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Objective: Esophageal cancer is the most common second primary cancer (SPC) in patients with head and neck cancer (HNC). Esophageal SPC has a negative impact on survival. Elevated mean corpuscular volume (MCV) is an accepted predictor of esophageal cancer risk. The aim of this study was to elucidate the usefulness of elevated MCV as an indicator of a high risk for esophageal SPC. Methods: We retrospectively reviewed the medical records of patients with oropharyngeal, hy-popharyngeal, and laryngeal squamous cell carcinoma who underwent chemoradiotherapy be-tween 2003 and 2012. We excluded patients younger than 20 years or who had received treat-ment for esophageal cancer and who had a histologically unproven lesion. Patients were divided into two groups according to their MCV. The cut-off for MCV was defined by receiver operating characteristics curve analysis. The primary endpoint was the cumulative incidence of esophageal SPC.Results: A total of 295 patients were included. The median follow-up period for surviving patients was 7.4 years and the optimal cut-off point was 99.0 fL. One hundred ninety-five patients (66%) had an MCV < 99.0 fL and 100 (34%) had an MCV > 99.0 fL. The 5-year cumulative incidence in patients with an MCV < 99.0 fL and > 99.0 fL was 8.7% and 27%, respectively. In the multivariate analysis, an MCV > 99.0 fL (HR = 2.2; 95%CI, 1.1-4.2) was an independent risk factor. Conclusion: MCV > 99.0 fL was found to be a risk factor for esophageal SPC. We, therefore, recommend that patients with an MCV > 99.0 fL should undergo intensive monitoring.

Recently, Schlafen family member 11 (SLFN11) has been reported to increase the sensitivity of cancer cells to DNA-damaging agents, including platinum derivatives; thus, SLFN11 may be a predictive biomarker for platinum-based chemoradiotherapy (CRT). In this study, we examined whether SLFN11 expression was associated with the therapeutic outcome of platinum-based CRT in head and neck squamous cell carcinoma (HNSCC). We performed immunohistochemical analyses for SLFN11 expression in 161 HNSCC tissues from patients who had been administered cisplatin-based CRT and examined the correlation between SLFN11 expression and progression-free survival (PFS). Additionally, SLFN11 expression was examined in 10 paired samples obtained before and after CRT in patients with local failure. Furthermore, in vitro experiments were performed using several HNSCC cell lines and isogenic SLFN11-knockout cells to assess the association between SLFN11 expression and drug sensitivity. PFS was found to be significantly better in the SLFN11-positive group than in the SLFN11-negative group among the 161 patients (5-year PFS: 78.8% vs. 52.8%, respectively, p < 0.001). Similar results were observed for the PFS at each primary site. The percentage of SLFN11 positivity was lower in tumor samples from patients with local failure after CRT than that in the corresponding primary tumors before CRT in 8 of 10 cases. Results of the in vitro assay demonstrated that SLFN11-knockout cells exhibited reduced sensitivity to DNA-damaging agents but not to the non-DNA-damaging agent docetaxel. Our findings suggest that SLFN11 may serve as a potential biomarker for predicting the response of HNSCC patients to platinum-based CRT.

Introduction Sequential boost intensity-modulated radiotherapy (SQB-IMRT) uses two different planning CTs (pCTs) and treatment plans. SQB-IMRT is a form of adaptive radiotherapy that allows for responses to changes in the shape of the tumour and organs at risk (OAR). On the other hand, dose accumulation with the two plans can be difficult to evaluate. The purpose of this study was to analyse patterns of loco-regional failure using deformable image registration (DIR) in hypopharyngeal cancer patients treated with SQB-IMRT. Methods Between 2013 and 2019, 102 patients with hypopharyngeal cancer were treated with definitive SQB-IMRT at our institution. Dose accumulation with the 1st and 2nd plans was performed, and the dose to the loco-regional recurrent tumour volume was calculated using the DIR workflow. Failure was classified as follows: (i) in-field (>= 95% of the recurrent tumour volume received 95% of the prescribed dose); (ii) marginal (20-95%); or (iii) out-of-field (<20%). Results After a median follow-up period of 25 months, loco-regional failure occurred in 34 patients. Dose-volume histogram analysis showed that all loco-regional failures occurred in the field within 95% of the prescribed dose, with no marginal or out-of-field recurrences observed. Conclusion The dosimetric analysis using DIR showed that all loco-regional failures were within the high-dose region. More aggressive treatment may be required for gross tumours.

Background: In head and neck cancers, histopathological information is important for the determination of the tumor characteristics and for predicting the prognosis. The aim of this study was to assess the utility of diffusion-weighted T2 (DW-T2) mapping for the evaluation of tumor hisinlogical grade in patients with head and neck squamous cell carcinoma (SCC). Methods: The cases of 41 patients with head and neck SCC (21 well/moderately and 17 poorly differentiated SCC) were retrospectively analyzed. All patients received MR scanning using a 3-Tesla MR unit. The conventional T2 value, DW-T2 value, ratio of DW-T2 value to conventional T2 value, and apparent diffusion coefficient (ADC) were calculated using signal information from the DW-T2 mapping sequence with a manually placed region of interest (ROI). Results: ADC values in the poorly differentiated SCC group were significantly lower than those in the moderately/well differentiated SCC group (P<0.05). The ratio of Dvv-T2 value to conventional T2 value was also significantly different between poorly and moderately/well differentiated SCC groups (P<0.01). Receiver operating characteristic (ROC) curve analysis of ADC values showed a sensitivity of 0.76, specificity of 0.67, positive predictive value (PPV) of 0.62, negative predictive value (NPV) of 0.8, accuracy of 0.71 and area under the curve (AUC) of 0.73, whereas the ROC curve analysis of the ratio of DW-T2 value to conventional T2 value showed a sensitivity of 0.76, specificity of 0.83, PPV of 0.76, NPV of 0.83, accuracy of 0.8 and AUC of 0.82. Conclusions: DW-T2 mapping might be useful as supportive information for the determination of tumor histological grade in patients with head and neck SCC.

Background: In head and neck cancers, histopathological information is important for the determination of the tumor characteristics and for predicting the prognosis. The aim of this study was to assess the utility of diffusion-weighted T2 (DW-T2) mapping for the evaluation of tumor hisinlogical grade in patients with head and neck squamous cell carcinoma (SCC). Methods: The cases of 41 patients with head and neck SCC (21 well/moderately and 17 poorly differentiated SCC) were retrospectively analyzed. All patients received MR scanning using a 3-Tesla MR unit. The conventional T2 value, DW-T2 value, ratio of DW-T2 value to conventional T2 value, and apparent diffusion coefficient (ADC) were calculated using signal information from the DW-T2 mapping sequence with a manually placed region of interest (ROI). Results: ADC values in the poorly differentiated SCC group were significantly lower than those in the moderately/well differentiated SCC group (P<0.05). The ratio of Dvv-T2 value to conventional T2 value was also significantly different between poorly and moderately/well differentiated SCC groups (P<0.01). Receiver operating characteristic (ROC) curve analysis of ADC values showed a sensitivity of 0.76, specificity of 0.67, positive predictive value (PPV) of 0.62, negative predictive value (NPV) of 0.8, accuracy of 0.71 and area under the curve (AUC) of 0.73, whereas the ROC curve analysis of the ratio of DW-T2 value to conventional T2 value showed a sensitivity of 0.76, specificity of 0.83, PPV of 0.76, NPV of 0.83, accuracy of 0.8 and AUC of 0.82. Conclusions: DW-T2 mapping might be useful as supportive information for the determination of tumor histological grade in patients with head and neck SCC.

Purpose We have performed superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) for patients with maxillary sinus cancer. The promising treatment outcomes of this non-surgical treatment were reported in past studies. However, few clinical studies have been conducted to evaluate the outcome of salvage surgery following RADPLAT. The purpose of this study was to analyze the treatment outcomes of salvage surgery for patients with recurrent maxillary sinus cancer after RADPLAT. Methods We assessed 45 patients who had recurrence following RADPLAT between 1999 and 2017, and conducted a retrospective analysis. We excluded patients who did not complete RADPLAT. Patients were not considered to have completed RADPLAT if they underwent intra-arterial cisplatin less than three times or received a total radiation dose of less than 60 Gy. The primary endpoint was overall survival. The median follow-up period for surviving patients after recurrence was 5.1 years. Results Twenty-five of the 45 (56%) patients underwent salvage surgery. The 5-year overall survival rate was 68% in patients who underwent salvage surgery, while all patients who did not undergo salvage surgery died during the observation period. Fifteen of 24 (63%) patients with local recurrence underwent salvage surgery. Eight patients did not undergo salvage surgery because of unresectable disease; five of the eight patients had unresectable posterior extension. All nine patients with nodal recurrence underwent neck dissection. Conclusion Treatment outcomes of salvage surgery following RADPLAT were favorable enough for it to be generally recommended. To reduce unresectable recurrence, the posterior section should be eradicated by RADPLAT.

The aim of this study was to investigate the utility of amide proton transfer (APT) imaging for the determination of human papillomavirus (HPV) status in patients with oropharyngeal squamous cell carcinoma (SCC). Thirty-one patients with oropharyngeal SCC were retrospectively evaluated. All patients underwent amide proton transfer imaging using a 3T magnetic resonance (MR) unit. Patients were divided into HPV-positive and -negative groups depending on the pathological findings in their primary tumor. In APT imaging, the primary tumor was delineated with a polygonal region of interest (ROI). Signal information in the ROI was used to calculate the mean, standard deviation (SD) and coefficient of variant (CV) of the APT signals (APT mean, APT SD, and APT CV, respectively). The value of APT CV in the HPV-positive group (0.43 +/- 0.04) was significantly lower than that in the HPV-negative group (0.48 +/- 0.04) (P = .01). There was no significant difference in APT mean (P = .82) or APT SD (P = .13) between the HPV-positive and -negative groups. Receiver operating characteristic (ROC) curve analysis of APT CV had a sensitivity of 0.75, specificity of 0.8, positive predictive value of 0.75, negative predictive value of 0.8, accuracy of 0.77 and area under the curve (AUC) of 0.8. The APT signal in the HPV-negative group was considered heterogeneous compared to the HPV-positive group. This information might be useful for the determination of HPV status in patients with oropharyngeal SCC.

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of thesepatientshad a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% formucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of thesepatientshad a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% formucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.

Objective: Despite of rapid advances in endoscopic surgery, the gold standard for sinonasal squamous cell carcinoma (SNSCC) surgery has remained the open approach with en-block resection due to the aggressive nature of SNSCC, including frequent recurrence and high mortality rate. For that reason, few studies have focused on SNSCC treated by endoscopic surgery alone. The objective of this study was to evaluate the usefulness of endoscopic surgery for patients with SNSCC. Methods: A retrospective analysis was performed for 15 consecutive SNSCC patients who underwent endoscopic surgery without an open approach. We carefully selected patients whose tumor attachment sites could be fully visualized and completely resected through an endonasal approach. Results: Of the fifteen patients, 4 patients (27%) were diagnosed with T1, 7 (47%) with T2, 4 (27%) with T3, and no patients with T4a or T4b disease. Four of the 15 (27%) patients showed positive surgical margins. The 5-yr overall survival, disease-specific survival, and local control rate was 72.4%, 79.6%, and 92.9%, respectively. The 5-yr disease-specific survival for T1, T2, and T3 disease was 100% and 75% and 75%, respectively. Patients with negative surgical margins had a better disease-specific survival rate than did those with positive surgical margins (p = 0.0253). Conclusion: Endoscopic surgery for patients with SNSCC appears to afford an effective method in selected cases. The achievement of negative surgical margins with a good view of the tumor attachment site was considered to be critical to the management of SNSCC. (c) 2020 Oto-Rhino-Laryngological Society of Japan Inc. Published by Elsevier B.V. All rights reserved.

Background We investigated whether prophylactic percutaneous endoscopic gastrostomy (PEG) is used effectively for patients treated with definitive concurrent chemoradiotherapy (CCRT) and the predictors of the need for PEG. Methods 326 patients with laryngeal, oropharyngeal or hypopharyngeal cancers were retrospectively reviewed. Results The PEG tube use group had more favorable results than the total parenteral nutrition and nasogastric tube groups in terms of rate of serum albumin loss, incidence of severe fever and aspiration pneumonia, CCRT completion rate and hospitalization period. However, it was inferior to oral intake. Analysis of the relative risk of requiring enteral or parenteral nutrition revealed that performance status (PS) 2, primary site (supraglottis, oropharynx, or hypopharynx), N3 disease, and cisplatin were predictors of the need for nutritional support. Conclusions Prophylactic PEG is effective for patients treated with definitive CCRT and is especially required for patients with PS2 or oropharyngeal cancer.

Objective: Despite of rapid advances in endoscopic surgery, the gold standard for sinonasal squamous cell carcinoma (SNSCC) surgery has remained the open approach with en-block resection due to the aggressive nature of SNSCC, including frequent recurrence and high mortality rate. For that reason, few studies have focused on SNSCC treated by endoscopic surgery alone. The objective of this study was to evaluate the usefulness of endoscopic surgery for patients with SNSCC. Methods: A retrospective analysis was performed for 15 consecutive SNSCC patients who underwent endoscopic surgery without an open approach. We carefully selected patients whose tumor attachment sites could be fully visualized and completely resected through an endonasal approach. Results: Of the fifteen patients, 4 patients (27%) were diagnosed with T1, 7 (47%) with T2, 4 (27%) with T3, and no patients with T4a or T4b disease. Four of the 15 (27%) patients showed positive surgical margins. The 5-yr overall survival, disease-specific survival, and local control rate was 72.4%, 79.6%, and 92.9%, respectively. The 5-yr disease-specific survival for T1, T2, and T3 disease was 100% and 75% and 75%, respectively. Patients with negative surgical margins had a better disease-specific survival rate than did those with positive surgical margins (p = 0.0253). Conclusion: Endoscopic surgery for patients with SNSCC appears to afford an effective method in selected cases. The achievement of negative surgical margins with a good view of the tumor attachment site was considered to be critical to the management of SNSCC. (c) 2020 Oto-Rhino-Laryngological Society of Japan Inc. Published by Elsevier B.V. All rights reserved.

Background: The revised 8th edition of the AJCC/UICC staging system was released in January 2017, and depth of invasion (DOI) was added to the new criteria for T classification in oral cavity cancer. In this study, we evaluated whether the 8th edition presents the prognosis and risk of nodal metastasis in patients with squamous cell carcinoma of tongue more accurately than did the 7th edition. Methods: The data for 112 patients were obtained and reclassified based on the criteria presented in the 8th edition. Results: Seven patients previously staged as T1 based on the criteria in the 7th edition were reclassified as T2 based on the 8th edition, while 19 T2 patients were reclassified as T3, and 9 T4a patients were reclassified as T3. T3 in the 8th edition represents a homogenous population showing the same prognosis, while T2 in the 8th edition represents a heterogenous population. Nodal metastasis was significantly correlated with T classification in both editions and DOI. However, neither the T classification in the 7th or 8th edition, nor DOI could predict the probability of potential nodal metastasis in patients with cN0 disease. Conclusions: The classification on T3 in the 8th edition can be seen as reasonable with regard to prognosis. Nodal metastasis was significantly correlated with T classification and DOI; however, the probability of subsequent nodal metastasis in patients with T2N0 was almost same for the criteria in the 7th and 8th editions, therefore, the same careful management as before is required for patients with N0 disease.