Oncology Reviews最新文献

Many drugs currently used in cancer chemotherapy exert their toxic action mainly by inhibiting ribosome biogenesis (RiBi). This is due to the fact that after inhibition of rRNA transcription ribosomal proteins, no longer used for ribosome building, bind to and neutralize the activity of the murine double minute 2 protein (MDM2, HMD2 in humans), thus hindering cell proliferation and possibly inducing apoptotic cell death. Here, we discuss the existing literature showing how RiBi rate and genomic alterations of ribosomal proteins (RP mutations/deletions) influence the degree of MDM2 inhibition after treatment with RiBi inhibitors in cancer cells. There is evidence that a high RiBi rate is associated with a high RPs release with strong inhibition of MDM2 activity and consequent induction of apoptotic cell death in response to RiBi inhibitors, whereas a low RiBi rate or RP mutations/deletions are associated with a degree of MDM2 inhibition insufficient to kill cancer cells. In the latter case, in cells with wild type p53, association with drugs which stabilize p53 with different mechanisms may overcome cancer cells resistance to RiBi inhibition, whereas in cancers lacking functional p53 addition of MDM2 inhibitors should be considered. From this, the necessity to evaluate the rate of ribosome biogenesis together with the presence of RP mutations/deletions in cancer tissues for predicting the sensitivity of cancer cells to RiBi inhibitors in order to choose more appropriate therapeutic protocols.

Introduction: Pleural effusion, an atypical accumulation of fluid in the pleural space, has been identified as a potential indicator of several diseases, including lung cancer. The presence of biomarkers in malignant pleural effusion has been a subject of investigation; however, the expression of microRNAs has received limited attention. The objective of this study is to present a narrative review of the current scientific literature regarding the presence of microRNAs in malignant pleural effusion and their association as new biomarkers in the diagnosis of lung cancer.

Method: A comprehensive search was conducted using the databases: PubMed, ScienceDirect, and EBSCO to identify all original scientific articles published through 30 April 2025. The following terms were utilized in the search: "MicroRNA AND pleural effusion AND lung cancer", "microRNA AND pleural effusion AND lung adenocarcinoma", "microRNA AND pleural effusion AND lung squamous cell carcinoma", "miRNA AND pleural effusion", miRNA AND pleural effusion AND lung cancer", "miRNA AND pleural effusion AND lung adenocarcinoma", "miRNA AND pleural effusion AND lung squamous cell carcinoma".

Results: A total of 17 studies were identified that distinguished between 106 microRNAs. These studies demonstrated the most significant overexpression and downexpression in lung cancer patients compared to patients without malignancy. However, eight of these studies distinguished between 17 microRNAs expressions and exhibited elevated area under the curve values, sensitivity, and specificity for the involvement in several hallmarks of lung cancer.

Conclusion: The regulatory mechanisms governing microRNAs in malignant pleural effusion are intricate and involve multiple genes that play pivotal roles in several cancer mechanisms. These mechanisms encompass but are not limited to, processes such as cell growth, migration, drug resistance, proliferation, apoptosis, invasion, angiogenesis, and apoptosis.

Introduction: Oral cavity and pharyngeal cancer (OPC) affects over 580,000 people globally each year, with tobacco and alcohol being key risk factors. This meta-analysis quantifies the excess risk of OPC associated with cigarette smoking and its patterns.

Methods: We carried out a systematic review and meta-analysis of case-control and cohort studies assessing the association between cigarette smoking and OPC risk, including articles published up to February 2025. Using a combined umbrella and traditional review approach, we estimated pooled relative risks (RR) by smoking status, intensity, duration, and time since quitting.

Results: Out of 137 eligible articles, 115 original studies were included in this meta-analysis. Relative to never smokers, the pooled risk of OPC was 3.58 (95% CI: 3.03-4.24; n = 54) among current smokers, 1.61 (95% CI: 1.44-1.81; n = 53) among former smokers, and 2.45 (95% CI: 2.19-2.75; n = 80) among ever smokers. Subsite-specific analyses showed RRs of 3.39 (95% CI: 2.64-4.35; n = 25) for oral cancer and 4.24 (95% CI: 2.96-6.09; n = 18) for pharyngeal cancer in current versus never smokers. Risk rose steeply with both smoking intensity and duration, doubling after 6 cigarettes per day or 7 years of smoking, before reaching a plateau around an RR of 5 at 20 cigarettes per day or 20 years. The risk declined linearly with longer time since quitting, with a 50% reduction observed within 10 years of cessation.

Conclusion: Our findings reaffirm the substantial impact of smoking on OPC risk and stress the need for efforts to avoid smoking initiation and support cessation.

Background: The optimal role of surgical cytoreduction in metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains uncertain, as supporting evidence is largely retrospective and rarely compares surgery with contemporary systemic therapy. Using a national cancer registry, we evaluated overall survival (OS) associated with cytoreductive surgery compared with systemic therapy alone.

Methods: Adult patients with stage IV well-differentiated GEP-NENs were identified in the National Cancer Database (2004-2020). Demographic, tumor, and facility variables stratified patients. Treatment groups included cytoreductive surgery (CRS) alone, CRS plus systemic chemotherapy, and systemic therapy alone. Overall survival (OS) was compared using Kaplan-Meier (KM) analysis and multivariable Cox proportional hazards models.

Results: Among 3,183 patients with stage IV GEP-NENs, 69.8% underwent cytoreductive surgery (CRS) alone, 6.7% received CRS plus systemic chemotherapy, and 23.4% received systemic therapy alone. Median overall survival (OS) differed significantly by treatment: CRS alone, 140.9 months; CRS plus chemotherapy, 96.2 months; and systemic therapy alone, 51.6 months (p < 0.001). The survival advantage of CRS persisted across histologic grades, including both G1-G2 tumors (140.9 vs. 96.2 vs. 53.6 months, p < 0.001) and G3 well-differentiated tumors (39.8 vs. 13.1 vs. 9.6 months, p < 0.001). Survival benefits were also observed across primary tumor sites. In midgut NENs, median OS was 157.6 vs. 99.2 vs. 87.5 months (p < 0.001), and in pancreatic NENs, 117.5 months vs. not reached vs. 50.8 months (p < 0.001). On multivariable analysis, older age, lower SES, higher comorbidity burden, colon or rectal primaries, positive margins, and higher tumor grade were associated with worse survival. Longer time from diagnosis to surgery (>35 days) was associated with improved survival. CRS remained independently associated with improved OS (HR 0.80, 95% CI 0.67-0.94), while receipt of systemic chemotherapy was associated with increased mortality (HR 1.71, 95% CI 1.36-2.17).

Conclusion: Surgical cytoreduction was associated with significantly improved survival compared with systemic therapy alone in metastatic GEP-NENs, with consistent benefits across histologic grades and primary tumor sites. These findings support considering CRS in appropriately selected patients and underscore the need for prospective validation.

Background: A significant subset of breast cancer cases is attributable to inherited pathogenic genetic variants. Germline genetic testing (GGT), particularly for BRCA1 and BRCA2, represents a critical tool for precision oncology, enabling individualized risk stratification and the development of tailored therapeutic strategies.

Methods: Consecutive newly diagnosed breast cancer patients eligible for GGT testing according to the latest American Society of Clinical Oncology (ASCO) guidelines were enrolled.

Results: During the study period, 1,570 patients were enrolled, median age 51 (22-96) years, majority (n = 1,352, 86.1%) were Jordanian. Based on age criteria, 1,346 (85.7%) patients were eligible for testing. Another 134 (8.5%) were found eligible for testing because of other indications including personal or family history of breast and other cancers (n = 121, 7.7%), triple-negative disease (n = 9, 0.57%) and male gender (n = 4, 0.25%). In total, 1,480 (94.3%) patients were eligible for GGT as per ASCO guidelines, leaving only 90 (5.7%) patients not candidates for testing. Pathogenic/likely pathogenic variants were identified in 23 (7.8%) patients.

Conclusion: Applying universal GGT for all newly diagnosed breast cancer patients, regardless of their age or risk factors, would slightly increase the pool of eligible patients, the burden of which can be justified given its impact on improving referral rate.

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.