Tadalafil is used to treat erectile dysfunction after prostate cancer treatment, but its role as a preventive agent is undefined.
To determine primarily whether tadalafil preserved erectile function ...in men treated with radiotherapy for prostate cancer, and secondarily to determine whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected.
Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013.
One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy (63%) or brachytherapy (37%). Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year.
Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary end points were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year, predictors of tadalafil response; and adverse events.
Among 221 evaluable participants, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo (P = .49); an absolute difference of 5% (95% CI, -9% to 19%). A significant difference was also not observed at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; P = .93). Tadalafil was not associated with significantly improved overall sexual function or satisfaction; a significant difference was not observed in any domain subscale. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners.
Among men undergoing radiotherapy for prostate cancer, daily use of tadalafil compared with placebo did not result in improved erectile function. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients.
clinicaltrials.gov Identifier: NCT00931528.
External beam radiation therapy (EBRT) dose escalation has been tested in multiple prospective trials. However, the impact on patient reported outcomes (PROs) associated with higher doses of EBRT ...remain poorly understood. We sought to assess the differences in PROs between men treated with a dose of 70.2 Gy versus 79.2 Gy of EBRT for prostate cancer.
The phase 3 clinical trial RTOG 0126 randomized 1532 patients with prostate cancer between March 2002 and August 2008 to 79.2 Gy over 44 fractions versus 70.2 Gy over 39 fractions. Eligible patients participated in the PRO data collection. PROs completed included the International Index of Erectile Function Questionnaire (IIEF), Functional Alterations due to Changes in Elimination (FACE), and the Spitzer Quality of Life Index (SQLI). The timepoints for the IIEF were collected pre-entry and at 6, 12, and 24 months. The FACE and SQLI were collected pre-entry and at 3, 6, 12, 18, and 24 months. The impact of EBRT dose to normal structures (penile bulb, rectum, and bladder) on PROs was also examined. Mixed effects models were used to analyze trends across time.
In total, 1144 patients completed baseline IIEF forms and of these, 56%, 64%, and 61% completed the IIEF at 6, 12, and 24 months, respectively; 1123 patients completed the FACE score at baseline and 50%, 61%, 73%, 61%, and 65% completed all 15 items for the FACE metric at timepoints of 3, 6, 12, 18, and 24 months, respectively. Erectile dysfunction at 12 months based on the single question was not significantly different between arms (38.1% for the standard dose radiation therapy arm vs 49.7% for the dose escalated radiation therapy arm; P = .051). Treatment arm (70.2 vs 79.2) had no significant impact on any PRO metrics measured across all collected domains. Comprehensive dosimetric analyses are presented and reveal multiple significant differences to regional organs at risk.
Compliance with PRO data collection was lower than anticipated in this phase 3 trial. Examining the available data, dose escalated EBRT did not appear to be associated with any detriment to PROs across numerous prospectively collected domains. These data, notwithstanding limitations, add to our understanding of the implications of EBRT dose escalation in prostate cancer. Furthermore, these results illustrate challenges associated with PRO data collection.
Malnutrition is a common complication in children with cancer. Cancer treatment and malnutrition can disrupt gut microbiome diversity and composition. The gut microbiome is of broad interest to ...better understand the mechanisms of malnutrition in cancer therapy. This study aimed to compare the gut microbiome between children with solid tumors postchemotherapy and healthy controls, and investigated the association of the putative microbiome differences with diet. Study participants were 27 children (7-18 years) with solid tumors within the first year after the completion of chemotherapy and 22 healthy controls. The study groups did not have a statistically significant difference in age, race, sex, and body mass index. At study intake, the participants completed the Block Kids Food Screener for dietary intakes in the past week. Fecal specimens were collected and analyzed for the gut microbiome. The cancer and control groups differed in gut microbial β-diversity and abundance analyses. The macronutrient intakes such as carbohydrates, fiber, beta-carotene, and vitamin B6 were positively associated with α-diversity. Children with adequate vitamin B6 had a higher Chao1 diversity index than children with inadequate or excessive intake (
= 0.0004). Children with excessive selenium intake had a trend for higher Pielou's_e index than children with inadequate intake (
= 0.091). Maintaining a healthy gut microbiome is critical among children with cancer. This study provides new insights on the linkages between dietary intakes and the gut microbiome in children with solid tumors postchemotherapy. These findings, if replicated in future independent studies, may help anticipate malnutrition and plan for personalized nutrition approaches during chemotherapy in pediatric cancers.
Metabolic differences between human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) and smoking-associated HNSCC may partially explain differences in prognosis. The ...former relies on mitochondrial oxidative phosphorylation (OXPHOS) while the latter relies on glycolysis. These differences have not been studied in blood.
We extracted metabolites using untargeted liquid chromatography high-resolution mass spectrometry from pretreatment plasma in a cohort of 55 HPV-associated and 82 smoking-associated HNSCC subjects. Metabolic pathway enrichment analysis of differentially expressed metabolites produced pathway-based signatures. Significant pathways (
< 0.05) were reduced via principal component analysis and assessed with overall survival via Cox models. We classified each subject as glycolytic or OXPHOS phenotype and assessed it with survival.
Of 2,410 analyzed metabolites, 191 were differentially expressed. Relative to smoking-associated HNSCC, bile acid biosynthesis (
< 0.0001) and octadecatrienoic acid beta-oxidation (
= 0.01), were upregulated in HPV-associated HNSCC, while galactose metabolism (
= 0.001) and vitamin B6 metabolism (
= 0.01) were downregulated; the first two suggest an OXPHOS phenotype while the latter two suggest glycolytic. First principal components of bile acid biosynthesis HR = 0.52 per SD; 95% confidence interval (CI), 0.38-0.72;
< 0.001 and octadecatrienoic acid beta-oxidation (HR = 0.54 per SD; 95% CI, 0.38-0.78;
< 0.001) were significantly associated with overall survival independent of HPV and smoking. The glycolytic versus OXPHOS phenotype was also independently associated with survival (HR = 3.17; 95% CI, 1.07-9.35;
= 0.04).
Plasma metabolites related to glycolysis and mitochondrial OXPHOS may be biomarkers of HNSCC patient prognosis independent of HPV or smoking. Future investigations should determine whether they predict treatment efficacy.
Blood metabolomics may be a useful marker to aid HNSCC patient prognosis.
Head and neck cancer (HNC) patients may experience multiple co-occurring neuropsychological symptoms (NPS) cluster, including fatigue, depression, pain, sleep disturbance, and cognitive impairment. ...While inflammation has been attributed as a key mechanism for some of these symptoms, its association with the NPS as a cluster of symptoms is unknown. Thus, the aim of this study was to examine the association between peripheral inflammation and NPS cluster among HNC patients over cancer treatment (radiotherapy with or without chemotherapy).
HNC patients were recruited and followed at pre-treatment, end of treatment, three months and one-year post-treatment. Plasma inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNFA), soluble tumor necrosis factor receptor-2 (sTNFR2), interleukin-1 beta (IL1-β), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemotactic protein-1 (MCP-1), and interleukin-1 receptor antagonist (IL-1RA) and patient-reported NPS cluster were collected at the 4 time points. Associations between inflammatory markers and the NPS cluster were analyzed using linear mixed-effects models and generalized estimating equations (GEE) models controlling covariates.
147 HNC patients were eligible for analysis. 56% of the patients received chemoradiotherapy as treatment. The highest NPS cluster score was reported at the end of treatment, which gradually decreased over time. An increase in inflammatory markers including CRP, sTNFR2, IL-6 and IL-1RA was associated with higher continuous NPS cluster scores (p<0.001, p = 0.003, p<0.001, p<0.001; respectively). GEE further confirmed that patients with at least two moderate symptoms had elevated sTNFR2, IL-6, and IL-1RA (p = 0.017, p = 0.038, p = 0.008; respectively). Notably, this positive association between NPS cluster and inflammatory markers was still significant at one-year post-treatment for CRP (p = 0.001), sTNFR2 (p = 0.006), and IL-1RA (p = 0.043).
Most HNC patients experienced NPS clusters over time, especially immediately after the end of treatment. Elevated inflammation, as represented by inflammatory markers, was strongly associated with worse NPS cluster over time; this trend was also notable at one-year post-treatment. Our findings suggest that peripheral inflammation plays a pivotal role in the NPS cluster over cancer treatment, including long-term follow-ups. Interventions on reducing peripheral inflammation may contribute to alleviating the NPS cluster in cancer patients.
•Head and neck cancer patients experienced neuropsychological symptoms (NPS) cluster from pre- to post-treatment.•Worse NPS was observed immediately after the end of treatment.•Elevated peripheral inflammation was strongly associated with worse NPS cluster over cancer treatment.
Among cancer patients in the United States, African American cancer patients have the highest mortality rate and shortest survival rate. Although depression is known as a predictor of mortality in ...cancer and a potential barrier to health care utilization, research on depression in African American patients is limited. Cancer pain can interfere with an individual’s ability to cope with depression.
To identify factors that are associated with a positive screening of depressive symptoms assessed by the PHQ-8 in African American patients treated for cancer pain.
Secondary data analysis of a cross-sectional study of opioid adherence.
Medical oncology, palliative care, and radiation oncology clinics in Atlanta, Georgia.
African American patients with cancer pain in the parent study.
Independent samples t-test was used to assess variable correlations with and without depressive symptoms. Adjusted logistic regression was conducted to identify factors that were associated with presence of depressive symptoms.
Mean patient age was 55.6 years, and nearly 38% had a PHQ-8 score of >10 indicating presence of moderate to severe depressive symptoms. Participants with depressive symptoms had significantly higher means for anxiety and pain interference with mood than those without depressive symptoms. Factors that were significantly associated with depressive symptoms were anxiety, pain interfering with mood, and lack of involvement with a religious congregation.
The findings of this study help to identify African American cancer patients at risk for depression and demonstrates the need for increased screening for depression in this underserved population.
Evidence suggests that intravaginal practices (IVPs) women use to cleanse their vagina or enhance sexual pleasure may be associated with unhealthy changes in the vaginal microbiome (VM). However, the ...effects of these practices in postmenopausal women are unknown.
The objective of this pilot study was to characterize the VM communities of postmenopausal women, identify types and frequency of IVPs, and explore associations between the VM and IVPs in postmenopausal women.
We analyzed the VM data of 21 postmenopausal women in Atlanta, Georgia, from vaginal swabs collected at a routine gynecological visit. 16S rRNA gene sequencing in the V3-V4 region was used to characterize the VM. In addition, we described the IVPs of these women, identified by using our newly developed instrument: the Vaginal Cleansing Practices Questionnaire. The associations between the VM and IVPs were explored by comparing the alpha diversities, beta diversities, and the relative abundances at both the community level and individual genus level.
The most abundant known bacterial genus found in the VM samples was Lactobacillus (35.7%), followed by Prevotella (21.4%). Eleven women (52%) reported using at least one type of IVP since menopause. The most common type of IVP was soap and water to clean inside the vagina. The use of IVPs was not associated with any alpha diversity metric, including Shannon index, inverse Simpson index, and Chao1 index; beta diversity metric, including Bray-Curtis and Jaccard distances; nor relative abundances at the community and individual genus level. Sociodemographic factors were also not associated with any alpha diversity metric.
Clinicians must assess IVPs and other vaginal and sexual hygiene practices of women of all ages to educate and promote healthy behaviors. More than half of the postmenopausal women in this pilot study use IVPs. Understanding the reasoning behind participants' use of IVPs and their perceptions of the possible effects of these practices will require further research. Although the small sample did not show associations with the VM, more extensive studies are warranted.
Radiation (RT) dose to the central nervous system (CNS) has been implicated as a contributor to treatment-related fatigue in head and neck cancer (HNC) patients undergoing radiation therapy (RT). ...This study evaluates the association of RT dose to CNS structures with patient-reported (PRO) fatigue scores in a population of HNC patients.
At pre-RT (baseline), 6th week of RT, and 1-month post-RT time points, Multidimensional Fatigue Inventory (MFI-20) scores were prospectively obtained from 124 patients undergoing definitive treatment for HNC. Medulla, pons, midbrain, total brainstem, cerebellum, posterior fossa, and pituitary dosimetry were evaluated using summary statistics and dose–volume histograms, and associations with MFI-20 scores were analyzed.
Maximum dose (Dmax) to the brainstem and medulla was significantly associated with MFI-20 scores at 6th week of RT and 1-month post-RT time points, after controlling for baseline scores (p<0.05). Each 1Gy increase in medulla Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.026), and 0.25 (p=0.037), at the 6th week of RT and 1-month post-RT, respectively. Each 1Gy increase in brainstem Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.027), and 0.25 (p=0.037) at the 6th week of RT, 1-month post-RT, respectively. Statistically significant associations were not found between dosimetry for the other CNS structures and MFI-20 scores.
In this analysis of PRO fatigue scores from a population of patients undergoing definitive RT for HNC, maximum dose to the brainstem and medulla was associated with a significantly increased risk of acute patient fatigue.
To explore the association between pretreatment body mass index (BMI) and post-treatment sexual function in women treated for endometrial cancer. .
28 postmenopausal women treated with vaginal ...brachytherapy (VBT) took part in this multisite exploratory secondary analysis at the University of Pennsylvania and Northwestern University. .
Secondary data analysis was used to determine if pretreatment BMI is associated with post-VBT sexual function in postmenopausal women treated for endometrial cancer at baseline and at six months post-treatment. Because of small sample size, participants were dichotomized according to enrollment BMI.
Both groups had poor sexual function at baseline. Although improved function was observed with time, neither group reached a score indicating healthy sexual function. .
Understanding factors that influence sexual health in patients with gynecologic cancer can improve post-treatment quality of life. .
Abstract Context Clinical trials use clinician-graded adverse events (AEs) and patient-reported outcomes (PROs) to describe symptoms. Objectives The aim of the study was to examine the agreement ...between PROs and AEs in the clinical trial setting. Methods Patient-level data were pooled from seven North Central Cancer Treatment Group, two Southwest Oncology Group, and three Radiation Therapy Oncology Group lung studies that included both PROs and AE data. Ten-point changes (on a 0–100 scale) in PRO scores were considered clinically significant differences (CSDs). PRO score changes were compared to AE grade (Gr) categories (2+ yes vs. no and 3+ yes vs. no) using Wilcoxon rank-sum or two-sample t -tests between Gr categories. Incidence rates and concordance of CSD in PRO scores and AE Gr categories were compiled. Spearman correlations were computed between PRO scores and AE severity. Results PROs completed by patients ( n = 1013) were the Uniscale, Lung Cancer Symptom Scale (LCSS), Functional Assessment of Cancer Therapy–Lung (FACT-L), Symptom Distress Scale, and/or Functional Living Index-Cancer. Significantly worse PRO score changes were found for the FACT-L in patients with Gr 2+ AEs. Worse scores were seen for the Uniscale for patients with Gr 2+ AEs ( P = 0.07) and LCSS for patients with Gr 3+ AEs ( P = 0.09). Agreement between incidence of any Gr 2+ (Gr 3+) AE and a CSD in PROs ranged from 27% to 67% (36%–61%). Correlations between PRO scores and AE severity were low: −0.06 Uniscale, −0.03 LCSS, 0.10 FACT-L, −0.11 Symptom Distress Scale, and −0.51 Functional Living Index-Cancer. Conclusion These results support previous work and an a priori hypothesis that AEs and PROs measure differing aspects of the disease experience and are complementary.
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