bluuebunny/crossref_metadata_2025 huggingface dataset:
A quality improvement program to increase performance with clinical oncology pathways.
Authors: Espirito Janet L. , Arlen Aimee , Garey Jody S. , Sheth Sheetal , Turnwald Brian , Clayton Matthew , Flinn Jennifer , Butler-Dorian Carla , Nelson Greg C. , Hoverman J. Russell , Patt Debra A. , Cartwright Thomas H. , Busby Leslie T. , Beveridge Roy A. , Neubauer Marcus A. ,   on behalf of the Pathways Task Force
Published: February 2017

65

Background: Several organizations have created oncology pathways (pws) to support evidence-based medicine, and both standardize and improve the quality of care. Information is scarce; however, regarding the requirements for successful implementation of a pws program and monitoring of adherence. Methods: We assessed the efficacy of a quality assurance initiative called Practice Pathways Improvement (PPI) program to increase pws adherence to The US Oncology Network’s physician-developed Level I Pathways. We queried our electronic health record (EHR) iKnowMed to collect data before and after program initiation. Education was provided to address policies and procedures; leadership roles and responsibilities; integration of pws into the EHR and workflow; and the importance of correct data entry into the EHR. We then measured metrics including levels of assessable data (AD) (complete data, no missing or conflicting elements); On-Pathway adherence (ON-PW); and documented rationale for exceptions (EX) of Off-Pathway treatments. Metric performance reports were distributed monthly. Results: Since 2010, 10 practices of varying size (6-342 medical oncologists) and sites (2-47) voluntarily participated. Program duration ranged from 6-12 months (mos). There were 42,266 regimens evaluated during the program, covering 19 disease pws. Baseline averages, results at program end, and current averages (avg) for AD, ON-PW, and EX are shown in the Table. As of June 2012, average follow up was 19 mos (range 13-25). A normal approximation shows significance of p < 0.001. Conclusions: Implementation of a quality assurance initiative containing operational, leadership, and workflow elements along with continued education is important for successful pws adherence. Tailored program components are necessary to meet individual practice needs. Establishing a foundation for a pws process is important to maintain performance over time. As the reimbursement landscape in oncology evolves, the ability to demonstrate quality of care is essential. [Table: see text]
Rates of diagnostic imaging in long-term survivors of young adult malignancies.
Authors: Daly Corinne , Urbach David , Stukel Therese A. , Deitel Wayne , Nathan Paul C. , Paszat Lawrence Frank , Baxter Nancy N.
Published: February 2017

69

Background: In general, clinical practice guidelines do not recommend the use of diagnostic imaging in long-term surveillance of cancer survivors. Although warranted diagnostic imaging has clinical benefits, the overuse of imaging in cancer survivors may lead to false-positive results, more invasive tests, economic burden and unnecessary radiation exposure. The objective of this study was to determine rates of diagnostic imaging in long-term young adult cancer survivors (YAS) compared to cancer-free controls in Ontario, Canada. Methods: We conducted a population-based retrospective study. Young adults aged 20 to 44 diagnosed with an invasive malignancy between 1992 and 1999 who lived at least 5 years without recurrent disease were identified in the Ontario Cancer Registry. YAS were matched 1:5 to randomly selected cancer-free controls on calendar year of birth, sex, and place of residence. The rate at which YAS received plain radiography, CT, ultrasound and nuclear medicine studies was compared to rates received by controls using Poisson regression. Results: 20,911 survivors and 104,524 controls met our inclusion criteria. YAS received all types of diagnostic imaging at significantly higher rates than controls in the 10 year period after 5-year recurrence-free survival. YAS received CT scanning at a rate 3.6-fold higher than controls (95% confidence interval [CI]: 3.37, 3.62). In contract, the difference in rates of ultrasound between the two groups was more modest (rate ratio [RR] = 1.40, 95% CI: 1.38, 1.43). YAS also received plain radiography (RR =1.66, 95% CI: 1.64, 1.69) and nuclear studies (RR=1.97, 95% CI: 1.89, 2.04) at significantly higher rates than controls, resulting in a 4.6-fold adjusted higher diagnostic radiation dose than controls. Conclusions: Survivors received significantly higher rates of all diagnostic studies after 5-year survival compared to their age-matched cancer-free counterparts. Hazards associated with overuse of imaging such as radiation exposure and heightened anxiety about test results need to be considered. Both patients and providers should be educated about the role of diagnostic imaging in long-term surveillance including the utility of studies without radiation, such as ultrasound.
Rational use of intensity-modulated radiation therapy (IMRT) as determined by radiation oncologists in cooperation with Blue Cross Blue Shield of Massachusetts (BCBSMA).
Authors: Mamon Harvey J. , Steingisser Lee , Fallon John , Walsh Gerard , Jacobson Joseph O.
Published: February 2017

73

Background: IMRT is a sophisticated radiation technique that allows more precise delivery than conventional external beam radiation (EBRT). Prospective randomized data indicating which patients are most likely to benefit from IMRT are limited, and the rate of IMRT utilization varies widely. Methods: BCBSMA reached out to radiation oncologists to develop a consensus regarding the use of IMRT. Initial discussions started in 2009. The process included discussions within radiation oncology departments and meetings and conference calls with BCBSMA. In April 2011 a survey was sent to radiation oncologists, followed by the formation of a Physician Advisory Council consisting of representatives of 11 large academic and private practices. The council met in June 2011 and continued to develop guidelines over a series of conference calls. Results: The BCBSMA IMRT policies went into effect on 9/1/11. No policies for the use of EBRT were created. It was agreed that IMRT is appropriate for cancers of the head and neck, prostate, and anus. For other sites, emphasis was placed on the QUANTEC recommendations regarding acceptable doses to normal tissues. To justify the use of IMRT, radiation oncologists were asked to demonstrate that conventional EBRT resulted in excess dose to normal tissues, and that IMRT could lower the doses to an acceptable range. In addition, a process was set up for peer-to-peer review to consider the application of IMRT to cases outside of the guidelines. Preliminary analysis of claims compared the case rat /1,000 BCBSMA members over a 6 month pre-IMRT policy implementation base period to a 6 month post-implementation case rate. The number of IMRT cases during the study period was decreased by 20% while the EBRT cases/1,000 members during the study period increased by 14%. During the two prior years, the IMRT cases/1,000 members for IMRT increased 20%, while the EBRT cases/1000 members decreased 3%. Conclusions: The experience in Massachusetts suggests that practicing physicians and insurers can work together to achieve a consensus regarding the appropriate application of high-technology treatments potentially impacting their rate of utilization.
EMR-linked cancer tracker facilitates lung and liver cancer care.
Authors: Taddei Tamar H. , Hunnibell Laura , DeLorenzo Anne , Rosa Mirta , Connery Donna , Vogel Donna , Garla Vijay , Taylor Caroline , Rose Michal G.
Published: February 2017

77

Background: VA Connecticut Healthcare System has developed a web-based, EMR-linked Cancer Care Tracking System (CCTS) to facilitate tracking and follow-up of patients with imaging abnormalities concerning for lung or liver cancer. The tracker was developed to facilitate the efforts of a multidisciplinary team at the center of which is a cancer navigator. Methods: CCTS was first envisioned in 2007 when VACT hired a care navigator and implemented a radiology coding system to identify potential cancers. This created the need for a tool to process abnormal images and track the clinical steps required to reach a definitive diagnosis and treatment plan. CCTS was initially used for lung cancers and was expanded to track hepatocellular carcinoma (HCC) in 2009 with additional funding. In addition to case discovery, it offers easy access to patient information with live links to the VA EMR, a surveillance feature, and scheduling, alerting, and reporting functions. In 2011, the system was enhanced with a natural language processing (NLP) program that automatically identifies radiology reports describing potentially malignant lung or liver lesions. Results: CCTS has been in daily operation since February 2010, with 1,778 patients and 2,503 patients tracked in 2010 and 2011, respectively. Addition of NLP technology significantly increases the accuracy of identification of patients with lung or liver nodules. The NLP system identified 21% of all new cases with potential malignancies whose management could have been delayed through coding omissions or errors. Benefits of CCTS and our cancer care coordination program have included a decrease of 25 days in the time from abnormal image to treatment of lung cancer, a significant increase in the diagnosis of stage I/II lung cancers from 32% to 48%, and an increase in the incidence of liver cancer from 1% to 5% of all cancers at VACT. Conclusions: A web-based, EMR-linked cancer care tracking system (CCTS) improves cancer detection, prevents loss to follow-up, provides a safety net for radiology coding omissions or errors, and improves provider efficiency. CCTS is an innovative tool to support multidisciplinary cancer care and has broad applicability to any electronic medical record.
Raising the bar: Breast cancer biomarkers IHC4 harmonization from University of California-Athena pathology collaboration.
Authors: Bishop John W. , Engelberg Jesse , Apple Sophia , Balassanian Ronald , Borowsky Alexander D. , Cardiff Robert D. , Carpenter Philip M. , Chen Yunn-Yi , Datnow Brian , Elson Sarah , Hasteh Farnaz , Lin Fritz , Moatamed Neda A. , Perkovich Brandon , Zhang Yanhong
Published: February 2017

80

Background: Breast cancer treatment depends on the accurate analysis of immunohistochemical biomarkers (IHC4): estrogen and progesterone receptors, Ki-67, HER2. The Athena Harmonization project was undertaken to reduce technical and scoring variances between different laboratories and different pathologists. Methods: Initial assessment: Five breast cancer samples were sectioned and distributed to 5 UC campuses, where IHC4 and HER2 FISH tests were done per usual methods. Samples were selected to cover the range of negative, positive, and moderate for each antigen. Stained slides were circulated to 10 pathologists for scoring. Digital whole slide images (WSI) were made and scored. Technical variance reduction: A Delphi voting process identified an ideal histology slide for each IHC4 antigen. Laboratories adjusted techniques to match the appearance of the ideal slides, followed by pathologist and quantitative image analysis (QIA) validation. Scoring variance reduction: A digital pathology training tool was created where pathologists scored breast cancer tissue microarrays with known scores for the IHC4 antigens. Results: Scoring variance did not exceed clinical thresholds, although there were significant technical and scoring variances between laboratories that could affect research outcomes. The mean values and variance were similar for WSI and glass slides, except for HER2 (higher scores on WSI but without benefit of workstation calibration). Each laboratory adjusted technical parameters to more closely match the ideal IHC4. Early QIA data indicate reduced variance between adjusted and ideal histology slides. Conclusions: Considerable and significant technical and interpretational variances between five University of California laboratories can be overcome by harmonizing protocols, setting new inter-institutional standards for pathology and histology best practices. Quantitative image analysis and whole slide imaging were instrumental. Subsequent harmonization will include cases near thresholds for clinical treatment guidelines.
Early recognition and treatment of febrile neutropenia in a community hospital.
Authors: Mulvey Therese M. , Tripp Carme M. , Camara Gina , Blanchard Elizabeth M.
Published: February 2017

90

Background: Febrile neutropenia (FN) is a medical emergency leading to significant morbidity if unrecognized. The use of G-CSF has made FN a less frequent presentation to community hospitals. Significant delays in antibiotic initiation were seen in our community hospital system. Antibiotic selection was variable and blood cultures were often not obtained prior to antibiotics. In November 2011, a FN program was initiated to increase recognition of patients at risk for FN, reduce time to antibiotic initiation, improve antibiotic selection using guideline driven antibiotic (GDA) selection, and decrease morbidity. Methods: A FN Card was developed providing a link to the hospital website detailing the approach to FN, obtaining blood cultures, and use of GDA for patients with or without venous access devices. Patients were educated to carry the card with them and present the card to the triage nurse on ER arrival if their home temperature was over 100.4F. A nurse driven protocol was developed for assessment, blood cultures, and early initiation of GDA and an educational program was provided to the ER staffs at all hospitals in our system. Results: In the 6 month lead up to the initiation of the FN program, 31 patients were identified with FN; 22 as the result of malignancy or therapy, 9 because of benign disease. The median time to antibiotics was 6.3 hours, no patient received GDA, and 32% had blood cultures performed. Three months after initiation of the program, 26 patients presented to the ERs over a 12-week period; 20 from malignant disease or its therapy, 6 from benign disease. Seven patients had received a FN card in clinic and 2 presented the card to the ER triage nurse. Median time to GDA was 2 hours and all 26 patients received GDA, 22 patients (85%) had blood cultures performed prior to GDA. Conclusions: A FN educational program including a FN Card linked to the hospital web site resulted in a significant increase in the number of patients recognized early presenting with FN, reduced time to antibiotic initiation, improved GDA selection and improved blood culture rates before GDA. Data regarding reducing morbidity are pending.
S0221: Comparison of two schedules of paclitaxel as adjuvant therapy for breast cancer.
Authors: Budd G. Thomas , Barlow William E. , Moore Halle C. F. , Hobday Timothy J. , Stewart James A. , Isaacs Claudine , Salim Muhammad , Cho Jonathan K. , Rinn Kristine , Albain Kathy S. , Chew Helen K. , Burton Gary Von , Moore Timothy David , Srkalovic Gordan , McGregor Bradley Alexander , Flaherty Lawrence E. , Livingston Robert B. , Lew Danika , Gralow Julie , Hortobagyi Gabriel N.
Published: February 2017

CRA1008

Background: S0221 is a SWOG-coordinated phase III adjuvant chemotherapy intergroup trial in node-positive and high-risk node-negative operable breast cancer which hypothesized that 1) the weekly AC+G regimen is superior to ddAC x 6 and 2) 12 weeks of weekly paclitaxel (wP) is superior to q 2 week paclitaxel x 6 (ddP). Methods: Between December 2003 and November 2010, 2,716 patients were randomized in a 2 x 2 factorial design to 1) AC+G vs ddAC and 2) P 80 mg/m2/week x 12 vs P 175 mg/m2 q 2 weeks x 6. If there was no significant interaction between the factors, the trial was powered to find a disease-free survival hazard ratio (HR) ≤ 0.82 for weekly vs q 2 week for each factor. At the first interim analysis, the AC randomization was halted for futility, and S0221 was closed to accrual 10 November 2010. S0221 reopened 15 December 2010, after which time all patients received 4 cycles of ddAC and randomization to P weekly x 12 and ddP x 6 continued. Accrual halted at a total of 3,294 in January 2012. Results: By September 7, 2012, 487 events and 340 deaths had occurred, prompting the third planned interim analysis. The Data Safety and Monitoring Committee recommended reporting the results since the futility boundary was crossed. A Cox model adjusting for the AC arms had a HR = 1.08 (95% CI 0.90-1.28; p=0.42), with the 99.5% CI excluding the original alternative hypothesis that the HR=0.82. There was no significant interaction of the two factors. Estimated 5-year progression-free survivals were 82% for weekly P and 81% for ddP. Toxicity data were available for 1,385 patients treated with ddP and 1,367 treated with weekly P. Grade 5 toxicity occurred in 4 patients on ddP and 2 on weekly P. Percent grade 3-4 toxicity per arm are shown in the Table. Conclusions: Either ddPx6 or weekly P x 12 are acceptable schedules of P administration. The differences in leukopenia likely reflect ascertainment bias against weekly P. If this is accepted, weekly P x 12 produces less overall toxicity than 6 cycles of ddP. Support: NCI grants CA32102, CA38926, CA21115, CA21076, CA77597, CA25224, CA77202, CCSRI15469, and Amgen, Inc. Clinical trial information: NCT00070564. [Table: see text]
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.
Prediction of the probability of breast cancer-related lymphedema after axillary lymph node dissection.
Authors: Soran Atilla , Ibrahim Ahmad , DeGore Lori , Johnson Ronald
Published: February 2017

140

Background: Early detection and timely intervention demonstrate the greatest promise of reducing incidence of late-stage lymphedema (LE) in breast cancer patients undergoing axillary lymph node dissection (ALND). A nomogram was developed for predicting the risk of arm LE in this group. This study’s aim was to test the preoperative prediction model for the early diagnosis of clinical and subclinical LE in ALND including patients prospectively monitored by bioimpedance spectroscopy (BIS). Methods: Patients with pre-existing clinical LE were selected from our existing database. In addition, data on subclinical LE was prospectively collected through our LE monitoring program. This program tracks patients from a baseline, using an L-Dex U400 measurement preoperatively or postoperatively (if no clinical LE), and at 3-6 month intervals. The 5 year probability of LE after ALND was calculated using The Cleveland Clinic Risk Calculator. The discrimination of the nomogram was assessed by calculating the area under (AUC) the receiver operating characteristic curve (ROC); AUC values between 0.7–0.8 represent considerable discrimination. Results: A total of 334 patients who underwent ALND were included in this study; 116 patients with previously diagnosed clinical LE and 218 patients at-risk of LE (monitored with BIS since 2010). Since BIS monitoring began, a total of 58 patients were diagnosed with subclinical LE; a total of 174 patients with clinical or subclinical LE (LE group). The mean age was 60.6+11.4 years in LE group and 57.8+12.03 years in No-LE group (p=0.03). BMI was higher in LE group compared with no LE group (29.8 + 7.4 vs.28.3+6.3 kg/m2(p=0.05). The AUC value was calculated from the nomogram (AUC=0.609). Conclusions: The recently created preoperative prediction model for the diagnosis of LE in ALND is not accurate in predicting who will develop clinical or subclinical LE. Periodic monitoring of women at high risk for LE, with modern technology, helps early detection and timely intervention for LE, which can minimize or eliminate more advanced LE among women undergoing ALND.
Tracking viewership of survivorship topics from an online educational resource for breast cancer survivors: Findings from the Pink Ribbon Survivors Network Curriculum for Recovery Library.
Authors: Fisher Robert E. , Adams Kelly Ann
Published: February 2017

141

Background: The Pink Ribbon Survivors Network created a virtual library, The Curriculum for Recovery Library, as part of its online resources for breast cancer survivors and the health care providers who care for them. The website's library became available on July 11, 2012. 199 articles are organized into 19 categories within the library. Within each category, article titles are directly linked to their online text. The library is hosted on the organization's website: www.PinkRibbonSurvivorsNetwork.org. Methods: Through the website's administrative site, we tracked and reviewed the number of visits to each of the 19 categories's content in The Curriculum for Recovery Library between July 11, 2012 and April 21, 2013. Results: The five following categories were most were accessed by our viewership, in descending order: " Fatigue," "Doubt and Hope," "Your Survivorship Document," "Diet/Exercise/Selfcare," and "Leaving a Legacy." The tally has been determined by review of the first 2,800 viewings of the website, during this 9 month period. Conclusions: When given free access to 19 categories relevant to survivorship, our data reveals that treatment related fatigue and doubt about a breast cancer survivor's future are the most sought after categories among our viewership population. This data will help to prioritize research and resources for breast cancer survivors in the future.
Correlation of molecular alterations with efficacy of everolimus in hormone-receptor–positive, HER2-negative advanced breast cancer: Results from BOLERO-2.
Authors: Rugo Hope S. , Hortobagyi Gabriel N. , Piccart-Gebhart Martine J. , Burris Howard A. , Campone Mario , Noguchi Shinzaburo , Perez Alejandra T. , Deleu Ines , Shtivelband Mikhail , Provencher Louise , Masuda Norikazu , Dakhil Shaker R. , Anderson Ian , Chen David , Damask Amy , Huang Alan , McDonald Robert , Taran Tanya , Sahmoud Tarek , Baselga Jose
Published: February 2017

142

Background: Everolimus (EVE) plus exemestane (EXE) more than doubled progression-free survival (PFS) while maintaining quality of life vs EXE alone in postmenopausal women with hormone receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (BOLERO-2 phase III; NCT00863655). PFS benefit was seen in all clinically defined subgroups. We evaluated genetic variations of a broad panel of cancer-related genes and explored their correlations with EVE benefit. Methods: Exon sequence and gene copy number variations were analyzed in 182 cancer-related genes by next-generation sequencing (NGS). Correlations with PFS were evaluated using univariate and multivariate Cox models. Results: NGS data (>250x coverage) were successfully generated from archival tumor specimens from 227 patients (NGS population, 157 in EVE + EXE arm and 70 in EXE arm) whose baseline characteristics and clinical outcome were comparable to the trial population (PFS HR = 0.40 and 0.45, respectively). The treatment benefit of EVE + EXE over EXE was maintained in the subgroups defined by each of the 9 genes with a mutation rate >10% (e.g., PIK3CA, FGFR1, CCND1) or when less frequently mutated genes (e.g., PTEN, AKT1) were included in their respective pathways. Patients with 0 or 1 genetic alteration in PI3K or FGFR pathways or CCND1 had a greater treatment effect from EVE (HR = 0.27, 95% CI 0.18-0.41, adjusted by covariates, in 76% of the NGS population), indicating the value of these pathways for predicting sensitivity to EVE in this setting. Conclusions: This is the first global registration trial in which efficacy-predictive biomarkers were explored by correlating broad genetic variations with clinical efficacy. The preliminary results suggest that a large subgroup of patients (76%), defined by minimal genetic variations in the PI3K or FGFR pathways or CCND1, derives the most benefit from EVE therapy (HR = 0.27 vs 0.40 for the full NGS population). These exploratory results and their implication in understanding the interplay of multiple pathways in tumor cells and testing new hypotheses for targeted combination therapies in HR+/HER2– BC will be further investigated. Clinical trial information: NCT00863655.