Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition ...to the best standard of care, in men with castration-resistant prostate cancer and bone metastases.
In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223.
At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval CI, 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events.
In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).
The aim of this study was to characterize the prevalence of self-reported adverse health outcomes (AHOs), track changes in AHOs, and examine their impact on health-related quality of life (HrQoL) in ...testicular cancer survivors (TCSs) who were diagnosed between 1980 and 1994. These assessments were conducted during two survey waves (SWs), with the first occurring ∼12 years after surgery-only or platinum-based chemotherapy (PBCT), and the second ∼28 years after initial treatment. The study primarily focused on ‘typical AHOs’, which included Peripheral Sensory Neuropathy (PSN), Raynaud’s phenomenon, Tinnitus, and Hearing loss.
A total of 427 TCSs were included in the evaluation, distributed as follows: surgery-only group (n = 155), PBCT-standard group with ≤850 mg cisplatin (n = 222), and PBCT-high group with >850 mg cisplatin (n = 50). For comparison of HrQoL, men from the general population served as a control group (referred to as ‘Norms’). The statistical significance level was set at P < 0.05, and clinical importance, in terms of testing HrQoL differences, was defined as Δ ≥2.5 points.
A higher number of TCSs who underwent PBCT reported experiencing typical AHOs compared with those who had surgery only. The highest prevalence rates were observed among TCSs who had undergone PBCT-high. Further, the number of TCSs describing typical AHOs, except Raynaud’s phenomenon, increased during the observation period of 16 years. At the last SW, a median of 4 AHOs (any type) were reported after PBCT-high compared with a median of 2 AHOs after Surgery-only or after PBCT-standard. With Surgery-only as reference, PBCT-high, but not PBCT-standard, was associated with decreasing physical HrQoL in the last SW (A2 Regression coefficient: −4.3; P = 0.008). When comparing all TCSs with Norms no clinically important difference in physical and mental HrQoL was observed at either SW. However, at the last SW, TCSs after PBCT-high therapy represented a subgroup of TCSs with clinically important impairment of HRQoL. Of the typical AHOs, only PSN reduced HrQoL. Chronic fatigue, pain, anxiety/depression, sexual dysfunction, unemployment, being single, and low education were additional covariates.
After a median of 28 years since their treatment, HrQoL in TCSs was found to be comparable to that of Norms. This similarity held true even though AHOs, especially after PBCT-high, were becoming more prevalent among TCSs. The study revealed that individuals with a history of PBCT-high are at a high risk of experiencing a significantly increased prevalence of long-term AHOs, which subsequently leads to diminished HrQoL. It is crucial to recognize and provide specialized attention to these TCSs during lifelong follow-up care.
•TCSs report persisting side effects after surgery with or without cisplatin-based chemotherapy.•Peripheral Sensory Neuropathy and ototoxicity worsen during long-term follow-up, while Raynaud phenomena remain stable.•Thirty years after treatment quality of life is similar in most TCSs and untreated age-comparable men from the general population.•TCSs with more than four chemotherapy cycles have the highest risk of reduced quality of life and need early rehabilitation.•Post-cisplatin-related hearing loss should preferably be monitored by pure tone audiometry in aging TCSs.
Purpose
The majority of childhood, adolescent, and young adult cancer survivors (CAYACS) are at risk of late effects but may not receive long-term follow-up care for these. Here, we investigated (1) ...self-reported late effects, (2) long-term follow-up care, and (3) factors associated with receiving follow-up care in a population-based sample of Norwegian long-term CAYACS.
Methods
Survivors were identified by the Cancer Registry of Norway. All > 5-year survivors diagnosed between 1985 and 2009 with childhood cancer (CCS, 0–18 years old, excluding CNS), breast cancer (BC, stages I–III), colorectal cancer (CRC), leukemias (LEUK), non-Hodgkin lymphoma (NHL), or malignant melanoma (MM) at age 19–39 years were mailed a questionnaire (NOR-CAYACS study). Descriptive statistics and logistic regression models were used to analyze occurrence of late effects, long-term follow-up care for these, and associated factors.
Results
Of 2104 responding survivors, 1889 were eligible for analyses. Of these, 68% were females, with a mean age of 43 years at survey, on average 17 years since diagnosis, and diagnosed with CCS (31%), BC (26%), CRC (8%), NHL (12%), LEUK (7%), and MM (16%). Overall, 61.5% reported the experience of at least one late effect, the most common being concentration/memory problems (28.1%) and fatigue (25.2%). Sixty-nine percent reported not having received long-term follow-up care focusing on late effects. Lower age at survey (
p
= 0.001), higher education (
p
= 0.012), and increasing number of late effects (
p
= < 0.001) were associated with increased likelihood of follow-up care in the multivariate model.
Conclusions
The majority of survivors reported at least one late effect, but not receiving specific follow-up care for these. This indicates a need for structured models of long-term follow-up to ensure adequate access to care.
BACKGROUND To compare first-time parenthood probability and pregnancy outcome between cancer patients and the general population. METHODS Data from a hospital registry on cancer patients aged 15–35 ...years at diagnosis, including date/type of diagnosis, treatment and date of death, were merged with data from the Cancer Registry and the Medical Birth Registry, providing date of childbirth, IVF, pregnancy outcomes and demographics. RESULTS The first-time parenthood probability at the age of 35 years was 63% in male patients (n = 463) and 64% in the male general population (n = 367 068). Figures in female patients were 66% (n = 284) compared with 79% in the female general population (n = 349 576) (P = 0.007). A total of 487 male and 251 female cancer patients were childless pre-diagnosis, and 130 male and 104 female cancer patients had one child before diagnosis and at least one birth post-diagnosis. Congenital anomalies were more frequent in first-borns to previously childless male patients adjusted odds ratio (ORadj): 1.5; 95% confidence interval (CI): 1.1–2.3. The risk of low birth weight and preterm delivery after cancer was increased in infants born to female patients, as was perinatal mortality (ORadj 2.3; 95% CI: 1.1–5.0) among post-diagnosis first births. CONCLUSIONS The first-time parenthood probability in 35-year old cancer patients is ∼60%, which in female patients is significantly reduced compared with the general population. Post-diagnosis pregnancies to female patients are high-risk pregnancies.
Background:: Limited research has been done on mental health and health-related quality of life (QOL) of primary caregivers (PCs) to patients staying at home with advanced cancer. This study examines ...anxiety, depression, and QOL in PCs of patients with cancer in the late palliative phase. Patients and methods:: The sample consisted of 49 PCs of women with breast cancer and 47 PCs of men with prostate cancer. QOL was rated with the Medical Outcome Study Short Form (SF-36), and mental health with the Hospital Anxiety and Depression Scale (HADS). The findings were compared with age-adjusted norm data (norm). Results:: Physical QOL was significantly higher than norm in both genders, while mental QOL was significantly lower in male PCs. The level of anxiety was significantly higher than norm in both genders. No significant difference for level of depression was found in either gender, while caseness of HADS-defined depression was significantly more prevalent in female PCs compared with norm. Conclusion:: PCs of both genders had significantly more anxiety than norm samples. Health care personnel in contact with PCs should consider screening them for mental symptoms and QOL and, if necessary, recommend further evaluation by their doctors.
Abstract Purpose To evaluate the prognostic significance of age at diagnosis, extent of the disease (EOD) and socioeconomic (SES) and sociodemographic status (civil status, residency) on cause ...specific survival (CSS) in patients with malignant ovarian germ cell tumours (MOGCTs). To explore the cumulative incidence of a second cancer in 10-year MOGCT survivors. Patients and methods 2541 patients with MOGCT, reported to the Surveillance, Epidemiology and End Results programme (1978–2010), were identified. The above mentioned prognostic factors were assessed separately for dysgerminoma and non-dysgerminoma, using Kaplan–Meier estimates and Cox Hazards Models, providing 95% confidence intervals (95% CI). Results Five-year CSS was 97% (95% CI, 96–98%), and 92% (95% CI, 91–93%), respectively for dysgerminoma, and non-dysgerminoma. Age >40 years at diagnosis and presence of metastases were significantly associated with cause specific mortality. Among non-dysgerminoma patients, decreasing SES (hazard ratio (HR), 1.59; 95% CI, 1.11–2.28) and treatment before 1990 (HR, 2.65; 95% CI, 1.83–3.85) increased mortality. In the adjusted analysis, patients from Michigan were almost 2.5 times more likely to die from MOGCT than patients from other states (HR, 2.48; 95% CI, 1.17–5.25). Second cancer was diagnosed in 10% of 10-year survivals who underwent radiotherapy and in 2% of survivals in non-radiotherapy group ( p = .002). Conclusions Increased attention should be directed towards the management of elderly MOGCT patients and those with non-dysgerminoma histology with low SES. Radiotherapy should be avoided as much as possible. Survival differences related to residency may occur when new cancer treatments are introduced.
Background: A possible explanation of the excess cardiovascular risk in testicular cancer (TC) survivors is development of metabolic syndrome. The association between metabolic syndrome and TC ...treatment is examined in long-term survivors.
Patients and methods: In a national follow-up study (1998–2002), 1463 TC survivors (diagnosed 1980–1994) participated. Patients >60 years were excluded in the present study, leaving 1135 patients eligible. The patients were divided in four treatment groups: surgery (n = 225); radiotherapy (n = 446) and two chemotherapy groups: cumulative cisplatin dose (Cis) ≤850 mg (n = 376) and Cis >850 mg (n = 88). A control group consisted of 1150 men from the Tromsø Population Study. Metabolic syndrome was defined according to a modified National Cholesterol Education Program definition.
Results: Both chemotherapy groups had increased odds for metabolic syndrome compared with the surgery group, highest for the Cis >850 group odds ratio (OR) 2.8, 95% confidence interval (CI) 1.6–4.7. Also, the Cis >850 group had increased odds (OR 2.1, 95% CI 1.3–3.4) for metabolic syndrome compared with the control group. The association between metabolic syndrome and the Cis >850 group was strengthened after adjusting for testosterone, smoking, physical activity, education and family status.
Conclusion: TC survivors treated with cisplatin-based chemotherapy have an increased risk of developing metabolic syndrome compared with patients treated with other modalities or with controls.
Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of ...CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment.
Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998–2002) and survey II (2007–2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression.
Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four-fold for high levels of neuropathy compared with no neuropathy, and two- to three-fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively.
The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important.
Testicular cancer (TC) is the most common neoplasm in males aged 15 to 40 years and approximately 65%–75% have clinical stage I (CSI) disease. Both surveillance and adjuvant chemotherapy may be ...applied with indistinguishable long-term survival rates. Therefore, the patient should decide based on risk factors and potential benefits and harms rather than adopting a uniform recommendation for all.
Testicular cancer (TC) is the most common neoplasm in males aged 15–40 years. The majority of patients have no evidence of metastases at diagnosis and thus have clinical stage I (CSI) disease Oldenburg J, Fossa SD, Nuver J et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi125–vi132; de Wit R, Fizazi K. Controversies in the management of clinical stage I testis cancer. J Clin Oncol 2006; 24: 5482–5492.. Management of CSI TC is controversial and options include surveillance and active treatment. Different forms of adjuvant therapy exist, including either one or two cycles of carboplatin chemotherapy or radiotherapy for seminoma and either one or two cycles of cisplatin-based chemotherapy or retroperitoneal lymph node dissection for non-seminoma. Long-term disease-specific survival is ∼99% with any of these approaches, including surveillance. While surveillance allows most patients to avoid additional treatment, adjuvant therapy markedly lowers the relapse rate. Weighing the net benefits of surveillance against those of adjuvant treatment depends on prioritizing competing aims such as avoiding unnecessary treatment, avoiding more burdensome treatment with salvage chemotherapy and minimizing the anxiety, stress and life disruption associated with relapse. Unbiased information about the advantages and disadvantages of surveillance and adjuvant treatment is a prerequisite for informed consent by the patient. In a clinical scenario like CSI TC, where different disease-management options produce indistinguishable long-term survival rates, patient values, priorities and preferences should be taken into account. In this review, we provide an overview about risk factors for relapse, potential benefits and harms of adjuvant chemotherapy and active surveillance and a rationale for involving patients in individualized decision making about their treatment rather than adopting a uniform recommendation for all.
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