tbuckley/cabot-search huggingface dataset:
Differences in the characteristics of younger and older MSI-H colorectal cancer (CRC) as determined by universal reflex testing.
Authors: Aaron J Franke, William Paul Skelton, Maira Gaffar, Forat Lutfi, Samantha Welniak, Michael Feely, Jason Scott Starr, Hiral D. Parekh, Atif Iqbal, Sanda Tan, Carmen Joseph Allegra, Thomas J. George
Journal: Journal of Clinical Oncology (2018)

3593 Background: DNA mismatch repair deficient (dMMR) or microsatellite instability high (MSI-H) CRC is found in ~15% of early stage and ~5% of metastatic disease. Universal or reflex testing to identify dMMR/MSI-H has been proposed. The CRC incidence in young patients (pts) is also rising with unclear etiology. We present a large, single-institutional database of universal reflex dMMR/MSI-H testing in CRC comparing clinicopathologic and molecular profiles of younger (≤50) and older ( > 50) pts. Methods: For all CRC pts diagnosed at University of Florida between 2009-2017, reflex somatic testing for dMMR by IHC (MLH1, PMS2, MSH2, MSH6), MSI by PCR (Promega MSI kit) and NGS was performed with appropriate positive and negative controls. IHC protein loss was confirmed by second GI pathologist. Equivocal IHC results triggered MSI testing. Review of associated clinical EMR data was retrospectively performed and analysis conducted with student's t-test. Study was IRB approved. Results: 375 pts were analyzed by ≤50yo (n = 80; median age 44, range 17-50) or > 50yo (n = 295; median age 66, range 51-98). There was 100% concordance of MMR and MSI of all patient samples. dMMR/MSI-H incidence was 14% (11/80) in pts ≤50, compared to 22% (64/295) in pts > 50 (p < 0.001). For stage IV CRC, dMMR/MSI-H incidence was 4% vs. 13% (p = 0.003) between the age groups. Younger pts presented with more advanced disease (36% Stage III, 36% Stage IV) compared to older pts (32% Stage III, 26% Stage IV). Associated BRAF mutations were more common in pts > 50 (20% vs. 67%; p = 0.005). Conclusions: In our dataset, younger CRC pts are diagnosed with more advanced disease but with dMMR/MSI-H cancers at the expected rate. However, we identified more (likely sporadic) dMMR/MSI-H stage IV cancers in pts > 50yo than expected. Further studies to identify risk factors for younger patients and the ultimate clinical impact of universal reflex MSI testing is warranted to maximize IO therapy offering and survival.
TCT-639 Comparison of Patients with and without Dialysis prior to TAVI in 2000 Consecutive Implantations with a 3 year follow up
Authors: Gerhard Schymik, Peter Bramlage, Valentin Herzberger, Jens Bergmann, Armin Luik, Holger Schroefel, Claus Schmitt, Panagiotis Tzamalis
Journal: Journal of the American College of Cardiology (2018)
Long term effect of nivolumab in patients with non-small cell lung cancer.
Authors: Mette Sprauten, Vidar Flote, Odd Terje Brustugun, Aslaug Helland
Journal: Journal of Clinical Oncology (2018)

e21156 Background: Advanced lung cancer has a poor prognosis, with a 5-year survival of 2.7% (Cancer in Norway, 2015). After data from CheckMate017 were published (Brahmer J et al, NEJC 2015), Nivolumab was the first PD1-inhibitor to be introduced in the treatment of NSCLC patients, and was made available by BMS in a “named-patient-use program”. In Norway, a total of 58 patients were included, and we present long-term data of survival in this cohort Methods: The 58 patients had previously received 1- 4 lines of treatment and had progressive disease when included during June- September 2015. They all received Nivolumab every two weeks at our Hospital. Details regarding treatment, time from treatment start until progression or death were recorded. Results: Median age was 64.6 years (range 32.3-88.2), and performance status ECOG 0-2. Thirty-eight had received two or more prior lines of therapy. After 2.7 years, 11 (19%) patients are still alive after receiving a median of 42 cycles of nivolumab (range 1 -66). For all 58 patients, the median number of cycles was 9 (range 1-66). Median survival after start nivolumab was 11.5 months (range 0.5- 32.4 months) for the 58 patients. Two patients received immunotherapy for more than 2 years, the rest ended Nivolumab treatment at the latest 2 years after inclusion. Of the 11 patients still alive, 7 have stable disease without further treatment, ongoing for a median of 12.8 months (range 7.8-18.3). One is still on nivolumab with stable disease, while the remaining three have received other treatment. Conclusions: In concordance with recent data from the phase 1b CA209-003 study (Brahmer et al, Cancer Rs 2017), we report a plateau of 11 (19%) long-term survivors in our cohort of NSCLC patients, with ongoing response at the longest, 32.4 months after treatment induction. Interestingly, 7 of 11 survivors have had stable disease as long as 12.8 months after ending nivolumab treatment.
Quantification and monitoring of treatment response in <i>EGFR</i> mutant non-small cell lung cancer patients using Digital PCR and Therascreen in plasma cell-free tumour DNA.
Authors: Vienna Ludovini, Annamaria Siggillino, Maria Sole Reda, Fortunato Bianconi, Rita Chiari, Sara Baglivo, Lorenza Pistola, Francesca Romana Tofanetti, Roberta Matocci, Clelia Mencaroni, Giulio Metro, Chiara Bennati, Vincenzo Minotti, Lucio Crino
Journal: Journal of Clinical Oncology (2016)

e23037 Background: The identification of activating epidermal growth factor receptor (EGFR) mutations is essential for deciding therapy of non-small cell lung cancer (NSCLC) patients. Circulating cell-free tumor DNA (cftDNA) holds promise as a non-invasive methodology for tumor monitoring in solid malignancies. Among advanced NSCLC patients with an acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs), about 50% carry T790M mutation, but its frequency in EGFR-TKI-naıve patients and dynamic change during therapy remains unclear. We hypothesized that EGFRmutation analysis detection in cftDNA for NSCLC may be feasible for monitoring treatment response to EGFR-TKIs and also predict drug resistance. Methods: EGFR sensitive mutations and T790M were analyzed using digital PCR (d-PCR) and Therascreen EGFR Plasma RGQ PCR in longitudinally (at baseline, at 4, 8, 20, 60, 120, 180, 270, 360 days) collected plasma samples (n = 50) from 8 tissue-confirmed EGFR-mutant NSCLC patients treated with an EGFR-TKI (Gefitinib N = 4; Erlotinib N = 1; Afatinib N = 3). Tumor assessment was assessed according to RECIST criteria 1.1 every two months. Results: The sensitivity of d-PCR and Therascreen assay in plasma versus tissue were 71.4% versus 28.6%, respectively. D-PCR identified higher frequency of T790M than Therascreen in pre-TKI (37.5% vs 0 %) plasma samples. Of four patients who developed progression disease (PD), in the samples of progression, T790M was detected by dPCR and Therascreen in 75% vs 0%, respectively. Therascreen method revealed EGFR mutations only when mean copy/µl number was up to 2.04 (range: 0.31- 4.1) detected in d-PCR. EGFR sensitive mutations decreased at PD while T790M mutation increased in 75% of patients. Patients with concomitant pre-TKI EGFR 19 deletion and T790M showed a PD before of 12 months compared to those with L858R. Conclusions: Qualitative and quantitative T790M in plasma cftDNA by d-PCR provided a non-invasive and sensitive assay to predict EGFR-TKI prognosis. However, our study is ongoing and further results will be presented at the meeting. We thank Italian Association for Cancer Research (AIRC) for supporting the study.
Underlying host immune dysregulation in cancer patients developing immune-related adverse events.
Authors: David E. Gerber, Shaheen Khan, Xin Luo, Saad A. Khan, Farjana Fattah, Jessica Saltarski, Yvonne Gloria-McCutchen, Jason Park, Yang Xie, Quan Li, Edward Wakeland
Journal: Journal of Clinical Oncology (2018)

3030 Background: Immune checkpoint inhibitors may cause potentially severe immune-related adverse events (irAEs). To determine the role of host immune status in the development of irAEs, we evaluated baseline and post-treatment serum cytokine and IgG levels in patients receiving checkpoint inhibitors. Methods: We collected serum from patients treated with checkpoint inhibitors before treatment, after 2-3 weeks, and after 6 weeks. We quantified cytokine profiles using a multiplex panel. Total IgG was determined using ELISA. We analyzed the association between these biomarkers and the presence of irAEs using t tests and ANOVA. Results: A total of 78 subjects were enrolled, including 65 cancer patients receiving checkpoint inhibitors and 13 healthy controls. Among cancer patients, mean age was 65 years, 55% were women, and 83% had lung cancer. Immune-related AEs occurred in 35% of cases as follows: pneumonitis (n = 11), endocrinopathy (n = 6), dermatitis (n = 2), arthritis (2), encephalitis (1), complex (2). There was a significant increase in chemokines CXCL9, CXCL10, CXCL11 and CXCL13 in patients at 2 weeks post-immunotherapy and in chemokines CXCL9, CXCL10, CXCL11, CXCL13, IL-10, and CCL26 at 6 weeks post treatment. Patients who developed irAEs had significantly lower levels of CXCL9, CXCL10, CXCL11 and CCL19 at baseline and exhibited far greater increases in CXCL9 and CXCL10 levels at 6 weeks post treatment compared to patients without irAEs (P< 0.05 for all analyses). Baseline total serum IgG levels were significantly lower in patients who developed irAEs (P< 0.05). Cytokine and IgG levels were stable over time in healthy controls. Conclusions: In this study, patients with irAEs had lower baseline levels and greater post-treatment increases in multiple cytokine levels, as well as lower baseline levels in total IgG. Analogous to the elevated risk of autoimmune disease in individuals with HIV/AIDS, these findings suggest that immune dysregulation may be associated with the development of irAEs.
Association between hospital volume and overall survival (OS) of stage 3 and 4 cutaneous malignant melanoma (MMel).
Authors: Anuhya Kommalapati, Sri Harsha Tella, Apar Kishor Ganti, Alissa S. Marr
Journal: Journal of Clinical Oncology (2018)

9524 Background: Therapeutic advances altered the course of MMel in the last decade. The therapeutic and survival disparities of MMel were evaluated based on hospital volume using the National Cancer Data Base (NCDB). Methods: Patients with MMel diagnosed between 2004 & 2015 were included and classified into tertiles based on hospital volume. Cox regression analysis was performed to adjust for covariates, including patient demographics, tumor characteristics, LDH, insurance & therapy received. Kaplan Meier estimates of OS were compared with log-rank test. Results: A total of 50, 254 MMel patients were treated at 1317 facilities. The median age at diagnosis was 62 & 67 y for stages 3 & 4, respectively. The median annual facility volumes were 10 & 6 patients/yr for stages 3 & 4, respectively. Multivariable analysis showed that facility volume was an independent predictor of OS (p < 0.0001). Stage 3 (n = 34, 666): Hospitals were classified into (T: mean cases/year) T1: < 4.56; T2:4.57-15.25; T3:≥15.2 cases/year. The unadjusted median OS by facility volume was: T1: 77 months (m), T2: 94 m, and T3: 124 m (P < .0001). Compared with patients treated at T3 facilities, patients treated at lower-tertile facilities had significantly higher risk of death [T2 hazard ratio (HR), 1.11 (95% CI, 1.06-1.16); T1 HR, 1.18 (CI, 1.09-1.27)]. Stage 4 (n = 15,588): T1:1-3; T2: 3-8.67; T3: > 8.68. The unadjusted median OS by facility volume for stage 4 MMel was: T1: 6 m, T2: 8 m, and T3: 11 m (P < .0001). Compared with patients treated at T3 facilities, patients treated at lower-tertile facilities had significantly higher risk of death [T2 HR, 1.18 (CI, 1.13-1.23); T1 HR, 1.21 (CI, 1.14-1.30)]. Patients at T3 facilities (vs T1) were more likely to receive chemotherapy (36 vs 27%) and immunotherapy (27 vs 12%) (p < 0.01). Conclusions: Patients who were treated for MMel at high-volume centers ( > 15 cases in stage 3; > 8 cases/yr in stage 4) had significantly improved survival and were more likely to receive chemotherapy and immunotherapy for stage 4 disease. Therapy received % Survival % Stage 3 Stage 4 Stage 3 Stage 4 Surgery Chemo Immuno Surgery Chemo Immuno 3 yr% 5 yr% 3 yr% 5 yr% T1 (32%) 92 9 26 29 27 12 66 55 19 14 T2 (35%) 94 7 26 30 29 15 70 58 22 17 T3 (33%) 93 7 27 31 36 27 73 63 25 20
Patient and provider preferences for physician roles in breast cancer survivorship care.
Authors: Archana Radhakrishnan, Steven J. Katz, Sarah T. Hawley, Lauren P. Wallner
Journal: Journal of Clinical Oncology (2018)

10051 Background: Adoption of team-based models for cancer survivorship has lagged in part due to uncertainty around which physician—oncologist or primary care provider (PCP)—should lead which elements of delivery. We assessed patient, oncologist, and PCP preferences for who leads multiple aspects of survivorship after primary breast cancer treatment. Methods: SEER data from LA and Georgia was used to identify and survey women newly diagnosed with breast cancer between 2014-15 (N = 3672, 70% response rate). Participants identified their oncologist (N = 491) and PCP (N = 518) who were also surveyed (61.9% oncologist, 60.8% PCP response rates). Patients and providers were each asked their preference (oncologist- vs. PCP-led) for which physician should lead cancer-related (mammograms) and non-cancer related survivorship care (other cancer screenings, general preventive care and comorbidity management). Distributions of patient and provider preferences was tabulated for each of the four services. The level of overall agreement amongst all three (%) was then calculated for each service (N = 237 triads). Results: Agreement within patient-oncologist-PCP triads for physician role preferences (Table) was highest for follow-up mammograms (81% of triads, majority preferred oncologist-led care) and comorbidity management (81% of triads, majority preferred PCP-led care), and intermediate for general preventive care (62% of triads, majority preferred PCP-led care). Agreement was lowest for other cancer screenings (32% of triads): 95% of patients, 62% of oncologists, and 57% of PCPs preferred oncologists lead other cancer screenings. Conclusions: Breast cancer patients, oncologists, and PCPs largely agreed on who should lead follow-up mammograms and comorbidity management, but disagreed most on who should direct other cancer screenings during survivorship. Targeting efforts to clarify physician roles, especially for cancer vs. non-cancer related care, will be important to maximize the quality of team-based models of survivorship care. N = 237 Triads Follow-up mammograms Other cancer screenings General preventive care Comorbidity management Prefer oncologist-led (%) Patients 95 95 19 11 Oncologists 97 62 13 2 PCPs 89 57 10 6
The average relative dose intensity of R-CHOP as an independent prognostic factor determining overall survival in diffuse large B cell lymphoma patients.
Authors: Monika Długosz-Danecka, Sebastian Szmit, Tomasz Ogórka, Katarzyna Krawczyk, Ewa Łątka, Aleksander Bartlomiej Skotnicki, Wojciech Jurczak
Journal: Journal of Clinical Oncology (2018)

e19542 Background: Prognosis of diffuse large B cell lymphoma (DLBCL) patients depends on lymphoma and patient-related risk factors, best summarized in IPI (International Prognostic Index). The aim of the study was to determine whether the average relative dose intensity (ARDI) of anthracycline containing regimen could be an IPI-independent prognostic factor. Methods: We analysed 223 white Caucasian DLBCL patients, who completed at least four cycles of first-line R-CHOP immunochemotherapy (Rituximab, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone). ARDI was calculated by specially developed software, in each individual patient, simultaneously with chemotherapy prescription. It allowed to address instantly all revealed causes of decreased ARDI. Importance of ARDI for progression-free/overall survival (PFS/OS) was evaluated. Results: ARDI was decreased due to prolonged interval between immunochemotherapy cycles caused by neutropenia and infections (absolute neutrophil count < 1,0 x 109/l) in 49.32% (110/223) or reduction of cytostatic doses in 19.73% (44/223) patients mainly as the consequence of cardiotoxicity or neutropenia (85,18% and 14,81% respectively, estimating in the group of patients with reduced doses of cytostatics). Progression free and overall survival (PFS and OS) varied significantly for ARDI > 90%, 89-80% and < 80% respectively (p < 0.00001). Multivariate analysis confirmed that ARDI > 90% was an IPI independent predictor of prolonged PFS (Hazard Ratio (HR), Confidence Interval (CI): HR = 0.31; 95%CI: 0.20-0.47; p < 0.000001) and OS (HR = 0.32; 95%CI: 0.21-0.48; p < 0.000001). Even with real time ARDI analysis it was possible to maintain it above 90% in 161 of 223 patients (72%). Further improvement may be possible only after implementing primary neutropenia prophylaxis and primary cardioprotection. Conclusions: DLBCL patients with ARDI > 90% have significantly better outcome regardless of IPI, therefore we postulate to regard adequate dose density as an official recommendation.
A phase I study of pembrolizumab in combination with enadenotucirev (EnAd) (SPICE) in subjects with metastatic or advanced carcinoma.
Authors: Wael A. Harb, Virginie Cerec, Hilary McElwaine-Johnn, Brian Champion, Simon Alvis, Nitin Jain, Christopher Ellis, Kerry Fisher, John William Beadle
Journal: Journal of Clinical Oncology (2016)

TPS3112 Background: EnAd is a tumor-selective chimeric Ad11/Ad3 group B oncolytic adenovirus developed using a process of directed evolution. Phase I clinical studies have identified a well-tolerated dose and regimen for EnAd monotherapy. EnAd shows a high level of selective replication and cell killing for a broad range of carcinoma cell lines with little replication in normal and non-carcinoma cells. Woller et al. have shown that an oncolytic virus can stimulate immune cell activity and that this stimulation can synergize with checkpoint inhibitor (CPI) activity and can reverse CPI resistance. This emerging data supports the rationale for the combination study of EnAd with CPI, pembrolizumab (anti-PD-1 antibody). SPICE is a phase I multi-center, open label, nonrandomized clinical study in subjects with metastatic or advanced carcinoma. The study design allows for an initial dose escalation stage, followed by a dose expansion stage which will include treatment of tumors normally non-responsive to CPI. Methods: In the initial dose escalation phase, 3 cohorts of patients with metastatic or advanced colorectal, urothelial, squamous cell head and neck and salivary gland carcinomas are administered intravenously an increasing dose of enadenotucirev and pembrolizumab in a standard
The OMNI patient registry: A prospective observational registry to assess vascular safety in patients with CML and Ph+ ALL treated with ponatinib.
Authors: Annette Stemhagen, Deyaa Adib, Stephanie Lustgarten, Lisa McGarry, Ruth Du Moulin, Sergio Santillana
Journal: Journal of Clinical Oncology (2017)

TPS7073 Background: Ponatinib is an oral TKI with potent activity against BCR-ABL1. The pivotal PACE study (NCT01207440) formed the basis for approval of ponatinib in the US for the treatment of patients with resistant/intolerant CML or Ph+ ALL, or those with the T315I mutation. Long-term follow-up of PACE showed a higher cumulative incidence of vascular occlusive events (VOEs) than reported at the time of approval — dose reductions were later implemented to mitigate VOEs. VOEs comprise arterial occlusive events (AOE) and venous thromboembolic events. The exposure-adjusted incidence of AOEs has not increased over time in PACE; in patients with a history of ischemic disease, the relative risk of serious AOEs was 2.6 in those with ≥2 vs 0 risk factors. The primary objective of this patient registry is to assess VOEs occurring during ponatinib use in routine clinical practice in the US. Methods: OMNI (NCT02455024) is a prospective observational registry of eligible patients (Table) with CML or Ph+ ALL for whom the decision to initiate treatment with ponatinib has already been made for the approved US indications. Patients voluntarily enroll into the registry, which is non-interventional with no protocol-mandated tests/procedures — all treatment decisions are made at the discretion of the health care practitioner in consultation with their patient. Study duration is anticipated as ~30 mo (~18-mo enrollment followed by 12 mo of data collection, which will occur every 3 mo). The primary analysis will be performed 12 mo after last patient enrolled and will estimate the incidence of VOEs by duration of ponatinib exposure. To understand differences between those with and without VOEs, exploratory analyses will be performed, considering factors such as patient demographics, risk factors for developing VOEs, dose and duration of ponatinib treatment, and concomitant medications. VOE outcomes also will be assessed. Enrollment will begin in 2017, with a target of ≥300 patients. Clinical trial information: NCT02455024. [Table: see text]
Changes in insurance coverage associated with health care reform for cancer survivors aged 19-64 years.
Authors: Amy J. Davidoff, Gery P Guy, Xin Hu, Felisa A Gonzales, Xuesong Han, Zhiyuan Zheng, Donatus U. Ekwueme, Ahmedin Jemal
Journal: Journal of Clinical Oncology (2017)

6527 Background: Beginning in 2014, Medicaid eligibility was expanded in over half of states, enrollment was simplified, and insurance marketplaces were created in all states with premium subsidies for selected individuals, as a result of implementation of the Affordable Care Act (ACA). We examine changes in insurance coverage for cancer survivors overall, and for targeted subgroups affected by specific ACA elements. Methods: We pooled data for cancer survivors aged 19-64 years from the 2012-2015 National Health Interview Survey. Using information on family structure, income, and employment, and linked state-specific Medicaid eligibility policies, we assigned survivors to 3 targeted groups: 1) Medicaid eligible pre-ACA; 2) Medicaid expansion eligible; 3) eligible for premium tax credits for Marketplace plans; and 3 groups not targeted for benefit: a) eligibility gap (income &lt; 100% federal poverty level (FPL) in states not expanding Medicaid); b) with alternative “affordable” coverage; and c) high income ( &gt; 400% FPL). Linear probability regressions examined pre(2012-13)/post(2014-15) coverage changes by eligibility category, adjusting for demographic characteristics. Results: Among 4,115 (wtd N = 6.90M) cancer survivors, insurance pre-ACA was 69% private, 15.2% public, and 12.2% uninsured. Post-ACA, overall public coverage increased by 3.2 percentage points (pct pt) (p = .036), whereas the percent uninsured decreased by 4.5 pct pt (p &lt; .001). Relative to the high income category, the adjusted percent uninsured decreased by 8.4 pct pt (95% CI:1.2-15.5) among pre-ACA Medicaid eligible, by 16.7 pct pt (95% CI:8.9-24.4) among the newly Medicaid eligible, and by 11.3 pct pt (95% CI:1.0-23.4; p = .069) among premium subsidy eligible. No coverage gains were observed for the other 2 categories. Approximately 531,000 cancer survivors remained uninsured after ACA implementation, with over half eligible for either Medicaid (12%) or subsidized Marketplace plans (44%). Conclusions: In the first 2 years post-ACA, cancer survivors experienced substantial increases in insurance coverage, with changes limited to targeted subgroups. Over half of remaining uninsured were eligible for coverage.