tbuckley/cabot-search huggingface dataset:
Factors related to unemployment in long-term lymphoma survivors after high-dose chemotherapy with autologous stem cell transplantation.
Authors: Cecilie E. Kiserud, Unn Merete Fagerli, Knut Halvor B Smeland, Stein Kvaløy, Harald Holte, Alv A Dahl
Journal: Journal of Clinical Oncology (2015)

e20641 Background: This study investigates work status in lymphoma survivors at a mean of 10 years after high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT). We also explore factors associated with unemployment at follow-up. Methods: All survivors aged ≥ 18 years at HDT-ASCT for lymphomas in Norway1987-2008, alive at the end of 2011 and aged < 65 years at survey were eligible for this retrospective, cross-sectional study performed in 2012/2013. Participants responded to a mailed questionnaire assessing work status, fatigue, quality of life, mental distress, and lifestyle. Work status was dichotomized as either working (paid work or currently on sick-leave) or non-working (disability pension, economical support while unemployed, on rehabilitation, home-makers, or students). Logistic regression analyses were performed with non-work status as outcome. A p-value < 0.05 was considered statistically significant. Results: The response rate was 78%, and among 281 participants mean age at survey was 52.3 years, with 60% males and 64% working (73% among males and 50% among females). Compared to the working group the non-working group was significantly older, had significantly higher proportion of females, lower education, comorbidity, higher levels of fatigue, and lower levels of all SF-36 dimensions. The proportions of Type D personality, caseness of anxiety and depression, and memory problems were significantly higher in the non-working group. No significant between-group differences were observed for type of lymphoma or treatment-related variables, posttraumatic growth or lifestyle variables (smoking, physical activity, and risky alcohol intake). In multivariable analysis only older age and female sex remained significantly associated with non-working status at survey. Conclusions: Although 64% of the participating lymphoma survivors 10 years after HDT-ASCT are working, special attention should be given to females and older survivors as to their work ability.
Interest in and outcomes with return of individual genetic research results for inherited susceptibility to breast cancer.
Authors: Angela R. Bradbury, Linda J. Patrick-Miller, Brian L. Egleston, Kara Noelle Maxwell, Amanda Brandt, Jamie Brower, Laura Digiovanni, Jessica M. Long, Jacquelyn Powers, Jill Stopfer, Katherine L. Nathanson, Susan M. Domchek
Journal: Journal of Clinical Oncology (2015)

e12503 Background: There is ongoing debate over the obligation, risks, benefits and utilities of returning individual genetic research results (IRR) identified in gene discovery or translational research. Participant interest in, optimal methods to communicate, and patient reported outcomes of returning IRR are unknown. Methods: Breast cancer patients who participated in genetic research were contacted and offered the opportunity to receive germline IRR for 25 high and moderate penetrance genes now clinically available. Participants completed informed consent, telephone pre- (V1) and post-test (V2) counseling using a tiered-binned genetic counseling model, and surveys evaluating cognitive and affective responses. Results: 278 IRR were available and 189 research participants were living, had contact information and consent for recontact. 50 (26%) have completed V1; 36 (19%) are considering counseling. Only 7 (4%) declined and 89 (47%) could not be reached; 7 (4%) were ineligible. Those completing V1 were more likely to be white (p < 0.01), married (p < 0.02), have a college degree (p = 0.02) and to have been seen in the clinical program (p = < 0.01). In multivariable analyses only being clinical program participants (OR 3.2, p < 0.01) and married (OR 2.5, p = 0.02) were associated with completing V1. 86% (37/43) of research participants elected to receive IRR (V2). Knowledge increased (+2.1, SD 5.3, p = 0.02), and general anxiety (-1.9, SD 2.6, p < 0.01), state anxiety (-3.7, SD 7.8, p < 0.01), depression (-0.8, SD 1.8, p < 0.01) and uncertainty (-1.5, SD 3.3, p < 0.01) decreased after receipt of IRR, which included 1 high-penetrance (MSH2), 7 moderate penetrance mutations (MRE11A, ATM, CHEK2, RAD50, MYH) and 4 variants of unknown significance (VUS). Those with a positive result had greater decreases in uncertainty and increases in satisfaction. When recommended, CLIA testing confirmed all IRR. Conclusions: Many research participants could not be reached and some were not interested in receiving IRR. Receipt of IRR with a standardized tiered-binned genetic counseling is not associated with significant increases in anxiety and distress and some outcomes may vary by IRR.
Impact of a functional polymorphism in the IL12B promoter region on survival in patients with malignant melanoma
Authors: D. Schadendorf, S. Ugurel, A. Paschen, K. Kern, B. Hill, G. Morahan, J. Müller-Berghaus
Journal: Journal of Clinical Oncology (2006)

8001 Background: Interleukin-12 (IL-12), a heterodimeric cytokine, is important in the generation of a Th1-biased immune response. Several polymorphisms have been described in IL12B, the gene encoding the p40 subunit of IL-12. A bi-allelic polymorphism within the IL12B promoter region has been reported to show association with diseases as diverse as severe childhood asthma and fatal cerebral malaria. Methods: In order to define the molecular basis for these disease associations we investigated the secretion of IL-12 by human monocyte-derived dendritic cells. The amount of IL-12p40 and p70 produced by DCs from normal blood donors was determined following CD40L activation. Subsequently, we therefore sought to investigate the frequency of IL12B genotypes and their impact on the outcome of patients with malignant melanoma. Genomic DNA was isolated from 75 normal blood donors and 80 melanoma cell lines and used for genotyping the IL12B polymorphism. Corresponding clinical data were retrieved from the in-house melanoma database. Results: Allele frequency for IL12Bpro-1 is 0.45 and for IL12Bpro-2 0.55. Homozygotes for the IL12B promoter polymorphism showed a 10-fold difference in median p70 secretion in response to CD40 ligation. Remarkably, this difference resulted from the inability of most allele 1 homozygotes to secrete heterodimeric IL-12. In contrast, most of the donors homozygous for allele 2 had detectable secretion. Distribution of genotypes in melanoma patients was not significantly different from normal blood donors. Kaplan-Meier survival analysis showed significantly decreased survival of patients homozygous for the longer allele, previously defined as being associated with decreased IL-12 secretion (log-rank p=0.015). Subgroup analysis indicated that this survival advantage was seen exclusively in female patients. Conclusions: The recently described IL12B promoter polymorphism is highly correlated with secretion of bioactive IL-12 and has a significant impact on the clinical course of disease in patients with melanoma and may therefore be useful for prognostic stratification. No significant financial relationships to disclose.
Use of clinical history (CH) for Lynch syndrome (LS) risk assessment: An economic decision analysis.
Authors: Sarmad Sadeghi, Afsaneh Barzi, Michael W. Kattan, Neal J. Meropol
Journal: Journal of Clinical Oncology (2012)

1514 Background: Previous studies comparing screening strategies (STs) for LS concluded that immunohistochemistry (IHC)-based STs are most cost effective. However, these analyses generally exclude clinical history (CH)-based criteria due to concerns for reliability, e.g. Amsterdam (Ams), Bethesda (Beth), MMRpro (Mpro), MMRpredict (Mpre) and PREMM (PRE). We conducted a comprehensive comparison of all STs. Methods: Using assumptions from published reports we performed a cost effectiveness analysis (CEA) with a societal viewpoint using TreeAge software. 20 STs for proband (Pd) and general population (GP) screening in a cohort of 100,000 assumed a 3% LS prevalence (Prev) in Pd and 0.23% in GP, 5 first degree relatives (FDRs) per LS diagnosis (Dx), 50% LS Prev in FDRs, and 90% genetic testing (GT) compliance in Pds and GP and 52% in FDRs. We used the number of LS Dxs as effectiveness measure (EM). Sensitivity, accuracy, and incremental cost effectiveness ratios (ICERs) were calculated. Results: The ST of Mpro followed by GT is highly sensitive and has an accuracy of .997. Assuming 1-1.4 life years saved per Dx based on prior studies, this strategy is also cost effective. Strategies with greater sensitivity were dominated or not cost effective. Table shows results in order of increasing cost per Dx. Conclusions: This comprehensive comparison suggests that Mpro is an appropriate first step in screening for LS in Pds, and its routine use may be considered as a quality measure in the management of colorectal cancer. IHC + BRAF, GT should be reserved for Pds where CH is incomplete. [Table: see text]
Biomarkers To Predict Outcome after Allogeneic Hematopoietic Cell Transplant (HCT).
Authors: Shira N. Dinner, Andrew Artz, Masha Kocherginsky, Jodie Ulaszek, Daniel Pollyea, Lucy Godley, Richard A. Larson, Olatoysi Odenike, Elizabeth Rich, Wendy Stock, Koen van Besien, Amittha Wickrema
Journal: Blood (2007)
The access to oncology drugs in France, Germany, Italy, Spain, and the United Kingdom: A comparison based on data from 1998 to 2007
Authors: N. E. Wilking, B. Jönsson
Journal: Journal of Clinical Oncology (2009)

6525 Background: Drugs constitute a key element in the treatment of solid tumors and in haematology. We have analysed the access and uptake of oncology drugs in 27 countries over a 10 year period (1998–2007) based on sales data provided by IMS Health ( www.comparatorreports.se ). Methods: In this special analysis we study a set of “mature” cancer drugs ( irinotecan, aromatase inhibitors (AIs), oxaliplatin, docetaxel, rituximab, gemcitabine, trastuzumab and imatinib) available in 2002 or before and a set of “new” cancer drugs (bortezomib, cetuximab, bevacizumab, pemetrexed, erlotinib, sorafinib, sunitinib and dasatinib) available in 2003 or later. The “mature” drugs have been selected based on the fact that they have been available for a long period of time (at least 5 years) and that there is accumulated evidence based on clinical trials, epidemiological studies and clinical experience that they have had a major and clinically relevant impact on the outcome in different areas of oncology. Results: We see very different patterns of use in countries studied. The total use of cancer drugs (€/capita) in 2007 is highest in France and lowest in the UK, with the other countries at a relatively similar level in between. The pattern of use of “new drugs” follows that of “mature drugs”, but the very low use of new drugs in UK is noticeable. The differences seen between groups are also reflected in the use of individual drugs, although for example AIs and trastuzumab in the “mature” group have a more uniform use across the countries. The expected survival for cancer patients have been, in general, lower in the UK compared to other western European countries, but further studies are needed to establish the impact of treatment patterns on population outcome. Conclusions: The similarity in use of both “mature” and “new” oncology drugs indicate that differences in access, found for example between France and UK, is related to health care system factors rather that evidence on outcome of use of the drugs. [Table: see text] [Table: see text]
Influence of molecular alterations on site-specific (ss) time to recurrence (TTR) following adjuvant therapy in resected colon cancer (CC) (Alliance Trial N0147).
Authors: Ryan Eldredge Wilcox, Qian Shi, Frank A. Sinicrope, Daniel J. Sargent, Nathan R. Foster, Jeffrey P. Meyers, Richard M. Goldberg, Suresh Nair, Anthony Frank Shields, Emily Chan, Sharlene Gill, Morton S. Kahlenberg, Steven R. Alberts
Journal: Journal of Clinical Oncology (2015)

3590 Background: Influence of tumor molecular alterations on ssTTR after resection of stage 3 CC has not been well studied. Phase 3 trial N0147 (adjuvant FOLFOX +/- cetuximab) provided an opportunity to assess possible correlations. Methods: 3098 stage 3 CC pts were enrolled and sites of all recurrences were reviewed centrally: liver, lung, peritoneal, local ( < 5 cm of anastomosis), regional, and other metastatic. Genetic markers include MMR, mutations (mut) in KRAS exon 2 (codons 12, 13), BRAF V600E exon 15. Cumulative incidence rate (CIR) was estimated for ss recurrences. Associations between biomarkers and TTR across sites (interaction) were assessed by a frailty Cox model. Association between biomarker and ssTTR were evaluated by multivariable Cox model when the site-biomarker interaction effect presents, adjusting for age, T/N stage, type of surgery, tumor sidedness, and treatment. Results: Most common recur sites were liver, regional, peritoneal, and lung, with 3 yr CIR of 8.4%, 8.3%, 5.5% and 5.4%, respectively, with no difference between treatment arms (p = 0.9). Interactions between sites of recurrence and BRAF (p = .006) or MMR (p = .018) status were significant and marginal for combined KRAS/BRAF (p = .10). Compared to wild type (wt) pts, BRAF mut pts had shorter TTR for peritoneal HR2.14; 95% CI, 1.36-3.37; padj= .001] and metastatic sites [HR, 1.19; 95 CI, 1.07-3.42; padj= .033], but not for liver or lung. KRAS mut/BRAF wt pts had shorter TTR for liver (HR, 1.55; 95% CI, 1.19-2.03) and lung (HR, 1.81, 95% CI, 1.32-2.50), and KRAS wt/BRAF mut pts had shorter TTR for peritoneal (HR, 2.14; 95% CI, 1.36-3.37) compared to double wt pts. dMMR pts had longer TTR for liver (HR, 0.44; 95% CI, 0.25-0.78; padj= .002 ) and peritoneal (HR, 0.46; 95% CI, 0.25-0.82; padj= .004) compared to pMMR pts. Conclusions: Status of MMR and BRAF, but not KRAS (alone), influences site of recurrence and TTR. Accordingly, these biomarkers may assist in treatment and follow-up approaches. Clinical trial information: NCT00079274.
Bacterial virulence phenotypes of <i>Escherichia coli</i> and host susceptibility determine risk for urinary tract infections
Authors: Henry L. Schreiber, Matt S. Conover, Wen-Chi Chou, Michael E. Hibbing, Abigail L. Manson, Karen W. Dodson, Thomas J. Hannan, Pacita L. Roberts, Ann E. Stapleton, Thomas M. Hooton, Jonathan Livny, Ashlee M. Earl, Scott J. Hultgren
Journal: Science Translational Medicine (2017)

Risk for urinary tract infections is determined by a combination of host susceptibility determinants and diverse Escherichia coli phenotypes.
Stereotactic body radiotherapy for patients with relapsing prostate cancer with bones or nodes oligometastases.
Authors: Pierre-Antoine Laurent, Etienne Martin, François Cousin, Magali Quivrin, Fabienne Bidault, Frederic Mazoyer, Aurelie Bertaut, Gilles Crehange
Journal: Journal of Clinical Oncology (2017)

263 Background: To analyze patients treated by stereotactic body radiotherapy (SBRT) for node or bone oligometastatic recurrence of a prostate cancer previously locally treated, To identify possible pronostic factors of early biochemical failure (BF) after SBRT. Methods: We reviewed patients with a rising PSA treated by SBRT between November 2011 and April 2016 for bone or node oligometastases, diagnosed on a 18F Fluorocholine positron emission tomography-computed tomography (PET-CT) following biochemical failure of a prostate cancer after a local curative treatment. Recurrence-free survival (RFS) was the primary end-point defined as the time interval between SBRT and biochemical failure. Biochemical failure was defined as 2 consecutive elevations of PSA with last dosage superior to PSA dosage before treatment, or clinical failure. PSA value before SBRT, location of metastases, number of lesions treated, concomitant androgen deprivation therapy were analyzed to identify pronostic factors of poor response to SBRT. Results: With a median follow-up from time of SBRT of 12 months, we treated 40 patients and 56 metastatic lesions, with a local-control rate of 85%. 19 patients were treated for 1 to 3 bone lesions and 21 patients for 1 to 3 node lesions. 8 patients with bone oligometastases and 13 patients with node oligometastases had a recurrence (p=0.55). The main sites of failure after SBRT were lymph nodes only (7 ; 33%), bone only (7 ; 33 %), and synchronous node and bone (4 ; 19%). A 2 nd and 3 rd course of radiotherapy was delivered in 8 and 1 patients. Median RFS was 345 days (134-426) in the node SBRT group and 494 days (85-877) in the bone SBRT group (p=0.27). On bivariate analysis, a PSA nadir up to 0.51 ng/mL after SBRT was identified as a pronostic factor of a worse RFS (p=0.0038). This result was not confirmed in multivariate analysis (p=0.87). Conclusions: SBRT for node oligometastases showed a non significant lower rate of RFS when compared to SBRT in bone oligometastases. A larger cohort with a longer follow up is needed to determine whether node and bone oligometastases have similar outcomes after SBRT.
Health Disparities and Triple-Negative Breast Cancer in African American Women
Authors: Lisa A. Newman, Linda M. Kaljee
Journal: JAMA Surgery (2017)

Variation in cancer incidence and outcome has well-documented correlations with racial/ethnic identity. In the United States, the possible genetic and ancestral hereditary explanations for these associations are confounded by socioeconomic, cultural, and lifestyle patterns. Differences in the breast cancer burden of African American compared with European/white American women represent one of the most notable examples of disparities in oncology related to racial/ethnic identity. Elucidating the source of these associations is imperative in achieving the promise of the national Precision Medicine Initiative.Population-based breast cancer mortality rates have been higher for African American compared with white American women since the early 1980s, largely reflecting declines in mortality that have been disproportionately experienced among white American patients and at least partly explained by the advent of endocrine therapy that is less effective in African American women because of the higher prevalence of estrogen receptor-negative disease. The increased risk of triple-negative breast cancer in African American women as well as western, sub-Saharan African women compared with white American, European, and east African women furthermore suggests that selected genetic components of geographically defined African ancestry are associated with hereditary susceptibility for specific patterns of mammary carcinogenesis. Disentangling health care access barriers, as well as reproductive, lifestyle, and dietary factors from genetic contributions to breast cancer disparities remains challenging. Epigenetics and experiences of societal inequality (allostatic load) increase the complexity of studying breast cancer risk related to racial/ethnic identity.Oncologic anthropology represents a transdisciplinary field of research that can combine the expertise of population geneticists, multispecialty oncologists, molecular epidemiologists, and behavioral scientists to eliminate breast cancer disparities related to racial/ethnic identity and advance knowledge related to the pathogenesis of triple-negative breast cancer.
Tacrolimus and Short-Term Methotrexate (mini-MTX) for Graft Versus Host Disease (GVHD) Prophylaxis after Unrelated Single Unit Cord Blood Transplant (CBT) in Pediatric Patients.
Authors: Demetrios Petropoulos, Laura L. Worth, Susannah E. Koontz, Mary S. Choroszy, Ka Wah Chan, Elizabeth J. Shpall, Richard E. Champlin, Laurence J. Cooper
Journal: Blood (2007)
Outcomes of patients (pts) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) with bone marrow necrosis (BMN) at initial diagnosis.
Authors: Aditya Shetty, Carlos E. Bueso-Ramos, Jorge E. Cortes, Gautam Borthakur, Sherry Pierce, Tapan M. Kadia, Naval Guastad Daver, Deborah A. Thomas, Hagop M. Kantarjian, Farhad Ravandi
Journal: Journal of Clinical Oncology (2014)

e18017 Background: Bone marrow necrosis (BMN) at initial diagnosis in acute leukemias is a rare pathological finding with only few cases reported in the literature. The purpose of this study was to determine the clinical impact of BMN at initial diagnosis in pts with ALL and AML. Methods: We performed a chart review of pts with ALL and AML with BMN at initial diagnosis, treated at our institution. Results: 640 ALL pts and 1051 AML pts were treated at our institution between 2000 and 2013. BMN was identified in 20 (3.1%) and 25 (2.4%) pts with ALL and AML at initial diagnosis. The most common cytogenetic findings in pts with ALL included t(9;22)(q34;q11) in 3 pts (15%) and t(8;14)(q24;q32) in 5 pts (25%). 16 pts (80%) were treated with a hyper-CVAD based induction regimen. 17 pts (85%) achieved complete remission (CR). The median CR duration was 48.7 months (range, 1.7-137.1 months). 11 pts (55%) have died at the time of this analysis with a median overall survival of 61.5 months (range, 0-120 months) compared with 71 months in a control group treated in the same period (p=0.33). The most common cytogenetic findings in pts with AML included complex (≥ 3 chromosomal abnormalities) in 11 pts (44%) and normal in 7 pts (28%). No FLT3-ITD mutations were detected in 19 pts, while 4 of 12 evaluated pts had NPM1 mutation. By FAB classification, 5 pts (20%) were M4 and 9 pts (36%) M5. 12 pts (48%) received an ara-C-based induction regimen, while 6 pts (24%) received a hypomethylator- based induction regimen. 8 pts (32%) achieved a CR. The median CR duration was 5.8 months (range, 0.7-82.4 months). 18 pts (72%) have died at the time of this analysis with a median overall survival of 3.2 months (range, 0-120 months) compared with 13.9 months in a control group (p=0.02). Conclusions: BMN is a rare entity in both in ALL and AML. Compared with historical controls, the presence of BMN appears to be associated with Burkitt’s morphology in ALL. Although patients with ALL and bone marrow necrosis have a shorter overall survival, this did not reach statistical significance. In AML, BMN at diagnosis is more common in those with M4 and M5 histology and is associated with a significantly worse overall survival.
Correlation of PET Scan Negativity and Higher Absolute Lymphocytes: Monocytes (ALC:AMC) Ratio As Prognostic Markers in Classical Hodgkin Lymphoma Patients Treated with ABVD Chemothearapy at a Single Center in Saudi Arabia
Authors: Ibraheem H Motabi, Syed Ziauddin A. Zaidi, Shahid Iqbal, Atta Munawar Gill, Imran Khan Tailor, Nawal Faiez Alshehry, Assem A Elghazaly, Samer Homoud S Almudaibigh, Mubarak S. AlGhamdi, Ghulam Murtaza, Ahmed Butt
Journal: Blood (2015)