Proton beam therapy outcomes for localized unresectable hepatocellular carcinoma

Abstract

Background and purpose: This study documents the utilization and efficacy of proton beam therapy (PBT) in western patients with localized unresectable hepatocellular carcinoma (HCC). Methods and methods: Forty-six patients with HCC, Child-Pugh class of A or B, no prior radiotherapy history, and ECOG performance status 0-2 received PBT at our institution from 2007 to 2016. Radiographic control within the PBT field (local control, LC) and overall survival (OS) were calculated from the start of PBT. Results: Most (83%) patients had Child-Pugh class A. Median tumor size was 6 cm (range, 1.5-21.0 cm); 22% of patients had multiple tumors and 28% had tumor vascular thrombosis. Twenty-five (54%) patients received prior treatment. Median biologically effective dose (BED) was 97.7 GyE (range, 33.6-144 GyE) administered in 15 fractions. Actuarial 2-year LC and OS rates were 81% and 62%; median OS was 30.7 months. Out-of-field intrahepatic failure was the most common site of disease progression. Patients receiving BED ≥90 GyE had a significantly better OS than those receiving BED <90 GyE (49.9 vs. 15.8 months, p = 0.037). A trend toward 2year LC improvement was observed in patients receiving BED ≥90 GyE compared with those receiving BED <90 GyE (92% vs. 63%, p = 0.096). On multivariate analysis, higher BED (p = 0.023; hazard ratio = 0.308) significantly predicted improved OS. Six (13%) patients experienced acute grade 3 toxicity. Conclusions: High-dose PBT is associated with high rates of LC and OS for unresectable HCC. Dose escalation may further improve outcomes.

Proton versus photon radiotherapy for primary hepatocellular carcinoma: A propensity-matched analysis

“…Chadha et al reported a series of 46 HCC patients treated with proton radiotherapy. Patients receiving a BED ≥90 Gy (RBE) had significantly better OS [7]. In the present study, the BED was signi cantly higher in the proton group and would be an essential factor contributing to better OS.…”

“…This physical advantage over photon beams could therefore reduce unwanted spreading of the dose to the surrounding normal liver and adjacent organs [5]. Retrospective data from eastern and western countries have shown promising clinical results for proton radiotherapy [6,7]. The three-year local control rate ranges from 70-95% depending on the tumor and the patients' baseline characteristics, and the risk of toxicity is quite low.…”

Hypofractionated Proton Beam Radiotherapy in Patients With Unresectable Liver Tumors: Multi-institutional Prospective Results From the Proton Collaborative Group

“…These patients were treated across 9 institutions between 2013 and 2019. The median number of patients treated per institution was 3 (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Of the 63 patients, 30 had HCC, 25 had ICC, 4 had carcinoid tumors, 1 had spindle cell carcinoma, 1 had a liver metastasis, and 2 had unknown lesions.…”

Hypofractionated proton beam radiotherapy in patients with unresectable liver tumors: multi-institutional prospective results from the Proton Collaborative Group

“…However, other studies evaluating proton therapy have established BED cut-offs as high as 90 GyE. 11 Despite the above, proton therapy as a treatment modality remains somewhat controversial given its cost and lack of level I evidence for overall survival, thus prompting the ongoing phase III NRG trial randomizing patients to protons versus photons in patients with HCC. 6 Strengths of the current study include its prospective registry nature and multidisciplinary contributions, affording reasonable sample size for this relatively rare disease entity.…”

“…[8][9][10] Similarly, there have been prospective studies supporting this approach in ICC. 5,10 A dose-response relationship for both clinical entities has been suggested, 11,12 but dose-escalation is ultimately limited by liver tolerance. The risk of radiation-induced liver disease (RILD) is in uenced not only by the dose and volume of liver irradiated but also by the patient's underlying liver disease.…”