Increased toxicities associated with dose escalation of stereotactic body radiation therapy in prostate cancer: results from a phase I/II study.

Abstract

BACKGROUND:

This dose-escalation study evaluated the toxicity and efficacy of different stereotactic body radiation therapy (SBRT) doses for selecting an optimal dose for prostatic adenocarcinoma (PCa).

MATERIALS AND METHODS:

This clinical trial was registered at UMIN (UMIN000014328). Patients with low- or intermediate-risk PCa were equally assigned to 3 SBRT dose levels: 35, 37.5, and 40 Gy per 5 fractions. The primary endpoint was the occurrence rate of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) adverse events at 2 years, while the secondary endpoint was the 2-year biochemical relapse-free (bRF) rate. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events version 4.0.

RESULTS:

Seventy-five patients (median age, 70 years) were enrolled from March 2014 to January 2018, of whom 10 (15%) and 65 (85%) had low- and intermediate-risk PCa, respectively. The median follow-up time was 48 months. Twelve (16%) patients received neoadjuvant androgen deprivation therapy. The 2-year occurrence rates of grade 2 late GU and GI toxicities were 34 and 7% in all cohorts, respectively (35 Gy: 21 and 4%; 37.5 Gy: 40 and 14%; 40 Gy: 42 and 5%). The occurrence risk of GU toxicities significantly increased with dose escalation (p = 0.0256). Grades 2 and 3 acute GU toxicities were observed in 19 (25%) and 1 (1%), respectively. Grade 2 acute GI toxicity was observed in 8 (11%) patients. No grade ≥3 GI or ≥4 GU acute toxicity or grade ≥3 late toxicity was observed. Clinical recurrence was detected in 2 patients.

CONCLUSIONS:

An SBRT dose of 35 Gy per 5 fractions is less likely to cause adverse events in patients with PCa than 375- and 40-Gy SBRT doses. Higher doses of SBRT should be applied with caution.

• Authors: Takero Hirata, Osamu Suzuki, Keisuke Otani, Akimitsu Miyake, Keisuke Tamari, Yuji Seo, Fumiaki Isohashi, Naoki Kai, Koji Hatano, Kazutoshi Fujita, Motohide Uemura, Ryoichi Imamura, Setsuo Tamenaga, Yutaro Yoshino, Yasutoshi Fumimoto, Yasuo Yoshioka, Norio Nonomura, Kazuhiko Ogawa
• Journal: Acta oncologica (Stockholm, Sweden) (Acta Oncol) Vol. 62 Issue 5 Pg. 488-494 (May 2023) ISSN: 1651-226X [Electronic] England
• PMID: 37203203 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase I, Journal Article)

Chemical References

• Prostate-Specific Antigen
• Androgen Antagonists

Topics

• Male
• Humans
• Aged
• Prostatic Neoplasms (pathology)
• Prostate-Specific Antigen
• Radiosurgery (adverse effects, methods)
• Androgen Antagonists (adverse effects)
• Neoplasm Recurrence, Local (radiotherapy)
• Gastrointestinal Diseases (epidemiology, etiology)