Expert Review of Anticancer Therapy最新文献

Introduction: Prognosis in patients with HCC is largely determined by stage at diagnosis, highlighting the importance of effective early detection strategies. HCC surveillance is associated with increased early detection and reduced HCC-related mortality and is currently recommended in patients with cirrhosis or chronic HBV infection.

Areas covered: We performed a targeted literature review to identify limitations of current HCC surveillance practices and strategies for improvement.

Expert opinion: Semi-annual ultrasound continues as the cornerstone modality for HCC surveillance but has limited sensitivity for detecting early-stage HCC, particularly in patients with obesity and non-viral etiologies. Although sensitivity for early-stage HCC can be improved by using ultrasound with alpha fetoprotein, this strategy misses over one-third of HCC at an early stage. Emerging imaging and biomarker-based surveillance strategies currently remain in varying stages of validation and are not yet ready for routine use in practice. The cost-effectiveness of surveillance in patients with non-cirrhotic liver disease related to hepatitis C or metabolic dysfunction-associated steatotic liver disease continues to be debated, although subgroups with advanced fibrosis may warrant surveillance. Finally, the effectiveness of surveillance is diminished by underuse in clinical practice, particularly in racial minority and low-income groups, highlighting a need for interventions to increase utilization.

Research design and methods: Data were obtained from the SEER database for women diagnosed with EOC between 2004 and 2020. Clinical features, treatment regimens and overall survival (OS) were analyzed. Cox regression was conducted to identify prognostic factors associated with EOC. We employed 5-fold cross-validation to improve the accuracy of the model. Random Survival Forest (RSF), Gradient Boosting Survival Analysis (GBSA) and Support Vector Machine (SVM) were used to develop ML models, then compared with the Cox model. The predictive performance of these models was assessed using AUC, concordance index (C-index), and Brier scores.

Results: A total of 12,949 EOC patients were selected from the SEER database. We identified 14 independent prognostic factors for OS and constructed predictive models. The GBSA model demonstrated superior AUC, C-index, and Brier scores across different time points, outperforming the Cox model. SHAP analysis showed that FIGO stage, grade, and lymph node dissection were the most important features in the GBSA model.

Conclusions: The GBSA model outperforms traditional methods in survival prediction, offering a valuable tool for clinicians to make informed decisions about patient prognosis.

Background: To explore the safety of PD-L1 inhibitors vs. PD-1 inhibitors in extensive-stage small-cell lung cancer (ES-SCLC) and non-small-cell lung cancer (NSCLC).

Research design and methods: PubMed, EMBASE, and the Cochrane Library were searched up to 20 December 2023. Randomized controlled trials on patients with NSCLC/ES-SCLC treated with PD-1/PD-L1 inhibitor were included and synthesized with Bayesian network meta-analysis.

Results: This meta-analysis included 58 studies. Regarding grade ≥3 treatment-related adverse events (TRAEs), PD-L1 inhibitors had better safety compared with PD-1 inhibitors when combined with chemotherapy in resectable NSCLC, presenting larger surface under the cumulative ranking (SUCRA) (0.577 vs. 0.168), similar with those in advanced NSCLC and ES-SCLC. The safety of PD-L1 inhibitors was better than PD-1 inhibitors regarding grade ≥3 pneumonia in resectable NSCLC when combined with chemotherapy (0.648 vs. 0.307), as well as in advanced NSCLC and ES-SCLC. When combined with chemotherapy, PD-L1 inhibitors had better safety regarding grade ≥3 pneumonitis, compared to PD-1 inhibitor (resectable NSCLC: 0.934 vs. 0.019; advanced NSCLC: 0.618 vs. 0.584; ES-SCLC: 0.505 vs 0.059).

Conclusion: PD-L1 inhibitors might be a safer option than PD-1 inhibitors regarding grade ≥3 TRAEs and pneumonia, monotherapy or combined with chemotherapy, and when combined with chemotherapy regarding grade ≥3 pneumonitis.

Registration: PROSPERO (CRD42024620372).

Introduction: Globally, prostate cancer (CaP) is a leading cause of death and disability among men and a substantial public health burden. Despite advancements in cancer treatment, chemoresistance remains a significant issue in cancer therapy, accounting for the majority of patient relapses and poor survival. Cancer stem cells (CSCs) are considered the main cause of cancer recurrence, chemoresistance, and poor survival of patients. These CSCs acquire stemness and chemoresistance by certain mechanisms such as enhanced DNA repair processes, increased expression of drug efflux pumps, resistance to apoptosis, and altered cell cycle and tumor microenvironment (TME).

Area covered: We cover the latest developments in this field and give an overview of future research directions.

Expert opinion: CSCs show dysregulation of several signaling pathways, mostly related to conferring chemoresistance phenotype, such as high drug efflux, apoptotic resistance, quiescent cell cycle, tumor microenvironment, and DNA repair. There are several research articles published on this topic. However, still, this field warrants further investigations to identify the therapeutic molecule that can either chemosensitize CSCs or kill them effectively. This can only be possible when we know the complete mechanisms to comprehend the fundamental causes of cancer stemness and therapy resistance.

Background: Despite adjuvant external beam radiation therapy (EBRT) has long been the standard treatment for glioblastoma (GBM), a significant subset of patients chooses to refuse it. We aimed to investigate the factors influencing EBRT refusal in GBM.

Research design and methods: Patients with GBM were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Both univariable and multivariable logistic regression analyses were employed to evaluate the adjusted odds ratios (aOR) for the refusal of EBRT in relation to various clinical and demographic characteristics.

Results: Among the 29,994 patients analyzed, 675 (2.3%) opted to refuse adjuvant EBRT. Patients aged ≥ 55 years (55-64: aOR 1.63, 95% CI 1.04-2.61, p = 0.03; 65-74: aOR 1.80, 95% CI 1.17-2.87, p = 0.009; 75+: aOR 2.01, 95% CI 1.28-3.24, p = 0.002), being single (aOR 1.68, 95% CI 1.19-2.35, p = 0.002), with a household income of $55,000 to $64,999 (aOR 1.94, 95% CI 1.24-3.07, p = 0.004), and not undergoing chemotherapy (aOR 114, 95% CI 80.2-170.2, p < 0.001) had significantly higher odds of refusing adjuvant EBRT.

Conclusions: This study underscores the necessity for targeted communication strategies by physicians regarding the benefits of adjuvant EBRT.

Background: This study explores the disparity in ER, PR, HER-2, and Ki-67 status between primary breast tumors (PBT) and axillary lymph node metastasis (ALNM) at initial admission in patients undergoing neoadjuvant chemotherapy (NAC).

Research design and methods: Demographic-clinicopathological characteristics and histopathological response to NAC in both PBT and ALNM were recorded. Immunohistochemical analysis of ER, PR, HER-2, and Ki67 was performed separately in PBT and ALNM, with discordance rates compared. The disparity in biomarkers was assessed in relation to the histopathological response to NAC in both PBT and ALNM.

Results: In 96 female patients, discordance rates between PBT and ALNM were 16.67% for ER, 16.67% for PR, 20.83% for HER-2, and 15.63% for Ki-67. Statistically significant differences in ER and PR discordance between PBT and ALNM were observed. Additionally, a significant difference in histopathological response to NAC was noted based on ER discordance.

Conclusion: Precise assessment of ER and HER-2 status in axillary lymph node biopsy specimens is crucial in breast cancer patients with ALNM, potentially optimizing systemic and surgical treatment selection.

Introduction: metastasis-directed treatment (MDT) is progressively expanding its scope in the treatment of metastatic renal cell carcinoma (mRCC), finding application both in cases of oligometastatic disease, whether synchronous or metachronous, and in oligo-progression during systemic therapy (ST). This updated narrative review incorporates recent advancements in managing oligometastatic and oligo-progressive RCC. A PubMed literature search using keywords related to mRCC and its treatments was made. Observational studies, clinical trials, and reviews were analyzed, selecting the most relevant articles based on evidence strength.

Areas covered: we analyzed the current role of surgery, both on the primary than on metastatic sites, and the recent advantages in both radiotherapy, ST and focal therapies. Lastly, we focused on single metastatic sites of interest.

Expert opinion: nowadays personalized tailored treatments are the key, integrating multimodal approaches like metastasectomy, radiotherapy, and ST. While the role of cytoreductive nephrectomy remains debated, metastasectomy and radiotherapy demonstrates potential in managing both oligometastatic and oligo-progressive disease, either alone or in synergy with ST, though more robust evidence is needed. Future research should focus on identifying biomarkers for treatment selection, optimizing therapy timing, and refining patient stratification to enhance outcomes.

Background: Prostatic ductal adenocarcinoma (PDA) is a rare malignant tumor, and research on its clinical features and prognosis is scarce. This study aims to develop prognostic nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) in patients with PDA.

Research design and methods: Among the 1,049 identified patients, an 8:2 random division yielded development and validation cohorts. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors, which were then incorporated into nomograms predicting 1-, 3-, and 5-year OS and CSS for patients with PDA. The prognostic nomograms were evaluated using Concordance index (C-index) and receiver operating characteristic (ROC) curve, with internal validation performed through Decision Curve Analysis (DCA).

Results: Independent prognostic factors, including age, marital status, lymph node status, distant metastasis, surgery method, chemotherapy, and Gleason score, were incorporated into the developed nomograms. The results of training (C-index: OS = 0.74, CSS = 0.69; AUC value: OS = 0.822-0.892, CSS = 0.836-0.873) and internal validation (C-index: OS = 0.78, CSS = 0.77) indicated our nomograms had good performance The clinical decision curve indicated that the nomogram had a good clinical net benefit.

Conclusions: This study successfully established and validated prognostic nomograms tailored for PDA patients.