Stereotactic body proton therapy for liver tumors: Dosimetric advantages and their radiobiological and clinical implications

Abstract

Background and Purpose: Photon Stereotactic Body Radiotherapy (SBRT) for primary and metastatic tumors of the liver is challenging for larger lesions. An in silico comparison of paired SBRT and Stereotactic Body Proton Therapy (SBPT) plans was performed to understand the potential advantages of SBPT as a function of tumor size and location. Methods and materials: Theoretical tumor volumes with maximum diameter of 1-10 cm were contoured in the dome, right inferior, left medial, and central locations. SBRT and SBPT plans were generated to deliver 50 Gy in 5 fractions, max dose < 135%. When organs-at-risk (OAR) constraints were exceeded, hypothetical plans (not clinically acceptable) were generated for comparison. Liver normal tissue complication probability (NTCP) models were applied to evaluate differences between treatment modalities. Results: SBRT and SBPT were able to meet target goals and OAR constraints for lesions up to 7 cm and 9 cm diameter, respectively. SBPT plans resulted in a higher integral gross target dose for all lesions up to 7 cm (mean dose 57.8 ± 2.3 Gy to 64.1 ± 2.2 Gy, p < 0.01). Simultaneously, SBPT spared dose to the uninvolved liver in all locations (from 11.5 ± 5.3 Gy to 8.6 ± 4.4 Gy, p < 0.01), resulting in lower NTCP particularly for larger targets in the dome and central locations. SBPT also spared duodenal dose across all sizes and positions (from 7.3 ± 1.1 Gy to 1.1 ± 0.3 Gy, p < 0.05). Conclusion: The main advantages of SBPT over SBRT is meeting plan goals and constrains for larger targets, particularly dome and central locations, and sparing dose to uninvolved liver. For such patients, SBPT may allow improvements in tumor control and treatment safety.

Simultaneous Multiple Liver Metastasis Treated with Pencil Beam Proton Stereotactic Body Radiotherapy (SBRT)

“…Proton liver therapy has been evaluated in several prior studies, including PBS proton therapy, although proton ultrahypofractionated SBRT experience is limited, and much long-term clinical data is limited to passively scattered beams [3,4]. Early proton liver therapy reports demonstrated reduced side effects concordant with reduced liver dose to 700 cm 3 normal liver, and other organs at risk, particularly dome and central tumors .3 cm [5,6]. In a phase II study of proton liver SBRT for patients with limited extrahepatic disease and median dose 40 GyRBE in 5 fractions (median biologically effective dose ¼ 72 Gy) using passively scattered beams, local control was 70.1% at 1 year.…”

“…However, there are technical challenges to effectively delivering ultrahypofractionated proton liver therapy, such as onboard imaging, motion management, and technology (scattered beams vs PBS) [5]. While respiratory management with deep breath-hold, gating, and compression is well-characterized in photon therapy, it is less well characterized in protons, even though geometric distortion is the predominant driver for poor proton conformality [9][10][11].…”

Clinical results of active scanning proton therapy for primary liver tumors

“…Before 2019, apart from several RT/PT planning comparisons confirming the dosimetric advantages of PT, 30–32 the only report comparing clinical outcomes among photon-based RT and PT in the treatment of HCC was the meta-analysis published by Qi et al in 2015. 33 The authors analyzed the clinical results published on charged particles (including PT and carbon ions), SBRT, and 3D conformal RT (CRT) between 1993 and 2014.…”

Proton Therapy in the Management of Hepatocellular Carcinoma

“…The proton plans spared the normal liver to a greater degree and decreased the mean liver dose compared to photons plans (8.4 vs. 12.2 Gy, p = 0.01) only for tumors located at the dome or in central locations with diameters of 3 cm and above. In a later study, the researchers included even larger tumors (up to 10 cm) and were able to show that stereotactic body proton therapy (SBPT) plans maintained an adequate target coverage and OAR sparing up to a tumor diameter of 9 cm (vs. 7 cm for photon stereotactic body radiation therapy (SBRT)) [ 14 ]. This translates into a lower liver normal tissue complication probability for SBPT plans in cases of larger lesions, particularly if they are located centrally or in the dome of the liver.…”