Neoadjuvant Treatment Research Articles

Event-free survival (EFS), a common endpoint in neoadjuvant/perioperative oncology trials, allows for accelerated treatment evaluation while awaiting results of overall survival (OS). However, the surrogacy of EFS for OS in muscle-invasive bladder cancer (MIBC) has yet to be established. This meta-analysis evaluated EFS as a surrogate endpoint for OS in neoadjuvant-treated MIBC. A systematic literature review identified neoadjuvant or perioperative clinical trials for MIBC reporting both EFS and OS. Treatment effect association was evaluated by assessing the association of the hazard ratio (HR) of EFS with that of OS. Survival outcome associations were evaluated by assessing the associations of survival rates and median survival times between EFS and OS, respectively. These associations were meta-analyzed using weighted linear regression. The strength of association was quantified using coefficient of determination (R2). Seven eligible trials were identified for the analysis of treatment effect association and 17 trials were included in the analyses of survival outcome associations. Strong association was observed between EFS and OS at treatment effect level (R2 = 0.80 [95% confidence interval (CI): 0.38-0.99]). Consistently, significant survival outcome associations were observed between 3-year EFS and 5-year OS (R2 = 0.80 [95% CI: 0.28-0.93]) and between median EFS time and median OS time (R2 = 0.97 [95% CI: 0.45-1.00]). EFS is strongly associated with OS in respect to treatment effects and survival outcome measures in clinical trials for MIBC following neoadjuvant treatment. EFS can be considered as a surrogate endpoint for OS when evaluating neoadjuvant treatments for MIBC.

Attrition with adjuvant, neoadjuvant, and perioperative immunotherapy-based treatment protocols in patients with resectable non-small-cell lung cancer. A meta-analysis of prospective trials.

Histological Grade Has Clinical Validity in Neoadjuvant-Treated Breast Cancer: A Multicenter Study.

PKCζ regulates autophagy in pancreatic ductal adenocarcinoma via BAG3: a novel therapeutic vulnerability.

Background: Resectable gastric and gastroesophageal junction cancer (GC/GEJC) treatment patterns in the real-world are poorly described. This study described real-world perioperative treatment and outcomes for patients in the US with resectable GC/GEJC. Methods: Data from the Flatiron Health Enhanced Datamart were analyzed for adult patients diagnosed with resectable GC/GEJC between 1 January 2016 and 1 January 2023. The primary objective was to describe perioperative treatments (neoadjuvant only, adjuvant only, both). Secondary objectives included real-world event-free survival (rwEFS) and real-world overall survival (rwOS). Results: Data from 1717 patients (901/816 with GC/GEJC) were included. Median age of patients with GC/GEJC was 68.0/69.0 years, 62.4%/83.3% were male, and 97.3%/96.7% had adenocarcinoma, respectively. For GC/GEJC, 71.1%/47.9% underwent surgery, of which 15.6%/70.1% received neoadjuvant treatment only, 26.4%/5.6% received adjuvant treatment only, 25.0%/17.4% received both, and 33.1%/6.9% received no perioperative treatment, respectively. For GC, the most frequent neoadjuvant treatment was FLOT (43.0% neoadjuvant only; 53.8% both) and the most frequent adjuvant treatments were chemoradiotherapy (39.6% adjuvant only) and FLOT (43.1% both). For GEJC, chemoradiotherapy was the most frequent neoadjuvant (66.4% neoadjuvant only; 67.6% both) and adjuvant only (54.5%) treatment. When patients received both, the most frequent adjuvant treatment was nivolumab (45.6%). For GC/GEJC, median rwEFS (95% CI) was 29.1 (24.7–38.7)/20.8 (17.4–23.7) months for patients who had planned or cancelled surgery and 11.3 (9.6–13.5)/12.7 (11.6–15.4) months for patients without planned surgery. Median rwOS (95% CI) was 50.9 (43.7–62.4)/38.6 (31.4–47.2) months for patients who had planned or cancelled surgery and 15.4 (13.1–18.6)/21.0 (17.6–22.6) months for patients without planned surgery. Conclusions: Real-world data showed lower use of perioperative treatments for resectable GC/GEJC than expected. rwEFS and rwOS remain poor. Optimization of perioperative treatments is needed to improve long-term outcomes.

Molecular Therapy and Targeted Treatment for Cancer (with Surgical Lenses).

Prospect of Newcastle disease virus in clinical neurological tumour diseases.

Quantitative habitat concentration analysis of triple negative breast cancer on MRI correlates with pathologic response to combination neoadjuvant immuno/chemotherapy.

The aim of this study was to investigate the prognostic and predictive properties of four specific genes in triple-negative breast cancer (TNBC). We focused on ADIPOQ, GAS5, GATA4, and YAP1, which are known for their roles in key molecular pathways related to tumorigenesis, such as adipokine signaling, lncRNA regulation, transcriptional control, and Hippo signaling, but have not been sufficiently explored in the context of epigenetic regulation in breast cancer. Using the methylospecific PCR (MSP) method, we analyzed the methylation of the four genes in the tumor tissues collected from 57 TNBC patients. We evaluated their association with response to neoadjuvant treatment and clinicopathological characteristics. Additionally, we performed a bioinformatic analysis of methylation and expression data from The Cancer Genome Atlas (TCGA) TNBC cohort to explore their relationships with overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), progression-free interval (PFI), and relapse-free survival (RFS). No significant associations were observed between methylation patterns and clinicopathological characteristics in the patients. However, in silico analysis of the TNBC cohort identified ADIPOQ methylation as having the most significant associations, correlating with all five survival endpoints, including OS, DSS, DFI, PFI, and RFS. GAS5 methylation was significantly associated with OS, DSS, and RFS, and GATA4 methylation showed significant associations with PFI, whereas YAP1 methylation was significantly associated with OS and RFS. In addition, GAS5 expression was linked to DSS, DFI and RFS. This study highlights the potential prognostic significance of the epigenetic regulation of ADIPOQ in TNBC. The in silico findings shed light on the molecular pathways associated with TNBC progression and warrant further investigation to validate their role in clinical outcomes and underlying biological mechanisms.

Quality of Life After Two Sequences of Total Neoadjuvant Treatment in Patients With Locally Advanced Rectal Cancer in the Randomized CAO/ARO/AIO-12 Phase 2 Trial.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. Although neoadjuvant chemotherapy (NACT) has some effectiveness in TNBC, a portion of patients still do not benefit from them. The critical role of DNA replication stress (DRS) in cancer therapy has been recognized, but its study in TNBC NACT remains relatively limited. Affymetrix microarray data were obtained from the GEO database for both training and test sets. These data were processed using the “affy” R package. The Boruta algorithm and SVM-RFE method were employed for key gene selection, and an integrated model based on multiple algorithms was developed to establish a risk score. Additionally, the tumor microenvironment (TME) was analyzed, and the correlation between risk score and drug sensitivity was explored, incorporating several drug databases. Through the analysis of TNBC patients’ responses to NACT, we found a close correlation between DRS and TNBC treatment responses and identified eight key genes. The developed ensemble model (ENS) demonstrated high AUC values of 0.922, 0.886, and 0.858 across the three independent datasets, respectively, indicating its strong ability to accurately predict the effectiveness of NACT. The study also revealed that patients with higher risk score are more prone to recurrence and metastasis, and have a rich TME composition. Additionally, drug sensitivity analysis offers potentially effective personalized treatment options for high-risk TNBC. This study successfully constructed an ensemble model to predict TNBC patients’ response to NACT. Additionally, it was discovered that the risk score held significant value in analyzing the correlation between TNBC patients’ TME and drug sensitivity. These findings offer important new insights into personalized treatment strategies for TNBC.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21932-4.

BackgroundThis study investigates the effectiveness of neo-adjuvant chemo-radiotherapy (neo-CRT) in patients with clinical stage II and III mucinous rectal adenocarcinoma (MRA) and compares clinical outcomes with those of non-mucinous rectal adenocarcinoma (NMRA).MethodsA retrospective analysis was performed on patients diagnosed with clinical stage II or III rectal adenocarcinoma, confirmed via pelvic imaging, who underwent curative surgical procedures from January 2009 to December 2023. Exclusion criteria encompassed stage I and IV cases, those treated as emergencies, and patients with inflammatory bowel disease. Patients were classified into neo-adjuvant treatment groups and compared based on tumor type (MRA vs NMRA) using statistical analyses.ResultsOf 550 cases, 359 met inclusion. Most patients were young adults (58% aged 20–30), reflecting unusually early onset in Yemen. Neo-CRT was administered to 180 patients (93 MRA, 87 NMRA), while 179 (87 MRA, 92 NMRA) did not receive it. NMRA tumors were 3.24× more likely to downstage than MRA (P = 0.0007; OR = 3.235). After CRT, yp Stage II occurred in 40.23% of NMRA (95% CI: 30.68–50.68%) versus 17% of MRA (95% CI: 10.99–26.15%), while yp Stage III persisted in 60% versus 82.80% respectively (P = 0.0003). Pathological complete response (pCR) was seen in 11% of NMRA but <2% of MRA. Survival analysis showed MRA as the strongest adverse factor (CSS HR = 2.07, 95% CI: 1.39–3.09, P = 0.0002; OS HR = 1.79, 95% CI: 1.25–2.57, P = 0.0013), with advanced stage also predictive of poorer outcomes (CSS HR = 1.65, P = 0.043; OS HR = 1.87, P = 0.006). Neo-CRT itself conferred no survival benefit (CSS HR = 0.98, P = 0.91; OS HR = 1.24, P = 0.24). Disease-free survival (DFS) was lower in MRA (52% vs 72%, P = 0.004) and local recurrence higher (26% vs 5%, P = 0.0004), while Neo-CRT produced no significant survival benefit (15% vs 19%, P = 0.40).ConclusionBoth MRA stages II and III showed inferior cancer-free and overall survival outcomes. The justification for neo-adjuvant therapy necessitates a careful evaluation of potential benefits versus risks in MRA patients. The younger age of Yemeni colorectal cancer patients warrants further epidemiological studies to explore genetic and environmental risk factors. It also highlights the urgent need for tailored screening protocols, public health interventions, and awareness campaigns.

CD8-Guided Immunochemotherapy Improves Pathological Complete Response Rates in High Tumor Burden Triple-Negative Breast Cancer.

Bladder cancer is a highly prevalent disease in the Western World, and the treatment paradigm is actively evolving. For decades, the most commonly used standard of care for localized muscle-invasive disease has been neoadjuvant chemotherapy followed by open radical cystectomy with urinary diversion. Considering the high postoperative morbidity of this procedure, efforts have focused on improving patient outcomes. Over the past decade, substantial advances have been introduced in imaging, prehabilitation, perioperative care, robotic surgery and organ-sparing techniques. Bladder preservation after complete clinical response to neoadjuvant treatment or after trimodal treatment is increasingly being implemented. In addition, novel biomarkers are increasingly being used to monitor treatment response and select patients for adequate therapy. Last, innovative approaches, such as intraoperative imaging, sentinel lymph-node biopsy or the use of artificial intelligence, are currently under investigation.

Safety Profile of Neoadjuvant Chemoimmunotherapy with Nivolumab for Patients with Resectable NSCLC in the Real-world (CReGYT-04 Neo-Venus).

This study aimed to evaluate preoperative MRI risk factors for metastatic disease in patients who underwent neoadjuvant chemoradiotherapy (nCRT) and curative surgery, followed or not by adjuvant chemotherapy (ChT). Single-center post hoc analysis of a randomized clinical trial data to evaluate the effect of adjuvant ChT in comparison to observation in patients with rectal cancer receiving nCRT and surgical resection. Preoperative MRI variables were retrospectively reviewed by three observers. Clinical, surgical, and pathological variables were included in univariate and multivariate analysis, and metastasis risk was assessed. A subgroup analysis was further performed to evaluate the effect of ChT on metastasis incidence in both good and poor responders to neoadjuvant treatment. A total of 132 patients (54% female, median age 55 years) were included. Poor mrTRG (HR = 2.53, 95% CI 1.32-5.65) and stage pIII disease (HR 1.94, 95% CI 1.09-3.45) were associated with increased metastatic risk. Although the rate of metastasis was lower in the treated group (9.1%) than in the control group (26.1%) among the patients who achieved a good response (mrTRG 1-2), the difference was not statistically significant (p = 0.19). The subgroup analysis revealed no difference in metastasis rates between patients with poor response receiving or not receiving adjuvant ChT. Response assessed by mrTRG is a preoperative prognostic factor associated with increased metastasis-free survival. MRI restaging could not predict the clinical benefits of adjuvant oxaliplatin-based ChT. Question To patients who have rectal cancer, the prediction of risk for metastatic disease during baseline staging to indicate systemic chemotherapy remains challenging. Findings MR-assessed poor tumor regression grade after neoadjuvant chemoradiotherapy (mrTRG3-5) and pathological postoperative nodal positivity are associated with increased metastatic risk. Clinical relevance The unpredictable response to neoadjuvant chemoradiotherapy is a significant driver of prognosis. The metastasis rates among good and poor responders receiving or not receiving adjuvant chemotherapy were similar. Challenges remain in selecting the population that will benefit from additional treatment.

Accurate information about locoregional breast cancer treatments following neoadjuvant systemic therapy (NST) is essential for meaningful interpretation of oncological outcomes but reporting is currently poor. We developed a core outcome set (COS) to improve the quality and consistency of locoregional outcome reporting in breast cancer NST trials. The COS was developed in three phases according to COS-STAD guidance, with the generation of a list of relevant outcome domains, prioritisation of outcomes through two rounds of an international online multi-stakeholder Delphi survey and a consensus meeting. 159 unique locoregional outcomes were classified into 101 outcome domains for inclusion in the Delphi survey, which was completed by 470 international professionals. The final 15-item COS, which included the pre-NST surgical plan, details of surgery performed following completion of treatment and details of radiation therapy, was agreed at an in-person consensus meeting. Widespread COS implementation will improve the quality and value of future NST trials.

BACKGROUNDGastric cancer is a malignant tumor with high morbidity and mortality worldwide. Neoadjuvant chemotherapy (NAC), defined as chemotherapy administered before the primary treatment (usually surgery) to reduce tumor size and control micrometastases, has emerged as a crucial therapeutic strategy for locally advanced gastric cancer. Pathological complete response (pCR), characterized by the absence of viable tumor cells in the resected specimen after neoadjuvant treatment, is recognized as a strong predictor of favorable prognosis. However, the factors influencing the achievement of pCR remain incompletely understood.AIMTo identify and analyze the predictive factors associated with achieving pCR after NAC in gastric cancer patients, thereby providing evidence-based guidance for clinical decision-making.METHODSA retrospective analysis was performed on 215 patients from Shandong Cancer Hospital and Tai’an Central Hospital with locally advanced gastric cancer who underwent NAC followed by radical surgery at our hospital between January 2015 and December 2023. Comprehensive clinical and pathological data were collected, including age, gender, tumor location, Lauren classification, clinical staging, chemotherapy regimens, number of chemotherapy cycles, and baseline hematological indicators. The baseline hematological indicators included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, albumin level, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9. Univariate and multivariate logistic regression analyses were employed to determine the independent predictive factors for pCR.RESULTSAmong 215 gastric cancer patients, 41 (19.1%) achieved pCR after NAC. Multivariate analysis identified five independent predictive factors for pCR: Lauren intestinal type [odds ratio (OR) = 3.28], lower clinical T stage (OR = 2.75), CEA decrease ≥ 70% after NAC (OR = 3.42), pre-treatment NLR < 2.5 (OR = 2.13), and ≥ 4 chemotherapy cycles (OR = 2.87). The fluorouracil, leucovorin, oxaliplatin, docetaxel regimen achieved the highest pCR rate (27.5%), and oxaliplatin-containing regimens were superior to cisplatin-containing regimens (22.3% vs 12.7%, P = 0.034). Patients with both low NLR and platelet-to-lymphocyte ratio had the highest pCR rate (33.8%), while those with both high inflammatory markers had the lowest rate (10.7%). Earlier clinical stage disease (cT3N+ vs cT4N+: 28.6% vs 13.0%) and lower lymph node burden were associated with higher pCR rates.CONCLUSIONThe achievement of pCR after NAC in gastric cancer patients is closely associated with Lauren intestinal type, lower clinical T stage, a significant decrease in CEA after chemotherapy, low pre-treatment NLR, and an adequate number of chemotherapy cycles.

The Effect of Neoadjuvant Treatment on the Number of Lymph Node Dissection and Prognosis in Locally Advanced Rectal Cancer and Other Factors Affecting Lymph Node Metastasis

Rectal cancer is one of the most common malignant tumors in China, with more than half of patients diagnosed at the locally advanced stage. Currently, the standard treatment for locally advanced rectal cancer (LARC) primarily involves neoadjuvant chemoradiotherapy followed by radical surgery. The advent of immune checkpoint inhibitors has revolutionized the neoadjuvant treatment landscape for mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) rectal cancer. However, most rectal cancer patients exhibit mismatch repair-proficient/microsatellite stable (pMMR/MSS) status and show poor responsiveness to immunotherapy. In recent years, multiple studies have demonstrated that neoadjuvant short-course radiotherapy followed by chemotherapy and immunotherapy can improve the pathological complete response rate in pMMR/MSS LARC patients. Nevertheless, controversies persist regarding patient selection, efficacy evaluation, adverse event management, postoperative adjuvant therapy, and follow-up strategies. Considering the Colorectal Surgery Group of the Surgery Branch of the Chinese Medical Association, in collaboration with the Colorectal and Anal Surgery Committee of the Chinese Research Hospital Association, the Chinese Colorectal Cancer Clinical Research Collaborative Group, and related experts, has developed this consensus document by referencing domestic and international research advancements. The aim is to provide standardized guidance for the clinical application of this treatment approach.