KRAS status predicted by pretreatment MRI radiomics was associated with lung metastasis in locally advanced rectal cancer patients.

BACKGROUND: Mutated KRAS may indicate an invasive nature and predict prognosis in locally advanced rectal cancer (LARC). We aimed to establish a radiomic model using pretreatment T2W MRIs to predict KRAS status and explore the association between the KRAS status or model predictions and lung metastasis. METHODS: In this retrospective multicentre study, LARC patients from two institutions between January 2012 and January 2019 were randomly divided into training and testing cohorts. Least absolute shrinkage and selection operator (LASSO) regression and the support vector machine (SVM) classifier were utilized to select significant radiomic features and establish a prediction model, which was validated by radiomic score distribution and decision curve analysis. The association between the model stratification and lung metastasis was investigated by Cox regression and Kaplan‒Meier survival analysis; the results were compared by the log-rank test. RESULTS: Overall, 103 patients were enrolled (73 and 30 in the training and testing cohorts, respectively). The median follow-up was 38.1 months (interquartile range: 26.9, 49.4). The radiomic model had an area under the curve (AUC) of 0.983 in the training cohort and 0.814 in the testing cohort. Using a cut-off of 0.679 defined by the receiver operating characteristic (ROC) curve, patients with a high radiomic score (RS) had a higher risk for lung metastasis (HR 3.565, 95% CI 1.337, 9.505, p = 0.011), showing similar predictive performances for the mutant and wild-type KRAS groups (HR 3.225, 95% CI 1.249, 8.323, p = 0.016, IDI: 1.08%, p = 0.687; NRI 2.23%, p = 0.766). CONCLUSIONS: We established and validated a radiomic model for predicting KRAS status in LARC. Patients with high RS experienced more lung metastases. The model could noninvasively detect KRAS status and may help individualize clinical decision-making.

MRI radiomics independent of clinical baseline characteristics and neoadjuvant treatment modalities predicts response to neoadjuvant therapy in rectal cancer.

BACKGROUND: To analyse the performance of multicentre pre-treatment MRI-based radiomics (MBR) signatures combined with clinical baseline characteristics and neoadjuvant treatment modalities to predict complete response to neoadjuvant (chemo)radiotherapy in locally advanced rectal cancer (LARC). METHODS: Baseline MRI and clinical characteristics with neoadjuvant treatment modalities at four centres were collected. Decision tree, support vector machine and five-fold cross-validation were applied for two non-imaging and three radiomics-based models' development and validation. RESULTS: We finally included 674 patients. Pre-treatment CEA, T stage, and histologic grade were selected to generate two non-imaging models: C model (clinical baseline characteristics alone) and CT model (clinical baseline characteristics combining neoadjuvant treatment modalities). The prediction performance of both non-imaging models were poor. The MBR signatures comprising 30 selected radiomics features, the MBR signatures combining clinical baseline characteristics (CMBR), and the CMBR incorporating neoadjuvant treatment modalities (CTMBR) all showed good discrimination with mean AUCs of 0.7835, 0.7871 and 0.7916 in validation sets, respectively. The three radiomics-based models had insignificant discrimination in performance. CONCLUSIONS: The performance of the radiomics-based models were superior to the non-imaging models. MBR signatures seemed to reflect LARC's true nature more accurately than clinical parameters and helped identify patients who can undergo organ preservation strategies.

Phase 1 trial of apatinib combined with intensity-modulated radiotherapy in unresectable hepatocellular carcinoma.

BACKGROUND: To investigate the maximum tolerated dose (MTD) of apatinib delivered during and after intensity-modulated radiotherapy (IMRT) for unresectable hepatocellular carcinoma (HCC). METHODS: Patients with unresectable HCC who were not eligible for radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), or residual/ recurrent after the prior local treatment were enrolled. Patients were scheduled to be treated with IMRT at 50-60 Gy/25-30 fractions. Oral apatinib tablets were administered concurrently with IMRT and continued thereafter. We used a 3 + 3 dose-escalation design, with three dose levels of apatinib (250, 500, and 750 mg). Grade 3 or more severe adverse events (AEs) were defined as dose-limiting toxicities (DLTs). The treatment response was calculated using the Modified Response Evaluation Criteria in Solid Tumours. RESULTS: Nine patients with Barcelona Clinic Liver Cancer Stage C were included. One patient withdrew from the apatinib 250 mg group and another patient was added. No DLTs occurred in the apatinib 250 mg group. Five patients were included in the apatinib 500 mg group, and 2 cases of DLT (grade 3 leukopenia) were found among them. Dose escalation was terminated and the MTD was determined to be 250 mg. Common grade 1-2 AEs included fatigue, hypertension, dizziness, bone marrow suppression, and hyperbilirubinemia. The median follow-up time for all patients was 16.0 months. Three patients achieved complete response and another three achieved partial response. The objective response rate was 6/9 (66.7%), and the disease control rate was 9/9 (100%). Three patients relapsed out of the radiation field. The median progression-free survival was 17.0 months, and the median overall survival was 16.7 months. CONCLUSIONS: When combined with IMRT, apatinib 250 mg daily was recommended for a phase 2 study of unresectable HCC. The antitumor activity of the combination treatment was encouraging. The safety and efficacy of apatinib combined with IMRT for unresectable HCC should be further investigated in future studies. TRIAL REGISTRATION: Registration No. ChiCTR1800018309 . Registered 11 September 2018. Retrospectively registered, https://www.chictr.org.cn/showproj.aspx?proj=30461 .

Dentate line invasion as a predictive factor of poor distant relapse-free survival in locally advanced lower rectal cancer with anal sphincter involvement.

BACKGROUND: While an important surgical landmark of the dentate line has been established for locally advanced lower rectal cancer (LALRC), the prognostic significance of dentate line invasion (DLI) has not been well defined. This study aimed to explore the impact of DLI on prognosis in LALRC patients with anal sphincter involvement after neoadjuvant chemoradiotherapy followed by surgery. METHODS: We analyzed 210 LALRC patients and classified them into DLI group (n = 45) or non-DLI group (n = 165). The exact role of DLI in survival and failure patterns was assessed before and after propensity-score matching(PSM). Finally, 50 patients were matched. RESULTS: Before matching, patients in the DLI group had poorer 5-year distant relapse-free survival (DRFS) (P < 0.001), disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P = 0.022) than those in the non-DLI group, with the exception of local recurrence-free survival (LRFS) (P = 0.114). After PSM, the 5-year DRFS, DFS, OS, and LRFS were 51.7% vs. 79.8%(P = 0.026), 51.7% vs. 79.8%(P = 0.029), 71.6% vs. 85.4%(P = 0.126), and 85.7% vs. 92.0%(P = 0.253), respectively, between the two groups. DLI was also an independent prognostic factor for poor DRFS with (Hazard ratio [HR] 3.843, P = 0.020) or without matching (HR 2.567, P = 0.001). The DLI group exhibited a higher rate of distant metastasis before (44.4% vs. 19.4%, P < 0.001) and after matching (48.0% vs. 20.0%, P = 0.037) and similar rates of locoregional recurrence before (13.3% vs.7.9%, P = 0.729) and after matching (16.0% vs.12.0%, P = 1.000). CONCLUSIONS: DLI may portend worse DRFS and distant metastasis in LALRC patients with anal sphincter involvement, and this may be an important variable to guide clinicians.

MRI-based radiomics model for preoperative prediction of 5-year survival in patients with hepatocellular carcinoma.

BACKGROUND: Recurrence is the major cause of mortality in patients with resected HCC. However, without a standard approach to evaluate prognosis, it is difficult to select candidates for additional therapy. METHODS: A total of 201 patients with HCC who were followed up for at least 5 years after curative hepatectomy were enrolled in this retrospective, multicentre study. A total of 3144 radiomics features were extracted from preoperative MRI. The random forest method was used for radiomics signature building, and five-fold cross-validation was applied. A radiomics model incorporating the radiomics signature and clinical risk factors was developed. RESULTS: Patients were divided into survivor (n = 97) and non-survivor (n = 104) groups based on the 5-year survival after surgery. The 30 most survival-related radiomics features were selected for the radiomics signature. Preoperative AFP and AST were integrated into the model as independent clinical risk factors. The model demonstrated good calibration and satisfactory discrimination, with a mean AUC of 0.9804 and 0.7578 in the training and validation sets, respectively. CONCLUSIONS: This radiomics model is a valid method to predict 5-year survival in patients with HCC and may be used to identify patients for clinical trials of perioperative therapies and for additional surveillance.

lncRNA SNHG1 promotes the progression of hepatocellular carcinoma by regulating the miR-7-5p/IGF2BP2 axis.

Long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) plays a crucial role in the occurrence and progression of various tumors. This study investigates the function of lncRNA SNHG1 in hepatocellular carcinoma (HCC). We discovered that lncRNA SNHG1 is significantly upregulated in HCC and markedly enhances cell proliferation, migration, and invasion, while simultaneously suppressing apoptosis in HCC cells. Furthermore, lncRNA SNHG1 was found to downregulate miR-7-5p expression. Overexpression of lncRNA SNHG1 counteracted the suppression of HCC cell migration, proliferation, and invasion caused by miR-7-5p mimics, and reversed the miR-7-5p mimics' enhancement of apoptosis in HCC cells. Additionally, miR-7-5p was shown to negatively regulate IGF2BP2, with the silencing of IGF2BP2 diminishing the abilities of HCC cells to proliferate, migrate, and invade, and increasing their propensity for apoptosis. Overexpression of lncRNA SNHG1 negated these effects. Thus, lncRNA SNHG1 fosters HCC progression by upregulating IGF2BP2 expression through targeting miR-7-5p.

The ypT may better predict the efficacy of neoadjuvant chemoradiotherapy than tumor regression grade in locally advanced rectal cancer patients diagnosed ypT1-4N0.

PURPOSE: This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan-Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. RESULTS: The median follow-up was 35.8 months (range 2.8-71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. CONCLUSIONS: For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.

Clinicopathological factors predict residual lymph node metastasis in locally advanced rectal cancer with ypT0-2 after neoadjuvant chemoradiotherapy.

PURPOSE: Residual lymph node metastases (RLNM) remained a great concern in the implementation of organ-preserving strategies and led to poor prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to identify the clinicopathological factors correlated with RLNM in LARC patients with ypT0-2 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 417 patients histologically diagnosed middle-low LARC after NCRT and total mesorectal excision (TME), whose pathological staging was ypT0-2. All patients received pelvic magnetic resonance imaging (MRI) before NCRT. The radiation doses were 50-50.6 Gy for the planning gross tumor volume and 41.8-45 Gy for the planning target volume, respectively. A nomogram for predicting RLNM was constructed using a binary logistic regression. Nomogram performance was assessed by receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: After surgery, 191 patients (45.8%) were ypT0, 43 patients (10.3%) were ypT1 and 183 patients (43.9%) were ypT2, and a total of 49 patients (11.8%) were found the presence of RLNM. Multivariable analyses identified MRI-defined mesorectal fascia (MRF)-positive, high-grade histopathology at biopsy, advanced ypT-category, and the presence of perineural invasion (PNI) as the predictive factors. The nomogram, incorporating all these predictors, showed good discrimination and calibration efficacy, with the areas under the ROC curve of 0.690 (95% CI: 0.610-0.771). Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. CONCLUSION: The nomogram model can predict RLNM in patients with ypT0-2 tumors. It can help select suitable patients for performing organ-preserving strategies after NCRT.

4D-MRI assisted stereotactic body radiation therapy for unresectable colorectal cancer liver metastases.

This study evaluated the feasibilities and outcomes following four-dimensional magnetic resonance imaging (4D-MRI) assisted stereotactic body radiation therapy (SBRT) for unresectable colorectal liver metastases (CRLMs). From March 2018 to January 2022, we identified 76 unresectable CRLMs patients with 123 lesions who received 4D-MRI guided SBRT in our institution. 4D-MRI simulation with or without abdominal compression was conducted for all patients. The prescription dose was 50-65 Gy in 5-12 fractions. The image quality of computed tomography (CT) and MRI were compared using the Clarity Score. Clinical outcomes and toxicity profiles were evaluated. 4D-MRI improved the image quality compared with CT images (mean Clarity Score: 1.67 vs 2.88, P < 0.001). The abdominal compression reduced motions in cranial-caudal direction (P = 0.03) with two phase T2 weighted images assessing tumor motion. The median follow-up time was 12.5 months. For 98 lesions assessed for best response, the complete response, partial response and stable disease rate were 57.1 %, 30.6 % and 12.2 %, respectively. The local control (LC) rate at 1 year was 97.3 %. 46.1 % of patients experienced grade 1-2 toxicities and only 2.6 % patients experienced grade 3 hematologic toxicities. The 4D-MRI technique allowed accurate target delineation and motion tracking in unresectable CRLMs patients. Favorable LC rate and mild toxicities were achieved. This study provided evidence for using 4D-MRI assisted SBRT as an alternative treatment in unresectable CRLMs.

Recombinant adenovirus-p53 (Gendicine) sensitizes a pancreatic carcinoma cell line to radiation.

OBJECTIVE: In this study, we examine the effects of recombinant adenovirus-p53 (rAd-p53) on the pancreatic carcinoma cell line SW1990. Specifically, we determine if expression of rAd-p53 sensitizes these cells to radiation. METHODS: Following transfection of SW1990 cells with rAd-p53, we measured expression of P53, P21 and Bax by immunocytochemistry. Both transfected and control cell lines were irradiated with a range of doses, and the survival fractions (SF) were calculated. Dose survival curves were constructed and modeled for comparison. RESULTS: Transfection of SW1990 cells with rAd-p53 resulted in increased expression of P53, P21 and Bax in a time-dependent manner. At 96 h after transfection, 89.92% of cells expressed P53, 56.8% expressed P21, and 76.50% expressed Bax. The SF following radiation was lower in the rAd-p53 transfected cells compared to the control cells, suggesting that rAd-p53 sensitizes SW1990 cells to radiation (D0 for the experimental and control groups was 2.199 and 2.462, respectively). CONCLUSIONS: Use of the adenoviral vector is an effective means of transfecting SW1990 cells with wild-type P53, and this sensitizes the cell line to irradiation. This work suggests that combining rAd-p53 with radiation therapy in pancreatic cancer may be therapeutically beneficial.

Quantitative assessment of adaptive radiotherapy for prostate cancer using deep learning: Bladder dose as a decision criterion.

BACKGROUND: Adaptive radiotherapy (ART) can incorporate anatomical variations in a reoptimized treatment plan for fractionated radiotherapy. An automatic solution to objectively determine whether ART should be performed immediately after the daily image acquisition is highly desirable. PURPOSE: We investigate a quantitative criterion for whether ART should be performed in prostate cancer radiotherapy by synthesizing pseudo-CT (sCT) images and evaluating dosimetric impact on treatment planning using deep learning approaches. METHOD AND MATERIALS: Planning CT (pCT) and daily cone-beam CT (CBCT) data sets of 74 patients are used to train (60 patients) and evaluate (14 patients) a cycle adversarial generative network (CycleGAN) that performs the task of synthesizing high-quality sCT from daily CBCT. Automatic delineation (AD) of the bladder is performed on the sCT using the U-net. The combination of sCT and AD allows us to perform dose calculations based on the up-to-date bladder anatomy to determine whether the original treatment plan (ori-plan) is still applicable. For positive cases that the patients' anatomical changes and the associated dose calculations warrant re-planning, we made rapid plan revisions (re-plan) based on the ori-plan. RESULTS: The mean absolute error within the region-of-interests (i.e., body, bladder, fat, muscle) between the sCT and pCT are 41.2, 25.1, 26.5, and 29.0HU, respectively. Taking the calculated results of pCT doses as the standard, for PTV, the gamma passing rates of sCT doses at 1 mm/1%, 2 mm/2% are 87.92%, 98.78%, respectively. The Dice coefficients of the AD-contours are 0.93 on pCT and 0.91 on sCT. According to the result of dose calculation, we found when the bladder volume underwent a substantial change (79.7%), the bladder dose is still within the safe limit, suggesting it is insufficient to solely use the bladder volume change as a criterion to determine whether adaptive treatment needs to be done. After AD-contours of the bladder using sCT, there are two cases whose bladder dose D mean > 4000 cGy ${{\mathrm{D}}}_{{\mathrm{mean}}} > 4000{\mathrm{\ cGy}}$ . For the two cases, we perform re-planning to reduce the bladder dose to D mean = 3841 cGy ${{\mathrm{D}}}_{{\mathrm{mean}}} = 3841{\mathrm{\ cGy}}$ , D mean = 3580 cGy ${{\mathrm{D}}}_{{\mathrm{mean}}} = 3580{\mathrm{\ cGy\ }}$ under the condition that the PTV meets the prescribed dose. CONCLUSION: We provide a dose accurate adaptive workflow for prostate cancer patients by using deep learning approaches, and implement ART that adapts to bladder dose. Of note, the specific replanning criterion for whether ART needs to be performed can adapt to different centers' choices based on their experience and daily observations.

Towards deep-learning (DL) based fully automated target delineation for rectal cancer neoadjuvant radiotherapy using a divide-and-conquer strategy: a study with multicenter blind and randomized validation.

PURPOSE: Manual clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy is pivotal but labor-intensive. This study aims to propose a deep learning (DL)-based workflow towards fully automated clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy. MATERIALS & METHODS: We retrospectively included 141 patients with Stage II-III mid-low rectal cancer and randomly grouped them into training (n = 121) and testing (n = 20) cohorts. We adopted a divide-and-conquer strategy to address CTV and GTV segmentation using two separate DL models with DpuUnet as backend-one model for CTV segmentation in the CT domain, and the other for GTV in the MRI domain. The workflow was validated using a three-level multicenter-involved blind and randomized evaluation scheme. Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (95HD) metrics were calculated in Level 1, four-grade expert scoring was performed in Level 2, and head-to-head Turing test in Level 3. RESULTS: For the DL-based CTV contours over the testing cohort, the DSC and 95HD (mean ± SD) were 0.85 ± 0.06 and 7.75 ± 6.42 mm respectively, and 96.4% cases achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.3%. For GTV, the DSC and 95HD were 0.87 ± 0.07 and 4.07 ± 1.67 mm respectively, and 100% of the DL-based contours achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.0%. CONCLUSION: The proposed DL-based workflow exhibited promising accuracy and excellent clinical viability towards automated CTV and GTV delineation for rectal cancer neoadjuvant radiotherapy.

MRI-based radiomics to predict neoadjuvant chemoradiotherapy outcomes in locally advanced rectal cancer: A multicenter study.

Background and purpose: Predicting tumour response would be useful for selecting patients with locally advanced rectal cancer (LARC) for organ preservation strategies. We aimed to develop and validate a prediction model for T downstaging (ypT0-2) in LARC patients after neoadjuvant chemoradiotherapy and to identify those who may benefit from consolidation chemotherapy. Materials and methods: cT3-4 LARC patients at three tertiary medical centers from January 2012 to January 2019 were retrospectively included, while a prospective cohort was recruited from June 2021 to March 2022. Eight filter (principal component analysis, least absolute shrinkage and selection operator, partial least-squares discriminant analysis, random forest)-classifier (support vector machine, logistic regression) models were established to select radiomic features. A nomogram combining radiomics and significant clinical features was developed and validated by calibration curve and decision curve analysis. Interaction test was conducted to investigate the consolidation chemotherapy benefits. Results: A total of 634 patients were included (426 in training cohort, 174 in testing cohort and 34 in prospective cohort). A radiomic prediction model using partial least-squares discriminant analysis and a support vector machine showed the best performance (AUC: 0.832 [training]; 0.763 [testing]). A nomogram combining radiomics and clinical features showed significantly better prognostic performance (AUC: 0.842 [training]; 0.809 [testing]) than the radiomic model. The model was also tested in the prospective cohort with AUC 0.727. High-probability group (score > 81.82) may have potential benefits from ≥ 4 cycles consolidation chemotherapy (OR: 4.173, 95 % CI: 0.953-18.276, p = 0.058, pinteraction = 0.021). Conclusion: We identified and validated a model based on multicenter pre-treatment radiomics to predict ypT0-2 in cT3-4 LARC patients, which may facilitate individualised treatment decision-making for organ-preservation strategies and consolidation chemotherapy.

Retrospective cohort study for thrombocytopenia during concurrent chemoradiotherapy for rectal cancer.

Background: The aim of this article was to establish the clinical prognostic models and identify the predictive radiation dosimetric parameters for thrombocytopenia during concurrent chemoradiotherapy for rectal cancer. Methods: In this retrospective cohort study, patients with rectal adenocarcinoma undergoing concurrent long-term chemoradiotherapy were included. The primary outcome of interest was grade 2 or higher (2+) thrombocytopenia (platelet(PLT) count <75,000/µL). Secondary outcomes included: grade 1 or higher thrombocytopenia (PLT count<100,000/µL) and the PLT count during chemoradiotherapy and its nadir. The risk prediction model was developed by logistic regression to identify clinical predictors of 2+ thrombocytopenia. Univariate linear regression models were used to test correlations between radiation dosimetric parameters and the absolute PLT count at nadirs. Results: This retrospective cohort comprised 238 patients. Fifty-four (22.6%) patients developed thrombocytopenia during concurrent chemoradiotherapy, while 15 (6.3%) patients developed 2+ thrombocytopenia. Four independently associated risk factors, including age, Alb level, PLT count, and chemotherapy regimen, were included in the final model and used to form a 2+ thrombocytopenia probability estimation nomogram. The C-index was 0.87 (95% CI: 0.78-0.96). The calibration plot showed a moderate agreement, and the Brier score was 0.047 (95% CI: 0.025-0.070). The total absolute volume of bone marrow irradiated by 5 Gy, 10 Gy and 15 Gy of radiation (BM-V5ab, BM-V10ab, BM-V15ab), calculated by the volume of bone marrow multiplied by the corresponding Vx, were identified as new predictors. The nadir of PLT was found to be negatively correlated with BM-V5ab (ß = -0.062, P =0.030), BM-V10ab (ß = -0.065, P =0.030) and BM-V15ab (ß = -0.064, P =0.042). Conclusion: The occurrence of 2+ thrombocytopenia during concurrent chemoradiotherapy for rectal cancer can be predicted by the patient's baseline status and chemoradiotherapy regimen, and low dose irradiation of bone marrow can affect the level of platelets during the treatment.

Prognostic impact of sarcopenia in patients with locally advanced adenocarcinoma of the esophagogastric junction treated with neoadjuvant chemoradiotherapy.

Background: Few studies have evaluated the significance of sarcopenia in predicting the outcomes of patients with adenocarcinoma of the esophagogastric junction (AEG), especially those who received neoadjuvant chemoradiotherapy (NCRT). We aimed to identify the sarcopenic status and its impact on the outcomes of patients with locally advanced AEG who received NCRT followed by radical surgery or systemic therapy. Materials and methods: Patients with T3-4N+M0 AEG with accessible abdominal computed tomography (CT) before and after NCRT were retrospectively analyzed. Body composition parameters, particularly the skeletal muscle index (SMI), were assessed using a CT-based method, and sarcopenia was defined using a predetermined SMI cutoff value. Survival analysis was conducted using the Kaplan-Meier method. A Cox proportional hazards regression model was used to identify independent prognostic factors. Receiver operating characteristic curve analysis was carried out, and the area under the curve (AUC) was calculated to test the prognostic accuracy of different factors. Results: A total of 63 patients were enrolled, 65.1 and 79.4% of whom developed pre- and post-NCRT sarcopenia, respectively. Patients with pre-NCRT sarcopenia had lower radical surgery rates (70.7 vs. 95.5%, p = 0.047) than those without sarcopenia; however, sarcopenic status did not affect other short-term outcomes, including treatment-related toxicity and efficacy. Pre-NCRT sarcopenia was identified as an independent predictive factor for poor overall survival (OS) [adjusted hazard ratio (HR), 6.053; p = 0.002] and progression-free survival (PFS) (adjusted HR, 2.873; p = 0.031). Compared with nutritional indices such as the Nutritional Risk Screening 2002, weight loss during NCRT, and post-NCRT sarcopenia, pre-NCRT sarcopenia was regarded as the best predictive index for the 5-year OS (AUC = 0.735) and PFS rates (AUC = 0.770). Conclusion: Pre-NCRT sarcopenia may be an independent predictive factor for OS and PFS rates in patients with locally advanced AEG receiving multimodal treatment.

Gut microbiota-mediated nucleotide synthesis attenuates the response to neoadjuvant chemoradiotherapy in rectal cancer.

Preoperative neoadjuvant chemoradiotherapy (nCRT) is a standard treatment for locally advanced rectal cancer (LARC) patients, yet little is known about the mediators underlying the heterogeneous patient response. In this longitudinal study, we performed 16S rRNA sequencing on 353 fecal specimens and find reduced microbial diversity after nCRT. Multi-omics data integration reveals that Bacteroides vulgatus-mediated nucleotide biosynthesis associates with nCRT resistance in LARC patients, and nonresponsive tumors are characterized by the upregulation of genes related to DNA repair and nucleoside transport. Nucleosides supplementation or B. vulgatus gavage protects cancer cells from the 5-fluorouracil or irradiation treatment. An analysis of 2,205 serum samples from 735 patients suggests that uric acid is a potential prognosis marker for LARC patients receiving nCRT. Our data unravel the role of intestinal microbiota-mediated nucleotide biosynthesis in the response of rectal tumors to nCRT, and highlight the importance of deciphering the cross-talk between cancer cells and gut microorganisms during cancer therapies.

Hyperfractionation versus Conventional Fractionation of Preoperative Intensity-Modulated Radiotherapy with Oral Capecitabine in Locally Advanced Mid-Low Rectal Cancer: A Propensity Score Matching Study.

Purpose: In theory, the hyperfractionated radiotherapy can enhance biological effect dose against tumor and alleviate normal tissue toxicity. This study is to assess the efficacy and safety of preoperative hyperfractionated intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced rectal cancer (LARC). Methods: We retrospectively screened patients with LARC from January 2015 to June 2016. Patients that received hyperfractionated IMRT or conventional fractionated IMRT were eligible in the hyperfractionation (HF) group or conventional fractionation (CF) group, respectively. The primary outcome was the complete response rate. Secondary outcomes included toxicity, postoperative complications, anus-reservation operation rate, local recurrence and distant metastases rate, overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Results: 335 patients were included in the analysis. The complete response rate for the hyperfractionated and conventional fractionated IMRT was 20.41% vs. 23.47% (P = 0.583). The anus-reservation operation rate was 68.37% vs. 65.31% (P = 0.649). There were no cases of grade 4 toxicity during radiotherapy; the rate of grade 3 toxicity and postoperative complications was both comparable between groups. However, in the CF group, more patients had a second operation due to complications (0.0% vs. 5.68%, P = 0.011). The cumulative local regional recurrence and distant metastases rates of the HF group and CF group were 5.10% vs. 9.18% (P = 0.267) and 22.45% vs. 24.49% (P = 0.736), respectively. The 5-year OS, CSS, and DFS in the HF group and CF group were 86.45% vs. 73.30% (P = 0.503), 87.34% vs. 75.23% (P = 0.634), and 70.80% vs. 68.11% (P = 0.891), respectively. Conclusions: The preoperative hyperfractionated IMRT with oral capecitabine, with an acceptable toxicity and favorable response and survival, could reduce the rate of secondary surgery.

Initial clinical experience of surface guided stereotactic radiation therapy with open-face mask immobilization for improving setup accuracy: a retrospective study.

PURPOSE: To propose a specific surface guided stereotactic radiotherapy (SRT) treatment procedure with open-face mask immobilization and evaluate the initial clinical experience in improving setup accuracy. METHODS AND MATERIALS: The treatment records of 48 SRT patients with head lesions were retrospectively analyzed. For each patient, head immobilization was achieved with a double-shell open-face mask. The anterior shell was left open to expose the forehead, nose, eyes and cheekbones. The exposed facial area was used as region-of-interest for surface tracking by AlignRT (VisionRT Inc, UK). The posterior shell provided a sturdy and personalized headrest. Patient initial setup was guided by 6DoF real-time deltas (RTD) using the reference surface obtained from the skin contour delineated on the planning CT images. The endpoint of initial setup was 1 mm in translational RTD and 1 degree in rotational RTD. CBCT guidance was performed to derive the initial setup errors, and couch shifts for setup correction were applied prior to treatment delivery. CBCT couch shifts, AlignRT RTD values, repositioning rate and setup time were analyzed. RESULTS: The absolute values of median (maximal) CBCT couch shifts were 0.4 (1.3) mm in VRT, 0.1 (2.5) mm in LNG, 0.2 (1.6) mm in LAT, 0.1(1.2) degree in YAW, 0.2 (1.4) degree in PITCH and 0.1(1.3) degree in ROLL. The couch shifts and AlignRT RTD values exhibited highly agreement except in VRT and PITCH (p value < 0.01), of which the differences were as small as negligible. We did not find any case of patient repositioning that was due to out-of-tolerance setup errors, i.e., 3 mm and 2 degree. The surface guided setup time ranged from 52 to 174 s, and the mean and median time was 97.72 s and 94 s respectively. CONCLUSIONS: The proposed surface guided SRT procedure with open-face mask immobilization is a step forward in improving patient comfort and positioning accuracy in the same process. Minimized initial setup errors and repositioning rate had been achieved with reasonably efficiency for routine clinical practice.

Prognostic significance of albumin-bilirubin score in patients with unresectable hepatocellular carcinoma undergoing combined immunotherapy and radiotherapy.

INTRODUCTION: We aimed to explore the prognostic value of albumin-bilirubin (ALBI) scores in unresectable hepatocellular carcinoma (HCC) treated with combined immune checkpoint inhibitors (ICIs) and radiotherapy (RT). METHODS: Patients with unresectable HCC receiving combined ICI and RT (July 2018 to February 2021) were retrospectively enrolled and analysed. Cox regression modelling was implemented to identify prognostic factors. Survival analysis was performed using the Kaplan-Meier method. Survival was compared using log-rank tests. RESULTS: A total of 38 patients were enrolled. The median follow-up was 16.5 months (range: 6.7-29.9). The objective response rate (ORR) was 28.9%, including complete response in three (7.9%) patients. The median progression-free survival (PFS) was 5.6 months (95% confidence interval (CI): 3.2-8.0), and the median overall survival (OS) was 12.9 months (95% CI: 8.3-17.6). In the multivariate Cox regression analysis, ALBI score and age were identified as independent prognostic factors for PFS and OS. Patients with grade 1 ALBI scores who were ≥53 years of age (the low-risk group) had statistically significantly higher ORRs (50.0% vs. 13.6%) and prolonged median PFS (15.3 vs. 2.7 months) and OS (not reached vs. 10.1 months). Grade 3 haematological toxicities and/or liver function abnormalities occurred in 15 (39.5%) patients; treatment was not interrupted. No grade 4 or higher side effects were observed. CONCLUSION: Combined ICI and RT is an effective modality for treating unresectable HCC with moderate side effects. ALBI scores merits consideration when applying this combined treatment modality. These results should be validated within large cohort studies.

Is Elective Inguinal or External Iliac Irradiation During Neoadjuvant (Chemo)radiotherapy Necessary for Locally A dvanced Lower Rectal Cancer With Anal Sphincter Invasion?

PURPOSE: To investigate the impact of excluding irradiation of inguinal lymph nodes (ILNs) and external iliac lymph nodes (ELNs) during neoadjuvant (chemo)radiotherapy in a locally advanced lower rectal cancer (LALRC) with anal sphincter invasion. METHODS AND MATERIALS: A total of 214 LALRC patients with anal sphincter invasion according to pre-treatment magnetic resonance imaging who underwent neoadjuvant (chemo)radiotherapy followed by surgery between September 2010 and May 2019 were enrolled. ILNs and ELNs were clinically negative pre-treatment and were excluded from irradiation. Failure rates and patterns of ILNs and ELNs and survival were analyzed. Nomograms for predicting ILN and ELN failure risk were also constructed. RESULTS: The median follow-up was 53.3 months. The 3-year failure rates were 3.7% for ILNs and 3.3% for ELNs. Only 1 patient developed isolated ILN failure, and no patient experienced isolated ELN failure. Multivariate analyses demonstrated that lower edge of tumors invaded or located below the dentate line (odds ratio [OR], 7.513; P = .013), high histological grade (OR, 6.892; P = .017), and perineural invasion (OR, 7.111; P = .023) were significantly related to ILN failure. Both perineural invasion (OR, 8.923; P = .011) and high histological grade (OR, 8.129; P = .011) showed a strong correlation with ELN failure. The concordance index of nomograms for predicting ILN and ELN failure risk were 0.842 and 0.880, respectively. The 3-year local recurrence free survival, disease-free survival, and overall survival were 94.6% (95% confidence interval [CI], 91.3%-97.9%), 77.7% (95% CI, 71.8%-83.6%), and 91.9% (95% CI, 87.8%-96.0%), respectively, for the whole cohort. CONCLUSIONS: Excluding ILNs and ELNs from irradiation was associated with an acceptably low failure risk for LALRC invading the anal sphincter. These findings help to refine existing guidelines for clinical target volume delineation of ILNs and ELNs during neoadjuvant (chemo)radiotherapy in rectal cancer.