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Comparative Study
. 2022 Mar;126(5):726-735.
doi: 10.1038/s41416-021-01620-6. Epub 2021 Dec 9.

Impact of KRAS, BRAF and microsatellite instability status after cytoreductive surgery and HIPEC in a national cohort of colorectal peritoneal metastasis patients

S G Larsen  1 , M A Goscinski  2 , S Dueland  3 , S E Steigen  4 , E Hofsli  5   6 , A Torgunrud  6 , M Lund-Iversen  7 , V J Dagenborg  2 , K Flatmark  2   8 , H Sorbye  9
Affiliations
Comparative Study

Impact of KRAS, BRAF and microsatellite instability status after cytoreductive surgery and HIPEC in a national cohort of colorectal peritoneal metastasis patients

S G Larsen et al. Br J Cancer. 2022 Mar.

Abstract

Background: Patients with metastatic colorectal cancer (mCRC) carrying BRAF (mutBRAF) or KRAS mutation (mutKRAS) have an inferior prognosis after liver or lung surgery, whereas the prognostic role in the context of peritoneal metastasis (PM) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been less investigated.

Methods: In total, 257 patients with non-appendiceal PM-CRC were included from the Norwegian National Unit for CRS-HIPEC.

Results: In total, 180 patients received CRS-HIPEC with Mitomycin C, 77 patients received palliative surgery only. In the CRS-HIPEC group, mutBRAF was found in 24.7%, mutKRAS 33.9% and double wild-type 41.4% without differences in survival. MSI was found in 29.3% of mutBRAF cases. Patients with mutBRAF/MSI had superior 5-year survival compared to mutBRAF with MSS (58.3% vs 25.2%, P = 0.022), and better 3-year disease-free survival (DFS) compared to mutKRAS (48.6% vs 17.2%, P = 0.049). Peritoneal Cancer Index and the number of lymph node metastasis were prognostic for OS, and the same two, location and gender prognostic for DFS in multivariate analysis.

Conclusions: PM-CRC with CRS-HIPEC patients has a surprisingly high proportion of mutBRAF (24.7%). Survival was similar comparing mutBRAF, mutKRAS and double wild-type cases, whereas a small subgroup with mutBRAF and MSI had better survival. Patients with mutBRAF tumours and limited PM should be considered for CRS-HIPEC.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Kaplan–Meier plot showing time from surgery on the x axis and estimated overall survival on the y axis.
a Overall survival of CRS-HIPEC versus palliative surgery. The blue line represents the CRS-HIPEC group and the green dashed line represents the patients in the palliative group. Log-rank test shows a significant difference between the two groups with P < 0.001. b Overall survival comparing mutation status after palliative resection. Kaplan–Meier plot with time from surgery on the x axis and estimated overall survival on the y axis. The blue line represents the KRAS-mutated tumours (mutKRAS) tumours and the green dotted line represents the BRAF-mutated (mutBRAF) tumours. The gold dashed line represents the patients with KRAS and BRAF wild-type (double wt) tumours. Log-rank test shows a significant difference between the three groups with P < 0.001.
Fig. 2
Fig. 2. Kaplan–Meier plot with time from surgery on the x axis and estimated overall survival or disease free survival on the y axis.
a Overall survival after CRS-HIPEC based on mutation status. The blue line represents the KRAS-mutated tumours (mutKRAS) tumours and the green dotted line represents the BRAF-mutated (mutBRAF) tumours. The gold dashed line represents the patients with KRAS and BRAF wild-type (double wt) tumours. Log-rank test shows significant difference between mutBRAF vs mutKRAS, P = 0.046 and between mutBRAF vs double wt, P < 0.001. b Disease-free survival after CRS-HIPEC based on mutation status. Kaplan–Meier plot with time from surgery on the x axis and estimated overall survival on the y axis. The blue line represents the KRAS-mutated tumours (mutKRAS) and the green dotted line represents the BRAF-mutated (mutBRAF) tumours. The gold dashed line represents the patients with KRAS and BRAF wild-type (double wt) tumours. Log-rank test is ns. c Overall survival comparing mutation and microsatellite instability (MSI) status. Kaplan–Meier plot with time from surgery on the x axis and estimated overall survival on the y axis. The blue line represents the KRAS-mutated tumours (mutKRAS) tumours and the green dotted line represents the BRAF-mutated microsatellite stable (MSS) (mutBRAF/MSS) tumours. The gold dashed line represents the patients with KRAS and BRAF wild-type (double wt) tumours and the black dashed/dotted line represents the BRAF-mutated microsatellite instable (MSI (mutBRAF/MSI) tumours. Log-rank test shows a significant difference between mutBRAF groups with MSI or MSS with P = 0.022. d Disease-free survival after CRS-HIPEC based on mutation and microsatellite instability (MSI) status. Kaplan–Meier plot with time from surgery on the x axis and estimated overall survival on the y axis. The blue line represents the KRAS-mutated tumours (mutKRAS) tumours and the grey dotted line represents the BRAF-mutated microsatellite stable (MSS) (mutBRAF/MSS) tumours. The gold dashed line represents the patients with KRAS and BRAF wild-type (double wt) tumours and the black dashed/dotted line represents the BRAF-mutated microsatellite instable (MSI) (mutBRAF/MSI) tumours. Log-rank test shows a significant difference between mutBRAF/MSI group and mutKRAS group with P = 0.049.
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References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2018;68:394–424. - PubMed
    1. Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244:254–9. - PMC - PubMed
    1. Thomassen I, van Gestel YR, Lemmens VE, de Hingh IH. Incidence, prognosis, and treatment options for patients with synchronous peritoneal carcinomatosis and liver metastases from colorectal origin. Dis Colon Rectum. 2013;56:1373–80. - PubMed
    1. McCormack PM, Burt ME, Bains MS, Martini N, Rusch VW, Ginsberg RJ. Lung resection for colorectal metastases. 10-year results. Arch Surg. 1992;127:1403–6. - PubMed
    1. van Gestel YR, de Hingh IH, van Herk-Sukel MP, van Erning FN, Beerepoot LV, Wijsman JH, et al. Patterns of metachronous metastases after curative treatment of colorectal cancer. Cancer Epidemiol. 2014;38:448–54. - PubMed

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