| Autor: |
Cercek, Andrea, Dos Santos Fernandes, Gustavo, Roxburgh, Campbell S.D., Ganesh, Karuna, Ng, Shu Y., Sanchez-Vega, Francisco, Yaeger, Rona, Segal, Neil H., Reidy, Diane L., Varghese, Anna, Markowitz, Arnold J., Wu, Chao, Szeglin, Bryan C., Sauve, Charles, Salo-Mullen, Erin, Tran, Christina, Patel, Zalak, Krishnan, Asha, Tkachuk, Kaitlyn, Nash, Garrett M., Guillem, Jose G., Paty, Philip B., Shia, Jinru, Schultz, Nikolaus, Garcia-Aguilar, Julio, Diaz Jr., Luis A., Goodman, Karyn, Saltz, Leonard B., Weiser, Martin R., Smith, J. Joshua, Stadler, Zsofia K. |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| ISSN: |
1078-0432 |
| Popis: |
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%) experienced tumor downstaging; one patient had stable disease, comparable to 48 pMMR rectal cancers. Of 13 patients undergoing surgery, 12 (92%) had early-stage disease. Forty-two (84%) of the 50 patients tested positive for Lynch syndrome (LS) with enrichment of germline MSH2 and MSH6 mutations when compared to 193 LS-associated colon cancer patients (MSH2, 57% vs 36%; MSH6, 17% vs 9%; P < .003). Conclusions: Over one-fourth of dMMR rectal tumors treated with neoadjuvant chemotherapy exhibited disease progression. Conversely, dMMR rectal tumors were sensitive to chemoradiation. MMR status should be performed upfront in all locally advanced rectal tumors with careful monitoring for response on neoadjuvant chemotherapy and genetic testing for LS in dMMR rectal cancer patients. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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