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To evaluate and validate the minor lymphatic pathway for distant metastases in cervical cancer. This is a retrospective cohort of cervical cancer patients underwent curative concurrent chemoradiotherapy. We used original dataset from 1 university hospital and validation dataset from 3 university hospitals. Lymphadenopathy status in CT imaging was reviewed by radiologist in either the obturator and external iliac nodes (major pathway) or the internal iliac and presacral nodes (minor pathway). We then used Cox regression to adjust for all potential confounders, including paraaortic nodes, T stage, histology, age, total treatment time, total number of nodes, total short axis of nodes. 397 and 384 patients were in the original and validation datasets (median follow-up period, 59.5 month's). The minor pathway was independent prognostic factor in multivariable analysis [HR=2.64; 95%CI=1.07–6.55; P = 0.036] and [HR=14.84; 95%CI=3.15–70.01; P = 0.001] in original and validation datasets, respectively. Whereas, the major pathway was statistically non-significant. Further validation showed that the minor pathway had the highest HR for distant metastases with both the EMBRACE (HR=6.05; 95% CI=1.30–28.08; P = 0.022) and the FIGO 2018 (HR=7.43; 95% CI=2.94–18.78; P <0.001) in the original dataset. A similar result was found with the validation dataset: EMBRACE, HR=30.91; 95% CI=2.78–343.62; P = 0.005; and FIGO 2018, HR=42.41; 95% CI=8.83–203.60; P <0.001.This is the first clinical study to validate that the minor lymphatic pathway was predominantly associated with distant metastases in cervical cancer. This finding should be validated in larger cohort to further integrate in standard staging for prediction of distant metastases. [ABSTRACT FROM AUTHOR]

The Albumin-Bilirubin (ALBI) score offers a simpler, less subjective alternative for evaluating liver function in patients with hepatocellular carcinoma (HCC). However, data on its application in assessing hepatotoxicity post-EBRT are limited. This study aims to establish ALBI score change thresholds as indicators for hepatotoxicity that correlate with a worse survival outcome. The development cohort consisted of 329 HCC patients who received liver-targeted EBRT across two centers from 2008 to 2023. ALBI score change was defined as the difference between baseline and the score within four months post-EBRT. Recursive partitioning analysis was used to identify thresholds that correlate with overall survival (OS), which were evaluated using Cox-regression. Findings were compared to changes in Child-Pugh (CP) score by 2 points (CP+2) and externally validated with a dataset from an independent center (N = 114). Continuous changes in the ALBI score were significantly associated with OS (Hazard Ratio (HR) 2.3, 95% CI = 1.7-2.8). ALBI changes of >0.25 (grade 1) and >0.5 (grade 2) were identified as optimal thresholds. For the development cohort, CP+2 showed superior discriminative performance; however, when stratifying by baseline liver status (Table 1), grade 1 ALBI change demonstrated improved predictive capability in CP-B/C patients (HR 4.4, 95% CI = 2.4-7.8). Overall, these findings were confirmed in the external validation cohort, with grade 2 ALBI score changes being most prognostic for survival (HR 5.0, 95% CI = 2.9-8.5). Multivariable Cox models including CP+2 or ALBI changes and baseline liver status demonstrated higher concordance for ALBI score changes across all datasets. Furthermore, ALBI score changes correlate better with mean liver dose (point-biserial correlation r = 0.29/0.22 for grade 1/2) compared to CP+2 (r = 0.14) ALBI score changes of >0.25 (grade 1) and >0.5 (grade 2) are an alternative to CP+2 to evaluate radiation hepatotoxicity and have the potential to assess significant changes more accurately depending on the patient's baseline liver function. Their increased correlation to dose to the normal liver makes them more suitable for dose-response models aimed at individualizing dose to minimize risk of liver complications after EBRT. [ABSTRACT FROM AUTHOR]

Background: In Thailand, individuals with hepatocellular carcinoma (HCC) who develop portal vein tumor thrombosis (PVTT) have a restricted treatment option because to the extent of the disease, poor underlying liver function, and non-coverage of immuno/targeted therapy. Radiotherapy (RT) plays an increasingly important function in these patients. To investigate the feasibility, efficacy, and adverse event rates, we performed a retrospective analysis of patients with HCC with PVTT who underwent 3-dimensional conformal radiation (3DCRT), intensity-modulated radiation (IMRT), volumetric-modulated radiotherapy (VMAT), and stereotactic body radiotherapy (SBRT) in a single-institution., Objectives: To examine clinical results in terms of overall survival (OS), local control (LC), response of primary tumor and PVTT, hepatic and gastrointestinal adverse reaction, and prognosis variables for OS and LC., Materials and Methods: Between July 2007 and August 2019, non-metastatic HCC with PVTT patients treated with RT were retrospectively reviewed and evaluated., Results: The analysis included data from 160 patients. The mean age of the patients was 60.8 years ((95% CI 58.2-62.0). The median diameter of the tumor was 7.7 cm (range: 1-24.5). 85 (54.5%) individuals had PVTT in the main or first branch. At 1.8-10 Gy per fraction, the mean biologically effective dose (BED) as α/β ratio of 10 was 49.6 (95% CI 46.7-52.5) Gy10. The median survival time was 8.3 (95% CI 6.1-10.3) months. Survival rates at one and two years were 39.6% and 17.1%, respectively. Estimated incidence of local failure using competing risk analysis were 24% and 60% at 1 and 2 years, respectively. The overall response rate was 74%, with an 18.5 percent complete response rate. In multivariate analysis, tumor size, overall response, and radiation dose were all significant prognostic variables for OS. Hepatic unfavorable events of grade 3 and 4 were for 14.1% of the total. There was no occurrences of grade 3-4 gastrointestinal toxicity, either acute or late. Additionally, there were no treatment-related mortality., Conclusions: Advanced RT is regarded as a safe and effective therapeutic option for HCC with PVTT. Overall survival was clearly related to tumor size, radiation dose, and tumor/PVTT response. Individuals with BED 56 Gy10 had significantly better overall survival than patients with BED 56 Gy10. A prospective randomized trial is required to validate these outcomes in order to corroborate these findings., Competing Interests: The authors have declared that no competing interests exist.

Background: Stereotactic body radiation therapy (SBRT) using flattening filter free (FFF) has been commonly used, however, its outcomes and predictive factors in lung tumors are limiting. Thus, we aim to assess the clinical outcomes of this approach and identify factors associated with outcomes in patients with early stage non-small cell lung cancer (NSCLC) and oligometastatic/oligoprogressive lung tumor (OLT)., Methods: Patients who underwent lung SBRT with FFF were retrospectively reviewed. All patients were delivered using volumetric modulated arc therapy (VMAT) technique. The primary outcome was local control (LC). The secondary outcomes were overall survival (OS) and toxicities. We assessed the association between LC and various factors in OLT., Results: From February 2014 to July 2019, ninety-four patients and 129 lesions with median follow-up time of 30 months were included in the analysis. Twenty-six patients with 26 lesions were early NSCLC, while 68 patients with 103 lesions were OLT, 41.7% of which were from colorectal cancers (CRC) and 18.5% were from primary lung cancers. Two-year LC was 88.9% and 85.7% for early NSCLC and OLT, respectively. Two-year OS was significantly higher for early NSCLC than OLT (83.3% vs. 68.7%, P=0.035). In the multivariate analysis for OLT, CRC origin (hazard ratio, HR 10.59, 95% CI: 2.29-48.95, P=0.003) and gross tumor volume (GTV) mean BED 10 ≤147 Gy (HR 5.16, 95% CI: 1.13-23.59, P=0.034) were significantly associated with higher local failure (LF). Most of the acute grade 1-2 toxicities were radiation pneumonitis (26.5%). No grade 3-5 event was observed., Conclusions: This study confirmed the clinical efficacy and safety of lung SBRT using FFF-technique. Our findings support the role of using a high BED 10 regimen to achieve good LC for OLT and the potential role for dose escalation for primary CRC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-3174). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

Purpose: To predict the probability of radiation-induced liver toxicity (RILT) and implement the normal tissue complication probability (NTCP) model-based approach considering confidence intervals (CIs) to select patients for new treatment techniques, such as proton beam therapy, based on a certain NTCP reduction (ΔNTCP) threshold for primary liver cancer patients., Methods and Materials: Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 RILT was scored. The Lyman NTCP models predicting the probability of CTCAE grade ≥2 RILT as a function of the fraction-size adjusted mean liver dose (MLD), using reference fraction size = 2 Gy/fraction and α/β ratio = 2 Gy, were fitted using the maximum likelihood method. At certain combinations of MLDs, ΔNTCP with a CI was evaluated by the delta method., Results: Of the 239 patients, the incidence of CTCAE grade ≥2 RILT was 55% (46% in the Child-Pugh (CP)-A vs. 81% in the CP-B/C, p < 0.001). Among 180 CP-A patients, 40% who had viral hepatitis infections experienced toxicity vs. 32% in the nonhepatitis subgroup. The MLD was 18 Gy in the toxicity group vs. 16.1 Gy in the nontoxicity group (p = 0.002). The estimated NTCP model parameters specific to the patient subgroups and the ΔNTCP with CI assuming a particular CP classification and viral hepatitis infection status were considerably different which possible changed treatment decision., Conclusions: Patients with CP-A and viral hepatitis infection or CP-B/C cirrhosis had greater susceptibility to CTCAE grade ≥2 RILT. The estimated NTCP and ΔNTCP for individual patients along with a consideration of uncertainties improve the reliability of the NTCP model-based approach., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)