Intraoperative blood transfusion does not impact overall and recurrence-free survival after curative hepatectomy for hepatocellular carcinoma: A propensity-score-matched and inverse probability of treatment-weighted study.

INTRODUCTION: Our primary objective was to determine if receiving intraoperative blood transfusion was a significant prognostic factor for overall and recurrence-free survival after curative resection of hepatic cellular carcinoma (HCC). METHODOLOGY: Between 2001 and 2018, 1092 patients with histologically proven primary HCC who underwent curative liver resection were retrospectively reviewed. Primary study endpoints were recurrence-free survival (RFS) and overall survival (OS). The main analysis was undertaken using propensity-score matching (PSM) to minimize confounding and selection biases in the comparison of patients with or without transfusion. RESULTS: There were 220 patients who received and 666 patients who did not receive intraoperative blood transfusion. The PSM cohort consisted of 163 pairs of patients. After PSM, the only perioperative outcome that appeared to significantly affect whether patients would receive blood transfusion was median blood loss (p = 0.001). In the PSM cohort, whether patients received blood transfusion was neither associated with OS (p = 0.759) nor RFS (p = 0.830). When the volume of blood transfusion was analyzed as a continuous variable, no significant dose-response relationship between blood transfusion volume and HR for OS and RFS was noted. CONCLUSION: Intraoperative blood transfusion had no significant impact on the survival outcomes in patients who receive curative resection in primary HCC.

Adjuvant Capecitabine Following Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Clinical Trial.

Importance: Induction or adjuvant chemotherapy with concurrent chemoradiotherapy (CCRT) are first-line treatment options for treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Adjuvant platinum regimens are, however, poorly tolerated, highlighting the unmet need for an efficacious, tolerable adjuvant regimen. Objective: To investigate the efficacy and safety of adjuvant capecitabine with CCRT for the treatment of patients with LA-NPC. Design, Setting, and Participants: This open-label randomized clinical trial recruited patients from March 31, 2014, to July 27, 2018, at 3 institutions in China, with at least 3 years of follow-up. The data collection cutoff date was February 9, 2022. Eligibility included stage III-IVb nasopharyngeal carcinoma and at least 1 of the following: T3-4N2 or T1-4N3; plasma Epstein-Barr virus DNA titer higher than 20 000 copies/mL; primary gross tumor volume larger than 30.0 cm3; fluorodeoxyglucose F 18 positron emission tomography/computed tomography maximum standard uptake value of the primary gross tumor volume larger than 10.0; or multiple nodal metastases and any larger than 4.0 cm. Interventions: Patients were randomly assigned 1:1 to receive either capecitabine (1000 mg/m2 twice daily for 14 days every 3 weeks for 8 cycles) or observation following CCRT (100 mg/m2 cisplatin every 3 weeks for 2 to 3 cycles, depending on duration of radiotherapy). Main Outcomes and Measures: Failure-free survival in the intention-to-treat cohort was assessed using Kaplan-Meier survival curves compared with the log-rank test. Unstratified Cox proportional hazards regression models were used to estimate hazard ratios, with corresponding 95% CIs based on the Wald test. Results: There were 180 patients enrolled (median [IQR] age, 47 [40-55] years; 143 [79.4%] men). Among 90 patients in the capecitabine group, 76 (84.4%) had at least 2 high-risk factors; among 90 patients in the control group, 80 (88.9%) had at least 2 high-risk factors. All patients completed CCRT, except 1 patient in the capecitabine group who received 1 cycle of cisplatin. Of the 90 patients in the capecitabine group, 85 (94.4%) received capecitabine, with 71 (78.9%) completing 8 cycles. With a median (IQR) follow-up of 58.0 (49.5-80.1) months, 18 events were recorded in the capecitabine group vs 31 events in the control group. Failure-free survival was improved with adjuvant capecitabine (3 years, 83.3% vs 72.2%; 5 years, 78.5% vs 65.9%; hazard ratio, 0.53 [95% CI, 0.30-0.94]; P = .03). The incidence of grade 3 treatment-related adverse events (TRAEs) was higher in the capecitabine group than in the control group (54 of 90 patients [60.0%] vs 46 of 90 patients [51.1%]). Treatment-related adverse events included xerostomia (17 [18.9%] vs 9 [10.0%] patients), mucositis (21 [23.3%] vs 15 [16.7%] patients), and anorexia (8 [8.9%] vs 4 [4.4%] patients). The incidence of grade 3 delayed treatment-related adverse events was comparable in both groups (9 of 83 [10.8%] vs 7 of 81 [8.6%] patients). Conclusions and Relevance: In this randomized clinical trial, adjuvant capecitabine at the full dose following CCRT was well tolerated and improved failure-free survival among patients with LA-NPC and high-risk factors. Further investigations assessing optimal dose and duration are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02143388.

Effect of age on the short- and long-term outcomes of patients undergoing curative liver resection for HCC.

BACKGROUND: Few studies have evaluated the outcomes of curative liver resection (LR) in octogenarian patients, analysed cancer-specific survival (CSS) with HCC-related death or explored the age-varying effect of HCC-related death in elderly patients undergoing LR. We aim to determine the effect of age on the short and long-term outcomes of LR for HCC. METHODOLOGY: Between 2000 and 2018, 1,092 patients with primary HCC who underwent LR with curative intent were retrospectively reviewed. The log-rank test and Gray's test were used to assess the equality of survivor functions and competing risk-adjusted cumulative incidence functions between patients in the three age categories respectively. Regression adjustment was used to control for confounding bias via a Principal Component Analysis. Quantile, Firth logistic, Cox, and Fine-Gray competing risk regression were used to analyse continuous, binary, time-to-event, and cause-specific survival respectively. Restricted cubic splines were used to illustrate the dose-effect relationship between age and patient outcomes. RESULTS: The study comprised of 764 young patients (<70 years), 278 septuagenarians (70-79 years old) and 50 octogenarians (≥80 years). Compared to young patients, octogenarians had significantly lower 5-year OS(62.1% vs 37.7%, p < 0.001). However, there was no significant difference in 1-year RFS(73.1% vs 67.0%, p = 0.774) or 5-year CSS (5.4% vs 15.2%, p = 0.674). Every 10-year increase in age was significantly associated with an increase length of stay (p < 0.001), postoperative complications (p = 0.004) and poorer OS(p = 0.018) but not significantly associated with major complications (p = 0.279), CSS(p = 0.338) or RFS(p = 0.941). CONCLUSION: Age by itself was associated with OS after LR for HCC but was not a significant risk factor for HCC-related death.

Efficacy, toxicity, and quality-of-life outcomes of ultrahypofractionated radiotherapy in patients with localized prostate cancer: A single-arm phase 2 trial from Asia.

AIMS: Ultra-hypofractionated radiotherapy (UHF-RT) is widely utilized in men with localized prostate cancer (PCa). There are limited data in Asian cohorts. We report the outcomes of a single-arm, phase II trial of UHF-RT from an Asian center. METHODS: We recruited men with histologically confirmed, nonmetastatic localized PCa. UHF-RT regimens were 36.25 Gy (Cohort A) and 37.5 Gy (Cohort B) delivered in five fractions every other day over 1.5-2.5 weeks. Primary endpoint was physician-scored late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs). Quality-of-life (QoL) was assessed by Expanded Prostate Cancer Index Composite (EPIC) at baseline, 1- and 2-year post-UHF-RT. RESULTS: Between March 2014 and August 2019, 105 men were recruited; four were subsequently excluded from analysis. Median age was 68.0 (Interquartile range (IQR): 63.8-73.0) years. 26 (24.8%) and 68 (64.8%) men had NCCN-defined low-and intermediate-risk PCa, respectively. No late ≥G3 GU or GI toxicities were reported in both cohorts. Peak incidence of acute ≥G2 GU AEs at 14 days post-UHF-RT was 23.6% (17/72) and 24.0% (6/25) in Cohorts A and B, respectively; ≥G2 GI AEs were observed in 9.7% (7/72) and 36.0% (9/25), respectively. Late ≥G2 GU and GI AEs occurred in 4.7% and 3.1% of Cohort A patients, and 5.0% in Cohort B at 12 months, with no AEs at 24 months. EPIC scores changed minimally across all domains. At a median follow-up of 44.9 months, we recorded one (1.3%) biochemical relapse by the Phoenix criteria (Cohort A). CONCLUSION: UHF-RT is well tolerated in Asian men and can be a recommended fractionation schema for localized PCa.