Cancer treatment reviews最新文献

Clonal hematopoiesis (CH) refers to the expansion of hematopoietic stem and progenitor cells carrying somatic mutations and is increasingly identified in oncology through cell-free DNA testing. Once regarded mostly as a precursor to myeloid neoplasms and a contributor to cardiovascular disease, CH is now recognized as a major determinant of clinical outcomes in patients with cancer. Specific anticancer agents selectively promote the expansion of clones with DNA damage response gene mutations, particularly those with TP53 or PPM1D mutations, which are strongly associated with myeloid neoplasms post cytotoxic therapy (MN-pCT). The extent of clonal growth varies with treatment and, in some cases, may regress once therapy is withdrawn. In addition to therapy-driven clonal selection, inflammatory stress accelerates clonal expansion, creating a self-reinforcing cycle that contributes to atherosclerosis and other inflammation-associated complications. In oncology, CH-derived immune cells can infiltrate the tumor microenvironment and remodel local immunity, influencing tumor growth and treatment response. This tissue-infiltrating form of CH, termed tumor-infiltrating CH, has been associated with inferior survival in some cancer cohorts. Together, these findings establish CH as both a clinical challenge and an opportunity in modern oncology. Dedicated CH clinics and molecular tumor boards are emerging to address its implications for risk stratification, treatment selection, and survivorship care. This review examines the biology and clinical impact of CH in oncology, including its mutational spectrum, clonal evolution, role in MN-pCT, effects on inflammation and the tumor microenvironment, and emerging strategies for risk assessment and patient management.

Background: The integration of immunotherapy (IO) with perioperative chemotherapy represents an advance in locally advanced, resectable gastroesophageal cancers. However, randomized controlled trials (RCTs) have yielded discordant findings with respect to event-free survival (EFS) and overall survival (OS), particularly when differing chemotherapy backbones and IO agents are employed. Understanding the sources and implications of these discrepancies is essential for optimizing treatment strategies. Here, we sought to compare outcomes between perioperative FLOT-based and cisplatin/fluoropyrimidine based regimens when combined with IO, and to evaluate the consistency of FLOT-only arms across major RCTs in locally advanced gastroesophageal cancers.

Methods: RCTs investigating the role of perioperative combination chemotherapy with IO in patients with locally advanced gastro-esophageal cancer were included. Kaplan-Meier curves were digitally reconstructed to obtain individual patient data. Survival analyses incorporated testing for the proportional hazards assumption and were supplemented with piecewise and pooled random-effects analyses to address time-dependent effects and between-study heterogeneity.

Results: No significant difference in EFS was observed between the FLOT-durvalumab and FLOT-pembrolizumab arms (HR = 0.907, 95 %-CI: 0.637-1.290, p = 0.586). FLOT-IO regimens showed superior EFS compared to Cis/fluoropyrimidine-IO (HR = 0.790, 95 %-CI: 0.647-0.966, p = 0.021) as well as FLOT-only (HR = 0.732, 95 %-CI: 0.610-0.878, p < 0.001). While EFS curves for FLOT-only arms converged on long-term follow-up, OS curves diverged, with increased heterogeneity across FLOT-only arms apparent beyond 24 months. Notwithstanding, these analyses should be interpreted with caution due to the lack of patient-level covariate adjustment across trials.

Conclusion: As we await the mature OS data from MATTERHORN, the addition of IO to perioperative FLOT should be considered the preferred standard-of-care in resectable, locally-advanced gastro-esophageal adenocarcinoma. Our comparative analyses suggest that FLOT remains a favored chemotherapy backbone for perioperative IO, but confirmation from future randomized trials with mature survival data is needed.

Background: Local resection (LR) methods for rectal cancer are generally considered in the palliative setting or for patients deemed a high anaesthetic risk. This systematic review and meta-analysis aimed to compare oncological outcomes of LR and radical resection (RR) for early rectal cancer in the context of staging and surveillance assessment.

Methods: A literature search of MEDLINE, Embase and Emcare databases was performed for studies that reported data on clinical outcomes for both LR and RR for early rectal cancer from January 1995 to April 2023. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed. The quality of assessment was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2.0 tool for randomised controlled trials.

Results: Twenty studies with 12,022 patients were included: 6,476 patients had LR and 5,546 patients underwent RR. RR led to an improvement in 5-year overall survival (OR 1.84; 95 % CI 1.54-2.20; p < 0.0001; I² 20 %) and local recurrence (OR 3.06; 95 % CI 2.02-4.64; p < 0.0001; I² 39 %) when compared to LR. However, when staging and surveillance methods were clearly adopted in LR cases, there was an improvement in R0 rates (96.7 % vs 85.6 %), 5-year disease-free survival (93.0 % vs 77.9 %) and overall survival (81.6 % vs 79.0 %) compared to when staging and surveillance was not reported/performed.

Conclusions: LR may be appropriate for selected patients without poor prognostic factors in early rectal cancer. This study also highlights that there is currently no single standardised staging or surveillance approach being adopted in the management of early rectal cancer. A more specified and standardised preoperative staging for patient selection as well as clinical and image-based surveillance protocols is needed.