Radium Treatment Research Articles

Increase of prostate-specific antigen doubling time predicts survival in metastatic castration-resistant prostate cancer patients undergoing radium therapy.

Radium-223 (Ra-223) is an important treatment modality for bone-dominant metastatic castration-resistant prostate cancer (mCRPC). However, there is currently a lack of effective markers to monitor treatment response during treatment. We aim to investigate the response in prostate-specific antigen doubling time (PSADT) as a potential marker for assessing Ra-223 treatment in mCRPC patients. We retrospectively collected data from mCRPC patients who underwent radium treatment at our institution between August 2020 and June 2023. Prostate-specific antigen (PSA) measurements prior to treatment and during treatment were collected. Baseline PSADT was calculated from PSA measurements prior to Ra-223 treatment; interim PSADT was calculated from PSA measurements before Ra-223 treatment and prior to the fourth course injection. Overall survival was calculated from the start of treatment to the date of death. Univariable and multivariable analysis using the Cox proportional hazards model were performed to examine the association of factors with overall survival. We included 35 patients from our institution, with a median overall survival of 13.3months. Eighteen (51.4%) completed all six courses of treatment. PSA dynamic response (interim PSADT > baseline PSADT or decreased PSA) was observed in 20 patients. Overall survival was associated with a PSA dynamic response (HR = 0.318, 95% CI 0.133-0.762, p = 0.010) when compared to patients without response. Dynamic changes in PSADT were associated with survival in mCRPC patients receiving radium therapy. Comparing interim and baseline PSADT could serve as a valuable marker for determining treatment benefits.

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

Radium (Ra)-223 is an established treatment option for patients with metastatic castrate-resistant prostate cancer (mCRPC) who have symptomatic bone metastases without soft tissue disease. Studies have indicated genetic aberrations that regulate DNA damage response (DDR) in prostate cancer can increase susceptibility to treatments such as poly ADP-ribose polymerase inhibitors and platinum-based therapies. This study aims to evaluate mCRPC response to Ra-223 stratified by tumor genomics. This is a retrospective study of mCRPC patients who received Ra-223 and genetic testing within the Mayo Clinic database (Arizona, Florida, and Minnesota) and Tulane Cancer Center. Patient demographics, genetic aberrations, treatment responses in terms of alkaline phosphatase (ALP) and prostate-specific antigen (PSA), and survival were assessed. Primary end points were ALP and PSA response. Secondary end points were progression-free survival (PFS) and overall survival (OS) from time of first radium treatment. One hundred and twenty-seven mCRPC patients treated with Ra-223 had germline and/or somatic genetic sequencing. The median age at time of diagnosis and Ra-223 treatment was 61.0 and 68.6 years, respectively. Seventy-nine (62.2%) had Gleason score ≥ 8 at time of diagnosis. 50.4% received prior docetaxel, and 12.6% received prior cabazitaxel. Notable alterations include TP53 (51.7%), BRCA 1/2 (15.0%), PTEN (13.4%), ATM (11.7%), TMPRSS2-ERG (8.2%), RB deletion (3.4%), and CDK12 (1.9%). There was no significant difference in ALP or PSA response among the different genetic aberrations. Patients with a TMPRSS2-ERG mutation exhibited a trend toward lower OS 15.4 months (95% confidence interval [CI] 10.0-NR) versus 26.8 months (95% CI 20.9-35.1). Patients with an RB deletion had a lower PFS 6.0 months (95% CI 1.28-NR) versus 9.0 months (95% CI 7.3-11.1) and a lower OS 13.9 months (95% CI 5.2-NR) versus 26.5 months (95% CI 19.8-33.8). Among mCRPC patients treated with Ra-223 at Mayo Clinic and Tulane Cancer Center, we did not find any clear negative predictors of biochemical response or survival to treatment. TMPRSS2-ERG and RB mutations were associated with a worse OS. Prospective studies and larger sample sizes are needed to determine the impact of genetic aberrations in response to Ra-223.

Utilization of Radium-223 in Metastatic Prostate Cancer Patients and Novel Prognostic Indicators In Radium-223 Patients

Radium-223 (R-223) is a radiopharmaceutical treatment approved for patients with metastatic castration resistant prostate cancer with symptomatic bony metastases. We sought to examine the utilization and patterns of care of this treatment at a large NCCN and NCI comprehensive cancer center. We also looked to examine predictors of survival after radium treatment in our dataset. A professionally curated, prospectively gathered institutional database was queried for prostate cancer patients treated with R-223 from 2013 to 2019. We analyzed this cohort for patterns of care including the time from initiation of systemic treatment to the initiation of R-223, the number and type of treatment courses prior to R-223 and the number of treatments following R-223. Kaplan Meier analyses and Cox proportional hazards modeling was used to examine an endpoint of overall survival (OS) from the time of administration of R-223 in sub-groups including those who received R-223 early in their treatment course, as well as those with high and low hemoglobin levels prior to R-223 administration. We identified 74 unique patients who were treated with R-223 over the study period at a single institution. The median OS for all patients following R-223 administration was 537 days. On average Radium-223 was initiated over four years following the initiation of the first systemic therapy (1508 days, range 183-6820 days). On average R-223 was the 5th systemic therapy course these patients received (range 2-11). We found that patients who received R-223 later in their treatment course, defined as the 4th systemic therapy or later, had an increased risk of death compared to those who received R-223 as an earlier line (HR 4.59 95% CI 1.36-15.42). Patients received an average of 0.64 systemic treatments following R-223 (range 0-5). For the majority of patients (n = 41, 55%) R-223 was the last treatment received. The most common treatments following R-223 were taxane chemotherapies (docetaxel, cabazitaxel) and antiandrogens (abiraterone, enzalutamide). We stratified patients based on pre-treatment hemoglobin levels and found that those with hemoglobin levels below the mean had a statistically increased risk of death (HR 1.99 95% CI 1.02-3.86). In our analysis of patterns of utilization of R-223 at a single NCCN and NCI member institution we found that R-223 tends to be utilized as a later line agent for patients with metastatic prostate cancer and is often one of the last treatments they receive. We also found that early receipt of R-223 and higher pre-treatment hemoglobin levels were correlated with better survival outcomes. Given these findings, and the favorable side-effect profile of radium-223 reported on the ALSYMPCA trial relative to the placebo group, consideration should be given to using R-223 early in the course of therapy for patients with metastatic prostate cancer with bone disease.

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.

Growing Academic Physiatry: The Impact of the Baruch's Grants on Harvard Medical School and Columbia College of Physicians and Surgeons. Part II.

Growing Academic Physiatry: The Impact of the Baruch's Grants on Harvard Medical School and Columbia College of Physicians and Surgeons. Part II.

Formation of radioactive waste in Estonian water treatment plants

In northern Estonia, higher levels of Ra-226 and Ra-228 concentrations give rise to problems with water treatment plants (WTPs) using Cambrian-Vendian (Cm-V) aquifer. During water treatment processes, radionuclides accumulate in the filter material to a level where the material could be classified as a radioactive material. In order to understand the scope of the problem, a nation-wide survey was carried out among the Cm-V fed treatment plants. Filter material and water samples were collected from 18 Estonian WTPs to analyse the activity concentration of Ra-226 and Ra-228 in filter materials and also the radium treatment efficiency was determined. Sixteen WTPs exceeded the exemption levels of 1 kBq * kg−1 set by the EC directive 2013/59/Euratom. The quantity of filter material exceeding the exemption levels was approximately 300 tons, average concentrations values for Ra-226, Ra-228 and Th-228 were, accordingly, 7.6 kBq * kg−1, 8.0 kBq * kg−1 and 5.6 kBq * kg−1. That includes WTPs not designed for radium removal. The results suggest a need to investigate further NORM generation in WTPs, as uncontrollable disposal of NORM may occur.

Genomic and phenotypic evidence for prostate cancer osteomimicry in circulating tumor cells from men with metastatic castration resistant prostate cancer (mCRPC) treated with radium-223.

160 Background: Radium-223 is a targeted alpha therapy that improves survival in men with mCRPC. The biologic basis for radium-223 efficacy is not completely understood. We hypothesized that PC osteomimicry, a form of epithelial plasticity leading to an osteoblastic phenotype, may contribute to the intralesional deposition of radium-223 and subsequent irradiation of the tumor microenvironment. Methods: We conducted a pharmacodynamic study of radium-223 in men with bone predominant mCRPC to investigate genomic and phenotypic alterations in circulating tumor cells (CTCs), ctDNA, and metastases. Prior to radium and 3 and 6 months after radium, liquid and metastatic biopsies were collected, including CTCs for phenotypic characterization and CTC/ctDNA genomic analysis. The primary objective was to describe the prevalence of CTC bone alkaline phosphatase (BAP) over time. We measured radium-223 decay products in tumor and surrounding normal bone during treatment. Results: We enrolled 20 men with heavily pre-treated symptomatic bone predominant mCRPC and treated with radium-223 over a median of 6 doses. 55% had elevated serum BAP. PFS was 5.5 mo; OS was 13.3 mo; 10% had unfavorable (≥5) to favorable ( < 5) Cellsearch CTC conversion; 5% had ≥30% PSA decline. We found evidence of persistent CTC BAP expression in both EpCAM+ and EpCAM- CTCs in the majority of men over time during radium treatment. We identified genomic gain of key osteomimicry regions in CTC DNA, including loci for BAP, osteopontin, and OB-cadherin. Radium-223 uptake was observed in tumor to a greater degree than surrounding normal bone. CTC DNA and matched ctDNA and CTC cultures suggested persistence of CTCs with aggressive genomic alterations such as AR, FOXA1, and MYC gain and PTEN and RB1 loss. We established multiple CTC cultures and one CTC PDX; cells exhibited evidence of epithelial plasticity with BAP expression. Conclusions: Osteomimicry may contribute to the uptake of Radium-223 within bone metastases and may thereby enhance the therapeutic benefit of radium-223. We found genomic and phenotypic evidence of osteomimicry in CTCs and CTC cultures from men with mCRPC. Clinical trial information: NCT02204943.

New dosimetry for childhood skin hemangioma treatments with 226Ra needles or tubes

BackgroundThe Stockholm Hemangioma Cohort is important for evaluation of late effects after exposure to ionizing radiation during childhood. Dose estimates in this cohort were based on both measurements and calculations using an old treatment planning system. MethodsWe compare previously published and calculated dose estimates with new ones, obtained by Monte Carlo simulations, which mimic the hemangioma treatments with 226Ra needles and tubes. The distances between the 226Ra sources and the thyroid and breasts, respectively, were reassessed. ResultThe Monte Carlo calculations showed significantly lower dose values than those obtained earlier. The differences depended both on the modeling of the sources and on further individualized distances from the sources. The mean value of the new calculated doses was 25% of the old breast doses and 46% of the old thyroid doses. ConclusionNew dosimetry for hemangioma treatments gives significantly lower organ doses for the few cases receiving the highest absorbed dose values. This implies that radiation risk estimates will increase and have to be recalculated. For retrospective studies it is now possible to calculate organ doses from radium treatments using modern treatment planning systems by modeling the source geometry carefully and apply the TG-43 formalism. It is important to be aware of the large uncertainties in calculated absorbed dose values.

Transient, Transverse Melanonychia Associated with Graves Disease and Acute Hepatitis

Melanonychia is a black, tan, or brown streak within the nail plate subsequent to activation of melanocytes in the nail matrix. We present a case of a Haitian girl who presented with transverse melanonychia involving all 10 fingernails in the setting of hyperthyroidism and acute liver injury. Melanonychia has been described only one time in the literature in the setting of hyperthyroidism though this patient also underwent radium treatment which could have led to nail changes.

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

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.

Oncological organizations and institutions in Poland before the Second World War

During the first four decades of the 20th century many oncological organizations and institutions were established in Poland. On 6 June, 1906 the Committee for Cancer Research and Control was founded. After the year 1918 when Poland regained its independence many more cancer control organizations came into being. The organizations created at that time were: the Polish Committee for Cancer Control (Warsaw 1921), the Cancer Control Society of Lódź (Lódź 1927), the Vilnius Committee for Cancer Control (Vilnius 1931), the Polish Cancer Control Institute Association in Lviv (Lviv 1929), the Polish Cancer Control Association (Warsaw 1938). These cancer control organizations undertook multiphase activities (prophylactic, educational, organizational, scientific and research) by creating outpatient and inpatient oncological care institutions, on which base numerous scientific and research papers were produced. The effect of that work was the creation of the Radium Treatment Institute in Lódź and the Research and Therapeutic Institute for Cancer Control in Vilnius, as well as founding oncological hospital wards and clinics. The most important achievement was building and opening the very modern Radium Institute in Warsaw. The initiator of the Institute, which in 1939 had 90 beds on its disposal, was Maria Skłodowska-Curie herself. Cancer control organizations members and activists conducted many propaganda actions on malignant diseases, shared they observations and research findings during meetings, conferences and assemblies in Poland and abroad.

Bilateral basal cell carcinoma of the lower eyelids following radium treatment for blepharitis

Bilateral basal cell carcinoma of the lower eyelids following radium treatment for blepharitis

The "Ineffable Freemasonry of Sex": Feminist Surgeons and the Establishment of Radiotherapy in Early Twentieth-Century Britain

In 1924 the London Committee of the Medical Women's Federation was instrumental in establishing a clinic for the purpose of investigating the radium treatment of cervical cancer. The scheme was later to evolve into a hospital, the Marie Curie, where adherence to the methods developed in Stockholm served to establish radiotherapy as an alternative to surgery in cancer of the cervix. This article examines the women's contribution in the light of feminist and professional struggles over the relative merits of surgery and radiotherapy. It argues that radiotherapy was an issue of special interest to women surgeons, not only because of the long history of feminist opposition to gynecological surgery, but also because it could widen women's access to the medical profession in the face of male exclusion from training posts and honorary appointments at voluntary hospitals.

Cancer of the tongue: Preliminary report on radium treatment

Cancer of the tongue: Preliminary report on radium treatment

II. Radium treatment of buccal carcinoma

Journal Article II. Radium treatment of buccal carcinoma Get access G E Birkett G E Birkett Honorary Radiolgist Manchester and District Radium Institute Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 17, Issue 67, January 1930, Pages 498–517, https://doi.org/10.1002/bjs.1800176715 Published: 06 December 2005

Measured dosage in the radium treatment of carcinoma of the urinary bladder

Measured dosage in the radium treatment of carcinoma of the urinary bladder

Interstitial radium treatment of carcinoma of the breast: Description of a radical technique

Journal Article Interstitial radium treatment of carcinoma of the breast: Description of a radical technique Get access R G Hutchison R G Hutchison Assistant Director Holt Radium Institute, Manchester Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 22, Issue 87, January 1935, Pages 465–474, https://doi.org/10.1002/bjs.1800228709 Published: 06 December 2005

Radium treatment of cancer. By Stanford Cade, F.R.C.S., Assistant Surgeon, and Joint Lecturer on Surgery and Teacher of Practical Surgery, Westminster Hospital. Royal 8vo. Pp. 158 + viii, with 49 illustrations and 13 coloured plates. 1929. London: J. & A. Churchill. 15s. net

Radium treatment of cancer. By Stanford Cade, F.R.C.S., Assistant Surgeon, and Joint Lecturer on Surgery and Teacher of Practical Surgery, Westminster Hospital. Royal 8vo. Pp. 158 + viii, with 49 illustrations and 13 coloured plates. 1929. London: J. & A. Churchill. 15s. net Get access Radium Treatment of Cancer. By StanfordCade, F.R.C.S., Assistant Surgeon, and Joint Lecturer on Surgery and Teacher of Practical Surgery, Westminster Hospital. Royal 8vo. Pp. 158 + viii, with 49 illustrations and 13 coloured plates. 1929. London: J. & A. Churchill. 15s. net. British Journal of Surgery, Volume 16, Issue 64, April 1929, Pages 704–705, https://doi.org/10.1002/bjs.1800166434 Published: 05 December 2005

The radium treatment of carcinoma of the breast

The radium treatment of carcinoma of the breast

Victor Bonney. The Gynaecological Surgeon of the Twentieth Century.

Chamberlain, G. Victor Bonney. The Gynaecological Surgeon of the Twentieth Century. 140 pages, figures. New York, London : The Parthenon Publishing Group , 2000 . Price GBP 19.95, USD 29.95 . We tend to forget or neglect the giants on whose shoulders we stand. Before reading the present biography about Victor Bonney, my only link to the name was through Bonney’s test in examination for stress incontinence, which never raised my curiosity enough to search for the man behind the name. Geoffrey Chamberlain has put the matter straight by giving a painstaking account of Bonney’s life and accomplishments, from his birth in Chelsea in 1872 until he died in 1953. Robert Shaw states in the Foreword that Bonney was indeed a leading, if not the fore most, gynecological surgeon of the first half of the twentieth century. As a young doctor he entered into gynecological surgery at Chelsea Hospital by coincidence, in 1899. The next year he trained in obstetrics at Queen Charlotte’s Hospital, and from there went steadily up the ladder, specializing in gynecological surgery and becoming a Hunterian professor at the Royal College of Surgeons at the age of 35. In 1905 Ernst Wertheim visited the United Kingdom and demonstrated his radical hysterectomy for cancer of the cervix, unfortunately with a fatal result, as the patient died of peritonitis three days later. In those days, before radium treatment for advanced stages of the disease was established, radical surgery remained the patients’ only hope of survival. Bonney took up the challenge and performed a series of radical hysterectomies with favorable results. Before the advent of modern anesthetics, antibiotics and blood transfusions, radical operations demanded much more surgical skill than today. He also became a proponent for conservative management of the myomatous uterus, doing myomectomies instead of removing the whole organ. His record was the removal of 234 fibroids from one uterus. This may have been an effect of his wife’s experience. Shortly after their wedding in 1905, she had a hysterectomy because of heavy bleeding, rendering the Bonney’s childless. Bonney deservedly achieved great fame as a gynecological surgeon, but ironically had the same experience as Wertheim had had in London, when a patient died on the operating table when he demonstrated his skills to colleagues on a tour to New Zealand in 1927. The moral of the story is left to the reader. Chamberlain gives a vivid account of Bonney’s private life: his obsession with motor cars in the early years of the twentieth century, devotion to opera, fondness of dancing, painting, friendship with others high and mighty like Rudyard Kipling, and his chain smoking, preferably of cigars. He wrote textbooks. The most famous of these, A Textbook of Gynaecological Surgery, appeared in 1911, and the 6th edition appeared in 1952. Bonney’s affiliation with the Royal College of Surgeons and his opposition to the foundation of the Royal College of Obstetricians and Gynaecologists is a recurring theme. He was clearly a man of conservative attitudes, who held his ground to the last minute and a bit beyond. The chapters are in chronological order, following world events. During the Second World War Bonney, who turned seventy in 1942, took on a locum gynecological post in Cheltenham for the duration of the war. He was then described as ‘a dapper little man, beautifully but quietly dressed with a double gold Albert across his waistcoat and carrying a gold-headed cane’. He charmed all the women (patients and nurses alike) by calling them ‘Darling’. Those of you who are curious to learn how the speciality of obstetrics and gynecology evolved and how surgery in the early years was its mainstay, will enjoy reading this book. It primarily addresses British readers, but as medicine is universal, it will appeal to all. It contains a set of photographs, mainly of the family album type. The binding of my copy was poor, pages loosened too easily.