Clinical Medicine Insights-Oncology最新文献

Background: Surgical intervention, complemented by radiotherapy and chemotherapy with temozolomide, constitutes the conventional treatment protocol for patients with newly diagnosed grade 4 glioma. We have conducted a research to evaluate the efficacy and safety of an integrated treatment regimen that incorporates tumor-treating fields with concurrent chemoradiotherapy.

Methods: This retrospective research analyzed the clinical data of 39 adults who were newly diagnosed with World Health Organization (WHO) grade 4 gliomas at the First Affiliated Hospital of Nanjing Medical University, between February 2022 and April 2023. Each participant received a concurrent treatment regimen consisting of temozolomide (75 mg/m² daily), tumor-treating fields (200 kHz), and brain irradiation (60 Gy delivered in 30 fractions). Maintenance treatment comprised ongoing temozolomide and tumor-treating fields. Adverse events were documented in accordance with the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0) and specific grading criteria for dermatological adverse events associated with tumor-treating fields.

Results: Among the 39 enrolled patients, disease progression was observed in 22 individuals (56.4%), with a median progression-free survival (PFS) of 14.2 months (95% confidence interval [CI]: 13.1-14.3 months). The median overall survival (OS) was 18.2 months (95% CI: 17.3 months to not reached). Patients diagnosed with glioblastoma had a median PFS of 13.1 months (95% CI: 12.9-14.2 months) and a median OS of 18.2 months (95% CI: 17.3 months to not reached). In contrast, patients diagnosed with astrocytoma had a median PFS of 14.3 months (95% CI: 12.8 months to not reached) and a median OS of 17.0 months (95% CI: 10.6 months to not reached). Twenty-five patients (64.1%) experienced dermatological adverse events, and 30 (77.0%) experienced mild hematological adverse reactions related to chemoradiotherapy.

Conclusion: The application of tumor-treating fields concurrent with post-surgery chemoradiotherapy is both safe and effective for treating patients with newly diagnosed WHO grade 4 gliomas, exhibiting only limited toxicity.

Background: The clinical impact of heart failure (HF) on postoperative outcomes following video-assisted thoracic surgery (VATS) for lung cancer resection remains controversial. This study aimed to assess patient and hospital characteristics related to the type of surgery, as well as the independent impact of HF on surgical outcomes.

Methods: We conducted a retrospective analysis using data from the National Inpatient Sample database. A total of 20 693 patients aged 18 years or older, diagnosed with lung cancer, and undergoing lobectomy or sublobar resection via VATS between 2016 and 2020 were included. Patients were stratified based on the presence of HF. The HF-present cohorts were matched to HF-absent controls using a 1:2 nearest-neighbor propensity score-matching (PSM) analysis. The matched cohorts were then compared across several endpoints, including mortality, length of stay (LOS), hospitalization costs, and postoperative complications.

Results: After PSM, the study included 1781 patients who underwent lobectomy and 1157 who underwent sublobar resection, with 594 and 386 patients, respectively, having concurrent HF. In both the lobectomy and sublobar resection groups, patients with HF demonstrated significantly higher in-hospital mortality rates (P < .001), longer LOS (P < .001), increased total hospital charges (P < .001), and a greater risk for overall postoperative complications (P < .001).

Conclusions: Among patients with lung cancer undergoing VATS, the presence of HF is associated with an increased risk of postoperative complications. This finding underscores the necessity for enhanced monitoring and care for patients with HF should be treated during the postoperative recovery phase.

Background: Bile duct carcinoma (BTC) is an uncommon malignant tumor of the gastrointestinal tract. Management is limited after the progress of first-line treatment. Immune checkpoint inhibitors (ICIs) have been proven popular in solid tumors. Immunotherapy plus chemotherapy has been a standard scheme in the management of multiple types of cancer. However, their efficacy and safety still need further exploration in patients who diagnosed BTC. This research mainly discusses the efficacy of immunotherapy in the second-line use of cholangiocarcinoma.

Methods: In total, 126 individuals with BTC diagnosis from 2014 to 2024, who were treated with first-line or neoadjuvant treatment but were evaluated for progression or intolerance, were retrospectively included. All patients received standard chemotherapy, 57 received ICIs in combination with targeted therapy or not, and 69 did not. Patients were divided into simple chemotherapy (SC) and CT. Differences in efficacy, adverse events, progression-free survival (PFS), overall survival (OS), progressive disease (PD), and efficacy of multiple factors and efficacy were analyzed. The primary endpoint is defined as OS. The secondary endpoint is defined as PFS, objective response rate (ORR), disease control rate (DCR), and treatment-related adverse reactions (TRAEs).

Results: The PFS and OS of 4.68 and 30.26 months for ICIs with or without targeted therapy were proven statistically significant (P = .0012; P < .001). The ORR was 5.26% (3/57) in the CT group and 1.45% (1/69) in the SC group, and the DCR was 54.39% (31/57) compared with 33.33% (23/69). Cox analysis showed that TNM stage, T stage, histology grade, CA199 level, and treatment assessment grade were associated with OS (P < .05). Histologic differentiation (P = .009) and CA199 reduced (P = .003) were proven as independent prognostic factors. The highest grade of 3 to 4 adverse reactions (TRAEs) was a reduction in hemoglobin (29.37%).

Conclusion: Our work concluded that immunocombined chemotherapy with or without specific treatment showed significant antitumor activity and acceptable safety. Immune checkpoint inhibitors are likely to be a reliable second-line therapy for advanced BTC.

Background: In Hong Kong, breast cancer is the commonest female cancer. In addition to intrinsic risk factors that cannot be modified, other factors may be potentially modifiable. The objective of this report was to determine modifiable risk factors in association with breast cancer among Chinese women in our locality.

Methods: This is a case-control study that enrolled breast cancer patients from the Hong Kong Breast Cancer Registry and healthy matched controls from the local community between 2014 and 2017. Potential risk factors were analyzed using multiple logistic regression.

Results: In total, 5186 breast cancer patients and 5571 controls were recruited. Several modifiable risk factors were identified. Self-perceived high stress level (adjusted odd ratios [AOR]= 3.44; 95% confidence intervals [CI] = 3.13-3.78), dairy-rich diet (AOR = 3.33; 95% CI = 2.01-5.52), delayed child-bearing (AOR = 2.23; 95% CI = 1.79-2.79), meat-rich diet (AOR = 1.77; 95% CI = 1.54-2.04), ever use of oral contraceptives (AOR = 1.34; 95% CI = 1.22-1.47), nulliparity (AOR = 1.21; 95% CI = 1.08-1.35), and being overweight/obese (AOR = 1.21; 95% CI = 1.10-1.32) were found to be associated with an increased risk of breast cancer. On the other hand, breastfeeding (AOR = 0.76; 95% CI = 0.69-0.83) and exercise (odds ratio = 0.62; 95% CI = 0.56-0.68) were associated with decreased risk.

Conclusions: In our locality, high-stress level, meat- and dairy-rich diet, reproductive history, use of oral contraceptives, and being overweight/obese were identified to be modifiable risk factors for breast cancer. Lifestyle modification may help reduce breast cancer incidence in the coming decades.

Background: The correlation between fibrinogen levels and adrenocortical carcinoma (ACC) remains unclear. This study aimed to explore the value of preoperative plasma fibrinogen as a biomarker for ACC.

Methods: We identified 40 patients with ACC and 170 patients with adrenal adenoma (AA) who underwent surgery at our institution between 2015 and 2022. Plasma fibrinogen levels and postoperative tumor recurrence information of the patients were also recorded. For intergroup comparisons, data obtained from the AA and ACC groups were evaluated using a t-test. The cutoff value of fibrinogen level was determined using a receiver operating characteristic (ROC) curve.

Results: Mean fibrinogen levels in the AA and ACC groups were 2.81 ± 0.59 g/L and 3.88 ± 1.75 g/L, respectively (P < .001). Fibrinogen level, which can help distinguish between AA and ACC, was evaluated using the ROC curve. The cutoff fibrinogen level was estimated as 3.87 g/L according to the Youden index. With this value, the sensitivity was 62.5%, specificity was 95.7%, and the area under the ROC curve (AUC) was 0.74 (P < .001). Fibrinogen level, which can help distinguish between recurrence and non-recurrence, was evaluated using the ROC curve. The cutoff fibrinogen level was estimated as 3.96 g/L according to the Youden index. The sensitivity, specificity, and AUC were 90%, 71.4%, and 0.85, respectively (P < .001).

Conclusion: According to the data in this study, plasma fibrinogen could be used to distinguish ACC from AA. Most importantly, plasma fibrinogen may be used to identify recurrence of postoperative ACC.

Despite the expanding therapeutic options available to cancer patients, therapeutic resistance, disease recurrence, and metastasis persist as hallmark challenges in the treatment of cancer. The rise to prominence of generative artificial intelligence (GenAI) in many realms of human activities is compelling the consideration of its capabilities as a potential lever to advance the development of effective cancer treatments. This article presents a hypothetical case study on the application of generative pre-trained transformers (GPTs) to the treatment of metastatic prostate cancer (mPC). The case explores the design of GPT-supported adaptive intermittent therapy for mPC. Testosterone and prostate-specific antigen (PSA) are assumed to be repeatedly monitored while treatment may involve a combination of androgen deprivation therapy (ADT), androgen receptor-signalling inhibitors (ARSI), chemotherapy, and radiotherapy. The analysis covers various questions relevant to the configuration, training, and inferencing of GPTs for the case of mPC treatment with a particular attention to risk mitigation regarding the hallucination problem and its implications to clinical integration of GenAI technologies. The case study provides elements of an actionable pathway to the realization of GenAI-assisted adaptive treatment of metastatic prostate cancer. As such, the study is expected to help facilitate the design of clinical trials of GenAI-supported cancer treatments.

Background: Serum Cystatin S (CST4), a secretory protein that inhibits cellular matrix degradation, significantly influences the tumor microenvironment and tumor progression. However, the prognostic value of serum CST4 in gastric cancer (GC) remains unclear. This study aims to explore serum CST4's utility in GC prognostic assessment.

Methods: A cohort of 334 patients with GC who underwent radical gastrectomy was assessed. Preoperative serum CST4 levels were measured alongside traditional tumor markers, correlating with clinical data and patient outcomes. The cohort was divided into training and test sets at a ratio of 3:1 for Cox regression analyses, which identified CST4 as an independent risk factor for overall survival (OS) and disease-free survival (DFS). A prognostic model was developed, validated with calibration curves, and its predictive value was evaluated using receiver operating characteristic (ROC) curves. In addition, CST4 expression was correlated with immune cell infiltration using data from The Cancer Genome Atlas (TCGA). Patients were stratified by median CST4 levels, and Kaplan-Meier curves for OS and DFS were plotted.

Results: Cystatin S was confirmed as an independent risk factor for OS and DFS. Integrating CST4 with traditional markers and TNM pathological staging significantly enhanced the predictive value for prognosis. Cystatin S's impact on tumor progression is likely mediated through modulation of the immune microenvironment, including immune suppression and evasion.

Conclusion: Cystatin S is an effective biomarker for GC prognostic assessment, assisting in the evaluation of prognosis and the selection of treatment strategies for patients with GC.

Background: Gut microbiota are associated with the pathological features and development of colorectal cancer (CRC); however, how gut microbiota changes in patients with CRC is unknown. This study investigated the role of gut microbiota in the development and progression of CRC by retrospectively comparing the structural differences between the gut microbiota of patients with CRC and healthy individuals.

Methods: Together with clinical data, we collected fecal samples from patients with CRC (n = 18) and healthy controls (n = 18) and performed 16S rRNA gene sequencing and alpha and beta diversity analysis to compare microbiota richness and diversity. Based on the differences in microbiota between the CRC and control groups, we identified disease-specific microbial communities after relevant factors. PICRUSt2 software was used to predict the differential microbial functions.

Results: The CRC and control groups differed in both composition and abundance of intestinal microbiota. Firmicutes and Bacteroidetes were the most abundant phyla in both groups, while Verrucomicrobi was significantly more abundant in the CRC group. Megamonas, Lachnospira, and Romboutsia were more abundant in the control group; 18 genera differed significantly in abundance between the groups, which were found to involve 21 metabolic pathways. The distribution and abundance of gut microbiota differed significantly between patients with CRC with and without lymph node metastasis; at the genus level, the abundance of Rothia and Streptococcus was significantly higher and that of Bacteroides, Parabacteroides, and Oscillibacter was significantly lower in patients with lymph node metastasis.

Conclusions: The gut microbiota is altered in CRC patients compared with healthy individuals, with specific changes in the microbiota associated with clinical and pathological features such as tumor stage, lymph node involvement, and tumor differentiation. Our findings elaborate to some extent on the link between the gut microbiota and CRC.

Background: Triple negative breast cancer (TNBC) is a deadly subtype of breast cancer with limited treatment options. Currently, programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have become the first choice for breast cancer immunotherapies. Despite paclitaxel being considered a cornerstone drug in breast cancer treatment, the effectiveness, safety, and optimal drug selection for its combination with PD-1/PD-L1 inhibitors remain uncertain.

Methods: We conducted a systematic review and network meta-analysis, performing a comprehensive literature search across PubMed, Embase, and the Cochrane Library from the inception of each database through May 18, 2024. Selected trials were those that assessed the efficacy and safety of paclitaxel-based PD-1/PD-L1 therapies for the treatment of TNBC. The primary endpoint assessed was overall survival (OS), while secondary outcomes included progression-free survival (PFS), adverse events (AEs), overall response rate (ORR), and Pathological complete response (pCR). This study is registered in PROSPERO under registration number CRD42023429651.

Results: A total of 8 RCTs meeting our eligibility criteria were included, involving 4626 patients who received either Paclitaxel (Paclitaxel-placebo/chemotherapy) or a combination of durvalumab, pembrolizumab, atezolizumab, toripalimab with paclitaxel. The pooled results demonstrated that Durvalumab combined with Paclitaxel significantly reduced the hazard ratio for OS (surface under the cumulative ranking [SUCRA]: 91.05%) and PFS compared with Paclitaxel alone (SUCRA: 83.52%). Additionally, Durvalumab plus Paclitaxel significantly improved the ORR compared with Paclitaxel (odds ratio [OR]: 2.30; 95% credible interval [CrI]: 1.10-5.20). For safety outcomes, Atezolizumab plus Paclitaxel showed a favorable profile in AEs, with no significant differences observed between groups. In the pCR study, Pembrolizumab plus Paclitaxel was the most effective treatment option (SUCRA: 81.85%).

Conclusions: When combined with paclitaxel, PD-1/PD-L1 inhibitors exhibit a favorable survival benefit. The combination of Durvalumab and paclitaxel represents the optimal treatment option. In the future, attention should be paid to the TNBC subtypes and drug dosage, as these factors may help to design personalized TNBC treatment programs.