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Abstract
Background and purpose: Our study aimed to compare the oncologic outcomes and toxicities between passive scattering (PS) proton beam therapy (PBT) and pencil-beam scanning (PBS) PBT for primary hepatocellular carcinoma (HCC).

Materials and methods: The multidisciplinary team for liver cancer identified the PBT candidates who were ineligible for resection or radiofrequency ablation. We retrospectively analyzed 172 patients who received PBT for primary HCC from January 2016 to December 2017. The PS with wobbling method was applied with both breath-hold and regular breathing techniques, while the PBS method was utilized only for regular breathing techniques covering the full amplitude of respiration. To maintain the balance of the variables between the PS and PBS groups, we performed propensity score matching.

Results: The median follow-up duration for the total cohort was 14 months (range, 1-31 months). After propensity score matching, a total of 103 patients (70 in the PS group and 33 in the PBS group) were included in analysis. There were no significant differences in the rates of overall survival (OS), in-field local control (IFLC), out-field intrahepatic control (OFIHC), extrahepatic progression-free survival (EHPFS), and complete response (CR) between the matched groups. In the subgroup analyses, no subgroup showed a significant difference in IFLC between the PS and PBS groups. There was also no significant difference in the toxicity profiles between the groups.

Conclusion: There are no differences in oncologic outcomes, including OS, IFLC, OFIHC, EHPFS, and CR rates, or in the toxicity profiles between PS and PBS PBT for primary HCC.

Fig. 1. Kaplan-Meier’s curves for (A) overall survival, (B) in-field local control (C), out-field intrahepatic control, (D) extrahepatic progression-free survival, and (E) complete response.

PS, passive scattering; PBS, pencil-beam scanning

Fig. 2. Subgroup analysis for in-field local control

IFLC, in-field local control; PS, passive scattering; PBS, pencil-beam scanning; ALBI, albumin-bilirubin; ECOG-PS, Eastern Cooperative Oncology Group performance status; AFP, alpha-fetoprotein; PBT, proton beam therapy; Med., median; ∅max, maximum diameter; BCLC, Barcelona Clinic Liver Cancer

Fig 3. The comparison of dosimetry between pencil-beam scanning (PBS) and passive scattering (PS) proton beam therapy (PBT) of 66 GyRBE in 10 fractions. The PBS (A) shows better conformality than PS PBT (B) along the proximal edge (white arrows). Due to the better conformality, the dose at the chest wall (pink line) and rib (yellow line) are lower in the PBS (solid line) than PS (dotted line) as dose-volume histogram shows (C). The orange, sky blue, and blue lines represent the dose-volume histogram of gross tumor volume, clinical target volume, and normal liver, respectively (C).

Affiliations

Gyu Sang Yoo  1 , Jeong Il Yu  1 , Sungkoo Cho  2 , Sang Hoon Jung  2 , Youngyih Han  1 , Seyjoon Park  2 , Yoonjin Oh  2 , Boram Lee  2 , Hee Chul Park  3 , Do Hoon Lim  1 , Moon Seok Choi  4 , Hojeong Won  5
1 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
2 Department of Radiation Oncology, Samsung Medical Center, Seoul, Republic of Korea.
3 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: rophc@skku.edu.
4 Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
5 Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea.