bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocrine therapy in early breast cancer: Encouraging observations in a nontrial setting.
Authors: Dent Susan Faye , Campbell Michelle M. , Crawley Freya , Clemons Mark J. , Song Xinni
Published: March 2020

587

Background: Poor adherence to adjuvant endocrine therapy (ET) in women with hormone receptor positive (HR +) early breast cancer (EBC) is well documented. Given the availability of multiple ET strategies [aromatase inhibitor (AI) upfront, tamoxifen (TAM) to AI, AI after 5 years TAM], we evaluated the delivery of ET in a non-trial setting. Methods: Post-menopausal women with HR + EBC treated with ET (that included an AI) at The Ottawa Hospital Cancer Center between 01/99 and 12/06 were included. Data was retrospectively collected and included: demographics, choice/duration of ET, adherence and toxicities. Results: In 626 patients (pts), median age 59 years (r: 30-92) with stage I (195 pts; 31 %), stage II (339 pts; 54 %) and stage III (88 pts; 14 %) EBC. Treatment strategies included: AI (s) only (251 pts; 40 %); TAM followed by AI (s) (323 pts; 51.6 %); AI (s) followed by TAM (16 pts; 2.6 %); TAM-AI (s)-TAM (24 pts; 3.8 %) and unknown (12 pts; 1.9 %). Prescribed AI therapy (upfront or sequential) was discontinued in 39 % of cases mainly due to toxicity (62.5 %) after median of 6, 9, or 12 months (ms) on exemestane, anastrazole and letrozole respectively. Common toxicities included: arthralgias (40.6 %), hot flushes (34 %), fatigue (25 %), myalgias (24.7 %) and osteoporosis (22.5%). In cases (177) where AI therapy was discontinued due to toxicity: 98 received no further ET, 29 TAM and 50 another AI. The majority of pts received at least 5 years of ET (79 %; median duration 64 ms; r 1-156 ms) and 376 pts (60 %) completed at least 5 years of AI therapy (median duration 59 ms; r: 1-124 ms). 9.9 % of pts are still receiving ET. Conclusions: This is one of the first non-clinical trial studies to demonstrate, that despite poor adherence to initial ET, the majority of women are able to complete five years of treatment (79 %). These results are encouraging and reflect the practical use of mutilple endorcrine strategies that have been shown to be efficacious in this pt population.
Regional variation in Medicare spending and survival among older adults with advanced cancer.
Authors: Brooks Gabriel , Li Ling , Sharma Dhruv B , Schrag Deborah
Published: March 2020

6003

Background: There is substantial regional variation in medical spending in the United States. Whether this variation extends to spending for cancer care and is associated with cancer survival outcomes is unknown. Methods: Patients aged 65 and older with incident advanced cancer were identified from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. Advanced cancers included lung (stage IIIB/IV), pancreas (stage III/IV) colorectal, breast and prostate (stage IV). Medicare spending from 2 months pre-diagnosis until death or 12 months post-diagnosis was totaled in 2010 USD for Medicare-enrolled advanced cancer patients from 80 hospital referral regions (HRR’s). HRRs were then ranked by mean composite 14-month spending and grouped into quintiles. The hazard ratio for death was assessed in each disease cohort for the comparison between the quintiles with lowest (Q1, referent) and highest (Q5) composite spending. Results: Mean composite 14-month spending ranged from $143,870 to $303,902 in HRR’s with the lowest and highest spending (Mason City, IA and Los Angeles, CA). As shown in the table, increased spending was associated with decreased risk of death for lung, colorectal and pancreas cancer but not for prostate or breast cancer. Conclusions: There is substantial regional variation in Medicare spending for patients with advanced cancer. This variation is associated with modest differences in risk of death between the lowest and highest quintiles of spending for lung, colorectal and pancreas cancer. [Table: see text]
Effect of early palliative care on health care costs in patients with metastatic NSCLC.
Authors: Greer Joseph A. , McMahon Pamela M , Tramontano Angela , Gallagher Emily R. , Pirl William F. , Jackson Vicki A. , Temel Jennifer S.
Published: March 2020

6004

Background: Introducing palliative care soon after diagnosis for patients with metastatic non-small cell lung cancer (NSCLC) leads to improvements in quality of life, mood, end-of-life care, and possibly survival. We sought to investigate whether early palliative care is also associated with health care cost savings. Methods: This secondary analysis is based on a randomized controlled trial of 151 patients with newly-diagnosed, metastatic NSCLC presenting to an outpatient clinic at a tertiary cancer center between 6/2006 and 7/2009. Participants received either early palliative care integrated with standard oncology care or standard oncology care alone. We queried participants’ electronic health records as well as our institution’s billing database to collect data on frequency and costs of outpatient clinic visits, inpatient hospitalizations, chemotherapy administration, and hospice services. The primary outcome was the difference in average resource use costs during the final month of life between groups. Results: By 18-month follow up, 133 (88.1%) participants had died, and 125 (82.8%) had available data for this analysis. Participants in the early palliative care group had a mean cost savings of $2,282 (median=$2,432) per patient in total health care expenditures during the final month of life compared to the standard care group. The difference was primarily accounted for by lower costs for inpatient visits (mean saving per patient=$3,110) and chemotherapy administration (mean saving per patient=$640). Although expenditures for outpatient clinic visits were similar between groups, the costs for hospice services were greater for the early palliative care group because of the longer lengths of stay in hospice care (mean cost per patient=$1,125). Conclusions: Early palliative care for individuals diagnosed with metastatic NSCLC not only improves multiple patient outcomes but also may be associated with lower hospital resource use costs, primarily through decreased inpatient visits and chemotherapy administration at the end of life.
Who gets a referral to oncologists and subsequent treatments for stages III and IV non-small cell lung cancer (NSCLC)?
Authors: Goulart Bernardo Haddock Lobo , Fedorenko Catherine R. , Mummy David G , Blough David K , Koepl Lisel , Satram-Hoang Sacha , Reyes Carolina M. , Ramsey Scott David
Published: March 2020

6007

Background: We identified the physicians initially involved in the management of stages III and IV NSCLC, and explored associations of patient and their initial physician factors with referrals to oncologists and subsequent receipt of guideline-based therapies (GBTs) endorsed by the National Comprehensive Cancer Network. Methods: Using a retrospective cohort design, we identified patients with a new diagnosis of stages III and IV NSCLC from 01/01/2000 to 12/31/2005 included in the Surveillance, Epidemiology, and End Results-Medicare database. After collecting patient sociodemographic, tumor, and treatment data, we linked Unique Physician Identifier Numbers (UPINs) from Medicare claims to the American Medical Association Masterfile database to identify the initial physicians and subsequent referrals to cancer specialists, defined as surgeons, radiation oncologists and oncologists. We used logistic regression to explore associations between: 1) patient and initial physician independent variables with referrals to oncologists; 2) referrals to different combinations of cancer specialists with receipt of stage-specific GBTs, adjusted for confounders. The follow-up period was 12 months or up to 12/31/2006. Results: For 28,977 patients, mean age was 75 years, 53% were male, 83% were white, 51% had stage IV, 37% initially saw an internal medicine doctor, 84% saw at least an oncologist, 31% saw all 3 types of cancer specialists, and 44% received GBTs. Younger age, white race, stage IV, higher income, lower co-morbidity index, initial physicians other than family practice doctors, and referral to pulmonologists were associated with higher likelihood of referral to oncologists (P<0.01 for all factors). Compared to those who saw only an oncologist, those who saw only a surgeon and/or a radiation specialist were less likely to receive GBTs (OR=0.3; 95%CI=0.3-0.4). Among patients who had no referrals or who saw specialties other than oncology, 14% received GBTs. Conclusions: Seeing an oncologist is a critical step in the standard treatment of advanced NSCLC. Yet, race, income, and the type of initial physician may constitute barriers of access to oncologists, which can result in substandard care.
An assessment of the collective efforts of clinical trials to provide evidence-based practice guidelines in cancer care.
Authors: Lloyd Shane , Buscariollo Daniela L. , Gross Cary P. , Makarov Danil V. , Yu James B.
Published: March 2020

6019

Background: It is unclear how many of the recommendations in the National Comprehensive Cancer Network (NCCN) guidelines are based Category 1 (C1: “high level evidence”), or whether current cancer research efforts are focusing on the knowledge gap between guidelines and supporting evidence. We defined the knowledge gap as the percent of NCCN recommendations based on lower levels of evidence, and assessed the relation between the knowledge gap and cancer research efforts in terms of clinical trial enrollment. Methods: We examined the active, phase 3 randomized controlled trials (RCTs) listed on clinicaltrials.gov for the 17 most prevalent solid tumors. We used the NCCN guidelines to tally the percentage of C1 recommendations. We used the Pearson coefficient and linear regression to examine whether enrollment in active phase 3 RCTs is associated with 1) the knowledge gap and 2) measures of burden to society including prevalence, incidence, person years life lost (PYLL) and disability adjusted life years (DALY). Results: We identified 834 treatment recommendations for the 17 included cancer types. Overall, 15% of the NCCN recommendations were rated as C1, varying from 40% for hepatobiliary to 0% for endometrial cancer. There was no association between RCT enrollment and the proportion of C1 recommendations in univariate or multivariate analyses. RCT enrollment positively correlated with measures of burden to society including prevalence (p-value < 0.001), incidence (p-value 0.001), and DALY (p-value 0.038). Breast and prostate cancers have a large amount of RCT enrollment per PYLL and a relatively small knowledge gap. Melanoma, ovarian, and endometrial cancers have a moderate amount of RCT enrollment per PYLL and a relatively large knowledge gap. Lung, esophagus, bladder and CNS cancers have a low amount of RCT enrollment per PYLL and a moderate to large knowledge gap. Conclusions: RCT enrollment is not correlated to the knowledge gap. Current planned enrollment in RCTs is partially predicted by burden to society, with the strongest correlation to incidence and prevalence. Most recommendations in the NCCN guidelines are not based on C1 evidence.
Results of a cluster randomized trial to evaluate a nursing lead supportive care intervention in newly diagnosed breast and colorectal cancer patients.
Authors: Sussman Jonathan , Howell Doris , Bainbridge Daryl , Brazil Kevin , Schiff Susan , Whelan Timothy Joseph , Wiernekowski Jennifer
Published: March 2020

6035

Background: Patient transitions during the early phases of cancer care from initial diagnosis through oncology consultation are often poorly coordinated resulting in unmet need, poor continuity, and resultant distress. It has been proposed that better coordination of care during this period would improve the care experience from the patient’s perspective. We designed a randomized trial to test a community based nursing lead coordination of care intervention in newly diagnosed breast and colorectal cancer patients. Methods: Cluster randomized control trial in 193 newly diagnosed breast and colorectal cancer patients enrolled through surgical practices within 7 days of cancer surgery in Toronto, Canada. Surgical practices were randomized between a standardized nursing intervention and a control group involving usual care practices. The intervention consisted of a standardized in person supportive care assessment with ongoing supportive care by telephone or in person that included linkage to community services using protocol specified guidelines according to identified needs. The primary outcomes measured at 8 weeks were validated patient reported outcomes (PROs) of 1) unmet need (SCNS) and 2) continuity of care (CCCQI). Secondary outcomes included 1) quality of life (EORTC QLQ-C30), 2) health resource utilization, and 3) level of uncertainty with care trajectory (MUIS) at 8 weeks. Results: 121 breast and 72 colorectal patients were randomized through 28 surgical practices. The intervention group had a median of 6 nursing contacts over the study period. There were no differences between groups on PROs of unmet need, continuity of care, quality of life, or uncertainty. Health service utilization did not differ between groups. Conclusions: A specialized oncology nursing intervention early in the care trajectory did not result in improved supportive care outcomes for patients. [Table: see text]
Which women with breast cancer do, and do not, undergo receptor status testing? A population-based study.
Authors: Sharp Linda , De Camargo Cancela Marianna , Comber Harry
Published: March 2020

6036

Background: Receptor status is a determinant of breast cancer (BC) treatment and prognosis. Clinical practice guidelines advise that all women diagnosed with BC may undergo estrogen (ER), progesterone (ER) and human epidermal growth factor 2 (HER2) receptor tests. We conducted a population-based study to investigate what proportions of women undergo testing and predictors of test receipt. Methods: Incident BCs (ICD10 C50) diagnosed 2006-2008 were identified from the National Cancer Registry Ireland. Receptor tests were identified from registration records augmented by review of selected medical records. For each of the three receptors separately, logistic regression was used to identify which socio-demographic (age, marital status, smoking status, area of residence, and deprivation category) and clinical factors (grade, tumour size (T), nodal status (N), distant metastasis (M)) were associated with undergoing testing. Adjusted odds ratios (OR) and 95% confidence intervals were computed. Results: 7619 BCs were included. 7% were not tested for any of the receptors. 73% were tested for all three. Considering each receptor separately, 90% had an ER test, 86% a HER2 test and 80% a PR test. Women with T4 tumours were less likely to have ER and HER2 tests, and more likely to have a PR test, than women with T1 tumours. After adjustment for clinical variables, age was not a significant predictor for ER and HER2 testing, while older women (≥70) were more likely than younger women to have a PR test. For all three tests, non-married women were significantly less likely to be tested (ER: OR=0.65, 95%CI 0.52-0.8; PR: OR=0.81, 95%CI 0.7-,0.93; HER2: OR=0.72, 95%CI 0.62-0.85) and current smokers more likely (ER: OR=1.55, 95%CI 1.14-2.1: PR: OR=1.38, 95%CI 1.15-1.66; HER2: OR=1.25, 95%CI 1.01-1.55). Area of residence at diagnosis was a significant predictor of having each test, although the geographical patterns varied. Conclusions: More than one-quarter of women with BC do not have one or more of the receptor tests. After adjusting for clinical variables, socio-demographic factors were significant predictors of test receipt. In the interests of equity, the reasons underlying these associations should be further investigated.
Somatic mutation spectrum of non-small cell lung cancers (NSCLCs) from African Americans (AAs).
Authors: Lammers Philip Edward , Matthews-Smith Velmalia , Yun Ya-Lin , Pan Yumei , Zaja-Milatovic Snjezana , Sullivan Amy , Eisenberg Rosana , Gonzalez Adriana , Shyr Yu , Wolff Steven N. , Schwartz Ann G. , Pao William , Carbone David Paul
Published: March 2020

6038

Background: In the AA population, previous studies have presented conflicting data on the frequency of EGFR mutations (Reinersman JTO 2011;Leidner JCO 2009), while frequencies of other gene mutations and translocations, including anaplastic lymphoma kinase (ALK), have not been described. Methods: 161 archival FFPE tumor specimens from self reported AA patients with any stage NSCLC from 1997-2010 were collected from 3 sites in Tennessee (132 samples) and one site in Michigan (29 samples). Samples were evaluated for known recurrent driver mutations in EGFR, KRAS, BRAF, NRAS, AKT1, PI3KCA, PTEN, HER-2, MEK1 by standard SNaPshot/sizing assays, and translocations in ALK by FISH. Clinical data was collected on 119 patients. Chi-square was used to compare the frequency of mutations in subgroups and Kaplan-Meier and log rank were used to calculate and compare PFS between groups. Results: 5.0% of tumors had EGFR mutations, 14.9% had KRAS mutations, 0.6% had a BRAF, AKT1, PI3KCA, or HER2 mutation, and 0% had NRAS, PTEN, or MEK1 mutations. Of 35 ‘pan-negative’ non-squamous specimens, 0 had ALK translocations. PFS was the same in those with and without KRAS mutation (p=0.74) and showed a trend towards improvement in those with EGFR mutation (p=0.08). The frequency of EGFR mutations was higher in samples from Detroit versus those from Tennessee (17% vs 2.3%, p<0.01), as was the frequency of adenocarcinoma (62% vs 44%, p<0.05). The frequency of EGFR mutations in never smokers was higher in the samples from Detroit versus Tennessee (83% vs 7.1%, p<0.01). Conclusions: In the largest tumor mutational profiling study of NSCLC from AAs to date, EGFR mutations occurred less frequently than would be expected from a North American population. We noted a regional difference, with fewer EGFR mutations in Tennessee than in Michigan, a finding that may have been the result of more adenocarcinoma samples from Michigan. The rates of other mutations and translocations including ALK were low. While lung cancer tumors should continue to undergo routine molecular testing to prioritize therapy, future comprehensive genotyping efforts should focus on identifying novel driver mutations in this population. Funding: 5RC1CA162260 R01CA060691 R01CA87895.
Lapatinib in HER2+ early breast cancer: Quality of life analysis.
Authors: Boyle Frances , Smith Ian Edward , O'Shaughnessy Joyce , Ejlertsen Bent , Kaufmann Manfred , Buzdar Aman , Fumoleau Pierre , Gradishar William John , Martin Miguel , Moy Beverly , Piccart-Gebhart Martine J. , Pritchard Kathleen I. , Lindquist Deborah , Amonkar Mayur , Huang Yingjie , Williams Lisa Simone , Wang Qing , Finkelstein Dianne M , Goss Paul Edward
Published: March 2020

604

Background: TEACH, a randomized, double-blind, multi-center, phase III study evaluated the efficacy and safety of 12 months lapatinib (N=1571) versus placebo (N=1576) in women with HER2+ EBC. Patients receiving lapatinib more often reported treatment-related AEs (87% vs 47%) in the Intent-to-treat (ITT) population. The comparison of recurrence-free survival was not significant (p=.053). This analysis focuses on QOL in the ITT. Methods: Participants on TEACH completed the Short Form-36 version 2 (SF-36v2) at baseline and every 6 mo. for 24 mo. SF-36v2 captures physical, social, mental, emotional domains of patient perceptions; summary scores of physical and mental components are derived from domain scores using norm based scoring method. Changes in the domain and summary scores were compared between two groups using ANCOVAs. Missing post-baseline data were imputed using the last observation carried forward method. A clinically relevant change in scores was defined as a 3-5 point change. Results: For randomised patients who completed the SF-36, QOL scores decreased relative to baseline for all domains and summary scores across all assessments and treatment arms, however the decreases were small and not clinically meaningful. There were no statistically significant (p< 0.05) or clinically meaningful differences between arms for the summary scores relative to baseline (Table). Conclusions: In HER2 positive EBC one year treatment with lapatinib is associated with a significant increase in AEs but it does not have a significant detrimental impact on QOL when compared to placebo. [Table: see text]
Effectiveness of a screening intervention to identify clinical-trial-eligible patients.
Authors: Chen Leo , Grant Janice , Kennecke Hagen F.
Published: March 2020

6069

Background: Advancements in cancer therapy require clinical trials, but only 3% of all cancer patients (CP) participate in trials causing many studies to be delayed or fail to complete. Literature indicates that accrual to clinical trials is primarily driven by MD related factors. The objective of this study was to evaluate whether the screening and identification of potentially eligible patients (PEP) for specific clinical trials would lead to an increased rate of accrual (RA). Methods: During a 4 month period, the charts of CP attending the outpatient clinics of 12 MDs were reviewed to determine eligibility for 21 phase II-IV trials for CP with BR, GI, GU, GY, or LG cancer. Trials were included if they had been open for ≥ 4 months and would remain open ≥ 8 months from the start of the intervention. A screening coordinator with minimal clinical background reviewed the electronic record of new and followup CP to determine eligibility according to protocol specified criteria. PEP were identified for medical oncologist by attaching notices to CP charts. Participating MDs were surveyed regarding the helpfulness and accuracy of the forms. A negative-binomial regression model was used to compare RA and find 95% CI for relative rates. Results: Between May 1 to August 31, 2011 a total of 2,098 charts were screened for eligibility for 21 trials, and 120 PEP were identified. Of these, 15 were randomized to the referred study, 4 to a different study, and 4 CP were offered but declined the referred study. Four month RA for included trials were 61 before, 73 during and 51 after the intervention. Relative rates adjusted for MD bookings were 0.85 (95% CI: 0.67, 1.06, p = 0.15) before and 0.70 (95% CI: 0.54, 0.90, p < 0.005) after, relative to during the intervention. 33 completed questionnaires were received: 22 (67%) were helpful and 23 (70%) were accurate. Screening required a 1.0 Full Time Equivalent position during the period of the intervention. Conclusions: Manual screening of patient records to determine clinical trial eligibility is labor intensive and increases enrolment to specific clinical trials. Notifications were deemed mostly helpful and accurate by oncologists. Screening interventions should be considered to improve clinical trial accrual.
Colorectal cancer survivors' needs and preferences for survivorship information.
Authors: Salz Talya , McCabe Mary S. , Blinder Victoria Susana , Elkin Elena B. , Kemeny Margaret , Saltz Leonard , Temple Larissa K. F. , Oeffinger Kevin C.
Published: March 2020

6073

Background: We assessed colorectal cancer (CRC) survivors’ needs and preferences for information to guide development of a survivorship care plan. Methods: We conducted a survey of survivors treated for stage I-III CRC at two hospitals in New York City. Participants completed treatment 6-24 months before the interview and had not received a survivorship care plan. We evaluated whether survivors knew their basic treatment history, whether they understood ongoing risks, and their preferences for receiving survivorship information. Results: 175 CRC survivors completed the survey between June 2010 and November 2011. Survivors generally remembered basic information about their diagnosis and treatment: 88% accurately reported the location of their cancer; 95-100% accurately reported whether they had surgery, chemotherapy, or radiation; and 90-95% correctly reported the completion date (within 6 months) for each treatment. Survivors knew less about the risks of local and distant recurrences (69% and 77% correct, respectively) and of getting another CRC compared to unaffected individuals (40% correct). More than three quarters of participants received information about their cancer, their treatment history, ongoing oncology visits, and testing to be done by the oncologist (77-86% across categories). Across these categories of information, 93-99% of those who received information found it useful. Most survivors did not receive information about symptoms to report to their doctors, returning to work, financial issues, or legal issues (59-95% across categories); but those who received this information found it useful (67%-100% across categories). Conclusions: Even without receiving survivorship care plans, CRC survivors generally understood their cancer diagnosis and treatment. However, many lacked knowledge of ongoing risks, prevention, and nonmedical survivorship issues. Most survivors found the survivorship information they received useful. The greatest benefit of survivorship care plans to survivors may not be summarizing past care as much as helping survivors understand their risks and plan for the future.
Characterizing fatigue associated with sunitinib (SU) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Cella David , Davis Mellar P. , Bushmakin Andrew G. , Cappelleri Joseph C , Hahn Elizabeth A , Korytowsky Beata , Bhattacharyya Helen , Sandin Rickard , Beaumont Jennifer L , Matczak Ewa , Motzer Robert John
Published: March 2020

6092

Background: Fatigue is common in cancer pts and associated with use of tyrosine kinase inhibitors (TKIs) such as SU. Limited data exist on the time pattern of fatigue with TKI therapy. Methods: Data from treatment-naïve mRCC pts in SU arms of two clinical trials were analyzed retrospectively. Study 1; 375 pts were randomized to SU 50 mg/d on a 4 weeks-on-2-weeks-off schedule (Schedule 4/2), for up to 30 cycles. Study 2; pts were randomized to SU 50 mg/d Schedule 4/2 (Group 1; n=146) or 37.5 mg/d continuous daily dosing (CDD; Group 2; n=146). In both trials, fatigue was measured with the question to pts: “I feel fatigued” over the past week (5-point rating scale, not at all-very much), and with the provider-rated Common Terminology Criteria for Adverse Events (CTCAE). In addition to descriptive profiles, Study 1 used two modeling approaches; repeated measures model (M1), with time as a categorical predictor; and random intercept-slope model (M2), with time as a continuous predictor. Study 2 calculated mean absolute values of within-cycle rate of change (from one assessment to the next) through the first 6 treatment cycles. Results: In Study 1, representing fatigue across cycles, M1 showed that the initial increase in patient-reported fatigue was worst during Cycle 1; mean values at all subsequent cycles were numerically better. For CTCAE fatigue, M1 showed that all but one of the pair-wise comparisons of the cycle means were not significantly different. M2 showed that the overall trend for patient-reported fatigue and CTCAE fatigue was not statistically different from zero. In Study 2, the mean absolute rate of change for fatigue during 6 treatment cycles was greater for Group 1 (4/2) compared to Group 2 (CDD): 0.042 vs. 0.032, respectively; P=0.003, t-test. Conclusions: In Study 1, pts reported notable fatigue in Cycle 1, which improved or stabilized, thereafter. In Study 2, Schedule 4/2 was associated with more within-cycle fluctuation in fatigue. These findings illustrate how SU-associated fatigue occurs early in therapy and continues with more within-cycle fluctuation associated with 4/2 dosing. This may help patient-clinician communications and interventions that support maintaining effective therapy.
Development of a disease-specific measure of quality of life in myelodysplastic syndromes (MDS): The “QUALMS-1”.
Authors: Abel Gregory Alan , Lee Stephanie , Stone Richard M. , Steensma David P. , Young Nancy , Houk Alice , Hastings B Taylor , Martins Yolanda , Klaassen Robert
Published: March 2020

6103

Background: Studies assessing the quality of life (QoL) experienced by patients with MDS have almost universally relied upon generic measures; however, disease-specific QoL tools can allow for more sensitive assessments of the impact of changes in disease status. Methods: Using a clinical impact method of instrument development, individual and combined focus groups were conducted with 32 members of our institution’s MDS community (patients, their caregivers, and health care providers) to identify MDS-relevant QoL domains and associated question topics. Participants’ rankings of the importance of the domains and question topics were compared, collapsing patients/caregivers into one group and physicians/other providers into another. A draft scale was constructed taking a greater number of questions from the more highly-ranked domains. Results: “Fatigue” was ranked as the most important domain (see table). None of the 12 domains were ranked significantly differently by patients/caregivers versus providers. The two groups ranked 5 of 60 question topics differently: “Too tired for routine tasks” (providers higher; p= .05); “limited availability of support beyond the family” (providers higher; p= .02); “organizing life around transfusion/MD appointments” (providers higher, p= .03); “bruising” (patients/caregivers higher, p= .05) and “anger over diagnosis” (providers higher, p= .03). Conclusions: A high level of agreement in the rankings of domains and question topics between MDS patients/caregivers and providers suggests that the QoL experience of MDS patients is consistently compromised. The resulting 38-item draft QUALMS-1 tool is now being piloted (cognitive debriefing and behavioral coding) in a new cohort of MDS patients, with the ultimate goal of validation in a multi-institutional setting. [Table: see text]
Comparative effectiveness of erlotinib versus no treatment for advanced non-small cell lung cancer patients in the Veterans Administration.
Authors: Kim Benjamin , He Ren , Antonio Anna Liza M , Asch Steven M , Malin Jennifer
Published: March 2020

6105

Background: Erlotinib (E) is FDA-approved for second-line treatment of unselected advanced non-small cell lung cancer (aNSCLC) patients. Clinical trials have shown increased response rates with E in aNSCLC patients having East Asian ethnicity, female gender, never-smoking history, or adenocarcinoma histology. The objective of this study was to compare the real-world effectiveness of E versus no treatment (NT) for first- and second-line treatment of aNSCLC patients in the Veterans Administration (VA). Methods: All incident aNSCLC cases diagnosed in the VA during 2007 were identified through the VA Central Cancer Registry, a subset of which underwent medical record abstraction through the VA External Peer Review Program. Abstracted records were then merged with national VA Decision Support System pharmacy and Corporate Data Warehouse encounters data through 2010. Treatment lines were determined through adaptation of a published algorithm. The impact of E versus NT on overall survival for each treatment line was then evaluated using 1:N greedy propensity score matching (PSM) and 2-stage residual inclusion (2SRI) estimation. Results: Among 1965 aNSCLC patients assessed for first-line treatment, 78 (4%) received E and 782 (40%) received NT; among 1124 assessed for second-line treatment, 128 received E (7%) and 638 (33%) received NT. 1:3 PSM of E cases to NT controls showed no difference in overall survival by Kaplan-Meier estimation in the first- (median 2.6 vs. 2.9 mos., p-value=0.86) and second-line (3.4 vs. 3.2 mos., p=0.85) settings. Chemotherapy use by Veterans Integrated Service Network was selected as the instrumental variable for 2SRI. Expected mean survival of E versus NT was similarly not statistically prolonged in the first- (E:NT survival time ratio 2.55, p=0.35) and second-line (2.49, p=0.32) settings. Conclusions: For a population with few aNSCLC patients having 3 out of the 4 clinicopathologic characteristics associated with improved response, E did not appear to confer a survival advantage over NT. Linking mutation results to observational datasets may improve comparative effectiveness research of personalized medicine in oncology.
Cancer survivorship outcomes in immigrants.
Authors: Butow Phyllis Noemi , Aldridge Lynley , Bell Melanie , Sze Ming , Eisenbruch Maurice , King Madeleine , Jefford Michael , Schofield Penelope , Duggal-Beri Priya , Goldstein David
Published: March 2020

6111

Background: Immigration is increasing world-wide. Cancer survivorship is now recognised as a period of difficult adjustment for all patients, and possibly more so for immigrants. We explored disparities in quality of life outcomes for immigrant (IM) versus Anglo-Australian (AA) cancer survivors. Methods: In a cross-sectional design, cancer survivors were recruited through the New South Wales, Queensland and Victorian Cancer Registries in Australia. IM participants, their parents and grandparents were born in a country where Chinese, Greek, or Arabic is spoken and spoke one of those languages. AAs were born in Australia and spoke English. All were diagnosed with cancer 1-3 years previously. Questionnaires (completed in preferred language) included the Hospital Anxiety and Depression Scale (anxiety/ depression), FACT-G (quality of life) and Supportive Care Needs Survey (unmet needs). Outcomes were compared between AA and IM groups in adjusted regression models that included age, gender, socio-economic status, education, marital status, religion, time since diagnosis and cancer type (prostate, colorectal, breast and other). Results: There were 599 participants (response rate 41%). Consent was unrelated to demographic and disease variables. AA and IM groups were similar except that immigrants had higher proportions in the low and highly educated groups (p < 0.0001), and higher socioeconomic status (p = 0.0003). In adjusted analyses (see table), IMs had clinically significant higher depression (possible range 0-21), greater unmet information and physical needs, and lower quality of life than AAs. The possible range for the latter three is 0-100. Conclusions: Immigrants experience poorer outcomes in cancer survivorship, even after adjusting for socio-economic, demographic and disease differences. Interventions are required to improve their adjustment after cancer. Results highlight areas of unmet need that might be better addressed by the health system (particularly with regard to provision of information and support. [Table: see text]
Competing event risk stratification may improve the design and efficiency of clinical trials: Secondary analysis of SWOG 8794.
Authors: Rose Brent Shane , Zakeri Kaveh , Gulaya Sachin , D'Amico Anthony Victor , Mell Loren K.
Published: March 2020

6121

Background: Efficiency of clinical trials may be improved by stratifying according to competing event risk. We aimed to test whether effect and sample size estimates would be altered when adjusting for competing event risk, using data from the SWOG 8794 trial of adjuvant radiation therapy (RT) for high-risk post-operative prostate cancer. Methods: The primary outcome was metastasis-free survival (MFS), defined as time to first occurrence of metastasis or death from any cause (i.e., competing mortality (CM)). We developed separate risk scores for time to metastasis and CM using backward stepwise competing risks regression. Risk factors for metastasis were PSA, Gleason score, and seminal vesicle invasion, and for CM were age, performance status, and Charlson comorbidity index. Treatment effects were estimated using Cox models adjusted for risk scores. We identified an enriched subgroup of 75 patients at high risk of metastasis and low risk of CM, based on risk score cutoffs. Sample size estimates assumed type I and II error of 0.10 and 0.20, and accrual and follow-up times of 6 and 6 years. Results: The mean CM risk score was significantly lower in the RT vs. control arm (p=0.001). The effect of RT on MFS (HR 0.70; 95% CI, 0.53-0.92; p=0.010) was attenuated when controlling for metastasis and CM risk (HR 0.76; 95% CI, 0.58-1.00; p=0.049). The hazard for CM was reduced by RT (HR 0.82; 95% CI, 0.59-1.14; p=0.24), but this effect was attenuated when controlling for CM risk (HR 0.94; 95% CI, 0.67-1.31; p=0.71). In contrast, there was no difference in the adjusted and unadjusted HRs for metastasis (0.50; 95% CI, 0.31-0.81; p=0.005 and 0.49; 95% CI, 0.30-0.81; p=0.005). Compared to the whole cohort, the enriched subgroup had the same baseline 10-year incidence of MFS (40%; 95% CI 22-57%), but a higher incidence of metastasis (30% (95% CI, 15-47%) vs. 20% (95% CI, 15-26%)). A randomized trial in an enriched population could have achieved 80% power with 44% less patients (313 vs. 709 patients, respectively), due to the differing event composition. Conclusions: Stratification based on competing event risk may improve the design and efficiency of clinical trials. These findings should be externally validated.
Multidisciplinary assessment and reporting of fitness to drive in brain tumor patients: A gray matter.
Authors: Louie Alexander V. , Chan Esther , Hanna Michelle , Palma David , Bauman Glenn , Fisher Barbara , Rodrigues George , Sathya Abhinay , D'Souza David
Published: March 2020

6130

Background: In some jurisdictions, there is a legal requirement for physicians to report medically unfit drivers. Objectives of this study are to determine physician knowledge and attitudes on reporting legislation and driving assessment, and review our institution’s experience in evaluating fitness to drive in brain tumour patients. Methods: Physicians caring for brain tumour patients in South-western Ontario were identified by public databases and surveyed by mail. Survey questions elicited demographics, opinions, and factors influencing the decision to report. Patients receiving brain radiotherapy at our institution between January and June 2009 were identified and details of driving assessment were extracted. Fisher’s exact test and a logistic regression model were used to determine differences in responses between specialists and family physicians and factors influencing reporting. Results: Surveys (n=467) were distributed with 198 (43%) responses. Most (76%) felt that reporting guidelines were unclear. Neurologists (43%) and Family Physicians (22%) were felt to be the most responsible to report unfit drivers. Compared to specialists, Family Physicians were less likely: to be comfortable with reporting (p=0.02), to consider reporting (p<0.001), or discuss the implications of driving (p<0.001). Perceived barriers in assessing fitness to drive included: lack of tools to assess (57%) and the impact on the patient-physician relationship (34%). 158 patients were retrospectively reviewed. Forty-eight patients (30%) were reported to the provincial licensing authority and 64 (41%) were advised not to drive. 53 patients experienced seizures, of which 36 (68%) had a documented discussion on driving. Only 30 (56%) of these patients were reported to the licensing authority despite legal requirements. Age, primary disease, previous neurosurgery and seizures were predictive of reporting (p<0.05). On logistic regression modeling, seizures (OR 12.4) and primary CNS disease (OR 15.5) remained predictive of reporting. Conclusions: Despite guidelines and laws, the assessment of fitness to drive in patients with brain tumours is not routinely conducted or documented in a multidisciplinary setting.
Can MRI accurately identify which patients with operable breast cancer will have a pathologic complete response after neoadjuvant therapy?
Authors: Nessim Carolyn , Trop Isabelle , Robidoux Andre , Mamounas Eleftherios P , Boileau Jean-Francois
Published: March 2020

616

Background: With the introduction of targeted therapy based on tumor subtypes, an increasing number of patients that receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR). Previous studies have shown that the accuracy of MRI is poor at predicting the response to neoadjuvant chemotherapy in locally advanced and often non-resectable breast cancers, where the rate of pCR is low. The purpose of this study is to evaluate MRI’s ability to predict a pCR in operable breast cancers after neoadjuvant therapy. Methods: All patients enrolled in the NSABP B-40, B-41, FB-5 and FB-6 protocols in a single tertiary care centre, that had an MRI done before and after neoadjuvant therapy were reviewed. A radiologist, blinded to the pathology results, interpreted the pre- and post- treatment MRI’s and made a prediction as to whether or not patients would have a pCR. In this study, a true negative was defined as a reading of a complete response on MRI that was confirmed as a pCR on final pathology. pCR was defined as having no residual invasive or in situ disease in the breast. Results: 129 women with a median age of 51 years were identified. 90% had invasive ductal carcinoma; 8% had invasive lobular. 58% were ER+, 21% were triple negative and 21% were Her2+. 16% of patients had a pCR. 25% of patients had no residual invasive cancer in the breast. pCR rates for ER+ tumors was 5%, triple negative 37%, and Her2+ 26%. 19% of patients that had a pCR had a total mastectomy. The sensitivity and specificity of MRI for predicting residual disease were 88% and 52% respectively. The positive predictive value was 90% and the negative predictive value was 46% with an accuracy of 82%. Conclusions: MRI has limited value for determining which patients had a pCR after neoadjuvant chemotherapy, even in operable breast cancers. When residual disease is suspected on MRI, it is unlikely that a pCR has been achieved. Surgical excision following neoadjuvant therapy remains the gold standard to identify which patients have achieved a pCR. Other modalities will need to be used in order to accurately determine which patients would be eligible for studies evaluating non operative management following neoadjuvant therapy.
Neuromedin U: A potential predictive biomarker for HER2-targeted drugs.
Authors: Rani Sweta , Germano Serena , Madden Stephen F. , Corcoran Claire , Breslin Susan , O'Brien Neil A. , McDermott Martina , Browne Brigid , O'Donovan Norma , Crown John , O'Driscoll Lorraine
Published: March 2020

617

Background: Not all HER2-positive breast cancer patients respond to HER2-targeted drugs and some, who initially respond, subsequently relapse. There is a need to identify biomarkers for improved patient selection. Here we aimed to identify gene expression changes associated with response to HER2-targeted drugs. Methods: To identify mRNA changes associated with resistance, whole genome microarrays were used to profile conditioned medium (CM) from HER2-positive cell lines (SKBR3, HCC1954) and their lapatinib (L)-resistant variants (SKBR3-LR, HCC1954-LR). Neuromedin U (NmU) over-expression, identified in this way, was confirmed in the L-resistant cells and corresponding CM by qPCR and ELISA. Pooled data from 21 published expression datasets (n=3489 patients) was mined to relate NmU mRNA to tumour subtype and patients' outcome. NmU cDNA and siRNAs were used to over-express and knock-down expression of NmU, respectively, prior to assessing it’s association with response to L, Trastuzumab (T) and Neratinib (N). Results: Analysis of the tumour data showed NmU expression to be particularly associated with poor outcome for patients with HER2-positive tumours (p=0.000005). In cell lines, we identified NmU mRNA and protein to be at significantly higher levels in L-resistant cells and corresponding CM, compared to that of L-sensitive SKBR3 and HCC1954. This trend was observed for T-resistant and N-resistant SKBR3 cells (SKBR3T, SKBR3N) and their CM, compared to sensitive parent SKBR3 cells and CM. NmU cDNA over-expression in SKBR3 and HCC1954 increased resistance to L, T and N. Knock-down of NmU endogenous levels in SKBR3-LR and innately L-resistant MDA-MB-361 and T47D sensitised these cells to L, T and N. Further analysis of our NmU over-expressing and knock-down cells indicated NmU to also be associated with increased motility, invasion and anoikis resistance. Conclusions: NmU expression is prognostic of poor outcome in HER2-positive breast tumours. In cell line models, NmU over-expression is associated with resistance to L, T and N. Taken together, we propose NmU as a possible prognostic and predictive biomarker for HER2-positive cancers, with potential also as a co-target to help circumvent resistance to these drugs. [SFI: 08/SRC/B1410]
Presentation and treatment of HER2-positive metastatic breast cancer patients already treated with adjuvant trastuzumab.
Authors: Torrejon Davis Yuri , Di Cosimo Serena , Sanchez-Olle Gessami , Balmaña Judith , Bellet Meritxell , Gomez Patricia , Saura Cristina , Perez-Garcia Jose Manuel , Muñoz-Couselo Eva , Vidal Maria , Ortega Vanesa , De Mattos-Arruda Leticia , Oliveira Mafalda , Mulet-Margalef Nuria , Tabernero Josep , Cortes Javier
Published: March 2020

619

Background: The introduction of trastuzumab in the clinical armamentarium has profoundly changed the natural history of HER2 positive breast cancer (BC). However, about 15% of patients with HER2 early BC treated with adjuvant trastuzumab continue to relapse. We aimed to analyze these patients with respect to clinical presentation and response to treatment. Methods: Data were retrieved from the institutional BC database of Vall d’Hebron. All the cases relapsing after exposure to adjuvant trastuzumab were analyzed. Change in expression of hormone-receptor (HR) and HER-2 status between primary tumour and corresponding local recurrence or distant metastasis was also evaluated Results: A total of 270 patients were identified. Twenty-six patients (9.6%) relapsed (Table). Overall median time from diagnosis to relapse was 27.1 months (24.1-30.1) being 29.1 months (14.3-44.1) in HR positive and 23.1 (9.9-36.2) in HR negative cases (p=0.037). Median time from last dose of trastuzumab to relapse was 7.6 (2.7-12.7) months, being 10.6 (0-27.9) and 3 months (0-7.6) in HR positive and negative cases, respectively (p=0.026). Sixteen patients have already progressed to first-line therapy with a median time to progression (TTP) of 7.4 months with no statistical difference among HR positive and HR negative (4.4 and 9.8 months, p=0.3). No difference was found in TTP to first line therapy among early (before 12 months) and delayed (after 12 months) progression on adjuvant trastuzumab. Among the 17 cases with primary tumor and matched metastatic biopsy, HER-2 negativization was detected in 2 cases; whereas a change in estrogen and progesterone receptors was seen in 17.6% and 29.4% of cases, respectively. Conclusions: Patients with HER2+/HR negative treated with adjuvant trastuzumab seems to have a significantly shorter time to relapse compared with the HER2+/HR+ tumors. In these patients biopsy of metastatic lesions might help to define the best treatment options. [Table: see text]