Effect of comorbidities/comedications on sunitinib outcomes for metastatic renal cell carcinoma: the STAR-TOR registry

Aim: Examine the effects of baseline hypertension (HTN) and statin or proton pump inhibitor (PPI) use on sunitinib treatment outcomes in STAR-TOR, a real-world registry. Materials & methods: Presence or absence of HTN and use or nonuse of statins or PPIs were determined at registry entry. End points included overall survival (OS) and progression-free survival (PFS). Results: Data were from 557 patients. Presence or absence of HTN did not affect OS or PFS. PFS (median [95% CI]) was longer in statin users (9.4 [6.5–13.6] months) versus nonusers (6.9 [5.7–8.2] months) (p = 0.0442). OS was shorter in PPI users (20.2 [14.9–28.3] months) versus nonusers (25.7 [22.7–33.0] months) (p = 0.0212). Conclusion: Comorbidities and comedications may affect real-world sunitinib treatment outcomes. Clinical Trial Registration: NCT00700258 ( ClinicalTrials.gov )

Non-existent ClinicalTrials.gov identifiers in abstracts indexed by PubMed

Prospective registration plays an important role in ensuring the transparency and reliability of clinical trials. Preregistration of clinical trials has been required by the ICMJE since 2005 and mandated by law for most clinical trial types since 2007. It is one of the roles of peer reviewers of a clinical trial publication to confirm that there is concordance between the registry entry and the submitted publication. On October 22, 2019, abstracts for all articles indexed by PubMed with publication type “Clinical Trial” and a publication date after January 1, 2003 were downloaded. Clinical trial registry identifiers were automatically extracted and tested for the existence of a corresponding entry on ClinicalTrials.gov. Among 38,001 published clinical trial registry numbers, 215 (0.6%) do not correspond to a legitimate clinical trial registry entry. While there is a small proportion of non-existent NCT numbers in our sample, even a single non-existent NCT number in a publication represents a failure on the part of journals who publish clinical trials to systematically ensure that reviewers always check clinical trial registry entries for concordance with the text submitted for publication. These results cast doubt on how frequently editors and reviewers evaluate clinical trial reports in light of their corresponding registry entries.

Sharing health research data – the role of funders in improving the impact

Recent public health emergencies with outbreaks of influenza, Ebola and Zika revealed that the mechanisms for sharing research data are neither being used, or adequate for the purpose, particularly where data needs to be shared rapidly. A review of research papers, including completed clinical trials related to priority pathogens, found only 31% (98 out of 319 published papers, excluding case studies) provided access to all the data underlying the paper - 65% of these papers give no information on how to find or access the data. Only two clinical trials out of 58 on interventions for WHO priority pathogens provided any link in their registry entry to the background data. Interviews with researchers revealed a reluctance to share data included a lack of confidence in the utility of the data; an absence of academic-incentives for rapid dissemination that prevents subsequent publication and a disconnect between those who are collecting the data and those who wish to use it quickly. The role of the funders of research needs to change to address this. Funders need to engage early with the researchers and related stakeholders to understand their concerns and work harder to define the more explicitly the benefits to all stakeholders. Secondly, there needs to be a direct benefit to sharing data that is directly relevant to those people that collect and curate the data. Thirdly more work needs to be done to realise the intent of making data sharing resources more equitable, ethical and efficient. Finally, a checklist of the issues that need to be addressed when designing new or revising existing data sharing resources should be created. This checklist would highlight the technical, cultural and ethical issues that need to be considered and point to examples of emerging good practice that can be used to address them.

Sharing health research data – the role of funders in improving the impact

Recent public health emergencies with outbreaks of influenza, Ebola and Zika revealed that the mechanisms for sharing research data are neither being used, or adequate for the purpose, particularly where data needs to be shared rapidly. A review of research papers, including completed clinical trials related to priority pathogens, found only 31% (98 out of 319 published papers, excluding case studies) provided access to all the data underlying the paper - 65% of these papers give no information on how to find or access the data. Only two clinical trials out of 58 on interventions for WHO priority pathogens provided any link in their registry entry to the background data. Interviews with researchers revealed a reluctance to share data included a lack of confidence in the utility of the data; an absence of academic-incentives for rapid dissemination that prevents subsequent publication and a disconnect between those who are collecting the data and those who wish to use it quickly. The role of the funders of research needs to change to address this. Funders need to engage early with the researchers and related stakeholders to understand their concerns and work harder to define the more explicitly the benefits to all stakeholders. Secondly, there needs to be a direct benefit to sharing data that is directly relevant to those people that collect and curate the data. Thirdly more work needs to be done to realise the intent of making data sharing resources more equitable, ethical and efficient. Finally, a checklist of the issues that need to be addressed when designing new or revising existing data sharing resources should be created. This checklist would highlight the technical, cultural and ethical issues that need to be considered and point to examples of emerging good practice that can be used to address them.

THE SURVEY OF CANCER PATIENTS IN THE REGION OF GUNTUR: BASED ON HOSPITAL REGISTRY

<p><strong>Objective: </strong>This survey was conducted to estimate the number of cancer patients in the region of Guntur-based on sex, age and cancer groups. The data were obtained from the hospital-based registries from Bommidala Cancer Institute, NRI Hospital<strong>, </strong>Balaji Cancer Care Center<strong>, </strong>and Govt. General Hospital, which was scrutinized and analysed.</p><p><strong>Methods: </strong>The hospital registry entry was considered suitable for assessing the cancer cases in the region of Guntur. In addition, data of NCRP were utilised for comparing the obtained results.</p><p><strong>Results: </strong>The data comprehensively constitutes of 309 patients. Out of which men were 74 (23.95%), and women were 235 (76.05%) who had obtained treatment for various cancer conditions between March-May, 2016. In these hospitals, cancers pertaining to the cervix-83 (31.32%), breast-52 (19.62%), ovary–17 (6.41%), lymphoid-11 (4.15%), pharynx-10 (3.77%), endometrium-10 (3.77%), astrocytoma-08 (3.02%), colon-07 (2.64%), larynx-06 (2.26%), rectum–06 (2.26%), oesophagus–05 (1.88%), post cricoids-04 (1.50%), stomach–04 (1.50%), liver–03 (1.13%) were the leading sites in order. While among these cases, radiation therapy patients were 194 (62.78%), chemotherapy patients were 78 (25.24%), and surgery patients were 37 (11.97 %).</p><p><strong>Conclusion: </strong>Survey reports the highest incidence of cancer cases to be cervix cancer among the women while it was pharyngeal cancer which precedes lung cancer among the men. This hospital-based registry survey is a report that provided internal consistency, reliability and validity.</p>

OSTEOPOROSIS IN THE COMMUNITY: FINDINGS FROM A NOVEL COMPUTERIZED REGISTRY IN A LARGE HEALTH ORGANIZATION IN ISRAEL

Background: Osteoporosis is a growing public health concern due to its rising prevalence and excess morbidity and mortality. Automated patient registries have gained great importance in health and disease management of major chronic diseases, but are rarely used in osteoporosis. Objectives: To construct an automated, population-based registry of osteoporosis. Setting: The electronic medical records and pharmacy databases of a 2 million member health organization in Israel (Maccabi Healthcare Services). Methods: Included in the registry were adults who were diagnosed with osteoporosis diagnosis, had major osteoporotic fractures, or purchased relevant medications, between 2000 and 2013. In addition, we included patients with low bone density as extracted from over 140,000 measurements reports, using an automated optical character recognition (OCR) system. Two-thirds of the cases were validated by more than one inclusion criterion. Results: A total of 118,141 osteoporosis patients were identified. The point prevalence of osteoporosis among members aged 50 or above in 2013 was 19%. The mean age at registry entry was 62 (SD=12) and 66 (SD=14) years for females and males, respectively. The highest annual risk of developing osteoporosis (27 per 1000) was recorded among females aged 65-75. In 28% of the patients, there was no indication of treatment with osteoporosis therapy. Conclusions: To the best of our knowledge, this is one of the first real-world automated registries of osteoporosis. Similar registries may provide valuable data for real-time monitoring of trends, quality of care, and outcome research in osteoporosis and its complications.

Dietary Habits and Weight Maintenance Success in High Versus Low Exercisers in the National Weight Control Registry

Background:The National Weight Control Registry (NWCR) was established to examine characteristics of successful weight loss maintainers. This study compares the diet and behavioral characteristics and weight regain trajectories of NWCR members with differing physical activity (PA) levels at baseline.Methods:Participants (n = 3591) were divided into 4 levels of self-reported PA at registry entry (< 1000, 1000 to < 2250, 2250 to < 3500, and ≥ 3500 kcals/week). We compared self-reported energy intake (EI), macronutrient composition, eating behaviors (dietary restraint, hunger, and disinhibition), weight loss maintenance strategies, and 3 year weight regain between these 4 activity groups.Results:Those with the highest PA at registry entry had lost the most weight, and reported lower fat intake, more dietary restraint, and greater reliance on several specific dietary strategies to maintain weight loss. Those in the lowest PA category maintained weight loss despite low levels of PA and without greater reliance on dietary strategies. There were no differences in odds of weight regain at year 3 between PA groups.Conclusions:These findings suggest that there is not a “one size fits all strategy” for successful weight loss maintenance and that weight loss maintenance may require the use of more strategies by some individuals than others.

Prognostic Relevance of the Kinetics of Worsening of Cytopenias in Lower-Risk MDS: A Substudy From the European Leukemianet Low Risk MDS (EUMDS) Registry

Abstract 700 Purpose: Prognosis of lower (IPSS low/int-1) risk MDS is heterogeneous. Current prognostic systems rely on single time point cytopenia values (Hb level, ANC, PLT counts) at diagnosis (classical or revised IPSS [IPSS-R] Greenberg, Blood 2012) or during evolution (time-dependent IPSS/WPSS). Capturing the dynamics of continuous parameters can yield independent prognostic information as exemplified by lymphocyte time doubling in CLL. We analyzed the prognostic relevance of the kinetics of Hb, ANC and PLT in lower-risk MDS patients (pts) included in the prospective EUMDS registry. Methods: Among the first 1000 pts included in the EUMDS registry, those fulfilling the following criteria were analyzed here: a) IPSS low/int-1; b) ≥3 visits (planned every 6 months) with ≥12 months follow-up; c) not treated with hypomethylating agents, G-CSF, hydroxyurea or lenalidomide. Dynamics of Hb, ANC, and PLT were studied by deriving linear models of each variable for each pt. Only pts with ≥3 measures of Hb, ANC and PLT and with stable or worsening corresponding cytopenia (model slope ≤0) were considered in each analysis, regardless of the goodness of fit (R2) of models. Time (T) to lose 1 g/dL of Hb (THb), 1.0 x109/L of ANC (TANC) and 50 x109/L of PLT (TPLT) were derived with the formula: T ∼ 1/slope. All survival analyses were made from the date of registry entry to last follow-up, death, or progression to AML. Unless specified, survival analyses were Cox models using continuous variables accounting for interactions. Results: 530 pts met study inclusion criteria (M/F: 314/216, median age: 73y). WHO diagnosis was 5q- syndrome, RA, RARS, RCMD, RCMD-RS, RAEB-1 and MDS-U in 5, 21, 20, 38, 7, 8 and 2% respectively (resp). IPSS risk was low, int-1 and low/int-1 (cytogenetics not available) in 55%, 38% and 7% resp. At registry entry, median Hb, ANC and PLT were 10.4 g/dL, 2.4 x109/L and 187 x109/L resp. and 23% were RBC transfusion-dependent; 293 received an ESA. The median number of available blood counts was 4 (range 3–9). THb, TANC and TPLT could be determined because of a stable or worsening cytopenia (slope ≤0) in 250/508, 258/495 and 301/509 pts with ≥3 values. There was no significant correlation between the number of values available and the goodness-of-fit (R2) of linear models (all P>0.3). Median THb TANC and TPLT were 23.5 (interquartile range [IQR]: 42.2), 28.7 (IQR: 52.1) and 26.9 (IQR: 49.2) months respectively. Because these figures are derived from linear models, they can be simply rescaled by a proportional extrapolation for daily practice (eg. −1 x109/L ANC at 28.7 months = −0.41 x109/L [12/28.7] at 12 months). THb, TANC and TPLT were not correlated to age, cytogenetic risk, IPSS, IPSS-R or baseline simplified WPSS (Malcovati. Haematologica 2011; all P>0.2). TANC and TPLT (but not THb) were shorter in pts with baseline RBC transfusion dependence (P=.02 and .003, resp.). With a median follow-up of 20.9 months in the 530 pts, 19 patients have progressed (AML: 14, RAEB: 5) and 71 patients have died; 3-year estimates of overall (OS) and progression-free (PFS) survivals were 74.4% and 73.6%. All further analyses are shown for OS and give similar results for PFS. In univariate analysis, longer TANC (hazard ratio [HR] for 6-months increments: 0.88 [95% CI: 0.80–0.97], P=.008) and TPLT (HR: 0.01 [95% CI: 0.001–0.30], P=.007) but not THb (P=.07) were associated with prolonged OS. Pts with a ≥1 x109/L decrease in ANC in less than the median time of 28.7 months (N=129) had a 3-year OS of 66.3% [95% CI: 55.0–79.9%] vs 89.3% [79.7–100%]. Pts with a ≥50 x109/L decrease in PLT in less than the median of 26.9 months (N=151) had a 3-year OS of 59.4% [46.8–75.4%] vs 85.6% [77.5–94.6%] (Figure, both P<10−4). There was no significant difference in the cause of death between those subgroups. In multivariate analysis, the prognostic impact of TANC and TPLT remained independent of baseline IPSS (P=.006 and P=.01 resp.) or IPSS-R (both P=.01), and of simplified time-dependent WPSS (P=.004 and P=.03). A landmark analysis at 2 years, using only retrospective data to derive TANC and TPLT is planned. Conclusion: In lower-risk MDS with stable or worsening cytopenias, kinetics of decline can be approximated to be linear to allow easy prognostic use in clinical practice. Faster decline of ANC and to a lesser extent of PLT counts, but not of Hb level (possibly because of transfusions and use of ESA), is associated with shorter OS and PFS, independently of IPSS, IPSS-R and WPSS. Disclosures: Germing: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Thrombosis in MPN with Thrombocythemia Is Associated with Higher Platelet Count At the Time of the Event: Data From the Czech Registry of Patients Treated with Anagrelide,

Abstract 3857 Background: Recent studies of prognostic parameters in Ph- myeloproliferative neoplasms with thrombocythemia (MPN-t) indicate that WBC counts at diagnosis, rather than platelet (Plt) counts, determine the risk of thrombosis. We have studied these and other risk parameters in our patient cohort. Patients: 843 prospectively assigned patients from the Czech segment of the International registry of patients treated with anagrelide (ANG; Thromboreductin®) were studied. The male: female ratio was 2:3, the median age was 51 (0–96) years. The majority of patients (68.1%) was pretreated by other cytoreducing drugs. According to PVSG criteria, the diagnoses were the following: essential thrombocythemia – 569, primary myelofibrosis – 155, polycythemia vera – 92, or other – 27 patients. Data from the time of diagnosis, from the time of registry entry (at the start of ANG therapy) and from the time of the thrombotic event were evaluated. The median follow-up since registry entry was 33 (0–117) months and the follow-up comprised 2505 patient-years. All patients were treated with ANG and in 80% of follow-up reports, acetylsalicylic acid (ASA) was mentioned to be given in parallel. In 18% of entries (from registration and follow-up), administration of another cytoreducing drug (mainly hydroxyurea or interferon) in combination with ANG was noted. Results: Of 449 thrombotic events reported, 335 occurred in history (i.e. before registry entry) and 114 during follow-up. The numbers of arterial, venous, and microcirculatory events in history were 147, 124 and 64, respectively. Of the 114 thrombotic events in 88 patients during follow-up (3.79 events/100 patient-years), 45 were classified as major. There were 61 arterial, 16 venous and 37 microcirculatory events. ANG ± ASA therapy dramatically decreased the number of venous events (7.8-fold), while arterial and microcirculatory events were reduced 2.4-fold and 1.7-fold, respectively. At diagnosis, the strongest predictors of all thrombotic events jointly were JAK2 V617F mutation (P=0.001), hereditary or acquired thrombophilia (P<0.001), hypertension (P=0.006), smoking (P=0.02) and diabetes mellitus (P=0.04). Also previous thrombosis predicted a subsequent thrombotic event (P=0.002). Age >65 yrs was a less powerful predictor (P=0.08). WBC and hematocrit levels positively correlated with the thrombotic risk (P=0.002 and P=0.006, respectively), whereas Plt counts correlated inversely with all thrombotic events (P=0.012) but correlated positively with microcirculatory events (P=0.01). Some of the factors (age, hypertension, diabetes, and smoking) powerfully predicted rather arterial events, whereas others (f.V “Leiden” mutation, protein C deficiency, elevated f.VIII levels, presence of antiphospholipid antibodies) were connected preferentially with venous events. However, when full blood cell counts from the time of the thrombotic events were studied and compared to mean levels of all entries during follow-up, we could detect higher platelet counts at the time of the thrombotic event (454 vs 420 G/L, P=0.007), while we could not demonstrate any significance of the WBC counts at the time of the event. The correlation of the Plt count was marked in all types of events and was most conspicuous in microcirculatory events. Thrombotic events during follow-up were also associated with lack of ASA therapy: only 6/16 (37.5%) patients at the time of the venous event, 35/61 (57.4%) patients at the time of the arterial event and 11/37 (29.7%) patients at the time of the microcirculatory event received ASA therapy (whereas ASA administration was reported in 80.0% of follow-up entries). Conclusions: The current study indicates that during ANG ± ASA therapy, the incidence of thrombosis is very low in MPN-t and especially the rate of venous events is extraordinarily low. The predictors of the thrombotic events are similar as previously published by others. Above that, we have proven the usefulness of detection of the so-called thrombophilic states. However, in contrast with the prevailing current opinion, we have shown that higher platelet counts (and not WBC counts) are important at the time of thrombosis, albeit at diagnosis the Plt counts may inversely and WBC counts positively correlate with the thrombotic risk. This discrepancy may result from treatment: patients with higher Plt counts at diagnosis may receive more cytoreducing and/or antiaggregation therapy. Disclosures: Schwarz: AOP Pharmaceuticals: Consultancy.