Therapeutic Advances in Medical Oncology最新文献

Background: The differences in lymph node metastasis (LNM) between patients with early-stage squamous cell carcinoma (SCC) and adenocarcinoma (ADC) cervical cancer remained to be clarified.

Objectives: To compare the differences of LNM between early-stage SCC and ADC cervical cancer patients receiving radical surgery and adjuvant radiotherapy.

Designs: A retrospective large cohort study.

Methods: The pelvic LNM rate was estimated and compared. Univariate and multivariate logistic regression analyses were applied to identify the risk factors for pelvic LNM. The cumulative survival rates were estimated and compared with Kaplan-Meier methods and log-rank test, respectively. The propensity score matching (PSM) was utilized for adjustment of baseline characteristics.

Results: A total of 577 cervical cancer patients were included in the analysis. Pelvic LNM could be observed in 22.7% (51/225) of ADC and 25.9% (91/352) of SCC patients (p = 0.39). Lympho-vascular space involvement (LVSI) was the only risk factor for pelvic LNM in SCC patients while LVSI and parametrial involvement (PI) were risk factors for ADC patients. No significant survival differences were observed between SCC patients with LNM and those without (All p > 0.05). However, ADC patients without pelvic LNM appeared superior to those with LNM in 5-year overall survival whether before (70.7% vs 91.9%; p < 0.001) or after (78.7% vs 92.4%; p = 0.024) PSM. Moreover, consolidate chemotherapy after radiation improved the 5-year disease-free survival (DFS) for SCC patients with pelvic LNM (74.9% vs 96.8%; p = 0.019) while not for ADC patients (68.9% vs 64.1%; p = 0.8).

Conclusion: No significant difference in pelvic LNM rate was observed between ADC and SCC patients. The presence of LNM seemed to further impair the oncological outcomes for ADC while not for SCC patients. Consolidate chemotherapy appeared to improve the DFS for SCC while not for ADC patients.

Background: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for non-small cell lung cancer, but the role of race/ethnicity is not well understood.

Design: This is a retrospective study of non-small cell lung cancer (NSCLC) patients receiving ICI.

Objective: We evaluated the role of race/ethnicity in ICI response and immune-related adverse events (irAEs) in NSCLC patients.

Methods: NSCLC patients treated with ICIs from 2014 to 2022 at Los Angeles General Medical Center and Norris Comprehensive Cancer Center were included. Primary endpoints were irAE incidence, time on ICI treatment (TOT), overall survival (OS), and progression-free survival (PFS). TOT, OS, and PFS were evaluated using the Kaplan-Meier method. Landmark analysis was performed of patients receiving >6 month ICIs. Fisher's exact test was performed for analysis of variables between groups.

Results: In total, 211 NSCLC patients receiving ICIs were analyzed, including 86 (40.8%) Asian American/Pacific Islander (AAPI), 65 (30.8%) non-Hispanic White/Caucasian (NHW), 37 (17.5%) Hispanic/Latino (HIS), and 23 (10.9%) African American/Black (AA). Among stage IV patients, median OS for AAPI was 23.2 months (95% confidence interval (CI) 16.0-not reached (NR)), 23.6 months (95% CI 6.9-38.8) for NHW, 12.7 months for AA (95% CI 2.2-37.0), and 11.0 months (95% CI 4.8-14.8) for HIS (p = 0.008). Median TOT and PFS were similar among race/ethnicities. 48.3% of AAPI developed irAE versus 27.3% for AA, 27.0% for HIS, and 39.4% for NHW. Landmark analysis showed that AAPI had longer median OS 60.6 months (95% CI 20.6-NR), while HIS had shorter median OS 15.4 months (95% CI 8.9-NR; p < 0.01). Among patients who experienced irAEs, median OS for AAPI was 60.6 months (95% CI 20.6-NR), compared to NHW at 48.4 months (95% CI 20.5-NR), AA at 35.7 months (95% CI 2.2-NR), and HIS at 15.2 months (95% CI 6.3-31.0; p = 0.0211). There was no difference in median OS among patients who did not experience irAEs. Multivariate analysis for OS in stage IV patients showed that HIS versus AAPI (hazard ratio: 2.27; 95% CI 1.30-3.95) was a significant variable.

Conclusion: Our study demonstrates that AAPIs and NHW had higher irAE incidence and longer OS. Validation studies evaluating the role of race/ethnicity in ICI response and toxicity are merited.

[This retracts the article DOI: 10.1177/1758835919874649.].

Background: The incidence of early-onset colorectal cancer (EO-CRC), defined as a diagnosis before 50 years of age, is increasing worldwide. However, its clinical characteristics and outcomes compared to average-onset colorectal cancer (AO-CRC) remain under debate, especially in the setting of locally advanced rectal cancer (LARC).

Objectives: This study aimed to compare clinical characteristics, treatment responses, and survival outcomes between patients with early-onset and average-onset locally advanced rectal cancer.

Design: A multicenter retrospective cohort study.

Methods: We retrospectively analysed 305 patients with stage II-III rectal cancer treated between 2012 and 2022 across three Italian oncology centrers. Patients were categorised as EO-RC (⩽50 years) or AO-RC (>50 years). All patients underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision. Pathological and radiological responses were evaluated, and survival outcomes were assessed through Kaplan-Meier methods.

Results: Early-onset patients accounted for 10.5% of the cohort. Clinical and pathological characteristics were broadly similar between groups, although EO-RC patients had a higher prevalence of proficient mismatch repair status. Radiological and pathological response rates were comparable. After a median follow-up of 120 months, the 10-year overall survival (OS) was 73.3% in EO-RC and 91.9% in AO-RC (HR 7.60, 95% CI 2.22-26.06; p = 0.0012). Disease-free survival (DFS) at 10 years was 57.1% in EO-RC and 70.9% in AO-RC (HR 1.80, 95% CI 0.86-3.78; p = 0.1177).

Conclusion: Early-onset rectal cancer patients exhibit similar response rates and DFS compared to older patients, but appear to have worse OS. Further studies are needed to explore biological factors and post-recurrence treatment strategies that may influence these outcomes.

Non-small cell lung cancer is among the most prevalent cancers worldwide, with its high metastatic potential driving poor prognosis and mortality. Advances in molecular testing and high-throughput sequencing have highlighted the roles of driver genes (EGFR, ALK, KRAS) and key non-driver genes (TP53, STK11, KEAP1) in NSCLC metastasis. These mutations influence tumor invasiveness, drug resistance, and organ-specific metastatic patterns-EGFR and ALK mutations favor brain metastasis, KRAS mutations are linked to bone, liver, and multiple lung metastases, while TP53, STK11, and KEAP1 mutations increase multi-organ metastatic risk. This review summarizes the associations between genetic mutations and metastatic sites, explores underlying molecular mechanisms, and discusses mutation-based risk prediction and personalized therapeutic strategies. With multi-omics integration and further clinical research, genetic profiling may become a key tool for guiding metastasis prevention, early intervention, and treatment optimization in NSCLC.

Background: Neoadjuvant therapy provides substantial clinical benefits for patients with locally advanced tongue squamous cell carcinoma (TSCC). It improves the rate of complete tumor resection, decreases recurrence risk, and extends survival. However, accurate post-therapy risk stratification depends on the identification of reliable prognostic biomarkers.

Objectives: This retrospective study assessed several immune microenvironment biomarkers-tumor-associated tissue eosinophils (TATEs), neutrophils (TANs), lymphocytes (TILs), and tertiary lymphoid structures (TLSs)-in 108 patients with stage III or IV TSCC who received neoadjuvant chemotherapy (n = 44) or immunochemotherapy (n = 64) between 2013 and 2022.

Design: Retrospective cohort study.

Methods: Post-treatment hematoxylin and eosin (H&E)-stained specimens were evaluated to quantify biomarker infiltration. Associations between biomarker levels, pathological response, and survival outcomes were analyzed.

Results: A low stromal TATE (S-TATE) density (⩽20/mm²) was significantly correlated with higher rates of pathological complete response (pCR) (p < 0.001). In contrast, elevated S-TATE levels were associated with lymph node metastasis (p = 0.011) and vascular or neural invasion (p = 0.004). Multivariate analysis identified S-TATE  > 20/mm² as an independent predictor of reduced overall survival (HR = 3.52, 95% CI: 1.01-12.32; p = 0.049) and shorter progression-free survival.

Conclusion: S-TATE serves as an independent prognostic indicator in patients with locally advanced TSCC receiving neoadjuvant therapy. Quantifying S-TATE in post-treatment specimens may help tailor adjuvant therapy intensity and refine surveillance strategies. Patients with elevated S-TATE levels should receive closer follow-up.

Background: Neoadjuvant systemic therapy (NST) is often used to treat locally advanced breast cancer (BC) or patients with early-stage BC at high risk for micrometastatic spread. Pathological complete response (pCR) to NST in BC is associated with excellent prognostic outcomes; however, rates vary significantly. Tumor-infiltrating lymphocytes (TILs) are associated with NST response, suggesting potential as predictive biomarkers.

Objective: To develop a computer vision approach to quantify spatial TIL parameters and a multiparametric machine learning (ML) model for predicting NST response.

Design: Retrospective, single institution study of 411 BC patients, combining clinical and graph-level pre-treatment histopathology data to predict response to NST using ML.

Methods: Pre-treatment core needle biopsies were prepared, stained with hematoxylin and eosin, and digitized into whole slide images. Convolutional neural networks were applied to segment and classify regions of invasive carcinoma and TILs. Spatial features were extracted based on the coordinates of the TILs within invasive regions, including metrics from Delaunay triangulation, Voronoi diagram analysis, and minimum spanning trees, as well as features capturing cell density and nuclear count. Clinicopathological features were incorporated to support multiparametric modeling. Multiple ML classification models were trained to predict pCR. Logistic regression, K-nearest neighbor, support vector, random forest, Gaussian Naïve Bayes, and extreme gradient boosting models were tested, and model performances were reported.

Results: ML models using clinical and graph-based features achieved high predictive accuracy. The best performing graph feature model reached an area under the receiver operating characteristic curve (AUC) of 0.924. Ensemble models integrating clinical and graph features showed the highest performance, with an AUC of 0.955. Notably, for triple-negative BC, significant differences in predictive performance were demonstrated between clinical and graph feature models (p = 0.026) and between clinical and ensemble models (p = 0.006).

Conclusion: Multiparametric modeling utilizing clinicopathological and graph features obtained from TILs is associated with pCR in BC patients treated with NST.

Background: Breast cancer frequently results in brain metastases (BCBM), leading to poor outcomes. Central nervous system (CNS) involvement entails significant challenges in advanced breast cancer (ABC) patients.

Objectives: To characterize BCBM patients according to surrogate clinical BC subtypes and evaluate the interval between ABC and BCBM detection, both at ABC diagnosis (BCBM1 cohort) and for those who develop BCBM subsequently (BCBM2 cohort). Secondary objectives included analyzing the time-related outcomes by BC subtype.

Design: RegistEM is an ongoing ambispective, observational study of ABC patients diagnosed since January/2016.

Methods: We describe the characteristics of BCBM patients reported by January 22, 2024, categorized by BC subtype on the most recent tumor sample obtained before first-line therapy.

Results: At the cutoff date, 346/1947 (18%) patients diagnosed with ABC between January/2016 and December/2019 developed BCBM, and 288/346 (83%) died. All patients were female, predominantly Caucasian (98%), with a median age of 55 years at ABC diagnosis. The distribution by subtype was 170/346 (49%) HR+/HER2-, 68/346 (20%) HR+/HER2+, 54/346 (16%) HR-/HER2+, and 51/346 (15%) HR-/HER2- (triple negative (TN)). One-fourth (85/346) were in the BCBM1 cohort, with 22/85 (26%) having BCBM as the only metastatic location; in this cohort, median time to BCBM was 38 months, with shorter intervals in HR-/HER2+ and TN subtypes (17 and 18 months, respectively). In the BCBM2 cohort (261/346), the median time to BCBM was 24 months, with the shortest interval in TN (13 months). Median survival from BCBM diagnosis was 26 months (95% confidence interval (CI), 20-35) in BCBM1 and 9 months (95% CI, 7-12) in BCBM2 (hazard ratio, 2.3; 95% CI, 1.7-3.0); TN subtype showed the poorest results (median of 6 months; 95% CI, 3-13).

Conclusion: TN and HER2+ BC subtypes progressed faster to BCBM and had worse outcomes. Survival differed significantly between the two cohorts, BCBM1 and BCBM2. Continued research is essential to improve the treatment and prevention strategies.

Background: Immune checkpoint inhibitor (ICI)-based combination therapy has transformed the therapeutic landscape of advanced hepatocellular carcinoma (aHCC). However, durable clinical benefit remains limited to a subset of patients, highlighting the need for approaches that enhance efficacy.

Objectives: The MONTBLANC study presents a novel investigational strategy utilizing triple immunotherapy through the combination of the anti-programmed cell death ligand 1 antibody durvalumab, the anti-cytotoxic T-lymphocyte-associated antigen-4 tremelimumab, and the anti-vascular endothelial growth factor bevacizumab in patients with aHCC.

Methods and analysis: This randomized, open-label, phase II clinical trial examines two distinct therapeutic regimens through parallel study arms: upfront triple-agent administration or doublet therapy with durvalumab and tremelimumab, followed by the addition of bevacizumab upon disease progression or lack of objective radiological response. The primary endpoint is the overall response rate. Secondary endpoints include overall survival, progression-free survival, safety, and patient-reported outcomes.

Ethics: The ethics review boards of all participating sites have approved the study protocol. The trial will be performed in accordance with the Declaration of Helsinki, Good Clinical Practice Standards, and the applicable laws and regulations. All patients must provide written informed consent.

Discussion: The MONTBLANC study aims at guiding the design of future trials in aHCC by assessing efficacy signals of upfront triple or response-adapted treatment escalation with durvalumab, tremelimumab, and bevacizumab.

Trial registration: The MONTBLANC clinical trial is registered at the US National Institutes of Health (ClinicalTrials.gov, NCT05844046) and the European Union Drug Regulating Authorities Clinical Trials Database (clinicaltrialsregister.eu, 2022-001201-48).

Background: Concurrent chemoradiotherapy (cCRT) is essential for stage III unresectable non-small cell lung cancer (NSCLC) but increases the risk of radiation pneumonitis (RP), especially with immunotherapy (IO). Induction chemotherapy (ICT) controls tumor progression but damages lung tissue, raising RP risk. Research on the RP risk from ICT, cCRT, and IO consolidation is poorly investigated.

Objectives: We evaluated whether ICT increases RP incidence and affects survival in the IO era.

Design: This was a retrospective analysis conducted at a single cancer center.

Methods: Retrospective data from stage III unresectable NSCLC patients treated with cCRT and IO between 2018 and 2024 were analyzed. Patients were divided into cCRT without ICT (N = 55) and ICT before cCRT groups (N = 103). The cumulative incidence of RP was evaluated using competing risk analysis (Gray's test and Fine-Gray models), with death as a competing risk. Multivariable Cox regression was used to analyze overall survival, progression-free survival, and RP risk among ICT regimen subgroups.

Results: The ICT before cCRT group showed a higher incidence of ⩾Grade 2 RP compared to the cCRT without ICT group (Gray's test, SHR = 1.964, 95% confidence interval (CI): 1.137-3.394, p = 0.013), with no survival benefit. Subgroup analysis based on ICT regimens, compared with the Etoposide + Platinum regimen, Pemetrexed + Platinum regimen (hazard ratio (HR): 0.277, 95% CI: 0.090-0.854, p = 0.025), Paclitaxel + Platinum regimen (HR: 0.294, 95% CI: 0.094-0.926, p = 0.037), and Docetaxel + Platinum regimen (HR: 0.059, 95% CI: 0.010-0.356, p = 0.002) were associated with a lower incidence of ⩾Grade 2 RP.

Conclusion: ICT followed by cCRT showed a higher incidence of ⩾Grade 2 RP compared to cCRT alone in patients with unresectable stage III NSCLC receiving consolidation immunotherapy.