tbuckley/cabot-search huggingface dataset:
Rituximab maintenance after induction with abbreviated FCR in previously untreated elderly (≥ 65 years) CLL patients: Results of the randomized CLL 2007 SA trial from the French FILO Group (NCT00645606).
Authors: Caroline Dartigeas, Eric Van Den Neste, Herve Maisonneuve, Christian Berthou, Marie-Sarah Dilhuydy, Sophie De Guibert, Stephane Leprêtre, Philippe Rodon, Therese Aurran, Jean-Pierre Vilque, Beatrice Mahe, Marie C. Bene, Florence NGuyen-Khac, Remi Letestu, Alain Delmer, Pierre Feugier, Vincent Levy, Julie Leger, Philippe Colombat, Veronique Leblond
Journal: Journal of Clinical Oncology (2016)

7505 Background: A promising concept to improve outcome in CLL is maintenance with immunotherapy after induction with FCR to improve quality and duration of response. Methods: Treatment-naive, ≥ 65 y, fit pts with B-CLL and no del17p, received an induction with 4 cycles of FCR, a shortened schedule chosen to reduce the risk of cumulative toxicity in elderly pts with physiological decline. Pts in CR/PR were randomly allocated to maintenance 500 mg/msq rituximab (RTX arm) q2m x 2 y or observation (OBS arm). Primary objective was to demonstrate an improvement in 3-y PFS from randomization from 50% in OBS arm to 66% in RTX arm. 406 patients were required. At randomization, pts were stratified for IGHV status, del11q and response. Median FU from randomization is 43.6 m. Results: 409 pts were randomized (202 in RTX arm; 207 in OBS arm). Median age was 71.3 y, 66.3% were males, 25.7/11.0% were in CR/CRi and 62.8% in PR post-FCR, 21.3% had del11q and 54.8% unmutated IGHV. Median PFS in RTX arm was 59.3 m (95% CI: 49.6; not reached) as compared to 49.0 m (95% CI: 40.9; 60.5) in OBS arm (HR 0.597, 95% CI: 0.437; 0.814, P.0011), corresponding to a 3-y PFS of 83.0% and 64.2% in each arm, respectively. Estimated 3-y OS was 92.6% and 87.2% in RTX and OBS arm, respectively (NS). Rituximab maintenance significantly improved PFS in pts with or without del11q and in those with unmutated IGHV. SAEs for hematological toxicity were declared in 6.9% and 1.9% (P.027), and SAEs for infectious toxicity in 18.8% and 10.1% (P.036) of the pts, in RTX and OBS arms, respectively. Sixty-nine deaths occurred post-randomization, 32 in RTX arm and 37 in OBS arm. Secondary cancer (excluding BCC) occurred in 15,3% (incl. 5 MDS) and 11.1% (incl. 3 MDS) of pts in RTX and OBS arm, respectively. Conclusions: Two-y maintenance rituximab significantly improved PFS as compared to observation in selected elderly CLL pts in response after FCR induction. This benefit was also observed in pts with unfavorable characteristics. Maintenance was feasible but associated with a higher incidence of toxic events. Benefit from maintenance will be further analyzed according to MRD eradication. Clinical trial information: NCT00645606.
Spatial analysis of radiation oncology access disparities within Illinois: Implications for rural cancer care.
Authors: Mustafaa Mahmood, Whitney E. Zahnd, Sabha Ganai
Journal: Journal of Clinical Oncology (2018)

e18644 Background: Radiation therapy is a mainstay of cancer care. However, radiation oncology practices (RadOncs) are often concentrated in urban areas, posing a travel burden to rural patients. We hypothesized that rural-urban disparities exist in the form of increased travel time to RadOncs. Methods: Data on currently-licensed RadOncs were obtained via the Illinois Department of Financial and Professional Regulation with geocoding of unique practice locations. Illinois state (n = 12,096,388) zip-code level demographics including age, education, race, and income were obtained. Zip-code level rurality was based on approximations of USDA Rural-Urban Commuting Area (RUCA) codes using a 2- and 4-group classification scheme. Travel time between the centroid of each zip code and nearest radiation oncologist was calculated using the network analyst tool in ARCGIS. T-tests and ANOVA were used to evaluate difference in travel time with respect to level of rurality. Choropleth maps of travel time to the nearest radiation oncologist within Illinois borders were also created. Results: A greater proportion of Illinois residents within isolated-rural (87.6%) and small-rural areas (78.4%) lived over 30 minutes away from RadOncs, in comparison to those in large-rural (28.7%) and urban (3.5%) areas. Residents living over 30 minutes away from RadOncs were more likely to be without a college education and with second-quartile median household income. Mean travel time to RadOncs was 45 ± 21 (SD) min in rural areas vs 21 ± 16 min in urban areas (p < 0.001). Travel time varied across 4-group RUCA comparison (p < 0.001), and was greater for isolated-rural regions (51 ± 18 min) and small-rural regions (50 ± 22 min) in comparison to large-rural regions (33 ± 18 min). Conclusions: Rural populations experience greater travel times than those in urban areas, supporting our hypothesis that there are disparities in access to RadOncs. A majority of the 0.86-million people in isolated- and small-rural Illinois live over 30 minutes away from RadOncs, with doubling of travel time between rural and urban locales. Rural-urban differences in workforce persist as travel barriers to RadOncs. Further outreach is necessary to improve access to care.
Abstract 15493: Akt1-Mediated Skeletal Muscle Growth Enhances Blood Flow Recovery After Hind Limb Ischemia by Activating Heme Oxygenase-1 in Macrophage
Authors: Yoshiro Onoue, Yasuhiro Izumiya, Shinsuke Hanatani, Toshihumi Ishida, Satoru Yamamura, Yuichi Kimura, Satoshi Araki, Seiji Hokimoto
Journal: Circulation (2016)

Background: Supervised exercise is established intervention for patients with peripheral artery disease (PAD). In addition to aerobic exercise, it has been recognized that resistance exercise has beneficial effects for these patients. However, underling mechanism by which growing muscle improves blood flow is unclear. Hypothesis: Skeletal muscle growth enhances angiogenesis by modulating macrophage phenotype in ischemic lesion. Methods: We utilized skeletal muscle-specific, inducible Akt1 transgenic (Akt1 TG) mice, that can lead to the growth of functional skeletal muscle. Skeletal muscle specific heme oxygenase-1 (HO-1) knockout mice were generated by crossing HO-1-Flox mice with ACTA1-Cre mice. These mice were subjected to unilateral femoral artery ligation to induce hind limb ischemia, and blood flow recovery was assessed by laser Doppler and immunohistochemistry. Adenovirus-mediated Akt1 overexpression experiments were performed in C2C12 myotubes. Results: Blood flow recovery after hind limb ischemia ...
First-in-human phase 1 study of MK-1248, an anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) monoclonal antibody, as monotherapy or in combination with pembrolizumab in patients with advanced solid tumors.
Authors: Ravit Geva, Mark Voskoboynik, Amy M Beebe, Jennifer Gwo, Konstantin Dobrenkov, Elliot Chartash, Georgina V. Long
Journal: Journal of Clinical Oncology (2018)

3029 Background: MK-1248 is a humanized IgG4 agonist monoclonal antibody (mAb) that targets GITR. GITR is expressed on regulatory T cells (Treg), resting CD4+ and CD8+ T cells, NK (natural killer) cells and NK T cells. Ligation of GITR decreases Treg-mediated suppression and enhances T cell proliferation, effector functions, and survival. Methods: MK-1248 was tested alone or in combination with pembrolizumab at a starting dose of 0.12 mg in both arms. Pembrolizumab dose was fixed at 200 mg. Both study drugs were administered intravenously every 3 weeks. Total number of intended doses of MK-1248 and pembrolizumab was 4 and 35, respectively. The study objective was to determine safety and tolerability, maximum tolerated dose (MTD), pharmacokinetic (PK), and pharmacodynamic (PD) profiles of MK-1248 as a monotherapy and in combination with pembrolizumab. Results: Data were available from 37 pts: 20 pts treated with MK-1248 monotherapy and 17 pts treated with MK-1248 + pembrolizumab combination therapy. Tumor types: colorectal cancer (8 pts), melanoma (5 pts), renal cell carcinoma (4 pts) and 20 pts with 16 other solid tumors. Maximum dose of MK-1248 tested: 170 mg (monotherapy) and 60 mg (combination). MK-1248 was well tolerated. Of the 37 pts treated, 36 pts (97.3%) had ≥1 adverse event (AE) and 17 pts (48.6%) had ≥1 treatment-related AE. Common AEs were: vomiting, anemia, decreased appetite, abdominal pain, cough, diarrhea, nausea, fatigue, headache and pyrexia. Infusion related reactions occurred in 6 (16.2%) pts. Eighteen pts had Grade 3-5 AEs (48.6%), 3 (8.1%) were treatment-related. Serious adverse events (SAE) occurred in 6 pts (30.0%) in monotherapy arm and 5 pts (29.4%) in combination arm. No DLT or treatment-related deaths were observed. One CR and 2 PR were observed in the study. Conclusions: MK-1248 at the dose up to 170 mg as monotherapy and 60 mg in combination with pembrolizumab was well tolerated with no dose limiting toxicities or treatment-related deaths. Responses were observed when MK-1248 was administered in combination with pembrolizumab. Clinical trial information: NCT02553499.
A randomized, double-blinded, placebo-controlled phase II trial of gemcitabine (gem) plus nab-paclitaxel (nab-P) plus apatorsen (A) or placebo (Pl) in patients (pts) with metastatic pancreatic cancer (mPC): The RAINIER trial.
Authors: Andrew H. Ko, Patrick Brian Murphy, James D. Peyton, Dianna Shipley, Ahmed Al-Hazzouri, Francisco Antonio Rodriguez, Mark Sanders Womack, Henry Q. Xiong, David Michael Waterhouse, Margaret A. Tempero, Shuangli Guo, Cassie Michelle Lane, Christopher Earwood, Laura M. DeBusk, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2016)

4119 Background: Over expression of heat shock protein 27 (Hsp27) in PC promotes tumor growth and metastasis, and is associated with poor prognosis. A is an antisense oligonucleotide that binds to Hsp27 mRNA and inhibits production of Hsp27 protein. This randomized, double-blinded, phase II trial evaluates the efficacy of gem/nab-P plus A or Pl in pts with mPC. Methods: Pts with untreated mPC were randomized 1:1 to Arm A (gem, nab-P, A) or Arm B (gem, nab-P, Pl). 3 loading doses of 600mg A IV or Pl IV were given, then 600 mg A or Pl weekly with chemotherapy in 28 day cycles. Both arms received gem 1000mg/m2 IV +nab-P 125mg/m2 IV on days 1, 8, and 15. Pts were re-staged every 2 cycles. Serum Hsp27 levels were drawn at baseline and on treatment. The primary endpoint was overall survival (OS); secondary endpoints were progression free survival (PFS), response rate (RR), CA 19-9 response, and toxicity. Results: 132 pts were randomized: median age 66 yrs, 57% male, 47% ECOG 0. Toxicities were similar between arms. The most frequent G 3/4 treatment-related AEs reported in > 10% of subjects included anemia (20%), neutropenia (17%), fatigue (16%), thrombocytopenia (14%), and nausea (13%) on Arm A and anemia (27%), neutropenia (19%), thrombocytopenia (13%), and fatigue (11%) on Arm B. Serious AEs were numerically higher in arm A (16 vs 9 pts). Overall RR on both arms was 18%. With a median follow-up of 9.2 mo, median PFS was 2.7 vs 3.8 months for arms A and B, respectively (hazard ratio 1.0), while median OS was 5.3 vs. 6.9 months (HR 1.2). Of the 14% of pts with high baseline serum level of Hsp27 ( > 9.3 ng/mL), median PFS and OS was longer in arm A than in arm B (PFS 3.3 vs 0.9 mo, HR 0.4; OS 3.3 vs 1.0 mo, HR 0.6). Conclusions: The addition of A to chemotherapy for pts with first-line mPC did not improve outcomes in the ITT population, although OS for the entire cohort did worse than expected. There was a trend toward improvement in PFS and OS in the A arm for pts with high baseline serum Hsp 27, a poorer-prognosis subgroup. Further study of A plus chemotherapy may be warranted in mPC pts preselected for this biomarker. Clinical trial information: NCT01844817.
Clinicopathological presentation of extranodal lymphomas of head and neck: A single institution experience over the last decade.
Authors: Amitoj Gill, Kamila Izabela Cisak, Rahul Gosain, Cesar Augusto Perez
Journal: Journal of Clinical Oncology (2017)

e19042 Background: Non-Hodgkin’s lymphoma can have an extranodal presentation in about 33% of cases. Up to one third of these extranodal lymphomas (ENL) develop in the head and neck region. We looked at the clinicopathological presentation of ENL diagnosed at an academic institution. Methods: All patients with ENL of head and neck diagnosed between 2008 and 2016 at a single institution were included. Analysis was done for histologic subtype of lymphoma, primary site, immunohistochemical profile (Bcl-2,Bcl-6 and Ki67) and prognostic factors. Results: A total of 68 patients were included of which 41 (60%) were females and 27 (40%) were males. Median age at diagnosis was 64 (range 26 to 92) and a large number of the patients were Caucasian (74%). Diffuse Large B-Cell Lymphoma (DLBCL) was most commonly seen followed by Marginal Zone B Cell Lymphoma (MZBCL). The most common site of presentation was Tonsils/Waldeyer's ring (21%) followed by Nasopharynx (15%) and Orbital/Periorbital areas (15%). Among the patients with indolent Lymphomas (non-DLBCL), most presented with stage I (per Ann Arbor staging) at diagnosis (60%). On the other hand, stage III was the most common stage at diagnosis for the patients with DLBCL (30%). Higher Bcl-6 expression (52%) was noted in DLBCL with majority (81%) having a Ki67 expression of more than 30%. The 2-year overall survival for the DLBCL subgroup was 77% (95% CI 0.61 - 0.93). A high Neutrophil to Lymphocyte ratio (NLR) was associated with worse overall survival in patients with DLBCL. Conclusions: MZBCL was the most common indolent ENL of the head and neck, but DLBCL was the most common type of all ENL of the head and neck. NLR was associated with worse outcomes in patients with DLBCL. [Table: see text]
TCT-94 Continuous infusion of saline for assessment of absolute hyperemic flow and minimal microvascular resistance: validation in humans using [15O]H2O PET
Authors: Henk Everaars, Guus de Waard, Stefan Schumacher, Frederik Zimmermann, Peter van de Ven, Adriaan Lammertsma, Marco Götte, Akira Kurata, Koen Marques, Niels van Royen, Paul Knaapen
Journal: Journal of the American College of Cardiology (2018)
Opioid use in rural breast cancer patients.
Authors: Emilio Paul Araujo-Mino, Ajaz Bulbul, Adriana Bautista, Lisa Lentkowski, Masoud Khorsand-Sahbaie
Journal: Journal of Clinical Oncology (2018)

10124 Background: The Epidemic opioid overuse spans different communities and cancer patients frequently develop pain from their disease, cancer therapy or sequela for which opioids are commonly used. Breast Cancer is a common malignancy seen across different practices. Methods: This is a retrospective study evaluating BC patients Stages I-III from January 2013 until January 2018 in three rural community cancer practices in Southeast New Mexico who had been prescribed opioids during their cancer diagnosis and treatment. Exclusions were development of Stage IV, other concurrent malignancies, remote history of cancer for which use opioid data was missing. Chi-square and logistic regression were performed to identify correlation and predictors of long term opioid use respectively. Results: A total of 664 patients were identified; among these 150 (23%) were prescribed an opioid at some point. 54 were excluded according to prespecified criteria. The rate of opioid use was 72% (69/96) at 3 months, 62 % at 6 months (60/96) and 52% (50/96) at 12 months. 72% of user at 3 months (50/69) were also using opioids at 12 months from initial prescription x2 40.8 p=<0.001. Also 83% (50/60) of opioid use at 6 months were opioid user at 12 months x2 62.6 p=<0.001. Patient with smoking history, type of initial opioid (tramadol), opioid prescribed by surgeon, history of mental health and residence in smaller rural communities were more likely to continue using long term opioid, however it was not statistically significant. Conclusions: Curable breast cancer patients with increased short-term use of opioids at 3 months are significantly associated with continued long-term use at one year. Several factors in the rural community may need to be further evaluated in larger studies.
Survival analysis of 409 consecutive patients with newly diagnosed acute myeloid leukemia treated with intensive induction therapy, with or without the addition of gemtuzomab-ozagomicin (GO).
Authors: Cristina Papayannidis, Anna Candoni, Michele Malagola, Giovanni Marconi, Elena Tenti, Marco Manfrini, Giorgia Simonetti, Elisa Zuffa, Mariachiara Abbenante, Sarah Parisi, Stefania Paolini, Chiara Sartor, Eugenia Franchini, Emanuela Ottaviani, Maria Chiara Fontana, Antonella Padella, Viviana Guadagnuolo, Renato Fanin, Domenico Russo, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2016)

7043 Background: Young patients affected by non APL-Acute Myeloid Leukemia (AML) achieve complete remission (CR) using conventional induction chemotherapy in about 55-70%. The addition of Gemtuzumab Ozogamicin (GO) demonstrated to improve clinical outcome, in terms of CR rates. We retrospectively evaluated and compared the efficacy of different induction schedules, in terms of CR rates and Overall Survival (OS), administered to two groups of AML patients. Group 1 (n = 139) was treated with a GO (MyFLAI or MyAIE schedules); group 2 (n = 270) received a non-GO based regimen including or not Fludarabine (FLAI, FLAN, FLAG, 3+7 or DAE). Methods: From 1997 to 2014, 409 patients with newly diagnosed AML were treated in 3 Italian Institutions. According to karyotype (performed in 392/409 patients), FLT3 (available for 244/409 patients), and NPM1 mutational status (available for 157/409 patients), based on the NCCN-2013 risk stratification criteria, 35.2% of the patients were considered at High Risk (HR) (31.6% and 36.4% in the two groups, respectively) and 7.6% at low risk (LR) (7.8% and 7.0%, respectively). Results: The complete remission (CR) rate after induction was 81.4% and 70.4% for Group 1 and 2, respectively (p = 0.008). Deaths during induction (DDI), occurring in the first 50 days from 1st line therapy, were 4/139 (2.9%) in Group 1 and 22/270 (8.1%) in Group 2. Patients treated with GO showed a better OS than patients of Group 2; the 5-years OS in the two groups was 54.01% and 34.9%, respectively, and different according to age (54.0% and 34.9% respectively (p < 0.001) in patients < 60 years, 30.2% and 13.5% respectively (p = 0.001) in patients > = 60 years). Notably, the analysis on subgroup of HR patients showed a significantly better OS in Group 1 than in Group 2 (p = 0.007, 5-year OS 47.7%; 21.0% respectively) and EFS. Conclusions: We may therefore conclude that adding GO to any induction regimen is an independent and strong predictor of better OS and higher CR rate. This new approach to AML front line treatment could be recommended in SR and HR AML patients, in which showed an advantage in terms of OS if compared with other standard regimens.
Efficacy and safety of anti-VEGF therapy in metastatic unresectable hepatocellular carcinoma: A meta-analysis.
Authors: Lakshmi Manogna Chintalacheruvu, Avanija Buddam, Arun Kanmanthareddy, Apar Kishor Ganti
Journal: Journal of Clinical Oncology (2017)

e15632 Background:Conventional chemotherapy has limited role in metastatic unresectable hepatocellular carcinoma (HCC). Sorafenib is currently approved for metastatic unresectable HCC. We wanted to assess the efficacy and safety of other tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor (VEGF) receptor such as brivanib, linifanib and regorafenib in metastatic HCC. Methods: We have searched electronic databases Pubmed, Google scholar to identify published trials using brivanib, linifanib and regorafenib in HCC. The outcomes evaluated were overall survival, time to disease progression (TTDP) and adverse effects. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were then computed using the appropriate model for categorical variables. We used STATA 13.0 and Comprehensive Meta Analysis 2.0 software for all analyses. Results: We included seven randomized control studies. A combined analysis of these seven randomised control trials showed improved overall survival (OS) in VEGF-TKI group when compared to placebo HR - 0.79; (95% CI 0.62-1.00). However, there was no significant survival benefit of the newer VEGF receptor inhibitors when compared to sorafenib (HR - 1.05; 95% CI 0.95-1.17). The time to disease progression (TTDP) was significantly better in VEGF-TKI group as compared to placebo (HR - 0.61; 95% CI 0.39-0.97). However, there was no significant difference in TTDP between VEGF-TKI group and Sorafenib (HR - 0.88; 95% CI 0.66-1.16). Adverse effects were noted to be higher in VEGF-TKI group when compared to placebo (HR- 1.07; 95% CI 1.01-1.13). Conclusions: Treatment with TKI targeting VEGF receptor is associated with a significant improvement in OS and TTDP with tolerable side effect profile. Inhibiting the VEGF receptor pathway could lead to improved outcomes in HCC.
Results from the safety interim analysis of the Adjuvant chemoRadioTherapy In Stomach Tumors 2 (ARTIST 2) randomized, multi-center clinical trial.
Authors: Se Hoon Park, Jeeyun Lee, Do Hoon Lim, Kyoung-Mee Kim, Ji Yeong An, Min-Gew Choi, Jun-Ho Lee, Tae Sung Sohn, Jae-Moon Bae, Sung Kim, Jun Ho Ji, In Gyu Hwang, Jung Hun Kang, Dae Young Zang, Dong Bok Shin, Sung Yong Oh, Won Ki Kang
Journal: Journal of Clinical Oncology (2018)

e16029 Background: ARTIST 2 trial is being conducted to compare disease-free survival (DFS) in patients with D2-resected, node-positive, stage II or III gastric cancer (GC), treated with adjuvant chemotherapy and chemoradiotherapy. Methods: Eligible patients were randomized to receive adjuvant treatment with (A) oral S-1 for 12 months, (B) S-1 and oxaliplatin (SOX) for 6 months, or (C) SOX plus chemoradiotherapy (SOXRT). Stratification factors included stage, type of surgery and the Lauren classification. To test if experimental arms (B or C) lower the annual hazard rate of relapse at 3 year by 50%, the target number of patients was 300 per arm. In the present interim analysis, we report the safety outcomes in patients treated with adjuvant chemotherapy or chemoradiotherapy. Results: Among a total of 514 patients registered between Feb 2013 and Dec 2017, 499 patients who completed or discontinued the assigned study treatments were included in the present analysis: median age of 67 years (range, 28-82), diffuse type histology in 248 patients (55%), and stage II and III in 127 (28%) and 322 (72%), respectively. All the three treatment arms were generally well-tolerated, with the overall treatment completion rate was 94% (96% in arm A, 93% in arm B and 92% in arm C). The median delivered dose of radiotherapy in arm C was 4,500 cGy (range, 0-4,500). The most frequently observed adverse events in arm A, B and C were fatigue (29%) in the arm A, and peripheral neuropathy in the arm B and C (59% and 50%, respectively). We observed no treatment-related deaths. Conclusions: We found no significant safety concerns in the ARTIST 2 clinical trial (ClinicalTrials.gov, NCT0176146). According to the independent data monitoring committee (IDMC) recommendation, patient accrual is under way. Clinical trial information: NCT0176146.