Mismatch Repair Deficient Rectal Cancer and Resistance to Neoadjuvant Chemotherapy.

Mismatch Repair Deficient Rectal Cancer and Resistance to Neoadjuvant Chemotherapy. Clin Cancer Res. 2020 Mar 06;: Authors: Cercek A, Dos Santos Fernandes G, Roxburgh CS, Ganesh K, Ng S, Sanchez-Vega F, Yaeger R, Segal NH, Reidy-Lagunes DL, Varghese AM, Markowitz A, Wu C, Szeglin B, Sauvé CG, Salo-Mullen E, Tran C, Patel Z, Krishnan A, Tkachuk K, Nash GM, Guillem J, Paty PB, Shia J, Schultz N, Garcia-Aguilar J, Diaz LA, Goodman K, Saltz LB, Weiser MR, Smith JJ, Stadler ZK Abstract PURPOSE: Evaluate response of mismatch repair deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: dMMR rectal tumors at Memorial Sloan Kettering were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty dMMR rectal cancer patients were identified by immunohistochemistry and/or microsatellite instability analysis, with initial treatment response compared to a matched pMMR rectal cancer cohort. Germline and somatic mutation analyses were evaluated. Patient-derived dMMR rectal tumoroids were assessed for chemotherapy sensitivity. RESULTS: Of 21 patients receiving neoadjuvant chemotherapy (fluorouracil/oxaliplatin), 6 (29%) had progression of disease. In comparison, no progression was noted in 63 pMMR rectal tumors (P = 0.0001). Rectal cancer dMMR tumoroids reflected this resistance to chemotherapy. No genomic predictors of chemotherapy response were identified. Of 16 patients receiving chemoradiation, 13 (93%) e...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research

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ConclusionThe patient presented represents the first reported case where both next generation sequencing (NGS) forBRCA LOH and MMR IHC testing of her breast cancer were performed and underscores the importance of using NGS including the reported mutational allelic frequency (MAF) and IHC use to predict the likely responsiveness to the recently approved PARP inhibitors and checkpoint inhibitor therapies (Robson et al in N Engl J Med 377:523 –533, 2017, Lemery et al in 377(15):1409–1412,https://doi.org/10.1056/NEJMp1709968, 2017), key because the gatekeeper transforming event for tumors related to inherited cance...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
ConclusionsResults of the Idylla ™ MSI Assay were highly concordant with results of routine tests and lower failure rates were observed. Further advantages are the lack of need for matched normal tissue, the low dependence on pre-analytical conditions, the simplified workflow, the short turnaround times, the automated result inte rpretation, and the very limited hands-on work.Editorial acknowledgementTeams involved in the MSI, Idylla MSI Assay, Colon Rectal Cancer, Multicenter Study.Legal entity responsible for the studyIrblleida.FundingBiocartis.DisclosureX. Matias-guiu: Non-remunerated activity/ies: Biocartis.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThe ‘pelvis-first’ approach to proctectomy is advantageous for patients with a highly redundant sigmoid colon. Transabdominal division of the levator ani during APR ensures excellent circumferential margin. Although Lynch syndrome-associated rectal cancer can show excellent response to NCRT,3 patients undergoing watchful delay of surgery require close monitoring and prompt triggering of salvage proctectomy when tumor regrowth is observed.4,5
Source: Annals of Surgical Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: The combination of an increasing incidence of colorectal cancer in those under 50 years of age and the predominance of left-sided cancer suggests that screening by flexible sigmoidoscopy starting at age 40 in average-risk individuals may prevent cancer by finding asymptomatic lesions. See Video Abstract at http://links.lww.com/DCR/A579.
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research
A new study released by the National Cancer Institute shows colon and rectal cancers have increased dramatically and steadily in young and middle-age adults in the United States over the past four decades. Dr. Yixing Jiang, a Medical Oncologist at the University of Maryland Greenebaum Comprehensive Cancer Center, answers all the questions you’re now asking yourself about colon cancer. Q. What are the risk factors for colon cancer? A. The risks for developing colon cancer are: obesity; insulin resistance diabetes, red and processed meat; tobacco; alcohol; family history of colorectal cancer; certain hereditary syndrom...
Source: Life in a Medical Center - Category: Universities & Medical Training Authors: Tags: Cancer Health Tips colon cancer maryland research study treating colon cancer Source Type: blogs
Inflammatory bowel disease (IBD), consisting mainly of ulcerative colitis and Crohn's disease (CD), is characterized by chronic inflammation of the colon (and in the case of CD, other parts of the GI tract). As such, it is often considered the prototypical model of inflammation-associated carcinogenesis. After the well-known genetic syndromes that greatly predispose individuals to colorectal cancer (CRC), such as Lynch Syndrome and familial adenomatous polyposis (FAP), IBD is considered the third most common cause of high-risk CRC. Curiously, colitis-associated CRC (so-called CAC) shares several clinicopathological feature...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: High-Risk Cohorts and Genetic Susceptibility Source Type: research
Chemoprevention offers an attractive option to prevent the occurrence of cancer in high risk cancer syndromes, such as familial adenomatous polyposis (FAP) and Lynch syndrome. However, data, especially from clinical trials, is sparse. This presentation will review the state of art concepts of chemoprevention in regards to these hereditary GI cancer syndromes.Lynch Syndrome: In the randomized CAPP2 trial, 861 participants with Lynch syndrome took either daily aspirin (600 mg) or placebo for up to 4 years; the primary endpoint was the development of CRC (1). After a mean follow-up of 55.7 months, participants taking daily as...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Prevention Source Type: research
Conclusions: The CCFR has shed light on many environmental factors, genetics and tumor characteristics that are related to both incidence and survival. Information gained from studies using this resource provides insight into the biology of this common cancer and importantly may help target messaging on prevention, inform the development of interventions, or tailor recommendations for CRC survivorship care. The greater scientific community has access to this rich resource.Citation Format: Polly A. Newcomb. Understanding more about risk and prognostic factors: Lessons from the Colon Cancer Family Registry. [abstract]. In: P...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Outcomes, Survivorship, and Health Disparities Source Type: research
Abstract Endometrial cancer in the lower uterine segment (LUS) is associated with Lynch syndrome with MLH1 or MSH2 germline mutation. Here, we report a case of carcinoma of the LUS diagnosed with Lynch syndrome based on MSH6 germline mutation in a 46‐year‐old woman with abnormal vaginal bleeding. She had had rectal cancer at age 39 with a family history of colon cancer (father, 75 years), pancreatic cancer (paternal grandmother, 74 years), and colon cancer (maternal grandmother, 85 years). Magnetic resonance imaging showed a tumor in the LUS. Endometrial biopsy revealed endometrioid adenocarcinoma G1. As her cancer his...
Source: Journal of Obstetrics and Gynaecology Research - Category: OBGYN Authors: Tags: Case Report Source Type: research
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Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Short Report Source Type: research
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