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

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background </jats:bold>Proton radiotherapy has a dosimetric advantage over photon radiotherapy. Many retrospective studies have shown promising results with proton radiotherapy in treating hepatocellular carcinoma (HCC). However, clinical evidence demonstrating the benefit of protons over photons is still limited. We therefore compared the clinical outcomes of the two modalities using medical research databases from our medical foundation.<jats:bold>Methods </jats:bold>We conducted a propensity score-matched cohort study based on our multi-institution medical organization research database. From January 2007 to January 2018, a total of 413 patients (photon: 349; proton: 64) who were diagnosed with HCC and primarily treated with radiotherapy with curative intent were enrolled. Overall survival (OS) and radiation-induced liver disease (RILD) were assessed. Stratified analysis was also performed to evaluate the heterogeneous effects of the two arms.<jats:bold>Results </jats:bold>A total of 110 patients (photon: 55; proton: 55) were analyzed in the propensity-matched series. The matched groups were balanced for baseline tumor risk factors. Cox regression analysis revealed a significant survival benefit in the proton group (<jats:italic>p</jats:italic>=0.032, HR 0.56, 95% CI 0.33-0.96). The median overall survival in the proton group was not reached and that in the photon group was 17.4 months. The biological equivalent dose of radiotherapy was significantly higher in the proton group than in the photon group (median, 96.56 Gray [relative biological effectiveness] vs. 62.5 Gray, <jats:italic>p</jats:italic>&lt;0.001). The risk of RILD was significantly lower in the proton group (11.8% vs. 36%, <jats:italic>p</jats:italic>=0.004).<jats:bold>Conclusions </jats:bold>Proton radiotherapy could deliver a higher radiation dose than photon radiotherapy without increasing the risk of RILD and result in a better overall survival rate for those diagnosed with HCC and treated with radiotherapy with curative intent.</jats:p>

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience

“…A propensity-matched analysis from Taiwan also found a significantly improved median survival for patients who received proton therapy compared with those who received photon therapy (not reached vs 17.4 months, P < .01). 23 Similarly, they reported a significantly decreased risk of radiation-related liver injury in the proton group compared with the photon group (12 vs 36%, P < .01). The current report includes 11 patients (30%) with CP 7 to 9 disease, and notably, 3 of these patients (8%) had CP 9 disease (the latter were not included in the previously mentioned MDACC retrospective series).…”

Proton beam therapy to bridge or downstage locally advanced hepatocellular carcinoma to living donor liver transplantation

“…A proton beam has the physical advantage of creating a "Bragg peak" with a finite range of energy deposition with no exit dose beyond the target (Figure 3D). Therefore, compared with photon modalities, it is possible to solely irradiate a targeted liver tumor with higher doses using PBT while sparing surrounding tissues and organs (15), with consequently improved clinical outcomes (16,17). Retrospective data have shown promising clinical results for PBT.…”

A study on predicting cases that would benefit from proton beam therapy in primary liver tumors of less than or equal to 5 cm based on the estimated incidence of hepatic toxicity

“…In future clinical trials, much caution is needed for hepatic toxicity analysis of differences between PBT and XRT. Cheng et al and Sanford et al compared patients who undergo PBT or XRT for liver tumors, retrospectively, and reported improved survival and lower adverse event incidence with PBT [7] , [8] . Their studies are important in showing the benefits of PBT, however, the patients included in both studies had not been stratified by factors influencing liver doses.…”

“…In primary liver tumors, photon-based stereotactic body radiotherapy has been widely used and reported to have favorable treatment results [1] , [2] , [3] , [4] , [5] . For a more precise treatment, proton beam therapy (PBT) has also been applied, and improved results have been reported [6] , [7] , [8] , [9] . Due to its physical properties, PBT can be expected to reduce the dose to the normal liver.…”