Critical appraisal of the potential role of intensity modulated proton therapy in the hypofractionated treatment of advanced hepatocellular carcinoma

Purpose: To investigate the role of intensity-modulated proton therapy (IMPT) for hepatocellular carcinoma (HCC) patients to be treated with stereotactic body radiation therapy (SBRT) in a risk-adapted dose prescription regimen. Methods: A cohort of 30 patients was retrospectively selected as “at-risk” of dose de-escalation due to the proximity of the target volumes to dose-limiting healthy structures. IMPT plans were compared to volumetric modulated arc therapy (VMAT) RapidArc (RA) plans. The maximum dose prescription foreseen was 75 Gy in 3 fractions. The dosimetric analysis was performed on several quantitative metrics on the target volumes and organs at risk to identify the relative improvement of IMPT over VMAT and to determine if IMPT could mitigate the need of dose reduction and quantify the consequent potential patient accrual rate for protons. Results: IMPT and VMAT plans resulted in equivalent target dose distributions: both could ensure the required coverage for CTV and PTV. Systematic and significant improvements were observed with IMPT for all organs at risk and metrics. An average gain of 9.0 ± 11.6, 8.5 ± 7.7, 5.9 ± 7.1, 4.2 ± 6.4, 8.9 ± 7.1, 6.7 ± 7.5 Gy was found in the near-to-maximum doses for the ribs, chest wall, heart, duodenum, stomach and bowel bag respectively. Twenty patients violated one or more binding constraints with RA, while only 2 with IMPT. For all these patients, some dose de-intensification would have been required to respect the constraints. For photons, the maximum allowed dose ranged from 15.0 to 20.63 Gy per fraction while for the 2 proton cases it would have been 18.75 or 20.63 Gy. Conclusion: The results of this in-silico planning study suggests that IMPT might result in advantages compared to photon-based VMAT for HCC patients to be treated with ablative SBRT. In particular, the dosimetric characteristics of protons may avoid the need for dose de-escalation in a risk-adapted prescription regimen for those patients with lesions located in proximity of dose-limiting healthy structures. Depending on the selection thresholds, the number of patients eligible for treatment at the full dose can be significantly increased with protons.

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Intensity-Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience

Advances in Radiation Oncology ◽

10.1016/j.adro.2021.100675 ◽

2021 ◽

pp. 100675

Author(s):

R.S. Bhangoo ◽

T.C. Mullikin ◽

J.B. Ashman ◽

T.W. Cheng ◽

M.A. Golafshar ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Experience ◽

Proton Therapy ◽

Intensity Modulated Proton Therapy ◽

Intensity Modulated ◽

Initial Clinical Experience

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Intensity-modulated proton therapy using dose-painting pencil beam scanning for high-risk hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.558 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 558-558

Author(s):

Stephanie K. Schaub ◽

Stephen R. Bowen ◽

Matthew J. Nyflot ◽

Smith Apisarnthanarax

Keyword(s):

Hepatocellular Carcinoma ◽

Local Control ◽

Proton Therapy ◽

Gross Tumor Volume ◽

Tumor Volume ◽

Pencil Beam ◽

Intensity Modulated Proton Therapy ◽

Intensity Modulated ◽

Pencil Beam Scanning ◽

Grade 3

558 Background: High rates of local control are achievable with hypofractionated proton therapy with passive techniques for hepatocellular carcinoma (HCC), but may have limitations when tumors are adjacent to organs-at-risk (OARs), which may result in tumor underdosage and lead to inferior local control. We present the first reported series of HCC patients treated with pencil beam scanning (PBS) intensity-modulated proton therapy (IMPT) using a simultaneous-integrated boost and protection (SIB/SIP) technique to escalate tumor dose while protecting adjacent OARs. Methods: Twenty-five HCC patients were treated between 2015-2019 with a 15-fraction regimen using IMPT SIB/SIP. SIB/SIP dose levels generally ranged from 36.0-67.5 GyRBE to minimize dose to OARs at their respective dose-limiting thresholds (e.g. luminal gastrointestinal organs, chest wall). Radiation-induced liver disease (RILD) was defined by a Child-Pugh (CP) score increase of 2 or greater and/or any RTOG grade 3 enzyme elevation. Other toxicities were graded by CTCAEv5.0. Overall survival (OS), progression-free survival (PFS), and local control were calculated using the Kaplan-Meier method. Results: Patients most commonly had BCLC stage B or C disease (84%) and CP-A (80%) and ALBI grade 2 (60%) liver function. Median gross tumor volume (GTV) size and volume were 12.3 cm (range 2.17-20.57) and 461 cc (range 4.68-2439), and 32% had gross vascular invasion. Median mean and minimum dose delivered to the gross tumor volume (GTV) was 64.0 GyRBE (EQD2 76.1, BED 91.3, range 54.3-69.6) and 45.1 GyRBE (EQD2 48.9, BED 58.7, range 33.4-67.7), respectively. Median mean dose to liver minus GTV was 15.0 GyRBE (range, 8.2-19.6). 1-year OS, PFS, and local control were 66%, 32%, and 84%, respectively. No isolated local failures occurred. Two patients experienced RILD with no RILD-related deaths. Two grade 3 non-GI toxicities occurred: 1 rib fracture and 1 pneumonitis. No acute or late GI grade ≥2 occurred. Conclusions: In our series of HCC patients with large tumors near OARs, IMPT SIB/SIP allows for tumor dose escalation while sparing of OARs and results in favorable local control and acceptable toxicities.

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