This is another small-sample piece on radionuclides and Homologous Repair Defects. Dr. Sartor also made an additional comment on this piece right here. I'm hoping to see genetic profiling becoming a standard procedure for all cancer patients.
"TAKE-HOME MESSAGE
Somatic tumor and germline DNA testing are becoming more meaningful in the management of patients with advanced prostate cancer. This study evaluated the potential impact of germline or somatic homologous recombination deficiency (HRD) mutations on radium-223 efficacy in metastatic castrate-resistant prostate cancer (mCRPC) with bone metastasis. A total of 190 mCRPC patients for whom germline and/or somatic DNA sequencing data were available were reviewed. Of these patients, 28 had received standard-of-care radium-223 at a single center between 2013 and 2018. The authors found 36% of radium-223 patients had an HRD mutation (BRCA2 was the most prevalent). HRD-positive patients showed greater alkaline phosphatase response and a trend toward longer overall survival (median, 36.9 vs 19.0 months) compared with HRD-negative patients.
Based on these data, the authors suggest that patients who have inherited or acquired DNA repair gene mutations derive greater benefit from radium-223 compared with patients without these mutations.
– Gautam Jayram, MD"
And Dr. Sartor's comments:
"This is a small but important article that looks at the alpha-emitting bone-targeted radiopharmaceutical radium-223 in patients with or without homologous recombination repair deficiency mutations. The investigators found that individuals treated with radium who had a homologous recombination repair deficiency seemed to respond better, as measured by greater degrees of alkaline phosphatase response, longer time to alkaline phosphatase progression, and a trend toward longer survival.
It is limited by a relatively small sample size and they only had 10 men with homologous repair deficiency mutations. However, these data build upon previous publications, which suggest a similar increased efficacy in radium-treated patients with DNA repair mutations.
The implications are that DNA-damaging agents, in particular, alpha particles, may be preferentially effective in men with homologous recombination repair deficiencies and that in addition to PARP inhibitors and carboplatinum, the radiopharmaceuticals might be considered advantageous in this class of agents. There are case reports with PSMA targeted with tissue 177 that suggest similar findings and that’s probably more than enough, but that’s an interesting finding."
Help: Metastasized Castration Resistant Prostate Cancer!
Metastatic prostate cancer of bone and bone marrow
Can Radium 223 kill PCa in the prostate and can Docetaxel kill bone Mets?
