bluuebunny/crossref_metadata_2025 huggingface dataset:
Trastuzumab-related cardiotoxicity among older breast cancer patients.
Authors: Chavez-Mac Gregor Mariana , Zhang Ning , Buchholz Thomas A. , Zhang Yufeng , Niu Jiangong , Elting Linda S. , Hortobagyi Gabriel N. , Giordano Sharon Hermes
Published: March 2020

600

Background: The use of trastuzumab in the adjuvant setting is associated with reduction in mortality and recurrence. Although trastuzumab is extremely well tolerated, its use is associated with congestive heart failure (CHF). The incidence of this complication in the general population remains largely unknown, especially in older patients. In this study we evaluated the rates and risk factors associated with trastuzumab-related CHF in a large cohort of older breast cancer patients. Methods: Breast cancer patients ≥ 66 years with full Medicare coverage, diagnosed with stage I-III breast cancer between 2005-2007, and treated with chemotherapy were identified in the Surveillance, Epidemiology and End Results-Medicare (SEER-Medicare) database. Chemotherapy and trastuzumab use, comorbidities and CHF were identified using ICD-9 and HCPCS codes. Analyses included descriptive statistics, Cox proportional hazard model using trastuzumab as a time-dependent variable and logistic regression. Results: A total of 3,983 patients were included, 847 (21.7%) of them received trastuzumab, median age of the entire cohort was 71 years old. Among trastuzumab users the rate of CHF was 28.6% compared to 18.1% in non-trastuzumab users (p<.0001). After adjusting for demographic and clinical characteristics, comorbidities, and type of chemotherapy used, trastuzumab users were more likely to develop CHF than non-trastuzumab users (HR 1.74; 95% CI 1.47-2.06). Among trastuzumab users, older age did not further increase the risk, however history of coronary artery disease (OR 2.23; 95%CI 1.56-3.19), heart valve disease (OR 1.41; 95%CI 1.41-2.88) and emphysema -as a proxy for smoking- (OR 2.03; 95% CI 1.13-3.63) significantly increased the risk of CHF. There was a trend for increased risk of CHF associated with anthracycline use (OR 1.36; 95% CI 0.93-2.00). Conclusions: In this large cohort of older breast cancer patients, the risk of CHF among trastuzumab users was 1.74 times higher than non-trastuzumab users, which is higher than what has been reported in younger clinical trial participants. Among older breast cancer patients treated with trastuzumab, cardiac comorbidities and emphysema may identify high risk patients.
Improving the quality of breast cancer surgical treatment decisions.
Authors: Katz Steven J. , Griggs Jennifer J. , Janz Nancy K. , Hawley Sarah T.
Published: March 2020

6024

Background: Ensuring breast cancer treatment decisions are high quality (i.e., informed and preference-concordant) is a key component of patient centered care. Methods: A web-based decision tool, including an interactive preference clarification exercise, was developed over a one-year period with input from health communication experts, clinicians, and women with breast cancer. Newly diagnosed early stage breast cancer patients from two cancer centers were recruited and randomized to view the tool before or after completing a survey. Mean scores for key outcome measures, including surgical treatment knowledge (4 true/false questions), decision satisfaction (12 questions each with a 5-point Likert scale from strongly agree to strongly disagree), and preference-concordant decisions, were compared between the groups using t-tests. Concordance between preferences and surgical choices was evaluated using the chi-square test. Results: 110 subjects were recruited and 105 completed the study. Their mean age was 57 years, 60% had a college degree or more, and 81% were white. Those viewing the website first had higher scores on several decision outcomes than those taking the survey first (Table). Knowledge scores were also higher among those viewing the website before the survey (3.0 vs. 2.61, p=.23). The risk of recurrence was the most important treatment attribute, followed by retaining the natural breast, in both groups. Concordance between treatment choice and computer generated treatment was 65% for website first and 61% for survey first groups. Conclusions: A tool focused on improving knowledge and preference-concordant decisions produced positive results on breast cancer surgical treatment decision making. Further work should assess the impact of the tool in larger and more diverse populations. [Table: see text]
Does unblinding of treatment assignment impact participant perceptions in clinical trials?
Authors: Partridge Ann H. , Sepucha Karen , O'Neill Anne M. , Miller Kathy , Motley Christine , Swaby Ramona F. , Schneider Bryan P. , Dang Chau T. , Northfelt Donald W. , Sledge George W. ,   Eastern Cooperative Oncology Group
Published: March 2020

6025

Background: Blinding patients to treatment regimen is an important component of high quality randomized clinical trials although concern exists about how receipt of a placebo will impact participants’ views. In ECOG5103, patients were randomized to receive adjuvant chemotherapy for breast cancer with either placebo (arm A) or bevacizumab (arms B and C) and treatment assignment was unblinded by 24 weeks. We sought to determine if unblinding was associated with differential changes in participants’ views. Methods: The Decision-Making/Quality of Life component (DM-QOL) included all patients enrolling on E5103 between 1/5- 6/8/10. Women were surveyed pretreatment and after unblinding. Wilcoxon rank sum testing was used to examine differences. Results: 572 patients on DM-QOL started protocol therapy; 118 on arm A, 454 on arm B/C; the two groups (arm A vs. B/C) were well balanced. 516 patients participated in pretreatment, 514 in unblinding survey. Pretreatment, 32% reported >moderate chance of recurrence in 5 years, 27% >moderate chance of serious problem from treatment, 99% feeling at least somewhat informed, 98% at least somewhat confident in study participation, most “extremely” confident. Overall, median response scores did not change over time, with no statistically significant differences between the groups in changes in perceptions of: recurrence risk (p=0.45); chances of a serious problem (p=0.12), feeling informed (p=0.99). However, they differed in confidence about study participation (p=0.04): after unblinding, a higher % of placebo-treated patients had increased confidence (38% vs. 25%), and a higher % of bevacizumab-treated patients had decreased confidence (29% vs. 22%), although 44% across all arms had no change. Conclusions: In a placebo-controlled, double-blinded RCT, unblinding did not significantly affect most participants’ views, regardless of receipt of placebo or experimental drug. However, confidence in study participation may have been affected by knowledge of receipt of bevacizumab; publicity surrounding this experimental therapy may have affected results.
Is care coordination associated with improved care quality for comorbid conditions in cancer survivors?
Authors: Snyder Claire Frances , Frick Kevin D. , Herbert Robert J. , Blackford Amanda L. , Neville Bridget A. , Lemke Klaus , Wolff Antonio C. , Carducci Michael Anthony , Earle Craig
Published: March 2020

6026

Background: Many cancer survivors have comorbid conditions, adding complexity to their already complicated care and requiring greater care coordination. We assessed the role of care coordination in comorbid condition care for cancer survivors. Methods: Using SEER-Medicare, we examined 7 published indicators of quality comorbid condition care in survivors of loco-regional breast, prostate, or colorectal cancer who were diagnosed in 2004, in fee-for-service Medicare, and survived ≥3 years. Comorbid condition care was evaluated during the transition from initial cancer treatment to survivorship (i.e. days 366-1095 post-diagnosis). Coordination risk was categorized as Likely, Possible, or Unlikely using an index developed and tested as part of the ACG case-mix adjustment and predictive modeling tool. The index factors in the number of unique providers, number of specialties, the percentage majority source of care, and generalist visits. We tested the hypothesis that lower coordination risk would be associated with better comorbid condition care using logistic regression, adjusting for socio-demographics, cancer type, and comorbidity. Results: The sample included 8661 survivors (53% prostate, 22% breast, 26% colorectal; mean age 75; 65% male, 85% white). Our hypothesis was not supported. Compared to patients with Unlikely coordination issues, patients with Likely coordination issues were more likely to receive appropriate care on 4 indicators and less likely on 1. Possible coordination issues were associated with better care on 1 indicator and worse care on 1 indicator. To explore this finding further, we conducted post-hoc analyses examining the role of each component of the coordination risk index. Having more unique providers was generally associated with better comorbid condition care, in contrast to the calculation of the index which considers more unique providers a greater risk for coordination issues. Conclusions: These findings suggest that traditional metrics of care coordination may not be valid for survivors of cancer. Understanding the role of care coordination in cancer survivorship care requires development and application of alternative coordination measures.
Quantitative HER2 levels and steroid receptor expression in primary breast cancers and in matched brain metastases.
Authors: Biernat Wojciech , Duchnowska Renata , Trojanowski Tomasz , Mandat Tomasz , Kowalczyk Anna , Czartoryska-Arlukowicz Bogumila , Radecka Barbara , Jarosz Bozena , Staszkiewicz Rafal , Kalinka-Warzocha Ewa , Chudzik Malgorzata , Sperinde Jeff , Haddad Mojgan , Paquet Agnes , Lie Yolanda , Winslow John William , Weidler Jodi Marie , Huang Weidong , Petropoulos Christos J. , Jassem Jacek ,   Polish Brain Metastasis Consortium
Published: March 2020

603

Background: Breast cancer patients with HER2-positive tumors are at high risk for brain metastases. In the current study we examined expression of ER, PR and HER2 in primary breast tumors and in matched brain metastases, as changes of their levels might reflect modes of escape from therapy. Methods: Fifty-three pairs of matched formalin-fixed paraffin-embedded samples from primary breast cancers and brain metastases were assayed for ER and PR status by immuno-histochemistry, whereas HER2 expression was quantified using the novel HERmark assay. Nuclear staining of ER and PR >10%, and relative fluorescence of HER2 >17.8/mm2 were considered as positive results. Results: HER2 levels in brain metastases were generally higher than in the primary tumors (p = 3e-6), with a median increase of 1.9-fold (range 0.08 to 199-fold). There were also substantial differences in ER and PR status between primary tumors and brain metastases. Loss of steroid receptor positivity in brain metastases was more frequent than its gain (ER: 46% vs. 26%; p = 0.16; PR: 57% vs. 23%; p = 0.044). These changes resulted in a net increase in the number of HER2-positive/ER-negative brain metastases, which more than doubled the proportion of primary breast tumors with this phenotype (26% vs. 11%, respectively; p = 0.08). Additionally, HER2 levels in the primary tumors significantly correlated with overall survival when stratified by ER status (p = 0.011). Conclusions: Brain metastases of breast cancer show significant changes in steroid receptor status and in quantitative HER2 levels compared to matched primary tumors. These data provide a rationale for future studies and may help in designing treatment strategies that target the most likely escape pathways of breast cancer.
Timeliness of care and stage at diagnosis of non-small cell lung cancer (NSCLC) with the implementation of a cancer care coordination program (CCCP) at a VA medical center.
Authors: Alsamarai Susan , Chao Herta H. , Yao Xiaopan , Deng Yanhong , Rose Michal G.
Published: March 2020

6033

Background: Timeliness of care improves patient satisfaction and may improve outcomes. A CCCP was established in Nov 2007 to improve timeliness of care of NSCLC patients at the Veterans Affairs Connecticut (VACT) Healthcare System. Methods: We performed a retrospective cohort analysis of patients diagnosed with NSCLC at VACT between 2005-2010. We compared timeliness of care and stage at diagnosis before and after the implementation of the CCCP. Results: Data from 352 patients was analyzed: 163 with initial abnormal imaging between 1/1/2005 and 10/31/2007, and 189 with imaging between 11/1/2007 and 12/31/2010. Variables associated with a longer interval between the initial abnormal image and the initiation of therapy were: (1) earlier stage (mean of 130 days for stages I/II vs. 87 days for stages III/IV, p<0.001),(2) lack of cancer-related symptoms (145 vs 60 days, p<0.001), (3) presence of medical co-morbidities (111 vs 76 days, p=0.01), and (4) depression (127 vs 98 days, p=0.029). Substance abuse increased the interval from initial abnormal image to tissue diagnosis by 29 days (p=0.032) but did not affect the interval from image to treatment. The mean interval between diagnosis and initiation of treatment was 19 days longer in blacks vs. non-blacks (55 vs 36 days, p=0.0118) although the overall time from abnormal image to diagnosis and to treatment was not statistically different. In a multivariate model adjusting for stage, histology, reason for initial imaging, and presence of a primary care provider, implementation of a CCCP resulted in a mean reduction of 25 days in the time between the first abnormal image and initiation of cancer treatment (126 to 101 days, p=0.0154). The percent of patients diagnosed at stages I and II increased from 32% to 48% (p=0.0065) after the implementation of a CCCP. Conclusions: A centralized, multidisciplinary, hospital-based CCCP can improve timeliness of NSCLC care, and may also help ensure that incidental, early stage lung cancers are treated.
Do patient-reported symptoms predict for emergency department visits? A population-based analysis.
Authors: Barbera Lisa Catherine , Atzema Clare , Sutradhar Rinku , Seow Hsien , Howell Doris , Husain Amna , Sussman Jonathan , Earle Craig , Liu Ying , Dudgeon Deborah Jane
Published: March 2020

6039

Background: Since 2007 in Ontario, Canada, the Edmonton Symptom Assessment System (ESAS) has been routinely used to assess symptoms in cancer patients in both ambulatory and home-care settings. The purpose of this study was to determine the relationship between individual patient symptoms, and their severity, with the likelihood of an emergency department (ED) visit. Methods: The cohort includes all cancer patients in Ontario who completed an ESAS assessment between January 2007 and March 2009. We linked multiple provincial health databases to describe the cohort and determine if an ED visit occurred within 7 days of the patient’s first ESAS. Multivariate logistic regression was used to determine the association between symptom scores (absent: score 0; mild: 1-3; moderate: 4-7; severe: 8-10) and the likelihood of an ED visit. Results: The cohort included 45,118 unique patients whose first assessment contributes to the study. 3.8% (n=1732) had an ED visit. The patients with ED visits were more likely to be men, to have lung or gastro-intestinal cancer, to have had recent radio or chemotherapy, and to have a shorter survival. The proportion of patients with ED visits increased from 2% to 10-12% as individual symptom scores increased from 0 to 10. Anxiety and depression were not associated with ED visits in the model, regardless of severity. Pain, nausea, drowsiness, appetite and shortness of breath with moderate or severe scores were associated with ED visits. Tiredness and wellbeing were the only symptoms to show a significant association for mild, moderate and severe scores. A well being score of 7-10 (reference score=0) had the highest odds ratio of 1.8 (95% CI 1.4-2.3). Conclusions: Worsening symptoms clearly contribute to ED visits. While specific symptoms like pain are obvious targets for management in the outpatient setting, constitutional symptoms like wellbeing or fatigue are associated with even higher odds. Though difficult to manage, such symptoms also warrant detailed assessment in order to optimize patient outcomes.
Electronic prompt to improve outpatient code status documentation for advanced lung cancer.
Authors: Temel Jennifer S. , Greer Joseph A. , Gallagher Emily R. , Jackson Vicki A. , Lennes Inga Tolin , Park Elyse R. , Pirl William F.
Published: March 2020

6048

Background: Rates of documentation of end-of-life care preferences in the medical record remain low, even among patients with incurable malignancies.  The goal of this study was to assess the impact of electronic prompts to encourage oncology clinicians to document code status in the outpatient electronic health record (EHR) of patients with advanced lung cancers. Methods: We conducted two clinician focus groups (n=15) at an affiliated academic medical center to determine the appropriate content and timing of the electronic reminders.  Based on the focus groups, we developed email reminders that were timed to the start of each new chemotherapy regimen.  Between 6/09 and 1/11, 102 eligible patients with advanced lung cancer were approached, and 100 (98%) agreed to participate in the prospective study.  Email reminders were sent to oncology clinicians at the patient's next outpatient visit and with each new chemotherapy regimen.  Using a pre-post design, we compared study participants to a retrospective cohort of 100 consecutive historical controls who began chemotherapy for advanced lung cancer at least one year prior to the start of this study.  The primary outcome measure was the documentation of code status in the EHR.   Results: Study participants were similar to historical controls, with no significant differences in age, gender, performance status, histology or initial cancer therapy received.  At one year follow-up, 33/98 (34%) of participants had a code status documented in the outpatient EHR compared with 12/83 (15%) of historical controls, p=0.003.  Mean time to code status documentation was significantly shorter in study participants (8.6 months [95% CI 7.6-9.5]) compared with controls (10.5 months [95% CI 9.8-11.3]), p=0.004. Conclusions: Email prompts triggered by changes in chemotherapy improved the rate and timing of code status documentation in the EHR.
Influence of comorbidity on guideline concordant care for breast cancer: Findings from the Center for Disease Control and Prevention National Program of Cancer Registry (NPCR) patterns of care study.
Authors: Kimmick Gretchen Genevieve , Fleming Steven , Sabatino Susan A , Wu Xiao-cheng , Hwang Wenke , Wilson J. Frank , Lund Mary Jo B. , Cress Rosemary , Anderson Roger T.
Published: March 2020

6052

Background: Comorbidity burden predicts cancer treatment and may influence outcome. We explore the relationship of specific comorbid illnesses with receipt of guideline concordant care for early stage breast cancer. Methods: The NPCR’s Patterns of Care study reabstracted the medical records of breast cancer cases diagnosed in 2004 from 7 cancer registries. We included women with nonmetastatic in situ and invasive breast cancer, known hormone receptor status, node status, and tumor size. Guideline-concordant management, including surgery, radiation, chemotherapy and endocrine components, was based on NCCN guidelines using tumor size, nodal and hormone receptor status. Comorbidity was measured according to the Adult Comorbidity Evaluation Index (ACE). Multivariate logistic regression models were used to determine factors associated with guideline-concordant care, and included overall ACE scores and 26 separate ACE comorbidity categories, as well as age, race, hormone receptor status, and HER2 status. Results: The study sample included 6904 women (mean age 58.7 and range 20-99 years, 76% white, 45% with ACE comorbidity score of 0, 70% ER and/or PR+, 13% HER2+). Overall, 64% received guideline-concordant care. Receipt of guideline-concordant care varied by overall comorbidity burden (71% for none; 65% for minor; 63% for moderate; 50% for severe; p<0.05). The presence of hypertension (OR 1.26, 95% CI 1.08-1.48) predicted receipt of guideline concordant care, whereas, peripheral artery disease (OR 0.44, 95% CI 0.21-0.93), diabetes (OR 0.78, 95% CI 0.63-0.97) and dementia (OR 0.31, 95% CI 0.13-0.74) predicted lack of guideline concordant care. Older age, black race, and hormone receptor positivity were associated with less, and HER2 positivity with receipt of more guideline-concordant care. Conclusions: Overall those with more comorbidity burden received less guideline-concordant care. However, the effects vary by specific conditions. The odds of receiving guideline-concordant care was greater in those with hypertension and less in those with peripheral arterial disease, diabetes, and dementia.
A neoadjuvant, randomized, open-label phase II trial of afatinib (A) versus trastuzumab (T) versus lapatinib (L) in patients (pts) with locally advanced HER2-positive breast cancer (BC).
Authors: Rimawi Mothaffar F. , Aleixo Sabina B. , Alarcon Rozas Ashley , Matos Neto Joao Nunes , Caleffi Maira , Vinholes Jeferson J.F. , Figueira Alicardo Cesar , Souza Sulene Cunha , Reiriz Andre B. , Arantes Heloisa , Uttenreuther-Fischer Martina Maria , Osborne C. Kent
Published: March 2020

606

Background: A is an oral, irreversible, ErbB Family Blocker. This Phase II study investigated A, L and T monotherapy in pts with locally advanced HER2 (ErbB2)-positive BC in a 6-wk preoperative treatment window. Methods: This international, multi-institutional, open-label, randomized, Phase II study included pts with HER2-positive locally advanced disease Stage IIIa–c and inflammatory BC with no evidence of distant metastatic disease, at least one tumor lesion ≥5 cm in diameter, and an ECOG score 0–1. Pts agreed to fresh tumor biopsies for biomarker analyses at trial entry, and at 3 and 6 wks of treatment. Pts received 50 mg A once daily, 1500 mg L once daily, or T 2 mg/kg weekly after a loading dose of 4 mg/kg for 6 wks. Results: 73 pts were screened and 29 pts randomized and treated* (10 pts A, 8 pts L, 11 pts T). All pts were female, median age 49 (range 25–88) yrs, 28/29 pts had Stage III disease, 3/29 pts had inflammatory BC, median tumour size was 6.4 cm, and median time to treatment was 1.4 months (range 0–3.4). After 6 wks of treatment, OR was assessed using RECIST 1.0 (Table). Best objective response during treatment was 80%, 75%, and 36.4% in the pts treated with A, L, and T, respectively. Drug-related AEs assessed by CTCAE v.3.0 occurred in all pts treated with A, 75% of pts treated with L, and 45.5% of patients treated with T (largely GI and skin-related AEs for A and L, and GI and musculoskeletal AEs for T). Three pts treated with A and one pt with L had drug-related AEs of CTCAE Grade 3. Conclusions: Afatinib showed a high OR rate in this Phase II trial of a 6-wk preoperative treatment window and compared favorably to two approved agents in HER2-positive BC, albeit at a slightly higher rate of AEs. Further trials will be needed to identify the potential role of A as a single agent or in combination with other agents in HER2-positive BC. [Table: see text]
Clinical and cost impact of diagnostic slide review.
Authors: Cuff Justin , Yarlett Daniel , Arber Daniel
Published: March 2020

6072

Background: Diagnostic error is postulated to represent a significant source of preventable mortality, morbidity, and cost. A primary pathologic diagnosis of cancer has a relatively high error rate necessitating cost effective solutions to mitigate diagnostic related harm. Methods: A review of 773 consecutive inbound transfers to Stanford, with review of prior pathology material, was performed to measure diagnostic discrepancy. Information was collected about the originating practice size and type, subspecialty area, additional testing, and a description of the disagreement. For a subset of cases, itemized payment data was collected to explore the financial impact of slide review. Results: We found that 9% of cases have diagnostic discrepancies when comparing the incoming working diagnosis with the result of the pathology slide review. Major diagnostic discrepancies, likely to alter treatment, were identified in 3% of cases. Discrepancy rates differed significantly between subspecialty areas (p<0.01) although few areas were spared major error. Disagreements about classification were common as were over/under calling malignancy, grading errors, and incorrect ordering or interpretation of ancillary testing. The subset of cases (n=107) with billing information demonstrated ~42,800 unique charge events associated with these episodes of care. The mean charge for patients was $292,813 (median $130,467). Typical of charge data the dollar amounts exhibited strong right-skew. Average reimbursement was $76,017 (median $23,999) and the median charge:reimbursement ratio was 3.3. When analyzing cases by service line, only 1.4% of charges related to the diagnostic review of the prior pathology material, demonstrating a remarkably small impact on the overall cost. While additional testing was performed on 10% of cases, there was no evidence that cases with a discrepancy were associated with increased overall costs. Conclusions: Diagnostic slide review on prior material is relatively inexpensive in terms of the cost of overall care and permits the detection of significant errors that may affect treatment planning. Pathology slide review represents a clinically impactful and low cost way to prevent errors in diagnosis from becoming errors in management.
Speed of accrual into published phase III oncology trials: A comparison across geographic locations.
Authors: Ruther Nancy R. , Jumonville Alcee , Mathiason Michelle A. , Emmel Ann E. , Wee Sandra K , Go Ronald S.
Published: March 2020

6074

Background: There is a perception that patient accrual may be slower in the US than it is in Europe (Wang-Gillam A et al, J Clin Oncol 2010;28:3803-3807). However, a systematic study has not been performed. We seek to determine the speed at which patients are accrued into published phase III oncology trials across geographic locations and to identify factors that may influence this process. Methods: We searched MEDLINE and identified all original phase III oncology therapeutic trials published in 2006-2010 (N = 567). Trials with no reported activation and completion dates were excluded (n = 20). Accrual speed per trial was expressed as patients per month and was calculated by dividing the number of patients enrolled by number of months a trial was open. Results: The 547 trials included in our study enrolled 281,340 patients. Most trials were for adults only (95.6%), late stage cancers (77.5%), and involved multinational participation (44.1%). Funding sources were cooperative groups (45.5%), industry (33.8%) and academic centers (20.5%). The top 5 cancers studied were hematologic (19.2%), gastrointestinal (16.5%), lung (16.3%), breast (15.4%), and gynecologic (8.4%). Trial results were negative (57.4%), positive (38.2%), or equivalent (4.4%). The mean (+SD) accrual speeds varied according to trial location (multinational [25.0+25.4], US [13.3+16.5], other countries [11.4+15.7], Europe [8.7+11.8]; [P= .001]), funding source (industry [28.3+24.7], cooperative groups [13.3+19.0], academic [6.8+6.5]; [P= .001]), and cancer type (breast [24.0+29.4], gastrointestinal [20.2+24.2], lung [19.3+22.7], gynecologic [15.3+19.2], hematologic [11.2+10.7]; [P= .001]). After adjusting for funding source, accrual speeds were significantly different across trial locations only in 2 cancers: gastrointestinal (multinational [25.2+3.7], US [24.1+8.2], Europe [11.5+3.7], other [7.5+8.5]; P= .046) and gynecologic (multinational [28.9+5.4], other [10.5+7.8], US [6.6+5.3], Europe [4.2+5.9]; P= .004) studies. Conclusions: Among published phase III oncology trials, multinational studies accrued patients faster in gastrointestinal and gynecologic cancers and at a similar speed in other cancers.
Racial disparities in depressive symptom prevalence and selective serotonin reuptake inhibitor (SSRI) utilization in cancer patients: An analysis from ECOG E2Z02: Symptom Outcomes and Practice Patterns (SOAPP).
Authors: Zhao Fengmin , Wagner Lynne I. , Pirl William F. , Miller Andrew H. , Fisch Michael
Published: March 2020

6076

Background: Rates of diagnosis and treatment of depression in primary care vary widely by race. It is unclear whether such disparity exists in oncology. Methods: 3106 patients with cancer of the breast, prostate, colon/rectum, or lung were enrolled from multiple sites in a longitudinal study of symptoms. Patient-reported depressed mood (PRD) on a 0-10 numerical rating scale and clinician-reported psychological distress (CRD) were used to identify depressive patients at baseline. Patients also rated depressed mood 4-5 weeks after baseline. A 2-point change was considered clinically significant for change in PRD. Logistic regression models were used to examine the effect of race on prevalence of depression and antidepressant use. Ordinal logistic regression models examined the effect of race on changes in depression. Results: Of the 3106 patients, 2648 were white, 364 were black, and 94 were other race. At baseline, 20% had moderate/severe PRD; CRD was 28%. Black patients had higher rates of depression than whites, but the difference was not significant after adjusting for other covariates (PRD: 24% vs. 20%, adjusted OR=1.1, P=0.6; CRD: 30% vs. 27%, adjusted OR=1.06, P=0.8). Improvement in depressed mood varied by baseline PRD score (57% with severe depression, 51% with moderate, and 14% with mild). In patients with moderate/severe depression at baseline, blacks were less likely to have depression improvement than whites (adjusted OR=0.41, P=0.008 for moderate depression, adjusted OR=0.35, P=0.01 for severe depression). Among patients with depression defined by CRD, 29% were taking an SSRI (blacks: 14%, whites: 31%), Blacks were less likely to take an SSRI than whites (adjusted OR=0.38, P=0.01). Conclusions: Less than one third of patients with depressive symptoms are taking SSRI antidepressants. Black race is not only associated with less improvement in depressive symptoms over time but also lower probability of SSRI utilization.
The relationship between symptom burden and perceived comorbidity in outpatients with common solid tumors.
Authors: Ritchie Christine , Manola Judith , Kvale Elizabeth , Snyder Claire Frances , Fisch Michael
Published: March 2020

6080

Background: Cancer patients have high symptom burden, but it is unclear whether comorbid conditions are associated with patient-reported symptom burden (the number and severity of symptoms). Methods: The Eastern Cooperative Oncology Group (ECOG) enrolled 3106 patients with invasive cancer of the breast, colon/rectum, prostate and lung, regardless of phase of care or stage of disease. At baseline, patients completed the M.D. Anderson Symptom Inventory (MDASI) and were also asked how bothered they were by difficulties related to health problems other than cancer. Symptom burden (SB) was defined as the number of symptoms scored 7 or higher on the 13-item MDASI physical scale. Variance-weighted least squares regression was used to identify factors associated with increasing levels of being bothered by comorbid conditions. Results: About 65% of patients were at least a little bothered by symptoms associated with comorbidities. There was a strong association between increased bother by comorbidities and increased SB (p<0.0001). Among those not bothered by difficulties related to comorbidities, ≥1 symptom was rated 7 or worse by 29% of patients, compared to 51% in patients bothered by difficulties related to comorbidities (Fisher’s exact p<0.0001). Except for hair loss, the severity of all symptoms was higher in those patients reporting bother due to other perceived comorbidities. Factors associated with increased bother include SB (p<0.0001), taking medications for diabetes (p<0.0001), impaired ECOG performance status (p=0.03), older age (p=0.004), and being perceived by the clinician as having higher degree of difficulty for providing care (p<0.0001). Conclusions: Symptom burden varies significantly according to the degree to which cancer patients perceive bother that they attribute to comorbid health problems. Perception of comorbidity is worth exploring as a stratification factor in symptom research and as an indicator for complexity in patient care.
The impact of race/ethnicity concordance between patients and their navigators in time to diagnostic resolution of breast and cervical cancer screening abnormalities.
Authors: Charlot Marjory , Santana M. Christina , Chen Clara A , Palmisano Joseph N , Bak Sharon , Heeren Timothy C , Battaglia Tracy Ann , Freund Karen M
Published: March 2020

6097

Background: Patient navigators have been shown to reduce cancer disparities among racial/ethnic minorities by improving timely diagnosis and treatment of cancer. For a group of navigators who received cultural competency training, we sought to determine if racial/ ethnic concordance of the navigator and patient improved time to diagnostic resolution of cancer screening abnormalities. Methods: Demographic data on 1466 patients and their 23 navigators from the Boston Patient Navigation Research Program were used to assess concordance by race and ethnicity. All participants with either breast (n=751) or cervical (n=715) screening abnormalities were followed up to one year. Kaplan-Meier survival curves and proportional hazards regression models examined the effect of race/ethnicity concordance on time to definitive diagnosis, adjusting for age, race, language, economic status, insurance status, and severity of screening abnormality. Analyses were performed separately for the breast and cervical groups. Results: Of the 1466 patients, 32% were White, 27% Black, 31% Hispanic, and 10% Asian. Navigators were 61% White, 17% Black, 13% Hispanic and 9% Asian. Fifty eight percent of patient-navigator pairs were concordant by race/ethnicity. Overall rate of diagnostic resolution of cancer screening abnormalities within 365 days was high at 90%. In both the breast and cervical cancer screening groups, racial/ethnic concordance was not associated with time to diagnostic resolution, with an aHR 1.03 (95% CI: 0.85, 1.25) for breast patients and HR 1.02 (95% CI: 0.85, 1.21) for cervical patients. Conclusions: Patient-navigator racial/ethnic concordance is not associated with time to diagnostic resolution of cancer screening abnormalities, in part because overall rates of diagnostic resolution were high. Our data suggest that with cultural competency training, navigators can be equally effective with patients from different ethnic and cultural backgrounds.
Assessment of cancer registries (CR) in low- and middle-income countries (LMCs).
Authors: Zullig Leah L. , Vanderburg Sky , Johnson Doug , Oneko Olola , Muiruri Charles , Ntabaye Moshi , Abernethy Amy Pickar , Bartlett John , Zafar Yousuf
Published: March 2020

6102

Background: CRs are crucial for cancer control, yet few global standards exist. This study identifies characteristics of quality CRs in LMCs and globally. Methods: A Medline search was conducted in PubMed to identify peer-reviewed articles describing: 1) CR development and functionality 2) types of CRs and 3) implementation, development and utility of CRs in LMCs. We examined articles describing CRs and assessed benchmarking data that could be used to define quality characteristics. Full-text, English-language articles were reviewed. References cited were searched for additional articles. We categorized characteristics into 4 domains: comparability, completeness, validity and timeliness. Results: The literature search yielded 16 key characteristics within 4 domains that may define high quality CRs. In the “comparability” domain, the key characteristic was use of standard definitions. CRs in the US, Europe and China generally adhere to the International Classification of Diseases for Oncology and histological verification of disease; in 2007 only 40% of African registries did so. In the “completeness” domain the key characteristic was population coverage. African CRs monitor 8% of the population, the Costa Rican registry covers 90%, US and Madras cancer registries reach 96%. In the “validity” domain the key criterion was pathologic diagnosis confirmation. Most LMC CRs are not pathology-based. CRs in wealthier settings like Hong Kong report histologic confirmation in >85% of cases. In the “timeliness” domain standards for timely data reporting are largely undocumented. Conclusions: No consensus exists on characteristics of quality CRs in a global context. The current study provides an initial set of metrics. A Delphi panel of international experts is planned to further address this. Based on this literature review, CRs in LMCs have limited reporting, validation and regional population coverage.
Chemotherapy associated myelosuppression and disease-free and overall survival: A systematic review and evidence summary.
Authors: Poniewierski Marek S. , Wogu Adane , Culakova Eva , Rosen Alexander , Kuderer Nicole Maria , Crawford Jeffrey , Dale David C. , Lyman Gary H.
Published: March 2020

6129

Background: Myelosuppression remains the major dose-limiting toxicity of cancer chemotherapy. The risk of myelotoxicity is associated with the specific drugs, doses and schedule utilized along with patient differences in drug metabolism and tolerance. Several retrospective studies have suggested that patients surviving early myelosuppression may experience improved disease-free and overall survival. Methods: A literature search was conducted of studies published between 1980 - 2011 reporting a relationship between chemotherapy-associated myelosuppression and cancer recurrence and/or mortality. Eligibility was restricted to adult cancer patients receiving chemotherapy and reporting disease recurrence or mortality in relationship to myelosuppression. Dual blinded study identification and data extraction were employed. Hazard ratio (HR) estimates for clinical outcomes were based on random effects models. Results: A total of 1,896 studies were identified in the initial search. A total of 25 studies analyzing results in 14,029 (range 23 – 4,626) patients were deemed to be eligible. Studies included cancers of the breast (7), lung (8), ovary (3), gastrointestinal (5), and Hodgkin lymphoma (2). Overall, neutropenia was observed in 7,577 (54%) patients. Overall survival was reported in 17 studies, recurrence or progression free survival in 11, and both in 5. Outcomes were based on HRs in 16, median survival in 14 and neither in 2. The HRs for survival and progression/recurrence free survival with and without myelosuppression were 0.66 [95%CI: 0.56-0.78; P<.001] and 0.72 [95%CI: 0.60-0.87; P<.001], respectively. There was no difference in estimated HRs in studies employing landmark analysis. Conclusions: Myelosuppression appears to be associated with lower risk of recurrence and death across cancer types and settings. These data do not distinguish between the effects of chemotherapy dose intensity versus patient variation drug metabolism resulting in greater efficacy and toxicity in some patients. Nevertheless, these results suggest that reducing chemotherapy dose intensity to avoid myelosuppression may not be a prudent strategy even in patients with advanced disease.
Relationship between whole-body tumor burden and quality of life in patients with neurofibromatosis.
Authors: Plotkin Scott Randall , Merker Vanessa L. , Bredella Miriam A. , Cai Wenli , Kassarjian Ara , Harris Gordon J , Muzikansky Alona , Askenazi Manor , Nguyen Rosa , Wenzel Ralph , Mautner Victor-Felix
Published: March 2020

6136

Background: NF1, NF2, and schwannomatosis are a group of related genetic disorders in which affected individuals share the predisposition to develop multiple nerve sheath tumors. While previous studies have investigated the relationship between cutaneous tumor burden and quality of life, the relation between internal tumors and quality of life is unknown. Methods: As part of an IRB-approved research study, we performed whole-body MRI and administered the short form (SF)-36 to 245 adult subjects with NF. The number and location of internal nerve sheath tumors in each patient was identified by a board-certified radiologist and tumor volume was calculated using semi-automated volumetric analysis. One sample t-tests were used to compare subjects’ SF-36 scores to general population means. Independent linear regression analyses controlling for age and gender effects were used to relate whole-body tumor count, volume, and distribution (via Gini coefficient) to each domain of the SF-36. Results: 245 patients (142 with NF1, 53 with NF2, 50 with schwannomatosis) completed the study. On the SF-36, subjects with NF1 showed reduced quality of life in the physical role, emotional role, and mental health domains compared to the normal population (p<0.05). Subjects with NF2 showed reductions in the physical functioning, physical role, general health, and social functioning domains while subjects with schwannomatosis showed reductions in the physical role and bodily pain domains (p<0.05). In linear regression analysis, increased tumor number, increased tumor volume, and decreased Gini coefficient were correlated with decreased physical functioning in patients with NF2 (p<0.01). There was also a trend for increasing tumor volume to be correlated with decreased physical role and increased bodily pain in patients with NF1 and with increased bodily pain in patients with schwannomatosis (p<0.10). Conclusions: In our multi-institutional cohort, patients with all forms of neurofibromatosis show selected deficits in quality of life. Internal tumor burden does not correlate with these deficits, with the exception of physical function in NF2 patients.
Predictive factors on the receipt and completion of adjuvant chemotherapy in a mixed sociodemographic cohort of patients.
Authors: Polite Blase N. , Smith David M , Cipriano Toni
Published: March 2020

6137

Background: African Americans are more likely to die from breast, colon and lung cancer compared to whites. They are also less likely to receive and complete recommended therapy. The reasons for this are unknown. Methods: Breast, colon, and lung cancer patients eligible for adjuvant chemotherapy (stage IB-III breast, stage IIB-III colon, and Stage IB, II lung) and who received surgery at 2 urban medical centers, were approached between 2008 and 2010 and completed a self-administered survey focusing on sociodemographic factors, including social support, anxiety, depression, co-morbidities, trust and God Locus of Control (e.g., Whatever happens to my cancer is God’s will). These variables were related to receipt and completion of chemotherapy. 191 patients were approached, 161 consented and 30 refused (16%); out of the 161, 23 were deemed ineligible because of previous cancers, non-curative stage or receipt of chemotherapy in the neoadjuvant setting. Results: Final sample consisted of 138 pts. Median age: 54; sex:81% F; Race/Ethnicity:47% AA, 38% white, 9% Hispanic, 6% Asian/PI; Cancer Type: 73% Breast, 21% Colon, 6% Lung. Compared to whites, AA were more likely to have incomes<20K (35% vs. 10%, p=.0002), have any comorbidities (80% vs. 57%, p=0.006), and have high levels of God Locus of Control (56% vs 27%, p=0.003). There were no differences by race in chemotherapy receipt (89% vs. 88%) or relative dose intensity (RDI) of chemo>=85% (58% vs. 67%). No factor in our model predicted chemotherapy receipt or RDI at a significant level. Pts with high God Locus of Control were somewhat more likely to start chemotherapy (OR 1.7, p=0.25) but were less likely to complete therapy (OR 0.55, p=0.19). The magnitude of these relationships held after controlling for age, race, comorbidities, cancer type, functional status, and social support. Conclusions: In a mixed sociodemographic cohort of patients, receipt and completion of adjuvant chemotherapy was similar by measured sociodemographic variables. Only high God Locus of Control was suggestive of being less likely to complete chemotherapy. Further attention and research on the role of religious beliefs in the cancer decision making process is warranted.
Susceptibility of HER2+ breast cancer cells to poly (ADP-ribose) polymerase (PARP) inhibition independent of an inherent DNA repair defect.
Authors: Yang Eddy Shih-Hsin , Nowsheen Somaira , Cooper Tiffiny , LoBuglio Albert F. , Bonner James A.
Published: March 2020

621

Background: HER2 overexpression in breast cancer confers increased tumor aggressiveness. Targeted therapy against HER2 has improved outcomes, but resistance and disease progression ultimately occurs, thus necessitating novel therapeutic strategies. PARP inhibitors target homologous recombination (HR) deficient tumors, such as the BRCA-associated breast and ovarian cancers. In this study, we report unexpected susceptibility of HER2+ breast cancer cells to PARP inhibition alone independent of an inherent HR deficiency. Methods: Cell viability was measured using colony formation and ATPLite assays. Tumor growth delay was assessed in vivo in mice bearing breast cancer xenografts. Proteins were detected by immunoblotting. HR was assayed using radiation (IR)-induced Rad51 foci or a GFP-based HR assay. NFκB activity was measured using a NFκB-driven luciferase assay. Results: Surprisingly, PARP inhibition with ABT-888 alone reduced the colony forming ability and cell viability of the HER2+ breast cancer cell lines BT474, SKBR3, MDA-MB361, and HCC1954 (~70 – 99% reduction at 10μM). This susceptibility did not correlate with an inherent HR deficit. Interestingly, HER2 overexpression itself may be one mechanism of susceptibility to ABT-888 as evidenced by increased cellular cytotoxicity and in vivo tumor growth delay of MCF7 cells stably expressing HER2. Further dissection of the mechanism revealed that NFκB transcriptional activity was significantly inhibited by ABT-888 (>95%) which corresponded with reduced levels of phosphorylated p65 and total IKKα, and a concomitant increase in IkBα. Furthermore, overexpression of p65 abrogated cellular sensitivity to ABT-888. Conclusions: HER2+ breast cancer cells are highly susceptible to PARP inhibition despite being HR proficient. This may be, in part, due to inhibition of NFκB. Further investigation of whether the addition of PARP inhibition to HER2 targeted therapy will delay the onset of resistance to therapy is warranted to potentially improve outcomes in HER2+ breast cancer patients.