bluuebunny/crossref_metadata_2025 huggingface dataset:
Nomogram predicting treatment-related urinary incontinence for men with localized prostate cancer treated by radical prostatectomy (RP), external-beam radiotherapy (EBRT), or brachytherapy (PI).
Authors: Klink Joseph C. , Sanda Martin G. , Litwin Mark S. , Ferrer Montserrat , Regan Meredith M. , Saigal Christopher , Kwan Lorna , Gao Tianming , Klein Eric A. , Kattan Michael W. , Stephenson Andrew J.
Published: February 2017

49

Background: RP, EBRT, and PI for the treatment of clinically localized prostate cancer may negatively impact urinary continence. Predictions of treatment-related urinary problems from patient-reported, prospective data may be useful in treatment decision-making. Methods: Patient-reported data on treatment-related urinary incontinence was obtained from four prospective, longitudinal, health-related quality-of-life (HRQOL) protocols comprising 2,668 patients treated between 1999 and 2011 by RP (n = 1,294), EBRT (n = 630), and PI (n = 744). A single HRQOL instrument was not uniformly used for each study, although questions pertaining to the quantity (pad use) and frequency of urinary incontinence (“never” to “more than once per day”) were identical among the studies. Patient responses were obtained at baseline and at two years after treatment. The endpoint of the model was urinary continence defined as no pad use and leakage of urine less than once per day. Cox proportional hazards regression analysis was used to model the clinical information and follow-up data. Internal validation was performed using bootstrapping. Results: Overall, 1,937 (92%) of patients with complete data available were considered to be continent at baseline. Significant differences in baseline characteristics such as patient age, ethnicity, and disease severity existed between the treatment groups. The overall continence rate at two years was 66%, 88%, and 87% for patients treated by RP, EBRT, and PI, respectively (p < 0.001). In multivariable analysis, age (p = 0.001), baseline frequency of incontinence (p < 0.001), EBRT (p < 0.001), PI (p < 0.001), and ethnicity (p < 0.001) were associated with urinary continence. A nomogram based on the predictive parameters had a concordance index of 0.74 and predictions were well-calibrated with observed outcome. Conclusions: An externally-validated nomogram that predicts two-year urinary continence after treatment for localized prostate cancer has been developed and will be useful for patient counseling regarding treatment options.
How is race/ethnicity associated with patient reporting of cancer pain in recently diagnosed colorectal and lung cancer?
Authors: Martinez Kathryn Anne , Dy Sydney Morss
Published: February 2017

50

Background: Racial and ethnic disparities in the quality of cancer pain treatment are widely documented. The purpose of this study was to examine adjusted differences by race/ethnicity in the odds of reporting pain and differences in pain severity. Methods: This study used data from Cancer Care Outcomes Research and Surveillance Consortium (CanCORS), a nationally representative cohort study of colorectal and lung cancer patients. Patients were identified following incident colorectal or lung cancer diagnosis via rapid case ascertainment. Surveys were administered between three and five months following diagnosis. Pain was assessed via patient self-report using the Brief Pain Inventory. Control variables included sex, age, education, wealth, fatalism, marital status, survey language, self-reported health status, depression, cancer stage, and care at a Veterans Administration (VA) facility. Each control variable was first individually assessed as a potential mediator in the relationship between race/ethnicity and pain severity. Final models were fully adjusted with all control variables. Results: Among 3,216 individuals with colorectal cancer (16.4% black), 40% reported pain; among 2,545 with lung cancer (12% black), 57% reported pain. The odds of reporting pain did not differ by race/ethnicity in lung or colorectal cancer patients in adjusted analyses. None of the included covariates significantly mediated this relationship. However, among those reporting pain, pain severity was higher for black relative to white patients in both lung (p=0.002) and colorectal cancer (p=0.000). Conclusions: The odds of reporting presence of pain did not differ by race/ethnicity. However, among those reporting pain, blacks reported higher pain severity than whites in both cancer types, even after adjusting for patient and health status characteristics. Differential pain severity by race/ethnicity, particularly for black patients, may be an important consideration in assessing the quality of cancer pain management.
Use of surgery and chemoradiation in stage II and III rectal cancer: A retrospective comparison of treatment modalities in major insurance types using the NCDB.
Authors: Warlaumont Mary , Brin Lauren , Fuller Timothy , Whittaker Naomi , Silberstein Peter
Published: February 2017

64

Background: The standard of care (SOC) for stage II/III rectal cancer is neoadjuvant chemoradiation plus surgical resection. We aim to compare the treatment practices for patients with stage II and III rectal cancer in major insurance types. Methods: Using data from the National Cancer Database (NCDB), we analyzed the treatment patterns of 91,782 patients diagnosed with stage II/III rectal cancer from 2000 to 2009. The NCDB includes data from 70% of all U.S. cancer patients. This is the largest study of this kind to date. Results: In stage II/III rectal cancer, patients with private insurance received more SOC treatment (70.3%) than patients with VA Insurance (56.6%), Medicare (46.9%), Medicaid (66.5%), or no insurance (61.7%) (p<.0001). VA patients received less SOC treatment than Medicaid or noninsured patients (p<.0001). Medicare patients (26.9%) were treated with surgery alone more often than patients with private insurance (9.8%), Medicaid (10.4%), VAH (12.2%), or no insurance (9.4%) (p<.0001). VA (4.8%) and Medicare (4.3%) patients more often did not receive any “First Course Treatment” than patients with private insurance (1.3%) (p<.0001). Patients over 70 years old received less SOC treatment (42.2%) than patients under 70 years old (68.9%) (p<.0001) and received more surgery without chemotherapy or radiation (29.3%) than patients less than 70 years old (9.2%) (p<.0001). Conclusions: Stage II/III rectal cancer patients with private insurance received more SOC treatment than VA, Medicare, Medicaid or uninsured patients. VA patients received less SOC treatment than Medicaid or uninsured patients. [Table: see text]
Effect of intervention on quality measures of symptom management in the Michigan Oncology Quality Consortium (MOQC).
Authors: Smerage Jeffrey B. , Abstoss Katie , Severson Jane , Muir J. Cameron , Martin Claudia Jane , DeHority Kevin G. , Blayney Douglas W.
Published: February 2017

70

Background: Michigan oncology practice groups that participated in MOQC [JOP 5(6):281, 2009] used the Quality Oncology Practice Initiative (QOPI) tool. Adherence to processes of disease specific care was high, but poor in domains associated with palliative care. These measures did not change over time [Health Affairs. 31(4):718, 2012]. These findings prompted us to test interventions to improve quality in palliative care domains. Methods: MOQC created a process, based on the IHI Framework for Spread, to assist oncology practice groups in establishing their own primary Palliative Care services, including the implementation of Edmonton Symptom Management Scale. 8 practice groups formed teams of local change agents to participate in the Palliative Care Demonstration (PC Demo) project. The teams participated in 3 in-person and 4 online learning sessions over 8 months, led by palliative care and quality experts. Teams were provided tools, training materials, and necessary support to implement the improvements and measure their success. The learning network facilitated the sharing of best practices and lessons learned throughout the process. The teams presented their results broadly to other MOQC participants at project conclusion. Results: Success was measured using palliative care-focused ASCO QOPI results. PC Demo sites consecutively improved their scores in many of the QOPI measures, and their rate of improvement from Fall 2011 to Spring 2012 was greater than that of their peers. Conclusions: We observed that collecting and distributing data in our consortium was insufficient to improve palliative oncology care. Providing practice groups with the appropriate infrastructure improved their capacity and capability to make the necessary changes to improve performance. [Table: see text]
A Web-based decision support platform to reduce non-evidence-based treatment of non-small cell lung cancer.
Authors: Grund Stephen H. , Forastiere Arlene A. , Flood William A. , Whyler Elaine , Kozlovski Vlad , Wong Yu-Ning
Published: February 2017

71

Background: Published reports indicate 30% to 40% of oncology treatments deviate from evidence-based standards. Little is known about the extent of deviation from guidelines in lung cancer. Methods: eviti is a web-based decision support platform that incorporates all recognized guidelines (ASCO, NCI, NCCN, ASTRO, and others) and supporting literature. An automated precertification code is issued if planned treatment is evidence-based and meets payer language. Variances may be discussed in a peer-to-peer (P2P) with staff oncologists. We analyzed all treatment plans submitted for patients with stage I to IV NSCLC between 1/1/2011 and 5/10/2012 to understand reasons for non-compliance with practice guidelines. There were seven payers with a total of 650,000 covered lives encompassing 43 states. Results: 561 treatment plans were submitted. 241 (43%) received an automatic code, and another 256 (46%) were given preauthorization codes after submission of medical records. 117 treatment plans required a P2P. 26% of cases that required a P2P resulted in a change to evidence based treatment (31 cases or 5% of total cases submitted). 64 (11%) did not meet evidence-based standards and did not receive a code for pre-certification. The most common deviations were: 1. Non-evidence-based therapeutic regimen 59% (38 cases); 2. Use of supportive drugs not consistent with guidelines 23% (15 cases); 3. Non-evidence-based variation in dose and/or schedule of chemotherapy 6% (4 cases). In 7 cases the payer declined payment despite recommendation for coverage. 139 submitted treatment plans were for second line or greater and 88 were for third line or greater. Conclusions: After review for medically justified deviations and peer to peer discussions, decision support for automated pre-certification based on adherence to evidence-based standards reduced non-standard treatment plans from 30 to 11%. A Web-based, point-of-care decision-support that connects payers and providers can reduce unwarranted deviation from evidence-based standards, reducing variability and improving quality. Any such tool should promote compliance with evidence-based cancer care but allow flexibility for medically justified variances.
Developing a comprehensive smoking cessation program in patients with lung cancer: The role of social smoking environments.
Authors: Eng Lawson , Su Jie , Qiu Xin , Palepu Prakruthi R. , Hon Henrique , Fadhel Ehab , Harland Luke , La Delfa Anthony , Habbous Steven , Kashigar Aidin , Cuffe Sinead , Leighl Natasha B. , Pierre Andrew , Selby Peter , Goldstein David P. , Liu Geoffrey , Xu Wei
Published: February 2017

75

Background: Smoking during cancer treatment negatively impacts outcome, survival, and quality of life. Social smoking environments (SSEs) (i.e., smoking in household, peers, and spouse) influence cessation rates in non-cancer patients, but are understudied in cancer patients. Methods: Lung cancer patients, recruited from Princess Margaret Hospital (2006-2012) were given baseline and follow-up questionnaires (median of 2 years apart) evaluating changes in smoking habits and SSEs. Multivariate logistic regression and Cox-proportional hazard models evaluated the association of socio-demographics, clinicopathological and SSE factors with smoking cessation and time to quitting, respectively. Results: 721 patients completed both questionnaires. Of the 261 current smokers at diagnosis, 180 (69%) had quit by follow-up. Among 318 ex-smokers, 5 re-started smoking after diagnosis. All of the 140 never smokers remained non-smoking. Home smoke exposure (OR=9.4; 95% CI: 3.4-26.2; p=2.0 x 10E-5), spousal smoking (OR=4.7, 95% CI:1.7-12.6; p=3.0 x 10E-3) and peer smoking (OR=2.6; 95% CI:1.1-6.1; p=0.03) were each associated with reduced cessation, adjusted for a base multivariate model that included education and past history of depression. Individuals with no SSE factors had a much higher chance of quitting smoking when compared to patients with multiple areas of SSEs (0 vs. 3, OR=16.4; 95% CI: 4.1-66.7; p=7.3 x 10E-5). Similar results were seen when using time-to-quitting as the outcome (0 vs 3, OR=4.4, 95% CI=1.4-14.1, p=0.01). Time to quitting analysis found that 60% of patients with at least one SSE who did quit, did so within 6 months of diagnosis. Subgroup analysis revealed similar associations in early- and late-stage patient groups. Conclusions: SSE is a key factor in smoking cessation, where household smoke exposures reduces the chance of quitting up to 9-fold. SSEs should be a key consideration when developing smoking cessation programs in lung cancer patients, as part of quality improvement strategies. Approaches incorporating household members or spouses into the smoking cessation intervention, around the time of diagnosis, should be researched further. GL and WX are co-senior authors.
Utilizing network quality committees to improve reporting and adherence to evidence-based clinical pathways.
Authors: Patt Debra A. , Hoverman J. Russell , Lindsey Gay , Jastrzembski Deedra , Taniguchi Cynthia , Turnwald Brian , Espirito Janet L. , Garey Jody S. ,   on behalf of the Texas Oncology Quality Committees
Published: February 2017

76

Background: In an era of evidence based medicine, several different evidence based pathways for cancer treatment exist. Few, however, contain decision support, are implemented into an electronic health record (EHR) or have demonstrated their effectiveness to provide value-based care. Providing systems to make a Pathways program operational and improve adherence supports a culture of value-based care. Methods: Physician designed evidence based pathways for a large network of community oncologists was rolled out over a statewide practice. A team of pharmacists and data managers designed a program to support implementation of this pathways initiative. Physician-led quality committees were created at the practice level to troubleshoot and characterize the process of making adherence operational and improving upon other quality metrics, variance reporting, and patient satisfaction. Treatments were charted in the EHR and available for reporting. Documentation of rationale for off-pathway exceptions was also captured. Assessable data, adherence, and exception documentation were measured prior to the onset of the committees and again with follow-up for 1 year after initiation of the committees from March 2011 through February 2012. Results: Within this large practice of 342 physicians, there were 39 quality committees created. During this time assessable data, adherence, and justification of exceptions to evidence-based pathways changed. At the beginning of the time period, assessable data was 84% and improved to 90% after a year. Adherence to pathways was 60% and improved to 68% over the same time interval. Exception documentation also improved from 14% to 25%. Conclusions: Formalizing an internal physician-driven operational procedure to improve upon quality can increase the reporting and adherence to physician created evidence-based pathways across a network of community oncologists and moves to change a culture of value-based excellence within community oncology practices. Continuous and internally driven adherence to value-based metrics improve compliance over time. Internal systems such as these are essential to make evidence-based pathways operational.
Development of a collaborative improvement network by a state affiliate of the American Society of Clinical Oncology.
Authors: Hertler Andrew Allan , Hammond Denis Brin , Larmon Steven S. , Openshaw Thomas H. , Thomas Christian , Weisberg Tracey ,   Northern New England Clinical Oncology Society (NNECOS)
Published: February 2017

79

Background: Participation in the Quality Oncology Practice Initiative (QOPI) by members of the Northern New England Oncology Society (NNECOS) has been historically low (two practices consistently participating). A survey of members identified a lack of resources (time, personnel, financial) as the principal obstacles. In alignment with NNECOS’ mission “To assure the availability of and access to high quality oncology care in our region,” NNECOS sought to determine if it could establish a Collaborative Improvement Network (CIN) in which 1) experienced practices mentor inexperienced practices in QOPI, and 2) practices benchmark results against each other, sharing best practices. Methods: Six practices from the NNECOS member states of Maine, New Hampshire, and Vermont agreed to join the CIN and participate in the fall 2010 and spring 2011 QOPI data collection. Meetings were held following each QOPI data collection and blinded results were compared. High achievers on individual metrics shared their processes/tools with all the participants in the CIN. Results: To develop consistency in data collection, a joint training program for abstractors was developed. There was rapid agreement to eliminate the blinding of results, allowing candid discussions about the barriers to success and strategies for overcoming those barriers. The following tools that successful practices had used were shared: a “one page chemotherapy treatment summary,” chemotherapy consent forms, an oral chemotherapy procedure, and a “chair-side smoking cessation program.” Interventions piloted included a “hardwired chemotherapy treatment summary” and a “hardwired intervention for emotional distress.” Improvement was seen in “plan of care for severe pain” (72% to 85%), “signed consent for chemotherapy” (59% to 81%), and “infertility risk discussions” (14% to 35%). The CIN continues to operate, with 8 of the 17 practices in the three states participating. It is currently engaged in a project to implement specific performance improvement processes for end-of-life care. Conclusions: We have shown that it is possible for an ASCO State Affiliate to sponsor and develop a CIN.
Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: A phase III randomized trial of the Gynecologic Oncology Group.
Authors: Tewari Krishnansu Sujata , Sill Michael , Long Harry J. , Ramondetta Lois M. , Landrum Lisa Michelle , Oaknin Ana , Reid Thomas J , Leitao Mario M. , Michael Helen E , Monk Bradley J.
Published: February 2017

3

Background: Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab (B), a humanized anti-VEGF monoclonal antibody, has shown single-agent activity in pretreated recurrent disease. We aimed to evaluate B in chemotherapy (CTX)-naive recurrent/persistent/metastatic cervical cancer. Methods: Using a 2x2 factorial design, patients were randomly assigned to CTX with or without B 15 mg/kg. The CTX regimens included cisplatin 50 mg/m2 plus paclitaxel 135-175 mg/m2 and topotecan 0.75 mg/m2 d1-3 plus paclitaxel 175 mg/m2d1. Cycles were repeated every 21 days until disease progression, unacceptable toxicity, or complete response. Overall survival (OS) was the primary endpoint with a reduction in the hazard of death by 30% using anti-VEGF therapy considered important (90% power, 1-sided alpha=2.5%). Final analysis was planned when 346 deaths were observed. Results: 452 patients were accrued from 4/6/09 to 1/3/12. The scheduled interim analysis occurred after 174 patients had died and showed that the topotecan-paclitaxel backbone was not superior to the cisplatin-paclitaxel backbone. A second interim analysis was conducted after 271 deaths. A total of 225 patients received CTX alone and 227 patients received CTX plus B. The randomized treatment groups were similar with regard to age, histology, performance status, previous platinum as a radiosensitizer, and recurrence, persistence, or advanced disease. The B-to-no-B hazard ratio (HR) of death was 0.71 (97.6% CI 0.54-0.95; 1-sided p=0.0035). Median survival was 17 m (CTX plus B) and 13.3 m (CTX alone). The RR were 48% (CTX plus B) and 36% (CTX alone) (p=0.0078). Treatment with B was associated with more grade 3-4 bleeding (5 vs 1%) thrombosis/embolism (9 vs 2%), and GI fistula (3 vs 0%). Conclusions: For the first time a targeted agent significantly improved OS in gynecologic cancer. The second interim analysis crossed the boundary for efficacy, warranting early release of this information. The nearly 4-month increase in median OS with the addition of B to CTX in women with recurrent cervical cancer is considered to be clinically significant. Clinical trial information: NCT00803062.
Inherited mutations in breast cancer genes in African American breast cancer patients revealed by targeted genomic capture and next-generation sequencing.
Authors: Churpek Jane E. , Walsh Tom , Zheng Yonglan , Casadei Silvia , Thornton Anne M. , Lee Ming K. , Churpek Matthew , Huo Dezheng , Zvosec Cecilia , Liu Fang , Niu Qun , Zhang Jing , Fackenthal James , King Mary-Claire , Olopade Olufunmilayo I.
Published: February 2017

CRA1501

Background: African American (AA) women are disproportionately affected by early-onset and triple-negative breast cancer (TNBC). One explanation for these disparities may be a higher frequency of inherited mutations among AA women in genes in DNA repair pathways, including BRCA1 and BRCA2. Using targeted genomic capture and next generation sequencing (NGS), we screened DNA from AA women with breast cancer for mutations in all 18 known breast cancer genes. Methods: A total of 249 unrelated AA women with breast cancer were ascertained through the Cancer Risk Clinic at The University of Chicago. Genomic DNA was extracted from peripheral blood and 3 micrograms were used for targeted capture and sequencing. Average read depth across the 1.4 MB targeted region was 320-fold. Sequence reads were aligned and all classes of variants identified: point mutations, small insertions and deletions, and large genomic rearrangements. Only unambiguously damaging mutations were called: stops, complete genomic deletions, and missenses demonstrated experimentally to cause loss of protein function. Variants were validated by PCR or Taqman analysis. Results: Fifty-six of 249 subjects (22%) carried at least one loss-of-function mutation, distributed among BRCA1 (n=26), BRCA2 (n=20), CHEK2 (n=3), PALB2 (n=3), ATM (n=5), and PTEN (n=1). The majority of mutations were unique. Damaging mutations were carried by 30% of patients with TNBC, 27% of patients diagnosed at age ≤45, 49% with a second breast primary, and 30% with a family history of either breast or ovarian cancer in any close relative. Conclusions: We present the first comprehensive screen of all known breast cancer susceptibility genes among AA women using NGS. Mutation carrier frequencies are >25% for major subsets of patients defined by tumor or host characteristics. These high carrier frequencies suggest the importance of screening for mutations in all breast cancer genes in all AA breast cancer patients diagnosed at a young age, with a family history, or with TNBC as a way to identify at-risk family members for life-saving interventions.
A randomized study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel versus docetaxel alone for second-line therapy of lung adenocarcinoma (GALAXY-1).
Authors: Ramalingam Suresh S. , Goss Glenwood D. , Andric Zoran Gojko , Bondarenko Igor , Zaric Bojan , Ceric Timur , Poddubskaya Elena Vladimir , Ciuleanu Tudor-Eliade , Spicer James F. , Felip Enriqueta , Hirsh Vera , Manegold Christian , Rosell Rafael , Khuri Fadlo Raja , Vukovic Vojislav M. , Teofilovici Florentina , El-Hariry Iman , Guo Wei , Bahcall Safi R. , Fennell Dean
Published: February 2017

CRA8007

Background: Heat shock protein 90 chaperone function is critical for the biological effects of several oncoproteins. Ganetespib (G) is a highly potent 2nd-generation Hsp90 inhibitor with a favorable safety profile and single-agent clinical activity. Methods: Based on synergistic preclinical interactions between docetaxel (D) and G, we conducted a randomized (1:1), international open-label study of D with or without G. Patients with advanced lung adenocarcinoma, one prior systemic therapy, and ECOG PS 0/1 were included. D was given at 75 mg/m2 on day 1 of a three-week cycle. In the experimental arm, D was given on day 1 and G at 150 mg/m2 on days 1 and 15. The co-primary endpoints were PFS in patients with elevated LDH (eLDH) levels, or tumors harboring KRAS mutations. Key secondary endpoints were OS and PFS in all adenocarcinoma patients. Target enrollment was 240 adenocarcinoma, 120 eLDH, and 80 mKRAS patients. Statistical tests are 1-sided. Results: Enrollment of 255 adenocarcinoma patients completed in November 2012; results are reported for this population. Patient characteristics were balanced (median age 60 years, males ~60%, PS 0 ~40% and never-smoker ~25%). For D+G vs. D the median number of cycles delivered was 5 vs. 4; the grade 3/4 adverse events were neutropenia 38% vs. 37%; fatigue 4% vs. 3%; anemia 7% vs. 6%; diarrhea 3% vs. 0; fever with neutropenia 8% vs. 2%. At the time of abstract submission OS HR was 0.69 (90% CI 0.48 to 0.99, p=0.093), the PFS HR was 0.70 (90% CI 0.53 to 0.94, p=0.012), and the ORR was 15% vs 11%, favoring D+G. For patients that were enrolled >6 months after diagnosis of advanced NSCLC (N=175; 69%), a prespecified stratification factor, the OS HR was 0.41 (90% CI 0.25 to 0.67, p=0.0009), the PFS HR was 0.47 (90% CI 0.32 to 0.69, p=0.0005), and the ORR was 16% vs 12%. Updated results for both populations above, as well as for the eLDH and mKRAS subsets, will be presented. Conclusions: D+G demonstrated improvement in OS, PFS, and ORR over D alone for second-line therapy of lung adenocarcinoma. A phase III study in second-line advanced adenocarcinoma patients (> 6 months from diagnosis) is ongoing (GALAXY-2). Clinical trial information: NCT01348126.
Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538).
Authors: Sznol Mario , Kluger Harriet M. , Hodi F. Stephen , McDermott David F. , Carvajal Richard D. , Lawrence Donald P. , Topalian Suzanne Louise , Atkins Michael B. , Powderly John D. , Sharfman William Howard , Puzanov Igor , Smith David C. , Wigginton Jon M. , Kollia Georgia , Gupta Ashok Kumar , Sosman Jeffrey Alan
Published: February 2017

CRA9006^

Background: The monoclonal antibody nivolumab blocks PD-1, an inhibitory immune checkpoint receptor expressed by activated T cells. Pts with previously treated MEL or other tumors received nivolumab IV Q2W during dose escalation and/or cohort expansion in a phase I trial (Topalian et al., NEJM 2012;366:2443). Methods: Pts received ≤12 cycles (4 doses/cycle) of treatment until discontinuation criteria were met. Cohorts of MEL pts were expanded at 0.1, 0.3, 1, 3, and 10 mg/kg. We report overall survival data and long-term safety and response data from the MEL pts treated on this study. Results: 107 MEL pts received nivolumab as of July 2012. 103/107 pts (97%) were ECOG PS ≤1 and approximately 25% received ≥3 prior therapies. Median OS was 16.8 months across doses and 20.3 months at the 3 mg/kg dose selected for phase III trials. 44% and 40% of pts were alive at 2 and 3 yrs (Table). ORs were observed at all doses (highest at 3 mg/kg) (Table). Of 29 responders who initiated treatment ≥1 year prior to data analysis, 16 had responses lasting ≥1 year. Drug-related AEs (any grade) occurred in 82% of pts, with Gr 3-4 drug-related AEs in 21% of pts; the most common included lymphopenia (3%), fatigue, and increased lipase (2%). Gr 3-4 drug-related diarrhea (2%), endocrine disorders (2%), and hepatitis (1%) was observed. No Gr ≥3 drug-related pneumonitis was observed in the MEL cohort. Conclusions: In this large cohort of pretreated MEL pts, nivolumab produced durable OS and responses with an acceptable safety profile. OS compares favorably with historical data. Data updated as of Feb 2013 will be reported. Phase III registration trials have been initiated. Clinical trial information: NCT00730639. [Table: see text]
Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3).
Authors: Heinemann Volker , Fischer von Weikersthal Ludwig , Decker Thomas , Kiani Alexander , Vehling-Kaiser Ursula , Al-Batran Salah-Eddin , Heintges Tobias , Lerchenmueller Juergen , Kahl Christoph , Seipelt Gernot , Kullmann Frank , Stauch Martina , Scheithauer Werner , Hielscher Joerg , Scholz Michael , Mueller Sebastian , Schaefer Britta , Modest Dominik Paul , Jung Andreas , Stintzing Sebastian
Published: February 2017

LBA3506

Background: In patients (pts) with KRAS, wild-type metastatic colorectal cancer (mCRC) a head to head comparison of anti-EGFR- and anti-VEGF-directed first-line therapy has not been reported with regard to the FOLFIRI backbone. The AIO KRK-0306 study was therefore designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab in mCRC pts not pretreated for metastatic disease. Methods: Pts were randomized to FOLFIRI (Tournigand regimen) every two wks plus cetuximab (400 mg/m² day 1, followed by 250 mg/m² wkly = arm A) or bevacizumab (5 mg/kg every two wks = arm B). The intent-to-treat (ITT) population comprised all pts who had at least completed one application of therapy. While recruitment initially was independent of KRAS status, an amendment confined inclusion to KRAS wildtype (WT) tumors. Recruitment was completed in October 2012. The primary study endpoint was objective response rate (ORR, investigators read). Results: Among 735 pts of the ITT-population, KRAS-WT was identified in 592. Of these, 297 pts were randomized to arm A and 295 to arm B. Median age was 64 years, 66% of pts were male, and ECOG PS 0-1 was observed in 98% of pts. Median duration of treatment was 4.7 mo vs 5.3 mo, respectively. While in the ITT analysis, ORR was comparable in arms A vs B (62% vs 57%, odds ratio 1.249), a significant superiority was found for assessable pts in arm A. Median PFS of the ITT population was nearly identical (10.3 vs 10.4 mo, HR 1.04, p=0.69), however, overall survival (OS) showed a significantly better outcome in arm A vs arm B (28.8 vs 25.0 mo, HR 0.77, p=0.0164, 95% CI: 0.620-0.953). Sixty-day mortality was low in both arms (1.01% vs 2.71%). Conclusions: ORR was comparable between arms in the ITT analysis, but favored arm A in assessable pts. Significantly superior OS was observed in KRAS-WT patients receiving cetuximab plus FOLFIRI as first-line treatment. Clinical trial information: NCT00433927.
SAMIT: A phase III randomized clinical trial of adjuvant paclitaxel followed by oral fluorinated pyrimidines for locally advanced gastric cancer.
Authors: Yoshida Kazuhiro , Tsuburaya Akira , Kobayashi Michiya , Yoshino Shigefumi , Takahashi Masazumi , Takiguchi Nobuhiro , Tanabe Kazuaki , Takahashi Naoto , Imamura Hiroshi , Tatsumoto Naokuni , Hara Akinori , Nishikawa Kazuhiro , Fukushima Ryoji , Kurita Akira , Kojima Hiroshi , Miyashita Yumi , Oba Koji , Buyse Marc E. , Morita Satoshi , Sakamoto Junichi
Published: February 2017

LBA4002

Background: Adjuvant chemotherapy with tegafur/uracil (UFT) used to be a tentative Japanese standard treatment and has been replaced by S-1 according to the result of the ACTS-GC trial, although there has been no direct comparison. Paclitaxel (PTX) has been widely used as one of the key drugs for unresectable GC. A randomized phase III trial with a two-by-two factorial design was planned to assess the survival benefit of sequential use of PTX and oral fluorinated pyrimidines (FPs) in comparison with FPs alone, and to compare UFT and S-1. Methods: Patients with serosa-invading GC who underwent R0/1 resection with extended (D2) lymph node dissection were randomized to receive either UFT 267mg/m2 daily (arm A), S-1 80mg/m2 daily for 2 weeks every 3 weeks (B), weekly PTX 80 mg/m2 followed by UFT (C), or PTX followed by S-1 (D) for 24 weeks. The primary endpoint was disease-free survival (DFS). 708 patients per groups were necessary to detect a hazard ratio of 0.8 with 90% power for superiority of the sequential arms, C+D, vs. A+B (two-sided 5.0% significance level). The number of patients was set to 370 per arm (total 1480) with an 88% power for noninferiority (1.33 as the margin) of UFT vs. S-1. Results: Between August 2004 and October 2007, 1,495 patients from 232 centers were randomized with the full analysis set of 1,433. Demographics were well balanced among arm A (n=359), B (n=364), C (n=355), and D (n=355); mean age was 64, 86% were PS 0, 68% of tumors were 8 cm or greater and 85% were clinically node positive. Grade 3-4 neutropenia or anorexia occurred in 11% or 6%, 13% or 7%, 13% or 2%, and 23% or 5% for arm A, B, C, and D, respectively. Other % grade 3-4 toxicities were less than 5%. Median follow-up was 1,875 days and 728 events occurred. Difference in DFS between C+D and A+B were not statistically significant (HR=0.92, 95%CI 0.80-1.07, p= 0.273). HR of A+C vs. B+D was 1.23 (95%CI 1.07-1.43) and hence the null hypothesis was not rejected. Conclusions: There was a trend for better DFS for sequential use of PTX followed by FPs. Comparison between the FPs demonstrated that UFT was inferior to S-1. Sequential PTX/S-1 is safe and effective for locally advanced GC in an adjuvant setting. Clinical trial information: C000000082.
Phase III trial of a 3-weekly versus 5-weekly schedule of S-1 plus cisplatin (SP) combination chemotherapy for first-line treatment of advanced gastric cancer (AGC): SOS study.
Authors: Ryu Min-Hee , Baba Eishi , Lee Kyung Hee , Boku Narikazu , Park Young Iee , Hyodo Ichinosuke , Nam Byung-Ho , Esaki Taito , Ryoo Baek-Yeol , Song Eun-Kee , Cho Sanghee , Lee Sung Sook , Kang Won Ki , Yang Sung Hyun , Zang Dae Young , Shin Dong Bok , Park Sook Ryun , Shinozaki Katsunori , Takano Toshimi , Kang Yoon-Koo ,   on behalf of SOS Investigators
Published: February 2017

LBA4024

Background: 5-weekly S-1 plus cisplatin (SP5: S-1 80-120 mg/body/day on D1-21, cisplatin 60 mg/m2 on D8, every 5 weeks) has become a standard first-line chemotherapy for AGC in Japan based on the SPIRITS trial (Lancet Oncol. 2008;9:215). To strengthen the low-dose intensity of cisplatin in this SP5 for greater efficacy, a 3-weekly S-1 plus cisplatin (SP3: S-1 80 mg/m2/day on D1-14, cisplatin 60 mg/m2on D1, every 3 weeks) has been developed in Korea (Cancer Chemother Pharmacol. 2008;61:837). Methods: This SOS study was a multicenter, randomized, open-label, phase III study to evaluate whether SP3 was non-inferior/superior to SP5 in terms of progression-free survival (PFS) determined by a blinded central radiology review according to RECIST v1.1. Patients (pts) with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma and with no prior chemotherapy were randomized 1:1 to receive either SP3 or SP5 until disease progression or unacceptable toxicities. Results: Between February 2009 and January 2012, a total of 625 pts were randomized from 42 sites in Korea and Japan. Median age was 59.6 years. 99% of pts had ECOG performance status 0-1. 16% of pts had prior gastrectomy. 62% of pts had measurable lesions. With a median follow-up of 34.7 months (range, 14.2-48.8) in surviving pts, SP3 was significantly noninferior and superior to SP5 in PFS (median 5.5 months vs. 4.9 months; HR 0.82, 95% CI 0.68-0.99, p=0.0418). Overall response rate (ORR) was also better with SP3 than with SP5 (60% vs. 50%, p=0.029). However, OS of both groups was equivalent (median 14.1 vs. 13.9 months; HR 0.99, 95% CI 0.81-1.21, p=0.9068). Treatment was well tolerated in both arms, while SP3 was associated with more frequent G3/4 anemia (19% vs. 9%) and neutropenia (39% vs. 9%). Dose intensity was higher in SP3 than in SP5 for both agents (median 331 vs. 317 mg/m2/week for S-1, p<0.001; median 18 vs. 12 mg/m2/week for cisplatin, p<0.001). Conclusions: SP3 was noninferior and superior to SP5 in terms of PFS and ORR. However, considering the small benefit in PFS and no difference in OS, both SP3 and SP5 can be recommended for the first-line treatment of AGC. Clinical trial information: NCT00915382.
The breast cancer lifestyle intervention study.
Authors: Chun Jennifer , Friedman Erica Brooke , Schnabel Freya Ruth , Eddy Martha , Schwartz Shira , Kern Elizabeth , Kiely Deirdre , Guth Amber , Axelrod Deborah M.
Published: February 2017

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Background: Maintaining a healthy weight after breast cancer diagnosis has been associated with improved survival outcomes. Lifestyle interventions are particularly important in overweight women who are at an increased risk of overall and breast-cancer specific death compared to non-overweight women. The purpose of this study is to examine the barriers and acceptance of a lifestyle intervention program among overweight women with newly diagnosed breast cancer. Methods: The Breast Cancer Database of NYU Langone Medical Center was queried for women who were newly diagnosed with breast cancer and who had a body mass index (BMI) ≥25kg/m2. Eligible patients participated in the Moving for Life (MFL) exercise program for 16 sessions. Questionnaires were administered at baseline and at the end of the intervention. Descriptive statistics were used to summarize patient characteristics and paired t-tests were used to see if there were any significant differences before and after the intervention. Results: A total of 40 women were eligible to participate in the MFL exercise program. A total of 20 women declined to participate due to location, transportation limitations, and conflicts in schedule. Of the 18 women who enrolled in the MFL program, 13 (72%) were regular attendees and completed the study. The median age was 61 years (range: 38-76) and the average baseline BMI was 31kg/m2(range: 25-42). After completing the MFL intervention, there was a significant decrease in weight and BMI (p=0.04). The average weight loss was 10lbs. Participants also reported a greater enjoyment of exercise (p=0.02), as well as a decrease in pain related to treatment (p=0.05). Conclusions: Moving for Life is a unique exercise program for breast cancer patients and had a high rate of acceptance and completion in a cohort of overweight breast cancer patients. This study resulted in a statistically significant average weight loss of 10lbs, as well as a greater enjoyment of exercise and decrease in treatment-related pain which may impact long-term lifestyle changes. Longitudinal follow-up at 6- and 12-months will allow assessment of secondary endpoints, including exercise frequency and attitudes about exercise, allowing us to examine sustainability and changes in behaviors and attitudes over time.
Who gets treated at commission on cancer-approved programs and does it make a difference in survival?
Authors: Caggiano Vincent , Parise Carol
Published: February 2017

114

Background: Commission on Cancer (CoC) approval has promoted improvements in cancer care in the United States. The purpose of this study is to determine if there are differences in who is treated at CoC approved versus non-approved sites and if CoC approval is associated with survival. Methods: We examined 130,655 cases of stages I-IV first primary female invasive breast cancer from the California Cancer Registry diagnosed between 2000-2010. Odds ratios (95% CI) adjusted for stage, age, grade, year of diagnosis, and ER/PR/HER2 were computed to determine if there were differences by race: white, black, Hispanic, Asian/Pacific Islander (API) and American Indian (AI); SES (low, intermediate, high) or location (urban versus rural) in the likelihood of treatment at CoC sites. Cox regression was used to assess the risk of cancer specific mortality at CoC approved versus non-approved sites. Results: CoC-approved hospitals were more likely to be urban (89%) than rural (11.2%). Race and SES were associated with being treated at CoC sites. In the lowest SES group, blacks (OR=0.82; 95% CI=0.77, 0.89) and Hispanics (OR=0.90; 95%CI=0.86, 0.95) were less likely than whites to be treated at CoC sites. Similar ORs were seen in the intermediate SES group for blacks and Hispanics. In the highest SES stratum, blacks (OR=0.67; 95%CI=0.62, 0.74), Hispanics (OR=0.76; 95%CI=0.72,0.81), and APIs (OR=0.79; 95%CI=0.75,0.83) were less likely to be treated at CoC sites. Unadjusted survival was better for CoC sites (87% vs 85%). For Stage I, only whites treated at CoC approved sites had decreased risk of mortality (HR=0.86; 95%CI=0.79, 0.95). For Stage 2, whites (HR=0.87; 95%CI=0.82, 0.93) and APIs (HR=0.71; 95%CI=0.59, 0.86) had decreased risk of mortality. Blacks (HR=0.82; 95%CI=0.70,0.99) had slightly decreased risk of mortality. For stages III and IV, no difference in risk of mortality was apparent for any race at CoC-approved sites. Conclusions: Patients treated at CoC approved sites vary by race/ethnicity and SES. While the risk of mortality is reduced for some race/ethnicities in Stages 1 and 2 when treated at CoC-approved sites, for stages III and IV patients, CoC-approval does not make a difference in risk of mortality.
Radiation exposure in patients (pts) with newly diagnosed breast cancer (BC) within first year (yr) from diagnostic procedures (DP).
Authors: Chaudhary Lubna , Knapp Sarah , Hester Samuel , Wen Sijin , Xiao Jie , Marano Gary , Kurian Sobha , Hazard Hannah , Layne Ginger , Jacobson Geraldine Meerbott , Abraham Jame
Published: February 2017

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Background: Radiation exposure is associated with an increased risk of secondary cancers. Few studies have examined radiation exposure from DP in BC. Methods: We retrospectively analyzed the cumulative radiation doses (millisievert [mSv]) of routine DP done in 305 pts during the 1st yr following BC diagnosis between Jan 2008-Oct 2010. Data regarding the frequency of DP including mammograms, sentinel lymph node biopsies, X-rays, computed tomographic (CT) and/or positron emission tomographic (PET) scans, MUGA scans and bone scans were collected. Mean radiation doses of DP were obtained from Departments of Nuclear Medicine and Radiation at our institution. Kruskal-Wallis test and post-hoc pairwise comparisons were used to assess the influence of various factors including age, histology, ER/PR (Estrogen/Progesterone) status and stage on the amount of radiation exposure. Results: Mean radiation exposure relative to various factors is shown in the Table. Pts < 40yrs had a significantly higher radiation dose as compared to pts > 60yrs (35.9mSv vs. 19.2mSv; p = 0.009). Pts with DCIS (ductal carcinoma in situ) had a significantly less radiation exposure as compared to IDC (infiltrating ductal carcinoma) and ILC (invasive lobular carcinoma) (8.5mSv vs. 26.7mSv and 22.4mSv respectively; p< 0.0001). Stage ≥ IIB disease was associated with a significantly higher radiation exposure (p< 0.0001). Stage ≥ IIIA was the only factor associated with a higher radiation dose from PET/CTs (p< 0.0001). Conclusions: Radiation exposure from DP is significant in the 1st yr of BC diagnosis, especially for younger and advanced stage pts. Risk is small but relevant, especially in younger pts. [Table: see text]
Impact of physician and center case volume on the adequacy of cardiac monitoring during adjuvant trastuzumab in breast cancer.
Authors: Kumachev Alexander , Chin-Yee Nicolas J. , Yan Andrew , Tomlinson George A. , Earle Craig , Trudeau Maureen E. , Ko Dennis , Krzyzanowska Monika K. , Pal Raveen , Brezden Christine B. , Gavura Scott , Lien Kelly , Chan Kelvin K.
Published: February 2017

128

Background: A recent study suggests that cardiotoxicity from adjuvant trastuzumab (T-mab) is associated with inadequate cardiac monitoring (Ng et al. SABCS 2012). Few studies have examined the impact of centre or physician (MD) case volume (vol) on the quality of care in systemic therapy, including the adequacy of cardiac monitoring during T-mab treatment. Methods: All breast cancer patients treated with adjuvant T-mab in Ontario between 2003-2009 were identified through a provincial drug funding program. Patient demographics, hospitalizations, cardiac risk factors, cardiac imaging, comorbidities, treatment centres and MDs were ascertained. Annual case vol was calculated as the number of patients treated per year with adjuvant T-mab by each MD and centre. Cumulative case vol was calculated as the total number of patients treated with adjuvant T-mab. Centre and MD vol were divided into terciles (T1, T2 and T3) by the year of diagnosis. Inadequate cardiac monitoring was defined as per recent guidelines and per Ng et al. Hierarchical multivariable logistic regression models were constructed to examine factors associated with inadequate cardiac monitoring. Results: Our cohort consisted of 3,777 patients, 214 MDs and 68 centres. Of the total patients, 16.5% were over age 65; 30.3%, 9.4%, and 1.2% had previous diagnoses of hypertension, diabetes, and heart failure (HF), respectively; 24.3% did not receive adequate cardiac monitoring. Inadequate cardiac monitoring was associated with lower cumulative MD vol (T1: 27.9%, T2: 23.3%, T3: 20.8%, p < 0.0001) and lower annual centre vol (T1: 32.5%, T2: 19.7%, T3: 20.7%, p < 0.0001) in univariate analyses, and remained significant after adjusting for age, comorbidities, previous HF, socioeconomic status based on income, rural residence and calendar period. After adjusting for patient clustering at the MD, centre, and regional levels, lower cumulative MD vol (p=0.012), but not annual centre vol, remained a significant predictor for inadequate cardiac monitoring. Conclusions: Our findings suggest improved cardiac monitoring with greater MD experience, supporting the notion of centralization of systemic therapy to high vol MDs to optimize outcomes.