tbuckley/cabot-search huggingface dataset:
Tremelimumab: A monoclonal antibody against CTLA-4—In combination with radiofrequency ablation (RFA) in patients with biliary tract carcinoma (BTC).
Authors: Austin G. Duffy, Drew Pratt, David E Kleiner, Donna Mabry, Suzanne Fioravanti, Melissa Walker, William Douglas Figg, Seth M. Steinberg, Victoria Anderson, Elliot Levy, Venkatesh Krishnasamy, Bradford J. Wood, Tim F. Greten
Journal: Journal of Clinical Oncology (2017)

88 Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and results in inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. Radiofrequency ablation (RFA) has been shown to induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment. Methods: Patients with refractory BTC were enrolled in a study of monthly Tremelimumab (10mg/kg, 6 doses) combined with RFA (to one lesion) performed on week 6. Tumor biopsies were performed at time of RFA with regular PBMC collection for intensive immunemontoring. Results: 17 pts enrolled. Characteristics: M:F 8:9; Median age 57(range 36-67); BTC subtype - intrahepatic/exrahepatic: 12/5. 13/17 had metastatic disease. All pts were chemorefractory with 12/17 having received at least 2 regimens. While on study, 6 pts had early PD within 6 weeks; 11 were able to undergo RFA. No DLT encountered. Most common toxicity was pruritus. There were no objective responses. Of evaluable pts N = 6 (55%) had stable disease as a best response. Conclusions: Tremelimumab in combination with subtotal RFA in patients with advanced BTC is safe and feasible. No objective responses have so far been seen in this predominantly primary intrahepatic BTC population. Full efficacy and immune monitoring data will be presented. Clinical trial information: NCT01853618.
A phase II trial of JX-594, a targeted multimechanistic oncolytic vaccinia virus, followed by sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Jeong Heo, Caroline Breitbach, Mong Cho, Tae-Ho Hwang, Chang Won Kim, Ung Bae Jeon, Hyun Young Woo, Ki Tae Yoon, Jun Woo Lee, James Burke, Theresa Hickman, Kara S DuBois, Lara Longpre, Richard H. Patt, David H. Kirn
Journal: Journal of Clinical Oncology (2012)

e14566 Background: JX-594 is a targeted oncolytic vaccinia virus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus GM-CSF expression is accompanied by tumor vascular disruption and anti-tumoral immunity (Reviewed in Nat Rev Cancer 2009). JX-594 was well-tolerated intravenously (IV) (Nature 2011) and intratumorally (IT) (Lancet Oncol 2008). Complementary anti-tumor effects are predicted with JX-594 followed by sorafenib due to acute vascular disruption effects with JX-594 and anti-angiogenic effects with sorafenib. Methods: Treatment-refractory HCC patients received JX-594 for three weeks (Day 1 IV, Day 8 IT and Day 22 IT) followed by sorafenib. An IT boost dose of JX-594 at Week 12 was optional. The primary objective of the study was to determine the safety of JX-594 followed by sorafenib in patients with advanced HCC. Secondary objectives include disease control rate (DCR) based on mRECIST and/or Choi response criteria at Day 6 (optional), Day 25 (after JX-594 only), 6 and 12 weeks. Results: Twenty (20) patients were treated in this study; fifteen (15) were refractory to sorafenib. The sequential treatment regimen was well-tolerated. Transient flu-like symptoms (Grade 1-2) and transient leukopenia (lymphopenia, neutropenia) were the most common adverse events following JX-594 therapy. Sorafenib toxicities were consistent with the expected toxicity profile. At the time of this interim analysis, thirteen patients were evaluable for radiographic response by Choi criteria (mRECIST pending). After JX-594 alone at Day 25, 10 of 13 evaluable patients (77%) had Choi tumor responses (range 19-48% reduced enhancement). Following subsequent sorafenib therapy, 11 of 13 patients (85%) had Choi responses at Week 6-12, including 9 of 10 (90%) sorafenib-failure patients. Conclusions: JX-594 was well-tolerated and associated with Choi tumor responses following IV and IT injections in patients with advanced HCC. Subsequent sorafenib was associated with the expected toxicity profile. Further trials of JX-594 in HCC patients are warranted.
Denosumab for the treatment of bisphosphonate-refractory hypercalcemia of malignancy (HCM).
Authors: Mimi I-Nan Hu, Ilya Glezerman, Sophie Leboulleux, Karl L. Insogna, Rasim A. Gucalp, Waldemar Misiorowski, Bennett Winston Yu, Paul Zorsky, Diego Tosi, Alberto Bessudo, Arnaud Jaccard, Giuseppe Tonini, Huei Wang, Ada Braun, Rajul K. Jain
Journal: Journal of Clinical Oncology (2013)

e20512 Background: HCM, caused primarily by tumor-induced bone resorption, is treated with intravenous (IV) bisphosphonates (BisP), but patients (pts) can relapse or become refractory. Denosumab binds to RANK ligand (RANKL) to inhibit osteoclast-mediated bone resorption. Methods: In this single-arm, open-label, proof-of-concept study, pts with HCM (corrected serum calcium [CSC] &gt;12.5 mg/dL [CTCAE grade ≥3]) despite IV BisP treatment ≥7 and ≤30 days before screening received subcutaneous denosumab 120 mg on days 1, 8, 15, and 28, then every 4 weeks. The primary endpoint was the proportion of pts with CSC ≤11.5 mg/dL (CTCAE grade ≤1) within 10 days of denosumab initiation. Results: The study enrolled33 pts (64% men; mean age 60 years; 76% with advanced solid tumors, 39% with bone metastases [BM]), with a median (25 th , 75 th percentile [Q1, Q3]) follow-up of 56 (18, 79) days. Median (Q1, Q3) baseline CSC was 13.7 (13.2, 14.2) mg/dL; 19 pts (58%) had HCM symptoms. Median (Q1, Q3) time from last BisP treatment to first dose was 17 (13, 22) days. At day 10, 21 pts (64%) reached CSC ≤11.5 mg/dL, including 54% of pts with BM and 70% without BM. Over the course of the study, 23 pts (70%) reached CSC ≤11.5 mg/dL, by a median (95% confidence interval [CI]) of 9 (5–19) days. A complete response (CSC ≤10.8 mg/dL, as defined by previous studies) occurred in 12 pts (36%) at day 10, and in 21 pts (64%) during the study, by a median (95% CI) of 23 (11–43) days. Among pts who reached CSC ≤11.5 mg/dL, the median (95% CI) duration of response was 104 (9–not estimable) days. The most frequently reported serious adverse events were worsening of HCM (5 pts, 15%) and dyspnea (3 pts, 9%). Two pts had isolated episodes of CSC levels ≤8.0 mg/dL (CTCAE grade 2); no pts had CSC &lt;7.0 mg/dL (grade 3). No osteonecrosis of the jaw was reported. Conclusions: In this study of pts with HCM despite recent IV BisP treatment, denosumab effectively lowered serum calcium to grade ≤1 in 64% of pts within 10 days, and induced durable responses. These findings are particularly meaningful given that pts entered this study with grade ≥3 HCM within a median 17 days after receiving IV BisP. No unexpected safety findings were identified. Denosumab may offer a new treatment option for HCM in these pts. Clinical trial information: NCT00896454.
Long-term risk of heart failure associated with adjuvant trastuzumab in breast cancer patients.
Authors: Hart Adam Goldhar, Andrew Yan, Dennis Ko, Craig Earle, George A. Tomlinson, Maureen E. Trudeau, Murray Krahn, Monika K Krzyzanowska, Raveen Pal, Christine B. Brezden, Scott Gavura, Kelly Lien, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2014)

9504 Background: The late cardiac effect of adjuvant trastuzumab (T) and its potential interaction with anthracycline in the general population have not been well studied. The purpose of this retrospective population-based cohort study was to determine the long-term risk of heart failure (HF) associated with adjuvant T and chemotherapy, compared to chemotherapy alone. Methods: Female breast cancer patients in Ontario, diagnosed between 2003 and 2009 were identified by the Ontario Cancer Registry and linked to administrative databases to ascertain demographics, cardiac risk factors, comorbidities, and use of adjuvant T and other chemotherapy. Patients with pre-existing HF were excluded. The main endpoint was new diagnosis of HF, obtained using an algorithm of admission and physician claims data. Group differences were assessed by the Kaplan-Meier (KM) method and multivariable piecewise Cox regression. Competing risk analysis using the Fine and Gray method and propensity score matching analysis were performed. Results: 19,074 women with breast cancer treated with adjuvant chemotherapy were identified, of whom 3 371 (17.7%) also received adjuvant T. Anthracycline use was 84.9% overall. The groups did not differ significantly in demographics, comorbidities, or cardiac risk factors. After a median follow-up of 5.9 years, patients treated with T and chemotherapy were more likely to develop HF than patients on chemotherapy alone (5-year KM estimates of 5.3% vs. 2.6%; p<0.0001 (log-rank)). After adjusting for confounders, adjuvant T remained independently associated with incident HF in the first 1.5 years (HR=5.77, 95% CI 4.38-7.62, p=0.0004), but not thereafter (HR=0.87, 95% CI 0.57-1.33, p=0.53). Anthracycline did not increase the risk of HF with T synergistically (interaction p=0.23). Competing risk and propensity score analyses revealed similar results. Conclusions: In this large population-based cohort study of breast cancer patients with long-term follow-up, adjuvant T was associated with increased risk of HF in breast cancer survivors, within the first 1.5 years of initiating treatment, but not thereafter. This provides reassurance about the long-term cardiac safety of adjuvant T in the general population.
Results of the Phase 3 Study of Lenalidomide Versus Placebo As Maintenance Therapy Following Second-Line Treatment for Patients with Chronic Lymphocytic Leukemia (the CONTINUUM Trial)
Authors: Robin Foà, Anna Schuh, Andrey Zaritskey, Sergey Semochkin, David Simpson, Miklos Egyed, Samuel Vokurka, Jeannine Kassis, Jennie Zhang, Brendan Purse, Asher A. Chanan-Khan
Journal: Blood (2016)
Role of Protein Disulfide Isomerase (PDI) In the Expression of Tissue Factor (TF) Procoagulant Activity on Apoptotic Myeloblasts
Authors: Brigitte Spath, Ali Amirkhosravi, Monica Davila, John L. Francis, Barbara Eifrig, Carsten Bokemeyer, Florian Langer
Journal: Blood (2010)
Platelet microparticles (PMP): A predictive factor of overall survival in hormone-refractory prostate cancer (HRPC) patients treated by chemotherapy
Authors: A. Banu, D. Helley, E. Banu, A. M. Fischer, F. Scotte, A. Bouziane, S. Oudard
Journal: Journal of Clinical Oncology (2006)

4639 Background: Several studies suggest a causal relationship between platelets activation and cancer metastasis. Activated platelets release PMP, VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) which could play a role in patient outcome. Methods: Eligible chemonaive HRPC patients (pts) were required to have: ECOG performance status (PS) ≤2, progressive disease after antiandrogen withdrawal. Before chemotherapy, we quantified PMP in whole blood by flow cytometry using an anti-CD41 monoclonal antibody and plasmatic VEGF and bFGF by ELISA. As primary endpoint, we prospectively evaluated the impact of PMP on overall survival (OS) by Cox regression and log-rank test. Secondary, we studied the correlation between PMP and platelets, and their relationship with OS, incorporating an interaction term in the modelling (PMP and platelets). Results: Between July 2001 and April 2004, thirty-eight HRPC pts were treated by chemotherapy [docetaxel (92%), mitoxantrone (8%)] in our center. Median age was 69 years, with median values of hemoglobin 125 g/L, baseline prostate-specific antigen (PSA) 37.7 ng/mL, PMP 6 867 per μL, VEGF 18.1 pg/mL and bFGF 2.8 pg/mL. Significant correlations were observed between PMP and ECOG PS, hormone-sensitivity duration, Gleason and platelets. Median OS was significantly lower in pts with high PMP values (&gt;6 788 per μL), compared to low PMP pts: 16.7 months (95% CI, 5.1–28.2) vs 25.2 months (95% CI, 20.2–30.3), P = 0.025, log-rank. Univariate analysis by Cox regression showed a significant relationship between OS and PMP level [HR = 0.41 (95% CI, 0.19–0.92), P = 0.04]. PMP kept their significance after adjusting by multivariate analysis for baseline hemoglobin, number of metastatic sites, and PSA doubling-time [HR = 0.37 (95% CI, 0.16–0.87), P = 0.02)]. An interaction term (PMP and platelets) was also predictive on OS (P = 0.01). Conclusions: PMP and their interaction with platelets were a predictive factor of OS in HRPC pts. Our analysis showed that the dynamic interaction between PMP and platelets has a major impact on outcome of HRPC pts. No significant financial relationships to disclose.
Impact of targeted therapy (TT) on survival of metastatic renal cell carcinoma (mRCC) patients treated with high dose interleukin-2 (HD IL-2): Analysis of the PROCLAIMHD IL-2 National Registry.
Authors: Joseph Clark, Michael Morse, Michael K.K. Wong, David F. McDermott, Howard Kaufman, Gregory A. Daniels, Hong Hua, Sandra Aung
Journal: Journal of Clinical Oncology (2015)

e15609 Background: PROCLAIMSM (www.proclaimregistry.com) is an IL-2 registry with over 40 participating sites with a retrospective (retro) (N = 97, locked) and prospective cohort (N > 400 on-going). Previously, we reported a median overall survival (mOS) of 50.9 months (mo) with a median follow-up of 37.1 mo in mRCC patients treated with HD IL-2 between 2007 and 2012 from the retro cohort (ASCO 2014). Here we update survival and report on the prospective cohort. Methods: Inclusion criteria required patients receive at least one dose of IL-2. IRBs waived consent for retro patients, therefore post IL-2 treatment data is unavailable. Prospective patients received their first dose of HD IL-2 prior to 2013 with post IL-2 treatment data collected. Survival for both cohorts is current to January 2015. Results: The overall response rate (ORR) for the 123 patients in the prospective cohort is 17.9%. Complete response (CR), partial response (PR), and stable disease (SD) patients have a 2.5 year survival rate of 100%, 87%, and 73% respectively. The mOS is 29.6 mo at a median follow-up of 23.2 mo. The mOS was not reached (NR) in patients treated with only HD IL-2 and was 13.1, and 29.6 mo in those who had prior or post TT (Table 1). The treatment-related mortality rate in the combined retro and prospective cohorts is 0.9% (4/435). Conclusions: PROCLAIM prospective and retro cohorts demonstrate that SD, previously grouped with the non-responders, has high survival rates. Although limited by numbers (15 patients), TT prior to IL-2 data appears less desirable. These data support that HD IL-2 has favorable safety profile compared to data in the original package insert and is effective first line therapy for eligible patients with mRCC. Clinical trial information: NCT00686959. Updated January 2015 Retrospective Cohort (2007-2012) N = 97, 11 sites Prospective Cohort (2011-2012) N = 123, 23 sites Median Overall Survival (mOS) months 48.8 months 29.6 months Median follow-up 43.1 months 23.2 months 2.5 year survival rate CR/PR/SD (%) 100/85/69 100/87/73 ORR (CR+PR) 21.5% 17.9% CBR (CR+PR+SD) 45.5% 55.3% mOS no prior TT/prior TT (months) 48.8(n = 82)/ 15.3(n = 15) (p = 0.06) NR(n = 111)/ 13.1(n = 12) (p = 0.01)
Clinical outcomes of systemic therapy for patients with desmoids
Authors: V. P. Camargo, R. G. Maki
Journal: Journal of Clinical Oncology (2009)

10585 Background: Desmoids are rare, slow growing, histologically benign tumors without metastatic potential. Methods: We examined outcomes of patients with desmoid tumors receiving systemic therapy at a single institution, to provide a basis for examination of newer agents. Retrospective chart review of 682 patients with desmoid tumors (1982–2006) from a prospectively collected sarcoma database. The activity of NSAIDs was not addressed. Patients without measurable disease, those receiving therapy we could not document, and those receiving prophylactic therapy were excluded. Results: A total of 70 patients received 163 lines of well-documented systemic therapy starting before 1/1/2007. Nine patients died, 7 of progressive disease/surgical complications, and two with Gardner syndrome-related malignancies. Demographics: 45 females (65%), median age 30 (range 15–75), 21 with Gardner syndrome (30%), median follow-up 68 months, and median of 2 lines of therapy (1–7). Intra-abdominal primary location was most common (29/70=41%). Tamoxifen, doxorubicin (including Caelyx/Doxil), imatinib, and methotrexate combinations were most commonly used. Five partial responses were observed with anthracyclines (43 courses administered), 2 with hormonal therapy (32 courses), and 1 with imatinib (35 courses), for 8 PR s. Conclusions: Anthracycline-containing regimens, hormonal therapy, and tyrosine kinase inhibitors have modest activity against desmoid tumors. The choice of therapy for these morbid and potentially fatal tumors should balance the efficacy of treatments with their short- and long-term side effects. No significant financial relationships to disclose.
Does cancer treatment-related financial distress worsen over time?
Authors: Lena Van Nimwegen, Christel Rushing, Fumiko Ladd Chino, Greg Samsa, Ivy Altomare, James A Tulsky, Peter A Ubel, Jonathan Nicolla, Amy Pickar Abernethy, Jeffrey M. Peppercorn, Yousuf Zafar
Journal: Journal of Clinical Oncology (2014)

6559 Background: Patients with cancer are at risk for experiencing financial distress. Prior studies have indicated that objective financial burden follows trends associated with treatment course. However, little is known about whether patients’ subjective financial distress follows similar trends during the course of their treatment. The ability to predict risk of financial distress in relation to time on treatment may facilitate timing of interventions to alleviate financial distress. Methods: This was a cross-sectional study of insured adults with solid tumors on anticancer therapy for ≥1 month. Consecutive patients were surveyed, in person, at a referral center and 3 rural oncology clinics. Participants were asked about financial distress (via a validated measure) and out-of-pocket costs. Medical records were reviewed for disease and treatment data. We used the Spearman Rank Correlation Coefficient test and multivariable logistic regression to assess the correlation between months on treatment and financial distress. Results: 300 participants (86% response rate) had a median age of 60 years (range 27-91). 79% had incurable cancer. 56% had private insurance. Median income was $60,000/yr. Median OOP costs were $592/mo. The median FD score (7.4 out of 10, SD 2.5) corresponded to moderate FD with 16% reporting high/overwhelming FD. The median time on treatment was 4.6 months (range 1-156 months). Treatment duration was not correlated with financial distress (p=0.89). In adjusted analyses, having curable disease (p=0.02) was associated with higher odds of experiencing high/overwhelming financial distress. Conclusions: Severity of cancer treatment-related financial distress did not correlate with time on treatment. However, patient and disease characteristics may predict risk of financial distress. Consistent with prior studies, patients receiving curative treatment might be at higher risk of experiencing financial distress possibly due to higher costs incurred in the initial period following diagnosis. Sociodemographic characteristics might be useful for targeting early interventions in patients who are at risk for treatment-related financial distress.
Multicentric descriptive study of the lung cancer treatment
Authors: M. Quintana, C. Pallares, I. Martinez, I. Gich, X. Bonfill
Journal: Journal of Clinical Oncology (2006)

20109 Background: Given the insufficient available information on the clinical characteristics and the results of the lung cancer treatment at a population level, we performed a large multicentric descriptive study in the main hospitals in our city. Methods: We analyzed the patients diagnosed and treated for lung cancer during 1999 in five University Hospitals in Barcelona (Spain). We performed a retrospective analysis of the individual data obtained from the clinical records using a specifically validated questionnaire. A descriptive analysis was performed, stratifying for type of tumor, stage, and institution. The follow-up for the complete population was 5 years. Results: We included 836 patients (94.6% male, 5.4% female) with an average age of 64 years. Karnofsky was ≥ 70% in 85% of patients. Histologic distribution was non-small cell (NSCLC) 85.5%, small-cell (SCLC) 14.5%. 42% of cases were stage IV (38% NSCLC, 67.8% SCLC). First treatment was performed in 82% of cases with therapeutic intention (52% was chemotherapy). Pulmonary resection with lobectomy and platinum-based chemotherapy were the more frequent treatments. Complete remission was obtained in 25% of cases. Survival was 42.0, 17.9 and 12.6% at 1, 3 and 5 years respectively (NSCLC: 43.8, 19.4, 13.1%; SCLC: 31.9, 9.5, 9.5%). The mean interval first visit - treatment start was 2 months. The mean of direct costs per patient was 9000 €. The cost per life-year gained was 5200 € for NSCLC and 7600 € for SCLC patients. Conclusions: The obtained results allow to describe the clinical characteristics of a wide cohort of patients diagnosed of lung cancer and their survival to 5 years. Globally, these results are similar to those who have been published in our country and others, and constitute a very thorough referent for assessing the impact of future therapeutic advances. The comparison among hospitals can also be the matter of further analysis for identifying the causes of the observed differences. Equally, specific strategies for some patients’ subgroups could be designed in order to improve the cost-effectiveness of their treatment. No significant financial relationships to disclose.
Signals of the Inflammatory Microenvironment Promote a Mutation-Associated Functional Dysregulation of the Circulating Megakaryocyte Progenitors of Myelofibrosis
Authors: Daria Sollazzo, Dorian Forte, Marco Romano, Margherita Perricone, Simona Luatti, Giovanni Martinelli, Nicola Vianelli, Michele Cavo, Francesca Palandri, Lucia Catani
Journal: Blood (2016)