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Impact of Primary Tumor Laterality on Adjuvant Hepatic Artery Infusion Pump Chemotherapy in Resected Colon Cancer Liver Metastases: Analysis of 487 Patients

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Hepatic artery infusion (HAI) chemotherapy is associated with overall survival (OS) in patients with resected colon cancer liver metastases (CLM). The prognostic impact of primary tumor location in CLM following hepatic resection in patients receiving regional HAI is unknown. This study seeks to investigate the prognostic impact of HAI in relation to laterality in this patient population.

Methods

Consecutive patients with resected CLM, with known primary tumor site treated with and without HAI, were reviewed from a prospective institutional database. Correlations between HAI, laterality, other clinicopathological factors, and survival were analyzed, and Cox proportional hazard regression was used to determine whether laterality was an independent prognostic factor.

Results

From 1993 to 2012, 487 patients [182 with right colon cancer (RCC), 305 with left colon cancer (LCC)] were evaluated with a median follow-up of 6.5 years. Fifty-seven percent (n = 275) received adjuvant HAI. Patients with RCC had inferior 5-year OS compared with LCC (56% vs. 67%, P = 0.01). HAI was associated with improved 5-year OS in both RCC (68% vs. 45%; P < 0.01) and LCC (73% vs. 55%; P < 0.01). On multivariable analysis, HAI remained associated with improved OS (HR 0.52; 95% CI 0.39–0.70; P < 0.01) but primary tumor site did not (HR 0.83; 95% CI 0.63–1.11; P = 0.21). Additional significant prognostic factors on multivariable analysis included age, number of tumors, node-positive primary, positive margins, RAS mutation, two-stage hepatectomy, and extrahepatic disease. Cox proportional hazard regression determined no significant interaction between HAI and laterality on OS [parameter estimate (SEM), 0.12 (0.28); P = 0.67].

Conclusions

Our data show an association of adjuvant HAI and increased OS in patients who underwent curative hepatectomy, irrespective of primary tumor location. Laterality should therefore not impact decision-making when offering adjuvant HAI.

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References

  1. Jass JR: Subsite distribution and incidence of colorectal cancer in New Zealand, 1974–1983. Dis Colon Rectum 34(1):56–9, 1991.

    Article  CAS  Google Scholar 

  2. Obrand DI, Gordon PH: Continued change in the distribution of colorectal carcinoma. Br J Surg 85(2):246–8, 1998.

    Article  CAS  Google Scholar 

  3. Benedix F, Kube R, Meyer F, et al: Comparison of 17,641 patients with right- and left-sided colon cancer: differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum 53(1):57–64, 2010.

    Article  Google Scholar 

  4. Bufill JA: Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med 113(10):779–88, 1990.

    Article  CAS  Google Scholar 

  5. Weiss JM, Pfau PR, O’Connor ES, et al: Mortality by stage for right- versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results—Medicare data. J Clin Oncol 29(33):4401–9, 2011.

    Article  Google Scholar 

  6. Breivik J, Lothe RA, Meling GI, et al: Different genetic pathways to proximal and distal colorectal cancer influenced by sex-related factors. Int J Cancer 74(6):664–9, 1997.

    Article  CAS  Google Scholar 

  7. Hsu YL, Lin CC, Jiang JK, et al: Clinicopathological and molecular differences in colorectal cancer according to location. Int J Biol Markers 34(1):47–53, 2019.

    Article  CAS  Google Scholar 

  8. Shen H, Yang J, Huang Q, et al: Different treatment strategies and molecular features between right-sided and left-sided colon cancers. World J Gastroenterol 21(21):6470–8, 2015.

    Article  CAS  Google Scholar 

  9. Loupakis F, Yang D, Yau L, et al: Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst 107(3), 2015.

  10. Meguid RA, Slidell MB, Wolfgang CL, et al: Is there a difference in survival between right- versus left-sided colon cancers? Ann Surg Oncol 15(9):2388–94, 2008.

    Article  Google Scholar 

  11. Tejpar S, Stintzing S, Ciardiello F, et al: Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: Retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol 3(2):194–201, 2017.

    Article  Google Scholar 

  12. Yahagi M, Okabayashi K, Hasegawa H, et al: The worse prognosis of right-sided compared with left-sided colon cancers: a systematic review and meta-analysis. J Gastrointest Surg 20(3):648–55, 2016.

    Article  Google Scholar 

  13. Sasaki K, Andreatos N, Margonis GA, et al: The prognostic implications of primary colorectal tumor location on recurrence and overall survival in patients undergoing resection for colorectal liver metastasis. J Surg Oncol 114(7):803–9, 2016.

    Article  Google Scholar 

  14. Wang K, Xu D, Yan XL, et al: The impact of primary tumour location in patients undergoing hepatic resection for colorectal liver metastasis. Eur J Surg Oncol 44(6):771–7, 2018.

    Article  Google Scholar 

  15. Creasy JM, Sadot E, Koerkamp BG, et al: The impact of primary tumor location on long-term survival in patients undergoing hepatic resection for metastatic colon cancer. Ann Surg Oncol 25(2):431–8, 2018.

    Article  Google Scholar 

  16. Kemeny MM, Adak S, Gray B, et al: Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy—an intergroup study. J Clin Oncol 20(6):1499–505, 2002.

    PubMed  Google Scholar 

  17. Kemeny N, Huang Y, Cohen AM, et al: Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 341(27):2039–48, 1999.

    Article  CAS  Google Scholar 

  18. Kemeny NE, Gonen M: Hepatic arterial infusion after liver resection. N Engl J Med 352(7):34–5, 2005.

    Article  Google Scholar 

  19. Groot Koerkamp B, Sadot E, Kemeny NE, et al: Perioperative hepatic arterial infusion pump chemotherapy is associated with longer survival after resection of colorectal liver metastases: a propensity score analysis. J Clin Oncol 35(17):1938–44, 2017.

    Article  Google Scholar 

  20. Gholami S, Kemeny NE, Boucher TM, et al: Adjuvant hepatic artery infusion chemotherapy is associated with improved survival regardless of KRAS mutation status in patients with resected colorectal liver metastases. Ann Surg. 2019.

  21. Missiaglia E, Jacobs B, D’Ario G, et al: Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol 25(10):1995–2001, 2014.

    Article  CAS  Google Scholar 

  22. Nitsche U, Stögbauer F, Späth C, et al: Right sided colon cancer as a distinct histopathological subtype with reduced prognosis. Dig Surg 33(2):157–63, 2015.

    Article  Google Scholar 

  23. Brulé SY, Jonker DJ, Karapetis CS, et al: Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17. Eur J Cancer 51(11):1405–14, 2015.

  24. Charlton ME, Kahl AR, Greenbaum AA, et al: KRAS testing, tumor location, and survival in patients with stage iv colorectal cancer: SEER 2010-2013. J Natl Compr Canc Netw 15(12):1484–93, 2017.

    Article  Google Scholar 

  25. Amin MB, Greene FL, Edge SB, et al: The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 67(2):93–9, 2017.

  26. Fong Y, Fortner J, Sun RL, et al: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230(3):309–18, 1999. (discussion 318–21).

  27. Cucino C, Buchner AM, Sonnenberg A: Continued rightward shift of colorectal cancer. Dis Colon Rectum 45(8):1035–40, 2002.

    Article  Google Scholar 

  28. Innocenti F, Ou FS, Qu X, et al: mutational analysis of patients with colorectal cancer in CALGB/SWOG 80405 identifies new roles of microsatellite instability and tumor mutational burden for patient outcome. J Clin Oncol 37(14):1217–27, 2019.

    Article  CAS  Google Scholar 

  29. Lanza G Jr., Maestri I, Ballotta MR, et al: Relationship of nuclear DNA content to clinicopathologic features in colorectal cancer. Mod Pathol 7(2):161–5, 1994.

    PubMed  Google Scholar 

  30. Saltzstein SL, Behling CA: Age and time as factors in the left-to-right shift of the subsite of colorectal adenocarcinoma: a study of 213,383 cases from the California Cancer Registry. J Clin Gastroenterol 41(2):173–7, 2007.

    Article  Google Scholar 

  31. Venook, AP, Niedzwiecki D, Lenz HJ, et al: CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). J Clin Oncol 32(Suppl 15):LBA3-LBA3, 2014.

  32. Venook AP, Ou FS, Lenz HJ, et al: Primary (1°) tumor location as an independent prognostic marker from molecular features for overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol 35(Suppl 15):3503, 2017.

  33. Holch JW, Ricard I, Stintzing S, et al: The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials. Eur J Cancer 70:87–98, 2017.

    Article  Google Scholar 

  34. Dupré A, Malik HZ, Jones RP, et al: Influence of the primary tumour location in patients undergoing surgery for colorectal liver metastases. Eur J Surg Oncol 44(1):80–6, 2018.

    Article  Google Scholar 

  35. Price TJ, Beeke C, Ullah S, et al: Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease? Cancer 121(6):830–5, 2015.

    Article  Google Scholar 

  36. Imai K, Yamashita YI, Miyamoto Y, et al: Implication of primary tumor location for the indication of preoperative chemotherapy in patients with colorectal liver metastases. HPB (Oxford) 21(4):405–12, 2019.

    Article  Google Scholar 

  37. Rahbari NN, Reissfelder C, Schulze-Bergkamen H, et al: Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy. BMC Cancer 14:174, 2014.

    Article  Google Scholar 

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Acknowledgement

This work was supported in part by the NIH/NCI P30 CA008748 Cancer Center Support Grant.

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Correspondence to Michael D’Angelica MD, FACS.

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Gholami, S., Stewart, S., Kemeny, N. et al. Impact of Primary Tumor Laterality on Adjuvant Hepatic Artery Infusion Pump Chemotherapy in Resected Colon Cancer Liver Metastases: Analysis of 487 Patients. Ann Surg Oncol 28, 3685–3694 (2021). https://doi.org/10.1245/s10434-020-09369-7

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