tbuckley/cabot-search huggingface dataset:
Venous thrombotic events in Philadelphia chromosome-like acute lymphoblastic leukemia.
Authors: Anand Ashwin Patel, Meredith Sellers, Yanming Zhang, Shira Naomi Dinner
Journal: Journal of Clinical Oncology (2018)

e19007 Background: Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of B-cell ALL. Approximately 75% of Ph-like ALL cases have mutations causing over-activation of the JAK-STAT pathway, which has been associated with an increased risk of venous thrombotic events (VTEs). This retrospective analysis evaluated the frequency of VTEs in Ph-like ALL. Methods: We assessed 67 consecutive newly diagnosed B-cell ALL patients ≥18 years old seen at our institution from 2011-2016. FISH was used to identify Ph-like ALL patients. Select samples were also assessed by next generation sequencing. Demographics and clinical data were collected through February 1, 2017. Results: We identified 12/67 (18%) patients with Ph-like ALL. Demographics, cytogenetic data, and occurrence of VTEs are summarized in Table 1. Eight (66.7%) patients developed a VTE. All eight patients had mutations involved in JAK-STAT pathway over-activation. Median time to VTE was 1.2 months (range 0-4.1 months). Seven of the eight patients with VTEs received asparaginase and it was subsequently discontinued in three of them. Three of the four patients that did not develop a VTE received asparaginase. Median overall survival in patients with a VTE was 15 months (range 3-35.5 months) while median overall survival in patients without a VTE was 24.7 months (range 11.4-49.2 months). Conclusions: Our analysis demonstrated an extremely high incidence of VTEs in Ph-like ALL. Despite the small sample size, this suggests the need for larger studies to evaluate the relationship between Ph-like ALL and VTE, particularly in patients receiving asparaginase. Patient Age Gender Ph-like ALL Defining Abnormality Venous Thrombotic Event? 1 20 F CRLF2/P2RY8 fusion Yes (LE DVT) 2 22 F IGH/EPOR fusion Yes (central catheter (CC)-associated UE DVT) 3 64 M IGH/CRLF2 fusion No 4 25 M IGH/CRLF2 fusion No 5 49 M IGH/CRLF2 fusion Yes (UE DVT) 6 29 M IGH/CRLF2 fusion Yes (CC-associated UE DVT) 7 24 M IGH/CRLF2 fusion No 8 18 M ETV6-PAX5 fusion No 9 31 F IGH/CRLF2 fusion Yes (superior sagittal thrombosis) 10 92 F IGH/CRLF2 fusion Yes (central catheter-associated UE DVT) 11 53 F IGH/EPOR fusion Yes (UE DVT, LE DVT, PE) 12 23 M CRLF2/IGH + Yes (LE DVT, IVC Thrombus)
A phase 1/2, multicenter, dose-escalation and expansion study of combination therapy with venetoclax, daratumumab, and dexamethasone (with and without bortezomib) in subjects with relapsed or refractory multiple myeloma.
Authors: Orlando Bueno, Rachel Slimp, Michelle Jacobson, John Carl Pesko, Hong Li, Jeremy A. Ross, Kevin Freise, Paulo Cesar Maciag
Journal: Journal of Clinical Oncology (2018)

TPS8061 Background: Despite the introduction of new compounds to manage relapsed/refractory (R/R) multiple myeloma (MM) over the last decade, none are curative. Trials investigating novel agents or combinations are critical to advancing therapy. Overexpression of BCL-2 may contribute to the pathogenesis of t(11;14)-positive MM. Venetoclax (Ven) is a selective, potent, orally bioavailable BCL-2 inhibitor with activity in R/R t(11;14)-positive MM. Daratumumab, bortezomib, and dexamethasone is an FDA-approved triplet for MM. The addition of Ven to this regimen (± bortezomib) may result in additive antitumor effects via complementary mechanisms. Methods: This phase 1/2, multicenter study of Ven, daratumumab, and dexamethasone, with or without bortezomib, in R/R MM (NCT03314181) will have 2 parts, each with a dose-escalation and dose-expansion phase. Part 1 will evaluate Ven, daratumumab, dexamethasone (VenDd) in t(11;14)-positive patients who have had ≥ 3 prior therapies including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double refractory to both. The dose escalation phase will evaluate safety and tolerability; the randomized, blinded, expansion phase will assess the objective response rate of VenDd versus placebo-Dd. Part 2 will examine VenDd and bortezomib (VenDVd) in patients who have received 1 to 3 prior therapies and are not PI-refractory. The dose escalation phase will evaluate safety and tolerability; the single-arm, open-label expansion phase will assess efficacy per the International Myeloma Working Group (IMWG) criteria. A Bayesian Optimal Interval (BOIN) design will be used to guide dose escalation/de-escalation decisions in Parts 1 and 2. Secondary objectives will include progression free survival, duration of response, time-to-progression, minimal residual disease negativity, and pharmacokinetics and immunogenicity profiles of the Ven/daratumumab combinations. Exploratory objectives include evaluation of pharmacodynamic and predictive biomarkers associated with outcomes. Clinical trial information: NCT03314181.
Is cancer associated thrombosis (CAT) a neglected issue? Greek management of thrombosis (GMaT) in cancer patients.
Authors: Nikolaos Tsoukalas, Pavlos Papakotoulas, Athina Christopoulou, Alexandros Ardavanis, Georgios Koumakis, Christos Papandreou, George Papatsibas, Pavlos Papakostas, Charalampos Andreadis, Gerasimos Aravantinos, Nikolaos Ziras, Charalambos P. Kalofonos, Epaminontas Samantas, Sougleri Maria, Paris Makrantonakis, George E. Pentheroudakis, Athanasios Athanasiadis, Evangelos Bournakis, Ioannis I. Varthalitis, Ioannis Boukovinas
Journal: Journal of Clinical Oncology (2018)

e18868 Background: Cancer has multiple processes that increase thrombogenicity. Thrombosis is the 2nd cause of death in cancer patients. CAT is common, could delay anti-cancer therapy and increase costs. Oncologists should be aware of CAT and its clinical significance. Methods: A prospective observational study conducted by HeSMO in Greek Oncology units, for 1 year, aiming to record CAT clinical management and to identify possible risk factors. Patients with active cancer received antithrombotic agents for treatment or thromboprophylaxis were enrolled, after signing informed consent. Results: In total, 546 patients enrolled from 18 oncology units. Primary cancers were: lung 24%, pancreas 13,4%, breast 8.8%, colorectal 8,1%, stomach 8,1%, ovarian 6.6% and other 39,1%. 120 patients received Low Molecular Weight Heparin (LMWH) for Venus ThomboEmbolism (VTE) treatment (Group A), 426 for thromboprophylaxis (Group B) while no one received oral agents. Group A: 35% of 120 VTEs were diagnosed incidentally and treated as symptomatic [mean duration 5.51 months (SD+/-3.42)]. Recurrences occurred in 3 (2.5%) patients. Four (3%) patients experienced a grade 1 bleeding. Group B: 213 (50%) patients received LMWH at prophylactic doses while the rest received therapeutic doses [mean duration 4.42 months (SD +/- 2.68)]. 126 (30%) patients had Khorana score ≥3. Even though, 300 (70%) patients had Khorana score ≤2, 68% were metastatic and 58% was receiving High Thrombotic Chemotherapy Agents (HTCA, e.g. platinum, 5-FU, gemcitabine). 16 (3.8%) patients experienced VTE while 9 (56%) of them were incidental. Notably, lower VTE risk [OR: 0.32 (95% CI 0.10, 1.0) p = 0.04] was observed in patients on therapeutic doses LMWH while higher VTE risk [OR: 3,14 (1.01, 9,9)] was observed in patients on prophylactic doses LMWH. Six (1,4%) grade 1 bleedings were recorded. Conclusions: Oncologists use LMWH for the CAT management. Incidental VTE is a common and insidious clinical entity. Therapeutic doses of LMWH for thromboprophylaxis are effective and safe. Although Khorana score is a useful model for CAT risk assessment some other factors such as disease stage and HTCA might been taken into consideration. Further research is needed. Clinical trial information: NCT03292107.
Clinical experience with pembrolizumab in metastatic heavily pre-treated patients with solid cancers in a single center.
Authors: Raya Leibowitz-Amit, Einat Shacham-Shmueli, Talia Golan, Iris Gluck, Amir Onn, Leor Zach, Rony Weitzen, Einav Nili Gal-Yam, Damien Urban, Jair Bar, Jacob Korach, Raanan Berger
Journal: Journal of Clinical Oncology (2016)

e14549 Background: Pembrolizumab (pembro), an anti-PD1 monoclonal antibody, was recently approved for melanoma and NSCLC. Early signals of pembro activity were observed in several other solid cancers. Following this, and in accord with the concept of ‘the patient’s right to try’, our institutional ethical board approved it for off—label use in metastatic heavily pretreated cancer patients (pts). Our primary aim was to retrospectively assess the subjective clinical and radiological responses to pembro in this heterogeneous population. Methods: All non-hematological, non-melanoma adult ( > 18 years) cancer pts who received pembro (1-2 mg/kg, every 3 weeks) off-trial were retrospectively identified using pharmacy and electronic medical records. Radiological response was defined as a complete or partial decrease in tumor burden on computerized scans that was deemed clinically meaningful. Descriptive statistics were calculated with medians and percentages (Excel, Microsoft). Results: From Sep-14 to Dec-15, 96 pts received pembro off-trial. Pts were generally heavily pretreated (a median of 2 prior treatment lines) with compromised performance status. Pts were treated for a wide range of malignancies, including urothelial (17%), gastric (13%), ovarian (12%), NSCLC (13%) and cervical (9%) cancers. Median number of treatment cycles was 3 (range 1-13). Treatment was stopped in 54 pts (56%) due to clinical deterioration or death before radiological assessment. Fourteen pts (15%) had subjective clinical benefit on treatment. Two pts (2%) had radiological complete response and seven (7%) had partial radiological response; The response rate (RR) for the entire cohort was 9%. No responses were observed in 35 pts with ECOG PS = 3/4 (table). The RR associated with pembro when given as first or second line was 16% (7/43 pts) and 4% (2/51 pts) when given as third line or higher. Conclusions: Pembro has modest activity in non-selected, heavily pre-treated pts with metastatic solid malignancies. Poor performance status is associated with lack of response to Pembro. 3/4 (n = 35, 41%) 2 (n = 30, 35%) 0/1 (n = 20, 24%) ECOG PS % n % n % n response 0 0 0 0 10 2 CR 0 0 7 2 25 5 PR 1 1 3 mixed 0 1 1 SD 34 26 9 PD/not applicable 0 0 7 2 35 7 RR (CR+PR)
Identifying and interpreting actionable molecular alterations from next-generation sequencing results in the community: A Sarah Cannon molecular cancer conference.
Authors: Holli Hutcheson Dilks, Andrew McKenzie, Suzanne Fields Jones, Davey B. Daniel, Edward Arrowsmith, Michael A. Stipanov, Bertrand Marquess Anz, Darrell Johnson, An Tran, Benjamin Rolland Nadeau, Sylvia Lynne Krueger, Brooke R. Daniel, Derek Weldon Holland, Kimberly Tucker, Mick Correll, David R. Spigel, Howard A. Burris
Journal: Journal of Clinical Oncology (2018)

6601 Background: Next-generation sequencing (NGS) data can often be difficult to interpret and act upon for treating medical oncologists. Sarah Cannon developed a Molecular Cancer Conference (MCC) in May 2017 at a community clinic in Chattanooga, TN with the goal of helping medical oncologists identify and interpret molecular alterations from NGS results obtained in routine clinical practice. Herein, we report the workflow and effectiveness of the MCC in identifying actionable results and guidance in care. Methods: Molecular profiles from one community medical oncology office were reviewed by a MCC committee over a six month pilot period. The committee – made up of medical oncologists and research staff at the site, and a human geneticist, cancer cell biologist, and clinical pharmacologist linked in remotely from Sarah Cannon Research Institute in Nashville, TN via web-conference. The MCC met every 2 weeks to review all tissue- and blood-based NGS results from the interim. Mutations were analyzed using public databases and published literature; and patient diagnosis and clinical trial molecular inclusion/exclusion criteria were used to guide therapy and clinical trial recommendations, as well as approved therapies. Results: From 175 reports, 3608 molecular alterations were detected (avg. = 20.6 mut/pt; including VUSs) by commercially available NGS labs. Clinical trials were discussed for 148 patients (85%), and 26 patients (15%) were enrolled on clinical trials. Uncommon alterations were identified including a FGFR2-VCL fusion in cholangiocarcinoma, ERBB2 amplifications in NSCLC, and two unique ERBB2 VUSs in a HNSCC. Each of these mutations was treated with a targeted therapy as part of a clinical trial protocol. Conclusions: Sarah Cannon’s MCC was established to review and analyze patient molecular profile reports for community-based medical oncologists. Utilization of the MCC resulted in patients being screened for and enrolled on clinical trials. These findings highlight the feasibility and impact of having an expert committee review complex results and provide scientific advice to help guide care for patients in the community.
A Pilot Study of the Impact of a Single Dose of Zolendronic acid on Biomarkers in Breast Cancer.
Authors: May Thet Cho, Jun Gong, Shiuan Chen, Hua Yu, Louise Wong, Robin Smith, Laura Kruper, Joanne E. Mortimer
Journal: Journal of Clinical Oncology (2016)

e23248 Background: In randomized trials for early stage breast cancer, patients who received adjuvant zolendronic acid (ZA) had superior disease-free survival and greater tumor shrinkage. Preclinical data suggest that ZA has anti-cancer properties by modulating angiogenesis and tumor immune environment. This is a pilot study to assess changes in tumor biomarkers and immunological function in response to a single dose of ZA in paired tumor specimens (from core biopsy and definitive surgery). Methods: Postmenopausal women with early stage invasive ductal breast carcinoma who have estrogen receptor and/or progesterone receptor positive tumor for which a lumpectomy or mastectomy was planned prior to systemic therapy were enrolled. A single dose of ZA 4 mg IV was given 10-14 days prior to their planned definitive surgery. Fourteen biomarkers in tumor tissues were assayed; 10 by gene microarray (VEGF, IL1β, IL-6, TNF α, MMP-1, MMP-2, MMP-9, TGF, IFN-alpha and STAT3) and 4 by RT-PCR (P13K, PTEN, IGF-1-R, EGFR). Patient blood samples were drawn at baseline, at 48-72 hrs after the single dose of ZA, and at the time of surgery and assayed for cytokines and chemokines by using 30-plex Luminex panels. Results: Eight patients were enrolled in the study (median age 65 and range 57-75); 4 Caucasians, 2 Hispanics and 1 Asian; 6 were stage I, 1 was stage II, and 1 was stage III). 30-plex luminex assays showed MIG, IP-10, and IL-12 increases in days 1-3 of ZA therapy from baseline with normalization by days 10-24. MCP-1, IL2R, MIP-1b, and Eotaxin were found to have changes in days 1-3 from baseline with mixed responses by days 10-24. EGF, G-CSF, HGF, IFN-alpha, IFN-gamma, and RANTES showed no clear pattern of response among the eight patients. Tumor markers and proteomics from pair tumor samples will be presented. Conclusions: Changes in multiple tumor biomarkers and immunological markers such as MIG, IP-10, IL-12, MCP-1, IL2R, MIP-1b, Eotaxin, IFN-alpha, and IFN-gamma are seen within 2 weeks of a single dose of ZA that allow us to better understand the immunologic and molecular effects of ZA in cancer cells. Clinical trial information: NCT01409811.
Patterns of HPV testing and treatment decision in patients with SCCHN.
Authors: Giovanni Zanotti, Jean-Francois Martini, Roberto Uehara, Pamela Hallworth, Katherine Byrne
Journal: Journal of Clinical Oncology (2017)

e17526 Background: Human papillomavirus (HPV) is one of the main risk factors associated with squamous cell carcinoma of the head and neck (SCCHN). Although it is a prognostic factor, SCCHN patients are not routinely tested for HPV status because it may not be informative for therapy initiation. The objective of this study was to understand the real world testing patterns, and treatment decision of SCCHN patients. Methods: Real world data was gathered using Adelphi’s Disease-Specific Programme (DSP) - a real world, cross-sectional survey conducted in the USA, France, Germany and the UK (April - September 2016). The DSP incorporated 182 physician interviews (54 US, 128 EU) covering all stages of SCCHN caseloads and treatment patterns. Physicians also provided data for 8 consecutive consulting SCCHN patients regarding treatment patterns, progression, and symptoms. Results: A total of 2193 SCCHN patient cases were captured. HPV testing was carried out in 42% of patients within the DSP data set with no particular difference across the 4 countries. Of those tested, 35% of patients were HPV positive. Testing was mainly performed at the local level (51%, onsite or local hospital) apart from Germany where central testing was higher (73%). In over half of patients cases (54%) , physicians are unaware of the type of test performed for the HPV status determination; in fact, up to 10 different types of tests were used to determine the HPV status in this real world experience. Platinum based cetuximab and fluorouracil was used in 30% of the HPV positive patients while 20% received platinum monotherapy. In 2nd line, docetaxel/paclitaxel monotherapy was used in 22% of the patients. HPV negative patients also mainly received platinum based cetuximab and fluorouracil (27%) in 1 st line, while in 2 nd line, docetaxel/paclitaxel monotherapy was used in 20% of the patients. Conclusions: This analysis of real world treatment patterns and outcomes among SCCHN patients shows that HPV testing is not widely carried out for either patient characterization or to guide treatment decisions within this disease. Therapy choices were generally consistent standard clinical guidelines.
Complementary and Alternative Medicine Therapies for Psoriasis
Authors: A. Caresse Gamret, Alexandra Price, Raymond M. Fertig, Hadar Lev-Tov, Anna J. Nichols
Journal: JAMA Dermatology (2018)

<h3>Importance</h3> Up to 51% of patients with psoriasis report the use of complementary and alternative medicine (CAM) in their treatment regimen, although it is unclear which CAM therapies are effective for treatment of psoriasis. <h3>Objective</h3> This review compiles the evidence on the efficacy of the most studied CAM modalities for treatment of patients with plaque psoriasis and discusses those therapies with the most robust available evidence. <h3>Evidence Review</h3> PubMed, Embase, and ClinicalTrials.gov searches (1950-2017) were used to identify all documented CAM psoriasis interventions in the literature. The criteria were further refined to focus on those treatments identified in the first step that had the highest level of evidence for plaque psoriasis with more than 1 randomized clinical trial supporting their use. This excluded therapies lacking randomized clinical trial (RCT) data or showing consistent inefficacy. <h3>Findings</h3> Primary CAM therapy searches identified 457 articles, of which 107 articles were retrieved for closer examination. Of those articles, 54 were excluded because the CAM therapy did not have more than 1 RCT on the subject or showed consistent lack of efficacy. An additional 7 articles were found using references of the included studies, resulting in a total of 44 RCTs (17 double-blind, 13 single-blind, and 14 nonblind), 10 uncontrolled trials, 2 open-label nonrandomized controlled trials, 1 prospective controlled trial, and 3 meta-analyses. Compared with placebo, application of topical indigo naturalis, studied in 5 RCTs with 215 participants, showed significant improvements in the treatment of psoriasis. Treatment with curcumin, examined in 3 RCTs (with a total of 118 participants), 1 nonrandomized controlled study, and 1 uncontrolled study, conferred statistically and clinically significant improvements in psoriasis plaques. Fish oil treatment was evaluated in 20 studies (12 RCTs, 1 open-label nonrandomized controlled trial, and 7 uncontrolled studies); most of the RCTs showed no significant improvement in psoriasis, whereas most of the uncontrolled studies showed benefit when fish oil was used daily. Meditation and guided imagery therapies were studied in 3 single-blind RCTs (with a total of 112 patients) and showed modest efficacy in treatment of psoriasis. One meta-analysis of 13 RCTs examined the association of acupuncture with improvement in psoriasis and showed significant improvement with acupuncture compared with placebo. <h3>Conclusions and Relevance</h3> The CAM therapies with the most robust evidence of efficacy for treatment of psoriasis are indigo naturalis, curcumin, dietary modification, fish oil, meditation, and acupuncture. This review will aid practitioners in advising patients seeking unconventional approaches for treatment of psoriasis.
US-guided percutaneous radiofrequency versus microwave ablation for benign thyroid nodules: A prospective multicenter study.
Authors: Zhigang Cheng
Journal: Journal of Clinical Oncology (2017)

e17593 Background: To evaluate the clinical outcomes between radiofrequency ablation (RFA) and microwave ablation (MWA) in treating benign thyroid nodules (BTNs) with a prospective multicenter study. Methods: The prospective multicenter study achieved the registration of Chinese Clinical Trial Registry (Number: ChiCTR-ONRC-13003087). From January of 2013 to December of 2015, the total number of 1,252 patients with 1351 benign thyroid nodules (BTNs) at eight participating institutions was enrolled in the multicenter study. The ablation devices were applied in the study including RFA system of VIVA RF generator (VIVA RF generator, STARmed, Goyang, Korea) and MWA system of KY-2000 2450MHz microwave system (KY-2000, Kangyou Medical, Nanjing, China). All the procedures of RFA or MWA were performed under ultrasound (US) guidance in each center. Results: The number of target nodules treated by RFA and MWA were 687 in 649 cases and 664 in 603 cases, respectively. For the estimation of efficacy, the mean maximal diameter reduction ratios (MDRRs) of RFA vs. MWA groups at the 3rd, 6th, 12th month and last follow-up were 36.4±17.3% vs. 36.0±23.0% (p = 0.765), 54.1±22.7% vs. 49.3±28.0% (p = 0.005), 64.5±22.1% vs. 57.9±40.1% (p = 0.008) and 65.5±26.0% vs. 58.2±33.5% (p = 0.028), respectively. The mean volume reduction ratios (VRRs) of RFA vs. MWA groups at the 3rd, 6th, 12th month and last follow-up were 67.6±20.3% vs. 64.4±43.5% (p = 0.143), 84.1±13.5% vs. 78.4±48.2% (p = 0.016), 89.6±20.0% vs. 82.5±49.7% (p = 0.035) and 91.3±12.6% vs. 81.1±70.4% (p = 0.045), respectively. For the estimation of safety, for all the complications and side effects encountered at the peri-ablation and follow-up period in two groups, the major, minor complication and side effect rates of RFA vs. MWA group were all no statistical significances with 4.78% vs. 6.63% (p = 0.156), 2.00% vs. 2.49% (p = 0.562) and 4.93% and 4.64% (p = 0.812), respectively. Conclusions: As a conclusion of the prospective multicenter study, both RFA and MWA under US guidance percutaneously are safe and effective techniques for selected patients with BTNs. Larger MDRR and VRR can be achieved in RFA group than the ones in MWA group at 6-month and later follow-up. Clinical trial information: ChiCTR-ONRC-13003087.