Oncology Reviews最新文献

This review focused on trials investigating the front-line covalent BTK inhibitors (cBTKi) and venetoclax (V) combination administered in a fixed-duration (CAPTIVATE, GLOW, AMPLIFY trials) or minimal residual disease (MRD)-guided manner (MDACC, FLAIR, ERADIC, HOVON NEXT STEP, SEQUOIA arm D trials) in patients with chronic lymphocytic leukemia (CLL). We reviewed data from these studies to highlight their therapeutic activity and toxicity profile. Despite the heterogeneity in patients' characteristics, treatment schedule, and duration, most patients achieved deep responses with undetectable MRD and prolonged progression-free survival (PFS) with BTKi + V regimens. MRD-guided treatments yielded higher PFS rates, including patients with high-risk genetic characteristics, such as those with unmutated IGHV and TP53 disruption. The cBTKi + V regimen is easy to manage and relatively well tolerated. However, cBTKi-related cardiovascular toxicities remain a limiting concern, especially for the use of cBTKi + V in some older patients.

Introduction: Vascular anomalies (VAs), comprising vascular tumors and malformations, are commonly diagnosed based solely on clinical evaluation and imaging. Soft-tissue sarcomas (STSs) may mimic VAs clinically and radiologically, leading to misdiagnosis, delayed treatment, and suboptimal outcomes. In this systematic review, we aimed to summarize patients with a pathological diagnosis of STSs who were initially misdiagnosed with benign VAs, highlighting diagnostic pitfalls.

Materials and methods: In this systematic review (PROSPERO ID: CRD42024615285), we followed the PRISMA 2020 guidelines. The inclusion criteria comprised patients with histologically confirmed STSs who had been initially misdiagnosed as benign VAs based on clinical or radiological features. Literature from five databases was reviewed without language or date restrictions. One additional case of alveolar soft-part sarcoma initially misdiagnosed and mistreated as an arteriovenous malformation from the authors' institution was added to the analysis.

Results: The systematic search yielded a total of 96 patients with STS initially misdiagnosed as benign VAs (95 from 77 publications and one from our own case). The median age at presentation was 6 months (range: newborn-88 years). The most frequent symptom was a swelling or mass (75%). In most cases, the misdiagnosis was both clinical and radiological. The median diagnostic delay was 5.5 months. Fifty-nine (61.5%) patients received treatment for the misdiagnosed benign VA, including local interventions (51.0%) and systemic therapies (17.7%). The most commonly misdiagnosed STS subtypes were infantile fibrosarcoma, alveolar soft-part sarcoma, rhabdomyosarcoma, dermatofibrosarcoma protuberans, angiosarcoma, and Ewing sarcoma.

Conclusion: Several STS subtypes may mimic benign VAs clinically and radiologically. The misuse of outdated terminology and limited awareness among clinicians contribute to diagnostic delays. To avoid misdiagnoses, the care for patients with benign VAs should be provided by specialists familiar with the classification and natural history of these lesions. In patients diagnosed with benign VAs based on clinical or imaging features only, all findings should clearly support the diagnosis. Any ambiguity warrants prompt referral to a tertiary center. A biopsy should be considered in doubtful or atypical cases.

Background: Tongue diagnosis (TD), a key component of traditional East Asian medicine, employs a unique pattern-based diagnostic system. Digital TD enables quantitative assessment of tongue characteristics, like body and coating color, enhancing objectivity and reproducibility. While abnormal tongue features (including dark red, bluish, or pale appearance) have been documented in patients with cancer, the relationship between longitudinal changes in tongue characteristics and immune checkpoint inhibitor (ICI) treatment response or survival outcomes in non-small-cell lung cancer (NSCLC) remains underexplored. This multicenter, prospective, observational study investigated whether longitudinal tongue changes differ by ICI response and predict survival in patients with NSCLC.

Methods: We enrolled patients with stage IIIB, IIIC, or IV NSCLC scheduled to receive second-line or subsequent pembrolizumab or atezolizumab following first-line platinum-based therapy failure. Digital tongue images were collected every 9 weeks from baseline to week 45. Linear mixed models evaluated temporal parameter changes and compared responders (durable clinical benefits ≥6 months) versus nonresponders. Multivariate Cox models adjusted for sex and age assessed tongue lightness changes as a prognostic value for progression-free survival (PFS) and overall survival (OS). Survival distributions were compared using Kaplan-Meier curves.

Results: Of 170 enrolled participants, 140 were included in the analysis. Early in treatment, tongue lightness decreased in the body, fur, root, and center areas in both responders and nonresponders; however, the darkening was more pronounced in nonresponders, with significant visit-by-response interaction effects. In multivariate Cox analysis, lightness changes of the tongue body were significantly associated with PFS (hazard ratio [HR] = 0.93; 95% confidence interval [CI], 0.88-0.99; p = 0.019) and showed a trend for OS (HR = 0.93; 95% CI, 0.86-1.00; p = 0.062). Lightness changes of the tongue center were also significantly associated with PFS (HR = 0.95; 95% CI, 0.90-0.99; p = 0.027). Kaplan-Meier analysis confirmed that patients with a greater decrease in tongue body lightness had significantly shorter OS (p = 0.049).

Conclusion: Digital TD diagnosis, particularly monitoring tongue lightness changes, may provide a valuable noninvasive prognostic tool for patients with NSCLC undergoing ICI therapy. It offers information for both PFS and OS, potentially complementing current biomarkers for cancer immunotherapy.

Introduction: Early prognostication in non-muscle-invasive bladder cancer (NMIBC) is essential for optimizing therapy and follow-up. Epigenetic mechanisms, particularly DNA methylation, have emerged as promising biomarkers for predicting disease outcome.

Materials and methods: A systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the prognostic significance of promoter DNA methylation in NMIBC. Comprehensive searches of PubMed, Web of Science, Embase, MEDLINE, and the Cochrane Library (January 2010-October 2022) identified eligible studies. The Newcastle-Ottawa scale was used for quality assessment, and pooled hazard ratios with 95% confidence intervals were calculated using random-effects models.

Results: Eleven studies with 3,065 NMIBC patients were analyzed. Promoter methylation was significantly associated with poor progression-free survival (pooled hazard ratios (HR) = 2.88; 95% CI = 2.03-4.09; p < 0.0001) and recurrence-free survival (pooled HR = 2.65; 95% CI = 1.93-3.63; p < 0.0001). Although overall survival showed pathway-specific variation (pooled HR = 0.96; 95% CI = 0.36-2.60; p = 0.94), methylation of adhesion and apoptosis-related genes exhibited the strongest associations. Subgroup analyses revealed a greater prognostic impact in Asian cohorts (p < 0.0001), suggesting regional differences in epigenetic susceptibility.

Conclusion: Promoter DNA methylation constitutes a robust prognostic biomarker for recurrence and progression in NMIBC, with stronger effects in Asian populations. Standardization of validated gene panels, assay thresholds, and cross-regional prospective validation will be essential for clinical translation. Integrating methylation-based classifiers into risk stratification models could improve individualized management and long-term outcomes in NMIBC.

Introduction: Well-differentiated papillary thyroid carcinoma (PTC) generally carries an excellent prognosis; however, certain pathological features such as gross extrathyroidal extension and tumor diameter ≥2 cm have been associated with structural disease recurrence. This study aimed to identify the key clinical and histopathological factors associated with disease-free survival in patients undergoing total thyroidectomy for PTC.

Methods: A retrospective cohort study was conducted including 750 patients who underwent total thyroidectomy with or without neck dissection between 2014 and 2024 at a tertiary academic cancer center. Clinical, pathological, and oncological follow-up data were analyzed over a maximum follow-up period of 100 months. Kaplan-Meier survival analysis, log-rank testing, and Cox proportional hazards regression were employed for statistical evaluation.

Results: The structural recurrence rate was 4%, and overall survival reached 99%. In the multivariate analysis, only gross extrathyroidal extension (HR 3.29; p = 0.008) and tumor diameter (HR 1.32; p = 0.013) were independently associated with recurrence. Variables such as age, smoking status, perineural invasion, vascular invasion, and central lymph node involvement did not show significant associations with structural recurrence.

Conclusion: Gross extrathyroidal extension and increased tumor diameter were identified as the primary prognostic factors for structural recurrence in patients with PTC. Multicenter studies are warranted to validate these findings in the broader Brazilian population.

Constitutional mismatch repair deficiency (CMMRD) is a rare pediatric cancer predisposition syndrome primarily characterised by central nervous system (CNS), gastro-intestinal (GI) tumours and hematological malignancies, along with NF1-like cutaneous features. The PMS2-related subtype (PMS2-CMMRD) is the most common molecular form of CMMRD, exhibiting variable severity and both early and late-onset clinical presentations. Although pathogenic and likely pathogenic PMS2 heterozygous variants are relatively frequent in healthy population, CMMRD incidence is generally rare in humans and genotype-phenotype correlations are still limited. To better characterise PMS2-CMMRD group, we collected clinical cases described in literature, using three alternative methods (VarChat, VarSome and LitVar2), starting from 102 pathogenic/likely pathogenic PMS2 variants (<50 bp) reported in ClinVar by clinical and research laboratories. PMS2-CMMRD cases were split into two distinct groups based on tumour onset age: early (diagnosis under 10 years) and later-onset (diagnosis after 10 years). Significant differences in tumour distribution were observed, with CNS tumours being most prevalent in the early-onset group, while GI tumours were more common in the later-onset group. Six PMS2 variants were associated with either early or later-onset CMMRD. Future validation through larger prospective cohort studies is necessary to confirm our findings and better understand the natural history of PMS2-CMMRD to inform clinical decision-making in PMS2-Lynch syndrome (PMS2-LS).

Gastric cancer (GC) remains a major global health challenge due to its high incidence and mortality. Emerging evidence underscores the critical role of RNA methylation, a key layer of epigenetic regulation, in GC pathogenesis. This review synthesizes current knowledge on various RNA modifications, including m⁶A, m⁵C, m¹A, and m⁷G, in GC. We critically evaluate the functions of their regulatory proteins (writers, erasers, readers) in modulating oncogenic signaling, metastasis, and tumor immunity. Among these, m⁶A and m⁵C modifications currently present the most compelling evidence, demonstrating significant correlations with patient prognosis and therapy resistance. Furthermore, we explore the translational potential of targeting the RNA methylation machinery, discussing both promising avenues and existing challenges in drug development. This comprehensive analysis aims to provide deeper mechanistic insights and highlight novel therapeutic opportunities for GC.

Introduction: Osteosarcoma is the most common malignant tumor of bone tissue in adolescents, and precise pathological diagnosis is the primary foundation for establishing the most effective treatment plan. The pathological evaluation of tumor necrosis after chemotherapy is crucial for assessing therapeutic efficacy in osteosarcoma patients. However, pathologists often face several challenges during the diagnosis and evaluation process.

Methods: To address these needs, we designed and developed a multi-model cascaded deep learning framework utilizing an advanced Vision Mamba (ViM) model as the core network architecture. The study employed one of the most comprehensive osteosarcoma datasets, sourced from: (1) real-world data from 68 osteosarcoma patients collected at Chongqing General Hospital, and (2) publicly available osteosarcoma assessment data from the University of Texas Southwestern/UT Dallas. Pathological images were annotated using the Palgo pathology image artificial intelligence self-training platform according to algorithm requirements. A triple verification mechanism of annotation, review, and archiving was implemented, and Palgo's integrated interactive algorithm correction mechanism was used to continuously refine the data annotation process.

Results and discussion: The model demonstrated Dice coefficient values of 0.83 or higher in tumor segmentation, osteosarcoma osteoid matrix segmentation, necrotic area segmentation, lung metastatic tumor segmentation, and lung metastatic osteoid matrix segmentation. For necrosis classification, overall osteosarcoma subtypes, and localized osteosarcoma subtypes, the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) all exceeded 90%. The proposed model exhibited excellent performance, indicating high potential for future clinical application in osteosarcoma patients. This framework shows promise for enhancing the precision and efficiency of pathological diagnosis and evaluation in osteosarcoma management.

Objective: To Compare the effects between thulium laser en bloc resection of bladder tumor (ERBT) and conventional transurethral resection of bladder tumor (TURBT) on catheter-related bladder discomfort (CRBD) in patients with bladder cancer.

Methods: Between January 2022 and December 2024, we retrospectively collected the demographic and clinical data for patients with bladder cancer. A total of 79 patients in the conventional TURBT group and 58 patients in the thulium laser ERBT group completed the study. Both demographic and outcome variables were recorded; and we compared the incidence and severity of CRBD at 1, 6 and 24 h postoperatively, score of postoperative pain at 1, 6 and 24 h and patient satisfaction at 24 h following the surgery.

Results: There were no significant differences in age, gender proportion, tumor multiplicity, tumor size and location, and duration of surgery between the two groups (P > 0.05). Pathological examination revealed that the ERBT had a higher rate of detrusor presence than TURBT (P = 0.04). The incidence and severity of postoperative CRBD were lower in ERBT group than TURBT group at 1 and 6h (P < 0.001), while there were no statistically significant difference between the two groups (P = 0.17) at 24 h. The VAS scores of postoperative pain were significantly lower in ERBT group than in TURBT group at 1 and 6 h postoperatively (P = 0.001 and P = 0.02, respectively). But at 24 h, there was no statistically significant difference (P = 0.08). As to postoperative patient satisfaction at 24 h, the result of ERBT group was significantly lower than TURBT group (P = 0.02). Additionally, the ERBT group had significantly less intraoperative blood loss and shorter postoperative irrigation duration (P = 0.001). No significant difference was found in the duration of indwelling catheter between the two groups (P = 0.07).

Conclusion: The results suggest that compared to conventional TURBT, thulium laser ERBT significantly reduce CRBD incidence and severity, lower postoperative pain, and improve postoperative patient satisfaction. However, as a single-center retrospective study, these findings require further validation by large-scale, prospective, multicenter trials.