Stereotactic body radiotherapy for primary hepatic malignancies - Report of a phase I/II institutional study

Ashley A Weiner, Jeffrey Olsen, Daniel Ma, Pawel Dyk, Todd DeWees, Robert J Myerson, Parag Parikh, Ashley A Weiner, Jeffrey Olsen, Daniel Ma, Pawel Dyk, Todd DeWees, Robert J Myerson, Parag Parikh

Abstract

Background and purpose: To report outcomes and toxicities of a single-institution phase I/II study of stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular cancer (HCC) and intrahepatic cholangiocarcinoma (IHC).

Materials and methods: Patients with Child-Pugh score less than 8 were eligible. A total of 32 lesions in 26 patients were treated with SBRT. Kaplan-Meier survival analysis was performed. Toxicities were graded by CTCAEv4 criteria and response was scored by EASL guidelines.

Results: Median prescribed dose was 55Gy (range 40-55Gy) delivered in 5 fractions. Mean tumor diameter was 5.0cm and mean GTV was 107cc. Median follow-up was 8.8months with a median survival of 11.1months, and one-year overall survival was 45%. Overall response rate was 42% and one-year local control was 91%. Nine patients experienced a decline in Child-Pugh class following treatment, and two grade 5 hepatic failure toxicities occurred during study follow-up.

Conclusions: Primary hepatic malignancies not amenable to surgical resection portend a poor prognosis, despite available treatment options. Though radiation-induced liver disease (RILD) is rare following SBRT, this study demonstrates a risk of hepatic failure despite adherence to protocol constraints.

Keywords: Cholangiocarcinoma; Hepatocellular carcinoma; SBRT.

Conflict of interest statement

Conflict of Interest: The following authors report the following potential conflicts of interest (authors not listed reported no potential conflicts): Dr. Olsen reports grants, travel expenses and speaker’s fees from ViewRay, Inc. Dr. Parikh reports grants from Philips Healthcare and Varian Medical Systems, ownership in Holaira, Inc, and acts as a consultant for Medtronic/Covidien.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1
Figure 1
A. Overall survival (OS) from time of SBRT start. Median OS 11.1 months, one-year OS 45%. B. Progression-free survival (PFS) from time of SBRT start. Median PFS 15.2 months, one-year PFS 50%.

References

    1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.
    1. Dhanasekaran R, Hemming AW, Zendejas I, George T, Nelson DR, Soldevila-Pico C, et al. Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma. Oncol Rep. 2013;29:1259–67.
    1. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30:1434–40.
    1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J-F, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.
    1. Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF. Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys. 1995;31:1237–48.
    1. Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys. 2002;53:810–21.
    1. Méndez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen BJM, Nowak PCJM, et al. Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase iii study. Acta Oncol. 2006;45:831–7.
    1. Tse RV, Hawkins M, Lockwood G, Kim JJ, Cummings B, Knox J, et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2008;26:657–64.
    1. Bujold A, Massey CA, Kim JJ, Brierley J, Cho C, Wong RKS, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013;31:1631–9.
    1. Scorsetti M, Comito T, Cozzi L, Clerici E, Tozzi A, Franzese C, et al. The challenge of inoperable hepatocellular carcinoma (HCC): results of a single-institutional experience on stereotactic body radiation therapy (SBRT) J Cancer Res Clin Oncol. 2015
    1. Culleton S, Jiang H, Haddad CR, Kim J, Brierley J, Brade A, et al. Outcomes following definitive stereotactic body radiotherapy for patients with Child-Pugh B or C hepatocellular carcinoma. Radiother Oncol. 2014;111:412–7.
    1. Kopek N, Holt MI, Hansen AT, Høyer M. Stereotactic body radiotherapy for unresectable cholangiocarcinoma. Radiother Oncol. 2010;94:47–52.
    1. Goodman KA, Wiegner EA, Maturen KE, Zhang Z, Mo Q, Yang G, et al. Dose-escalation study of single-fraction stereotactic body radiotherapy for liver malignancies. Int J Radiat Oncol Biol Phys. 2010;78:486–93.
    1. Feng M, Ben-Josef E. Radiation therapy for hepatocellular carcinoma. Semin Radiat Oncol. 2011;21:271–7.
    1. Son SH, Choi BO, Ryu MR, Kang YN, Jang JS, Bae SH, et al. Stereotactic body radiotherapy for patients with unresectable primary hepatocellular carcinoma: dose-volumetric parameters predicting the hepatic complication. Int J Radiat Oncol Biol Phys. 2010;78:1073–80.
    1. Dyk P, Weiner A, Badiyan S, Myerson R, Parikh P, Olsen J. Effect of high-dose stereotactic body radiation therapy on liver function in the treatment of primary and metastatic liver malignancies using the Child-Pugh score classification system. Pract Radiat Oncol. 2015;5:176–82.
    1. Vallet-Pichard A, Rerolle J-P, Fontaine H, Larousserie F, Peraldi M-N, Kreis H, et al. Veno-occlusive disease of the liver in renal transplant patients. Nephrol Dial Transplant. 2003;18:1663–6.
    1. Cárdenes HR, Price TR, Perkins SM, Maluccio M, Kwo P, Breen TE, et al. Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma. Clin Transl Oncol. 2010;12:218–25.
    1. Andolino DL, Johnson CS, Maluccio M, Kwo P, Tector AJ, Zook J, et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2011;81:e447–53.
    1. Kang J-K, Kim M-S, Cho CK, Yang KM, Yoo HJ, Kim JH, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. 2012;118:5424–31.
    1. Schefter TE, Kavanagh BD, Timmerman RD, Cardenes HR, Baron A, Gaspar LE. A phase I trial of stereotactic body radiation therapy (SBRT) fo liver metastases. Int J Radiat Oncol Biol Phys. 2005;62:1371–1378.
    1. Sanuki N, Takeda A, Oku Y, Eriguchi T, Nishimura S, Aoki Y, et al. Influence of liver toxicities on prognosis after stereotactic body radiotherapy for hepatocellular carcinoma. Hep Res. 2015;45:540–547.
    1. Tang C, Liao Z, Gomez D, Levy L, Zhuang Y, Gebremicheal RA, et al. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer outcomes. Int J Radiat Oncol Biol Phys. 2014;89:1084–91.
    1. Huang J, DeWees TA, Badiyan SN, Speirs CK, Mullen DF, Fergus S, et al. Clinical and dosimetric predictors of acute severe lymphopenia during radiation therapy and concurrent temozolamike for high-grade glioma. Int J Radiat Oncol Biol Phys. 2015;92:1000–7.
    1. Lario M, Munoz L, Ubeda M, Borrero MJ, Martinez J, Monserrat J, et al. Defective thymopoeisis and poor peripheral homeostatic replenishment of T-helper cells cause T-cell lymphopenia in cirrhosis. J Hepatol. 2013;59:723–30.

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