OBJECTIVE:Pathologic complete response (pCR) after neoadjuvant therapy predicts favorable outcomes in esophageal squamous cell carcinoma (ESCC). In this era of neoadjuvant immunochemotherapy (nICT), the prognosis of patients achieving nICT-induced pCR remains unclear. This study aimed to characterize recurrence patterns and identify prognostic factors in this population. METHODS:A multicenter retrospective cohort study was conducted across 26 Chinese centers from 2019 to 2023. Patients with ESCC who underwent surgery after nICT and achieved pCR were included. Prognostic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated using Cox regression analysis. RESULTS:Among 2135 patients receiving nICT, 474 (22.2%) achieved pCR. After a median follow-up of 32.8 months, 60 patients (12.7%) experienced recurrence, with a median interval of 17.8 months (interquartile range, 8.7-26.7) after surgery. Most recurrences (75%) occurred within 2 years, predominantly as distant metastases (63.3%), with the lung being the most common site. The 2-year RFS and OS were 89.6% and 92.1%, respectively. Advanced clinical nodal stage (cN2-3) was identified as an independent prognostic factor for inferior RFS (adjusted hazard ratio, 1.83; 95% CI, 1.10-3.05; P = .02) but not OS, whereas adjuvant treatment was not associated with improved survival (adjusted hazard ratio, 1.29; 95% CI, 0.69-2.42; P = .42). CONCLUSIONS:Patients with ESCC achieving pCR after nICT exhibited excellent short-term survival but a persistent risk of distant recurrence. Advanced clinical nodal stage is associated with higher recurrence risk, which warrants further validation. Risk-adapted postoperative management may be preferable to routine adjuvant treatment.
PURPOSE:The neoCARHP aimed to investigate the efficacy and safety of investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel) plus trastuzumab and pertuzumab, with carboplatin (TCbHP) or without carboplatin (THP), in stage II and III human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS:The neoCARHP was a multicenter, randomized, phase III, noninferiority study. Eligible patients were women age 18 years or older with previously untreated, stage II and III, HER2-positive invasive breast cancer. Patients were randomly assigned (1:1) to receive six 3-week cycles of TCbHP or THP. The primary end point was pathologic complete response (pCR) rate in the breast and axilla (ypT0/is ypN0) in the modified intention-to-treat (mITT) population (all randomly assigned patients receiving at least one dose of study treatment). Safety was evaluated in all patients who received any study treatment. RESULTS:Between April 30, 2021, and August 27, 2024, 774 patients were randomly assigned and 766 were included in the mITT population (382 in THP and 384 in TCbHP). pCR was achieved in 245 (64.1% [95% CI, 59.1 to 69.0]) patients in the THP group and 253 (65.9% [60.9-70.6]) in the TCbHP group (absolute difference, -1.8% [95% CI, -8.5 to 5.0]; odds ratio, 0.93 [95% CI, 0.69 to 1.25]; Pnoninferiority = .0089). The THP group had fewer grade 3 and 4 adverse events (20.7% v 34.6%) and serious adverse events (1.3% v 4.7%) than the TCbHP group. The most common grade 3 and 4 adverse events with THP were neutropenia (6.8% v 16.4% with TCbHP), leukopenia (5.5% v 14.8%), and diarrhea (2.6% v 4.2%). No treatment-associated deaths occurred. CONCLUSION:THP provided noninferior pCR rates and improved tolerability compared with TCbHP. Omitting carboplatin may be applicable in HER2-positive breast cancer.
PURPOSEThe neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment. However, which patients deserve most from the nCT need further clarify. This trial aimed to assess the non-inferiority of nCT with capecitabine plus oxaliplatin (CAPOX) versus nCRT with capecitabine in LARC with uninvolved mesorectal fascia (MRF).METHODSPatients with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT group) or CRT with concurrent Capecitabine (nCRT group). The primary end point is 3-year locoregional recurrence-free survival (LRRFS). Secondary end points, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and adverse events (AEs), were also reported.RESULTSA total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n = 300; nCRT, n = 289). LRRFS was analyzed with a median follow-up of 48 months. 3-year LRRFS was 97.4% (95% CI, 95.5 to 99.3) in the nCRT group and 96.3% (95% CI, 94.0 to 98.6) in the nCT group, resulting in a hazard ratio (HR) of 1.40 (95% CI, 0.53 to 3.68). The nCT and nCRT achieved similar 3-year DFS (89.2% v 87.9%; HR, 0.88 [95% CI, 0.54 to 1.44]) and 3-year OS (95.0% v 94.1%; HR, 0.86 [95% CI, 0.42 to 1.76]). The nCT group showed a lower incidence of grade 2 to 4 long-term AEs (16.0% v 26.3%, P = 0.002) and proctitis (33.6% v 41.7%, P = 0.049) compared with nCRT group.CONCLUSIONSThe non-inferiority of nCT was not confirmed with a very low incidence of local recurrence in both group. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.
Fecal Microbiota Transplantation (FMT) involves the transfer of gut microbiota from healthy donors to recipients, aiming to reestablish microbial equilibrium within the gastrointestinal tract. The human gut harbors a complex and diverse microbial ecosystem, comprising bacteria, viruses, and fungi, that is essential for maintaining intestinal homeostasis. Emerging evidence indicates a strong association between gut microbial dysbiosis and the pathogenesis of Ulcerative Colitis (UC). FMT has been shown to modulate microbial composition, alter immune signaling pathways, enhance intestinal barrier function, and influence the production of proinflammatory mediators, thereby affecting disease progression. This review critically examines the efficacy, safety, modulatory factors, combination therapies, and predictive strategies associated with FMT in the context of UC. The findings suggest that FMT represents a highly promising therapeutic modality for UC. Overall, this review aims to provide a comprehensive and impartial synthesis of current knowledge regarding FMT, offering deeper insights into its therapeutic potential and clinical applicability in UC management.
To evaluate the prognostic value of nine non-invasive fibrosis scores in predicting all-cause and cardio-cerebrovascular disease (CCD) mortality among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). This study included 4,377 U.S. adults with MASLD, identified using the NHANES 1999–2018 fasting subsample, with follow-up through December 2019. The nine fibrosis scores evaluated were the non-alcoholic fatty liver disease (NAFLD) fibrosis score, Fibrosis-4 (FIB-4), BARD score, aspartate transaminase-to-platelet ratio index (APRI), Forns score, hepatic steatosis index, NAFLD liver fat score, Steatosis-associated Fibrosis Estimator (SAFE) score, and metabolic dysfunction–associated fibrosis 5 (MAF-5). Kaplan-Meier survival curves, Cox proportional hazards models, and random survival forest (RSF) models were used to assess associations and predictive performance of these scores on mortality outcomes. The study cohort had a median age of 52.7 years and was 48.6
