RATIONALE AND OBJECTIVES:Post-SABR radiologic appearances in the lung are dynamic and may imitate local failure. Although radiologic changes after SABR have been described, the dynamic evolution and predictors of pseudoprogression remain unclear. We aimed to characterize serial computed tomography (CT) evolution after SABR and examine its association with pseudoprogression. MATERIALS AND METHODS:We retrospectively included patients who underwent SABR and had ≥24 months radiologic follow-up without definite local recurrence. The maximum diameter of the evolving post-SABR lesion was referenced to the initial (pre-SABR) tumor. Pseudoprogression was defined as any >20% increase in maximum diameter during follow-up that was followed by radiographic stabilization and lacked pathologic or clinical evidence of recurrence. RESULTS:We evaluated 109 lesions from 104 patients (median follow-up, 53 months). Mass-like consolidation developed in 94/109 (86%) lesions. CT evolution followed three phases with typical onset: initiation-reticular infiltrates adjacent to the index tumor (median 3 months; range 1-9); development-increasing density with patchy/streaky opacities and/or fibrotic consolidation (median 4.5 months; range 1.5-15.5); and mass-like consolidation-organization/absorption or retraction culminating in a final mass-like consolidation (median 13 months; range 5.5-39). A total of 74 (68%) lesions showed a >20% increase vs the initial tumor, and 50% occurred during the third phase. Planning target volume (PTV) was an independent predictor of pseudoprogression (adjusted odds ratio 0.98, 95% CI 0.97-0.99; P = 0.002). CONCLUSION:Dynamic CT evolution after SABR commonly manifests as mass-like consolidation with high rates of pseudoprogression. PTV independently predicts this phenomenon, underscoring the need for cautious interpretation of radiographic enlargement during follow-up.

Structural and functional abnormalities of tumor vasculature are key factors limiting drug delivery and therapeutic efficacy. This review aims to systematically summarize the mechanisms and evidence regarding how aerobic exercise improves drug delivery and enhances tumor treatment response by remodeling tumor vascular function. By synthesizing recent studies, we summarize the effects of different aerobic exercise modalities (intensity, duration, frequency) on tumor vasculature and the synergistic effects of combining exercise with pharmacotherapy. Aerobic exercise can increase pericyte coverage and enhance vascular stability, reduce vascular permeability and tumor interstitial fluid pressure (IFP) to improve drug penetration, enhance tumor blood flow perfusion and oxygenation to alleviate the hypoxic microenvironment, and modulate tumor metabolism and acid-base balance. These effects collectively promote the distribution and accumulation of drugs within tumor tissue, thereby enhancing treatment efficacy. The effects of exercise are influenced by its intensity, duration, frequency, and tumor type, with moderate-intensity, regular regimens (e.g., 3–5 times per week) being the most substantiated. Aerobic exercise serves as an effective non-pharmacological adjuvant that can significantly improve drug delivery and enhance anti-tumor treatment outcomes through multi-dimensional remodeling of tumor vascular function and the tumor microenvironment. Future prospective clinical studies, incorporating imaging and molecular biomarkers, are needed to further define optimal exercise protocols and their role in individualized integrated cancer therapy.

Introduction Radiation-induced temporal lobe injury (RI-TLI) is one of the most common late-stage complications after radiotherapy for nasopharyngeal carcinoma (NPC), which seriously affects patients’ cognitive function and quality of life. However, the mechanism by which RI-TLI affects the gray matter (GM) and white matter (WM) across the whole brain, leading to cognitive impairment, is currently unclear in NPC patients. Methods One year after the end of radiotherapy, 32 NPC patients with RI-TLI (RI-TLI group) and 38 NPC patients without RI-TLI (nRI-TLI group) were included in this study. The Montreal Cognitive Assessment (MoCA) was applied to evaluate the differences of cognitive function between RI-TLI and nRI-TLI groups. In addition, T1 structural magnetic resonance imaging data were acquired, and then the whole-brain voxel-based morphometry was employed to compare the differences of GM and WM between groups. The relationships between GM and WM of abnormal brain regions and MoCA scores were explored. Finally, receiver operating characteristic (ROC) curve was performed to determine the suitability of altered brain structure for distinguishing RI-TLI from nRI-TLI. Results Compared with nRI-TLI group, RI-TLI group exhibited decreased attention, delayed recall scores and total scores of MoCA. In addition, RI-TLI group exhibited decreased GM volume in the right middle temporal gyrus, left hippocampus, right superior temporal gyrus, right superior frontal gyrus and decreased GM density in the left superior frontal gyrus, right superior frontal gyrus, right supplementary motor area. Moreover, RI-TLI group demonstrated decreased WM volume in the right inferior temporal gyrus, left hippocampus, right superior temporal gyrus, right medial superior frontal gyrus and decreased WM density in the left superior frontal gyrus, right superior frontal gyrus. The attention scores of MoCA were positively associated with GM volume of the right superior temporal gyrus, right superior frontal gyrus, GM density of the left superior frontal gyrus, right superior frontal gyrus, WM density of the left superior frontal gyrus. The delayed recall scores of MoCA were positively related to GM volume of the left hippocampus, WM density of the left superior frontal gyrus. The total scores of MoCA were positively associated with GM volume of the left hippocampus, WM volume of the left hippocampus, right superior temporal gyrus, WM density of the left superior frontal gyrus. ROC analysis demonstrated that altered GM and WM might be helpful for distinguishing RI-TLI from nRI-TLI. Conclusion: Compared to nRI-TLI patients, RI-TLI patients exhibit more severe cognitive impairment alongside decreased GM and WM in both the temporal lobe and prefrontal regions. The observed structural alterations are associated with the severity of cognitive deficits and may serve as potential neuroimaging markers for RI-TLI.

The applicability of the ninth version AJCC/UICC N classification for nasopharyngeal carcinoma (NPC) in non-endemic regions remains uncertain, particularly regarding the incorporation of advanced extranodal extension (ENE) into the N3 category. We conducted a retrospective multicenter study including 1356 patients with NPC treated between 2011 and 2021 in eastern China. All patients were staged according to both the eighth and ninth version systems. Survival outcomes, including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and regional recurrence-free survival (RRFS), were analyzed using Kaplan–Meier and Cox regression methods. Model performance was evaluated using the concordance index (C-index) and Akaike information criterion (AIC). Under the ninth version, 136 patients with advanced ENE were upstaged from N1–N2 to N3, resulting in clearer separation between N3 and N0–N2 groups across all endpoints. No statistically significant differences in survival outcomes were observed between patients upstaged to N3 and those with conventional N3 disease. The ninth version showed statistically significant but small increases in C-index compared with the eighth version. However, time-dependent AUC differences varied across survival endpoints and follow-up time points. Within the N3 subgroup, advanced ENE was associated with significantly worse OS, PFS, and DMFS, and remained an independent predictor of OS (HR 1.78, p = 0.032) and DMFS (HR 2.05, p = 0.009). In conclusion, the ninth version N classification showed modest incremental prognostic performance in this non-endemic cohort, driven primarily by the identification of high-risk N3 disease. These findings support the staging relevance of advanced ENE, although prospective validation incorporating additional clinical and biological predictors remains necessary.

INTRODUCTION:Chemotherapy-induced neurologic dysfunction was experienced by colorectal cancer (CRC) survivors. However, the exact mechanism remains unclear. METHODS:We recruited CRC survivors who had undergone 2-3 month-long FOLFOX and FOLFIRI chemotherapy. Cognition was assessed at enrollment and after chemotherapy. FMRIdata were acquired and preprocessed. ReHowas calculated and compared to examine the differences of brain activities. ROCcurve was performed to evaluate the capacity of ReHo values in distinguishing patients after FOLFOX, FOLFIRI and HCs. Relationships between ReHo values, chemotherapy cycles and cognitive scores were evaluated. The mediating effects of ReHo values on the relationships between chemotherapy cycles and cognitive function were also evaluated. RESULTS:CRC patients exhibited decreased ReHo values in the left superior frontal gyrus (dorsolateral), inferior frontal gyrus (opercular part), right superior frontal gyrus (medial), inferior frontal gyrus (opercular part), middle temporal gyrus and increased ReHo values in the right rolandic operculum after FOLFIRI chemotherapy when compared with the group of FOLFOX. ROC analysis revealed that ReHo values might be helpful for distinguishing CRC patients after FOLFOX, FOLFIRI chemotherapy and HCs. Relationships were identified between cognitive scores, chemotherapy cycles and ReHo values of the prefrontal regions in CRC patients after chemotherapy. ReHo values of the left inferior frontal gyrus (opercular part) partially mediated the correlations between chemotherapy cycles and cognitive scores. CONCLUSION:The prefrontal cortex might be the preferred brain regions attacked by the central neurotoxicity of both FOLFOX and FOLFIRI, and the latter had wider implications on the regional brain activity.

This multicenter Phase II clinical study assessed the efficacy and safety of hypofractionated radiotherapy (HFRT) in combination with a PD-1 inhibitor, granulocyte macrophage-colony stimulating factor (GM-CSF), and thymosin-α1 in patients with heavily treated metastatic solid tumors. Patients were enrolled between September 2022 and May 2024. HFRT was administered to targeted tumors, and GM-CSF was administered for 14 days from day 1 of radiotherapy. Thymosin-α1 was injected concurrently twice weekly until disease progression. Immunotherapy with camrelizumab was started following HFRT and repeated every 3 weeks. GM-CSF was administered daily for 7 days before each cycle of immunotherapy. By June 15, 2024, there were 37 study participants. The median follow-up duration was 5.97 months (range 0.40–20.9). Median progression-free survival was 3.5 months (95

IntroductionNasopharyngeal carcinoma (NPC) is a common malignant tumor primarily treated by radiotherapy with or without chemotherapy. Chemoradiotherapy frequently contributes to cognitive impairments, which are associated with abnormal brain activity. This study aimed to longitudinally explore the stage-specific changes of regional spontaneous brain activity in NPC patients during different phases of chemoradiation treatment.MethodsTwenty patients diagnosed with stage III-IV NPC were enrolled in this study from January 2022 to December 2023. All patients received two cycles of chemotherapy (1st follow-up) followed by one cycle of chemotherapy plus radiotherapy (2nd follow-up). Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from all patients at baseline, 1st follow-up and 2nd follow-up. Based on rs-fMRI data after preprocessing, the metrics of regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) values were calculated and compared to measure the changes of regional spontaneous activity in the brain.ResultsThe NPC patient group showed increased ReHo values in the right middle cingulate gyrus at the 1st follow-up when compared with baseline. In addition, the NPC patient group exhibited increased ReHo values in the left calcarine fissure at the 2nd follow-up when compared with the 1st follow-up. The NPC patient group demonstrated decreased fALFF values in the right inferior temporal gyrus at the 2nd follow-up when compared with baseline.ConclusionThis longitudinal study revealed distinct stage-specific brain activity changes during chemoradiotherapy in NPC patients. Chemotherapy induced transient compensatory increases in ReHo in the middle cingulate gyrus, while subsequent radiotherapy led to increased activity in the calcarine fissure. Combined treatment resulted in decreased spontaneous activity in the inferior temporal gyrus, a key component of the default mode network. These temporal dynamics suggest evolving compensatory mechanisms followed by eventual functional alterations, providing neurobiological insights into the progressive nature of treatment-related cognitive impairments and potential biomarkers for monitoring brain changes during cancer treatment.

The emergence of pathology foundation models has revolutionized computational histopathology, enabling highly accurate, generalized whole-slide image analysis for improved cancer diagnosis, and prognosis assessment. While these models show remarkable potential across cancer diagnostics and prognostics, their clinical translation faces critical challenges including variability in optimal model across cancer types, potential data leakage in evaluation, and lack of standardized benchmarks. Without rigorous, unbiased evaluation, even the most advanced PFMs risk remaining confined to research settings, delaying their life-saving applications. Existing benchmarking efforts remain limited by narrow cancer-type focus, potential pretraining data overlaps, or incomplete task coverage. We present PathBench, the first comprehensive benchmark addressing these gaps through: multi-center in-hourse datasets spanning common cancers with rigorous leakage prevention, evaluation across the full clinical spectrum from diagnosis to prognosis, and an automated leaderboard system for continuous model assessment. Our framework incorporates large-scale data, enabling objective comparison of PFMs while reflecting real-world clinical complexity. All evaluation data comes from private medical providers, with strict exclusion of any pretraining usage to avoid data leakage risks. We have collected 15,888 WSIs from 8,549 patients across 10 hospitals, encompassing over 64 diagnosis and prognosis tasks. Currently, our evaluation of 19 PFMs shows that Virchow2 and H-Optimus-1 are the most effective models overall. This work provides researchers with a robust platform for model development and offers clinicians actionable insights into PFM performance across diverse clinical scenarios, ultimately accelerating the translation of these transformative technologies into routine pathology practice.

Objective To study the impact of transducer arrays on the deep-site dosimetry of radiotherapy with concurrent tumor treating fields (TTFields) for glioblastoma. Methods Firstly, the covering style of transducer arrays to CIRS-038 phantom was designed to simulate the "extreme situation": four arrays were attached to the phantom as a style similar with that in clinical scene and, meanwhile, to assure that layer of interest of CIRS-038 was surrounded by twelve electrodes (three in each array). Then, eight patients undergone glioblastoma radiotherapy were selected, and the planed dose of each patient was delivered to the phantom with dosimetry film inside without and with transducer arrays. For the phantom with arrays, CBCT was used to check the dedicated covering style before dose delivery. Finally, Gamma-based consistency analysis was performed for two dose distributions for each plan (without/with arrays). Results The covering style of the TTFields array met the requirements in 8 cases before dose delivery. Gamma indexes under the four criteria (2%/2 mm, 2%/3 mm, 3%/2 mm and 3%/3 mm) were (93.16±5.16)%, (96.08±3.49)%, (96.77±2.54)% and (97.96±1.61)%, respectively. Conclusion Even in extreme situation (twelve electrodes covering the same cross-section), the perturbation of the TTFields arrays to the deep-site dose distribution of the radiotherapy for glioblastoma is weak and acceptable.

Purpose To evaluate the efficacy and safety of induction immunochemotherapy followed by hypo-fractionated radiotherapy (Hypo-RT) for locally advanced unresectable non-small cell lung cancer (LA-NSCLC). Methods This retrospective analysis involved the data of 35 patients with unresectable stage III LA-NSCLC receiving immunotherapy plus Hypo-RT from January 1, 2019, to December 31, 2023. At least two cycles of induction immunochemotherapy were initially administered, followed by a definitive Hypo-RT at 4Gy per fraction. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS) and grade ≥3 non-hematologic toxicities. Time-to-event outcomes for the entire cohort were calculated using the Kaplan-Meier method. Results At a median follow-up of 31.5 months (95% confidence interval, 26.1 to 36.9 months), median OS did not reach, with 1, 2, and 3-year OS rates of 100.0%, 82.5%, and 77.3%, respectively. Disease progression or death was recorded in 18 (51.4%) patients, with a median PFS of 28.0 months (95% CI, 9.4 to 46.6 months). The 1, 2, and 3-year PFS rates were 74.3%, 55.7%, and 47.6%, respectively. Conclusion Induction immunochemotherapy followed by Hypo-RT demonstrated promising efficacy and acceptable toxicity in patients with LA-NSCLC. Studies on Hypo-RT combined with induction and consolidation immunotherapies are warranted in the future. Micro-abstract This study retrospectively evaluated 35 patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with induction immunochemotherapy followed by hypofractionated radiotherapy (hypo RT). During a median follow-up of 31.5 months, the 1-year, 2-year, and 3-year overall survival (OS) rates were 100%, 82.5%, and 77.3%, respectively, with the median OS not reached. Disease progression or death occurred in 51.4% of patients, with a median progression-free survival (PFS) of 28.0 months. The 1-year, 2-year, and 3-year PFS rates were 74.3%, 55.7%, and 47.6%, respectively. This combined treatment demonstrated promising efficacy and manageable toxicity, warranting further research.

Aims Adenosine metabolism in the breast cancer microenvironment is critical for tumor immunity. However, the prognostic significance of adenosine in breast cancer remains unclear. We aimed to dynamically monitor serum adenosine levels in patients with HER2-positive metastatic breast cancer (MBC) patients and to explore its predictive significance in trastuzumab therapy. Methods The sequencing and clinical data were downloaded from TCGA and GSE176078. Adenosine-related differentially expressed genes was analyzed by “DESeq2” package. Multivariate Cox and lasso-penalized Cox regressions were used to construct prognostic risk signatures. The risk scores were calculated from the identified expression of the hub genes. Bioinformatic analyses were performed using R with related packages. We also enrolled the metastatic breast cancer patients with HER2-positive from in our center and classified them into different groups according to the clinical outcomes assessed by enhanced CT. The adenosine levels were dynamically detected, and the difference in immune microenvironment between the subgroups was assessed by the immune cells that were recorded in our center. Results A total of 109 breast cancer patients with HER2-positive MBC were enrolled, and the expressions of 22 adenosine-related genes were filtered and matched from the TCGA database. The survival model based on the 15 differentially expressed genes was established, and the risk scores of each patient were the prognostic risk factors. Single-cell transcriptome sequencing data identified transcriptomic differences in patients with HER2-positive breast cancer. We also confirmed the predictive value of serum adenosine in the clinical progression of HER2-positive MBC patients. The different immune microenvironment between the subgroups supported the reliability of the predictive ability of adenosine in HER2-positive MBC patients. Conclusions The dynamic change of adenosine is a predictive biomarker for monitoring disease progression. The adenosine metabolism-based signature has the potential application in the prognosis of HER2-positive MBC patients.

To study dosimetric effects of leaf positioning errors (LPEs) of the Halcyon(2.0) dual-layer MLC on the long-course chemoradiotherapy (LCCRT) with 45∼50.4 Gy in 25∼28 fractions for rectal cancer. Nine Halcyon(2.0)-based LCCRT plans of rectal cancer were retrospectively involved. Four types of LPEs were introduced: (1) Uniformly distributed dual-layer random LPEs (Dual-R); (2) Proximal-layer systemic LPEs (P-S); (3) Distal-layer systemic LPEs (D-S); (4) Dual-layer systemic LPEs (Dual-S). The sensitivities of D98%, D2% and the Equivalent Uniform Dose (EUD) of PTV to various LPEs were investigated as well as varying ranges of EUDs of OARs. The sensitivities of D98% and EUD of PTV to Dual-R was -0.65%/mm and -0.38%/mm; the sensitivities of both indices to the P-S and D-S were similar to each other, ranging from 1.92%/mm to 2.87%/mm; both indices were more sensitive to the Dual-S and values were 4.97%/mm and 3.84%/mm respectively. The EUD changes of the bladder, and left and right femoral heads were from -13.23% to 14.82%. Single-side systemic LPEs lower than 0.7 mm are acceptable for Halcyon(2.0)-based LCCRT, while dual-layer systemic LPEs lower than 0.4 mm are acceptable, considering relative changes of 2% for D98% of PTV as threshold.

To evaluate the impact of the residual setup errors from differently shaped region of interest (ROI) and investigate if surface-guided setup can be used in radiotherapy with concurrent tumor treating fields (TTFields) for glioblastoma. Fifteen patients undergone glioblastoma radiotherapy with concurrent TTFields were involved. Firstly, four shapes of region of interest (ROI) (strip-shaped, T-shaped, ⊥ -shaped and cross-shaped) with medium size relative to the whole face were defined dedicate for patients wearing TTFields transducer arrays. Then, ROI-shape-dependent residual setup errors in six degrees were evaluated using an anthropomorphic head and neck phantom taking CBCT data as reference. Finally, the four types of residual setup errors were converted into corresponding dosimetry deviations (including the target coverage and the organ at risk sparing) of the fifteen radiotherapy plans using a feasible and robust geometric-transform-based method. The algebraic sum of the average residual setup errors in six degrees (mm in translational directions and ° in rotational directions) of the four types were 6.9, 1.1, 4.1 and 3.5 respectively. In terms of the ROI-shape-dependent dosimetry deviations, the D98

e16032 Background: Combining immune checkpoint inhibitors with chemotherapy has emerged as the standard treatment for advanced esophageal cancer. Radiotherapy could alleviate symptoms related to dysphagia. Additionally, it holds the potential to enhance the efficacy of immunotherapy, albeit with an associated risk of increased immunotoxicity. The combination of radiotherapy and immunochemotherapy for advanced esophageal cancer necessitates further investigation into its safety and efficacy. Methods: The medical records of consecutively treated patients with advanced esophageal cancer who underwent immunochemotherapy were retrospectively reviewed. The primary inclusion criteria were as follows: 1. Newly treated, imaging-confirmed stage IV esophageal carcinoma; 2. Radiotherapy administered within 6 cycles of immunochemotherapy; 3. Irradiation dose ≥ 30 Gy; 4. Target area must encompass esophageal neoplasms. The primary endpoints were overall survival (OS) and safety (RECIST 1.1). OS was defined as the time from initial treatment to the date of death. The secondary endpoint was progression-free survival (PFS), defined as the time from initial treatment to cancer progression or death. Median overall survival (mOS) time and median progression-free survival (mPFS) time were used to evaluate efficacy, while the incidence of adverse events (AEs) (CTCAE 5.0) was used to evaluate safety and feasibility. Kaplan-Meier survival analysis was conducted using SPSS25 software. Results: 122 patients were screened and 40 patients were finally included. The median age was 69. A total of 30 male patients were included. Three cases were stage IVa and 37 cases were stage IVb. Distant metastatic sites in these patients were lung (50%), liver (30%), bone (17.5%) and others. All cases were treated with immunochemotherapy as first-line treatment with median 4 cycles. Immunochemotherapy regimens are based on platinum and all treated with programmed death-1 inhibitors. Twenty-three cases were concurrent radiotherapy in combined with chemoimmunotherapy and 17 cases were sequential. For radiation therapy, the median dose was 50Gy in 25 fractions. The incidence of grade 3 and above AEs was shown in 20(50%) cases. Four (10%) patients showed treatment-related grade 5 toxicity (immune pneumonia, myocarditis, hepatitis and myocarditis complicated with hepatitis) which all occurred within 1-4 months after radiotherapy. With a median follow-up of 22.0 months, 26 (65%) cases experienced tumor progression (loco-regional progression only in 3, systemic progression only in 18, and both loco-regional and systemic progression in 5 patients), while 27 patients (67.5%) died. mOS and mPFS were 18.0 months and 6.2 months, respectively. Conclusions: Radiotherapy combined with immunochemotherapy for advanced esophageal cancer showed potential efficacy but relatively high toxicities.

Background:Intracranial metastasis that failed standard systematic treatment is common in advanced non-small cell lung cancer (NSCLC), contributing significantly to morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of anlotinib combined with whole-brain radiotherapy (WBRT) for NSCLC with brain metastases (BMs) that progressed or developed after at least one line of prior treatment and compare the outcomes with that of the contemporary institutional control. Methods:NSCLC patients with multiple BMs that progressed or developed after at least one line of prior systematic treatment and treated with WBRT subsequently between 2019 and 2021 were selected retrospectively for analysis. Based on whether concurrent anlotinib had been used in combination with WBRT, the cases were divided into the anlotinib group and control group. The primary endpoints were intracranial progression-free survival (iPFS) and safety. Results:A total of 76 patients met the inclusion criteria of the study. Of the 76 patients, 34 received concurrent WBRT and anlotinib followed by anlotinib maintenance and 42 were treated with WBRT alone or in combination with other systemic agents at the physicians' discretion. The median follow-up for the entire cohort was 21 months. The median iPFS for the anlotinib and control group was 6.7 months (95% CI, 4.6-9.9) and 5.3 months (95% CI, 4.0-6.5), respectively (log-rank P = 0.04). There was no difference in overall survival between the two groups (log-rank P = 0.38). In the anlotinib group, treatment-related adverse events were reported in 15 patients (44.1%), with acute or late grade 3-5 adverse events identified in 14.7% of patients (n = 5). Conclusions:WBRT plus anlotinib, as a convenient chemo-free regimen, may represent an overall safe and effective procedure in advanced NSCLC with multiple BMs that progressed or developed after standard systematic treatment.

e14624 Background: Thoracic radiotherapy (TRT) is widely used in the treatment of thoracic tumors (TTs) including esophageal and lung cancers. Previous studies suggest that it may increase the risk of myocardial injury. The use of immune checkpoint inhibitors combined with chemotherapy (ICC) in TTs is becoming prevalent, and immune myocarditis is of interest to clinicians. Markers of myocardial injury (MMIs) (e.g., cTnT, CK-MB) have been used with high sensitivity and specificity for the diagnosis of immune myocarditis. Previous studies have focused on severe immune myocarditis due to its high lethality, and less attention has been paid to myocarditis with mildly elevated MMIs. However, ICC are increasingly being used in the treatment of earlier-stage TTs (e.g., neoadjuvant treatment of NSCLC), so the safety of treatment is particularly crucial. The main objective of this study was to analyze the effect of ICC with or without TRT on the MMIs in patients with TTs. Methods: This is a single-center retrospective study with the following main inclusion criteria: 1, pathologically confirmed esophageal and lung cancers only; 2, treated with ICC; 3, presence of comparable serial MMIs results from 1 week prior to the start of treatment to 12 weeks after the end of treatment; 4, TRT allowed in the same period. Primary exclusion criteria: 1，Elevation of MMIs occurs before ICC. 2，For patients who have received TRT, MMIs elevated before radiotherapy. As Chinese Society of Clinical Oncology PD-1 treatment-related myocarditis diagnostic criteria, cTnT was defined as elevated when it was significantly higher than baseline (20 μg/mL) and CK-MB was defined as elevated when it was 2.5 times higher than the upper limit of normal (≥62.5 U/L); Elevation of cTnT and CK-MB after treatment was used as the primary observation and a chi-square test was performed using the SPSS version 25. Results: This study investigated patient data from Jan 1st,2019 to Sep 20th,2022 for a total of 196 patients with esophageal squamous cancer and 298 patients with lung cancer (SCLC vs NSCLC = 13:285) who met the enrollment criteria. The median age was 64 years (29-89 years), male vs female = 406:88. 256 patients received ICC plus radiotherapy (Group A) and 238 patients without radiotherapy (Group B). The median dose of TRT was 50.4 Gy (12 - 60 Gy). The median cycles of use of Immune checkpoint inhibitors (including PD-1 and PD-L1 inhibitors) was 5 (1- 43). The proportion of all patients with post-treatment elevations of cTnT was 12.2% (29/238), including 11.9% (13/109) and 12.4% (16/129) in group A and B, p > 0.05. The whole proportion of patients with elevated CK-MB was 2.7% (13/473), including 3.2% (8/251) and 2.3% (5/222) in group A and B, p > 0.05. Conclusions: Elevated MMIs were common after the use of ICC in patients with TTs with or without radiotherapy, and TRT did not increase the risk of elevation of MMIs.

Abstract Background Super enhancers (SE) play pivotal roles in cell identity and diseases occur including tumorigenesis. The depletion of SE‐associated lncRNA transcripts, also known as super‐lncRNA, causes the activity of SE to be dysregulated. Methods We screened and identified an elevated metastasis‐associated SE‐lncRNA SUCLG2‐AS1 in nasopharyngeal carcinoma (NPC) using RNA‐sequencing, real‐time quantitative polymerase chain reaction (RT‐qPCR) and bioinformatics. Western blotting, RT‐qPCR, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation, chromatin immunoprecipitation, RNA pull‐down and 3C (chromosome conformation capture assays) were used for mechanistic studies. Results SUCLG2‐AS1 was correlated with a poor prognosis. SUCLG2‐AS1 promotes NPC cell invasion and metastasis while repressing apoptosis and radiosensitivity in vitro and in vivo. Mechanistically, high SUCLG2‐AS1 expression occurred in an m6A‐dependent manner. SUCLG2‐AS1 was found to be located in the SE region of SOX2, and it regulated the expression of SOX2 via long‐range chromatin loop formation, which via mediating CTCF (transcription factor) occupied the SE and promoter region of SOX2, thus regulating the metastasis and radiosensitivity of NPC. Conclusions Taken together, our data suggest that SUCLG2‐AS1 may serve as a novel intervention target for the clinical treatment of NPC.

Background:Transmembrane serine protease 2 (TMPRSS2) mediates the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. The relevant research indicates the intestine to be a target of SARS-CoV-2 infection, and thus we aimed to investigate the correlation between TMPRSS2 expression and the prognosis, molecular features, and immunotherapy response in patients with colorectal cancer (CRC).Methods:The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study and a total of 1,385 patients were identified. The CIBERSORT algorithms were used to evaluate the relative infiltration levels of immune cell types in the tumor microenvironment (TME). The correlation between TMPRSS2 expression and immunotherapy response rate was assessed in another 2 independent cohorts.Results:TMPRSS2 expression was significantly downregulated in cancer tissue compared to the adjacent normal tissue, and patients with CRC with lower TMPRSS2 expression showed notably poorer prognosis. Functional enrichment analysis found that low TMPRSS2 expression was significantly associated with cancer metastasis-related pathways. Further analysis based on the miRWalk tool and JASPAR database identified a list of microRNAs (miRNAs) and transcriptional factors targeting TMPRSS2. Distinct differences in immune cell infiltration and tumor purity reflected by estimate and mutant-allele tumor heterogeneity score were observed between patients with low and high TMPRSS2 expression levels. Interestingly, patients with a low TMPRSS2 expression level showed a higher response rate to immunotherapy.Conclusions:CRC cells may be more resistant to SARS-CoV-2 infection due to the decreased expression of TMPRSS2, which could be a newly identified biomarker for prognosis and immunotherapy response prediction in patients with CRC.

Respiratory motion may compromise the dose delivery accuracy in liver stereotactic body radiation therapy (SBRT). Motion management can improve treatment delivery. However, external surrogate signal may be unstable and inaccurate. This study reports the first case of liver SBRT based on internal electromagnetic motion monitoring (Calypso, Varian Medical Systems, USA) in China. The patient with a primary liver cancer was treated with respiratory-gated SBRT guided by three implanted electromagnetic transponders. The treatment was carried out in breath-hold end-exhale with beam-on when the centroid of the three transponders drifted within 5 mm (left–right (LR), anterior–posterior (AP) and cranio-caudal (CC) directions) from the planned position. The motion monitoring treatments were delivered in breath-hold end-exhale mode with the energy of 6 MV in FFF mode with 1200 monitor units (MU) per minute. For each fraction, QA results, intertransponder distances, geometric checks as well as tumor motion logs were explicitly recorded. Comparing with the plan data, distance variances between each two transponders were − 0.56 ± 0.32 mm, 0.17 ± 0.33 mm and − 0.82 ± 0.68 mm. Geometric residual, the pitch, roll and yaw angles were 0.48 ± 0.21 mm (threshold 2.0 mm), 2.17° ± 1.85° (threshold 10°), − 2.42° ± 1.51° (threshold 10°) and 1.67° ± 1.07° (threshold 10°), respectively. The delivery time of the five fields were 13.8 s, 13.1 s, 11.2 s, 11.6 s, and 11.6 s with the average value of 12.3 ± 1.1 s. Treatment duration of each fraction ranged from 6.2 to 21.4 min, with the average value of 11.3 ± 5.0 min. The first case of liver SBRT patient of China based on internal electromagnetic motion monitoring was performed. The system had a high tracking accuracy, and it did not delay the treatment time. In addition, the patient did not show any severe side effects except for grade I myelotoxicity. The internal electromagnetic motion monitoring system provides a real-time and direct way to track liver tumor targets.

AbstractBackgroundThis study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian®) plus cisplatin (SP regimen) and 5‐fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA‐NPC).MethodsEligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy. Progression free survival (PFS) was primary endpoint. Secondary endpoints included overall survival (OS), loco‐regional relapse free survival (LRRFS), distant metastasis free survival (DMFS) and toxicity.ResultsIn this study, 68 patients received SP as CCRT, and 67 received FP. Objective responses were noted in 97.1% of the patients in the SP group and in 97.0% of the patients in the FP group (P = 1.00). At the end of a median 36 months follow‐up period, the estimated 3‐year PFS rates were 70.1% for SP and 66.6% for FP, respectively. The 3‐year LRRFS, DMFS and OS rates were 88.9%, 74.7% and 84.0%, respectively, for the SP group, and 92.3%, 71.0% and 73.7%, respectively, for the FP group. Overall, there was no difference between treatment groups with regard to response or survival. The most frequent acute toxicities monitored in both groups were bone marrow suppression, gastrointestinal side effects and oral mucositis (OM). The overall incidence of grade 3‐4 OM in the FP group (47.8%) was higher than in the SP group (11.8%). However, the incidence of other adverse effects observed in both groups was similar (P > .05).ConclusionsThese data indicate that SP and FP therapies have similar efficacy in treating LA‐NPC. The SP regimen showed a tolerable safety profile along with a lower frequency of severe OM and therefore, an improved life quality. In conclusion, SP was a well tolerated, effective, regimen for LA‐NPC treatment.