781 results on '"Amylou C. Dueck"'
Search Results
202. PF675 JAK2V617F AND MPL MUTATIONS ARE ASSOCIATED WITH WORSENED SYMPTOM BURDEN THAN CALR IN THE MYELOPROLIFERATIVE NEOPLASMS: FINDINGS FROM THE MYMPN PATIENT REGISTRY
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L. Whyte, S. Verstovsek, D. Pearl, J. Mascarenhas, R. Scherber, R. Mesa, Amylou C. Dueck, A. Moliterno, M. Woehrle, and Christine J. Harrison
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medicine.medical_specialty ,Patient registry ,business.industry ,Internal medicine ,medicine ,Symptom burden ,Hematology ,business - Published
- 2019
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203. PS1501 QUALITY OF LIFE IN PATIENTS UNDERGOING CHIMERIC ANTIGEN RECEPTOR (CAR) - T CELL THERAPY VS. AUTOLOGOUS AND ALLOGENEIC STEM CELL TRANSPLANT FOR HEMATOLOGIC MALIGNANCIES
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Morie A. Gertz, Shaji Kumar, Joan M. Griffin, Nora N Bennani, Jonas Paludo, Carrie A. Thompson, Yi Lin, Rahma Warsame, Mustaqeem A. Siddiqui, Surbhi Sidana, Kathleen J. Yost, Patrick B. Johnston, Andrea L. Cheville, Michelle Burtis, S. M. Ansell, J. Villasboas Bisneto, Amylou C. Dueck, Angela Dispenzieri, S. V. Rajkumar, and Gita Thanarajasingam more...
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Quality of life ,business.industry ,Cancer research ,CAR T-cell therapy ,Medicine ,In patient ,Hematology ,Stem cell ,business ,Chimeric antigen receptor - Published
- 2019
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204. Comprehensively understanding fatigue in patients with myeloproliferative neoplasms
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Holly L. Geyer, Heidi E. Kosiorek, Archie McCallister, Zhenya Senyak, Mary Cotter, Ruben A. Mesa, Michael Boxer, Robyn M. Scherber, Claire N. Harrison, Matthew M. Clark, Amylou C. Dueck, and Barbara Van Husen more...
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Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Essential thrombocythemia ,Population ,medicine.disease ,Patient Health Questionnaire ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Quality of life ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Etiology ,business ,Psychiatry ,education ,Body mass index ,Depression (differential diagnoses) ,Myeloproliferative neoplasm ,030215 immunology - Abstract
BACKGROUND Patients with myeloproliferative neoplasms (MPNs) experience a high persistence, prevalence, and severity of fatigue. There is currently only limited information regarding factors that contribute to fatigue in patients with MPNs. METHODS A 70-item, Internet-based survey regarding fatigue was developed by MPN investigators and patients/advocates and hosted by the Mayo Clinic Survey Research Center. RESULTS Fatigue was found to be prevalent and severe among international survey respondents (1788 respondents). Higher body mass index (P 2 on the Patient Health Questionnaire, indicating a high probability of depression. Higher Brief Fatigue Inventory score, Myeloproliferative Neoplasm Total Symptom Score, and individual symptom items were all associated with a higher likelihood of depressive symptoms (P more...
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- 2015
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205. The relationship among gastroparetic symptoms, quality of life, and gastric emptying in patients referred for gastric emptying testing
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John K. DiBaise, M. C. Roarke, Michael D. Crowell, Jessica Noelting, Amylou C. Dueck, and Neal Patel
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Adult ,Male ,medicine.medical_specialty ,Gastroparesis ,Physiology ,Nausea ,Logistic regression ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Bloating ,Quality of life ,Surveys and Questionnaires ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Gastric emptying ,Endocrine and Autonomic Systems ,business.industry ,digestive, oral, and skin physiology ,Middle Aged ,medicine.disease ,Postprandial ,Gastric Emptying ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business - Abstract
Symptoms suggestive of gastroparesis are non-specific and conflicting reports exist regarding the ability of symptoms to predict the presence of gastroparesis. Our aim, therefore, was to evaluate the relationships between gastroparetic symptoms and their impact on quality of life and determine their relationship with clinical factors and gastric emptying.Gastric emptying scintigraphy, sociodemographic features, health care resource utilization, gastroparetic symptoms, and quality of life using validated questionnaires were obtained from consecutive patients referred for gastric emptying testing (GET). Descriptive analyses were conducted and logistic regression was performed to evaluate associations with abnormal gastric emptying after controlling for other covariates.Two hundred and sixty-six patients participated (195 females; mean age, 49.1 ± 17.6 years); 75% met Rome III criteria for functional dyspepsia. Gastric emptying was delayed in 28.2% at 4 h; the delay was mild in 48%, moderate in 20% and severe in 32%. Nausea/emesis and postprandial fullness, but not bloating, were significantly greater in those with delayed emptying. Postprandial fullness was most severe. Weak correlations were identified between symptom severity and the severity of gastric emptying delay. Quality of life was also lower in the delayed emptying group. Logistic regression analysis demonstrated associations between delayed gastric emptying and lower quality of life and increased symptom severity.In patients referred for GET, gastroparetic symptoms were more severe in those with delayed emptying. A decrease in quality of life in those with delayed gastric emptying was also present; this was not related to the severity of the delay in gastric emptying. more...
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- 2015
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206. Psychological distress in Rome III functional dyspepsia patients presenting for testing of gastric emptying
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Rafiul S. Islam, Michael D. Crowell, John K. DiBaise, Amylou C. Dueck, and M. C. Roarke
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Adult ,Male ,medicine.medical_specialty ,Physiology ,Population ,03 medical and health sciences ,0302 clinical medicine ,Alexithymia ,Quality of life ,Surveys and Questionnaires ,Internal medicine ,Humans ,Medicine ,Dyspepsia ,Radionuclide Imaging ,education ,Depression (differential diagnoses) ,education.field_of_study ,Gastric emptying ,Endocrine and Autonomic Systems ,business.industry ,Gastroenterology ,Middle Aged ,medicine.disease ,Distress ,Gastric Emptying ,030220 oncology & carcinogenesis ,Anxiety ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Somatization ,Stress, Psychological ,Clinical psychology - Abstract
Background There have been conflicting results from studies that have evaluated psychological disturbances in functional dyspepsia (FD). We conducted a comprehensive survey of psychological measures in patients undergoing gastric emptying testing (GET) in order to determine the relationship among psychological distress, gastric emptying, and dyspeptic symptoms. Methods Consecutive patients referred for GET were prospectively enrolled. Details regarding patient characteristics, health care utilization, dyspeptic symptoms, quality of life, and psychological dysfunction were obtained. Depression, anxiety, somatization, stress, positive and negative affect, and alexithymia were queried using validated questionnaires. We compared those dyspeptic patients who met Rome III criteria for FD to those who did not meet these criteria. Key Results Two hundred and nine patients (160 female; mean age 46.6 years ± 17.3 years) participated. Around 151 patients (72%) met Rome III criteria for FD. In the entire group, a high level of depression, anxiety, somatization, and perceived stress was present compared to population norms. Health care seeking behavior and symptom severity were greater in those with FD and quality of life was lower compared to non-FD. Gastric emptying did not differentiate the two groups and similar degrees of psychological distress were present whether emptying was delayed or normal. Conclusions & Inferences In patients referred for GET, substantial psychological distress is present. The degree of distress was similar regardless of whether the patient met Rome III FD criteria or not. Further evaluation of psychological dysfunction in FD patients may lead to improved diagnosis and determination of the most appropriate treatment. more...
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- 2015
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207. Myeloproliferative neoplasm patient symptom burden and quality of life: Evidence of significant impairment compared to controls
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Glen James, Mary Frances McMullin, Mike Clarke, Robyn M. Scherber, Frank de Vocht, Ruben A. Mesa, Andrew S Duncombe, Lesley A. Anderson, and Amylou C. Dueck
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education.field_of_study ,medicine.medical_specialty ,Polycythaemia ,business.industry ,Confounding ,Population ,Symptom burden ,food and beverages ,Hematology ,medicine.disease ,Clinical trial ,Quality of life ,Internal medicine ,medicine ,Physical therapy ,Myelofibrosis ,education ,business ,Myeloproliferative neoplasm - Abstract
The myeloproliferative neoplasms (MPN) including polycythaemia vera (PV), essential thrombocythaemia and primary myelofibrosis (PMF) are rare diseases contributing to significant morbidity. Symptom management is a prime treatment objective but current symptom assessment tools have not been validated compared to the general population. The MPN-symptom assessment form (MPN-SAF), a reliable and validated clinical tool to assess MPN symptom burden, was administered to MPN patients (n = 106) and, for the first time, population controls (n = 124) as part of a UK case–control study. Mean symptom scores were compared between patients and controls adjusting for potential confounders. Mean patient scores were compared to data collected by the Mayo Clinic, USA on 1,446 international MPN patients to determine patient group representativeness. MPN patients had significantly higher mean scores than controls for 25 of the 26 symptoms measured (P more...
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- 2015
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208. Rates of residual disease with close but negative margins in breast cancer surgery
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Idris Tolgay Ocal, Barbara A. Pockaj, Richard Gray, Nabil Wasif, Ann E. McCullough, Derek A. Senior, Erin M. Garvey, and Amylou C. Dueck
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Adult ,Reoperation ,medicine.medical_specialty ,Neoplasm, Residual ,Databases, Factual ,Lymphovascular invasion ,medicine.medical_treatment ,Estrogen receptor ,Breast Neoplasms ,Disease ,Mastectomy, Segmental ,Breast cancer ,Humans ,Medicine ,Neoplasm Invasiveness ,Prospective Studies ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Centimeter ,business.industry ,Hazard ratio ,Antineoplastic Protocols ,General Medicine ,Middle Aged ,medicine.disease ,Confidence interval ,Surgery ,Female ,Neoplasm Recurrence, Local ,business ,Mastectomy - Abstract
A recent multidisciplinary consensus defined an adequate breast cancer margin as no ink on tumor. The purpose of this study was to analyze rates of residual disease at re-excision by margin width.A prospective database at a single institution was reviewed from 2000 to 2012. Institutional protocol had been to perform re-excision surgery when margins were2 millimeters (mm).There were 2520 procedures. Re-excision surgery was performed for 12% of breast conserving therapy (BCT) procedures and 2% of mastectomies; residual disease was present in 38% and 26%, respectively. The rates of residual disease for all patients with positive, 0.1-0.9 mm, and 1.0-1.9 mm margins were 40%, 38%, and 33%, respectively. Age, race, menopause status, width of closest final margin, tumor histology, hormone receptor status, triple-negative disease and presence of lymphovascular invasion (LVI) were not significantly associated with the presence of residual disease. The presence of multiple margins2 mm trended toward significance (p = 0.06). Median follow-up was 43 months. The five-year local recurrence rates (5-year LR) were 1.1% for mastectomy patients and 1.9% for BCT patients.Breast cancer patients with margins of excision2 mm have a substantial risk of residual disease but the rates far exceed LR rates. These findings suggest that using residual disease rates to determine the appropriate margin width is not reliable, but also serve as a note of caution to track LR rates as institutions conform to new national guidelines for margin management. more...
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- 2015
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209. Validation of a gastric cancer nomogram using a cancer registry
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Sanjay P. Bagaria, Nabil Wasif, Richard Gray, Awais Ashfaq, Amylou C. Dueck, Lee J. McGhan, John T. Kidwell, and Barbara A. Pockaj
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Oncology ,education.field_of_study ,medicine.medical_specialty ,business.industry ,Population ,Hazard ratio ,Cancer ,Retrospective cohort study ,General Medicine ,Nomogram ,medicine.disease ,digestive system diseases ,Surgery ,Cancer registry ,Internal medicine ,medicine ,Adenocarcinoma ,education ,business ,Survival rate - Abstract
Background A Memorial Sloan Kettering (MSKCC) nomogram predicts disease specific survival (DSS) for gastric adenocarcinoma. The goal of this study is to use a cancer registry to compare nomogram predicted survival with actual survival in the general population. Methods All patients undergoing surgery for gastric adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database (1988–2012) were studied. Results 6954 patients were identified. Majority of cancers were in the antrum (30.2%), and had intestinal histology (73.7%). Median follow-up was 8.2 years. Five year DSS for nomogram risk groups (0–25%, 26–50%, 51–75%, and 76–100%) was 23%, 48%, 57%, and 81% respectively. Actual DSS was 7–15% lower than nomogram predicted DSS. Relative to patients in the 76–100% 5-year DSS risk group, patients in the 0–25%, 26–50%, and 51–75% groups had significantly higher risks of death with hazard ratios of 6.84 (95%CI 6.12–7.65), 3.30 (95%CI 2.83–3.86), and 2.64 (95%CI 2.30–3.03), respectively (all P more...
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- 2015
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210. Limitations of fibrosis grade as diagnostic criteria for post polycythemia vera and essential thrombocytosis myelofibrosis
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Amylou C. Dueck, Ricardo Valdez, Ruben A. Mesa, Srdan Verstovsek, Naveen Pemmaraju, Heidi E. Kosiorek, Naval Daver, and Krisstina L. Gowin
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Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Gastroenterology ,Article ,Polycythemia vera ,Fibrosis ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Medicine ,Clinical phenotype ,Myelofibrosis ,Polycythemia Vera ,Thrombocytosis ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Blood smear ,Oncology ,Marrow fibrosis ,Sub threshold ,Female ,business ,Thrombocythemia, Essential - Abstract
Background The clinical phenotype of patients with myeloproliferative neoplasms (MPNs) including primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET) whom manifest WHO grade 1 marrow fibrosis is poorly defined. Current IWG-MRT criteria require 2+ marrow fibrosis for diagnosis of post PV/ET myelofibrosis (MF). In contrast, the 2008 WHO definition of PMF does not require a minimum fibrosis threshold. Methods We retrospectively analyzed the clinical characteristics of 91 MPN patients with 1+ marrow fibrosis. We compared the clinical phenotype of sub threshold fibrosis PV/ET with that manifested by PMF. We applied the IWG-MRT criteria for post-PV/ET MF with the fibrosis component omitted and evaluated for percentage of criteria fulfillment. Results When IWG-MRT criteria were applied to the PV/ET group, 38/58 (66%) of patients fulfilled criteria for diagnosis of post-PV/ET myelofibrosis except for the 2+ fibrosis requirement. Comparison of sub threshold fibrotic PV/ET clinical phenotype to PMF revealed similar characteristics including heavy symptomatic burden (57% and 52%), presence of splenomegaly (43% and 55%), leukoerythroblastic blood smear (38% and 45%), and median hemoglobin (12.8 g/dL and 11.1 g/dL). Conclusion MPN progression represents a biological spectrum and definitions of progression in ET/PV may benefit from criteria not restricted by degree of fibrosis. more...
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- 2015
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211. Multidisciplinary Shared Decision Making in the Management of Ductal Carcinoma In Situ of the Breast
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Richard Gray, Nabil Wasif, Heidi E. Kosiorek, Michele Y. Halyard, William W. Wong, Amylou C. Dueck, Priya Parikh, and Barbara A. Pockaj
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Adult ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Decision Making ,Breast Neoplasms ,Mastectomy, Segmental ,Article ,Surgical oncology ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Neoplasm Invasiveness ,Prospective Studies ,Prospective cohort study ,Survival rate ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Radiotherapy ,business.industry ,Carcinoma, Ductal, Breast ,Middle Aged ,Ductal carcinoma ,Prognosis ,Combined Modality Therapy ,Confidence interval ,Survival Rate ,Radiation therapy ,Carcinoma, Intraductal, Noninfiltrating ,Hormonal therapy ,Female ,Surgery ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business ,Adjuvant ,Follow-Up Studies - Abstract
Controversy continues regarding the use of adjuvant radiation therapy (RT) and hormonal therapy (HT) for patients undergoing breast-conserving therapy (BCT) for ductal carcinoma in situ (DCIS). A prospective database was queried to identify women 18 years of age or older treated for DCIS from 2002 to 2013. BCT was completed for 300 patients with a median age of 66 years. The median DCIS size was 0.7 cm (range 0.1–6.0 cm). The DCIS grades were high (44 %), intermediate (37 %), and low (19 %). The closest margin was wider than 3 mm in 80 % and wider than 5 mm in 63 % of the cases. Adjuvant RT was administered to 183 patients (61 %), and the RT status of 9 patients (3 %) was unknown. RT was associated with age, DCIS size, comedo necrosis, grade, and treatment in 2002–2007 versus 2008–2013. Adjuvant HT was administered to 86 estrogen receptor-positive patients (39 %), and the HT status of 4 patients (2 %) was unknown. The median follow-up period was 63 months (range 4–151 months). The 5-year overall local recurrence (LR) rate was 4 % (95 % confidence interval [CI] 2.1–7.4 %). The 5-year LR rate was 3.9 % (95 % CI 1.8–8.6 %) for the RT patients and 4.1 % (95 % CI 1.6–10.7 %) for the patients not receiving RT. Of 13 LRs, 10 (77 %) were DCIS, and 3 (23 %) were invasive including one node-positive recurrence. Multidisciplinary and joint decision making in the treatment of DCIS results in a substantial and increasing number of patients forgoing adjuvant RT, adjuvant HT, or both. Reasonable 5-year LR rates suggest that such decision making can appropriately allocate patients to adjuvant therapies. more...
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- 2015
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212. Endpoint comparison for bone mineral density measurements in North Central Cancer Treatment Group cancer clinical trials N02C1 and N03CC (Alliance)
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Charles L. Loprinzi, Stephanie L. Hines, Kelli N. Burger, Pamela J. Atherton, Amylou C. Dueck, Jasvinder A. Singh, Angelina Tan, Paul J. Novotny, Xinghua Zhao, E. A. Perez, Heshan Liu, Jeff A. Sloan, and Brent Diekmann more...
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Adult ,Oncology ,medicine.medical_specialty ,Bone density ,Endpoint Determination ,Cancer clinical trial ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Breast Neoplasms ,Zoledronic Acid ,Article ,Absorptiometry, Photon ,Breast cancer ,Double-Blind Method ,Bone Density ,Internal medicine ,medicine ,Humans ,Osteoporosis, Postmenopausal ,Aged ,Aged, 80 and over ,Bone mineral ,Lumbar Vertebrae ,Bone Density Conservation Agents ,Diphosphonates ,Femur Neck ,business.industry ,Imidazoles ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Clinical trial ,Treatment Outcome ,Physical therapy ,Female ,business ,Risedronic Acid - Abstract
Bone mineral density (BMD) measurement can vary depending upon anatomical site, machine, and normative values used. This analysis compared different BMD endpoints in two clinical trials. Trial results differed across endpoints. Future clinical trials should consider inclusion of multiple endpoints in sensitivity analysis to ensure sound overall study conclusions.Methodological issues hamper efficacy assessment of osteoporosis prevention agents in cancer survivors. Osteoporosis diagnosis can vary depending upon which bone mineral density (BMD) anatomical site and machine is used and which set of normative values are applied. This analysis compared different endpoints for osteoporosis treatment efficacy assessment in two clinical studies.Data from North Central Cancer Treatment Group phase III clinical trials N02C1 and N03CC (Alliance) were employed involving 774 patients each comparing two treatments for osteoporosis prevention. Endpoints for three anatomical sites included raw BMD score (RawBMD); raw machine-based, sample-standardized, and reference population-standardized T scores (RawT, TSamp, TRef); and standard normal percentile corresponding to the reference population-standardized T score (TPerc). For each, treatment arm comparison was carried out using three statistical tests using change and percentage change from baseline (CB, %CB) at 1 year.Baseline correlations among endpoints ranged from 0.79 to 1.00. RawBMD and TPerc produced more statistically significant results (14 and 19 each out of 36 tests) compared to RawT (11/36), TSamp (8/36), and TRef (7/36). Spine produced the most statistically significant results (26/60) relative to femoral neck (20/60) and total hip (13/60). Lastly, CB resulted in 44 statistically significant results out of 90 tests, whereas %CB resulted in only 15 significant results.Treatment comparisons and interpretations were different across endpoints and anatomical sites. Transforming via sample statistics provided similar results as transforming via reference or machine-based norms. However, RawBMD and TPerc may be more sensitive to change as clinical trial endpoints. more...
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- 2015
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213. Genomic Analysis Reveals That Immune Function Genes Are Strongly Linked to Clinical Outcome in the North Central Cancer Treatment Group N9831 Adjuvant Trastuzumab Trial
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Jian-Bing Fan, Monica M. Reinholz, Karla V. Ballman, Beiyun Chen, Eric P. Winer, Ann E. McCullough, Amylou C. Dueck, Julie Gralow, Xochiquetzal J. Geiger, Edith A. Perez, S. Keith Anderson, E. Aubrey Thompson, Yan W. Asmann, George W. Sledge, Kathleen S. Tenner, Robert B. Jenkins, Jeanette E. Eckel-Passow, Krishna R. Kalari, and Jin Jen more...
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Oncology ,Cancer Research ,Chemotherapy ,medicine.medical_specialty ,Proportional hazards model ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Combination chemotherapy ,Genomic signature ,medicine.disease ,Breast cancer ,Trastuzumab ,Internal medicine ,Immunology ,medicine ,skin and connective tissue diseases ,business ,Adjuvant ,medicine.drug - Abstract
Purpose To develop a genomic signature that predicts benefit from trastuzumab in human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods DASL technology was used to quantify mRNA in samples from 1,282 patients enrolled onto the Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer (North Central Cancer Treatment Group N9831 [NCCTG-N9831]) adjuvant trastuzumab trial. Cox proportional hazard ratios (HRs), adjusted for significant clinicopathologic risk factors, were used to determine the association of each gene with relapse-free survival (RFS) for 433 patients who received chemotherapy alone (arm A) and 849 patients who received chemotherapy plus trastuzumab (arms B and C). Network and pathway analyses were used to identify key biologic processes linked to RFS. The signature was built by using a voting scheme. Results Network and functional ontology analyses suggested that increased RFS was linked to a subset of immune function genes. A voting scheme model was used to define immune gene enrichment based on the expression of any nine or more of 14 immune function genes at or above the 0.40 quantile for the population. This model was used to identify immune gene–enriched tumors in arm A and arms B and C. Immune gene enrichment was linked to increased RFS in arms B and C (HR, 0.35; 95% CI, 0.22 to 0.55; P < .001), whereas arm B and C patients who did not exhibit immune gene enrichment did not benefit from trastuzumab (HR, 0.89; 95% CI, 0.62 to 1.28; P = .53). Enriched immune function gene expression as defined by our predictive signature was not associated with increased RFS in arm A (HR, 0.90; 95% CI, 0.60 to 1.37; P = .64). Conclusion Increased expression of a subset of immune function genes may provide a means of predicting benefit from adjuvant trastuzumab. more...
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- 2015
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214. Quality of life and disease understanding: impact of attending a patient‐centered cancer symposium
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Leslie Padrnos, Robyn M. Scherber, Rachel Stigge, Pamela Glassley, Annette Aguirre, Donald W. Northfelt, Ruben A. Mesa, Joseph R. Mikhael, Amylou C. Dueck, and Robert M. Bennett
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Adult ,Male ,Gerontology ,Health Knowledge, Attitudes, Practice ,Cancer Research ,Population ,Disease ,patient education ,Quality of life (healthcare) ,McNemar's test ,Patient Education as Topic ,cancer symposia ,Neoplasms ,Intervention (counseling) ,Cancer education ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Survivors ,education ,Original Research ,Aged ,Aged, 80 and over ,education.field_of_study ,Modalities ,business.industry ,Congresses as Topic ,Middle Aged ,humanities ,cancer survivorship ,quality of life ,Oncology ,Knowledge base ,educational intervention ,Female ,business ,Patient education - Abstract
To evaluate the impact of a patient-centered symposium as an educational intervention on a broad population of cancer patients. We developed a comprehensive patient symposium. Through voluntary questionnaires, we studied the impact of this cancer symposium on quality of life, cancer-specific knowledge, and symptom management among cancer patients. Symposium attendees were provided surveys prior to and 3 months following the educational intervention. Surveys included (1) EORTC-QLQ-C30; (2) disease understanding tool developed for this conference; (3) validated disease-specific questionnaires. Changes over time were assessed using McNemar's tests and paired t-tests for categorical and continuous variables, respectively. A total of 158 attendees completed the pre-convention survey. Most respondents reported at least "quite a bit" of understanding regarding treatment options, screening modalities, symptomatology, and cancer-related side effects. Attendees endorsed the least understanding of disease-related stress, risk factors, fatigue management, and legal issues related to disease/treatment. At 3 months, there was improvement in understanding (12 of 14 areas of self-reported knowledge especially regarding nutrition, and stress/fatigue management). However, no significant change was seen in QLQ-C30 functioning, fatigue, pain, or insomnia. A patient symposium, as an educational intervention improves a solid knowledge base amongst attendees regarding their disease, increases knowledge in symptom management, but may be insufficient to impact QoL as a single intervention. more...
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- 2015
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215. Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development
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Robyn M. Scherber, Holly L. Geyer, Amylou C. Dueck, and Ruben A. Mesa
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Constitutional symptoms ,medicine.medical_treatment ,Immunology ,Population ,Review Article ,Polycythemia vera ,Myeloproliferative Disorders ,lcsh:Pathology ,medicine ,Animals ,Humans ,Myelofibrosis ,education ,Polycythemia Vera ,Fatigue ,Myeloproliferative neoplasm ,Inflammation ,education.field_of_study ,business.industry ,Essential thrombocythemia ,Microcirculation ,Pruritus ,Cell Biology ,medicine.disease ,Treatment Outcome ,Cytokine ,Primary Myelofibrosis ,Splenomegaly ,Disease Progression ,Cytokines ,Symptom Assessment ,Cognition Disorders ,business ,lcsh:RB1-214 ,Thrombocythemia, Essential - Abstract
Myeloproliferative neoplasms (essential thrombocythemia, ET; polycythemia vera, PV; myelofibrosis, MF) are monoclonal malignancies associated with genomic instability, dysregulated signaling pathways, and subsequent overproduction of inflammatory markers. Acknowledged for their debilitating symptom profiles, recent investigations have aimed to determine the identity of these markers, the upstream sources stimulating their development, their prevalence within the MPN population, and the role they play in symptom development. Creation of dedicated Patient Reported Outcome (PRO) tools, in combination with expanded access to cytokine analysis technology, has resulted in a surge of investigations evaluating the potential associations between symptoms and inflammation. Emerging data demonstrates clear relationships between individual MPN symptoms (fatigue, abdominal complaints, microvascular symptoms, and constitutional symptoms) and cytokines, particularly IL-1, IL-6, IL-8, and TNF-α. Information is also compiling on the role symptoms paradoxically play in the development of cytokines, as in the case of fatigue-driven sedentary lifestyles. In this paper, we explore the symptoms inherent to the MPN disorders and the potential role inflammation plays in their development. more...
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- 2015
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216. Abstract PD5-07: The impact of early lapatinib-induced rash on disease-free and overall survival in patients treated within the ALTTO phase III randomized trial
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Ian Bradbury, Henry L. Gomez, István Láng, B H Xu, Antonio C. Wolff, Kathleen I. Pritchard, Amir Sonnenblick, Michael Untch, E. A. Perez, M.J. Piccart, Yingjie Huang, I. E. Smith, Frances M. Boyle, Fergus Daly, E. de Azambuja, Dominique Agbor-Tarh, Christian Jackisch, Hatem A. Azim, and Amylou C. Dueck more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,030503 health policy & services ,Disease free ,Lapatinib ,Rash ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Overall survival ,In patient ,medicine.symptom ,0305 other medical science ,business ,medicine.drug - Abstract
Background: We have previously shown in a phase III neoadjuvant trial that early development of lapatinib-induced rash (i.e. within 6 weeks after lapatinib initiation) is independently associated with a higher chance of obtaining a pathological complete response (Azim et al; JCO 2013). In the current study, we aimed to investigate whether early lapatinib-induced rash is associated with improved survival in the context of a large phase III adjuvant trial. Methods: This analysis is based on the ALTTO trial (BIG 2-06, Alliance N063D), in which patients with HER2-positive early breast cancer were randomized to adjuvant trastuzumab, lapatinib, their sequence or their combination for a total duration of 1 year. In this sub-study, we evaluated whether the development of rash (any grade) within 6 weeks of lapatinib initiation was associated with disease-free (DFS) and overall survival (OS). All analyses were tested in a multivariate model adjusted for treatment arm, treatment completion and trial stratification factors. Results: A total of 6,098 lapatinib-treated patients were included in the current analysis; of whom 2,006 patients (32.9%) developed early lapatinib-induced rash, 1,025 (16.8%) developed rash after 6 weeks and 3,067 (50.3%) did not develop rash. No differences in patient characteristics were observed between the three groups apart from a higher frequency of younger patients (≤ 50) in the early rash group (54% vs. 47% and 44%, p Conclusions: The results support our previous findings in the neoadjuvant setting that early development of skin rash within the first 6 weeks can identify patients who derive superior benefit of lapatinib treatment. Citation Format: Azim Jr HA, Sonnenblick A, Agbor-Tarh D, Bradbury I, Daly F, Huang Y, Dueck AC, Pritchard K, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Perez E, Piccart M, de Azambuja E. The impact of early lapatinib-induced rash on disease-free and overall survival in patients treated within the ALTTO phase III randomized trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD5-07. more...
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- 2016
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217. NIMG-74. RADIOMICS OF TUMOR INVASION 2.0: COMBINING MECHANISTIC TUMOR INVASION MODELS WITH MACHINE LEARNING MODELS TO ACCURATELY PREDICT TUMOR INVASION IN HUMAN GLIOBLASTOMA PATIENTS
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Jing Li, Bernard R. Bendok, Lauren DeGirolamo, Leslie C. Baxter, Kristin R. Swanson, Jennifer Eschbacher, Pamela R. Jackson, Andrea Hawkins-Daarud, Teresa Wu, Peter Nakaji, Kyle W. Singleton, Amylou C. Dueck, Kamala Clark-Swanson, Nathan Gaw, Leland S. Hu, Kris A. Smith, and Samuel McGee more...
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0301 basic medicine ,Cancer Research ,business.industry ,Computational biology ,medicine.disease ,03 medical and health sciences ,Abstracts ,030104 developmental biology ,Text mining ,Oncology ,Radiomics ,medicine ,Neurology (clinical) ,business ,Glioblastoma - Abstract
In glioblastoma (GBM), contrast enhanced (CE)-MRI delineates bulk tumor with contrast-enhancement but poorly characterizes invasive tumor in the nonenhancing T2W abnormality. There is extensive literature in both machine-learning (ML) and mechanistic mathematical oncology seeking to accurately predict diffuse tumor invasion from multi-parametric MRI. ML offers strengths of a data-driven iterative approach, while mechanistic (proliferation-invasion, PI) modeling incorporates spatial relationships with expected drop-offs of tumor cell density from central regions of MRI enhancement. In this study, we build and cross-validate a first-of-its-kind hybrid (ML-PI) model. We collected 82 image-guided biopsies from 18 primary GBM patients throughout CE T1W and nonenhancing T2W regions. For each biopsy, we obtained neuropathologist estimates of tumor cell density and spatially matched MRI (CE T1W, T2W) from which we extracted texture features. PI maps of tumor invasion were generated from MRI-based patient-specific estimates of the net rates of invasion and proliferation. Then, the PI maps were incorporated with a ML model that uses texture features to predict cell density to minimize the prediction error on biopsy samples (ML strength) while making sure tumor-wide prediction (biopsied and unbiopsied regions) conformed with glioblastoma biology (PI strength). We optimized this hybrid ML-PI model using leave-one-out-cross-validation, and compared its performance with PI and ML alone. We used Pearson correlation (r) between cross-validated predicted tumor cell density and true tumor cell density. We focused on prediction within the nonenhancing zone (n=32) because accurate estimation of invasive tumor cell density in this zone has important clinical value for radiation and surgical planning. PI-ML showed significantly stronger correlation (r=0.76) compared to PI (r=0.44) and ML (r=0.04) models alone (p value more...
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- 2017
218. Feasibility study of online yoga for symptom management in patients with myeloproliferative neoplasms
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Jules Mitchell, Amylou C. Dueck, Ruben A. Mesa, Krisstina Gowin, Linda Larkey, Ryan Eckert, Jennifer Huberty, and Brenda Ginos
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Male ,medicine.medical_specialty ,Anxiety ,Education, Distance ,03 medical and health sciences ,0302 clinical medicine ,Polycythemia vera ,hemic and lymphatic diseases ,Internal medicine ,Neoplasms ,medicine ,Humans ,In patient ,Myelofibrosis ,Online Only Articles ,Fatigue ,Aged ,Myeloproliferative Disorders ,Essential thrombocythemia ,business.industry ,Symptom management ,Depression ,Yoga ,Palliative Care ,Symptom burden ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,030220 oncology & carcinogenesis ,Feasibility Studies ,Female ,business ,030215 immunology - Abstract
Myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are clonal, progressive, hematological malignancies resulting in the risk of vascular events, splenomegaly, and significant symptom burden, with a high prevalence of fatigue.[ more...
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- 2017
219. Optimization of DSC-MRI Echo Times for CBV Measurements using Error Analysis in a Pilot Study of High-Grade Gliomas
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Mark D. Does, Amylou C. Dueck, Ashley M. Stokes, C.C. Quarles, Kathleen M. Schmainda, Leslie C. Baxter, and Laura C. Bell
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Adult ,Male ,Contrast Media ,Pilot Projects ,computer.software_genre ,Article ,030218 nuclear medicine & medical imaging ,White matter ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Precontrast ,Nuclear magnetic resonance ,Voxel ,Error analysis ,Image Processing, Computer-Assisted ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Arterial input function ,Aged ,Retrospective Studies ,Propagation of uncertainty ,business.industry ,Brain Neoplasms ,Echo-Planar Imaging ,Glioma ,Cerebral Arteries ,Middle Aged ,Mr imaging ,White Matter ,Preload ,medicine.anatomical_structure ,Female ,Neurology (clinical) ,business ,computer ,030217 neurology & neurosurgery ,Algorithms - Abstract
BACKGROUND AND PURPOSE: The optimal TE must be calculated to minimize the variance in CBV measurements made with DSC MR imaging. Simulations can be used to determine the influence of the TE on CBV, but they may not adequately recapitulate the in vivo heterogeneity of precontrast T2*, contrast agent kinetics, and the biophysical basis of contrast agent–induced T2* changes. The purpose of this study was to combine quantitative multiecho DSC MRI T2* time curves with error analysis in order to compute the optimal TE for a traditional single-echo acquisition. MATERIALS AND METHODS: Eleven subjects with high-grade gliomas were scanned at 3T with a dual-echo DSC MR imaging sequence to quantify contrast agent–induced T2* changes in this retrospective study. Optimized TEs were calculated with propagation of error analysis for high-grade glial tumors, normal-appearing white matter, and arterial input function estimation. RESULTS: The optimal TE is a weighted average of the T2* values that occur as a contrast agent bolus transverses a voxel. The mean optimal TEs were 30.0 ± 7.4 ms for high-grade glial tumors, 36.3 ± 4.6 ms for normal-appearing white matter, and 11.8 ± 1.4 ms for arterial input function estimation (repeated-measures ANOVA, P CONCLUSIONS: Greater heterogeneity was observed in the optimal TE values for high-grade gliomas, and mean values of all 3 ROIs were statistically significant. The optimal TE for the arterial input function estimation is much shorter; this finding implies that quantitative DSC MR imaging acquisitions would benefit from multiecho acquisitions. In the case of a single-echo acquisition, the optimal TE prescribed should be 30–35 ms (without a preload) and 20–30 ms (with a standard full-dose preload). more...
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- 2017
220. Untapped Potential of Observational Research to Inform Clinical Decision Making: American Society of Clinical Oncology Research Statement
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Amylou C. Dueck, Derek Raghavan, Clifford A. Hudis, Laura A. Levit, Kala Visvanathan, Sandra L. Wong, and Gary H. Lyman
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Cancer Research ,medicine.medical_specialty ,Clinical Decision-Making ,MEDLINE ,Alternative medicine ,Postmarketing surveillance ,Medical Oncology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,medicine ,Electronic Health Records ,Humans ,030212 general & internal medicine ,Randomized Controlled Trials as Topic ,Medical education ,Evidence-Based Medicine ,business.industry ,Research statement ,Evidence-based medicine ,Observational Studies as Topic ,Oncology ,030220 oncology & carcinogenesis ,Observational study ,business - Abstract
ASCO believes that high-quality observational studies can advance evidence-based practice for cancer care and are complementary to randomized controlled trials (RCTs). Observational studies can generate hypotheses by evaluating novel exposures or biomarkers and by revealing patterns of care and relationships that might not otherwise be discovered. Researchers can then test these hypotheses in RCTs. Observational studies can also answer or inform questions that either have not been or cannot be answered by RCTs. In addition, observational studies can be used for postmarketing surveillance of new cancer treatments, particularly in vulnerable populations. The incorporation of observational research as part of clinical decision making is consistent with the position of many leading institutions. ASCO identified five overarching recommendations to enhance the role of observational research in clinical decision making: (1) improve the quality of electronic health data available for research, (2) improve interoperability and the exchange of electronic health information, (3) ensure the use of rigorous observational research methodologies, (4) promote transparent reporting of observational research studies, and (5) protect patient privacy. more...
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- 2017
221. Determination of mild, moderate, and severe pain interference in patients with cancer
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Yi Qian, Tito R. Mendoza, Jeffrey Zhang, Charles S. Cleeland, Amylou C. Dueck, Qiuling Shi, Haijun Ma, and Debajyoti Bhowmik
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Psychometrics ,Concordance ,Sensitivity and Specificity ,Severity of Illness Index ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Risk Factors ,Severity of illness ,Epidemiology ,Activities of Daily Living ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Brief Pain Inventory ,Young adult ,Exercise ,Aged ,Pain Measurement ,Aged, 80 and over ,Performance status ,Reproducibility of Results ,Cancer Pain ,Middle Aged ,humanities ,United States ,Clinical trial ,Anesthesiology and Pain Medicine ,Mood ,Neurology ,030220 oncology & carcinogenesis ,Physical therapy ,Quality of Life ,Female ,Neurology (clinical) ,Psychology - Abstract
Effective assessment and management of pain in patients with cancer is strengthened by the patient's report of how much pain interferes with daily functioning. This requires a clear delineation of different levels of pain interference. We derived optimal cutpoints for differentiating between mild, moderate, and severe pain interference assessed by the Brief Pain Inventory (BPI) and describe the prevalence and characteristics of pain-induced functional impairment in patients with cancer. Data were pooled across 3 Phase III pivotal trials. Patient-completed questionnaires included the EuroQol 5 dimensions questionnaire (EQ5D), Functional Assessment of Cancer Therapy-General Measure (FACT-G), and BPI. Optimal cutpoints for categorizing pain interference into 3 levels were derived using analysis of variance, with different cutpoint sets for BPI total interference (BPI-PITS, the average score of all 7 items), activity-related interference (BPI-WAW, the average score of work, general activity, and walking), and mood-related interference (BPI-REM, the average score of relations with others, enjoyment of life, and mood) as independent variables and EQ5D-visual analog scale and total FACT-G score as dependent variables. To validate the cutpoints, we assessed whether interference categories were in concordance with Eastern Cooperative Oncology Group performance status (ECOG-PS) levels. The optimal cutpoints were (2,5) for BPI-PITS, (2,6) for BPI-WAW, and (2,5) for BPI-REM. The mild (2), moderate (2-5 or 2-6), and severe (5 or6) pain interference groups were significantly concordant with ECOG-PS levels (P0.0001). We empirically derived patient-reported pain interference categories in relation to clinician-rated performance status. These cutpoints may facilitate the conduct and interpretation of clinical evaluation, symptom epidemiology, and clinical trials. more...
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- 2017
222. Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia
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Aref Al-Kali, Katalin Kelemen, Gretchen Taylor, Natalie Ertz-Archambault, Lisa Z. Sproat, Ruben A. Mesa, James M. Foran, Raoul Tibes, Janna C. Castro, Laura Finn, Robert Marino, Susanne M. Gauthier, Jeanne Palmer, Heidi E. Kosiorek, and Amylou C. Dueck more...
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Male ,Cancer Research ,medicine.medical_specialty ,Myeloid ,Azathioprine ,Myeloid Neoplasm ,Autoimmune Diseases ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Odds Ratio ,Humans ,Lupus Erythematosus, Systemic ,Psoriasis ,Cyclophosphamide ,Original Investigation ,Aged ,Retrospective Studies ,Aged, 80 and over ,Lupus erythematosus ,business.industry ,Mercaptopurine ,Myelodysplastic syndromes ,Incidence ,Myeloid leukemia ,Odds ratio ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,United States ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Azathioprine sodium ,Methotrexate ,Oncology ,030220 oncology & carcinogenesis ,Case-Control Studies ,Myelodysplastic Syndromes ,Immunology ,Female ,Mitoxantrone ,business ,Immunosuppressive Agents ,030215 immunology ,medicine.drug - Abstract
Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon.To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm.This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio.Odds ratio (OR) assessment for AID-directed therapies.Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P .001). Notable but insignificant case cohort use among cytotoxic agents was found for exposure to cyclophosphamide (OR, 3.58; 95% CI, 0.91-14.11) followed by mitoxantrone hydrochloride (OR, 2.73; 95% CI, 0.23-33.0). Methotrexate sodium (OR, 0.60; 95% CI, 0.29-1.22), mercaptopurine (OR, 0.62; 95% CI, 0.15-2.53), and mycophenolate mofetil hydrochloride (OR, 0.66; 95% CI, 0.21-2.03) had favorable ORs that were not statistically significant. No significant association between a specific length of time of exposure to an agent and the drug's category was observed.In a large population with primary AID, azathioprine exposure was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm. more...
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- 2017
223. Symptom burden profile in myelofibrosis patients with thrombocytopenia: Lessons and unmet needs
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Robyn M. Scherber, Claire N. Harrison, Ruben A. Mesa, Stefanie Slot, Junqing Xu, Jean-Jacques Kiladjian, Zefeng Xu, Pablo J. Muxi, Chiara Paoli, Harry C. Schouten, Lydia Roy, Peter A. W. te Boekhorst, Robert Peter Gale, Norman Maldonado, Thomas Lehmann, Karin Bonatz, Maria Luisa Ferrari, Federico Sackmann, Jean Christophe Ianotto, Peihong Zhang, Giovanni Barosi, Alessandro Rambaldi, Bjorn Andreasson, Peter L. Johansson, Xiujuan Sun, Allison H. Scotch, Ana Kerguelen Fuentes, Jean-Yves Cahn, Deepti Radia, Suzan Commandeur, Zhijian Xiao, Jan Samuelsson, Heidi E. Kosiorek, Francisco Cervantes, Yue Zhang, Gabriel Etienne, Heike L. Pahl, Françoise Boyer, Martin Griesshammer, Francesco Passamonti, Konstanze Döhner, Gunnar Birgegård, Sonja Zweegman, Carlos Besses, Alessandro M. Vannucchi, Dana Ranta, Frank Stegelmann, Dolores Hernández-Maraver, Amylou C. Dueck, Holly L. Geyer, Tiziano Barbui, Andreas Reiter, Hematology, Internal Medicine, Internal medicine, and CCA - Cancer Treatment and quality of life more...
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Male ,Quality of life ,medicine.medical_specialty ,Ruxolitinib ,Cancer Research ,Anemia ,Myeloproliferative neoplasm ,Myelofibrosis ,Symptomatology ,Thrombocytopenia ,Hematology ,Oncology ,Severity of Illness Index ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Weight loss ,Trombocitopènia ,Surveys and Questionnaires ,Internal medicine ,hemic and lymphatic diseases ,Severity of illness ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Leukopenia ,Mielofibrosi ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Female ,Symptom Assessment ,medicine.symptom ,business ,Needs Assessment ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Myelofibrosis is a myeloproliferative neoplasm associated with progressive cytopenias and high symptom burden. MF patients with thrombocytopenia have poor prognosis but the presence of thrombocytopenia frequently precludes the use of JAK2 inhibitors. In this study, we assessed quality of life and symptom burden in 418 MF patients with (n = 89) and without (n = 329) thrombocytopenia using prospective data from the MPN-QOL study group database, including the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and Total Symptom Score (MPN10). Thrombocytopenia, defined as platelet count 9/L (moderate 51–100 × 109/L; severe ≤50 × 109/L), was associated with anemia (76% vs. 45%, p < 0.001), leukopenia (29% vs. 11%, p < 0.001), and need for red blood cell transfusion (35% vs. 19%, p = 0.002). Thrombocytopenic patients had more fatigue, early satiety, inactivity, dizziness, sad mood, cough, night sweats, itching, fever, and weight loss; total symptom scores were also higher (33 vs. 24, p < 0.001). Patients with severe thrombocytopenia were more likely to have anemia (86% vs. 67%, p = 0.04), leukopenia (40% vs. 20%, p = 0.04), and transfusion requirements (51% vs. 20%, p = 0.002) but few differences in symptoms when compared to patients with moderate thrombocytopenia. These results suggest that MF patients with thrombocytopenia experience greater symptomatic burden than MF patients without thrombocytopenia and may benefit from additional therapies. more...
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- 2017
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224. Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PROCTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial
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Joan K. Moore, Ann Setser, Kevin L. Stephans, Lawrence Berk, Tito R. Mendoza, Amylou C. Dueck, Deborah Watkins Bruner, Sandra A. Mitchell, Ann M. O'Mara, Shannon Fogh, Albert S. DeNittis, Lori M. Minasian, Lauren J. Rogak, Stephanie L. Pugh, Andreas Rimner, Antonia V. Bennett, Thomas Gergel, Bryce B. Reeve, Ethan Basch, Andrea Denicoff, Kevin S. Roof, Marcha L. Gatewood, and Deborah Schrag more...
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Time Factors ,Apitherapy ,MEDLINE ,Pain ,Treatment of lung cancer ,Article ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Microcomputers ,Randomized controlled trial ,law ,Esophagitis ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Patient Reported Outcome Measures ,030212 general & internal medicine ,Adverse effect ,Aged ,Aged, 80 and over ,Internet ,Radiation ,business.industry ,Common Terminology Criteria for Adverse Events ,Chemoradiotherapy ,Honey ,Middle Aged ,National Cancer Institute (U.S.) ,United States ,Clinical trial ,Clinical research ,Oncology ,030220 oncology & carcinogenesis ,Physical therapy ,Feasibility Studies ,Patient Compliance ,Female ,Self Report ,Symptom Assessment ,Deglutition Disorders ,business - Abstract
Purpose To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Results Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling “too sick.” Conclusions Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies. more...
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- 2017
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225. Feasibility assessment of patient reporting of symptomatic adverse events in multicenter cancer clinical trials
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Douglas Weckstein, Pamela J. Atherton, Lori M. Minasian, Ethan Basch, William M. Sikov, Ann M. O'Mara, Rachel A. Freedman, William Kevin Kelly, Lisa A. Carey, Hope S. Rugo, Andrew L. Himelstein, Maura N. Dickler, Charles S. Kuzma, Jeffrey J. Kirshner, Drew K. Seisler, Electra D. Paskett, Rebecca S. Heist, Amylou C. Dueck, Andrea Denicoff, Lauren J. Rogak, Alan P. Venook, Deborah Schrag, Mark A. Socinski, David D. Biggs, and Diana Lake more...
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pediatrics ,Nausea ,Oncology and Carcinogenesis ,Alternative medicine ,MEDLINE ,Antineoplastic Agents ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,7.1 Individual care needs ,Clinical Research ,Internal medicine ,Neoplasms ,medicine ,80 and over ,Adverse Drug Reaction Reporting Systems ,Humans ,030212 general & internal medicine ,Patient Reported Outcome Measures ,Young adult ,Adverse effect ,Aged ,Cancer ,Quality of Health Care ,Aged, 80 and over ,business.industry ,Prevention ,Common Terminology Criteria for Adverse Events ,Middle Aged ,medicine.disease ,Clinical trial ,Oncology ,030220 oncology & carcinogenesis ,Public Health and Health Services ,Feasibility Studies ,Female ,Self Report ,Patient Safety ,Management of diseases and conditions ,medicine.symptom ,business - Abstract
IMPORTANCE: In cancer clinical trials, symptomatic adverse events (AEs), such as nausea, are reported by investigators rather than by patients. There is increasing interest to collect symptomatic AE data via patient-reported outcome (PRO) questionnaires, but it is unclear whether it is feasible to implement this approach in multicenter trials. OBJECTIVE: To examine whether patients are willing and able to report their symptomatic AEs in multicenter trials. DESIGN, SETTING, AND PARTICIPANTS: A total of 361 consecutive patients enrolled in any 1 of 9 US multicenter cancer treatment trials were invited to self-report 13 common symptomatic AEs using a PRO adaptation of the National Cancer Institute���s Common Terminology Criteria for Adverse Events (CTCAE) via tablet computers at 5 successive clinic visits. Patient adherence was tracked with reasons for missed self-reports. Agreement with clinician AE reports was analyzed with weighted �� statistics. Patient and investigator perspectives were elicited by survey. The study was conducted from March 15, 2007, to August 11, 2011. Data analysis was performed from August 9, 2013, to March 21, 2014. RESULTS: Of the 361 patients invited to participate, 285 individuals enrolled, with a median age of 57 years (range, 24-88), 202 (74.3%) female, 241 (85.5%) white, 73 (26.8%) with a high school education or less, and 176 (64.7%) who reported regular internet use (denominators varied owing to missing data). Across all patients and trials, there were 1280 visits during which patients had an opportunity to self-report (ie, patients were alive and enrolled in a treatment trial at the time of the visit). Self-reports were completed at 1202 visits (93.9% overall adherence). Adherence was highest at baseline and declined over time (visit 1, 100%; visit 2, 96%; visit 3, 95%; visit 4, 91%; and visit 5, 85%). Reasons for missing PROs included institutional errors in 27 of 48 (56.3%) of the cases (eg, staff forgetting to bring computers to patients at visits), patients feeling ���too ill��� in 8 (16.7%), patient refusal in 8 (16.7%), and internet connectivity problems in 5 (10.4%). Patient-investigator CTCAE agreement was moderate or worse for most symptoms (most �� < 0.05), with investigators reporting fewer AEs than patients across symptoms. Most patients believed that the system was easy to use (234 [93.2%]) and useful (230 [93.1%]), and investigators thought that the patient-reported AEs were useful (133 [94.3%]) and accurate (119 [83.2%]). CONCLUSIONS AND RELEVANCE: Participants in multicenter cancer trials are willing and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators. This approach may improve the precision of AE reporting in cancer trials. more...
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- 2017
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226. Public Perceptions of Presymptomatic Testing for Alzheimer Disease
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Jessica B. Langbaum, Rachel A. Lindor, Richard J. Caselli, Jason Scott Robert, Bruce R. Henslin, Gary E. Marchant, Katherine S. Hunt, and Amylou C. Dueck
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Male ,Gerontology ,Article ,Alzheimer Disease ,Prevalence ,Humans ,Medicine ,Presymptomatic Testing ,Genetic Predisposition to Disease ,Genetic Testing ,Retrospective Studies ,Genetic testing ,Multiple choice ,medicine.diagnostic_test ,business.industry ,Psychiatric assessment ,Arizona ,Retrospective cohort study ,General Medicine ,Odds ratio ,Middle Aged ,Test (assessment) ,Population Surveillance ,Biomarker (medicine) ,Female ,business ,Attitude to Health - Abstract
Objective To explore the self-expressed desire for, envisioned reaction to, and basic understanding of presymptomatic Alzheimer disease (AD)–related genetic and biomarker tests. Patients and Methods The Alzheimer's Prevention Registry is an online community of people at least 18 years of age who are interested in AD prevention research for purely informational purposes or to be considered for possible research participation in future studies. Information about presymptomatic testing and an online multiple choice format survey were posted from November 1, 2012, through June 20, 2013, on the registry website. Results Of 4036 respondents, 80.8% (3195/3952) wanted genetic testing if paid by insurance and 58.7% (2261/3851) if it would cost them at least $100. A total of 80.2% (3112/3879) wanted biomarker testing. If at high risk for AD, 90.5% (3478/3841) endorsed that they would "pursue a healthier lifestyle," but 11.6% (427/3706) endorsed "seriously consider suicide." The implication of a positive genetic test result was incorrectly understood by 13.1% (500/3812) and 32.6% (1255/3848) failed to view a positive biomarker test result as evidence of increased risk for or the presence of AD. Conclusion Despite efforts to increase public awareness of AD, our survey results suggest that greater education of the public is needed. Interested patients should probably undergo psychological screening to identify those at high risk of adverse psychological outcomes, and disclosure of presymptomatic test results should be anchored to tangible constructive action plans, such as healthy lifestyle changes, long-term care planning, and, when available and appropriate, participation in research trials. more...
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- 2014
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227. Implications of breast cancer with diabetes mellitus on patient outcomes and care
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Sravan K. Nagi Reddy, Curtiss B. Cook, Nina J. Karlin, Patricia M. Verona, and Amylou C. Dueck
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medicine.medical_specialty ,biology ,business.industry ,Hazard ratio ,medicine.disease ,Surgery ,Transthyretin ,Breast cancer ,Time to recurrence ,Metabolic control analysis ,Internal medicine ,Diabetes mellitus ,biology.protein ,Overall survival ,medicine ,business ,Glycemic - Abstract
SUMMARY Aims: The aim of this study was to determine the impact of diabetes mellitus (DM) on short-term overall survival and time to recurrence (TTR) in breast cancer patients, and examine the impact of breast cancer on glycemic control in DM. Methods: From a data set of newly diagnosed breast cancer patients (2007–2011), we identified 109 patients with DM and 109 matched controls. Results: Hemoglobin A1c among cases did not significantly change over 1 year (p = 0.10). Cases and controls showed no differences in OS (hazard ratio: 1.25; 95% CI: 0.49–3.17) during the median follow-up of 2.2 years (range: 0.1–4.9 years) and no differences in TTR (hazard ratio: 1.00; 95% CI: 0.14–7.10). Conclusion: DM did not adversely affect metabolic control, short-term OS or TTR. more...
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- 2014
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228. Reply to Comment on 'Personality Changes During the Transition from Cognitive Health to Mild Cognitive Impairment'
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Dona E.C. Locke, Blake T. Langlais, Bryan K. Woodruff, Richard J. Caselli, and Amylou C. Dueck
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Personality changes ,business.industry ,Transition (fiction) ,Medicine ,Geriatrics and Gerontology ,business ,Cognitive impairment ,Cognitive health ,Clinical psychology - Published
- 2018
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229. Expansion of Prior Existing TP53 Mutated Clones in Polycythemia Vera Patients Treated with Idasanutlin
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John Mascarenhas, Emmanuelle Verger, Jean-Jacques Kiladjian, Minal Patel, Ronald Hoffman, Min Lu, Heidi E. Kosiorek, Jane Houldsworth, Bridget K. Marcellino, Amylou C. Dueck, Noushin Farnoud, Michael Rossi, Erin McGovern, Raajit K. Rampal, Bruno Cassinat, and Meenakshi Mehrotra more...
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business.industry ,Human leukocyte interferon ,Immunology ,Myeloproliferative disease ,Cell Biology ,Hematology ,Anagrelide ,medicine.disease ,Blast Phase ,Biochemistry ,Leukemia ,Polycythemia vera ,Cancer research ,Medicine ,IDASANUTLIN ,business ,neoplasms ,Protein p53 ,medicine.drug - Abstract
Treatment of polycythemia vera (PV) with the Murine Double Minute 2 (MDM2) antagonist, idasanutlin, in a phase 1 trial was reported by our group to be well tolerated with a high overall response rate (Mascarenhas et al, Blood. 2019 Jun 5). A global, phase 2 trial is currently underway evaluating idasanutlin in hydroxyurea (HU) resistant/intolerant PV patients (NCT03287245). MDM2, a negative regulator of TP53 is upregulated in PV CD34+ cells and inhibition of MDM2 targets PV hematopoietic stem/progenitor cells (HSPC) (Lu et al, Blood. 2014;124(5):771-90). Additional trials of MDM2 antagonists have shown promise, however, there is concern that these agents have the potential to induce TP53 mutations or promote expansion of TP53 mutated clones. Resistance to MDM2 inhibitors has been evaluated in solid tumor cell lines and attributed to either the emergence of de novoTP53 mutations or the selection of TP53 mutated clones. (Michaelis et al, Cell Death Dis. 2011;2:e243; Skalniak et al, Cancers. 2018;10(11)). The effect of MDM2 inhibition on TP53 mutant clones is of particular interest in myeloproliferative neoplasms (MPNs). TP53 mutations have been reported with a low allele burden in ~15% of chronic MPN patients (Kubesova et al, Leukemia. 2018;32(2):450-61), however, TP53 loss of heterozygosity and rapid expansion of TP53 mutant clones is associated with transformation to blast phase (Lundberg et al, Blood 2014,123:2220-8). As reported, in the idasanutlin PV trial, 1/13 patients were identified to have a baseline pathogenic TP53 mutation in hematopoietic cells (VAF 5.5%), using a deep sequencing assay with a limit of detection (LOD) of VAF 0.5%. This patient was a non-responder to idasanutlin and upon treatment had an increasing JAK2V617F and TP53 mutant VAF. End of study hematopoietic cell specimens of all patients were deep sequenced (LOD 0.1%) and revealed that 4 additional patients harbored detectable TP53 mutations after idasanutlin treatment with VAF ranging from 1-12%. In each sample, 1-5 unique TP53 mutations were identified, all within the hotspot domain of the TP53 gene. Deeper sequencing of baseline and follow-up samples revealed these mutations were present at a subclonal level (VAF 0.1-5.5%) and increased over time, indicating that treatment with the MDM2 antagonist promoted expansion of already existing TP53 mutant clones (Table 1, Figure 1). None of the patients who lacked a TP53 mutation at baseline developed a TP53 mutant clone with idasanutlin treatment. There was no clear association of presence of TP53 mutations with prior HU, anagrelide or interferon exposure. There has been careful monitoring of patients to determine whether the expanding TP53 clone has clinical ramifications. Patients were on study for a median of 54 weeks (23-131). The only patient who exemplified resistance to idasanutlin was the single patient with a high burden TP53 mutation (37%). All other patients were taken off study due to patient choice/toxicity. Furthermore, all TP53 mutant and non-mutant patients have had stable disease with no evidence of progression to MF or AML. Sequencing of 2 patients post-discontinuation of idasanutlin revealed that the VAF of the TP53 mutant clones decreased since the agent was discontinued. Updated patient molecular data post-treatment discontinuation will be reported at the meeting. To investigate whether idasanutlin induces de novo TP53 mutations in PV myeloid cells we performed long term HSPC cultures. Mononuclear cells from 6 distinct PV patients were treated continuously with idasanutlin (500 nM) over ~6 weeks and DNA from both treated and untreated colonies were analyzed using next generation sequencing with a LOD of 2% VAF and no TP53 mutations were detected. The combined in vitro and clinical data reveals that treatment with an MDM2 antagonist is not associated with the emergence of de novoTP53 mutations but rather the expansion of prior existing TP53 clones. This does not appear to have clinical repercussions, however, close monitoring of these patients is essential. We recommend that patients be screened for TP53 mutations prior to treatment with an MDM2 antagonist and that if present the TP53 mutant VAF be followed during their treatment course. Resistance to MDM2 inhibition is likely dependent on the TP53 mutant VAF and further studies will need to clarify the ideal dosing schedule of MDM2 antagonists and/or combinatorial therapy to prohibit TP53 mutant clonal expansion. Disclosures Houldsworth: Cancer Genertics: Other: stock in; Sema4: Employment. Rossi:Sema4: Employment. Kiladjian:AOP Orphan: Honoraria, Research Funding; Celgene: Consultancy; Novartis: Honoraria, Research Funding. Rampal:Agios, Apexx, Blueprint Medicines, Celgene, Constellation, and Jazz: Consultancy; Constellation, Incyte, and Stemline Therapeutics: Research Funding. Mascarenhas:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Roche: Consultancy, Research Funding; Merck: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Promedior: Research Funding; Merus: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hoffman:Merus: Research Funding. more...
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230. Significance of Abnormalities of PPM1D in Myeloproliferative Neoplasms
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Harry Fruchtman, Heidi E. Kosiorek, Michal Bar-Natan, Min Lu, Amylou C. Dueck, Noushin Farnoud, Ronald Hoffman, John Mascarenhas, Vesna Najfeld, Raajit K. Rampal, Joseph Tripodi, and Bridget K. Marcellino more...
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Oncology ,medicine.medical_specialty ,Acute leukemia ,Myeloid ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Loss of heterozygosity ,Leukemia ,Polycythemia vera ,medicine.anatomical_structure ,Internal medicine ,Chromosome abnormality ,medicine ,Myelofibrosis ,business ,Myeloproliferative neoplasm - Abstract
The TP53 pathway has been shown to be dysregulated in myeloproliferative neoplasms (MPN) through several different mechanisms, including TP53 mutations, TP53 deletions and Murine Double Minute 2 (MDM2) overexpression. Downregulation of the TP53 pathway likely plays a role in MPN progression as evidenced by the association of TP53 loss of heterozygosity with transformation to acute leukemia and the presence of inactivating mutations of TP53 found in a proportion of MPN-blast phase (MPN-BP) cases (Kubesova et al, Leukemia. 2018;32(2):450-61). Furthermore, MDM2 inhibition induces TP53 pathway upregulation and consequent targeting of hematopoietic stem and progenitor cells in polycythemia vera (PV) and myelofibrosis (MF). The MDM2 inhibitor, idasanutlin, has shown activity in a Phase I trial of high-risk PV patients (Mascarenhas et al. Blood. 2019 Jun 5). An additional regulator of TP53 is protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D) which by dephosphorylating TP53 and stabilizing MDM2 regulates the DNA damage response pathway and apoptosis. Somatic activating mutations of PPM1D are present in both solid and hematologic malignancies and are specifically associated with therapy-related myeloid disorders (Hsu et al. Cell Stem Cell. 2018 Nov 1;23(5):700-13). Grinfeld et al. (N Engl J Med. 2018 Oct 11;379(15):1416-30) recently reported that in their genomic analysis of 2035 MPN patients, PPM1D was the eighth most common mutated gene in MPNs at 1.9% frequency. To determine whether there was an association of PPM1D mutations with MPNs we analyzed the genomic data of patients who participated in several clinical trials executed by the Myeloproliferative Neoplasm Research Consortium (MPN-RC). Of 89 MPN-BP patients, 5 patients harbored a PPM1D mutation with a median variant allele frequency (VAF) of 17%. In comparison, 4 out of 135 high risk PV and ET patients harbored a PPM1D mutation with a median VAF of 24%. All mutations were truncating which is consistent with previous reports of PPMID mutations in malignancies. The PPM1D gene is located on the long arm of chromosome 17 (17q23.2) and we hypothesized that cytogenetic aberrations involving this gene locus might also contribute to abnormalities of PPM1D function. Through analysis of our cytogenetic database, 16/1,124 (1.4%) MPN patients were found to have cytogenomic abnormalities involving the region containing the PPM1D gene. Eight of these patients had karyotypic abnormalities, including 3 pts with isochromosome 17q resulting in a gain of 17q and a loss of 17p, including the TP53 gene. The other 4 patients had structural variations of 17q which might lead to aberrant expression of PPM1D. One patient by FISH analysis had gain of 17q. Ten patients had cytogenomic aberrations of 17q detected through analysis of array comparative genomic hybridization and single nucleotide polymorphism (aCGH+SNP), 2 of which had concurrent karyotypic abnormalities of 17q. All patients had a gain or copy neutral loss of heterozygosity (cnLOH) of the 17q22-24.2 region. CnLOH of this region could lead to aberrant overexpression of the PPM1D gene. One of the 8 patients with cnLOH of 17q harbored a PPM1D mutation. Of the 16 patients with 17q cytogenomic abnormalities, 7 (44%) had MPN-BP and 7 (44%) patients had ET or ET that progressed to myelofibrosis (MF) or MPN-BP indicating an association of these abnormalities with advanced disease. By quantitative real time-PCR we determined the PPM1D transcript levels in mononuclear cells from 31 MPN patients without known PPM1D mutations (7 polycythemia vera (PV), 6 ET, 14 MF, 4 MPN-BP) and compared the transcript levels to mononuclear cells from healthy control patients. Forty-two percent (13/31) patients had overexpression of PPM1D (>1.5 fold increase range). Fold increase ranged from 1.5-8 and overexpression was present in the following diagnoses: 4/7 PV, 1/6 ET, 8/14 MF and 0/4 MPN-BP. We have provided evidence that a number of abnormalities of PPM1D including activating mutations, cytogenetic aberrations and transcript overexpression are present in a significant proportion of MPN patients. These abnormalities in PPM1D can be additional events that lead to the downregulation of TP53 and contribute to MPN disease progression. We propose that inhibitors of PPM1D may be used in combination with other drugs that upregulate TP53 to treat MPN patients. Disclosures Rampal: Constellation, Incyte, and Stemline Therapeutics: Research Funding; Agios, Apexx, Blueprint Medicines, Celgene, Constellation, and Jazz: Consultancy. Mascarenhas:CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Roche: Consultancy, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Promedior: Research Funding; Merus: Research Funding. Hoffman:Merus: Research Funding. more...
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231. A Standardized Equation Model of Quality of Life in Myeloproliferative Neoplasms
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Holly L. Geyer, Hans Carl Hasselbalch, Martin M. Goros, Jonathan Gelfond, Robyn M. Scherber, Ruben A. Mesa, Amylou C. Dueck, and Sarah Friis Christensen
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cancer ,Myeloproliferative disease ,Cell Biology ,Hematology ,Profile of mood states ,medicine.disease ,Biochemistry ,Quality of life (healthcare) ,Internal medicine ,medicine ,business ,Apnea of prematurity - Abstract
Background: Quality of life (QOL) is predictive of survival in many malignancy types, including myeloproliferative neoplasms (MPNs; Scherber 2017, Sloan 2012, Montazeri 2009, Nilsson 2017). We have previously characterized that an association exists between symptom burden and QOL among MPN patients, but due to the disease specificity of symptoms, symptoms rather than QOL remains a key therapeutic endpoint (Scherber 2017, NCCN Guidelines). Despite these advancements, our understanding of the extent that different patient and disease characteristics, including symptoms, contribute to overall QOL has remained elusive. In this analysis, we utilized information from a large survey of MPN patients to develop a model of QOL that establishes the degree that individual variables contribute to QOL, including psychosocial variables, comorbidities, and MPN disease symptoms. Methods: The FATIGUE survey of MPN patients (Scherber 2016) investigated self-reported symptoms using the MPN10 (Scherber 2012), depression utilizing the Profile of Mood States-Brief (POMS-B, McNair 1971), Patient Health Questionnaire (PHQ-2, Kroenke 2003) and Mental Health Inventory (MHI-5, Berwick 1991), and QOL utilizing a single numeric analog scale (range 0-10) regarding overall quality of life. Linear regression analysis was utilized to establish the relationship between individual symptoms and QOL, and a structural equation model (SEM) was used to identify complex relationships among patient demographics, behavioral factors, comorbidities, and QOL. Results: A total of 914 patients from the online survey lived in the USA and provided data for this analysis. Average age was 62 with 67% of patients being female and the mean BMI was 25. Education varied across middle school or high school education (22%), undergraduate or college degree (44%), masters (26%), to doctorate (8%). 43% of respondents were employed. Fatigue (β coefficient 0.23, p SEM Model: We developed the SEM model in Figure 1. Out of all variables analyzed, MPN total symptom burden demonstrated the strongest association with (β 0.89) with QOL, followed by depression (β 0.76). Comorbidities, including COPD and renal issues, age, and body mass index abnormalities had some impact on symptoms (all β Conclusions: Previous clinical trials of JAK inhibition have targeted improvement in symptoms as a key endpoint, and ultimately demonstrated improvements in overall survival. The mechanism of this survival benefit has not been fully explored. This analysis suggests that symptoms and mood are strongly associated and potentially a major contributor to QOL among MPN patients, whereas other major comorbidities and age are not as strongly correlated. Efforts are underway to analyze more comprehensive datasets to better understand the role of other variables, including marriage status and financial concerns, on QOL. Disclosures Scherber: Blueprint: Other: Ad board; Incyte: Consultancy; Gilead: Consultancy. Hasselbalch:Novartis: Research Funding; AOP Orphan Pharmaceuticals: Other: Data monitoring board. Mesa:Baxalta: Consultancy; LaJolla: Consultancy; Genentech: Consultancy; Celgene Corporation: Research Funding; Samus: Research Funding; AbbVie: Research Funding; NS Pharma: Research Funding; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses; CTI: Research Funding; Galena Biopharma: Consultancy; Pfizer: Research Funding; Incyte: Other: travel, accommodations, expenses, Research Funding; Genotech: Research Funding; AOP Orphan Pharmaceuticals: Honoraria, Other: travel, accommodations, expenses; PharmaEssentia: Research Funding; Gilead Sciences: Research Funding; Promedior: Research Funding; Shire: Honoraria; Sierra Oncology: Consultancy. more...
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232. Patient Experience of Chimeric Antigen Receptor (CAR)-T Cell Therapy Vs. Stem Cell Transplant: Longitudinal Patient Reported Adverse Events, Cognition and Quality of Life
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Jose C. Villasboas, Surbhi Sidana, Shaji Kumar, Angela Dispenzieri, Stephen M. Ansell, Yi Lin, Andrea L. Cheville, Rahma Warsame, Mustaqeem A. Siddiqui, Morie A. Gertz, Jonas Paludo, S. Vincent Rajkumar, Michelle Burtis, Joan M. Griffin, N. Nora Bennani, Kathleen J. Yost, Carrie A. Thompson, Amylou C. Dueck, and Gita Thanarajasingam more...
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Oncology ,medicine.medical_specialty ,Palliative care ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biochemistry ,Chimeric antigen receptor ,Cell therapy ,Quality of life ,Internal medicine ,Patient experience ,medicine ,Stem cell ,Adverse effect ,business ,health care economics and organizations - Abstract
Introduction: With the expanding use of CAR-T cell therapy, which is associated with serious adverse effects (AEs), there is a need to characterize the patient's experience over time to guide patient/provider education, and help optimize symptom management. This study reports on longitudinal evaluation of patient-reported quality of life (QOL) and symptom burden of CAR-T cell therapy compared with established forms of cellular therapy i.e autologous stem cell transplant (autoSCT) and allogeneic SCT (alloSCT). Methods: Patients with hematologic malignancies were prospectively recruited in three cohorts: CAR-T, autoSCT and alloSCT. The primary endpoint was change in QOL from baseline, using the FACT-G questionnaire. Secondary endpoints were patient-reported AEs (PRO-AEs) using 7 items from the PRO-CTCAE and assessment of cognition/memory using the NeuroQOLv2 questionnaire. PRO-CTCAE data was graded using a composite score (combining frequency, severity, and interference) and rates, using a method adjusting for pre-existing baseline symptoms, were compared using Fisher's exact test. We also evaluated the time profile of PRO-AEs using the Toxicity over Time (ToxT) approach, a longitudinal approach to AE analysis (Thanarajasingam Lancet Onc 2016). Patients completed questionnaires at baseline, week 2 and monthly thereafter. Results: From 07/2018 to 06/2019, 93 patients were recruited (CAR-T: 20; autoSCT: 37; alloSCT: 36). At data cut-off, week 2 and months 1, 2 and 3 data were available in 74, 62, 46 and 35 patients, respectively. There was no difference in patient age across the 3 groups (median age 63, range 23-77; p=0.26). Baseline QOL by FACT-G total score (mean=83.4, SD=14.7; p=0.77), side effect bother by FACT-G GP5 (66/93 [71%] a little bit or less; p=0.72), activities and function (70/93 [75%] fairly normal activities or no limitations; p=0.68) and cognition by NeuroQOL t-score (mean=52.2, SD=8.13; p=0.39) were similar across 3 groups at baseline. The CAR-T group experienced significantly less worsening in QOL (FACT-G) than both autoSCT and alloSCT groups (Fig. 1a). Worsening in overall QOL nadired at week 2, after which QOL gradually returned to baseline in all groups. When comparing changes from baseline in overall QOL, statistically significant differences between groups were evident at week 2 (CAR-T vs autoSCT p The most common PRO-AEs (Table 1) in the CAR-T group were decreased appetite (59%), diarrhea (53%) and fatigue (44%). There was no statistically significant difference in the PRO-AEs between CAR-T and autoSCT groups. However, patients undergoing alloSCT had significantly higher proportion of PRO-AEs vs the CAR-T group, except for neuropathy and sad feelings. AutoSCT and alloSCT groups had significant worsening of FACT-G side effect bother (GP5) at week 2, which was significantly different from that of the CAR-T group, following which the side effect bother gradually returned to baseline. (Fig. 1c) This was the first application of ToxT to PRO-CTCAE data (graphs not shown). Bar charts of maximum grade frequency and stream plots of mean grade over time demonstrate that mouth sores, fatigue, diarrhea and decreased appetite peak at week 2 and improve by month 3, and are of lesser severity in the CAR-T vs autoSCT and alloSCT groups. The trajectory of maximum grade across all PRO-AEs was similar by group as overall side effect burden by FACT-G GP5. Heatmap visualization demonstrated significant intra-patient variability and allowed inspection of data completeness. No difference in cognition and memory was observed across the three groups over the first three months. (Fig. 1d) Conclusion: This study is the first to our knowledge to provide comprehensive PRO data comparing QOL, patient-reported AEs and cognition in CAR-T cell therapy vs. auto- and alloSCT, and the first application of ToxT to PRO-CTCAE data. Short-term QOL, including physical and functional WB domains was better in the CAR-T group vs. SCT groups. These data can serve as a guide for patient education and symptom management in CAR-T cell therapy. Co-senior authors: SKK & ACD Disclosures Paludo: Celgene: Research Funding; Celgene: Research Funding; Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding. Gertz:Johnson and Johnson: Speakers Bureau; Celgene: Consultancy; Appellis: Consultancy; Amyloidosis Foundation: Research Funding; DAVA oncology: Speakers Bureau; Physicians Education Resource: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Medscape: Consultancy, Speakers Bureau; Prothena Biosciences Inc: Consultancy; Teva: Speakers Bureau; Research to Practice: Consultancy; Annexon: Consultancy; Alnylam: Consultancy; International Waldenstrom Foundation: Research Funding; Ionis/Akcea: Consultancy; Spectrum: Consultancy, Research Funding; i3Health: Other: Development of educational programs and materials; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Springer Publishing: Patents & Royalties. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Ansell:Trillium: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding. Bennani:Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Kite Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. more...
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233. Identifying Cytokine Biomarkers of Response to Pegylated-Interferon Therapy in Polycythemia Vera and Essential Thrombocythemia: Correlative Analysis from the MPN-RC 111/112 Trials
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Aishwarya Krishnan, Heidi E. Kosiorek, Abdulraheem Yacoub, Ross L. Levine, Ronald Hoffman, Andrew Dunbar, Rona Singer Weinberg, Erin McGovern, Young Park, John Mascarenhas, Raajit K. Rampal, Minal Patel, and Amylou C. Dueck more...
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medicine.medical_specialty ,business.industry ,Essential thrombocythemia ,Immunology ,Alpha interferon ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Discontinuation ,Cytokine release syndrome ,European LeukemiaNet ,Pegylated interferon ,Internal medicine ,Cohort ,Medicine ,business ,Adverse effect ,health care economics and organizations ,medicine.drug - Abstract
Background: Pegylated Interferon-alpha (PEG-IFNa) improves hematologic parameters and reduces mutant allele fraction in patients with myeloproliferative neoplasms (MPNs); however, widespread clinical use is limited by frequent discontinuation due to side effects. Identifying biomarkers of response to PEG-IFNa therapy might identify patient subsets most likely to derive benefit from this therapy. Serum pro-inflammatory cytokine levels are increased in MPN patients and associated with adverse clinical outcomes. The effect of PEG-IFNa therapy on cytokine levels in MPN patients and correlation with clinical response has not been elucidated. We hypothesized that identification of cytokine signatures could predict for clinical/molecular response to PEG-IFNa in MPNs. Methods: Pre- and post-treatment serum samples were collected from available patients enrolled on the Myeloproliferative Disorders Research Consortium (MPD-RC) 111/112 trials-multicenter studies assessing efficacy of PEG-IFNa in patients with high-risk polycythemia vera/essential thrombocythemia either up front or in the setting of hydroxyurea failure/intolerance. Serum was prepared using the Millipore MAP Human 41-Cytokine Magnet Bead System (Millipore; Cat:HCYTOMAG-60K) and run on the Luminex FLEXMAP 3D platform. Data was analyzed using Luminex xPonent 4.3 software. Correlative mutational data on 156 genes implicated in myeloid malignancies was also available for all patients. Age-matched serum from healthy individuals (N=6) was obtained from AllCellsTM for use as wild-type (WT) controls. Baseline cytokine samples were compared between groups of interest by use of Wilcoxon rank-sum test. Change from baseline in cytokines for each group were compared to the null hypothesis of zero change. P values Results: Pre- and post-treatment serum samples were available on 29 MPN patients from the MPN-RC 111/112 cohorts. 21 patients were classified as complete responders (CRs) vs. 8 non-responders (NRs) using European LeukemiaNet criteria. Baseline cytokine levels were generally increased in both CRs and NRs compared to WT, including significant increases in Eotaxin (p=0.023), IL3 (p=0.048), IP10 (p=0.04), and TNFa (p=0.006) (Table 1), as well as a non-significant trend increase in IL8 (p=0.076). Notably, other cytokines were decreased at baseline in comparison to WT, including EGF (p Conclusions: Preliminary findings suggest individual cytokines are affected by PEG-IFNa in MPNs. Furthermore, baseline levels of GRO, MDC, PDGFaabb, and IP10 correlate with response to PEG-IFNa. These data may identify MPN patients most likely to respond to PEG-IFNa therapy and those for whom this therapy may be most appropriate. Further analysis with a larger cohort of treatment-naïve patients is underway to validate these findings and identify additional molecular and cytokine signatures of response to PEG-IFNa therapy. Disclosures Yacoub: Agios: Speakers Bureau; Hylapharm: Equity Ownership; Dynavax: Equity Ownership; Cara: Equity Ownership; Ardelyx: Equity Ownership; Incyte: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Mascarenhas:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Roche: Consultancy, Research Funding; Merck: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Promedior: Research Funding; Merus: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees. Levine:Lilly: Honoraria; Qiagen: Membership on an entity's Board of Directors or advisory committees; Imago Biosciences: Membership on an entity's Board of Directors or advisory committees; Loxo: Membership on an entity's Board of Directors or advisory committees; Prelude Therapeutics: Research Funding; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Research Funding; Gilead: Consultancy; Amgen: Honoraria; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Novartis: Consultancy. Hoffman:Merus: Research Funding. Rampal:Constellation, Incyte, and Stemline Therapeutics: Research Funding; Agios, Apexx, Blueprint Medicines, Celgene, Constellation, and Jazz: Consultancy. more...
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234. Final Results of Prospective Treatment with Pegylated Interferon Alfa-2a for Patients with Polycythemia Vera and Essential Thrombocythemia in First and Second-Line Settings
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Ellen K. Ritchie, Amylou C. Dueck, Claire N. Harrison, Vittorio Rosti, Mary Frances McMullin, Craig M. Kessler, Joseph Vadakara, Lonette Sandy, Alessandro Rambaldi, Damiano Rondelli, Richard T. Silver, Olivia Siwoski, Tiziano Barbui, Maria R. Baer, Alessandro M. Vannucchi, Marina Kremyanskaya, Mohamed E. Salama, Abdulraheem Yacoub, Heidi E. Kosiorek, Adam J. Mead, Ronald Hoffman, Casey O'Connell, Josef T. Prchal, Ruben A. Mesa, Jean-Jacques Kiladjian, Elliott F. Winton, Joanne Ewing, Raajit K. Rampal, John Mascarenhas, Murat O. Arcasoy, Elizabeth O. Hexner, Valerio De Stefano, and Rona Singer Weinberg more...
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medicine.medical_specialty ,Intention-to-treat analysis ,Surrogate endpoint ,Essential thrombocythemia ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Pegylated interferon alfa-2a ,Second line ,Polycythemia vera ,Internal medicine ,medicine ,Adverse effect ,business ,Peginterferon alfa-2a ,medicine.drug - Abstract
Background Interferons are recognized as active agents in the treatment of patients with high risk essential thrombocythemia (ET) or polycythemia vera (PV), both in the upfront setting as well as beyond. Several trials have shown high rates of hematologic and molecular responses with the use of interferons, however, data on direct comparison of interferon activity in patients with early disease in comparison to patients refractory or resistant to prior therapies, such as hydroxyurea (HU) are lacking. We conducted a controlled analysis of the activity of pegylated interferon alfa-2a (PEG) in two prospective parallel clinical trials conducted in these two unique patient populations. Methods The MPD-RC 111 (NCT01259817) was an international, multicenter, phase 2 open-label clinical trial that evaluated PEG therapy in patients with high risk PV and high-risk ET who were either refractory or intolerant (R/I) to HU by modified ELN criteria. The MPD-RC 112 trial (NCT01258856) enrolled patients with high risk ET/PV who were treatment-naïve (TN) (HU Results Patients ET: 39 TN and 65 R/I ET patients were available for this analysis. Median disease duration was 2.9 months in TN and 37.3 months in R/I patients. Baseline characteristics and demographics were similar in the two cohorts except lower baseline hemoglobin level in RI patients. (Table1A) PV: 43 TN and 50 R/I PV patients were included. Median disease duration was 2.5 months in TN and 54.8 months in R/I patients. Baseline characteristics only differed by lower frequency of phlebotomy rate in R/I patients. (Table1B) Baseline symptoms scores and quality of life were similar in TN and RI groups (Table 2) Response ET: CR/PR/ORR at 12 months were observed in 43.1%/26.2%/69.2% in R/I ET patients and in 43.6%/25.6%/69.2% in TN ET patients (p=0.99 for ORR). (Table 3, Figure 1) PV: CR/PR/ORR at 12 months were observed in 22%/38%/60% in R/I PV patients, and in 27.9%/58.1%/86% in TN PV patients (p=0.005 for ORR). (Table 3, Figure 1) Safety PEG was equally well tolerated throughout both treatment groups with treatment discontinuation due to adverse events occurring in 14.6% in TN patients and 13.9% in R/I patients. The mean (SD) dose of PEG was 102.7 (52.3) mcg in R/I ET patients and 128.7mcg (46.4) in R/I PV patients. For TN patients, mean dose was 85.7mcg (59.7) in ET and 93.5 mcg (44.0) in PV. Adverse events were consistent with historic reports of PEG use and the distribution of events was similar in R/I and TN patients. (Table 4) Conclusion This intention to treat response analysis included TN and R/I ET and PV patients with balanced baseline characteristics who received prospective therapy with PEG. Patients with ET had a higher overall response rate at 12 months that was equivalent in patients who were treatment-naïve and in patients who were intolerant or refractory to HU. By contrast, patients with PV who were treatment-naïve had a higher ORR than patients those intolerant or refractory to HU. We conclude that treatment with PEG is an effective therapeutic option both treatment naïve PV and ET as well as those previously treated with HU, however PEG as a second line agent is especially effective in ET patients. Disclosures Yacoub: Hylapharm: Equity Ownership; Agios: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Ardelyx: Equity Ownership; Cara: Equity Ownership; Dynavax: Equity Ownership. Mascarenhas:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Roche: Consultancy, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Promedior: Research Funding; Merus: Research Funding. Mesa:AbbVie: Research Funding; Samus: Research Funding; Incyte: Research Funding; Sierra Onc: Consultancy; Genotech: Research Funding; Promedior: Research Funding; Novartis: Consultancy; Celgene: Research Funding; CTI Biopharma: Research Funding; La Jolla Pharma: Consultancy. Rampal:Agios, Apexx, Blueprint Medicines, Celgene, Constellation, and Jazz: Consultancy; Constellation, Incyte, and Stemline Therapeutics: Research Funding. Silver:PharmEssentia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. McMullin:Daiko Sanyo: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Speakers Bureau; Italopharma: Membership on an entity's Board of Directors or advisory committees. Ewing:Novartis: Honoraria, Other: Meeting attendance sponsorship ; Bristol Myers-Squibb: Other: Meeting attendance sponsorship . O'Connell:Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Shionogi: Membership on an entity's Board of Directors or advisory committees. Mead:Bristol Myers-Squibb: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel/accommodation expenses, Research Funding, Speakers Bureau; CTI: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Pfizer: Consultancy. De Stefano:Alexion: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Baer:Astellas: Research Funding; Al Therapeutics: Research Funding; Abbvie: Research Funding; Incyte: Research Funding; Forma: Research Funding; Kite: Research Funding; Takeda: Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kremyanskaya:La Jolla: Consultancy; Incyte, Celgene, Constellation, Protagonist.: Research Funding. Hexner:novartis: Research Funding. Rambaldi:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, travel support. Ritchie:Genentech: Other: Advisory board; Tolero: Other: Advisory board; agios: Other: Advisory board; Pfizer: Other: Advisory board, travel support; Celgene: Other: Advisory board; Jazz Pharmaceuticals: Research Funding; Celgene, Novartis: Other: travel support; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; Celgene, Incyte, Novartis, Pfizer: Consultancy. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Honoraria, Research Funding; Celgene: Consultancy. Harrison:Promedior: Honoraria; Incyte: Speakers Bureau; Sierra Oncology: Honoraria; Celgene: Honoraria, Speakers Bureau; Janssen: Speakers Bureau; CTI: Speakers Bureau; AOP: Honoraria; Shire: Speakers Bureau; Roche: Honoraria; Gilead: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Hoffman:Merus: Research Funding. OffLabel Disclosure: Pegylated Interferon Alfa-2a for in Patients with Polycythemia Vera or Essential Thrombocythemia more...
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235. PCN457 THE SISAQOL INITIATIVE: ESTABLISHING INTERNATIONAL STANDARDS AND RECOMMENDATIONS FOR THE ANALYSIS OF PATIENT-REPORTED OUTCOMES AND QUALITY OF LIFE DATA IN ONCOLOGY RANDOMIZED CLINICAL TRIALS
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Carolyn C. Gotay, E. M. Basch, C. Quinten, W.S. Ashley, Rajeshwari Sridhara, Ingolf Griebsch, Laura Lee Johnson, Galina Velikova, Michael Koller, M. J. B. Taphoorn, Martine Piccart, Elisabeth Piault-Louis, Francesca Martinelli, Mogens Grønvold, Jaap C. Reijneveld, Katherine M. Soltys, Jeff A. Sloan, Madeleine King, Laurence Collette, Daniel William O'Connor, Kathy Oliver, Alicyn Campbell, S. Christoph, Daniel C. Malone, Amylou C. Dueck, Madeline Pe, Melanie Calvert, Lien Dorme, Nancy Devlin, A. Bottomley, C. Coens, Sandra A. Mitchell, Kim Cocks, Charles S. Cleeland, Henning Flechtner, Paul G. Kluetz, and Jammbe Z. Musoro more...
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medicine.medical_specialty ,business.industry ,Health Policy ,Public health ,Public Health, Environmental and Occupational Health ,law.invention ,Business economics ,Quality of life (healthcare) ,Randomized controlled trial ,law ,Family medicine ,medicine ,business ,Health policy - Published
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236. Evaluation of minimal important difference (MID) for the European organisation for research and treatment of cancer (EORTC) pancreatic cancer module (PAN26) in patients with surgically resected pancreatic adenocarcinoma
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Margaret A. Tempero, Hanno Riess, Amylou C. Dueck, D-Y. Oh, T. Macarulla Mercade, C.-P. Li, J. Marcus, Andrew Eugene Hendifar, Michele Reni, M. Botterman, N. Joshi, Brian Lu, and J. Braverman
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0301 basic medicine ,Health related quality of life ,medicine.medical_specialty ,business.industry ,Bowel habit ,Stock options ,Hematology ,Shire ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Quality of life ,Pancreatic pain ,030220 oncology & carcinogenesis ,Family medicine ,medicine ,In patient ,business - Abstract
Background PAN26 was developed as a supplement to the EORTC QLQ-C30 to assess pancreatic cancer–specific health-related quality of life (HRQoL) issues. Despite its use in clinical trials, PAN26 MID has not been established. In undertaking the most comprehensive evaluation to date of PAN26’s measurement properties in patients with surgically resected pancreatic cancer receiving adjuvant therapy, we used distribution-based minimum detectable change (MDC) and anchor-based methods to determine PAN26 scale MIDs using the data collected during the Adjuvant Pancreatic Adenocarcinoma Clinical Trial (APACT). Table . 687P PAN26 anchor (QLQ-C30 overall health) and distribution-derived MID Scale/Item Anchor Distribution Estimate SE 1/2 BLSD SEM Altered bowel habit – a 12.5 11.8 Body image 6.4 0.3 13.1 13.5 Digestive symptoms 6.0 0.3 13.4 16.2 Hepatic – a 7.6 11.4 Pancreatic pain 5.6 0.2 9.7 9.7 Satisfaction with health care – a 12.1 15.3 Sexual dysfunction 5.4 0.4 17.3 19.7 Bloated 4.9 0.3 12.8 15.9 Dry mouth 5.1 0.3 13.4 15.6 Gas – a 14.5 16.2 Indigestion 4.8 0.3 12.8 15.7 Limited activities 8.0 0.3 15.4 21.7 Low weight 5.3 0.3 14.8 20.5 Taste different 7.5 0.3 13.6 19.7 Troubled by tx adverse events 8.8 0.3 12.6 15.8 Weak arms/legs 9.1 0.3 13.1 15.7 Worried about future health 6.3 0.3 15.5 16.3 BLSD, baseline standard deviation; SE, standard error; SEM, standard error of measurement (based on intraclass correlation). a Low r ( Methods PAN26 and QLQ-C30 scores were assessed in 12-week intervals at screening (BL), middle and end of treatment, and up to 2.5 years of follow-up. MDC values were calculated via BL standard deviation (SD) and reliability-biased standard error of measurement approaches. Anchor-based values were determined via a linear mixed model in which QLQ-C30 overall health (OH; Item 29) served as a serial patient global impression of severity anchor for predicting PAN26 scores. Pattern-mixture models (PMM) were fit to assess the impact of attrition on estimates. Results MDC values were in the 12 to 15 range (Table). These findings were consistent with SD-based values inferred from earlier studies, although our results extended to standalone items. Anchor-based MIDs were almost twice as sensitive as MDC, with values in the 5 to 9 range (PMM values almost identical). Anchor values could not be inferred for the PAN26 bowel, hepatic, and healthcare scales and gas item due to their low (r Conclusions The MID estimates for PAN26 subscales can help clinicians and researchers interpret the changes in HRQoL and determine sample sizes in the design of future clinical trials. Editorial acknowledgement Pharmerit International. Legal entity responsible for the study The authors. Funding Celgene Corporation. Disclosure M. Reni: Non-remunerated activity/ies, Personal Fees: Celgene, Baxalta, Shire, Eli Lilly, Pfizer, Novocure, Novartis, AstraZeneca. J. Braverman: Full / Part-time employment: Celgene Corporation. T. Macarulla Mercade: Honoraria (self): Roche, Sanofi, Tesaro, Shire, Genzyme; Advisory / Consultancy: Baxalta, Celgene, H3B, QED, Shire; Speaker Bureau / Expert testimony: Celgene, Sanofi/Aventis, Shire; Research grant / Funding (self): Agios, Aslan, AstraZeneca, Bayer, Celgene, Genetech, Hallozyme, Immunomedics, Lilly, Merimarck, Millennium, Novartis, Novocure, Pfizer, Pharmacyclics, Roche; Travel / Accommodation / Expenses: Bayer, H3B, Merck, Sanofi. D. Oh: Advisory / Consultancy: Genentech/Roche, AstraZeneca, Novartis, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks; Research grant / Funding (institution): AstraZeneca, Novartis, Array, Eli Lilly. H. Riess: Non-remunerated activity/ies, Personal Fees: Celgene, Roche, Shire. M.A. Tempero: Advisory / Consultancy: AbbVie, Advance Medical, BioPharm Communications, BMS, Celgene, Eisai, Ignyta, Pharmacyslics, Pharmcyte Biotech, Tocagen; Advisory / Consultancy: AstraZeneca, CPRIT, Immunovia; Research grant / Funding (institution): Halozyme. B. Lu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Celgene Corporation. J. Marcus: Full / Part-time employment: Pharmerit international; Advisory / Consultancy, Research grant / Funding (self): Celgene Corporation. N. Joshi: Full / Part-time employment: Pharmerit International; Advisory / Consultancy: Celgene Corporation. M. Botterman: Honoraria (institution): Celgene, Bayer, Daiichi, BMS. All other authors have declared no conflicts of interest. more...
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237. Radiation Therapy Treatment Effect on Overall Survival: Results of a Prospective Registry of Patient-Reported Outcomes in a Large-Volume Multi-Site Practice
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Amylou C. Dueck, Thomas B. Daniels, K. Klein, Thomas M. Pisansky, Lisa A. McGee, Kimberly S. Corbin, Christopher L. Hallemeier, A. Amundson, S.S. Park, C.R. Choo, Todd A. DeWees, Brian J. Davis, William W. Wong, Ivy A. Petersen, Thomas J. Whitaker, N.N. Laack, Robert W. Mutter, Michael A. Golafshar, Carlos Vargas, and B.J. Stish more...
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Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,medicine.medical_treatment ,Multi site ,Radiation therapy ,Oncology ,Overall survival ,Medicine ,Radiology, Nuclear Medicine and imaging ,Treatment effect ,Radiology ,business ,Volume (compression) - Published
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238. P1-480: APOE-DEPENDENT VERBAL LEARNING EFFECTS IN COGNITIVELY UNIMPAIRED OLDER ADULTS
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Dona E.C. Locke, Amylou C. Dueck, Bryan K. Woodruff, Yi Su, Michael Malek-Ahmadi, Bruce R. Henslin, Vivek Devadas, Eric M. Reiman, and Richard J. Caselli
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Apolipoprotein E ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,medicine.medical_specialty ,Developmental Neuroscience ,Epidemiology ,Health Policy ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Audiology ,Psychology ,Verbal learning - Published
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239. Quality of life (QOL) in patients undergoing CAR-T therapy versus stem cell transplant (SCT)
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Jose Villasboas Bisneto, Shaji Kumar, Gita Thanarajasingam, Kathleen J. Yost, Rahma Warsame, Mustaqeem A. Siddiqui, Yi Lin, Joan M. Griffin, N. Nora Bennani, Surbhi Sidana, Angela Dispenzieri, Patrick B. Johnston, Amylou C. Dueck, Andrea L. Cheville, Michelle Burtis, Carrie A. Thompson, Morie A. Gertz, Jonas Paludo, Stephen M. Ansell, and S. Vincent Rajkumar more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Cell therapy ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,In patient ,Car t cells ,Stem cell ,business ,Adverse effect ,030215 immunology - Abstract
6594 Background: Given the significant short-term adverse effects of CAR-T cell therapy, it is important to evaluate its impact on QOL of patients in addition to efficacy, compared with established forms of cellular therapy like SCT. Methods: QOL was evaluated prospectively in patients undergoing CAR-T therapy, autoSCT & alloSCT for hematologic malignancies. QOL was assessed with FACT-G at baseline, 2 weeks and monthly for 6 months thereafter. Functional well-being (FWB), physical WB (PWB) emotional WB (EWB) & social WB (SWB) and change over time were compared across groups. Results: 45 patients were recruited (CAR-T: 10; Auto SCT: 22; Allo SCT: 13) with follow up for 2 weeks & 1 month available for 23 &15 patients, respectively (Table). There was no statistically significant difference in baseline total QOL scores (p=0.13), though scores were lower in the alloSCT group (85,84,68). EWB &FWB were numerically higher in the CAR-T group, followed by autoSCT group. At 2 weeks, overall QOL decreased by only 2 points in CAR-T group vs. 22 & 18 points in auto & alloSCT groups (p=0.09). Change in PWB vs. baseline was less pronounced in the CAR-T group (-1, -9, -13, p=0.03). At 1 month, overall QOL was 6 points lower than baseline in CAR-T group vs. 3 and 14 points lower in auto & alloSCT groups, respectively (p=0.34). Importantly, PWB had at least returned to baseline in the CAR-T group. Conclusions: Preliminary data show that patients undergoing CAR-T cell therapy do not experience a more significant decline in QOL compared with auto & allo SCT, and may experience fewer physical side effects in the short-term. Accrual & follow-up are ongoing. [Table: see text] more...
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240. Use, attitudes, and perceptions of tumor genomic testing: Survey of TAPUR physicians
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Carol B. White, Richard L. Schilsky, Amylou C. Dueck, Allison W. Kurian, Nicole L. Butler, Sarah T. Hawley, Mary Lou Smith, Pam K. Mangat, Elda Railey, Suanna S. Bruinooge, and Stacy W. Gray
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Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,Perception ,media_common.quotation_subject ,Family medicine ,medicine ,Profiling (information science) ,Personalized medicine ,business ,media_common - Abstract
6531 Background: This survey of Targeted Agent and Profiling Utilization Registry (TAPUR) Study physicians examined use, attitudes, and perception of tumor genomic testing (TGT), defined as any DNA test performed on tumor specimen/plasma. TAPUR is a multibasket study of marketed agents targeting tumor genomics. Methods: 333 physicians at 54 TAPUR sites were surveyed (2016-2017). Survey domains included use of TGT, barriers to ordering TGT, and genomic confidence. Surveys included 3 scenarios for TGT ordering 1) pretreated advanced cancer patients (pts) without options, 2) newly diagnosed, untreated, metastatic pts and 3) early stage/potentially curable pts with standard options. Data were analyzed with descriptive statistics. Results: 112 physicians responded (33%). The table displays demographics and genomic confidence. Respondents reported a median of 25% of their pts had TGT in past 12 months for trials/routine care (range 0-85%). Barriers to testing included access to tumor specimen (86%), insurance coverage (67%), concerns that results will not be actionable (55%), and test issues (wait time, unsure which test/lab to use, test accuracy) (54%). TGT was ordered most often for scenario 1 (96%) and 2 pts (70%). Few respondents (32%) would order testing in scenario 3. Of those who reported testing for scenarios 1 & 2, most told pts that results could inform treatment/prognosis/trials (97%) or may be uninformative (84%). In all scenarios, pt expectations of TGT results were discussed prior to testing. A minority reported frequently telling pts in advance that results could inform heritable cancer susceptibility (37%). Conclusions: Confidence in using TGT was high. TGT was performed most for pts with advanced cancer and few options. Availability of specimens was largest barrier reported, indicating the importance of blood-based tests. Few respondents discussed implications of germline findings in advance, despite growing evidence of germline findings in somatic testing. [Table: see text] more...
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241. Treatment completion and toxicity of trastuzumab or trastuzumab + lapatinib in older patients (pts): BIG 2-06; NCCTG N063D (Alliance)
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Christos Sotiriou, Richard D. Gelber, Olena Werner, Noam Pondé, Martine Piccart, Dominique Agbor-Tarh, Aminah Jatoi, Alvaro Moreno-Aspitia, Christian Jackisch, Amylou C. Dueck, Evandro de Azambuja, Florentine Hilbers, Lissandra Dal Lago, and Larissa A. Korde more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Treatment completion ,business.industry ,Lapatinib ,03 medical and health sciences ,0302 clinical medicine ,Older patients ,Trastuzumab ,030220 oncology & carcinogenesis ,Internal medicine ,Toxicity ,medicine ,business ,030215 immunology ,medicine.drug - Abstract
11553 Background: Little is known about the toxicity of trastuzumab (T) or of trastuzumab + lapatinib (T + L), approved in the advanced setting, in older pts. We have performed a sub-analysis of the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial focused on treatment completion and toxicity of T and T+L in older pts (aged ≥65 years (yr)). Methods: The ALTTO trial (NCT00490139, NCCTG N063D) randomised 8381 pts with early HER2+ BC into 4 arms and we included the T and T+L arms in our analysis. Eligible pts for our study were those having received at least one dose of assigned treatment. Treatment completion was evaluated through the rate of temporary treatment interruptions (TTI), permanent treatment discontinuations (PTD) and lapatinib dose reductions (LDR). Toxicity was evaluated via a selected set of adverse events of interest (AEIs). Risk factors for TTI, PTD, LDR and AEIs were assessed, including comorbidities and polypharmacy at baseline (defined as use 5 or more co-medications) and AEIs during treatment. Results: A total of 430 pts≥65-year-old were identified for this sub-analysis, out of a total of 4190 pts with a median age of 68 yrs (range 65-80). Older pts were more likely to have comorbidities (70% vs 38%). Treatment completion was worse among older pts in the T+L arm but not in the T arm (Table). AEIs were more common in the T+L arm in all patients, with older patients having higher AEI rates (78.04% in older vs 63.38% in younger), particularly diarrhea (60.75% vs 38.0%). Identified risk factors (multivariate) for worse treatment completion in the T and T+ L arms included concomitant use of chemotherapy and the occurrence of grade 3 adverse events, among others. Conclusions: T + L has worse treatment completion and is more toxic in older patients, while T was well tolerated. Identifiable risk factors at baseline and during the course of treatment could be used to aid in regimen selection and management for both T and T + L in their respective indications. Support: UG1CA189823, Novartis;https://acknowledgments.alliancefound.org. [Table: see text] more...
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242. Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III colon cancer and deficient mismatch repair (ATOMIC, Alliance A021502)
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Deirdre Jill Cohen, Jeffrey A. Meyerhardt, Kabir Mody, Andrew B. Nixon, Robert J. Behrens, Alexandra Levasseur, Nicolas Sommer, Tyler Zemla, Eileen M. O'Reilly, Amylou C. Dueck, Fang-Shu Ou, Christopher H. Lieu, Frank A. Sinicrope, Asha Dhanarajan, Federico Innocenti, and Walter R. Peters more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Atezolizumab ,Internal medicine ,medicine ,Adjuvant therapy ,Chemotherapy ,biology ,business.industry ,medicine.disease ,Stage III Colon Cancer ,030220 oncology & carcinogenesis ,biology.protein ,DNA mismatch repair ,Antibody ,business ,030215 immunology - Abstract
e15169 Background: In metastatic colorectal cancer with deficient DNA mismatch repair (dMMR), anti-PD-1 antibody monotherapy produced high tumor response rates and extended progression-free survival compared to lack of benefit for cancers with proficient MMR. In an ongoing phase III randomized trial, we will determine if the addition of the anti-PD-L1 antibody, atezolizumab (Genentech), to adjuvant FOLFOX can improve patient disease-free survival (DFS) vs FOLFOX alone in patients with stage III colon cancers with dMMR. By blocking the PD-1/PD-L1 interaction, atezolizumab may activate T cells, thereby, restoring their ability to detect and attack tumor cells. Limited data suggest that FOLFOX may increase intratumoral cytotoxic CD8+ T cells that could serve as ‘immune priming'. Methods: Patients with curatively resected stage III colon carcinomas with evidence of dMMR are randomized to modified FOLFOX6 for 6 months (12 cycles) alone (control arm) or combined with atezolizumab (840 mg IV q2 wk) with continuation of the antibody as monotherapy for an additional 6 months (total duration of 12 months) [experimental arm]. Patients will be stratified by T, N stage and tumor sidedness. Local testing for MMR proteins is allowed. Atezolizumab must begin by/with cycle 2. One cycle of FOLFOX is allowed pre-registration. The targeted accrual goal of 700 patients and 165 disease-free survival (DFS) events will provide 90% power to detect an effect size expressed as hazard ratio of 0.6 for the primary endpoint of DFS at two-sided alpha of 0.05. Interim analyses are planned at 50% and 75% of events. Secondary endpoints include overall survival, treatment tolerability, and quality of life. Results: This study is being conducted by the Alliance for Clinical Trials in Oncology, was approved by NCI CTEP and activated in 09/2017. The study is actively accruing and, as of 02/11/2019, 152 patients are enrolled. We are actively exploring an international collaboration. Conclusions: This is a current clinical trial in progress. Clinical trial information: NCT02912559. more...
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243. Longitudinal toxicity analysis with novel summary metrics of lenalidomide maintenance in follicular lymphoma in ECOG-ACRIN 2408
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Gita Thanarajasingam, Andrew Quon, Erik A. Ranheim, Amylou C. Dueck, Andrew M. Evens, Thomas E. Witzig, Paul J. Novotny, Ranjana H. Advani, Randy D. Gascoyne, Thomas M. Habermann, Brad S. Kahl, and Fangxin Hong more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Follicular lymphoma ,medicine.disease ,Internal medicine ,Toxicity ,Medicine ,business ,Adverse effect ,Lenalidomide ,medicine.drug ,Time profile - Abstract
6511 Background: Conventional adverse event (AE) analysis (ToxC) focuses on incidence of grade (gr) 3+ toxicities, and fails to capture AE time profile. Novel metrics that reflect chronic low gr and overall AE burden are needed. We applied the Toxicity over Time (ToxT) approach to ECOG-ACRIN 2408 to depict time-dependent toxicity of lenalidomide (L) with rituximab maintenance (MR) in follicular lymphoma (FL), and we developed a novel summary metric of symptomatic AE burden, the maximum gr over time (MGOT). Methods: In E2408, high risk FL patients (pts) were randomized (1:2:2) to: A) bendamustine-rituxumab (BR) x 6 then MR x 2 years (yrs) vs B) BR-bortezomib x 6 then MR x 2 yrs vs C) BR x 6 then MR x 2 yrs + L x 1 yr (MRL). Analysis included 3 laboratory and 5 symptomatic AEs of highest incidence during maintenance on arms A and C. Treatment-related AEs of any gr were analyzed by ToxC and ToxT. Repeated measures, time-to-event (TTE) and area under the curve (AUC) analyses capture trends over time in ToxT. MGOT combines the 5 symptomatic AEs. Results: 104 randomized pts (30 MR, 74 MRL) were included. For the laboratory AEs, by ToxC, neutropenia incidence was significantly higher in MRL (84%) than MR (47%, p < .001). ToxT additionally shows neutropenia does not worsen over time (10/14/20% gr 1/2/3+ at c1, 6/21/12% gr 1/2/3+ at c12). For the symptomatic AEs, ToxC indicates 2% gr 3+ GI AEs. However, gr 1-2 GI AEs are more common on MRL (59%) than MR (26%, p < .001). ToxT AUC captures a higher burden of GI AEs over time on MRL(2.8) vs MR(1.4, p = .002). TTE depicts sooner GI AE onset in MRL (10% vs 0% gr 2+ GI by day 50, p = 0.03). Bar charts of incidence and grade by cycle illustrate this improves over time (34/7/4% gr 1/2/3+ at c1, 13/0/0% gr 1/2/3+ at c12). ToxT MGOT analyses demonstrate earlier time to gr 2+ symptomatic AE on MRL vs MR (63% vs 31% by day 50, p < .001) and suggest that overall AE burden over time is higher for patients on MRL(AUC 18.2) than MR(11.8, p < .001). Conclusions: ToxT depicts AE time profile and can guide AE interventions. Summary metrics suggest that symptomatic AEs occur earlier and their burden over time is higher on MRL. We are implementing ToxT in patient-reported AE data to better characterize pt tolerability. more...
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- 2019
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244. A Phase Ib Study of the combination of the Aurora Kinase Inhibitor Alisertib (MLN8237) and Bortezomib in Relapsed Multiple Myeloma
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Allison C. Rosenthal, Katherine Gano, Amylou C. Dueck, A. Keith Stewart, Jacob P. Laubach, Ravi Vij, Shaji Kumar, and Craig C. Hofmeister
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0301 basic medicine ,Bortezomib ,business.industry ,Treatment outcome ,Aurora inhibitor ,Hematology ,Bioinformatics ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Aurora kinase ,chemistry ,030220 oncology & carcinogenesis ,Alisertib ,medicine ,Cancer research ,business ,Multiple myeloma ,medicine.drug - Published
- 2015
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245. Predictive Testing for Alzheimer’s Disease
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Bruce R. Henslin, Jessica B. Langbaum, Katherine S. Hunt, Heidi E. Kosiorek, Amylou C. Dueck, Jason Scott Robert, Gary E. Marchant, and Richard J. Caselli
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Male ,medicine.medical_specialty ,Depression ,Extramural ,MEDLINE ,Disease ,Article ,Healthy Volunteers ,Suicidal Ideation ,Psychiatry and Mental health ,Clinical Psychology ,Alzheimer Disease ,medicine ,Humans ,Female ,Geriatrics and Gerontology ,medicine.symptom ,Psychiatry ,Predictive testing ,Psychology ,Gerontology ,Suicidal ideation ,Clinical psychology - Published
- 2015
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246. Depressive Symptoms in Healthy Apolipoprotein E ε4 Carriers and Noncarriers
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Amylou C. Dueck, David S. Knopman, Dona E.C. Locke, Yonas E. Geda, Richard J. Caselli, and Cynthia M. Stonnington
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Adult ,Male ,Apolipoprotein E ,Oncology ,Heterozygote ,medicine.medical_specialty ,Longitudinal study ,Apolipoprotein E4 ,Neuropathology ,Disease ,Neuropsychological Tests ,Personality Assessment ,Alzheimer Disease ,Internal medicine ,medicine ,Humans ,Dementia ,Memory impairment ,Risk factor ,Depression (differential diagnoses) ,Aged ,Aged, 80 and over ,Intelligence Tests ,Psychiatric Status Rating Scales ,Memory Disorders ,Depression ,Middle Aged ,medicine.disease ,Antidepressive Agents ,Psychiatry and Mental health ,Cross-Sectional Studies ,Female ,Psychology ,Follow-Up Studies ,Clinical psychology - Abstract
A variety of studies have suggested that depression in patients with mild cognitive impairment (MCI) increases the risk of progression to Alzheimer’s disease dementia.1–4 Studies evaluating the possible impact of depression on the risk of transitioning from normal cognitive aging to MCI have been mixed.4–6 Geda and colleagues5 have suggested 4 possible mechanisms for this possible link between depression and incident MCI. One of those 4 possibilities is that depressive symptoms may be an “early noncognitive manifestation of dementia”; that is, depressive symptoms could be a part of the preclinical course of Alzheimer’s disease. Similarly, others have hypothesized that depressive symptoms may be an early manifestation of rather than a risk factor for dementia and Alzheimer’s disease, suggesting that the underlying neuropathology that causes MCI or dementia may also cause depressive symptoms.2 If depressive symptoms exhibit a similar gradual progression as do memory changes, then one would predict a gradual transition during the preclinical stage that reaches clinical proportions during MCI. Apolipoprotein E (APOE) e4 is the most prevalent known genetic risk factor for Alzheimer’s disease. We have previously shown that age-related memory decline accelerates preclinically in APOE e4 carriers who remain cognitively normal relative to noncarriers who remain cognitively normal.7 Although there is not a 100% correlation between APOE status and development of Alzheimer’s disease, this preclinical memory decline is consistent with the prominent memory impairment that eventually characterizes amnestic MCI and Alzheimer’s disease dementia, supporting the hypothesis that divergence of memory performance maybe an indicator of subclinical Alzheimer’s disease pathology in this genetically at-risk group. If depression is intrinsic to the Alzheimer’s disease syndrome, then a similar increase in depressive symptoms could be expected preclinically in those at genetic risk for Alzheimer’s disease. The primary aim of this longitudinal investigation is to evaluate whether depressive symptomatology increases preclinically, analogous to accelerated memory decline. more...
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- 2013
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247. Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplantation in Adults Using Fludarabine, Carmustine, Melphalan, and Antithymocyte Globulin: Outcomes Depend on Disease Risk Index but Not Age, Comorbidity Score, Donor Type, or Human Leukocyte Antigen Mismatch
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Craig B. Reeder, James L. Slack, Jared Klein, Jeffery A. Betcher, Roberta H. Adams, Jose F. Leis, Pierre Noel, Nandita Khera, Veena Fauble, Lisa Sproat, and Amylou C. Dueck
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Adult ,Male ,Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,Myeloid ,Chronic lymphocytic leukemia ,Gastroenterology ,Young Adult ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Transplantation, Homologous ,Cumulative incidence ,Reduced toxicity conditioning ,Myelofibrosis ,Aged ,Antilymphocyte Serum ,Retrospective Studies ,Transplantation Chimera ,Transplantation ,business.industry ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Carmustine ,Survival Analysis ,Allogeneic stem cell transplant ,Fludarabine ,Surgery ,Leukemia ,Treatment Outcome ,medicine.anatomical_structure ,Hematologic Neoplasms ,Female ,Antithymocyte globulin ,business ,Vidarabine ,medicine.drug - Abstract
Although reduced-intensity conditioning has become standard of care for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT), the optimum regimen has yet to be defined, and may depend on pretransplantation patient– and/or disease-specific risk factors. We report here results in 100 adults, ages 18 to 69, with high-risk hematologic malignancy who received conditioning with fludarabine, carmustine, melphalan, and rabbit antithymocyte globulin (FBM-A). Outcomes were stratified using the disease risk index (DRI) as published by Armand et al. (Blood 2012;120:905-913). Median age was 56, and patients were ineligible for standard myeloablative conditioning because of age, organ dysfunction, or prior autologous HCT. Patients underwent transplantation for myeloid (acute myelogenous leukemia, n = 40; myelodysplastic syndrome, n = 24; myelofibrosis, n = 13; other myeloid, n = 2) or lymphoid (acute lymphoblastic leukemia, n = 8; non-Hodgkin lymphoma, n = 8; Hodgkin lymphoma, n = 4, chronic lymphocytic leukemia, n = 1) malignancy. Donors were related in 26 patients (22 matched, 4 mismatched at 1 antigen) and unrelated in 74 (mismatched at 1 or 2 HLA loci in 33); grafts were peripheral blood stem cells in 97 patients, bone marrow in 2, and double cord in 1. According to the DRI, 68 patients were classified as low (n = 1) or intermediate risk (n = 67), and 32 were classified as high (n = 28) or very high risk (n = 4). With a median follow-up of surviving patients of 18 months, the Kaplan-Meier estimate of overall survival at 2 years for patients in the low/intermediate risk group is 80%, compared with 66% in the high/very high group (P = .11). Two-year cumulative incidence of relapse and nonrelapse mortality in the low/intermediate group are 9.9% and 15%, versus 25% and 19% in the high/very high group (respective P values .07 and .81). The cumulative incidence of acute graft-versus-host (GVHD) grades III to IV at 100 days was 8.1%, and the incidence of National Institutes of Health–defined moderate to severe chronic GVHD was 22% at 2 years. No deaths were attributable to chronic GVHD. Survival was not influenced by age, hematopoietic comorbidity index score, donor type, donor gender, or presence of mismatch. We conclude that FBM-A is an effective and safe conditioning regimen for adults up to age 69 with hematologic malignancies who have low-, intermediate-, or high-risk scores according to the DRI. more...
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- 2013
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248. Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2-positive breast cancer receiving chemotherapy with or without trastuzumab: Results from North Central Cancer Treatment Group adjuvant trial N9831
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Peter A. Kaufman, Alvaro Moreno-Aspitia, David W. Hillman, Julie R. Gralow, Monica M. Reinholz, Amylou C. Dueck, Walter P. Carney, Kathleen S. Tenner, Wilma L. Lingle, Jacqueline M. Lafky, Leila A. Kutteh, Edith A. Perez, Stephen Dyar, and Nancy E. Davidson more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Cyclophosphamide ,Proportional hazards model ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Cancer ,medicine.disease ,Metastatic breast cancer ,Surgery ,Breast cancer ,Trastuzumab ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
BACKGROUND Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2-positive metastatic breast cancer. In this study, the authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9831 clinical trial. METHODS The objectives were to describe sHER2 levels during treatment and at the time of recurrence in patients who were randomized to treatment arms A (standard chemotherapy), B (standard chemotherapy with sequential trastuzumab), and C (standard chemotherapy with concurrent trastuzumab). Baseline samples were available from 2318 patients, serial samples were available from 105 patients, and recurrence samples were available from 124 patients. The cutoff sHER2 value for the assay was 15 ng/mL. Statistical methods included repeated measures linear models, Wilcoxon rank-sum tests, and Cox regression models. RESULTS There were differences between groups in terms of age, menopausal status, and hormone receptor status. Within treatment arms A, B, and C, patients who had baseline sHER2 levels ≥15 ng/mL had worse disease-free survival than patients who had baseline sHER2 levels more...
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- 2013
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249. Effect of body mass index on tumor characteristics and disease-free survival in patients from the HER2-positive adjuvant trastuzumab trial N9831
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Edith A. Perez, Alvaro Moreno-Aspitia, Barbara A. Pockaj, Karla V. Ballman, Jennifer A. Crozier, and Amylou C. Dueck
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Oncology ,Cancer Research ,medicine.medical_specialty ,Proportional hazards model ,business.industry ,Hazard ratio ,Cancer ,Overweight ,medicine.disease ,Confidence interval ,Surgery ,Breast cancer ,Internal medicine ,medicine ,Adjuvant therapy ,medicine.symptom ,skin and connective tissue diseases ,business ,Body mass index - Abstract
BACKGROUND Data suggest that weight, and specifically body mass index (BMI), plays a role in breast cancer development and outcome. The authors hypothesized that there would be a correlation between BMI and clinical outcome in patients with early stage, human epidermal receptor 2 (HER2)-positive breast cancer enrolled in the N9831 adjuvant trial. METHODS Patients were grouped according to baseline BMI as follows: normal (BMI more...
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- 2013
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250. Transoral laser microsurgery followed by radiation therapy for oropharyngeal tumors: The mayo clinic arizona experience
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Samir H. Patel, Michele Y. Halyard, Richard E. Hayden, William W. Wong, Matthew A. Zarka, Michael L. Hinni, Amylou C. Dueck, and Kelly K. Curtis
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,Neck dissection ,Retrospective cohort study ,Microsurgery ,medicine.disease ,Surgery ,Radiation therapy ,Oropharyngeal Neoplasm ,Otorhinolaryngology ,medicine ,Transoral laser microsurgery ,Stage (cooking) ,business - Abstract
Background The purpose of this study was to report the treatment outcomes of patients with advanced oropharyngeal cancer treated with transoral laser microsurgery (TLM) followed by radiation therapy (RT) at Mayo Clinic in Arizona. Methods A retrospective study of 80 patients treated from January 1, 2000 to November 7, 2011 was performed. All patients had stage III/IV oropharyngeal tumors and underwent TLM with neck dissection. Adjuvant RT was then given. Thirty-seven patients received concurrent adjuvant chemotherapy. The primary outcome was locoregional control. Results Median follow-up was 47.3 months (range, 9.7–139.2 months). The 3-year locoregional control, recurrence-free survival, and overall survival rates were 98.6% (95% confidence interval [CI], 91% to 100%), 91.1% (95% CI, 81% to 96%), and 93.7% (95% CI, 84% to 98%), respectively. There were a total of 5 treatment failures, 1 regional and 4 distant. Twenty-six patients underwent neck only RT with exclusion of the primary site. Conclusion TLM followed by RT for advanced oropharyngeal cancer results in excellent locoregional control rates. © 2013 Wiley Periodicals, Inc. Head Neck 36: 220–225, 2014 more...
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- 2013
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