tbuckley/cabot-search huggingface dataset:
Patient-reported levels of concern in the Childhood Cancer Survivor Study (CCSS).
Authors: Todd M. Gibson, Chenghong Li, Gregory T. Armstrong, Deo Kumar Srivastava, Wendy M. Leisenring, Ann Mertens, Tara M. Brinkman, Lisa Diller, Paul C. Nathan, Melissa M. Hudson, Leslie L. Robison
Journal: Journal of Clinical Oncology (2016)

10576 Background: Survivors of childhood cancer are at increased risk for adverse health outcomes. However, it is unclear whether specific concerns expressed by survivors are consistent with actual risks. Methods: We examined levels of concern in 9,196 adult survivors of childhood cancer (mean age 27.1 years) and 3,106 adult siblings. Participants reported their level of concern relative to future health, reproduction, cancer and insurance according to a five point scale. We compared survivors and siblings for extreme concern levels, and referenced published relative risks (RR) from CCSS to contrast concerns with actual risk of related events. We used Poisson regression to identify concern-related factors. Results: The proportion of “Very concerned” survivors ranged from 16.4% for ability to get health insurance to 30.1% for future health (Table). Survivors were more likely than siblings to report being very concerned about future health, reproduction and insurance. The disparities in concern between survivors and siblings for future health and cancer were less than the disparities in actual risk for severe/life-threatening/fatal chronic conditions and subsequent neoplasms, respectively. Radiation treatment was associated with survivors being “very concerned” about future health (RR=1.2, 95% confidence interval (CI)=1.1-1.3) and developing a cancer (RR=1.3, CI=1.2-1.4). Conclusions: Childhood cancer survivors were more likely to be very concerned about future health-related issues compared to siblings, but levels of concern were not always commensurate with actual risk. Concern Actual Risk Very Concerned Not at All Concerned RR† Survivor (%) Sibling (%) RR* 95% CI Survivor (%) Sibling (%) RR* 95% CI Future Health 4.9 30.1 22.8 1.2 1.1-1.3 9.0 9.2 1.0 0.9-1.2 Ability to Have Children Female 1.2 23.8 12.3 1.2 1.0-1.5 38.0 53.8 1.1 1.0-1.1 Male 1.8 19.5 8.1 1.6 1.2-2.1 37.4 62.1 0.9 0.8-1.0 Develop a Cancer 8.5 23.7 19.9 1.1 1.0-1.2 16.4 15.7 1.0 0.9-1.1 Ability to Get Health Insurance 1.2 16.4 6.4 2.1 1.8-2.4 34.4 57.3 0.6 0.5-0.7 † CCSS published RR vs. siblings (outcomes: chronic health conditions, having a child, subsequent neoplasm, or being insured). * Adjusted for demographics, income, and current status for related outcome.
A phase II study of pembrolizumab and docetaxel for aggressive RAI refractory thyroid carcinomas or salivary gland cancers: The iPRIME study.
Authors: Tanguy Y. Seiwert, Jonas A. De Souza, Everett E. Vokes, Nishant Agrawal
Journal: Journal of Clinical Oncology (2017)

TPS6099 Background: Both aggressive, radioactive iodine refractory thyroid cancers as well as high-grade salivary gland cancers respond poorly to chemotherapy, and there is no widely used standard of care. Targeted thearpies as well as cytotoxic chemotherapy (e.g. doxorubicin, or taxanes) are commonly used, but are only modestly effective. Both salivary gland and thyroid cancers have been shown to have tumor infiltrating lymphocytes, tumor inflammation, and PD-L1 expression ( Ayers, AACR 2015). Early data with anti-PD-1 immunotherapy using pembrolizumab (Keynote 28) show activity in ≤10a% of patients in a biomarker selected population (Keynote 28 thyroid and salivary gland cohorts). However, most patients are not PD-L1 positive and were not eligible. Recently synergy of anti-PD-1 checkpoint blockade with cytotoxic chemotherapy was reported in several studies (e.g. Langer et al, Keynote 21G) . Mechanistically chemotherapy may increase tumor inflammation, and eradicate immusupressive myeloid derived suppressor cells (MDSCs). Data suggest a significant increase in the response rate e. g. in KN21G from 29% to 55%. Furthermore the depths of responses and durability improve, including patients with PD-L1 negative tumors. Methods: We hypothesize that the combination of PD-1 checkpoint blockade and cytotoxic chemotherapy will show synergistic activity in aggressive thyroid cancers and salivary gland cancers. Eligible patients will have radioactive iodine refractory, aggressive thyroid cancer (cohort A, N = 25 pts), or progressive salivary gland cancers (cohort B, N = 25 pts). There will be no PD-L1 or other biomarker selection. Patients must have progressed on prior therapy. Patients will receive docetaxel at a dose of 75mg/m2 Q21 days as well as pembrolizumab 200mg flat-dose Q21 days intravenously. The primary outcome of this study is response rate. The addition of pembrolizumab to chemotherapy will increase the response rate from 20% (H0) to 40% (H1). A simon two-stage design will be used for each cohort (cohorts A and B) with an estimate 81% power in each arm. Patient screening and enrollment are expected to begin mid 2017. Clinical trial information: pending.
Treatment patterns and effectiveness outcomes in patients with stage IV, renal cell carcinoma.
Authors: Ronda Copher, Junji Lin, Debanjana Chatterjee, Prashant Ramesh Joshi, Maxine D. Fisher, Mark S. Walker, Jiandong Kerr, Yousef Zakharia
Journal: Journal of Clinical Oncology (2018)

e16571 Background: As new agents receive approval for the treatment of patients with metastatic renal cell carcinoma (mRCC), it is important to understand the changing treatment landscape in the real-world setting. This study describes patient characteristics, treatment patterns, and effectiveness outcomes for these patients in a community oncology setting. Methods: Retrospective medical records data from adults diagnosed with stage IV/metastatic RCC (ICD-9, 189; ICD-10, C64, C65) between 7/11/2000 and 3/29/2016 were collected from 10 community oncology practices across US. Descriptive analyses were performed on patient characteristics and treatment patterns. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis and Cox regression. Results: Among 417 patients, 65.7% were male, 75.8% white, and median age was 65 years (range 27-93 years). At initial RCC diagnosis, 53.2% were Stage IV (M1) and 62.4% had clear cell histology. Diabetes (22.1%) was the most prevalent comorbidity. Of 355 patients with systemic treatment in 1st line, 278 (78.3%) used tyrosine kinase inhibitors (TKIs), followed by 52 (14.6%) with mammalian target of rapamycin inhibitors (mTORs) (in 2nd line of 220 patients, 118 (53.6%) on TKIs, 71 (32.3%) on mTORs). Most commonly used 1st line agent was sunitinib (n = 152, 42.8%) while pazopanib and everolimus (n = 48, 21.8%, for each) were most frequently used 2nd line agents. Median PFS was 6.2 (TKIs) and 2.99 (mTORs) months from start of 1st line treatment; 5.3 (TKIs) and 3.2 (mTORs) months from start of 2nd line. Median OS was 27.8 (TKIs) and 14.8 (mTORs) months from start of the 1st line treatment. Cox models showed a 64% higher risk of progression in 1st line and a 61% higher risk of death after start of 1st line for patients on 1st line mTORs compared to TKIs. Stage IV at initial RCC diagnosis, lower BMI, and impaired composite performance were also associated with higher risk for progression and death. Conclusions: TKIs are widely used as 1st and 2nd line therapies for mRCC. The study suggests that use of TKIs in 1st line is associated with better PFS and OS in the study population. Future studies should investigate generalizability beyond a community oncology setting.
CNS-resident classical DCs play a critical role in CNS autoimmune disease
Authors: David A. Giles, Patrick C. Duncker, Nicole M. Wilkinson, Jesse M. Washnock-Schmid, Benjamin M. Segal
Journal: Journal of Clinical Investigation (2018)

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS), induced by the adoptive transfer of myelin-reactive CD4+ T cells into naive syngeneic mice. It is widely used as a rodent model of multiple sclerosis (MS). The development of EAE lesions is initiated when transferred CD4+ T cells access the CNS and are reactivated by local antigen-presenting cells (APCs) bearing endogenous myelin peptide/MHC class II complexes. The identity of the CNS-resident, lesion-initiating APCs is widely debated. Here we demonstrate that classical dendritic cells (cDCs) normally reside in the meninges, brain, and spinal cord in the steady state. These cells are unique among candidate CNS APCs in their ability to stimulate naive, as well as effector, myelin-specific T cells to proliferate and produce proinflammatory cytokines directly ex vivo. cDCs expanded in the meninges and CNS parenchyma in association with disease progression. Selective depletion of cDCs led to a decrease in the number of myelin-primed donor T cells in the CNS and reduced the incidence of clinical EAE by half. Based on our findings, we propose that cDCs, and the factors that regulate them, be further investigated as potential therapeutic targets in MS.
Balance of plasminogen and free plasmin as indicator of acute postoperative pancreatitis of pancreatic stump after pancreatoduodenal resection.
Authors: Larisa Kozlova, Oleg Ivanovich Kit, Elena Mikhaylovna Frantsiyants, Evgeniy N. Kolesnikov, Umar Muhmadovich Gaziev, Vladimir Trifanov, Roman E. Myagkov
Journal: Journal of Clinical Oncology (2016)

e15682 Background: Early diagnosis and prevention of acute postoperative pancreatitis (APP) are crucial for the preservation of life of the patient exhausted by pancreatic cancer (PC). The purpose of the study was to analyze the content of plasminogen (PG) and free plasmin (FP) in the blood plasma (BP) of patients with PC. Methods: BP of 79 patients with PC (T3 N0 M0 ) was studied before the surgery and 1 day after it: PG by ELISA, FP by spectrophotometric method; the results were compared with the norm (N) of donors. 8 patients (10.1%) developed APP of pancreatic stump. Results: BP of 8 patients showed FP activity 1.8 times higher than PG before the surgery; PG was 1.4 times higher than N, FP activity – 9.2 times higher, PG/FP coefficient – 4.6 times lower, and the balance was considered as pathological. APP signs in all 8 patients were observed on day 2-4 after the surgery. PG in BP of 71 patients without APP before the surgery exceeded the N by 4.4 times, after surgery – by 3.1 times; FP: before the surgery 3.4 times, after – 2.0 times higher than the N. PG/FP before the surgery was 1.4 times, after – 5.7 times higher than the N. The BP examination was repeated for all patients after the surgery to monitor the results. PG/FP increased 1 day after the surgery by 5.6-28.3 times in all patients without APP excluding 1 case (increase in PG/FP by 22.2%) due to decrease in FP and concurrent increase in PG. PG/FP coefficient was practically unchanged in 8 patients with APP; PG/FP in donors amounted for 2.3. Conclusions: APP of pancreatic stump can be predicted by PG/FP coefficient in BP of PC patients 1-2 days before the surgery. APP development was associated with the results obtained before the surgery in 88.1% of the cases, its absence – in 98.5% of the cases.
Impact on immune effectors of anti-tumor antibodies isolated from cancer patients.
Authors: Amy Manning-Bog, Gilson Baia, Jeff Defalco, Iraz T Aydin, Michael G Harbell, Patricia Zuno-Mitchell, Judevin Lugar Sapugay, Danhui Zhang, Felix Chu, Beatriz Millare, Alexander Scholz, May Sumi, Sheila Fernandez, Nicole Haaser, Jonathan Eliot Benjamin, Ngan Nguyen, Wayne Volkmuth, William H. Robinson, Norman M Greenberg, Daniel Emerling
Journal: Journal of Clinical Oncology (2018)

e15015 Background: It is unclear exactly how B cells and their antibodies (Abs) influence the anti-cancer immune response. We've proposed that anti-tumor Abs drive or amplify anti-tumor immune effectors. To test this, we isolated and characterized Abs from single B cells of patients having effective anti-cancer responses and assessed activities of recombinant versions of these Abs in mouse tumor models. Methods: Immune Repertoire Capture (IRC) technology was used to generate paired chain IgG Ab sequences from thousands of blood plasmablasts (activated B cells) isolated from over 20 cancer patients during periods of long term non-progression. From the thousands of plasmablast lineages identified, we selected over 500 for further analyses based on evidence of clonal expansion and other features. Results: We recombinantly expressed one or more Ab sequences from each of these selected plasmablast lineages and found that they bind non-autologous human tumor tissues and commercially available human tumor cell lines at a high rate. In immunostaining, several recombinant Abs bound tumor types other than that of the source patient. Moreover, a fraction of the Abs bound murine tumor cells and tissue. We assessed whether cross species-reactive Abs, recombinantly expressed on mouse Fc, inhibit tumor growth in mouse syngeneic models, which have fully intact immune systems. Some recombinant plasmablast Abs caused regression of, and durable immunity toward, established tumors. For some Abs, the magnitude of regression surpassed that seen with anti-PD1 treatment. Administration of recombinant Abs in combination with immune modulators showed additive or synergistic effects. Treatment with one of these Abs caused significant tumor infiltration by T cells, NK cells, and iNOS+ macrophages, indicating that the Ab can initiate or amplify non-humoral immune effectors. Conclusions: Taken together, our data support the hypothesis that anti-tumor Abs from non-progressing cancer patients can initiate or amplify a progressive immune response, resulting in enhanced and durable anti-tumor immunity. Further studies will examine the molecular and cellular mechanisms by which these Abs enhance anti-tumor responses involving multiple immune cell types.
TCT-42 An Early Feasibility Study to Assess Safety and Effectiveness of the Transfemoral JenaValve Pericardial TAVR System in the Treatment of Patients With Symptomatic Severe Aortic Stenosis (AS)
Authors: Hendrik Treede, Stephan Baldus, Sanjeevan Pasupati
Journal: Journal of the American College of Cardiology (2018)
Impact of a gene expression profiling risk score and web-based melanoma outcome calculator on the precision of AJCC-based prognostic assessment.
Authors: Georg Brunner, Johanna Schmitz, Matthias Borowski
Journal: Journal of Clinical Oncology (2018)

9582 Background: AJCC staging of primary cutaneous melanoma (CM), based on clinico-pathological criteria, is limited in its ability to provide a precise prognosis for all patients. To improve risk assessment, a prognostic eight-gene expression profiling (GEP) risk score was identified in CMs and adjacent stroma, predicting clinical outcome, independently of and synergistically with AJCC staging. For the same purpose, a web-based melanoma outcome calculator (MOC) was developed (www.CancerMath.net). This study evaluated single and combined prognostic performance of both tools in complementing AJCC-based prediction of melanoma-specific survival (MSS). Methods: Five-yr MSS probabilities were prognosticated by multivariate Cox models, including GEP score + AJCC parameters or MOC parameters. To assess prognostic improvement, the models were compared to each other and to a reference model based on AJCC parameters only (Breslow, ulceration, node status). Data analyses (n=529 CMs, AJCC stages IA-IIIC, median follow-up 65 months) had been pre-specified. Results: GEP score and MOC both improved precision of 5-yr MSS prediction by AJCC (sensitivity + specificity increased by GEP: 14%, p<0.001; by MOC: 11%, p<0.001, by GEP + MOC: 15%, p<0.001). Combining GEP score and MOC improved precision of 5-yr MSS prognosis by MOC alone (sensitivity + specificity increased by 3%, p=0.006). Kaplan-Meier estimates clearly indicated that precision of AJCC-based MSS prediction can be corrected by both tools (p<0.001 by logrank test), independently and synergistically (Table 1). Conclusions: GEP score (based on 125 CMs) and MOC (based on > 92.000 CMs) are independent and equivalent prognostic tools, which improve the precision of AJCC-based MSS prediction. Correction was highest when the tools were combined. GEP score is a prognostic parameter that complements AJCC staging as well as MOC. Correction of AJCC-based 5-yr MSS prediction by the prognostic tools (kaplan-meier estimates). Entire sample cohort 75% Increase in MSS GEP low risk +6% MOC low risk +6% GEP low risk + MOC low risk +10% Decrease in MSS GEP high risk -10% MOC high risk -6% GEP high risk + MOC high risk -15%
Timing of initiation of defibrotide (DF) post-diagnosis of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after hematopoietic stem cell transplantation (HSCT): Final data from an expanded-access protocol.
Authors: Stephan A. Grupp, Paul G. Richardson, Angela R. Smith, Brandon Triplett, Nancy A. Kernan, Joseph Harry Antin, Leslie Lehmann, Sergio Giralt, Wei Liang, Robin Hume, William Tappe, Robert Soiffer
Journal: Journal of Clinical Oncology (2017)

7047 Background: VOD/SOS is an unpredictable, potentially life-threatening complication of HSCT. VOD/SOS with multi-organ dysfunction (MOD) may be associated with &gt; 80% mortality. DF is approved to treat hepatic VOD/SOS with renal/pulmonary dysfunction post-HSCT in the US and to treat severe hepatic VOD/SOS post-HSCT in the European Union. Methods: In an expanded-access study, VOD/SOS patients (pts) with or without renal/pulmonary MOD after HSCT or chemotherapy received DF 25 mg/kg/d (6.25 mg/kg q6h) for a recommended ≥21 days. For these exploratory analyses, D ay +100 survival rates in HSCT pts were examined post hoc by time from diagnosis to start of DF for (1) all pts before/after days 1, 2, 3, 4, 7, and 14, using Fisher’s exact test and (2) pts starting DF on a particular day: 0, 1, 2, 3, 4, 5, 6, 7, 8–14, and ≥15, by Cochran-Armitage test for trend across days. Causes of treatment delay were not assessed. Results: In the final dataset, timing of initiation was available for 1000 HSCT pts (512 with MOD) who received ≥1 dose of DF. In 31.0% of pts, DF was started the day of diagnosis; in 92.9%, by Day 7. In the analysis of initiation before/after days 1, 2, 3, 4, 7, and 14 post-diagnosis, earlier initiation was associated with significantly higher Day +100 survival rates for all days ( P≤.001), except Day 14 (2.6% of pts started DF after Day 14). The trend test for particular initiation days also showed a significant trend over time for higher Day +100 survival with earlier DF initiation post-diagnosis ( P&lt; .001). Adverse events (AEs) and serious AEs occurred in 70.8% and 53.4% of pts. Other than VOD/SOS and MOD, the most common AE was hypotension (11.7%) and most common serious AE was respiratory failure (7.3%). Conclusions: In this exploratory analysis of final study data, earlier DF initiation post-VOD/SOS diagnosis improved Day +100 survival, confirmed by the Cochran-Armitage test ( P&lt; .001). No specific day provides a clinically meaningful cutoff for better Day +100 survival, suggesting that later intervention retains value if treatment must be delayed. Support: Jazz Pharmaceuticals. Clinical trial information: NCT00628498.
Examining How Race, Ethnicity, and Ancestry Data Are Used in Biomedical Research
Authors: Vence L. Bonham, Eric D. Green, Eliseo J. Pérez-Stable
Journal: JAMA (2018)

This Viewpoint discusses the need for a consensus on how race, ethnicity, and ancestry data are reported in biomedical research to avoid inappropriately describing racial and ethnic groups as discrete population groups.
TCT-617 Diagnostic Accuracy of 3-Dimensional and 2-Dimensional Quantitative Coronary Angiography for Predicting Physiological Significance of Coronary Stenosis
Authors: Junqing Yang, Daixin Ding, Jelmer Westra, Yunxiao Chang, Su Zhang, Niels Holm, Bo Xu, Shengxian Tu
Journal: Journal of the American College of Cardiology (2018)
Can comorbidities predict survival of patients with multiple myeloma treated with autologous stem cell transplantation?
Authors: Aleksandra Pivkova Veljanovska, Zlate Stojanoski, Lazar Chadievski, Lidija Cevreska, Borce Georgievski, Sonja Genco Genadieva-Stavrik
Journal: Journal of Clinical Oncology (2016)

8023 Background: Considering the high prevalence of comorbidities in multiple myeloma (MM) patients, comorbidity has an important issue for the management of myeloma. However, the impact of comorbidity on clinical outcomes has not been fully investigated. We retrospectively analyzed patients with myeloma treated with autologous stem cell transplantation. Comorbidities were assessed based on the Charlson comorbidity index (CCI), Hematopoietic stem cell transplantation comorbidity index (HCT-CI) and Performance status with ECOG and Karnofsky index. Methods: A total of 110 patients with MM treated with autologous stem cell transplantation were analyzed between 2000 and 2015. Comorbid conditions and disease-related complications were examined during autologous stem cell transplantation and stem cell mobilization and the impact on overall survival (OS) and non-relapse mortality (NRM). Results: Age of transplanted MM patients was median 52 years (range 40-65) with median 13 months (range 4-46) from diagnosis to transplant. At transplant setting 40% of patients had low HCT-CI, 56% were with intermediate HCT-CI and 29% were with high HCT-CI. According to CCI 64% of patients had score 2, 22% were with score 3 and 13% of patients score 4. ECOG was 0 in 79% of MM patients treated with autologous transplantation. Factors that affect overall survival (OS) in autologous MM recipients were: HCT-CI, Karnofsky score, number of CD34+cells/kg and time from diagnosis until transplant (p < 0.05). Factors that affect TRM/NRM were HCT-CI, ECOG, Karnofsky, number of hospital days and body weight (p < 0.05). Conclusions: MM treatment patterns have been dynamic over time. Comorbid conditions and myeloma-related complications increase as patients progress and may worsen MM patients' prognoses over time. A comprehensive assessment of comorbidity can help to explain the huge heterogeneity of myeloma outcome.