The impact of genetic mutations on response to radium-223 treatment for castration-resistant prostate cancer with bone metastases.

e17587 Background: Radium (Ra)-223 has become the cornerstone treatment in patients with metastatic castrate-resistant prostate cancer (mCRPC) with bone metastases. Ra-223 has been shown to suppress abnormal bone formation by inducing DNA double-strand breaks in tumor cells. This can reduce skeletal-related events, as well as improve survival and quality of life. Studies have indicated mutations that regulate DNA damage response in prostate cancer as susceptible to PARP inhibitors and platinum-based therapies. This study aims to evaluate mCRPC response to Ra-223 stratified by tumor genomics. Methods: This is a retrospective study of mCRPC patients who received Ra-223 and genetic testing within the Mayo Clinic database (Arizona, Florida, and Minnesota). Patient demographics, genetic mutations, treatment responses in terms of alkaline phosphatase (ALP) and prostate-specific antigen (PSA), and survival were assessed. Primary end points were progression-free survival (PFS) and overall survival (OS) from time of first radium treatment. Results: 239 mCRPC patients treated with Ra-223 were identified. Germline and/or somatic genetic sequencing was available in 50 patients, who had a median age of 61 years at time of diagnosis and 68 years at time of Ra-223 treatment. Median Gleason score at time of diagnosis was 8.0. 100% of patients received prior androgen deprivation therapy. 72% received prior docetaxel, and 18% received prior cabazitaxel. Notable mutations included TP53 (45.2%), TMPRSS2-ERG (28.6%), PTEN (26.2%), BRCA1/2 (14.3%), ATM (9.3%), CDK12 (7.1%), and Rb (4.9%). TMPRSS2-ERG was the second most commonly found mutation, with median OS 12.7 mo versus 15.4 mo in patients without TMPRSS2-ERG mutations (p = 0.099). In patients with CDK12 mutations (2 of 28 tested positive), PFS was 10.4 mo versus 5.6 mo in patients without CDK12 mutations (p = 0.157). The assessment of ALP and PSA response to radium treatment stratified by genetic mutation did not reach statistical significance. Conclusions: Among mCRPC patients treated with Ra-223 at Mayo Clinic, TMPRSS2-ERG was the second most commonly found genetic mutation and had observed worse survival outcomes that approached statistical significance. Prospective studies and increased sample sizes are needed to determine the impact of genetic mutations in response to Ra-223.

Sarcomatoid Tumor following Radium Treatment

Haemangiomas are benign skin lesions that usually regress spontaneously, but radiotherapy has previously been used to assist the regression and healing of the lesions. Radium and X-rays were used as a treatment for benign skin lesions such as haemangioma until the carcinogenic effect of ionising radiation in humans was described. We report a patient diagnosed with a sarcomatoid carcinoma. Her past history was of particular interest since she had received radium treatment for a haemangioma at the same location more than 70 years before.

Edgar Haydon (1859–1942): General practitioner and radium pioneer

Summary Edgar Haydon was a general practitioner in Newton Abbot, Devon, in the late 19th and early 20th centuries. He introduced radium therapy to the cottage hospital in this small market town in 1914 at a time when many cities lacked this facility. He raised funds for the building of a cancer wing and an extension to the hospital that were completed in 1927. This paper describes his fund-raising efforts, some of his cases and the way in which radium treatment influenced the number of cancers treated in the hospital. The hospital's records are fragmentary and leave many questions unanswered about the practicalities of radium treatment in those early years.

Feasibility of an Epidemiologic Study of Submariners Who Received Radium Irradiation Treatment

Thousands of World War II veterans reportedly received nasopharyngeal irradiation with radium-tipped applicators for treatment of middle ear pressure problems known as aerotitis media. Because of concerns about adverse health effects of radiation exposure, including the increased risk of head and neck cancer, the feasibility of identification of a large number of veterans with documented exposure for an epidemiologic study was investigated. The irradiation treatments were found to have occurred at the New London Naval Medical Research Department, at several Naval Hospitals, and aboard ships during the period from 1945 to 1952. Documentation of the treatment on veterans' medical records was sparse and inconsistent. Only 8 of 668 records reviewed were found to have evidence of the radium treatment: 7 from 33 self-reported veterans and 1 from 635 names on submarine school class rosters and submarine muster rolls. There appears to be no practical way to identify from military service and medical records a large number of submariners who received the treatment.