tbuckley/cabot-search huggingface dataset:
Defining the role of PCI in NSCLC: A review and meta-analysis of the literature.
Authors: Timothy J Brown, Matt Christopher Brennan, Michael J. Glantz
Journal: Journal of Clinical Oncology (2015)

e18516 Background: Non-small-cell lung cancer accounts for 85% of lung cancer diagnoses worldwide. The brain is a devastating and frequent site of metastasis. Although nearly all studies on prophylactic cranial irradiation (PCI) in NSCLC demonstrate a significant benefit in the rate of brain metastasis, the practice remains controversial. We present the results of a critical appraisal and meta-analysis of the literature to define the role of PCI in NSCLC. Methods: Primary outcomes were 1-year survival and the rate of brain metastases. A literature search querying Medline and the Cochrane Database was completed using the search terms: prophylactic cranial irradiation AND non-small cell lung carcinoma. Studies meeting eligibility requirements were graded for level of evidence using ASCO, Cochrane, and AAN criteria. Relevant data was extracted, and 1-year survival rates were estimated using pixel coordinates when not explicitly stated. Meta-analyses using both fixed and random effects models were performed. Heterogeneity was assessed using I2and probability of Q, and publication bias was assessed with funnel plots Results: The literature search produced 274 articles; 112 were unique citations and 17 were identified as potentially eligible for analysis. Of these, 11 studies provided information on the rate of brain metastases, and 5 provided data on 1-year survival. Although 5 studies were randomized, controlled trials, no study provided greater than Class III evidence. The meta-analysis showed a relative risk for the frequency of brain metastases between the PCI and non-PCI groups of 0.29 [95% CI 0.25-0.35,], p < 0.001, number needed to treat (NNT) = 10. The relative risk (PCI vs. no PCI) for 1 year survival rate was 1.09 [95% CI 1.04-1.14], p < 0.001, NNT = 100. Confidence in these results using GRADE criteria was low to very low. Conclusions: A quantitative systematic review of the literature suggests a substantial reduction in the rate of brain metastases in patients with NSCLC receiving PCI, and a modest increase in one-year survivors. Despite multiple randomized controlled trials, the quality of the evidence is low, but the flaws in study methodology are remediable. A multi-national effort to resolve this critical question should be a priority.
Cross-cultural rating of satisfaction with cancer care.
Authors: Pascal Jean-Pierre, Ying Cheng, Kevin Fiscella, Ashley Jean-Pierre, Harisa Saphic, Thomas Burish, Keith Mesidor, William Kim
Journal: Journal of Clinical Oncology (2015)

e17613 Background: Accurate evaluation of patient satisfaction is an important dimension of quality of cancer screening and treatment. We applied ordinal logistic regression to assess uniform, non-uniform and total Differential Item Functioning (DIF) for the Patient Satisfaction with Cancer-related Care (PSCC) measure items in English vs. Spanish speaking cancer patients. Methods: The sample included 18 to 86 years old patients who completed the PSCC in English (N = 1067; 82.5% female) and Spanish (N = 229; 100% female 100%). We used total scale score and latent satisfaction estimate separately as matching variable to assess uniform, non-uniform, and total DIF for the PSCC items using ordinal logistic regression analysis. We used language as the grouping variable, i.e., the English speaking group is the reference group and the Spanish speaking group the focal group. Results: Using the total scale score (TSS), we found uniform DIF for 10 out of 29 PSCC items. For example, item 1 showed uniform DIF (χ2 = 5.959, df = 1, p = 0.015). Positive and significant regression coefficient (Wald = 5.849, p = 0.016) suggested that on average English speakers reported higher satisfaction on item 1 even at the same total score level. Non-uniform and total DIF were not evaluated using TSS because of missing data. Using latent satisfaction estimate (i.e., factor score), and treating missing data with mean substitution, we found significant uniform DIF for the same items, and significant non-uniform and total DIF for items 7 (regression coefficient of interaction between latent satisfaction and language = 0.518, SE = 0.188, Wald = 7.547, p = 0.006; χ2 = 25.594, df = 2, p = 0.000,) and 14 (regression coefficient of interaction between latent satisfaction and language = 0.392, SE = 0.198, Wald = 3.908, p = 0.048; χ2 = 14.856, df = 2, p = 0.001).. The interaction effect (latent satisfaction level by Language) was not statistically significant for other items (p > 0.05). Conclusions: Traditional methods of cross-cultural psychometric validation may not fully account for cultural and linguistic issues (as well as other group differences) in testing. Mediation models that systematically test underlying causes of DIF of the PSCC items are needed.
Association of TP53 codon 72 polymorphism with TP53 mutation in triple-negative breast cancer (TNBC) patients.
Authors: Mathilde Födermayr, Miriam Sebesta, Margaretha Rudas, Anna Sophie Berghoff, Elisabeth Bergen, Regina Promberger, Matthias Preusser, Peter Christian Dubsky, Michael Gnant, Guenther G. Steger, Ansgar Weltermann, Christoph Zielinski, Otto Zach, Rupert Bartsch
Journal: Journal of Clinical Oncology (2014)

1130 Background: A high rate of TP53 mutations was observed in TNBC, suggesting a role in TNBC carcinogenesis. Missense mutations cause single amino acid substitutions with altered protein function. Non-missense (nonsense, frameshift, splice site) mutations lead to functional loss or complete deletion of protein p53. Other reports have focused on TP53 polymorphisms. Codon 72 polymorphism (SNP rs1042522) is found in a proline-rich region of exon 4, encoding alleles Pro72 (ancestral form; CCC) or Arg72 (CGC) and varies with geographical latitude, accumulating towards the south; it is also common in African-Americans, where a high incidence of TNBC is evident. Effect of anticancer therapy may be influenced, as Pro72 is apparently less effective in apoptosis induction. Here, we investigated the incidence of Arg72 and Pro72 and the association of this polymorphism with TP53 mutations in a Caucasian population of TNBC patients (pts). Methods: DNA was extracted from formalin-fixed paraffin-embedded tissue of operation specimen. For investigating TP53 mutation status (exons 4-9) DNA was PCR amplified and sequenced. For correlation of two parameters, the Fisher’s exact test was used. Results: In a cohort of 35 consecutive TNBC pts, 25 TP53 mutations in 23 pts (65.7%) were observed: 13 missense (52%), 5 nonsense (20%), 4 frame shift (16%), 2 splice site (8%), 1 silent mutation (4%). Distribution of codon 72 polymorphism was 60% Arg/Arg, 11.4% Pro/Pro (p<0.001), 28.6% Pro/Arg (p=0.016). Non-missense mutations occurred mostly in pts carrying the hetero- or homozygous allele Pro72: Nonsense mutations showed a significant association with Pro/Arg (4/5; p=0.03), frameshift mutations with Pro/Pro (2/4; p=0.02) compared to Arg/Arg carriers. No correlation of TP53 mutation status or codon 72 polymorphism with clinical outcome was observed. Conclusions: Non-missense TP53 mutations leading to functional loss or deletion of protein p53 were significantly associated with homo- or heterozygous Pro72 carriers, despite the high rate of homozygous Arg72 carriers in our Caucasian TNBC pts cohort. Further studies elucidating a potential association of Pro72 with TNBC carcinogenesis and treatment response are warranted.
A phase II study of preoperative (preop) bevacizumab (bev) followed by dose-dense (dd) doxorubicin (A)/cyclophosphamide (C)/paclitaxel (T) in combination with bev in HER2-negative operable breast cancer (BC).
Authors: Sara M. Tolaney, Dan G. Duda, Yves Boucher, Shom Goel, John Martin, Marek Ancukiewicz, Hannah Potler, Jaoa Incio, Jennifer A. Ligibel, Steven J. Isakoff, Dai Fukumura, Eric P. Winer, Ian E. Krop, Rakesh K. Jain
Journal: Journal of Clinical Oncology (2012)

1026 Background: Two recent preop studies evaluating bev showed conflicting results, particularly in hormone receptor (HR)+ BC. Identification of predictive markers and their relationship to the pharmacodynamic effects of bev would facilitate the identification of BCs most likely to benefit from bev. To accomplish these goals, we conducted a unique preop trial with a run-in of single agent bev followed by ddACT with bev in two cohorts, one with HR+HER2– BC, and a smaller triple negative (TN) cohort. Methods: Pts with HR+, HER2– or TN BC were eligible if their tumor (T) was ≥1.5 cm and high grade, or had axillary LN involvement; or if T≥2.5cm and was low/intermediate grade. Treatment consisted of a single dose of bev 10 mg/kg, followed two wks later by A 60 mg/m 2 and C 600 mg/m 2 with bev 10 mg/kg q2 wks x 4, followed by T 175 mg/m 2 with bev 10 mg/kg q2 wks x 3, followed by T 175 mg/m 2 x1. Research core biopsies and interstitial fluid pressure (IFP) were assessed pre- and post- bev alone. Pathologic response was confirmed centrally and Miller-Payne (MP) was assessed. Results: 84 pts with HR+ and 20 pts with TN breast cancer were enrolled. Amongst HR+ pts, 74 had surgical tissue centrally reviewed, and 6 (8%) had a pCR. Amongst TN pts, 18 pts had tissue centrally reviewed and 8 (44%) had a pCR. Grade was found to predict MP response in both HR+ and TN pts (p=0.001). Several biomarkers were evaluated as predictors of response to bev. Baseline sVEGFR1 correlated with MP response to treatment among TN pts (p=0.015). Single-agent bev reduced the mean vascular density by 18.5% (p=0.049) in HR+ patients and the mean IFP in the overall cohort and HR+ patients by 20 (p=0.020) and 24.5% (p=0.001), respectively. The reductions in IFP correlated with higher levels of sVEGFR2 (p=0.003). The IFP decreased &gt; 50% in 24/65 pts and did not change in others. Gene expression profiling by PAM50 is underway. Conclusions: The addition of bev to preop chemotherapy is well tolerated. Tumor grade appears to predict MP response in HR+ and TN tumors, and sVEGFR1 may be a predictor of MP response to bev in TN tumors. Further work for biomarker predictors of response to bev is ongoing.
Corrections to “Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies”
Authors: J. Naidoo, D.B. Page, B.T. Li, L.C. Connell, K. Schindler, M.E. Lacouture, M.A. Postow, J.D. Wolchok
Journal: Annals of Oncology (2016)
Do Functional Movement Screen (FMS) composite scores predict subsequent injury? A systematic review with meta-analysis
Authors: Robert W Moran, Anthony G Schneiders, Jesse Mason, S John Sullivan
Journal: British Journal of Sports Medicine (2017)

Aim This paper aims to systematically review studies investigating the strength of association between FMS composite scores and subsequent risk of injury, taking into account both methodological quality and clinical and methodological diversity. Design Systematic review with meta-analysis. Data sources A systematic search of electronic databases was conducted for the period between their inception and 3 March 2016 using PubMed, Medline, Google Scholar, Scopus, Academic Search Complete, AMED (Allied and Complementary Medicine Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Health Source and SPORTDiscus. Eligibility criteria for selecting studies Inclusion criteria: (1) English language, (2) observational prospective cohort design, (3) original and peer-reviewed data, (4) composite FMS score, used to define exposure and non-exposure groups and (5) musculoskeletal injury, reported as the outcome. Exclusion criteria: (1) data reported in conference abstracts or non-peer-reviewed literature, including theses, and (2) studies employing cross-sectional or retrospective study designs. Results 24 studies were appraised using the Quality of Cohort Studies assessment tool. In male military personnel, there was ‘strong’ evidence that the strength of association between FMS composite score (cut-point ≤14/21) and subsequent injury was ‘small’ (pooled risk ratio=1.47, 95% CI 1.22 to 1.77, p&lt;0.0001, I 2 =57%). There was ‘moderate’ evidence to recommend against the use of FMS composite score as an injury prediction test in football (soccer). For other populations (including American football, college athletes, basketball, ice hockey, running, police and firefighters), the evidence was ‘limited’ or ‘conflicting’. Conclusion The strength of association between FMS composite scores and subsequent injury does not support its use as an injury prediction tool. Trial registration number PROSPERO registration number CRD42015025575.
High Response Rates with the Combination of Bortezomib, Dexamethasone and the Pan-Histone Deacetylase Inhibitor Romidepsin in Patients with Relapsed or Refractory Multiple Myeloma in a Phase I/II Clinical Trial
Authors: Simon James Harrison, Hang Quach, Kally Yuen, Andrew Strayer, Michael C. Copeman, S. Peinert, M. Bishton, M. Wolf, H. Januszewicz, MK Kenealy, K. Herbert, David Westerman, D. Carney, J. F Seymour, R. W Johnstone, David Ritchie, Miles Prince
Journal: Blood (2008)
A phase I dose-escalation study of volasertib (BI 6727) combined with nintedanib (BIBF 1120) in advanced solid tumors.
Authors: Filippo G. De Braud, Stefano Cascinu, Gianluca Spitaleri, Korinna Pilz, Laura Clementi, Dan Liu, Patricia Glomb, Tommaso De Pas
Journal: Journal of Clinical Oncology (2013)

2556 Background: Volasertib (V) is a potent and selective cell cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinases. Nintedanib (N) is a triple angiokinase inhibitor of VEGF, PDGF, and FGF receptors. Both have shown clinical activity with a manageable safety profile in patients (pts) with advanced solid tumors. This study was designed to determine the maximum tolerated dose (MTD) of V combined with N in these pts. Methods: Cohorts of 3–6 pts received V (100–450 mg IV Q3W) + oral standard dose N (200 mg BID continuously, except V infusion day). Treatment continued until clinical progression. Up to 12 pts were treated at the MTD for additional safety data. Primary endpoint was the MTD; secondary endpoints were pharmacokinetics (PK), overall safety, and preliminary efficacy. Results: 30 pts were treated (median age, 56.5 yr; ECOG PS 0/1/2, 33%/60%/7%; ≥3 prior therapies, 87%). At V doses &gt;200 mg, 7 pts experienced 13 dose-limiting toxicities (DLTs) during cycle 1: increased alanine aminotransferase [ALT] or aspartate aminotransferase [AST], neutropenia and thrombocytopenia. The MTD was V 300 mg (Table). At the MTD, the most common all grade (Gr) adverse events (AEs) were neutropenia (69%), asthenia and thrombocytopenia (62% each), increased ALT, increased AST and diarrhea (54% each). Median (range) duration on treatment was 4 (1–18) cycles. Treatment was discontinued due to progressive disease (80%), DLT (3%) and other non-AE related reasons (17%). 2 objective responses were observed (1 complete [breast cancer] and 1 partial [NSCLC]), both with the 300 mg dose. 6 pts had SD for ≥ 6 mo. PK data will be presented at the meeting. Conclusions: MTD of V + standard dose N (200 mg BID) was determined to be 300 mg Q3W (the same as the recommended phase II single agent dose of V in solid tumors). This combination had a manageable safety profile without unexpected or overlapping toxicities and showed preliminary antitumor activity. Clinical trial information: NCT01022853. [Table: see text]
Imported malaria
Authors: M. L. Willcox, J. Mant, T. O'Dempsey
Journal: BMJ (2013)

A 19 year old student phoned an official health service telephone helpline with a 10 day history of aching legs, vomiting, diarrhoea, and abdominal pain.She mentioned a recent trip to Uganda but was reassured and told she had "flu."The next day her boyfriend took her to see her doctor, where she mentioned general malaise, tiredness, and occasional nausea; the doctor diagnosed a viral illness and advised her to keep taking paracetamol.Three days later a friend found her dead in bed in her university halls of residence.The coroner recorded death due to cerebral malaria. 1 What is malaria?Malaria is an infection caused by protozoa of the genus Plasmodium.Five species infect humans (P falciparum, P vivax, P ovale, P malariae, and P knowlesi).Most of the fatal cases are caused by P falciparum.
High-Dose Cytarabine Alone Versus Cytarabine Plus Anthracycline for Consolidation Therapy in Non-Promyelocytic Acute Myeloid Leukemia
Authors: Sung-Hyun Kim, So Yeon Kim, Ji Hyun Lee, Suee Lee, Sung Yong Oh, Hyo-Jin Kim, Dae Sik Kim, Ka-Won Kang, Se Ryeon Lee, Yong Park, Hwa Jung Sung, Chul Won Choi, Byung Soo Kim
Journal: Blood (2015)
Outcomes of anticoagulant (AC) or antiplatelet (AP) use in patients (pts) with chronic lymphocytic leukemia (CLL) or indolent non-Hodgkin’s lymphoma (iNHL) in idelalisib (IDELA) trials.
Authors: Jacqueline Claudia Barrientos, Paolo Ghia, John Pagel, Gilles A. Salles, Jeff Porter Sharman, Stephan Stilgenbauer, Oksana Gurtovaya, Yeonhee Kim, Betsy Philip, Andrew David Zelenetz
Journal: Journal of Clinical Oncology (2015)

8563 Background: IDELA, a selective oral PI3Kδ inhibitor, is approved for use in relapsed CLL (in combination with rituximab [R]) and iNHL (as monotherapy). Both diseases occur mainly in the elderly, who have comorbidities that increase thrombotic risk. This post hoc analysis characterized the use and outcomes of AC/AP therapy, which was allowed in IDELA registrational clinical trials. Methods: In the phase 3 Study 312-116 (NCT01539512), frail pts with relapsed CLL (including those with any degree of thrombocytopenia) were randomized to receive a combination of continuous IDELA 150 mg BID or placebo (PBO) with 8 R doses. In the phase 2 Study 101-09 (NCT01282424), pts with refractory iNHL received IDELA 150 mg BID until disease progression or unacceptable toxicity. Grade 1, 2, and ≥3 bleeding events were analyzed using MedDRA preferred terms and CTCAE. Results: The 2 trials included 343 pts. In the CLL study, 18 pts (16%) on IDELA + R and 31 (29%) on PBO + R had grade ≥3 thrombocytopenia at baseline. Concomitant AC/AP use was frequent (45% in each study); the most common were aspirin, enoxaparin, and warfarin. AC/AP use was more frequent in pts treated with IDELA + R vs PBO + R. The incidence of bleeding events was similar with IDELA, IDELA + R, and PBO + R. Grade ≥3 bleeding events occurred in 1 IDELA + R, 1 PBO + R, and 3 IDELA pts. Conclusions: AC/AP use involved 45% of the IDELA registrational trial population. Overall, rates of bleeding events were moderate and similar with IDELA + R vs IDELA + PBO; grade ≥3 events were uncommon. There was no specific trend with regard to AC/AP and bleeding events in the 2 arms of the CLL study. Clinical trial information: NCT01282424 and NCT01539512. n (%) CLL iNHL IDELA + R n=110 PBO + R n=108 IDELA Monotherapy n=125 Pts receiving AC/AP 60 (55) 38 (35) 56 (45) Aspirin 42 (38) 21 (19) 30 (24) Enoxaparin 11 (10) 6 (6) 19 (15) Warfarin 8 (7) 9 (8) 11 (9) Pts with ≥1 bleeding event (any grade) Overall 15 (14) 20 (19) 17 (14) Grade 1/2 14 (13) 19 (18) 14 (11) Pts on AC/AP n=60 n=38 n=56 Event at any time 10 (17) 6 (16) 14 (25) Event on AC/AP 7 (12) 5 (13) 8 (14) AC at any time 9 4 13 AP at any time 5 3 6 Patients not on AC/AP n=50 n=70 n=69 Event at any time 5 (10) 14 (20) 3 (4)
Unrelated Donor Hematopoietic Stem Cell Transplantation for the Treatment of Advanced Multiple Myeloma: The John Theurer Cancer Center Experience,
Authors: Michele L. Donato, David H. Vesole, David S. Siegel, Barbara Adler-Brecher, Eiswarya Chichili, Andrew L Pecora, Phyllis McKiernan, Melissa Baker, Themba Nyirenda, Elizabeth Bilotti, Andre Goy, Scott D Rowley
Journal: Blood (2011)
The effect of age on outcome in prospective, phase III NRG Oncology/RTOG trials of radiotherapy (XRT) +/- chemotherapy in locally advanced (LA) head and neck cancer (HNC).
Authors: Julie Ann Kish, Qiang Zhang, Corey J. Langer, Felix Nguyen-Tan, David Ira Rosenthal, Randal S. Weber, Marcy A List, Stuart J. Wong, Adam S. Garden, Jay Scott Cooper, Andy Trotti, James A. Bonner, Christopher U Jones, Sue S Yom, Jeff M. Michalski, Christopher J. Schultz, John A Ridge, George Shenouda, Quynh-Thu Le
Journal: Journal of Clinical Oncology (2015)

6003 Background: The effect of advanced age on outcome for single agent XRT and combined modality therapy in LA-HNC is not well defined. Methods: The effect of age (< 70 vs ≥ 70 years) on survival and toxicity was examined in LA-HNC patients (pts) on RTOG 9003 testing 3 altered fractionation (fx) XRT schedules versus standard daily XRT (SFX); RTOG 0129 comparing concurrent SFX + cisplatin (DDP) to accelerated fx with concomitant boost XRT (AFX-C) + DDP; and RTOG 0522, testing AFX-C + concurrent DDP +/- cetuximab. Results: Secondary analysis included 2,688 pts. Median followup for surviving pts was 5.2 years (range 0.01 to 20.3) overall, 14.1 yrs in RTOG 9003, 7.9 years in RTOG 0129, and 4.6 years in RTOG 0522. Pts age ≥ 70 were more likely to be female with poorer PS, heavier smoking history and p16 (-) status (p < 0.001 each). Adjusting for covariates, patients age ≥ 70 had worse survival regardless of smoking or p16 status. Adverse effect of patients age ≥ 70 may have been worse in p16 (+) pts (HR 2.07 vs. 1.30; interaction p = 0.09), (n = 34). Maximum grade stomatitis and other toxicities were similar by age cohort and tx arms on RTOG 9003. In the DDP-based studies, the elderly experienced more grade 3-5 thrombocytopenia (p = 0.02), anemia (p = 0.03), nephrotoxcity (p = 0.01) and possibly ototoxicity (p = 0.06) but less mucositis (p = 0.04). Conclusions: Pts age ≥ 70 were under-represented in RTOG trials evaluating tx for LA-HNC relative to their population overall. Their survival was inferior compared to pts age < 70; this was more apparent in combined modality, DDP-based trials, which featured heightened nephrotoxicity, myelosuppression, and ototoxicity. Delineation of causes of death and tx compliance will provide insight into future trial design. NCI grants U10CA21661, U10CA180868, U10CA180822, U10CA37422 and UG1CA189867. Funded in part under grant with PA Dept of Health which disclaims responsibility for any analyses, interpretations or conclusions and BMS. Trial Total accrual N(%) ≥ 70 yrs Hazard Ratio(HR) for death(95% CI) P Value 9003 1076 207(19.2) 1.34(1.15-1.57) < 0.001 0129 721 48(6.7) 2.34(1.68-3.26) < 0.001 0522 891 54(6.1) 2.45(1.69-3.53) < 0.001 Combined 2688 309(11.5) 1.55(1.35-1.77) < 0.001