tbuckley/cabot-search huggingface dataset:
Impact of hospital volume on outcomes of patients undergoing chemotherapy for acute myeloid leukemia (AML): A matched cohort study.
Authors: Smith Giri, Ranjan Pathak, Vijaya Raj Bhatt, Michael Gary Martin
Journal: Journal of Clinical Oncology (2015)

e18067 Background: There is a growing evidence that hospital volume affects survival among patients with various medical and surgical conditions. Whether hospital volume affects outcomes following chemotherapy among patients with AML remains unknown. Methods: We utilized the Nationwide Inpatient Sample (NIS) database to identify all US in-patients undergoing chemotherapy for AML from 2009-2011 using ICD 9 codes. Hospitals were divided into quartiles, based on the annual number of cases of AML admitted for chemotherapy and classified into high volume (above 75th percentile) and low volume Centers (below 75th percentile). We used propensity matching methods to control for variables including age, sex, comorbidity (using Charleson comorbidity index), insurance status, income status (in quartiles), hospital size, location, ownership and day of admissions in the study cohorts. Chisquared tests and analysis of variance (ANOVA) was used for bivariate analysis. Statistical analysis was done using STATA 13.0 (College Station, TX). Results: Out of 15,446 hospitalizations for chemotherapy, 3640 were selected for final analysis after propensity matching. This comprised of 1150 (31%) cases in high volume centers and 2489 (69%) cases in low volume centers. The mean age was 51.0 years in high volume center and 52.3 years in low volume centers (p value 0.25). The in-hospital mortality was 1.59% in high volume centers which was significantly lower than a mortality rate of 4.97% in the low volume centers (OR 3.26; 95% CI 1.98-5.38, p value < 0.001). Meanwhile, the mean length of hospital stay (14.2 days versus 14.5 days; p value 0.88) and mean cost of hospitalization ($102653 versus $101945; p value 0.96) were similar in the two study cohorts. Conclusions: Our study shows a clear volume-outcome relationship among US inpatients undergoing chemotherapy for AML. Future studies should focus on the reasons behind such differences.
Post hoc analysis of relationship between baseline white blood cell count and survival outcome in a randomized phase III trial of decitabine in older patients with newly diagnosed acute myeloid leukemia.
Authors: Chris Arthur, Jaroslav Cermak, Jacques Delaunay, Jiri Mayer, Grzegorz Mazur, Xavier G. Thomas, Agnieszka Wierzbowska, Mark M. Jones, Peter G. Tarassoff, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2012)

6559 Background: In a large phase III trial (N=485), patients (pts) ≥65y with newly diagnosed acute myeloid leukemia (AML) received 1-h IV infusion of decitabine (DAC) 20 mg/m 2 for 5 consecutive days every 4 wk or treatment choice (TC) with supportive care or cytarabine 20 mg/m 2 subcutaneous injection for 10 consecutive days every 4 wk (NCT00260832; Kantarjian et al. JCO, in press). Enrolled pts had white blood cell (WBC) count &lt;40 x10 9 /L; baseline WBC counts were relatively low (median [range] DAC: 3.1 x10 9 /L [0.3-127.0]; TC: 3.7 x10 9 /L [0.5-80.9]). This post hoc analysis assessed baseline WBC count and survival outcome. Methods: Overall survival (OS) and progression-free survival (PFS) were summarized by baseline WBC subgroups (&lt;1, 1-5, &gt;5 x10 9 /L). Results: Mature survival data (2010) were based on intent-to-treat (ITT) population (446 deaths: TC, n=227; DAC, n=219). OS was 5.0 mo for TC vs 7.7 mo for DAC (nominal P=.037). For each WBC subgroup, differences in OS for TC vs DAC were not significant (NS), but hazard ratios (HR) favored DAC for all subgroups (Table). There was a significant difference in PFS in favor of DAC for patients with baseline WBC 1–5 x10 9 /L (P=.005; HR=0.67) and &gt;5 x10 9 /L (P=.027; HR=0.71). Conclusions: These data are consistent with overall results, with a trend toward improved outcome with DAC regardless of baseline WBC count in older pts with newly diagnosed AML. Further analyses are warranted. [Table: see text]
Development of a screening tool to assess prostate cancer health literacy.
Authors: Ashwin A. Kotwal, Viraj A. Master, Ashesh B. Jani, Gertrude Fraser, Andrew M Wolf, Daniel Shin-Ping Wang, Howard Duncan, Kwesi Ewur, Angela Marie Taber, Kerry L. Kilbridge
Journal: Journal of Clinical Oncology (2017)

127 Background: Poor comprehension of prostate cancer (PCa) related terms can create barriers to informed discussions on screening, treatment, and measuring outcomes, and contribute to disparities in African American (AA) men. We developed a screening tool to assess for low PCa-related health literacy. Methods: We assessed PCa-related literacy in a sample of 189 AA men, age &gt;40 years from diverse socioeconomic status (SES) using a 27-item scale derived comprehension of commonly used terms for urinary, bowel and sexual function. Using item-response models we examined differential item functioning by education. We developed rapid screening tools based on understanding of 1 or 2 words to predict overall comprehension. Receiver operating characteristic curves assessed the sensitivity and specificity for individuals understanding less than a pre-specified threshold of 70% on the overall scale, defined as “low literacy.” Results are being tested in an independent sample of 110 AA men. Results: The 27-item scale had good internal reliability (Cronbach alpha = 0.93). 47% of the sample met criteria for low literacy. Lower education groups had relatively poor comprehension of sexual function terms compared to higher education groups. 1-item scales using comprehension of the term “rectal urgency” had a sensitivity of 95% for identifying low literacy, “erection” had a specificity of 98%, and “vaginal intercourse” had a sensitivity of 91% and specificity of 81%. Combining “vaginal intercourse” and “rectal urgency” yielded a 2-item scale with strong characteristics (sensitivity 88%, specificity 89%), as did combining “vaginal intercourse” and “erection” (sensitivity 94%, specificity 81%). Conclusions: Rapid screening tools assessing PCa-related literacy performed well in a community sample of AA men with varied SES. Providers can use these tools to identify those at risk of poor comprehension to tailor outcome measurement and shared decision making. [Table: see text]
Results of a phase I/II study (NCT01365559) of carfilzomib (CFZ) replacing bortezomib (BTZ) in BTZ-containing regimens for BTZ-treated patients (pts) with relapsed and refractory multiple myeloma (MM).
Authors: James R. Berenson, James D. Hilger, Robert Dichmann, Dipti Patel-Donnelly, Ralph V. Boccia, Alberto Bessudo, Laura Stampleman, Donald Gravenor, Shahrooz Eshaghian, Hilda Chamras, Youram Nassir, Regina A. Swift, Robert A. Vescio
Journal: Journal of Clinical Oncology (2013)

8599 Background: Recent data has shown that single-agent CFZ can produce responses among MM pts refractory to previous treatment regimens including those containing BTZ. We conducted an intrapatient phase I/II trial investigating the safety and efficacy of CFZ as a replacement for BTZ in BTZEcontaining regimens to which pts have progressed. Methods: Eligible pts progressed while receiving their most recent BTZEcontaining regimen after at least 4 doses of BTZ at ≥1.0 mg/m² in ≤4 weeks per cycle. CFZ replaced BTZ in each regimen via intravenous administration over 30 min on days 1, 2, 8, 9, 15, and 16 of each cycle. Treatment continued using the same dose(s) and schedule(s) of each drug administered in the BTZEcontaining regimen. CFZ doses were escalated on each of the first 4 cycles from 20 to 27, 36, and 45 mg/m² or until a maximum tolerated dose (MTD) was reached for that regimen. Results: Of 37 enrolled pts, 33 were evaluable for efficacy and 37 for safety. Pts received a median of 4 prior treatments (range, 1-23) and 2 different BTZ-containing regimens (range, 1-13). Pts were treated with CFZ and a variety of different combinations of agents, including: bendamustine, clarithromycin, cyclophosphamide, dexamethasone, melphalan, methylprednisolone, pegylated liposomal doxorubicin, thalidomide, lenalidomide, and ascorbic acid. Pts have completed a median of 3 cycles with 12 pts going on to maintenance. One of 14 combinations, CFZ + ascorbic acid + cyclophosphamide, has reached a MTD at 45 mg/m 2 . Clinical benefit was seen in 23 (70%) evaluable pts (complete response = 6%; very good partial response = 18%; partial response = 21%; minor response = 24%) with another 18% showing stable disease. The median time to progression is 8.8 mo. (95% CI: 6.4-11.1 mo.) with 21 pts progressing overall and 9 progressing on study treatment. The most common ≥ G3 adverse events were lymphopenia (35% of pts), thrombocytopenia (19%), neutropenia (11%), and anemia (8%). Conclusions: These results suggest that replacement of BTZ with CFZ in a BTZ-containing combination regimen to which a MM patient is failing often leads to responses and is well-tolerated. Clinical trial information: NCT01365559.
Health-related quality of life (HRQoL) in patients with advanced neuroendocrine tumors (NET) of gastrointestinal origin in the phase 3 RADIANT-4 trial.
Authors: Simron Singh, Jonathan R. Strosberg, Lida Bubuteishvili-Pacaud, Evgeny Degtyarev, Maureen Neary, Matthias Hunger, Jennifer Eriksson, Jean-Francois Ricci, Nicola Fazio, Matthew H. Kulke, Marianne E. Pavel, James C. Yao
Journal: Journal of Clinical Oncology (2017)

285 Background: In the RADIANT-4 trial, everolimus (EVE) plus best supportive care (BSC) improved progression-free survival (PFS) compared to placebo (PBO) plus BSC in 302 patients with advanced progressive nonfunctional NET of gastrointestinal (GI) or lung origin (Yao, Lancet 2015) and in patients of GI origin only (Singh, ASCO-GI 2016). In addition, HRQoL was maintained with no statistically or clinically relevant differences in patients receiving EVE compared to PBO in the full sample (Pavel, ASCO 2016) and in patients with NET of GI origin (Pavel, NANETS 2016). Complementary analyses are presented to assess treatment effect on HRQoL in the subpopulation of patients with NET of GI origin. Methods: HRQoL was measured with FACT-G, a 27-item validated questionnaire with 4 domains: physical (PWB), social/family (SWB), emotional (EWB), and functional wellbeing (FWB). FACT-G was completed at baseline and every 8 weeks until month 12, then every 12 weeks until study drug discontinuation. Linear mixed models (LMM) were fitted to analyze mean FACT-G total (scale: 0 – 108) and subscale scores over time. A responder analysis in terms of cumulative distribution functions (CDF) of patients mean change from baseline across the entire study period was also conducted. Results: The subgroup of patients with NET of GI origin included 211 patients (141 on EVE and 70 on PBO) with NET of ileum, rectum, jejunum, stomach, duodenum, colon, caecum, appendix, or cancer of unknown primary (CUP), generally known as GI origin. In LMM, FACT-G total score at week 8 was 79.9 (95% CI: 77.7, 81.1) for EVE and 79.9 (95% CI: 77.0, 82.8) for PBO, declining to 77.1 (95% CI: 73.9, 80.4) and 78.7 (95% CI: 73.4, 83.9) at week 48. At each time point, differences in mean scores between treatment arms were lower than the minimally important difference (MID) of 7 points. Differences in mean subscale scores between treatment arms also did not exceed the MID (3 points). CDF plots showed no differences in distributions for the FACT-G total score (p = 0.9348). Conclusions: In addition to PFS benefits, HRQoL is maintained in patients with NET of GI origin receiving EVE despite usual toxicities of active cancer treatment. Clinical trial information: NCT01524783.
An evaluation of survivorship care plan program.
Authors: Debra Spoljaric, Brittany Depp, Allison A. King
Journal: Journal of Clinical Oncology (2017)

62 Background: The Commission on Cancer mandated the development and implementation of survivorship care plans (SCP) in 2015. Minimal evidence exists to suggest SCP are meaningful to survivors and primary care physicians (PCP). We sought to evaluate the usefulness of the SCP as perceived by both survivors and PCP. Methods: Phase I was 8-month pilot using a 7-page SCP detailing medical information and follow up sections addressed to the survivor and to the PCP. To evaluate patient and PCP views on the SCP, a telephone survey was created for patients and a two-page Likert scale survey for PCP was faxed. Phase I evaluations revealed 90% of survivors did not look past page 2 of the document and 16% of PCP felt it was too long and busy to read. The SCP was edited for a 3-page version and implemented in Phase II over 11-months. Results: In Phase I, 78 SCP were delivered to survivors, 58% were surveyed. Of PCP, 24% responded. In Phase II, 895 SCP were delivered, and 274 (31%) survivors surveyed. In Phase I and II, when asked to identify themselves as a cancer survivor, 282 (88%) confirmed and 21 (7%) were unsure. After reviewing the SCP, 93.1% understood their plan of care; 79.6% understood potential late effects; 33% were aware of support or resources available; 96% would recommend to another cancer survivor to get one. In Phase II, 16% (43) of PCP responded. Overall replies were positive: 61% found resource list helpful; 66% wanted more specific information about patient potential late effects; 87% agreed knowing symptoms of late effects is helpful. 70% wanted clarity on follow up tests needed and who should order. PCP overwhelmingly agreed (88%) the SCP is helpful. 90% agreed that knowing ongoing side effects of treatment was important. Conclusions: Survivors liked having their cancer treatment in one concise document and PCP physicians feel that the SCP is meeting their basic needs. PCP are interested in more specific long term side effects to monitor in their patients and direction on what follow-up tests are needed and who is ordering them. Further research is needed to study the impact of SCP on survivors’ health.
Hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL): 25-year experience at the University of Minnesota
Authors: M. B. Tomblyn, T. E. DeFor, M. MacMillan, P. D. Higgins, K. E. Dusenbery, D. J. Weisdorf
Journal: Journal of Clinical Oncology (2007)

7001 Background: HCT is frequently used for management of ALL. Methods: We reviewed the records of 623 consecutive patients (63% male, median age 13 years) treated with myeloablative TBI-containing conditioning and either autologous or allogeneic transplantation between 1980 and 2005 at the University of Minnesota. Donor types were autologous (34%), related (45%), unrelated (16%) or cord (11%). Disease status at transplant was CR1 (24%), CR2 (50%), CR3 (18%) and relapse (8%). Univariate and multivariate analyses were performed for clinical endpoints including overall survival (OS), progression free survival (PFS), relapse, treatment-related mortality (TRM), and Grades II-IV acute and chronic graft versus host disease (GVHD). Results: Median follow-up among survivors was 8.3 years (1.0–22.9). The estimated incidence of acute GVHD was 42% and chronic GVHD was 16%. At 5 years, OS, PFS, and relapse were estimated at 29%, 26%, and 43% respectively. 5-year OS for each group: autologous (17%, 12–22%), related (35%, 29–41%), matched unrelated (42%, 29–55%), mismatched unrelated (21%, 11–33%), and cord blood (46%, 33–59%). TRM at 2 years was 28%. Multivariate analysis for OS, PFS, relapse and TRM for donor type is shown ( Table ). Acute GVHD was more frequent with unrelated donors (p&lt;0.01) but similar for related donors and cords. Presence of acute GVHD led to improved PFS (RR 0.6, 0.4–0.7, p&lt;0.01) and decreased relapse (RR 0.5, 0.3–0.8, p&lt;0.01) at 1 year. 5-year OS improved significantly from 1980–1984 (28%, 20–37%) to 2000–2005 (45%, 33–56%), p &lt; 0.01. Conclusions: Allogeneic HCT results in a durable PFS, although TRM is increased with unrelated mismatched donors. As expected, autologous HCT results in increased relapse rates. Despite significant mismatch, umbilical cord HCT led to similar OS, PFS, relapse, TRM and chronic GVHD compared to related donor HCT. Development of acute GVHD decreases relapse, resulting in improved PFS. No significant financial relationships to disclose. [Table: see text]
Evolution of bosutinib (BOS) toxicity in patients (pts) with Ph+ leukemia after resistance/intolerance to prior therapy.
Authors: Carlo Gambacorti-Passerini, Tim H. Brummendorf, Jorge E. Cortes, Jeffrey H. Lipton, Dong-Wook Kim, Eric Leip, Kathleen Wyant Turnbull, Hagop M. Kantarjian, Hanna Jean Khoury
Journal: Journal of Clinical Oncology (2013)

7099 Background: BOS is an oral dual Src/Abl tyrosine kinase inhibitor (TKI) approved for treatment of Ph+ CML following resistance/intolerance to prior therapy. Prior reports from this phase I/II trial indicated the BOS safety profile was primarily characterized by myelosuppression, gastrointestinal events, and rash. The current analysis compares the incidence of toxicity in Year 1 (Y1) for pts on treatment ≤1 y and within Y1 and Year 2 (Y2) for pts on treatment for &gt;1 y. Methods: BOS 500 mg/d was evaluated in 3 cohorts: chronic phase (CP) CML after imatinib only (CP 2L cohort; n = 286); CP CML after imatinib + dasatinib and/or nilotinib (CP 3L cohort; n = 119); and accelerated/blast phase CML or ALL after prior TKI therapy (ADV cohort; n = 164). Results: The most common treatment-emergent adverse events (TEAEs) in each cohort occurred more frequently within Y1 than Y2 (Table). The incidence for grade 3/4 events followed a similar pattern. AEs were the most common reason for BOS discontinuation in Y1 (CP 2L, 53%; CP 3L, 32%; ADV, 41%). Of the pts whose primary reason for discontinuing BOS was an AE during the first 2 y, most did so during Y1 (CP 2L, n = 51/60 [85%]; CP 3L, n = 22/24 [92%]; ADV, n = 24/25 [96%]); the most common reasons during Y1 were thrombocytopenia (12%; 9%; 4%), increased ALT (6%; 4%; 2%), neutropenia (3%; 6%; 0%), diarrhea (4%; 3%; 0%), and vomiting (3%; 4%; 1%). Serious AEs were more common among pts who discontinued BOS ≤1 y versus on treatment &gt;1 y in the CP 3L and ADV cohorts, but similar in the CP 2L cohort (Table). Conclusions: Discontinuation due to AEs was observed primarily in Y1. For pts on BOS for &gt;1 y, the incidence of common TEAEs decreased substantially after Y1, suggesting BOS tolerability improves after long-term exposure. Clinical trial information: NCT00261846. [Table: see text]
An injury prevention pyramid for elite sports teams
Authors: Philip Alexander Coles
Journal: British Journal of Sports Medicine (2017)

There are numerous factors that influence injury rates in elite sporting teams, and many of them are intricately related. To achieve sustained success in decreasing injury rates, we must understand not only each of those potential factors in isolation, but also the relationships that exist between them. Rarely is one session, or one event, the true isolated cause of an injury. Typically, there has been a confluence of many events over time, which has led to the pivotal point where one event then simply becomes ‘the straw that broke the camel’s back’. The ‘High Performance Unit’ should take the lead in responsibility for preventing injuries, but for them to achieve long-term success,they must collaborate closely with coaches, management and the players themselves, in creating an integrated approach to preventing injuries. While there may be significant debate about the relative influence of individual factors on injury rates, there should be little debate that each of the factors discussed in the following model will have some effect. For sustained success, it is more productive to think of each factor as a building block in a pyramid, as opposed to an independent entity. Although this does not mean that addressing one aspect in isolation cannot be effective in the short term, it recognises if you do not have the foundation blocks right, then your likelihood of achieving consistent and long-lasting success is decreased. We should also be aware, that the culture of an organisation as a whole, and the psycho-social influences on each individual player within it, can have a modifying effect on the model at every stage.1 

The first building block in the injury prevention pyramid for elite sporting teams is player recruitment and / or list management. Ultimately, if you recruit or maintain a list of players who are either not suitable for the …
Phase Ia/b study of combination carboplatin, paclitaxel, and ridaforolimus in patients with solid, endometrial, and ovarian cancers.
Authors: Hye Sook Chon, Ji-Hyun Lee, Amber B Herschberger, Robert M Wenham
Journal: Journal of Clinical Oncology (2012)

TPS3114 Background: mTOR is a member of the PI3K family. Ridaforolimus (RIDA) is a mTOR inhibitor that has demonstrated tolerability as intravenous (IV) and oral formulations. PI3K/AKT/mTOR signalling is associated with resistance to taxanes. In cancer (ca) cells, inhibition of mTOR signalling counteracts AKT-mediated resistance to drugs inhibiting tubulin. Paclitaxel and carboplatin (PC) have broad activity including endometrial, ovarian, and many cancers. mTOR inhibition with PC has synergistic and additive effects in solid tumors. A common defect in endometrioid ca is mutation of PTEN, causing activation of the PI3K/AKT/mTOR pathway. RIDA improved PFS over hormonal therapy of metastatic endometrial cancer in a randomized phase II study (Oza AM, et al. J Clin Oncol. 2011;29 [suppl; abstr 5009]). In 35 patients in a phase II study of RIDA, there were 7.7% partial response (PR) and 58% with stable disease with median duration 6.6 months (Mackay H et al. J Clin Oncol. 2011;29 [suppl; abstr 5013]). Ovarian ca ultimately develops a phenotype resistant to taxanes that may be overcome with mTOR inhibition. RIDA may therefore potentiate the response of endometrial, ovarian, and other solid cancers to PC. Methods: Patients (pts) with advanced solid ca and measureable disease and up to 3 prior therapies received P (175mg/m 2 IV) and C (AUC 5 to 6 mg/ml/min IV) on day (D)1 of each 3-week cycle. RIDA in escalating cohorts of 10-40 mg is administered orally daily for 5 days per week (D1-5, D 8-12, D 15-19) in phase IA cohorts. Samples for pharmacokinetics of RIDA and P and pharmacodynamics (PD) are collected. More than 1 anticipated DLT of thrombocytopenia or neutropenia in the latter part of the cycle shifts the escalation of RIDA to an alternate schedule (D1-5, D 8-12). Escalation continues in a 3X3 design until 40 mg/day of RIDA or MTD. Seven pts have been enrolled; 5 ovarian, 1 endometrial, 1 urethral ca. The second cohort of an alternate schedule has been filled and evaluation continues. Further characterization of tolerability, efficacy, and PD are planned at the MTD in the phase IB expansion cohorts of 15 ovarian/15 endometrial cancers.