50-Gy Stereotactic Body Radiation Therapy to the Dominant Intraprostatic Nodule: Results From a Phase 1a/b Trial
| Autor: | Jean Bourhis, Véronique Vallet, Jean-Yves Meuwly, Lana E. Kandalaft, Fernanda G. Herrera, Petra Baumgartner, Anne-Christine Thierry, Dominik Berthold, George Coukos, Patrice Jichlinski, Massimo Valerio, Alexandre Harari, Berardino De Bari, Thomas Tawadros |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Maximum Tolerated Dose medicine.medical_treatment T-Lymphocytes Urology Aged Aged 80 and over Disease Progression Dose Fractionation Radiation Humans Immune System Magnetic Resonance Imaging Middle Aged Prostate/radiation effects Prostate-Specific Antigen Prostatic Neoplasms/radiotherapy Quality of Life Radiometry Radiosurgery Radiotherapy Dosage Radiotherapy Planning Computer-Assisted Radiotherapy Intensity-Modulated T-Lymphocytes/immunology 030218 nuclear medicine & medical imaging 03 medical and health sciences Prostate cancer 0302 clinical medicine medicine Radiology Nuclear Medicine and imaging Radiation business.industry Dose fractionation Prostate Prostatic Neoplasms Common Terminology Criteria for Adverse Events medicine.disease Prostate-specific antigen Oncology Tolerability Prostatic acid phosphatase 030220 oncology & carcinogenesis International Prostate Symptom Score business |
| Zdroj: | International journal of radiation oncology, biology, physics, vol. 103, no. 2, pp. 320-334 |
| ISSN: | 1879-355X |
| Popis: | Purpose Although localized prostate cancer (PCa) is multifocal, the dominant intraprostatic nodule (DIN) is responsible for disease progression after radiation therapy. PCa expresses antigens that could be recognized by the immune system. We therefore hypothesized that stereotactic dose escalation to the DIN is safe, may increase local control, and may initiate tumor-specific immune responses. Patients and Methods Patients with localized PCa were treated with stereotactic extreme hypofractionated doses of 36.25 Gy in 5 fractions to the whole prostate while simultaneously escalating doses to the magnetic resonance image–visible DIN (45 Gy, 47.5 Gy, and 50 Gy in 5 fractions). The phase 1a part was designed to determine the recommended phase 1b dose in a “3 + 3” cohort-based, dose-escalation design. The primary endpoint was dose-limiting toxicities defined as ≥grade 3 gastrointestinal (GI) or genitourinary (GU) toxicity (or both) by National Cancer Institute Common Terminology Criteria for Adverse Events (version 4) up to 90 days after the first radiation fraction. The secondary endpoints were prostate-specific antigen kinetics, quality of life (QoL), and blood immunologic responses. Results Nine patients were treated in phase 1a. No dose-limiting toxicities were observed at either level, and therefore the maximum tolerated dose was not reached. Further characterization of tolerability, efficacy, and immunologic outcomes was conducted in the subsequent 11 patients irradiated at the highest dose level (50 Gy) in the phase 1b expansion cohort. Toxicity was 45% and 25% for grades 1 and 2 GU, and 20% and 5% for grades 1 and 2 GI, respectively. No grade 3 or worse toxicity was reported. The average (±standard error of the mean) of the QoL assessments at baseline and at 3-month posttreatment were 0.8 (±0.8) and 3.5 (±1.5) for the bowel (mean difference, 2.7; 95% confidence interval, 0.1-5), and 6.4 (±0.8) and 7.27 (±0.9) for the International Prostate Symptom Score (mean difference, 0.87; 95% confidence interval, 0.3-1.9), respectively. A subset of patients developed antigen-specific immune responses against prostate-specific membrane antigen (n = 2), prostatic acid phosphatase (n = 1), prostate stem cell antigen (n = 4), and prostate-specific antigen (n = 2). Conclusions Irradiation of the whole prostate with 36.25 Gy in 5 fractions and dose escalation to 50 Gy to the DIN was tolerable and determined as the recommended phase 1b dose. This treatment has promising antitumor activity, which will be confirmed by the ongoing phase 2 part. Preliminary QoL analysis showed minimal impact in GU, GI, and sexual domains. Stereotactic irradiation induced antigen-specific immune responses in a subset of patients. |
| Databáze: | OpenAIRE |
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