Retrospective study to evaluate oncologic safety of laparoscopic surgery for obese colorectal cancer patients
Ontology highlight
ABSTRACT:
DISEASE(S): Obese Colorectal Cancer Patients Who Underwent Open Or Laparoscopic Surgery (bmi Is 25 And More)
PROVIDER: 2648635 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:This dataset spans two studies which investigate the clinico-pathology and molecular features of infant medulloblastoma, defined as children aged <5 years at diagnosis. Both abstracts follow. Background Infant medulloblastoma (iMB; <3-5-years old at diagnosis) is a major challenge in paediatric oncology. The favourable-risk SHH iMB molecular group with desmoplastic histology (40% of iMB) is commonly spared upfront craniospinal irradiation (CSI) to avoid neurocognitive side-effects. However, clinical studies of the remaining non-WNT/non-SHH iMB group (~60% of iMBs) have not been undertaken, and it is currently considered uniformly high-risk. Understanding the potential for its biological subclassification and clinical stratification is an essential goal towards improved outcomes. This study therefore aimed to directly compare different therapeutic approaches in non-WNT/non-SHH iMB and determine relationships between outcomes and clinico-molecular features. Methods We assembled a global cohort of non-WNT/non-SHH iMBs (n=375). Inclusion criteria was a principal non-WNT/non-SHH MB classification (Group 3 or Group 4); confidence score >0.8) using DNA methylation array-based classification. The survival cohort (n=313) was defined by availability of complete progression-free (PFS) and overall (OS) survival data. Using these cohorts, we characterised their molecular pathology, treatments received, and relationships to outcomes, principally PFS. Findings The total collected cohort (n=375) comprised 262 males and 110 females, with a median age of 3.0 (IQR 2.53-4.0) years. Molecular group 3 tumours (iMBGrp3) predominated (n=246, 66%), primarily molecular subgroups 2 (n=75; 32%), 3 (n=46; 19%) and 4 (n=98; 42%). Regimens incorporating upfront CSI were most common (54% of patients); such patients had significantly better PFS than those treated with focal or no radiotherapy (5-year PFS; CSI, 57.9%; Focal-radiotherapy, 35.3%; No radiotherapy, 26.8%; p<0.001), and equivalent PFS to CSI-treated non-infant patients. Upfront chemotherapy -only approaches were used in 33% (66/199) of iMBGrp3; high-dose (HIGH-DOSE) chemotherapy produced better survival rates (45.7%, 5-year PFS) than intraventricular methotrexate-based (21.1%, 5-year PFS) or standard-dose (11%, 2-year PFS) chemotherapy (p=0.003). Subgroup 4 represents a novel chemo-sensitive iMB group, with 64.3% 5-year PFS using high-dose -chemotherapy-only and with evidence of rescue post-relapse. MYC-amplified iMBGrp3 ( subgroup2/3) have dismal prognosis (0% 2-year overall survival (OS)), with rapid progression regardless of treatment. Remaining subgroup 2/3 patients treated with Chemotherapy-only had 30% 5-year PFS, showed some evidence of post-relapse rescue, and could be randomised to test alternative therapeutic strategies. Interpretation Non-WNT/non-SHH iMB outcomes are associated with specific biomarkers and therapy received. Capturing this ‘real-world’ experience identifies favourable ( subgroup 4) and very-high-risk ( subgroup 2/3-MYC) patient groups, providing a critical foundation for first biomarker-driven iMBGrp3 clinical trials. Background Medulloblastoma in infants (iMB; <5 years) presents the challenge of achieving cure while minimizing deleterious cranio-spinal irradiation (CSI)-associated late-effects. Non-randomised Phase-II studies have examined upfront CSI omission and chemotherapy intensification for favourable-risk desmoplastic/nodular (DN) tumours associated with the SHH molecular group (iMBSHH). Comparison of these therapies in large molecularly-defined iMBSHH cohorts, alongside investigations of prognostic biomarkers in therapy-specific context, is urgently required to define future therapeutic strategies. Methods A multi-national cohort of molecularly and clinically-annotated iMBSHH (n=267), not previously reported in clinical trials, was assembled. We investigated molecular pathology, upfront treatments, and relationships to outcome, in this ‘real-world’ setting. Findings iMBSHH patients treated upfront with intensified chemotherapy-only regimens (n=132) based on intraventricular methotrexate (IVT-MTX; 5-year progression-free survival (PFS), 72.6%) or high-dose (HD; 73.0%) therapy, achieved (PFS) outcomes comparable to upfront CSI-based regimens (n=49; 74.0%)(p=0.51). Lower-intensity standard-dose chemotherapy-only regimens were inferior (SD; 48.4% PFS)(p=0.006). Rescue was common post-relapse after IVT-MTX/HD protocols and translated into 5-year overall survival (OS) of 85.6% and 88.6%, respectively. iMBSHH encompassed SHH-1 (38%), SHH-2 (47%) and SHH-3 (14%) WHO subgroups. In CSI-naïve iMBSHH, SD associated with worse PFS in SHH-1 (p=0.001), but not SHH-2. Non-DN/MBEN histology (21.2% of iMBSHH) conferred worse PFS in upfront CSI-treated and SD (p<0.001 and p=0.003, respectively) groups. Metastatic disease only associated with prognosis with upfront IVT-MTX-only therapies (p=0.013), while established high-risk features of non-infant MBSHH (TP53-mutation, LCA-histology, MYCN-amplification) only associated with poor prognosis in older SHH-3 (7/7 relapsed). Finally, CSI-naïve PFS findings were validated in a re-evaluation of smaller historical trials cohorts. Interpretation iMBSHH outcomes and prognostic biomarkers are therapy-dependent. Non-metastatic iMBSHH treated with HD or IVT-MTX chemotherapy-only have equivalent favourable outcomes, independent of histology and subgroup. With outcomes established, clinical trials must now focus on quality-of-life following different intensified approaches, to identify kindest curative strategies.
2026-05-29 | GSE317378 | GEO
Project description:Primary outcome(s): 5-year-recurrence free survival
| 2655497 | ecrin-mdr-crc
Project description:Purpose: Our study aimed to disclose the specific gene expression profile representing peritoneal relapses inherent in primary gastric cancers and to identify patients at high risk of peritoneal relapse in a prospective study on the basis of the molecular prediction. Experimental Design: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly we constructed molecular prediction system and validated the robustness and prognostic validity of the analysis by 500 times multiple random sampling in 56 retrospective set consisting of 38 relapse free and 18 peritoneal relapse patients. Secondly we applied this prediction to 85 prospective set to assess the predictive accuracy and prognostic validity. Results: In retrospective phase, 500 times multiple random sampling analysis yielded 68% predictive accuracy in average and 22 gene expression profile associated with peritoneal relapse was identified. This prediction could identify significantly poor prognostic patients. In prospective phase, the molecular prediction yielded 76.9% overall accuracy. KaplanâMeier analysis with peritoneal relapse free survival showed a significant difference between âgood signature groupâ and âpoor signature groupâ (Log-rank p=0.0017). Multivariate analysis by Cox regression hazards model revealed that the molecular prediction was the only independent peritoneal relapse prognostic factor. Conclusions: Gene expression profile inherent in primary gastric cancer tissues can be useful to predict peritoneal relapse prospectively after curative surgery and individualize postoperative management to improve the prognosis of advanced gastric cancers. Of 141 samples, 56 represented the retrospective phase and 85 represented the prospective phase.
2010-05-23 | E-GEOD-15081 | biostudies-arrayexpress
Project description:Purpose: Our study aimed to disclose the specific gene expression profile representing peritoneal relapses inherent in primary gastric cancers and to identify patients at high risk of peritoneal relapse in a prospective study on the basis of the molecular prediction. Experimental Design: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly we constructed molecular prediction system and validated the robustness and prognostic validity of the analysis by 500 times multiple random sampling in 56 retrospective set consisting of 38 relapse free and 18 peritoneal relapse patients. Secondly we applied this prediction to 85 prospective set to assess the predictive accuracy and prognostic validity. Results: In retrospective phase, 500 times multiple random sampling analysis yielded 68% predictive accuracy in average and 22 gene expression profile associated with peritoneal relapse was identified. This prediction could identify significantly poor prognostic patients. In prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis with peritoneal relapse free survival showed a significant difference between ‘good signature group’ and ‘poor signature group’ (Log-rank p=0.0017). Multivariate analysis by Cox regression hazards model revealed that the molecular prediction was the only independent peritoneal relapse prognostic factor. Conclusions: Gene expression profile inherent in primary gastric cancer tissues can be useful to predict peritoneal relapse prospectively after curative surgery and individualize postoperative management to improve the prognosis of advanced gastric cancers.
2009-03-04 | GSE15081 | GEO
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