tbuckley/cabot-search huggingface dataset:
Outcome of RAS mutated lung adenocarcinoma (ADC ) patients (pts) on standard chemotherapy (chemo) and immune checkpoint inhibitors (immuneCI).
Authors: Nuria Pardo Aranda, Fiorella Ruiz, Alex Martinez Marti, Alejandro Navarro, Susana Cedres Perez, Iris de la Fuente, Neus Baste, Ana Vivancos, Josep M Miquel, Rodrigo Dienstmann, Enriqueta Felip
Journal: Journal of Clinical Oncology (2016)

e20597 Background: Matched therapies in EGFR mut and ALK fusions in ADC have dramatically improved pt outcome. RAS mut,the most frequent oncogene alteration, is not directly targetable with agents currently available for clinical use. We studied the efficacy of chemo and immunCI in RAS mut ADC and explored a potential interaction between coexisting RAS/TP53 mut and clinical benefit. Methods: Out of 235ADC with targeted mut profiling (mass spectrometry Sequenom or Amplicon MiSeq) at out institution, 59 had RAS mut (25%). From this population, 53 were eligible for retrospective analysis of clinical endpoints. Primary objective was to determine time to treatment failure (TTF) on first-line platinum-based chemo and subsequent immuneCI. Secondary objectives were to estimate survival after relapse (SAR) according to immuneCI exposure and correlative analyses with other gene mut Results: 51pts had KRAS mut tumors, most frequent variants being G12C(21), G12V(9), G12D(6), G13(5) while 2 pts had NRAS mut tumors(Q61). Coexisting events included TP53 mut(15/24), STK11 mut(4/24) and PIK3CA mut(2/53). Out of 42 pts that received systemic therapy for metastatic disease, 34 had first-line platinum-based chemo and 17 received maintenance chemo. 10 patients received immuneCI in the relapsed setting (6 nivolumab, 3 atezolizumab, 1 pembrolizumab). Median TTF on first-line platinum based chemo plus maintenance was 6.7 months (CI95% 4.7-8.7); median TTF on single-agent immuneCI was 13.2 months (CI95% 7.1-not reached). Pts with coexisting KRAS/TP53 mut maintained the favorable outcome with immuneCI (n = 6, median PFS 12.1 months). SAR was longer in pts that received immuneCI (not reached at 30 months) as compared to chemotherapy-only pts (15.2 months, CI95% 12.2-41.5; HR 0.46, log-rank P = 0.19). Conclusions: RAS mutated ADC pts have favorable outcomes when exposed to standard chemo and immuneCI. Stratified correlative analyses are recommended in clinical trials assessing the benefit of immuneCI in all-comers population.
Quantitative multiplex immunofluorescence to identify candidate biomarkers of response to anti-PD1 in metastatic melanoma.
Authors: Claire-Audrey Bayan, Robyn Denise Gartrell, Kimberly Mayumi Komatsubara, Jaya Sarin Pradhan, Douglas Kanter Marks, Yan Lu, Margaret Borgardus, Syed Shabee Hasan, Adriana Lopez, Thomas D Hart, Larisa J. Geskin, Bret Taback, Richard D. Carvajal, Gary K. Schwartz, Basil Horst, Yvonne M. Saenger
Journal: Journal of Clinical Oncology (2018)

e21600 Background: Predictive biomarkers for stratification of treatment with immunotherapy are urgently needed. Quantitative multiplex immunofluorescence (qmIF) allows for staining of multiple markers and quantitative analysis of a single formalin fixed paraffin embedded (FFPE) slide. The study aim is to identify biomarkers of response to anti-programmed cell death-1 (anti-PD-1) immunotherapy using (qmIF) in patients with metastatic cutaneous melanoma. Methods: We identified 15 patients with stage IV cutaneous melanoma treated with an anti-PD-1. Pre-treatment tumor tissue was stained using qmIF for DAPI (nuclei), CD3 (T cell), CD8 (cytotoxic T cell (CTL)), CD68 (macrophage), HLA-DR (activation), SOX10 (tumor), and Ki67 (proliferation). Mutispectral images were acquired with Vectraand analyzed using inForm software and RStudio. Results: Preliminary data for 8 patients (5 responders and 3 non-responders) was analyzed. We find that the ratio of SOX10+HLADR+/Total Tumor correlates with progression free survival (PFS) (p = 0.0185) and trends towards significance in predicting response to anti-PD-1 (p = 0.07). Nearest neighbor analysis finds that CTLs tend to be farther from SOX10+HLA-DR+ tumor cells in non-responders. QmIF and mRNA expression analysis (nanoString) of the complete cohort is ongoing. Conclusions: Consistent with the literature, we find that HLA-DR expression on tumor cells correlates with progression free survival (PFS) and response to anti-PD-1. Furthermore, CTLs tended to be closer to SOX10+HLA-DR+ tumor cells in responders. Previous reports show that HLA-DR is a potentially useful predictive biomarker and its expression in melanoma is important for anti-PD-1 activity, possibly through the promotion of a more inflammatory tumor microenvironment. Our preliminary results support this finding using qmIF, and the use of HLA-DR as a predictive biomarker of response to anti-PD-1 inhibition in metastatic melanoma merits further investigation.
A novel role for 17-Β estradiol and testosterone in osteosarcoma tumorigenesis and metastasis.
Authors: Jake N. Lichterman, Robert Post, Luke Menken, Bishoy Saad, Justin Delgado, Lauren Sall, Matthew Karr, PIotr Kozlowski, Kurt Degenhardt
Journal: Journal of Clinical Oncology (2017)

e23012 Background: Pulmonary metastases still remains the leading cause of mortality in osteosarcoma, with a 5-year survival rate of less than 30%. 17-β estradiol and testosterone are known to promote tumorigenesis and metastasis in other cancers, but its role in osteosarcoma tumorigenesis and metastasis is unclear. An understanding of the mechanism that these hormones have in osteosarcoma tumorigenesis and metastasis will lead to new therapeutic strategies using currently available targeted therapies used in breast and prostate cancer. Methods: We began by assessing the in vitro characteristics of two human osteosarcoma cell lines treated with 17-β estradiol or testosterone via proliferation and invasion assays. For the in vivo experiments, NCR nu/nu mice were injected with two luciferase-tagged human osteosarcoma cell lines and treated with 17-β estradiol and testosterone slow-release pellets. We first injected the mice subcutaneously and monitored tumor growth via caliper measurements. In the second experiment we injected the cell lines intratibially and monitored primary tumor growth in the bone and monitored metastasis formation in the lungs via IVIS bioluminescent imaging. Quantification of luciferase signal (photons/second) in the lungs was performed via the Xenogen Living Image software. H&amp;E and immunohistochemistry for luciferase expression was performed on lung tissue to quantify tumor burden in the lungs. Statistical analysis was performed using Graphpad Prism. Results: Treatment with 17-β estradiol and testosterone increased cell proliferation and invasion in a dose-dependent manner. We observed increased tumor growth with both 17-β estradiol and testosterone in the subcutaneous model. In the intratibial experiment, testosterone increases primary tumor growth, but has no effect on metastasis. 17-β estradiol decreases primary tumor growth, but increases metastasis in a cell line independent manner. Conclusions: This study demonstrates a novel role for the puberty-related sex steroid hormones, 17-β estradiol and testosterone, in osteosarcoma tumor growth and metastasis. Uncovering the mechanism behind this phenomenon will uncover new therapeutic options for this devastating disease.
Durable clinical responses observed from non-Hodgkin lymphoma patients treated with autologous CAR-T cells targeting CD19.
Authors: Yarong Liu, Bo Zhu, Qingzhu Jia, Feng He, Hongliang Fang, Jing Chen, Zixiao Shi, Tao Jin, Baofeng Wei, Ronglin Xie, Qi-Jing Li, Pin Wang
Journal: Journal of Clinical Oncology (2018)

3045 Background: Cellular immunotherapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) cells has shown to be one of the most promising immunotherapeutic strategies for cancer treatment. Herein we report an encouraging result from a phase 1 clinical trial to evaluate a CD19 CAR-T therapy for treating relapse/refractory B-cell non-Hodgkin's lymphoma (NHL). Methods: A phase 1 clinical trial was conducted to evaluate safety and efficacy of CD19 CAR-T therapy for patients with relapsed and/or refractory NHL. A total of 22 patients with CD19+ B-cell NHL at stage III/IV were enrolled in this study; these patients had received 4-12 (median 8) rounds of various chemotherapies prior to the enrollment. All patients were pre-conditioned with Cy (800 mg/m2) once (d -5) and Flu (25 mg/m2) daily for 3 days (d -5 to d -3) followed by administration of a total dose of 1x106 cells/kg CD19 CAR-T cells via either a single infusion or a 3-day split-dose (10, 30, and 60%) infusion regimen. The efficacy was assessed by RECIST1.1 and the toxicity was evaluated by CTCAE 4.02. The CAR-T cell expansion and persistence were measured by quantitative PCR (qPCR) and flow cytometry. Results: Of the 22 patients, only one exhibited over grade 3 cytokine release syndrome (CRS) and was resolved after active treatments. Moreover, no central nervous system toxicity was observed. The overall response rate (ORR) for the 18 evaluable patients was 72.2%. Complete remission (CR) and ORR for six months were both at 36.7%. The median progress-free survival was 4 months (95% confidence interval (CI), 0.5 to 7.5) and a median overall survival was 11 months (95% CI, 4.7 to 17.3). It was observed that local radiation prior to cell therapy could enhance CAR-T cell infiltration. Further analysis revealed a biomarker which could be used to identify beneficial patients. Interestingly, pseudo-progression occurred on some patients and two rounds of CAR-T expansion were seen in several patients. One patient has experienced ongoing CR, B cell deficiency, and persistence of CAR-T cells for > 21 months. Conclusions: Our data indicate that this CD19 CAR-T product can offer substantial clinical benefit for NHL patients with manageable toxicities. Clinical trial information: NCT02652910.
Phase III randomized, open-label study comparing the efficacy and safety of AG-221 <i>vs</i> conventional care regimens (CCR) in older patients with advanced acute myeloid leukemia (AML) with isocitrate dehydrogenase (IDH)-2 mutations in relapse or refractory to multiple prior treatments: the <i>IDH</i>ENTIFY trial.
Authors: Martin S. Tallman, Robert D. Knight, Axel G. Glasmacher, Hartmut Dohner
Journal: Journal of Clinical Oncology (2016)

TPS7074 Background: Mutant IDH (mIDH) enzymes produce an oncometabolite, 2-hydroxyglutarate (2HG), that can prevent DNA and histone demethylation required for lineage-specific myeloid progenitors to differentiate into mature cells. mIDH2 occurs in 8-19% of AML patients (pts) (Döhner, NEJM 2015) and can survive chemotherapy, leading to relapse (Chan, Nature Med 2015). AG-221 is a first in class, potent, selective, oral inhibitor of mIDH2. In a phase 1 dose-finding/expansion study of AG-221 in 159 pts with mIDH2+ AML relapsed-refractory (R/R) after 1 to 6 prior AML treatment (Tx) regimens, hematologic response rate was 38%, including 18% complete remission rate (Stein, ASH 2015). The international IDHENTIFY study (NCT02577406) in pts with mIDH2+ AML is the first randomized trial to evaluate an AML Tx in older pts R/R to multiple prior Tx courses—a pt population with few Tx options. Methods: Eligible pts are age ≥60 years with primary or secondary mIDH2+ AML and R/R after 2 or 3 prior Tx regimens. Physicians preselect the most appropriate of 4 CCR, given in 28-day cycles, for each pt (Table). Pts are then randomized 1:1 to AG-221 or to CCR and receive the preselected Tx. Randomization is stratified (yes/no) by prior intensive chemotherapy, primary refractory, and prior allogeneic HSCT. Assuming median OS of 5 months with CCR (Roboz, JCO, 2014) and 8 months with AG-221 (60% improvement) and a drop-out rate of ~10%, 280 pts will allow enough events (193 deaths) to achieve ≥90% power to detect a statistically significant OS difference at a Type I error rate of 0.05 (two-sided). Enrollment began in Oct. 2015 and continues through 2019. Clinical trial information: NCT02577406.Tx Arm* Dose Endpoints CCR 75 mg/m2 SC QD x7d Primary: Overall Survival (OS) Azacitidine 20 mg SC BID x10d Secondary: Overall response rate (IWG AML criteria), event-free survival, time to and duration of response, 1-year survival, quality of life Low-dose ara-C 0.5-1.5 g/m2 IV QD x3-6d Intermediate-dose ara-C 100 mg PO QD x28d Best supportive care (BSC) only AG-221
Electronically generating the treatment summary (TS) and survivorship care plan (SCP) for cancer survivors from a tumor registry.
Authors: Franco Regina, Matthew Francis Hudson, Julia Yates, Leighton Patricia, Stephanie Hoopes, McCormick Douglas, Perkins Leann, Kathleen Brant, Mark Allen O'Rourke
Journal: Journal of Clinical Oncology (2016)

10084 Background: Delivery of a TS/SCP for cancer survivors encounters barriers that include the time and effort to create the TS/SCP. The GHS Cancer Institute developed a process to electronically generate the TS/SCP using the tumor registry. Methods: The process begins with generating a report of new stage 0, I, II, and III cancer cases, using the tumor registry software, Metriq. That report is converted to an Excel file of new cancer cases. The survivorship nurse navigator reviews the Excel file and corrects or completes data for each case as needed. The Excel file is used to populate, by mail merge, the fields of the TS/SCP’s, including name, date of birth, date of diagnosis, cancer site, cancer stage, and tumor features such as estrogen receptor status; the dates and type of surgery, radiation therapy, chemotherapy, and endocrine therapy; and the names of the physicians in the care team. The TS/SCP for each case is entered into the appropriate EMR and the action is documented in the EMR, such that an order is generated to contact the patient and schedule a visit in the dedicated survivorship clinic to receive the TS/SCP, screen for distress, and to learn about available resources. Patients coming in for their TS/SCP visit who have not completed their planned surgery, radiation therapy, or chemotherapy receive a preliminary TS/SCP and have the option to receive the final TS/SCP at another visit or by mail. Results: The time (minutes) to prepare a TS/SCP decreased from 20 in 1-2015 to 6 in 1-2016. Chart audit revealed that the percent of charts with TS/SCP’s rose from 13.3% in 1-2015 to 33.3% in 1-2016. Conclusions: Tumor registry software can be used to efficiently generate TS/SCP’s. The time in minutes to prepare a TS/SCP and the percent of audited charts with a TS/SCP improved in the first year.
Variations between physicians in hospice referrals of advanced cancer patients.
Authors: Xiao Wang, Louise Knight, Anne Evans, Thomas J. Smith
Journal: Journal of Clinical Oncology (2016)

10027 Background: Hospice is the accepted best practice for advanced cancer patients with life expectancies of six months or fewer. However, a growing number of patients enroll in hospice for ≤ 7 days, a marker for poor quality of care and patient and family dissatisfaction. In the present study, we examined the variation in referrals between individual and groups of oncologists to assess a potential source of suboptimal hospice use and define targets for intervention. Methods: We conducted a retrospective chart review of 452 advanced cancer patients referred to hospice from July 1, 2013 to March 31, 2015, measuring hospice length of stay (LOS). We analyzed patient length of stay (LOS) under hospice services – specifically looking at median and very short stays (%LOS ≤ 7) – to examine the variation between individual and divisions of oncologists. Results: Of 394 successfully referred patients, median LOS was 14.5 days, consistent with national data. %LOS ≤ 7 was 32.5%, including 5.1% who died before reaching hospice. There was significant interdivisional variation in LOS, both by overall distribution (p < 0.01) and %LOS ≤ 7 (p < 0.01), shown in Table 1. In addition, there was dramatic variation in median LOS by individual oncologist (range 4–88, physicians with 5+ patients), indicating differences in hospice referral practices between care providers (cv > 125%). As one example, median LOS of oncologists in the Division of Thoracic Malignancies varied from 4 to 36.5 days, despite similarities in patients. Conclusions: Nearly 1 in 3 cancer patients that use hospice had LOS ≤ 7, a marker for poor quality. There is significant LOS variability between patients of different divisions and of different physicians, despite similarities in disease course. Our findings suggest differences in perspectives, knowledge, and/or familiarity with hospice between different oncologists, and highlight a need for increased education and training to set a high standard of care. Length of service by division. Division n Median LOS (days) %LOS ≤ 7 Hematologic 61 7 54.1% Neuro-Oncology 24 33.5 12.5% Breast 25 20 28.0% Gastrointestinal 114 16 24.6% Thoracic 79 18 27.8% Head & Neck 8 37 37.5% Melanoma & Sarcoma 30 8 50.0% Genitourinary 53 16 32.1% TOTAL 394 14.5 32.5%
Comparison of somatic mutation profiles from cell free DNA (cfDNA) versus tissue in metastatic urothelial carcinoma (mUC).
Authors: Michael L. Cheng, Maha Shady, Catharine Kline Cipolla, Samuel Funt, Maria E. Arcila, Hikmat Al-Ahmadie, Jonathan E. Rosenberg, Dean F. Bajorin, Michael F. Berger, Dana Tsui, David B. Solit, Gopa Iyer
Journal: Journal of Clinical Oncology (2017)

4533 Background: Next-generation sequencing (NGS) of cfDNA is an emerging non-invasive strategy to define tumor mutation profiles that counters spatial and temporal limitations of sequencing single tissue specimens. We examined the feasibility of NGS of cfDNA in mUC and compared mutation profiles from cfDNA to results of tissue NGS previously performed in the clinical setting. Methods: Plasma cfDNA was collected in mUC pts and analyzed using a capture-based NGS assay (MSK-IMPACT) targeting 341-468 genes. NGS profiles from cfDNA and archival tumor tissue (using the same assay) were analyzed in parallel with an established bioinformatics pipeline to identify somatic variants. Results: In 26 pts, NGS analysis of cfDNA detected ≥1 somatic mutations (range 1-21) in 69% (18/26). For 15 pts, NGS data was available from archival tissue (11 primary tumors, 3 metastases, and matched primary/metastatic tissue in 1 case). The interval between cfDNA and tissue collection ranged from 35 days to &gt; 4 yrs. 73% (11/15) of pts received intervening treatment, including 47% (7/15) with chemotherapy, 67% (10/15) with immunotherapy, and 40% (6/15) with both. In 40% (6/15), cfDNA harbored alterations not found in archival tumor tissue. In 73% (11/15), some mutations within archival tissue were not detected in cfDNA, including hotspot HER2 S310F and FGFR3 S249C mutations. Tumor and cfDNA mutation profiles were identical in 20% (3/15), with the tumor/cfDNA interval in this group ranging from 35 days to &lt; 1.5 yrs. Somatic alterations including hotspot ERCC2 P463A and PIK3CA E545K mutations were detected in cfDNA from 3 pts where archival tumor tissue NGS failed. Thus, cfDNA identified new mutations in 50% (9/18) of pts for whom cfDNA identified somatic mutations and tissue NGS was previously attempted. Conclusions: NGS of cfDNA from mUC pts is feasible and successfully detected actionable alterations when archival tumor sequencing failed. The differences between tumor and cfDNA mutation profiles in many pts may reflect tumor evolution or intratumor heterogeneity. Mutation profiles in mUC may be incompletely assessed with NGS of archival tissue, and further investigation of plasma cfDNA for genomic profiling is warranted.
Abstract 12171: A Double-Blind Randomized Controlled Trial Comparing the Effectiveness of External Loop Monitor and Automatic Real Time Continuous Tele-ecg Cardiac Monitor in Detecting Atrial Fibrillation Among Patients With Tia: A Pilot Study
Authors: Wadea M Tarhuni, Maher El-Masri
Journal: Circulation (2013)

Background: Atrial fibrillation (AF), including paroxysmal AF, is known to be a major risk factor in the development of TIA and ischemic stroke.1-5 Early detection of AF is therefore key to timely ...
PROeverywhere: Bridging the unmet needs of patient reported outcome with a mobile app.
Authors: Kin Wai (Tony) Hung, Natasha Banerjee, Jeffrey M. Miller
Journal: Journal of Clinical Oncology (2018)

e18570 Background: Patient reported outcome (PRO) data are critical for informing patient-centered care and have been shown to enhance our ability to communicate with patients, to control their symptoms, and to impact their survival. However, PRO data are not commonly collected in routine cancer care due to challenges such as cost, technological rigidity of existing electronic health records (EHR), and misalignment of stakeholders’ incentives. Methods: In an effort to bridge the unmet needs of PRO collection and integration into routine cancer care, we aim to develop an effective, scalable, and sustainable symptom monitoring and management system that can be accessed worldwide. The system will be developed using Xcode, the integrative development environment of Apple Inc., with the Swift programing language. Results: On Nov 28th, 2017, we launched a free, mobile PRO application system on the Apple App Store – PROeverywhere. PROeverywhere is designed for reporting twelve common symptoms from the National Cancer Institute’s Common Terminology Criteria for Adverse Events. These symptoms include appetite loss, constipation, nausea/vomiting, diarrhea, shortness of breath, insomnia, fatigue, depression, anxiety, memory problems, pain, and neuropathy. Symptoms are reported in a 5-point scale – no symptom, mild, moderate, severe, and disabling. PROeverywhere has the functions to record symptoms, summarize the reporting in physical printout, and automatically store and analyze the input symptoms into graphical interpretations. PROeverywhere can be downloaded worldwide with its database securely powered by Google Firebase. Conclusions: PROeverywhere is developed to enable PRO data to be shared more easily and regularly in routine cancer care. Implementation of this free mobile application would allow for consistency in collection of PRO data with the potential to impact patient outcomes globally.