Phase 3 Study of Surgery Combined With Neoadjuvant Chemotherapy(XELOX) in Colorectal Cancer With Resectable Liver Metastasis
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasm Metastasis,Colorectal Cancer,Resectable Liver Metastasis,Colorectal Neoplasms,Liver Neoplasms
PROVIDER: 2051744 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:The Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC) trial reported an acceptable safety profile for neoadjuvant Oxaliplatin and Capecitabine (Xelox) +/- AZD8931 in oesophageal adenocarcinoma (OAC) but limited efficacy. We evaluated the impact of neoadjuvant Xelox +/-AZD8931 on biological pathways using a unique software-driven solution. Transcriptomic profiles from 25 pre-treatment FFPE OAC biopsies and 17 matched resection specimens, treated with Xelox+AZD8931 (n=16) and Xelox alone (n=9), were analysed using the Almac claraT total mRNA report. Tumour Infiltrating Lymphocytes (TILs) were assessed digitally using QuPath software. Hierarchical clustering identified three molecular subgroups classified by activation of innate immune signalling. The Immune High subgroup was associated with HER2 positivity, increased pathological response and a marked reduction in immune signalling and TILs following neoadjuvant therapy. The Immune Low cluster was pre-dominantly HER2/EGFR negative and EGFR positivity was associated with the Immune Mixed subgroup. Neoadjuvant therapy induced angiogenesis and EMT signalling and a reduction in DNA repair signatures with AZD8931 also promoting an immunosuppressive microenvironment. OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2 positive/Immune High tumours.
2024-09-01 | E-MTAB-13741 | biostudies-arrayexpress
Project description:PurposeThis paper is aimed at comparing the short-term efficacy of the combination of docetaxel, oxaliplatin, and capecitabine (DOX) with the combination of oxaliplatin and capecitabine (XELOX) as neoadjuvant chemotherapy regimens for the treatment of patients with resectable gastric or gastroesophageal junction adenocarcinoma.MethodsA total of 300 patients aged 20-60 years with resectable gastric or gastroesophageal junction adenocarcinoma who were evaluated with cT3/4Nany were randomly assigned into 3 groups: DOX group (n = 100, treated with neoadjuvant DOX plus adjuvant XELOX), XELOX group (n = 100, treated with perioperative XELOX), and surgery group (n = 100, treated with adjuvant XELOX).ResultsA total of 93, 92, and 95 patients were enrolled in the DOX, XELOX, and surgery groups, respectively. The pathological complete response (pCR) rate was 16.1% in the DOX group and 4.3% in the XELOX group (P = 0.008). There were 56 (61.3%) patients in the DOX group who presented with surgical complications, 22 (23.9%) patients in the XELOX group, and 37 (38.9%) patients in the surgery group. The most common grade 3-4 adverse events in these three groups were neutropenia (32.3%, 30.4%, and 21.1%), leucopenia (21.5%, 22.8%, and 15.8%), nausea (15.1%, 16.3%, and 12.6%), and fatigue (10.8%, 7.6%, and 8.4%).ConclusionsNeoadjuvant DOX is an effective and feasible regimen and might represent an option for young and middle-aged patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma.
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Project description:Interventions: Patients receive FOLFOX regimen or XELOX (oxaliplatin plus capecitabin) and MoAb as neoadjuvant protocol
Primary outcome(s): Progression-free survival
Study Design: Single arm Non-randomized
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Project description:Neoadjuvant PD-1 blockade may be efficacious in patients with high-risk, resectable oral-cavity, head-and-neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 patients displaying 33% responsiveness. Pretreatment tumor-based detection of FLT4 mutations and PTEN signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival. In contrast, preexisting and/or acquired mutations (in CDKN2A, YAP1, JAK2) correlate with innate resistance and/or tumor recurrence. Immunologically, tumor response after therapy entails T-cell receptor repertoire diversification in peripheral blood and intratumoral expansion of preexisting T-cell clones. A high ratio of regulatory to Th17 T cells in pretreatment blood predicts innate resistance, low cytolytic T-cell signature in pretreatment tumor, and low T-cell receptor repertoire diversity in pretreatment blood. Our study provides a molecular framework to advance neoadjuvant anti-PD-1 therapy for patients with resectable head-and-neck cancer.
2021-09-30 | GSE179730 | GEO
Project description:This is a single arm, open-label phase II study to evaluate the efficacy and safety of Capecitabine plus oxaliplatin (XELOX) in the peri-operative treatment of patients with potentially resectable liver metastasis from colorectal cancer.
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Project description:AimWe investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells.MethodsWe classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences.ResultsThere were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural-killer group 2, member D (NKG2D)- positive NK cells in PBMC and percentage of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, NKp30-, and signal regulatory protein ? (SIRP?)-positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRP? in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)-2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups.ConclusionColorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.
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Project description:Co-mutations of the KRAS and STK11 genes in advanced non-small cell lung cancer (NSCLC) are associated with immune checkpoint blockade (ICB) resistance. While neoadjuvant chemoimmunotherapy is now a standard of care treatment for early-stage NSCLC, the clinical and immunologic impact of KRAS and STK11 co-mutations in this setting are unknown. We evaluated the clinical outcomes and intratumoral T cell profiles of resected KRAS-mutant tumors treated with neoadjuvant ICB. Relative to KRASmut/STK11wt tumors, KRASmut/STK11mut exhibited significantly higher recurrence risk. Single-cell transcriptomics showed enhanced oxidative phosphorylation with evidence of decreased PGE-2 signaling and increased IL-2 signaling in CD8+ tumor-infiltrating lymphocytes (TIL) from KRASmut/STK11mut tumors, a finding that was mirrored in KRASwt tumors that relapsed. TIL from KRASmut/STK11mut tumors expressed high levels of molecules associated with tumor residence, including CD39 and ZNF683 (HOBIT). These divergent T cell transcriptional fates suggest T cell maintenance and residence may be detrimental to anti-tumor immunity in the context of neoadjuvant ICB for resectable NSCLC, regardless of KRAS mutation status. Our work provides a basis for future investigations into the mechanisms underpinning PGE-2 and IL-2 signaling as they relate to T cell immunity to cancer and to divergent clinical outcomes in KRASmut/STK11mut NSCLC treated with neoadjuvant ICB.
2024-10-24 | GSE280232 | GEO
Project description:BackgroundThe prognosis of patients under existing neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy requires improvement. Whereas programmed cell death 1 (PD-1) inhibitors have shown promising response in advanced esophageal cancer, they have not been used in the perioperative treatment of resectable locally advanced esophageal cancer. Whether immunotherapy can be incorporated into neoadjuvant therapy has became a challenging question for researchers.Case presentationWe present a case of a 65-year-old male who had a history of progressive dysphagia for approximately 1 month. He underwent pertinent studies including computed tomography (CT)，gastroscopy，and pathological biopsy resulting in a diagnosis of medium-low differentiated squamous carcinoma of the thoracic segment of the esophagus (cT2N2M0 stage III). After 4 cycles of neoadjuvant chemotherapy combined with immunotherapy, gastroscopy showed the lesion in the esophagus was no longer present. Subsequently, the patient received thoracoscopic radical resection of esophageal cancer and achieved a pathological complete response (pCR) in postoperative pathological evaluation. During the whole treatment, no adverse effect was recorded and to date no evidence of recurrence has been recorded.ConclusionOur report suggest that neoadjuvant chemotherapy combined with immunotherapy not only improve the R0 resection and pCR rate in patients with resectable locally advanced esophageal cancer, but also the adverse effects are within the control range. However, the selection of therapeutic strategy, predictors of response to treatment, and interval time between neoadjuvant treatment and surgery still await more reliable evidence-based studies with large prospective samples.
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