Analysis of the Parotid Glands on an Energy Spectrum CT Iodine Map to Evaluate Irradiation-Induced Acute Xerostomia in Patients With Nasopharyngeal Carcinoma.

Objective: This prospective study aims to evaluate acute irradiation-induced xerostomia during radiotherapy by utilizing the normalized iodine concentration (NIC) derived from energy spectrum computed tomography (CT) iodine maps. Methods: In this prospective study, we evaluated 28 patients diagnosed with nasopharyngeal carcinoma. At 4 distinct stages of radiotherapy (0, 10, 20, and 30 fractions), each patient underwent CT scans to generate iodine maps. The NIC of both the left and right parotid glands was obtained, with the NIC at the 0-fraction stage serving as the baseline measurement. After statistically comparing the NIC obtained in the arterial phase, early venous phase, late venous phase, and delayed phase, we chose the late venous iodine concentration as the NIC and proceeded to analyze the variations in NIC at each radiotherapy interval. Using the series of NIC values, we conducted hypothesis tests to evaluate the extent of change in NIC within the parotid gland across different stages. Furthermore, we identified the specific time point at which the NIC decay exhibited the most statistically significant results. In addition, we evaluated the xerostomia grades of the patients at these 4 stages, following the radiation therapy oncology group (RTOG) xerostomia evaluation standard, to draw comparisons with the changes observed in NIC. Results: The NIC in the late venous phase exhibited the highest level of statistical significance (P < .001). There was a noticeable attenuation in NIC as the RTOG dry mouth grade increased. Particularly, at the 20 fraction, the NIC experienced the most substantial attenuation (P < .001), a significant negative correlation was observed between the NIC of the left, right, and both parotid glands, and the RTOG evaluation grade of acute irradiation-induced xerostomia (P < .001, r = -0.46; P < .001, r = -0.45; P < .001, r = -0.47). The critical NIC values for the left, right, and both parotid glands when acute xerostomia occurred were 0.175, 0.185, and 0.345 mg/ml, respectively, with AUC = 0.73, AUC = 0.75, and AUC = 0.75. Conclusion: The NIC may be used to evaluate changes in parotid gland function during radiotherapy and acute irradiation-induced xerostomia.

Intracellular Criegee's mechanism-based synergistic ozone therapy mediated by oleogels for cancer treatment.

Broad cellular components-initiated efficient chemical reactions that occur in malignant cells may contribute to exploring emerging strategies for cancer treatment. Herein, an ozonated oleogel (OG(O)) was developed to achieve cancer ozone therapy (O3-T) based on intracellular Criegee's reaction. By integrating the chemo-drug, the ozone-loaded oleogel (Dox@OG(O)) was prepared as a chemotherapeutic agent for local O3-T, associated with chemotherapy (CT)/radiotherapy (RT)/immunotherapy and wound healing. The in vitro results showed that, Dox@OG(O) could achieve high ozone loading efficiency and ensure its stability. This Oleogel-mediated O3-T could directly destroy tumor cells via intracellular Criegee's reaction occurred on cell membranes, as well as the effects of tumor microenvironment (TME) regulation by the generation of oxygen/reactive oxygen species (ROS) and depletion of glutathione (GSH). Meanwhile, under the stimulation of X-ray, an accelerated free radical's production was observed, further combined with the radio-sensitivity after TME regulation, an effective anti-tumor effect would be achieved. Further on, in vivo results demonstrated that the locally implanted Dox@OG(O) could effectively inhibit the growth of both primary and secondary tumors. Considering these results above, it will serve as inspiration for future studies investigating of O3-T, especially for postoperative skin diseases.

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.

Impact of chrono-radiotherapy on the prognosis and treatment-related toxicity in patients with locally advanced nasopharyngeal carcinoma: A multicenter propensity-matched study.

The timing of radiotherapy (RT) delivery has been reported to affect both cancer survival and treatment toxicity. However, the association among the timing of RT delivery, survival, and toxicity in locally advanced nasopharyngeal carcinoma (LA-NPC) has not been investigated. We retrospectively reviewed patients diagnosed with LA-NPC who received definitive RT at multiple institutions. The median RT delivery daytime was categorized as morning (DAY) and night (NIGHT). Seasonal variations were classified into the darker half of the year (WINTER) and brighter half (SUMMER) according to the sunshine duration. Cohorts were balanced according to baseline characteristics using propensity score matching (PSM). Survival and toxicity outcomes were evaluated using Cox regression models. A total of 355 patients were included, with 194/161 in DAY/NIGHT and 187/168 in WINTER/SUMMER groups. RT delivered during the daytime prolonged the 5-year overall survival (OS) (90.6% vs. 80.0%, p = 0.009). However, the significance of the trend was lost after PSM (p = 0.068). After PSM analysis, the DAY cohort derived a greater benefit in 5-year progression-free survival (PFS) (85.6% vs. 73.4%, p = 0.021) and distant metastasis-free survival (DMFS) (89.2% vs. 80.8%, p = 0.051) in comparison with the NIGHT subgroup. Moreover, multivariate analysis showed that daytime RT was an independent prognostic factor for OS, PFS, and DMFS. Furthermore, daytime RT delivery was associated with an increase in the incidence of leukopenia and radiation dermatitis. RT delivery in SUMMER influenced only the OS significantly (before PSM: p = 0.051; after PSM: p = 0.034). There was no association between toxicity and the timing of RT delivery by season. In LA-NPC, the daytime of radical RT served as an independent prognostic factor. Furthermore, RT administered in the morning resulted in more severe toxic side effects than that at night, which needs to be confirmed in a future study.

Automatic detection of thyroid nodules with a real-time artificial intelligence system in a real clinical scenario and the associated influencing factors.

BACKGROUND: At present, most articles mainly focused on the diagnosis of thyroid nodules by using artificial intelligence (AI), and there was little research on the detection performance of AI in thyroid nodules. OBJECTIVE: To explore the value of a real-time AI based on computer-aided diagnosis system in the detection of thyroid nodules and to analyze the factors influencing the detection accuracy. METHODS: From June 1, 2022 to December 31, 2023, 224 consecutive patients with 587 thyroid nodules were prospective collected. Based on the detection results determined by two experienced radiologists (both with more than 15 years experience in thyroid diagnosis), the detection ability of thyroid nodules of radiologists with different experience levels (junior radiologist with 1 year experience and senior radiologist with 5 years experience in thyroid diagnosis) and real-time AI were compared. According to the logistic regression analysis, the factors influencing the real-time AI detection of thyroid nodules were analyzed. RESULTS: The detection rate of thyroid nodules by real-time AI was significantly higher than that of junior radiologist (P = 0.013), but lower than that of senior radiologist (P = 0.001). Multivariate logistic regression analysis showed that nodules size, superior pole, outside (near carotid artery), close to vessel, echogenicity (isoechoic, hyperechoic, mixed-echoic), morphology (not very regular, irregular), margin (unclear), ACR TI-RADS category 4 and 5 were significant independent influencing factors (all P < 0.05). With the combination of real-time AI and radiologists, junior and senior radiologist increased the detection rate to 97.4% (P < 0.001) and 99.1% (P = 0.015) respectively. CONCLUSONS: The real-time AI has good performance in thyroid nodule detection and can be a good auxiliary tool in the clinical work of radiologists.

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.

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.

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.

Ultrasound findings of hepatic epithelioid hemangioendothelioma: comparison with other malignant hepatic tumors.

PURPOSE: To investigate and compare the ultrasonic features of hepatic epithelioid hemangioendothelioma (HEHE) and other common hepatic malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepatic metastatic tumor (HMT). METHODS: A total of 37 patients with pathologically proven HEHE, 37 HCC cases, 37 ICC cases, and 37 HMT cases were enrolled from single hospital. The clinical characteristics and ultrasonic features of all cases were summarized and statistically analyzed. RESULTS: There were significant differences in sex and age between the HEHE group and other three groups (P < 0.001). The probability of HEHE infection with hepatitis B virus was lower than that of HCC and ICC groups (P < 0.05). The probability of elevated serum tumor markers in HEHE was significantly lower than that in the other three groups (P < 0.05). On conventional ultrasound (CUS), the probability of multiple lesions in HEHE was significantly higher than that in the other three groups (P < 0.05). On contrast-enhanced ultrasound (CEUS), the time to wash out in HEHE was significantly shorter than that of the other three groups (P < 0.001). The proportion of synchronous or slow enhancement in HEHE was significantly higher than that of the other three groups (P < 0.001). The proportion of HEHE with iso- or hypo-enhancement was significantly higher than in HCC and HMT groups (P < 0.05). CONCLUSION: HEHE mainly performed multiple hypoechoic lesions on CUS and displayed greater odds of synchronous enhancement in arterial phase, iso- or hypo-enhancement in peak time and wash out more quickly on CEUS, which allowed for differentiation from other common malignant tumors.

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.

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.

N6-methyladenosine Methyltransferase METTL3 Enhances PTGER2 Expression to Increase Ovarian Cancer Stemness and Chemoresistance.

BACKGROUND: Ovarian cancer is the second leading cause of gynecologic cancer-associated deaths. Cancer stemness and chemoresistance are responsible for ovarian cancer metastasis and the poor prognosis of patients. In this study, we determined the function of N6-methyladenine (m6A) RNA methylation and prostaglandin E receptor 2 (PTGER2) in ovarian cancer progression. METHODS: The m6A RNA methylation-associated PTGER2 in ovarian cancer was identified using bioinformatics analysis. The role of PTGER2 in ovarian cancer was elucidated in cell lines and clinical samples with cellular and molecular experiments. RESULTS: In this investigation, bioinformatics analysis based on a public cancer database was used to elucidate the impact of m6A modification on the prognosis of patients with ovarian cancer. Moreover, PTGER2 was identified as a potential oncogene associated with the distant metastasis of ovarian cancer and poor patient prognosis. Interestingly, PTGER2 expression was experimentally shown to be enhanced by N6-adenosine-methyltransferase 70 kDa subunit (METTL3)-mediated m6A modification. In addition, PTGER2 enhanced cancer stem cell self-renewal properties, the epithelial-mesenchymal transition, and DNA damage repair, thus potentiating cell stemness, therapy resistance to carboplatin, proliferation, and metastasis of ovarian cancer. Importantly, PTGER2 expression in clinical samples was associated with distant metastasis, predicted poor patient prognosis, and independently served as a prognostic predictor in ovarian cancer. CONCLUSIONS: Our work defines PTGER2 as an oncogene and reveals that PTGER2 is a prognostic predictor and novel therapeutic target for the management of ovarian cancer.

Particle radiotherapy in the era of radioimmunotherapy.

Radiotherapy (RT) is one of the key modalities for cancer treatment, and more than 70% of tumor patients will receive RT during the course of their disease. Particle radiotherapy, such as proton radiotherapy, carbon-ion radiotherapy (CIRT) and boron neutron capture therapy (BNCT), is currently available for the treatment of patients Immunotherapy combined with photon RT has been successfully used in the clinic. The effect of immunotherapy combined with particle RT is an area of interest. However, the molecular mechanisms underlying the effects of combined immunotherapy and particle RT remain largely unknown. In this review, we summarize the properties of different types of particle RT and the mechanisms underlying their radiobiological effects. Additionally, we compared the main molecular players in photon RT and particle RT and the mechanisms involved the RT-mediated immune response.

Activating and optimizing the In-Plane interface of 1 T/2H MoS2 for efficient hydrogen evolution reaction.

Implanting the octahedral phase (1 T) into the hexagonal phase (2H) of the molybdenum disulfide (MoS2) matrix is considered one of the effective methods to enhance hydrogen evolution reaction (HER) performances of MoS2. In this paper, hybrid 1 T/2H MoS2 nanosheets array was successfully grown on conductive carbon cloth (1 T/2H MoS2/CC) via facile hydrothermal method and the 1 T phase content in 1 T/2H MoS2 is regulated to gradually increase from 0 % to 80 %. 1 T/2H MoS2/CC with 75 % 1 T phase content exhibits optimal HER performances. The DFT calculation results show that S atoms in 1 T/2H MoS2 interface exhibit the lowest hydrogen adsorption Gibbs free energies (ΔGH*) compared with other sites. The improvement of HER performances are primarily attributed to activating the in-plane interface regions of the hybrid 1 T/2H MoS2 nanosheets. Furthermore, the relationship between 1 T MoS2 content in 1 T/2H MoS2 and catalytic activity was simulated by a mathematical model, which shows that the catalytic activity presents a trend of increasing and then decreasing with the increase of 1 T phase content.

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.

Combining chemotherapy and tislelizumab with preoperative split-course hypofraction radiotherapy for locally advanced rectal cancer: study protocol of a prospective, single-arm, phase II trial.

INTRODUCTION: Short-course radiotherapy (SCRT) with systemic therapy has the potential to further improve the long-term efficacy in patients with locally advanced rectal cancer (LARC). To maximise the benefits of neoadjuvant therapy for improved prognosis, it is important to determine the optimal mix of chemotherapy, immunotherapy and SCRT. METHODS AND ANALYSIS: Fifty treatment-naïve patients with operable LARC (T3-4 and/or N+) will be recruited. Patients will be synchronously treated with capecitabine plus oxaliplatin (CAPOX) chemotherapy, tislelizumab and preoperative split-course hypofraction radiotherapy (SCHR) (5×7 Gy) before surgery. Chemotherapy for CAPOX starts on day 1 of every 21-day cycle: on day 1, oxaliplatin 130 mg/m2 will be injected intravenously. On days 1-14, capecitabine 1000 mg/m2 was ingested two times a day. Simultaneously, tocilizumab 200 mg will be given intravenously on the first day of every 21-day cycle. A single 7 Gy SCHR treatment (day 7 of each 21-day cycle) will be delivered five times during the seventh day of treatment. The primary endpoint will be pathological complete response. The secondary outcomes will be the 3-year disease-free survival, local recurrence rate, overall survival, sphincter-sparing surgery rate, R0 resection rate, predictive biomarkers and quality of life. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (XAHFMU) (No. 2021YF025-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT05176964.

Stereotactic Body Radiotherapy Boost with the CyberKnife for Locally Advanced Cervical Cancer: Dosimetric Analysis and Potential Clinical Benefits.

(1) Aim: To compare the treatment plans of stereotactic body radiotherapy (SBRT) with CyberKnife (CK) and high-dose-rate (HDR) intracavitary/interstitial brachytherapy (IC/ISBT) and examine the feasibility of CK-SBRT as a viable alternative to BT in patients with locally advanced cervical cancer (LACC). (2) Methods: A BT plan of 28 Gy in four fractions delivered previously to 20 patients with LACC was compared with a CK plan based on the same CT images with structures delineation for BT. The SBRT treatment plan was further divided according to two different approaches, with the high-risk planning target volume (HR-PTV) defined by the high-risk clinical target volume (HR-CTV) without and with a 5 mm margin, which were named CK-CTV plan and CK-PTV plan, respectively. The dose distributions and dosimetric parameters of the target volumes and organs at risk (OARs) were recorded and compared for the three boost plans. Radiobiological metrics were calculated based on the EUD for the hybrid plans. Additionally, the relationship between tumor volume and tolerance doses for the OARs in the BT plan and CK-PTV plan was investigated. (3) Results: Target coverage was better with the CK plan than with the BT plan, as the D95%, D98%, HI and CI of the CK-CTV plan and CK-PTV plan were higher than those of the BT plan; an exception was the D50%. Similarly, the TCP of the target was also significantly in favor of the CK hybrid plans (p < 0.01). For the OARs, the CK-CTV plan was superior to the BT plan as regards the rectum D2cc, bladder D2cc and bladder Dmax. The CK-PTV plan could achieve dosimetric parameters comparable to those of the BT plan for OARs concerning the small residual tumor volume. The NTCP of the rectum for the WPI+CK-CTV plans was significantly lower than that of the WPI+BT plans (p < 0.01). (4) Conclusions: CK-based SBRT can achieve better target coverage, dose sparing for the OARs and radiobiological effects compared with the BT plan for tumors that are not excessively large. CK-based SBRT could be an alternative option to administer a radiation boost for patients with LACC.

Prognostic value of mesorectal package area in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy: A retrospective cohort study.

Background: The aim of this study is to explore the most effective inflammation, magnetic resonance imaging (MRI), and nutrition markers for survival and pathology complete response (pCR) in patients with locally advanced rectal cancer (LARC). Methods: A total of 278 patients with LARC undergoing neoadjuvant chemoradiotherapy (NCRT) and radical surgery from 2016 to 2019 were included. The X-tile method was used to select the optimal cutoff points for the mesorectal package area (MPA), advanced lung cancer inflammation index (ALI), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) scores. Cox regression analysis was used to identify risk factors of disease-free survival (DFS). To discover pCR risk factors, logistic regression analysis was employed. A predictive nomogram for DFS was constructed. Results: According to the least absolute shrinkage and selection operator analysis, the MPA was the only significant predictor for the DFS in patients with LARC. Kaplan-Meier (K-M) analysis demonstrated that groups with higher MPA, PNI, SII, NLR, MLR, and ALI score had improved DFS (all P < 0.05). Receiver operating characteristic (ROC) analysis revealed that the MPA and PNI could accurately predict the pCR in patients with LARC after NCRT. The MPA score and NLR score were found to be independent predictors of DFS after NCRT using Cox regression analysis. Logistical regression analysis demonstrated that the MPA score, PNI score, and pre-NCRT cN stage were all independent predictors of pCR in patients with LARC after NCRT. Recursive partitioning analysis and time-independent ROC curve analysis demonstrated that MPA score was the most important predictor of pCR and prognosis in patients with LARC after NCRT. Conclusions: MPA was identified as the most effective marker for MRI, and the prognostic value was further confirmed by time-ROC analysis. More intense adjuvant treatment could be considered for lower-MPA score patients with LARC after NCRT. Obesity in the pelvis encourages the understanding of the prognosis prediction of patients with LARC after NCRT.

Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial.

INTRODUCTION: Radiation-induced lung injury (RILI) is one of the most clinically-challenging toxicities and dose-limiting factors during and/or after thoracic radiation therapy for oesophageal squamous cell carcinoma (ESCC). With limited effective protective drugs against RILI, the main strategy to reduce the injury is strict adherence to dose-volume restrictions of normal lungs. RILI can manifest as acute radiation pneumonitis with cellular injury, cytokine release and cytokine recruitment to inflammatory infiltrate, and subsequent chronic radiation pulmonary fibrosis. Pirfenidone inhibits the production of inflammatory cytokines, scavenges-free radicals and reduces hydroxyproline and collagen formation. Hence, pirfenidone might be a promising drug for RILI prevention. This study aims to evaluate the efficacy and safety of pirfenidone in preventing RILI in patients with locally advanced ESCC receiving chemoradiotherapy. METHODS AND ANALYSIS: This study is designed as a randomised, placebo-controlled, double-blinded, single-centre phase 2 trial and will explore whether the addition of pirfenidone during concurrent chemoradiation therapy (CCRT) could prevent RILI in patients with locally advanced ESCC unsuitable for surgery. Eligible participants will be randomised at 1:1 to pirfenidone and placebo groups. The primary endpoint is the incidence of grade >2 RILI. Secondary endpoints include the incidence of any grade other than grade >2 RILI, time to RILI occurrence, changes in pulmonary function after CCRT, completion rate of CCRT, disease-free survival and overall survival. The follow-up period will be 1 year. In case the results meet the primary endpoint of this trial, a phase 3 multicentre trial with a larger sample size will be required to substantiate the evidence of the benefit of pirfenidone in RILI prevention. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Fujian Union Hospital (No. 2021YF001-02). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2100043032.