tbuckley/cabot-search huggingface dataset:
A polymer-coated, paclitaxel-eluting stent (Eluvia) versus a polymer-free, paclitaxel-coated stent (Zilver PTX) for endovascular femoropopliteal intervention (IMPERIAL): a randomised, non-inferiority trial
Authors: William A Gray, Koen Keirse, Yoshimitsu Soga, Andrew Benko, Anvar Babaev, Yoshiaki Yokoi, Henrik Schroeder, Jeffery T Prem, Andrew Holden, Jeffrey Popma, Michael R Jaff, Juan Diaz-Cartelle, Stefan Müller-Hülsbeck, Thomas Albrecht, Kenji Ando, Anvar Babaev, Michael J Bacharach, William Bachinsky, Danielle Bajakian, Robert Beasley, James Benenati, Andrew Benko, Mark Burket, Joseph Cardenas, Tony Das, Randall De Martino, Hannes Deutschmann, Daniel Dulas, Robert Feldman, Mark Fugate, Lawrence Garcia, Jaafer Golzar, Rao Gutta, Patrick Hall, Stewart Hawkins, Steve Henao, Benjamin Herdrich, Keisuke Hirano, Andrew Holden, Safwan Jaalouk, Sean Janzer, Daizo Kawasaki, Koen Keirse, Yazan Khatib, Kimihiko Kichikawa, Ethan Korngold, Christian Loewe, Louis Lopez, Henry Lui, Toshiaki Mano, Robert Mendes, Akira Miyamoto, Stefan Müller-Hülsbeck, Masato Nakamura, David O'Connor, Takao Ohki, James Park, Richard Powell, Antonis Pratsos, Jeffery Prem, Vikram Rao, John Rashid, Robert Rhee, Jason Ricci, Dierk Scheinert, Herman Schroë, Henrik Schroeder, Peter O Simon, Gagan Singh, Kongteng Tan, Paul Tolerico, Thodur Vasudevan, Frank Vermassen, Martin Werner, Bret Wiechmann, Hiroyoshi Yokoi, Yoshiaki Yokoi, Thomas Zeller
Journal: The Lancet (2018)
A randomized phase Ib/II study of the selective small molecule axl inhibitor bemcentinib (BGB324) in combination with either dabrafenib/trametinib or pembrolizumab in patients with metastatic melanoma.
Authors: Oddbjorn Straume, Cornelia Schuster, Gro Gausdal, James Lorens, Bjorn T. Gjertsen
Journal: Journal of Clinical Oncology (2018)

9548 Background: Upregulation of the receptor tyrosine kinase Axl has been linked with both a reduced response to PD-1 blockade and the development of therapy resistance to BRAF directed therapies in melanoma. Bemcentinib (BGB324) is a first-in-class orally bioavailable selective inhibitor of Axl which is currently explored in several ph II clinical trials. BGBIL006 (NCT02872259) is an open label phase Ib/II trial designed to explore whether combination with bemcentinib improves ORRs to standard of care therapies in pts with metastatic melanoma (MM). Methods: Dose escalation of bemcentinib in combination with 150mg twice daily / 2mg daily D/T in newly diagnosed, BRAF pos. MM with high tumour load followed a 3+3 design (part 1). In part 2, pts were randomized 2:1 to receive D/T or pembro +/- bemcentinib at RP2D, respectively, based on mutation status and tumour load. Pts were allowed to switch D/T with pembro and vice versa upon progression (part 3). Tumor responses were assessed per investigator using RECIST v1.1. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) in a selection of pts pre-dose and at C2D1. Results: In part 1, 6 newly diagnosed pts were enrolled (age 34-71, male 66%, LDH > 1 x ULN 50%). There was1 dose limiting toxicity (G3 rash). As of Feb 7 2018, a further 13 pts have been enrolled into part 2 of the study. The most common treatment-related AEs (TRAEs) were diarrhea (42%), pyrexia (37%), fatigue (31%) and rash (31%). Grade 3 TRAEs were observed in 3 (16%) pts. No G4 AEs or treatment related deaths occurred. The bemcentinib RP2D (200 mg daily) is well tolerated in combination with both D/T and pembro with AE profiles consistent with those reported for either therapeutic approach alone. Protein biomarkers candidates predictive of pt benefit following bemcentinib treatment were identified. Conclusions: Bemcentinib can be administered in combination with established first line therapies in patients with melanoma. Safety and efficacy as well as biomarker candidates will continue to be explored. Clinical trial information: NCT02872259.
A phase 3 randomized, controlled, open-label study of selinexor, bortezomib, and dexamethasone (SVd) versus bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (RRMM).
Authors: Sosana Delimpasi, Ludek Pour, Holger W Auner, Meletios A. Dimopoulos, Alon Rappaport, Lisa Fortin, Jatin J. Shah, Sharon Shacham, Michael G. Kauffman, Nizar J. Bahlis
Journal: Journal of Clinical Oncology (2018)

TPS8056 Background: Selinexor is an oral, selective inhibitor of nuclear export that specifically blocks exportin 1, leading to the nuclear accumulation & reactivation of tumor suppressor proteins. Twice weekly (BIW) bortezomib in combination with dexamethasone (Vd) is an established therapy in relapsed and refractory multiple myeloma (RRMM). While the activity of bortezomib (bort) BIW in combination with other agents is efficacious, prolonged use is limited due to peripheral neuropathy (PN) (50-60%) as well as acquired resistance to bort. Preclinical studies have shown that selinexor, when combined with bort, can restore sensitivity of bort-resistant MM, inhibiting tumor growth and increasing survival in murine MM xenografts. In a Ph 1b/2 study, the combination of weekly selinexor with weekly bort and dex (SVd) was well tolerated and highly active with an ORR of 83% in patients (pts) with PI non-refractory MM, furthermore PN was limited to 14%. In addition, in pts with PI refractory MM, an ORR of 43% was observed, supporting selinexor can resensitize myeloma to PI based therapies. Methods: The BOSTON trial (NCT03110562) is a global Ph III study of selinexor in combination with weekly bort and dex (QW SVd) vs BIW bort in combination with dex (BIW Vd), in pts with RRMM who have received 1 to 3 prior anti-MM regimens. The QW regimen of SVd may provide for a higher ORR and improved duration of response as well as provide for a considerable reduction (~40%) in overall bort dose vs BIW Vd arm, which may be associated with better tolerability (e.g., PN) compared with second-line Vd-based regimens. After progressive disease is confirmed by an Independent Review Committee, pts in the Vd arm may crossover to SVd. Crossover to Sd is allowed as compassionate use for pts who are not able to tolerate continued treatment with bort. Progression Free Survival (PFS) and ORR are primary endpoints. Secondary endpoints include overall survival and duration of response. An ORR primary analysis is planned after the last pt randomized has had the opportunity to complete at least 2 MM evaluations. Clinical trial information: NCT03110562.
ERBB pathway alterations in advanced gastric signet-ring cell carcinoma (SRCC) and the implications for targeted therapy.
Authors: Jia Wei, Bo Xu, Shenying Jin, Lixia Yu, Baorui Liu
Journal: Journal of Clinical Oncology (2017)

e15586 Background: Studies have shown that ERBB3 mutations are associated with poor clinical prognosis and ERBB3 targeted therapeutics can be effective against ERBB3 mutant-driven tumors. ERBB signal pathway plays a very important role in the initiation and progression of gastric cancer, however the ERBB2 expression and mutation rate is relative low especially in gastric SRCC. Thus, ERBB3 might be a promising target for the treatment in SRCC patients. The aim of this study is to speculate the prognostic and targeted therapy value in gastric SRCC by evaluating the mutation rate and type of ERBB3. Methods: 92 patients with histological diagnosis of advanced gastric SRCC were retrospectively selected. ERBB3 mutation was evaluated by next generation sequencing from formalin-fixed paraffin-embedded (FFPE) samples. ERBB2 expression was tested by immunohistochemistry. Correlations between ERBB2/3 status and clinical pathologic characteristics and overall survival (OS) were performed. Results: All of the 92 patients were diagnosed as local advanced or metastatic gastric SRCC (92.4% were stage III, 7.6% were stage IV). All the patients received 5-FU-based first-line chemotherapy. 14 out of all 92 patients were ERBB3 mutated SRCC, in which only 2 samples were ERBB2 positive. 12 of all the 14 mutations were in the extracellular domain, 2 were in the transmembrane region. There was no correlation between ERBB3 mutation and serosa invasion (P = 0.389) or lymph node metastasis (P = 1.000). The median OS was 20.5 months (95% CI = 10.05to 30.95 months) for patients with ERBB3 mutation, and 19.0 months (95% CI = 15.54 to 22.46 months) for patients without ERBB3 mutation (P = 0.567). There was no difference in OS according to HER2 positive or negative in ERBB3 mutated patients (14.8 months vs 20.5 month, P = 0.374). Conclusions: Our study demonstrated 15.2% of gastric SRCC patients harboring ERBB3 mutation, providing a potential subgroup of gastric SRCC for targeted treatment on ERBB pathway. No difference of OS was observed, probably due to the relative small sample size and low ERBB2 positive rate in SRCC patients. Further investigation on ERBB3 is warranted to clarify mechanisms of ERBB pathway in gastric SRCC.
Allogeneic hematopoietic stem cell transplantation for mantle cell lymphoma in a heavily pretreated patient population.
Authors: Daniel Allen Kobrinski, Scott E. Smith, Zeina Al-Mansour, Stephanie Bochen Tsai, Brendan Martin, Patrick J. Stiff
Journal: Journal of Clinical Oncology (2017)

7558 Background: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only potential curative treatment option for patients with MCL due to its potent graft-versus-lymphoma (GVL) effect. Survival following allo-SCT for MCL is variable due to high rates of non-relapse mortality (NRM). Methods: We retrospectively identified all patients who were treated with an allo-SCT for MCL at Loyola University Medical Center between January 1, 1999 and January 1, 2016. Probability estimates for overall survival (OS) and non-relapse mortality (NRM) at 5 years were calculated from the date of allo-SCT to the date of patient death or last known follow-up. Significance was determined using a cox proportional hazard (CPH) model. Rates of acute graft-versus-host disease (aGVHD) and relapse were also reported. Results: Patient characteristics (n = 29) are listed in Table. Median follow-up in surviving patients is 10 years (range 5-14 years). A majority of patients (n = 23, 79%) had 3 or more lines of treatment prior to allo-SCT. The 5 year rates of OS and NRM for all patients are 42% and 53%, respectively. Univariate analysis showed a lower risk of death in patients who received TBI-based conditioning (HR: 0.19, 95 CI: 0.04 – 0.81, p = 0.03), and those who had HLA-matched related donor (MRD) transplants (HR: 0.29, 95 CI: 0.11 – 0.79, p = 0.02). Patients who received more than 3 lines of prior treatment had a higher risk of death (HR: 2.77, 95% CI: 1.05-7.34, p = 0.04). Low rates of grade III/IV aGVHD (n = 4) and relapse (n = 4) occurred in our patient population. Two patient deaths were attributable to aGVHD, and the majority of other deaths were due to treatment-related toxicities. Conclusions: In an era of numerous effective non-curative salvage therapies, the optimal timing of allo-SCT for MCL needs further clarification. Our data supports early opposed to delayed allo-SCT for select high-risk patients with MCL who have a MRD. [Table: see text]
Profiling and treatment patterns in NSCLC patients with CNS (brain) metastases in Europe and Asia.
Authors: Ettore Mari, Sheila Mpima, Filippo Guglielmetti, Fil S. Manuguid, Sari Heitner Enschede, Paola Nasuti
Journal: Journal of Clinical Oncology (2018)

e21085 Background: Between 25% and 40% of NSCLC patients develop CNS metastases, a high unmet medical need with median survivals of 3–14 months. Using a large oncology real-world patient database, we evaluated the profile and the patterns of treatment for NSCLC patients with or without brain metastases. Methods: Anonymized NSCLC pts-level data collected through a large cross-sectional survey between January and December 2017 in EU5 (France, Germany, Italy, Spain & UK) and APAC3 (China, Japan, Korea) was used. Results: Data from 2,004 (11%) NSCLC patients with brain mets and 15,882 (89%) without brain mets (total 17,886) were analysed and compared. More patients with CNS mets are tested for EGFRm, ALK, PD-L1/PD-1 than patient with no brain mets. EGFRm: same incidence in EU5, higher in APAC3 patients with brain mets; more EGFRm positive patients with brain mets tend to be treated with 2nd / 3rd generation EGFR-TKI in EU5 and with 1st generation EGFR-TKIs in APAC3. Patients with brain mets are more likely to be treated beyond 2nd-line and less likely to be treated with Pt-based chemotherapy in first-line. Conclusions: This data provides an updated picture of the real life patterns of care in Europe and Asia for NSCLC patients with or without CNS metastases, with some marginal differences. These data could represent a baseline referral for future evaluations on the impact on the patterns of care of the introduction of new agents targeting CNS metastases from NSCLC. All patients (N = 17886) All patients (N = 17886) EU5 (N = 11988) EU5 (N = 11988) APAC3 (N = 5898) APAC3 (N = 5898) with CNS mets (n = 2004) w/out CNS mets (n = 15882) with CNS mets (n = 1145) w/out CNS mets (n = 10843) with CNS mets (n = 859) w/out CNS mets (n = 5039) % % % % % % > 2 therapy lines 12 4 9 4 14 6 1st line Pt-based doublet 28 40 28 35 28 50 Not Tested for EGFRm / ALK / PD-L1/PD-1 16 30 13 27 18 36 EGFRm +ve DelExon19/L858ROn 1st Gen EGFR-TKIon 2nd / 3rd Gen EGFR-TKI 36 26 24 23 51 33 84 80 82 79 85 80 53 55 46 59 58 50 30 26 43 31 22 19 ALK +ve on ALK inhibitor 15 9 17 9 11 10 86 78 91 84 69 58 PD-L1/PD-1 +ve on checkpoint inhibitor 39 43 38 44 41 38 51 57 56 60 38 38
Macroecology to Unite All Life, Large and Small
Authors: Ashley Shade, Robert R. Dunn, Shane A. Blowes, Petr Keil, Brendan J.M. Bohannan, Martina Herrmann, Kirsten Küsel, Jay T. Lennon, Nathan J. Sanders, David Storch, Jonathan Chase
Journal: Trends in Ecology & Evolution (2018)
Impact of chemotherapy on survival for low risk versus high risk early stage ovarian cancer.
Authors: Rachel Hope Occhiogrosso, Margaret Steinhoff, Phinnara Has, Christina Raker, Paul DiSilvestro
Journal: Journal of Clinical Oncology (2016)

e17066 Background: Past analyses have demonstrated that adjuvant chemotherapy is indicated for high-risk early stage ovarian cancers (EOCs) (stages IC and II, grade III cancers) only, though prospective trials are limited in this disease setting. Identifying low-risk patients minimizes chemotherapy toxicities in those with tumors least likely to recur. Methods: A retrospective IRB-approved review of women diagnosed with EOCs at Women and Infants’ Hospital from 1995-2009 was performed. 608 cases were found and 369 met inclusion criteria. Records were reviewed and coded for patient characteristics, surgical information, and outcomes. Data was analyzed with STATA. Results: Adjuvant post-operative chemotherapy was given to 67.1% of EOC patients; it was administered to 92.8% classified as “high risk” vs. 52.2% for “low risk” patients. Additionally, age, stage, grade, and histology were associated with likelihood of chemotherapy administration (p = 0.004, p < 0.0001, p < 0.0001, p < 0.0001, respectively). Chemotherapy use was not significantly associated with 10-year recurrence-free survival (RFS) or overall survival (OS) among all patients (p = 0.4, p = 0.2). When stratified by risk, high-risk patients had significantly lower RFS and OS (p = 0.04, p = 0.05). Among high-risk patients, those who received chemotherapy had higher 10-year RFS than those who did not (71.2% vs. 46.7%), but this did not reach significance (p = 0.07), and there were no significant differences in OS (p = 0.3). In the low-risk cohort, RFS did not reach significance, but those who received chemotherapy had a 10-year OS benefit (p = 0.03). Conclusions: Patient factors predictive of chemotherapy administration were identified, but the overall cohort did not demonstrate a chemotherapy survival benefit. When stratified by risk, different patterns emerged. Although the standard recommendation for low risk EOC is observation, a majority were given chemotherapy, yielding a statistically significant OS benefit contrary to past reports. Conversely, we could not demonstrate a significant RFS or OS benefit for chemotherapy administration in the high-risk group. The survival impact of chemotherapy for EOC patients remains ill-defined and requires further research.
EGFR analysis of 21,039 patients with NSCLC: Age-related gradual increase of the L858R mutation frequency in adenocarcinomas and high occurrence of ex19del/L858R mutations in squamous cell carcinomas from females and/or nonsmokers.
Authors: Evgenii Imianitov, Irina Demidova, Marat Gordiev, Maxim Filipenko, Tatiana Kekeeva, Yuri Moliaka, Polina Gervas, Valeriy Kozhemyako, Dmitriy I. Vodolazhsky, Svetlana Aleksakhina, Ekaterina Kharitonova, Ilya Tsimafeyeu, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2017)

9040 Background: EGFR testing in Russia is carried out upon the patronage of Russian Society of Clinical Oncology (RUSSCO), and the results are accumulated in a centralized database. Squamous cell carcinomas (SCC) constitute 60-70% of NSCLC incidence in Russia, however physicians are often discouraged to send NSCLC-SCC for EGFR testing due to low frequency of mutations. Methods: We considered all NSCLC patients analyzed by means of PCR for the presence of EGFR mutations (ex19del and L858R) within years 2012-2017. Results: 21,039 NSCLC patients were tested. EGFR analysis was successful in 20,768 patients (98.7%). EGFR mutations were detected in 3566/17717 (20.1%) adenocarcinomas (AdCa) of the lung (ex19del: 2203 (12.4%); L858R: 1363 (7.7%)). There was an evident age-related increase in the frequency of L858R substitution in AdCa patients (p =0.000, Table). This set of patients included 1,139 NSCLC-SCC cases, and the EGFR mutation was observed in 41 (3.6%) subjects. Among 189 females with NSCLC-SCC, ex19del or L858R were detected in 25 (13.2%) cases. Stratification by smoking status revealed EGFR mutation in 19/242 (7.9%) non-smokers. Conclusions: Elderly NSCLC patients have particularly increased probability to be diagnosed with L858R mutation. In the real-world setting, patients with NSCLC-SCC may have high frequency of EGFR mutations, either due to imprecise histological subtyping or due to yet unknown reasons. All female and non-smoking patients with NSCLC have to undergo EGFR testing irrespectively of tumor histology. [Table: see text]
The role of radiation therapy to the primary site in locally advanced and metastatic pancreatic cancer ( 2004-2015 National Cancer Data Base (NCDB) review).
Authors: Nibal Saad, Shreya Sinha, Wajihuddin Syed, Adham Adel Jurdi
Journal: Journal of Clinical Oncology (2018)

e16257 Background: Chemotherapy (CT) alone or with radiation therapy (RT) is used to treat locally advanced pancreatic cancer. There is conflicting data, however, about the benefit of RT in addition to CT in the management of locally advanced pancreatic cancer. RT is used also in metastatic disease for symptoms control, but it is not known if it adds any survival benefits. Methods: We performed a retrospective review of patients with locally advanced unresectable and metastatic pancreatic cancer who received CT and RT to the pancreas using NCDB between (2004-2015). First objective was to compare the overall survival (OS) between patients who received CT and RT in metastatic and locally advanced disease then between each of those subgroups using Kaplan Meier survival curves. Results: Between 2004-2015, 85,733 patients had locally advanced or metastatic pancreatic cancer. 83,526 (97.4%) of them received CT alone, and 2,207 (2.6%) patients received CT as well as RT to the pancreas. 1 year OS was 28.2% (0.279-0.285) in the patients who received CT alone vs. 40.5% (0.384-0.426) in patients who received CT and RT to the pancreas (p < 0.0001). 27,562 patients were diagnosed with locally advanced disease. 1,731 (6.3%) patients received CT and RT. 1 yrs OS was 35.8 % (0.352-0.364) in the patients who received CT alone vs. 43.8% (0.414-0.461) in patients who received CT and RT (p < 0.0001). Among 55,700 patients who had metastatic disease and received CT, only 426 (1%)of them received RT to the pancreas. 1 year OS in this group of patients was 24.2 % (0.239-0.246) compared with 26.3% (0.222-0.306) in patients with metastatic disease who were treated with CT only (p = 0.418) Conclusions: Radiation treatment, when added to chemotherapy, increases 1yr OS by about 8% in locally advanced pancreatic cancer, but not in metastatic pancreatic cancer.
Cytogenetic alteration and expression of Let-7a microRNA in relation to its target gene NRAS in a family with myelodysplastic syndrome (MDS).
Authors: Zahra Mozaheb, Mohamad Hasanzadeh Nazarabadi, Shermine Heydari, Majid Mojarad
Journal: Journal of Clinical Oncology (2016)

e18547 Background: Myelodysplastic syndrome (MDS) comprise a heterogeneous group of clonal hematopoietic stem cell malignancies that characterized by a maturation defect in hematopoietic progenitor cells, peripheral cytopenia(s) and clonal instability with enhanced risk of transformation to acute myeloid leukemia ( AML). The incidence of the disease increase in elderly and it is not common in young people under 50 years old. MDS is predominantly a sporadic disease and the familial occurrence of MDS/AML is very rare but can provide a useful resource for investigation. Patients with the familial MDS, which more than one member of family might be affected, are younger at presentation than individual with sporadic disease. Most of the family reported in literature reviewed demonstrates a pattern of autosomal dominant inheritance.Methods: A family of 16 members with and without the history of MDS in three generation was studied, six patients with MDS and 10 people was healthy. The grandfather of this family was died because of acute myeloblastic leukemia. Chromosomal analysis was performed for all of them, and the expression of the Let-7a miRNA and NRAS was measured by the real time PCR technique. Results: 14 members of the family were with normal karyotype; whereas only two patients revealed abnormal karyotype, one patient with partial trisomy in 1p34, and the other with chromosome translocation in t(13:14). The expression of the Let-7a miRNA and its target NRAS gene was decreased in this family as compare with the controls group (p. value < 0.0001), by T-independent test analysis.In this family NRAS gen, as an oncogen and target of Let-7a miRNA, were decreased contrary to what is expected. Conclusions: In this study, chromosomal abnormalities were very rare; whereas the expression of let-7a miRNA decrease significantly in patient compare with control samples. These miRNA may be having potential for prognosis marker in MDS patients.