Frontiers in Oncology最新文献

Non-small-cell lung cancer (NSCLC) is a leading cause of morbidity and mortality globally, due in large part to the development of NSCLC-associated brain metastases (L-BM). Upon initial presentation, 11-26% of patients with NSCLC will have L-BM, while half of patients with NSCLC will develop L-BM over the course of their disease. The emergence of PD-1/PD-L1 immunotherapy and targeted therapies for EGFR, ALK, and ROS1 mutations has transformed the treatment landscape and improved outcomes for select patient populations. CNS progression remains a major challenge due to therapy resistance, the blood-brain barrier (BBB), and the unique molecular and transcriptomic adaptations exhibited by NSCLC brain metastases which differs markedly from primary lung tumors. In this review, we examine the molecular drivers of CNS metastasis, oncogenic signaling-targeted therapies, and next-generation CNS drug-delivery strategies including intraventricular or intranasal administration, focused ultrasound, nanocarriers, and efflux transporter modulation. Furthermore, we provide a comprehensive update on recent and ongoing preclinical and clinical studies, highlighting novel CNS-penetrant agents with demonstrated intracranial efficacy. Understanding these mechanisms and refining targeted approaches are critical to improving CNS disease control, survival outcomes, and quality of life for NSCLC patients with brain involvement.

Introduction: Head-to-head comparative evidence of the relative efficacies of atezolizumab plus bevacizumab (Atezo+Bev) and tremelimumab plus durvalumab (Treme+Dur) as first-line therapies for advanced hepatocellular carcinoma (HCC) remains limited. Thus, in the present study, we compared the real-world efficacy and safety of these two modalities using a target trial emulation approach.

Methods: Using the TriNetX Research Network, we identified adults (≥20 years) with HCC (ICD-10 C22.0) who initiated first-line Atezo+Bev or Treme+Dur (November 2022- November 2024). Propensity score matching (1:1) was used to balance the baseline characteristics. The primary outcome measure was overall survival (OS). Secondary outcomes included 1- or 2-year OS and organ-specific immune-related adverse events (irAEs) within 12 months, based on pre-specified ICD-10 definitions.

Results: After matching, 640 patients were included in each group. Residual imbalance persisted in hepatic reserve markers (albumin, international normalized ratio, and platelet count; standardized mean differences >0.1). One-year OS was numerically higher in the Atezo+Bev group than in the Treme+Dur group (61% vs 55%; hazard ratio [HR], 0.806; 95% confidence interval [CI], 0.665-0.976; p = 0.027). Two-year OS (HR, 0.864; 95% CI, 0.723-1.031; p = 0.105) and overall OS showed no significant differences (median: 19.4 vs 19.0 months [591 vs 578 days]; HR, 0.886; 95% CI, 0.743-1.057; p = 0.179). Most irAEs were similar; however, the time-to-first hepatic irAEs favored Atezo+Bev (HR, 0.678; 95% CI, 0.487-0.943; p = 0.020). Notably, respiratory irAEs occurred significantly earlier in the Treme+Dur group than in the Atezo+Bev group (mean onset: 2.4 vs 3.2 days; p = 0.031).

Conclusions: In this real-world target trial emulation, Atezo+Bev and Treme+Dur demonstrated broadly comparable long-term OS rates when used as first-line therapies for HCC. While baseline hepatic reserve plays an important role, the treatment regimen itself may contribute to earlier onset of hepatic and respiratory irAE. Careful monitoring for early-onset hepatic dysfunction and respiratory irAEs may be warranted in patients treated with Treme+Dur combination therapy.

Objective: Dinutuximab beta (dB) immunotherapy is used as maintenance treatment for relapsed/refractory neuroblastoma (NBL); however, comparative studies directly comparing dB with no dB therapy in this setting are lacking. This study aimed to indirectly compare dB (with or without interleukin-2) with no immunotherapy in patients with relapsed NBL.

Methods: Three studies of dB (APN311-202, APN311-304, and APN311-303) with individual patient data, along with two historical control cohorts (INBR and R1) were included. Both unadjusted (naïve) and population-adjusted comparisons of overall survival (OS) were performed, with adjustment conducted using inverse probability or odds weighting. Harmonized inclusion criteria were applied across all study populations. The adjusted comparison used the propensity score reweighting to balance the cohorts based on key baseline prognostic factors.

Results: The base-case unadjusted indirect comparison revealed that dB (with or without IL-2) significantly prolonged OS compared to historical controls not treated with dB (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.31- 0.79; p<0.001). Similarly, in the adjusted comparison, dB significantly prolonged OS compared to historical controls (HR, 0.53; 95% CI, 0.35; 0.79, p=0.002). All sensitivity unadjusted and adjusted comparisons supported the results of the base-case analysis.

Conclusion: Dinutuximab beta significantly prolonged OS compared to historical control cohorts not treated with dB in both unadjusted and adjusted indirect comparisons.

Background: Gastric cancer (GC) remains a leading cause of cancer mortality globally, with a multifactorial etiology involving infectious, behavioral, and dietary risk factors. However, age-specific variations in these factors are not well understood.

Methods: We conducted a hospital-based retrospective study of 903 pathologically confirmed GC cases recruited from several tertiary medical centers in south China. Participants were stratified into three age groups (≤30, 31-55, and >55 years). Key variables-including Helicobacter pylori infection, smoking, obesity, dietary habits, and medical history-were analyzed using chi-square tests and multivariable logistic regression to assess age-related differences in risk factor prevalence and associations.

Results: The prevalence of H. pylori infection and smoking significantly increased with age (p < 0.05), and both factors are known contributors to gastric cancer risk in prior studies. Smoked/grilled food consumption showed a significant association with GC, particularly among older adults (OR = 2.05, 95% CI: 1.29-3.27, p = 0.002). Obesity and low fruit/vegetable intake were not statistically significant. Socioeconomic indicators, including urban employee basic medical insurance (UEBMI) coverage, also exhibited age-related patterns but showed mixed associations with GC risk.

Conclusion: This study highlights age-specific disparities in GC risk profiles and underscores the cumulative exposure patterns of H. pylori infection, smoking, and dietary carcinogens. However, given the retrospective and hospital-based design, causal relationships cannot be established, and selection bias may exist. Despite these limitations, the findings provide an epidemiological basis for age-tailored prevention strategies, emphasizing early eradication of H. pylori, smoking cessation, and dietary interventions for high-risk populations.

Background: The hospital spending of patients with esophageal squamous cell carcinoma (ESCC) have been increasing over years, imposing a heavy economic burden on these patients. However, little is known about the association between spending and their overall survival (OS).

Methods: We recruited 11,037 ESCC patients who were admitted between August, 2009 and December, 2018 at the Southern Center (Cancer Hospital of Shantou University Medical College), and between January, 2012 to December, 2017 at the Northern Center (Anyang Cancer Hospital). Spending terciles were the exposure measure, and OS was the outcome. OS in terciles 2 and 3 was compared with OS in tercile 1 (the lowest spending tercile) using Cox regression models. Analyses were stratified by TNM stage and study center.

Results: Monthly hospital spending followed an "L-shaped" trend. After a maximum follow-up of 12.52 years, the median survival time was 4.70 years. Higher spending was associated with worse OS in stage 0-II patients (adjusted HR_{tercile 3 vs 1} = 1.55, 95% CI: 1.27-1.89), but with better OS in stage III-IV patients (adjusted HR_{tercile 2 vs 1} = 0.82, 95% CI: 0.74-0.90; adjusted HR_{tercile 3 vs 1} = 0.73, 95% CI: 0.64-0.83). These associations were consistent across both the Southern and Northern Centers.

Conclusions: The findings suggest that early-stage ESCC patients may benefit from more conservative treatment approaches, whereas advanced-stage patients require comprehensive and sufficient treatment.

This paper reports a rare case of a 4-year-old male child with acute lymphoblastic leukemia (ALL) presenting initially with bone marrow necrosis (BMN) as the chief clinical manifestation. The child sought medical attention due to fever, bone pain, and fatigue. Laboratory tests indicated pancytopenia. Initial bone marrow cytomorphology examination revealed disrupted cellular architecture, suggesting possible BMN, and single-site flow cytometry detected no definitive abnormalities, highlighting the diagnostic complexity caused by BMN. Through multi-site bone marrow aspiration and biopsy, the diagnosis was ultimately confirmed as common B-cell ALL (common-B-ALL). Treatment followed the South China Children's Cancer Collaborative Group SCCCG-ALL-2023 protocol, incorporating blinatumomab immunotherapy based on risk stratification. The child responded well to treatment and is currently in the maintenance chemotherapy phase, with minimal residual disease (MRD) monitoring consistently indicating complete remission. This case emphasizes the importance of early recognition of rare presentations like BMN-onset in pediatric ALL, the necessity of multi-site bone marrow examination, and the crucial role of individualized treatment strategies.

Purpose: The aim of this study was to evaluate the feasibility of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) contrast-enhanced magnetic resonance imaging (CE-MRI) for determining the gross tumor volume (GTV) of hepatocellular carcinoma (HCC).

Methods: A retrospective analysis was conducted on 12 patients diagnosed with HCC (18 lesions) who received radiotherapy and underwent magnetic resonance (MR) simulation. Six series images, including MR T₁-weighted image (T₁WI) and contrast-enhanced T₁WI (CE-T₁WI) at 15 s, 45 s, 75 s, 150 s, and >20 min after Gd-EOB-DTPA injection, were obtained, and the GTV was determined in the different temporal images. The differences in mean signal intensity (SI), SI contrast between the HCC and liver tissue, volume and shape of HCC GTV among different phases were compared.

Results: (1) The mean SI of liver tissue reached its peak enhancement at >20 min, showing a 140.90 ± 64.69% increase, compared with T₁WI (p < 0.05). (2) Compared with CE-T₁WI_-20min, the mean SI of the HCC increased by -41.19~18.09% from T₁WI, CE-T₁WI_-15s to CE-T₁WI_-150s. Conversely, the mean SI of liver tissue decreased by 5.27~55.87% over the same period. Consequently, the SI contrast between HCC and liver tissue decreased by 53.30~89.37%. (3) The maximum GTV volume determined by CE-T₁WI_-20min was (22.80 ± 18.57) cm³, coinciding with the highest value of SI contrast (0.29 ± 0.16). (4) Compared with GTV_-20min, GTV_-T1WI and GTV_-15s~GTV_-150s had volume reductions of 6.73~19.35%. (5) Compared with GTV_-20min, the Dice similarity coefficients (DSC) of GTV_-T1WI and GTV_-15s~GTV_-150s ranged from 0.745 to 0.819. Additionally, the shape change trend of GTV in the CE-T₁WI images was generally consistent with the volume change trend.

Conclusion: CE-T₁WI MR images acquired more than 20 min post-injection of Gd-EOB-DTPA exhibited significant advantages in determining the GTV boundaries and enhancing the contrast of SI between HCC and liver tissue. The CE-T₁WI_-20min sequence is recommended for determining HCC GTV.

Background: Up to 80% of patients with resected pancreatic cancer experience recurrence within 2 years. We evaluated the feasibility and accuracy of a personalized, tumor-informed circulating tumor DNA (ctDNA) test for the early detection of recurrence risk during long-term postoperative surveillance.

Methods: We recruited 43 patients with pancreatic cancer who underwent curative surgical resections. A personalized panel was developed to detect ctDNA in plasma based on whole-exome mutation information derived from tumor tissues. A total of 139 plasma samples were analyzed to assess recurrence risk and the efficacy of adjuvant therapy.

Results: A personalized ctDNA monitoring panel was successfully customized in 35 of 43 cases. Sixteen patients relapsed within a median of 15.7 months (range: 5.4-30.0 months) postsurgery. For the 11 patients with positive ctDNA, the median lead time from initial ctDNA positivity to radiological relapse was 4.59 months (range: 0.88-15.61). After completion of adjuvant chemotherapy (ACT), 94.3% (33/35) of patients contributed 52.5% (73/139) of the ctDNA testing samples. These samples exhibited an elevated rate of ctDNA detection (48.5%, 16/33) compared to samples obtained prior to and during the commencement of ACT, with a negative predictive value of 82.4% (14/17) and a positive predictive value of 75.0% (12/16). The presence of ctDNA was significantly correlated with shorter disease-free survival and overall survival.

Conclusions: Long-term dynamic ctDNA monitoring after pancreatic cancer resection, particularly following the completion of ACT, is predictive of recurrence risk. The proactive implementation of ctDNA monitoring after ACT in patients with resectable pancreatic cancer has important implications for clinical practice.

Objective: To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) for postoperative adjuvant chemotherapy for colorectal cancer.

Methods: CNKI, VIP, Wanfang, CBM, PubMed, and Web of Science were searched for the randomized controlled trials (RCT) of TCM participating in postoperative adjuvant chemotherapy for colorectal cancer. The search period was from January 1, 2018 to December 31, 2024. Cochrane bias risk assessment tool was used to evaluate the quality of included studies, and RevMan5.4 was used for meta-analysis.

Results: A total of 41 randomized controlled trials involving 2918 patients with colorectal cancer was ultimately included. The results demonstrated that the combination of TCM with chemotherapy was superior to chemotherapy alone in several aspects. These included the objective response rate (ORR), improvement of TCM-related symptoms, levels of tumor markers CEA and CA199, immune function indicators (CD3⁺, CD4⁺, CD4⁺/CD8⁺, NK cells), and quality of life as measured by the KPS score. Additionally, the combination therapy reduced CD8⁺ levels and mitigated abnormal laboratory indicators caused by chemotherapy, such as leukopenia, thrombocytopenia, decreased hemoglobin, and abnormal liver and kidney function. Furthermore, it alleviated chemotherapy-related adverse effects (AEs), including nausea, vomiting, and peripheral nerve toxicity.

Conclusions: TCM may be associated with improvements in quality of life and reduce chemotherapy side effects in postoperative colorectal cancer patients, though large-scale rigorous trials are needed to confirm efficacy and safety.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42025635900.