Novel molecular classification of colorectal cancer and correlation with long-term survival.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15514-e15514
Author(s):  
Fayaz Hussain Mangi ◽  
Tanweer Ahmed Shaikh ◽  
Daniel Soria ◽  
Jawaid Naeem Qureshi ◽  
Ikram Uddin Ujjan ◽  
...  

e15514 Background: Colorectal cancer (CRC) is a heterogeneous disease, however there is limited information available regarding molecular classification and correlation with long term clinical outcome. Methods: Over the period of 11 years (2008 to 2018) totals 435 patients of colorectal cancer were reported and their tumour blocks and complete set of clinical information was available for 201 patients. Immunohistochemistry was done for ER, PR, HER 2-neu, Ki-67, Bcl-2, E-Cadherin, P53, CEA, EGFR, and VEGF. PDL1, CDX-2 and CK 20. The biological pattern characterized by partitioned clustering method as described using R software. Survival analysis was done by using Kaplan Meier method. Results: There were 201 patients including 54.7% male and females were 45.3 %. Median survival was 28 months. Cluster analysis showed four novel clusters (Table), with major difference based on Ki67, CDX2 and p53. These classes showed difference in median survival, where common class 1 showed higher survival while common cluster 4 showed poor survival. Conclusions: There are at least four distinct molecular classes of colorectal cancer which can be potentially utilized in clinical practice. Pattern of Novel molecular classification of colorectal cancer and correlation with long term survival.[Table: see text]

2010 ◽  
Vol 28 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Dominique Elias ◽  
François Gilly ◽  
Florent Boutitie ◽  
François Quenet ◽  
Jean-Marc Bereder ◽  
...  

Purpose Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. Patients and Methods A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. Conclusion This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.


2013 ◽  
Vol 15 (4) ◽  
pp. 469-479 ◽  
Author(s):  
S. Leu ◽  
S. von Felten ◽  
S. Frank ◽  
E. Vassella ◽  
I. Vajtai ◽  
...  

2007 ◽  
Vol 32 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Marcella Arru ◽  
Luca Aldrighetti ◽  
Renato Castoldi ◽  
Saverio Di Palo ◽  
Elena Orsenigo ◽  
...  

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi166-vi166
Author(s):  
Alexander Haddad ◽  
Jordan Spatz ◽  
Megan Montoya ◽  
Sara Collins ◽  
Sabraj Gill ◽  
...  

Abstract Glioblastoma (GBM) leads to severe systemic and local immunosuppression, and immunotherapies have had limited clinical success. Here, we evaluated the treatment efficacy of RLI, a superagonist of T-cell activator IL-15, delivered to tumor cells using a tumor-selective retroviral replicating vector (RRV) in the syngeneic murine SB28 and Tu2449 GBM models, which are both engineered to be poorly immunogenic with low-mutational burden and known resistance to immunotherapy, and hence more accurate biomimetic models of human GBM. RRV-RLI replicated and spread effectively in cultured murine GBM cells with robust production of functional RLI (165.4 ± 5.3 ng/mL). Stereotactic injection of RRV-RLI into pre-established intracerebral SB28 tumors significantly reduced tumor growth on bioluminescent imaging, and increased median survival compared to control mice (55 vs. 19 days, p=0.002), leading to long-term survival in 12% of treated mice. In the Tu2449 model, imaging results showed complete eradication of intracerebral tumors after RRV-RLI treatment, with long-term survival (median not reached) in > 85% of treated mice, compared to a median survival of 12.5 days in control mice (p=0.001). RRV-RLI treated tumors showed significantly increased CD8 T-cell infiltration, without altering immunosuppressive cell populations. Similarly, broad anti-tumor inflammatory changes, including increased expression of genes involved in T-cell activation and killing, were observed in the NanoString nCounter platform using a 770-gene panel representing various immune cell types. Notably, RLI was not detected in the blood of treated mice, and tumor-localized RRV-RLI gene delivery showed no adverse systemic immune effects in either model. In summary, RRV-mediated RLI immunotherapy results in immunostimulatory and pro-inflammatory changes to the tumor microenvironment and achieves a significant survival benefit in two poorly immunogenic syngeneic murine models of GBM. This tumor-localized immunomodulatory gene therapy has the potential to safely reverse the T-cell depleted immunophenotype of GBM.


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