Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Randa
R
Tao
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Sunil
S
Krishnan
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Priya R
PR
Bhosale
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Milind M
MM
Javle
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Thomas A
TA
Aloia
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Rachna T
RT
Shroff
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Ahmed O
AO
Kaseb
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Andrew J
AJ
Bishop
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Cameron W
CW
Swanick
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Eugene J
EJ
Koay
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Howard D
HD
Thames
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Theodore S
TS
Hong
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA.
Prajnan
P
Das
Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Prajnan Das, and Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX; and Theodore S. Hong, Harvard Medical School, Boston, MA. ccrane@mdanderson.org.
Christopher H
CH
Crane
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000532:radiotherapy*; D018281:Cholangiocarcinoma / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020266:Radiotherapy, Conformal; D012189:Retrospective Studies; D015996:Survival Rate