tbuckley/cabot-search huggingface dataset:
Accessing tissue for research: Pathology provider policies and attitudes to tumor sample use.
Authors: Elizabeth Chien Hern Liow, Andrew Mant, Phillip Parente, Carmel Jo Pezaro
Journal: Journal of Clinical Oncology (2018)

e18561 Background: Increasingly, archival or fresh tumor tissue is required for participation in clinical trials. Patients, clinicians, and researchers have varying attitudes regarding the use of tissue samples for research1,2, further complicated by ambiguity over legal ownership of stored tissue. Pathology providers are key stakeholders in tissue management and therefore we undertook qualitative research to explore opinions and identify issues. Methods: We obtained ethics approval to conduct semi-structured interviews with representatives from private and public pathology laboratories in Melbourne, Australia. We explored the views and policies regarding tissue ownership, use and release for research purposes. Data were analyzed thematically. Results: We undertook 6 interviews in public and private pathology units. These units differ in respect to funding source, as public departments are government-funded. Data saturation was reached. The majority of pathology providers nominated the laboratory as owners of tissue specimens; some referenced a custodian role. There appeared to be no clear guidelines addressing prioritization of tissue use. Decisions over tissue release were predominantly made by unit heads. A common preference was to retain all tissue indefinitely, storage capacity permitting. In general, there were reservations regarding release of tissue blocks, with most respondents citing an obligation to retain tissue for future diagnostic testing, including emerging genomic analyses. The reluctance to release tissue blocks appeared greater in public providers. Release of slides was favored, at the cost of additional unit resources for preparation. Conclusions: The complex issues surrounding tissue ownership and research use merit review in the context of increasing translational research efforts and the growing trend mandating tissue for trial participation. Consensus amongst interested parties, ensuring patients’ ethical interests, may facilitate more effective use of tissue specimens for research. Skene, Loane. Nature Reviews Genetics 2002. 3:145-8. Charo, R. Alta. NEJM 2006. 355:1517-9.
Adverse events with G-CSF for neutropenia in cancer.
Authors: Debra E. Irwin, Brenna L. Brady
Journal: Journal of Clinical Oncology (2018)

e18762 Background: Granulocyte colony stimulating factor (G-CSF) is used to treat chemotherapy-induced neutopenia. This study examined patient characteristics and adverse events (AE) for G-CSF, including biosimilar products, in cancer patients. Methods: Cancer patients new to G-CSF treatment between 7/1/2015 and 11/30/2016 were identified in the MarketScan Database. The first administration of filgrastim (FIL), tbo-filgrastim (TBO), or filgrastim-sdnz (SNDZ) served as the index date. Patients has to be enrolled for ≥ 60 days prior and ≥ 30 days following index. Characteristics were evaluated during the baseline period; AEs were examined over the 30 day follow-up. FIL was the reference group. Results: A total of 5,470 patients (FIL: 4,155, TBO: 771, SNDZ: 544) qualified for the study. Over 4% of FIL use was in pediatric patients compared to < 1% for SNDZ and TBO (p < 0.01); use in elderly patients was similar across the 3 groups. FIL patients were more likely to be male (45%) compared to TBO (40%) and SNDZ (36%) patients (p < 0.01) and were more likely be diagnosed with leukemia and less likely to be diagnosed with breast, gastrointestinal, lymphoma, and respiratory cancers compared to TBO and SNDZ (p < 0.01). There were no significant differences across groups for most AEs (pyrexia, rash, nausea, vomiting, headache, epistaxis, diarrhea, arthralgia, leukocytosis, spleen rupture, acute respiratory syndrome, capillary leak syndrome). TBO patients were more likely than FIL patients to experience cough (5.4 vs 3.4%), dizziness (3.0% vs 1.3%), dyspnea (9.5 vs 7.2%), fatigue (10.2 vs 7.1%), and thrombocytopenia (15.6 vs 12.7%) (p < 0.05). SNDZ patients evidenced lower rates of arthralgia (0.9 vs 3.4%), anemia (18.6 vs 24.8%), fatigue (4.2 vs 7.1%), and thrombocytopenia (7.9 vs 12.7%), but increased rates of dizziness (3.1 vs 1.3%), compared to FIL patients (p < 0.05). Conclusions: Differences observed in demographic and clinical characteristics of the populations receiving the rG-CSFs may be due to the differences in labeled indications such as cancer type or age, reimbursement policies, or provider preferences. Safety profiles were similar with only slight differences in AE rates potentially due to underlying differences in baseline characteristics of the populations.
Updated results from the phase II study of hyper-CVAD in combination with ofatumumab as frontline therapy for adults with CD20 positive (CD20+) acute lymphoblastic leukemia (ALL).
Authors: Ghayas C. Issa, Hagop M. Kantarjian, Farhad Ravandi, Deborah A. Thomas, Maria Khouri, Guillermo Garcia-Manero, Rebecca S. Garris, Jorge E. Cortes, Nicholas James Short, Koji Sasaki, Heather M Schroeder, Tapan M. Kadia, Srdan Verstovsek, Naval Guastad Daver, Nitin Jain, Marina Konopleva, Susan Mary O'Brien, Elias Jabbour
Journal: Journal of Clinical Oncology (2016)

7042 Background: Chemoimmunotherapy is standard of care for patients (pts) with CD20+ ALL. Ofatumumab targets a unique small-loop epitope on CD20 and is more potent in vitro than rituximab. The combination of ofatumumab with hyper-CVAD may improve outcomes in ALL. Methods: 53 pts with Ph- CD20+ ALL, newly diagnosed (n = 49) or previously treated with 1 course of therapy (n = 4, 3 of whom were in CR at enrollment), received 8 cycles (cy) of hyper-CVAD (cy 1, 3, 5, 7) alternating with methotrexate (MTX) and cytarabine (cy 2, 4, 6, 8); ofatumumab was given during cy 1-4. Pts then received POMP maintenance for approximately 30 months (mos), interrupted by intensification with MTX/pegylated asparaginase in mos 6 and 18 and hyper-CVAD plus ofatumumab in mos 7 and 19. Results: Median age was 41 years (range: 18–71); median WBC was 4.6 x 109/L (range: 1-201 x 109/L). 19 pts (36%) had diploid karyotype. 32 pts (60%) had CD20 expression > 20%, 5 (9%) 10-20 % and 13 (25%) 1-10%. Of 50 pts evaluable for response, 49 (98%) achieved complete remission (CR) after 1 cycle; 1 pt died of sepsis during cycle 1. 48/52 pts (92%) became negative for minimal residual disease (MRD) as assessed by multicolor flow cytometry; of them 34 (67%) at CR. Median time to MRD negativity was 0.7 mos (range: 0.4-7.8). Median number of cy given was 7 (range: 1-8). Median times to neutrophil and platelet recovery after cycle 1 were 18 and 21 days, respectively. 67% of pts had febrile neutropenia during induction and 89% during consolidation. Grade ≥ 3 toxicity included high AST/ALT in 13 pts (32%), hyperbilirubinemia in 7 (17%), neuropathy in 3 (7%) and infusion reaction in 3 (7%). With a median follow-up of 16 mos (range: 1-53), 44 pts (83%) are alive: 41 in CR, 16 of whom are receiving POMP maintenance and 5 have completed all treatment. 6 pts received an allogeneic stem cell transplant after a median of 5 mos from treatment start (range: 4-8). 9 pts have died: 6 of relapse, 2 of sepsis and 1 of intracranial hemorrhage. The 2-year CR duration and overall survival rates were 74% and 83%, respectively. Conclusions: The combination of ofatumumab with hyper-CVAD is safe and highly effective in pts with CD20+ Ph- ALL. Clinical trial information: NCT01363128.
Outcomes of secondary cancers among myeloma survivors.
Authors: Jorge J. Castillo, Adam J. Olszewski
Journal: Journal of Clinical Oncology (2017)

8043 Background: With increasing survival, myeloma patients (pts) experience second cancers. We analyzed receipt of surgery and cancer-specific survival (CSS) among myeloma survivors with common solid tumors, in comparison with pts without myeloma. Methods: We extracted Surveillance, Epidemiology, and End Results (SEER) data on pts diagnosed with common cancers in 2004-2013. Among them, we identified myeloma survivors, and we matched each to 50 randomly sampled controls with the same cancer by age, sex, race, and year of diagnosis. We then compared CSS, cumulative incidence function (CIF) for death from the index cancer (but not from myeloma), and receipt of surgery (for non-metastastic, stage-matched tumors only) using a Cox (for hazard ratio, HR), Fine-Gray (for subhazard ratio, SHR), and conditional logistic models, respectively. Results: Myeloma survivors were significantly older ( P&lt;.001), and more often black (except in bladder cancer) than pts with respective cancers from the general population. In the case-control analysis, breast ( P=.002) and lung cancers ( P=.003) were more often diagnosed at an early stage among myeloma survivors. Receipt of surgery did not significantly differ, except for lower use of prostatectomy in myeloma survivors (odds ratio, 0.59, 95%CI, 0.44-0.81). CSS significantly differed only in lung cancer, and was better among myeloma survivors even when stratified by stage. CIF of cancer death was significantly lower for myeloma cases with lung and colorectal cancer. Conclusions: Despite additional competing mortality from recurrent myeloma, myeloma survivors have similar CSS and CIF of death after common cancers compared with other pts. This highlights the need to treat them similarly to other pts, without assuming a poor prognosis. Better outcomes in lung cancer are not fully explained by earlier detection, suggesting a biological difference. [Table: see text]
Abstract 17513: Edoxaban for the Prevention of Thromboembolism in Patients With Bioprosthetic Valves in ENGAGE AF-TIMI 48
Authors: Anthony Carnicelli, Raffaele De Caterina, Jonathan Halperin, Giulia Renda, Christian Ruff, Marco Trevisan, Francesco Nordio, Michele Mercuri, Elliot Antman, Robert Giugliano
Journal: Circulation (2016)

Background: Randomized data with NOACs in patients (pts) with atrial fibrillation (AF) and bioprosthetic valves (BPV) are scarce. We compared outcomes in pts with BPV and in pts with valvular heart...
Association between Beck depression inventory, Montgomery-Asberg depression rating scale and genotypes of the CYP17 steroid metabolism gene in breast cancer.
Authors: Riika Susanna Korhonen, Ari Hirvonen, Tuomas Selander, Paula Ollonen, Matti Eskelinen
Journal: Journal of Clinical Oncology (2016)

e21544 Background: Life-time exposure to steroid hormones appear to play important aetiology in breast cancer (BC). In addition, psychological factors, such as stressful and adverse life events, are widely thought to play a role in the aetiology of BC. Therefore, we carried out a prospective study to examine associations between Beck depression inventory (BDI), Montgomery-Asberg depression rating scale (MADRS), and CYP17 steroid metabolism gene genotypes in BC. Methods: In the Kuopio Breast Cancer Study 115 women with breast symptoms were evaluated for the total BDI score versus the total MADRS score before any diagnostic procedures were carried out. In addition, three different genotypes (A1/A1, A1/A2, A2/A2) of the CYP17 gene were determined by PCR based methods in breast cancer patients. Results: The total BDI score versus the total MADRS score were highly significantly correlated in the groups of the healthy study patients (HSS), patients with benign breast disease (BBD) and breast cancer (BC) (p < 0.001). Similarly, the pessimistic thoughts in BDI versus MADRS were highly significantly correlated in the HSS, BBD and BC groups (p = 0.002, p < 0.001, p < 0.001, respectively). The kappa values for the total BDI score versus the total MADRS score were highly significantly correlated in the HSS, BBD and BC groups (p < 0.001). The kappa values for pessimistic thoughts in BDI versus MADRS in the HSS, BBD and BC groups were also statistically significant (p = 0.017, p < 0.001, p < 0.001, respectively). The CYP 17 genotypes did not have any significant effect in the studied outcomes. Conclusions: The novel finding in the present work is a high agreement between the total BDI score versus total MADRS score in breast disease. Similarly, the pessimistic thoughts in BDI versus MADRS were highly significantly correlated. Clinical trial information: DNRO 14/12/1989.
QUADRUPLE THREAT: A phase II trial of RRx-001 followed by etoposide-platinum re-challenge in previously treated small cell lung cancer.
Authors: Sukhmani Kaur Padda, Christina E. Brzezniak, Saiama Naheed Waqar, Heather A. Wakelee, Patrick C. Ma, Michal G. Rose, Thomas Reid, Alexander I. Spira, Ellice Yuen-Ming Wong, Karen Grace Zeman, Bryan Oronsky, Nacer D Abrouk, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2018)

e20575 Background: RRx-001 is a first-in-class epi-immunotherapeutic drug that targets tumor-associated macrophages and cancer stem cells to reverse chemotherapy resistance in small cell lung cancer (SCLC). QUADRUPLE THREAT (QT) is a multicenter open-label phase II trial of RRx-001 followed by etoposide plus platinum (EP) in patients with previously treated SCLC. Methods: Patients (pts) with platinum resistant/refractory (R/R) SCLC or previous receipt of ≥2 lines of therapy were treated with 4 mg RRx-001 IV once per week. At progression, RRx-001 was discontinued and patients were re-challenged with IV etoposide 80-100 mg/m2 (Days 1, 2, and 3) and cisplatin 60-80 mg/m2 on Day 1 or carboplatin AUC 5-6 on Day 1 for up to 4-6 cycles. The co-primary endpoints were overall response rate (ORR) by RECIST 1.1 criteria and overall survival (OS). Results: 26 patients were enrolled from 10 institutions in the United States. The median age was 62.9 years (range 35.7 - 84.0), 16 pts (62%) were males and 57% had platinum R/R disease. The median number of doses of RRx-001 before starting platinum-based chemotherapy on study was 5 (range 2-23 doses). Among the 12 evaluable pts that have completed RRx-001 and initiated platinum/etoposide, 9 (75%) had disease control (≥SD), 4 (33%) of which achieved an objective response, with 3 partial responses and 1 complete response per RECIST 1.1 assessment. One out of 12 pts (8%) achieved partial response on RRx-001 alone prior to starting platinum-based chemotherapy. All 4 patients that achieved response had platinum R/R disease. None of the evaluable patients came off study prior to starting platinum-based chemotherapy. The median follow-up was 3.9 months, with an estimated median and 1-year OS of 7.5 months (CI 95% 5.8, NA) and 45.6%, respectively. RRx-001 was well-tolerated and subsequent EP was associated with a < 10% incidence of ≥ grade 3 cytopenias, which was less than expected based on historical data with EP. Conclusions: RRx-001 with EP re-challenge is a well-tolerated regimen with encouraging anti-tumor activity and possible myeloprotective properties in platinum R/R or heavily pretreated SCLC. The trial has completed accrual. Clinical trial information: NCT02489903.
TCT-618 Angiogram Based Fractional Flow Reserve in Patients with Multi-Vessel Disease
Authors: Hiroyuki Omori, Yoshiaki Kawase, Toru Tanigaki, Tetsuo Hirata, Yoshihiro Sobue, Hideaki Ota, Hiroki Kamiya, Munenori Okubo, Orna Valzer, Guy Witberg, Ran Kornowski, Hitoshi Matsuo, Hiroyuki Omori
Journal: Journal of the American College of Cardiology (2018)
Prognostic significance of bone marrow cellularity in myelodysplastic syndromes: a retrospective analysis.
Authors: Kiyomi Morita, Abdullah Ali, Diego Coutinho, Muhammad Umair Mushtaq, Azra Raza
Journal: Journal of Clinical Oncology (2016)

e18550 Background: Bone marrow (BM) of myelodysplastic syndrome (MDS) patients is usually hypercellular to compensate for ineffective hematopoiesis. A subset of MDS patients present with normo- or hypocellular BM, reflecting the disease heterogeneity. We retrospectively reviewed MDS patients to clarify the prognostic significance of BM cellularity. Methods: A total of 174 patients with MDS were analyzed. For patients with multiple BM tests, the earliest BM showing a definitive MDS diagnosis was used. Results: Median age at BM exam was 74 (30-95) years. WHO classification included 2 RA, 18 RARS, 16 RCUD, 74 RCMD, 29 RAEB1, 22 RAEB2, 1 isolated del (5q) and 12 unknown. BM cellularity was available for 154 patients. Hypocellular ( ≤ 30%), normocellular (30-70%) and hypercellular ( > 70%) BM was observed in 17% (n = 27), 38% (n = 58) and 45% (n = 69) of cases. Gene mutation data for ASXL1, EZH2, TP53, ETV6 and RUNX1 were available for 70 patients: there was no correlation between mutational status and BM cellularity. Cellularity showed an impact on International Prognostic Scoring System Revised (IPSS-R) category and WHO classification (p = 0.016, p = 0.015): a significant difference of cellularity was observed between IPSS-R high and very low and between RCUD and RAEB1 (p = 0.017, p = 0.024). Patients with hypercellular BM (Hyper-BM) showed significantly worse overall survival (OS) than those without Hyper-BM (median OS: 1.99 vs. 3.13 years, p = 0.023). Cox regression model for Hyper-BM MDS revealed that hemoglobin (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.18-0.66, p = 0.001), platelet (HR 0.98, CI 0.98-1.00, p = 0.026), BM blast (HR 0.73, CI 0.59-0.91, p = 0.006) and IPSS-R karyotype subscore (HR 3.59, CI 1.56-8.23, p = 0.003) were independent prognostic markers. Conclusions: BM hypercellularity is associated with worse OS, higher IPSS-R risk and advanced WHO classification. Hypercellular MDS can be further risk-stratified based on blood count and cytogenetics. BM cellularity can be considered as a variable to be incorporated into risk-classification system for better prognostic assessment for MDS.
Which side is better? The impact of primary tumor side in early stage colorectal cancer (CRC).
Authors: Margaret Lee, Andrew Mackinlay, Christine Semira, Antonio Jose Jimeno, Belinda Lee, Natalie Gunn, Jeanne Tie, Rachel Wong, Suzanne Kosmider, Ben Tran, Kathryn Maree Field, Peter Gibbs
Journal: Journal of Clinical Oncology (2017)

e15106 Background: Multiple studies have indicated the prognostic and potential predictive significance of primary tumor side in metastatic CRC. To date, the few studies examining its impact in early stage disease have either combined data across multiple stages or restricted analysis to overall survival (OS) data. A by stage analysis of the impact of tumor side on recurrence risk is critical if it is to impact adjuvant therapy decisions. Methods: We examined data from a multi-site Australian registry of consecutive patients diagnosed from 2003-2016. Tumors at and distal to the splenic flexure, including the rectum, were considered a left primary (LP). Rectal patients treated with initial chemoradiation were excluded. Clinico-pathologic and outcome data were examined. Data analysis was provided by the healthcare group at IBM Research Australia. Results: A total of 6123 patients were identified, of which 1046 (17.1%) had initial stage I, 1892 (30.9%) had stage II, 1708 (27.9%) had stage III, and 1477 (24.1%) had stage IV disease. Most patients were male (55.2%), and had a LP (n = 3818, 62.4%). Median age at diagnosis was 68.8 years, was higher in patients with a right primary (RP) (71.6 versus 67.0 years for LP, p &lt; 0.001), with more females in the RP group (51.1% vs 41.0% for LP, p &lt; 0.001). The proportion of RP varied by stage, highest in stage II (44.9%), lowest in stage IV (31.5%). For all stage IV disease, including metachronous cases, OS was worse with a RP (HR 1.32, 95% CI 1.14-1.53). For early stage cases, distant recurrence free survival (DRFS) was similar for RP vs LP for stage I (HR 0.63, 95% CI 0.32-1.23), better for stage II RP (HR 0.72, 95% CI 0.55-0.95) and worse for stage III RP disease (HR 1.22, 1.01-1.48). OS did not differ for RP vs LP for stage I or II disease, but was worse for stage III disease with a RP (HR 1.39, 95% CI 1.13-1.70). Furthermore, post recurrence survival was poorer in stage III RP disease (HR 1.61, 95% CI 1.33-1.96). Conclusions: Primary tumor side has potential as an important prognostic marker in early stage CRC. Our novel finding of a variable impact by stage indicate that an assessment of cohorts where recurrence data is available is critical to fully understanding the implications of tumor side for adjuvant therapy decision making.
Comprehensive Phenotypic Characterization of Human Invasive Lobular Carcinoma Cell Lines in 2D and 3D Cultures
Authors: Nilgun Tasdemir, Emily A. Bossart, Zheqi Li, Li Zhu, Matthew J. Sikora, Kevin M. Levine, Britta M. Jacobsen, George C. Tseng, Nancy E. Davidson, Steffi Oesterreich
Journal: Cancer Research (2018)

Abstract Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer following invasive ductal carcinoma (IDC) and characterized by the loss of E-cadherin–mediated adherens junctions. Despite displaying unique histologic and clinical features, ILC still remains a chronically understudied disease, with limited knowledge gleaned from available laboratory research models. Here we report a comprehensive 2D and 3D phenotypic characterization of four estrogen receptor–positive human ILC cell lines: MDA-MB-134, SUM44, MDA-MB-330, and BCK4. Compared with the IDC cell lines MCF7, T47D, and MDA-MB-231, ultra-low attachment culture conditions revealed remarkable anchorage independence unique to ILC cells, a feature not evident in soft-agar gels. Three-dimensional Collagen I and Matrigel culture indicated a generally loose morphology for ILC cell lines, which exhibited differing preferences for adhesion to extracellular matrix proteins in 2D. Furthermore, ILC cells were limited in their ability to migrate and invade in wound-scratch and transwell assays, with the exception of haptotaxis to Collagen I. Transcriptional comparison of these cell lines confirmed the decreased cell proliferation and E-cadherin–mediated intercellular junctions in ILC while uncovering the induction of novel pathways related to cyclic nucleotide phosphodiesterase activity, ion channels, drug metabolism, and alternative cell adhesion molecules such as N-cadherin, some of which were differentially regulated in ILC versus IDC tumors. Altogether, these studies provide an invaluable resource for the breast cancer research community and facilitate further functional discoveries toward understanding ILC, identifying novel drug targets, and ultimately improving the outcome of patients with ILC. Significance: These findings provide the breast cancer research community with a comprehensive assessment of human invasive lobular carcinoma (ILC) cell line signaling and behavior in various culture conditions, aiding future endeavors to develop therapies and to ultimately improve survival in patients with ILC. Cancer Res; 78(21); 6209–22. ©2018 AACR.