Efficacy and safety of PLDR-IMRT for the re-irradiation of recurrent NPC: A prospective, single-arm, multicenter trial.

Salvage treatment of locoregionally recurrent nasopharyngeal carcinoma (NPC) requires weighing the benefits of re-irradiation against increased risks of toxicity. Here, we evaluated the outcomes of patients treated with intensity-modulated-based pulsed low-dose-rate radiotherapy (PLDR-IMRT) to enhance the curative effect of salvage treatment and reduce RT-related SAEs. A prospective clinical trial was conducted from March 2018 to March 2020 at multiple institutions. NPC patients who experienced relapse after radical therapy were re-irradiated with a median dose of 60 Gy (50.4-70 Gy)/30 f (28-35 f) using PLDR-IMRT. Thirty-six NPC patients who underwent PLDR-IMRT for locoregional recurrence were identified. With a median follow-up of 26.2 months, the objective response rate (ORR) of the entire cohort was 91.6%. The estimated mPFS duration was 28 months (95% CI: 24.9-31.1), and the estimated mLRFS duration was 30.4 months (95% CI: 25.2-35.5). The overall survival (OS) rate for all patients was 80.6%, the progression-free survival (PFS) rate was 75% and the cancer-specific survival (CSS) rate was 88.9% at 1 year. The LRFS and DMFS rates were 88.9% and 91.7%, respectively, at 1 year. A combination of systematic therapies could provide survival benefits to patients who experience NPC relapse (p < 0.05), and a Karnofsky performance status (KPS) score of ≥90 was a favorable factor for local control (p < 0.05). The incidence of acute SAEs (grade 3+) from PLDR was 22.2%, and the incidence of chronic SAEs was 19.4% among all patients. PLDR-IMRT combined with systematic therapy can effectively treat patients with locoregionally recurrent nasopharyngeal carcinoma and causes fewer adverse events than the rates expected with IMRT.

Downregulation of microRNA-21 inhibited radiation-resistance of esophageal squamous cell carcinoma.

BACKGROUND: MicroRNA-21 (miR-21) was previously reported being dysregulated in many kinds of cancer including esophageal squamous cell carcinoma (ESCC). In the present study, we aimed to investigate the role of miR-21 in ESCC, especially in its effects on radiation-sensitivity of ESCC. METHODS: Expression of miR-21 was detected in 63 pairs ESCC tumor and adjacent non-tumoral tissues using qRT-PCR, correlation between miR-21 and clinicopathological feature of ESCC was analyzed. The role of miR-21 in the proliferation, cell cycle and apoptosis of ESCC cells during irradiation were studied. RESULTS: MicroRNA-21 expression was significantly increased in ESCC tumor tissues. Expression of miR-21 was positively associated with advanced clinical stage. Under irradiation, overexpression of miR-21 increased cell proliferation and cells in S phase, and inhibited cell apoptosis of ESCC cells. In contrast, knockdown of miR-21 had an opposite effect. CONCLUSIONS: Downregulation of miR-21 inhibited the radiation-resistance of ESCC, whereas overexpression of miR-21 increased the radiation-resistance. MiR-21 is a potential novel target for developing specific treatment interventions in ESCC in future.

The PDZ Domain of the E Protein in SARS-CoV Induces Carcinogenesis and Poor Prognosis in LUAD.

BACKGROUND: In both lung adenocarcinoma (LUAD) and severe acute respiratory syndrome (SARS), uncontrolled inflammation can be detected in lung tissue. The PDZ-binding motif (PBM) in the SARS-CoV-1 E protein has been demonstrated to be a virulence factor that induces a cytokine storm. METHODS: To identify gene expression fluctuations induced by PBM, microarray sequencing data of lung tissue infected with wild-type (SARS-CoV-1-E-wt) or recombinant virus (SARS-CoV-1-E-mutPBM) were analyzed, followed by functional enrichment analysis. To understand the role of the screened genes in LUAD, overall survival and immune correlation were calculated. RESULTS: A total of 12 genes might participate in the initial and developmental stages of LUAD through expression variation and mutation. Moreover, dysregulation of a total of 12 genes could lead to a poorer prognosis. In addition, the downregulation of MAMDC2 and ITGA8 by PBM could also affect patient prognosis. Although the conserved PBM (-D-L-L-V-) can be found at the end of the carboxyl terminus in multiple E proteins of coronaviruses, the specific function of each protein depends on the entire amino acid sequence. CONCLUSIONS: In summary, PBM containing the SARS-CoV-1 E protein promoted the carcinogenesis of LUAD by dysregulating important gene expression profiles and subsequently influencing the immune response and overall prognosis.

Comprehensive Evaluation of a Deep Learning Model for Automatic Organs-at-Risk Segmentation on Heterogeneous Computed Tomography Images for Abdominal Radiation Therapy.

PURPOSE: Our purpose was to develop a deep learning model (AbsegNet) that produces accurate contours of 16 organs at risk (OARs) for abdominal malignancies as an essential part of fully automated radiation treatment planning. METHODS AND MATERIALS: Three data sets with 544 computed tomography scans were retrospectively collected. Data set 1 was split into 300 training cases and 128 test cases (cohort 1) for AbsegNet. Data set 2, including cohort 2 (n = 24) and cohort 3 (n = 20), were used to validate AbsegNet externally. Data set 3, including cohort 4 (n = 40) and cohort 5 (n = 32), were used to clinically assess the accuracy of AbsegNet-generated contours. Each cohort was from a different center. The Dice similarity coefficient and 95th-percentile Hausdorff distance were calculated to evaluate the delineation quality for each OAR. Clinical accuracy evaluation was classified into 4 levels: no revision, minor revisions (0% < volumetric revision degrees [VRD] ≤ 10%), moderate revisions (10% ≤ VRD < 20%), and major revisions (VRD ≥20%). RESULTS: For all OARs, AbsegNet achieved a mean Dice similarity coefficient of 86.73%, 85.65%, and 88.04% in cohorts 1, 2, and 3, respectively, and a mean 95th-percentile Hausdorff distance of 8.92, 10.18, and 12.40 mm, respectively. The performance of AbsegNet outperformed SwinUNETR, DeepLabV3+, Attention-UNet, UNet, and 3D-UNet. When experts evaluated contours from cohorts 4 and 5, 4 OARs (liver, kidney_L, kidney_R, and spleen) of all patients were scored as having no revision, and over 87.5% of patients with contours of the stomach, esophagus, adrenals, or rectum were considered as having no or minor revisions. Only 15.0% of patients with colon and small bowel contours required major revisions. CONCLUSIONS: We propose a novel deep-learning model to delineate OARs on diverse data sets. Most contours produced by AbsegNet are accurate and robust and are, therefore, clinically applicable and helpful to facilitate radiation therapy workflow.

Feasibility of delta radiomics-based pCR prediction for rectal cancer patients treated with magnetic resonance-guided adaptive radiotherapy.

Magnetic resonance-guided adaptive radiotherapy (MRgART) represents the latest frontier in precision radiotherapy. It is distinguished from other modalities by the possibility of acquiring high-contrast soft tissue images, combined with the ability to recalculate and re-optimize the plan on the daily anatomy. The extensive database of available images offers ample scope for using disciplines such as radiomics to try to correlate features and outcomes. This study aimed to correlate the change of radiomics feature along the treatment to pathological complete response (pCR) for locally advanced rectal cancer (LARC) patients. Twenty-eight LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT) with a short course (25 Gy, 5 Gy × 5f) MRgART at 1.5 Tesla MR-Linac were enrolled. The T2-weighted images acquired at each fraction, corresponding target delineation, pCR result of the surgical specimen, and clinical variables were collected. Seven families of features [First Order, Shape, Gray-level Co-occurrence Matrix (GLCM), Gray-level Dependence Matrix (GLDM), Gray-level Run Length Matrix (GLRLM), Gray-level Size Zone Matrix (GLSZM), and Neighborhood Gray Tone Difference Matrix (NGTDM)] were extracted, and delta features were calculated from the ratio of features of each successive fraction to those of the first fraction. Mann-Whitney U test and LASSO were utilized to reduce the dimension of features and select those features that are most significant to pCR. At last, the radiomics signatures were established by linear regression with the final set of features and their coefficients. A total of 581 radiomics features were extracted, and 2,324 delta features were calculated for each patient. Nineteen features and delta features, and one clinical variable (cN) were significant (p< 0.05) to pCR; seven predictive features were further selected and included in the linear regression to construct the radiomics signature significantly discriminating pCR and non-pCR groups (p< 0.05). Delta features based on MRI images acquired during a short course MRgART could potentially be used to predict treatment response in LARC patients undergoing nCRT.

Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation.

Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects. This study aimed to explore its radio-sensitizing effects and the underlying mechanisms. Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis. Bioinformatic molecular docking prediction and following validation by surface plasmon resonance (SPR) technology, cellular thermal shift assay (CETSA), and isothermal titration calorimetry (ITC) were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha (HSP90α). The effects of ginsenoside Rg5 on HSP90-cell division cycle 37 (CDC37) interaction, the client protein stability, and the downstream regulations were further explored. Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis. It could bind to HSP90α with a high affinity, but the affinity was drastically decreased by HSP90α Y61A mutation. Co-immunoprecipitation (Co-IP) and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner. It reduced irradiation-induced upregulation of the HSP90-CDC37 client proteins, including SRC, CDK4, RAF1, and ULK1 in A549 cell-derived xenograft (CDX) tumors. Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/ß ratio and restored irradiation-induced downregulation of p62 expression. In A549 CDX tumors, ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage. In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.

Prognostic value of sarcopenia in patients with lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors.

Objectives: It remains controversial whether sarcopenia has any significant impact on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Therefore, in this study, we aimed to assess the association between sarcopenia and clinical outcomes in patients with advanced NSCLC receiving EGFR-TKIs or ICIs as a first-line therapy. Methods: We retrospectively enrolled 131 patients with advanced NSCLC treated with first-line EGFR-TKIs or ICIs between 1 March 2019 and 31 March 2021. To estimate sarcopenia, we calculated skeletal muscle index (SMI) as the ratio of skeletal muscle area (cm2) to height squared (m2). Associations between sarcopenia and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and log-rank tests, respectively. A Cox proportional hazards regression model was used to assess the factors associated with OS and PFS. The Student's t-test or Mann-Whitney U test was used to compare the SMI between patients with or without objective response and disease control. The chi-squared test was used to compare adverse events (AEs) between patients with and without sarcopenia. Results: Among the 131 patients, 35 (26.7%) were diagnosed with sarcopenia. Sarcopenia was an independent predictor of poor OS and PFS (p < 0.05) overall and in the EGFR-TKI- and ICI-treated cohorts. Among all patients, those with sarcopenia showed significantly shorter OS and PFS than those without sarcopenia (median OS and PFS: 13.0 vs. 26.0 months and 6.4 vs. 15.1 months; both p < 0.001). These associations were consistent across the subtypes of most clinical characteristics. Statistically significant differences between the objective response (OR) and non-OR groups were also observed in the mean SMI (OR group, 43.89 ± 7.55 vs. non-OR group, 38.84 ± 7.11 cm2/m2; p < 0.001). In addition, we observed similar results with disease control (DC) and non-DC groups (DC group, 42.46 ± 7.64 vs. non-DCR group, 33.74 ± 4.31 cm2/m2; p < 0.001). The AEs did not differ significantly between the sarcopenia and non-sarcopenia groups. Conclusion: Sarcopenia before treatment might be a significant predictor of poor clinical outcomes (shorter OS and PFS, fewer ORs, less DC) in patients with advanced NSCLC treated with EGFR-TKIs or ICIs as the first-line therapy.

Extraction parameter optimized radiomics for neoadjuvant chemotherapy response prognosis in advanced nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Neoadjuvant Chemotherapy (NAC) followed by concurrent chemoradiotherapy (CCRT) is promising in improving the survival rate for advanced nasopharyngeal carcinoma (NPC) patients relative to CCRT alone. However, not all patients respond well to NAC. Therefore, we aimed to develop and evaluate a modified radiomics model for the NAC response prognosis in NPC patients. METHODS: A total of 165 patients with biopsy-proven locally advanced NPC were retrospectively selected from the database of our hospital. 85 out of them were for training and cross-validation, while the other 80 patients were for independent testing. All patients were treated with NAC and underwent MRI inspection, including T1-weighted (T1), T2-weighted (T2), and contrast-enhanced T1-weighted (T1-cs) sequences before and after two cycles of NAC. We classified the patients into the response or non-response groups by the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). Radiomics features were extracted from the primary and lymph node gross tumor volume in each sequence. To further improve the predictive performance, the permutation of multiple combinations of extraction parameters has first ever been investigated in the NAC prognosis for NPC patients. The model was constructed by logistic regression and cross-validated by bootstrapping with a resampling number of 1000. Independent testing was also implemented. In addition, we also applied an imbalance-adjusted bootstrap strategy to decrease the bias of small samples. RESULTS: For the cross-validation cohort, the resultant AUC, sensitivity, and specificity in terms of 95% confidence interval were 0.948 ± 0.004, 0.849 ± 0.005, and 0.840 ± 0.010. For the independent testing cohort, the model reached an AUC of 0.925, a sensitivity of 0.821, and a specificity of 0.792. There was a significant difference in the estimated radiomics score between the response and non-response groups (P < 0.005). CONCLUSIONS: An MRI-based radiomics model was developed and demonstrated promising capability for the individual prediction of NAC response in NPC patients. In particular, we have optimized the multiple combinations of texture extraction parameters with the permutation test and observed an encouraging improvement of the prediction performance compared to the previously published studies. The proposed model might provide chances for individualized treatment in NPC patients while retrenching the cost of clinical resources.

Level Ib CTV delineation in nasopharyngeal carcinoma based on lymph node distribution and topographic anatomy.

BACKGROUND AND PURPOSE: To analyze the distribution pattern of lymph nodes (LNs) metastasis of level Ib in nasopharyngeal cancer (NPC) and propose shrinkage of clinical target volume (CTV) boundaries to avoid unnecessary radiation for some space with very low-risk of involvement. MATERIALS AND METHODS: Pretreatment images of pathologically proven NPC patients were reviewed and those with positive level Ib LN metastasis was enrolled. The geometric center of each level Ib LN in the neck was marked on a template CT. The spatial relationship of nodes with key structures in level Ib was analyzed. Modified level Ib CTV according to the 2013 International CTV consensus was proposed based on the LN distribution pattern. A PlanIQ Feasibility DVH module was implemented to evaluate the feasibility analysis of the best possible sparing of organs at risk (OAR) with modified Ib CTV. RESULTS: A total of 1518 NPC patients were reviewed and 54 with positive level Ib nodes were enrolled. Four sub-level anatomical regions were defined within the gross area of level Ib. Of 106 positive nodes identified, none, one, 88, and 17 were found in the intraglandular (IG), medial mandibular (MM), supra perivascular (SP), and infra perivascular (IP) sub-level, respectively. This study proposes sparing the IG and MM sub-level and including the area within a specified distance from the submandibular gland (11 mm for SP, 17 mm for IP) for CTV coverage. Compared with planning based on CTV-consensus, planning based on CTV-proposed results in a significantly reduced CTV volume, and mean dose (Dmean) of both the ipsilateral SMG and bilateral SLG. CONCLUSIONS: Based on detailed analysis of the relationship between positive node distribution and several important anatomical structures, modified level Ib CTV for prophylactic irradiation was proposed to reduce the dose of OAR irradiation.

Automatic Delineation of Gross Tumor Volume Based on Magnetic Resonance Imaging by Performing a Novel Semisupervised Learning Framework in Nasopharyngeal Carcinoma.

PURPOSE: We aimed to validate the accuracy and clinical value of a novel semisupervised learning framework for gross tumor volume (GTV) delineation in nasopharyngeal carcinoma. METHODS AND MATERIALS: Two hundred fifty-eight patients with magnetic resonance imaging data sets were divided into training (n = 180), validation (n = 20), and testing (n = 58) cohorts. Ground truth contours of nasopharynx GTV (GTVnx) and node GTV (GTVnd) were manually delineated by 2 experienced radiation oncologists. Twenty percent (n = 36) labeled and 80% (n = 144) unlabeled images were used to train the model, producing model-generated contours for patients from the testing cohort. Nine experienced experts were invited to revise model-generated GTV in 20 randomly selected patients from the testing cohort. Six junior oncologists were asked to delineate GTV in 12 randomly selected patients from the testing cohort without and with the assistance of the model, and revision degrees were compared under these 2 modes. The Dice similarity coefficient (DSC) was used to quantify the accuracy of the model. RESULTS: The model-generated contours showed a high accuracy compared with ground truth contours, with an average DSC score of 0.83 and 0.80 for GTVnx and GTVnd, respectively. There was no significant difference in DSC score between T1-2 and T3-4 patients (0.81 vs 0.83; P = .223), or between N1-2 and N3 patients (0.80 vs 0.79; P = .807). The mean revision degree was lower than 10% in 19 (95%) patients for GTVnx and in 16 (80%) patients for GTVnd. With assistance of the model, the mean revision degree for GTVnx and GTVnd by junior oncologists was reduced from 25.63% to 7.75% and from 21.38% to 14.44%, respectively. Meanwhile, the delineating efficiency was improved by over 60%. CONCLUSIONS: The proposed semisupervised learning-based model showed a high accuracy for delineating GTV of nasopharyngeal carcinoma. It was clinically applicable and could assist junior oncologists to improve GTV contouring accuracy and save contouring time.

Post-treatment serum triglyceride: An effective biomarker for body fat mass and overall survival in esophageal squamous cell cancer patients treated with chemoradiotherapy.

Objectives: Although lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass. Materials and methods: We conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients' serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan-Meier curves and a Cox proportional hazards model. Results: Of the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3-92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37-0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels. Conclusion: Post-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.

Lymph drainage and cervical fascia anatomy-oriented differential nodal CTV delineation at the supraclavicular region for esophageal cancer and nasopharyngeal cancer.

PURPOSE: To determine the differences in supraclavicular lymph node metastasis between esophageal cancer (EC) and nasopharyngeal cancer (NPC) and explore the feasibility of differential supraclavicular clinical target volume (CTV) contouring between these two diseases based on the involvement of different fascial spaces. MATERIALS AND METHODS: One hundred patients with supraclavicular nodes positive for EC or NPC were enrolled, and their pre-treatment images were reviewed. The distribution patterns of nodes between the two diseases were compared in the context of node levels defined by the 2017 Japanese Esophageal Society and 2013 International Consensus on Cervical Lymph Node Level Classification. Grouping supraclavicular nodes based on sub-compartments formed by the cervical fascia was discussed, and the feasibility of differential CTV contouring based on the differences in the involvement of these sub-compartments between EC and NPC was explored. RESULTS: The 2013 Consensus on cervical node levels and 2017 Japanese Esophageal Society node station could not practically guide supraclavicular CTV contouring. We divided the supraclavicular space into six sub-compartments: the para-esophageal space (PES), carotid sheath space (CSS), sub-thyroid pre-trachea space (STPTS), pre-vascular space (PVS), and vascular lateral space (VLS) I and II. EC mainly spread to the PES, STPTS, CSS, and VLS I, whereas NPC tended to spread to the CSS, VLS I, and VLS II. These combinations of sub-compartments may help constitute the supraclavicular CTVs for EC and NPC. CONCLUSIONS: The fascia anatomy-based sub-compartments sufficiently distinguished metastasis to the supraclavicular space between EC and NPC, thus facilitating differential CTV contouring between these two diseases.

FOXG1 mediates the radiosensitivity of glioma cells through regulation of autophagy.

BACKGROUND/AIM: Upregulation of Forkhead box G1 (FOXG1) has recently been observed in many cancers, while its effect on radiosensitivity in glioma is still unclear. In this study, we hypothesized that FOXG1 be a major player in radioresistance of glioma as well as the underlying mechanism. METHODS: Immunohistochemistry (IHC) was conducted to assess FOXG1 expression in glioma tissues and glioma-adjacent tissues. Western Blot was implemented to detect the expression of autophagy-related proteins. CCK-8, colony formation and flow cytometry assays were implemented to assess cell viability, proliferation and apoptosis, respectively. Transmission electron microscope (TEM) was used to observe autophagic vesicles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was applied to detect the expression of FOXG1. RESULTS: The present study demonstrated that FOXG1 was highly expressed in glioma tissues. FOXG1 expression level was up-regulated in glioma cells following exposure to X-ray irradiation. FOXG1 can attenuate radiosensitivity of glioma cells. Moreover, it revealed that FOXG1 attenuate radiosensitivity of glioma cells by promoting autophagy. CONCLUSIONS: The present study suggests that FOXG1 is a pivotal molecule for circumventing radiation-induced cell death in malignant glioma cells through the regulation of autophagy, and it may be a target for the treatment of human brain glioma.

Comparative Study of Auto Plan and Manual Plan for Nasopharyngeal Carcinoma Intensity-Modulated Radiation Therapy.

PURPOSE AND OBJECTIVE: Auto planning might reduce the manual time required for the optimization and could also potentially improve the overall plan quality. The aim of this study is to demonstrate the statistical comparison of automatic (AU) and manually (MA) generated nasopharyngeal carcinoma (NPC) intensity-modulated radiation therapy (IMRT) plans. MATERIALS AND METHODS: The study included 105 nasopharyngeal carcinoma patients, admitted to our hospital. The patients underwent IMRT treatments. The clinically delivered plans were performed with Eclipse (Version 11.0) using manual optimization. The same plans were optimized successively in PinnacleTM3 (version 9.10) treatment planning system using the auto plan software package module. D95 (dose of 95% volume) and D98 (dose of 98% volume) were calculated for the targets and maximum dose (Dmax) and mean dose (Dmean) for the organ at risks (OARs); moreover, the average doses of each target and OARs for 105 patients were evaluated. RESULTS: There is no significant difference in the homogeneity of the target between AU and MA treatment plans, while a significant difference is observed for what is concerning the OARs or most of OARs in 105 patients, OAR doses were significantly reduced in AU plan. For OARs which have no significant difference between AU and MA plans are highlighted, the mean dose of OARs in AU plans was at least not higher than MA plans. CONCLUSION: Nasopharyngeal carcinoma IMRT plans made by an automatic planning tool met the clinical requirements for target prescription dose; moreover, the dose of normal tissues was lower than in MA plans. Clinical physicists' time can be saved and the influence of factors such as the lack of experience in treatment planning can be avoided.

DeepLRHE: A Deep Convolutional Neural Network Framework to Evaluate the Risk of Lung Cancer Recurrence and Metastasis From Histopathology Images.

It is critical for patients who cannot undergo eradicable surgery to predict the risk of lung cancer recurrence and metastasis; therefore, the physicians can design the appropriate adjuvant therapy plan. However, traditional circulating tumor cell (CTC) detection or next-generation sequencing (NGS)-based methods are usually expensive and time-inefficient, which urge the need for more efficient computational models. In this study, we have established a convolutional neural network (CNN) framework called DeepLRHE to predict the recurrence risk of lung cancer by analyzing histopathological images of patients. The steps for using DeepLRHE include automatic tumor region identification, image normalization, biomarker identification, and sample classification. In practice, we used 110 lung cancer samples downloaded from The Cancer Genome Atlas (TCGA) database to train and validate our CNN model and 101 samples as independent test dataset. The area under the receiver operating characteristic (ROC) curve (AUC) for test dataset was 0.79, suggesting a relatively good prediction performance. Our study demonstrates that the features extracted from histopathological images could be well used to predict lung cancer recurrence after surgical resection and help classify patients who should receive additional adjuvant therapy.

Histological subtype remains a prognostic factor for survival in nasopharyngeal carcinoma patients.

OBJECTIVES: There is currently no consensus on the prognostic significance of the histological subtype of nasopharyngeal carcinoma (NPC). The aim of the current study was to evaluate the impact of histological subtype on survival in NPC patients based on the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: Patients with NPC were identified within the SEER database (2004-2015). The effects of histological subtype on cause-specific survival (CSS) in NPC patients were evaluated using univariate and multivariate Cox regression analyses. Subgroup analysis according to histological subtype in NPC patients was carried out by 1:1 propensity score matching (PSM). RESULTS: A total of 4085 NPC patients were selected from the SEER database, including 1929 with keratinizing squamous cell carcinoma (KSCC), 2203 with nonkeratinizing carcinoma (NKC), and 53 with basaloid squamous cell carcinoma (BSCC). The 3-year and 5-year CSS rates were 61.76% and 55.07% for KSCC patients, 79.57% and 72.09% for NKC patients, and 77.55% and 74.03% for BSCC patients, respectively. Multivariate analysis identified sex, age, marital status, race, T stage, N stage, M stage, radiotherapy, chemotherapy, and histological subtype as significant prognostic factors for CSS in NPC patients. KSCC was found to be associated with worse CSS than NKC on Kaplan-Meier analysis and subgroup analysis after 1:1 PSM. CONCLUSIONS: Histological subtype determines the long-term survival outcomes of patients with NPC. Moreover, the NKC subtype has the best prognosis, while the KSCC subtype has the worst prognosis. LEVEL OF EVIDENCE: NA Laryngoscope, 130:E83-E88, 2020.

Nomogram for predicting the overall survival of patients with inflammatory breast cancer: A SEER-based study.

OBJECTIVES: Inflammatory breast cancer (IBC) is a rare malignancy that is a unique biologic subtype of breast cancer. A nomogram to predict the overall survival (OS) of IBC patients is lacking. The aim of the study was to construct and validate a nomogram to predict the OS of IBC patients based on the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: Patients diagnosed with IBC between 2010 and 2016 were selected from the SEER database. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was constructed to predict the 1-, 3- and 5-year OS of these patients. The nomogram was internally and externally validated by Harrell's C-indexes and calibration plots. RESULTS: Patients were randomly divided into a training set (n = 2464) and a validation set (n = 1052). The training set was used to establish a nomogram. Multivariate analysis identified that race, age at diagnosis, breast cancer subtype, grade, N stage, M stage, radiation, chemotherapy, and surgery were significant prognostic factors for the OS. The internally and externally validated Harrell's C-indexes were 0.763 and 0.786, respectively. The calibration plots for predictions of the 1-, 3-, and 5-year OS were in excellent agreement. CONCLUSIONS: A nomogram was constructed to predict the OS for IBC patients based on the SEER database and to provide accurate and individualised survival predictions.

Nasopharyngeal carcinoma: A review of current updates.

Nasopharyngeal carcinoma (NPC) is a rare malignancy worldwide, but it is endemic in a few areas including Southern China, Southeast Asia, North Africa and the Arctic. The underlying mechanisms behind this remarkable geographic distribution remain unclear. Although Epstein-Barr virus (EBV) infection has been suggested as a necessary cause of undifferentiated NPC, EBV itself is not sufficient to cause this malignancy. Other co-factors, such as environmental risk factors, and/or genetic susceptibility, may interact with EBV to play a role in the carcinogenesis of NPC. Survival rates differ significantly between NPC patients in early stages and late stages. Due to the close associations between EBV infection and NPC risk, EBV-related biomarkers have been used for early detection and screening for NPC in a few high-incidence areas. In the present review article the latest updates are discussed.

An automated dose verification software for brachytherapy.

PURPOSE: To report an implementation method and the results of independent brachytherapy dose verification software (DVS). MATERIAL AND METHODS: The DVS was developed based on Visual C++ and adopted a modular structure design. The DICOM RT files exported from a treatment planning system (TPS) were automatically loaded into the DVS. The DVS used the TG-43 formalism for dose calculation. A total of 15 cervical cancer patients who underwent brachytherapy were retrospectively selected to test the DVS. Dosimetric parameters and γ analysis (0.1 cm, 5%) were used to evaluate the dose differences between the DVS and the TPS. RESULTS: Compared with the TPS dose, the γ pass rates of the dose calculated by the DVS were higher than 98%. For the clinical target volume (CTV), the dosimetric differences were less than 0.63% for D90% and D100%. For the bladder, rectum, and sigmoid, the agreement of D0.1cc, D1cc, and D2cc were within a 0.78% level. CONCLUSIONS: With minimal human-computer interactions, the DVS can verify the accuracy of doses calculated by the TPS.

Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for stage IV esophageal squamous cell carcinoma: a retrospective controlled study.

BACKGROUND: The purpose of this study is to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) versus chemotherapy alone for patients with stage IV esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients were retrospectively enrolled at the authors's institution from January 2010 to October 2015. Of the 141 patients enrolled, 55 (39.0%) received CCRT and 86 (61.0%) received chemotherapy alone. The outcomes and adverse events (AEs) were compared between the two groups. RESULTS: The baseline clinical characteristics of the two groups were similar. However, the CCRT group showed a significantly better primary tumor objective response rate (ORR) than that of the chemotherapy group (74.5% versus 45.3%, p = 0.001). The 1-year, 2-year, 3-year overall survival (OS) rates and median OS were 58.0% versus 43.0%, 25.5% versus 14.0%, 10.7% versus 4.7%, and 14 months versus 11 months for patients treated with CCRT or chemotherapy, respectively (p = 0.007). The 1-year and median progression-free survival (PFS) were 29.8% versus 14.9% and 8 months versus 6 months (p = 0.005). Multivariate analysis identified CCRT (p = 0.013) and solitary metastasis (p = 0.037) as independent factors for greater OS. The frequency of leucocytopenia (grade 3 or higher) was significantly higher in the CCRT group than in the chemotherapy-alone group (p = 0.040), whereas the rates of other AEs did not differ. CONCLUSIONS: In this study, it is suggested that CCRT is more effective than chemotherapy alone for stage IV ESCC, yielding better primary responses and survival outcomes with tolerable side effects.