Oncology最新文献

Introduction: In recent years, the therapeutic scenario of metastatic biliary tract cancers (BTCs) beyond first-line has profoundly changed owing to target therapies. human epidermal growth factor receptor-2 (HER2) represents a promising molecular target that is frequently altered in BTC. The present meta-analyses aimed to describe the response rates and survival outcomes in patients with HER2-positive locally advanced/metastatic BTC treated with anti-HER2 therapies. Moreover, the study is intended to provide an update on the evolving therapeutic scenario of HER2-overexpressed BTC.

Methods: We performed a systematic review of the literature to identify clinical trials investigating any regimen comprising a HER2-targeted therapy for metastatic BTC, and we conducted three subsequent meta-analyses on second-line phase II trials. The first one was performed to compare the group of HER2 3+ versus the group of HER2 2+ BTC patients for objective response rate (ORR). The second one compared patients according to the tumor location (gallbladder carcinoma [GBC] or extrahepatic cholangiocarcinoma [eCCA] versus intrahepatic cholangiocarcinoma [iCCA]) for ORR. The third one evaluated the overall outcomes in terms of overall survival (OS) and progression-free survival (PFS).

Results: Patients with advanced BTC and HER2 3+ had better ORR compared to HER2 2+, with a 3.7-fold higher probability of experiencing objective responses (HR 3.70, 95% CI, 1.34-10.25, p = 0.0119). Likewise, patients with GBC or eCCA had a 2.74-fold higher probability of experiencing an objective response compared to patients with iCCA (HR 2.74, 95% CI, 1.12-6.73, p = 0.0275). The weighted pooled analysis of trials with anti-HER2 agents in second line or beyond revealed an mPFS of 4.9 months (95% CI, 4.2-5.6), while mOS was 10.8 months (95% CI, 9.0-12.8).

Conclusions: Our meta-analyses have revealed improved efficacy in patients with HER2 3+ metastatic BTC and in patients with GBC or eCCA treated with anti-HER2 therapies, with a considerable mPFS and mOS in the overall population of the phase II trials analyzed. Further studies are paramount to confirm our preliminary results.

Introduction: Access to highly specialized interventional oncology procedures such as transarterial chemoembolization (TACE) and radioembolization (TARE) may be limited in nonmetropolitan areas of the USA. This study aimed to evaluate whether disparities in access to TACE and TARE exists in these regions.

Methods: This study characterizes the distribution of these procedures across regions by metropolitan status through utilization of a large commercial healthcare claims database (Truven Merative Marketscan). Patients with a diagnosis of primary hepatocellular carcinoma (n = 41,280) were categorized into those who received TACE (n = 1,780) or TARE (n = 1,179). Chi-squared tests of association were utilized to analyze regional data.

Results: Statistical analyses showed significant differences between most regional comparisons with most patients receiving these procedures originating from metropolitan areas overall.

Conclusion: Though limited to TACE and TARE, this study reveals a disparate distribution of TACE and TARE utilization across regions with preference toward metropolitan over nonmetropolitan areas, which may represent a barrier for access to care for nonmetropolitan patients, though this remains to be studied.

Introduction: Atezolizumab plus bevacizumab (ATZ + BV) is used for the treatment of Barcelona Clinic Liver Cancer (BCLC) stage B unresectable hepatocellular carcinoma (u-HCC) patients. However, the efficacy of ATZ + BV in various BCLC stage B conditions, especially the up-to-seven criteria in/out, has not been fully investigated.

Methods: We enrolled 83 BCLC stage B u-HCC patients with Child-Pugh class A who were treated with ATZ + BV as the first-line systemic chemotherapy in the study. All patients were evaluated for initial responses by dynamic computed tomography or magnetic resonance imaging after the initiation of ATZ + BV, and therapeutic efficacy was assessed.

Results: When stratified by up-to-seven criteria, progression-free survival (PFS) was significantly prolonged in patients with up-to-seven in (in vs. out: median 21.0 vs. 8.2 months, p = 0.006), and the Cox proportional hazard model showed that up-to-seven out/in was the significant factor contributing to PFS (out vs. in: HR 2.58, p = 0.007). We next evaluated PFS stratified by the maximum intrahepatic tumor diameter and number of intrahepatic tumors, which constitute the up-to-seven criteria. The number of tumors was a significant factor contributing to PFS (>7 vs. ≤7: HR 1.75, p = 0.040), but maximum tumor size was not (>5 cm vs. ≤5 cm: HR 1.19, p = 0.588).

Conclusion: In BCLC stage B u-HCC patients treated with ATZ + BV, a high number of intrahepatic tumors were associated with poor PFS. Therefore, it may be better to consider additional treatment strategies in these patients.

Introduction: The prognostic value of the modified Glasgow Prognostic Score (mGPS), a systemic inflammatory response marker, has been reported in various cancers. However, its role in patients with metastatic colorectal cancer (mCRC) undergoing first-line FOLFOXIRI + bevacizumab (BV) therapy remains unclear. In this study, we aimed to evaluate the prognostic significance of pretreatment mGPS and other inflammatory markers in this patient population.

Methods: This study retrospectively reviewed 133 patients with mCRC treated with first-line FOLFOXIRI + BV. We assessed the prognostic value of pretreatment mGPS and other inflammatory markers (neutrophil-to-lymphocyte, platelet-to-lymphocyte, and lymphocyte-to-monocyte ratios) in relation to progression-free survival (PFS) and overall survival (OS).

Results: Higher mGPS (score 2) was significantly associated with poor PFS and OS. Multivariate analysis identified mGPS 2 as an independent predictor of worse PFS (hazard ratio: 2.76, p = 0.004) and OS (hazard ratio: 3.43, p < 0.001). No significant associations were found between other inflammatory markers and survival outcomes.

Conclusions: Pretreatment mGPS is a simple and useful prognostic factor for mCRC patients receiving FOLFOXIRI + BV therapy and may serve as a convenient indicator for accurate prognosis prediction and treatment decision-making.

Introduction: MiRNAs play important roles in development of various cancers including gastric cancer. Exosomes are extracellular vesicles for translocating molecules. This study aimed to investigate the tumor suppressive roles of miR-379-5p in gastric cancer and to investigate the roles of exosomes in transporting miR-379-5p from intracellular to extracellular.

Methods: Fifty-three pairs of gastric cancer and non-tumor tissue samples were collected. Five cell lines were applied. Functional assays including cell proliferation, cell migration and invasion, and cell adhesion assay were performed. Targets of miR-379-5p were screened and validated by Western blot. Expressions of endogenous miR-379-5p in gastric cancer cells and exosomal miR-379-5p in cell culture medium were evaluated by RT-qPCR. Medium of culturing AGS or BCG23 was applied for culturing MKN45 and HEK293T.

Results: The results indicated that miR-379-5p was significantly downregulated in gastric cancer tissue samples and cell lines. Enforced expression of miR-379-5p inhibited gastric cancer cell proliferation, migration, and invasion, while miR-379-5p mimic enhanced cell adhesion to extracellular matrix. IGF1R was a potential target of miR-379-5p in gastric cancer. Expression of miR-379-5p was dramatically higher in exosomes in cell culture medium than its endogenous expression. Exosomes from cell culture medium of AGS or BCG23 could regulate endogenous expression of miR-379-5p in HEK293T cells.

Conclusions: MiR-379-5p was significantly downregulated and it functioned as a tumor suppressor in gastric cancer. MiR-379-5p was highly expressed in exosomes of culture medium than its endogenous expression. MiR-379-5p could be translocated from cells into cell culture medium and entered certain cell types via exosomes.

Introduction: Artificial intelligence (AI) is increasingly being researched and developed in the medical field and holds the potential to transform healthcare after successful implementation. For patients with colorectal cancer liver metastases (CRLM), many AI models have been developed, but knowledge about translation of these models in the clinical workflow is lacking. Therefore, this systematic review aimed to provide a contemporary overview of the current maturity status of AI models for patients with CRLM.

Methods: A systematic search of the literature until November 2, 2023, was conducted in PubMed, Embase.com, and Clarivate Analytics/Web of Science Core Collection to identify eligible studies. Studies using AI and/or radiomics for patients with CRLM were considered eligible. Data on the study aim, study design, size of dataset, country, type of AI application, level of validation and clinical implementation status (NASA technology readiness levels) were collected. Risk of bias and applicability of the individual studies were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST).

Results: A total of 117 studies were included. Ninety-seven studies (83%) have been published in the last 5 years. The most common study design was retrospective (96%). Thirty-five studies (30%) utilized a dataset of fewer than 50 patients with CRLM. Internal validation was performed in 63% of the studies and external validation in 17%. The remaining studies did not report validation. Half of the studies were classified as high risk of bias. None of the included studies performed real-time testing, workflow integration, clinical testing, or clinical integration.

Conclusion: Although a rapid increase in research describing the development of AI models for patients with CRLM has been observed in recent years, not a single AI model has been translated into clinical practice.

Introduction: Immune checkpoint inhibitors (ICIs) have improved lung cancer treatment but are associated with an increased risk of cardiotoxicity. We investigated whether statins could mitigate ICI-associated cardiovascular risks in lung cancer patients.

Methods: We performed a retrospective, propensity score-matched cohort study utilizing the TriNetX database. We identified lung cancer patients receiving ICIs between April 2013 and June 2023. We created two cohorts: statin users and non-users. The primary efficacy outcome was major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction, ischemic stroke, and heart failure. The secondary efficacy outcomes were myocarditis and cardiac arrest. Safety outcomes were all-cause mortality and serious immune-related adverse events (irAEs).

Results: A total of 16,650 lung cancer patients undergoing ICIs were identified, consisting of 6,812 statin users and 9,838 non-users. After propensity score matching, 4,379 patients were well-matched in baseline characteristics. Over a follow-up period of 12 months, statin use was associated with a lower risk of MACE (HR: 0.87, 95% CI: 0.78-0.98), primarily driven by reductions in myocardial infarction (HR: 0.75, 95% CI: 0.58-0.97) and heart failure (HR: 0.85, 95% CI: 0.74-0.98). For safety outcomes, statin use was associated with a reduction in all-cause mortality (HR: 0.83, 95% CI: 0.77-0.90) and did not result in an increased risk of serious irAEs.

Conclusion: The use of statins in lung cancer patients with cardiovascular risk factors and without previous cardiovascular events undergoing immunotherapy was associated with a reduction in MACE and all-cause mortality without an increased risk of serious adverse events.

Introduction: Predicting post-treatment prognosis in hepatocellular carcinoma (HCC) patients undergoing conventional transarterial chemoembolization (cTACE) is challenging due to tumor heterogeneity. We here assessed the utility of the modified albumin-bilirubin grade and α-fetoprotein (mALF) score for predicting the prognosis of cTACE-treated HCC patients.

Methods: This retrospective observational study included 206 early- and intermediate-stage HCC patients who had undergone cTACE. We calculated baseline and post-treatment mALF scores by assigning one point for a modified albumin-bilirubin grade of 2b or 3 and one point for an alpha-fetoprotein level of ≥100 ng/mL.

Results: The baseline mALF scores were 0, 1, and 2 points for 66 patients (32%), 95 patients (47%), and 45 patients (21%), respectively, and their median survival times were 42.3 months, 21.1 months, and 14.0 months, respectively. The baseline mALF score was also associated with overall survival, independent of the Barcelona Clinic Liver Cancer stage and the tumor burden score (hazard ratio, 1.97; 95% confidence interval, 1.56-2.49; p < 0.001). One month after cTACE, the mALF score had decreased in 26 patients and increased in 31 patients. In those with a baseline mALF score of 0 or 1, the increased mALF score was significantly associated with shorter survival periods after cTACE.

Conclusion: The baseline mALF score was useful in stratifying HCC patients undergoing cTACE, according to post-treatment prognosis. Increased mALF scores after cTACE were associated with poor prognosis in patients with a baseline mALF score of 0 or 1. Assessment of baseline and post-treatment mALF scores may help in predicting prognosis in HCC patients following cTACE.

Introduction: Despite recent advancements, outcomes for unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (atezo/bev) remain suboptimal, with drug resistance posing a major challenge. This study evaluated the efficacy of additional locoregional treatments (LRTs) for oligo-atezo/bev-resistant lesions.

Methods: We retrospectively analyzed patients with intermediate-stage and advanced-stage HCC who developed drug-resistant lesions during first-line atezo/bev therapy. Patients were divided into two groups: the combination therapy group (n = 10) receiving additional LRT and the atezo/bev alone group (n = 26). Progression-free survival (PFS) 1 was measured from atezo/bev therapy initiation to progressive disease (PD) or death, whereas PFS2 was calculated from atezo/bev therapy initiation to PD of second-line therapy or death. The PFS1 in the combination therapy group was compared to the PFS1 and PFS2 in the atezo/bev alone group. Two analyses were performed for the PFS and overall survival (OS): one including the total cohort and the other restricted to those eligible for LRT upon the appearance of atezo/bev-resistant lesions. Changes in the hepatic reserve before and after LRT were also assessed.

Results: LRT, followed by continued atezo/bev therapy, safely eradicated drug-resistant lesions in the combination therapy group, without compromising the hepatic reserve. All patients in the combination therapy group transitioned to second-line treatment due to preserved hepatic reserve after PD. The PFS1 in the combination therapy group was longer than the PFS1 and PFS2 in the atezo/bev alone group in both the total cohort and LRT-eligible subgroup. Similarly, the OS in the combination therapy group was longer than in the atezo/bev alone group in both analyses.

Conclusion: LRTs may provide a viable option for managing oligo-drug-resistant lesions during first-line atezo/bev therapy for unresectable HCC when safely administered.

Background: Kidney transplant recipients are increasing, as is their life expectancy. Due to immunosuppression, skin cancers are the neoplasms more common in this population.

Summary: Cancer immunotherapy is the choice treatment for squamous cell non-melanoma skin cancer (NMSC) patients who are not candidates for local therapies such as radiotherapy and surgery. For basal cell carcinomas requiring systemic therapies, hedgehog inhibitors (HHis) are necessary. Traditionally, special populations, such as solid organ transplant recipients, were excluded from clinical studies. We reviewed the literature on immunotherapy and HHis for NMSC in this specific population.

Key messages: Immunotherapy may be administered to selected patients following a thorough multidisciplinary evaluation. Factors such as prior episodes of rejection, high proteinuria, and elevated anti-donor antibody levels should be considered relative contraindications. Similarly, HHis may be prescribed with caution in selected patients, with careful monitoring of renal function and the potential development of additional squamous cell carcinomas.