Cancer treatment and research communications最新文献

Background: Trilaciclib is a transient cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that reduces the incidence of chemotherapy-induced myelosuppression (CIM). In this pooled analysis, we evaluated the multilineage myeloprotection, antitumor efficacy, and safety of trilaciclib treatment in patients with extensive-stage small-cell lung cancer (ES-SCLC). Moreover, myeloprotection effect in 1 L, 2 L/3 L population and effect by risk category were explored.

Materials and methods: Patients with ES-SCLC who received trilaciclib were included. Trilaciclib was administered before chemotherapy in four randomized, double-blind, placebo-controlled studies (NCT02499770, NCT03041311, NCT02514447, and NCT04902885), and data were subsequently extracted. The primary endpoints were the duration of severe neutropenia (DSN) in cycle 1 and/or the incidence of severe neutropenia (SN).

Results: The data from 325 patients receiving trilaciclib (n = 164) or placebo (n = 161) were pooled. Trilaciclib demonstrated a clinically and statistically significant reduction in DSN in cycle 1 and in the incidence of SN and febrile neutropenia (FN) in the overall, 1 L, 2 L/3 L populations. The myeloprotection effect was greater in patients with a higher number of FN risk categories. Overall, the median progression-free survival was 5.3 months in the trilaciclib and 4.9 months in the placebo group. The median overall survival was 10.9 months in the trilaciclib and 10.1 months in the placebo group. Trilaciclib showed better capability of reducing CIMs incidence compared with prophylactic G-CSF in the overall and 1 L population.

Conclusions: Trilaciclib prior to chemotherapy in patients with ES-SCLC reduced incidence of CIM and need for supportive care in CIM across all treatment settings.

Micro abstract: Area and reason for the study: Extensive-stage small-cell lung cancer (ES-SCLC). To analyze the effect of trilaciclib on Chinese and Caucasian patients. Approach taken, including aspects such as the sample size: This pooled analysis included one study in China and three studies in western countries, and the overall sample size was 325. Overall result: Trilaciclib provides protection from CIM. General significance of the findings: The consistent efficacy of trilaciclib can be observed from pooled data across different treatment lines. All information should be accessible to a nonexpert audience.

Clear cell renal cell carcinoma (ccRCC) poses a significant global health challenge as its incidence continues to rise, resulting in a substantial annual mortality rate. Major clinical challenges to current ccRCC treatments include high drug-resistance rates as well as dose-limiting adverse events; underlining the need to identify additional 'druggable' targets. TGF-β1, VEGF, and PD-L1 are potential therapeutic targets in ccRCC. This study analyzed their expression in human ccRCC cell lines and patient tumor biopsies. Data obtained from western blotting demonstrated higher levels of TGF-β1 and PD-L1 and lower levels of VEGF in sarcomatoid ccRCC cell lines compared to non-sarcomatoid ccRCC cell lines. In patient samples, TGF-β1 was significantly upregulated in both non-sarcomatoid and sarcomatoid ccRCC tumors. It was demonstrated through two assays (cellular thermal shift assay and a size exclusion assay) that methylseleninic acid (MSA) binds specifically and directly to TGF-β1. MSA treatment significantly downregulated TGF-β1, PD-L1, and VEGF in a dose- and time-dependent manner in both non-sarcomatoid and sarcomatoid ccRCC cell lines. Seleno-L-methionine (SLM) treatment in a nude mouse xenograft model showed a significant tumor growth inhibition and TGF-β1 downregulation at non-toxic doses. These findings suggest that selenium-mediated downregulation of TGF-β1, PD-L1, and VEGF could be a viable therapeutic strategy for ccRCC.

Purpose: There is evidence that adding cetuximab can overcome resistance to irinotecan, but a similar analysis with Panitumumab isn't readily available. This study evaluated the activity of each anti-EGFR plus irinotecan as a salvage third-line treatment for metastatic colorectal cancer.

Methods: This is a retrospective cohort of metastatic colorectal cancer patients who progressed to irinotecan monotherapy and were exposed to an anti-EGFR antibody as a third line of treatment. This study was conducted at a single cancer center in Brazil. The primary outcome was overall survival. The secondary outcomes were objective response rate, stratified by primary tumor sidedness, progression-free survival, and toxicity.

Results: This analysis included 412 patients who had progressed on irinotecan and were KRAS wild-type. One hundred eighty-two received Irinotecan plus Cetuximab (I + C group) and 230 Irinotecan plus Panitumumab (I + P group). There was no significant difference in median overall survival between treatment groups (9.1 months [I + C] vs 10.1 months [I + P]; p = 0.76). There was also no difference in progression-free survival (3.63 months [I + C] vs 3.73 months [I + P]; p = 0.19) and objective response rate (23.0 % [I + C] vs 22.3 % [I + P]; p = 0.97). Patients with right-sided tumors had worse overall survival than left-sided (6.2 months vs 10.1 months; p = 0.003) but presented a better objective response rate with panitumumab (8.3 % [I + P] vs 3.3 % [I + C]). There were more infusion reactions with cetuximab.

Conclusions: Panitumumab and cetuximab have similar activity when combined with irinotecan as treatment for patients with disease progression with an irinotecan regimen, potentially rescuing the irinotecan activity.

Unresectable stage III non-small cell lung cancer (NSCLC) carries a poor prognosis. The PACIFIC trial established consolidation durvalumab after chemoradiation as a standard treatment; however, its efficacy in patients with driver mutations remains uncertain. This retrospective cohort study analyzed data from three oncology centers in Hong Kong, covering the period from January 2019 to December 2022. Among the 118 patients who underwent definitive chemoradiation, 33 had common driver mutations, including EGFR mutations, ALK rearrangements, ROS1 rearrangements, and RET fusions. The addition of durvalumab did not improve real-world recurrence-free survival (rwRFS) in patients with these mutations (hazard ratio [HR] 0.852, 95 % confidence interval [CI] 0.394 - 1.843, p= 0.683). In contrast, rwRFS significantly improved for patients without common mutations (HR 0.342, 95 % CI 0.203 - 0.577, p< 0.001). These findings suggest that consolidation durvalumab may not be beneficial for patients with common driver mutations, underscoring the need for personalized treatment strategies in this population.

Angiosarcomas are a type of soft-tissue sarcoma characterized by aggressive malignant tumors originating from endothelial cells of blood vessels or lymphatic vessels. Limited studies have been done to explore the molecular pathophysiology of the disease, with rather limited studies involving transcriptomic analyzes. This study was undertaken to identify the shared molecular signatures and gene modules associated with angiosarcomas of various origin. Transcriptomic data analysis of publicly available data was done followed by WGCNA to identify shared signature gene modules. The Maximal Clique Centrality algorithm was applied to gene modules, and unclustered network analysis was conducted on differentially expressed genes to identify true hub genes. The expression of candidate genes in various cancer types was analyzed using GEPIA. WGCNA analysis identified five significant modules, with the most enriched module being associated with angiogenesis and cell junction regulators. The intersection of true hub genes from MCC analysis of WGCNA modules and high-degree nodes from an unclustered network revealed eight consistently overexpressed genes in all angiosarcoma samples.Among the eight enriched genes, CHRNA5 and CTLA4, are exclusively overexpressed in angiosarcoma and not in other cancers of the same tissue origin, with significant drug-protein interactions suggesting their potential as therapeutic targets.

Background and aim: Non-small cell lung cancer (NSCLC) is the most common lung cancer found in elderly patients. Aging and chronic inflammation are related to its pathogenesis. Functional status, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio describe a chronic inflammation and correlate to the survival of older adults with advanced-stage (IIIB-IV) NSCLC. This study aims to determine functional status, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio as prognostic factors to 1-year survival in elderly patients with NSCLC stage IIIB-IV.

Methods: Survival analysis with a cohort retrospective study is conducted on elderly patients with NSCLC stage IIIB-IV in Dharmais National Cancer Center Hospital between January 2020 and June 2022. Medical records were collected, comprising complete blood count prior to chemotherapy or radiotherapy, assessment of functional status through the Barthel Index for Activities of Daily Living (ADL), and 1-year survival post-diagnosis. Factors potentially influencing outcomes included diabetes mellitus, anemia, chronic obstructive pulmonary disease, and chronic kidney disease. Statistical analyses were performed using SPSS 20.0, employing the log-rank method for bivariate analysis and Cox regression for multivariate analysis.

Results: In a cohort of 108 patients, the majority were aged 60-69 years (74.1 %), male (66.7 %), diagnosed at stage IV (80.5 %), and with adenocarcinoma subtype (75.0 %). Significant correlations were observed between the lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio with the 1-year survival rate in elderly patients with stage IIIB-IV NSCLC (p = 0.015 and p = 0.001, respectively). Functional status did not show a significant correlation with 1-year survival overall (p = 0.540), but significant correlations were noted in patients receiving chemotherapy (p = 0.044) and radiotherapy (p = 0.009).

Conclusion: The lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio provide significant prognostic insights regarding 1-year survival in elderly patients diagnosed with stage IIIB-IV non-small cell lung cancer (NSCLC). In contrast, the functional status of these patients does not demonstrate a significant correlation with one-year survival.

The incidence of cancer continues to increase worldwide, resulting in significant physical, emotional, and financial challenges for individuals, families, communities, and healthcare systems. Cancer is projected to be responsible for approximately 10 million deaths in 2020, accounting for one in six deaths globally. Prostate, colon, lung, and breast cancers are the most common types of cancer. In India, it is estimated that there will be around 2.7 million cancer patients by 2020. Personalized medicine has the potential to offer an alternative approach to cancer treatment. Precision medicine, often known as personalized medicine, is a new cancer treatment technique that focuses on tailoring medication to each patient's specific genetic, biochemical, and lifestyle factors. The goal is to optimize tumor response while minimizing therapy side effects, resulting in improved patient care and quality of life. Personalized medicine allows for the creation of focused medicines that address specific gene mutations by leveraging knowledge about a patient's cancer, including its genetic makeup. Ongoing research seeks to detect gene modifications in diverse cancer types, produce novel diagnostic tools, and develop treatments that particularly target these genetic changes. In recent years, personalized medicine has achieved major advances in the treatment of solid tumors, with the promise to improve treatment precision, reduce side effects, as well as enhance outcomes for patients in cancer therapy. This review aims to objectively evaluate the transformation of cancer treatment, emphasizing the shift towards a more precise methodology.

Background: Pleural carcinosis originates from various cancers. Its management consists in systemic therapies combined to dyspnea relief procedures. Prior studies have tested hyperthermic intrathoracic chemotherapy to treat pleural carcinosis with interesting patient survival results. However, these approaches were limited by local toxicity. Pre-clinical data have shown that hyperthermia combined to local pleural chemotherapy increased the immune response against tumors. Recently, pressurized intraperitoneal aerosol chemotherapies (PIPAC) showed improved cytostatic penetration in abdominal carcinosis with a 10-fold-lower chemotherapy dose and minimal side-effects. This approach was also tested in limited numbers of patients with pleural carcinosis but never combined with hyperthermia.

Methods: Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin (PITHAC) is an open-label dose-escalation phase I trial. Patients with pleural carcinosis, eligible for the surgical management of their pleural effusion can be enrolled. Cisplatin (7.5-12-5-35-70 mg/m2) heated at 39±1 °C is delivered into the thoracic cavity before the surgical effusion management. Initially, the study consists in a dose escalation of the four different cisplatin doses. The primary endpoint is the maximal tolerated dose of cisplatin administered by PITHAC. The secondary and translational endpoints are adverse events and the immune response directed against cancer following PITHAC. There is then an expansion phase at the recommended cisplatin dose on an additional 15 patients with identical outcomes.

Discussion: Pressurized intrathoracic delivery of chemotherapy under hyperthermic conditions was never tested so far. We plan to determine the safety of such an approach in patients managed for pleural carcinosis. If proven safe, PITHAC could be combined with systemic immunotherapies for the management of cancer.

Trial registration: ClinicalTrials.gov Identifier: NCT06281860.

Background: The World Health Organization's fifth edition of tumor series classification was published in 2019 and adopted the term 'Neuroendocrine neoplasm (NEN)' to encompass all tumor classes with predominant neuroendocrine differentiation (NED). Based on the updated classification of the NEN, we conducted a case series using the Clinical Data Warehouse platform of SMC.

Methods: In this retrospective study, breast NENs and invasive breast carcinomas no special type (IBCNST) with NED, were defined as 'NENS'. Based on pathology slide findings, a pathologist reclassified the diagnoses. Clinical presentation, tumor characteristics, and clinical outcomes of breast 'NENS' were reviewed retrospectively.

Results: A total of 34,370 patients were diagnosed with breast cancer from 1995 to 2022 in SMC, and 14 (0.04 %) patients were diagnosed with breast 'NENS': eight NECs, three NETs, and three IBCNST with NED. The patients' median age was 48.5 years. All patients were treated with curative intent surgery; five patients received neoadjuvant chemotherapy, twelve patients received radiotherapy, six patients received adjuvant chemotherapy, and eight patients received hormone therapy. The median follow-up period for the eight patients with breast NEC was 20.4 months. The median disease-free and overall survival were 14.2 months and 23.6 months, respectively. Patients with NET or IBCNST with NED (n = 6) had an overall favorable outcome, with no deaths, with only one case of disease recurrence.

Conclusion: The incidence of primary breast NENS' was very low (0.04 %) in this single-center study. Among them, primary breast NEC was associated with poor overall survival. Novel treatments are thus required to improve the prognosis of primary breast NEC.

Introduction: Altered body composition is associated with adverse survival in multiple cancers. We determined the prevalence, prognostic significance and clinicopathological correlates of sarcopenia and adipopenia in Pleural Mesothelioma (PM) patients receiving chemotherapy.

Methods: We performed a multi-centre retrospective cohort study. Clinical data and CT images were retrieved for 111 patients from 4 UK centres. Skeletal muscle (at L3 and T4) and fat tissue areas (at L3 only) were measured on pre- and post-chemotherapy CT scans (ImageJ software) and normalised for height. Pre-chemotherapy sarcopenia and adipopenia were defined using validated thresholds, where available or indices <25th percentile. Muscle/fat loss were defined by < 0 % change (%∆) between CT scans. Extreme muscle/fat loss were defined by <25th percentile of %∆. Overall survival associations were evaluated using Kaplan-Meier methodology ± Cox proportional hazards models.

Results: T4 and L3 measurements were possible in 111/111 and 91/111 (82 %). L3 sarcopenia was observed at baseline in 35 % (32/91); all other features were observed in 25 % at baseline, as defined a priori. Body composition changes during chemotherapy were heterogeneous. Overall, 61.5 % and 53.1 % patients lost muscle at L3 and T4. 60.4 % lost fat (at L3 only). Extreme T4 muscle loss and total fat loss were independently prognostic (HR 2.99, p < 0.001; HR 1.92, p = 0.014). Pre-chemotherapy T4 muscle indices were inversely associated with age. No associations were observed with tumour volume, histology, weight, inflammatory markers.

Conclusion: T4 muscle indices were feasible in all cases and outperformed L3 values in prognostication. Extreme T4 muscle and total fat loss were independently prognostic.