Cancer Incidence in World Trade Center Rescue and Recovery Workers, 2001–2008

Background: World Trade Center (WTC) rescue and recovery workers were exposed to a complex mix of pollutants and carcinogens. Objective: The purpose of this investigation was to evaluate cancer incidence in responders during the first 7 years after 11 September 2001. Methods: Cancers among 20,984 consented participants in the WTC Health Program were identified through linkage to state tumor registries in New York, New Jersey, Connecticut, and Pennsylvania. Standardized incidence ratios (SIRs) were calculated to compare cancers diagnosed in responders to predicted numbers for the general population. Multivariate regression models were used to estimate associations with degree of exposure. Results: A total of 575 cancers were diagnosed in 552 individuals. Increases above registry-based expectations were noted for all cancer sites combined (SIR = 1.15; 95% CI: 1.06, 1.25), thyroid cancer (SIR = 2.39; 95% CI: 1.70, 3.27), prostate cancer (SIR = 1.21; 95% CI: 1.01, 1.44), combined hematopoietic and lymphoid cancers (SIR = 1.36; 95% CI: 1.07, 1.71), and soft tissue cancers (SIR = 2.26; 95% CI: 1.13, 4.05). When restricted to 302 cancers diagnosed ≥ 6 months after enrollment, the SIR for all cancers decreased to 1.06 (95% CI: 0.94, 1.18), but thyroid and prostate cancer diagnoses remained greater than expected. All cancers combined were increased in very highly exposed responders and among those exposed to significant amounts of dust, compared with responders who reported lower levels of exposure. Conclusion: Estimates should be interpreted with caution given the short follow-up and long latency period for most cancers, the intensive medical surveillance of this cohort, and the small numbers of cancers at specific sites. However, our findings highlight the need for continued follow-up and surveillance of WTC responders

A Phase 2, Single-Arm, Open-Label Trial To Evaluate the Effectiveness of Darbepoetin alfa for the Treatment of Anemia in Patients with Low-Risk Myelodysplastic Syndrome

Abstract Patients (pts) with myelodysplastic syndromes (MDS) often develop clinically significant anemia due to ineffective hematopoiesis. Using the erythropoiesis-stimulating protein (ESP) epoetin alfa to treat anemia results in an average response rate of approximately 30% (40% when used with G-CSF) in low-risk MDS pts. Darbepoetin alfa (DA) (150 to 300 mcg/week) also effectively increases hemoglobin (Hb) concentrations and reduces red blood cell transfusion requirements in these pts. This study is a phase 2, single-arm, open-label trial (with a planned sample size of 200 pts), evaluating the efficacy of DA 500 mcg given SC every 3 weeks (Q3W) for treating anemia in low-risk MDS pts during the 13-week (wk) test period. Eligible pts had low or intermediate-1 risk MDS (IPSS/FAB criteria), anemia (Hb ≤11 g/dL), and no previous or ongoing chemotherapy or biologic response modifiers (except for ESPs [stopped ≥7 days and ≤1 month before enrollment] and G-CSF [allowed for infection before enrollment]). The primary endpoint is the proportion of pts achieving an erythroid response during the test period. Secondary endpoints include the change in Hb from baseline at wk 13, transfusion incidence, and impact on pt-reported fatigue. This study has completed enrollment and data are available from a planned interim analysis of the first 100 pts; 63 pts were not treated with an ESP before enrollment (ESP-naive ([EN]). Of the EN pts, 51% were female, 81% were white, 73% had low-risk MDS, 22% had intermediate-1 risk MDS, 60% had refractory anemia (RA), 30% had RA with ringed sideroblasts (RARS), and 10% had RA with excess blasts (RAEB). Results for EN pts are shown in the table. Of the 37 pts treated with an ESP before enrollment, the crude percentage (95% CL) with an overall (major plus minor) erythroid response was 36% (20, 53), the crude percentage (95% CL) with a major erythroid response was 21% (7, 35), and the crude percentage (95% CL) that required transfusions during wks 1 to 13 was 32% (17, 48 ). During the test period, 16% of all pts reported a serious adverse event (none were considered treatment-related). Injection site pain (reported by 4% of pts) was the most common treatment-related adverse event. No thromboembolic events have been reported. Interim results from this fully-enrolled study indicate that DA 500 mcg Q3W appears to be well tolerated and capable of increasing Hb levels in low-risk MDS pts. Final results for the primary endpoint will be presented. ESP-Naive Pts, N = 63 No. of Patients Evaluated (n) Crude % (95% CL) pts with overall erythroid response 77% (66, 88) 57 Crude % (95% CL) pts with major erythroid response 47% (34, 60) 57 Mean (95% CL) baseline Hb 9.9 (9.6, 10.1) g/dL 56 Mean (95% CL) change in Hb at wk 13 (last value carried forward approach) 1.1 (0.8, 1.4) g/dL 56 Crude % (95% CL) pts with transfusions (wks 1 to 13) 17% (8, 27) 63 Mean (95% CL) baseline FACT-F score 29.8 (25.9, 33.8) 46 Mean (95% CL) change in FACT-F score at wk 13 (available data) 5.7 (2.3, 9.0) 4

Transition to Independence: Characteristics and Outcomes of Mentored Career Development (KL2) Scholars at Clinical and Translational Science Award Institutions.

PURPOSE: To describe the transition from mentored to independent research funding for clinical and translational scholars supported by institutional KL2 Mentored Career Development programs. METHOD: In 2013, faculty leaders at Clinical and Translational Science Award institutions completed an online survey, reporting characteristics of scholars in their KL2 programs from 2006–2013. The primary outcome variable was a report that the scholar had received independent research funding as a principal investigator. Data analysis included descriptive summaries and mixed effects regression models. RESULTS: Respondents from 48 institutions (of 62 eligible; 77%) provided information about 914 KL2 scholars. Of those, 620 (68%) were medical doctors, 114 (12%) had other clinical training, and 177 (19%) were non-clinician PhDs. Fifty-three percent (487) were female; 12% (108/865) were members of racial or ethnic groups underrepresented in medicine (URM). After completing KL2 training, 96% (558/582) remained engaged in research. Among scholars who completed KL2 training two or more years earlier, 39% (149/374) had received independent funding. Independent funding was from non-National Institutes of Health (NIH) sources (120 scholars) more often than from NIH (101 scholars). The odds of a non-clinician attaining independent funding were twice those of a clinician (odds ratio 2.05, 95% confidence interval 1.11–3.78). Female and URM scholars were equally as likely as male and non-URM scholars to attain independent funding. CONCLUSIONS: KL2 programs supported the transition to independent funding for clinical and translational scientists. Female and URM scholars were well represented. Future studies should consider non-NIH funding sources when assessing the transition to research independence

The Efficacy and Safety of Darbepoetin Alfa for Treating Anemia in Low-Risk Myelodysplastic Syndrome Patients: Results after 53/55 Weeks

Abstract Myelodysplastic syndromes (MDS) are hematopoietic disorders characterized by peripheral cytopenias and risk of progression to leukemia. MDS patients (pts) are often anemic, resulting in increased red blood cell transfusions (tfns) and fatigue. Previous studies have shown that 150mcg/week (wk) or 300mcg/wk of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) can raise hemoglobin (Hb) levels in low-risk MDS pts (Patton et al. J Support Oncol.2005;3:419–426). We present data from a phase 2, single-arm, open-label study on the efficacy of 500mcg DA administered every three wks (Q3W) for treating anemia in low-risk MDS pts. Eligibility criteria included ≥18 years, anemia (Hb ≤11g/dL), and low- or intermediate-1-risk MDS (IPSS definition). If pts did not respond by wk 7, the dosing frequency was escalated to Q2W. After the last DA dose on wk 52, the end of study (EOS) was wk 53 (Q2W dosing) or wk 55 (Q3W dosing). The primary endpoint was the percentage of pts with an erythroid response (International Working Group criteria) by wk 13. Secondary 53/55-wk endpoints included incidence of erythroid responses, incidence of tfns, and the change in Hb levels and FACT-F score from baseline (BL). Results were stratified by whether pts had prior ESA therapy: ESA-naive (ESA-N) vs prior ESA-treated (ESA-T). A previous interim analysis showed that low-risk MDS pts could achieve an erythroid response after 13 wks of DA 500mcg Q3W (Gabrilove et al. Blood.2005;106:abstract2541). This is the first reported summary after 53/55 wks (n=148). Of 98 ESA-N pts, 47% were men, 85% were white, and the mean (SD) age was 74 (10) years; the 50 ESA-T pts had similar demographics. Both ESA-N and ESA-T pts had similar BL Hb (Table). By wk 53/55, the percentage (95% CL) of pts with a major erythroid response (≥2g/dL Hb rise from BL or tfn independence) was 56% (46, 66) in ESA-N pts and 30% (17, 43) in ESA-T pts. Both ESA-N and ESA-T pts had a clinically meaningful rise (≥3 points) in FACT-F score from BL. Of the 148 pts, 89% reported adverse events (AEs) with the most common AE being fatigue, 7% had AEs considered related to DA treatment, and 1.4% had thromboembolic events. These results suggested that DA 500mcg Q3W was well tolerated and increased Hb levels in the MDS pts in this study. ESA-N, N=98 ESA-T, N=50 KM%= Kaplan-Meier percentage Crude % (95% CL) pts with a major erythroid response 56% (46, 66) 30% (17, 43) Crude % (95% CL) pts with a minor erythroid response 15% (8, 22) 20% (9, 31) Mean (SD) BL Hb, g/dL 9.8 (1.0) [n=84] 10.0 (1.2) [n=41] Mean (SD) Hb change (BL to wk 53/55) (last value carried forward) 1.1 (1.6) [n=84] 0.2 (1.7) [n=41] Crude % (95% CL) pts achieved target Hb (11g/dL) 68% (58, 78) [n=87] 46% (31, 60) [n=46] Mean (SD) Hb after reached Hb target, g/dL 11.7 (0.8) [n=68] 11.6 (0.9) [n=25] KM% (95% CL) pts with tfns (wk 1 to EOS) 29% (19, 39) 43% (27, 59) KM% (95% CL) pts with tfns (wk 5 to EOS) 28% (19, 38) [n=96] 43% (26, 60) [n=45] Mean (SD) change in FACT-F score (BL to wk 53/55) 5.8 (8.6) [n=45] 7.2 (9.3) [n=15

Understanding Career Success and Its Contributing Factors for Clinical and Translational Investigators.

PURPOSE: To understand the factors that facilitate career success for career development awardees in clinical and translational science and reconceptualize understand ing of career success for this population. METHOD: In 2013-2014, the authors conducted semistructured interviews with former NIH KL2 or K12 scholars from nine Clinical and Translational Science Award-funded institutions. Participants either had or had not secured independent funding at least two years after the end of their last K award. Questions covered the factors that facilitate or hinder junior investigators' transition to independent funding. Interviews were recorded and transcribed, and the transcripts were analyzed thematically. RESULTS: Forty individuals participated, with equal representation by men and women and by independently and not independently funded investigators. Personal factors that facilitated success included networks, persistence and resilience, initiative, autonomy, and personal and professional balance. Organizational factors included appropriate mentorship, protected research time, and institutional resources and support.Even independently funded participants described challenges regarding career direction. Five participants without independent funding modeled a broad spectrum of successful career paths, having assumed leadership positions not reliant on grant funding. Alternative definitions of career success included improving public health, enjoying work, seeing mentees succeed, and receiving external acknowledgment of successes. CONCLUSIONS: Awareness of the factors that facilitate or hinder career success can help junior faculty, mentors, and institutional leaders support career development in clinical and translational science. New definitions of career success are needed, as are career paths for faculty who want to engage in research in roles other than principal investigator