Journal of Cancer Research and Clinical Oncology最新文献

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.

To evaluate the impact of comorbidities on treatment allocation and prognosis in anaplastic thyroid cancer, 137 patients from 10 German tertiary cancer centers treated with radiotherapy between 2001 and 2020 were analyzed. Four validated comorbidity scores were applied to assess comorbidity burden. The primary objective was to identify prognostic factors for the survival rate at 6 months after radiotherapy and discriminate the comorbidity scores using concordance statistics, ROC curve net reclassification index, and integrated discrimination improvement for 6-month survival. The median overall survival (OS) of the entire cohort was 4 months (95% CI = 2.72-5.28). The 6-, 12- and 24-months survival rates were 42.1%, 29.0% and 15.0%, respectively. In the univariate analysis, Karnofsky Performance Score (KPS) (> 70%, p < 0.001), UICC stage (p < 0.001), treatment modality (p < 0.001), intention of treatment (p < 0.001) as well as lower scores in the conventional Charlson Comorbidity Index (cCCI, p < 0.001), the updated Charlson Comorbidity Index (uCCI, p < 0.001) were associated with improved OS. KPS (> 70%, p = 0.06) and type of therapy (p = 0.087) showed a trend in multivariate analysis. Higher comorbidity burden (cCCI and uCCI) was associated with less intensive treatment and lower cumulative radiation doses in univariable analyses. However, after adjustment for age and metastatic status, none of the comorbidity indices remained independently associated with the use of multimodal therapy or the prescribed EQD2 dose (p > 0.05). Age, but not metastatic status, was linked to a reduced likelihood of receiving multimodal treatment. In contrast, KPS emerged as the only independent predictor of higher EQD2 dose levels in the multivariable models.

Background: Hematological malignancies, including leukemia, lymphoma, and multiple myeloma, are among the most aggressive cancers, with high mortality rates and limited early diagnostic tools. Exosomes, nano-sized extracellular vesicles secreted by numerous cells including tumor cells, have emerged as promising biomarkers due to their stability, non-invasive isolation, and disease-specific molecular cargo, particularly non-coding RNAs (ncRNAs).

Method: This systematic review, conducted following PRISMA 2020 guidelines, evaluated the diagnostic and prognostic potential of exosomal ncRNAs in hematological malignancies by analyzing 16 studies from five databases (Scopus, PubMed, Embase, Web of Science, and ProQuest).

Result: Key findings revealed that exosomal microRNAs, such as miR-532, miR-10b, and miR-21 in acute myeloid leukemia, miR-326 in acute lymphoblastic leukemia, and miR-494 in chronic myeloid leukemia, exhibit significant differential expression between patients and healthy controls, correlating with disease progression, treatment resistance, and survival outcomes. Moreover, long non-coding RNAs and circular RNAs were identified as potential biomarkers in myelodysplastic syndromes and leukemia. This review highlights the role of exosomal ncRNAs in liquid biopsies for early detection and monitoring. However, heterogeneity in isolation methods and sample sizes emphasizes the need for standardized protocols.

Conclusion: These findings highlight the transformative potential of exosomal ncRNAs in precision oncology, offering novel ways for non-invasive diagnostics, prognostic stratification, and targeted therapies in hematological malignancies. Additional studies are necessary to validate these biomarkers and explore their clinical applications.

Background/objectives: Pancreatic cancer surgery frequently results in positive margins and local recurrence despite multimodal treatment. This study evaluated whether combining neoadjuvant stereotactic body radiotherapy (SBRT) with intraoperative electron radiotherapy (IOeRT) during resection could improve local control and surgical outcomes.

Methods: A retrospective analysis was performed on 15 patients with resectable or borderline resectable pancreatic adenocarcinoma treated between 2021 and 2023. All patients received image-guided, motion-managed SBRT (35-40 Gy/5 fractions to PTV_high; 25 Gy/5 fractions to PTV_low) followed by surgical resection and IOeRT (median 10 Gy; 12 Gy when margins were at risk). Toxicities were graded by CTCAE v5.0 and postoperative complications by Clavien-Dindo criteria. Follow-up included imaging and CA 19-9 every 3 months. Survival was estimated using Kaplan-Meier analysis.

Results: Mean patient age was 66 years; 60% had tumors in the pancreatic body and 40% in the head. Two-thirds were borderline resectable and received neoadjuvant chemotherapy. Margin-negative resection was achieved in 86.7%, including two complete pathologic responses in BRCA2-mutated tumors. Median overall and progression-free survival were 30 and 16 months, respectively. One patient (6.7%) developed isolated local recurrence, while distant metastases occurred in over half. Toxicities were mainly grade 1-2 fatigue, nausea, or pain; surgical complications were grade 1-2 in 53%, grade 3 in 7%, and grade 5 in 7%.

Conclusions: Neoadjuvant SBRT with IOeRT during pancreatic cancer resection is feasible, achieves high rates of negative margins, and provides promising local control. Distant progression remains the dominant mode of failure.