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Impact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative period

https://doi.org/10.33878/2073-7556-2024-23-4-48-56

Abstract

AIM: assess the impact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative period.

PATIENTS AND METHODS: a pilot prospective study included 30 patients with colorectal cancer and synchronous liver metastases (mCRC). The combined treatment included 3 cycles of neoadjuvant FOLFOXIRI chemotherapy with the addition of targeted agents: cetuximab (24 patients with wtKRAS) and bevacizumab (6 patients with mtKRAS) followed by radical surgery.

RESULTS: the clinical and radiological response of colorectal cancer liver metastases to neoadjuvant chemotherapy (NACT) was complete in 4 (13.3%) patients and partial in 26 (86.7%) patients. Partial response to NACT in the primary tumor occurred in all patients. Adverse events of NACT were detected in 12 (40%) patients, 1 (3.3%) of them produced grade III toxicity. All patients underwent radical surgery (R0) 3–4 weeks after NACT, 28 (93.3%) of them underwent simultaneous colorectal and liver resection. Postoperative complications occurred in 21 (70%) patients, including grade I and grade IIIa complications (according to Сlavien-Dindo classification) — 22 (73.3%) and 2 (6.7%), respectively. Histology revealed pathologic complete response (pCR) of liver metastases in 1 (3.6%) case and pathological grade 3 regression of the primary tumor (TRG3, Mandard A.M.) in 23 (76.7%) patients. Two (6.7%) patients with complete clinical and radiological response of liver metastases, who did not undergo liver resection, had no evidence of disease progression 12 months after the treatment.

CONCLUSION: in mCRC with synchronous liver metastases, NACT according to the FOLFOXIRI regimen in combination with targeted agents with a moderate toxicity profile provide significant carcinocidal effect without having a negative impact in the perioperative period. The study is ongoing to analyze 2-year disease-free and overall survival of patients.

About the Authors

N. V. Yunusova
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences ; Siberian State Medical University of the Ministry of Health of Russia
Russian Federation

Natalia V. Yunusova

Kooperativny per., 5, Tomsk, 634009

Moskovsky trakt, 2, Tomsk, 634050



A. Yu. Dobrodeev
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation

Aleksey Yu. Dobrodeev

Kooperativny per., 5, Tomsk, 634009



D. N. Kostromitsky
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation

Dmitry N. Kostromitsky

Kooperativny per., 5, Tomsk, 634009



S. G. Afanasyev
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation

Sergey G. Afanasyev

Kooperativny per., 5, Tomsk, 634009



A. S. Tarasova
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation

Anna S. Tarasova

Kooperativny per., 5, Tomsk, 634009



R. V. Ermolenko
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation

Roman V. Ermolenko

Kooperativny per., 5, Tomsk, 634009



N. N. Babyshkina
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences ; Siberian State Medical University of the Ministry of Health of Russia
Russian Federation

Natalia N. Babyshkina

Kooperativny per., 5, Tomsk, 634009

Moskovsky trakt, 2, Tomsk, 634050



T. A. Dronova
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation

Tatyana A. Dronova

Kooperativny per., 5, Tomsk, 634009



A. A. Ponomareva
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation

Anastasia A. Ponomareva

Kooperativny per., 5, Tomsk, 634009



I. V. Larionova
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation

Irina V. Larionova

Kooperativny per., 5, Tomsk, 634009



References

1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209–249. doi: 10.3322/caac.21660

2. Oki E, Ando K, Nakanishi R, et al. Recent advances in treatment for colorectal liver metastasis. Ann Gastroenterol Surg. 2018 Apr 17;2(3):167–175. doi: 10.1002/ags3.12071

3. Morine Y, Shimada M, Utsunomiya T. Evaluation and management of hepatic injury induced by oxaliplatin-based chemotherapy in patients with hepatic resection for colorectal liver metastasis. Hepatol Res. 2014 Jan;44(1):59–69. doi: 10.1111/hepr.12107

4. Khan K, Wale A, Brown G, et al. Colorectal cancer with liver metastases: neoadjuvant chemotherapy, surgical resection first or palliation alone? World J Gastroenterol. 2014 Sep 21;20(35):12391–406. doi: 10.3748/wjg.v20.i35.12391

5. Ihnát P, Ostruszka P, Vávra P, et al. Treatment strategies for patients with colorectal carcinoma and synchronous liver metastases. Rozhl Chir. 2018 Summer;97(10):451–454.

6. Masi G, Loupakis F, Salvatore L, et al. Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol. 2010 Sep;11(9):845–52. doi: 10.1016/S1470-2045(10)70175-3

7. Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015 Oct;16(13):1306–15. doi: 10.1016/S1470-2045(15)00122-9

8. Cremolini C, Antoniotti C, Rossini D, et al. GONO Foundation Investigators. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2020 Apr;21(4):497–507. doi: 10.1016/S1470-2045(19)30862-9

9. Bendell JC, Zakari A, Peyton JD, et al. A Phase II Study of FOLFOXIRI Plus Panitumumab Followed by Evaluation for Resection in Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only. Oncologist. 2016 Mar;21(3):279–80. doi: 10.1634/theoncologist.2015-0439

10. Modest DP, Martens UM, Riera-Knorrenschild J, et al. FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109). J Clin Oncol. 2019 Dec 10;37(35):3401– 3411. doi: 10.1200/JCO.19.01340

11. Hu H, Wang K, Huang M, et al. Modified FOLFOXIRI With or Without Cetuximab as Conversion Therapy in Patients with RAS/BRAF Wild-Type Unresectable Liver Metastases Colorectal Cancer: The FOCULM Multicenter Phase II Trial. Oncologist. 2021 Jan;26(1):e90–e98. doi: 10.1634/theoncologist.2020-0563

12. Vigano L, Sollini M, Ieva F, et al. Chemotherapy-Associated Liver Injuries: Unmet Needs and New Insights for Surgical Oncologists. Ann Surg Oncol. 2021 Aug;28(8):4074–4079. doi: 10.1245/s10434-021-10069-z

13. Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670–6. doi: 10.1200/JCO.2006.09.0928

14. Chow FC, Chok KS. Colorectal liver metastases: An update on multidisciplinary approach. World J Hepatol. 2019 Feb 27;11(2):150– 172. doi: 10.4254/wjh.v11.i2.150

15. Chandra P, Sacks GD. Contemporary Surgical Management of Colorectal Liver Metastases. Cancers (Basel). 2024 Feb 26;16(5):941. doi: 10.3390/cancers16050941

16. Nordlinger B, Sorbye H, Glimelius B, et al. EORTC Gastro- Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro- Intestinal Trials Group (AGITG); Fédération Francophone de Cancérologie Digestive (FFCD). Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008 Mar 22;371(9617):1007–16. doi: 10.1016/S0140-6736(08)60455-9

17. Dan RG, Creţu OM, Mazilu O, et al. Postoperative morbidity and mortality after liver resection. Retrospective study on 133 patients. Chirurgia (Bucur). 2012 Nov-Dec;107(6):737–41.

18. Hoekstra LT, van Gulik TM, Gouma DJ, Busch OR. Posthepatectomy bile leakage: how to manage. Dig Surg. 2012;29(1):48–53. doi: 10.1159/000335734

19. Filicori F, Keutgen XM, Zanello M, et al. Prognostic criteria for postoperative mortality in 170 patients undergoing major right hepatectomy. Hepatobiliary Pancreat Dis Int. 2012 Oct;11(5):507–12. doi: 10.1016/s1499-3872(12)60215-x

20. Ribeiro HS, Costa WL Jr, Diniz AL, et al. Extended preoperative chemotherapy, extent of liver resection and blood transfusion are predictive factors of liver failure following resection of colorectal liver metastasis. Eur J Surg Oncol. 2013 Apr;39(4):380–5. doi: 10.1016/j.ejso.2012.12.020

21. Cescon M, Vetrone G, Grazi GL, et al. Trends in perioperative outcome after hepatic resection: analysis of 1500 consecutive unselected cases over 20 years. Ann Surg. 2009 Jun;249(6):995– 1002. doi: 10.1097/SLA.0b013e3181a63c74

22. Blazer DG, Kishi Y, Maru DM, et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol. 2008;26(33):5344–51. doi: 10.1200/JCO.2008.17.5299

23. Adam R, Wicherts DA, de Haas RJ, et al. Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? J Clin Oncol. 2008;26(10):1635–41. doi: 10.1200/JCO.2007.13.7471

24. Kishi Y, Zorzi D, Contreras CM, et al. Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases. Ann Surg Oncol. 2010 Nov;17(11):2870–6. doi: 10.1245/s10434-010-1166-1

25. Fornaro L, Lonardi S, Masi G, et al. FOLFOXIRI in combination with panitumumab as first-line treatment in quadruple wild-type (KRAS, NRAS, HRAS, BRAF) metastatic colorectal cancer patients: a phase II trial by the Gruppo Oncologico Nord Ovest (GONO). Ann Oncol. 2013 Aug;24(8):2062–7. doi: 10.1093/annonc/mdt165

26. van Vledder MG, de Jong MC, Pawlik TM, et al. Disappearing colorectal liver metastases after chemotherapy: should we be concerned? J Gastrointest Surg. 2010 Nov;14(11):1691–700. doi: 10.1007/s11605-010-1348-y

27. Kim SS, Song KD, Kim YK, et al. Disappearing or residual tiny (≤ 5 mm) colorectal liver metastases after chemotherapy on gadoxetic acid-enhanced liver MRI and diffusion-weighted imaging: Is local treatment required? Eur Radiol. 2017 Jul;27(7):3088–3096. doi: 10.1007/s00330-016-4644-4

28. Martin J, Petrillo A, Smyth EC, et al. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol. 2020;11(10):761–808. doi: 10.5306/wjco.v11.i10.761

29. Zendel A, Lahat E, Dreznik Y, et al. “Vanishing liver metastases” — A real challenge for liver surgeons. Hepatobiliary Surg Nutr. 2014;3(5):295–302. doi: 10.3978/j.issn.2304-3881.2014.09.13


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Yunusova N.V., Dobrodeev A.Yu., Kostromitsky D.N., Afanasyev S.G., Tarasova A.S., Ermolenko R.V., Babyshkina N.N., Dronova T.A., Ponomareva A.A., Larionova I.V. Impact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative period. Koloproktologia. 2024;23(4):48-56. https://doi.org/10.33878/2073-7556-2024-23-4-48-56

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