Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

Lymph node metastases and elevated postoperative calcitonin: Predictors of poor survival in medullary thyroid carcinoma.

Background Total thyroidectomy is the treatment of choice for medullary thyroid carcinoma (MTC), but the extent of neck dissection is controversial. Lymph node metastases, distant metastases, and old age are known predictors of poor survival. Patients Patients treated for primary MTC at Helsinki University Hospital from 1990 to 2009 were included (n = 54). Their clinical characteristics, treatment, and outcome were analysed retrospectively, these patients were followed until death or their last follow-up date. Results At last follow-up (3.4-23 years), of 54 MTC patients, 19 (35%) were disease-free, 17 (32%) were alive with disease, and 12 (22%) had died of MTC; six patients died of unrelated causes (11%). All disease-free patients were node negative and had normal postoperative calcitonin level. Of 19 disease-free patients, only four (21%) had undergone lymph node dissection. All patients who died of MTC were Stage IV at diagnosis and died with distant metastases. Disease-specific five-and 10-year survival was 84% and 76.2%. Advanced T-stage (p = 0.004), lymph node metastases (p < 0.001), distant metastases (p < 0.001), stage (p < 0.001), and elevated postoperative calcitonin (p < 0.001) significantly associated with survival. Conclusions Lymph node metastasis and elevated postoperative calcitonin are important prognostic factors. Patients with lymph node metastasis and/or elevated postoperative calcitonin with present treatments cannot become disease-free, but most of them can live a long life with metastasis.

[The treatment of adult glioma is multiphasic]. / Gliooma kuriin. Aikuisten gliooman hoito on monivaiheista.

The prognosis of glioma has improved. Even patients with glioblastoma surviving over two years is not rare. The quality of life has improved because of earlier diagnosis and more precise surgical and radiotherapy techniques. In grade 3-4 gliomas treatment modalities are combined. In grade 2 there are several options for postoperative treatment. Recurrencies are treated actively irrespective of the initial histological grade of the tumor. Chemotherapy is used both combined with radiotherapy and as a single treatment at recurrence. The best results are achieved with close co-operation among different specialities in neuro-oncology, most effectively in weekly meetings. Fluent flow of information between health care units promotes the best quality of life for glioma patients.

[Follow-up of papillary and follicular thyroid cancer--when and where?]. / Papillaarisen ja follikulaarisen kilpirauhas- syövän seuranta--mitä ja missä?

While papillary and follicular thyroid cancer usually has an excellent prognosis, recurrent and aggressive forms of the disease do occur. The success of surgical excision and radioiodine therapy is evaluated by ultrasonography of the neck, and TSH-stimulated serum thyreoglobulin. Based on investigational results, the patients are divided into three groups: the cancer does not exist, may exist or remains. This classification determines the thyroxine dose and follow-up arrangements. In cancer-free patients, thyroxine therapy will be implemented as in ordinary hypothyreoidism. For others a thyroxine dose will be used that lowers the serum TSH below reference values.

Dosimetry software Hermes Internal Radiation Dosimetry: from quantitative image reconstruction to voxel-level absorbed dose distribution.

OBJECTIVE: The aim of this work is to validate a software package called Hermes Internal Radiation Dosimetry (HIRD) for internal dose assessment tailored for clinical practice. The software includes all the necessary steps to perform voxel-level absorbed dose calculations including quantitative reconstruction, image coregistration and volume of interest tools. METHODS: The basics of voxel-level dosimetry methods and implementations to HIRD software are reviewed. Then, HIRD is validated using simulated SPECT/CT data and data from Lu-DOTATATE-treated patients by comparing absorbed kidney doses with OLINDA/EXM-based dosimetry. In addition, electron and photon dose components are studied separately in an example patient case. RESULTS: The simulation study showed that HIRD can reproduce time-activity curves accurately and produce absorbed doses with less than 10% error for the kidneys, liver and spleen. From the patient data, the absorbed kidney doses calculated using HIRD and using OLINDA/EXM were highly correlated (Pearson's correlation coefficient, r=0.98). From Bland-Altman plot analysis, an average absorbed dose difference of -2% was found between the methods. In addition, we found that in Lu-DOTATATE-treated patients, photons can contribute over 10% of the kidney's total dose and is partly because of cross-irradiation from high-uptake lesions close to the kidneys. CONCLUSION: HIRD is a straightforward voxel-level internal dosimetry software. Its clinical utility was verified with simulated and clinical Lu-DOTATATE-treated patient data. Patient studies also showed that photon contribution towards the total dose can be relatively high and voxel-level dose calculations can be valuable in cases where the target organ is in close proximity to high-uptake organs.

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

INTRODUCTION: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. METHODS: Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. RESULTS: Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. CONCLUSION: Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

Low vs. high radioiodine activity to ablate the thyroid after thyroidectomy for cancer: a randomized study.

BACKGROUND: Radioactive iodine is commonly administered following thyroidectomy for differentiated thyroid carcinoma to ablate the thyroid remnant. The optimal administered activity of radioiodine is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Adult subjects (n = 160) diagnosed with papillary or follicular thyroid carcinoma were randomly allocated to receive either 1100 MBq (30 mCi) or 3700 MBq (100 mCi) activity of radioiodine ((131)I) following thyroidectomy. The study participants were prepared for ablation using thyroid hormone withdrawal. Ablation was considered successful when serum thyroglobulin concentration was less than 1 ng/mL and no uptake was present in (131)I scan. Ablation was successful following one administration of radioiodine in 42 (52%; 95% CI, 41% to 63%) of the 81 evaluable study participants who received 1100 MBq, and in 43 (56%, 45% to 67%) of the 77 subjects who received 3700 MBq activity (P = .61). There was no difference between the groups in the numbers of repeat radioiodine treatments needed to complete ablation (P = .27). The higher activity was associated with more nausea and taste disturbances, and a longer stay in a radioprotected isolation unit. None of the participants died from thyroid cancer during a median follow up of 51 months; three subjects in the 3700 MBq group and none in the 1100 MBq group were diagnosed with distant metastases during follow-up. In a meta-analysis of four randomized studies that compared the 1100 and 3700 MBq activities, the 1100 MBq activity tended to be associated with a higher risk of unsuccessful ablation (relative risk 1.148, 95% CI 0.974 to 1.353, P = .10). CONCLUSIONS/SIGNIFICANCE: The results provide no conclusive evidence that 3700 MBq activity is more effective for ablation of the thyroid remnant than 1100 MBq activity. The 3700 MBq activity is associated with more adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00115895.

Temozolomide treatment in glioma--experiences in two university hospitals in Finland.

Thirty-two patients with relapsing glioma were treated with temozolomide in two university hospitals in Finland. One patient (3%) had complete response and 9 (28%) partial response, with 8 patients (25%) showing stable disease. Median progression-free survival for these 18 patients (56%) was 7 months (range 2-11+). The remaining either had progressive disease (25%) or only clinical evaluation (19%). Karnofsky score improved in 34% of patients and decreased in 3%. Symptoms were alleviated in 44% and deteriorated in 9%. Grade 3-4 toxicity was detected in 9% of the patients. Only 4% of the days in treatment were spent in hospital. An average 1.8 neuroradiological investigations, 6.9 laboratory visits, and 5.3 visits to the oncologist were made. This study confirms that temozolomide has positive effects on the outcome of often heavily pretreated glioma patients. High drug costs are compensated by prolonged home care and even the possibility to maintain working capacity.