes using ultrasonography", which evaluated lymph nodes metastasis based on size change and presence of degeneration. Materials and methods: This prospective study included 34 head and neck squamous cell carcinoma patients with cervical lymph nodes metastasis. Thirty-two patients who completed treatment were analyzed. Ultrasonography was performed at 4 and 8 weeks after chemoradiotherapy and we judged whether a favorable prognosis could be expected or whether additional treatments should be considered. Ultrasonography and PET-CT were performed at 12 weeks after chemoradiotherapy. Neck dissection was performed if residual disease was suspected based on the PET-CT findings. Results: The accuracy and negative predictive value of ultrasonography were 81.3% and 96.3%, respectively. According to the Ultrasonography findings, the size of lymph nodes metastasis after chemoradiotherapy was significantly smaller than those before chemoradiotherapy (p < 0.05). The fluid and blood flow of lymph nodes metastasis showed a significantly reduced at 12 weeks after chemoradiotherapy (p < 0.05, p < 0.05, respectively). The echo density significantly changed from low to high echoic density after chemoradiotherapy (p < 0.05). Conclusions: Ultrasonography was useful for evaluating cervical lymph nodes metastasis after chemoradiotherapy for head and neck squamous cell carcinoma.

Treatment outcome and pattern of recurrence of sinonasal squamous cell carcinoma with EGFR-mutation and human papillomavirus.

The objective of our study was to clarify the clinical features of EGFR-mutated sinonasal squamous cell carcinoma (SNSCC) and human papilloma virus (HPV)-related SNSCC. Patients with SNSCC treated from April 2008 to June 2019 at our institution were retrospectively reviewed. We examined EGFR mutation and HPV status for all patients. Main outcomes were overall survival, recurrence, and outcome of each treatment modality. A total of 85 patients with SNSCC were enrolled in this study. EGFR mutations and HPV DNA were detected in 24 (28%) and 7 (8%) patients, respectively. Patients with EGFR-mutated SNSCC showed a worse overall survival (OS) than those with EGFR wild-type in the multivariate analysis (p = 0.037). No death was observed in HPV-positive SNSCC. The cumulative incidence of local recurrence was significantly higher in EGFR mutant than EGFR wild-type tumors (p = 0.03). In patients with EGFR mutations, treatment with induction chemotherapy significantly improved OS (p = 0.01). EGFR-mutated SNSCC have a high-risk feature for recurrence and requires intensive attention for treatment and observation. A new treatment approach, such as EGFR tyrosine kinase inhibitors, may be needed.

Serum CD109 levels reflect the node metastasis status in head and neck squamous cell carcinoma.

BACKGROUND: Various biomarkers are being developed for the early diagnosis of cancer and for predicting its prognosis. The aim of this study is to evaluate the diagnostic significance of serum CD109 in head and neck squamous cell carcinoma (HNSCC). METHODS: The serum CD109 levels in a total of 112 serum samples collected before and after surgery from 56 HNSCC patients were analyzed with an enzyme-linked immunosorbent assay (ELISA). The clinical factor that showed a statistically significant association with both the preoperative serum CD109 level, and the CD109 index: which was defined as the ratio of the preoperative serum CD109 level to the postoperative serum CD109 level, were assessed. The correlations between the serum CD109 levels and lymph node density (LND), pathological features such as lymphatic invasion, and serum SCC antigen levels were also assessed. RESULTS: The ELISA measurement revealed that preoperative serum CD109 levels were elevated in patients with node metastasis-positive and stage IV disease, in comparison to those with node metastasis-negative and Stage I+II+III disease, respectively. A multiple regression analysis indicated that serum CD109 level was significantly associated with the node metastasis status. A Spearman's rank correlation analysis also revealed a positive correlation between the preoperative serum CD109 level and LND. Furthermore, the probabilities of the overall and relapse-free survival were significantly lower in patients with a preoperative serum CD109 level of ≥38.0 ng/ml and a CD109 index of ≥1.6, respectively, than in others. There was no significant correlation between the serum CD109 and SCC antigen levels. CONCLUSIONS: The serum CD109 levels were elevated in patients with advanced stage disease, reflecting the node metastasis status. CD109 in sera could be a novel prognostic marker for HNSCC involving lymph node metastasis.