bluuebunny/crossref_metadata_2025_split huggingface dataset:
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]
Use of HER2 score correction for putative chromosome 17 (Chr-17) aneusomy to increase eligibility for anti-HER2 therapy.
Authors: Minca Eugen C. , Portier Bryce P. , Wang Zhen , Lanigan Christopher , Budd G. Thomas , Tubbs Raymond R. 
Published: March 2020

620 Background: HER2 amplification or overexpression status directs therapy choice in breast carcinoma. HER2/Chr-17 ratio is commonly assessed by fluorescence in-situ hybridization (FISH) using a CEP17 centromeric reference probe and ASCO/CAP scoring criteria. However, α-centromeric reference probes may underestimate true HER2 status in cases with para-centromeric amplification. Here we present comprehensive algorithmic testing of an alternative Chr-17 reference locus for resolution of putative CEP17-aneusomic cases in a consecutive series, within a single health system. Methods: 150 of 1256 consecutive breast carcinoma cases accessioned in 2011 within the Cleveland Clinic Health System displayed a mean CEP17 copy number greater than 3.0 by FISH (aneusomy). The patients were reflex-HER2 tested by FISH with a reference probe for the D17S122 locus (17p12) and a corrected HER2/Chr-17 ratio was calculated. Cases with equivocal HER2/D17S122 ratio (1.8-2.2) were further reflex tested for HER2 overexpression by immunohistochemistry (IHC). Results: Of 117 initially non-amplified cases by HER2/CEP17, 20 (17%) were revised to amplified and 18 (15.3%) to equivocal by HER2/D17S122. Of 3 initially equivocal cases, 1 was revised to amplified and 1 remained equivocal. Of the 19 equivocal cases by HER2/D17S122, 3 were revised to positive by IHC. Overall, for CEP17 aneusomic cases tested using this algorithmic approach, 24 of 120 (20%) patients with initial non-amplified or equivocal HER2 status became eligible for anti-HER2-based therapy, which was also considered in 10 equivocal cases with a HER2/D17S122 ratio of 2.0 - 2.2. A significantly lower proportion of initially amplified cases was revised as non-amplified by HER2/D17S122 (1 of 30, 3.3%, p<0.05). Conclusions: Our data, collected within a single health system for a consecutive case series, underscores the clinical limitations of commonly used FISH probes for HER2 testing and demonstrates that algorithmic use of a non-centromeric Chr-17 reference probe alters HER2 status and increases eligibility for anti-HER2 based therapy in a significant proportion of patients.