Proton beam therapy delivered using pencil beam scanning vs. passive scattering/uniform scanning for localized prostate cancer: Comparative toxicity analysis of PCG 001-09

Mark V Mishra; Rahul Khairnar; Søren M Bentzen; Gary Larson; Henry Tsai; Christopher Sinesi; Carlos Vargas; George Laramore; Carl Rossi; Lane Rosen; Mingyao Zhu; William Hartsell

doi:10.1016/j.ctro.2019.08.006

Proton beam therapy delivered using pencil beam scanning vs. passive scattering/uniform scanning for localized prostate cancer: Comparative toxicity analysis of PCG 001-09

Clin Transl Radiat Oncol. 2019 Aug 31:19:80-86. doi: 10.1016/j.ctro.2019.08.006. eCollection 2019 Nov.

Authors

Mark V Mishra¹, Rahul Khairnar², Søren M Bentzen³, Gary Larson⁴, Henry Tsai⁵, Christopher Sinesi⁶, Carlos Vargas⁷, George Laramore⁸, Carl Rossi⁹, Lane Rosen¹⁰, Mingyao Zhu¹, William Hartsell¹¹

Affiliations

¹ Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, United States.
² Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, MD, United States.
³ Department of Epidemiology & Public Health, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United States.
⁴ ProCure Proton Therapy Center, Oklahoma City, OK, United States.
⁵ ProCure Proton Therapy Center, Somerset, NJ, United States.
⁶ Hampton University Proton Therapy Institute, Hampton, VA, United States.
⁷ Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, AZ, United States.
⁸ University of Washington, Department of Radiation Oncology, Seattle, WA, United States.
⁹ California Protons Cancer Therapy Center, San Diego, CA, United States.
¹⁰ Willis-Knighton Proton Therapy Center, Shreveport, LA, United States.
¹¹ Northwestern Medicine Chicago Proton Center, Warrenville, IL, United States.

Abstract

Background and purpose: Patient-level benefits of proton beam therapy (PBT) relative to photon therapy for prostate cancer (PC) continue to be the focus of debate. Although trials comparing the two modalities are underway, most are being conducted using "conventional" PBT (passive scattering/uniform scanning [PS/US]) rather than pencil beam scanning (PBS). The dosimetric benefits of PBS are well-known, but comparative data are limited. This analysis compares PBS toxicity rates with those of PS/US in a prospective multicenter registry.

Methods: We evaluated acute/late gastrointestinal (GI) and genitourinary (GU) toxicity rates for men with low-to-intermediate risk PC enrolled in PCG 001-09. Acute toxicities with the two techniques were compared using χ² tests, and the cumulative incidence methods for late toxicity. Multivariable analyses (MVAs) for acute toxicity were performed using logistic regression, and cox proportional hazards models for late toxicity.

Results: Patients were treated using PS/US (n = 1105) or PBS (n = 238). Acute grade ≥2 GI toxicity in PBS did not significantly differ from that with PS/US (2.9% and 2.1%, respectively; P = 0.47). Acute grade ≥2 GU toxicity was significantly higher with PBS (21.9% and 15.1%; P < 0.01). In MVA, PBS was significantly associated with increased acute grade ≥2 GU toxicity (RR = 1.57, p < 0.001). Late grade ≥2 GI and GU toxicities did not differ significantly between groups.

Conclusions: This is the first multi-institutional comparative effectiveness evaluation of PBT techniques in PC. Differences in acute GU toxicity warrant further evaluation, and highlight the urgent need for prospective data using PBT.

Keywords: CTCAE, Common Terminology Criteria for Adverse Events; Comparative effectiveness, Toxicity; GI, gastrointestinal; GU, genitourinary; LET, linear energy transfer; MVA, multivariable analysis; PARTIQoL, Prostate Advanced Radiation Technologies Investigating Quality of Life; PBS, pencil beam scanning; PBT, proton beam therapy; PC, prostate cancer; PCG, Proton Collaborative Group; PS/US, passive scattering/uniform scanning; Passive scattering, uniform scanning; Pencil beam scanning; Prostate cancer; Proton therapy; RBE, relative biological effectiveness; RT, radiation therapy.