Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era.

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

Sesamolin serves as an MYH14 inhibitor to sensitize endometrial cancer to chemotherapy and endocrine therapy via suppressing MYH9/GSK3ß/ß-catenin signaling.

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecological cancers. Herein, we aimed to define the role of specific myosin family members in EC because this protein family is involved in the progression of various cancers. METHODS: Bioinformatics analyses were performed to reveal EC patients' prognosis-associated genes in patients with EC. Furthermore, colony formation, immunofluorescence, cell counting kit 8, wound healing, and transwell assays as well as coimmunoprecipitation, cycloheximide chase, luciferase reporter, and cellular thermal shift assays were performed to functionally and mechanistically analyze human EC samples, cell lines, and a mouse model, respectively. RESULTS: Machine learning techniques identified MYH14, a member of the myosin family, as the prognosis-associated gene in patients with EC. Furthermore, bioinformatics analyses based on public databases showed that MYH14 was associated with EC chemoresistance. Moreover, immunohistochemistry validated MYH14 upregulation in EC cases compared with that in normal controls and confirmed that MYH14 was an independent and unfavorable prognostic indicator of EC. MYH14 impaired cell sensitivity to carboplatin, paclitaxel, and progesterone, and increased cell proliferation and metastasis in EC. The mechanistic study showed that MYH14 interacted with MYH9 and impaired GSK3ß-mediated ß-catenin ubiquitination and degradation, thus facilitating the Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition. Sesamolin, a natural compound extracted from Sesamum indicum (L.), directly targeted MYH14 and attenuated EC progression. Additionally, the compound disrupted the interplay between MYH14 and MYH9 and repressed MYH9-regulated Wnt/ß-catenin signaling. The in vivo study further verified sesamolin as a therapeutic drug without side effects. CONCLUSIONS: Herein, we identified that EC prognosis-associated MYH14 was independently responsible for poor overall survival time of patients, and it augmented EC progression by activating Wnt/ß-catenin signaling. Targeting MYH14 by sesamolin, a cytotoxicity-based approach, can be applied synergistically with chemotherapy and endocrine therapy to eventually mitigate EC development. This study emphasizes MYH14 as a potential target and sesamolin as a valuable natural drug for EC therapy.

Novel utilization and quantification of Xsight diaphragm tracking for respiratory motion compensation in Cyberknife Synchrony treatment of liver tumors.

PURPOSE: The Xsight lung tracking system (XLTS) utilizes an advanced image processing algorithm to precisely identify the position of a tumor and determine its location in orthogonal x-ray images, instead of finding fiducials, thereby minimizing the risk of fiducial insertion-related side effects. To assess and gauge the effectiveness of CyberKnife Synchrony in treating liver tumors located in close proximity to or within the diaphragm, we employed the Xsight diaphragm tracking system (XDTS), which was based on the XLTS. METHODS: We looked back at the treatment logs of 11 patients (8/11 [XDTS], 3/11 [Fiducial-based Target Tracking System-FTTS]) who had liver tumors in close proximity to or within the diaphragm. And the results are compared with the patients who undergo the treatment of FTTS. The breathing data information was calculated as a rolling average to reduce the effect of irregular breathing. We tested the tracking accuracy with a dynamic phantom (18023-A) on the basis of patient-specific respiratory curve. RESULTS: The average values for the XDTS and FTTS correlation errors were 1.38 ± 0.65  versus 1.50 ± 0.26 mm (superior-inferior), 1.28 ± 0.48  versus 0.40 ± 0.09 mm (left-right), and 0.96 ± 0.32  versus 0.47 ± 0.10 mm(anterior-posterior), respectively. The prediction errors for two methods of 0.65 ± 0.16  versus 5.48 ± 3.33 mm in the S-I direction, 0.34 ± 0.10  versus 1.41 ± 0.76 mm in the A-P direction, and 0.22 ± 0.072  versus 1.22 ± 0.48 mm in the L-R direction. The coverage rate of FTTS slightly less than that of XDTS, such as 96.53 ± 8.19% (FTTS) versus 98.03 ± 1.54 (XDTS). The prediction error, the motion amplitude, and the variation of the respiratory center phase were strongly related to each other. Especially, the higher the amplitude and the variation, the higher the prediction error. CONCLUSION: The diaphragm has the potential to serve as an alternative to gold fiducial markers for detecting liver tumors in close proximity or within it. We also found that we needed to reduce the motion amplitude and train the respiration of the patients during liver radiotherapy, as well as control and evaluate their breathing.

Prediction of liver metastasis and recommended optimal follow-up nursing in rectal cancer.

We aimed to analyze and investigate the clinical factors that influence the occurrence of liver metastasis in locally advanced rectal cancer patients, with an attempt to assist patients in devising the optimal imaging-based follow-up nursing. Between June 2011 and May 2021, patients with rectal cancer at our hospital were retrospectively analyzed. A random survival forest model was developed to predict the probability of liver metastasis and provide a practical risk-based approach to surveillance. The results indicated that age, perineural invasion, and tumor deposit were significant factors associated with the liver metastasis and survival. The liver metastasis risk of the low-risk group was higher at 6-21 months, with a peak occurrence time in the 15th month. The liver metastasis risk of the high-risk group was higher at 0-24 months, with a peak occurrence time in the 8th month. In general, our clinical model could predict liver metastasis in rectal cancer patients. It provides a visualization tool that can aid physicians and nurses in making clinical decisions, by detecting the probability of liver metastasis.

Novel biomarkers to predict treatment response and prognosis in locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy.

PURPOSE: To identify genes associated with treatment response and prognosis for locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (NCRT). METHODS: In our cohort, gene expression profiles of 64 tumor biopsy samples before NCRT were examined and generated. Weighted gene co-expression network analysis was performed to identify gene modules. External validation datasets included GSE3493, GSE119409, and GSE133057. The expression of candidate genes was evaluated using immunohistochemistry (IHC). TIMER was used to assess immune infiltration. RESULTS: We identified and validated the capability to predict the treatment response of CCT5 and ELF1 using our data and external validation datasets. The trends of survival differences of candidate genes in the GSE133057 dataset were similar to our cohort. High levels of CCT5 and ELF1 expression were associated with NCRT resistance and poor prognosis. Furthermore, the expression of CCT5 and ELF1 were also assessed in 117 LARC patients' samples by the IHC method. Based on IHC results and Cox analysis, the risk score model with CCT5 and ELF1 was constructed and performed well. The risk score was an independent prognostic factor for progression-free survival and overall survival in LARC patients and was then used to build nomogram models. The underlying mechanisms of CCT5 and ELF1 were explored using gene set enrichment analysis. The underlying pathway including apoptosis, cell cycle, and other processes. CCT5 and ELF1 expressions were significantly correlated with immune cell infiltration. CONCLUSION: CCT5 and ELF1 were determined as biomarkers for treatment response and prognosis in LARC patients. The risk score model and nomograms helped predict treatment response and survival outcomes for LARC patients undergoing NCRT.

Impact of glucocorticoids on the efficacy of neoadjuvant chemoradiotherapy and survival of patients with locally advanced rectal cancer: a retrospective study.

BACKGROUND: Preclinical studies suggest that glucocorticoids (GCs) promote the proliferation and development of colorectal cancer. Because GCs are broadly prescribed for treatment-related adverse events in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (NCRT), it's essential to assess the effect of GCs on clinical outcomes. METHODS: LARC cases treated with NCRT followed by surgery were assessed retrospectively. Evaluation of the relationship between GCs use (GCs vs. non-GCs) and neoadjuvant rectal (NAR) score (as a three-level categorical dependent variable) was performed using multivariable multinomial logistic regression (MLR). We also examined the relationship between the accumulated dose of GCs and NAR using multivariate MLR. Survival analysis of disease-free survival (DFS) and overall survival (OS) was performed using the Kaplan-Meier method. Multivariate Cox regression was used to assess confounding factors that could influence OS and DFS. RESULTS: This retrospective cohort study included 790 patients with newly diagnosed non-metastatic LARC (T3-4/N + M0) who received NCRT followed by surgery between January 2012 and April 2017. The end of the follow-up period was May 11, 2022. Among the 790 patients with LARC, 342 (43.2%) received GCs treatment and 448 (56.8%) did not during the NCRT-to-surgery period. GCs medication was significantly different between mid-NAR (8-16) and low-NAR (< 8) (odds ratio [OR], 0.615; 95% CI, 0.420-0.901; P = 0.013), and the high-NAR (> 16) and low-NAR (0.563; 0.352-0.900; 0.016). Patients exposed to GCs, had a decreased 5-year OS (GCs vs. non-GCs = 80.01% (95% CI, 75.87%-84.37%) vs. 85.30% (82.06%-88.67%), P = 0.023) and poorer 5-year DFS (73.99% (69.45%-78.82%) vs. 78.7% (75.14%-82.78%), P = 0.045). The accumulated dose of GCs was an independent risk factor for OS (hazard ratio [HR], 1.007 [1.001-1.014], 0.036) and DFS (1.010 [1.004-1.017], 0.001). CONCLUSIONS AND RELEVANCE: Our study revealed that GCs were associated with reduced efficacy of NCRT and worse clinical outcomes in patients with LARC during the NCRT-to-surgery period.

A large-scale study integrating nutritional indicators and clinicopathological parameters to evaluate prognosis, follow-up, and postoperative chemotherapy decisions in rectal cancer patients.

OBJECTIVE: The aim of this study was to evaluate the role of nutritional indicators and clinicopathological parameters in predicting the progression and prognosis for pathological stage II-III rectal cancer (RC) patients without neoadjuvant radiotherapy. In addition, we sought to explore the high-risk population who may require postoperative chemotherapy. METHODS: A total of 894 consecutive RC patients were enrolled in this study. Univariate and multivariate Cox analysis were performed to identify the independent risk factors for PFS and OS. The nomogram and calibration curves were conducted according to multivariable analysis result. Kaplan-Meier survival curves and log-rank tests were performed for different groups. Finally, random survival forest (RSF) model was developed to predict the probability of progression. RESULTS: Our results revealed that CEA level, pathological stage, tumor deposit, and PNI were independently associated with PFS in RC patients. Similarly, the results indicated that CEA level, pathological stage, tumor deposit, PNI, and NRI were independently associated with OS. RSF model revealed that group 1 had the highest risk of progression at the 12th month of follow-up, group 2 had the highest risk of progression at the 15th month of follow-up, while group 3 had the highest risk of progression at the 9th month of follow-up. Besides, subgroup analysis suggested that the high-risk group needs postoperative adjuvant chemotherapy, while patients in the low- and moderate-risk groups may not need postoperative adjuvant chemotherapy. Finally, we validated our results with the SEER database. CONCLUSIONS: In conclusion, we demonstrated that preoperative nutritional indicator and clinicopathological parameters could act as auxiliary prognostication tools for RC patients without neoadjuvant radiotherapy. We also established follow-up strategies for different groups of patients. Collectively, incorporating nutritional assessment into risk stratification for RC resection is crucial and should be an integral part of preoperative planning.

The value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma staged with PET/CT.

BACKGROUND: Limited evidence supports the omission of routine bone marrow (BM) examination (biopsy and aspiration) in patients with nasal-type extranodal NK/T-cell lymphoma (ENKTCL). This study was aimed at assessing whether BM examination provides valuable information for positron emission tomography/computed tomography (PET/CT)-based staging in this patient population. PATIENTS AND METHODS: Patients newly diagnosed with ENKTCL who underwent initial staging with both PET/CT and BM examination between 2013 and 2020 were retrospectively identified in two Chinese institutions. Overall, 742 patients were included; the BM examination was positive in 67 patients. RESULTS: Compared with BM biopsy alone, the combination of BM biopsy and aspiration assessment did not afford any additional diagnostic value. No patient with a positive BM biopsy was found to have early-stage disease by PET/CT. BM biopsy or PET/CT led to upstaging from stage III to IV as a result of BM involvement in 21 patients. In 135 patients with distant organ involvement, BM involvement was associated with worse overall survival (OS) and progression-free survival (PFS) compared with the corresponding durations in patients without BM involvement (2-year OS: 35.9% vs. 60.4%, p < .001; PFS: 26% vs. 40.7%, p = .003). No difference in survival was noted between groups judged positive based on PET/CT and BM biopsy. CONCLUSION: Compared with aspiration, BM biopsy led to the detection of more BM lesions. Baseline PET/CT can be safely used to exclude BM involvement in early-stage disease. Overall, routine BM examination affords diagnostic or prognostic value over PET/CT in patients with advanced-stage nasal-type ENKTCL.

Preoperative chemoradiotherapy with capecitabine and triweekly oxaliplatin versus capecitabine monotherapy for locally advanced rectal cancer: a propensity-score matched study.

BACKGROUND: Distant metastasis has been the main failure pattern for locoregionally advanced rectal cancer (LARC) patients, and intensified neoadjuvant chemotherapy has become a popular research topic. The present study aimed to compare the survival outcomes, acute toxicities and surgical complications in LARC patients who received preoperative chemoradiotherapy with triweekly oxaliplatin and capecitabine (triweekly XELOX) or capecitabine. METHODS: Between 2007 and 2017, patients with clinically staged II-III rectal cancer who were treated with preoperative chemoradiotherapy using either triweekly XELOX (oxaliplatin 130 mg/m2 plus capecitabine 825 mg/m2) or capecitabine were included. Variables potentially influencing chemotherapy treatment selection were used to generate propensity scores (PS). The association between chemotherapy regimens and survival endpoints, including distant metastasis-free survival (DMFS), overall survival (OS) and disease-free survival (DFS), were evaluated and adjusted with PS. The acute toxicities and surgical complications were also compared. RESULTS: A total of 810 patients were included in the analysis; 277 (34.2%) patients received triweekly XELOX, and 533 (65.8%) received capecitabine. The pathological complete response (pCR) rates were 20.2 and 19.9% (P = 0.912) for the groups treated with triweekly XELOX and capecitabine, respectively. The 5-year DMFS, OS and DFS with triweekly XELOX versus capecitabine were 75.6% vs. 77.6% (P = 0.555), 79.2% vs. 83.3% (P = 0.101), and 69.9% vs. 73.7% (P = 0.283), respectively. Triweekly XELOX was not associated with an increased risk of severe toxicity during chemoradiotherapy, but it increased the risk of postoperative complications compared to capecitabine. After PS adjustment, the differences between the two groups remained insignificant in pCR rate, survival outcomes, and acute toxicities, and the difference in surgical complications disappeared. CONCLUSIONS: Triweekly XELOX or capecitabine concurrent with neoadjuvant radiotherapy leads to similar long-term survival outcomes, acute toxicities and surgical complications in LARC patients.

Necessity of external iliac lymph nodes and inguinal nodes radiation in rectal cancer with anal canal involvement.

BACKGROUND AND PURPOSE: We aimed to explore the necessity of the external iliac lymph nodes (EIN) along with inguinal nodes (IN) region in clinical target volume (CTV) for rectal carcinomas covering the anal canal region. MATERIALS AND METHODS: This research premise enrolled 399 patients who had primary low rectal cancer detected below the peritoneal reflection via magnetic resonance imaging (MRI) and were treated with neoadjuvant radiotherapy (NRT), without elective EIN along with IN irradiation. We stratified the patients into two groups based on whether the lower edge of the rectal tumor extended to the anal canal (P group, n = 109) or not (Rb group, n = 290). Comparison of overall survival (OS), locoregional recurrence-free survival (LRFS), disease-free survival (DFS), as well as distant metastasis-free survival (DMFS) were performed via inverse probability of treatment weighting (IPTW) along with multivariable analyses. We compared the EIN and IN failure rates between the two groups via the Fisher and Gray's test. RESULTS: P group showed a similar adjusted proportion along with five-year cumulative rate of EIN failure compared with the Rb group. The adjusted proportion and five-year cumulative rate of IN failure in the P group was higher in comparison to the Rb group. There were no remarkable differences in the adjusted five-year OS, DFS, DMFS or LRFS between the two groups. Anal canal involvement (ACI) exhibited no effect on OS, LRFS, DFS, or DMFS. CONCLUSIONS: During NRT for rectal cancer with ACI, it may be possible to exclude the EIN and IN from the CTV.

Clinical utility of a new immobilization method in image-guided intensity-modulated radiotherapy for breast cancer patients after radical mastectomy.

OBJECTIVE: To investigate clinical utility of a new immobilization method in image-guided intensity-modulated radiotherapy (IMRT) for breast cancer patients after radical mastectomy. MATERIALS AND METHODS: Forty patients with breast cancer who underwent radical mastectomy and postoperative IMRT were prospectively enrolled. The patients were randomly and equally divided into two groups using both a carbon-fiber support board and a hollowed-out cervicothoracic thermoplastic mask (Group A) and using only the board (Group B). An iSCOUT image-guided system was used for acquiring and correcting pretreatment setup errors for each treatment fraction. Initial setup errors and residual errors were obtained by aligning iSCOUT images with digitally reconstructed radiograph (DRR) images generated from planning CT. Totally 600 initial and residual errors were compared and analyzed between two groups, and the planning target volume (PTV) margins before and after the image-guided correction were calculated. RESULTS: The initial setup errors of Group A and Group B were (3.14±3.07), (2.21±1.92), (2.45±1.92) mm and (3.14±2.97), (2.94±3.35), (2.80±2.47) mm in the left-right (LAT), superior-inferior (LONG), anterior-posterior (VERT) directions, respectively. The initial errors in Group A were smaller than those in Group B in the LONG direction (P < 0.05). No significant difference was found in the distribution of three initial error ranges (≤3 mm, 3-5 mm and > 5 mm) in each of the three translational directions for the two groups (P > 0.05). The residual errors of Group A and Group B were (1.74±1.03), (1.62±0.92), (1.66±0.91) mm and (1.70±0.97), (1.68±1.18), (1.58±0.98) mm in the three translational directions, respectively. No significant difference was found in the residual errors between two groups (P > 0.05). With the image-guided correction, PTV margins were reduced from 8.01, 5.44, 5.45 mm to 3.54, 2.99, 2.89 mm in three translational directions of Group A, respectively, and from 8.14, 10.89, 6.29 mm to 2.67, 3.64, 2.74 mm in those of Group B, respectively. CONCLUSION: The use of hollowed-out cervicothoracic thermoplastic masks combined with a carbon-fiber support board showed better inter-fraction immobilization than the single use of the board in reducing longitudinal setup errors for breast cancer patients after radical mastectomy during IMRT treatment course, which has potential to reduce setup errors and improve the pretreatment immobilization accuracy for breast cancer IMRT after radical mastectomy.

Prognostic Value of Pretreatment Serum CA199 in Patients with Locally Advanced Rectal Cancer Treated with CRT Followed by TME with Normal Pretreatment Carcinoembryonic Antigen Levels.

BACKGROUND: Elevated pretreatment carcinoembryonic antigen (CEA) levels are related to poor prognosis in patients with locally advanced rectal cancer (LARC) treated with neo-CRT followed by TME. In patients with normal pretreatment CEA levels, the prognostic significance of carbohydrate antigen 199 (CA199) is controversial. OBJECTIVES: The aim of this study was to explore the prognostic value of pretreatment serum CA199 in patients with LARC who had normal pretreatment CEA levels treated with neo-CRT followed by curative surgery. METHODS: A retrospective study of 456 patients with LARC treated with neo-CRT followed by TME between January 2006 and May 2017 was performed. We employed the maximal χ2 method to determine the CA199 threshold of 9.1 U/mL based on the difference in survival and divided patients into 2 groups. Group 1: patients with pretreatment s-CEA < 5 ng/mL and CA199 ≥ 9.1 U/mL. Group 2: patients with pretreatment s-CEA < 5 ng/mL and CA199 < 9.1 U/mL. Overall survival (OS) across CA199 was assessed using Cox proportional hazard regression models (PS:CEA ≥ 5 ng/mL was seen as elevated). RESULTS: Multivariate analyses demonstrated that the following factors were significantly related to OS in patients with LARC with normal pretreatment CEA levels: ypT (odds ratio [OR] 1.863, p = 0.030), ypN (OR 1.622, p = 0.026), and pretreatment CA199 levels (OR 1.886, p = 0.048). CONCLUSION: Pretreatment CA199 is an independent factor for OS in patients with LARC with normal pretreatment CEA levels, which may reach the clinic to guide individualized decision-making.

A study of the MR imaging manifestations with injection of sedative at the buttocks in pediatric patients.

BACKGROUND: During the MRI examination, pediatric patients sleep under the sedation so that the image artifacts caused by the patient motion could be minimized. However, the sedative injection at the buttocks might cause a difficulty in the diagnosis of the buttock diseases using the MRI manifestations. OBJECTIVE: This study aims to explore the imaging characteristics of MR for the pediatric patients with the sedative injected at the buttocks in order to correctly diagnose the diseases. METHODS: MR imaging data of 64 pediatric patients injected with the sedative at the buttocks were retrospectively collected, including 8 cases of buttock disease. The imaging manifestations were analyzed and compared. RESULTS: Out of 64 patients, 8 were diagnosed as the buttock diseases. MR imaging manifestations of the sedatives injected at the buttocks were the locally patchy and streaky long T1 and long T2 signals and were different from what were shown for the normal tissues and diseases. CONCLUSION: The sedative injected at the buttocks has the MRI manifestations different from the normal tissues and diseases. Correctly understanding the MRI manifestations for the pediatric patients with the injection of sedative at the buttocks would reduce the chances of the misdiagnosis on the diseases.

Ionizing radiation, but not ultraviolet radiation, induces mitotic catastrophe in mouse epidermal keratinocytes with aberrant cell cycle checkpoints.

Ultraviolet radiation (UVR) and ionizing radiation (IR) are common genotoxic stresses that damage human skin, although the specific damages to the genomic DNA are different. Here, we show that in the mouse glabrous skin, both UVR and IR induce DNA damage, cell cycle arrest, and condensed cell nuclei. However, only IR induces mitotic catastrophe (MC) in the epidermis. This is because UVR induces a complete blockage of pRB phosphorylation and cell cycle arrest in the G1 phase, whereas pRB phosphorylation remains positive in a significant portion of the epidermal keratinocytes following IR exposure. Furthermore, Cyclin B1 expression is significantly downregulated only by IR but not UVR. Finally, there are more MC cells in the epidermis of p53-/- mice after IR exposure as compared to wild-type mice. Our results suggest that although both IR and UVR are genotoxic, they show distinct impacts on the cell cycle machinery and thus damage the epidermal keratinocytes via different mechanisms.

Evaluation of dose calculations with inhomogeneity correction in intensity-modulated radiation therapy for esophagus cancer.

BACKGROUND: Differences often exist in the dose calculation accuracy caused by using different dose calculation algorithms in non-uniform tissues. OBJECTIVE: To evaluate the accuracy of dose calculation with inhomogeneity correction in intensity-modulated radiation therapy (IMRT) by comparing dose calculated in Monaco with measurements in lung-chest phantom for esophagus cancer treatments. METHODS: Finite size pencil beam (FSPB) and X-ray voxel Monte Carlo (XVMC) were used respectively for IMRT dose recalculations. Ten IMRT plans were recalculated and measured in the chest-lung phantom. The dose measurements using the Gafchromic ® (EBT3) dosimetry films were validated with open fields in the interfaces of materials with various physical densities. The accuracy of dose calculations was then evaluated by both point dose comparison and Gamma analysis against the film measurements. RESULTS: For regular open fields, the discrepancies of the point doses were less than 3.0% and 2.0% between measurement and calculations by FSPB and XVMC, respectively. For 6 MV IMRT plans, the average passing rates based on 3% /3 mm Gamma criteria were 82.8±1.0% and 96.4±0.7% for FSPB and XVMC, respectively. CONCLUSIONS: The XVMC algorithms more accurate in IMRT dose calculations with inhomogeneity correction for esophagus cancer.

S100A6 promotes cell proliferation in human nasopharyngeal carcinoma via the p38/MAPK signaling pathway.

An elevated level of S100A6 is associated with poor outcomes of many tumor types, but, how S100A6 contributes to nasopharyngeal carcinoma (NPC) progression remains unknown. Here, we investigated the expression and prognostic significance of S100A6 in NPC and explored the molecular mechanisms under-lying the role of S100A6 in NPC development. The results showed that S100A6 was markedly up-regulated in NPC tissues and cell lines compared to paired peritumoral normal tissues and a normal nasopharyngeal epithelial cell line, respectively. In tissues from 92 NPC patients, high S100A6 expression was associated with advanced N stage, locoregional failure and disease progression and was predictive of poor locoregional recurrence-free survival (LRRFS, P = 0.001) and progression-free survival (PFS, P = 0.001). Multivariate analysis showed that S100A6 is an independent prognostic factor for LRRFS and PFS. Silencing S100A6 using siRNA or shRNA significantly suppressed NPC cell proliferation, colony formation and p38/mitogen-activated protein kinase (MAPK) activity in vitro and inhibited tumor growth in a xenograft mouse model of NPC. In contrast, overexpressing S100A6 via plasmid transfection resulted in increased NPC cell proliferation and p38/MAPK activation. S100A6-induced proliferation was abolished by a p38 inhibitor. In summary, S100A6 may be a new prognostic marker of NPC and may promote NPC development via the activation of p38/MAPK signaling pathways. These findings suggest S100A6/p38/MAPK signaling as a potential therapeutic target for NPC. © 2016 Wiley Periodicals, Inc.

Preliminary study of clinical application on IMRT three-dimensional dose verification-based EPID system.

The three-dimensional dose (3D) distribution of intensity-modulated radiation therapy (IMRT) was verified based on electronic portal imaging devices (EPIDs), and the results were analyzed. Thirty IMRT plans of different lesions were selected for 3D EPID-based dose verification. The gamma passing rates of the 3D dose verification-based EPID system (Edose, Version 3.01, Raydose, Guangdong, China) and Delta4 measurements were then compared with treatment planning system (TPS) calculations using global gamma criteria of 5%/3 mm, 3%/3 mm, and 2%/2 mm. Furthermore, the dose-volume histograms (DVHs) for planning target volumes (PTVs) as well as organs at risk (OARs) were analyzed using Edose. For dose verification of the 30 treatment plans, the average gamma passing rates of Edose reconstructions under the gamma criteria of 5%/3 mm, 3%/3 mm, and 2%/2 mm were (98.58 ± 0.93)%, (95.67 ± 1.97)%, and (83.13 ± 4.53)%, respectively, whereas the Delta4 measurement results were (99.14% ± 1.16)%, (95.81% ± 2.88)%, and (84.74% ± 7.00)%, respectively. The dose differences between Edose reconstructions and TPS calculations were within 3% for D95% , D98% , and Dmean in each PTV, with the exception that the D98% of the PTV-clinical target volume (CTV) in esophageal carcinoma cases was (3.21 ± 2.33)%. However, the larger dose deviations in OARs (such as lens, parotid gland, optic nerve, and spinal cord) can be determined based on DVHs. The difference was particularly obvious for OARs with small volumes; for example, the maximum dose deviation for the lens reached (-6.12 ± 5.28)%. A comparison of the results obtained with Edose and Delta4 indicated that the Edose system could be applied for 3D pretreatment dose verification of IMRT. This system could also be utilized to evaluate the gamma passing rate of each treatment plan. Furthermore, the detailed dose distributions of PTVs and OARs could be indicated based on DVHs, providing additional reliable data for quality assurance in a clinic setting.

Structural Phase Transition Effect on Resistive Switching Behavior of MoS2 -Polyvinylpyrrolidone Nanocomposites Films for Flexible Memory Devices.

The 2H phase and 1T phase coexisting in the same molybdenum disulfide (MoS2 ) nanosheets can influence the electronic properties of the materials. The 1T phase of MoS2 is introduced into the 2H-MoS2 nanosheets by two-step hydrothermal synthetic methods. Two types of nonvolatile memory effects, namely write-once read-many times memory and rewritable memory effect, are observed in the flexible memory devices with the configuration of Al/1T@2H-MoS2 -polyvinylpyrrolidone (PVP)/indium tin oxide (ITO)/polyethylene terephthalate (PET) and Al/2H-MoS2 -PVP/ITO/PET, respectively. It is observed that structural phase transition in MoS2 nanosheets plays an important role on the resistive switching behaviors of the MoS2 -based device. It is hoped that our results can offer a general route for the preparation of various promising nanocomposites based on 2D nanosheets of layered transition metal dichalcogenides for fabricating the high performance and flexible nonvolatile memory devices through regulating the phase structure in the 2D nanosheets.

A Population-Based Tumor-Volume Model for Head-and-Neck Cancer During Radiotherapy with a Dynamic Oxygenated Compartment.

PURPOSE: With the coming era of digital wisdom medical technology, mathematical modelling of tumor becomes a key step to optimize and realize precision radiotherapy. The purpose of this study is to develop a mathematical model for simulating the change of head-and-neck tumor (HN) volume during radiotherapy. METHODS AND MATERIALS: A formula is developed to describe the dynamic change of oxygenated compartment within a tumor, which is combined with the LPL model to describe various cell processes during radiotherapy, including potentially lethal lesion repair and misrepair, cell proliferation/loss, and tumor reoxygenation. Parameter sensitivity analysis is performed to evaluate the impacts of the lesion-related and repair-related biological factors on radiotherapy outcome. RESULTS: We tested our model on 14 available HN cancer patients and compared the performance with three other models. The mean error of our model for the twelve good fit cases is 12.2%, which is considerable smaller than that of the LQ model (19.7%), GLQ model (19.1%) and FLCP model (16.6%). Correlation analysis results reveal that for small tumors, there is a positive correlation (correlation coefficient r=0.9416) between hypoxic fraction and tumor volume, whereas the correlation becomes negative and not significant (r=-0.4365) for large tumors. It is demonstrated from sensitivity analysis that the production rate of lethal lesions (ηl) has a far greater impact on tumor volume than other parameters. The hypoxic fraction has insignificant impact on tumor volume, but it has notable influence on the volume of surviving cells. The final volume of surviving cells athf=0.5 is almost 8 ×102 times that of hf=0.01. The potentially lethal lesion-related parameters (ηpl,εpl, ε2pl) have rather small impacts (<1%) on both tumor volume and the volume of surviving cells, which indicates that the repaired and misrepaired sublethal cells only take up a small portion of the total cancer cell population. CONCLUSIONS: A population-based tumor-volume model for HN cancer during radiotherapy with a dynamic oxygenated compartment was developed in this study. Comprehensively considering the damage process of tumor cells caused by radiation therapy, the accurate prediction of the volume change of head-and-neck tumors during treatment has been revealed. Meanwhile, various cell activities and their principles in the process of anti-tumor treatment were reflected, and it has positive clinical reference significance for radiobiology.

Excluding external iliac node irradiation during neoadjuvant radiotherapy decreases lower intestinal toxicity without compromising efficacy in T4b rectal cancer patients with tumours involving the anterior structures.

PURPOSE: To explore the impact of excluding the external iliac node (EIN) from the clinical target volume (CTV) during preoperative radiotherapy in T4b rectal cancer with anterior structure invasion. METHODS: We retrospectively identified 132 patients with T4b rectal cancer involving the anterior structures who received radiotherapy followed by surgery between May 2010 and June 2019. Twenty-nine patients received EIN irradiation (EIN group), and 103 did not (NEIN group). Failure patterns, survival and toxicities were compared between the two groups. RESULTS: The most common failure was distant metastasis (23.5%). 11 (8.3%) patients developed locoregional recurrence, 10 (9.7%) patients were in the NEIN group, and 1 (3.4%) was in the EIN group (P = 0.34). The EIN region failure was rare (1/132, 0.8%). The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 96.3% vs. 90.5%, 82.1% vs.73.7%, 75.9% vs. 78.0% and 72.4% vs. 68.3% (all P > 0.05) for the EIN group and NEIN group, respectively. The incidence of grade 3-4 acute toxicity in the lower intestine was significantly higher in the EIN group than in the NEIN group (13.8% vs. 1.9%, P = 0.02). The Dmax, V35 and V45 of the small bowel was decreased in the NEIN group compared to the EIN group. CONCLUSIONS: Exclusion of the EIN from the CTV in T4b rectal cancer with anterior structure invasion could reduce lower intestinal toxicity without compromising oncological outcomes. These results need further evaluation in future studies.