Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2016-01-20
Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis.
Abstract
Purpose
Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC.
Patients and methods
Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy).
Results
Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities.
Conclusion
Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection.
Related Questions
How do you sequence hypofractionated radiation and systemic therapy for patients with unresectable cholangiocarcinoma?
I have generally cared for patients analogously to that done in the initial NRG GI001 or ABC07 trial designs with the use of initial systemic therapy for 3-6 months followed by consolidative RT targeting a BED > 80.5, assuming a/b ratio of 10 Gy. Tao et al., PMID 26503201 In my practice, it’s most c...
What volumes and prescription doses do you use when treating patients with unresectable cholangiocarcinoma?
Extrahepatic (EHC) and intrahepatic (IHC) cholangiocarcinoma are very different diseases. EHC tends to remain locoregional more often than IHC. Curative therapy must include surgery in general, but radiation has an important role, especially in patients with R+ resections. The data are not clear for...
When do you consider local therapies (i.e. TACE) in patients with intrahepatic cholangiocarcinoma who do not tolerate or respond to chemothearpy or who are not surgical candidates?
The treatment of choice would be EBRT, ideally delivered to ablative doses or at least over 80 BED (Tao et al., PMID 26503201).For LC and OS benefits. This is an NCCN based recommendation based off of retrospective and single arm prospective (Hong et al., PMID 26668346) data. Two year LC 94% of IHCC...
Do you base liver SBRT dose fractionation on size, volume, or proximity of normal tissue?
I think about this differently than most people do. My goal is to deliver an ablative dose (100 Gy BED) regardless of the proximity of organs at risk or the size of the tumor. The more common thing to do is to reduce the dose of radiation below an ablative dose to 40 or 30 Gy in 5 fractions. I'm not...
Is it feasible to treat central liver tumors +/- portal vein thrombus with SBRT while minding central hepatobiliary tract constraints?
Remember that biliary strictures frequently cause death in these patients because stents don't always drain after these high doses of radiation. I have personally never caused a biliary stricture. The regimens that I am using with an SBRT technique are below the threshold for biliary stricture and r...
Is there an "ideal" method for abdominal motion control when treating upper abdomen malignancies?
When using doses that potentially exceed OAR tolerance (specifically luminal GI,common and main bile ducts, liver) in the upper abdomen it is important to not only have a solution for organ motion, but some form of high quality image guidance. When giving a BED of <60 Gy, there is no need to use the...