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Background. Pelvic irradiation to patients with prostate cancer is accompanied by urinary and intestinal reactions. In men older than 60 years, treatment-induced problems should be evaluated in relation to problems in an age-matched nonirradiated population. Methods. In the present study, problems in the urinary tract and intestine were evaluated with a self-assessment questionnaire using the linear-analogue scale. The questionnaire was mailed out to 200 patients and to an age-matched population 24-56 months after irradiation. Results. Twenty-five percent of the control group and 50% of the patient group reported some kind of problem in the urinary tract. The most common urinary problems in the control group and in the patient group, respectively, were urgency (19 and 42%), starting problems (22 and 33%), and leakage (11 and 32%). In the control and patient groups, 14 and 59%, respectively, reported some kind of gastrointestinal problems. The most common intestinal problems in the control and patient groups were respectively, mucus (4 and 38%), cramp (5 and 14%), leakage (2 and 27%), and blood (2 and 36%). Ninety percent of the patients' problems were minor. Conclusion. Pelvic irradiation induced a relatively large number of minor problems, evaluated with a self-assessment questionnaire and compared with an age-matched population of men, of approximately similar magnitude as with a physician's systematic evaluation. The most important urinary factors were urgency and leakage. The most important intestinal factors were blood, mucus, and leakage. The results support the ongoing efforts to use 3-D computed tomography-based conformal therapy to decrease irradiation dose to the rectum and bladder. Cancer 1994;74:2520-32.

Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RT-PC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation.

IMPORTANCE: Prostate cancer commonly metastasizes to bone, and bone metastases are associated with pathologic fractures, pain, and reduced survival. Bone disease is routinely visualized using the technetium Tc 99m (99mTc) bone scan; however, the standard interpretation of bone scan data relies on subjective manual assessment of counting metastatic lesion numbers. There is an unmet need for an objective and fully quantitative assessment of bone scan data. OBJECTIVE: To clinically assess in a prospectively defined analysis plan of a clinical trial the automated Bone Scan Index (aBSI) as an independent prognostic determinant of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). DESIGN, SETTING, AND PARTICIPANTS: This investigation was a prospectively planned analysis of the aBSI in a phase 3 multicenter randomized, double-blind, placebo-controlled clinical trial of tasquinimod (10TASQ10). Men with bone metastatic chemotherapy-naïve CRPC were recruited at 241 sites in 37 countries between March 2011 and August 2015. The statistical analysis plan to clinically evaluate the aBSI was prospectively defined and locked before unmasking of the 10TASQ10 study. The analysis of aBSI was conducted between May 25, 2016, and June 3, 2017. MAIN OUTCOMES AND MEASURES: The associations of baseline aBSI with OS, radiographic progression-free survival (rPFS), time to symptomatic progression, and time to opiate use for cancer pain. RESULTS: Of the total 1245 men enrolled, 721 were evaluable for the aBSI. The mean (SD) age (available for 719 men) was 70.6 (8.0) years (age range, 47-90 years). The aBSI population was representative of the total study population based on baseline characteristics. The aBSI (median, 1.07; range, 0-32.60) was significantly associated with OS (hazard ratio [HR], 1.20; 95% CI, 1.14-1.26; P < .001). The median OS by aBSI quartile (lowest to highest) was 34.7, 27.3, 21.7, and 13.3 months, respectively. The discriminative ability of the aBSI (C index, 0.63) in prognosticating OS was significantly higher than that of the manual lesion counting (C index, 0.60) (P = .03). In a multivariable survival model, a higher aBSI remained independently associated with OS (HR, 1.06; 95% CI, 1.01-1.11; P = .03). A higher aBSI was also independently associated with time to symptomatic progression (HR, 1.18; 95% CI, 1.13-1.23; P < .001) and time to opiate use for cancer pain (HR, 1.21; 95% CI, 1.14-1.30; P < .001). CONCLUSIONS AND RELEVANCE: To date, this investigation is the largest prospectively analyzed study to validate the aBSI as an independent prognostic imaging biomarker of survival in mCRPC. These data support the prognostic utility of the aBSI as an objective imaging biomarker in the design and eligibility of clinical trials of systemic therapies for patients with mCRPC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01234311

Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer.

Having advanced prostate cancer means living with considerable bodily problems, a living we know little about. Thus, the aim of this study was to illuminate meanings of living with bodily problems, as narrated by men with advanced metastasized hormone refractory prostate cancer. Eighteen participants were interviewed, and the text was analyzed using a phenomenological-hermeneutic approach. Findings show that meanings of living with bodily problems are to live in cyclical movements between experiencing wellness and experiencing illness. New, or changed, bodily problems mean losing wellness and experiences of being ill. Understanding and, to some extent, being in control of bodily problems, make it possible to reclaim wellness and to experience oneself as being well. Findings also show that pain and fatigue are the most prominent problems and that they have different meanings. Pain being a threat of dying in agony, whereas fatigue is more of an emissary of death. Reclaiming wellness versus adaptation and enduring versus suffering deriving from 2 different perspectives, the inside or life world perspective and the outside or professional perspective, are questions discussed in the article. One clinical implication for nursing is the risk of obstructing the patients' possibility of reclaiming wellness by focusing on symptoms and disease.

The treatment of prostate cancer induces adverse effects. Although quantitative studies have evaluated the influence of these adverse effects on the quality of life, few studies have tried to gain a deeper understanding of how men live after external beam radiotherapy of localized prostate carcinoma, which is the purpose of this study. Ten men were interviewed in their homes. The narrative interviews were tape recorded and transcribed into a text. The text was analyzed qualitatively by a content analysis. To bear the emotional experience of the illness by oneself is a self-chosen strategy. Some men expressed a sense of being exposed in meetings with female caregivers. The treatment induced changes in body functions influencing daily life. In this new life situation these men are striving to reach a sense of having control, which includes control over disease progression and waning body function. Despite the negative influence of the treatment, the men are striving to become reconciled with their new life. The experience of living after external beam radiotherapy of localized prostate carcinoma could be understood as striving to reach a sense of control and becoming reconciled with a new way of life.

Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.

Few self-assessment cancer-specific questionnaires / modules have yet been developed for radiotherapy-induced side effects. The aim of the present study was to test the reliability and responsiveness of a prostate cancer (PC)-specific questionnaire. Thirty-one patients with PC graded their urinary and intestinal symptoms and their sexual function on the questionnaire. A doctor and a nurse performed a structured interview and graded the patient's symptoms with the same questions. The procedure was performed at both the start and the end of the treatment. A high concordance regarding symptom detection was seen between the patient, nurse and the doctor. The inter-rater test shows intraclass correlation coefficient (ICC) values above 0.60 in all scales. The internal reliability exceeded the lower limit (Cronbach α >0.70) for all scales. The test–retest gave acceptable reliability for all scales (ICC ≥0.60). All scales indicated increased problems during radiotherapy. The questionnaire was proven to be valid for the evaluations of urinary and intestinal problems and for sexual function in PC patients.

The authors of this study previously evaluated pelvic irradiation–induced late side effects in patients with localized prostatic carcinoma 4 years after external irradiation by administering a validated self-assessment questionnaire (QUFW94), and compared the results with those of age-matched controls. The current study was designed to evaluate prospectively the patients' problems 8 years after radiotherapy and to compare them with those reported by the same controls. The questionnaire was sent out at a mean of 8 years (range, 72–104 months) after irradiation to 120 patients and 125 controls. For analysis of sexual function, the patient group was divided into two subgroups, one treated with radiotherapy only (RT) and one group treated with radiotherapy plus castration (RT+A). A value of >1 on a 0–10 scale indicated that the patient was having a problem. The mean age was 73 years for both patients and controls. No changes in urinary problems were seen between the 4-year and the 8-year follow-up in the 2 groups. Sixty percent and 54% of the patients (P = 0.096) and 24% and 31% of the controls (P = 0.988) reported urinary problems at the 4-year and 8-year follow-ups, respectively. No changes in gastrointestinal late side effects in the patient group were seen between the 4-year (65%) and the 8-year (62%) follow-ups (P = 0.490). However, there was a decrease in intestinal problems in the control group between the 4-year (12%) and the 8-year (9%) follow-ups (P = 0.001). The sexual problems did not change during the two periods, in the patient groups or in the control groups. Fifty-six percent and 65% of the RT group (P = 0.052), 67% and 54 % of the RT + A group (P = 0.555), and 27% and 33 % of the control group (P = 0.243) indicated some kind of sexual problem at the 4-year and 8-year follow-ups, respectively. The amount of pelvic irradiation–induced urinary late side effects, intestinal late side effects, and sexual function, evaluated with a self-assessment questionnaire, did not change between 4 and 8 years after RT. The age-matched controls reported no change in urinary or sexual problems despite advanced age, but there was a reported decrease in intestinal problems. Cancer 1999;85:678–88. © 1999 American Cancer Society.

Abstract: A study was carried out to investigate whether testosterone treatment is able to influence tumour growth in a rat prostatic adenocarcinoma previously treated with castration and high-dose fractionated irradiation. Copenhagen × Fisher rats bearing the androgen-sensitive, well-differentiated Dunning R3327-PAP tumour were castrated and thereafter treated with external beam radiation with photons from a 4-MV linear accelerator. One month after irradiation, substitution with subcutaneous testosterone was started. Tumour volumes and rat weights were monitored up to 256 days after castration, and at the end of the study a microscopic analysis of the tumours was performed. Irradiation delayed tumour growth as compared with untreated tumours. Castration delayed tumour growth, but a hormone-refractory relapse to doubled tumour volume was seen within 45 days. If testosterone was added after castration, the tumours grew rapidly. However, testosterone failed to increase tumour growth when given to rats treated with orchiectomy and irradiation. Histological examination showed that the irradiated tumours still contained tumour epithelial cells, but these cells apparently do not respond to testosterone stimulation. The well-differentiated and androgen-sensitive rat prostatic adenocarcinoma did not grow after irradiation despite stimulation with testosterone. This indicates that the malignant cells lose their androgen sensitivity after high-dose irradiation.

Abstract:  Estramustine (EaM), a carbamate ester of 17β-estradiol and nor-nitrogen mustard, is a cytotoxic compound with antitumoral effect in malignant glioma in vitro and in vivo . However, knowledge of the pharmacokinetics of EaM in experimental glioma is limited. The objective of this study was therefore to investigate further the distribution of EaM in the BT4C rat glioma model. Assessment of EaM uptake and distribution was performed by quantitative whole-body autoradiography. In addition, the uptake of EaM and its metabolites estromustine (EoM), estradiol, and estrone were analyzed by gas chromatography. EaM was taken up from the circulation and was found to be the main product in glioma tissue. Whole-body autoradiography after [14C]-EaM administration revealed a strong 14C label simultaneously in tumor and normal brain tissue at 0.5 h after drug administration. In tumor tissue, sustained high levels of 14C label were detected at 12 h after drug administration. In contrast to the tumor, radioactivity in normal brain tissue rapidly leveled off, indicating a retention of radioactivity in the tumor. The tumor/brain radioactivity ratio reached a peak of 4.5 at 12 h after drug administration. High levels of 14C label were also found in pulmonary tissue. By gas chromatography, EoM was found to be the main metabolite in plasma. However, EaM reached higher levels in tumor tissue, with the mean tumor/plasma ratio being 11.7 as compared with 2.0 for EoM. Only low plasma levels of the estrogen metabolites were detected. In conclusion, EaM is taken up in the BT4C rat glioma tissue and is retained in the tumor as compared with normal brain tissue and plasma. EaM showed a greater selectivity for tumor tissue, exhibiting a high tumor/plasma ratio as compared with EoM. The distribution pattern after administration of EaM, as evaluated by both whole-body autoradiography and gas chromatography, supports the earlier suggestion that the uptake is related to a protein with EaM-binding characteristics.

To study the effects of LH on total testicular blood flow and microcirculation, rats were treated with 2.5 or 25 μg LH sc and measurements were made on control rats and on LH-treated rats 1, 2, 3, 4, 6 and 12 h, after treatment. After treatment with 25 μg LH, total testicular blood flow, as measured with the radioactive microsphere method, was decreased at 6 h and increased at 12 h. Testicular microcirculatory blood flow was recorded with laser Doppler flowmetry and regular oscillations in blood flow, vasomotion, was observed in control rats. Vasomotion was not present 4 and 6 h after treatment with 25 μg LH, but returned at 12 h. Prior to and concomitantly with these changes in vasomotion, polymorphonuclear leukocytes accumulated in testicular microvessels and migrated into the interstitial tissue. These changes were followed, 6 h after treatment, by an increased vascular permeability, measured as increased testicular interstitial fluid volume. The lower dose of LH (2.5 μg), doubled plasma testosterone concentration and initially decreased interstitial fluid volume, and later induced a slight increase in blood vessel leukocytes. At the times studied, no changes could be observed in the other vascular parameters. In conclusion, it is suggested that LH, probably via some Leydig cell product, promotes regulatory effects on testicular microcirculation, but different magnitudes of LH stimulation induce different responses.

Conventional 4-field box radiotherapy technique induces high morbidity for patients with localized prostatic cancer. Using a patient daily diary, the present study compared side-effects after conventional radiotherapy with conformal radiotherapy for prostate cancer. Fifty-eight patients treated with the conventional technique (with or without sucralfate) were compared with 72 patients treated with conformal technique. The patient groups were compared with an age-matched control population. Patients treated with conformal technique were also evaluated regarding acute and late urinary problems. Results showed that patients treated with conformal technique reported significantly fewer side-effects as compared with conventional technique. Patients treated with sucralfate also showed slightly decreased intestinal morbidity in comparison to non-sucralfate group. Acute and late morbidity evaluated by the patients was decreased after conformal radiotherapy as compared with the conventional technique. Sucralfate may be of value if conformal radiotherapy is used for dose escalation in prostatic cancer patients.

The effects of ethane dimethyl sulfonate (EDS) on total testicular blood flow, microcirculation, and the testicular interstitial fluid volume (IFV) in rats were studied. In agreement with previous studies, treatment of control rats with human chorionic gonadotropin (hCG) induced an increase in IFV and total testicular blood flow as measured with radioactive microspheres. These effects of hCG were completely abolished in rats pretreated with EDS; in EDS-treated rats not receiving any hCG, there were decreases in IFV when compared with untreated control rats. Furthermore, the pulsatile pattern of testicular microcirculation registered with laser-Doppler flowmetry was abolished after EDS treatment, and this effect was not influenced by hCG treatment. The hCG-induced increase in IFV is associated with an increased accumulation of polymorphonuclear leukocytes locally in the testis, but this accumulation of leukocytes was not observed in rats pretreated with EDS. It was concluded from the present study that hCG-induced changes in total testicular blood flow and testicular microcirculation require functionally intact Leydig cells.

Radium-223 was minimally myelosuppressive. Multivariate analyses of data from ALSYMPCA patients identified baseline factors that may increase hematologic toxicity risk with radium-223. Extent of disease and degree of prostate-specific antigen elevation were predictive of grade 2-4 anemia; prior docetaxel, and decreased hemoglobin and platelets were predictive of grade 2-4 thrombocytopenia. Patients with these factors should be closely monitored during radium-223 therapy.

Cerium-labeled microspheres were used for blood-flow measurements in 7 New Zealand white rabbits with exercise-induced chronic Achilles paratenonitis and tendinosis. The blood flow increased 1.9 times more on the exercised side as compared with the contralateral, unexercised (control) side with respect to both the tendon and the paratenon. The blood flow of the tendon of the exercised leg showed a strong correlation with the blood flow in the paratenon of the ipsilateral side (r = 0.81). We concluded that the relative contribution of blood from the paratenon to the tendon remained unaltered in the exercised tendon and that degeneration of the tendon cannot be primarily explained by chronic circulatory impairment.