Ann Hepatobiliary Pancreat Surg.  2020 Feb;24(1):6-16. 10.14701/ahbps.2020.24.1.6.

The role of down staging treatment in the management of locally advanced intrahepatic cholangiocarcinoma: Review of literature and pooled analysis

• Kamarajah
• Giovinazzo F
• Roberts KJ
• Punia P
• Sutcliffe
• Marudanayagam R
• Chatzizacharias N
• Isaac J
• Mirza DF
• Muiesan P
• Dasari BV

• KMID: 2471183
• DOI: http://doi.org/10.14701/ahbps.2020.24.1.6

Abstract

BACKGROUNDS/AIMS
Approximately 60-80% of patients with intrahepatic cholangiocarcinoma (iCCA) are not suitable for surgical resection due to advanced disease at presentation. This review assesses the role of surgical resection followed by down staging treatment in the management of patients with locally advanced iCCA.
METHODS
A systematic review and pooled analysis were performed of the relevant published studies published between January 2000-December 2018. The primary outcome measure was overall survival. Secondary outcome measures were rates of clinical benefit, margin-negative (R0) resections, overall and surgery-specific complications, and post-operative mortality.
RESULTS
Eighteen cohort studies with 1880 patients were included in the review. The median overall survival in all patients was 14 months (range, 7-18 months). Patients undergoing resection following down staging had significantly longer survival than those who did not (median: 29 vs. 12 months, p<0.001). The Clinical Benefit Rate with this strategy (complete response+partial response+stable disease) was 64% (244/383), ranging from 33-90%. Thirty-eight percent of the patients underwent resections with a 60% R0 resection rate and 6% postoperative mortality.
CONCLUSIONS
Although the evidence to support the benefits of NAT for iCCA is limited, the review supports the use of down staging treatment and also surgical resection in the cohort with response to NAT in order to improve long-term survival in patients with locally advanced iCCA.

Keyword

Intrahepatic; Cholangiocarcinoma; Locally advanced; Down staging; Surgery

MeSH Terms

Cholangiocarcinoma*
Cohort Studies
Humans
Mortality
Outcome Assessment (Health Care)

Reference

1. Yao KJ, Jabbour S, Parekh N, Lin Y, Moss RA. Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database. BMC Gastroenterol. 2016; 16:117. PMID: 27655244.

2. Kamarajah SK. Evaluation of the AJCC 8th edition staging system for pathologically versus clinically staged intrahepatic cholangiocarcinoma (iCCA): a time to revisit a dogma? A Surveillance, Epidemiology, and End Results (SEER) analysis. J Gastrointest Cancer. 2019; 50:392–399. PMID: 29512000.

3. Endo I, Gonen M, Yopp AC, Dalal KM, Zhou Q, Klimstra D, et al. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg. 2008; 248:84–96. PMID: 18580211.

4. Nathan H, Pawlik TM. Staging of intrahepatic cholangiocarcinoma. Curr Opin Gastroenterol. 2010; 26:269–273. PMID: 20179593.

5. Le Roy B, Gelli M, Pittau G, Allard MA, Pereira B, Serji B, et al. Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. Br J Surg. 2018; 105:839–847. PMID: 28858392.

6. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010; 362:1273–1281. PMID: 20375404.

7. Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta analysis. Lancet Oncol. 2016; 17:801–810. PMID: 27160474.

8. Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ, Devitt P, et al. Trans-Tasman Radiation Oncology Group. Australasian Gastro-Intestinal Trials Group. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol. 2005; 6:659–668. PMID: 16129366.

9. Pasquali S, Yim G, Vohra RS, Mocellin S, Nyanhongo D, Marriott P, et al. Survival after neoadjuvant and adjuvant treatments compared to surgery alone for resectable esophageal carcinoma: a network meta-analysis. Ann Surg. 2017; 265:481–491. PMID: 27429017.

10. Herber S, Otto G, Schneider J, Manzl N, Kummer I, Kanzler S, et al. Transarterial chemoembolization (TACE) for inoperable intrahepatic cholangiocarcinoma. Cardiovasc Intervent Radiol. 2007; 30:1156–1165. PMID: 17508242.

11. Shitara K, Ikami I, Munakata M, Muto O, Sakata Y. Hepatic arterial infusion of mitomycin C with degradable starch microspheres for unresectable intrahepatic cholangiocarcinoma. Clin Oncol (R Coll Radiol). 2008; 20:241–246. PMID: 18222071.

12. Nehls O, Oettle H, Hartmann JT, Hofheinz RD, Hass HG, Horger MS, et al. Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. Br J Cancer. 2008; 98:309–315. PMID: 18182984.

13. Chen YX, Zeng ZC, Tang ZY, Fan J, Zhou J, Jiang W, et al. Determining the role of external beam radiotherapy in unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 84 patients. BMC Cancer. 2010; 10:492. PMID: 20840777.

14. Vogl TJ, Naguib NN, Nour-Eldin NE, Bechstein WO, Zeuzem S, Trojan J, et al. Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: results and prognostic factors governing treatment success. Int J Cancer. 2012; 131:733–740. PMID: 21976289.

15. Scheuermann U, Kaths JM, Heise M, Pitton MB, Weinmann A, Hoppe-Lotichius M, et al. Comparison of resection and transarterial chemoembolisation in the treatment of advanced intrahepatic cholangiocarcinoma--a single-center experience. Eur J Surg Oncol. 2013; 39:593–600. PMID: 23611755.

16. Kim YI, Park JW, Kim BH, Woo SM, Kim TH, Koh YH, et al. Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for advanced-stage unresectable intrahepatic cholangiocarcinoma. Radiat Oncol. 2013; 8:292. PMID: 24359879.

17. Kato A, Shimizu H, Ohtsuka M, Yoshidome H, Yoshitomi H, Furukawa K, et al. Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study. Ann Surg Oncol. 2013; 20:318–324. PMID: 23149849.

18. Yi SW, Kang DR, Kim KS, Park MS, Seong J, Park JY, et al. Efficacy of concurrent chemoradiotherapy with 5-fluorouracil or gemcitabine in locally advanced biliary tract cancer. Cancer Chemother Pharmacol. 2014; 73:191–198. PMID: 24322374.

19. Kato A, Shimizu H, Ohtsuka M, Yoshitomi H, Furukawa K, Takayashiki T, et al. Downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer patients treated with gemcitabine plus cisplatin combination therapy followed by radical surgery. Ann Surg Oncol. 2015; 22 Suppl 3:S1093–S1099. PMID: 26240009.

20. Rayar M, Sulpice L, Edeline J, Garin E, Levi Sandri GB, Meunier B, et al. Intra-arterial yttrium-90 radioembolization combined with systemic chemotherapy is a promising method for downstaging unresectable huge intrahepatic cholangiocarcinoma to surgical treatment. Ann Surg Oncol. 2015; 22:3102–3108. PMID: 25623598.

21. Konstantinidis IT, Groot Koerkamp B, Do RK, Gönen M, Fong Y, Allen PJ, et al. Unresectable intrahepatic cholangiocarcinoma: systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone. Cancer. 2016; 122:758–765. PMID: 26695839.

22. Omichi K, Cloyd JM, Yamashita S, Tzeng CD, Conrad C, Chun YS, et al. Neutrophil-to-lymphocyte ratio predicts prognosis after neoadjuvant chemotherapy and resection of intrahepatic cholangiocarcinoma. Surgery. 2017; 162:752–765. PMID: 28688518.

23. Cho Y, Kim TH, Seong J. Improved oncologic outcome with chemoradiotherapy followed by surgery in unresectable intrahepatic cholangiocarcinoma. Strahlenther Onkol. 2017; 193:620–629. PMID: 28424838.

24. Chang WW, Hsiao PK, Qin L, Chang CL, Chow JM, Wu SY. Treatment outcomes for unresectable intrahepatic cholangiocarcinoma: nationwide, population-based, cohort study based on propensity score matching with the Mahalanobis metric. Radiother Oncol. 2018; 129:284–292. PMID: 30279046.

25. Sumiyoshi T, Shima Y, Okabayashi T, Negoro Y, Shimada Y, Iwata J, et al. Chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. World J Surg. 2018; 42:2910–2918. PMID: 29511872.

26. Lunsford KE, Javle M, Heyne K, Shroff RT, Abdel-Wahab R, Gupta N, et al. Methodist-MD Anderson Joint Cholangiocarcinoma Collaborative Committee (MMAJCCC). Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. Lancet Gastroenterol Hepatol. 2018; 3:337–348. PMID: 29548617.

27. Eckmann KR, Patel DK, Landgraf A, Slade JH, Lin E, Kaur H, et al. Chemotherapy outcomes for the treatment of unresectable intrahepatic and hilar cholangiocarcinoma: a retrospective analysis. Gastrointest Cancer Res. 2011; 4:155–160. PMID: 22295126.

28. Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, et al. ABC-06 | a randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with ox aliplatin / 5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced / metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. J Clin Oncol. 2019; 37(Suppl 15):4003.

29. Currie BM, Soulen MC. Decision making: intra-arterial therapies for cholangiocarcinoma-TACE and TARE. Semin Intervent Radiol. 2017; 34:92–100. PMID: 28579676.