tbuckley/cabot-search huggingface dataset:
A randomized phase II study: Pazopanib (P) versus lapatinib (L) versus combination of pazopanib/lapatinib (L+P) in advanced and recurrent cervical cancer (CC)
Authors: B. Monk, L. Mas, J. J. Zarba, A. Oaknin, C. Tarpin, W. Termrungruanglert, J. A. Alber, J. Ding, N. W. Stutts, L. N. Pandite
Journal: Journal of Clinical Oncology (2009)

5520 Background: P and L are oral tyrosine kinase inhibitors. P targets VEGFR, PDGFR, and c-Kit. L targets EGFR and HER2 in CC, EGFR overexpression and markers of angiogenesis correlate with poor outcome; the prognostic value of HER2 overexpression remains unclear. Methods: Patients (pts) with measurable stage IVB, persistent or recurrent squamous or adenocarcinoma of the cervix not amenable to curative therapy; 0–1 prior regimens in the metastatic setting; ECOG PS 0–1; were randomized 1:1:1 to each of 3 treatment groups; not prescreened for EGFR or HER2 status. Treatment consisted of P 800mg QD; L 1,500 mg QD; L+P: P 400 mg + L 1,000 mg QD; the doses were escalated to P 800 mg + L 1,500 mg after 20 pts treated at 400 mg + 1,000 mg. Therapy continued until progression (PD), withdrawal due to adverse events (AEs), or withdrawal of consent. Primary endpoint was progression free survival (PFS); secondary overall survival (OS), tumor response (RR), safety. The study had 85% power to detect 80% improvement in PFS. A hierarchical testing procedure was applied comparing L+P vs L followed by L+P vs P and P vs L. The futility boundary was crossed for L + P vs L at the planned interim analysis and this arm was discontinued. Only the comparison of P vs L at the final analysis is reported. Results: Total N = 235 pts: 152 in the monotherapy arms: P (78); L (74). Baseline characteristics were balanced: median age 49 yrs (23–81). Stage IVB: 5%; recurrent 62%; persistent 34%. 86% had prior radiotherapy (45% with chemotherapy); 42% had prior chemotherapy for recurrent/persistent disease. P improved PFS (HR = 0.66; 90% CI 0.48, 0.91 p = 0.013) and OS (HR = 0.67; 90% CI 0.46, 0.99 p = 0.045; median OS for P is 50.7 wks; L is 39.1 wks) with RR for P of 9% and L 5%. Most common AEs (%) P/L were diarrhea (54/58), nausea (36/33), anorexia (28/32), vomiting (20/24); the most common Gr 3 AE was diarrhea (11/13); Gr 4 for any individual AE was ≤ 1%; 1 Gr 5 event of cachexia unrelated to L. Conclusions: PFS and OS were significantly prolonged with P compared to L. P and L both demonstrated a favorable toxicity profile in pts with advanced and recurrent CC. This study demonstrates the potential benefit of P in CC. Further exploration is indicated. [Table: see text]
Abstract 12326: Optimal Targeted Temperature in Comatose Survivors After Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation
Authors: Eisuke Kagawa, Keigo Dote, Masaya Kato, Shota Sasaki, Noboru Oda, Yoshinori Nakano, Yasuki Kihara
Journal: Circulation (2014)

Introduction: Even after the report of the Targeted Temperature Management trial, optimal targeted temperature (TT) in targeted temperature management for comatose survivors after cardiac arrest is still controversial.

Hypothesis: We assessed the hypothesis that lower TT provides improved outcomes in patients after cardiac arrest.

Methods: Adult comatose survivors of cardiac arrest without obvious extra-cardiac causes and treated with targeted temperature management were enrolled in this study. We assessed the association between TTs, and favorable outcomes. We divided the study patients into 2 groups according to TT < 34°C (33°C group) or not (34°C group). Favorable outcomes were defined as 90-day cerebral performance category of 1 or 2. P < 0.05 was defined as statistically significant.

Results: Among all the study patients (N = 221), there were no significant differences in age, sex, rate of initial shockable rhythms, bystander initiated cardiopulmonary resuscitation (CPR), time interval from collapse to return of spontaneous circulation between the patients of 33°C group and that of 34°C groups. The rate of performing extracorporeal CPR (ECPR) using venoarterial extracorporeal membrane oxygenation were higher in the patients of 33°C group than that of 34°C group (81% vs. 42%, P < 0.01). The rates of favorable outcomes were similar between the 2 groups (41% vs 34%, P = 0.34). In the patients treated with conventional CPR (N = 142), the rates of favorable outcomes were similar between the 2 groups (54% vs. 46%, P = 0.38). However, in the patients who were unresponsive to conventional CPR and treated with ECPR (N = 79), the rates of favorable outcomes were higher in the patients of 33°C group than that of 34°C group (28% vs. 5%, P < 0.01).

Conclusions: TT of 34°C to 36°C may be reasonable for patients treated with conventional CPR. In patients who were unresponsive to conventional CPR and treated with ECPR, TT < 34°C may be superior to TT of 34°C.
Relapse-specific mutations in cytosolic 5’-nucleotidase II in childhood acute lymphoblastic leukemia.
Authors: Julia Meyer, Jinhua Wang, Laura E. Hogan, Jay Patel, Zuojian Tang, Paul Zumbo, Sheng Li, Jiri Zavadil, Ross L. Levine, Timothy Cardozo, Stephen Hunger, Elizabeth A. Raetz, Debra J. Morrison, Christopher Mason, William L. Carroll
Journal: Journal of Clinical Oncology (2012)

9507 Background: Relapsed childhood acute lymphoblastic leukemia (ALL) carries a very poor prognosis despite intensive retreatment that often includes allogeneic stem cell transplantation, due to intrinsic drug resistance. Novel therapeutic approaches are urgently needed and identification of the biological pathways that mediate resistance might provide targets for the effective prevention and treatment of relapsed ALL. However, the spectrum of somatic mutations responsible for ALL relapse is not yet known. Methods: We profiled the transcriptome of matched diagnosis and relapse bone marrow specimens from 10 pediatric B lymphoblastic leukemia patients using massively parallel sequencing technology (RNA-seq) to identify novel mutations specific at disease recurrence. Results: Transcriptome sequencing identified 20 newly acquired novel non-synonymous mutations in 10 relapse specimens not present at initial diagnosis. Two patients harbored relapsed specific mutations in the same gene, NT5C2, which codes for the Cytosolic 5’-nucleotidase II protein at different sites in the protein sequence. Mutations were validated as relapse specific after Sanger resequencing of germline, diagnosis and relapse DNA. RNA-seq coverage of each mutation was &gt;100X, indicating that if a relapsed clone were present at diagnosis it made up &lt; 1% of the bulk leukemia. Full exon sequencing of NT5C2 was completed in 61 additional relapse specimens, identifying 5 additional mutations which were also confirmed as relapse specific. Structural modeling of the relapse-associated mutations in the encoded protein Cytosolic 5’-nucleotidase II suggests alteration of enzyme subunit association/dissociation. Clinically, patients who harbored NT5C2 mutations were more likely to relapse earlier following initial diagnosis than those patients without mutations (p=0.03). Conclusions: Mutations in NT5C2 are associated with the outgrowth of drug resistant cells in childhood ALL.
Strontium ranelate decreases the risk of hip fracture over 3 and 5 years in post menopausal women at high risk
Authors: Jean-Yves Reginster, D. Felsenberg, Steven Boonen, A. Diez-Perez, René Rizzoli, M. L. Brandi, Tim D Spector, Kim Brixen, S. Goemaere, C. Cormier, A. Balogh, Pierre D Delmas, Pierre J Meunier
Journal: Annals of the Rheumatic Diseases (2008)
67Ga lung scan. An aid in the differential diagnosis of pulmonary embolism and pneumonitis
Authors: A. H. Niden
Journal: JAMA (1977)

Twenty-three patients with clinical signs of pulmonary embolic disease and lung infiltrates were studied to determine the value of gallium citrate Ga 67 lung scan in differentiating embolic from inflammatory lung disease. In 11 patients without angiographically proved embolism, only seven had corresponding ventilation-perfusion defects compatible with inflammatory disease. In seven of these 11 patients, the gallium 67 concentration indicated inflammatory disease. In the 12 patients with angiographically proved embolic disease, six had corresponding ventilation-perfusion defects compatible with inflammatory disease. None had an accumulation of<sup>67</sup>Ga in the area of pulmonary infiltrate. Thus, ventilation-perfusion lung scans are of limited value when lung infiltrates are present. In contrast, the accumulation of<sup>67</sup>Ga in the lung indicates an inflammatory process. Gallium imaging can help select those patients with lung infiltrates who need angiography. (<i>JAMA</i>237:1206-1211, 1977)
Economic evaluations of sunitinib versus interferon-alfa (IFN-α) in first-line metastatic renal cell carcinoma (mRCC)
Authors: E. Remák, C. D. Mullins, E. Akobundu, C. Charbonneau, K. Woodruff
Journal: Journal of Clinical Oncology (2007)

6607 Background: A randomized phase III trial of sunitinib vs. IFN-a as first-line therapy for patients with mRCC is ongoing. An interim analysis of this study demonstrated superiority for the primary endpoint, progression-free survival (PFS), in the sunitinib arm vs. the IFN-a arm (median PFS = 11 months [95% CI: 10–12] vs. 4 months [95% CI: 4–6]; P&lt;0.000001). Because of the clinical significance of these results, the objective of this study was to demonstrate the economic value of sunitinib vs. IFN-a in this setting from a US third-party payer perspective. Methods: Two Markov models with a 5- and 10-year time horizon were developed to evaluate the cost- effectiveness of sunitinib vs. IFN-a. The models projected survival and costs in 6-week cycles based on extrapolation of the trial survival data. Model 1 looked at first-line treatment followed by palliative care only, while Model 2 incorporated second-line treatment. Effectiveness was measured in terms of progression-free months (PFM) in Model 1, and life-years (LY) gained and quality adjusted life-years (QALY) gained in Model 2. Resource utilization included drugs, tests, scans, monitoring, physician visits, hospitalizations and treatment of adverse events. Costs and survival benefits were discounted annually at 3% and 5% in Model 1 and 2, respectively. All costs were adjusted to 2006 US dollars. Scenario and probabilistic sensitivity analyses were conducted. Results: Projected PFS and overall survival were longer for sunitinib than for IFN-a. The incremental cost-effectiveness ratios of sunitinib vs. IFN-a over 5- and 10-years were $7,769 and $7,782/PFM, respectively, in Model 1. Model 2 results at 10 years were $67,215/LY and $52,593/QALY gained. The key drivers of the model results were survival and sunitinib drug costs. Both models were robust in the tested scenarios. Conclusions: Both analyses found that sunitinib is a cost-effective alternative to IFN-a as first-line treatment in mRCC, with cost-effectiveness ratios within the established threshold that society is willing to pay for health benefits (i.e. $50,000–100,000/LY or QALY). No significant financial relationships to disclose.
Harnessing the potential of radiation treatment of brain metastases to improve melanoma immunotherapy
Authors: Corey D McNeilly, Lukas W Pfannenstiel, Chaomei Xiang, Jennifer Yu, Brian R Gastman
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Radiation is an integral part of melanoma therapy, particularly for patients with symptomatic metastases. Efficient killing of tumor cells by radiation has been shown in immunocompromised mouse models to be enhanced greatly with transfer of a functioning immune system,
Abstract 16314: Stress Echocardiography is More Accurate for the Prediction of Coronary Artery Disease and with a Lower Cost to Diagnosis Compared to Exercise Electrocardiography in Patients with Recent Onset Suspected Cardiac Chest Pain
Authors: Konstantinos Zacharias, Shahram Ahmadvazir, Rajdeep Khattar, Roxy Senior
Journal: Circulation (2012)

Background: Exercise ECG (ExECG) is widely used to assess patients with suspected coronary artery disease (CAD). However stress echocardiography (SE) is a well established alternative technique for...
Combination of consecutive low-dose cisplatin with bleomycin, vincristine, and mitomycin for recurrent cervical carcinoma.
Authors: Y Shimizu, F Akiyama, S Umezawa, T Ishiya, K Utsugi, K Hasumi
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the efficacy and toxicity of combination chemotherapy with bleomycin, vincristine, mitomycin, and consecutive low-dose (CLD) administration of cisplatin (CLD-BOMP) for patients with recurrent cervical carcinoma. PATIENTS AND METHODS Ninety patients with recurrent cervical carcinoma and no prior chemotherapy were enrolled onto this study. The median age was 56 years. Eighty-seven of the 90 patients had received prior radiotherapy. The CLD-BOMP regimen was bleomycin 5 mg infused continuously days 1 through 7; vincristine 0.7 mg/m2 bolus day 7; mitomycin 7 mg/m2 bolus day 7; and cisplatin 10 mg/m2 infused over 4 hours days 1 through 7. The treatment was repeated at 3-week intervals. RESULTS All 90 patients were assessable for response, toxicity, and survival. After a median of four cycles (range, two to 10 cycles), we observed objective responses in 68 patients (76%), with 25 (28%) complete responses (CRs) and 43 (48%) partial responses (PRs; 95% confidence interval (CI), 66 to 85; 18 to 38; 37 to 59, respectively). Median survival for all 90 patients was 24.3 months (range, 2.3 to 100 months). The median survival for patients who achieved CR, PR, no change (NC), and progressive disease (PD) were not reached (NR), 23.6, 8.2, and 6.4 months, respectively. The median progression-free survival for patients who achieved CR and PR were NR and 12.3 months, respectively. There was no significant nausea or vomiting, nephrotoxicity, or pulmonary toxicity, which was attributable to the CLD-cisplatin and the adequate dosing schedule of bleomycin. The reduced toxicities allowed this regimen to be administered at the projected dose-intensities. CONCLUSION The CLD-BOMP regimen has significant antitumor activity with markedly reduced toxicity.
Clinical and prognostic significance of bone marrow abnormalities in the appendicular skeleton detected by low-dose whole-body multidetector computed tomography in patients with multiple myeloma
Authors: Y Nishida, Y Matsue, Y Suehara, K Fukumoto, M Fujisawa, M Takeuchi, E Ouchi, K Matsue
Journal: Blood Cancer Journal (2015)

Clinical significance of medullary abnormalities in the appendicular skeleton (AS) detected by low-dose whole-body multidetector computed tomography (MDCT) in patients with multiple myeloma (MM) was investigated. A total of 172 patients with monoclonal gammopathy of undetermined significance (MGUS) (n=17), smoldering MM (n=47) and symptomatic MM (n=108) underwent low-dose MDCT. CT values (CTv) of medullary density of AS⩾0 Hounsfield unit (HU) was considered as abnormal. Percentage of medullary abnormalities and the mean CTv of AS in patients with MGUS, smoldering MM and symptomatic MM were 18, 55 and 62% and -44.5 , -20.3 and 11.2 HU, respectively (P<0.001 and P<0.001). Disease progression of MM was independently associated with high CTv on multivariate analysis. In symptomatic MM, the presence of abnormal medullary lesions was associated with increased incidence of high-risk cytogenetic abnormalities (34.4% vs 7.7%; P=0.002) and extramedullary disease (10.4% vs 0%; P=0.032). It was also an independent poor prognostic predictor (hazard ratio 3.546, P=0.04). This study showed that CTv of AS by MDCT is correlated with disease progression of MM, and the presence of abnormal medullary lesions is a predictor for poor survival.
Long-term follow-up of patients with locally advanced or metastatic thymic malignancies: The Eastern Cooperative Oncology Group (ECOG) experience
Authors: P. J. Loehrer, W. Wang, S. Aisner, P. Bonomi, L. H. Einhorn, C. J. Langer, M. R. Green, R. B. Livingston, D. H. Johnson, J. Schiller
Journal: Journal of Clinical Oncology (2004)

7050 Background: Chemotherapy is active and appears to prolong survival in patients (pts) with advanced thymic cancer. However, limited data exists about the long-term outcomes after systemic therapy. Methods: To assess this, we reviewed records on 123 pts entered on five prospective ECOG phase II trials conducted from 1982 through 2003; these studies evaluated cisplatin as a single agent or as platinum-based combination chemotherapeutic regimens (i.e. cisplatin, doxorubicin, cyclophosphamide (PAC); cisplatin, ifosfamide, etoposide (VIP); carboplatin, paclitaxel). In 23 pts with Stage III disease, PAC was administered prior to definitive radiotherapy. All pts. had unresectable Stage III or IV, histologically proven thymoma (n=111) or thymic carcinoma (n=12) without previous systemic chemotherapy. Pretreatment characteristics included a median age of 50 yrs, M:F = 75:48, PS 0–1 = 83% and prior radiation therapy in 31%. Results: Overall, 46 (39%) pts. had an objective response (PR or CR), 46 had stable disease while the remainder had progression or were inevaluable for response. Combination regimens were associated with a higher objective response rate (p<0.0001) and improved overall survival (p=0.035) compared to single agent, cisplatin. Pts with thymic carcinoma were associated with a poorer response rate (p=0.047) and PFS (p=0.014) and a trend towards worse OS (p=0.064) than pts with thymoma. Conclusions: 1) Combination chemotherapy produces high response rates with some durable remissions observed in pts with thymoma. 2) Thymic carcinoma is associated with a worse therapeutic outcome than thymoma. 3) The majority of patients with unresectable thymic malignancies still progress and novel treatments are clearly needed. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Scientific Advisory Board
Electrocardiographic abnormalities in elite high school athletes: comparison to adolescent hypertrophic cardiomyopathy
Authors: Alex J Thompson, Bryan C Cannon, Philip L Wackel, Justin M Horner, Michael J Ackerman, Patrick W O'Leary, Benjamin W Eidem, Jonathan N Johnson
Journal: British Journal of Sports Medicine (2016)

Background In athletes, ECG changes from physiological cardiac remodelling are common but can overlap with findings from a pathological disorder. We compared ECG findings in a group of elite high school athletes to a cohort of adolescents with hypertrophic cardiomyopathy (HCM). Methods/results We prospectively performed 15-lead ECGs and echocardiograms in 147 elite high school athletes. Student-athlete ECGs were compared in blinded fashion to ECGs of 148 adolescents with HCM of similar age and ethnicity. Standard ECG hypertrophy criteria and established expert opinion guidelines (European Society of Cardiology, ESC and Seattle criteria) were analysed. All student-athletes had normal echocardiograms. Overall, 77/147 (52%) of student-athletes met standard ECG criteria for ventricular hypertrophy compared to 126/148 (85%) adolescents with HCM (p&lt;0.0001). There were 112/148 (76%) adolescents with HCM who had pathological Q-waves, T-wave inversion and/or ST-segment depression compared to 1/147 (1%) athletes (p&lt;0.0001). Most patients with HCM (84%, 124/148) had ≥1 abnormal ECG finding(s) according to Seattle criteria, compared to 1% of student-athletes (2/147). Similarly, 130/148 (88%) patients with HCM met group-2 ESC criteria (abnormal), compared to 36/147 (24%) student-athletes (p&lt;0.0001). Conclusions Over 50% of elite high school athletes with echocardiographically confirmed normal hearts satisfied standard voltage criteria for ventricular hypertrophy. Pathological Q-waves, T-wave inversion or ST-segment depression were most helpful in distinguishing adolescents with HCM from normals. Both ESC and Seattle criteria successfully stratified the student-athlete and HCM cohorts, however each had a false-negative rate &gt;10% for the HCM cohort. The Seattle criteria demonstrated a significantly lower false-positive rate (1%) than the ESC criteria (24%).
A randomized open-label study of darbepoetin alfa administered every 3 weeks with or without parenteral iron in anemic subjects with nonmyeloid malignancies receiving chemotherapy
Authors: A. Vandebroek, B. Gaede, S. Altintas, K. Smith, B. Yao, M. Schupp, L. Bastit
Journal: Journal of Clinical Oncology (2006)

8612 Background: Patients (pts) with cancer receiving chemotherapy often have chemotherapy-induced anemia (CIA) and reduced quality of life. Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) that can effectively treat CIA when administered once every 3 weeks (Q3W). In patients with CIA, limited data in the literature suggest that administration of intravenous (IV) iron with ESA therapy may increase clinical response. Methods: This randomized, multicenter, open-label, 16-week study evaluated the safety and efficacy of DA 500 mcg administered Q3W using the SureClick injection device in pts with CIA (Hb &lt; 11 g/dL) who received either IV iron or standard practice for iron administration (oral iron or no iron). The dose of IV iron was 200 mcg administered either Q3W with DA Q3W or, if required, as 2 doses (200 mcg total) within a 3-week period. Pts who received ≥ 1 dose of DA and who completed the 16-week study period by October 19, 2005 are included in this interim analysis (planned sample size = 400 pts). Accrual will have finished by conference time. Randomization was stratified by tumor type and baseline (BL) Hb (&lt; 10 or ≥ 10 g/dL). The incidence of adverse events and serious adverse events, in particular embolic/thrombotic events, was summarized. Efficacy endpoints were estimated using the crude % of pts (95% CI). Hb values within 28 days of a transfusion were not included in any efficacy analysis. Results: Of the 114 pts included in this interim analysis, 65% were women, 99% were Caucasian, the mean (SD) age was 60 years (12), and 26% had lung or gynecological tumors; study endpoints are shown in the table. Conclusions: Based on the interim results, the safety profile for pts receiving DA 500 mcg Q3W with IV iron appears to be comparable to pts receiving DA 500 mcg Q3W with oral iron or no iron. The % pts who achieved the target Hb (≥ 11 g/dL) appeared higher, and the % pts who required transfusions appeared lower, in the group receiving IV iron. [Table: see text] [Table: see text]
NPM1 Mutated AML Is Associated With Lower Expression Of Poor Prognostic Markers BAALC, ERG and MN1 In Adult Patients With Acute Myeloid Leukaemia
Authors: Poonkuzhali Balasubramanian, Ashok kumar Jayavelu, Ajay Abraham, Savitha Varatharajan, Sreeja Karathedath, Senthamizhselvi Anandan, Vivi Srivastava, Aby Abraham, Auro Viswabandya, Alok Srivastava, Vikram Mathews
Journal: Blood (2013)