bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter, randomized phase II trial of GM-CSF (GM) plus ipilimumab (Ipi) versus Ipi alone in metastatic melanoma: E1608.
Authors: Hodi F. Stephen , Lee Sandra J. , McDermott David F. , Rao Uma N. M. , Butterfield Lisa H. , Tarhini Ahmad A. , Leming Philip D. , Puzanov Igor , Kirkwood John M. ,   Eastern Cooperative Oncology Group
Published: February 2017

CRA9007 Background: CTLA-4 blockade and GM secreting tumor vaccine combinations demonstrate therapeutic synergy in multiple preclinical models. GM has activity in prostate and ovarian carcinoma and is being evaluated in phase III adjuvant trials for melanoma and lymphoma. GM enhances dendritic cell activation and potentiates antitumor T and B cell responses. GM may induce regulatory immune responses. A key issue is whether systemic GM might synergize with CTLA-4 blockade. Methods: Eligibility: measureable disease, ≤1 prior therapy, no CNS mets, ECOG PS 0-1, > 4 wks prior therapy, adequate end organ function, no autoimmune disease, no prior CTLA-4 blockade/CD137 agonist. OS was primary endpoint. Pts randomized to Arm A Ipi 10 mg/kg q3 wks IV x 4 then q12 wks plus GM 250 μg SC days 1-14 of 21 day cycles vs. Arm B Ipi 10 mg/kg as in Arm A alone. Due to known inflammatory effects of treatments, pts were permitted to continue up to 100% increase in SPD and four new lesions in absence of declining performance status and discretion of treating physician. Drug supply, funding from Sanofi/Bristol-Myers Squibb. Results: 245 pts were enrolled. Arms were balanced for demographics. Median follow up 13.3 mos. RR Arm A 11.3 % (6.1, 18.6), Arm B 14.7% (8.6,22.8) (not significant;NS). PFS Arm A 3 mos (2.9,4.3), Arm B 3.2 mos (3,4) (NS). Median OS Arm A not reached, Arm B 12.6 mos (9.2,-). One year OS for Arm A was 67.9% (59%,76%), Arm B 51.2% (42.6%, 61.3%) (stratified log rank p1=0.016, p2=0.033). HR for mortality on Ipi + GM/Ipi=0.65. Per study design (overall one-sided type I error 0.10), OS interim analysis was conducted at 69% info time. O’Brien-Fleming boundary was crossed for OS. Toxicity assessed for all cases regardless of eligibility. Gr 3-5 AEs 45% Arm A, 57% Arm B (p2=0.078). Gr 5 AEs: Arm A colonic perforation (1), cardiac arrest (1); Arm B multiorgan failure (2), colonic perforation (2), hepatic failure (1), respiratory failure (2). Conclusions: Ipi plus GM significantly improves OS over Ipi alone. No significant differences in toxicity were observed. A trend toward improved tolerability is noted in the GM arm. Clinical trial information: NCT01134614.
Randomized phase III trial of imatinib (IM) rechallenge versus placebo (PL) in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) after failure of at least both IM and sunitinib (SU): RIGHT study.
Authors: Kang Yoon-Koo , Ryu Min-Hee , Ryoo Baek-Yeol , Kim Hyun Jin , Lee Jong Jin , Yoo Changhoon , Nam Byung-Ho , Ramaiya Nikhil , Jagannathan Jyothi Priya , Demetri George D. 
Published: February 2017

LBA10502 Background: To palliate and prolong disease control after failure of all available treatment in advanced GIST, resumption of IM dosing has been commonly practiced based on evidence of rapid GIST progression after discontinuation of all TKIs. We evaluated the efficacy of IM rechallenge in pts with advanced GIST following failure of all TKIs. Methods: Eligible pts had metastatic and/or unresectable GIST with prior benefit from first-line IM (defined as disease control for > 6 months), progressive disease (PD) on first-line IM, PD on or intolerance to SU, and ECOG performance status 0-3. Pts were randomized 1:1 to receive best supportive care with either IM 400 mg po once daily or PL. At the time of PD, pts were unblinded and allowed to cross-over to open-label IM. The primary endpoint was progression-free survival (PFS) determined by blinded external radiology review according to RECIST v1.0. Secondary endpoints included overall survival (OS), time to progression, disease control rate (DCR) at 12 weeks, and safety. Results: Between July 2010 and January 2013, 81 pts were randomized (IM: 41, PL: 40) at a single Korean center. All baseline characteristics were balanced between the arms and 40% of pts received ≥ 3 prior TKIs. The planned final analysis in March 2013 demonstrated that the primary endpoint was met, with significantly greater PFS for pts randomized to IM vs. PL : 1.8 vs. 0.9 months, respectively (p=0.002), hazard ratio (HR) 0.45 (95% CI, 0.27-0.76). DCR at 12 weeks was 32% for IM vs. 5% for PL (p=0.003). With 92.5 % of PL pts rapidly crossing over to IM, median OS was 8.2 months for IM vs. 7.5 months for PL (HR of 0.99, p=0.982). The most common treatment-emergent AEs (> grade 3) during double-blind period in the IM arm included anemia (29%), fatigue (10%), and hyperbilirubinemia (7%). Conclusions: Rechallenge of IM significantly improves PFS and DCR in pts with advanced GIST after failure of at least IM and SU, likely by continuous kinase inhibition of the bulk of disease clones which retain IM sensitivity. However, TKI-resistant clones continue to progress leading to relatively brief duration of benefit. Clinical trial information: NCT01151852.
Bevacizumab, irinotecan, and radiotherapy versus standard temozolomide and radiotherapy in newly diagnosed, MGMT-nonmethylated glioblastoma patients: First results from the randomized multicenter GLARIUS trial.
Authors: Herrlinger Ulrich , Schaefer Niklas , Steinbach Joachim Peter , Weyerbrock Astrid , Hau Peter , Goldbrunner Roland , Friedrich Franziska , Stockhammer Florian , Ringel Florian , Braun Christian , Kohnen Ralf , Leutgeb Barbara , Belka Claus , Urbach Horst , Stummer Walter , Glas Martin 
Published: February 2017

LBA2000 Background: In patients with MGMT-nonmethylated glioblastoma (GBM), primary chemotherapy with temozolomide (TMZ) is at best moderately effective. There is an urgent need for more effective therapies in this large subgroup of GBM. Since results of phase II trials with the antiangiogenic agent bevacizumab (BEV) +/- irinotecan (IRI) are promising in recurrent GBM, the GLARIUS trial explored the efficacy of BEV/IRI as compared to standard TMZ in the first-line therapy of MGMT-non-methylated GBM. Methods: In the randomized, multicenter, open-label GLARIUS trial, adult patients with newly diagnosed, histologically confirmed and MGMT-non-methylated GBM received local radiotherapy (RT, 30 x 2 Gy) and were randomized (2:1) for experimental therapy with BEV (10 mg/kg q2w) during RT followed by maintenance BEV (10 mg/kg q2w) + IRI (125 mg/m² q2w (without enzyme-inducing antiepileptic drugs (EIAEDs)) or 340 mg/m² (with EIAEDs)) or standard therapy with daily TMZ (75 mg/m2) during RT followed by 6 courses of TMZ (150-200 mg/m2/day for 5 days q4w). The primary endpoint was progression-free survival rate after 6 months (PFS-6) as determined by central neuroradiological review. Results: The intent-to-treat population included 170 patients (67.1% male, median age 56 years (range 25-78 years), 48.8% complete resection rate, 78.8% of patients with KPS 90% or higher); 116 patients received BEV/IRI, 54 patients had TMZ. The frequencies of adverse events in both arms of the trial were within the expected range. The PFS-6 rate was significantly higher in the BEV/IRI arm (71.1%, 95% CI 58.1-80.8%) than in the TMZ arm (26.2%, 95% CI 13.1-41.4%, p<0.0001 logrank test). Conclusions: The significant and clinically meaningful increase in the primary endpoint PFS-6 upon BEV/IRI chemotherapy suggests that BEV/IRI is superior to standard TMZ therapy in newly diagnosed MGMT-nonmethylated GBM patients. Clinical trial information: 2009-010390-21.
Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma and methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter: Key results of the multicenter, randomized, open-label, controlled, phase III CENTRIC study.
Authors: Stupp Roger , Hegi Monika E. , Gorlia Thierry , Erridge Sara , Grujicic Danica , Steinbach Joachim Peter , Wick Wolfgang , Tarnawski Rafal , Nam Do-Hyun , Weyerbrock Astrid , Hau Peter , Taphoorn Martin JB , Nabors Louis B. , Reardon David A. , Van Den Bent Martin J. , Perry James R. , Hong Yong Kil , Hicking Christine , Picard Martin , Weller Michael ,   on behalf of the European Organisation for Research and Treatment of Cancer (EORTC), the Canadian Brain Tumor Consortium, and the CENTRIC Study Team
Published: February 2017

LBA2009 Background: Cilengitide (CIL) is a selective αvβ3 and αvβ5 integrin inhibitor. In a phase II study in patients with newly diagnosed glioblastoma, CIL added to standard temozolomide (TMZ) and radiotherapy (RT) was well tolerated and appeared to confer improved survival in patients with glioblastoma and methylated MGMT gene promoter (Stupp et al. J Clin Oncol. 2010;28:2712-8). Methods: This multicenter, randomized, controlled, open-label, phase III study randomized (1:1) patients (≥ 18 years) with newly diagnosed, histologically proven supratentorial glioblastoma (WHO Grade IV) and centrally determined MGMT gene promoter methylation. Treatment consisted of CIL 2000 mg twice weekly i.v. plus standard TMZ/RT→TMZ (concomitant and adjuvant temozolomide and radiotherapy; Stupp et al. N Engl J Med. 2005;352:987-96) or standard TMZ/RT→TMZ alone. CIL was to be administered for ≥ 18 months, or until disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) per investigator read and safety. Results: 272 patients received CIL plus TMZ/RT→TMZ, and 273 were treated with TMZ/RT→TMZ alone (intention-to-treat population). 54% and 52% of patients were male, and 42% and 44% had ECOG-PS ≥ 1, respectively. 75% of patients of both arms were ≥ 50 years old. Overall, baseline characteristics were well balanced across treatment arms. Median OS was 26.3 months in both arms (Hazard Ratio [HR] = 1.02 [95%CI: 0.81-1.29], p = 0.86). Median PFS per investigator read was 13.5 months in the CIL arm and 10.7 months in the control arm (HR = 0.93 [95%CI: 0.76-1.14], p = 0.48). Treatment was generally well tolerated and the known safety profile of CIL was confirmed. Conclusions: CIL failed to prolong PFS or OS in patients with newly diagnosed glioblastoma and methylated MGMT gene promoter. The previously reported safety profile of CIL in addition to standard therapy was confirmed. Clinical trial information: NCT00689221.
Accelerated breast MRI for breast cancer screening.
Authors: Kuhl Christiane K. , Schrading Simone , Strobel Kevin , Bieling Heribert 
Published: February 2017

1 Background: Current breast MRI protocols are designed for diagnostic, not for screening purposes, and are therefore time consuming to acquire and to read. We investigated whether an abridged breast MRI protocol, consisting only of the first post contrast subtracted (FAST) images and their maximum intensity projection (MIP), would be suitable for screening purposes. Idea was to trade some of the very high sensitivity of breast MRI for acquisition and interpretation speed. Long term goal is to increase the access to breast MRI by reducing the cost associated with the examination. Methods: 443 women at increased risk of breast cancer, with negative digital mammography, underwent 606 breast MRI screening studies. Images were prospectively read by experienced breast radiologists. Readers were asked to first review the MIPs and search for significant enhancement, then to evaluate the FAST images for possible further categorization of enhancement, and only thereafter, to analyse the full diagnostic breast MRI protocol. We compared diagnostic yield and accuracy of MIP and of FAST readings vs. that of the full protocol. Results: MR table time for the full protocol was 21 minutes, table time for FAST images and MIPs was under 3 minutes. Average time to read MIP and FAST image was 2.8 seconds and 28 seconds, respectively. A total 11 breast cancers (4 DCIS, 7 invasive, median size 8 mm, all intermediate or high grade), were diagnosed in the 603 examinations for an additional cancer yield of 18.2/1000. MIPs were positive in 9/11 (82%); FAST readings as well as the full protocol were positive in 10/11 (91%). NPV of the MIP and FAST readings was 99.6% (484/486) and 99.8%, respectively. Specificity of FAST readings was equivalent to that of the full protocol (94.4%), with 33 vs. 35 false-positive diagnoses. Conclusions: In this high risk screening cohort, an MR table time of 3 minutes and an expert radiologist reading time of 2 seconds for the interpretation of the MIP image was sufficient to establish absence of breast cancer with a negative predictive value of 99.6%. With the same abridged MR protocol and an expert reading time of under 30 seconds for interpretation of FAST images, sensitivity and specificity was identical to that of the full protocol, allowing an additional cancer yield of 18.2/1,000.
The impact treatment has on cardiovascular risks factors for breast cancer survivors.
Authors: Keyserlingk John R. , Jones David H. , Nestore Melisa , Comtois Alain Steve , Henophy Sara , Cousin Julie , Hu Helen 
Published: February 2017

106 Background: The Integrative Health and Wellness center at VM Medical was established to monitor the body composition, activity level and vital signs of both the regular patients and the cancer survivors during their annual mammography screening. To determine if body composition and basic cardiovascular function of cancer survivors may vary depending on the type of adjuvant therapy dispensed. Methods: Kinesiologists performed base line measurements on 4,414 patient at The VM Medical Breast Center. Measurements were obtained on 3,674 non-oncology female patients and 740 cancer survivors. The data included BMI, resting heart rate, blood pressure, total body fat, lean muscle and waist circumference. The cancer survivors were stratified into 8 different groups (G1-G8) according to the type of surgery they underwent and compared to the regular patients(R). A one way ANOVA was performed with Dunnet post hoc analysis, significance was set at p < 0.05. The two largest groups were; women who underwent surgery, chemotherapy, radiotherapy and hormone therapy (G5) 243 patients, as part of their treatment and women who underwent surgery, radiotherapy and hormone therapy (G6) 207 patients, as part of their treatment. The other 290 patients were separated into the other 6 treatment groups. Results: Significant differences were seen between the cancer survivors in all groups and the regular patients with p= 0.00 in 7 key variables. BMI(F=4.30) µ= 26.08 (R) vs µ= 27.10 (G6), resting heart rate (F= 6.24) µ= 73.04 bts/min (R) vs µ= 76.45 bts/min (G5), diastolic blood pressure (F= 4.65) µ= 74.18 mmHg (R) vs µ= 77.00 mmHg (G5), systolic blood pressure (F= 8.75) µ= 123.04 mmHg (R) vs µ= 130.14 mmHg (G6), lean muscle (F= 3.48) µ= 10.09 kgs (R) vs µ= 9.74 kgs (G6), total body fat (F=9.02) µ= 34.45% (R) vs µ= 37.49% (G6) and waist circumference (F= 4.44) µ= 84.91 cm (R) vs µ= 87.68 cm (G5). Conclusions: It would appear that different treatment protocols are associated with an increase in negative body composition and blood pressure measurements in cancer survivors. This information is important for the medical team to consider when directing the cancer survivors on healthy lifestyle choices post treatment.
Survival effects of erythropoiesis-stimulating agents (ESAs) in patients with breast cancer: A meta-analysis.
Authors: Leyland-Jones Brian , Aapro Matti S. , Moebus Volker , Nitz Ulrike , O'Shaughnessy Joyce , Pronzato Paolo , Untch Michael , Tomita Dianne , Bohac Gerry C. 
Published: February 2017

120 Background: New data are available from two trials of ESA use in patients with breast cancer receiving chemotherapy. We conducted a meta-analysis of trials of ESA use in this population. Methods: A literature search identified reports from 1997-2012 that included mortality data from controlled ESA trials (epoetin alfa, epoetin beta, darbepoetin alfa, biosimilars) in patients with breast cancer receiving chemotherapy. We used data from company databases for Amgen Inc. or Janssen Products LP studies and published data for other studies. Random-effects odds ratios (OR) were calculated to compare results for patients randomized to ESA to patients randomized to control. Analyses were stratified by metastatic stage; mixed stage or treatment; and adjuvant/neoadjuvant treatment. Results: We analyzed 9 studies (N = 4,713; ESA n = 2,346, control n = 2367) (Table).The overall stratified random-effects OR for death was 1.17 (95% confidence interval, 0.99-1.39). Details are presented in the Table. Conclusions: Overall survival OR remains consistent with prior data after including recent results. [Table: see text]
The impact of survivorship care plans on knowledge among breast cancer survivors.
Authors: Bulloch Kaleigh , Irwin Melinda , Chagpar Anees B. , Horowitz Nina Ruth , Killelea Brigid K. , Pusztai Lajos , Abu-Khalaf Maysa M. , DiGiovanna Michael , Chung Gina G. , Hofstatter Erin Wysong , Levy Arthur Louis , Sanft Tara Beth 
Published: February 2017

124 Background: Despite the Institute of Medicine’s recommendation that all cancer survivors be provided with a survivorship care plan (SCP), there is limited information as to whether SCPs improve knowledge. The purpose of this study was to examine the impact of SCPs on patient knowledge regarding tumor stage, cancer treatment and potential risk of long-term side effects, surveillance recommendations, and perceived knowledge of their therapy. Methods: 75 English-speaking women over the age of 18 were enrolled in this prospective study. The participants’ treatment progress was tracked through the electronic medical record and used to create the SCP, which was given to them at the completion of treatment (defined as the time patients had completed radiation and/or chemotherapy treatments and initiated on hormonal therapy, if applicable). Knowledge of stage, treatments, potential side effects, and surveillance recommendations were assessed before receiving the SCP and again two months later. Accuracy of responses was compared using the McNemar test. Results: The median patient age was 56.8 ± 12.5 and 47.1% were stage I, 37.3% were stage II, and 15.7% were stage III. Participants were statistically more accurate in identifying their stage after receiving their SCP than at baseline (72.6% vs. 92.2%, p = 0.0016). While many patients were more accurate in the identification of the cancer treatment they received after SCP, the only significant improvement was in identifying 5-Fluorouracil as chemotherapy received (65.5% vs. 89.7%, p=0.0196). Patients were more accurate in identifying potential side effects but were only statistically more accurate at identifying leukemia as a risk factor (36.0% vs. 46.9%, p=0.0348). At baseline and follow up patients perceived that they had a high level of understanding as it related to their cancer stage (60.4%, and 66.7%), treatment (69.4%, and 71.4%), and surveillance recommendations (61.4%, and 54.6%). Conclusions: SCPs appear to improve patient knowledge in several important areas including basic and specific treatment details, surveillance recommendations, and potential side effects. Delivery of a SCPs is one strategy to improve knowledge of treatments received.
Association of osteprotegerin, bone turnover, and bone loss after adjuvant chemotherapy in early-stage breast cancer.
Authors: Oostra Drew Randall , Lustberg Maryam B. , Pan Xueliang Jeff , Shapiro Charles L. 
Published: February 2017

134 Background: Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. RANK-RANK ligand (RANK-L) signaling is important in regulating osteoclast development and is essential in maintaining the balance between bone resorption and formation. Osteoprotegerin (OPG) is involved in RANK-RANKL signaling by acting as a decoy receptor for RANK and thus interrupting osteoclast activation and subsequent bone resorption. The objective of this study was to examine the relationship between OPG and bone health in women with early-stage breast cancer who develop CIOF. Methods: Premenopausal women with stage I and II breast cancers receiving adjuvant chemotherapy were evaluated, within 4 weeks of starting chemotherapy (baseline), at 6 months and at 12 months. They were evaluated with bone mineral density (BMD) at lumbar spine (LS), BMD at femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium (iCa), osteocalcin (OC) and osteoprotegerin (OPG) measurements. CIOF was defined as negative pregnancy test, 3 or more months of amenorrhea, and an FSH >30 MIU/mL at the 12 month time point. Results: Forty women with stage I and II breast cancer receiving adjuvant were included in this analysis. Thirty-one (77.5%) were identified as having CIOF. In the CIOF group, there was statistically significant decreases in BMD (at the LS and FN) at both 6 months and 12 months (all P's <0.001). The LS BMD decreased from 0.993 (0.935-1.123), to 0.976 (0.869-1.100) to 0.937 (0.834-1.062), at 6 and 12 months respectively (median and inter-quartile range). OPG was significantly increased at 6 months (median increase 0.30, P=0.015), and then went down at 12 months, but was still higher than baseline (although not statistically significant, median difference 0.2, p=0.70). Significant increases in OC were also noted at 6 and 12 months (both P<0.001). Conclusions: In the CIOF group, OPG increases in the first 6 months in CIOF and at 12 months was slightly decreased but still remained elevated over baseline. This is likely due to a compensatory response to rapid bone loss. This compensatory response has been reported in other diseases, but not in CIOF.
Socioeconomic and racial disparities in the selection and outcomes of a chest-wall boost in post-mastectomy radiation therapy.
Authors: Hess Clayton Burnett , Fish Kari , Daly Megan Eileen , Mayadev Jyoti 
Published: February 2017

14 Background: We investigated socioeconomic and racial disparities in the selection and outcomes of patients from the California Cancer Registry receiving post-mastectomy radiation therapy (PMRT) with or without a chest-wall boost (CWB). Methods: Records of 5,586 women with invasive breast cancer, diagnosed from 2005-2009, treated with PMRT were reviewed and stratified based on treatment with (n=2,482 [44%]) or without (n=3,104 [56%]) a CWB. Race and socioeconomic status (SES) between the cohorts were analyzed. Bivariate analyses of the impact of race and socio-demographic factors on breast cancer-specific survival (BCS) and overall survival (OS) were performed using the Kaplan-Meier method. Adjusting for potential confounders, we used multivariate proportional hazards models to identify predictors of BCS and OS, reported as hazard ratios (HR) with 95% confidence intervals (CI). Results: The majority of PMRT patients were white (58%), compared to Hispanic (20%), Asian/Pacific-Islander (15%), and black (6%). Most were of high SES (50%), compared to middle (21%) or low (29%). Non-white patients were more frequently of low SES (59% vs. 40%). Hispanic frequency (61%) of advanced-stage (3-4) disease was the highest of all races. Low SES was also associated with higher stage (37% vs. 60%) compared to high SES, which comparatively presented with lower-stage (1-2) disease (42% vs. 57%, p=0.0187). Low-SES patients were more likely to receive a CWB (31 vs. 26%) while high-SES patients were less likely (48% vs. 53%, p<0.0001). White women were more likely to be treated without a CWB (60 vs. 57%), while Hispanic women were less likely (23% vs. 18%, p=0.0003). Women not treated with a CWB with low SES had a lower BCS (HR 1.541 p=0.0114) and OS (HR 1.794. p=<0.001) compared to women of high SES. Black women not treated a CWB had lower OS (HR 1.712, p=0.0249) compared to similarly-treated white women. Conclusions: Low SES and Hispanic race were associated with advanced stage, and more commonly treated with a CWB. Low-SES and black women treated without a CWB had lower OS, while the former also had lower BCS. These findings suggest that economic and racial health-care disparities contribute to worse outcomes.