Tumor Vascularity Does Not Predict Response to Yttrium-90 Radioembolization for Hepatic Metastases from Colorectal Cancer

Abstract

The purpose of this study was to determine whether the degree of tumor vascularity based on imaging has an impact on tumor response and survival in patients with metastatic colorectal cancer (mCRC) to the liver undergoing yttrium-90 radioembolization. A retrospective study of 75 mCRC patients from a single-institution undergoing radioembolization was performed over a 7-year period. Tumors were categorized as hypo- or hypervascular based on digital subtraction angiography (DSA) and C-arm CT during mapping angiography. Tumor response and survival were compared between each group, after undergoing radioembolization. Hypervascular tumors were present in 37 of 75 (49%) patients according to DSA. Of 37 patients who underwent C-arm CT during the procedure, 22 (59%) had tumors classified as hypervascular. There were no significant differences in tumor response rates when vascularity was stratified by DSA or C-arm CT. Median progression-free survival (PFS) was 111 versus 128 days (p = 0.41) between DSA hypervascular and hypovascular cases, and median overall survival (OS) was 439 versus 342 days (p = 0.96). When stratified by C-arm CT, median PFS was 313 versus 244 days (p = 0.83) and median OS was 489 versus 342 days (p = 0.74) for hypervascular and hypovascular cases, respectively. Tumor vascularity based on DSA or C-arm CT does not predict imaging response or survival after radioembolization and should not be used as a criterion for selecting candidates for radioembolization for hepatic mCRC.

Keywords

radioembolization - locoregional therapy - liver-directed therapy

• References

• 1 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127 (12) 2893-2917
• 2 Fong Y, Kemeny N, Paty P, Blumgart LH, Cohen AM. Treatment of colorectal cancer: hepatic metastasis. Semin Surg Oncol 1996; 12 (04) 219-252
• 3 Steele Jr G, Ravikumar TS. Resection of hepatic metastases from colorectal cancer. Biologic perspective. Ann Surg 1989; 210 (02) 127-138
• 4 Helling TS, Martin M. Cause of death from liver metastases in colorectal cancer. Ann Surg Oncol 2014; 21 (02) 501-506
• 5 Wagner JS, Adson MA, Van Heerden JA, Adson MH, Ilstrup DM. The natural history of hepatic metastases from colorectal cancer. A comparison with resective treatment. Ann Surg 1984; 199 (05) 502-508
• 6 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
• 7 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
• 8 Willowson KP, Hayes AR, Chan DLH. et al. Clinical and imaging-based prognostic factors in radioembolisation of liver metastases from colorectal cancer: a retrospective exploratory analysis. EJNMMI Res 2017; 7 (01) 46
• 9 Schmeel FC, Simon B, Luetkens JA. et al. Prognostic value of pretreatment diffusion-weighted magnetic resonance imaging for outcome prediction of colorectal cancer liver metastases undergoing 90Y-microsphere radioembolization. J Cancer Res Clin Oncol 2017; 143 (08) 1531-1541
• 10 National Cancer Institute. Common Terminology Criteria for Adverse Events v4.0. NCI, NIH, DHHS. May 29, 2009. NIH publication 09–7473
• 11 Eisenhauer EA, Therasse P, Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45 (02) 228-247
• 12 Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18 (06) 695-706
• 13 Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496-509
• 14 Van Hazel G, Blackwell A, Anderson J. et al. Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol 2004; 88 (02) 78-85
• 15 Sharma RA, Van Hazel GA, Morgan B. et al. Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol 2007; 25 (09) 1099-1106
• 16 Saxena A, Bester L, Shan L. et al. A systematic review on the safety and efficacy of yttrium-90 radioembolization for unresectable, chemorefractory colorectal cancer liver metastases. J Cancer Res Clin Oncol 2014; 140 (04) 537-547
• 17 Nace GW, Steel JL, Amesur N. et al. Yttrium-90 radioembolization for colorectal cancer liver metastases: a single institution experience. Int J Surg Oncol 2011; 2011: 571261
• 18 Chua TC, Bester L, Saxena A, Morris DL. Radioembolization and systemic chemotherapy improves response and survival for unresectable colorectal liver metastases. J Cancer Res Clin Oncol 2011; 137 (05) 865-873
• 19 Mulcahy MF, Lewandowski RJ, Ibrahim SM. et al. Radioembolization of colorectal hepatic metastases using yttrium-90 microspheres. Cancer 2009; 115 (09) 1849-1858
• 20 Damm R, Seidensticker R, Ulrich G. et al. Y90 Radioembolization in chemo-refractory metastatic, liver dominant colorectal cancer patients: outcome assessment applying a predictive scoring system. BMC Cancer 2016; 16: 509
• 21 Stubbs RS, O'Brien I, Correia MM. Selective internal radiation therapy with 90Y microspheres for colorectal liver metastases: single-centre experience with 100 patients. ANZ J Surg 2006; 76 (08) 696-703
• 22 Ling CC, Michaels HB, Gerweck LE, Epp ER, Peterson EC. Oxygen sensitization of mammalian cells under different irradiation conditions. Radiat Res 1981; 86 (02) 325-340
• 23 Palcic B, Skarsgard LD. Reduced oxygen enhancement ratio at low doses of ionizing radiation. Radiat Res 1984; 100 (02) 328-339
• 24 Daşu A, Denekamp J. New insights into factors influencing the clinically relevant oxygen enhancement ratio. Radiother Oncol 1998; 46 (03) 269-277
• 25 Wenzl T, Wilkens JJ. Modelling of the oxygen enhancement ratio for ion beam radiation therapy. Phys Med Biol 2011; 56 (11) 3251-3268
• 26 Harris AL. Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2002; 2 (01) 38-47
• 27 Helmlinger G, Yuan F, Dellian M, Jain RK. Interstitial pH and pO₂ gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med 1997; 3 (02) 177-182
• 28 Krohn KA, Link JM, Mason RP. Molecular imaging of hypoxia. J Nucl Med 2008; 49 (Suppl (02) 129S-148S