International Journal of Clinical Oncology最新文献

The incidence and mortality of non-small cell lung cancer (NSCLC) remain high in China. Recently, several studies have shown a complex correlation between microflora and NSCLC. Compared to patients with healthy/benign lung disease, patients with NSCLC have distinct microflora within the tumor, airways as well as intestines. NSCLC can be diagnosed with the assistance of characteristic microflora and circulating microbial DNA. Microflora changes can affect the efficacy of immunotherapy and treatment-related adverse effects during lung cancer therapy. Modulating microflora imbalance through antibiotics/probiotics nebulization, oral probiotic, prebiotics, and dietary modifications can balance microflora and enhance the effectiveness of immunotherapy. Therefore, microbe-specific testing and targeted therapy have the potential to become a new method in the diagnosis and treatment of NSCLC. This review will explore the molecular mechanisms by which microbes influence lung cancer, and summarize the latest research advances in microbial biomarkers and therapeutic approaches for NSCLC.

Background: In the EMBRACE study, eribulin (ERI) monotherapy improved the overall survival (OS) of patients with HER2-negative advanced breast cancer (HER2-negative ABC). A post hoc analysis identified the baseline absolute lymphocyte count (ALC) as a predictive marker in the ERI arm; nevertheless, factors affecting post-ERI had not been well explored.

Patients and methods: We retrospectively analyzed clinical data of 370 patients receiving ERI for HER2-negative ABC between July 2011 and June 2024 across 3 institutions. Clinical data, including ALC, were extracted. Statistical analyses included the log-rank test and Cox hazard model. The OS was defined as survival from ERI initiation (OS1) and from ERI termination (OS2).

Results: Identical to the previous report, the OS1 was significantly improved in patients with ALC ≥ 1000/μL at ERI initiation and with ER-positive. Regarding the OS2, we identified independent factors which significantly improve the OS2 as follows: ALC ≥ 1000/μL at the termination of ERI, ≥ 120 days time-to-treatment-discontinuation of ERI, and first-line use of ERI. Furthermore, ALC was maintained during ERI therapy, whereas it significantly decreased in other regimens (P < 0.001).

Conclusion: An ALC ≥ 1000/μL at ERI completion was associated with an improved post-ERI OS (OS2). It is suggested that not only the factors at the initiation of ERI, but also the immunological status at the end of ERI, may have prognostic value after ERI.

Background: Until 1995, patients with newly diagnosed germinoma received 40-60 Gy of radiation to the primary site with or without chemotherapy (regimen A). After 2000, treatment shifted to chemotherapy followed by 24 Gy of whole-ventricle radiation therapy (WVRT) (regimen B). This study compares long-term intelligence outcomes between the two treatment regimens.

Methods: This retrospective analysis included 151 patients diagnosed with germinoma between 1983 and 2021. Intelligence was assessed using the Wechsler Adult Intelligence Scale (revised or 3rd edition) and the Wechsler Intelligence Scale for Children (3rd edition). Patient backgrounds were also collected.

Results: A total of 55 and 69 patients were treated with regimens A and B, respectively. The number of patients who underwent at least one longitudinal neurocognitive assessment was 35 and 29 for regimen A and 53 and 22 for regimen B, respectively. The median interval from initial treatment to the last neurocognitive assessment was 120 months. In the longitudinal intelligence assessments, the median intervals were 58 months from treatment to the first evaluation and 83 months from the first to the final assessment. Full-Scale Intelligence Quotient (FSIQ) scores declined in regimen A but were maintained in regimen B according to analysis of covariates and generalized linear mixed model analysis.

Conclusion: Chemotherapy followed by 24 Gy of WVRT appears to be associated with a smaller decline in FSIQ over a long-term follow-up.

Background: While simple hysterectomy is the standard treatment for adenocarcinoma in situ (AIS) and stage IA1 cervical cancer, minimally invasive surgery has been increasingly adopted. However, evidence on the safety and efficacy of total laparoscopic hysterectomy (TLH) for these conditions remains limited. We compared the safety and efficacy of TLH and total abdominal hysterectomy (TAH) in patients undergoing simple hysterectomy following diagnostic conization.

Methods: We conducted a multicenter retrospective study of 196 patients with cervical intraepithelial neoplasia grade 3 (CIN3), AIS, or stage IA1 cervical cancer who underwent simple hysterectomy following diagnostic conization. Patients were divided into TLH and TAH groups, and intraoperative and postoperative complications and oncologic outcomes were compared.

Results: Operative time was significantly longer in the TLH group, whereas intraoperative blood loss was lower and postoperative hospital stay shorter. No significant difference was noted in severe complication rates, although their patterns varied between groups. Recurrence occurred in one patient (0.5%), a case of CIN3 at the vaginal cuff in the stage IA1 TAH group. No recurrences were observed in patients with AIS or stage IA1 disease in the TLH group.

Conclusions: TLH following diagnostic conization for AIS or stage IA1 cervical cancer demonstrated oncologic efficacy comparable to TAH, with a favorable safety profile. TLH may be a reasonable treatment option for carefully selected patients.

Background: Cisplatin-based concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer; however, its nephrotoxicity and gastrointestinal toxicity often limit treatment eligibility and completion. Nedaplatin, a cisplatin analogue with reduced renal and gastrointestinal toxicity, has been increasingly used in East Asia, but its comparative efficacy and safety in cervical cancer have not been comprehensively evaluated.

Methods: We systematically searched MEDLINE, Embase, CENTRAL, CNKI, Ichushi Web, ICTRP, and ClinicalTrials.gov for randomized controlled trials comparing nedaplatin versus cisplatin-based CCRT. The primary efficacy outcome was all-cause mortality at 3 years, and the primary safety outcome was renal toxicity. Secondary outcomes included mortality at 1 and 5 years, progression or mortality, hematologic and gastrointestinal toxicities, liver dysfunction, and quality of life. Random-effects meta-analyses were performed using risk ratios.

Results: Seventeen trials met the eligibility criteria. All-cause mortality at 3 years did not differ significantly between the groups (RR 0.88; 95% CI 0.51-1.51; I² = 0%). Nedaplatin significantly reduced renal toxicity (RR 0.25; 95% CI 0.20-0.31; I² = 0%). Short-term outcomes favored nedaplatin, including lower 1 year mortality (RR 0.61; 95% CI 0.40-0.93) and fewer 1 year progression or mortality events (RR 0.63; 95% CI 0.44-0.91). The incidences of anemia and severe nausea/vomiting were also lower with nedaplatin. No eligible study assessed quality of life.

Conclusion: Nedaplatin showed fewer adverse effects and comparable or improved short-term outcomes compared with cisplatin. These findings support nedaplatin as a potential alternative for patients who are cisplatin-intolerant or frail. Confirmation in large, high-quality trials with long-term follow-up and patient-reported outcomes is warranted.

Background: Claudin-18 isoform-2 (CLDN18.2) is a novel biomarker and therapeutic target for gastric cancer (GC). It may exhibit the intratumoral heterogeneity and varying expressions between biopsy and surgically resected specimens as well as pre- and post-chemotherapy, which could impact patient selection for the targeted agents.

Methods: CLDN18.2 expression was immunohistochemically evaluated in pretreatment biopsy and surgically resected specimens from 183 patients with pT2-T4 GC who underwent upfront gastrectomy. The intratumoral heterogeneity was evaluated by classifying the distribution of CLDN18.2 positive cells as superficial, invasive-front, or random pattern. Furthermore, a separate cohort of 38 patients who underwent neoadjuvant chemotherapy without zolbetuximab were analyzed to compare the pre- and post-treatment CLDN18.2 status.

Results: CLDN18.2 positivity was observed in 31% (56/183) of patients. Among the 93 patients with 2 + /3 + expression in ≥ 10% of the tumor cells, 81 (87%) had heterogeneous expression patterns, including superficial (n = 46), random (n = 24), and invasive-front (n = 11) patterns. The overall biopsy-surgery concordance rate was 86% (157/183), but it decreased to 73% (59/81) in patients with a heterogeneous expression pattern. Notably, the concordance rate was particularly low in the superficial pattern, at only 65% (30/46). Among the 38 patients who underwent neoadjuvant chemotherapy, only 4 of 11 initially CLDN18.2-positive cases remained positive after treatment, although the overall concordance rate was 82% (31/38).

Conclusion: The CLDN18.2 expression demonstrated an acceptable concordance between biopsy and surgically resected specimens. However, high prevalence of heterogeneous expression and tendency for CLDN18.2 positivity to shift to negativity following chemotherapy existed.

Background: To determine the optimal extent of pelvic lymph node dissection in bladder cancer, evaluating the prognostic relevance of nodal sub-staging, and assessing the feasibility of sentinel lymph node biopsy and omission of contralateral dissection.

Methods: This retrospective study included 180 patients undergoing laparoscopic or robot-assisted radical cystectomy. Sentinel lymph node detection was assessed in 30 cases as a pilot. The obturator region was defined according to lymphatic drainage patterns. The prognostic impact of nodal sub-staging was evaluated using Kaplan-Meier and Cox proportional hazards models. Laterality of tumor location and node metastasis was also analyzed.

Results: Sentinel lymph node biopsy demonstrated a 63% detection rate with a 1.6% false-negative rate. Nodal metastases were observed in 8.9% of pN1 and 8.3% of pN2-3 cases, predominantly in the obturator region (87.5% and 100%, respectively). Lymph node metastases were most frequently located in the obturator region, including 87.5% of stage pN1 and 100% of stage pN2-3 cases. Cancer-specific survival was significantly better in pN1 than in pN2-3 cases (median 61 vs. 7 months, p < 0.001). Cox proportional hazards regression models identified pN2-3 as the strongest prognostic factor (HR for CSS: 25.4). Ipsilateral nodal metastasis was observed in 87.5% of lateral wall tumors.

Conclusions: Although sentinel lymph node biopsy demonstrated limited utility, the obturator region appears to represent the optimal diagnostic target for nodal metastasis. In pN1 disease, this region may be therapeutic, resembling sentinel nodes and showing limited spread with better prognosis than pN2-3 disease.

Background: Sarcopenia is a critical comorbidity in esophageal cancer patients undergoing neoadjuvant therapy (NAT), linked to poor surgical outcomes and survival. However, its reported prevalence varies widely, and a comprehensive synthesis of evidence is lacking.

Objective: To systematically evaluate and quantify the prevalence of the sarcopenia disease in in patients known to be diagnosed with esophageal cancer and receiving preoperative neoadjuvant therapy and examine its association with clinical outcomes.

Methods: Following PRISMA guidelines 2020, This systematic review and meta-analysis that was registered on PROSPERO (CRD420251109294), provides a comprehensive search through PubMed, SCOPUS, Web of Science, and the Cochrane Library to identify research papers reporting sarcopenia prevalence in esophageal cancer patients undergoing neoadjuvant chemotherapy or chemoradiotherapy. Pooled prevalence estimates and outcome associations were calculated using random-effects models. Subgroup and sensitivity analyses were performed to explore heterogeneity, and study quality was assessed using the Newcastle-Ottawa Scale.

Results: Twenty-six research studies comprising 3298 patients were included. The pooled prevalence of sarcopenia following neoadjuvant therapy was 48% (95% CI 38-58%), with considerable heterogeneity (I² = 95.7%). Sarcopenia was significantly associated with worse overall survival (HR: 2.10; 95% CI 1.72-2.57) but showed no statistically significant association with recurrence-free survival or postoperative complications. Most studies were of moderate to high quality, though differences in diagnostic criteria and assessment timing contributed to heterogeneity.

Conclusions: Sarcopenia is highly prevalent among patients with esophageal cancer undergoing neoadjuvant therapy. Although sarcopenia was consistently associated with poorer overall survival, these findings are derived from heterogeneous definitions, variable assessment timing, and unadjusted outcome analyses, and should therefore be interpreted as associative rather than causal. Standardized diagnostic criteria, incorporation of muscle strength assessment, and prospective studies are required in future research.

Colorectal cancer remains one of the leading causes of cancer-related mortality worldwide, and early detection is essential for improving outcomes. Advances in liquid biopsy technologies and microbiota research have shed new light on diagnostic and therapeutic strategies for colorectal cancer. Notably, circulating tumor DNA methylation has emerged as a sensitive and specific biomarker for early detection, recurrence surveillance, and treatment monitoring. Recent progress in methylation-based assays, including stool- and plasma-derived approaches, highlights their potential clinical utility; however, challenges remain in detecting minimal residual disease at the earliest stages. Parallel to these developments, the gut microbiota has been recognized as a critical modulator of colorectal carcinogenesis and treatment response. Specific bacterial species, such as Fusobacterium nucleatum, polyketide synthase-positive Escherichia coli, and enterotoxigenic Bacteroides fragilis, have been implicated in tumor initiation and progression through epigenetic reprogramming, including aberrant DNA methylation. Microbial metabolites, particularly short-chain fatty acids such as butyrate, influence DNA methyltransferase activity and histone modifications, linking microbial ecology to the host epigenome. Microbiota composition also affects responses to chemotherapy, radiotherapy, and immunotherapy, underscoring its potential as a predictive biomarker and therapeutic target. Integrating circulating tumor DNA methylation profiling with microbiota analysis provides a promising strategy for personalized colorectal cancer management, combining early detection with treatment outcome prediction. This review summarizes the current evidence and future directions at the interface of DNA methylation and the gut microbiota, emphasizing their synergistic role as composite biomarkers in precision oncology.

Background: Pulmonary metastasectomy (PM) is a treatment for lung metastases of bone and soft tissue sarcomas. However, the criteria for repeat PM after a second pulmonary recurrence remain unclear. We evaluated prognostic significance of the second disease-free interval (DFI-2; from initial PM to second pulmonary recurrence) and defined the criteria for repeat PM.

Methods: We retrospectively reviewed 60 patients who underwent PM for bone or soft tissue sarcomas (2000-2024), among whom 31 experienced a second pulmonary recurrence. Overall survival (OS) was analyzed using the Kaplan-Meier method and log-rank test. Cox proportional hazards models were used to identify independent prognostic factors. OS was compared between patients with DFI-2 < 6 and ≥ 6 months. The DFI-2 cut-off was determined to maximize Harrell's concordance index for OS.

Results: The median patient age, metastasis number, and metastasis size were 55 years, two, and 1.4 cm. The 5-year OS rate was 41.3%. Multivariable analysis identified DFI-1 < 12 months, ≥ 3 metastases, and incomplete resection as independent adverse factors. Among the 31 patients who developed second pulmonary recurrence, 16 underwent repeat PM, achieving the 5-year OS of 39.5%. Patients with DFI-2 ≥ 6 months had significantly better OS (median, 56.6 vs. 14.4 months, p < 0.001) and were more likely to undergo repeat PM (73.3% vs. 31.3%). All patients with DFI-2 < 6 months who underwent repeat PM experienced recurrence within 6 months.

Conclusions: DFI-2 ≥ 6 months predicts a favorable prognosis and may be a practical criterion for selecting candidates for repeat PM in bone and soft tissue sarcomas.