Neoadjuvant Treatment Research Articles

The poor prognosis of resectable esophageal squamous cell carcinoma (ESCC) poses an unmet need to identify early predictive and prognostic genomic biomarkers to improve treatment outcome and risk stratification. Mutational profiling was performed for 171 ESCC patients receiving curative neoadjuvant chemoradiation treatment (nCRT). The discovery cohort included 100 ESCC formalin-fixed paraffin-embedded (FFPE) tumor specimens; the validation FFPE cohort consisted of serial ctDNA samples from 71 patients. The discovery cohort identified hot-spot oncogenic NFE2L2 mutations exclusively localized at DLG and ETGE KEAP1-binding motifs in poor responders associated with incomplete pathological response (P = 0.004). Patients with NFE2L2 mutations in two independent FFPE cohorts had about 2-fold higher risk of death and recurrence. Serial ctDNA analysis further demonstrated oncogenic NFE2L2 mutations detected at post-nCRT were independent prognosticators for recurrence (HR = 5.90; P = 0.005) and survival (HR = 4.75; P = 0.013). Risk stratification based on pathological T and N stages, positive FFPE (HR = 4.50) and ctDNA NFE2L2 mutations (HR = 8.50) identified high-risk groups for recurrence (P = 0.001). Combined FFPE and ctDNA NFE2L2 mutation status predicted nCRT responses (P = 0.05) by ROC analysis. Tracking oncogenic NFE2L2 mutations at pre-treatment and post-surgery or serial ctDNA monitoring during treatment are useful nCRT predictors and independent prognosticators of survival for locally advanced ESCC.

Treatment of locally advanced rectal cancer (LARC), clinical stages II-III, typically involves multimodal treatment options. Over the past decade, the role of radiation therapy as a neoadjuvant treatment for LARC has evolved and is currently a part of total neoadjuvant therapy (TNT). Some recently published studies advocate for the omission of radiation therapy entirely, while others report on a non-operative approach that emphasizes the use of higher radiation therapy doses. This review aims to evaluate the latest literature on the current role of radiation therapy in the management of LARC, with a discussion of how to best select the most appropriate treatment protocol based on individual patient and tumor characteristics, comorbidities, and personal needs and preferences.

IntroductionDespite thoracotomy remaining the gold standard in the treatment of locally advanced NSCLC after induction treatment, robotic surgery may improve perioperative outcomes. The object of this study is to compare robotic surgery with thoracotomy for the treatment of NSCLC after neoadjuvant treatment, analyzing primary the postoperative complications and secondary the length of hospital stay, the daily drainage volume and the neutrophils-to-lymphocyte ratio.MethodsThe study was designed as a single center and retrospective analysis. Patients with locally advanced NSCLC underwent neoadjuvant treatment followed by surgery between 01/2017 and 12/2023 were evaluated.ResultsA total of 60 patients were collected. The most frequent clinical stage was IIIa (38,3%). Platinum based chemotherapy was delivered in 56 patients; it was associated with immunotherapy in 28 cases and to radiotherapy in 14 cases. All the patients underwent lobectomy and systematic lymphadenectomy, 25 via robotic surgery. There was no significant demographic difference between the two cohorts except for preoperative radiotherapy; over one-third of patients in the open cohort received radiotherapy, while no patients in the robotic cohort did (p<0.001). The hospital stay was statistically significantly shorter in the robotic group (6 days (4-17) vs 8 (5 - 29); p=0.02). Postoperative complication rates were lower (42,8% vs 20%, p=0.04) and the daily drainage output was significantly lower (p=0.0001). The NLR evaluated in V postoperative days was significantly lower in the robotic group (3.36 ± 1.99 vs 7.27 ± 2.59, p=0.0001).ConclusionDespite significant selection bias between cohorts, particularly regarding the use of preoperative radiotherapy which might have influenced the outcomes, robotic surgery appears feasible and yields comparable short-term outcomes for patients with locally advanced NSCLC following neoadjuvant therapy.

To conduct a meta-analysis evaluating the diagnostic accuracy of computed tomography (CT) for identifying T3-T4 colon cancer using histopathology as the reference standard. Secondary objectives included assessing CT's performance for detecting extramural vascular invasion (EMVI) and nodal involvement. This diagnostic accuracy meta-analysis followed PRISMA-DTA guidelines and searched MEDLINE, EMBASE, and Cochrane Library for studies published up to September 2024. Eligible studies evaluated CT for preoperative T staging (T3 or higher), EMVI, and/or nodal status in primary colon cancer, reporting sensitivity and specificity. Studies on rectal cancer, using specialized CT techniques, or not in English, were excluded. Pooled sensitivity and specificity for T staging, EMVI, and nodal status were calculated using a random-effects model. Subgroup analyses explored sources of heterogeneity. Thirty-two studies, including 222,948 patients (mean age 69 years; 50.5% female), were analyzed. For pT3-T4 staging, pooled sensitivity and specificity were 0.81 (95% CI: 0.76-0.85) and 0.75 (95% CI: 0.66-0.83). For pT3c-T4, sensitivity was 0.71 (95% CI: 0.62-0.79) and specificity was 0.83 (95% CI: 0.74-0.89). EMVI detection showed sensitivity of 0.40 (95% CI: 0.30-0.52) and specificity of 0.80 (95% CI: 0.71-0.87). A reliable pooled estimate for nodal status could not be determined. CT shows good diagnostic performance for identifying T3-T4 colon cancer and can detect high-risk features like EMVI. These findings support its role in selecting candidates for neoadjuvant therapies, although EMVI sensitivity remains limited. Question How accurate is CT for identifying T3-T4 colon cancer and detecting key prognostic factors like EMVI to support neoadjuvant treatment planning? Findings CT shows good accuracy for T3-T4 staging (sensitivity 0.81; specificity 0.75) and high specificity (0.80) but low sensitivity (0.40) for EMVI. Clinical relevance CT enables reliable identification of locally advanced colon cancer and high-risk features such as EMVI, supporting better patient selection and personalized neoadjuvant treatment planning.

BackgroundAs neoadjuvant therapies become increasingly crucial in the management of esophageal squamous cell carcinoma (ESCC), improving local control, R0 resection rates, and overall survival, determining the optimal neoadjuvant strategy remains a priority. This study retrospectively assesses the efficacy and safety of neoadjuvant immunochemotherapy (NICT), chemoradiotherapy (NCRT), and chemotherapy (NCT) in operable ESCC.MethodsAnalyzing preoperative clinical data from resectable ESCC patients treated with NICT, NCRT, or NCT at Shandong Cancer Hospital from January 2018 to August 2022, we focused on surgical complications, pathological responses, and survival outcomes.ResultsData from 300 patients (91 NICT, 113 NCRT, 96 NCT) were evaluated. The NICT group showed a lower incidence of surgical complications compared to NCRT (17.6% vs. 36.3%, p = 0.003) and was on par with NCT (17.6% vs. 22.9%, p = 0.365). NICT had less favorable complete pathological response rates than NCRT (p < 0.001) but outperformed NCT. Notably, the NICT cohort achieved superior 2-year recurrence-free (81.3%) and overall survival (93.4%) compared to NCRT (73.5% and 84.1%, p = 0.187 and p = 0.043) and NCT (44.8% and 61.5%, p < 0.001 for both).ConclusionDespite a slightly lower rate of pathological remission, NICT significantly reduced surgical complications and improved survival outcomes. It presents a compelling option in the neoadjuvant treatment of resectable ESCC, with the potential to supersede NCRT and NCT.

Background Neoadjuvant PD-1 blockade plus chemoradiotherapy has resulted in improved clinical response in pancreatic ductal adenocarcinoma (PDAC); however, the effects on pathological response (PR) and survival remain unknown. This study was to identify the survival and PR of patients with PDAC undergoing surgery after neoadjuvant treatment (NAT) with PD-1 blockade plus chemoradiotherapy. Methods A retrospective cohort study was performed for PDAC patients undergoing resection after NAT, analyzing PR and survival prediction using clinicopathological and survival data. Results 47 patients were enrolled with 26 received neoadjuvant PD-1 blockade plus chemoradiotherapy (combined group) and 21 received PD-1 blockade plus chemotherapy (non-combined group). 6 patients (23.1%) and no patients achieved complete PR (CPR) in the combined and non-combined group. Age and tumor size decrease were independently associated with PR assessed by the CAP and MDACC system (p < 0.05). In the combined group, the 2-year overall survival (OS) rate, median OS and median disease-free survival (DFS) were 75.2%, 30.5 and 23.2 months, which were all better than those in the non-combined group (42.6%, 23.3 and 16.8 months), albeit with no significant differences. Portal vein (PV)/superior mesenteric vein (SMV) invasion (p = 0.034), resectability status (p = 0.019) and preoperative CA19-9 levels (p = 0.002) were significant prognostic factors for OS. Preoperative CA19-9 levels (p = 0.001) was an independent prognostic factor for DFS. Conclusions NAT with PD-1 blockade plus chemoradiotherapy was associated with a higher CPR rate in resected PDAC. Age and tumor size decrease were predictive factors for PR. PV/SMV invasion, resectability status, and preoperative CA 19-9 levels were independent prognostic factors for survival.

Breast cancer (BC) is one of the most common forms of malignant neoplasms among women and is the leading cause of cancer-related mortality. This complex and heterogeneous disease is formed depending on the presence of overexpression of various receptors on the surface of tumor cells. Despite significant advances in the therapy of early and metastatic BC, many patients continue to demonstrate disease progression against the background of traditional treatment methods, which indicates immunosuppression or a defect in the immune system.The aim of this work is to review the scientific literature on the main mechanisms of antitumor immunity in patients with BC and the prospects for the use of immunotherapy.Previously, BC was not considered a particularly immunogenic tumor, but new data show that different tumor subtypes can exhibit immunogenicity, which opens up new prospects for the use of immune checkpoint inhibitors. Features of the tumor immune microenvironment and the presence of tumor infiltrating lymphocytes are becoming important markers that help predict responses to immunotherapy. The effectiveness of such approaches is demonstrated by clinical studies, where the use of immune checkpoint inhibitors in combination with chemotherapy has shown an improvement in the response to therapy. Such studies confirm that even in cases where there is a residual tumor after neoadjuvant treatment, the use of immunotherapy can increase survival. From the presented analysis of literature sources, it follows that BC carcinogenesis is accompanied by suppression of the antitumor activity of the immune system. Quantitative analysis of various predictors allows us to determine the effectiveness of immune drugs. Thus, given the diversity of BC subtypes and many factors affecting the effectiveness of treatment, it becomes obvious that careful patient selection and a personalized approach to immunotherapy are necessary to achieve optimal results. In the future, research in the field of biomarkers should be continued to better predict the response to immunotherapy and minimize adverse effects.

Randomized clinical trials have shown no benefit from adding anthracyclines to neoadjuvant treatment for HER2-positive breast cancer; however, the efficacy in inflammatory breast cancer (IBC) is unknown. Here we compared pathologic response rates for preoperative regimens with or without anthracyclines in HER2-positive primary IBC. We retrospectively reviewed patients diagnosed with HER2-positive primary IBC in 2014-2021 who received neoadjuvant therapy and modified radical mastectomy at MD Anderson Cancer Center, IBC Network institutions and Dana-Farber Cancer Institute. The primary outcome was a pathological complete response (pCR) rate. Secondary outcomes included time to local or regional recurrence (TLRR), event-free survival (EFS), and overall survival (OS). Univariate and multivariable analyses were performed with adjustments for clinically relevant covariates. Of the 101 patients included, 39 received docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), and 62 (docetaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) received THP-AC regimen. Median follow-up time was 3.02years. The pCR rates did not differ by regimen type (48.7% TCHP vs. 53.2% THP-AC, p = 0.659). Multivariable logistic regression adjusted for age and estrogen receptor positivity showed no association between pCR or regimen. The multivariable Cox model showed that the patients who received THP-AC had longer TLRR (hazard ratio [HR] 0.279, 95% CI 0.102-0.765, p = 0.0131) and EFS (HR 0.462, 95% CI 0.228-0.936, p = 0.032), with no difference in OS. These findings indicate that an anthracycline-containing neoadjuvant regimen is not associated with pCR, but may prolong disease control in patients with HER2-positive IBC. Further investigation of the optimal neoadjuvant regimen for such tumors is warranted.

Correlation between magnetic resonance imaging and definitive histological response in adenocarcinoma of middle and low rectum after neoadjuvant treatment.

Distal pancreatectomy with celiac axis resection (DP-CAR) for pancreatic ductal adenocarcinoma in a retrospective monocentric cohort: neoadjuvant treatment and three-axis embolization of the celiac axis are key factors of success.

Total neoadjuvant treatment with short-course radiotherapy followed by sintilimab plus capecitabine-oxaliplatin versus short-course radiotherapy followed by capecitabine-oxaliplatin in patients with locally advanced rectal cancer (SPRING-01): a single-centre, open-label, phase 2, randomised controlled trial.

The role and clinical significance of tumor-draining lymph nodes in tumor progression and immunotherapy.

Abstract Background Fluoropyrimidines (FP) are the cornerstone of adjuvant therapy in colorectal cancer (CRC). Treatment options are limited for the 4%-6% of patients who experience cardiotoxicity on FP treatment. The CardioSwitch study in patients with solid tumours showed that switching to S-1-based treatment is feasible, as an alternative to permanent FP discontinuation (1). Purpose This analysis aimed to evaluate safety and efficacy data for patients with localized CRC who were switched to S-1 after experiencing cardiotoxicity during FP treatment in the adjuvant or neoadjuvant setting. Methods This retrospective study included patients with stage II-III CRC who had a history of cardiotoxicity during FP treatment in the perioperative setting. Primary endpoints were recurrence of cardiotoxicity after switch to S-1-based therapy. Secondary endpoints were safety and survival, and these data were compared with data for all 413 adjuvant patients treated between 2010 and 2022 in the Uppsala region, Sweden. Results Eighty-nine patients were included from eight centres in three countries. Median age was 66 (range 28-82) years, 51% were female, and 92% had ECOG PS 0-1. The primary tumour location was right colon in 26%, left colon in 24%, and rectum in 54%. Baseline cardiovascular comorbidities were present in 45%. Initial treatment that caused cardiotoxicity was capecitabine-based in 92%, infusional 5-FU in 6%, and bolus 5-FU in 2%. Of these, oxaliplatin was added in 39%. Initial cardiotoxicity was grade 3-4 in 42% and occurred in the first 2 cycles in 93%. Cardiotoxicity occurred during neoadjuvant CRT or chemotherapy in 22% and during adjuvant therapy in 78% (Figure 1). Switch to S-1-based treatment occurred during neoadjuvant therapy in 15% and during adjuvant therapy in 85%. S-1 monotherapy was administered to 46%, 42% received S-1 plus oxaliplatin (SOX), and 12% received S-1 CRT. Four patients (4%) experienced recurrent cardiotoxicity on S-1-based treatment, the worst level was grade 1 in two and grade 2 in two. Adjuvant treatment completion rate was 96%: two patients discontinued due to recurrent tachycardia, one due to diarrhoea, and one due to ileitis/tuberculosis. Grade 2-4 non-haematologic and/or 3-4 haematologic toxicity occurred in 34%. Baseline characteristics of the patients with recurrence on S-1 included cardiovascular comorbidity in two, and all had ECOG PS 0-1, rectal cancer, and received adjuvant treatment. The five-year DFS rate was 69% and 5-year OS rate was 83%, with median follow-up 69 months, in line with population-based data of 73% and 76%, respectively, from the Uppsala cohort (Figure 2). Conclusions S-1-based neoadjuvant CRT and/or adjuvant treatment is effective, safe and feasible after cardiotoxicity on other FP-based treatment and enables patients to continue curative treatment as indicated.Cardiotoxicity during FP and S-1 Overall and Disease-free survival

Prediction of survival after de-escalated neoadjuvant therapy in HER2-positive early breast cancer: a pooled analysis of three WSG trials.

Muscle-Invasive Bladder Cancer Treatment Selection in an Emerging Treatment Era: A Patient Preference Study.

Longitudinal Analysis Reveals Dynamic Changes in Histopathologic Features in Responders to Neoadjuvant Treatment in a Stage III BRAF-Mutant Melanoma Cohort.

Delphi for management of N2 non-small cell lung cancer.

Role of Neoadjuvant Chemoradiation Therapy for Resectable and Borderline Resectable Pancreatic Adenocarcinoma-A Systematic Review and Meta-Analysis.

Breast cancer neoadjuvant therapy outcome prediction based on clinical patient and tumor features: A cross-sectional study.

Impact of systematic enteral nutrition on postoperative complications and oncological outcome in a curative multimodal strategy for esophageal cancer.