Testicular-cancer survivors experience compromised language following chemotherapy: Findings in a Swedish population-based study 3-26 years after treatment

Background. Studies suggest an increased risk for compromised cognitive function among cancer survivors. It is unclear to what extent chemotherapy is the cause and how the dysfunction, when present, affects everyday life. The objective was to study self-reported behaviours that may depend on cognitive function, among testicular-cancer survivors who received various cycles of cisplatin-based chemotherapy by comparing them with those who did not. Material and methods. We identified 1173 eligible men diagnosed with non-seminomatous testicular cancer treated according to the national cancer-care programs SWENOTECA I-IV between 1981 and 2004. During an 18-month qualitative phase we constructed a study-specific questionnaire including questions about specific activities and behaviour in everyday life. Results. We obtained information from 960 of 1173 (82%) testicular-cancer survivors diagnosed on average 11 years previously. The prevalence of "saying similar but incorrect words" at least once a week was 5% among those having received no chemotherapy versus 16% among those having received five or more cycles, giving a prevalence ratio ("relative risk", RR) of 3.3 with a 95% confidence interval of 1.5 to 7.1. The corresponding figure for "saying words in the wrong order" was 3.1 (1.7-5.8), for "difficulties understanding what other people mean" 3.1 (1.3-7.7), for "saying words other than planned" 2.2 (1.1-4.5) and for "difficulties completing sentences" 2.0 (1.0-3.6). The relative risks for those with a low level of education ranged between 4.9 (1.6-14.9) and 15.3 (1.9-120.5). Conclusion. Testicular-cancer survivors in Sweden who have received five or more cycles of cisplatin-based chemotherapy experience an increased incidence of long-term compromised language; the effect is primarily seen among men with a low level of education

Reduced vaginal elasticity, reduced lubrication, and deep and superficial dyspareunia in irradiated gynecological cancer survivors

Purpose. The purpose of this study was to examine whether or not vaginal elasticity or lack of lubrication is associated with deep or superficial dyspareunia. We investigated gynecological cancer survivors treated with radiation therapy. Methods. In a population-based study with 616 women answering a questionnaire (participation rate 78%) and who were treated with radiotherapy for gynecological cancer, we analyzed information from 243 women (39%) who reported that they had had intercourse during the previous six months. Analyses included log-binomial regression (relative risks) and multiple imputations by chained equations in combination with Bayesian Model Averaging, yielding a posterior probability value. Age range of this cancer recurrent-free group of women was 29-80. Results. Dyspareunia affected 164 of 243 of the women (67%). One hundred thirty-four women (55%) reported superficial pain, 97 women (40%) reported deep pain, and 87 women (36%) reported both types of dyspareunia. The relative risk (RR) of deep dyspareunia was 1.87 (CI 1.41-2.49) with impaired vaginal elasticity compared to normal vaginal elasticity. Age and lower abdominal swelling were separate risk factors for deep dyspareunia. However, effects remain after adjusting for these factors. Conclusion. The relative risk of deep dyspareunia was almost twice as high with impaired vaginal elasticity compared to normal vaginal elasticity. If we wish to treat or even prevent deep dyspareunia in women with gynecological cancer, we may use our knowledge of the pathophysiology of deep dyspareunia and increasingly provide dilators together with instructions on how to use them for stretching exercises in order to retain vaginal elasticity. Results highlight the need for studies with more precise questions distinguishing superficial from deep dyspareunia so that in the future we may be able to primarily try to avoid reduced vaginal elasticity and secondarily reduce the symptoms.Funding Agencies|Swedish Cancer Society; Cancer Research Funds of Radiumhemmet; King Gustav V Jubilee Clinic Cancer Foundation, Gothenburg; Swedish State under ALF, Stockholm; Swedish State under ALF, Gothenburg</p

Risk Factors of Developing Long-Lasting Breast Pain After Breast Cancer Radiotherapy

Purpose: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy. Methods and Materials: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastases had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, locoregional radiotherapy, axillary surgery, overweight, and smoking. Results: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers. Conclusions: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long-lasting breast pain compared to older women. Time since treatment may decrease the occurrence of pain. (C) 2012 Elsevier Inc

Symptoms 10-17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial

Background: Postoperative radiotherapy decreases the risk for local and improves overall survival in women with breast cancer. We have limited information on radiotherapy-induced symptoms 10-17 years after therapy. Material and methods: Between 1997 and 1997, women with lymph node-negative breast cancer were randomised in a Swedish multi-institutional trial to breast conserving surgery with or without postoperative radiotherapy. In 2007, 10-17 years after randomisation, the group included 422 recurrence-free women. We collected data with a study-specific questionnaire on eight pre-selected symptom groups. Results: Fox six symptom group (oedema in breast or arm, erysipelas, heart symptoms, lung symptoms, rib fractures, and decreased shoulder mobility) we found similar occurrence in both groups. Excess occurence after radiotherapy was observed for pain in the breast or in the skin, reported to occur "occasionally" by 38.1% of survivors having undergone radiotherapy and surgery versus 24.0% of those with surgery alone (absolute difference 14.1%; p = 0.004) and at least once a week by 10.3% of the radiotherapy group versus 1.7% (absolute difference 8.6%; p = 0.001). Daily life and analgesic use did not differ between the groups. Conclusion: Ten to 17 years after postoperative radiotherapy 1 in 12 women had weekly pain that could be attributed to radiotherapy. The symptoms did not significantly affect daily life and thus the reduced risk for local recurrence seems to outweight the risk for long-term symptoms for most women. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 97 (2010) 281-28

Use of win statistics to analyze outcomes in the DAPA-HF and DELIVER trials

BACKGROUND: The primary end point in most heart failure (HF) trials is a composite of time to a first worsening HF event or cardiovascular death. Prevention of recurrent events and improvements in symptoms/quality of life are also important for patients but are usually analyzed separately. Win statistics can integrate all these outcomes into a single composite end point, which is analyzed in hierarchical order, reflecting the clinical importance of each component. METHODS: The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF, n=4744) and Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER, n=6263) trials enrolled patients with New York Heart Association class II, III, or IV HF, elevated natriuretic peptides, and either an ejection fraction of 40% or less (DAPA-HF) or greater than 40% and left atrial enlargement/left ventricular hypertrophy (DELIVER). We examined the effects of dapagliflozin compared with placebo on a hierarchical composite outcome, including cardiovascular death, total (first and recurrent) HF hospitalizations, total urgent HF visits, and improvement/deterioration in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS; range from 0 to 100, with a higher score indicating fewer symptoms and physical limitations) at 8 months. RESULTS: For this composite outcome, the win ratio was 1.30 (95% confidence interval [CI], 1.23 to 1.36) in the pooled cohort, 1.33 (95% CI, 1.23 to 1.43) in the DAPA-HF trial, and 1.27 (95% CI, 1.18 to 1.36) in the DELIVER trial. Win odds and net benefit in overall patients were 1.19 (95% CI, 1.14 to 1.24) and 8.7% (95% CI, 6.6 to 10.9%), respectively. In the overall pooled cohort, the majority of wins and losses were accounted for by KCCQ-TSS; 52.4% were settled by the KCCQ-TSS tier in the pooled cohort. CONCLUSIONS: In both the DAPA-HF and DELIVER trials, dapagliflozin led to a significant improvement in composite outcomes that incorporated patient-reported outcomes along with total HF events, as well as cardiovascular deaths. These analyses provided a comprehensive presentation of win statistics and illustrated the utility and flexibility of win statistics in describing the effects of dapagliflozin in two recent clinical trials in patients with HF. (Funded by British Heart Foundation Centre of Research Excellence and others; clinical trial registration numbers, NCT03036124 and NCT03619213.