Neoadjuvant talimogene laherparepvec plus surgery vs surgery alone for resectable stage IIIB-IVM1a melanoma
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PROVIDER: PRJNA755196 | ENA |
REPOSITORIES: ENA
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Project description:This study was intended to describe transcriptional changes after TVEC treatment among immune related genes. Tumor gene expression analysis (nanostring, pan cancer immmune profiling panel) was performed to evaluate tumor inflammation status at baseline (in TVEC and control arms) and after treatment with TVEC. Objectives aimed to improve understanding of TVEC therapeutic mechanism of action, included assessment of baseline tumor inflammation status and assessment of change in tumor inflammation status.
2021-09-01 | GSE182162 | GEO
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:Pancreatic ductal adenocarcinoma (PDAC) has dismal five-year survival (<9%). We examined the impact of neoadjuvant FOLFIRINOX alone or in combination with radiation therapy (conventional radiotherapy, XRT, or stereotactic body radiotherapy, SBRT) on immunologically relevant genes in the PDAC tumor microenvironment (TME). We hypothesize conventional therapies may induce immune alterations in the TME that can be leveraged to enhance the efficacy of immunotherapy in PDAC. PDAC patients who underwent upfront surgical resection or who received neoadjuvant FOLFIRINOX with or without neoadjuvant radiotherapy followed by surgical resection were selected for study. The expression of 730 immunologically relevant transcripts was quantitated using the Nanostring PanCancer immune profiling panel (Platform GPL19965). This analysis identified189 genes that were differentially expressed at the RNA level on the basis of neoadjuvant therapy. On average specimens were obtained 6.6-17.0 weeks after the conclusion of neoadjuvant therapy, depending on treatment group. These data provide insight into the immunological effects of standard of care neoadjuvant therapy for resectable/borderline-resectable PDAC. This work provides data to guide strategic new combination therapies for pancreatic cancer.
2019-04-09 | GSE129492 | GEO
Project description:Early surgery is vital in the treatment of highly fatal pancreatic cancer (PC). But there is no valuable and non-invasive biomarker to screen PC currently. Studies showed many salivary molecules can detect several systemic diseases. We aimed to investigate whether salivary microRNAs (miRNAs) can act as a biomarker to detect resectable PC. By Agilent microarray salivary miRNAs were profiled from saliva samples from 8 patients with resectable PC and 8 healthy controls. Candidate biomarkers discovered from the profile were subjected to validation by qPCR.
2013-12-15 | E-GEOD-53325 | biostudies-arrayexpress
Project description:Trial 223 was a placebo-controlled trial of neoadjuvant anastrozole alone or with gefitinib in early breast cancer. We used patients from arm B and C: anastrozole 1mg/d for the duration of the 16 week period plus placebo 1 tablet/d orally for 2 weeks. Patients in arm B were followed by gefitinib 250mg/d orally for 14 weeks whereas patients in arm C continued with placebo for 14 weeks. 96 samples
2014-01-08 | E-GEOD-48906 | biostudies-arrayexpress
Project description:Glioblastoma is the most common primary malignant brain tumor in adults and associated with poor survival. Standard-of-care chemotherapy and radiation confer a median overall survival of under two years. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab, a programmed cell death protein 1 (PD-1) monoclonal antibody, in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical PD-1 blockade alone (hazard ratio = 0.39; P = 0.04, log-rank test). Neoadjuvant PD-1 blockade was associated with upregulation of T cell and interferon-γ-related genes, but downregulation of cell cycle related genes within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 (PD-L1) in the tumor microenvironment was observed more frequently in the neoadjuvant group than in tumors obtained from patients treated only in the adjuvant setting. Similarly, neoadjuvant pembrolizumab was associated with clonal T cell expansion and the overlap of T cell receptors between tumor and blood, decreased PD-1 expression in T cells and a decreasing peripheral monocytic population. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances the local and systemic anti-tumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor. This trial was registered with ClinicalTrials.gov under the identifier NCT02852655 (https://clinicaltrials.gov/ct2/show/NCT02852655).
2018-12-05 | GSE121810 | GEO
Project description:Trial 223 was a placebo-controlled trial of neoadjuvant anastrozole alone or with gefitinib in early breast cancer. We used patients from arm B and C: anastrozole 1mg/d for the duration of the 16 week period plus placebo 1 tablet/d orally for 2 weeks. Patients in arm B were followed by gefitinib 250mg/d orally for 14 weeks whereas patients in arm C continued with placebo for 14 weeks.
2014-01-08 | GSE48906 | GEO
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:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses. MiRNA expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery using Agilent human miRNA microarrays based on miRBase (release 18.0) GeneChip®.
2015-07-27 | E-GEOD-59974 | biostudies-arrayexpress
Project description:BackgroundThe impact of neoadjuvant chemoradiotherapy (nCRT) on early stage esophageal cancer is unknown. Here, we compared the outcomes after esophagectomy alone or nCRT plus surgery for clinically staged node-negative esophageal cancer.MethodsWe searched the Surveillance, Epidemiology, and End Results database for patients with clinically node-negative (cN0) esophageal cancer from 2004 to 2016 who underwent surgery alone or nCRT plus surgery. Propensity score matching and Cox regression analysis were used to identify covariates associated with overall survival and cancer-specific survival.ResultsA total of 1587 patients were retrospectively identified, of whom 49.8% (n = 791) received nCRT and 80.2% (n = 1273) were truly node-negative diseases. For the entire cohort, surgery alone was associated with a statistically significant but modest absolute increase in survival outcomes (P < 0.01). After matching, nCRT was associated with improved five-year overall survival for pT3-4N0 (localized) disease (59.6% vs. 37.7%; P < 0.001) and pathological node-positive disease (60.5% vs. 40.7%; P = 0.002). Cox multivariate regression analysis revealed that the addition of nCRT for truly node-negative patients with tumor length ≥ 3 cm, pT1-2N0 (early-staged) and localized disease were independent risk factors for survival than surgery alone (P < 0.01).ConclusionsCompared with surgery alone, patients with cN0 esophageal cancer with pathological node-positive or localized true node-negative disease gain a significant survival benefit from nCRT. However, nCRT plus surgery was associated with decreased survival for early-staged true node-negative patients. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN0 disease.
| S-EPMC7471040 | biostudies-literature