Overall survival prediction in metastatic castration-resistant prostate cancer treated with radium-223

ABSTRACT Objective Radium-223(223Ra) is indicated for patients (p) with metastatic castration resistant prostate cancer (mCRCP). Objectives The aim of this study was to evaluate the role of baseline clinical variables associated with overall survival (OS) and toxicity of 223Ra. Its purpose was to identify the factors that can predict a better response to treatment and provide information regarding the most appropriate time for the application of 223Ra. Materials and Methods Prospective study in 40p with mCRPC treated with 223Ra. End points were OS, progression-free survival and time to progression. The follow-up parameters were: doses received, hemoglobin (Hb), absolute neutrophil count (ANC), platelet count (PC), prostate specific antigen (PSA), alkaline phosphatase (ALP), Visual Analogue Scale for pain, Eastern Cooperative Oncology Group (ECOG) and WHO's Cancer Pain Ladder. The use of other treatments was also evaluated. Results Median OS was 17.1 months(mo) (CI95%6.5-27.7); 26/40p received complete treatment of 223Ra, without reaching a median OS and 14p received incomplete treatment with a median OS 13.6mo(CI95%1.6-25.6). Median follow-up was 11.2mo (range:1.3-45.2). The univariate analysis showed that factors as VAS, ECOG, Hb and ALP values were independently associated with OS. First line treatment with 223Ra was started in 11/40p, while 19p had been heavily pre-treated and 13p received concomitant treatment. Conclusions 223Ra therapy require an adequate selection of patients to obtain the greatest clinical benefit. Low basal Hb, hight basal ALP, bone marrow involvement and an altered ECOG were the main factors that decreased OS in our patients. 223Ra should be considered relatively early in the course of treatment.

Current Status and Growth of Nuclear Theranostics in Singapore / 대한핵의학회잡지

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

Metastatic castration-resistant prostate cancer and the challenge of a patient with chronic kidney disease in hemodialysis

At a time when the population shows increasing longevity, entities such as cancer and chronic kidney disease (CKD) are more frequently connected. In the United States, approximately 6% of the patients on hemodialysis have cancer. The challenge to manage oncologic patients with CKD in a hemodialytic program represents a great shortage of available information on the choice of the best drug, timing, dosage adjustments, dialysis method, and treatment safety. We present the case of a patient with prostate cancer and terminal CKD in hemodialysis, and the treatment sequence after the development of resistance to hormonal blockade therapy, which included docetaxel, enzalutamide, and radium-223.

Bone-targeted therapies to reduce skeletal morbidity in prostate cancer / 亚洲男科学杂志(英文版)

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

Radium-223 for the treatment of bone metastasis of prostate cancer / 中华男科学杂志

Over 80% of the patients with prostate cancer (PCa) develop bone metastasis, which seriously affects the patients' quality of life and remains a major cause of morbidity. Radium-223 (Ra-223), a newly approved agent targeting bone metastasis of PCa, can improve the quality of life and prolong the overall survival of the PCa patients with bone metastasis. This article presents an overview of the clinical trials recently published on the management of bone metastasis of PCa with Ra-223.

An updated review of case–control studies of lung cancer and indoor radon-Is indoor radon the risk factor for lung cancer?

Lung cancer is a leading cause of cancer-related death in the world. Smoking is definitely the most important risk factor for lung cancer. Radon (222Rn) is a natural gas produced from radium (226Ra) in the decay series of uranium (238U). Radon exposure is the second most common cause of lung cancer and the first risk factor for lung cancer in never-smokers. Case–control studies have provided epidemiological evidence of the causative relationship between indoor radon exposure and lung cancer. Twenty-four case–control study papers were found by our search strategy from the PubMed database. Among them, seven studies showed that indoor radon has a statistically significant association with lung cancer. The studies performed in radon-prone areas showed a more positive association between radon and lung cancer. Reviewed papers had inconsistent results on the dose–response relationship between indoor radon and lung cancer risk. Further refined case–control studies will be required to evaluate the relationship between radon and lung cancer. Sufficient study sample size, proper interview methods, valid and precise indoor radon measurement, wide range of indoor radon, and appropriate control of confounders such as smoking status should be considered in further case–control studies.

The Trend of Leprosy Treatment / 나학회지

Since Mycobacterium Leprae was founded by Dr. Armauer Hansen in 1873, leprosy was proven to infectious disease by a germ not from hereditaty, from a cause, or from sin. For it has no definite method of treatment, made a conclusion at the 1st international leprosy association meeting at Berlin in 1897, isolation is the only way to prevent the disease. So all country started to built a leprosarium and isolated the leprosy patients. Various methods and drugs were used for leprosy treatment including potassium iodide, arsenic, antimony, copper, sera, vaccines and aniline dyes and then X-ray, radium, electric current till 1925. Chaulmoogra oil was introduced to western world in 1854 by Dr. FJ Mouat and used for the leprosy treatment drug. Dr RM Wilson in Kwangju Leprosy Hospital started to use Chaulmoogra oil since 1909 and reported the results of it at JAMA in 1923. But it was replaced to sulfones in 1940'. Mordern treatment started in 1937 when Parke-Davis co. synthesized promin But promin is expensive and have to injection. Then Dapsone delivered from promin and it could be used per oral. Dr. RM Wilson In Aeyang Hospsoital (former Kwangju leposy hospial) started to use Dapson in 1946 with his son Dr. J Wilson. And it was the first episode to use DDS in Korea. When Dr. Cochraine came and visited all the leprosy centers in Korea in 1955 he noticed that some hospital like Aeyangwon and St. Nazarus used DDS but not other hospital. DDS was adopted as main drug of choice in Carville, Loisiana but noticed dapsone resistant bacilli and then WHO recommended the MDT from 1981.

Determination of 226Ra concentration in bottled mineral water and assessment of effective doses, a survey in Turkey

There is a rapid increase worldwide in the consumption of mineral waters which may contain different level of radioactive elements, especially [226]Ra, in addition to varying amounts of beneficial salts. Therefore, a comprehensive study was planned and carried out in order to determine concentration of [226] Ra natural radionuclide in bottled mineral waters that commercially available in Marmara Region of Turkey. The method used for [226] Ra concentration analysis bases on the measurement of Radon [[222] Rn] coming from [226] Ra dissolved in the water. The measurements were performed using RAD 7, a solid state alpha detector, with RAD H2O accessory manufactured by DURRIDGE COMPANY Inc. The [226] Ra concentration in mineral waters was found to vary from <0.074 to 0.625 Bql[-1] with an average value of 0.267 Bql[-1].The committed effective doses due to ingestion of 226Ra from the one year consumption of these waters were estimated to range from 10.8 to 90 microSvy[-1], from 9 to 75 microSvy[-1] and from 3.15 to 26.25 microSvy[-1], for infants, children and adults, respectively. The results obtained in this study indicate that the committed effective doses are below the WHO [World Health Organization] recommended reference level of 100 microSvy[-1]

Assessment of dose due to natural radio-nuclides in vegetables of high background radiation area in south-eastern part of Bangladesh

The aims of the study are to determine the radioactivity concentrations of [226]Ra, [238]U, [232]Th and [40]K in vegetables of a recently found high background radiation area of south-eastern part of Bangladesh and to detect the radiological risks to human from intake of these vegetables. 10 plant samples were collected randomly from different locations of the study area. The radio-nuclides in papaya were measured by direct gamma-ray spectrometry using HPGe detector. The average activity concentrations of [226]Ra, [238]U, 232Th and [40]K in papaya samples were 80.95 +/- 13.61, 64.77 +/- 38.47, 83.53 +/- 20.50 and 1691.45 +/- 244.98 Bq kg[-1] respectively. The annual effective ingestion dose due to intake of papaya was 1.1 mSv Y[-1]. The concentrations of radio-nuclides in the papaya samples found in present study were higher than the world average values suggested by the UNSCEAR. The annual effective ingestion dose was found 3.8 times higher than total exposure per person resulting from the ingestion of terrestrial radioisotopes

Measurement of [226]Ra, [232]Th, [137]Cs and [40]K activities of wheat and corn products in Ilam province - Iran and resultant annual ingestion radiation dose

Natural background radiation is the main source of human exposure to radioactive material. Soils naturally have radioactive mineral contents. The aim of this study is to determine natural [[238] U, [232] Th, [40] K] and artificial [[137] Cs] radioactivity levels in wheat and corn fields of Eilam province. HPGe detector was used to measure the concentration activity of [238]U and [232]Th, [40] K and [137] Cs in wheat and corn samples taken from different regions of Eilam province, in Iran. In wheat and corn samples, the average activity concentrations of [226] Ra, [232] Th, [40]K and [137] Cs were found to be 1,67, 0.5, 91.73, 0.01 and 0.81, 0.85, 101.52, 0.07Bp/ kg [dry weight], respectively. H[ex] and H[in] in the present work are lower than 1. The average value of H[ex] was found to be 0.02 and 0.025 and average value of H[in] to be found 0.025 and 0.027 in wheat fields samples and corn samples in Eilam provinces, respectively. The obtained values of AGDE are 30.49 mSv/ yr for wheat filed samples and 37.89 mSv/ yr for corn samples; the AEDE rate values are 5.28 mSv/yr in wheat filed samples and this average value was found to be 6.13 mSv/yr in corn samples in Eilam. Transfer factors [TFs] of long lived radionuclide such as [137]Cs, [226]Ra, [232] Th and [40]K from soils to corn and wheat plants have been studied by radiotracer experiments. The natural radioactivity levels in Eilam province are not at the range of high risk of morbidity and are under international standards

Activity concentrations of [232]Th, [226]Ra and [40]K and gamma radiation absorbed dose rate levels in farm soil for the production of different brands of cigarette tobacco smoked in Nigeria

Presently, the British-American Tobacco Company [BAT] located in Ibadan, Oyo State is the only tobacco producing company in Nigeria accounting for about nine different brands of cigarette tobacco smoked in the country. The tobacco leaves are produced from some farmlands located in Oke-Ogun area of Ibadan where special fertilizers are used for the growing of the tobacco leaves. The use of this fertilizer may enhance natural radionuclide contents in the farm soils and through root uptake be accumulated in the leaves. In this study, soil samples from three farmlands used for the production of the tobacco leaves were collected in order to determine the activity concentrations of [226]Ra, [232]Th and [40]K in the farm soil. Measurements for the determination of the activity concentrations were carried out using gamma-ray spectrometry comprising a lead-shielded 76 mm _ 76 mm NaI[Tl] detector crystal [Model 802 series, Bicron Nal] coupled to a Canberra series 10 plus multichannel analyzer [MCA] [model 1104] through an preamplifier base. Results of measurements showed that the average activity concentrations of the natural radionuclides in the soil samples across the three farms varied from 2550.4 +/- 154.6 to 3208.9 +/- 188.7 Bq kg[-1] for [40]K, 33.1 +/- 11.9 to 39.9 +/- 9.3 Bq kg[-1] for [226]Ra, while for [232]Th it varied between 51.98 +/- 8.4 and 56.08 +/- 17.51 Bq kg[-1]. The activity concentrations of these radionuclides and gamma absorbed dose rates due to the concentration of these radionuclides were found to be higher than world average values while those of the control farm values were lower to world averages and the tobacco leaf farms. From the results obtained the fertilizer type used on the farmlands for the tobacco leaf production was very rich in [40]K with typical values greater 2000 Bq kg-[1]. Also there may be possible high signatures of [210]Pb and [210]Po in the tobacco leaves and the cigarette samples smoked in the country. This is a subject for future research consideration given the fact that alpha radiation plays a major role in the etiology of lung cancer

Radium and Radon exhalation studies of soil

Everyone is exposed to radon because it is present everywhere with varying concentrations. Radon and its progeny are well established as lung carcinogenic. Track etch technique using LR-115 plastic track detectors has been used to measure the effective radium content and radon exhalation rates in soil samples collected from urban area of Etah district of Uttar Pradesh province in Northern India. The values of effective radium content are found to vary from 27.87 to 45.14 Bq.kg-[1] with a mean value of 34.98 Bq.kg-[1]. The mass exhalation rates of radon vary from 2.38 _ 10[-6] to 3.86 _ 10[-6] Bq.kg[-1].d[-1] with a mean value of 2.99 _ 10-6 Bq.kg[-1].d[-1]. The surface exhalation rates of radon have been found to vary from 6.19 _ 10[-5] to 10.03 _ 10[-5] Bq.m [-2].d[-1] with a mean value of 7.77 _ 10[-5] Bq.m [-2].d[-1]. Radon exhalation study is important for understanding the relative contribution of the material to the total radon concentration found inside the dwellings. The values of radium and radon exhalation rates are found to be below the safe limit recommended by OECD, 1979

Studying the natural radioactivity in some tobacco cigarettes imported to Iraq from unknown origins

Natural radioactivity isotope in ten tobacco leaf samples presented in different cigarettes imported to Iraq from unknown origins, were determined by gamma-ray spectrophotometer. The study revealed several naturally occurring radionuclides in these samples. Such isotopes were "Bi-214" which belongs to U-238 series and; "Pb-212, Bi-212, Ac-228" which belongs to Th-232 series, and K-40. Furthermore, the results show that the maximum concentrations of Pb-212, Bi-214, Bi-212, Ac-228 and K-40 radionuclides were [9.13, 59.08, 17.15, 3.1 and 102.61 Bq/Kg]. Such radioactive isotopes were respectively detected in Bisnuse club, Grip, again Bisnuse club, Najema and pin cigarette type. It is concluded from the results that Iraqi cigarettes are heavily contaminated with several radioactive isotopes. This may be reflected as a major health impact among Iraqi populations

Effect of high dose natural lonizing radiation on the immune system of the exposed residents of Ramsar town, Iran

Iran is one of several countries that has regions of high dose natural ionizing radiation. Two wellknown villages in the suburb of Ramsar Town in the Caspian Sea strip, Taleshmahaleh and Chaparsar, have background radiation that is 13 times higher than normal. This radiation is the result of Radium 226 and Radon gas both of which are highly water soluble. While people living in these regions do not suffer from any major health problems, we decided to study their immune responses to infection and inflammation in order to determine if their habitat affects their immune defense mechanisms as a way of compensating for their exposure to high dose environmental ionizing radiation. Our results showed that the total serum antioxidant level in the exposed people was significantly lower than the individuals not exposed to high dose natural ionizing radiation. The exposed individuals also had higher lymphocyte-induced IL-4 and IL-10 production, and lower IL-2 and IFN-gamma production. In addition, neutrophil NBT, phagocytosis, and locomotion were higher in the exposed group. In contrast, lymphocyte proliferation in response to PHA was unaffected. We conclude that the immune system of individuals exposed to high dose ionizing radiation has adapted to its environment by shifting from a Type 1 to a Type 2 response to promote antiinflammation. This may be because inflammatory Type 1 responses generate more free radicals than Type 2 responses, in addition to the free radicals generated as a result of high environmental radiation. Thus, the serum total antioxidant level in the exposed residents was lower than the unexposed group

radio nuclides in piping drinking water, cultivated soil and consumed food material from Zahedan city

The ionizing radiation can affect the human health and the life of other organizes living things in short time, especially when the dose of radiation exceed the ICRP standard. The amount and type of radioactive matter were not known in water, soil and food products of Zahedan. Therefore this study was aimed to survey the safety of such materials for the human being. Five different places in Zahedan city were chosen for sampling from water, soil and food materials and concentration and type of radionuclide were determined. Sieving, drying and mix Turing were amongst the method utilized for suitable preparation of the materials. The results show no existence of any artificial radio nuclides. However there were some natural radionuclides such as K-40, U238, Th232 and Ra226 in different dosages in the examined samples. The study confirmed that there is no risk of radio nuclides exposure with regard to the soil, water and food materials in Zahedan

Radium-contaminated water: a risk factor for cancer of the upper digestive tract.

There is a high incidence of oral, pharynx and esophagus cancer among males in Na Mom district in Songkhla Province in Thailand, an area where radium concentration in shallow well water is found to be higher than other areas in this province. A population-based case control study was conducted from June to November 2004 to determine the association of oral exposure to radium-contaminated water and cancer of the upper digestive tract in the district.Thirty-two confirmed cases and 128 sex and five-year birth cohort matched neighborhood controls were selected by multistage sampling from six villages in four sub-districts. All subjects were verified to have been permanent residents in the district for more than 10 years. Thirty cases were dead at the time of the study, thus their relatives were interviewed to determine their amount of water drinking, tobacco smoking, alcohol drinking, betel chewing and exposure to other potential risk factors in the past. The other two cases and all controls were directly interviewed.The concentration of radium in shallow well water at the subject's houses was estimated using a contour map of Ra-226 in the water at the location of their residence. The results showed a strong and dose-dependent associationb etween consumption of radium-contaminated shallow well water and cancer of the upper digestive tract. In multivariate analysis controlled for important risk factors of the cancer, the odds ratios for exposure to oral radium consumption 50-100 mBq/day and >100 mBq/day compared with <50 mBq/day were 2.83 (95% CI: 0.50-16.19) and 29.76 (95% CI: 4.39-201.6) respectively. The risk also increased with consumption of fresh water fish which might have been contaminated by dissolved radium in the water. This study offers the first evidence of the association between radium and cancer of the upper digestive tract to the world literature. Further studies with other methods such as area-wide correlation of radium-uranium concentration and the incidence of the cancer and case-control studies in other populations are needed to confirm the evidence.

Alpha radioactivity in Indian cement samples

The essential constituents of cements like lime, silica and alumina are derived from earth's crust in which radioactive elements like uranium, thorium etc are also present in varying amounts almost everywhere. These two elements are considered as the parent elements of uranium and thorium radioactive decay series in which radon and thoron are produced respectively as decay products. In the present study the samples of ordinary Portland cement [OPC], Portland pozzolana cement [PPC] and some other cementious finishing materials like white cement, Plaster of Paris [POP], cement putty etc were collected and analysed for radium and radon concentrations along with radon exhalation rates. Alpha sensitive LR-115 Type II plastic track detectors commonly known as "Solid State Nuclear Track Detectors" were used to measure the radium and radon concentration. The alpha particles emitted from the radon causes the radiation damaged tracks. The Chemical etching in NaOH at 60°C for about 90 minutes was done to reveal these latent tracks, which were then scanned and counted by an optical microscope of suitable magnification. By calculating the track density of registered tracks, the radon and radium concentrations along with exhalation rate of radon, were determined using required formulae. The radon and radium concentration in various brands of cements found to vary from 333 +/- 9.9 to 506 +/- 13.3 Bq m[-3] and from 3.7 +/- 0.1 to 5.6 +/- 0.2 Bq kg[-1] while in various cementious finishing materials used in the construction, these were found to vary from 378 +/- 19.7 to 550 +/- 9.8 Bq m[-3] and from 4.2 +/- 0.2 to 6.1 +/- 0.1 Bq Kg[-1], respectively. Based on the data the mass and surface exhalation rates were also calculated. The measurements indicate that there is marginal variation of the concentration of radium and radon in various brands of cements in India with lower levels in the cement samples having red oxide and higher levels in fly ash based cement samples but overall concentration levels of radon and radium are lower than that of average global values

Marie Curie, una gran científica, una gran mujer / Marie Curie, a great scientist, a great women

Marie Curie y su esposo Pierre, fueron los descubridores de la radioactividad, junto a los elementos polonio y radio. Marie dedicó más de treinta y cinco años de su carrera científica al estudio de esta entidad. Con tenacidad y esfuerzo logró destacarse en una época donde el machismo y la xenofobia estaban presentes en todas partes. Por sus méritos, fue la primera persona en recibir dos premios Nobel: el de Física en 1903 y el de Química en 1911. Para los autores de esta publicación es un orgullo traer nuevamente a la luz la vida y obra de esta extraordinaria mujer.

Uranium, radium and radon exhalation studies in geological samples belonging to some areas of punjab, using track etching technique.

With a view to prospect the uranium, radium and radon concentration and related health risk assessments in areas of Muktsar and Ferozepur districts in Punjab, the fission track registration technique has been used for the analysis of water and soil samples. Uranium content in water ranged from 5.47 to 10.19 microg/l(-1) and 6.28 to 11.74 microg/l(-1) for Muktsar and Ferozepur respectively. Uranium content in soil samples of Muktsar and Ferozepur ranged from 1.14 to 1.90 mg/kg(-1) and 1.26 to 2.44 mg/kg(-1) respectively. Radium concentration in these soil samples has been found to vary from 3.97 to 15.94 bq/kg(-1) and 7.24 to 24.14 bq/kg(-1) for Muktsar and Ferozepur respectively. The radon exhalation values were calculated in terms of area (E(A)) and mass (E(M)). The values of E(M) ranged from 4.9 to 20.6 (mbqkg(-1) hr(-1)) for Muktsar and 9.4 to 31.3 (mbqkg(-1)hr(-1)) for Ferozepur and values of E(A) ranged from 173 to 728 (mbqm(-2)hr(-1)) for Muktsar and 330 to 1102 (mbqm(-2)hr(-1)) for Ferozepur district. These values in general are low and not significant from health hazard point of view. The values of uranium concentration in water samples of these areas are lower than those reported for soil and water samples of Himachal Pradesh. These values are also lower than those reported by Singh et al. for the rocks belonging to uranium and copper mines of Bihar.