tbuckley/cabot-search huggingface dataset:
AB0850 Do symptoms of depression and anxiety influence treatment response and long-term physical health outcomes in ankylosing spondylitis?
Authors: M. Eusébio, C.A. Lopes, M. Bernardes, P. Pinto, H. Santos, J.L. Gomes, J. Tavares-Costa, J. Dias, A. Bernardo, L. Domingues, C. Crespo, S. Maia, F. Martins, J.C. Branco, F.M. Pimentel-Santos
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Psychological disturbances, frequently observed in inflammatory rheumatic diseases, seem to negatively influence patient's clinical status and treatment response. <h3>Objectives</h3> The aim of this study was to examine the longitudinal impact of depression (D)/anxiety (A) in treatment response, disease activity, physical disability and quality of life in patients with Ankylosing Spondylitis (AS). <h3>Methods</h3> Data from patients who fulfilled the modified New York criteria for AS were collected at baseline, weeks 2 and 14 post-treatment with Adalimumab. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate D/A symptoms severity. The primary outcomes were AS disease activity score – C reactive protein (ASDAS-CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) and AS Quality of Life (ASQoL) Scale. Secondary outcomes were patient and physician global assessment by Visual Analogue Scale (VAS), erythrocyte sedimentation rate (ESR), CRP and BASDAI question 1 (fatigue). Difference-in-differences estimation took into account the covariates gender, age at baseline and disease duration. <h3>Results</h3> Data from 54 patients were included. At baseline, D/A symptoms significantly influenced the mean value of BASFI (p=0.006; p=0.003) and ASQoL (p&lt;0.001; p=0.004). On the other hand, BASDAI (p=0.009), CRP (p=0.017), patient's VAS (p=0.003) and fatigue (p=0.015) were only influenced in the individuals with A symptoms, while the physician's VAS (p=0.005) was only influenced in patients with D symptoms. After 14 weeks of treatment, significant differences in ASQoL mean values were found in patients with both D/A symptoms at baseline (p=0.005; p=0.022) and in BASFI (p=0.044) and patient VAS (p=0.006) for the population showing only A symptoms at the baseline. Apart from the physician VAS (p=0.023), D/A baseline symptoms did not affect the treatment's response. <h3>Conclusions</h3> Psychological status does not seem to affect response to treatment with Adalimumab, even if the overall characteristics of the population are different at baseline between patients with/without D/A symptoms. <h3>Disclosure of Interest</h3> None declared
Cancer patterns and trends in Costa Rica: A population-based tumor registry study.
Authors: Omar Picado, Jordan Baeker Bispo, Layla Bouzoubaa, Raymond R. Balise, Gilberto Lopes, Erin N. Kobetz
Journal: Journal of Clinical Oncology (2018)

e13605 Background: Recent economic and social changes in low- and middle-income countries in Latin American have influenced the raise of non-communicable diseases including cancer. Data from cancer registries are critical for surveilling disease trends during periods of epidemiologic transition. The aim of this study is to generate population estimates of cancer incidence rates in Costa Rica and to evaluate geographical differences. Methods: The National Tumor Registry in Costa Rica was queried for cancer cases diagnosed between 2009 – 2014. Population data were used to calculate sex, country and region-specific age standardized rates (ASR) per 100,000 people using the World Health Organization's 2000 standard population. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to assess the effect of sex and geographic regions. Results: The overall cancer incidence rate in Costa Rica was 219.24 cases per 100,000. Females had a higher cancer rates relative to males (SIR: 1.1, 95% CI: 1.08 – 1.11, p < .001). The leading cancers were prostate (ASR: 53.09, 95% CI: 51.75 – 54.46), female breast (ASR: 48.73; 95% CI: 47.54 – 49.94), cervical (ASR: 30.78; 95% CI: 29.77 – 31.62), stomach (ASR: 17.45; 95% CI: 16.93 – 17.99), colorectal (ASR: 16.49; 95% CI: 15.98 – 17.00) and thyroid (ASR: 12.96; 95% CI: 12.54 – 13.40) cancers. San Jose had the highest breast and colon cancers rates whereas, Cartago had the highest rates for gastric and thyroid cancers. Conclusions: Costa Rica has a growing cancer burden involving preventable cancers. Continued monitoring of trends in incidence rates is needed to implement cancer control actions. Further involvement to create cancer prevention strategies and programs aimed to reduce cancer burden are warranted.
Real-world treatment sequencing in advanced non-small cell lung cancer (aNSCLC).
Authors: Janna Radtchenko, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2017)

e20593 Background: The rapidly expanding arsenal of systemic therapies for aNSCLC warrants a better understanding of treatment sequencing. This study evaluated the benefits of sequence choice through time to discontinuation (TTD). Methods: Using Inovalon’s MORE 2 Registry ® claims data for July 2013–2014, patients (pts) with aNSCLC identified by ICD-9 codes and treated with chemotherapy (chemo) or targeted therapy (TT; erlotinib, ceritinib, afatinib, or crizotinib) were selected. Pts &gt;18 years of age and treated with first-line (1L) therapy within 6 months of diagnosis were eligible. Pts with small cell lung cancer or secondary malignancies, or pts enrolled in a trial, were ineligible. TTD (time from 1L start to 2L stop + 90 days, or switch to 3L were analyzed by sequence group: chemo-to-chemo (A), chemo-to-TT (B), TT-to-chemo (C), and TT-to-TT (D). All-cause TTD was assessed using Kaplan–Meier curves. Pt characteristics were assessed using descriptive statistics. Results: Of 5,319 pts, 567 (11%) received 1L TT and 4,752 (89%) received 1L chemo; 2,198 pts (41%) progressed to 2L. Significant differences were noted between groups (table). Group D had the most women and longest mean follow-up time and TTD. Group C had the lowest mean age and greatest proportion of 3L pts. Group B had the highest mutation testing rate and second longest mean TTD. Conclusions: The positive impact of precision medicine on TTD is striking. The fact that chemo following 1L TT resulted in the lowest TTD calls this strategy into question. Research is warranted to address the continued role of salvage chemo in TT eligible aNSCLC. [Table: see text]
Efficacy and safety of apatinib with or without radiotherapy as second-line or beyond therapy in patients with advanced/recurrent esophageal squamous cell carcinoma.
Authors: Jiahua Lv, Tao Li, Qifeng Wang, Yu Fan, Junchao Wang, Jinyi Lang
Journal: Journal of Clinical Oncology (2018)

e16044 Background: The aim of this study was to evaluate the efficacy and safety of apatinib, an oral VEGFR2 inhibitor, with or without radiotherapy in the treatment of advanced/recurrent esophageal squamous cell carcinoma patients who failed from one or more lines of therapy. Methods: The advanced or recurrent esophageal squamous cell carcinoma patients, who experienced one or more lines of therapy and treated with apatinib with or without radiotherapy from June 2015 to October 2017, were retrospectively reviewed. All eligible patients received continuous apatinib treatment until disease progression, death, or intolerable toxicity. Survival and toxicities outcome were evaluated by Kaplan-Meier method and according to NCI-CTC4.0. Results: Forty-four patients were eligible. Patients characteristics were: median age 62 yrs, male/female 77.3/22.7%, ECOG PS 0/1/≥2 18.2/68.2/13.6%. 29 patients (65.9%) received 500 mg daily of apatinib, 7 patients received 250mg, 6 received 425mg and 2 received 750 mg daily. Dose modification occurred in 9 (20.5%) pts (reduction 5/11.4%; rise 4/9.1%). Twenty-seven(61.4%) patients received intensity modulated radiation therapy to primary tumor or metastatic sites. The best ORR and DCR were 34.1% and 77.3%, respectively. The median PFS and OS were 3.87 (95%CI, 3.07–4.88) and 5.93 (95%CI, 4.98–6.89) months, respectively. The toxicities associated with apatinib treatment was generally acceptable with 13 (29.5%) patients developed grade 3/4 toxicity. The most common adverse events in this study were hypertension(31.8%), hand-foot syndrome(27.2%), proteinuria(20.5%), fatigue (18.2%) and mouth mucositis(9.1%). Conclusions: Apatinib ± radiotherapy showed promising efficiency with tolerable toxicity for advanced/recurrent esophageal squamous cell carcinoma patients who failed from one or more lines of therapy.
Prognostic model for disease-free survival, lymphatic and/or hematogenous recurrence, in patients with early stage cervical cancer treated with radical hysterectomy: A Korean Gynecologic Oncology Group Study.
Authors: Chel Hun Choi, Min Kyu Kim, Duk-Soo Bae, Byoung-Gie Kim, Jeong-Won Lee, Tae-Joong Kim, Yoo-Young Lee
Journal: Journal of Clinical Oncology (2016)

e17000 Background: To develop a model to predict 5 year disease-free survival (DFS), lymphatic and/or hematogenous recurrence, in early stage cervical cancer treated with radical hysterectomy, which can be used to select low-risk patients potentially eligible for less radical surgery. Methods: We retrospective analyzed a multi-institutional cohort of early stage cervical cancer patients treated between 2000 and 2008. According to the order of data submission, data from four institutions were allocated to a model development cohort (n = 1041), and data from the remaining four institutions were allocated to an external validation cohort (n = 971). Patient information including body mass index, pretreatment complete blood count, glucose levels and clinical outcome was modeled using Cox proportional hazards regression analysis to predict 5-year DFS. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results: Multivariable analysis identified prognostic factors including histology, International Federation of Gynecology and Obstetrics stage, depth of invasion, pelvic and/or paraaortic node status, parametrial involvement, platelet count, and hemoglobin level. Model for 5-yr DFS, lymphatic recurrence, and hematogenous recurrence showed good discrimination and calibration, with a bootstrap-corrected concordance indices of 0.70, 0.69, and 0.73, respectively, and were well calibrated. Also, the validation set showed good discrimination with a bootstrapadjusted concordance index of 0.72, 0.70 and 0.74, respectively. Conclusions: We have developed a robust model to predict 5-yr DFS, lymphatic and/or hematogenous recurrence in patients with early stage cervical cancer. Further, we discussed how the low-risk patients selected from the model could facilitate clinical trials of less radical surgery to reduce complication of surgery.
Outcomes of patients with nucleoplasmin 1 (NPM1) mutated acute myeloid leukemia (AML) treated with hypomethylating agents (HMAs).
Authors: Mahesh Swaminathan, Elias Jabbour, Farhad Ravandi, Tapan M. Kadia, Gautam Borthakur, Marina Konopleva, Courtney Denton Dinardo, Sherry Pierce, Yesid Alvarado, Rita Elias Assi, Iman Adib Abou Dalle, Eran Tallis, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Journal of Clinical Oncology (2018)

7054 Background: Presence of NPM1 mutations (MU) is associated with improved outcomes in younger pts with AML treated with high doses of cytarabine. The outcomes of pts with NPM1 mutated AML treated with HMAs is unknown. It is important as HMAs are becoming standard of care in older pts with AML not candidates for intensive therapy. We investigated the outcomes of such group of pts treated with either azacitidine or decitabine or combinations at a single institution. Methods: We retrospectively analyzed outcomes of NPM1 mutated AML pts referred to a single institution from 2010 to 2017 treated with HMAs as monotherapy or in combination. Results: We identified 63 pts with median age of 68 (26-91); 34 pts (54%) were female. The median number of prior therapies was 0 (0-3). A total of 58/63 pts (92%) had available cytogenetics (CG). Thirty-seven pts (64%) had favorable, 20 (34%) had intermediate and 1 had adverse (2%) CG. All pts had NPM1 MU and 26 pts (41%) also had DNMT3A MU and 21 (33%) had FLT3-ITD. The overall response rate (ORR) was 75% (n = 47) [CR-30 (48%), CRp-5 (8%) and HIP-12 (19%)]; 73% in pts who received HMAs as monotherapy (n = 22) and 76% in combination therapy (n = 41). The median overall survival (OS) was 11.63 months and the relapse-free survival was 18.27 months. The ORR for pts with FLT-3 wild-type and FLT-3-ITD MU was 81% and 62% respectively, with median OS of 19.39 and 10.07 months, respectively. Thirty pts (48%) had MRD assessment available; 19 (63%) were negative and 11 (37%) were positive. Nine pts (14%) had NPM1 MU analysis at the time of response; 4 (44%) had no MU. Eleven pts (17%) had bone marrow transplant, of that 8 (73%) are alive; 3 (27%) died in CR, CRp and progressive disease due to sepsis, unknown cause and multi-organ failure (MOF) respectively. Two pts (3%) had early death due to MOF; 4 (6%) died, 2 from MOF and 2 from an unknown cause. Conclusions: This analysis indicates that although response rates are high in NPM1 mutated AML when treated with HMAs, survival maybe shorter than that reported with ara-C based therapies. Ara-C based therapy should therefore be used when possible but HMAs are an option. FLT-3 MU status is important for prognosis and may improve when adding FLT-3 inhibitor.
Prospective evaluation of the factors predicting the prognosis of advanced hepatocellular carcinoma (HCC) patients treated with sorafenib.
Authors: Takuya Adachi, Kazuhiro Nouso, Koji Miyahara, Chihiro Dohi, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Koichi Takaguchi, Shuji Uematsu, Shouta Iwadou, Yoshitaka Takuma, Hiroaki Hagihara, Hiroyuki Takabatake, Akinobu Takaki, Hiroyuki Okada
Journal: Journal of Clinical Oncology (2017)

e15674 Background: Several factors including pro-angiogenic cytokines have been reported as predictive markers for the treatment effect of sorafenib in patients with HCC; however, many of them were determined based on the results of retrospective studies. Methods: In this prospective cohort study (UMIN000009771), we recruited advanced HCC patients who were treated with sorafenib, and periodically measured serum levels of eight pro-angiogenic cytokines, which were risk factors for the prognosis reported by us and others. The effect of the cytokine expressions before and at 2 (4) weeks after starting sorafenib and at PD, on progression free survival (PFS), overall survival (OS), and post progression survival (PPS) were evaluated. The effect of early appearance of adverse events within 30 days, which were reported as other risk factors, was also evaluated. Results: Eighty patients were enrolled. Median PFS and OS were 3.1 and 11.7 months, respectively. There was no statistically significant variable that could predict PFS, which included patients’ characteristics, cytokines before the therapy, and early onset of adverse events. However, PFS of the patients who showed the decrease of platelet-derived growth factor after 2 weeks (HR2.78, 95%CI 1.35-6.21, P=0.005) or vascular endothelial growth factor after 4 weeks (HR3.31, 95%CI 1.59-6.83, P=0.001) compared to the values before sorafenib treatment was short. OS was short in patients with poor performance status, large tumor size (&gt;30mm), large tumor number (&gt;5), high des-gamma-carboxyprothrombin (DCP, &gt;100mAU/mL), high hepatocyte growth factor, and high angiopoietin-2 (Ang-2) before therapy, in addition to no hand foot syndrome within 30 days. Multivariate analysis with these factors revealed that high Ang-2 (HR2.25, 95%CI 1.08-4.86, p=0.029) and high DCP (HR3.55, 95%CI 1.25-12.7, p=0.014) were the independent risk factors for OS. High Ang-2 at PD could also be a marker of short PPS. Conclusions: The prediction of PFS, OS and PPS is possible by measuring serum pro-angiogenic cytokines at appropriate timing. Ang-2 is a key cytokine for predicting the prognosis of HCC patients treated with sorafenib.
Real world patient numbers for AML targeted therapies.
Authors: Marcos Tadeu dos Santos, Dave Smart, Eloise Aita, Peter Mark Krein, Jordan Clark
Journal: Journal of Clinical Oncology (2017)

e18510 Background: The standard of care for AML patients (pts) has not changed in 40 yrs. Molecular biomarkers FLT3 and IDH1/2 are being tested for prognosis and risk stratification and recent trial results show these will be effective for targeted therapies. We analyzed real world data from a leading clinical lab (BioReference Laboratories Inc) to evaluate the frequency of pts eligible for FLT3 and IDH therapies. Methods: FLT3 (ITD/TKD), IDH1 and IDH2 mutation status results from 384 AML patients from Mar 2015 - Dec 2016, tested by a validated NGS assay, OnkoSight™, were analyzed and frequencies compared with the literature. Results: Of 384 AML pts from 31 US States, 52 were FLT3+ (13.5%, expected (exp) 24-38%). We observed 41 IDH+ pts (10.7%, exp 8-18%), with 27 pts IDH2+ (7%, exp 8-9%) and 13 pts IDH1+ (3.4%, exp 9%). Mutations in both FLT3 and IDH were found in 10 pts (2.6% of AML pts, exp 9%). This equates to 19.2% of FLT3+ pts (exp 31%), 15.4% of IDH2+ pts (exp 26%) and 1.9% of IDH1+ pts (exp 5%). We identified 1 pt harboring an unexpected triple positive (FLT3, IDH1 &amp; 2) as IDH1 and 2 are considered mutually exclusive. Medicare was the single biggest payer (42%). Tests were requested by community based physicians in 92% of cases. Conclusions: The data suggest fewer pts may be eligible for FLT3 and IDH therapies in a real world setting than expected from the literature, possibly due to published data usually coming from cohorts of well characterized, filtered AML pts from research projects and/or clinical trials, which may not represent routine clinical testing. We find a lower level of FTL3 and IDH mutation overlap showing approx only 3% of all AML pts as eligible for at least two options of targeted therapies (exp 9%). [Table: see text]
Clinical data from the DeCidE<sup>1</sup> trial: Assessing the first combination of DPX-Survivac, low dose cyclophosphamide (CPA), and epacadostat (INCB024360) in subjects with stage IIc-IV recurrent epithelial ovarian cancer.
Authors: Oliver Dorigo, Janos Laszlo Tanyi, James Strauss, Amit M. Oza, Tanja Pejovic, Prafull Ghatage, Jeannine A. Villella, Stephan Fiset, Lisa Diana MacDonald, Lance Leopold, Gabriela Nicola Rosu
Journal: Journal of Clinical Oncology (2018)

5510 Background: DPX-Survivac is a novel T cell activating therapy containing a mix of HLA class I peptides designed to evoke a T cell response against survivin and previously optimized for immunogenicity when delivered with intermittent metronomic cyclophosphamide (CPA). It can induce robust, sustained and specific T-cell responses in subjects with ovarian cancer. Epacadostat (E) is a potent and selective inhibitor of indoleamine 2,3-dioxygenase 1 that may reverse tumor-associated immune suppression. This Phase 1b is evaluating if a de novo tumor-specific T cell response, combined with the alteration of the immune suppression will result in clinical benefits. Methods: Subjects with advanced ovarian cancer (stage IIc-IV with evidence of disease progression) were treated with DPX-Survivac (2x 0.25 mL priming doses q3w and up to 6x 0.1 mL boosting doses q8w), metronomic CPA (50 mg BID on alternating weeks), and epacadostat (up to 300 mg BID). Primary endpoints include safety and immunogenicity. Secondary endpoints include objective response by modified RECIST v1.1. Results: Fourteen subjects were enrolled in the initial dose cohort (E 100 mg BID), 10 of which were considered evaluable. The incidence of adverse events has been collected and the presence of survivin-specific activated T-cells detected in the blood. Three subjects reached an objective response of PR with 1 subject attaining a response of PR within 8 weeks of beginning treatment. Two subjects reached SD followed by PR, one of which is still ongoing, maintained for more than 6 months post-response; both have had disease control for more than 12 months. A best response of SD was shown in 3 of 10 subjects, with an additional subject showing SD (+6%) after an initial PD (+26%). Conclusions: The first triple combination of DPX-Survivac, low dose CPA, and epacadostat resulted in clinical responses in subjects with recurrent ovarian cancer. The combination was well-tolerated and immunogenicity to DPX-Survivac was demonstrated. The rate of response observed so far in this study is promising and warrants additional development. Clinical trial information: NCT02785250.
Sustaining change and defining the patient experience: A systemwide initiative to re-evaluate goals for timely patient navigation through medical oncology and infusion in a comprehensive cancer center.
Authors: David L Crosby, Megan Brown, Konstantin H. Dragnev, Megan Howe
Journal: Journal of Clinical Oncology (2018)

e18875 Background: In 2012, Norris Cotton Cancer Center in Lebanon, started a multi-year system-wide improvement process that addressed poor and inconsistent performance in infusion, clinic, and pharmacy service areas. By analyzing our operations, we created a system that allowed for a reliable and measurable patient experience. Towards the end of 2015, leaders from the infusion suite needed to assess previously defined targets to enhance system performance. Methods: Work followed a Lean Six Sigma methodology – Define, Measure, Analyze, Improve, and Control (DMAIC). Since previous workgroups were in the control phase by late 2015, a steady state had already been achieved. A one-week rapid process improvement workshop (RPIW) was initiated to re-evaluate the established metrics with the primary goal of improving infusion on-time performance. Multi-disciplinary clinical teams worked with quality improvement experts to identify and act on specific targets. Results: After changes were implemented within the 90 days post RPIW, patients started on treatment within 45 minutes of infusion appointment improved to 83% from a baseline of 63%. In addition, patients treated within 15 minutes of infusion appointment improved to 39% from a baseline of 28%. Conclusions: The RPIW provided an opportunity to demonstrate that our targets could be enhanced. However, there was considerable work that needed to be done to achieve our long term 15 and 45 min goals consistently. Our ability to sustain improvement relied on daily attention, follow-up, and a collective ability to prepare in advance. Consistent expectations from provider, nursing, and pharmacy leadership have led to improvements in getting laboratory results evaluated on patient visits prior to the day of infusion, receiving treatment plan orders in advance, nursing preparation prior to infusion, and pre-mixing of select chemotherapy regimens. These changes resulted in less performance variability to improve the patient experience.