Outcome of Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Mayo Clinic Experience

Jin, Zhaohui; Sanhueza, Cristobal T.; Johnson, Benny; Nagorney, David M.; Larson, David W.; Mara, Kristin C.; Harmsen, William; Smyrk, Thomas C.; Grothey, Axel; Hubbard, Joleen M.

doi:10.1634/theoncologist.2017-0289

Cited by 40 publications

(27 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some studies report a similar median OS of 16–21 months in dMMR/MSI mCRC . Interestingly, a study matched 75 cases of dMMR/MSI mCRC with 75 cases of pMMR/MSS mCRC (age, gender, disease sidedness and metachronous/synchronous) and no survival difference according to MMR status was identified . Finally, recent studies and our results argue against the concept that patients with dMMR/MSI mCRC have a worse OS than patients with pMMR/MSS mCRC.…”

Section: Discussioncontrasting

confidence: 45%

See 1 more Smart Citation

Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study

Tougeron

Sueur

Zaanan

et al. 2020

Intl Journal of Cancer

View full text Add to dashboard Cite

Mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI) colorectal cancers (CRC) represent about 5% of metastatic CRC (mCRC). Prognosis and chemosensitivity of dMMR/MSI mCRC remain unclear. This multicenter study included consecutive patients with dMMR/MSI mCRC from 2007 to 2017. The primary endpoint was the progression-free survival (PFS) in a population receiving first-line chemotherapy. Associations between chemotherapy regimen and survival were evaluated using a Cox regression model and inverse of probability of treatment weighting (IPTW) methodology in order to limit potential biases. Overall, 342 patients with dMMR/MSI mCRC were included. Median PFS and overall survival (OS) on first-line chemotherapy were 6.0 and 26.3 months, respectively. For second-line chemotherapy, median PFS and OS were 4.4 and 21.6 months. Longer PFS (8.1 vs. 5.4 months, p = 0.0405) and OS (35.1 vs. 24.4 months, p = 0.0747) were observed for irinotecan-based chemotherapy compared to oxaliplatin-based chemotherapy. The association was no longer statistically Additional Supporting Information may be found in the online version of this article. ratio; ICI: immune checkpoint inhibitors; IHC: immunohistochemistry; IPTW: inverse of probability of treatment weighting; mCRC: metastatic CRC; MSI: microsatellite instability; OS: overall survival; PFS: progression-free survival; pMMR: proficient mismatch repair; RR: response rate Tumor Markers and Signatures significant using IPTW methodology. In multivariable analysis, anti-VEGF as compared to anti-EGFR was associated with a trend to longer OS (HR = 1.78, 95% CI 1.00-3.19, p = 0.0518), whatever the backbone chemotherapy used. Our study shows that dMMR/MSI mCRC patients experienced short PFS with first-line chemotherapy with or without targeted therapy. OS was not different according to the chemotherapy regimen used, but a trend to better OS was observed with anti-VEGF. Our study provides some historical results concerning chemotherapy in dMMR/MSI mCRC in light of the recent nonrandomized trials with immune checkpoint inhibitors.What's new? Some reports suggest short overall survival (OS) and chemoresistance of mismatch repair-deficient and/or microsatellite instability-high metastatic colorectal cancers (dMMR/MSI mCRC). In a large multicenter series of dMMR/MSI mCRC we observed a relatively long OS but short progression-free survival. Irinotecan-based chemotherapy was not associated with better OS than oxaliplatin-based chemotherapy but anti-VEGF, as compared to anti-EGFR, was associated with a trend to longer OS. These results could help clinicians to choose treatment in patients with dMMR/MSI mCRC.

show abstract

Section: Discussioncontrasting

confidence: 45%

“…In a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies, the BRAF mutation was associated with worse outcomes in pMMR/MSS mCRC, but not in dMMR/MSI mCRC . Finally, the mechanism underlying the MMR deficiency does not seem to be associated with prognosis of stage IV dMMR mCRC …”

Section: Discussionmentioning

confidence: 96%

Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study

Tougeron

Sueur

Zaanan

et al. 2020

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…MSI-High status in adjuvant CRC is associated with improved stage-specific survival; however, the prognostic role of MSI-High status in the metastatic setting remains controversial [ 45 , 46 ]. Several studies have shown that MSI-High metastatic CRC patients have shorter overall survival compared with MSS patients [ 45 , 47 ]. This phenomenon could suggest that MSI-High cancers metastasize earlier, once cancer cells evade the host immune surveillance and are about to metastasize [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Role of Circulating Tumor Cells and Microsatellite Instability Status in Predicting Outcome of Advanced CRC Patients

Messaritakis

Sfakianaki

Vogiatzoglou

et al. 2020

JPM

View full text Add to dashboard Cite

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death due to its high metastatic potential. This study aimed to investigate the detection and heterogeneity of circulating tumor cells (CTCs) and the microsatellite instability (MSI) status in advanced CRC patients prior to any systemic front-line treatment. Peripheral whole blood was obtained from 198 patients. CTCs were detected using double immunofluorescence and a real time-polymerase chain reaction assay; whereas MSI status was evaluated using fragment analysis. Median age of the patients was 66 years, 63.1% were males, 65.2% had a colon/sigmoid tumor location and 90.4% had a good performance status (PS). MSI-High status was detected in 4.9% of the patients; 33.3%, 56.1% and 8.6% patients had at least one detectable CEACAM5+/EpCAM+, CEACAM5+/EpCAM− and CEACAM5−/EpCAM+ CTC, respectively, and 9.1% of the patients had CEACAM5mRNA-positive CTCs. Following multivariate analysis, age, PS and MSI were confirmed as independent prognostic factors for decreased time to progression, whereas age, PS and CTC presence were confirmed as independent prognostic factors for decreased overall survival. In conclusion, our data support the use of CEACAM5 as a dynamic adverse prognostic CTC biomarker in patients with metastatic CRC and MSI-High is considered an unfavorable prognostic factor in metastatic CRC patient tumors.

show abstract

“…Previous studies have demonstrated that MMR status of CRC is significantly correlated with their clinicopathological features [ 17 , 18 ] and serum tumour biomarkers (STMs) [ 19 , 20 ]. Though several prediction models based on pathological features have been developed, the complex pathological characteristics included in previous models required detailed pathological diagnosis [ [21] , [22] , [23] ], which not only caused a huge burden on the pathologists, but also lacked of instructive value for clinicians.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of MMR prediction model based on simplified clinicopathological features and serum tumour markers

et al. 2020

View full text Add to dashboard Cite

Background Although simplified clinicopathological features and serum tumour markers (STMs) were reported to be associated with the status of mismatch repair (MMR) in colorectal cancer (CRC) patients, their predictive value alone or in combination for MMR status remains unknown. Methods A retrospective analysis of 3274 participants with MMR testing and STMs measurements from two institutions was conducted. The prediction model was developed in the primary cohort that consisted of 1964 participants. Best subset regression was applied to select the most useful predictors from the primary dataset. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness. External validation was performed in an independent validation cohort of 1310 consecutive CRC patients. Findings Among the ten simplified clinicopathological features, seven variables were selected as the best subset of risk factors to develop pathology-based model, including age, tumour diameters, histology, tumour location, perineural invasion, the number of sampled lymph nodes (LNs) and positive LNs. The model showed good calibration and discrimination, with an AUC of 0.756 (95% CI, 0.722 to 0.789) in the primary cohort and 0.754 (95% CI, 0.715 to 0.793) in the validation cohort. After the addition of CEA and CA 72-4, the performance of pathology-based model was significantly improved in in both the primary cohort (AUC: 0.805 (0.774-0.835) vs. 0.756 (0.722-0.789), P < 0.001) and validation cohort (AUC: 0.796 (0.758-0.835) vs. 0.754 (0.715-0.793), P < 0.001). The results of decision curve analysis revealed that using our models to predict the status of MMR would add more benefit than either the detect-all-patients scheme or the detect-none scheme. Interpretation The models based on simplified clinicopathological features alone or in combination with STMs can be conveniently used to facilitate the postoperative individualized prediction of MMR status in CRC patients.

show abstract

Outcome of Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Mayo Clinic Experience

Abstract: This study clearly demonstrated the survival benefits that aggressive metastasectomy provides in selected microsatellite instability-high metastatic colorectal cancer patients. This could be meaningful practice-changing information that has been long awaited.

Cited by 40 publications

References 32 publications

Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study

Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study

Evaluation of the Role of Circulating Tumor Cells and Microsatellite Instability Status in Predicting Outcome of Advanced CRC Patients

Development and validation of MMR prediction model based on simplified clinicopathological features and serum tumour markers

Contact Info

Product

Resources

About