Predicting dose response to prostate cancer radiotherapy: validation of a radiation signature in the randomized phase III NRG/RTOG 0126 and SAKK 09/10 trials.
A Dal Pra, P Ghadjar, H M Ryu, J A Proudfoot, S Hayoz, J M Michalski, D E Spratt, Y Liu, C Schär, A M Berlin, D R Zwahlen, J P Simko, T Hölscher, J A Efstathiou, B Polat, H M Sandler, G Hildebrandt, M B Parliament, A-C Mueller, I S Dayes, L Plasswilm, R J M Correa, J M Robertson, T G Karrison, E Davicioni, W A Hall, F Y Feng, A Pollack, G N Thalmann, P L Nguyen, D M Aebersold, P T Tran, S G Zhao
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引用次数: 0
Abstract
Background: The SAKK 09/10 trial randomized biochemically recurrent prostate cancer patients to salvage radiation 64 Gy versus 70 Gy, and the NRG/RTOG 0126 randomized intermediate-risk prostate cancer patients to definitive radiation 70.2 Gy versus 79.2 Gy. We investigated a previously developed Post-Operative Radiation Therapy Outcomes Score (PORTOS) to identify preferential benefit from radiation dose escalation (DE).
Materials and methods: PORTOS was evaluated in patients enrolled in SAKK 09/10 and NRG/RTOG 0126 with available tissue that passed quality control (n = 226, 215). PORTOS was evaluated in the published post-operative groups in SAKK 09/10 and in tertiles in NRG/RTOG 0126 as cut-offs had not been established for biopsy samples and definitive radiation patients. Clinical and molecular correlates in a real-world dataset of 42 407 prostatectomy and 31 107 biopsy samples were also analyzed.
Results: In SAKK 09/10, the biomarker-treatment interaction was statistically significant between PORTOS (lower versus higher) and treatment arm for clinical progression-free survival. Only patients in the higher PORTOS group benefited from DE. In NRG/RTOG 0126, in patients with a lower tertile PORTOS, there was no difference in Phoenix biochemical failure (BF). However, for patients in the average and higher tertile PORTOS range, there was a significant benefit for DE for Phoenix BF. An interaction test indicated a significant difference in benefit for DE between higher and lower PORTOS groups. PORTOS was not strongly associated with clinicopathological variables in either trial or the large real-world dataset. In the latter, PORTOS was modestly associated with hypoxia signatures and strongly associated with immune signatures and subtypes.
Conclusion: In the SAKK 09/10 and RTOG 0126 randomized controlled trials, we demonstrated that PORTOS can potentially identify a subset of patients who benefit from DE, a subgroup that cannot be identified using clinicopathological or prognostic variables. These results suggest that PORTOS could be used clinically as a predictor of radiation response.
期刊介绍：
Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine.
The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings.
Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.
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