Clinical & Translational Oncology最新文献

Background: Gastric cancer (GC) presents significant management challenges. MPT-driven necrosis (MPTDN) plays a significant role in various conditions, but its connection with GC is unclear. This study aimed to investigate the predictive significance of MPTDN-related genes (MPTDNRGs) in GC and their effect on the tumor immune microenvironment (TIME).

Methods: RNA sequencing data for GC were sourced from TCGA and GEO databases. The mutation profiles and MPTDNRG expression between tumor and normal samples were assessed. Prognostic mRNAs were identified using univariate Cox regression and LASSO regression. GC patients were classified into high- and low-risk groups according to risk scores, followed by survival analysis and evaluation of correlations between MPTDN score and clinicopathological features, functional pathway, TIME, and responses to immunotherapy.

Results: MPTDNRGs exhibited a 64% mutation rate in GC, with 22 showing significant expression differences. Univariate Cox and LASSO regression identified 15 independently prognostic MPTDNRGs. The prognostic risk model stratified patients into two groups, revealing significant differences in overall and disease-free survival. A nomogram incorporating the signature and clinical characteristics showed strong specificity and sensitivity in predicting prognosis. The MPTDN score was significantly associated with clinical characteristics, functional pathways, and TIME. scRNA-seq analysis indicated higher MPTDN-signature expression in CD8 + T cells, malignant cells, and myofibroblasts. TIDE analysis suggested high-risk patients have reduced responses to immunotherapy, while low-risk patients could benefit more. Importantly, validation using urothelial carcinoma data confirmed a better prognosis for low-risk patients with immunotherapy.

Conclusion: This study highlights the importance of MPTDN-related signatures in predicting GC prognosis and guiding therapeutic decisions.

With the widespread use of neoadjuvant chemotherapy (NAC), the optimal management strategy for axillary lymph nodes following chemotherapy has become a hot topic of discussion. For patients with clinically positive axillary lymph nodes (cN +) (defined as axillary lymph nodes confirmed positive by pathology before NAC), axillary lymph node dissection (ALND) remains the current standard treatment. However, there is still no consensus on whether sentinel lymph node biopsy (SLNB) and other local axillary treatments following NAC can safely replace ALND to reduce injury and complications. This article provides a narrative review of strategies for managing axillary lymph nodes in this patient population.

Prostate cancer is one of the major causes of morbidity and mortality in men worldwide. Most patients with prostate cancer will turn into end-of-life stage when those tumor cells become metastatic castration-resistant prostate cancer (mCRPC). The mCRPC subsequently developed a resistance to androgen signaling. The current regimens for mCRPC therapy are still ineffective. Much evidence from in vitro and in vivo studies explored the roles of therapeutic interventions targeted at the mitochondria and programmed cell death for prostate cancer therapy. The present review will focus on the recent medications which targeted at mitochondria and programmed cell death in mCRPC and the significant findings from each study will be summarized and discussed. Development of therapeutic interventions, particularly at mitochondrial and cytotoxic targets for treatment of mCRPC without inducing cellular toxicity of normal tissues will be considered as the novel therapeutic strategy for mCRPC.

Introduction: Post-surgery radiotherapy to the breast and regional lymph nodes decreases locoregional tumour recurrence and related mortality. The FAST-Forward approach, with 5 daily fractions, shows non-inferiority to the conventional 15-fraction scheme with similar safety. Authors suggest Simultaneous Integrated Boost (SIB) for the tumour bed and regional nodal irradiation (RNI) for comparable toxicity.

Objectives and purposes: To describe acute and delayed toxicity in adjuvant radiotherapy patients using FAST-Forward scheme with SIB and analyze associations with patient characteristics.

Materials and methods: An observational, descriptive, retrospective study on 120 early breast cancer patients (pT1-3, pN0-1, M0), treated with surgery and adjuvant radiotherapy using the FAST-Forward scheme with SIB at our center. Some also received RNI. Study conducted from June 2021 to October 2023.

Results: Median age: 55 years (range 30-86). Main histological type: infiltrating ductal carcinoma (80%), with Luminal A as predominant molecular subtype (58.5%). Stage IA tumours (61%), pT1c (40%), G2 (50%). Treatment included: neoadjuvant chemotherapy (18.3%), adjuvant chemotherapy (23.5%), hormonal treatment (82.5%), surgery (99%). Radiotherapy with SIB in 90% of conservative surgeries with a median dose 30 Gy (range: 29-33.6). There was no significant association between acute/chronic toxicity and SIB found. However, there was increased risk of acute induration with neoadjuvant chemotherapy. Adjuvant chemotherapy was linked to significant rates of acute and delayed hyperpigmentation. The acute toxicity in first 6 months post-radiotherapy was only G1. The most frequent late toxicities were G1 indurations, edema, hyperpigmentation.

Conclusions: The FAST-Forward scheme with SIB and RNI in 5 daily fractions seems well-tolerated without severe acute or delayed toxicity.

Introduction: To evaluate the effect of fractionation and prognostic factors on local control (LC) in the treatment of vestibular schwannoma (VS).

Methods: The medical records of 104 patients with vestibular schwannoma who were treated with stereotactic radiosurgery (SRS) from January 2015 to September 2023 were retrospectively collected. SRS was performed using Cyberknife^® robotic lineer accelerator. The primary endpoint of this study was LC rates. The chi-square test or Fischer's exact test, where appropriate, was used to compare progression rates in patients with small (< 20 cc) and large tumors (≥ 20 cc) which were treated in different fractionation schemes.

Results: The median total prescribed dose was 18 Gy (range, 12-30 Gy). With a median 54.8 month follow-up period (range, 3.4-111.9 month), 12 (12%) patients had progressive disease. Regression in tumor size, and stable disease was observed in 49 (47%) and 43 (41%) patients, respectively. The 3-y LC rate was 89% in all cohort and similar between patients who received SRS in 1, 3, and 5 fractions (p = 0.074). LC rates were slightly lower in patients with large tumors than those with small tumors (83% vs 94%, p = 0.200). Patients with large tumors (≥ 20 cc) which was treated with SRS in 1 fraction had a higher rate of progression compared to patients with small tumors (< 20 cc) (100% vs 0%, p = 0.006). But there was no difference between progression rates in large and small tumors, which were treated in 3, and 5 fractions (p = 0.100 and p = 1.000, respectively). No prognostic factors were found to predict tumor progression.

Conclusion: Both SRS and fractionated stereotactic radiotherapy (FSRT) provides high LC in patients with VS, however, FSRT may be preferred for large tumors due to higher LC rates compared to single fraction SRS.

Background: Neoadjuvant systemic therapy (NAT) represents an attractive option for improved outcomes of early-stage breast cancer (BC) patients, as it can significantly reduce tumor burden thus permitting breast-conserving resections. Equally important, the eradication of viable cancer cells post-NAT, also known as pathological complete response (pCR), has emerged as a strong prognostic biomarker, reflecting tumor's biology and subsequent treatment responses. Yet to date, no validated markers predictive of pCR have been identified.

Methods: The present retrospective study aimed to explore the value of neutrophil-tolymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as potential predictors of pCR.

Results: Despite no statistically significant associations have been reported, NLR and PLR dynamics during NAT, as longitudinal inflammatory phenotypes, merit further investigation in larger cohorts.

Conclusion: In the future, the integration of a comprehensive inflammatory biomarker panel into clinical practice could assist in a priori treatment selection process.

Background: APC and MUTYH genes are key in hereditary attenuated adenomatous polyposis syndromes. Guidelines recommend genetic testing based on polyp count, often overlooking age despite its impact on polyp prevalence.

Aim: To enhance genetic testing strategies for suspected attenuated adenomatous polyposis by combining polyp count and age in a probability calculator.

Methods: Retrospective study of adult patients referred to NGS genetic testing for suspected attenuated adenomatous polyposis (accumulated history of < 100 adenomas) (discovery cohort, N = 138). Data included age, adenoma count, and test results. A multivariable logistic regression model was developed to associate positive genetic test results with age and adenoma count. The model was externally validated with 259 patients from two tertiary hospitals in our region (validation cohort, N = 259).

Results: In the discovery cohort, 13 (9.4%) patients had pathogenic mutations, being younger (OR:0.91, 95%CI 0.86-0.96) and having more adenomas (OR:1.08, 95%CI 1.04-1.13) compared to negative cases. The logistic regression model combining age and polyp count demonstrated an AUC of 0.92. Using a cutoff probability of 3.5%, the model achieved 100% sensitivity and 58% specificity in identifying positive cases. In the external validation, the model accurately predicted 14 out of 16 positive cases (88%). The remaining two positive cases were a patient with an AXIN2 mutation in heterozygosis, and a patient with a NTHL1 mutation in homozygosis. Performance evaluation of both hospitals yielded AUC values of 0.77 and 0.90.

Conclusions: Older individuals with fewer polyps are less likely have hereditary syndromes. Including age in genetic testing criteria can enhance patient selection and cost-effectiveness.

MicroRNAs (miRNAs) have emerged as important regulators of gene expression in various biological processes, including cancer. miR-182-5p has gained attention for its potential implications in gynecologic cancers, including breast, ovarian, endometrial, and cervical cancers. miR-182-5p dysregulation has been associated with multiple facets of tumor biology in gynecologic cancers, including tumor initiation, progression, metastasis, and therapeutic response. Studies have highlighted its involvement in key signaling pathways and cellular processes that contribute to cancer development and progression. In addition, miR-182-5p has shown potential as a diagnostic and prognostic biomarker, with studies demonstrating its correlation with clinicopathological features and patient outcomes. Furthermore, the therapeutic potential of miR-182-5p is being explored in gynecologic cancers. Strategies such as miRNA mimics or inhibitors targeting miR-182-5p have shown promise in preclinical and early clinical studies. These approaches aim to modulate miR-182-5p expression, restoring normal cellular functions and potentially enhancing treatment responses. Understanding the biologic and clinical implications of miR-182-5p in gynecologic cancers is crucial for the development of targeted therapeutic strategies and personalized medicine approaches. Further investigations are needed to unravel the specific target genes and pathways regulated by miR-182-5p. It is important to consider the emerging biologic and clinical implications of miR-182-5p in gynecologic cancers.