bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of randomized phase II studies (RP2s) and subsequent randomized controlled studies (RCTs) using identical systemic therapies
Authors: Bin J. C. , Pond G. R. , Chen E. X. 
Published: August 2020

e17515 Background: Previous research has shown that results from single-arm phase 2 studies are poor predictors of results from subsequent RCTs. It has been suggested that RP2s are more efficient in predicting outcomes of RCTs, and RP2s have increasingly been used in evaluating novel agents or therapeutic strategies. We attempted to determine if results from RP2s were concordant with outcomes of RCTs. Methods: We searched Medline and Cancerlit for RP2s evaluating systemic therapies for advanced solid malignancies, published from January 2000 to October 2008. Each publication was reviewed and a search was conducted for RCTs using identical therapies. Results of each RCT were reviewed and determined to be either “positive” or “negative” based on whether the stated primary endpoint of the study was met. Additional data such as year of publication, journal impact factor, number of patients enrolled, whether multiple centers were involved, response rates (RR), and survival data were collected. The rate of concordance between RP2s and RCTs was determined and univariate analyses were performed to determine potential predictors from RP2s of “positive” RCTs as well as concordance. Results: A total of 196 RP2s meeting study criteria were identified. However, only 16 had corresponding RCTs. Among these 16 RCTs, 11 showed concordance with RP2s results, for a rate of 68%. There was a moderately strong association between RRs from RP2s and corresponding RCTs, with a mean difference in RR of -3.8% (95% CI -10.6 to 3.0%). The difference in median survival was 1.0 mo (95% CI -1.0 to 3.2) and for time to progression it was -0.5 mo (95% CI -1.0 to 1.1) between RP2s and RCTs. No characteristics from RP2s could predict positivity or concordance with RCTs. Conclusions: Based on this small size of RP2s and RCTs, results from RP2s have relatively high concordance with results from RCTs. However, there were no significant predictors of concordance. No significant financial relationships to disclose.
Patient-reported outcomes in a randomized trial of everolimus with metastatic renal cell carcinoma patients
Authors: Beaumont J. , Cella D. , Hutson T. , Bracarda S. , Grünwald V. , Thompson J. , Ravaud A. , Urbanowitz G. , Hollaender N. , Motzer R. 
Published: August 2020

e17516 Background: Patient-reported outcomes (PRO), including health-related quality of life (HRQL), were assessed in a Phase III trial of everolimus in metastatic renal cell carcinoma (mRCC) patients. Methods: Patients with mRCC were randomized (n=416) to receive everolimus or placebo plus best supportive care. Patients completed the FACT-Kidney Symptom Index- Disease Related Symptoms (FKSI-DRS) and EORTC-QLQ C30 at baseline and monthly during treatment. Karnofsky Performance Status (KPS) was also assessed at baseline and monthly during treatment. Primary analyses included time to deterioration defined as a decrease from baseline of at least 3 points for FKSI-DRS, at least 10% for EORTC Physical Function (PF) and Global Quality of Life (QL) scales, and at least 10 points for KPS. Secondary analyses considered tumor progressions that occurred prior to deterioration or censoring date as FKSI deterioration events and compared time to PRO deterioration by tumor progression. Comparisons were made using stratified log-rank tests and Cox proportional hazard models. Results: Time to deterioration in KPS was longer in the everolimus arm, and time to deterioration in FKSI-DRS was slightly longer ( Table ). There was no difference in time to deterioration in PF or QL. Secondary analyses showed median time to deterioration in FKSI-DRS was approximately doubled for the everolimus arm compared to placebo, and patients who progressed experienced a more rapid deterioration in FKSI-DRS and QL scores. Conclusions: Compared to placebo everolimus delayed progression of disease-related symptoms and KPS. No effect on time to deterioration of PF or QL could be determined. Secondary analyses suggest a delay in deterioration in kidney cancer related symptoms via tumor control. [Table: see text] [Table: see text]
Declared pharmaceutical industry involvement in a random sample of abstracts from the ASCO Annual Meetings
Authors: Masson A. L. , Mangabeira A. , Saad E. D. , Prisco F. E. 
Published: August 2020

e17525 Background: The pharmaceutical industry (PI) plays an important role in drug development. We examined the extent and correlates of declared PI involvement in abstracts presented at ASCO Meetings 2001–2003 and 2006–2008. Methods: After stratification of abstracts into three categories of presentation ([1] oral, including plenary and oral presentations, and integrated symposia; [2] poster, including poster discussion and general poster; and [3] publication only), we randomly selected 10% of the abstracts for each of the 3-year periods of interest. Involvement by the PI was defined as declared sponsorship or by co-authorship in abstracts. Multivariate analysis (MVA) was done using logistic regression. Results: In the 2,206 abstracts analyzed, there was declared sponsorship or co-authorship by the PI in 425 (19.3%) of cases. Declared sponsorship (N = 73) was less frequent than co-authorship (N = 364). Declared sponsorship or co-authorship was present in 160 of 332 (48.2%) multinational studies, 222 of 969 (22.9%) multicenter, uninational studies, and 43 of 905 (4.3%) of single-institution studies (p < 0.001). For the 30.6% of abstracts stating the study phase in the title or text, PI involvement was present in 116 of 239 (48.5%) phase I studies, 95 of 364 (26.1%) phase II studies, and 26 of 72 (36.1%) phase III trials (p < 0.001). PI involvement was present in 280 of 1,080 (25.9%) US studies and in 145 of 1,126 (12.9%) non-US studies (p < 0.001). In MVA, significant predictors of PI involvement were multinationality (odds ratio [OR] = 6.61), phase I/II/III (versus other, OR = 3.65), and US nationality (OR = 2.98). Conclusions: Declared PI involvement is seen in nearly 20% of abstracts and is more frequent in multinational studies, clinical trials and studies with US nationality. Additional work is needed to assess the correlation between PI involvement, abstract quality and likelihood of future publication. No significant financial relationships to disclose.
Complementary and alternative medicine (CAM) and supportive care at leading cancer centers: A systematic analysis of websites
Authors: Brauer J. A. , El Sehamy A. , Metz J. M. , Mao J. J. 
Published: August 2020

e17528 Background: With increasing frequency, cancer patients and their family members are turning to the Internet to educate themselves about their disease and treatment options, including CAM and supportive care. However, very little is known about how national leading cancer centers represent these therapies via their websites. Methods: Simulating the patients’ perspective, we performed a systematic analysis of the websites of 41 National Cancer Institute (NCI) designated comprehensive cancer centers. Two researchers independently evaluated websites, recorded CAM information, and rated quality of the websites using a 4-item Likert scale (overall, information, presentation, and navigation) with Cronbach's alpha = 0.97. Rating was adequately correlated between the two raters (correlation coefficient 0.8). Results: Of 41 centers, 12 (29%) did not have functional websites with regards to information related to CAM. The most common CAM approaches mentioned were: acupuncture (59%), meditation/nutrition/spiritual support/yoga (56% for each), massage therapy (54%), and music therapy (51%). Twenty-three (56%) presented information on support groups, 19 (46%) on patient seminars, 18 (44%) on survivorship effort, and 17 (41%) on symptom management clinics. Twenty-nine (71%) of these websites had a telephone number available, 22 (54%) mentioned at least one ongoing research opportunity, and 19 (46%) provided links to the National Center for Complementary and Alternative Medicine website. Median rating of the quality of websites was 50 out of 100, with only 7 (17%) of centers receiving a composite score 80 (excellent) or better. Conclusions: While a growing number of leading cancer centers provide information about CAM and supportive oncology information for patients via their websites, the quality and ease of navigation of these sites remain highly variable. Effective development and redesign of many of the websites is needed to better inform and empower patients and families seeking CAM and supportive care information. No significant financial relationships to disclose.
Baseline and change from baseline in tumor burden compared with patient outcomes
Authors: Kaiser L. , Fridlyand J. , Fyfe G. 
Published: August 2020

e17530 Background: The impact of baseline tumor burden (bTB) and percentage reduction in tumor burden (dTB) on patient outcome has not been systematically studied in oncology clinical trials. We assess the relationship between both bTB and dTB and objective response (OR), progression free and overall survival (PFS and OS) in bevacizumab (B) and trastuzumab (T) trials. Methods: We analyzed 3 B and 1 T Ph 3 mBC and mCRC trials of > 1800 patients total. We used correlations and Cox models for the relationships between pairs of variables and multivariate Cox models to evaluate TB and PFS as independent predictors of OS. Here, we present the minimum dTB value until progression. Results: bTB is not related to dTB, OR rate or PFS time; it is negatively related to OS. dTB shows a strong positive relationship with PFS and OS. TB and PFS are independent predictors of OS, with PFS the better predictor. Results at earlier dTB assessments and within treatment arms are similar. Conclusions: Patients with high bTB are equally likely to respond to treatment and to have prolonged PFS as those with lower bTB, but high bTB is a negative predictor for OS. In contrast, greater percentage reductions in TB are strongly associated with better PFS and OS outcomes. Tumor burden and PFS are independent predictors of OS. Owing to these relationships, assessing bTB and dTB, as well as OR, PFS and OS, may improve the interpretation of phase II data. [Table: see text] [Table: see text]
Therapeutic care in metastatic renal cell carcinoma during the follow-up phase of the RECORD-1 phase III trial
Authors: Wiederkehr D. , Casciano R. , Stern L. , Zheng J. , Baladi J. 
Published: August 2020

e17531 Background: Following drug discontinuation for progression or adverse event in a clinical trial for relapsed or stage IV kidney cancer, supportive care including surgery, palliative radiotherapy, or bisphosphonates continue to be recommended by National Comprehensive Cancer Network (NCCN). However, published data on active therapeutic agents given to patients following study drug discontinuation in recent clinical trials is limited. Methods: World Health Organization Anatomical Therapeutic Chemical codes or therapeutic names, captured from the follow-up phase in a phase III clinical trial (RECORD-1) of patients with metastatic renal cell carcinoma (mRCC) patients, were used to describe antineoplastic therapies following discontinuation of study drug. Prior to trial, patients had progressed on at least one VEGFr-TKI therapy. Results: Of the 130 patients with follow-up after discontinuation of study drug, 78.5% received at least one of the following: corticosteroids, radiotherapy, protein kinase inhibitors, mTOR inhibitor, pyrimidine analogues, monoclonal antibodies, interferons, and investigational drugs. Among patients who received an active agent, nearly three-quarters (73.5%) utilized targeted therapy (protein kinase inhibitors, mTOR inhibitor, monoclonal antibodies). Conclusions: In a clinical trial setting with mRCC patients who have received several classes of systemic therapy, care delivered following study drug discontinuation often includes an active antineoplastic agent, despite the limited supportive evidence in this setting. While the placebo control with supportive care in a double-blind phase is acceptable to evaluate the efficacy and safety of a therapy for regulatory approval purposes, decision makers must also consider how these data may inform comparisons with the usual alternatives available to and used by physicians and patients in the non-trial setting. [Table: see text]
The importance of histology when evaluating the cost-effectiveness of pemetrexed plus cisplatin as first-line therapy for advanced non-small cell lung cancer
Authors: Muehlenbein C. E. , Klein R. W. , Liepa A. M. , Babineaux S. M. , Wielage R. C. , Schwartzberg L. S. 
Published: August 2020

e17533 Background: A recent randomized phase III study was the first to report survival differences between first-line platinum doublets based on non-small cell lung cancer (NSCLC) histology (Scagliotti et al, J Clin Oncol. 2008). Here, we estimate the cost-effectiveness of cisplatin/pemetrexed (Cis/Pem) compared to other common regimens in an overall NSCLC population and in histology subgroups. Methods: A semi-Markov model was developed to compare the two-year impact of Cis/Pem to cisplatin/gemcitabine (Cis/Gem), carboplatin/paclitaxel (Carb/Pac) and carboplatin/paclitaxel/bevacizumab (Carb/Pac/Bev) from the US payer perspective. Data from the randomized controlled clinical trial and a mixed treatment comparison model (Vansteenkiste et al, Proc. ITOC 2008) provided clinical inputs. Medicare reimbursement rates were used to determine drug costs. A retrospective claims database analysis was used to obtain estimates of other direct NSCLC-related costs, including drug administration and toxicity management. Nonsquamous histology subgroups explored were adenocarcinoma, large cell and not otherwise specified (NOS). Comparisons with Carb/Pac/Bev were limited to the nonsquamous histology subgroup. Results: In all patients regardless of histology, using Cis/Pem led to an incremental cost per life-year gained (LYG) of $104,577 vs. Cis/Gem and $231,291 vs. Carb/Pac. In the subset of patients with nonsquamous NSCLC (adenocarcinoma, large cell, or NOS), the incremental cost per LYG was $83,537 vs. Cis/Gem and $178,613 vs. Carb/Pac. Further specifying the population to include only those with adenocarcinoma or large cell NSCLC yielded an incremental cost per LYG of $72,325 vs. Cis/Gem and $132,547 vs. Carb/Pac. The incremental cost per LYG for Carb/Pac/Bev vs. Cis/Pem was more than $300,000. Conclusions: In an unselected advanced NSCLC population, Cis/Pem may not be considered cost-effective for first-line therapy; however, in its licensed indication of nonsquamous NSCLC, it can be considered cost-effective and even more so for patients with adenocarcinoma or large cell carcinoma. This analysis emphasizes the importance of histology in identifying the appropriate patient for Cis/Pem first-line chemotherapy. [Table: see text]
Use of radionuclide bone scans in multicenter clinical trials: Opportunities for quality improvement
Authors: Lovell A. , Ford R. , Monninger T. , Perlman E. 
Published: August 2020

e17534 Background: Radionuclide bone scans are widely utilized to screen for osseous metastases given their high sensitivity for detection of metastatic disease. However, the variance in image quality can significantly impact the diagnostic interpretation. Methods: Prospective assessment of image quality on 478 digital and hard copy planar bone scans received as part of several multi-center clinical trials was completed using a two reviewer paradigm. To improve image quality, the following steps were taken: an Internal Image Quality Task Committee was formed, a comprehensive training program for all internal quality control reviewers was completed, and a site qualification process was initiated prior to site selection and/or subject enrollment with direct feedback to the sites. Results: Significant image quality issues potentially limiting the diagnostic interpretation of the radionuclide scans were initially identified in 21% of the submitted radionuclide bone scans. Quality issues were based on: technical factors, poor imaging technique, and subject factors which could not be corrected. A discordance rate of 4.3% among the two reviewers was also measured. After institution of the above steps, the net result was a 58% decrease in the quality control issues that were previously identified. The most significant improvements occurred on the basis of the site qualification process where sites changed from sending hard copy to digital images and there was direct feedback from the Imaging Core Lab to the sites to correct identified issues. Conclusions: Image quality of bone scans in multicenter clinical trials can be improved with direct communication coupled with a site qualification process prior to subject enrollment. We suspect these quality improvements will impact event driven endpoints that rely on the accurate assessment of bone lesions. We further suspect this level of quality control will continue to increase in importance as technology evolves to include hybrid scanning techniques such as SPECT/CT. This parallels our experience in the level of quality control and site qualification required for deployment of FDG-PET imaging in multicenter clinical trials. [Table: see text]
Identification of the causes that influence recruitment in oncology clinical trials (OCT)
Authors: Fein L. E. , Romera A. , Micheri C. M. , Diaz M. I. , Sala R. A. 
Published: August 2020

e17562 Background: Prediction of patient recruitment in OCT is one of the most important variables to guarantee timely closure of the trial. Earlier data analysis and conclusions define further research or discontinuation of the development of a given drug. Methods: Retrospective analysis of the recruitment and clinical records of all the patients of the COR that were contacted to participate in an OCT from 2006 to 2008 to identify the causes according to which patients did not participate. Results: Total of candidates 346, 175 women (50.6%). Average age 60 years (range 36 to 89). 42 patients (12%) rejected to participate in an OCT. 80 patients (23%) were screening failures (SF). 59 patients (17%) for not fulfilling an inclusion criteria (IC). Non appropriate stage or absence of measurable disease at screening (35%), abnormal labs (14%) and state of receptors or biomarkers (9%). Total of clinically unpredictable IC SF was 57.5%. 21 patients (6%) were SF due to an exclusion criteria (EC). Presence of distant metastases (12,5%), abnormal labs (2.5%) and abnormal EKG (2.5%). Total of clinically unpredictable EC SF was 19%. Conclusions: 35% of candidate patients did not participate. The most frequent cause was SF (23%). 76.5% of these SF were impossible to determine when informed consent was signed. 12% of patients rejected to participate for different reasons. Our results did not identify a predominant modifiable reason to improve recruitment. For future feasibility analyses our estimation of 35% dropout will be considered standard. [Table: see text] No significant financial relationships to disclose.
The geography of ASCO Annual Meetings: Nationality of abstracts and recent trends
Authors: Saad E. D. , Mangabeira A. , Masson A. L. , Prisco F. E. 
Published: August 2020

e17567 Background: Although there have been previous analyses of various aspects of studies presented at ASCO Annual Meetings, to our knowledge no attempt has been made to investigate the nationality of abstracts. Methods: After stratification into three categories of presentation ([1] oral, including plenary and all oral presentations; [2] posters, including poster discussions; and [3] publication only [PO]), we took a random sample of 10% of the abstracts from 6 years, and assigned them nationalities using authors’ affiliations. For multinational studies, we assigned nationality following an algorithm developed for the study. Importantly, we did not appraise abstract quality or results. Results: We analyzed 2,206 of the 22,045 abstracts appearing in the Proceedings and LBA Booklets for 2001–2003 and 2006–2008. Categories were oral/poster/PO in 7.8/49.2/43.0%, and study phase (as declared by authors) was I/II/III/other, unknown or not applicable in 10.8/16.5/3.3/69.4% of abstracts. There were 332 (15.0%) multinational studies, and 1,866 (85.0%) were uninational (969 multicenter, and 905 from a single institution). The top 15 countries with higher % of studies were the US (49.0%), Italy (7.5%), Japan (5.9%), Germany (5.3%), France (4.3%), Spain (3.5%), Canada (3.4%), the UK (3.3%), South Korea (1.8%), China/Hong Kong (1.4%), Brazil (1.1%), India (1.0%), Greece and Belgium (0.9% each), and Turkey (0.8%). Exploratory analyses showed a temporal increase in multinational studies (p = 0.003), no temporal trend in the proportion of abstracts with US nationality (p = 0.315), and a higher proportion of oral and poster presentations for multinational studies (p < 0.001) and for abstracts with US nationality (p < 0.001). Conclusions: This bibliometric analysis provides a geographic overview of research presented at ASCO Annual Meetings and suggests that nearly half of all abstracts are from the US, with 20% of the 71 countries represented producing nearly 90% of all abstracts accepted for the meetings. Multinational collaboration seems to be increasing in clinical cancer research. No significant financial relationships to disclose.
5-azacytidine treatment results in myelodysplastic syndrome
Authors: Bakanay S. M. , Karakiliç E. , Civriz-Bozdag S. , Arat M. , Ozcan M. , Gurman G. , Ilhan O. , Beksac M. , Konuk N. , Arslan O. 
Published: August 2020

e18003 Background: Myelodysplastic syndrome (MDS) is a clonal disease of hematopoiesis characterized by dysplasia in one or more series. 5-azacytidine (5-AZA) which is one of the methyl transferase inhibitors, targets the epigenetic changes in MDS and has been used for the last few years. Phase III studies which compare 5-AZA with supportive therapies report response rates up to 60%. Methods: In this study the aim was to retrospectively analyze the response rates of 26 MDS patients who were treated with 5-AZA between years 2002–2008. The patients were; median age 58 (21–84); male/female = 16/10; RAEB-I (7 patients); RAEB-II (18 patients); ve CMML (1 patient); secondary MDS (2 patients). According to an international prognostic scoring system, 6 patients were intermediate-1; 9 patients were intermediate-2; and 11 patients were high risk. Nine patients received 5-AZA as first-line therapy. The median leukocyte counts, absolute neutrophil counts (ANC), hemoglobin values, and thrombocyte counts at the begining of the cycles were; 2.4 (0.5–23)x10e9/L, 0.7 (0.1–16.5)x10e9/L, 8.6(5.3–11.4) gr/dl, 41(4–35)x10e9/L, respectively. The karyotype analysis revealed del5q in 3 patients; -7/del7q in 6 patients; trisomy 8 in 7 patients, del20q, del11q and complex karyotype (del7q+del5q+delY) in 1 patient each. The median cycles completed were 2 (1–6). Results: Seven patient were not elligible for response evaluation. Nine patients (47%) did not respond to the therapy and 8 of them were lost. Ten patients (53%) responded to the therapy with complete remission (n=4), partial remission (n = 2) and hematological improvement (n = 4). The responders and non-responders were similar in terms of median age, sex and pretreatment leukocyte, ANC and hemoglobin levels. However, there was statistically significant difference in terms of initial thrombocyte counts, total number of cycles received and serum ferritin levels. The patients who received 5-AZA as first line therapy had beter response than others (71% versus 29%). Conclusions: The observed response to 5-AZA therapy was similar to the reported rates in the literature. The most important factors for response were initial thrombocyte counts, total number of cycles, other therapies received before 5-AZA and the serum ferritin levels. No significant financial relationships to disclose.