The survival outcomes for men with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination deficiencies (HRD) treated with radium-223: Princess Margaret Cancer Centre (PMCC) experience.
Bibliographic record
Abstract
179 Background: Radium-223 (223Ra) is a radiopharmaceutical that emits alpha particles and specifically targets bone metastases in mCRPC, where it has been shown to improve overall survival (OS). Since 223Ra induces double-strand DNA breaks, we hypothesized that patients with HRD may exhibit heightened sensitivity to 223Ra, resulting in improved survival outcomes compared to patients without HRD. Methods: This retrospective analysis was performed in men with mCRPC and bone metastases, with and without HRD, treated with 223Ra at PMCC. Demographics and disease characteristics were collected. Germline and/or somatic DNA sequencing data were identified. OS and progression free survival (PFS) were calculated using the Kaplan–Meier method; differences in outcomes were assessed using the log-rank test. Alkaline phosphatase (ALP) and prostate specific antigen (PSA) responses were calculated at 12 weeks post 223Ra treatment. Results: We identified 40 mCRPC patients who had germline and/or somatic DNA sequencing and received 223Ra between December 2015 and May 2022. The median age at the start of 223Ra was 76.5 (range: 66.5-80.8), and ECOG was 0/1 (75%). A total of 29 (72.5%) patients received 233 Ra following abiraterone or enzalutamide treatment while 10 (25%) received 233 Ra post docetaxel. Overall, 22 (54%) received ≥4 cycles of ²²³Ra. Median baseline PSA was 58.6 (range: 25.2-143) and median baseline ALP was 109 (range: 71.8-200). Germline/somatic HRD mutations were found in 9/40 (22.5%) patients (BRCA2 [n=6], CHEK2 [n=2], CDK12 [n=1]). Baseline characteristics were well balanced between HRD and non-HRD groups. With median follow up of 13.7 months, the median OS of HRD group vs. non-HRD group was 24 months (95%CI: 14-not evaluable [NE]) vs. 12 months (95%CI: 7-22); p=0.038). The median PFS of HRD group vs. non-HRD group was 5.7 months (95%CI: 3-NE) vs. 3.3 months (95%CI: 2.5-13.4); p=0.74). The median time to the next treatment of HRD group vs. non-HRD group was 4.2 months (95%CI: 3.1-NE) vs. 3.75 months (95%CI: 3.5-13.5); p=0.89. ALP response was 66.7% of HRD group vs. 58.1% of non-HRD group; p=0.72. PSA response was 33.3% of HRD group vs. 9.7% of non-HRD group; p=0.11. For all patients with ALP response, the three years survival probability of HRD group vs. non-HRD group was 33% vs. 11%; p=0.03. Conclusions: While the number of patients included in our review was small, our analysis suggested that patients with HRD may have a slight improvement in OS after 223Ra treatment. Validation in a prospective dataset is required, and whether HRD status has implications for other radiopharmaceuticals such as lutetium-177 remains to be seen.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".