Expert Review of Anticancer Therapy最新文献

Introduction: Triple-negative breast cancer (TNBC) continues to be a significant concern, especially among minority populations, where treatment disparities are notably pronounced. Addressing these disparities, especially among African American women and other minorities, is crucial for ensuring equitable healthcare.

Areas covered: This review delves into the continuum of TNBC treatment, noting that the standard of care, previously restricted to chemotherapy, has now expanded due to emerging clinical trial results. With advances like PARP inhibitors, immunotherapy, and antibody-drug conjugates, a more personalized treatment approach is on the horizon. The review highlights innovative interventions tailored for minorities, such as utilizing technology like text messaging, smartphone apps, and targeted radio programming, coupled with church-based behavioral interventions.

Expert opinion: Addressing TNBC treatment disparities demands a multifaceted approach, blending advanced medical treatments with culturally sensitive community outreach. The potential of technology, especially in the realm of promoting health awareness, is yet to be fully harnessed. As the field progresses, understanding and integrating the socio-economic, biological, and access-related challenges faced by minorities will be pivotal for achieving health equity in TNBC care.

Background: Circulating tumor DNA (ctDNA) in peripheral blood has become a promising noninvasive biomarker. However, the diagnostic potential of Wnt/β-catenin signaling pathway-related ctDNA for liver cancer is controversial. Here, we aimed to access the diagnostic potential and clinicopathological features of Wnt/β-catenin signaling pathway-related ctDNA in liver cancer and provide data support for its clinical diagnosis and treatment.

Methods: A comprehensive literature search was conducted to identify the relevant studies. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. The bivariate linear mixed models were used.

Results: The AUC (area under the curve), pooled sensitivity and specificity were 0.77, 0.42 and 0.98, respectively. The findings suggested that control type, sample source, research methods and thresholds were the potential sources of heterogeneity (p < 0.05). Additionally, this study also found that there were significant correlations between the hypermethylation of Wnt/β-catenin signaling pathway-related ctDNA and tumor size, TNM stage, distant metastasis, and HBV infection(p < 0.05).

Conclusion: This study confirmed that Wnt/β-catenin signaling pathway-related ctDNA had the better diagnostic potential for liver cancer and might be an effective complementary tool for serum AFP assays in the early diagnosis of liver cancer.

Prospero: (No. CRD42023404984).[Figure: see text].

Background: We aimed to develop a nomogram to predict the overall survival of elderly patients with Triple-negative invasive ductal breast carcinoma (TNIDC).

Research design and methods: 12165 elderly patients with nonmetastatic TNIDC were retrieved from the SEER database from 2010 to 2019 and were randomly assigned to training and validation cohorts. Stepwise Cox regression analysis was used to select variables for the nomogram based on the training cohort. Univariate and multivariate Cox analyses were used to calculate the correlation between variables and prognosis of the patients. Survival analysis was performed for high- and low-risk subgroups based on risk score.

Results: Eleven predictive factors were identified to construct our nomograms. Compared with the TNM stage, the discrimination of the nomogram revealed good prognostic accuracy and clinical applicability as indicated by C-index values of 0.741 (95% CI 0.728-0.754) against 0.708 (95% CI 0.694-0.721) and 0.765 (95% CI 0.747-0.783) against 0.725 (95% CI 0.705-0.744) for the training and validation cohorts, respectively. Differences in OS were also observed between the high- and low-risk groups (p < 0.001).

Conclusion: The proposed nomogram provides a convenient and reliable tool for individual evaluations for elderly patients with M0_stage TNIDC. However, the model may only for Americans.

Introduction: Chemotherapy has been traditionally used as neo-adjuvant therapy in breast cancer for down-staging of locally advanced disease in all sub-types. In the adjuvant setting, genomic assays have shown that a significant proportion of ER positive/HER2 negative patients do not derive benefit from the addition of chemotherapy to adjuvant endocrine therapy. An interest in hormonal treatments as neo-adjuvant therapies in ER positive/HER2 negative cancers has been borne by their documented success in the adjuvant setting. Moreover, cytotoxic chemotherapy is less effective in ER positive/HER2 negative disease compared with other breast cancer subtypes in obtaining pathologic complete responses.

Areas covered: Neo-adjuvant therapies for ER positive/HER2 negative breast cancers and associated biomarkers are reviewed, using a Medline survey. A focus of discussion is the prediction of patients that are unlikely to derive extra benefit from chemotherapy and have the highest probabilities of benefiting from hormonal and other targeted therapies.

Expert opinion: Predictive biomarkers of response to neo-adjuvant chemotherapy and hormonal therapies are instrumental for selecting ER positive/HER2 negative breast cancer patients for each treatment. Chemotherapy remains the standard of care for many of those patients requiring neo-adjuvant treatment, but other neo-adjuvant therapies are increasingly used.

Introduction: Chronic lymphocytic leukemia (CLL) management has witnessed a transformative shift with the advent of time-limited venetoclax and anti-CD20 monoclonal antibody (mAb) regimens, as exemplified by the groundbreaking MURANO and CLL14 trials.

Area covered: This article delves into the long-term follow-up data of fixed duration (FD) venetoclax combined with anti-CD20 mAb across various lines of CLL therapy. The data discussed here, not yet available in current literature, was unveiled at the 23^rd European Hematological Association (EHA) congress held in Frankfurt in June 2023.

Expert opinion: Combinations of venetoclax with anti-CD20 mAbs represent a compelling therapeutic option due to their finite treatment duration and remarkable achievement of undetectable minimal residual disease (uMRD). This not only ensures more enduring responses but also presents a manageable toxicity profile that suits a broad spectrum of CLL patients, including those who are elderly or less medically fit.Importantly, the integration of venetoclax/anti-CD20 mAb FD regimens may diminish the likelihood of CLL patients developing target mutations. This, in turn, enhances the potential for eliciting secondary clinical responses upon retreatment with venetoclax. Additionally, from an economic perspective, the cost-effectiveness of targeted therapy may further advocate for the selection of FD therapy as a frontrunner in CLL treatment.

Objectives: Neoadjuvant immunotherapy has emerged as a prominent research focus recently. For potentially operable patients, neoadjuvant therapy serves as a primary method to reduce tumor load and facilitate surgical interventions.

Methods: We retrieved articles from PubMed, Embase, Cochrane Library, American Society of Clinical Oncology, and European Society of Medical Oncology websites from inception to December 2023. Statistical analyses were performed using the R software. Primary outcomes assessed included major pathological response (MPR), pathological complete response (pCR), and treatment-related adverse events (trAEs).

Results: 29 studies encompassing 1163 patients were included. The MPR rate of neoadjuvant combination immunotherapy was 38% (95% confidence interval [CI]: 25%-52%), and the pCR rate was 33% (95%CI: 25%-42%). These values were significantly higher than those obtained with single agent immunotherapy (p < 0.001). The pooled incidence of overall trAEs was 83% (95%CI: 73%-92%), and grade (G) 3-4 trAEs was 22% (95%CI: 15%-29%), both significantly higher than those observed with single agent immunotherapy (p < 0.05).

Conclusion: This study demonstrated the efficacy of neoadjuvant combination immunotherapy. Given that the majority of the included trials were phase II with small sample sizes, further multicenter phase III randomized controlled trials should be conducted to validate the findings of the review.

Introduction: To provide an overview of the available literature data on clinical applications of positron emission tomography (PET) targeting the urokinase-type plasminogen activator receptor in oncology.

Methods: A literature search was conducted in PubMed, Web of Science and Scopus databases up to June 2023. The results were presented according to the PRISMA guidelines. The quality of the studies was assessed using the Critical Appraisal Skill Program checklist.

Results: Seven papers were selected for final analysis, involving 266 patients with solid tumors who underwent PET with uPAR-ligands. Thematic areas identified include feasibility studies (n = 2) on the safety, pharmacokinetics, and dosimetry of uPAR-targeting radiopharmaceuticals; uPAR-directed imaging in head and neck cancer (n = 2); uPAR PET in prostate cancer (n = 2); and the investigation of uPAR in neuroendocrine neoplasms (n = 1). Six of the seven studies used the radiopharmaceutical [⁶⁸Ga]Ga-NOTA-AE105 while one study used [⁶⁴Cu]Cu-DOTA-AE105. The studies showed protocol homogeneity, with static PET imaging at 20 minutes. The quality assessment revealed limitations such as small cohorts and the fact that all studies were performed by a single research group.

Conclusions: uPAR-PET appears to be a promising imaging tool in well-selected oncological settings, but it needs to be validated by multicentre collaboration.

Background: Dickkopf-1 (DKK1) exhibits abnormal expression in various cancers and correlates with poor prognosis. This study investigates DKK1's prognostic relevance in head and neck squamous cell carcinoma (HNSC).

Methods: We conducted a comprehensive search across literature and sequencing databases to gather eligible studies and HNSC datasets. We calculated pooled standardized mean differences (SMD) and 95% confidence intervals (CI) for clinical characteristics, as well as hazard ratios (HR) with 95% CIs for overall survival (OS) and progression-free/disease-free survival (PFS/DFS). Sensitivity analysis gauged result stability, and Egger's test assessed publication bias.

Results: Pooled results indicated that HNSC patients with higher T-stage exhibited elevated DKK1 expression levels, and this elevated expression was associated with shorter OS and PFS/DFS. While sensitivity analysis identified some studies significantly affecting pooled results, most were unaffected, and no publication bias was detected.

Conclusion: DKK1 holds promise as a potential biomarker for predicting poor prognosis in HNSC patients, but further research is needed for confirmation.

Objectives: We hypothesize that digital droplet polymerase chain reaction (ddPCR) would optimize the treatment strategies in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) relapsed patients. In this study, we compared the efficacy of third-generation TKIs with various T790M statuses via ddPCR and next-generation sequencing (NGS).

Methods: NGS was performed on blood samples of patients progressed from previous EGFR-TKIs for resistance mechanism. T790M-negative patients received further liquid biopsy using ddPCR for T790M detection.

Results: A cohort of 40 patients were enrolled, with 30.0% (12/40) T790M-positive via NGS (Group A). In another 28 T790M-negative patients by NGS, 11 (39.3%) were T790M-positive (Group B) and 17 (60.7%) were T790M-negative (Group C) via ddPCR. A relatively longer progression-free survival (PFS) was observed in group A (NR) and group B (10.0 months, 95% CI 7.040-12.889) than in group C (7.0 months, 95% CI 0.000-15.219), with no significant difference across all three groups (p = 0.196), or between group B and C (p = 0.412). EGFR-sensitive mutation correlated with inferior PFS (p = 0.041) and ORR (p = 0.326), and a significantly lower DCR (p = 0.033) in T790M-negative patients via NGS (n = 28).

Conclusion: This study indicates that ddPCR may contribute as a supplement to NGS in liquid biopsies for T790M detection in EGFR-TKIs relapsed patients and help to optimize the treatment strategies, especially for those without coexistence of EGFR-sensitive mutation.

Trial registration: www.clinicaltrials.gov identifier is NCT05458726.