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Exosomes are a new way of the communication between the tumor cell and macrophage in the micro-environment. The macrophage can be induced to different phenotypes according to the different tumors. In the present study, long-chain noncoding RNA HOTAIR (lncRNA HOTAIR) was highly expressed in LSCC and exosomes. The pathway of exosomal lncRNA HOTAIR inducing macrophage to M2 polarization in the LSCC was investigated. The carcinoma tissues and adjacent tissues were collected from 104 LSCC cases, and the positive relationship between CD163-/CD206-M2 macrophage infiltration and clinical phase, lymph node spreading and pathological phase in LSCC was observed. To examine the role of exosomal lncRNA HOTAIR, macrophages were co-cultured with LSCC-exosomes of high lncRNA HOTAIR expression or transferred with HOTAIR mimics. It was suggested that exosomal lncRNA HOTAIR can induce macrophages to M2 polarization by PI3K/p-AKT/AKT signaling pathway. Furthermore, exo-treated M2 macrophages facilitate the migration, proliferation, and EMT of LSCC.

BackgroundPhotoimmunotherapy is a treatment modality that induces targeted cell death by binding a molecular-targeted drug activated by infrared light to the tumor cells and subsequently illuminating the lesion with infrared light. For deep lesions, a needle catheter is used to puncture the tumor, and an illumination fiber (cylindrical diffuser) is inserted into the catheter lumen for internal illumination. However, it can be challenging to place the cylindrical diffusers in an appropriate position as the deep lesions cannot be often confirmed accurately during surgery.Materials and methodsWe have developed \"SlicerPIT\", a planning simulation software for photoimmunotherapy. SlicerPIT allows users to place the cylindrical diffuser with its illumination range on preoperative images in 2D and 3D and export the planning data to external image-guided surgical navigation systems. We performed seven cycles of photoimmunotherapy with SlicerPIT in three patients with recurrent head and neck cancer.ResultsPreoperative planning for photoimmunotherapy was conducted using SlicerPIT, which could be imported into the navigation system. During the operation, we punctured the needle catheters along with the treatment plan on the navigation screen. Subsequently, intraoperative CT imaging was performed and overlaid with the preoperative treatment plan to confirm the alignment of the cylindrical diffusers as planned, followed by infrared light illumination. Postoperative imaging showed necrosis and shrinkage of the entire tumor in all cycles.ConclusionSlicerPIT allows for detailed preoperative treatment planning and accurate puncture. It may be a valuable tool to improve the accuracy of photoimmunotherapy for deep lesions and improve patient outcomes.

Background Several studies have demonstrated that the seventh edition of the American Joint Committee on Cancer/American Joint Committee on Cancer (AJCC/UICC) TNM staging system does not consistently distinguish between prognostic subgroups for human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPSCC). The eighth edition of the AJCC/UICC TNM staging system came into effect for use with HPV-mediated OPSCC on or after 1 January 2017. This study confirms that the eighth edition of the AJCC/UICC TNM staging system for HPV-mediated OPSCC accurately reflects disease outcomes. Patients and methods We retrospectively analyzed 195 patients with OPSCC treated at Hokkaido University Hospital, Sapporo, Japan between 1998 and 2015. HPV status was evaluated by immunohistochemical analysis of p16. Results Of the 195 OPSCC patients evaluated, 111 (56.9%) were p16 positive and 84 (43.1%) were p16 negative. The 3-year overall survival rate (OS) was significantly lower in the p16-negative patients with stage III-IV in comparison with those with stage I-II (55.0 vs. 93.1%, respectively; p < 0.01). The 3-year OS did not differ significantly between stage I-II and stage III-IV in the p16-positive patients (86.7 vs 87.7%). According to the eighth edition of the AJCC/UICC TNM staging system, stage I-II and stage III can be differentiated on the basis of the 3-year OS in the p16-positive patients (90.9 vs 70.2%, respectively; p < 0.01). Conclusions The seventh edition of the AJCC/UICC TNM staging system is suitable for use with p16-negative patients; however, it does not effectively discriminate between p16-positive patients. Therefore, the eighth edition of the AJCC/UICC TNM staging system is more suitable for HPV-mediated OPSCC in Japan.

Mucoepidermoid carcinoma (MEC) is rare, but the most common primary malignancy of the salivary gland and not infrequent in young individuals. CRTC1/3‐MAML2 fusions are frequently detected in MEC and are useful as a diagnostic biomarker. However, there has been debate as to whether the fusions have prognostic significance. In this study, we retrospectively collected 153 salivary gland MEC cases from 11 tertiary hospitals in Japan. As inclusion criteria, the MEC patients in this study had curative surgery as the initial treatment, received no preoperative treatment, and had no distant metastasis at the time of the initial surgery. The MEC diagnosis was validated by a central pathology review by five expert salivary gland pathologists. The CRTC1/3‐MAML2 fusions were detected using FISH and RT‐PCR. In 153 MEC cases, 90 (58.8%) were positive for CRTC1/3‐MAML2 fusions. During the follow‐up period, 28 (18.3%) patients showed tumor recurrence and 12 (7.8%) patients died. The presence of the fusions was associated with favorable tumor features. Of note, none of the fusion‐positive patients died during the follow‐up period. Statistical analysis showed that the presence of the fusions was a prognostic indicator of a better overall survival in the total and advanced‐stage MEC cohorts, but not in the early‐stage MEC cohort. In conclusion, CRTC1/3‐MAML2 fusions are an excellent biomarker for favorable overall survival of patients with salivary gland MEC. Debate exists as to whether CRTC1/3‐MAML2 fusions have a prognostic significance in salivary mucoepidermoid carcinoma (MEC). We undertook a multiinstitutional study including 153 MEC cases, and found that the fusions were an excellent biomarker for better overall survival in the total and advanced‐stage MEC cohorts.

BackgroundSuperselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is a very promising treatment modality for locally advanced head and neck squamous cell carcinoma. However, there are some concerns regarding its potential for the control of neck lymph node metastasis. The objective of this study was to investigate whether RADPLAT provided inferior regional control compared to intravenous chemoradiotherapy (IV-CRT).MethodsA total of 172 patients with neck lymph node metastases, 66 of whom underwent RADPLAT and 106 IV-CRT, were enrolled in this study. We retrospectively compared regional control rates between RADPLAT and IV-CRT. Furthermore, to adjust for differences in factors related to patient background between the groups, we conducted inverse probability weighting (IPW) analysis using the propensity score.ResultsA comparison between the two groups revealed that the regional control rates were almost equal under unadjusted conditions; however, after adjustment by IPW analysis, the RADPLAT group had a relatively better regional control rate than did the IV-CRT group (1 year regional control rate: 86.6% vs. 79.4%). In addition, the analysis of relative risk factors for regional control in the RADPLAT group showed that the absence of intra-arterial cisplatin infusion into metastatic lymph nodes was the only independent risk factor (Hazard ratio: 4.23, p = 0.04).ConclusionThis study showed that the regional control rate in patients treated with RADPLAT was noninferior to that for IV-CRT. Locally advanced head and neck cancers is a good indication for RADPLAT, even if the patients have neck lymph node metastases.

Background Among salivary gland malignancies, the prognosis of salivary duct carcinoma (SDC) is assumed to be the poorest. However, because of its low incidence, reliable survival estimates and prognostic factors based on a large number of patients remain to be elucidated, thereby making it impossible to standardize the optimal treatment for SDC. Methods We performed this multi-institutional, retrospective analysis by collecting the clinical information of 141 patients with SDC without distant metastasis who underwent curative surgery as the initial treatment to elucidate overall survival (OS) and disease-free survival (DFS) along with their prognostic factors. Results The 3-year OS and DFS rates were 70.5 and 38.2 %, respectively. Multivariate analysis revealed that age ≥65 years ( p  < 0.001) and N1 and N2 ( p  = 0.047 and <0.001, respectively) were independent prognostic factors for OS, whereas the primary site of the minor salivary and sublingual gland ( p  < 0.001) and N2 ( p  < 0.001) were those for DFS. The most common treatment failure was distant metastasis (55 patients, 39.0 %). For early parotid SDC, neither total parotidectomy in the patients with early T stage nor nerve resection in the patients without facial nerve palsy showed survival benefits. Conclusions Advanced N stage independently affects both OS and DFS. Partial parotidectomy with facial nerve preservation could be a less invasive standard surgical procedure for parotid gland SDC in the early T stage without facial nerve palsy. Effective systemic therapy is imperative to improve DFS of SDC.

Background This study aimed to assess the utility of deep learning analysis using pretreatment FDG-PET images to predict local treatment outcome in oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods One hundred fifty-four OPSCC patients who received pretreatment FDG-PET were included and divided into training ( n  = 102) and test ( n  = 52) sets. The diagnosis of local failure and local progression-free survival (PFS) rates were obtained from patient medical records. In deep learning analyses, axial and coronal images were assessed by three different architectures (AlexNet, GoogLeNET, and ResNet). In the training set, FDG-PET images were analyzed after the data augmentation process for the diagnostic model creation. A multivariate clinical model was also created using a binomial logistic regression model from a patient’s clinical characteristics. The test data set was subsequently analyzed for confirmation of diagnostic accuracy. Assessment of local PFS rates was also performed. Results Training sessions were successfully performed with an accuracy of 74–89%. ROC curve analyses revealed an AUC of 0.61–0.85 by the deep learning model in the test set, whereas it was 0.62 by T-stage, 0.59 by clinical stage, and 0.74 by a multivariate clinical model. The highest AUC (0.85) was obtained with deep learning analysis of ResNet architecture. Cox proportional hazards regression analysis revealed deep learning-based classification by a multivariate clinical model ( P  < .05), and ResNet ( P  < .001) was a significant predictor of the treatment outcome. In the Kaplan-Meier analysis, the deep learning-based classification divided the patient’s local PFS rate better than the T-stage, clinical stage, and a multivariate clinical model. Conclusions Deep learning-based diagnostic model with FDG-PET images indicated its possibility to predict local treatment outcomes in OPSCCs.

BackgroundThe 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.MethodsThe data for 112 patients were obtained and reclassified based on the criteria presented in the 8th edition.ResultsSeven 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.ConclusionsThe 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.

BackgroundOwing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified.MethodsIn this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists.ResultsThe 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy.ConclusionsA higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.

PurposeTo develop a convolutional neural network (CNN) model to diagnose skull-base invasion by nasopharyngeal malignancies in CT images and evaluate the model’s diagnostic performance.Materials and methodsWe divided 100 malignant nasopharyngeal tumor lesions into a training (n = 70) and a test (n = 30) dataset. Two head/neck radiologists reviewed CT and MRI images and determined the positive/negative skull-base invasion status of each case (training dataset: 29 invasion-positive and 41 invasion-negative; test dataset: 13 invasion-positive and 17 invasion-negative). Preprocessing involved extracting continuous slices of the nasopharynx and clivus. The preprocessed training dataset was used for transfer learning with Residual Neural Networks 50 to create a diagnostic CNN model, which was then tested on the preprocessed test dataset to determine the invasion status and model performance. Original CT images from the test dataset were reviewed by a radiologist with extensive head/neck imaging experience (senior reader: SR) and another less-experienced radiologist (junior reader: JR). Gradient-weighted class activation maps (Grad-CAMs) were created to visualize the explainability of the invasion status classification.ResultsThe CNN model’s diagnostic accuracy was 0.973, significantly higher than those of the two radiologists (SR: 0.838; JR: 0.595). Receiver operating characteristic curve analysis gave an area under the curve of 0.953 for the CNN model (versus 0.832 and 0.617 for SR and JR; both p < 0.05). The Grad-CAMs suggested that the invasion-negative cases were present predominantly in bone marrow, while the invasion-positive cases exhibited osteosclerosis and nasopharyngeal masses.ConclusionsThis CNN technique would be useful for CT-based diagnosis of skull-base invasion by nasopharyngeal malignancies.