tbuckley/cabot-search huggingface dataset:
Mature results of the GETUG 13 phase III trial in poor-prognosis germ-cell tumors (GCT).
Authors: Karim Fizazi, Aude Flechon, Gwenael / Le Teuff, Jozef Mardiak, Lance C. Pagliaro, Lionnel Geoffrois, Pierre Kerbrat, Christine Chevreau, Remy Delva, Frederic Rolland, Christine Theodore, Guilhem Roubaud, Gwenaelle Gravis, Jean-Christophe Eymard, Jean-pierre Malhaire, Claude Linassier, Muriel Habibian, Maria Reckova, Christopher Logothetis, Stephane Culine
Journal: Journal of Clinical Oncology (2016)

4504 Background: Until 2014, standard treatment for poor-prognosis GCT was 4 BEP plus surgery and cure was achieved in only 50% of patients (pts) (IGCCCG 1997). The tumor marker decline rate identified pts with a better outcome (J Clin Oncol 2004, 22: 3868-76). The GETUG 13 phase III trial established that switching pts with an unfavorable decline to intensified chemotherapy results in improved progression-free survival (PFS) (Lancet Oncol 2014; 15: 1442-50). We assessed the long-term efficacy and toxicity in pts treated in GETUG 13. Methods: 263 pts with IGCCCG poor-prognosis GCT were treated with 1 BEP. hCG and AFP were assessed at day 21: 1) 51pts with a favorable decline continued BEP (Fav-BEP); 2) 203 pts with an unfavorable decline were randomized to receive either BEP (Unfav-BEP) or a dose-dense regimen (Unfav-dose-dense), consisting of paclitaxel-BEP plus oxaliplatin x 2 cycles, followed by 2 cycles of cisplatin, ifosfamide, and bleomycin + G-CSF. PFS and overall survival (OS) (logrank) and long-term toxicity (NCI-CTC criteria) were assessed. Results: The median follow-up is 5.6 years (range 0.3; 11.9). The 5-year PFS rate is 60% in the Unfav-dose-dense arm vs 47% in the Unfav-BEP arm (HR: 0.65 [0.43-0.97]; p=0.037). The 5-year OS rate is 70.4% and 60.8%, respectively (HR: 0.69 [0.43-1.11]; p=0.12). Side effects evolved favorably, with 3 pts in the Unfav-dose-dense arm reporting grade 3 motor neurotoxicity at 1 year but no reported toxicity ≥ grade 2 after year 2. The prognostic value of the tumor marker decline was confirmed: 70% vs 47% for 5-year PFS (p=0.006), and 78% vs 61% for OS (p=0.02). Salvage high-dose chemotherapy plus a stem cell transplant was implemented in 8% in the Unfav-dose-dense arm and 17% in the Unfav-BEP arm (p=0.035). Conclusions: With a mature follow-up, GETUG 13 shows that pts with poor-prognosis GCT and an unfavorable tumor marker decline after 1 BEP who are treated with intensified chemotherapy achieve significantly improved PFS, numerically better OS, minimal long-term toxicity, and a reduced need for high-dose salvage chemotherapy plus a stem cell transplant. These data support integrating this strategy as a standard of care for these rare pts. Clinical trial information: NCT00104676.
Treatment patterns and costs in cutaneous squamous cell carcinoma (CSCC) patients with nodal dissection, chemotherapy, and/or radiation therapy.
Authors: Emily S Ruiz, Chieh-I Chen, Katie Deering, Yingxin Xu, Andreas Kuznik, Medha Sasane, Fen Ye, Qing Harshaw, Michael L. Andria, Matthew G. Fury, Kanwarjit Singh, Chrysalyne Schmults
Journal: Journal of Clinical Oncology (2018)

e18703 Background: Unlike other cancers, information on CSCC is not captured in national cancer registries, and little is known about the management and costs of CSCC. In contrast, more is known about metastatic melanoma with total costs reported to be $12,111 per-patient-per-month (PPPM) in 2013. In this study, we describe treatments and costs of CSCC patients with nodal dissection, chemotherapy, and/or radiation therapy. Methods: Truven MarketScan®claims databases were used to conduct a retrospective analysis from January 1, 2012 to December 31, 2016. Patients were included if they met one of the following criteria: ≥1 lymph node dissection, ≥1 chemotherapy with radiation therapy in ≥2 treatment fields, or a secondary metastatic code concurrent with CSCC primary diagnosis. Index date was defined as the first date when 1 of the 3 criteria was met. All patients were required to have a primary CSCC diagnosis and ≥12 months of continuous enrollment prior to the index date. Treatments and costs were tabulated post-index. Results: A total of 999 CSCC patients (mean age: 69 [±13] years; 77% men) met the study criteria. Of these, 278 (28%) were immunocompromised (34% organ transplant recipients, 1% chronic lymphocytic leukemia,1% HIV, 64% other). At or post-index date, 886 (87%) patients had a surgical procedure, 742 (74%) patients underwent nodal dissection, 272 (27%) were given systemic therapy, and 245 (25%) received radiation. Of the 272 receiving systemic therapy, 58% received a platinum therapy, 34% EGFR therapy, and 22% other chemotherapies. The average follow-up was 16 (±14) months. Average total and CSCC-specific costs were $18,409.05 (±$54,890.57) and $7,385.82 (±$26,863.88) PPPM, respectively. Conclusions: Currently, there is no standard of care for patients with more advanced CSCC, highlighting the need for clinical studies in this population. These data indicate that many are managed with surgery and about a quarter receive systemic therapy and/or radiation. Care of patients with more advanced CSCC is associated with considerable cost, comparable to published costs for other skin cancers.
Predicting unreported clinical trial efficacy using an <i>ex-vivo</i> tumor platform: Pembrolizumab+pt+5-FU vs. extreme in recurrent head and neck squamous cell carcinoma.
Authors: Munisha Smalley, Saravanan Thiyagarajan, Biswanath Majumder, Nandini Pal Basak, Abhishek Basu, Padhma Radhakrishnan, Pradeep Kumar Kar, Manjusha Biswas, Basava U Shanthappa, Hans Gertje, Mark Lawson, K S Sabitha, K Jay G Ray, Govind Babu Kanakasetty, Pradip K Majumder, Aaron Goldman
Journal: Journal of Clinical Oncology (2018)

e18042 Background: PD-1 inhibition has shown promise in second-line, platinum (Pt) resistant HNSCC (e.g. KEYNOTE-055). To improve the outcome of PD-1 blockade, clinical trials are testing immunotherapy combinations such as, KEYNOTE-048, an unreported trial combining a PD-1 inhibitor (Pembrolizumab) with Pt/5-fluorouricil (5-FU) vs. cetuximab/Pt/5-FU (EXTREME) as frontline therapy for recurrent or metastatic HNSCC. A lack of pre-clinical models to profile immunotherapy has made efficacy prediction difficult. Methods: Using fresh tumor biopsies from HNSCC patients with metastatic or locally advanced disease (N = 39), we used CANscript, a clinically-validated ex-vivo tumor platform that preserves the native patient tumor and immune contexture. We tested three treatment schedules: Pembro, Pembro/Pt/5-FU, cetuximab/Pt/5-FU; reflecting treatment arms from the yet unreported KEYNOTE-048. Using phenotypic reflex to drug, ex-vivo, paired with a proprietary algorithm, we predicted clinical response (M-Score). We used PD-L1 status (IHC) and gene expression profiling to understand mechanistic changes following therapy. Results: We predicted, using M-Score, an ORR of 12.8% with Pembro, correlating to results from KEYNOTE-040 (14.6%). The EXTREME regimen showed 30.7% ORR, consistent with NCT00122460 data (36%). We predicted no benefit with Pembro/Pt/5-FU vs. EXTREME (30.7% vs. 30.7%). We also profiled ORR based on Pt type (Carboplatin vs. Cisplatin) with greater ORR from Pembro/Carbo/5-FU (43.7%) vs. Pembro/Cis/5-FU (21.7%). In contrast, we predicted EXTREME alone results in similar ORR regardless of Carbo or Cis therapy (31.3% vs. 30.4%). Conclusions: These results demonstrate the ability of the CANscript system to profile clinical response to immunotherapy. Our efforts may better inform clinical trial design thereby increasing the potential for trial success. If prediction for response to the novel combination in KEYNOTE-048 correlates, this would provide the first evidence that a human tumor model can be used to profile immunotherapy response, while also providing translational insights into mechanisms of response and resistance.
Supportive treatment for hematologic toxicities in the phase 3 RECOURSE trial of TAS-102 vs placebo with best supportive care in patients with metastatic colorectal cancer.
Authors: Robert J. Mayer, Eric Van Cutsem, Takayuki Yoshino, Alfredo Falcone, Rocio Garcia-Carbonero, Guillem Argiles, Alessandro Pastorino, Marc Peeters, Robert Winkler, Mona Wahba, Lukas Makris, Alberto Zaniboni, Yasuhiro Shimada, Kentaro Yamazaki, Yoshito Komatsu, Howard S. Hochster, Heinz-Josef Lenz, Ben Tran, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2016)

e15021 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil. Efficacy and safety of TAS-102 in patients (pts) with metastatic colorectal cancer refractory/intolerant to standard therapies were evaluated in the RECOURSE trial; enrollment criteria included ≥ 2 prior lines of standard chemotherapy. Primary results of RECOURSE demonstrated a significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 vs placebo (pbo) (hazard ratio = 0.68 and 0.48 for OS and PFS, respectively; both P< 0.0001). As this class of drug is associated with hematologic adverse events, pts must be monitored closely and measures such as colony-stimulating factors (CSF) given as clinically indicated. This analysis evaluates how hematologic toxicities were managed with agents such as granulocyte (G)-CSF and actions such as dose reductions in RECOURSE. Methods: RECOURSE data were analyzed for use of supportive therapy, eg, G-CSF for hematologic-related toxicities and the rate of dose reductions/delays in pts with these toxicities. Results: Of 533 pts in the TAS-102 group, 50 (9.4%) received G-CSF vs 0/265 in the pbo group; more TAS-102 pts also received antianemia products such as epoetin (25 [4.7%] TAS-102 vs 2 [0.3%] pbo). The incidence of hematologic toxicities that resulted in dose reductions/delays was 43.0% vs 1.1% for all grades and 29.6% vs 0.8% for Grade ≥ 3, TAS-102 vs pbo, respectively. The incidence of febrile neutropenia and hospitalization due to febrile neutropenia was 2.4%. Conclusions: The incidence of hematologic toxicity and consequent use of supportive therapies and use of dose reductions/delays were higher in the TAS-102 group vs pbo group. Low incidence of febrile neutropenia may be related to use of G-CSF, but further analyses to ascertain the role of G-CSF are ongoing. No specific proposal for hematologic toxicity management beyond standard supportive therapies is recommended as institutional or national guidelines are well established. Clinical trial information: NCT01607957.
Novel antiangiogenic drugs, immune checkpoint inhibitors, and chemotherapy in patients with aNSCLC who have aggressive disease: A systematic review.
Authors: Katherine B. Winfree, Claire Ainsworth, Annete Njue, Cliff Molife, Matthew Lyall, Min-Hua Jen, Marisa Bittoni, Anne Heyes, David Paul Carbone
Journal: Journal of Clinical Oncology (2018)

e21120 Background: This review aimed to summarize the clinical utility (efficacy, safety, and quality of life) of ramucirumab compared to nintedanib, immune checkpoint inhibitors (ICIs), and chemotherapy in second-line treatment for patients with advanced non-small cell lung cancer (aNSCLC) who do not respond well to first-line treatment (1LT) due to aggressive tumor behavior. Methods: We systematically searched the literature (database inception through October 2017) to identify randomized, controlled trials reporting efficacy and/or safety of ramucirumab, nintedanib, ICIs (atezolizumab, avelumab, durvalumab, nivolumab, or pembrolizumab), or chemotherapy (docetaxel, gemcitabine, nab-paclitaxel, paclitaxel, pemetrexed, or vinorelbine) in aNSCLC patients with aggressive disease (AD) characteristics, as defined by physician opinion. Results: The 14 identified studies had ≥ 1 subgroups with characteristics associated with AD: refractory and/or progressive disease (PD) as best response to prior treatment (11 studies), rapid progression (2), short duration on previous treatment (1), high tumor burden or size (2), and short duration since start of last treatment (4). Survival estimates were reported in 11 studies; response and safety data were available for 2 studies. Ramucirumab plus docetaxel and nintedanib plus docetaxel showed efficacy in patients with < 9 months since start of 1LT or with PD as best response to 1LT. For these two subgroups, both treatments had safety outcomes consistent with the overall aNSCLC population. Docetaxel and pemetrexed were beneficial in patients with < 3 months since start of 1LT and with PD as best response to 1LT, respectively. No studies reported on ICIs for AD. Varying definitions of AD and the lack of a common comparator limited indirect treatment comparisons of trials. Conclusions: There is limited evidence for patients with AD. Recent subgroup data for ramucirumab and nintedanib demonstrate benefit in patients with varying AD definitions. AD in the 1LT setting may be a poor prognostic factor for survival based on identified studies. Further studies assessing treatment benefits in aNSCLC patients with AD are needed.
Safety and resource use in the PROCLAIM study comparing 2 regimens of concurrent chemoradiation followed by consolidation chemotherapy in locally advanced nonsquamous non-small cell lung cancer (NSCLC).
Authors: Ramaswamy Govindan, Suresh Senan, Nicolas J. Dickgreber, Mariano Provencio, Yi-Long Wu, Konstantinos N. Syrigos, Bárbara Parente, Nadia Chouaki, Anwar Hossain, Belén San Antonio, Katherine B. Winfree, Everett E. Vokes
Journal: Journal of Clinical Oncology (2016)

8529 Background: Standard of care for inoperable stage III NSCLC is concurrent chemoradiotherapy. Safety and resource utilization are important for treatment decisions. Methods: Resource utilization among patients (pts) in PROCLAIM (NCT00686959) receiving pemetrexed+cisplatin (PemCis) and concurrent radiotherapy (RT) for 3 cycles, followed by 4 cycles of Pem consolidation (Arm A; N = 283) was compared with pts receiving etoposideCis (EtoCis) and concurrent RT for 2 cycles followed by consolidation platinum-based doublet for up to 2 cycles (Arm B; N = 272). Possible consolidation therapies in Arm B were EtoCis, vinorelbineCis, and paclitaxel+carboplatin. Overall efficacy and safety results by study phase were previously presented. A pt diary assessed swallowing issues. Results: Table shows resource utilization including hospitalizations, transfusions and selected concomitant medications. Study phase analyses are consistent with the overall treatment assessment. 33.8% of pts in Arm A vs 29.0% in Arm B reported swallowing diary score of ≥ 4, indicating an inability to swallow solids or liquids, which is comparable to Gr 2-4 dysphagia during the overall treatment (26.5% vs 23.2%, respectively). Conclusions: While overall resource use, including hospitalizations, was similar between treatment groups, the number of pts receiving transfusions, ESAs and CSFs was lower in Arm A, consistent with the previously reported lower incidence of Gr 3/4 anemia and neutropenia during overall treatment. Clinical trial information: NCT00686959. Arm A N = 283 Arm B N = 272 Pts with ≥ 1 hospitalization, n (%) 82 (29.0) 77 (28.3) Drug-related AEs 64 (22.6) 81 (29.8) Nondrug-related AEs 66 (23.3) 78 (28.7) Pts receiving ≥ 1 transfusion, n (%) 163 151 Total # of transfusions 274 (96.8) 259 (95.2) Pts receiving concomitant medication, n (%) 222 (78.5) 207 (76.1) Antiemetics and antinauseants 215 (76.0) 213 (78.3) Analgesics 192 (67.8) 174 (64.0) Anti-infectives (systemic) 9 (3.2) 21 (7.7) ESAs 23 (8.1) 65 (23.9) G-CSF/GM-CSF Abbreviations: ESAs, erythropoietic agents; G-CSF, granulocyte colony stimulating factor; GM-CSF, granulocyte macrophage colony stimulating factor.
Integrating palliative care in pediatric oncology: An evolving paradigm for comprehensive cancer care.
Authors: Deena R. Levine, Justin N. Baker
Journal: Journal of Clinical Oncology (2016)

e21590 Integrating Palliative Care in Pediatric Oncology: An Evolving Paradigm for Comprehensive Cancer Care Deena R. Levine, MD and Justin N. Baker, MD Background: The demonstrated benefit of integrating palliative care (PC) into cancer treatment has triggered an increased need for PC services. The trajectory of integrating PC in comprehensive cancer centers, particularly pediatric centers, is unknown. We describe our eight-year experience of initiating and establishing PC with the Quality of Life Service (QoLS) at St. Jude Children’s Research Hospital. Methods: We retrospectively reviewed records of patients seen by the QoLS (n= 615) from March 2007 to December 2014. Variables analyzed for each year, using descriptive statistics, included diagnostic groups, QoLS encounters, goals of care, duration of survival, and location of death. Results: Total QoLS patient encounters increased from 58 (2007) to 1297 (2014), new consults increased from 17 (2007) to 115 (2014), and mean encounters per patient increased from 5.06 (2007) to 16.11 (2014). Goal of care at initial consultation shifted from primarily comfort to an increasing goal of cure. The median number of days from initial consult to death increased from 52 days (2008) to 223 days (2014). Hospital-wide, patients receiving PC services before death increased from approximately 50% to nearly 100%. Conclusions: Since its inception, the QoLS experienced a dramatic rise in referrals and encounters per patient, utilization by all clinical services, a trend toward earlier consultation and longer term follow-up, increasing outpatient location of death, and near-universal PC involvement at the end-of-life. The successful integration of PC in a comprehensive cancer center, and resulting improved care provision over time, can serve as a model for other programs on a broad scale.
Amethyst NSCLC trial: Phase 2, parallel-arm study of receptor tyrosine kinase (RTK) inhibitor, MGCD265, in patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC) with activating genetic alterations in mesenchymal-epithelial transition factor (<i>MET</i>).
Authors: Igor I. Rybkin, Ebenezer A. Kio, Ashiq Masood, Merrill Kingman Shum, Balazs Halmos, Collin M. Blakely, Keith D. Eaton, Neelesh Sharma, John J. Nemunaitis, Steven J. Saccaro, Yanis Boumber, Raul R. Mena, Hamid R. Mirshahidi, Pasi A. Janne, James Christensen, Richard C. Chao, Vanessa Roberts Tassell, Demiana Faltaos, Marshall T. Schreeder
Journal: Journal of Clinical Oncology (2016)

TPS9099 Background: MGCD265 is an oral, potent, small molecule RTK inhibitor of MET and Axl, which are important for mediating signals for cell growth, survival, and migration. MET mutations and/or gene amplification have been reported in approximately 7% of NSCLC and function as oncogenic drivers that promote cancer development and progression. MET splice site mutations that result in the deletion of exon 14 (METex14del) represent a novel class of genetic alterations that have been implicated as oncogenic drivers in a subset of NSCLC. METex14del contains the Y1003 CBL ubiquitin ligase regulatory binding site that mediates CBL-dependent MET degradation and signal attenuation. Deletion of this region results in sustained activation of MET and its downstream signaling pathways. MGCD265 has demonstrated anti-tumor efficacy with robust tumor regression in xenograft models of METex14del and MET amplification. Additionally, confirmed partial responses have been observed in pts with MET-altered NSCLC treated with MGCD265 in the Phase 1 setting. Methods: This global Phase 2 trial is enrolling pts with NSCLC characterized by activating genetic MET alterations in tumor tissue or blood and who have received at least one prior platinum-containing regimen for advanced disease. Pts will be enrolled to one of four study arms based on the type of MET dysregulation: 1) mutations in tissue, 2) amplification in tissue, 3) mutations in blood, and 4) amplification in blood. The primary endpoint is Objective Response Rate (ORR) in accordance with RECIST 1.1; a Bayesian Predictive Probability Design is applied independently to each treatment arm. Secondary objectives are safety and tolerability, response duration, survival, correlations between tissue and blood testing, and PK/PD. Pts are treated with MGCD265 in 21-day cycles until RECIST-defined progression or unacceptable toxicity. The study is open for enrollment and recruitment is ongoing. Clinical trial information: NCT02544633.
Compliance of elderly head and neck squamous cell carcinoma (HNSCC) patients (pts) with concurrent chemoradiotherapy (CRT) in cetuximab versus cisplatin.
Authors: Eyad Kazan, Tiffanie Kleihneny, Nacera Sakek, Alice Thomas, Lucia Milian, Magali Edel
Journal: Journal of Clinical Oncology (2017)

e17553 Background: Cisplatin toxicities substantially increased in elderly patients with head and neck cancer, when it is given as CRT. Bio-radiotherapy using cetuximab could offer a less toxic alternative. The purpose of this retrospective study is to evaluate the compliance of cetuximab versus cisplatin in CRT for HNSCC pts 70 years of age or old pts. Methods: We included over 70 years old patients treated by radio chemotherapy in head and neck cancer. Severity of AE was measured by the percentage of the drug dose reduction. Dose is considered reduced if patient did not receive 200mg/m² in cisplatin group, and if he did not receive the seven planned cycles in cetuximab group. We recalculated the dose reduction percentage including over 65 years old patientes. Results: We enrolled 37 over 70 years pts, middle age 74.5(from 70 to 88). 23 pts were treated by cetximab-RT compared to 14 treated by cisplatin-RT. 30% of pts (7 of 23 pts) in cet-RT group received a dose reduction versus 28% (4 of 14 pts) in cisplatin-RT group. Then, compliance to cetuximab is comparable to cisplatin and dose reduction is close.This finding disclaim a general assumption that cetuximab is better tolerated than cisplatin concurrently to radiotherapy in elderly pts. When we recalculated the dose reduction including also over 65 years old pts, we endrolled 64 pts, dose reduction in cet-RT pts remains about 28% (10 of 35pts) versus only 17% (5 of 29) in cisplatin-RT group. A clear increasing in dose reduction of cisplatin appears once pts passed 70 years old. Finally, we redistributed the 35 cetuximab-RT pts according to period of treatment, the first group included pts treated between 2007 and 2011, dose reduction was 35% (7 of 20patients),the second group included pts treated between 2012 and 2016, dose reduction was only 20% (3 of 15). This supports that good handling of cetuximab's toxicities improves the treatment's compliance. Conclusions: Dose reduction in elderly pts is equal in cetuximab and cisplatin. Dose reduction to cisplatin clearly increases among over 70years old pts. Good handling of cetuximab improves the compliance to treatment
Nurturing care for children with developmental disabilities: a moral imperative for sub-Saharan Africa
Authors: Bolajoko O Olusanya, Petrus J de Vries, Bolajoko Olubukunola Olusanya, Melissa Gladstone, Jean Paul Rukabyarwema, Hannah Kuper, Mphelekedzeni C. Mulaudzi, Angelina Kakooza-Mwesige, Felix A. Ogbo, Jacob Olusegun Olusanya, Adrian C. Davis, Petrus J. de Vries
Journal: The Lancet Child & Adolescent Health (2018)
TCT-18 Novel concept of catheter-based treatment for tricuspid regurgitation (Cerclage-TR block): a preliminary animal experiment in a swine model
Authors: Min-Ku Chon, Soon-Myung Jung, Soo Yong Lee, Sang-Hyun Lee, Ki Won Hwang, Jeongsu Kim, Yong Hyun Park, Kook-Jin Chun, June Hong Kim
Journal: Journal of the American College of Cardiology (2018)
Abstract 19227: In-vivo Pet Imaging of Long-Term Microglia-Activation After Cardiac Arrest in Rats
Authors: David de la Puente Bethencourt, Daniel C Schroeder, Erik Popp, Johannes Zischler, Thorsten Annecke, Tim Hucho, Bernd Neumaier, Bernd W Böttiger, Heike Endepols
Journal: Circulation (2016)

Objective: Half of the survivors of cardiac arrest (CA) suffer from permanent impairment of cognitive functions. CA is a state of global cerebral ischaemia that causes delayed neuronal death in sel...