Head and neck small-cell carcinoma: A multicenter study of 39 cases from 10 institutions.

Objective: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC. Materials and methods: This study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available (n = 2) and for discrepant central pathological judgements (n = 6). The remaining 39 patients were processed for data analysis. Results: As pretreatment examinations, computed tomography (CT) was performed for the brain (n = 8), neck (n = 39), and chest (n = 32), magnetic resonance imaging (MRI) for the brain (n = 4) and neck (n = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity (n = 1), nasal cavity/paranasal sinuses (n = 16), nasopharynx (n = 2), oropharynx (n = 4), hypopharynx (n = 2), larynx (n = 6), salivary gland (n = 3), thyroid (n = 2), and others (n = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group (n = 27), non-CRT group (n = 8), and best supportive care group (n = 4). The CRT group included concurrent CRT (CCRT) (n = 17), chemotherapy (Chemo) followed by radiotherapy (RT) (n = 5), and surgery (Surg) followed by CCRT (n = 5). The non-CRT group included Surg followed by RT (n = 2), Surg followed by Chemo (n = 1), RT alone (n = 2), and Chemo alone (n = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group (n = 22) and the Chemo without concurrent RT group (n = 9). Conclusion: Neck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC.

Addition of S-1 to radiotherapy for treatment of T2N0 glottic cancer: Results of the multiple-center retrospective cohort study in Japan with a propensity score analysis.

OBJECTIVES: This multicenter retrospective cohort study aimed to evaluate the significance of adding S-1 to radiotherapy (RT) for the treatment of T2N0 glottic cancer using a propensity score matched analysis in Japan. MATERIALS AND METHODS: This study was conducted on 287 patients with T2N0 glottic cancer who were treated with definitive RT or chemoradiotherapy with S-1 (S-1 RT) between April 2007 and March 2017. Propensity score matched analysis was performed to ensure the well-balanced characteristics of the groups of patients who received RT alone and S-1 RT. Overall, progression-free and laryngectomy-free survivals and local control and laryngeal preservation rates were compared. RESULTS: Fifty-four pairs of patients were selected after performing propensity score matched analysis. Clinical characteristics were well-balanced between the two groups. The overall survival of patients in the S-1 RT group was significantly better than those in the RT alone group (P = 0.008). The progression-free and laryngectomy-free survivals of patients in the S-1 RT group were also better than those in the RT alone group; however, the differences were not significant. In contrast, patients in the S-1 RT group had slightly lower local control and laryngeal preservation rates compared with those in the RT alone group. The incidence of dermatitis in the S-1 RT group was significantly higher than that in the RT alone group in the matched population (P = 0.013). CONCLUSIONS: The addition of S-1 to RT for the treatment of T2N0 glottic cancer was not associated with better local control and laryngeal preservation rates in this study.

A prospective clinical trial of the second-look procedure for transoral surgery in patients with T1 and T2 laryngeal, oropharyngeal, and hypopharyngeal cancer.

BACKGROUND: Transoral surgery (TOS) has been widely applied for early T-stage head and neck cancer (HNC). The resection is performed with a minimum safety margin for function preservation under a limited surgical field; therefore, it is difficult to have a strong conviction about the complete resection. This study aims to evaluate the completeness of the initial TOS procedure; possibility of primary control by TOS alone; and predictive factors in patients with early T-stage laryngeal, oropharyngeal, and hypopharyngeal cancer. METHODS: Patients were treated by TOS at the primary site with or without neck dissection. The patients were divided into two groups based on the pathological evaluation of their surgical specimens: the control (observation) group, in that the resection was considered complete and the intervention (second-look procedure) group, in that incomplete tumor resection was suspected. The predictive factors for the possibility and/or limitations of complete resection by TOS were then analyzed. RESULTS: The study enrolled 26 and 25 patients in the control and intervention group, respectively. The success rate for single resection was 66% and the predictive factor was tumor depth obtained by enhanced computed tomography (CT) examination (odds ratio, 7.870, P = .0243). The success rate for definitive therapy by TOS alone was 83% and the predictive factor was poor differentiation observed on pathological examination (odds ratio, 6.800, P = .0248). CONCLUSIONS: TOS has the potential for both definitive resection and function preservation with minimal invasiveness. Identification of the risk factors for TOS is advantageous for accurate treatment selection in patients with early T-stage HNC.

Postoperative Bio-Chemoradiotherapy Using Cetuximab and Docetaxel in Patients With Cis-Platinum-Intolerant Core High-Risk Head and Neck Cancer: Protocol of a Phase 2 Nonrandomized Clinical Trial.

BACKGROUND: We confirmed the safety of postoperative bio-chemoradiotherapy using cetuximab and docetaxel in a small number of patients with cis-platinum-intolerant core high-risk head and neck cancer. OBJECTIVE: To assess treatment efficacy, we planned a phase 2 study of postoperative bio-chemoradiotherapy for patients with cis-platinum-intolerant core high-risk head and neck cancer and will compare the results to those of previously collected radiotherapy data. METHODS: Patients who underwent definitive surgery for oral cavity, laryngeal, oropharyngeal, or hypopharyngeal advanced cancer, whose postoperative pathological results indicated core high risk for recurrence (eg, positive margin in the primary site or extranodal extension) and who were cis-platinum-intolerant, will undergo postoperative bio-chemoradiotherapy. The primary end point is 2-year disease-free survival. RESULTS: The expected 2-year disease-free survival is set at 55%, and the calculated sample size is 35 patients, according to a statistical analysis based on previous reports. CONCLUSIONS: This treatment method is expected to improve the survival rate of patients with severe head and neck cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000031835; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000036355 (Archived by WebCite at http://www.webcitation.org/71fejVjMr).

Predictive value of the Hyodo score in endoscopic evaluation of aspiration during swallowing.

OBJECTIVE: The Hyodo scoring system during the endoscopic procedure has been proposed as a new tool for evaluating oral intake feasibility. However, the effectiveness of the information obtained from this procedure in predicting aspiration is not fully elucidated. The aim of this study was to assess the significance of clinical factors, including Hyodo scores, for predicting the risk of aspiration. METHODS: Five hundred and twenty-eight endoscopic swallowing examinations were performed. Clinical factors, including age, sex, disease type, history of aspiration pneumonia, cognitive function, presence of tracheostomy, presence of vocal cord paralysis, consciousness level on the Japan Coma Scale, ECOG Performance Status, serum albumin level and Hyodo score, were obtained for each examination. The relationship between each of these factors and the presence of aspiration during endoscopic procedure was evaluated. RESULTS: Three hundred and thirty-two patients (62.9%) were scored less than 5, 153 (29.0%) were scored between 5 and 8, and 43 (8.1%) were scored above 8. The number of patients with aspiration was 133 (25.2%). ROC analysis revealed that a cut-off point of 6 for Hyodo score was effective for predicting aspiration, with a sensitivity of 0.65 and a specificity of 0.86. History of aspiration pneumonia (OR 1.87, P<0.001), vocal cord paralysis (OR 2.23, P<0.001), PS≥3 (OR 2.47, P<0.001) and Hyodo score>6 (OR 9.08, P<0.001) were found to be independent predictive factors for aspiration. CONCLUSION: The Hyodo scoring method was easy for otolaryngologists to perform and the scores were useful for predicting aspiration with moderate sensitivity and high specificity. Hyodo score>6, history of aspiration pneumonia, vocal cord paralysis, and PS≥3 were independent predictive factors for aspiration and that a Hyodo score above 6 was the statistically strongest predictor for aspiration.

The applicability of new TNM classification for humanpapilloma virus-related oropharyngeal cancer in the 8th edition of the AJCC/UICC TNM staging system in Japan: A single-centre study.

OBJECTIVE: The purpose of this study is to validate the applicability of new TNM classification for human papillomavirus (HPV)-related oropharyngeal cancer (OPC) in the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system in Japan. METHODS: A total of 91 OPC patients treated with radiation-based therapy between November 2001 and July 2015 were analyzed retrospectively in this study. HPV infection status was evaluated using tumor p16 expression. RESULTS: 40 OPC patients (44.0%) had HPV-positive disease in this study. The distribution of disease stage of HPV-positive OPC patients dramatically changed from the 7th edition to the 8th edition of AJCC/UICC TNM classification. However, neither the 8th edition nor the 7th edition of the AJCC/UICC TNM staging system could adequately predict outcomes of HPV-positive OPC patients in our patient series. On the other hand, our multivariate analysis indicated that matted nodes and age ≥63 were independent prognostic factors for progression-free survival. In addition, HPV-positive OPC patients with stage I without matted nodes showed significantly better overall and progression-free survival compared with those with stage I with matted nodes and stages II and III in the 8th edition of the AJCC/UICC TNM staging system (P=0.008, and P=0.043, respectively). CONCLUSION: Our results suggested that matted nodes of HPV-positive OPC patients might be additionally examined to apply the 8th edition of AJCC/UICC TNM classification for more adequate predicting outcomes of HPV-positive OPC patients.

Lymph node ratio as a prognostic factor for survival in patients with head and neck squamous cell carcinoma.

OBJECTIVE: The purpose of this study is to validate the concept of lymph node ratio (LNR) in head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 63 patients with HNSCC who underwent resection of the primary tumor combined with neck dissection in our institution were analyzed in this study. LNR was defined as the number of positive lymph nodes divided by the total number of lymph nodes excised. LNR was categorized into two groups (<0.068 and ≥0.068) according to the results of receiver-operating characteristic plots for determination of the cut-off value. RESULTS: LNR≥0.068 was associated with poor overall survival (OS), progression-free survival (PFS) and locoregional recurrence-free survival (LRFS) after resection of the primary tumor combined with neck dissection in patients with HNSCC. Univariate and multivariate data analysis showed that LNR≥0.068 was an independent prognostic factor for OS, PFS and LRFS. Both pathological T stage status (pT3 or 4) and ≥3 positive LNs were also an independent prognostic factors for PFS in patients with HNSCC in our univariate and multivariate analysis. CONCLUSION: These results suggested that LNR could be useful tools in identifying HNSCC patients with poor outcomes.

The Second-Look Procedure for Transoral Videolaryngoscopic Surgery for T1 and T2 Laryngeal, Oropharyngeal, and Hypopharyngeal Cancer Patients: Protocol for a Nonrandomized Clinical Trial.

BACKGROUND: Transoral videolaryngoscopic surgery (TOVS) has been widely applied for early T stage head and neck cancer. The resection is performed with a minimum safety margin for function preservation under a limited surgical field of view, making it difficult to be certain of complete resection. OBJECTIVE: Our aim is the evaluation of the completeness of resection by initial TOVS resection, and the possibility of primary control by TOVS alone, allowing for repeat procedures for function preserving treatment in early T stage laryngeal, oropharyngeal, and hypopharyngeal cancer patients. METHODS: Patients are treated by TOVS for the primary site with or without neck dissection. Patients are divided in two groups based on the results of the pathological evaluation of the surgical specimen; the control group in which the resection is considered to be complete, and the intervention (second-look procedure) group in which incomplete tumor resection is suspected. The predictive factors for the possibility of complete resection by TOVS will then be analyzed. RESULTS: Patient enrollment started on January 1, 2014, and closed on March 31, 2016, with 54 patients. The control group consists of 27 patients, the intervention group is 21 patients, and 6 patients were excluded. There were no clinical differences between the control and intervention groups. The observation period will end on December 31, 2018. CONCLUSIONS: TOVS has potential for both definitive resection and function preservation with minimal invasiveness. Identifying the limitations of TOVS is beneficial to ensure accurate treatment selection in early T stage head and neck cancer patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry: UMIN000012485; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi? recptno=R000014472 (Archived by WebCite at http://www.webcitation.org/6v1b741Iw).

Efficacy and safety of postoperative bio-chemoradiotherapy using cetuximab and docetaxel for high-risk head and neck cancer patients in Japan.

PURPOSE: To confirm the efficacy and safety of cetuximab and docetaxel in postoperative radiotherapy for high-risk head and neck cancer patients who cannot to be administered high-dose cisplatin. PATIENTS AND METHODS: The eligibility criteria required stage III-IVB head and neck cancer patients who had undergone total resection, and for whom pathological evaluation revealed positive or close margins in the primary site and/or extracapsular nodal extension and/or two or more nodal metastases. In each case, the patients general condition prevented the use of high-dose cisplatin. Instead, they received cetuximab and docetaxel every week during a 66.6 Gy course of postoperative radiotherapy. RESULTS: Eleven patients were enrolled; the median follow-up period was 22 months, and the 1- and 2-year disease free survival rates were 91 and 55%, respectively. Grade 3 adverse events included oral mucositis, radiation dermatitis, reduced white blood cell and neutrophil counts, lung infection, aspiration, and hyponatremia; however, no grade 4 adverse events were observed. CONCLUSION: Administration of cetuximab and docetaxel during postoperative radiotherapy for high-risk poor condition head and neck cancer patients in poor general condition was both feasible and tolerable. With the safety of this treatment confirmed, we propose a phase trail to further clarify the efficacy of cetuximab and docetaxel use for high-risk cisplatin-intolerant patients.

Surgery-based versus radiation-based treatment strategy for a high metabolic volume laryngeal cancer.

OBJECTIVE/HYPOTHESIS: We previously reported that the metabolic tumor volume (MTV) of a primary tumor was an independent prognostic factor for survival in laryngeal carcinoma treated by radiotherapy (RT)-based protocol. The purpose of this study was to evaluate the difference in survival outcomes between surgery-based and RT-based treatment in patients with a MTV laryngeal cancer. STUDY DESIGN: An individual retrospective cohort study. METHODS: We reviewed the records of 63 patients with laryngeal cancer showing a primary tumor with a high MTV value (≥ 4.9 mL). The patients were separated into two groups by primary treatment strategy: 22 patients were included in the surgery group, and 41 patients were included in the RT group. Clinical factors and treatment modalities were analyzed for their association with survival. RESULTS: Multivariate analysis, including age, sex, subsite, T classification, nodal metastasis, and treatment modality, showed that the subsite (hazard ratio [HR] 2.55, P = 0.043) and treatment modality (HR 3.98, P = 0.019) were independent predictors for survival. The Kaplan-Meier curves for 2-year relapse-free survival rates and overall survival rates for patients in the surgery and RT groups were 74.2% versus 38.8% (P = 0.025) and 80.1% versus 66.7% (P = 0.078). CONCLUSIONS: Patients with a high metabolic volume laryngeal cancer treated by a surgery-based protocol showed better relapse-free survival and overall survival than did those undergoing RT-based treatment. Pretreatment MTV assessment could be useful in planning the treatment strategy for patients with a laryngeal cancer. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:862-867, 2017.

Prognostic significance of metabolic tumor volume in patients with piriform sinus carcinoma treated by radiotherapy with or without concurrent chemotherapy.

BACKGROUND: The purpose of this study was to elucidate the prognostic significance of the pretreatment metabolic tumor volume (MTV) in patients with piriform sinus carcinoma treated by radiation-based therapy. METHODS: This retrospective study included 100 patients with piriform sinus carcinomas who had received treatment by radiation-based therapy. The MTV values were obtained from pretreatment positron emission tomography (PET). The association between clinical factors, including the MTV, and survival was analyzed. RESULTS: Kaplan-Meier estimates revealed the 5-year disease-free survival (DFS) rates were significantly poorer for patients with a high MTV compared to those with a low MTV. In the multivariate analysis, MTV (p < .001), nodal metastasis (p = .011), and applied chemotherapy regimen (p = .004) were found to be independent prognostic factors for DFS. CONCLUSION: The locoregional MTV is a prognostic factor for DFS in patients with piriform sinus carcinoma treated by radiation-based therapy. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.

Chronic pharyngitis and laryngitis caused by gastroesophageal reflux.

A certain percentage of patients with gastroesophageal reflux disease (GERD) have laryn- gopharyngeal symptoms such as hoarseness, cough, and lump sensation in the throat. An updated meta-analysis showed that proton pump inhibitors (PPIs) reduced laryngopharyngeal symptoms significantly compared with placebo in patients suspected to have these symptoms caused by gastroesophageal reflux(GER). Although PPIs are often used to confirm the diagnosis of GERD (so-called "PPI test"), it is still not clear whether the -test can be applied to patients with laryngopharyngeal symptoms. We therefore have to conclude that no solid diagnostic tool is available to determine whether GER is an actual cause of chronic pharyngitis and laryngitis.