50-Gy Stereotactic Body Radiation Therapy to the Dominant Intraprostatic Nodule: Results From a Phase 1a/b Trial.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_8A5A6B3310C5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
50-Gy Stereotactic Body Radiation Therapy to the Dominant Intraprostatic Nodule: Results From a Phase 1a/b Trial.
Périodique
International journal of radiation oncology, biology, physics
Auteur(s)
Herrera F.G., Valerio M., Berthold D., Tawadros T., Meuwly J.Y., Vallet V., Baumgartner P., Thierry A.C., De Bari B., Jichlinski P., Kandalaft L., Coukos G., Harari A., Bourhis J.
ISSN
1879-355X (Electronic)
ISSN-L
0360-3016
Statut éditorial
Publié
Date de publication
01/02/2019
Peer-reviewed
Oui
Volume
103
Numéro
2
Pages
320-334
Langue
anglais
Notes
Publication types: Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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 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.
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).
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.
Mots-clé
Aged, Aged, 80 and over, Disease Progression, Dose Fractionation, Radiation, Humans, Immune System, Magnetic Resonance Imaging, Male, Maximum Tolerated Dose, 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
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/10/2018 12:50
Dernière modification de la notice
20/08/2019 15:49
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