Journal of Cancer Research and Clinical Oncology最新文献

Purpose: This study investigated the anatomical and pathological mechanisms of immature squamous metaplastic epithelium in Weber's glandular ducts at the tongue base in human papillomavirus (HPV)-independent oropharyngeal squamous cell carcinoma (OPSCC).

Methods: An analysis of 80 tongue base carcinoma cases clarified the anatomical connection to Weber's glands. Histological and immunohistochemical studies of these glandular ducts identified areas susceptible to cancer. A mouse model using 4-nitroquinoline-N-oxide was employed to simulate carcinogenic development.

Results: 42.5% of cases were linked to Weber's glands, with 20 directly connected to glandular ducts. Only one case was p16-positive, indicating that carcinogenesis in Weber's glandular ducts is largely non-HPV-mediated. The transformation zone with immature squamous metaplastic epithelium and CK17/p63+ reserve cells at Weber's glandular ducts were found, akin to cervical cancer susceptibility. CK17 studies indicated that the immature epithelium had "compromised barrier function" and "hyperproliferative activity", accelerating mutation and carcinogenesis. An atypical opening of the Weber's gland exposed the ductal epithelium to oncogenic factors, increasing carcinogenic risk. A mouse model confirmed the progression from metaplasia to carcinoma and the oncogenic potential of Weber's glandular ducts.

Conclusions: Weber's glandular ducts are an important origin of HPV-independent OPSCC. The first animal model replicating this process offers an essential platform for studying HPV-independent OPSCC.

Background: Acupuncture is a method of traditional Chinese medicine that has been adapted in the Western world. The objective of this study was to critically assess the evidence presented in randomized controlled trials (RCTs) about the effectiveness of acupuncture on fatigue in cancer patients.

Method: In April 2024 a systematic search was conducted searching five electronic databases to find studies concerning the use, effectiveness and potential harm of acupuncture therapy on cancer patients.

Results: From all (1599) search results, 15 studies with 1346 patients were included. Acupuncture methods varied (e.g., traditional-, electro-, mind-regulating and ATAS-acupuncture) and were compared to sham acupuncture, usual care, or other controls. Studies comparing acupuncture to sham acupuncture reported mixed results: while some found significant effects on cancer-related fatigue, others found no advantages. Studies comparing acupuncture to usual care or waitlist controls often reported positive effects. However, the reliability of these findings is limited, as 14 of 15 studies were rated as "high risk of bias" by the RoB-2 tool due to issues like insufficient blinding and incomplete data analysis. Only one study, with low risk of bias, showed a significant reduction in fatigue with acupuncture compared to sham acupuncture (p < 0.001). GRADE evaluation also showed very low certainty of evidence.

Conclusion: The heterogenous results and methodological limitations of the existing studies prevent us from drawing definitive conclusions about the effectiveness of acupuncture in the treatment of cancer-related fatigue. Despite the inclusion of 15 studies, the overall evidence remains insufficient due to widespread problems in study design and inconsistent results. This analysis highlights the need to use more rigorous designs and more comprehensive assessment tools in future studies to better understand the role of acupuncture in the management of fatigue after cancer treatment.

Purpose: High-dose ifosfamide (HD-IFO) remains an effective regimen for advanced bone and soft tissue sarcomas, but predictors of long-term benefit are poorly defined. This study evaluated clinical outcomes and prognostic factors using machine learning-assisted modeling in sarcoma patients treated with HD-IFO at a high-volume academic center.

Methods: We retrospectively analyzed 26 patients with histologically confirmed bone or soft tissue sarcoma who received HD-IFO (≥ 12 g/m² per cycle) between 2015 and 2025. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared across RECIST response categories using log-rank testing. Prognostic factors were identified using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with leave-one-out cross-validation. The top three variables were entered into multivariable logistic regression to estimate odds ratios (ORs) for OS > 24 months.

Results: Median PFS and OS from start of HD-IFO was 6.6 months (95% CI 4.4-9.8) and 24.7 months (95% CI, 14.7-34.2), respectively. Patients with progressive disease (PD) had significantly shorter OS than those with partial response (PR; p = 0.0047) or stable disease (SD; p = 0.0485). LASSO identified intervention prior to progression, prior tumor control ≥ 12 months, and absence of metastases as the strongest predictors for OS > 24 months. In multivariable analysis, intervention prior to progression (OR 24.18, 95% CI 1.81-1001.27, p = 0.037) and prior tumor control ≥ 12 months (OR 25.39, 95% CI 2.1-1008.9, p = 0.030) independently predicted OS > 24 months.

Conclusion: HD-IFO provides durable disease control in selected sarcoma patients, particularly those with sustained prior tumor control and intervention prior to progression.

Background: Circulating tumor DNA (ctDNA) shows promise for predicting recurrence in colorectal cancer liver metastases (CRLM) patients. We investigated the prognostic value of perioperative ctDNA, particularly 2 week postoperative minimal residual disease (MRD), in CRLM patients undergoing liver resection.

Methods: We prospectively collected blood samples from 94 CRLM patients before (after neoadjuvant therapy, if any) and 2 weeks after liver metastasectomy. 63 patients had both assessments. ctDNA status and variant allele fraction (VAF) were determined using targeted sequencing. Disease-free survival (DFS) was analyzed using Kaplan-Meier curves and Cox regression. Baseline characteristics were compared based on ctDNA status.

Results: Preoperative ctDNA status was not associated with DFS (p = 0.77). However, postoperative 2 week MRD status was a strong predictor; MRD-positive patients (N = 31) had significantly worse DFS than MRD-negative patients (N = 32) (p < 0.001). In multivariate analysis, postoperative MRD positivity (HR = 5.52, 95% CI: 2.46-12.39, p < 0.001) and multiple metastases (HR = 3.42, 95% CI: 1.42-8.25, p = 0.006) were independent predictors of DFS. Postoperative MRD positivity showed a trend towards association with higher primary tumor T stage (p = 0.095). Among MRD-negative patients, a higher maximum absolute VAF change (MaxΔVAF) suggested potentially worse DFS (p = 0.053), while it held no prognostic value in MRD-positive patients (p = 0.99).

Conclusions: Postoperative 2 week ctDNA (MRD) status is a potent, independent predictor of DFS in resected CRLM patients and outperforms preoperative ctDNA. Early MRD assessment should be considered for risk stratification and may help guide adjuvant treatment decisions. VAF dynamics might further refine prognosis, especially in MRD-negative cases.

Purpose: To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Previously reported FOCUS study results indicated melphalan/HDS treatment provides a clinically meaningful response rate and favorable benefit-risk ratio in patients with unresectable mUM.

Methods: Patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) every 6-8 weeks for up to 6 cycles. Post hoc analyses of efficacy and safety were conducted for patient subgroups based on demographic and baseline disease characteristics.

Results: 102 patients with mUM were enrolled; treatment was attempted in 95 patients; 91 patients received treatment. Subgroup analyses showed consistent tumor response regardless of age, sex, geographic region, presence/absence of extrahepatic lesions, and prior therapy. Patients with lower tumor burden had better objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) than those with higher tumor burden (ORR: 51.1 vs. 22.2%, p = 0.008; mPFS: 11.3 vs. 5.8 months, p = 0.007; mOS: 26.7 vs. 15.4 months, p = 0.008). Patients with 1-25% liver involvement had higher mOS than those with 26-50% liver involvement (22.4 vs. 16.9 months; p = 0.030); patients with low or normal lactate dehydrogenase (LDH) had higher mOS than those with elevated LDH (23.5 vs. 15.3 months; p = 0.019). The overall safety profile was similar across subgroups without evidence of cumulative toxicity with successive treatment cycles.

Conclusion: Results demonstrate a favorable benefit-risk profile for melphalan/HDS across clinically relevant subgroups. However, early treatment in patients with low tumor burden may offer best results.