Standard treatment for locally advanced cervical cancer is chemoradiotherapy, but many patients relapse and die of metastatic disease. We aimed to determine the effects on survival of adjuvant ...chemotherapy after chemoradiotherapy.
The OUTBACK trial was a multicentre, open-label, randomised, phase 3 trial done in 157 hospitals in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the USA. Eligible participants were aged 18 year or older with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, II, IIIB, or IVA disease), Eastern Cooperative Oncology Group performance status 0–2, and adequate bone marrow and organ function. Participants were randomly assigned centrally (1:1) using a minimisation approach and stratified by pelvic or common iliac nodal involvement, requirement for extended-field radiotherapy, FIGO 2008 stage, age, and site to receive standard cisplatin-based chemoradiotherapy (40 mg/m2 cisplatin intravenously once-a-week for 5 weeks, during radiotherapy with 45·0–50·4 Gy external beam radiotherapy delivered in fractions of 1·8 Gy to the whole pelvis plus brachytherapy; chemoradiotherapy only group) or standard cisplatin-based chemoradiotherapy followed by adjuvant chemotherapy with four cycles of carboplatin (area under the receiver operator curve 5) and paclitaxel (155 mg/m2) given intravenously on day 1 of a 21 day cycle (adjuvant chemotherapy group). The primary endpoint was overall survival at 5 years, analysed in the intention-to-treat population (ie, all eligible patients who were randomly assigned). Safety was assessed in all patients in the chemoradiotherapy only group who started chemoradiotherapy and all patients in the adjuvant chemotherapy group who received at least one dose of adjuvant chemotherapy. The OUTBACK trial is registered with ClinicalTrials.gov, NCT01414608, and the Australia New Zealand Clinical Trial Registry, ACTRN12610000732088.
Between April 15, 2011, and June 26, 2017, 926 patients were enrolled and randomly assigned to the chemoradiotherapy only group (n=461) or the adjuvant chemotherapy group (n=465), of whom 919 were eligible (456 in the chemoradiotherapy only group and 463 in the adjuvant chemotherapy group; median age 46 years IQR 37 to 55; 663 72% were White, 121 13% were Black or African American, 53 6% were Asian, 24 3% were Aboriginal or Pacific islander, and 57 6% were other races) and included in the analysis. As of data cutoff (April 12, 2021), median follow-up was 60 months (IQR 45 to 65). 5-year overall survival was 72% (95% CI 67 to 76) in the adjuvant chemotherapy group (105 deaths) and 71% (66 to 75) in the chemoradiotherapy only group (116 deaths; difference 1% 95% CI –6 to 7; hazard ratio 0·90 95% CI 0·70 to 1·17; p=0·81). In the safety population, the most common clinically significant grade 3–4 adverse events were decreased neutrophils (71 20% in the adjuvant chemotherapy group vs 34 8% in the chemoradiotherapy only group), and anaemia (66 18% vs 34 8%). Serious adverse events occurred in 107 (30%) in the adjuvant chemotherapy group versus 98 (22%) in the chemoradiotherapy only group, most commonly due to infectious complications. There were no treatment-related deaths.
Adjuvant carboplatin and paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer increased short-term toxicity and did not improve overall survival; therefore, it should not be given in this setting.
National Health and Medical Research Council and National Cancer Institute.
The goal of this study is to compare microbiome composition in three different sample types in women, namely stool brought from home vs. solid stool samples obtained at the time of an unprepped ...sigmoidoscopy vs. biopsies of the colonic mucosa at the time of an unprepped sigmoidoscopy, using alpha- and beta-diversity metrics following bacterial 16S rRNA sequencing. The findings may have relevance to health and disease states in which bacterial metabolism has a significant impact on molecules/metabolites that are recirculated between the gut lumen and mucosa and systemic circulation, such as estrogens (as in breast cancer) or bile acids.
Concomitant at-home-collected stool, endoscopically-collected stool, and colonic biopsy samples were collected from 48 subjects (24 breast cancer, 24 control.) After 16S rRNA sequencing, an amplicon sequence variant (ASV) based approach was used to analyze the data. Alpha diversity metrics (Chao1, Pielou's Evenness, Faith PD, Shannon, and Simpson) and beta diversity metrics (Bray-Curtis, Weighted and Unweighted Unifrac) were calculated. LEfSe was used to analyze differences in the abundance of various taxa between sample types.
Alpha and beta diversity metrics were significantly different between the three sample types. Biopsy samples were different than stool samples in all metrics. The highest variation in microbiome diversity was noted in the colonic biopsy samples. At-home and endoscopically-collected stool showed more similarities in count-based and weighted beta diversity metrics. There were significant differences in rare taxa and phylogenetically-diverse taxa between the two types of stool samples. Generally, there were higher levels of Proteobacteria in biopsy samples, with significantly more Actinobacteria and Firmicutes in stool (all
< 0.001, q-value < 0.05). Overall, there was a significantly higher relative abundance of
and
in stool samples (at-home collected and endoscopically-collected) and higher abundances of
in biopsy samples (all
< 0.001, q-value < 0.05).
Our data shows that different sampling methods can impact results when looking at the composition of the gut microbiome using ASV-based approaches.
Abstract Context Lung cancer patients experience multiple, simultaneous symptoms related to their disease and treatment that impair functioning and health-related quality of life (HRQL). Computer ...technology can reduce barriers to nonsystematic, infrequent symptom assessment and potentially contribute to improved patient care. Objectives To evaluate the efficacy of technology-based symptom monitoring and reporting in reducing symptom burden in patients with advanced lung cancer. Methods This was a prospective, multisite, randomized controlled trial. Two hundred fifty-three patients were enrolled at three sites and randomized to monitoring and reporting (MR) or monitoring alone (MA). Patients completed questionnaires at baseline, 3, 6, 9, and 12 weeks and symptom surveys via interactive voice response weekly for 12 weeks. MR patients' clinically significant symptom scores generated an e-mail alert to the site nurse for management. The primary endpoint was overall symptom burden; secondary endpoints included HRQL, treatment satisfaction, symptom management barriers, and self-efficacy. Results This randomized controlled trial failed to demonstrate efficacy of symptom monitoring and reporting in reducing symptom burden compared with monitoring alone in lung cancer. HRQL declined over 12 weeks in both groups ( P < 0.006 to P < 0.025); at week 12, treatment satisfaction was higher in MA than MR patients ( P < 0.012, P < 0.027). Adherence to weekly calls was good (82%) and patient satisfaction was high. Conclusion Feasibility of using a technology-based system for systematic symptom monitoring in advanced lung cancer patients was demonstrated. Future research should focus on identifying patients most likely to benefit and other patient, provider, and health system factors likely to contribute to the system's success.
Patient-reported outcomes (PROs), such as symptom scales or more broad-based health-related quality-of-life measures, play an important role in oncology clinical trials. They frequently are used to ...help evaluate cancer treatments, as well as for supportive and palliative oncology care. To be most beneficial, these PROs must be relevant to patients and clinicians, valid, and easily understood and interpreted. The Patient-Reported Outcomes Measurement Information System (PROMIS) Network, part of the National Institutes of Health Roadmap Initiative, aims to improve appreciably how PROs are selected and assessed in clinical research, including clinical trials. PROMIS is establishing a publicly available resource of standardized, accurate, and efficient PRO measures of major self-reported health domains (eg, pain, fatigue, emotional distress, physical function, social function) that are relevant across chronic illnesses including cancer. PROMIS is also developing measures of self-reported health domains specifically targeted to cancer, such as sleep/wake function, sexual function, cognitive function, and the psychosocial impacts of the illness experience (ie, stress response and coping; shifts in self-concept, social interactions, and spirituality). We outline the qualitative and quantitative methods by which PROMIS measures are being developed and adapted for use in clinical oncology research. At the core of this activity is the formation and application of item banks using item response theory modeling. We also present our work in the fatigue domain, including a short-form measure, as a sample of PROMIS methodology and work to date. Plans for future validation and application of PROMIS measures are discussed.
Purpose
Primary prophylactic granulocyte colony-stimulating factors (PP-CSFs) are prescribed alongside chemotherapy regimens that carry a significant risk of febrile neutropenia (FN). As part of ...S1415CD, a prospective, pragmatic trial evaluating the impact of automated orders to improve PP-CSF prescribing, we evaluated patients’ baseline knowledge of PP-CSF and whether that knowledge improved following the first cycle of chemotherapy.
Methods
Adult patients with breast, colorectal, or non-small-cell lung cancer initiating chemotherapy were enrolled in S1415CD between January 2016 and April 2020. Eight questions assessing knowledge of CSF indications, risks, benefits, and out-of-pocket costs were included in a baseline survey and in a follow-up survey at the end of the first cycle of chemotherapy. Responses were stratified by the trial arm and whether chemotherapy was low, intermediate, or high FN risk.
Results
Of the 3605 eligible patients, 3580 (99.3%) completed the baseline survey, and 3420 (95.5%) completed the follow-up survey. At baseline, 803 (22.4%) patients responded “Don’t know” to all 8 questions, and all patients averaged 2.75 correct questions. At follow-up, knowledge increased by 0.34 in the high-FN-risk group (
p
< 0.001) but declined for the other FN-risk groups. In multivariate analysis, receiving a high-FN-risk regimen and younger age were significantly associated with knowledge improvement.
Conclusion
Chemotherapy patients had poor knowledge of PP-CSF that improved only modestly among recipients of high-FN-risk chemotherapy. Further efforts to inform patients about the risks, benefits, and costs of PP-CSF may be warranted, particularly for those in whom prophylaxis is indicated.
Trial registration: NCT02728596, April 6, 2016.
Summary Background Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable ...breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer. Methods NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1–3 breast cancer. After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661). The primary endpoint was disease-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00009945. Findings Median follow-up was 90·7 months (IQR 82·7–100·0) and 3311 patients had data for this period. Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78–1·07; p=0·27). Moreover, no differences were recorded for overall survival (0·84, 0·67–1·05; p=0·13), recurrence-free interval (0·83, 0·67–1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55–1·07; p=0·12). Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55–1·00; p=0·047). Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57–0·99; p=0·045), bone metastasis-free interval (0·62, 0·40–0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43–0·91; p=0·014), but not for overall survival (0·80, 0·61–1·04, p=0·094). Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group. Grade 3 or higher liver dysfunction was noted in 23 of 1612 patients in the clodronate group and 12 of 1623 patients in the placebo group; grade 3–4 diarrhoea was noted in 28 patients in the clodronate group and in ten in the placebo group. There was one possible case of osteonecrosis of the jaw in the clodronate group. Interpretation Findings of NSABP B-34 suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. A meta-analysis of adjuvant bisphosphonate trials is suggested before recommendations for use in non-osteoporotic postmenopausal women with primary breast cancer are made. Funding National Cancer Institute, Bayer Oy (formerly Schering Oy).
We tested whether a low-literacy-friendly, multimedia information and assessment system used in daily clinical practice enhanced patient-centered care and improved patient outcomes. This was a ...prospective, parallel-group, randomized controlled trial with 2 arms, CancerHelp-Talking Touchscreen (CancerHelp-TT) versus control, among adults with Stage I–III breast or colorectal cancer receiving chemotherapy and/or radiation therapy in safety net settings. Each patient was assessed for outcomes at 4 timepoints: after starting treatment (baseline), during treatment, immediately after treatment, and at follow-up assessment. The primary outcomes were health beliefs, cancer knowledge, self-efficacy, and satisfaction with communication about cancer and its treatments. Health-related quality of life (HRQOL) was a secondary outcome. A total of 129 patients participated in the study (65 intervention and 64 control), and approximately 50% of these completed the study. Patients randomized to receive the CancerHelp-TT program had a significantly larger increase in their cancer knowledge in comparison to those randomized to the control arm (effect size = .48, P = .05). While effect sizes for differences between randomized groups in self-efficacy, health beliefs, HRQOL, and satisfaction with communication were small (.10–.48), there was a consistent trend that participants in the intervention group showed larger increases over time in all outcomes compared to the control group. The CancerHelp-TT software was favorably rated by intervention participants. The CancerHelp-TT program showed promise to increase vulnerable cancer patients’ cancer knowledge and adaptive health beliefs and attitudes. However, vulnerable patients may need additional interventional support in settings outside cancer clinics.
Upfront docetaxel (UD) with androgen deprivation therapy (ADT) has been demonstrated to improve survival outcomes in metastatic castration-sensitive prostate cancer (mCSPC). However, existing studies ...have included predominantly Caucasian patients.
To compare the efficacy of addition of UD to ADT in mCSPC to ADT alone among minority patients.
Retrospective study of mCSPC patients.
Patients treated with UD and ADT between January 2014 and December 2017 (UD + ADT, n = 44) were compared with those treated with ADT alone between January 2008 and January 2017 (ADT, n = 38); patients of Caucasian ethnicity were excluded. The outcome of interest was progression-free survival (PFS), which was estimated using Kaplan-Meier analysis and Cox proportional hazard analysis.
Overall, 63 (76.8%) patients were African American and 16 (19.5%) were Hispanic. Fifty-five (67%) patients had high-volume mCSPC. The median follow-up was 14 months 95% confidence interval (CI): 10.4-16.5 for UD + ADT and 42 months (95% CI: 17-66.9) for ADT. Median PFS did not differ between groups: UD + ADT: 16 versus ADT: 18 months hazard ratio (HR) for UD + ADT = 0.88, 95% CI: 0.48-1.62; P = 0.70. In patients with high-volume disease, median PFS remained similar (UD + ADT: 16 vs. ADT: 14 months (HR for UD + ADT = 0.64, 95% CI: 0.33-1.25; P = 0.19). On multivariable analysis, prolonged time to nadir PSA, HR = 0.83 (95% CI: 0.76-0.90), was independently associated with PFS. The most common toxicities in UD + ADT were anemia and fatigue. Major limitations include small sample size and potential for selection bias due to the retrospective study design.
In this retrospective review of a minority mCSPC cohort, UD + ADT was not associated with improved PFS compared with ADT alone. Although further study with larger sample size is needed, these results underscore the importance of ensuring accrual of minorities in clinical trials, reflective of the real-world setting.
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