bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression panel (TheraPrint) analyzed as predictors of response to neoadjuvant chemotherapy (NCT) in patients (pts) with stage II-III and inflammatory breast cancer (BC).
Authors: Somlo George , De Snoo Femke , Peeters Justine , Stork-Sloots Lisette , Simon Iris , Robinson Kim
Published: February 2017

8

Background: TheraPrint is a microarray-based gene expression panel of 125 genes identified as potential targets for prognosis and therapeutic response. These genes may hold the key to a greater level of personalized prognosis and therapy for BC pts. The aim of the current study was to assess the clinical relevance of the TheraPrint genes for either predictive and/or prognostic value in two patient cohorts treated with NCT. Methods: The 1st patient cohort are 68 Stage II-III BC pts treated with NCT. Expression data from Agilent full genome arrays, containing the MammaPrint, BluePrint and TheraPrint diagnostic profiles/probes (Somlo et al, 2009). Median FU 2.3 years. The 2nd patient cohort are 230 Stage I-III BC pts treated with NCT. Expression data from Affymetrix probe sets was publically available (Iwamoto et al, 2011). Median FU 5.2 years. To identify genes that are differentially expressed between responders (pCR/RCBI) and non-responders, a supervised analysis was performed. The analysis was performed across all pts and also within groups of HER2+ and HER2-. Univariate t-tests were performed, with results filtered by permutation p-value (p<0.05) and fold change of >1.5. Global test was also reported. In addition, survival data analysis was performed across all pts. Results: Overlapping genes between the 2 datasets that were significantly differentially expressed between responders and non-responders include: BCL2 (down-regulated) and CDH3, GRB7, KRT6B, KRT17 (up-regulated). When analysing the HER2- subgroup, 3 genes turned out to be differentially expressed between responders and non-responders in the 2 datasets: FLT1, PIK3R1 (down-regulated) and KRT6B (up-regulated). For the HER2+ subgroup, only one gene overlapped for the 2 datasets: IL2RA (up-regulated). The top canonical pathways for the significant genes have been analyzed, and in addition correlation of the TheraPrint gene expression with survival for these pt groups. Conclusions: This study has identified several genes from a panel of 125 TheraPrint genes with statistically significant correlation between expression and response to NCT.
Effect of pericytes on melanoma development.
Authors: Trevino-Villarreal Jose Humberto , Cotanche Douglas A. , Sepulveda Rosalinda , Rogers Rick A.
Published: February 2017

83

Background: Melanoma-associated stroma cells regulate tumor establishment, invasion, and dissemination through paracrine and heterotypic cell-cell interactions with cancer cells. Pericytes constitute a major noninflammatory component of the melanoma-associated stroma. Our study is designed to evaluate the role of pericytes in melanoma development. Methods: Tumors induced in GFP+/SCID mice with GFP-B16 cells were harvested after 14 days, enzyme digested, labeled against mesenchymal markers, and analyzed by flow cytometry (FC). The distribution of stromal subpopulations in tumors was investigated by immunofluorescence microscopy (IFM). Stromal pericytes from tumors and adipose tissue were FACS sorted, mixed with B16 cells at a 3:1 ratio, and injected into SCID mice. Tumor diameters were taken periodically with a scientific caliper, and used to determine tumor volumes using the ellipsoid formula. Results: FC analysis showed that the melanoma stroma was composed of CD45+ inflammatory cells, CD31+ endothelial cells, FAP+ myofibroblasts and CD146+ cells. IFM analysis showed that the CD146+ cells are perivascular CD31-/CD34-/α-SMA+ stromal pericytes that associated with TGF-β immunoreactive CD271+/CD146+B16 cells in perivascular tumor niches. Co-induction experiments were performed to investigate the effect of pericytes on melanoma development. We observed faster growth rates in the size of tumors co-induced with pericytes, compared with tumors induced with B16 cells alone. These co-induced tumors had bigger masses, more volume, were hypercellular, and had increase vascularization compared with control tumors. In addition, pericytes increased the B16 cell proliferation rate, as determined by higher expression of Ki-67 in the tumor fraction of co-induced tumors. Conclusions: Pericytes promote melanoma development by inducing angiogenesis and melanoma cell proliferation. Our results suggest that pericytes could be utilized as a therapeutic target for melanoma treatment.
The LIVESTRONG essential elements of survivorship care: Advancing quality survivorship care in clinical care settings.
Authors: Arvey Sarah R. , Rechis Ruth
Published: February 2017

155

Background: The American College of Surgeons Commission on Cancer (COC) has set a 2015 deadline for oncology practices to comply with new patient-centered standards of care to maintain accreditation. Despite this mandate, there is not a strong evidence base on best practices, or guidance on how to implement quality survivorship care services. In September 2011, the Lance Armstrong Foundation (LAF) and the LIVESTRONG Survivorship Center of Excellence Network (Network) convened researchers, providers, advocates, and cancer survivors who identified and prioritized a list of 20 Essential Elements of survivorship care. LAF and the Network continued work to refine this list with input from stakeholders with the goal of disseminating a framework for survivorship care delivery and advancing a research agenda to strengthen the evidence base for implementing these elements as standard care. Methods: LAF and the Network have refined definitions of the Essential Elements through an iterative process and in late 2012 will facilitate a technology-mediated consensus-building process among a broad group of stakeholders. Results: Refinement of the Essential Elements included defining each element in such detail that “basic” and “enriched” levels of implementation are described to guide providers in real-world settings. This work outlines a research agenda aimed to strengthen the evidence-base of the Essential Elements’ effectiveness in improving survivors’ outcomes. In October 2012, the refined definitions will be disseminated to a broad stakeholder audience and subject to review. Details of this iterative process, resulting definitions, and open-forum feedback will be reported here. Conclusions: Once complete, the Essential Elements will represent a consensus-driven platform that provides the cancer care community with a blueprint for the development and implementation of high-quality survivorship care and research. Additionally, the finalized Essential Elements will further facilitate the broad adoption of the new COC standards including the provision of a treatment summary and survivorship care plans, palliative care, psychosocial distress screening, and care coordination.
The Canadian partnership for quality radiotherapy: A model for radiation treatment quality and safety.
Authors: Cao Jeffrey Quoc , Bissonnette Jean-Pierre , Brundage Michael Donald , Dunscombe Peter , French John , Gillan Caitlin , Keresteci Margaret , Milosevic Michael , Parliament Matthew , Schella Jason
Published: February 2017

266

Background: Innovative, overarching national, and international strategies for the assurance of safe and high quality radiation treatment (RT) are needed, given the rate of technologic innovation and shifts in traditional roles associated with RT planning and delivery. Methods: The Canadian Partnership for Quality Radiotherapy (CPQR) was created as an interprofessional alliance of the Canadian Association of Radiation Oncology (CARO), Canadian Organization of Medical Physicists (COMP), Canadian Association of Medical Radiation Technologists (CAMRT) and Canadian Partnership Against Cancer (CPAC), aimed at developing and promoting coordinated national strategies for high quality and safe RT. Results: A steering committee of national leaders from each profession and content experts in RT quality and safety was created, with financial and strategic backing provided by the federal government through CPAC. The vision and strategy were communicated broadly to the RT treatment community and to other stakeholders provincially, nationally, and internationally. ‘Quality Assurance Guidance for Canadian Radiation Treatment Programs’ was published online in April 2011 and empowered programs across the country to evaluate their internal procedures against these indicators. This document was downloaded over 875 times in the first 6 months, a measure of the demand and broad uptake in Canada and internationally. This early success has fostered other foci of activity, including engagement by the Canadian medical physics community around synthesis of detailed quality control guidelines for equipment, a dialogue about national incident reporting, and support from international partners in relation to collaborative programs. The goal is to incorporate RT quality and safety indicators into national accreditation programs for cancer care to assure long-term sustainability. Conclusions: CPQR has established a model for quality and safety that is fostering the evolution of a new national quality culture. This model is applicable to other jurisdictions, recognizing that a coordinated international approach to setting guidelines and standards will ultimately lead to higher quality and safer RT on a global scale.
An electronic chemotherapy administration safety checklist: The safe transition from paper to computer.
Authors: Olsen MiKaela M. , Wilt Monica , Van de castle Barbara , Mooney Kathy , Cohen Melanie , Taffe Elizabeth , Swisher Marie , McCready Jackie , Daniel Denise , Krumm Sharon , Chen Allen Ray Sing
Published: February 2017

303

Background: This abstract describes the successful implementation of an electronic chemotherapy administration safety checklist and the outcomes that led to further enhancement of safe chemotherapy administration. The purpose of this abstract is to give an overview of the processes in transitioning from a paper checklist to an electronic version. Following the implementation of a paper chemotherapy administration safety checklist in 2002, this cancer center realized a significant reduction in chemotherapy errors reaching patients. The checklist became a model for many practitioners across the U.S. Our implementation of the Sunrise computerized provider order entry (CPOE) system in oncology inpatient units in 10/2009 included support for all of the 2009 ASCO/ONS chemotherapy ordering standards, and featured a two-way interface with the pharmacy system, and an electronic medication administration record. In the 12 months following its deployment, the rate of chemotherapy errors that reached the patient fell from 2.71 per 100 chemotherapy admissions using our paper system to 1.11 per 100 chemotherapy admissions using CPOE. With the advent of electronic documentation it became apparent that the paper checklist was outdated. Methods: An electronic chemotherapy checklist was implemented, replacing a paper version that had been in use for almost a decade. The proper design and implementation of the electronic version were essential to ensure that the safety achieved with the paper checklist was not compromised. After pilot testing, the checklist was implemented. Results: The electronic chemotherapy checklist was accepted by staff and resulted in a decrease in errors reaching the patient. Conclusions: The safe administration of chemotherapy is the number one priority at our cancer center. To our surprise the electronic checklist has been a welcomed addition to our armamentarium against chemotherapy errors. The checklist has enhanced independent safety checks due to required independent sign-on of the electronic system. The checklist also heightened awareness of chemotherapy safety checks, which were unchanged, leading us to believe that the paper version had become somewhat ineffective.
Use of iPad technology to determine cancer patient-reported preferences for and understanding of pharmacogenetic testing (PGT).
Authors: Martin Petra , Brown Catherine , Cuffe Sinead , Pringle Dan , Mahler Mary , Villeneuve Jodie , Niu Chongya , Charow Rebecca , Lam Christine , Shani Ravi M. , Hon Henrique , Otsuka Memori , Epsin-Garcia Osvaldo , Xu Wei , Alibbhai Shabbir , Jenkinson Jodie , Liu Geoffrey
Published: February 2017

319

Background: PGT in oncology can be used to predict the efficacy and toxicity of a particular treatment in an individual. Previous work by our group has demonstrated that among cancer patients willing to undergo chemotherapy, >98% wanted PGT testing if it could identify patients who would respond to chemo. However, in the original study using a paper questionnaire, 22% of patients did not understand the concept of PGT and its clinical implications. Therefore, we have devised a simpler, more visual questionnaire in electronic format using iPad technology and simple animations. We are assessing if patient understanding using this format is increased and also if patients prefer completing the survey with this novel technology. Methods: An interim analysis of a broad cross-section of cancer patients using an iPad was performed. PGT questions related to hypothetical efficacy, toxicity, time to test results, willingness to pay as well as understanding of PGT scenarios were assessed. Results: 135 cancer patients (87% adjuvant, 12% metastatic; 27% breast, 25% colon, 22% heme malignancy, 23% other) attending Princess Margaret Hosptial participated. 85% of patients accepted chemo that had a 5% absolute improvement in survival and <10% chance of side effects. 94% of patients chose to have PGT if it could identify subsets of patients who would benefit from chemo. The median that patients were willing to pay for PGT was $250 (range $0-$5,000), however the median that patients felt was a reasonable price was $100 ($0-$5,000). 11% of patients admitted that they did not understand the concept of PGT and its clinical implications. Conclusions: Almost all patients who were willing to undergo chemo were also willing to accept PGT. Fewer patients in this study compared with our original paper directed questionnaire described themselves as lacking an understanding of PGT (11% versus 22% respectively), suggesting that survey administration on an iPad with a visual characterization of question scenarios improved understanding. Final data from over 300 patients will be analyzed in the fall, which would include data on patient attitudes on use of such technology for communication and decision making.
Oral chemotherapy: A focus on interventions and access.
Authors: Mancini Robert , Wilson David , Modlin Jessie , Zuckerman Dan Sayam , Powell Colleen , Rapp Delisa , Collins Jill , Hutchinson Thea
Published: February 2017

44

Background: Oral chemotherapies are becoming more predominant with 40% of the currently available oral agents being approved in the last 7 years. Patient self-administration and the costs of these medications raise concerns about monitoring and access. As a result, nonfulfillment rates in the literature have been reported to range from 10-24% with rates directly correlated with cost of the medication. Methods: Patients who utilized the pharmacist-managed oral chemotherapy program were included for evaluation. Patients were excluded if they utilized external mail order pharmacies. Patient charts were audited for documented pharmacist-initiated interventions such as drug-interactions, lab monitoring, and dose adjustments. Patient nonfulfillment rates were evaluated by evaluating percentage of patients referred to number of prescriptions filled. Patients were classified as either filled, mail order, financial assistance or never started. Financial assistance patients were divided into free drug or co-pay assistance. Total amount of free drug obtained was assessed by multiplying the average number of cycles obtained by patients by the average wholesale price (AWP). Results: A total of 702 patients were served by the Oral Chemotherapy program between August 2009 and October 2011. In those patients, 82 drug-drug interactions and 24 patients required dose adjustments up front, mostly due to renal dysfunction. Compared to the 10-24% nonfulfillment rates in the literature, this program was able to keep rates less than 1% for patients who were unable to obtain medication for financial reasons. In this time period, underinsured patients were able to obtain >$1 million in free drug and >$200,000 in co-pay assistance funds thanks to our financial advocates. Conclusions: Collaboration within one health system between oncologists, pharmacists, nurses and social workers/financial advocates was able to ensure better quality of care by helping address medication issues upfront with minimal delays in access. In addition, this program was able to ensure that most patients were able to obtain their medication within a reasonable time period at a reasonable cost, reducing non-fulfillment rates compared to what has previously been reported in the literature.
aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer.
Authors: Gray Richard G. , Rea Daniel , Handley Kelly , Bowden Sarah Jane , Perry Philip , Earl Helena Margaret , Poole Christopher John , Bates Tom , Chetiyawardana Shan , Dewar John A. , Fernando Indrajit Nalinika , Grieve Robert , Nicoll Jonathan , Rayter Zenor , Robinson Anne , Salman Asad , Yarnold John , Bathers Sarah , Marshall Andrea , Lee Martin ,   on behalf of the aTTom Collaborative Group
Published: February 2017

5

Background: In estrogen-receptor-positive (ER+) early breast cancer, 5 years of tamoxifen reduces breast cancer death rates by about a third throughout years 0-14. It has been uncertain how 10 years of tamoxifen compares with this. Methods: During 1991-2005, 6,953 women with ER+ (n=2755), or ER untested (4198, estimated 80% ER+ if status known) invasive breast cancer from 176 UK centres were, after 5 years of tamoxifen, randomized to stop tamoxifen or continue to year 10. Annual follow-up recorded compliance, recurrence, mortality, and hospital admissions. Results: Allocation to continue tamoxifen reduced breast cancer recurrence (580/3468 vs 672/3485, p=0.003). This reduction was time dependent: rate ratio 0.99 during years 5-6 [95%CI 0.86-1.15], 0.84 [0.73-0.95] during years 7-9, and 0.75 [0.66-0.86] later. Longer treatment also reduced breast cancer mortality (392 vs 443 deaths after recurrence, p=0.05), rate ratio 1.03 [0.84-1.27] during years 5-9 and 0.77 [0.64-0.92] later; and overall mortality (849 vs 910 deaths, p=0.1), rate ratio 1.05 [0.90-1.22] during years 5-9 and 0.86 [0.75-0.97] later. Non-breast-cancer mortality was little affected (457 vs 467 deaths, rate ratio 0.94 [0.82-1.07]). There were 102 vs 45 endometrial cancers RR=2.20 (1.31-2.34, p<0.0001) with 37 (1.1%) vs 20 (0.6%) deaths (absolute hazard 0.5%, p=0.02). Combining the similar results of aTTom and its international counterpart ATLAS (Lancet 2013) enhances statistical significance of recurrence (p<0.0001), breast cancer mortality (p=0.002) and overall survival (p=0.005) benefits. Conclusions: aTTom confirms that, in ER+ disease, continuing tamoxifen to year 10 rather than just to year 5 produces further reductions in recurrence, from year 7 onward, and breast cancer mortality after year 10. Taken together with the reduction in breast cancer deaths seen in trials of 5 years of tamoxifen vs none, these results indicate that 10 years of adjuvant tamoxifen, compared to no tamoxifen, reduces breast cancer mortality by about one third in the first 10 years following diagnosis and by a half subsequently. Clinical trial information: ISRCTN17222211.
Oral HPV infection in HPV-positive oropharyngeal cancer cases and their spouses.
Authors: D'Souza Gypsyamber , Gross Neil D. , Pai Sara I. , Haddad Robert I. , Gillison Maura L. , Posner Marshall R.
Published: February 2017

CRA6031

Background: Incidence of human papillomavirus-positive oropharyngeal cancer (HPV-OPC) is increasing, and spouses of these patients have high anxiety about their own HPV-related cancer risk. Methods: Partner study of 149 HPV-OPC and 81 of their spouse/long-term partners. Data collection included a 30-second rinse and gargle (at diagnosis and again 1 year later for 103 cases and 46 partners), computer-assisted risk factor survey, tumor collection (cases), and visual oral examination (spouses). Oral rinse samples were tested for 36 types of HPV DNA using PGMY09/11 primers and line-blot amplification, and HPV16 copy-number using real-time PCR. Results: Cases were primarily male (89%), white non-Hispanic (92%), had performed oral sex (94%), and never-smokers (51%) with a median age of 56 years. Twelve-month survival was high among never- and ever-smoking HPV-OPC (100% vs 93%, p=0.18). The 81 spouses of HPV-OPC were primarily female (81%), white non-Hispanic (92%), never-smokers (54%), with a median age of 53 years. Spouses were significantly less likely than cases to have >10 lifetime oral sex partners (11% vs 39%, p<0.001). Prevalence of any oral HPV (65%) and oral HPV16 (52%) was high among HPV-OPC at diagnosis. Four (7.7%) of 52 HPV-OPC with HPV16 DNA detectable before therapy, had HPV16 persistently detected one year after diagnosis/therapy. Prevalence of any oral HPV DNA among partners was significantly lower than among HPV-OPC (7.3% vs 65%, p<0.001). Oral HPV prevalence was significantly higher among the 7 male partners than the 74 female partners (29% vs 5%, p=0.025). Oral HPV infections among partners included HPV16 (n=2), HPV62 (n=2), HPV 83 and 51 (1 each). Both partners with oral HPV16 infections were female and no longer had oral HPV16 detected at the one year follow-up. 64% of spouses had a visual oral exam, and no pre-cancers or cancers were identified. However, two (2.5%) enrolled spouses reported a personal history of cervical cancer, and 6 HPV-HNC cases (4.0%) reported a previous spouse who developed cervical or vaginal cancer. Conclusions: Oral HPV16 DNA is common among HPV-OPC, but not among their spouses. Spouses of HPV-OPC may have an elevated risk or history of cervical cancer.
Phase II study of selumetinib (sel) versus temozolomide (TMZ) in gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma (UM).
Authors: Carvajal Richard D. , Sosman Jeffrey Alan , Quevedo Fernando , Milhem Mohammed M. , Joshua Anthony Michael , Kudchadkar Ragini Reiney , Linette Gerald P. , Gajewski Thomas , Lutzky Jose , Lawson David H. , Lao Christopher D. , Flynn Patrick J. , Albertini Mark R. , Sato Takami , Paucar Daniel , Panageas Katherine S. , Dickson Mark Andrew , Wolchok Jedd D. , Chapman Paul B. , Schwartz Gary K.
Published: February 2017

CRA9003

Background: Gq/11 mutations are early oncogenic events in UM resulting in MAPK pathway activation. We demonstrated decreased viability in UM cell lines harboring Gq/11 mut with sel, a small molecule inhibitor of MEK1/2 (Ambrosini, CCR 2012). Methods: We conducted a 16 center randomized phase II study of hyd-sulfate sel 75 mg BID vs TMZ 150 mg/m2 daily for 5 days in 28-day cycles (or DTIC 1000 mg/m2 q21 days) for patients (pts) with metastatic UM with a Q209 Gq/11 mut who have not received prior TMZ/DTIC. The primary endpoint was progression free survival (PFS). Secondary endpoints included overall survival (OS) and response rate (RR). Select pts underwent tumor biopsies at baseline and after 14 (+/- 3 days) of sel. Our statistical plan required ≥80 pts randomized and ≥68 events to detect a PFS hazard ratio of 0.6 (p=0.1). Randomization was stratified by mut (Gq vs G11), M stage and number of prior therapies (tx). Tumor assessment occurred every 4 weeks (wks) for 8 wks and then every 8 wks using RECIST 1.1. Pts receiving TMZ who progressed could receive sel (TMZ→sel). Results: 80 pts were randomized. Sel (n=39): median age 66 (range 32-86), 54% male, 54% G11 mut, median ECOG PS 0 (range 0-1), 97% M1c, median prior tx 0 (range 0-2). TMZ (n=41): median age 60 (range 34-81), 63% male, 58% G11 mut, median ECOG PS 0 (range 0-1), 93% M1c, median prior tx 0 (range 0-2). 11/39 (28%) pts on sel experienced grade (gr) 3 toxicity (tox) manageable with dose modification (5 CPK elevation, 3 LFT elevation, 1 rash, 1 lymphopenia, 1 edema). 1/41 (2%) pt on TMZ experienced gr 3 tox (neutropenia). No gr 4/5 tox occurred. 28 pts on sel underwent paired tumor biopsies with inhibition of pERK and cyclinD1 observed by Western blot at day 14. At interim analysis (9/25/12), 55 pts were evaluable with 45 progression events and 16 deaths. Sel (n=27): median PFS 16 wks (95% CI 8-30.9), RR 11%, median OS 11.8 months (95% CI 4.8-not reached). TMZ (n=28): median PFS 4 wks (95% CI 3.7-15), RR 0%, median OS 4.7 months (95% CI 4.3-14.3). TMZ→sel (n=25): median PFS 8.1 wks (95% CI 7-15), RR 0%. Conclusions: Sel is the first drug to ever show improved clinical activity in UM relative to TMZ. Sustained target inhibition is observed with sel. Final results will be presented. Clinical trial information: NCT01143402.
Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: Final analysis of the EORTC AMAROS trial (10981/22023).
Authors: Rutgers Emiel J. , Donker Mila , Straver Marieke Evelien , Meijnen Philip , Van De Velde Cornelis J. H. , Mansel Robert E. , Westenberg Helen , Orzalesi Lorenzo , Bouma Willem H. , van der Mijle Huub , Nieuwenhuijzen Grard A. P. , Veltkamp Sanne C. , Slaets Leen , Messina Carlo G. M. , Duez Nicole J. , Hurkmans Coen , Bogaerts Jan , van Tienhoven Geertjan
Published: February 2017

LBA1001

Background: Sentinel node biopsy (SNB) is standard in assessing axillary lymph node status for cN0 breast cancer patients. In case of a positive SNB, if treatment is advised, axillary lymph node dissection (ALND) is the current standard. Although ALND provides excellent regional control, it may give harmful side effects. Axillary radiotherapy (ART) instead of ALND was hypothesized to provide comparable regional control and less side effects. Methods: From 2001 to 2010, patients with cT1E2N0 primary breast cancer were enrolled in the EORTC phase III non-inferiority AMAROS trial. Patients were randomized between ALND and ART in case of a positive SNB. Primary endpoint was 5-year axillary recurrence rate. Secondary endpoints were overall survival (OS), disease-free survival (DFS), quality of life (QOL), shoulder movement and lymphedema at 1 and 5 years. Results: Of the 4,806 patients entered in the trial, 744 in the ALND-arm and 681 in the ART-arm had a positive SNB, 60% with a macrometastasis. The two treatment-arms were comparable regarding age, tumor size, grade, tumor type, and adjuvant systemic treatment. With a median follow up of 6.1 years, the 5-year axillary recurrence rate after a positive SNB was 0.54% (4/744) after ALND versus 1.03% (7/681) after ART. The planned non-inferiority test was underpowered because of the unexpectedly low number of events. The axillary recurrence rate after a negative SNB was 0.8% (25/3131). There were no significant differences between treatment arms regarding OS (5 yr estimates: 93.27% ALND, 92.52% ART, p=0.3386) and DFS (5 yr estimates: 86.90% ALND, 82.65% ART, p=0.1788). Lymphedema was found significantly more often after ALND (1yr: 40% ALND, 22% ART, p<0.0001 and 5yr: 28% ALND, 14% ART, p<0.0001). There was a nonsignificant trend toward more early shoulder movement impairment after ART. These findings were compatible with a trend in two QOL items in the arm symptom scale: swelling (ART better) and movement (ALND better). There were no other differences in QOL. Conclusion: ALND and ART after a positive SNB provide excellent and comparable regional control. ART reduces the risk of short-term and long-term lymphedema compared to ALND. Clinical trial information: NCT00014612.
Clinical outcomes in patients with castrate-refractory prostate cancer (CRPC) metastatic to bone randomized in the factorial TRAPEZE trial to docetaxel (D) with strontium-89 (Sr89), zoledronic acid (ZA), neither, or both (ISRCTN 12808747).
Authors: James Nicholas David , Pirrie Sarah , Barton Darren , Brown Janet Elizabeth , Billingham Lucinda , Collins Stuart I. , Daunton Adam , Birtle Alison J. , Chakraborti Prabir Ranjan , Ford Daniel , Hussain Syed A. , Jones Helen , Pope Ann , Porfiri Emilio , Russell John Martin , Stanley Andrew , Staffurth John , McLaren Duncan , Parker Chris , Wylie James
Published: February 2017

LBA5000

Background: Bony metastatic CRPC has a poor prognosis and high morbidity. TRAPEZE is a factorial RCT using three agents, D, ZA, and Sr89. All have palliative benefits and are used in bony metastatic CRPC to control bone symptoms and (for D) to prolong survival. ZA was approved on the basis of reducing skeletal related events (SRE). Sr89 was approved to control pain from metastases and to reduce the need for subsequent bone treatments. ZA is commonly combined with D in practice but evidence that the combination is effective is lacking and costs considerable. Sr89 is generally used as a palliative therapy in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine clinical and cost-effectiveness scheduling. Methods: Patients were randomised to receive 6 cycles of D plus prednisolone: alone; with ZA; with a single dose of Sr89 after cycle 6 or both. Primary outcomes were clinical progression-free survival (CPFS: pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE free interval (SREFI); total SREs, and overall survival (OS). The log rank test and Cox regression modelling were used to determine clinical effectiveness. Results: TRAPEZE randomised 757 patients; median age 68.7 yrs; ECOG 0: 40% 1: 52% 2: 8%; prior RT 45%; median PSA 144 (IQR 51, 354). Provisional stratified log rank analysis of CPFS did not reach statistical significance for either agent (Sr89 p=0.11, ZA p=0.45). Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (HR=0.845; 95%CI 0.72, 0.99, p=0.036) and confirmed no effect of ZA (p=0.46). ZA did show a significant effect on SREFI (HR=0.76; 95%CI 0.63, 0.93, p=0.008). There was no effect of either agent on overall survival (Sr89 p=0.74, ZA p=0.91). Conclusions: Sr89 after six cycles of docetaxel improved CPFS but not OS. ZA did not improve CPFS or OS but did significantly improve median SREFI, mostly post progression, suggesting a role as post chemotherapy maintenance therapy. Further health economic and QoL analyses are pending. Clinical trial information: 12808747.
BOLERO-2: Efficacy and safety of first-line everolimus plus exemestane in advanced breast cancer.
Authors: Rugo Hope S. , Campone Mario , Gnant Michael , Neven Patrick , Pistilli Barbara , Baselga Jose , Bauly Hounayda , Taran Tanya , Sahmoud Tarek , Hortobagyi Gabriel N.
Published: February 2017

152

Background: In the BOLERO-2 study, progression-free survival (PFS) was significantly longer with the combination of everolimus and exemestane (EVE + EXE) compared with placebo and exemestane (PBO + EXE; hazard ratio = 0.45; p < .0001). Consistent efficacy results were observed in all subgroup analyses, such as in patients with visceral metastases and patients with disease recurrence during/after adjuvant therapy. This analysis of BOLERO-2 examines the efficacy of EVE + EXE in the subgroup of patients who received treatment immediately after recurrence during adjuvant therapy (i.e., as first-line therapy in the advanced setting). Methods: BOLERO-2 enrolled patients with hormone receptor–positive (HR+) advanced breast cancer with disease recurrence or progression after prior nonsteroidal aromatase inhibitors and compared EVE (10 mg/d) + EXE (25 mg/d) vs PBO + EXE. The primary end point was PFS by local investigator review. Results: A total of 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37) in the advanced setting. Of these patients, 74% of the EVE + EXE arm and 76% of the PBO + EXE arm had recurred after adjuvant endocrine therapy plus chemotherapy; 26% and 24%, respectively, had recurred after adjuvant endocrine therapy alone. Also, approximately 20% of patients entered the trial after recurring during or within 12 months of adjuvant therapy (21% EVE + EXE vs 16% PBO + EXE). The EVE + EXE group had significantly longer PFS compared with the PBO + EXE group (11.50 vs 4.07 months, respectively; hazard ratio = 0.39; 95% confidence interval, 0.25-0.62). Median PFS remained longer with EVE + EXE versus PBO + EXE, regardless of whether chemotherapy was included with the prior adjuvant hormonal therapy. Similar results were obtained from the analyses based on central review. The safety profile was consistent with the known profiles of each agent. Conclusions: EVE + EXE prolonged PFS in patients with HR+ advanced breast cancer who received treatment as first-line therapy. These results support the combination of EVE + EXE in patients with recurrence after adjuvant therapy. The recently initiated BOLERO-4 study is also evaluating the efficacy of EVE as a first-line therapy in patients with HR+ advanced breast cancer. Clinical trial information: NCT00863655.
Growth of tumorspheres exhibiting stem cell features from peripherally circulating tumor cells.
Authors: Pachmann Katharina , Pizon Monica , Zimon Dorothea , Pachmann Ulrich A.
Published: February 2017

32

Background: Even after the complete resection of a malignant tumor the menace remains, that cells that have dissociated from the tumor might resettle in distant organs and grow into life-threatening metastases. Therefore we have developed an approach (maintrac) to detect and monitor the circulating tumor suspect epithelial cells in blood. However, the question arises whether these cells have the potential to grow into metastases. Methods: Using a nondissipative approach with only one enrichment step of red blood cell lysis, the cells from the pellet, containing the white blood cells together with the putative tumor cells were cultured under conditions favoring the growth of epithelial cells. At 7, 14 and 21 days the cultured cells were stained with anti-EpCAM antibody and inspected for the appearance of epithelial antigen positive spheroids. Results: Peripherally circulating cells from patients with malignant tumors in different stages of disease were analyzed for the presence of circulating epithelial tumor suspect cells and the frequencies of tumorspheres. Tumorspheres could so far be grown from 79% of 36 patients in whom more than 1700/ml epithelial tumor suspect cells were detected. Numbers of tumorspheres varied from 1 to 29 /ml and correlated with the aggressiveness of the tumor. Surprsingly the numbers were highest in patients who had not yet received any systemic therapy after surgery. The size of the spheres increased from day 7 to day 21. The spheres were negative for CD24 and positive for CD44. They highly expressed ALDH1 and thus exhibited typical features of stem cells. Conclusions: Here, we demonstrate that the tumor suspect cells, detected in our approach contain a subpopulation with stem cell-like properties capable of growing into tumorspheres. The frequency and growth potential of cells capable of forming spheres seems to be dependent from the properties of the primary tumor. The possibility to grow tumorspheres from peripherally circulating tumor cells may open up a new field, where the relevant cells with stem cell properties from individual patients can now be specifically analysed further for genetic endowment, transcriptional activity, heterogeneity and stem cell markers.
Off-label prescribing of chemotherapy among older cancer patients.
Authors: Barcenas Carlos Hernando , Zhang Ning , Niu Jiangong , Zhang Yufeng , Zhao Hui , Giordano Sharon Hermes
Published: February 2017

130

Background: Off-label chemotherapy prescribing is thought to be common, but little data exist on the current patterns and predictors of off-label treatments for cancer patients. Methods: Patients from the Surveillance Epidemiology and End Results-Medicare database with a first cancer diagnosis between 1995 and 2009, age >65 years, who had claims for intravenous chemotherapy were included. Off-label chemotherapy use was evaluated for the following invasive cancers: breast (BC), n=26,702; colorectal (CRC), n=37,727; non-small cell lung cancer (NSCLC), n=49,263; small cell lung cancer (SCLC), n=13,364; and ovarian cancer (OV), n=8,552. Patients were considered as having received off-label treatment if they had at least one claim for an intravenous chemotherapy drug that did not have a Food Drug Administration labeled indication for the specific cancer on the date of administration. Generalized estimating (GEE) multivariable models were created for each cancer site to evaluate predictors of off-label chemotherapy use. Results: Patients with OV and CRC were older compared to patients with other tumor types. Distant stage disease was present in 12.5% of patients with BC, 26.7% with CRC, 55.5% with NSCLC, 63.2% with SCLC, and 82.7% with OV. Off-label chemotherapy use varied widely across tumor types. Overall, 23.8% of patients with BC, 14.6% with CRC, 86.2% with NSCLC, 97.7% with SCLC, and 46.7% with OV had at least one claim for an off-label chemotherapy agent. The GEE models showed that distant stage disease was significantly associated with increased off-label use for patients with BC (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.57-1.88), CRC (OR 1.44, 95% CI 1.32-1.58), OV (OR 1.85, 95% CI 1.54-2.21), and NSCLC (OR 1.07, 95% CI 1.00-1.14). Off-label use was more common among patients age >80 years with BC, but was significantly less common for older patients with CRC, NSCLC and OV. Conclusions: The use of off-label chemotherapy is common among patients with different cancer types, particularly among those patients with NSCLC and SCLC, but use varies between specific cancer types, stage of disease, and by age.
Developing CAHPS for cancer care prototype: Progress and next steps.
Authors: Garfinkel Steven , Frentzel Elizabeth , Evensen Christian , Keller San , Yost Kathleen J. , Sangl Judith , Arora Neeraj K.
Published: February 2017

134

Background: The CAHPS Survey for Cancer Care Prototype (application for CAHPS trademark in process) represents a significant advancement towards helping cancer care providers understand patients’ experiences of care. Although a number of standard commercial surveys are in use, currently none are available that both (1) capture the aspects of care most important to patients and (2) allow comparisons of those aspects of care across treatment centers and modalities. Methods: We developed a survey instrument that incorporated patient, clinician, and other stakeholder input throughout the development process. The survey measures patients’ perceptions of observable provider behaviors that are indicative of high quality care. Field test data were collected from 1,367 of 2,826 eligible patients (48% response rate) treated with surgery, radiation, or medical oncology from 6 accredited cancer treatment centers across the US. Classical psychometric methods were used to evaluate the measurement properties of composite scales per standard CAHPS methodology. Results: Based on a priori conceptualization, patient and stakeholder input, and empirical analyses, we identified 5 composites measuring shared decision-making, exchanging information about treatment, affective communication, access to care, and patient self-management. A confirmatory factor analysis using structural equation modeling showed an excellent fit (CFI > 0.96; RMSEA < 0.05) between the observed data and the structure for these five composites. Cronbach’s alpha for these composites ranged from 0.71-0.88, discriminant validity was good for all scales, and correlations with overall ratings of cancer care providers were moderate (0.31) to high (0.69). Evaluation of the precision with which the composites distinguish among cancer centers indicated that the measures were reliable; however, a second field test with a greater number and variety of centers will be needed to establish a standard sampling approach and confirm these results. Conclusions: We anticipate wide-spread adoption of this measure by cancer care providers to direct quality improvement efforts due to great interest and involvement in this project on the part of stakeholders.
A single-center, retrospective chart review evaluating outpatient code status documentation in the EPIC electronic medical record for patients with advanced solid tumor cancer.
Authors: Horton John M. , Hwang Michael , Ma Joseph D. , Roeland Eric
Published: February 2017

242

Background: A desired code status is a critical element of advance care planning ideally outlined in an advance directive. Preferably, advance care planning occurs in the non-emergent, outpatient setting. In the absence of a documented code status, full resuscitation is the default, which is not desired by all patients. Currently, unlike the inpatient setting, there is no single, convenient location for code status documentation in the outpatient EPIC electronic medical record (EMR). In order to propose a system-wide solution, a retrospective chart review was completed to assess the scope of the problem. Methods: 160 charts were randomly selected of advanced solid tumor cancer patients (stage III-IV) who received care by a medical oncologist at the UCSD Moores Cancer Center from 2008-2011. The primary objective was to determine the incidence of code status documentation. Secondary objectives included determining the clinical role of the documenter and the code status documentation location within the EMR. Results: 57 advanced cancer patients (36%) had code status documented in 9 different locations in the EMR. Of the 57 patients, only 4 (7%) had a code status documented in the outpatient setting. When documented, code status was located in the progress note (5%), demographics tab (26%), problem list (2%), and scanned media section (14%). Out of the 160 charts, the outpatient oncologist documented the code status in 1 chart. Inpatient EMR locations of the code status included the discharge summary (33%), history and physical (11%), and progress note (9%). Conclusions: In the absence of a standard EPIC outpatient code status documentation procedure, code status was infrequently and inconsistently documented. Consequently, a readily available and accurate code status is not present for emergencies in the outpatient setting. With this information, we will focus future efforts on a clearly defined, standard, and convenient location for outpatient code status documentation in the EPIC EMR.
Using IT solutions to empower your patients and improve quality and satisfaction scores.
Authors: Colman Gerard , Foster Todd L
Published: February 2017

249

Background: Provider organizations are being bombarded from every direction with demands to better patient experience, engage patients, manage populations, implement or enhance implementations of EHRs…the list goes on. Dr. Charles Safran testified to Congress in 2004 that “patients are the most underutilized resource in the U.S. health system.” Taking this to heart, MD Anderson’s recognized their complex registration process was perceived as overwhelming and new patients were experiencing feelings of uncertainty and a lack of control. Patients translated this into poor quality of care. Patients and their caregivers needed to be engaged during this emotionally trying time. Methods: PreCare was born from the desire to use technology to place the first appointment process into the patients’ hands. PreCare is a web site that allows patients to drive the process to expedite their first appointment and track progress transparently. It gives the patients the appropriate information at the appropriate time during their first appointment process. No longer are they bombarded with all information all at once. They could not possibly process it all so vital information was missed, resulting in poor quality of care. Results: Obtaining medical records faster has increased the quality of patient care. Approximately 24% of previously diagnosed patient diseases are changed or refined from their original diagnosis. Accurate diagnosis is critical as cancer treatments become more targeted. MD Anderson has noted improvements in clinical operations, increases in patient retention, reducing dependence on staff, manual processes, print materials and phone calls. Presenters will demonstrate the self-driven tools, lessons learned and the impact of using IT such as: a 4% increase in new referrals, reduction in costs, improvements in efficiency and increased satisfaction for staff, patients and their families. A 47% reduction in patient anxiety has been demonstrated. Conclusions: The overall system utilization is well above national averages, with as high as 74% utilization in key areas. All cancer patients have very high expectations. Our patients using PreCare find their quality of care far exceeds their expectations.
Development and economic trends in cancer therapeutic drugs: An updated analysis of modern and historical treatment costs compared to the contemporary GDP per capita.
Authors: Savage Philip
Published: February 2017

259

Background: Cancer drug development is a major industry and clincial success story with new cancer treatment drugs delivering improved healthcare for many more patients each year. Generally new cancer treatment drugs are viewed as being of 'high cost' and there is considerable debate as to how these new treatments can be funded for routine use. Accurate data on the trends of the relative costs of new treatments compared with earlier high cost cancer drugs is limited. In this sudy we have aimed to document all the newly licenced cancer drugs, by year of introduction, and compare the cost of a standard course of treatment relative to the current per capita GDP to allow an assessment of how relative costs of new drugs have changed over time. Methods: Drugs are classified by years of introduction, therapeutic classification, and an assessment of relative treatment cost using a contemporary 'standard' treatment compared with the relevant UK GDP per capita. Results: Prior to 1960, there were 5 cancer drugs available, 2 new drugs were introduced in the 1960s, 18 in the 1970s, 14 in the 1980s, 24 in the 1990s, 23 between 2000-2009 and 15 between 2010-12. Data will be presented on the cost relative to per capita GDP of a standard treatment for each new drug released from 1987 to current. The summary data indicates that the cost at introduction of an average new cancer drug treatment has increased from 33% of per capita GDP for 1995-99, 53% for 2000-2004, 67% for 2005-2009 and is now 114% for 2010-2012. Conclusions: The cost of new cancer drug treatments appears to be rising in absolute and relative terms. The data in this abstract may be of value to those interested in the history of cancer treatment development and the associated current economic issues.