tbuckley/cabot-search huggingface dataset:
A phase I trial of CD19-targeted EGFRt/19-28z/4-1BBL armored chimeric antigen receptor (CAR) modified T cells in patients with relapsed or refractory chronic lymphocytic leukemia.
Authors: Jae Hong Park, Isabelle Riviere, Xiuyan Wang, Brigitte Senechal, Yvette Bernal, Elizabeth Halton, Claudia Diamonte, Yongzeng Wang, Renier J. Brentjens, Michel Sadelain
Journal: Journal of Clinical Oncology (2017)

TPS7568 Background: Despite the recent progress in the therapy of CLL with BTK, PI3Kδ, and BCL2 inhibitors, CLL remains incurable and patients with high-risk disease features (i.e. del17p, complex karyotype) and patients whose disease progress after treatment with the above targeted agents continue to have extremely poor prognosis. CD19-specific chimeric antigen receptor (CAR) T cell therapy with various 2 nd generation CARs (19-28z or 19-41BBz) have demonstrated anti-tumor efficacy in CLL but the complete response (CR) rates in CLL have been suboptimal (20-45%) compared to CR rates in ALL (80-90%). The suboptimal activity of the current 2 nd generation CAR T cells can be due to the inhibitory tumor microenvironment (TM) of CLL. We believe one approach to over the hostile TM is through the use of CD19-CAR T cells further modified to express a second costimulatory ligand, 4-1BBL. A binding of 4-1BBL to its cognate receptor enhances T cell proliferation, IL-2 secretion, and survival and cytolytic activity of the T cells compared to 19-28z. 19-41BBz and 1928BBz (Zhao Z et al. Cancer Cell 2015;28:415-428). Methods: This phase I dose escalating trial is a single-center clinical trial (MSKCC) to study the safety and efficacy of autologous EGFRt/19-28z/4-1BBL + CAR T cells in patients with relapsed CLL. Given the concern for potential systemic toxicity the vector includes a "safety switch" in the form of a gene for the expression of truncated form of human epidermal growth factor receptor (EGFRt). Patients with relapsed CLL are eligible for the trial. Patients will receive conditioning chemotherapy of cyclophosphamide followed by escalating doses of CAR T cells (1x10 5 – 3x10 6 CAR T cells/kg). The primary endpoint is safety and maximum tolerated doses of the CAR T ells. Secondary objectives include response assessment by iwCLL criteria. The comprehensive treatment algorithms for CRS and neurotoxicity are based on our CAR T cell experience in other studies. The study will begin enrollment in February 2017 and enroll up to 30 patients. Clinical trial information: Pending.
Use of a cognitive computing system for treatment of colon and gastric cancer in South Korea.
Authors: Jeong-Heum Baek, Sung-Min Ahn, Alexandra Urman, Young Saing Kim, Hee Kyung Ahn, Park Sung Won, Won-Suk Lee, Sun Jin Sym, Heun Kyu Park, Yong-Soon Chun, Eun Kyung Cho, Woon-Kee Lee, Dongbok Shin, Young-Bo Kim, Irene Dankwa-Mullan, Andrew D Norden, Kyu Rhee, Uhn Lee
Journal: Journal of Clinical Oncology (2017)

e18204 Background: IBM Watson for Oncology (WFO) is a Memorial Sloan Kettering-trained cognitive computing system that provides oncologists with evidence-based treatment options for cancer. Treatments are presented in three categories: “Recommended”, “For Consideration” and “Not Recommended”. We examined the concordance of treatment options between WFO and the tumor board from Gachon University Gil Medical Centre (GMC), Incheon, South Korea. GMC is an urban center that cares for 50,000 cancer patients annually. Methods: We enrolled 340 patients with stage II, III and IV colon cancer and 185 with chemotherapy-naïve advanced gastric cancer, all treated between 2012 and 2016. Cases were processed using WFO, and the output was compared to blinded tumor board recommendations. Treatment options were considered concordant when the GMC recommendation was included in the “Recommended” or “For Consideration” categories. Results: Treatment recommendations were concordant in 248 (73%) of the 340 evaluated colon cancer cases. Of 250 patients treated in the adjuvant setting, 212 (85%) were concordant. Of 90 patients with metastatic disease, 36 (40%) were concordant. Treatment recommendations were concordant in 90 (49%) of 185 chemotherapy-naïve gastric cancer patients. Low concordance rates in gastric cancer were explained by two observations: (1) The trastzumab/FOLFOX regimen is not covered by the Korean National Health Insurance System, and (2) A regimen known as S-1 (tegafur, gimeracil, and oteracil) plus cisplatin is routinely used in Korea and is not used in the U.S. Conclusions: Treatment options suggested by WFO were concordant with the therapeutic decisions of GMC in the large majority of colon cancer patients treated in the adjuvant setting. Lower degrees of concordance were seen in patients with metastatic colon and gastric cancer, reflecting differences in practice patterns between the United States, where WFO was trained, and GMC, in Korea. Geography-specific customization is available in WFO and should enable physicians and patients to benefit from WFO worldwide. WFO's ability to learn from gastric cancer cases in a part of the world with increased incidence may reveal insights that are applicable elsewhere.
Integrating insulin-like growth factor-1 (IGF-1) score into Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) scores.
Authors: Reham Abdel-Wahab, Sahin Lacin, Ahmed S Shalaby, Manal Hassan, Lianchun Xiao, Jeffrey Morris, Hesham M. Amin, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2016)

4081 Background: Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) Staging are the only systems that include Child Tarcott Pugh score (CTP) to assess hepatic function. Recently, we developed and validated Insulin like growth factor-1 CTP (IGF-CTP) score which possessed a higher ability in predicting patients’ overall survival (OS) than CTP. Our current study aimed at evaluating whether integrating IGF-CTP into BCLC and CLIP can provide additional value in predicting OS. Methods: In both training (n = 310) and validation (n= 155) from MD Anderson Cancer Center, we used cox models to evaluate OS after adjustment for BCLC and CLIP parameters. Harrell’s C-index and U-statistics were used to assess the predictive capacity of the IGF-CTP-BCLC and IGF-CTP-CLIP. Results: In the training cohort, patients with IGF ≤26ng/ml had a shorter OS after adjusting for the effect of BCLC and CLIP with hazard ratio (HR) and 95% confidence interval (95%CI); [2.19 (1.6 – 2.98) and 1.52 (91.1 – 2.1)], respectively. A similar trend was found in the validation cohort and after adjusting for the effects of BCLC and CLIP parameters. C-index showed that integrating IGF-CTP score was significant in CLIP but not in BCLC, while, adding IGF-1 (cutoff point; 26ng/ml) to both BCLC and CLIP showed a higher predictive ability. (Table1) Conclusions: Integrating plasma IGF-1 into BCLC and CLIP led to a significantly better prediction for patients’ OS in two independent cohorts. Integrating IGF-CTP was significant only in CLIP score. However, BCLC classes are more heterogeneous because it is a treatment allocation system not only a prognostic system, therefore, future studies of BCLC in this setting are warranted for international validation of these scores. Training cohort C index (95% CI) [P value] Validation cohort C index (95% CI) [P value] CLIP 0.705 (0.66 – 0.75) 0.7 (0.63 – 0.77) IGF-CTP-CLIP 0.715 (0.67 – 0.76) [0.006] 0.72 (0.65 – 0.8) [0.015] IGF-CLIP 0.711 (0.67 – 0.75) [<0.0001] 0.73 (0.65 – 0.81) [<0.0001] BCLC 0.64 (0.6 – 0.68) 0.54 (0.5 – 0.58) IGF-CTP- BCLC 0.64 (0.61 – 0.67) [0.2] 0.57 (0.54 – 0.6) [0.3] IGF-BCLC 0.67 (0.63 – 0.71) [<0.0001] 0.65 (0.58 – 0.73) [<0.0001]
Autologous stem cell transplantation in multiple myeloma patients over age 75.
Authors: Ning Dong, Phyllis McKiernan, David Samuel DiCapua Siegel, David H. Vesole, Scott D. Rowley, Tracy Andrews, Andrea Ortega, Alan P. Skarbnik, Noa Biran, Joshua Ryan Richter, Andrew Pecora, Andre Goy, Rima Panchal, Nino Aleksidze, Michele Donato
Journal: Journal of Clinical Oncology (2018)

8025 Background: Autologous stem cell transplantation (ASCT) has improved the outcome of patients with Multiple Myeloma (MM) substantially and is now the standard of care. Patients over the age of 75 years are often denied this procedure due to toxicity concern. Since 35% of patients with MM fall into this age category, the safety and effectiveness of ASCT in this patient population needs to be studied. Methods: 604 patients with MM who received an ASCT at John Theurer Cancer Center of HUMC between 2005-2014 were evaluated. A total of 44 patients ≥ 75 years of age (range 75-84) and 560 patients younger than 75 at time of ASCT were included. The Kaplan–Meier method was used to compare survival between those two age groups. Results: Features of patients older than 75 were summarized in table 1. Melphalan 200mg/ m2 was our primary conditioning regiment (75% of all patients). MM patients who received ASCT at age 75 or older had similar PFS and OS when compared with younger patients; the 3-year PFS was 52% and 46%, respectively; median PFS was 36.1 months vs 33.7 months, respectively, p = 0.76; the 3-year OS was 84% vs 82%, respectively; median OS was 93.3 months vs 127.8 months, respectively, p = 0.27. Two patients died within 100 days after ASCT. One died from subdural hematoma on day +11 and the other from Staphylococcus aureus sepsis on day +25. Conclusions: MM patients over the age of 75 can have similar outcomes from ASCT compared to the younger population. Elderly patients with MM should not be denied ASCT merely based on age. Patient features of MM patients who received ASCT at age 75 or older. N = 44 Age, mean (range) 76.8 (75-84) Female 14 (32%) Mobilization Cyclophosphamide-based regiment 30 (68%) GCSF 14 (32%) Received plerixafor 8 (18%) CD34 cells collected (x 10e6/kg), mean (range) 12.7 (3.1-27.9) Days of CD34 collection, mean (range) 3.7 (2-9) Disease Status at HSCT CR 1 (2%) VGPR 12 (27%) PR 21 (48%) SD 6 (14%) PD 2 (5%) Unknown 2 (5%) Conditioning regiment Melphalan 200mg/ m2 33 (75%) Melphalan 140mg/m2 9 (20%) Other 2 (5%) Best Response post ASCT Stringent CR 9 (20%) CR 9 (20%) VGPR 11 (25%) PR 7 (16%) SD 2 (5%) PD 1 (2%) Unknown 5 (11%)
Quality of patient-reported outcome for long-term survival of early breast cancer trials.
Authors: Gunter Von Minckwitz, Jan Steffen, Serban Dan Costa, Wolfgang Janni, Marc Thill, Volkmar Müller, Tanja Neunhoeffer, Hans Georg Lenhard, Gabriele Feisel, Iris Schrader, Uwe E. Kullmer, Michael Wittenberg, Valentina Nekljudova, Sibylle Loibl
Journal: Journal of Clinical Oncology (2016)

e18121 Background: Follow up (FU) of long term survival in early breast cancer (BC) trials is highly important as treatment effects might change over time and have to be related to late or chronic toxicities. In countries without access to national cancer registries, collection of long term FU is often an unaccomplishable task due to the logistic and financial burden for study sites and sponsors. Patient-reported outcome (PRO) registries for long term FU, like the one established by the German Breast Group (GBG) (von Minckwitz Eur J Cancer 2012) might be an accomplishable option for data collection. Here, we analyzed the quality of the PRO by validation with data provided by the investigators. Methods: Since 2009 almost 6000 participants of GBG trials joined PRO, consenting for name, address, and unique study identifier to be collected by a trustee who sent pseudonymized questionnaires about basic health status approx. once per year. PRO data of 5417 patients from 18 trials with a total of 396 reported events, including deaths (2.5%) and relapses/2nd malignancies (5%), and with no answer/withdrawal (14%), was sent for validation to 210 sites. Results: We received answers from 67 (32%) sites with feedback on 1161 (21%) patients. Sites confirmed the PRO result in 675 (58%) cases. Sites provided more recent data for 210 (18%) patients (including 43 new events), specified a missing event date for 6 (0.5%) patients, changed the diagnosis for 1 patient (from 2nd malignancy to metastasis), had not data available for 262 (23%) patients, or reported contradictory results for 5 (0.4%) patients (1 under- and 4 over-reported events in PRO). Sites were able to provide information for 157/228 (70%) patients not answering via PRO (reporting 24 new events). Sites giving feedback did not know about 6% (10 of 176) of the events reported by PRO. Conclusions: PRO seems to provide valid as well as additional information on disease-free and overall survival of BC patients at much lower costs and effort. Combination of PRO with focused effort by the site on those patients not answering or reporting incomplete data is a practical and valid approach to obtain FU data.
Development of a clinical trial immunohistochemistry (IHC) assay using a novel antibody to CD38.
Authors: Karen Wakamiya, Marsha Hudson, Hayley Finkelstein, Mai Nguyen, Sara Alvarez, Brad Neill, Josette William, Debra Ann Hanks, Malinka Jansson, Adam Northrup, John David Alvarez, Emin Oroudjev
Journal: Journal of Clinical Oncology (2017)

7561 Background: CD38 is a type II transmembrane glycoprotein expressed on normal lymphoid and myeloid cells and can be highly expressed in hematologic malignancies. An IHC prototype assay was developed to detect CD38 expression in formalin-fixed, paraffin-embedded (FFPE) tissue specimens from three relapsed or refractory non-Hodgkin’s lymphoma (NHL) subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL) for selection of patients for treatment with daratumumab in a Phase 2 clinical trial (NCT02413489). Methods: This assay is based on EnVision FLEX IHC technology using CD38, clone DAK-CD38, primary antibody that has been developed and manufactured by Agilent Technologies. The assay staining protocol was developed for Dako PT Link and Autostainer Link 48. Specificity of DAK-CD38 staining was demonstrated by Western blot analysis of cancer cell lysates, as well as IHC on both normal and cancer tissue. Assay precision and robustness were evaluated using commercially procured FFPE DLBCL, FL and MCL specimens. Results: CD38 IHC DAK-CD38 detected a broad range of CD38 expression in DLBCL, FL, and MCL specimens. FFPE specimens derived from cancer cell lines exhibited a range of IHC staining intensity and confirmed the reported expression of CD38 in the scientific literature. All precision and robustness results met acceptance criteria for both IHC intensity and percent positive cells staining. Conclusions: Our studies demonstrate that the Dako CD38 IHC DAK-CD38 assay is sensitive, specific, precise, and robust for the detection of CD38 expression in DLBCL, FL and MCL. This assay may also have the potential to be used for the detection of CD38 in additional tumor types.
Loss of TP53 as a prognostic biomarker of poor survival in stage III colorectal cancer patients.
Authors: Lincoln Nadauld, Paul Van Hummelen, Li Charlie Xia, Kenneth Day, Hojoon Lee, John Bell, Susan M. Grimes, Matt Kubit, Mickey Miller, Giwon Shin, Christina Wood, Stephanie Greer, Helaman Escobar, Derrick S. Haslem, Hanlee Ji
Journal: Journal of Clinical Oncology (2018)

e15588 Background: Colorectal cancer is the third most common malignancy worldwide, and a major contributor to cancer-related deaths annually. National and international guidelines for the management of stage III colorectal cancer patients include recommendations for treatment with adjuvant chemotherapy. Despite the application of fluorouracil-based chemotherapy regimens, and advances in surgical approaches, the survival of stage III colorectal cancer patients remains disparate with few tools available for the prognostic stratification of patient survival. Improved biomarkers are required to better stratify stage III colorectal cancer patient with good versus poor prognoses. Methods: A whole genome copy number analysis of stage III colorectal cancer patient samples was performed on matched tumor and normal archival tissues from 154 stage III colorectal cancer patients. Included patients had undergone standard surgical resection and received fluorouracil-based adjuvant chemotherapy. Shallow coverage, whole genome sequencing analysis was performed on both tumor and matched normal tissue samples. Results: We analyzed the copy number changes from the 154 colorectal samples with Gistic2, lasso-based model selection, and multivariate cox regression analyses. Among the 130 cross-sample copy number regions reported by Gistic2 (Q < 0.05), we found a region on chromosome 17 (chr17.p11 to p13) containing the TP53 tumor suppressor that was deleted in > 42% of all samples. More importantly, its loss was significantly associated with worse survival (HR = 1.405, 95% CI = 1.106, 1.784), P = 0.00538 (Wald's test), indicating TP53 loss as a significant prognostic indicator of poor survival in stage III colorectal cancer patients. Conclusions: Whole genome copy number analyses at low coverage can identify prognostic subgroups among patients with stage III colorectal cancer. Specifically, loss of TP53 is statistically significantly associated with worse survival in this patient cohort, independent of age, gender, or other standard clinical characteristics. Confirmation of this finding in additional patient cohorts is indicated and could lead to regular analysis of this biomarker for prognostic patient stratification.
Changes in access to care and financial hardship associated with Affordable Care Act (ACA) implementation for cancer survivors aged 19-64 years.
Authors: Amy J. Davidoff, Xuesong Han, K Robin Yabroff, Xin Hu, Zhiyuan Zheng, Katherine S. Virgo
Journal: Journal of Clinical Oncology (2018)

6565 Background: In 2014, as part of the ACA implementation, Medicaid eligibility was expanded in over half of states and insurance marketplaces were created in all states, with premium subsidies for selected individuals. Our prior research indicated a 38% reduction in the uninsured rate for cancer survivors by 2015. Here we examine subsequent changes in access and financial hardship. Methods: We pooled data for cancer survivors aged 19-64 years from the 2012, 2013 & 2015 National Health Interview Survey (N = 2996). We examined perceived access barriers (unmet need, medication cost-related non-adherence (CRN)), ability to pay medical bills, worry about future bills, and food insecurity. Linear probability regressions examined changes between the 2012-2013 and 2015 periods. Models controlled for eligibility for both Medicaid and premium subsidies to purchase insurance, constructed using family structure, income and employment, and linked data on state-specific Medicaid expansion policies. Models also controlled for demographics and comorbidities. Results: Prior to ACA implementation, 18% of cancer survivors delayed healthcare due to cost, 13% had unmet need for medical care, 18% reported CRN, 31% reported being highly worried about paying future medical bills and 23% reported food insecurity. Post-ACA there were adjusted decreases of 4.5 percentage points (PPT) in delayed care, 4.8 PPT in any unmet need, 7.4 PPT decline in worry about future bills, all at p < .01. No reductions were observed in unmet drug need, medication CRN, or food insecurity. In 2015, 13% still reported delayed healthcare, 14% reported CRN, and 25% worried about ability to pay future medical bills. Conclusions: After the ACA implementation, cancer survivors experienced significant reductions in access burden and financial worry. Despite improvements, cancer survivors still experience healthcare access limits, and worry about future financial health. ACA coverage changes, participation, access and health outcomes for cancer survivors need ongoing monitoring, particularly given repeal of the individual mandate.
MERTK Promotes Resistance to Irreversible EGFR Tyrosine Kinase Inhibitors in Non–small Cell Lung Cancers Expressing Wild-type <i>EGFR</i> Family Members
Authors: Dan Yan, Rebecca E. Parker, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Journal: Clinical Cancer Research (2018)

Lung cancer is the leading cause of cancer-related death. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers and over 60% express wild-type EGFR (wtEGFR); however, EGFR tyrosine kinase inhibitors (TKIs) have limited effect in most patients with wtEGFR tumors. We previously identified MERTK tyrosine kinase as a potential therapeutic target in NSCLC and developed MRX-2843, a novel MERTK-selective inhibitor with favorable properties for clinical translation. The goal of this study was to determine whether MERTK and EGFR inhibitor combination therapy could provide antitumor efficacy against wtEGFR NSCLC.An unbiased screen of 378 kinase inhibitors was conducted to identify synergistic interactions with MRX-2843 and biochemical and therapeutic effects were determined in vitro and in vivo.Numerous irreversible EGFR TKIs, including CO-1686 and osimertinib, synergized with MRX-2843 to inhibit wtEGFR NSCLC cell expansion, irrespective of driver oncogene status. CO-1686 and MRX-2843 combination therapy inhibited MERTK, wtEGFR, and ERBB2/ERBB3 and decreased downstream PI3K-AKT, MAPK-ERK, and AURORA kinase (AURK) signaling more effectively than single agents. Inhibition of PI3K, AKT or AURK, but not MEK, synergized with CO-1686 to inhibit tumor cell expansion, suggesting their roles as key redundant resistance pathways. Treatment with MRX-2843 and CO-1686 or osimertinib prevented xenograft growth while single agents had limited effect. Tumor growth inhibition was durable even after treatment with combination therapy was stopped.Our data support the application of MRX-2843 in combination with an irreversible EGFR TKI as a novel strategy for treatment of patients with wtEGFR NSCLC.
P36 Diagnostic Accuracy and Complication Rate of CT-Guided Core Biopsies of Lung Lesions in a Thoracic Oncology Unit in Mexico
Authors: S. Campos Gomez, M.A. Morales-Ruíz, J.J. Valdés-Andrade, J. Esquivel-Gutiérrez, D.E. Aguirre-Quezada, J.L. Barrera Franco, G. Pacheco-Cuellar, K. Campos-Gomez
Journal: Journal of Thoracic Oncology (2018)