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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

5127 - Mismatch repair deficient rectal cancer is resistant to induction combination chemotherapy

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Andrea Cercek

Citation

Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281

Authors

A. Cercek1, G. Dos Santos Fernandes2, C. Roxburgh3, S. Ng4, R. Yaeger5, N. Segal5, K. Ganesh6, D. Reidy7, J..J. Smith8, G. Nash8, J. Guillem8, P. Paty8, J. Shia9, J. Garcia-Aguilar8, L. Diaz10, C. Crane11, K. Goodman12, L. Saltz13, M. Weiser8, Z. Stadler2

Author affiliations

  • 1 Medicine, Memorial Sloan Kettering Cancer Center, 10022 - New York/US
  • 2 Gi Medical Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 3 Surgical oncology, MSKCC, 100 - New YOrk/US
  • 4 Radiation oncology, MSKCC, 10065 - New York/US
  • 5 Medicine, MSKCC, New York/US
  • 6 Medicine, MSK, 10075 - New York/US
  • 7 Medicine, MSKCC, NEw YOrk/US
  • 8 Surgery, MSKCC, 10065 - New York/US
  • 9 Pathology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 10 Medicine, Memorial Sloan Kettering Cancer Center, 10065 - New York City/US
  • 11 Radiation oncology, Memorial Sloan Kettering Cancer Center, 10022 - New York/US
  • 12 Radiation oncology, MSKCC, 10065 - New YOrk/US
  • 13 Gastrointestinal Oncology Service, Department Of Medicine, Memorial Sloan Kettering Cancer Center, NY 10065 - New York/US
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Resources

Abstract 5127

Background

Although most rectal cancers are responsive to combination induction chemotherapy, the sensitivity of mismatch repair deficient (MMR-D) rectal cancers to chemotherapy remains uncertain.

Methods

MMR-D rectal tumor cases were retrospectively reviewed with tabulation of baseline characteristics, treatment modalities and clinical outcomes. Prevalence of germline mutations in the MMR genes, diagnostic of Lynch syndrome (LS), was compared to LS-associated colon cancer patients. We also assessed somatic mutational status for a subset of these patients.

Results

Twenty of the 49 patients received induction chemotherapy with 5FU and oxaliplatin, 15 received standard neoadjuvant chemoradiation, and 14 proceeded directly to surgery. Of the 15 patients treated with induction chemoradiation, 93% (n = 14) experienced radiographic response and tumor downstaging; and none of these patients showed evidence of disease progression. In contrast, of the 18 patients treated with induction chemotherapy alone, only 61% (n = 11) experienced tumor response and 28% (n = 5) of patients demonstrated progressive disease while on therapy. The majority of these cases, 82% (41/50) harbored germline mutations in the MMR genes and the observed prevalence of germline MSH2 and MSH6 mutations was significantly higher in the rectal (n = 41) versus colon (n = 244) cancer patients (rectal vs colon: MSH2: 57% vs 37%; MSH6: 20% vs 11%; p-value <0.0005).

Conclusions

Patients with MMR-D rectal tumors appear to have a high chance of disease progression on induction chemotherapy. As opposed to LS-associated colon cancers, LS-associated rectal cancers are more likely to harbor MSH2 or MSH6 germline mutations. Upfront testing for MMR status and initial treatment with chemoradiation in MMR-D rectal tumors should be undertaken until better therapies are available.

Clinical trial identification

Legal entity responsible for the study

Andrea Cercek.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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