tbuckley/cabot-search huggingface dataset:
Impact of geographic region on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.
Authors: Andre Poisl Fay, Rana R. McKay, Xun Lin, Ronit Simantov, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2017)

4583 Background: Health determinants vary according to the geographic region and may impact the outcomes of mRCC patients treated on clinical trials of targeted therapy. We investigate the OS by geographic region of mRCC patients treated in the targeted therapy era. Methods: We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Clinical characteristics and survival data were collected. Statistical analyses were performed using the Kaplan-Meier method and log-rank test in univariate analysis. Results: Overall, 4736 patients were included in the analysis. Patient characteristics differed according to geographic region (table). No statistically significant differences in OS were observed when comparing US/Canada (USC, reference) to other regions: Latin America (LA), Asia/Oceania/Africa (AOA), and Eastern Europe (EE). OS differed among patients enrolled on trials in the USC compared to Western Europe (WE) (20.3 vs.17.4 months, respectively; HR: 1.15; 95%CI 1.03-1.3 p = 0.015). All grade treatment-related adverse events (AE) were reported more frequently in USC. There were no significant differences in grade 3-5 AEs between groups. Conclusions: We highlight that despite differing baseline characteristics, OS was similar among most geographic regions. Factors such as disease biology, access to care, AE reporting, and quality of care that may contribute to potential differences in outcomes among regions need to be further characterized. [Table: see text]
Reducing unnecessary tests in oncology patients using best practice advisories in the Electronic Medical Record.
Authors: Luis E. Raez, Aharon Sareli, Juan Martinez, Brian Hunis, Brian E. Cauff, Scott Oxenhandler, Dawn Rogers
Journal: Journal of Clinical Oncology (2016)

e18239 Background: BPAs are used extensively within EMR to alert providers about drug interactions, allergies and the need to order indicated procedures. We hypothesized that BPAs could also be used to decrease the number of unnecessary tests and thereby to decrease costs in cancer care. The goals of our study were to: (1) Decrease unnecessary CT scans, (2) decrease unnecessary echocardiograms (ECHO), and (3) demonstrate that BPAs can be used as a cost saving tool.Methods:We created BPAs that fire when an oncology (ONC) or non-oncology (NON-ONC) provider orders either a CT scan or ECHO to alert the provider when ECHO or CT results were already available within the last 3 months including those results in the BPA message itself. We subsequently tracked the number of CTs and ECHO ordered, number of times the BPA was displayed to a provider, and the number of times the provider either continued with the order or cancelled it. Cost savings were estimated based on the number of tests cancelled and the average hospital charge per test.Results:During the 6 months from January to June 2015, orders for 3,421 CT scans triggered the BPA. 3,344 orders (97.3%) were placed anyway and 77 (2.3%) were canceled, after the provider was alerted that a recent CT result existed. NON-ONC providers initiated three times more CT orders than ONC providers (2,531 vs. 890) and cancelled them in response to the BPA 3 times more often than ONC providers (69/2,531 = 2.7% vs. 8/890 = 0.9%; p = 0.0015). The cost savings for averted CT scans were approximately $753,214 per year. During a 3 year period the ECHO BPA led to cancellation of 2,719 tests out of 14,192 ordered (19%). ONC providers cancelled 311 of 2,270 orders (13.7%) while NON-ONC providers cancelled 2,408 of 11,922 (20.2%) (p < 0.05). The cost savings based on avoided unnecessary ECHO are approximately $407,850 per year.Conclusions:BPAs reduced ordering of CT scans by 2.3% and ECHO by 19%, leading to significant cost savings. The BPAs are more effective in NON-ONC providers (3 times more with CT and 1.5 times more with ECHO). Appropriately designed BPAs display information automatically at the point of care, enabling clinicians to work more efficiently and reduce unnecessary testing.
Phase II randomized clinical trial comparing immunotherapy plus stereotactic ablative radiotherapy (I-SABR) versus SABR alone for stage I, selected stage IIa or isolated lung parenchymal recurrent non-small cell lung cancer: I-SABR.
Authors: Joe Y. Chang, Lei Feng, Steven H. Lin, James William Welsh, Mara Antonoff, Daniel Richard Gomez, John Heymach
Journal: Journal of Clinical Oncology (2018)

TPS8580 Background: Stereotactic ablative radiotherapy (SABR), which delivers high biologically effective radiation doses, can kill cancer cells, release tumor-associated antigens, and activate tumor-specific T cells, thereby functioning as a cancer-specific vaccine in situ. The combination of the immune-triggering effects of ionizing radiation with immune check point PD-1inhibitor may leverage the effects of radiotherapy, transforming what was once considered a local therapy to a novel systemic treatment. Further, the combined effects of local control plus systemic control may improve cure rate in early stage NSCLC. Methods: This is a randomized phase II trial (NCT03110978) designed to study SABR (biological effective dose > 100 Gy) with or without concurrent and adjuvant Nivolumab for total of 7 doses in early stage or isolated recurrent NSCLC. Inclusion criteria: stage I disease (tumor≤5cm, N0M0) OR selected cases of stage IIa disease (tumor > 5cm but≤7cm, N0M0), including multiple primary tumors, OR isolated lung-parenchymal recurrent or persistent NSCLC suitable for SABR. Tumor tissue /blood/stool samples will be collected before/during/after treatment and at the time of recurrence. Primary endpoints: Event-free survival , secondary malignancy and death; Secondary endpoints: overall survival; toxicity; exploratory analyses of potential predictive markers and immunologic mechanisms of action. Statistical design: It is considered significant with a decrease of the 4-year cumulative event rate from 46% to 23%. Assuming a one-sided type I error rate of 0.05, an accrual rate of 3.5 patients per month, and an additional 20 months of follow-up, a study with 70 patients in each arm will have 85% power to detect an improvement of 23% in 4-year EFS rate. One interim analysis will be done to allow early termination of the trial should evidence at that time reveal that I-SABR is superior to SABR-only or that no difference is found between the two treatment arms. Up to January 2018, 20 of planned 140 patients have been enrolled, met with anticipated enrollment rate. Clinical trial information: NCT03110978.
<i>PBRM1</i> genomic alterations in mesothelioma: Potential predictor of immunotherapy efficacy.
Authors: Jeffrey S. Ross, Laurie M. Gay, Ethan Sokol, Julia Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti H. Ramkissoon, Sugganth Daniel, Eric Allan Severson, Jonathan Keith Killian, Siraj Mahamed Ali, Alexa Betzig Schrock, Jon Chung, Garrett Michael Frampton, Lee A. Albacker, Robert John Corona, Michael D Mix, Anna Shapiro, Gennady Bratslavsky, Vincent A. Miller
Journal: Journal of Clinical Oncology (2018)

8562 Background: PBRM1, of the SWI/SNF family, modulates chromatin remodeling. PBRM1 genomic alterations (GA) are enriched in renal cell carcinoma and mesothelioma (MS). Recent evidence suggests that PBRM1 GA are strongly associated with neoantigen production and responsiveness to immune checkpoint inhibitors (ICPI). Methods: Comprehensive genomic profiling (CGP) was performed on 50 ng of DNA for 783 FFPE mesothelioma (MS) samples using a hybrid-capture, adaptor ligation-based next-generation sequencing assay to a median coverage depth of > 600X. The results were analyzed for all classes of GA and tumor mutational burden (TMB), determined on up to 1.2 Mb of DNA. Microsatellite instability (MSI) status was evaluated by principal component analysis of optimal homopolymer loci. GA were counted as relevant if known to disrupt PBRM1 or homozygous in the tumor. Results: Of 783 relapsed/refractory MS, 8 (1%) were pericardial (PCDMS), 187 (24%) peritoneal (PERMS), and 588 (75%) pleural (PLRMS) tumors (Table). Median ages were similar, but specimens from males were more common (72%) in PLRMS and females (56%) in PERMS. The PBRM1 GA frequency was 11% overall, from 7.7% (PLRMS) to 20.3% (PERMS). BAP1 GA were found in 84.1% of PBRM1-altered MS and NF2 GA in 28%. In PBRM1 wild type MS, BAP1 GA were in 43.7% and NF2 GA in 31.2%. The median TMB was low and TMB > 20 mut/Mb were very uncommon. There were very few instances of MS with high MSI. MS patients with PBRM1 GA responding to ICPI treatment will be presented. Conclusions: Immunotherapy strategies for the treatment of MS have recently emerged. PBRM1 GA are seen in 11% of MS and represent a potential predictive biomarker for therapy selection in this typically devastating disease. Further study of PBRM1 status in the ICPI treatment of MS in the clinical trial setting appears warranted. Total MS PCDMS PERMS PLRMS Cases 783 8 187 588 Median Age 67 66 59 66 Gender F 33% F 57% F 56% F 28% PBRM1 GA Frequency 82 (10.5%) 1 (14.3%) 38 (20.3%) 43 (7.7%) BAP1 (PBRM1 Mut; WT)NF2 69 (84.1%); 306 (43.7%) 23 (28.0%); 219 (31.2%) 0 (0%); 2 (28.6%) 1 (100%) 33 (86.8%); 69 (46.3%) 10 (26.3%); 35 (23.5%) 36 (83.7%); 235 (43.1%) 12 (27.8%); 185 (26.4%) Median TMB (mut/Mb) 1.7 2.4 1.7 1.2 TMB ≥ 20 mut/Mb 1% 0% 2% 1% MSI-High < 1% 0% 2% 0%
P05.91 Sellar atypical teratoid rhabdoid tumor (ATRT) in an adult: A case report and review of the literature
Authors: D Barsky, U Hadelsberg, L Gonen, N Margalit
Journal: Neuro-Oncology (2018)

Atypical teratoid rhabdoid tumor (ATRT) is a rear type of central nervous system (CNS) tumor, which is seen mostly in the pediatric population. However, there are a few dozen of cases reported in adults. This entity was first differentiated from a Wilm’s tumor in 1978. Since then much progress has been done in understanding the pathophysiology of this disease, but not has been done in terms of treatment and prognosis, thus ATRT remains a high mortality-disease with grim prognosis and outcome. a case of 54 year-old female, which presented with symptoms concurrent of a pituitary macroadenoma, which was found out to be a tumor of ATRT characteristics on pathology. the patient underwent surgery, and the tumor was completely removed, in endoscopic transphenoidal approach. ATRT is an uncommon entity, particularly in adults, it is very important to keep it on the differential diagnosis as it has a major influence on disease management, and outcome. Due to ATRT’s poor prognosis and its rarity, it is important the patient is treated by a surgeon, oncologist and radiation oncologist as a multimodality treatment increases survival rates.
PARAGON: A phase 2 study of anastrozole (An) in patients with estrogen receptor(ER) and / progesterone receptor (PR) positive recurrent/metastatic granulosa cell tumors/sex-cord stromal tumors (GCT) of the ovary.
Authors: Susana N. Banerjee, Monica Tang, Rachel O'Connell, Andrew R. Clamp, Rosemary Lord, Vinod Menon Mullassery, Marcia Hall, Charlie Gourley, Tony Bonaventura, Jeffrey C. Goh, Peter Sykes, Peter T. Grant, Orla McNally, Richard J Edmondson, Michael Friedlander
Journal: Journal of Clinical Oncology (2018)

5524 Background: GCTs occur predominantly in postmenopausal women and arise from sex cord stromal cells of the ovary. They generally have a good prognosis but can metastasize / recur after surgery. Patients (pts) are commonly treated with antiestrogens as GCTs frequently express high ER and/or PR. The pooled response rates with a range of hormonal therapies in the literature are ~ 70 % based on case reports and small retrospective series which form the evidence base for clinical practice. Aromatase inhibitors (AIs) are reported to be particularly active. There are no reported phase 2 studies of antiestrogens in GCT. We report the results of a phase 2 trial of anastrozole, an AI in recurrent / metastatic GCT. To our knowledge this is the first prospective trial of hormonal therapy in GCTs. Methods: Postmenopausal women with ER/PR +ve metastatic GCT measurable by RECIST v1.1 and/or elevated Inhibin were eligible for inclusion. Pts received An 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks. Results: There were 41 pts entered. 3 pts without measureable disease had an elevated Inhibin. 1 pt received prior tamoxifen. 1 pt was not evaluable for 3-month (m) CBR. The CBR at 3m was 80.0% which included 1 (2.5%; 95% CI: 0.4 – 12.9%) partial response (PR) and 77.5% stable disease. 8 (20%) had progressive disease by 3m. Median PFS was 8.6 m (95% CI 5.5 – 13.5m). There were delayed responses beyond 3 m with a total 4 pts (9.8%; 95% CI 3.9% – 22.5%) with a RECIST PR. 23 (59%) pts were progression free at 6m (1 pt was censored at 3 m and 16 had progressed by 6 m). 2 pts remain on treatment at 14.8 m and 53.5 m. An was well-tolerated with only 1 grade 3 toxicity – arthralgia. 1 pt stopped An due to side effects. Conclusions: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to An was much lower than the pooled results of the response rate to hormonal therapy reported in retrospective series. Translational research on tumor specimens is underway for predictors of response/resistance to An which will inform future studies. Clinical trial information: 12610000796088.
Model-based prediction of outcome of the atezolizumab Phase 3 study OAK in non-small cell lung cancer based on early tumor kinetic data.
Authors: Laurent Claret, Jin Y Jin, Helen Winter, Pei He, Marcus Ballinger, Achim Rittmeyer, David R. Gandara, Sandhya Girish, Amita Joshi, Rene Bruno
Journal: Journal of Clinical Oncology (2017)

e14517 Background: Standard early endpoints (ORR, PFS) are often poor predictors of overall survival (OS) for immunotherapies. Model-based tumor kinetic (TUK) metrics may offer an alternative (Claret, JCO 2009 and 2013). We investigated the predictive performance of TUK metrics using early data from atezolizumab clinical trials in patients (pts) with non-small cell lung cancer (NSCLC). Methods: OS benefit with atezolizumab (atezo) vs. docetaxel (doc) was observed in both Phase II POPLAR (hazard ratio 0.73, p = 0.040, n = 297, Fehrenbacher Lancet 2016) and Phase III OAK (HR = 0.73, p = 0.0003, n = 850, Rittmeyer Lancet 2016) studies although PFS was similar between arms. A multivariate model linking baseline patient characteristics and tumor growth rate (TGR, estimated using time profile of sum of longest diameters of target lesions, RECIST 1.1) to OS was developed using POPLAR data and qualified to predict outcome by PD-L1 status in both POPLAR and OAK. This model was used to predict OAK OS outcome based on patient characteristics and estimated TGR from TUK data at several OAK data cut-offs ranging from 10 to 122 weeks. Results: In POPLAR, TUK profile in atezo and doc arms crossed at about 25 weeks with more initial shrinkage in doc-treated patients and slower TGR in atezo-treated patients. A lognormal OS model with albumin and number of metastatic sites as independent baseline prognostic factors and estimated TGR predicted OS HR in sub-populations of pts based on baseline PD-L1 expression both in POPLAR as well as in OAK e.g model-predicted OAK HR: 0.73 [0.63-0.85]. Based a retrospective analysis on TUK data cuts, the POPLAR OS model predicted significant OS HR in OAK as soon as 40 week cut-off: HR: 0.67 [0.56-0.80] with success in 99% of the replicates with only 50% of the total number of tumor assessments. At this 40 week data cut, immature observed OS HR was 0.84 [0.59-1.21, p = 0.347] and HR only reached significance at 70 weeks. Conclusions: Model predictions based on TUK can be used to predict success early before maturation of OS data as shown with OAK. The model-based biomarker TUK metric TGR has strong potential as an alternative early endpoint to evaluate efficacy in cancer immunotherapy studies.
Computerized tomography (CT) assessed body composition (BC) and physical function in older adults with cancer.
Authors: Grant Richard Williams, Allison Mary Deal, Hyman B. Muss, Hanna Kelly Sanoff, Marc Weinberg, Shlomit Strulov Shachar
Journal: Journal of Clinical Oncology (2016)

10043 Background: Given the wide use of CT imaging in oncology care, this modality is frequently used in assessing muscle mass and attenuation [Martin et al. JCO 2013], yet in cancer no study to date has correlated these measurements with physical function. This study examines the association of single-slice CT assessed muscle measurements with physical function in older adults with cancer. Methods: Using the Carolina Senior Registry (CSR), an institutional registry (NCT01137825) that contains geriatric assessment (GA) data, we identified patients with CT imaging within 60 days +/- baseline GA. Skeletal muscle area (SMA) and density (SMD) were analyzed from CT scan L3 lumbar segments using radiological software [Chung et al. Medical Imaging 2009]. SMA and height (m2) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Integrated Density (SMID) was created by multiplying SMI x SMD. Differences were compared using two group t-tests. Results: Of the 207 patients with available CTs, 186 were sufficient for body composition analysis. The median age was 73, 56.5% female, 83.9% Caucasian, and 50.6% during treatment. Mean SMI 41.8 cm2/m2 (range 23-67), SMD 26.2 Hounsfield Units (HU) (range 3.9-47), and SMID 1103 Arbitrary Units (AU) (range 89-2760). Lower SMI was seen in patients with one or more falls (p=0.04) (table 1) and prolonged Timed Up and Go (TUG) (p=0.08). Impairments in instrumental activities of daily living (IADL), prolonged TUG, and lower Karnofsky Performance Status (KPS) were significantly associated with a lower SMD and SMID. Conclusions: BC measured by routine CT was significantly associated with poor physical function in older adults with cancer. Skeletal muscle quality (SMD), which reflects muscle lipid content, is more associated with physical function than quantity (SMI) and may be helpful in identifying older adults at risk for functional impairments. Physical function and body composition. SMI (cm2/m2) SMD (HU) SMID (AU) Normal vs impaired IADL 42.7 vs 40.6 28.3 vs 25.1* 1211 vs 1021** Normal vs prolonged TUG 42.8 vs 40.6 27.9 vs 23.8** 1202 vs 978** None vs ≥1 falls 42.6 vs 39.4* 26.7 vs 26.1 1136 vs 1054 KPS =>80 vs <80 42.1 vs 40.5 27.0 vs 22.0** 1144 vs 893** *p=<0.05 **p=<0.01
Comparison of digital PCR with real-time PCR calibrated to the International Scale for BCR-ABL monitoring.
Authors: Parth Shah, Furha Iram Cossor, Shiva Murarka, Hemangi Dixit
Journal: Journal of Clinical Oncology (2017)

e18545 Background: Monitoring BCR-ABL1 fusion transcripts is the cornerstone of management in chronic myeloid leukemia (CML). Real Time PCR(RTPCR) has been the tool of choice for its sensitivity and dynamic range. The International Scale was recently introduced to allow for standardization across laboratories. Chip based Digital PCR(dPCR) which allows for absolute quantitation may obliviate the need for such standardization by giving absolute results.It has the potential to increase sensitivity for detection of minimal residual disease. This assumes great significance as we move into the era of treatment free remission. Methods: A total of 31 EDTA-blood samples of CML patients with known values ranging from 0.003-0.5 IS were processed via an accredited RTPCR protocol calibrated to the IS scale and a parallel dPCR workflow without any specific calibration . The analysis of digital PCR samples was performed on the Thermofisher Cloud Platform. Results: Both RTPCR and dPCR yielded extremely concordant results. The Pearson correlation between the two methods was r = 0.6043 (95%CI: 0.318 to 0.789; p = 0.0003). The calculated BCR-ABL/ABL ratios were comparable with a median of 0.098 for RT-PCR calibrated to the IS (range 0.003-0.55; n = 26) and 0.11 for dPCR (range 0.003-0.37; n = 29). The mean difference for the ratios between the two methods used for the detection was around 0.08. Conclusions: We demonstrate here the capability of dPCR to provide a parallel result to an IS scale calibrated protocol without any standardization. This approach required no specific calibrators or standards and resulted in extremely cost effective testing. This freedom from routine calibration provides for a significantly more robust workflow and greatly increased reliability. Limitations do persist in dPCR on account of limited chip densities which are the main parameter for the Poisson statistics. This has limited the dynamic range on dPCR to a maximum of Log 4 for accurate quantification. However as chip densities and emulsion concentrations increase in these technologies, they are poised to introduce a new era in the quest of accurate quantification.
TCT-758 The future of heart pump technology: Hemodynamic monitoring of patients on temporary MCS without additional invasive catheters
Authors: Mir Basir, Mohammad Alqarqaz, Khaldoon Alaswad, Christian Moyer, Ahmad El Katerji, Scott Corbett, Thorsten Siess, Steven Keller, Brian Chang, Elazer Edelman, William O'Neill
Journal: Journal of the American College of Cardiology (2018)
Consolidative high dose chemotherapy and autologous stem cell transplant for patients with primary central nervous system lymphoma using thiotepa, busulfan, and cyclophosphamide conditioning regimen.
Authors: Patricia Ann Young, Davis Kipkemboi Kimaiyo, John P Chute, Gary J. Schiller, John Timmerman, Sven De Vos, Herbert Aaron Eradat
Journal: Journal of Clinical Oncology (2018)

e14077 Background: Establishing an approach for consolidative therapy for patients with primary CNS lymphoma (PCNSL) that has long-term efficacy and acceptable toxicity remains a challenge. Methods: We retrospectively evaluated patients undergoing consolidative autologous stem cell transplant (ASCT) at our institution using a uniform regimen of thiotepa, busulfan, and cyclophosphamide (TBC) for PCNSL in first complete remission (CR1) between December 3, 2007 and December 3, 2017. Inclusion criteria were patients ≥18 years old, PCNSL diagnosis (including ocular lymphoma), with consolidative TBC chemotherapy and ASCT in CR1. Exclusion criteria included patients with systemic disease, relapse of disease prior to ASCT, and secondary CNSL. Results: Twenty-one consecutive patients were identified that met criteria. The majority of patients (95%) received induction therapy with rituximab and high dose methotrexate for 2-4 cycles followed by rituximab / cytarabine / thiotepa for 1-2 cycles based on published data (Illerhaus et al, Blood 120, no. 21 (2012): 302). Consolidative therapy with TBC chemotherapy and ASCT was then performed. The median time from diagnosis to transplant was 5.1 months (range, 3.7-11.6 months). The median age at diagnosis was 56 years (range, 38-70 years). With a median followup after ASCT of 2.5 years, the 2-year overall survival (OS) was 95% (95% confidence interval (CI) 71%-99%). Among all PCNSL patients undergoing ASCT with TBC regimen (n = 27) beyond CR1, the median followup was 2.7 years with a 2-year OS of 92% (95% CI 73%-98%). Transplant related toxicities included cytopenias (100%), mucositis (71%), neutropenic fever (66%), infection (43%), and dermatologic sequelae (33%). Reversible neurotoxicity (14%) and hemorrhagic cystitis (5%) were also noted. No evidence of pulmonary toxicity or veno-occlusive disease were noted. Conclusions: High dose chemotherapy and autologous stem cell transplant using TBC conditioning for PCNSL in CR1 appears to have encouraging long term efficacy with manageable side effects.