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6079 Background: Overexpression of AR is identified as a potential molecular target of SGC treatment. Combined androgen blockade (CAB) with bicalutamide has been evaluated previously, but the clinical usefulness of CAB with a next generation AR inhibitor has been unclear in SGC. We prospectively assessed the efficacy and safety of APA+GOS for pts with AR-expressing SGC. Methods: Eligible pts had fLA/RM SGC, and AR expression with at least 1% of cell nuclei immunohistochemistry staining positive. Pts were treated with APA 240 mg orally once daily and GOS 3.6 mg subcutaneously once 28 days. Primary endpoint was overall response rate (ORR) by central review according to RECIST v1.1, and a response (complete response [CR] or partial response [PR]) was confirmed by repeat assessments at least 4 weeks after the initial evaluation showing a response. Primary analysis was performed based on first 24 response evaluable (RE) pts who had been observed at least 24 weeks (Primary RE pts). The ORR was tested using exact test based on the binominal distribution, the null hypothesis for ORR of 14% was rejected when at least 8 of the 24 Primary RE pts were responders, and the efficacy was to be declared. Key secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DOR), and time to response (TTR) in the Primary RE pts, and overall survival (OS), progression free survival (PFS), and safety in the treated pts. Results: Twenty-six of the 31 pts treated with APA+GOS were regarded as RE by central review. For the 24 Primary RE pts, ORR was 25.0% (6/24), while 37.5% (9/24) including unconfirmed PR. Clinical benefit rate and DCR in the Primary RE pts were 50.0% and 70.8%, respectively. At the data cut-off (Apr 28, 2021), 5 of 6 pts with confirmed response were still on protocol treatment. Median PFS and OS in the treated pts were 7.43 months (mos) and not reached, respectively, with the median follow-up period of 8.57 mos. Grade 3 or higher treatment-related adverse events were reported in 4/31 (12.9%) pts, and the events were rash maculo-papular (n=2), anemia (n=1), and leukopenia (n=1). Conclusions: This is the first prospective trial evaluating CAB with APA for AR-expressing SGC. Although this study did not meet the predefined criteria of efficacy, clinically meaningful activity with well-tolerated safety profile of APA+GOS was shown. Clinical trial information: NCT04325828. [Table: see text]

Background: The purpose was to compare survival differences between patients with external auditory canal (EAC) cancer treated according to the University of Pittsburgh modified TNM staging system and those treated in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual on the TNM staging system for cutaneous cancers of the head and neck. Methods: We performed a retrospective, single-institution review of 60 patients with EAC cancer treated with curative intent between September 2002 and March 2018. Survival outcomes were measured on the basis of the two staging systems. Results: The C-index values for the overall survival (OS) rate revealed that the University of Pittsburgh staging system had higher prognostic accuracy than the 8th edition of the AJCC staging system. Univariable and multivariable analysis showed that T classification according to the University of Pittsburgh staging system was an independent predictor of the OS rate (hazard ratio 5.25; 95% confidence interval 1.38-24.9; P = 0.015). Meanwhile, the AJCC staging system could not differentiate T2 from T3-4 cancers. Conclusion: The University of Pittsburgh staging system for patients with EAC cancer is a valuable tool for use in clinical decision-making and predicting survival outcome.

PURPOSE/OBJECTIVE(S) Sequential boost (SQB) is an IMRT approach that is considered comparable to simultaneous-integrated boost. Dosimetric analysis in SQB using two planning CTs requires advanced dose-accumulation techniques, such as a deformable image registration (DIR) workflow. The purpose of this study was to assess patterns of failure and identify dosimetric features for hypopharyngeal cancer patients treated with SQB-IMRT. MATERIALS/METHODS Between 2013 and 2019, 102 hypopharyngeal cancer patients were treated with definitive SQB-IMRT. In short, both the PTV-high risk, including the primary tumor and metastatic lymph nodes, and the PTV-low risk, including elective nodal regions, received 46 Gy at 2 Gy/fraction using the first planning CT. The PTV-high risk sequentially received an additional 24 Gy using a second planning CT. The doses for the first and second plans were accumulated and registered onto the second planning CT using the DIR workflow. All locoregional recurrences were contoured on the follow-up CT and registered with the second planning CT. Recurrences were classified as in-field (more than 95% of the recurrence volume (Vrec) received 95% of the prescribed dose), marginal (20-95%), or out-of-field (less than 20%). The toxicity was also evaluated using CTCAE ver4.0. RESULTS The median age was 66 years. Stage I, II, III and IV diseases were diagnosed in 3, 23, 20 and 56 patients, respectively. Eighty-three patients (81%) received concurrent chemoradiotherapy, and 19 patients (19%) received radiation therapy alone. The median total dose was 70 Gy. The median follow-up period was 22 months for all patients and 24 months for survivors. The 2-year overall survival rate and locoregional control rate were 79% and 57%, respectively. Thirty-four (33%) locoregional recurrences were observed. All locoregional failures were defined as in-field, and there was no marginal or out-of-field recurrence. The median mean dose and of the Vrec were 72.5 Gy (range, 71.6-74.1). In the patients who experienced locoregional failure, the median mean dose to the elective nodal region was assessed to be 60.1 (range, 55.4-68.4) Gy, and no recurrence occurred in the area. Late toxicities 6 months after RT were evaluated in 34 patients, and 24%, 3%, 25% and 2% of the patients experienced grade 2 and 3 dysphagia, grade 2 dry mouth and G2 dysgeusia, respectively. There were no grade 4/5 late toxicities. CONCLUSION In the detailed dosimetric analysis using DIR, all locoregional relapses after SQB-IMRT were in-field recurrences in the high-dose region. There was no recurrence in the prophylactic dose area, in which the accumulated dose reached as high as 60 Gy. More aggressive treatment for gross tumors and lower prophylactic doses may contribute to improved treatment outcomes and reduced side effects.

Salivary duct carcinoma (SDC) is morphologically similar to breast cancer, with HER2-overexpression reported. With regard to the pattern of disease onset, SDC can arise from de novo or carcinoma ex-pleomorphic adenoma (Ca-ex-PA). Recently, multiple molecular profiles of SDC as well as breast cancer have been reported, with significant differences in HER2 expression between Ca-ex-PA and de novo. We assessed the differences in gene expression between onset classifications. We conducted immunohistochemical analysis and HER2-DISH for 23 patients and classified SDCs into three subtypes as follows: “HER2-positive” (HER2+/any AR), “Luminal-AR” (HER2-/AR+), and “Basal-like” (HER2-/AR-). We assessed the expression levels of 84 functional genes for 19 patients by using a qRT-PCR array. Ten cases were classified as HER2-positive, seven cases as Luminal-AR, and six cases as Basal-like. The gene expression pattern was generally consistent with the corresponding immunostaining classification. The expression levels of VEGFA, ERBB2(HER2), IGF1R, RB1, and XBP1 were higher, while those of SLIT2 and PTEN were lower in Ca-ex-PA than in de novo. The functions of those genes were concentrated in angiogenesis and AKT/PI3K signaling pathway (Fisher’s test: p-value = 0.025 and 0.004, respectively). Multiple machine learning methods, OPLS-DA, LASSO, and RandomForest, also show that VEGFA can be a candidate for the characteristic differences between Ca-ex-PA and de novo. In conclusion, the AKT/PI3K signaling pathway leading to angiogenesis was hyper-activated in all SDCs, particularly in those classified into the Ca-ex-PAs. VEGFA was over-expressed significantly in the Ca-ex-PA, which can be a crucial factor in the malignant conversion to SDC.

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.

Richter syndrome (RS) is the development of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL). Most cases of diffuse large B-cell lymphoma variant of RS are clonally related to the original CLL. Here, we present a case of mantle cell lymphoma (MCL) that developed sequentially during the clinical course of CLL. A 72-year-old man had been diagnosed with CLL 16 years ago and was followed-up without treatment. He developed autoimmune hemolytic anemia 2 years ago, which resolved with rituximab and prednisolone treatment. Subsequently, he presented with fever, abdominal bloating, and fatigue. Progressive lymphocytosis and splenomegaly with elevated lactic dehydrogenase levels were suggestive of RS. Bone marrow examination revealed a small- to medium-sized lymphoid infiltrate, which was positive for CD5, CD20, CCND1, and SOX-11 and negative for CD23 and LEF1 on immunostaining. Fluorescence in situ hybridization analysis was positive for IgH/CCND1, which indicated MCL. Southern blot analysis showed that both the MCL and the previous CLL expressed different IgH gene rearrangement bands. At the time of relapse or progression of CLL, sequential development of MCL should be considered.

Objective The aim of the present study was to investigate the factors influencing semicircular canal function as evaluated by video Head Impulse Test (vHIT) in patients with vestibular schwannoma. Methods Twenty-four patients with untreated vestibular schwannoma underwent vHIT examination. The correlations between semicircular canal function and factors including age, tumor size, disease duration and hearing loss were evaluated. Results The functions of all three semicircular canals on the affected side evaluated by vHIT were significantly lower than those on the unaffected side. Although there were no significant correlations between semicircular canal function and age, tumor size or disease duration, a negative significant correlation between vestibulo-ocular reflex (VOR) gain as evaluated by vHIT and hearing loss was observed. Conclusions From the results of the relationship between hearing loss and VOR gain, the damage to the audio and vestibular systems in patients with VS may be correlated. As it has been suggested that tumor size was not a significant factor in the VOR gain evaluated by vHIT, multifactorial causes rather than the simple compression of the vestibular nerves alone may be related to the dysfunction of the semicircular canals in patients with vestibular schwannoma.

Lung is the most common target organ for distant metastasis of phyllodes tumor (PT), where the metastatic tumors are mostly seen as nodules or masses. We report here a rare case in which pure ground-glass opacity (GGO) was observed on chest CT about 3 years after the initial treatment of breast PT. After the lung lobectomy, we histologically confirmed that it should be diagnosed as a metastasis of PT. GGO rarely shows on metastatic tumors, and no reports have been made on GGO thus far in connection with metastasis of PT. Thus, in case GGO was found on the CT of patients having a history of PT, we suggest to take possible distant-metastasis into consideration.

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.

Background: To investigate the utility of quantitative morphological and intratumoral characteristics obtained by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) for the prediction of treatment outcome in patients with nasal or paranasal cavity squamous cell carcinoma (SCC). Methods: Twenty-four patients with nasal or paranasal cavity SCC who received curative non-surgical therapy (a combination of super-selective arterial cisplatin infusion and radiotherapy) were retrospectively analyzed. From pre-treatment FDG-PET data, a total of 13 parameters of quantitative morphological characteristics (tumor volume, surface area and sphericity), intratumoral characteristics (the maximum and mean standard uptake value, three intratumoral histogram and four textural parameters) and total lesion glycolysis (TLG) were respectively calculated. Information regarding the treatment outcome was determined from the histological diagnosis or clinical follow-up. Each of the 13 quantitative parameters as well as T- and N-stage was assessed for its relation to treatment outcome of local control or failure. Results: In univariate analysis, significant differences in surface area and sphericity between the local control and failure groups were observed. The Receiver Operating Characteristic (ROC) curve analysis showed that sphericity had the highest accuracy of 0.88. In the multivariate analysis, sphericity was revealed as an independent predictor of the local control or failure. Conclusions: The quantitative parameters of sphericity are useful to predict the treatment outcome in patients with nasal or paranasal SCC.

The molecular characteristics of therapeutically-relevant targets and their clinicopathological implications in salivary duct carcinomas (SDCs) are poorly understood. We investigated the gene alterations and the immunoexpression of crucial oncogenic molecules in 151 SDCs. The mutation rates that were identified, in order of frequency, were as follows: TP53, 68%; PIK3CA, 18%; H-RAS, 16%; BRAF, 4%; and AKT1, 1.5%. PIK3CA/H-RAS/BRAF mutations were more common in de novo SDC than in SDC ex-pleomorphic adenoma. Furthermore, these mutations were mutually exclusive for HER2 overexpression/amplification. TP53 mutations were frequently detected in cases with the aberrant p53 expression, and TP53 missense and truncating mutations were associated with p53-extreme positivity and negativity, respectively. DISH analysis revealed no cases of EGFR amplification. The rates of PI3K, p-Akt, and p-mTOR positivity were 34%, 22%, and 66%, respectively; PTEN loss was observed in 47% of the cases. These expressions were correlated according to the signaling axis. Cases with PI3K negativity and PTEN loss appeared to show a lower expression of androgen receptor. In the multivariate analysis, patients with SDC harboring TP53 truncating mutations showed shorter progression-free survival. Conversely, p-Akt positivity was associated with a favorable outcome. This study might provide information that leads to advances in personized therapy for SDC.

// Soichiro Takase 1, 2, * , Satoshi Kano 3, * , Yuichiro Tada 4, * , Daisuke Kawakita 5 , Tomotaka Shimura 2, 6 , Hideaki Hirai 2 , Kiyoaki Tsukahara 1 , Akira Shimizu 1 , Yorihisa Imanishi 7 , Hiroyuki Ozawa 7 , Kenji Okami 8 , Yuichiro Sato 9 , Yukiko Sato 10 , Chihiro Fushimi 4 , Takuro Okada 1 , Hiroki Sato 1 , Kuninori Otsuka 7 , Yoshihiro Watanabe 7 , Akihiro Sakai 8 , Koji Ebisumoto 8 , Takafumi Togashi 9 , Yushi Ueki 9 , Hisayuki Ota 9 , Toyoyuki Hanazawa 11 , Hideaki Chazono 11 , Robert Yoshiyuki Osamura 12 and Toshitaka Nagao 2 1 Department of Otolaryngology Head and Neck Surgery, Tokyo Medical University, Tokyo, Japan 2 Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan 3 Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan 4 Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan 5 Department of Otolaryngology Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 6 Department of Otorhinolaryngology, Showa University School of Medicine, Tokyo, Japan 7 Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan 8 Department of Otolaryngology Head and Neck Surgery, Tokai University School of Medicine, Isehara, Japan 9 Department of Head and Neck Surgery, Niigata Cancer Center Hospital, Niigata, Japan 10 Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan 11 Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan 12 Diagnostic Pathology Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan * These authors contributed equally to this work Correspondence to: Toshitaka Nagao, email: nagao-t@tokyo-med.ac.jp Keywords: salivary duct carcinoma, androgen receptor, p53, CK5/6, HER2 Received: June 22, 2017 Accepted: July 26, 2017 Published: August 02, 2017 ABSTRACT Salivary duct carcinoma (SDC) is an uncommon, aggressive malignant neoplasm histologically resembling high-grade mammary ductal carcinoma. SDC can arise de novo or ex pleomorphic adenoma. To clarify the correlation of biomarker immunoprofile with clinicopathological findings and clinical outcome of SDC, we conducted immunohistochemistry for EGFR, HER2, HER3, AR, CK5/6, p53, and Ki-67, along with HER2 fluorescence in situ hybridization in 151 SDCs. SDCs ex pleomorphic adenoma more commonly overexpressed EGFR, HER2, HER3, and Ki-67 than de novo SDCs ( P = 0.015, < 0.001, 0.045, and 0.02, respectively). In multivariate analysis, AR− and CK5/6+ were associated with shorter progression-free survival ( P = 0.027 and 0.004, respectively). Moreover, patients with p53-extreme negative/positive demonstrated poorer overall survival ( P = 0.007). On assessing the revised classification by the combination of biomarker expression, the percentages of each subtype were as follows: ‘apocrine A’ (AR+/HER2−/Ki-67-low) (24%), ‘apocrine B’ (AR+/HER2−/Ki-67-high) (18%), ‘apocrine HER2’ (AR+/HER2+) (35%), ‘HER2-enriched’ (AR−/HER2+) (12%), and ‘double negative’ (AR−/HER2−) (11%). ‘Double negative’ was further subclassified into ‘basal-like’ (EGFR and/or CK5/6+) (7%) and ‘unclassified’ (3%). Consequently, patients with ‘apocrine A’ showed a better progression-free survival than those with any other subtypes. Our revised immunoprofiling classification was valuable for predicting the survival and might be useful in personalized therapy for patients with SDC.

Atypical adenoma of the thyroid is a rare form of tumor, and its accurate diagnosis prior to surgical resection is difficult as the histological and pathological morphologies are very similar to those of anaplastic thyroid carcinoma (ATC), and its anaplastic transformation remains to be elucidated. We reported a case of a 75-year-old female with a thyroid isthmus nodule diagnosed repeatedly by FNAC as anaplastic carcinoma. Both the first and second FNAC specimen slides showed a large number of scattered or aggregated atypical cells consisting of large, pleomorphic nuclei with irregular membranes, chromatin clumps and prominent nucleoli. The morphology of the surgical specimen was similar to that of an anaplastic carcinoma and although it showed signs of transition from a normal follicular epithelium, there was no invasive growth or mitosis. This lesion was diagnosed as an atypical adenoma, and a papillary carcinoma was also present in the right lobe of the thyroid. Here we evaluate the molecular features of atypical adenomas in comparison with 9 ATC samples, and discuss whether or not atypical adenomas represent a form of premalignant lesion. Ki-67 expression was found to be very low in atypical adenomas whereas all ATC samples showed high levels of Ki-67 expression. Epithelial-mesenchymal transition (EMT) marker expression suggested that atypical adenomas maintain their epithelial phenotype to a higher degree than do ATCs. Differential diagnosis between ATC and atypical adenoma is difficult by cytological and histological methods alone, and Ki-67 and EMT marker expression may support the diagnosis.

Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses. It is reported that 5–15% of IPs undergo malignant transformation into squamous cell carcinoma (SCC), and the role of microRNAs (miRNA/miR) in this process remains to be elucidated. In the present study, whole miRNA profiles using samples of IP and SCC were investigated, in order to detect the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC lesions (n=5), which arose from IPs, were used for miRNA analysis. A total of 200 miRNAs exhibited a >2-fold differential expression between IP and SCC. miR-296-3p was markedly upregulated in SCC with a 23-fold difference. Computational analysis indicated that miR-296-3p targeted PTEN, which regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in the carcinogenesis of SCC. miR-296-3p directly regulated PTEN expression in head and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs (21.0%), as compared with those in the IPs (76.4%). Positive p21 staining was observed in 64.7% of IPs; this was a significantly increased rate compared with that for SCCs (26.3%, P=0.0086). The results of the present study indicated that there were marked changes in the miRNA expression signature during the malignant transition. miR-296-3p may serve an important role in the malignant transformation of IPs via the regulation of PTEN, combined with the subsequent inhibition of the PI3K/Akt signaling pathway, and may be a novel agent for cancer prevention.

Oral mucositis and body weight loss are the most critical conditions known to lead to the discontinuation of chemoradiotherapy for head and neck cancer. We investigated the effect of a nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)on body weight loss, oral mucositis, and the completion rate of chemoradiotherapy in patients with oropharyngeal and hypopharyngeal cancer.The study group comprised patients with oropharyngeal and hypopharyngeal cancer who were treated with concomitant cisplatin and 70 Gy of radiotherapy. These patients received 2 packs of Prosure®per day during chemoradiotherapy.A total of 17 patients were included in this study. The reduction in body weight was significantly improved compared with that in the historical control group that did not receive Prosure®(7.3% vs 10.3%, p0.01), and the rate of Grade 3-4 oral mucositis was significantly reduced for the patient groups that received Prosure®(CTCAE v3.0 GradeB3; 24% vs 58%, p0.05). The completion rate of chemoradiotherapy was not significantly different between both groups(77% vs 60%, NS).A nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)had effects on oral mucositis and body weight loss in head and neck cancer patients treated with chemoradiotherapy.

Purpose. Prophylactic neck dissection (PND) for patients with clinically N0 (cN0) tongue carcinoma remains controversial. We assessed the efficacy of PND for patients with cN0 tongue squamous cell carcinoma (SCC) and investigated the prognostic role of tumor thickness as assessed by diagnostic imaging in predicting the risk of nodal micrometastasis or late nodal recurrence. Methods. Eighty-eight patients with cN0 tongue carcinomas underwent surgical treatment. Tumor thickness was measured from magnetic resonance (MR) images or computed tomography (CT) scans. Results. The overall survival rates of patients with or without PND were 94% and 81%, respectively (p=0.2857). MR images or CT scans were available for 68 patients. A tumor thickness ≧10mm or ≧5mm did not increase the probability of nodal metastasis, with late nodal metastasis observed in 15% of patients with graphically undetected small tumors. Conclusions. PND appears to have the potential to improve overall survival for patients with cN0 tongue SCC. Careful follow-up management or PND is considered to be needed regardless of tumor thickness in the pre-treatment evaluation.

Background The purpose of this study was to analyze the relationship between pretreatment inflammatory markers and the prognosis of patients with oropharyngeal, hypopharyngeal, and laryngeal cancers. Methods The data for 285 patients treated with curative intent by concurrent chemoradiotherapy (CRT) were obtained and their pretreatment inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Results Significant relationships were observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4, N2b to N3, and clinical stage III to IV, whereas significant relationships were observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR were all significantly associated with decreases in overall survival (OS) and disease-free survival (DFS). Furthermore, multivariate analysis showed that LMR was an independent prognostic factor. Conclusion Pretreatment LMR was found to be an independent prognostic factor for patients with head and neck cancers treated by concurrent CRT. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Objective We retrospectively assessed the indications for superselective intra-arterial infusion of cisplatin with concomitant radiotherapy (RADPLAT) in patients with hypopharyngeal cancer (HPC). Methods Between April 2000 and March 2013, 41 previously untreated patients received superselective intra-arterial infusion of cisplatin (100–120 mg/m 2 per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional radiotherapy (65–70 Gy). Results During the median follow-up period of 5.5 years, a statistically significant difference in the 5-year overall survival was noted between patients with N0-1 ( n = 14) and N2b-3 disease ( n = 27). One-half of deaths were observed to be the result of distant metastasis. The 5-year local control and overall survival were significantly better in patients with unilateral than in those with bilateral primary tumors. All the patients with T4b disease ( n = 3) died of disease within 2 years. Conclusion Indications for RADPLAT in patients with HPC were defined as patients with unilateral tumors staged as T3-4a and N0-1.

To investigate the utility of quantitative morphological and intratumoral characteristics obtained byTwenty-four patients with nasal or paranasal cavity SCC who received curative non-surgical therapy (a combination of super-selective arterial cisplatin infusion and radiotherapy) were retrospectively analyzed. From pre-treatment FDG-PET data, a total of 13 parameters of quantitative morphological characteristics (tumor volume, surface area and sphericity), intratumoral characteristics (the maximum and mean standard uptake value, three intratumoral histogram and four textural parameters) and total lesion glycolysis (TLG) were respectively calculated. Information regarding the treatment outcome was determined from the histological diagnosis or clinical follow-up. Each of the 13 quantitative parameters as well as T- and N-stage was assessed for its relation to treatment outcome of local control or failure.In univariate analysis, significant differences in surface area and sphericity between the local control and failure groups were observed. The receiver operating characteristic (ROC) curve analysis showed that sphericity had the highest accuracy of 0.88. In the multivariate analysis, sphericity was revealed as an independent predictor of the local control or failure.The quantitative parameters of sphericity are useful to predict the treatment outcome in patients with nasal or paranasal SCC.

TAFRO syndrome is characterized by thrombocytopenia with unknown etiology. The assessment of immature platelet fraction (IPF) is useful for differential diagnoses that include thrombocytopenia. However, the significance of IPF in cases of TAFRO syndrome remains to be reported. We present a case of TAFRO syndrome wherein the patient demonstrated a marked increase in IPF without thrombocytopenia, which offers vital information concerning TAFRO diagnosis and the serial measurements of IPF during treatment. A 65-year-old man presenting with fever was admitted to our hospital. He exhibited mild splenomegaly and lymphadenopathy, as well as rapidly worsening renal failure and fluid retention. These indications prompted the initiation of corticosteroid therapy. A normal platelet count and aberrantly high IPF implied abnormal thrombopoiesis, and subsequent bone-marrow findings suggested TAFRO syndrome. The platelet counts started to decrease following the corticosteroid therapy, but the treatment refractoriness prompted the urgent administration of rituximab. Thereafter, the platelet count nadir remained for approximately one month, whereas the decreasing IPF trend preceded platelet recovery. In the present case, a high pre-treatment IPF was demonstrated before the emergence of thrombocytopenia, and a decreasing trend of IPF was observed before platelet recovery during treatment. Therefore, serial IPF measurements could be useful for the early diagnosis and prognostication of TAFRO syndrome.

AIMS Salivary duct carcinoma (SDC) is an uncommon, aggressive tumour that, histologically, resembles high-grade mammary ductal carcinoma, and is characterised by the expression of androgen receptor (AR). The androgen signalling pathway, a potential therapeutic target, can be regulated by FOXA1. This study aimed to evaluate the clinicopathological implications of FOXA1 in SDC. METHODS AND RESULTS We examined the relationship between the immunoexpression of FOXA1 and FOXA1 mutations and clinicopathological factors, including the biomarker status and clinical outcome, in 142 SDCs. FOXA1 was expressed in 128 SDCs (90.1%); the immunoexpression was heterogeneous. SDCs with a higher FOXA1 labelling index (LI) (≥20%) more frequently showed less advanced tumors on T classification (P = 0.002). FOXA1 LI was correlated positively with the AR expression value (r = 0.430, P

Conclusion: Grade ≥ 3 mucositis/stomatitis and inability to feed orally were problematic for patients undergoing cetuximab-based bioradiotherapy (BRT) as well as platinum-based chemoradiotherapy (CRT). Severe mucositis/stomatitis and radiation dermatitis should be addressed carefully in patients undergoing cetuximab-based BRT as well. Objectives: The efficacy of cetuximab-based BRT in locally advanced head and neck squamous cell carcinomas has been established. However, the safety of cetuximab-based BRT in comparison with platinum-based CRT is currently under investigation. Method: This study retrospectively analyzed 14 patients undergoing cetuximab-based BRT and 29 patients undergoing platinum-based CRT to compare the incidence of acute toxicities. In the BRT group, an initial cetuximab loading dose of 400 mg/m2 was delivered 1 week before the start of radiotherapy. Seven weekly infusions of 250 mg/m2 of cetuximab followed during the definitive radiotherapy. In the CRT group, cisplatin was administered at a dose of 40 mg/m2 weekly during the definitive radiotherapy. Results: The BRT group had a higher incidence of Grade ≥ 3 radiation dermatitis than did the CRT group (43% vs 3%, respectively, p < 0.01). The incidence rate of Grade ≥ 3 mucositis/stomatitis was 64.3% and 41.4% in the BRT and CRT group, respectively (p = 0.1484), while the incidence rate of the inability to feed orally was 38.5% and 55.2%, respectively (p = 0.2053).

The aim of this study was to evaluate the feasibility of induction docetaxel, cisplatin, and 5-fluorouracil chemotherapy followed by concurrent weekly cisplatin chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Between 2010 and 2013, 30 patients with Stage IV HNSCC were treated in Hokkaido University Hospital with three cycles of induction chemotherapy (docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2), day 1; and 5-fluorouracil 750 mg/m(2)/day 120 h continuous infusion, every 3 weeks) followed by concurrent weekly cisplatin (40 mg/m(2), on weeks 1, 2, 3, 5, 6 and 7) chemoradiotherapy. Three courses of induction chemotherapy were performed in 25 patients (83 %) with grade 3-4 toxicities during induction chemotherapy observed in 22 patients (73 %). The major toxicities were hematologic, with 22 cases (73 %) showing grade 3-4 neutropenia. Radiotherapy was completed (70 Gy) in 29 patients (97 %), while a total of 19 patients (63 %) completed five (13 patients) or six (6 patients) courses of chemotherapy. During concurrent chemoradiotherapy, no grade 4 hematological toxicities were observed. Grade 4 dermatitis was observed in one patient, and grade 3 mucositis was observed in 12 patients. There were no treatment-related deaths during the induction chemotherapy or concurrent chemoradiotherapy. The 1- and 2-year progression-free survival rates and the 1- and 2-year overall survival rates were 86 %, 72 %, and 89 %, 81 %, respectively. Sequential therapy composed of induction chemotherapy followed by concurrent weekly cisplatin chemoradiotherapy is feasible, showing encouraging results in patients with locally advanced HNSCC. Concurrent weekly cisplatin chemoradiotherapy following induction chemotherapy appears to be a suitable alternative to three-weekly high-dose cisplatin therapy.

Total laryngo-pharyngo-esophagectomy (TLPE) with gastric pull-up reconstruction is still considered to be associated with major complications and a significant risk of in-hospital death. Minimally invasive esophagectomy, avoiding thoracotomy and laparotomy, has been increasingly performed for esophageal malignancies with the hope of reducing mortality and morbidity, such as pulmonary complications. The aim in this study was to assess early and long-term morbidity as well as treatment outcomes in patients treated with TLPE with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision. From 2004 to 2013, 10 patients with a median age of 64 years (range 47-71 years) underwent minimally invasive TPLE with gastric pull-up reconstruction. Seven of the 10 patients had previously received radiotherapy. As for early postoperative complications, no patient died during the early postoperative period, and pneumonia was observed in 1, skin necrosis in 1, pseudomembranous enterocolitis in 1, arrhythmia in 2, hemorrhage in the neck in 2, anastomotic leakage in the neck in 3, and tracheal necrosis in 6 patients. Three patients developed tracheostomal stenosis as a long-term postoperative complication, and an anastomotic stricture was observed in one patient. All patients were able to achieve oral intake, but 3 patients required feeding tube support. In conclusion, postoperative systemic complications during the early postoperative period were considered to be acceptable, although wound complications such as tracheal necrosis and anastomotic leakage were commonly observed. Therefore, this minimally invasive procedure might help reduce mortality and morbidity in patients requiring TLPE with gastric pull-up reconstruction.

Background Osteoradionecrosis (ORN) of the hyoid bone sometimes induces severe front neck infection and can cause laryngeal stenosis and carotid rupture. Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy for head and neck cancer, there has been no basis for its evaluation. Our purpose is to present the clinical and MR imaging features of ORN of the hyoid bone. Methods The study group comprised patients with advanced oropharyngeal cancer treated with targeted intra-arterial cisplatin infusion with concomitant radiotherapy. ORN of the hyoid bone was identified on the basis of decreased signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI images was used to distinguish between inflammation and fibrosis. Results A total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of the hyoid bone were detected in 30% of patients after treatment, with 23% of them showing inflammation and 7.7% fibrosis. Two patients developed severe neck infection and received antibiotics and underwent surgical intervention by tracheostomy and resection of the hyoid bone. Conclusion Our MR imaging study showed that ORN of the hyoid bone is not particularly rare in patients with oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate images carefully to prevent the development of severe complication due to infection associated with ORN of the hyoid bone.

High-risk human papillomavirus (HPV) infection is associated with carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC) and patients with HPV-positive tumors have a significantly favorable prognosis. However, the underlying mechanism of this favorable clinical outcome remains unclear. Epithelial-mesenchymal transition (EMT) causes aggressiveness of cancer cells and we investigated the expression of the EMT markers and analyzed their correlation with HPV status and prognosis in order to examine the treatment response of HPV-positive OPSCCs. A total of 79 patients with OPSCC were examined in the present study. All high-risk HPV infections were determined with the multiplex PCR kit from each formalin-fixed paraffin-embedded (FFPE) sample. We performed immunohistochemical staining for E-cadherin and vimentin. Expression of the markers was graded and we statistically analyzed the correlation between tumor, node, metastasis (TNM) stages and prognosis. High-risk HPV-positive tumors were detected in 23 cases. The five‑year survival rate in HPV-positive and -negative tumors was 82.7 and 48.3%, respectively. High E-cadherin expression rate in HPV-negative samples was 76.7% and 43.4% in HPV-positive samples (p=0.007). Vimentin expression did not show a difference between HPV-positive and -negative tumors. HPV-negative patients presented significantly greater heterogeneity of E-cadherin expression compared to HPV-positive patients (p=0.0349). HPV-positive OPSCCs originally lost their epithelial cell phenotype compared with HPV-negative tumors. Therefore, the paradoxical favorable prognosis of HPV-positive OPSCC may be due to the intratumor homogeneity in EMT.

The suprasternal space is a narrow space between the superficial and deep layers of the investing layers of the deep cervical fascia above the manubrium of the sternum. The suprasternal space has been paid little attention as a space with the potential for lymph node metastasis from both thyroid cancer and head and neck cancer. We experienced 2 patients who were found to have a lymph node in the suprasternal space preoperatively. Both of them had well-differentiated thyroid papillary carcinomas and level III and IV lymph node metastases as well as metastasis in the suprasternal space. We have not previously dissected the suprasternal space prophylactically in other patients with thyroid papillary cancer, but no patient has developed metastasis in this space to date. The suprasternal space is not usually dissected in patients with thyroid cancer. However, suprasternal space metastasis has been reported to occur occasionally in patients with lymph node metastases in levels III and IV. We consider that dissection of the suprasternal space, which is not routinely performed, should be done when preoperative examination suggests lymph node metastasis in the suprasternal space as dissection of this space is less invasive, easy to achieve, and is not time consuming. Greater attention should be paid to the suprasternal space as an area with the potential for lymph node metastasis from thyroid cancer.

Our aim was to evaluate the feasibility of salvage operations for patients with persistent or recurrent cancer of the maxillary sinus after superselective intra-arterial infusion of cisplatin with concurrent radiotherapy. We retrospectively analysed the records of 61 patients with cancer of the maxillary sinus who were treated in this way. Chemotherapy comprised 100-120 mg/m(2) superselective intra-arterial infusions of cisplatin given a median of 4 times weekly (range 2-5). Concurrent radiotherapy was given in a median dose of 65 Gy (range 24-70 Gy). Persistent or recurrent cancer of the maxillary sinus was found in 17 patients, of whom 11 had salvage surgery. The disease was controlled in 8 of the 11, and 7 of the 11 survived with no evidence of disease. Their 5-year overall survival was 61%. Two of the 11 developed serious operative complications. Salvage surgery for patients with persistent or recurrent cancer of the maxillary sinus treated by superselective chemoradiotherapy is both safe and successful. Salvage surgery is a good option when this sort of persistent or recurrent cancer is followed up after the regimen of chemoradiotherapy described. (C) 2014 Elsevier Inc. All rights reserved.

In the case of oropharyngeal carcinoma, patients may present with symptoms similar to cervical lymphadenopathy, and the primary lesion may only be diagnosed after cervical mass extirpation/biopsy. We retrospectively analyzed the clinical course in 11 oropharyngeal carcinoma patients that were diagnosed after cervical mass extirpation/biopsy between 1998 and 2013. Before the diagnosis was made of oropharyngeal carcinoma, a cervical lymph node biopsy was performed in six patients; the lymph node was extirpated due to an initial diagnosis of lateral cervical cyst in four patients; and neck dissection was performed due to an initial diagnosis of primary unknown carcinoma in one patient. The primary tumor site in the oropharynx was the palatine tonsil in six patients and the lingual tonsil in five patients. Five of six patients with palatine tonsil carcinoma and three of five patients with lingual tonsil carcinoma were found to be positive for human papillomavirus (HPV). The duration from cervical lymph node extirpation/biopsy to final diagnosis was 1 to 13 months. All patients finally underwent radiation therapy or chemoradiotherapy, and they had no recurrence or metastasis. As the incidence of HPV-related oropharyngeal carcinoma increases, the number of oropharyngeal carcinomas assumed to be cervical lymphadenopathy due to the presenting symptoms may increase. It is important to investigate the oropharynx thoroughly so as to adequately differentiate the possibility of oropharyngeal carcinoma from that of cervical lymphadenopathy. Metastatic lymph nodes might present as cysts in cases of oropharyngeal carcinoma, it is therefore necessary to take the potential for metastatic lymph nodes in the oropharyngeal cancer into consideration when differentiating this disease from cervical cyst-shaped lesions.

Atypical adenoma of the thyroid is a rare form of tumor, and its accurate diagnosis prior to surgical resection is difficult as the histological and pathological morphologies are very similar to those of anaplastic thyroid carcinoma (ATC), and its anaplastic transformation remains to be elucidated. We reported a case of a 75-year-old female with a thyroid isthmus nodule diagnosed repeatedly by FNAC as anaplastic carcinoma. Both the first and second FNAC specimen slides showed a large number of scattered or aggregated atypical cells consisting of large, pleomorphic nuclei with irregular membranes, chromatin clumps and prominent nucleoli. The morphology of the surgical specimen was similar to that of an anaplastic carcinoma and although it showed signs of transition from a normal follicular epithelium, there was no invasive growth or mitosis. This lesion was diagnosed as an atypical adenoma, and a papillary carcinoma was also present in the right lobe of the thyroid. Here we evaluate the molecular features of atypical adenomas in comparison with 9 ATC samples, and discuss whether or not atypical adenomas represent a form of premalignant lesion. Ki-67 expression was found to be very low in atypical adenomas whereas all ATC samples showed high levels of Ki-67 expression. Epithelial-mesenchymal transition (EMT) marker expression suggested that atypical adenomas maintain their epithelial phenotype to a higher degree than do ATCs. Differential diagnosis between ATC and atypical adenoma is difficult by cytological and histological methods alone, and Ki-67 and EMT marker expression may support the diagnosis.

Objectives: Salivary gland cancer is a rare cancer that has no effective drug therapy available. It comprises salivary duct carcinoma (SDC) as a major histology, which resembles high-grade breast ductal carcinoma and often overexpresses HER2. The purpose of this study is to evaluate the efficacy and safety of trastuzumab and docetaxel therapy in patients (pts) with HER2-positive salivary gland carcinoma. Methods: We conducted a multicenter, single-arm Phase II study of trastuzumab and docetaxel for pts with HER2-positive recurrent and/or metastatic salivary gland carcinoma pursuant to the J-GCP. HER2 positivity was defined as immunohistochemistry (IHC) 3+ or IHC 2+/dual color in situ hybridization (DISH) +. Eligible pts were treated with trastuzumab 6 mg/kg (loading dose 8 mg/kg) and docetaxel 70 mg/m2 every 3 weeks up to 8 cycles. The primary endpoint was overall response rate (ORR) using RECIST v1.1 assessed by the blinded independent review committee (BIRC). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. This study required 16 pts, with ORR of 25% considered non-promising and 70% promising (two-sided alpha = 0.05; beta = 0.1) and with 2 withdrawal pts. Results: Sixteen pts were recruited in this trial. The median age was 59 (range 26-72), 3 pts were female, and all pts had performance status 0-1. All pts had carcinomas histologically compatible with SDCs by central pathology review of samples used for HER2 evaluation, 14 of which were readily confirmed as SDCs. All pts had HER2 IHC 3+ tumors. Two pts were previously untreated and had metastatic disease. The remaining 14 pts had recurrence after surgery that was followed by adjuvant chemoradiotherapy in 5 pts and by adjuvant radiotherapy in 6 pts. No pts were previously treated with chemotherapy alone. After excluding a pt without measurable lesions evaluated by BIRC, ORR by BIRC was 60% (9/15; 95% CI, 32.3~83.7) with one complete response. Median PFS was 8.5 months (95% CI, 6.0~12.7). Median OS was not reached at a median follow-up of 17.9 months in survivors. Common grade 3/4 adverse events (> 10%) were neutropenia (16 pts, 100%), leukopenia (15 pts, 93.8%), lymphopenia (3 pts, 18.8%), and febrile neutropenia (2 pts, 12.5%). Treatment-related death occurred in 1 pt (6.3%) due to hypoalbuminemia. Conclusions: This study demonstrated a promising efficacy with predictable toxicities. Trastuzumab and docetaxel therapy may be an effective treatment option in pts with HER2-positive recurrent and/or metastatic salivary gland carcinoma. Citation Format: Ichiro Kinoshita, Satoshi Kano, Yasushi Shimizu, Naomi Kiyota, Yuichiro Tada, Kei Ijichi, Tmoko Yamazaki, Akihiro Homma, Yoichi M. Ito, Kota Ono, Keiko Kobayashi, Toshiyuki Isoe, Yutaka Hatanaka, Hitoshi Tsuda, Shojiroh Morinaga, Yoshihiro Matsuno, Hirotoshi Dosaka-Akita. Phase II study of trastuzumab and docetaxel therapy in patients with HER2-positive recurrent and/or metastatic salivary gland carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT137.

The purpose of this study was to determine the predictive power for treatment outcome of a machine-learning algorithm combining magnetic resonance imaging (MRI)-derived data in patients with sinonasal squamous cell carcinomas (SCCs). Thirty-six primary lesions in 36 patients were evaluated. Quantitative morphological parameters and intratumoral characteristics from T2-weighted images, tumor perfusion parameters from arterial spin labeling (ASL) and tumor diffusion parameters of five diffusion models from multi-b-value diffusion-weighted imaging (DWI) were obtained. Machine learning by a non-linear support vector machine (SVM) was used to construct the best diagnostic algorithm for the prediction of local control and failure. The diagnostic accuracy was evaluated using a 9-fold cross-validation scheme, dividing patients into training and validation sets. Classification criteria for the division of local control and failure in nine training sets could be constructed with a mean sensitivity of 0.98, specificity of 0.91, positive predictive value (PPV) of 0.94, negative predictive value (NPV) of 0.97, and accuracy of 0.96. The nine validation data sets showed a mean sensitivity of 1.0, specificity of 0.82, PPV of 0.86, NPV of 1.0, and accuracy of 0.92. In conclusion, a machine-learning algorithm using various MR imaging-derived data can be helpful for the prediction of treatment outcomes in patients with sinonasal SCCs.

Background We analyzed the effects of local extension sites on survival in patients with locally advanced maxillary sinus cancer. Methods The criteria for inclusion in this study were as follows: (1) previously untreated maxillary sinus cancer; (2) squamous cell carcinoma; (3) T4 disease; and (4) curative-intent treatment. The data for 118 patients were obtained from 28 institutions across Japan and analyzed for overall survival and local control rates by local extension site. Results Sites with a poor prognosis included the cribriform plate, dura, nasopharynx, middle cranial fossa, and cranial nerves other than V2. There was a significant correlation among these sites, except for the cranial nerves. Additionally, the hard palate was the only site that correlated with nodal involvement and showed a poor treatment outcome. Conclusion Even in cases presenting with similar T4 maxillary sinus cancer, treatment should be performed in consideration of the local extension site. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1567–1572, 2014

Background: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). Methods: Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120mgm(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy). Results: One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n-5), brain necrosis (n-1), and ocular/ visual problems (n = 14) were observed as late adverse reactions. Conclusion: We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

Aim To assess potential prognostic factors in pharynx squamous cell carcinoma (SCC) patients by quantitative morphological and intratumoural characteristics obtained by 2-[18F]-fluoro-2-deoxy- d- glucose positron-emission tomography/computed tomography (FDG-PET/CT). Materials and methods The cases of 54 patients with pharynx SCC who underwent chemoradiation therapy were analysed retrospectively. Using their FDG-PET data, the quantitative morphological and intratumoural characteristics of 14 parameters were calculated. The progression-free survival (PFS) and overall survival (OS) information was obtained from patient medical records. Univariate and multivariate analyses were performed to assess the 14 quantitative parameters as well as the T-stage, N-stage, and tumour location data for their relation to PFS and OS. When an independent predictor was suggested in the multivariate analysis, the parameter was further assessed using the Kaplan–Meier method. Results In the assessment of PFS, the univariate and multivariate analyses indicated the following as independent predictors: the texture parameter of homogeneity and the morphological parameter of sphericity. In the Kaplan–Meier analysis, the PFS rate was significantly improved in the patients who had both a higher value of homogeneity (p=0.01) and a higher value of sphericity (p=0.002). With the combined use of homogeneity and sphericity, the patients with different PFS rates could be divided more clearly. Conclusion The quantitative parameters of homogeneity and sphericity obtained by FDG-PET can be useful for the prediction of the PFS of pharynx SCC patients, especially when used in combination.

Conclusion: It was proved that cyclin D1-positive status in surgical margins was an independent prognostic indicator of local recurrence. The expression of cyclin D1 in tumor-free surgical margins may better predict local recurrence in patients with head and neck squamous cell carcinoma (HNSCC) after surgical treatment with curative intent. Objective: This retrospective study aimed to determine the prognostic indicators for local recurrence in HNSCC. Methods: A total of 116 HNSCC patients who underwent surgical treatment with curative intent and had histopathologically tumor-free margins were eligible for this study. The expression of p53 and cyclin D1 was assessed by immunohistochemical staining in surgical margins as well as in tumor specimens. Results: In all, 63 patients (54.3%) had p53-positive tumor specimens and 34 patients (29.3%) had p53-positive margins. Seventy-six patients (65.6%) had cyclin D1-positive tumor specimens and 54 patients (46.6%) had cyclin D1-positive margins. A significant difference in local control rates was observed between patients with cyclin D1-positive and -negative margins (77.2% vs 91.5%, log rank test, p = 0.0139). Multivariate Cox proportional hazards testing indicated that the hazard ratio of cyclin D1-positive margins for local recurrence was 4.58 (95% confidence interval 1.14–21.69, p = 0.0304).

// Daisuke Kawakita 1 , Yuichiro Tada 2 , Yorihisa Imanishi 3 , Shintaro Beppu 1 , Kiyoaki Tsukahara 4 , Satoshi Kano 5 , Hiroyuki Ozawa 3 , Kenji Okami 6 , Yuichiro Sato 7 , Akira Shimizu 4 , Yukiko Sato 8 , Chihiro Fushimi 2 , Soichiro Takase 4 , Takuro Okada 2 , Hiroki Sato 4 , Kuninori Otsuka 3 , Yoshihiro Watanabe 3 , Akihiro Sakai 6 , Koji Ebisumoto 6 , Takafumi Togashi 7 , Yushi Ueki 7 , Hisayuki Ota 7 , Tomotaka Shimura 9 , Toyoyuki Hanazawa 10 , Shingo Murakami 1 , Toshitaka Nagao 9 1 Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 2 Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan 3 Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan 4 Department of Otolaryngology, Tokyo Medical University School of Medicine, Tokyo, Japan 5 Department of Otorhinolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan 6 Department of Otolaryngology-Head and Neck Surgery, Tokai University School of Medicine, Isehara, Japan 7 Department of Head and Neck Surgery, Niigata Cancer Center Hospital, Niigata, Japan 8 Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan 9 Department of Anatomic Pathology, Tokyo Medical University School of Medicine, Tokyo, Japan 10 Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan Correspondence to: Daisuke Kawakita, email: dk200811@gmail.com Keywords: salivary duct carcinoma, survival, mGPS, CRP, NLR Received: August 26, 2016 Accepted: November 09, 2016 Published: November 24, 2016 ABSTRACT The prognostic role of modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with salivary duct carcinoma (SDC) remains unclear. We conducted a multi-institutional retrospective cohort study of 140 SDC patients. The survival impact of these hematological markers was evaluated using multivariate proportional hazard models.High mGPS (≥1) was significantly associated with worse survival (3-year overall survival (OS): 16.7% vs 66.1%, p -value=0.003; 3-year progression-free survival (PFS): 0.0% vs 27.9%, p -value

Objective: We aimed to evaluate the prognostic factors and efficacy of treatment modalities for patients with temporal bone cancer, and to determine if definitive chemoradiotherapy (CRT) for advanced-stage disease can provide a substitute for highly invasive surgeries. Study Design: Retrospective case series. Setting: Tertiary referral center. Patients: Sixty-six patients with previously untreated squamous cell carcinoma of the temporal bone treated with curative intent between April 1997 and March 2015. Intervention: Surgery alone, radiotherapy (RT) alone, surgery followed by RT or definitive CRT. Main Outcome Measure: The overall survival (OS) rate. Results: The 5-year OS rate for each T classification was 100% for T1, 76.2% for T2, 55.6% for T3, and 36.7% for T4. Univariable and multivariable analysis showed that T classification was an independent predictor of the OS rate (hazard ratio 5.66; 95% confidence interval 1.51–27.0; p = 0.015). Analysis by treatment modality revealed that the 5-year OS rate for patients with T1–2 was 100% for surgery and 81.3% for RT alone. The rate for patients with T3–4 was 52.1% for definitive CRT and 55.6% for surgery followed by RT with or without chemotherapy. Conclusions: Patients with T1–2 benefited from surgical intervention without significant morbidity or mortality. Our findings also suggested that definitive CRT might be appropriate as the first-line treatment for T3–4, especially in cases with unresectable tumors.