The Future of Interventions for Stage IV Colorectal Cancers

Samantha Lloy; Mayin Lin; Jan Franko; Shankar Raman

doi:10.1055/s-0043-1761624

Clinics in Colon and Rectal Surgery, Table of Contents

Clin Colon Rectal Surg 2024; 37(02): 114-121
DOI: 10.1055/s-0043-1761624

Review Article

The Future of Interventions for Stage IV Colorectal Cancers

Samantha Lloy

¹General Surgery Residency Program, MercyOne Des Moines Medical Center, Des Moines, Iowa

,

Mayin Lin

¹General Surgery Residency Program, MercyOne Des Moines Medical Center, Des Moines, Iowa

,

Jan Franko

¹General Surgery Residency Program, MercyOne Des Moines Medical Center, Des Moines, Iowa

,

Shankar Raman

¹General Surgery Residency Program, MercyOne Des Moines Medical Center, Des Moines, Iowa

› Author Affiliations

Abstract

Future options for the management of stage IV colorectal cancer are primarily focused on personalized and directed therapies. Interventions include precision cancer medicine, utilizing nanocarrier platforms for directed chemotherapy, palliative pressurized intraperitoneal aerosol chemotherapy (PIPAC), adjunctive oncolytic virotherapy, and radioembolization techniques. Comprehensive genetic profiling provides specific tumor-directed therapy based on individual genetics. Biomimetic magnetic nanoparticles as chemotherapy delivery systems may reduce systemic side effects of traditional chemotherapy by targeting tumor cells and sparing healthy cells. PIPAC is a newly emerging option for patients with peritoneal metastasis from colorectal cancer and is now being used internationally, showing promising results as a palliative therapy for colorectal cancer. Oncolytic virotherapy is another emerging potential treatment option, especially when combined with standard chemotherapy and/or radiation, as well as immunotherapy. And finally, radioembolization with yttrium-90 (⁹⁰Y) microspheres has shown some success in treating patients with unresectable liver metastasis from colorectal cancer via selective arterial injection.

Keywords

colorectal cancer - precision cancer medicine - targeted genomic cancer therapy - oncolytic virotherapy - pressurized intraperitoneal aerosol chemotherapy (PIPAC) - yttrium-90 (⁹⁰Y) microsphere radioembolization

Full Text

References

References
1 Cancer of the Colon and Rectum - Cancer Stat Facts. SEER. Accessed May 28, 2022 at: https://seer.cancer.gov/statfacts/html/colorect.html
2 Rodriguez-Bigas MA, Lin EH, Crane CH. Stage IV Colorectal Cancer. Holland-Frei Cancer Medicine. 6th ed. Published online 2003. Accessed May 28, 2022 at: https://www.ncbi.nlm.nih.gov/books/NBK13267/
3 Hari DM, Leung AM, Lee JH. et al. AJCC-7TH Edition Staging Criteria for Colon Cancer: do the complex modifications improve prognostic assessment?. J Am Coll Surg 2013; 217 (02) 181-190
4 Colorectal Cancer - Statistics. Cancer.Net. Published June 25, 2012. Accessed August 2, 2022 at; https://www.cancer.net/cancer-types/colorectal-cancer/statistics
5 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 FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 2013; 14 (12) 1208-1215
6 Dueland S, Syversveen T, Solheim JM. et al. Survival following liver transplantation for patients with nonresectable liver-only colorectal metastases. Ann Surg 2020; 271 (02) 212-218
7 Ginsburg GS, Phillips KA. Precision medicine: from science to value. Health Aff (Millwood) 2018; 37 (05) 694-701
8 All of Us Research Program Overview. All of Us Research Program | NIH. Published June 22, 2020. Accessed June 26, 2022 at: https://allofus.nih.gov/about/program-overview
9 Ciombor K, Jones J, Strickler J, Bekaii-Saab T, Wu C. The current molecular treatment landscape of advanced colorectal cancer and need for the COLOMATE platform. Oncology (Williston Park) 2021; 35 (09) 553-559
10 Christofyllakis K, Bittenbring JT, Thurner L. et al. Cost-effectiveness of precision cancer medicine-current challenges in the use of next generation sequencing for comprehensive tumour genomic profiling and the role of clinical utility frameworks (Review). Mol Clin Oncol 2022; 16 (01) 21
11 Kondo T, Matsubara J, Quy PN. et al. Comprehensive genomic profiling for patients with chemotherapy-naïve advanced cancer. Cancer Sci 2021; 112 (01) 296-304
12 Le Tourneau C, Delord JP, Gonçalves A. et al; SHIVA investigators. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 2015; 16 (13) 1324-1334
13 Sicklick JK, Kato S, Okamura R. et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat Med 2019; 25 (05) 744-750
14 Diehl F, Schmidt K, Choti MA. et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008; 14 (09) 985-990
15 Loupakis F, Sharma S, Derouazi M. et al. Detection of molecular residual disease using personalized circulating tumor DNA assay in patients with colorectal cancer undergoing resection of metastases. JCO Precis Oncol 2021; 5: PO.21.00101
16 André T, de Gramont A, Vernerey D. et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol 2015; 33 (35) 4176-4187
17 Cercek A, Lumish M, Sinopoli J. et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med 2022; 386 (25) 2363-2376
18 Jabalera Y, Garcia-Pinel B, Ortiz R. et al. Oxaliplatin-biomimetic magnetic nanoparticle assemblies for colon cancer-targeted chemotherapy: an in vitro study. Pharmaceutics 2019; 11 (08) 395
19 Franko J, Yin J, Adams RA. et al; ARCAD collaborators. Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: pooled analysis from the ARCAD database. Eur J Cancer 2022; 174: 142-152
20 Franko J, Ibrahim Z, Gusani NJ, Holtzman MP, Bartlett DL, Zeh III HJ. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer 2010; 116 (16) 3756-3762
21 Franko J, Shi Q, Meyers JP. et al; Analysis and Research in Cancers of the Digestive System (ARCAD) Group. Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol 2016; 17 (12) 1709-1719
22 Verwaal VJ, van Ruth S, de Bree E. et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 2003; 21 (20) 3737-3743
23 Quénet F, Elias D, Roca L. et al; UNICANCER-GI Group and BIG Renape Group. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2021; 22 (02) 256-266
24 Solass W, Kerb R, Mürdter T. et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol 2014; 21 (02) 553-559
25 Alyami M, Sgarbura O, Khomyakov V. et al. Standardizing training for pressurized intraperitoneal aerosol chemotherapy. Eur J Surg Oncol 2020; 46 (12) 2270-2275
26 Nowacki M, Alyami M, Villeneuve L. et al. Multicenter comprehensive methodological and technical analysis of 832 pressurized intraperitoneal aerosol chemotherapy (PIPAC) interventions performed in 349 patients for peritoneal carcinomatosis treatment: an international survey study. Eur J Surg Oncol 2018; 44 (07) 991-996
27 Reymond MA, Solass W. PIPAC: Pressurized IntraPeritoneal Aerosol Chemotherapy – Cancer under Pressure. Walter de Gruyter GmbH & Co KG; Copyright 2014 Walter de Gruyter GmbH, Berlin/Boston: 2014
28 Tempfer CB. Pressurized intraperitoneal aerosol chemotherapy as an innovative approach to treat peritoneal carcinomatosis. Med Hypotheses 2015; 85 (04) 480-484
29 Gockel I, Jansen-Winkeln B, Haase L. et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal metastasized colorectal, appendiceal and small bowel cancer. Tumori 2020; 106 (01) 70-78
30 Tabchouri N, Buggisch J, Demtröder CR. et al. Pressurized intraperitoneal aerosol chemotherapy for colorectal peritoneal metastases. Ann Surg Oncol 2021; 28 (09) 5275-5286
31 Alyami M, Hübner M, Grass F. et al. Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications. Lancet Oncol 2019; 20 (07) e368-e377
32 Robella M, Vaira M, De Simone M. Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis. World J Surg Oncol 2016; 14: 128
33 Teixeira Farinha H, Grass F, Labgaa I, Pache B, Demartines N, Hübner M. Inflammatory response and toxicity after pressurized intraperitoneal aerosol chemotherapy. J Cancer 2018; 9 (01) 13-20
34 Jin KT, Du WL, Liu YY, Lan HR, Si JX, Mou XZ. Oncolytic virotherapy in solid tumors: the challenges and achievements. Cancers (Basel) 2021; 13 (04) 588
35 Kana SI, Essani K. Immuno-oncolytic viruses: emerging options in the treatment of colorectal cancer. Mol Diagn Ther 2021; 25 (03) 301-313
36 Wang B, Ogata H, Takishima Y. et al. A novel combination therapy for human oxaliplatin-resistant colorectal cancer using oxaliplatin and coxsackievirus A11. Anticancer Res 2018; 38 (11) 6121-6126
37 Shen W, Tu JK, Wang XH, Fu ZX. Oncolytic adenovirus mediated Survivin RNA interference and 5-fluorouracil synergistically suppress the lymphatic metastasis of colorectal cancer. Oncol Rep 2010; 24 (05) 1285-1290
38 Wu Z, Ichinose T, Naoe Y. et al. Combination of cetuximab and oncolytic virus canerpaturev synergistically inhibits human colorectal cancer growth. Mol Ther Oncolytics 2019; 13: 107-115
39 Ottolino-Perry K, Acuna SA, Angarita FA. et al. Oncolytic vaccinia virus synergizes with irinotecan in colorectal cancer. Mol Oncol 2015; 9 (08) 1539-1552
40 Esaki S, Goshima F, Kimura H, Murakami S, Nishiyama Y. Enhanced antitumoral activity of oncolytic herpes simplex virus with gemcitabine using colorectal tumor models. Int J Cancer 2013; 132 (07) 1592-1601
41 Skelding KA, Barry RD, Shafren DR. Enhanced oncolysis mediated by Coxsackievirus A21 in combination with doxorubicin hydrochloride. Invest New Drugs 2012; 30 (02) 568-581
42 Moehler M, Sieben M, Roth S. et al. Activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus H-1. BMC Cancer 2011; 11 (01) 464
43 Pokrovska TD, Jacobus EJ, Puliyadi R. et al. External Beam Radiation Therapy and Enadenotucirev: Inhibition of the DDR and Mechanisms of Radiation-Mediated Virus Increase. Cancers 2020; 12 (04) 798
44 Gao H, Zhang X, Ding Y, Qiu R, Hong Y, Chen W. Synergistic suppression effect on tumor growth of colorectal cancer by combining radiotherapy with a TRAIL-armed oncolytic adenovirus. Technol Cancer Res Treat 2019; 18: 1533033819853290
45 Touchefeu Y, Khan AA, Borst G. et al. Optimising measles virus-guided radiovirotherapy with external beam radiotherapy and specific checkpoint kinase 1 inhibition. Radiother Oncol 2013; 108 (01) 24-31
46 Zeh HJ, Downs-Canner S, McCart JA. et al. First-in-man study of Western Reserve strain oncolytic vaccinia virus: safety, systemic spread, and antitumor activity. Mol Ther 2015; 23 (01) 202-214
47 Jonker DJ, Tang PA, Kennecke H. et al. A randomized phase II study of FOLFOX6/bevacizumab with or without pelareorep in patients with metastatic colorectal cancer: IND.210, a Canadian Cancer Trials Group Trial. Clin Colorectal Cancer 2018; 17 (03) 231-239.e7
48 Park SH, Breitbach CJ, Lee J. et al. Phase 1b trial of biweekly intravenous Pexa-Vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus in colorectal cancer. Mol Ther 2015; 23 (09) 1532-1540
49 Geevarghese SK, Geller DA, de Haan HA. et al. Phase I/II study of oncolytic herpes simplex virus NV1020 in patients with extensively pretreated refractory colorectal cancer metastatic to the liver. Hum Gene Ther 2010; 21 (09) 1119-1128
50 Bell JC, Lichty B, Stojdl D. Getting oncolytic virus therapies off the ground. Cancer Cell 2003; 4 (01) 7-11
51 Li L, Liu S, Han D, Tang B, Ma J. Delivery and biosafety of oncolytic virotherapy. Front Oncol 2020; 10: 475
52 Chia SL, Lei J, Ferguson DJP, Dyer A, Fisher KD, Seymour LW. Group B adenovirus enadenotucirev infects polarised colorectal cancer cells efficiently from the basolateral surface expected to be encountered during intravenous delivery to treat disseminated cancer. Virology 2017; 505: 162-171
53 Chen H, Sampath P, Hou W, Thorne SH. Regulating cytokine function enhances safety and activity of genetic cancer therapies. Mol Ther 2013; 21 (01) 167-174
54 Coldwell D, Sangro B, Wasan H, Salem R, Kennedy A. General selection criteria of patients for radioembolization of liver tumors: an international working group report. Am J Clin Oncol 2011; 34 (03) 337-341
55 Lee EJ, Chung HW, Jo JH, So Y. Radioembolization for the treatment of primary and metastatic liver cancers. Nucl Med Mol Imaging 2019; 53 (06) 367-373
56 Voutsinas N, Lekperic S, Barazani S, Titano JJ, Heiba SI, Kim E. Treatment of primary liver tumors and liver metastases, part 1: nuclear medicine techniques. J Nucl Med 2018; 59 (11) 1649-1654
57 Kim YC, Kim YH, Uhm SH. et al. Radiation safety issues in y-90 microsphere selective hepatic radioembolization therapy: possible radiation exposure from the patients. Nucl Med Mol Imaging 2010; 44 (04) 252-260
58 Hendlisz A, Van den Eynde M, Peeters M. et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol 2010; 28 (23) 3687-3694
59 Seidensticker R, Denecke T, Kraus P. et al. Matched-pair comparison of radioembolization plus best supportive care versus best supportive care alone for chemotherapy refractory liver-dominant colorectal metastases. Cardiovasc Intervent Radiol 2012; 35 (05) 1066-1073
60 Dutton SJ, Kenealy N, Love SB, Wasan HS, Sharma RA. FOXFIRE Protocol Development Group and the NCRI Colorectal Clinical Study Group. FOXFIRE protocol: an open-label, randomised, phase III trial of 5-fluorouracil, oxaliplatin and folinic acid (OxMdG) with or without interventional Selective Internal Radiation Therapy (SIRT) as first-line treatment for patients with unresectable liver-only or liver-dominant metastatic colorectal cancer. BMC Cancer 2014; 14: 497
61 Gibbs P, Gebski V, Van Buskirk M, Thurston K, Cade DN, Van Hazel GA. SIRFLOX Study Group. Selective Internal Radiation Therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: the SIRFLOX study. BMC Cancer 2014; 14: 897
62 Virdee PS, Moschandreas J, Gebski V. et al. Protocol for combined analysis of FOXFIRE, SIRFLOX, and FOXFIRE-Global randomized phase III trials of chemotherapy +/- selective internal radiation therapy as first-line treatment for patients with metastatic colorectal cancer. JMIR Res Protoc 2017; 6 (03) e43
63 Wasan HS, Gibbs P, Sharma NK. et al; FOXFIRE trial investigators, SIRFLOX trial investigators, FOXFIRE-Global trial investigators. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol 2017; 18 (09) 1159-1171