A Case of Photoimmunotherapy for Nasopharyngeal Carcinoma Requiring Emergency Tracheostomy.

Introduction: Photoimmunotherapy (PIT) is a treatment wherein intravenous cetuximab sarotalocan sodium is administered followed by laser light irradiation. This treatment exhibits a specific antitumor effect if in tumors expressing the epidermal growth factor receptor, regardless of the carcinoma [Mitsunaga et al.: Nat Med. 2011;17(12):1685-91, Sato et al.: ACS Cent Sci. 2018;4(11):1559-69, Nakajima et al.: Cancer Sci. 2018;109(9):2889-96]. The current indications are unresectable, locally advanced, or locally recurrent head and neck cancer. If standard treatments, such as radiotherapy and chemotherapy, are available, they are given priority. However, a significant concern in PIT is the occurrence of airway emergencies related to pharyngeal edema. Prophylactic tracheostomy is often performed in cases of PIT involving the root of the tongue, hypopharynx, or larynx. Case Presentation: In this study, we administered transoral PIT to a patient diagnosed with radiation-induced nasopharyngeal carcinoma (squamous cell carcinoma (SCC) cT1N0M0 stage I). Although previous case reports and our own experiences did not report airway emergencies following PIT for nasopharyngeal carcinoma, a unique case occurred in our study [Omura et al.: Auris Nasus Larynx. 2023;50(4):641-5, Kushihashi et al.: Int J Otolaryngol Head Neck Surg. 2022;11(5, Sep):258-65]. The patient experienced poor oxygenation and a decreased level of consciousness early in the morning following the laser irradiation. Nasal endoscopy revealed airway narrowing due to upper airway edema, and intubation was challenging. Consequently, we performed emergency bedside tracheostomy and the patient's condition improved. Conclusion: Therefore, it is crucial to note that airway emergencies can be life-threatening and should be diligently monitored as a potential complication of PIT.

Brain metastases in patients with salivary duct carcinoma: A retrospective study.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with a 5-year survival rate of 40%. Although drug therapy has improved patients' prognosis, the impact of brain metastasis (BM) remains poorly understood. We aimed to retrospectively examine the incidence of BM in patients with SDC (n = 464) and develop a tool to estimate their prognoses. METHODS: We retrospectively examined 464 patients with SDC enrolled in a multicenter study. We investigated the incidence of BM, overall survival (OS) rates, and factors affecting prognosis in patients with BM. We also developed an SDC-graded prognostic assessment (GPA) score for disease prognostication. RESULTS: Sixty-five (14%) patients had BM. The median OS (mOS) was 13.1 months. On univariate and multivariate analyses, factors such as Eastern Cooperative Oncology Group Performance Status >1, human epidermal growth factor receptor 2-negative status, and locoregional uncontrolled disease were associated with poor OS. SDC-GPA scores according to the prognostic factors were 0, 1, 2, and 3 points, and mOS estimates were 50.5, 16.1, 3.9, and 1.2 months, respectively (p < 0.001). CONCLUSION: The SDC-GPA score emerged as a useful prognostication tool for patients with BM.

Prognostic value and clinicopathological roles of the tumor immune microenvironment in salivary duct carcinoma.

Salivary duct carcinoma (SDC) is an aggressive type of salivary gland carcinoma. Recently, immunotherapies targeting immune checkpoints, including PD1, PD-L1, CTLA4, and LAG3, have had a considerable prognostic impact on various malignant tumors. The implementation of such immune checkpoint inhibitor (ICI) therapies has also been attempted in cases of salivary gland carcinoma. The tumor immune microenvironment (TIME) is implicated in tumorigenesis and tumor progression and is closely associated with the response to ICI therapies. However, the TIME in SDC has not been fully explored. We examined the immunohistochemical expression of CD8, FOXP3, PD1, PD-L1, CTLA4, LAG3, and mismatch repair (MMR) proteins, tumor-infiltrating lymphocytes (TILs), and microsatellite instability (MSI) status in 175 cases of SDC. The associations between these TIME-related markers and the clinicopathological factors and prognosis were evaluated. An elevated expression of CD8, FOXP3, PD1, CTLA4, and LAG3 was associated with more aggressive histological features and an advanced N and/or M classification, elevated Ki-67 index, and poor prognosis. Furthermore, cases with a high PD-L1 expression exhibited more aggressive histological features and adverse clinical outcomes than those with a low expression. Alternatively, there was no significant correlation between TILs and clinicopathological factors. No SDC cases with an MSI-high status or MMR deficiency were found. The coexistence of both an immunostimulatory and immunosuppressive TIME in aggressive SDC might play a role in the presence of T-cell exhaustion. The contribution of multiple immune escape pathways, including regulatory T cells and immune checkpoints, may provide a rationale for ICI therapy, including combined PD1/CTLA4 blockade therapy.

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study.

BACKGROUND/AIM: Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities. PATIENTS AND METHODS: Data of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022 were analyzed. The endpoint was overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs). OS and PFS were analyzed comparatively with and without irAEs, and complete response (CR) or partial response (PR), and stable disease (SD) or progressive disease (PD) were compared. RESULTS: One hundred thirty-five patients received pembrolizumab alone, whereas the others received pembrolizumab with chemotherapy. For the pembrolizumab only group, the median OS and PFS were 22.7 and 5.1 months, respectively. There were significant differences in OS and PFS between CR or PR and SD or PD (p<0.01, p<0.01, respectively). For pembrolizumab with chemotherapy, the OS was not reached and median PFS was 7.0 months. There was a significant difference in PFS between CR or PR and SD or PD (p<0.01). There was a significant difference in PFS between patients with and without irAEs (p=0.02). CONCLUSION: The real-world therapeutic effect of pembrolizumab for R/M SCCHN was comparable to that observed in the KEYNOTE048 trial. In addition, irAEs and best overall response were considered as prognostic factors.

Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling.

Molecular targets and predictive biomarkers for prognosis in salivary duct carcinoma (SDC) have not been fully identified. We conducted comprehensive molecular profiling to discover novel biomarkers for SDC. A total of 67 SDC samples were examined with DNA sequencing of 464 genes and transcriptome analysis in combination with the clinicopathological characteristics of the individuals. Prognostic biomarkers associated with response to combined androgen blockade (CAB) treatment were explored using mRNA expression data from 27 cases. Oncogenic mutations in receptor tyrosine kinase (RTK) genes or genes in the MAPK pathway were identified in 55 cases (82.1%). Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway were identified in 38 cases (56.7%). Interestingly, patient prognosis could be predicted using mRNA expression profiles, but not genetic mutation profiles. The risk score generated from the expression data of a four-gene set that includes the ADAMTS1, DSC1, RNF39, and IGLL5 genes was a significant prognostic marker for overall survival in the cohort (HR = 5.99, 95% confidence interval (CI) = 2.73-13.1, p = 7.8 × 10-6). Another risk score constructed from the expression of CD3E and LDB3 was a strong prognostic marker for progression-free survival for CAB treatment (p = 0.03). Mutations in RTK genes, MAPK pathway genes, and PI3K/AKT pathway genes likely represent key mutations in SDC tumorigenesis. The gene expression profiles identified in this study may be useful for stratifying patients who are good candidates for CAB treatment and may benefit from additional systemic therapies.

Nivolumab for Platinum-refractory and -sensitive Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Nivolumab has antitumor efficacy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) who relapse within 6 months after platinum-based therapy; however, the efficacy of nivolumab for platinum-sensitive R/M HNSCC has not been shown. Therefore, this study compared the efficacy and safety of nivolumab for platinum-refractory and platinum-sensitive R/M HNSCC. PATIENTS AND METHODS: This was a retrospective study of patients who received nivolumab for R/M HNSCC who had been previously treated with platinum-based anticancer drugs. Patients were divided into a platinum-sensitive and a platinum-refractory group, and progression-free survival (PFS), overall survival (OS), the overall response rate (ORR) [complete response (CR) + partial response (PR)], the disease control rate (DCR) (CR + PR + stable disease), and the incidence of immune-related adverse events (irAEs) were compared between the two groups. RESULTS: We included 88 patients with squamous cell carcinoma: 60 with platinum-refractory disease and 28 with platinum-sensitive disease. The median PFS in the platinum-refractory and platinum-sensitive groups were 2.7 months and 5.3 months, respectively (p=0.03), and the median OS were 8.8 months and 17.1 months, respectively (p=0.06). There were no significant differences in the ORR, DCR, or incidence of irAEs between the two groups (p>0.99, p=0.11, and p>0.99, respectively). CONCLUSION: Nivolumab is a safe and effective treatment for platinum-sensitive R/M HNSCC.

Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma.

Background: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. Methods: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. Results: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB. Conclusion: Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

Preoperative S-1 Therapy for Head and Neck Carcinoma During the Waiting Period Before Surgery.

BACKGROUND/AIM: In patients with squamous cell carcinoma of the head and neck (SCCHN), delayed surgery can result in poorer postoperative function and prognosis due to the growth of the tumor and extended surgery. Further, delay may even make the tumor unresectable. To prevent tumor growth during the waiting period before surgery, S-1 has been administrated preoperatively at several facilities in Japan. To date, however, the safety and efficacy of preoperative S-1 remain unclear. PATIENTS AND METHODS: We conducted a retrospective cohort study of 118 patients with SCCHN treated with S-1 before radical surgery at 2 institutions in Japan. We evaluated the safety of S-1 therapy, which was evaluated by the incidence of grade 3 or greater adverse events (AEs). The rate of achievement of non-growth of tumors was also calculated. RESULTS: Regarding safety, 125 AEs of all grades were recorded in 71 patients (60%). Of these, grade 3 AEs were detected in 3 patients (3%), and no grade 4 or 5 AEs occurred. The nongrowth rate of primary lesions and lymph node metastases was 89% and 85%, respectively. CONCLUSION: Preoperative S-1 therapy might be useful, with acceptable toxicity, on an outpatient basis in patients with SCCHN.

Postoperative Complications and Swallowing Function after Jejunal and Skin Flap Reconstruction for Hypopharyngeal Carcinoma-A Multicenter Retrospective Study.

This study compared the incidence of perioperative complications and swallowing function between free jejunal flap reconstruction and cutaneous free tissue flap construction. We included 223 patients who underwent hypopharyngeal reconstruction using free flap. At discharge, +the free jejunal flap was associated with a Functional Oral Intake Scale (FOIS) score of 1-6 in 132 cases (70%) and a score of 7 in 56 cases (30%). Regarding the cutaneous free tissue flaps, FOIS scores of 1-6 were observed in 18 cases (51%), and a score of 7 was noted in 17 cases (49%). Donor site complications occurred in 12% of the patients who underwent free jejunal flap procedures and in none of the patients who underwent cutaneous free tissue flap procedures. We found that the free jejunal flap had a regular dietary intake rate in 56 patients (30%), whereas cutaneous free tissue flaps had a regular dietary intake rate in 17 patients (49%). Cutaneous free tissue flaps had a significantly higher regular dietary intake rate at discharge and a significantly lower incidence of donor site complications than free jejunal flaps. In conclusion, free-flap reconstruction may be a better method than free jejunal flap reconstruction for the treatment of hypopharyngeal cancer.

Comparison of Dosage of Nivolumab in Efficacy and Safety for Recurrent Metastatic Squamous Cell Carcinoma.

BACKGROUND/AIM: There are no real-world comparative data of nivolumab doses of 3 mg/kg and 240 mg/body for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We investigated the efficacy and safety of nivolumab in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) at different doses using real-world data. PATIENTS AND METHODS: R/M SCCHN patients who received nivolumab were divided into the 3 mg/kg and 240 mg/body groups and retrospectively examined for efficacy and safety. RESULTS: A total of 199 patients (3 mg/kg and 240 mg/body, 88 and 111 patients, respectively) were included. The 3 mg/kg vs. 240 mg/body groups had similar overall response rates (15% vs. 25, p=0.15), disease control rates (46% vs. 57%, p=0.15), overall survival (9.5 months vs. 10.9 months), and progression-free survival (3.7 months vs. 3.8 months, p=0.95). The incidence of immune-related adverse events was also similar in both groups. CONCLUSION: In R/M SCCHN patients, nivolumab showed similar efficacy and safety at doses of 3 mg/kg and 240 mg/body.

Prognostic Factors of Potential Early Recurrence of Hypopharyngeal Carcinoma.

BACKGROUND/AIM: Prognostic factors of hypopharyngeal carcinoma have been reported previously. However, recurrent cases of this disease occurring within 6 months of treatment have been excluded or poorly documented in many studies. We aimed to evaluate the prognostic factors of hypopharyngeal carcinoma recurrence within 6 months. PATIENTS AND METHODS: A total of 120 patients were eligible for this retrospective study. Recurrent cases of hypopharyngeal carcinoma occurring within 6 months of treatment were evaluated and compared with non-recurrent cases. RESULTS: Recurrence within 6 months was detected in 28/50 cases. In univariate analyses, classification markers (pT≥4a and cN≥2b) were statistically significant prognostic factors for early recurrence (p=0.04 and p=0.04, respectively); however, only pT≥4a was predictive of recurrence in multivariate analyses (p=0.02). CONCLUSION: Risk stratification according to the prognostic factor pT≥4a will allow physicians to identify patients who should be followed meticulously within the first 6 months.

Predictive and Prognostic Biomarker Identification in a Large Cohort of Androgen Receptor-Positive Salivary Duct Carcinoma Patients Scheduled for Combined Androgen Blockade.

Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed. mRNA from 76 R/M androgen receptor (AR)-positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens. AR, Notch, MAPK, TGFß, estrogen receptor (ER), Hedgehog (HH), and PI3K signaling pathway activity scores (PAS) were determined based on the expression levels of target genes. Additionally, 5-alpha reductase type 1 (SRD5A1) expression was determined. These markers were related to clinical benefit (complete/partial response or stable disease ≥6 months) and progression-free and overall survival (PFS/OS). SRD5A1 expression had the highest general predictive value for clinical benefit and positive predictive value (PPV: 85.7%). AR PAS had the highest negative predictive value (NPV: 93.3%). The fitting of a multivariable model led to the identification of SRD5A1, TGFß, and Notch PAS as the most predictive combination. High AR, high Notch, high ER, low HH PAS, and high SRD5A1 expression were also of prognostic importance regarding PFS and SRD5A1 expression levels for OS. AR, Notch PAS, and SRD5A1 expression have the potential to predict the clinical benefit of CAB treatment in SDC patients. SRD5A1 expression can identify patients that will and AR PAS patients that will not experience clinical benefit (85.7% and 93.3% for PPV and NPV, respectively). The predictive potential of SRD5A1 expression forms a rational basis for including SRD5A1-inhibitors in SDC patients' treatment.

General rules for clinical and pathological studies on oral cancer (2nd edition): a synopsis.

For doctors and other medical staff treating oral cancer, it is necessary to standardize the basic concepts and rules for oral cancer to achieve progress in its treatment, research, and diagnosis. Oral cancer is an integral part of head and neck cancer and is treated in accordance with the general rules for head and neck cancer. However, detailed rules based on the specific characteristics of oral cancer are essential. The objective of this article was to contribute to the development of the diagnosis, treatment, and research of oral cancer, based on the correct and useful medical information of clinical, surgical, pathological, and imaging findings accumulated from individual patients at various institutions. Our general rules were revised as the UICC was revised for the 8th edition and were published as the Japanese second edition in 2019. In this paper, the English edition of the "Rules" section is primarily presented.

The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy.

OBJECTIVE: Salivary duct carcinoma (SDC) is a highly aggressive and uncommon tumor arising not only de novo but also in pleomorphic adenoma. Androgen receptor (AR)- and HER2-targeted therapy have recently been introduced for SDC as promising treatment options; however, no predictive biomarkers have yet been established. EZH2 and H3K27me3 are closely linked to the development and progression of various cancers, and EZH2 is also expected to be a desirable therapeutic target. We therefore explored the clinicopathological and prognostic implications of EZH2 and H3K27me3 in a large cohort of SDC patients, focusing on their impact on the therapeutic efficacy of AR- or HER2-targeted therapy. MATERIALS AND METHODS: The EZH2 and H3K27me3 immunohistochemical expression and EZH2 Y646 gain-of-function mutation status were examined in 226 SDCs, and the relationship with the clinicopathological factors as well as clinical outcomes were evaluated within the three groups depending on the treatment: AR-targeted (combined androgen blockade with leuprorelin acetate and bicalutamide; 89 cases), HER2-targeted (trastuzumab and docetaxel; 42 cases), and conventional therapy (112 cases). RESULTS: EZH2 and H3K27me3 were variably immunoreactive in most SDCs. A positive correlation was found between the expression of EZH2 and H3K27me3. The EZH2 expression in the SDC component was significantly higher than that in the pre-existing pleomorphic adenoma component. EZH2 Y646 was not identified in any cases. EZH2-high cases more frequently had an advanced clinical stage and aggressive histological features than EZH2-low cases. An EZH2-high status in patients treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. In addition, a H3K27me3-high status in patients treated with AR-targeted therapy was related to a shorter overall survival. Conversely, there was no association between the EZH2 and H3K27me3 expression and the clinical outcomes in the conventional or HER2-targeted therapy groups. CONCLUSIONS: A high expression of EZH2 and H3K27me3 in SDC might be a predictor of a poor efficacy of AR-targeted therapy. Our data provide new insights into the role of EZH2 and H3K27me3 in therapeutic strategies for SDC.

Resection of Parapharyngeal Space Tumors Located in the Prestyloid Compartment: Efficacy of the Cervical Approach.

BACKGROUND: Parapharyngeal space tumors are rare. Among them, tumors in the prestyloid compartment are particularly suitable for surgery; however, there are no detailed reports of such surgery and their features remain unknown. METHODS: We conducted a retrospective cohort study. For 67 surgical cases of benign tumors in this compartment, we examined the patient and tumor characteristics, fine-needle aspiration cytology (FNAC), and intraoperative details such as surgical approach, use of complete excision, and postoperative complications. RESULTS: Pleomorphic adenomas (PAs) comprised 73.1% of the lesions. The diagnostic accuracy of FNAC to differentiate benign and malignant tumors was 97.7%. Of the treated lesions, 94.0% were removed via the cervical approach alone, including all PAs. The remaining 6.0% were resected via the cervical-parotid approach. The median operative time and bleeding volume were 89 min and 50 mL, respectively. Operative time using the cervical approach was significantly shorter (p = 0.021). All cases could be treated via complete surgical excision. Postoperative complications occurred in 32.8% of patients, with transient slight facial palsy being the most common. No fatal complications occurred and 92.5% of patients had no sequelae. There was no significant association between complications and surgical approach. CONCLUSION: Based on diagnosis by FNAC, with a high accuracy rate, most benign prestyloid tumors, especially PAs, were resected using the cervical approach alone, with a shorter operative time and without severe complications.

Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients.

No real-world, long-term outcomes of immunotherapy with nivolumab for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have yet been reported. Furthermore, the prognostic impact of the best overall response (BOR) of this therapy remains unclear. We conducted a multi-institutional cohort study of the long-term efficacy and safety of this therapy and investigated prognostic factors associated with survival. Further, we evaluated the relationship between BOR and survival. Median follow-up time was 25.9 months. Median overall survival (OS) was 9.6 months, and two-year survival rate was 25.0%. Median progression-free survival (PFS) was 3.7 months, and two-year PFS rate was 19.6%. BOR was assessed as complete response (CR) in 6%, partial response (PR) in 13%, stable disease (SD) in 30%, and progressive disease (PD) in 52% of the patients. Overall response rate was 18%, and disease control rate was 48%. For immune-related adverse events (irAEs), 38 irAEs were detected in 29 patients. On multivariate analysis, the development of irAEs was significantly associated with better OS and PFS. Better BOR was significantly associated with longer OS and PFS. These findings demonstrate the long-term efficacy and safety of nivolumab therapy for R/M SCCHN in a real-world setting. The magnitude of BOR and the development of irAEs might be useful surrogate markers of survival.

Multicentre, retrospective study of the efficacy and safety of nivolumab for recurrent and metastatic salivary gland carcinoma.

Although immune-checkpoint inhibitors (ICIs) are effective against various cancers, little is known regarding their role in salivary gland carcinoma (SGC) treatment. Therefore, we evaluated the efficacy and safety of nivolumab monotherapy in patients with recurrent and/or metastatic SGC. In this multicentre retrospective study, nivolumab (240 mg) was administered every 2 weeks. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were examined; the correlation between treatment outcomes and clinicopathological factors was analysed. Twenty-four patients were enrolled; the most common histopathology was salivary duct carcinoma. Eleven tumours were PD-L1-positive; no tumour was microsatellite instability-high. The ORR was 4.2%, and the median PFS and OS were 1.6 and 10.7 months, respectively. One patient continued nivolumab for 28 months without disease progression. One patient showed grade 4 increase in creatine phosphokinase levels and grade 3 myositis. Biomarker analysis revealed significantly increased OS in patients with performance status of 0; modified Glasgow prognostic score of 0; low neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and C-reactive protein; and high lymphocyte-to-monocyte ratio and in patients who received systemic therapy following nivolumab. Although nivolumab's efficacy against SGC was limited, some patients achieved long-term disease control. Further studies are warranted on ICI use for SGC.

Salvage Chemotherapy After Nivolumab for Recurrent or Metastatic Head and Neck Carcinoma.

BACKGROUND/AIM: The treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has remained challenging. The effect of salvage chemotherapy (SCT) after nivolumab has been identified recently in other cancer types. The aim of this study was to examine the efficacy of SCT after nivolumab treatment in patients with R/M HNSCC. PATIENTS AND METHODS: A retrospective study was conducted at four institutions in Japan. Fifty-six patients were enrolled in the study. RESULTS: The overall survival (OS) in SCT patients was significantly longer than that in best supportive care (BSC) patients. In the SCT patients, the median OS, median progression-free survival (PFS) and objective response rate (ORR) were 7.3 months, 2.3 months and 36%, respectively. Prognostic factor for OS and ORR was performance score (PS) and previous radiation, respectively. CONCLUSION: SCT after nivolumab is associated with better clinical outcomes in patients with R/M HNSCC compared to those receiving BSC.

Weekly Cetuximab and Paclitaxel for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Head and neck cancers account for 8% of all cancer cases worldwide. However, identifying the optimal treatment for recurrent or metastatic head and neck cancer (R/MHNSCC) has been challenging. The aim of this study was to evaluate the efficacy, safety, and prognostic factors of the outcome of patients with R/MHNSCC who were treated with weekly cetuximab and paclitaxel (Cmab-PTX). PATIENTS AND METHODS: The records of R/MHNSCC patients who were treated with Cmab-PTX in our institution between June 2013 and September 2017 were collected. We analyzed Overall survival (OS), progression-free survival (PFS), prognostic factors and adverse events. RESULTS: The records of 59 patients treated with Cmab-PTX were analyzed. The median PFS was 5.7 months, and the median OS was 11.8 months. Patients who had been administered cetuximab previously had shorter PFS and OS than those who had not. CONCLUSION: Cmab-PTX may be considered as a treatment option in head and neck R/MHNSCC patients.

Investigation of the Efficacy and Safety of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma.

BACKGROUND/AIM: Nivolumab, an anti-PD-1 inhibitor, has demonstrated efficacy in patients with several types of recurrent and metastatic (R/M) squamous cell carcinoma of the head and neck. We evaluated patients with R/M-NPC receiving nivolumab. PATIENTS AND METHODS: Twelve patients with R/M-NPC were enrolled at 4 institutions. The primary endpoint was overall survival, and secondary endpoints were i) progression-free survival (PFS), ii) overall response rate (ORR), iii) disease control rate (DCR), and iv) treatment-related toxicity. RESULTS: The 1-year survival rate was 75.8%, the median PFS was 2.8 months, and the 1-year PFS rate was 33.3%. The best therapeutic response was complete response in 2, stable disease in 3 and progressive disease in 7 patients. The ORR of all patients was 16.7% and the DCR was 41.7%. CONCLUSION: Nivolumab is a useful and relatively safe second-line systemic therapy in patients with R/M-NPC, and even patients who do not respond to nivolumab may survive for a long time.