Cholangiocarcinoma.org Statistics (CONTAINS SURVIVAL STATISTICS)

Thanks Eli for the distinction between ampullary and periampullary. I missed that completely.

There appears to be something left out of the following sentence in the paper. Are they trying to say something like distal cholangiocarcinoma account for 27% of the extrahepatic cholangiocarcinomas and perihilar cholangiocarcinoma accounts for 60-80%, or maybe 73% if the 27% is correct.

“Carcinoma of the distal bile duct: Cholangiocarcinoma is a rare malignancy of the biliary tract occurring in 27% in the distal bile duct, however the hepatic bifurcation is the most frequent involved site (60–80% of the cases).”

I’m still trying to find out where the 1973-2009 distal bile duct cancer is located in the SEER. I figure it must be there, but just coded unusually. I thought this may have something to do with it.

Bruce

Between 1987 and 1995, a phase III trial of the EORTC (European Organization for Research and Treatment of Cancer) Gastrointestinal Tract Cancer Cooperative Group to determine the effectiveness of adjuvant radiotherapy and 5-Fluorouracil after curative resection of cancer of the pancreas and periampullary region. The results are presented at the following link:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1420941/pdf/19991200s00006p776.pdf

The author state that the cancer in the periampullary region is periampullary carcinoma and it occurs in the ampulla of Vater, duodenum, and the distal common bile duct. The authors also state that in periampullary cancer, the 2-year survival rate was 63% in the observation group and 67% in the group that had adjuvant therapy, however p=0.737 for their analysis which means that the results were not statistically significant.

I became interested in this because it was a phase III test involving adjuvant therapy and the distal common bile duct was mentioned. My problem was that I couldn’t find if periampullary carcinoma was cholangiocarcinoma. The paper “Adjuvant treatment in biliary tract cancer: To treat or not to treat?” has 11 references to periampullary cancer including adenocarcinoma of ampulla of Vater (4), periampullary cancer (2) ampulla of Vater cancer (1) ampullary carcinoma (2), and ampullary adenocarcinoma (2), the second most references for a paper on biliary tract cancer, the first being gallbladder. I could not find mention of periampullary, ampulla or Vater in ICD-O-3 (International Classification of Diseases for Oncology, 3rd edition) although I did find it as Code 156.2 in the 1st edition, and C24.1 in the 2nd edition. In the 1st edition, it was coded with the “gallbladder and extrahepatic bile ducts” and in the 2nd edition, it was coded with “other and unspecified parts of biliary tract.”

Page 74 of the paper,

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993146/pdf/umj7902-070.pdf

states, “However, only 75% of periampullary tumours are truly of pancreatic origin . . . ” but doesn’t mention what the other 25% are.

Does anyone have more information about periampullary tumours and could they be cholangioncarnoma?

Bruce

Marion – OK, I fully understand the need for larger Phase III studies for chemo. But then, let me pose the question, “Where is the Phase III study that proves resection is better than no resection?” I think it is almost universally accepted that resection is better. What is that based on?

Bruce

Marion – If you mean there are no large (phase 3) randomized studies reflecting survival benefit derived from post resection adjuvant therapy, I agree with that.

However, there are small retrospective studies, based on small to large populations, that show there is a benefit. There are others that also say there is no benefit. Maybe others even show a negative impact.

Just glancing at some of the papers on my desk:

1. Murakami, “Gemcitabine-based adjuvant chemotherapy improves survival after aggressive surgery for hilar cholangiocarcinoma,”, 2009, 42 patients, “Five-year actuarial survival rates of patients who did or did not receive adjuvant gemcitabine-based chemotherapy were 57% and 23%, respectively (P=0.026).”

2. Shinohara, “Radiotherpy is associated with improved survival in adjuvant and palliative treatment of extrahepatic cholangiocarcinomas”, 2009, 4,758 patients, “The median overall survival time was 16 months for surgery and RT and 9 months for surgery alone.

3. Nakeeb, “Radiation therapy, chemotherapy and chemoradiation in hilar cholagiocarcinoma”, 2005, “A carefully controlled trial from the John Hopkins Hospital did not demonstrate any benefit for adjuvant radiation therapy. A number of phase II trials of chemotherapy have demonstrated modest response rates (20-40%)…… Neither radiation therapy nor chemotherapy alone has been proven to prolong survival in completely or partially resected patients or in unresected patients.”

4. Cereda, “Adjuvant treatment in biliary tract cancer: To treat or not to treat?”, 2011, “A retrospective series of 73 patients with gallbladder cancer treated between 1985 and 2004 at Mayo Clinic suggested that adjuvant CRT may obtain a statistically significant improvement in OS only for patients with lymph node involvement ….. A more recent phase III trial exploring the role of single agent adjuvant chemotherapy with either gemcitabine or 5-fluorouracil, in 304 patients with ampullary adenocarcinoma submitted to curative resection did not demonstrate a survival benefit for any of the adjuvant therapy arms when compared to surgery alone.”

And there are many more. I should look at all this in detail and try and figure out why the results vary so much.

Bruce

The following survival plot is for resected SEER cholangiocarcinoma patients. As for the intrahepatic cholangiocarcinoma plot, I used the database “Incidence – SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2012 Sub (1973-2010 varying)” and the Site and Morphology “CS Schema v0204.” This site has data coded as BileDucts Perihilar, BileDuctsDistal, BileDuctsIntraHepat, and BiliaryOther. Unfortunately, Klatskin data has been incorrected coded and placed in all four lists plus other unidentified locations. However, it appears all the Klatskin data is also coded in the site ICD-O-3 Hist/behav. There were 1362 cases of Klatskin in this site. These were duplicated in the other lists with 779 in the BilesDuctIntraHepat, 527 in the BilesDuctPerihilar (where they all should have been), 1 in BileDuctDistal, 31 in OtherBiliary, and 24 in unknown lists. The analyzed database for ECC was Perihilar & Distal without Klatskin and the Klatskin list form ICD-O-3 Hist/behav.

Again the survival curves below show that a single postive node substantially reduces survival for patients who have resected extrahepatic cholangiocarcinoma, although the reduction is not as much as for intrahepatic cholangiocarcinoma, 63.1% for ECC vs. 38.9% for ICC for median survivals.

Patients in the database were eliminated from the analysis based on the same criteria used for the intrahepatic cholangiocarcinoma analysis. A total of 336 patients were used in the analysis. These patients were diagnosed with extrahepatic cc from 1998 – 2010, median 2006. Their ages ranged from 12 – 87, median 65 years.

Median survival is 2.25 years for 0 positive LNs and 1.42 years for 1 positive LN. Statistical parameters for the analysis are Chsq = 17, 1 degree of freedom, p = 3.82 e-05.

The longest survivor in the database was a deceased man from Alameda County, CA with a resected Klatskin tumor, 22.8 years. He is not included in the analsis.

Bruce Baird