Background
The importance of capturing and reporting health‐related quality of life (HRQOL) in clinical trials has been increasingly recognized in the oncology field. As a result, the National Cancer ...Institute (NCI) began to provide support for correlative HRQOL studies in cancer treatment trials. The current study was conducted to assess the publication rate of HRQOL correlative studies in NCI‐supported treatment trials and to identify potential factors positively or negatively associated with publication rates.
Methods
The NCI conducted a retrospective review of existing NCI databases to identify cancer treatment trials that had obtained additional NCI funding for the assessment of HRQOL and to determine the extent to which funded HRQOL studies have been completed and published in a peer‐reviewed journal.
Results
Of the 108 included trials, 58 (54%) had a parent trial (PT) publication; of these, 36 trials (62%) had a published HRQOL result: 20 as an independent publication and 16 that were included and/or reported in the PT publication. The length of time between trial activation and closure, as well as the specific cancer, appeared to be associated with the publication rates.
Conclusions
The results of the current study demonstrated that approximately 45% of the PT publications were followed by a HRQOL publication within 1 year, to allow the knowledge to be used in patient treatment decision making. The authors believe the current analysis is an important first step toward a better understand of the challenges that researchers face when reporting HRQOL endpoints.
Greater than 60% of the National Cancer Institute–funded health‐related quality of life (HRQOL) correlative studies embedded in cancer treatment trials are found to have an associated publication in a peer‐reviewed journal. HRQOL publication rates vary based on the length of time between trial activation and closure and type of cancer.
Cancer therapeutics frequently lead to symptomatic adverse events (AE) that can affect treatment tolerability. The NCI has developed the Patient-Reported Outcomes version of the Common Terminology ...Criteria for Adverse Events (PRO-CTCAE) to assess symptomatic AEs by direct patient self-report. Although longitudinal assessment of patient-reported symptomatic AEs holds promise to better inform treatment tolerability, using patient-reported outcome (PRO) measures to assess symptomatic AEs has raised several regulatory and good clinical practice issues among those who conduct cancer clinical trials. These include concerns regarding trial monitoring, clinical review of PRO results by investigators and delegated clinical staff, whether PRO data on symptomatic AEs require investigational new drug (IND) safety reporting, and how the trial conduct and resultant PRO data will be assessed during clinical investigator site inspections. This article addresses current thinking regarding these issues in cancer clinical trials from the FDA, the NCI, and the Office for Human Research Protections. PRO measures, such as PRO-CTCAE, that assess symptomatic AEs in cancer trials are considered similar to other PRO assessments of symptoms, function, and health-related quality of life and can generate complementary data that may inform tolerability. Clarity on operational concerns related to incorporating PRO measures to inform tolerability is critical to continue the advancement of rigorous PRO assessment in cancer clinical trials.
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To examine whether blocking multiple points of the angiogenesis pathway by addition of sorafenib, a multi-kinase inhibitor against VEGFR2/3, Raf, c-Kit, and PDGFR, to bevacizumab would yield clinical ...activity in ovarian cancer (OvCa).
This phase II study tested bevacizumab plus sorafenib in two cohorts; bevacizumab-naïve and bevacizumab-exposed patients. Bevacizumab (5 mg/kg IV every 2 weeks) was given with sorafenib 200 mg bid 5 days-on/2 days-off. The primary objective was response rate using a Simon two-stage optimal design. Progression-free survival (PFS) and toxicity were the secondary endpoints. Exploratory correlative studies included plasma cytokine concentrations, tissue proteomics and dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI).
Between March 2007 and August 2012, 54 women were enrolled, 41 bevacizumab-naive and 13 bevacizumab-prior, with median 5 (2–9) and 6 (5–9) prior systemic therapies, respectively. Nine of 35 (26%) evaluable bevacizumab-naive patients attained partial responses (PR), and 18 had stable disease (SD) ≥ 4 months. No responses were seen in the bevacizumab-prior group and 7 (54%) patients had SD ≥ 4 months, including one exceptional responder with SD of 27 months. The overall median PFS was 5.5 months (95%CI: 4.0–6.8 months). Treatment-related grade 3/4 adverse events (≥5%) included hypertension (17/54 31%; grade 3 in 16 patients and grade 4 in one patient) and venous thrombosis or pulmonary embolism (5/54 9%; grade 3 in 4 patients and grade 4 in one patient). Pretreatment low IL8 concentration was associated with PFS ≥ 4 months (p = .031).
The bevacizumab and sorafenib combination did not meet the pre-specified primary endpoint although some clinical activity was seen in heavily-pretreated bevacizumab-naive OvCa patients with platinum-resistant disease. Anticipated class toxicities required close monitoring and dose modifications.
•Bevacizumab and sorafenib combination showed modest clinical activity in bevacizumab-naive recurrent ovarian cancer.•No RECIST responses were observed in women who had prior bevacizumab.•The toxicites of bevacizumab and sorafenib combination was manageable with dose reduction, monitoring and counseling.•Baseline plasma low IL8 levels were associated with clinical benefit.
In cancer clinical trials, symptomatic adverse events (AEs), such as nausea, are reported by investigators rather than by patients. There is increasing interest to collect symptomatic AE data via ...patient-reported outcome (PRO) questionnaires, but it is unclear whether it is feasible to implement this approach in multicenter trials.
To examine whether patients are willing and able to report their symptomatic AEs in multicenter trials.
A total of 361 consecutive patients enrolled in any 1 of 9 US multicenter cancer treatment trials were invited to self-report 13 common symptomatic AEs using a PRO adaptation of the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) via tablet computers at 5 successive clinic visits. Patient adherence was tracked with reasons for missed self-reports. Agreement with clinician AE reports was analyzed with weighted κ statistics. Patient and investigator perspectives were elicited by survey. The study was conducted from March 15, 2007, to August 11, 2011. Data analysis was performed from August 9, 2013, to March 21, 2014.
Of the 361 patients invited to participate, 285 individuals enrolled, with a median age of 57 years (range, 24-88), 202 (74.3%) female, 241 (85.5%) white, 73 (26.8%) with a high school education or less, and 176 (64.7%) who reported regular internet use (denominators varied owing to missing data). Across all patients and trials, there were 1280 visits during which patients had an opportunity to self-report (ie, patients were alive and enrolled in a treatment trial at the time of the visit). Self-reports were completed at 1202 visits (93.9% overall adherence). Adherence was highest at baseline and declined over time (visit 1, 100%; visit 2, 96%; visit 3, 95%; visit 4, 91%; and visit 5, 85%). Reasons for missing PROs included institutional errors in 27 of 48 (56.3%) of the cases (eg, staff forgetting to bring computers to patients at visits), patients feeling "too ill" in 8 (16.7%), patient refusal in 8 (16.7%), and internet connectivity problems in 5 (10.4%). Patient-investigator CTCAE agreement was moderate or worse for most symptoms (most κ < 0.05), with investigators reporting fewer AEs than patients across symptoms. Most patients believed that the system was easy to use (234 93.2%) and useful (230 93.1%), and investigators thought that the patient-reported AEs were useful (133 94.3%) and accurate (119 83.2%).
Participants in multicenter cancer trials are willing and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators. This approach may improve the precision of AE reporting in cancer trials.
Background
A previous study found evidence that a breast cancer risk prediction model preferentially selected for less aggressive tumors in Swedish women. In the US, the Gail model has been widely ...used and was used for entry criteria in two large breast cancer prevention trials. We assessed if higher risk levels from the Gail model were associated with less aggressive tumor characteristics and if risk levels were predictive of mortality and survival.
Methods
We used questionnaire data from women in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to calculate Gail risk levels (low < 1.66%; moderate 1.66–2.99%; high ≥ 3.00%). Women aged 55–74 were enrolled between 1993 and 2001 and had detailed information on breast cancer incidence and tumors collected. We calculated breast cancer incidence and mortality rates among all women by risk levels and examined breast cancer survival and tumor characteristics among women diagnosed with breast cancer. We used Chi-squared tests and multivariable logistic regression to assess the association between risk levels and tumor characteristics.
Results
The study population for this analysis included 45,402 women with 1908 cases of breast cancer. Women at high risk were associated with higher risk of breast cancer mortality compared to women with low risk rate ratio (RR) = 2.29 95% confidence interval (CI) 1.37–3.84). Higher risk levels were associated with lobular-type tumors moderate: adjusted odds ratio (aOR) = 1.57 95% CI 1.13–2.17; high: aOR = 1.78 95% CI 1.25–2.54 but were not associated with any other tumor characteristics or breast cancer survival.
Conclusions
We did not find evidence that higher risk levels from the Gail model are predictive of less aggressive breast cancer tumors.
Almost 3000 men who received a placebo in the Prostate Cancer Prevention Trial and who never had a prostate-specific antigen (PSA) level of more than 4.0 ng per milliliter during the seven years of ...the trial underwent a prostate biopsy at the end of the study. Biopsy revealed prostate cancer in 449 men (15 percent), 67 of whom had high-grade tumors.
A PSA level of 4.0 ng per milliliter or less does not rule out the presence of prostate cancer, including high-grade tumors.
When first described in 1979, prostate-specific antigen (PSA) was considered a useful marker for assessing treatment responses and follow-up among patients with prostate cancer.
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After the publication of reports on several series in which the need for a biopsy of the prostate was based on the results of PSA tests, the potential of the PSA level as a screening tool was recognized.
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Further experience led to the consensus that a PSA level of more than 4.0 ng per milliliter had predictive value for the diagnosis of prostate cancer.
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Disease detection subsequently increased dramatically.
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More recent data suggest that a . . .
In May 2016, the Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute, convened a workshop to discuss a conceptual framework for ...identifying and genetically testing previously diagnosed but unreferred patients with ovarian cancer and other unrecognized BRCA1 or BRCA2 mutation carriers to improve the detection of families at risk for breast or ovarian cancer. The concept, designated Traceback, was prompted by the recognition that although BRCA1 and BRCA2 mutations are frequent in women with ovarian cancer, many such women have not been tested, especially if their diagnosis predated changes in testing guidelines. The failure to identify mutation carriers among probands represents a lost opportunity to prevent cancer in unsuspecting relatives through risk-reduction intervention in mutation carriers and to provide appropriate reassurances to noncarriers. The Traceback program could provide an important opportunity to reach families from racial, ethnic, and socioeconomic groups who historically have not sought or been offered genetic counseling and testing and thereby contribute to a reduction in health disparities in women with germline BRCA mutations. To achieve an interdisciplinary perspective, the workshop assembled international experts in genetics, medical and gynecologic oncology, clinical psychology, epidemiology, genomics, cost-effectiveness modeling, pathology, bioethics, and patient advocacy to identify factors to consider when undertaking a Traceback program. This report highlights the workshop deliberations with the goal of stimulating research and providing a framework for pilot studies to assess the feasibility and ethical and logistical considerations related to the development of best practices for implementation of Traceback studies.
Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among ...high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study.
This analysis included asymptomatic high-risk women age ≥ 30 years who elected RRSO at enrollment. Women provided risk factor data and underwent preoperative cancer antigen 125 (CA-125) serum testing and transvaginal ultrasound (TVU). RRSO specimens were processed according to a standardized tissue processing protocol and underwent central pathology panel review. Research-based BRCA1/2 mutation testing was performed when a participant's mutation status was unknown at enrollment. Relationships between participant characteristics and diagnostic findings were assessed using univariable statistics and multivariable logistic regression.
Invasive or intraepithelial ovarian/tubal/peritoneal neoplasms were detected in 25 (2.6%) of 966 RRSOs (BRCA1 mutation carriers, 4.6%; BRCA2 carriers, 3.5%; and noncarriers, 0.5%; P < .001). In multivariable models, positive BRCA1/2 mutation status (P = .0056), postmenopausal status (P = .0023), and abnormal CA-125 levels and/or TVU examinations (P < .001) were associated with detection of clinically occult neoplasms at RRSO. For 387 women with negative BRCA1/2 mutation testing and normal CA-125 levels, findings at RRSO were benign.
Clinically occult cancer was detected among 2.6% of high-risk women undergoing RRSO. BRCA1/2 mutation, postmenopausal status, and abnormal preoperative CA-125 and/or TVU were associated with cancer detection at RRSO. These data can inform management decisions among women at high risk of ovarian/tubal cancer.
Abstract Context Patients with cancer are bothered by its diagnosis, treatment, and associated uncertainty. Lack of concordance (LOC) of patients' reporting of their symptoms and quality of life ...(QOL) with that of their clinicians has been observed in cancer care. However, information regarding the reporting of patients' bother due to aspects of cancer experience and their clinicians' assessment is lacking. Objectives To describe cancer patients' bother due to aspects of their disease experience and explore the concordance (LOC) or a lack thereof between patients' and clinicians' reporting of patients' bother and factors associated with it. Methods Data from a prospective study of cancer patients' symptoms was analyzed. LOC was defined as any discrepancy between patient-clinician pairs in reporting patients' bother due to disease, cancer treatment, comorbidity, and side-effects of symptom management. The relation of LOC to patients' quality of life (QOL) and distress was also explored. Results Of the 2597 patients analyzed, a perfect concordance was observed in 37%-42%. Clinicians underestimated the severity of bother in 62%-76% of discordant cases. LOC was significantly associated with patient-reported distress and poor QOL. Referral for symptom management was associated with the clinician's rating of patients' bother, and LOC was associated with likelihood of poor compliance with recommendations for symptom management. Conclusion Majority of clinicians tended to underestimate cancer patients' bother and this is associated with poor QOL of cancer patients and their distress. Future studies should examine the LOC and its correlates to confirm the results of this study.
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