tbuckley/cabot-search huggingface dataset:
Standardization of inpatient CPR/code status discussions and documentation within the division of hematology-oncology at UPMC Shadyside.
Authors: Rachel Rodenbach, Christine Ann Garcia, Mamta Bhatnagar, Edward Chu, Stanley M. Marks, Abigail Graham-Pardus, Jamie Kriner, Melissa Winfield, Christopher Minnier, Janet Leahy, Sharon Hanchett, Emily Baird, Joshua Levenson
Journal: Journal of Clinical Oncology (2018)

e18776 Background: Lack of discussion and/or documentation about resuscitation preferences has led to care incongruous with patient’s wishes as previously documented or reported to providers or family members. In December 2016, 49% of adult patients admitted to the inpatient oncology service at UPMC Shadyside had a code status discussion documented prior to discharge. The aim of this project is to improve the quality and rates of CPR status conversations. Methods: A workgroup was formed in January 2017 among key stakeholders representing oncology physicians and fellows, palliative care faculty, oncology nursing, advance practice providers (APPs), and internal medicine housestaff. A quality improvement (QI) proposal was developed and approved by the UPMC Quality Improvement Committee in February 2017. All oncology faculty, fellows, house staff, and APPs were reminded weekly to complete CPR status conversations and documentation. APPs were formally trained by palliative care specialists to discuss and document code status with all admitted patients. Hospital leadership received a monthly update of CPR status documentation rates, and a formal CPR status assessment best practice guidelines document was developed by the workgroup, endorsed by oncology leadership and shared among oncology providers. Results: Since project implementation in January 2017, CPR status assessment rates have improved from 49% to > 80% sustained over the past year. There were > 1400 more CPR status discussions documented in 2017 than in 2016. No patients received resuscitation against documented wishes, and no patients had resuscitation withheld against documented wishes on the inpatient hematology-oncology service at UPMC Shadyside. Conclusions: Standardization of CPR status assessment with formal training of clinicians and APPs resulted in a significant increase in the number of CPR status assessments on the inpatient setting. In the next Plan-Do-Study-Act cycle, we will be reviewing the data on patients who did not have their code status assessed, to address missed opportunities to improve our rates. We plan to expand the project to involve hospitalists and nocturnists.
Moore criteria application by an Argentinean public institution on patients with advanced cervical cancer (ACC).
Authors: Maria V. Caceres, Vanesa Lopez, Laura Marcela Albi, Ana Lucila Cagnoni, Mariana Savignano, Carolina Almada, Maria Gabriela Zapata Caamano, Gustavo Roganovich, Alfonso Javier Durand, Andrea Aguilar
Journal: Journal of Clinical Oncology (2017)

e17010 Background: Moore criteria allows stratifying the risk of patients with ACC, predicting the rate of response (RR), the progression free survival (PFS) and the overall survival (OS), being an important prognostic tool being an important prognostic tool that can be used on Argentine population. Methods: Prospective, observational and descriptive analysis of 41 patients with ACC treated at Roffo Hospital in Buenos Aires, from 10/2013 to 1/2017. 35/41 (85%) patients received the planned treatment (6 cycles of Carboplatin AUC x 5 day 1, Paclitaxel 175 mg/m2 day 1) +/- Bevacizumab 15 mg/m2 day 1 every 21 days until progression. 6 patients (15%) received no treatment (2 for socioeconomic reasons and 4 due to poor performance status). 7/35 (20%) were treated without antiangiogenic (3 for the presence of a rectal-vaginal fistula and 4 due to socioeconomic reasons). These risk factors proposed by Moore were analyzed in all of the patients: performance status, previous treatment with cisplatin, pelvic disease and progression-free interval &lt;365 days. Given the characteristics of our population, black race was not included as a prognostic factor. Results: 41 patients with ACC were analyzed: 19 (46%) were Stage IV, 5 (12%) had a persistent disease and 17 (42%) evidenced disease recurrence. Pursuant to Moore criteria, 19 patients (46%) were stratified as mid-risk, 18 (44%) as high-risk and 4 (10%) as low-risk. Treatment of mid-risk patients with Bevacizumab showed a 94% (17/18) clinical benefit rate (CBR) and the high-risk patients were 78 % (7/9) CBR. The 2 low-risk patients had partial response. Of the 7 patients treated without antiangiogenic, 2 mid-risk progressed; 1 low-risk had partial response and 4 high-risk showed 50% (2/4) partial response, and 50% (2/4) was pending at the moment this abstract was drafted. Conclusions: It is feasible to useMoore criteria to evaluate our population with ACC in order to estimate the prognosis of the disease. The percentage of low risk patients is poor in our population. Due to short follow-up time, only prognostic factors associated with CBR was assessed. Homologation of the black race factor with other socio-economical parameters related to access to healthcare is planned.
Deletions in HSP110 T17 and patient prognosis in stage III microsatellite instable (MSI) colon cancers: Findings from CALGB 89803 and NCCTG N0147.
Authors: Christina Sing-Ying Wu, Qian Shi, Jerneja Tomsic, Jeffrey P. Meyers, Wendy L Frankel, Cynthia Dawn Timmers, Leonard Saltz, Steven R. Alberts, Donna Niedzwiecki, Daniel J. Sargent, Heather Hampel, Albert De La Chapelle, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2016)

e15148 Background: MSI is detected in approximately 15% colorectal cancers, and associated with improved survival in early stage colon cancer. Heat shock protein 110 (HSP110) is a chaperone protein expressed in colon cancer and enhances cancer cell survival. Mutant HSP110, which is only present in MSI tumors, is due to deletions in a T17 mononucleotide repeat leading to synthesis of a truncated protein, and has a dominant negative effect on HSP110 function. Large T17 deletion size correlates with increased amount of mutant HSP110 transcript, and may be a biomarker for improved patient (pt) outcome. We correlated disease-free survival (DFS) with T17 deletion size in stage III MSI colon cancer pts who received adjuvant chemotherapy on CALGB 89803 or NCCTG N01477. Methods: Pts for this retrospective study were enrolled on CALGB 89803 or NCCTG N01477, had tissue for analysis, and were evaluable for DFS (primary endpoint). T17 deletion size was determined by PCR and fragment analysis. The pre-specified cut-off was 5 base pairs ( > 5 for large deletion, < 5 for small deletion), and stratified multivariate Cox PH regression models were performed to compare outcomes in the 2 groups. Results: A total of 414 samples were tested (104 from CALGB 89803 and 310 from NCCTG N0147) and 77 (19%) specimens failed testing. Of the 337 samples, 195 pts had large T17 deletions and 142 pts had small T17 deletions. Pt demographics, disease characteristics, and adjuvant treatment were comparable between the 2 groups. Large T17 deletion did not correlate with improved DFS, overall survival (OS), or time-to-recurrence (TTR). (Table) Conclusions: Large HSP110 T17 deletion size does not correlate with improved DFS in pts with Stage III MSI colon cancers. Time Variable Univariate Model Multivariate Model$ Events/ Total HR (95% CI) P- value* Events/ Total HR (95% CI) P-value* DFS 104/337 0.990 (0.854- 1.149) 0.8992 91/304 0.982 (0.839- 1.150) 0.8230 OS 92/337 0.985 (0.840- 1.154) 0.8489 79/304 0.969 (0.813- 1.153) 0.7206 TTR 85/337 0.947 (0.807- 1.113) 0.5095 76/304 0.923 (0.780- 1.092) 0.3518 *Wald Chi-square test $Adjusted for demographics, disease characteristics, and molecular biomarkers. Stratified by study
Clone evolution and genomic alteration analysis of osteosarcoma and matched lung metastasis.
Authors: Di Wang, Jie Wang, Xiaohui Niu, Zhen Huang, Zhijie Wang, Qing Zhang, Jianchun Duan, Hua Bai, Lin Hao
Journal: Journal of Clinical Oncology (2017)

11032 Background: Lung metastasis (LM), as the most common metastatic site, is the main reason resulting in treatment failure and death of osteosarcoma (OS). But there was no report about the clone evolution and genomic alteration in the process of LM of OS. Methods: Multiregion whole-genome sequencing and whole-exome sequencing were performed on ten patients with primary OS and matched lung metastatic tumors. A set of high confident somatic nucleotide variants (SNV), small insertion and deletion (indel) and copy number variation (CNV) in each sample were identified, then the n-dimensional Bayesian Dirichlet process was applied to define the constituent mutation clusters as clone or subclone. Neoantigen prediction and HLA typing were performed using NetMHC3.0 and POLYSOLVER algorithm, respectively. Results: There were diversified metastatic progression during lung metastasis of OS including linear evolution (7/10) and parallel evolution (3/10), and metastasis-to-metastasis spread was also found in a patient with multiple metastasis; Mutation accumulative effect during the metastasis of OS was evident, LM had much higher mutation load (fold change = 4.1, P-value &lt; 0.01) and neoantigen burden (fold change = 4.5, P-value &lt; 0.001) than the primary tumor; DNA mismatch repair (MMR) genes relevant deleterious mutation events were found in germline in 8/10 metastatic OS cases and MMR genes mutation were much more in LM than primary cancer; The genome instability of LM was prevalently much more significant than primary tumor, with higher copy number variation frequency (fold change = 7.01, P-value &lt; 0.01). Conclusions: The evolution of OS during LM was very complex with diversified metastatic progression. For the LM of OS, the novel therapy should be considering the much higher mutation load, especially those causing tumor neoantigens, higher genomic instability which were associated with tumor immune therapy. Furthermore, the findings of germline MMR genes mutation in primary OS which had occurred LM and more MMR genes mutation in LM of OS indicated potential clinical benefit on immune checkpoint inhibitor therapy and other small molecular drugs for MMR genes.
Relationship between disease activity and circulating endothelial and endothelial progenitor cells in multiple myeloma.
Authors: Patrick Alan Hagen, William Adams, Stephanie Bochen Tsai, Scott E. Smith, Patricia Patrick Simms, Patrick J. Stiff
Journal: Journal of Clinical Oncology (2018)

e20004 Background: A variety of tumor markers have been identified to define risk and predict and monitor treatment response in multiple myeloma (MM). Circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) may offer a non-invasive method to evaluate neoangiogenesis and its impact on bone marrow microvascular density which has been directly linked to inferior outcomes. Methods: 43 patients received a novel induction regimen of busulfan, melphalan, and bortezomib conditioning followed by autologous hematopoietic stem cell transplantation (AHSCT) in a single-center, open-label phase I/II trial. Peripheral blood samples were collected from 18 consecutively enrolled patients on trial at Day -6 and Day 0. Cell populations were detected by six-color flow cytometry with the final phenotype for CECs CD45-, CD31+, Syto16+, CD146+, CD133- and for CEPs CD45-, CD31+, Syto16+, CD146+, and CD133+. Results: Median age at transplant was 61 in this mostly high risk (13/18 ISS stage III) group. There was no meaningful change in CEC or CEP from Day -6 to Day 0 (table 1a). We found no difference in the risk of progression between those above and below the median CEP value at Day -6 (p = .21) or Day 0 (p = .59) (table 1b) and the change in CEP value from Day -6 to Day 0 was not associated with relapse (p = .53). Conclusions: CECs and CEPs in the peripheral blood did not correlate with disease activity and response. Alternate non-invasive means of disease monitoring in addition to standard para-protein studies need further exploration. Clinical trial information: NCT03.Table 1: Change in CEC and CEP a. Overall Change in CEC and CEP Valid N Day -6 Day 0 Exact p Median CEC (IQR) 18 0.331 (0.143-0.413) 0.586 (0.133-1.14) .054 Median CEP (IQR) 18 0.00162 (0.000178-0.00488) 0.00393 (0.000224-0.0316) .013 Note: IQR = Interquartile rangeNote: Units for CEP and CEC are in % of total nucleated cells isolated after Ficoll-Hypaque density-gradient centrifugation b. Risk of progression as function of CEP Value Valid N No Relapse Relapse Hazard Ratio (95% CI) p Day -6 18 2.42 (95% CI: 0.60 – 9.77) .21 CEP < 0.00162 6 (67%) 3 (33%) CEP < 0.00162 3 (33%) 6 (67%) Day 0 18 1.44 (0.38 – 5.40) .59 CEP < 0.00393 5 (56%) 4 (44%) CEP > = 0.00393 4 (44%) 5 (56%)
Impact of genetic polymorphisms of VEGF pathway on the response to bevacizumab in metastatic colorectal cancer (mCRC): Ancillary study of PRODIGE 9 trial.
Authors: Camille Sibertin-Blanc, Aurelie Fabre, Thomas Aparicio, Karine Le Malicot, Jaafar Bennouna, Francois Ghiringhelli, Julien Taïeb, Valerie Boige, Olivier Bouche, Roger Faroux, Eric Francois, Stephane Jacquot, Dominique Genet, Faiza Khemissa, Laurent Cany, Jean Baptiste Bachet, Claire Mulot, Jean Francois Seitz, Sylviane Olschwang, Laetitia Dahan
Journal: Journal of Clinical Oncology (2016)

3534 Background: Bevacizumab (Bev) is widely used in mCRC but there is no validated predictive factor. Several studies have reported the impact of SNPs in the Vascular Endothelial Growth Factor-A (VEGF-A) pathway genes on the Bev’s efficacy but results in the mCRC are yet inconstant. PRODIGE 9 is a phase III trial that compare the tumor control duration (TCD) under a 1st-line chemotherapy followed by either Bev maintenance (Arm A) or no treatment during chemotherapy-free intervals (CFI) (Arm B).The aim of our study was to evaluate the impact of genetic polymorphisms of VEGF A, VEGFR1, VEGFR2 and HIF1α on TCD, duration of 1stCFI, progression-free survival (PFS) and overall survival (OS). Methods: We included patients (pts) of the PRODIGE 9 study for whom biological consent was signed and a DNA sample was available. Ten polymorphisms were genotyped on germ line DNA using real-time Polymerase Chain Reaction. DNA was extracted from blood samples. Survival analyses were done using Kaplan-Meier method and Cox model. For tRR, a logistic regression was used. Results: Among the 491 pts randomized in PRODIGE 9, DNA was available for 314 pts: 160 in Arm A and 154 in Arm B . The median TCD, OS and PFS, were respectively 15.7, 22.6 and 9.2 months (m). For VEGFR-1 rs9582036, pts with CC genotype had significantly better TCD (median [95%CI] 22.4 m [14.7- NR]) compared to pts with AA and CA genotypes (14.4 m [11.7-17.1] (p = 0.04)) in arm A whereas there was no difference in the other arm. This tendency was observed also for the 1st CFI (median 4.6 m for pts CC vs 4.1 m for AC and AA), for the median OS (28.2 vs 22.5 m), the RR, but it was not statistically significant (table). Conclusions: In this prospective study, VEGFR-1 rs9582036 variants were associated with clinical outcome in terms of TCD for patients with mCRC treated by Bev-based therapy. Clinical trial information: NCT00952029.median (m) [95%CI] Arm A Arm B TCD 15.4 [12.5 ;17.4] 17.3 [13.4 ; 23.3]; p = 0.11 CC N = 14 CA+AA N = 146 p CC N = 16 CA+AA N = 138 p TCD 22.4 [14.75- ] 14.4 [11.7-17.1] 0.04 NR [9.5- ] 15.7 [12.7-21.9] 0.08 OS 28.2 [18.1-42.8] 22.5 [18.6-24.6] 0.5 22.66 [17.2- ] 22.1 [19.5-25.2] 0.28 1st CFI 4.6 [1.6-13.3] 4.14 [0.5-29.0] 0.30 3.15 [1.6-18.2] 4 [0.5-22.2] 0.49 *Not reached
TCT-515 SAVR vs TAVR in Patients with Previous Myocardial Infarction: A Nationwide Propensity-Matched Analysis
Authors: Rupak Desai, Hee Kong Fong, Bhrugesh Shah, Sonu Gupta, Dipen Zalavadia, Wardah Siddiq, Rushikkumar Bhuva, Kwan Lee, Rajesh Sachdeva, Gautam Kumar
Journal: Journal of the American College of Cardiology (2018)
A Phase I/Randomized Phase II Study of MLN0128 v.s Pazopanib in Patients with Locally Advanced/Unresectable and/or Metastatic Sarcoma:Alliance A091304.
Authors: William D. Tap, Michelle R. Mahoney, Anthony John Jaslowski, Laura E. Horvath, Gary K. Schwartz
Journal: Journal of Clinical Oncology (2016)

TPS11073 Background: MLN0128 (Millennium/Takeda) is a selective and highly potent ATP competitor of both mTORC1 and mTORC2. MLN0128 has demonstrated substantial activity in preclinical sarcoma models. Pazopanib is the first oral multikinase inhibitor that has a specific FDA-approved indication for the treatment of non-GIST soft tissue sarcomas. In a multicenter, placebo-controlled Phase 3 trial, pazopanib (800 mg) demonstrated a significant benefit in progression-free survival for patients with metastatic soft tissue sarcomas that had progressed on at least one prior therapy (median progression free survival [PFS] 4.6 months for pazopanib vs. 1.8 months for placebo). We describe an ongoing trial that is comparing TORC1/TORC2 inhibition with MLN0128 against pazopanib in certain sarcoma subtypes. Methods: This is a national (Alliance for Clinical Trials in Oncology) open-label phase I/II unblinded randomized study comparing progression-free survival of MLN0128 vs pazopanib in patients with locally advanced/unresectable or metastatic sarcoma. The primary endpoint of the Phase I portion of the study is to determine the safety and the maximum tolerable dose of MLN0128. The primary endpoint of the Phase II portion of the study is to determine the differences in PFS in patients with sarcoma who receive MLN0128 as compared to pazopanib. Patients on the Phase II will be randomized in a1:1 fashion. The trial is limited to sarcomas grouped as: 1) undifferentiated pleomorphic sarcomas/malignant fibrous histiocytomas, and high-grade sarcomas NOS; 2) leiomyosarcoma (uterine, extra-uterine); and 3) malignant peripheral nerve sheath tumors and synovial sarcomas. Crossover to MLN0128 is allowed at disease progression. Eligibility requires progression on at least one prior systemic therapy. Other eligibility includes: completion of central pathology review, ECOG performance status 0-1, and adequate organ function. Prior treatment with pazopanib or any P13K, AKT, or dual P13K/mTOR complex (TORCI/TORC2) inhibitors are prohibited. Enrollment continues, targeting134. Support: U10CA180821 Clinical trial information: NCT02601209.
Risk and cost of chemotherapy-induced thrombocytopenia (CIT) in US clinical practice.
Authors: Derek Weycker, Mark Hatfield, Ahuva Hanau, Alex Lonshteyn, Anjali Sharma, David Chandler
Journal: Journal of Clinical Oncology (2018)

e18911 Background: Thrombocytopenia is a serious complication associated with myelosuppressive chemotherapy that may disrupt cancer treatment (e.g., lead to dose delays/reductions) and increases the risk of bleeding complications. Limited information on incidence and costs of CIT in US clinical practice is currently available. Methods: A retrospective cohort design and data from two US private healthcare claims repositories (spanning 01/2010–12/2015, and including > 30M covered lives annually) were employed. Study population comprised adults who received selected myelosuppressive chemotherapy regimens for solid tumors or non-Hodgkin’s lymphoma. CIT was identified based on any of the following evidence: diagnosis code for thrombocytopenia or bleeding; procedure code for platelet transfusion; or drug code for thrombopoietin-receptor agonist. Incidence of CIT was evaluated during the chemotherapy course (max. no. cycles = 8), and associated resource utilization/costs were evaluated during the cycle of the CIT episode. Results: Among 215,508 cancer chemotherapy patients, CIT incidence during the course (mean no. cycles = 4.6) was 9.7% (95%CI: 9.6-9.8), and ranged from 6.1% (5.9-6.3) for regimens containing cyclophosphamide to 13.5% (12.7-14.3) for regimens containing gemcitabine. Among all patients, CIT incidence was > 2.5% in each cycle of chemotherapy during their courses. One-third of CIT episodes were managed in hospital, and for the subset of patients hospitalized with a principal diagnosis of CIT, mean cost of inpatient care was $33,181 (29,085-37,278) and mean length of stay was 4.6 (4.4-4.9) days. Expenditures for CIT-related care totaled $1,987 (1,850-2,125) per cancer chemotherapy patient, comprising $932 (798-1,066) for inpatient care and $1,053 (1,022-1,084) for outpatient care. Conclusions: In this retrospective evaluation of cancer chemotherapy patients, CIT incidence was high, especially among patients receiving gemcitabine-based regimens, and the associated costs of care were substantial. Accordingly, interventions aimed at identifying and targeting high-risk patients for preventative measures may yield substantial clinical and economic benefits.
Updated results: phase I trial of autologous CD19-targeted CAR T cells in patients with residual CLL following initial purine analog-based therapy.
Authors: Mark Blaine Geyer, Jae Hong Park, Isabelle Riviere, Xiuyan Wang, Terence Purdon, Michel Sadelain, Renier J. Brentjens
Journal: Journal of Clinical Oncology (2016)

7526 Background: Autologous T cells genetically modified to express CD19-targeted 19-28z chimeric antigen receptors (CARs) induce durable responses in a subset of patients (pts) with relapsed/refractory CLL; greater disease burden may limit efficacy. We conducted a phase I dose escalation study to assess safety and efficacy of consolidative outpatient CAR T cell therapy in pts with residual CLL following first-line pentostatin, cyclophosphamide (Cy) and rituximab (PCR). Methods: Pts with CLL achieving partial response (PR) following first-line PCR x6 cycles were enrolled. Autologous T cells were transduced with a retroviral vector encoding anti-CD19 scFv linked to CD28 costimulatory and CD3ζ signaling domains (19-28z). Pts received Cy 600 mg/m2followed 2 days later by escalating doses of 19-28z T cells, administered outpatient. Response was assessed by NCI-WG criteria at 3 months (m) and 6 m. Results: 8 CLL pts (unmutated IgHV, n = 7; del11q, n = 1), median age 58.5 (45-68), achieved PR following PCR and received 3x106 (n = 3), 1x107 (n = 3) or 3x107 (n = 2) 19-28z+ T cells/kg. 5 pts had clearly enlarged lymph nodes (LNs) prior to T cell infusion. 4/5 pts receiving ≥ 1x10719-28z T cells/kg were admitted with fevers with mild cytokine release syndrome; peak IL-6 ranged from 39 to > 10,000 pg/mL in these pts. No DLT was observed. Maximal detected CAR T cell persistence was 8 wks. Median follow up is 32.4 m (14-41). Best response after 19-28z T cells was clinical complete response (CR, n = 2), PR (n = 2), stable disease (n = 1), progression of disease (PD, n = 3). Of 3 pts with PD, 1 pt had rising ALC by time of infusion; 2 pts had marrow response (nPR, n = 1; MRD+ CR, n = 1) with PD in LNs. Median time to PD was 13.6 m. 5/7 evaluable pts have received further CLL-directed therapy. Conclusions: Outpatient 19-28z CAR T cell therapy is well tolerated in pts with residual CLL following initial PCR. 4/8 pts achieved clinical CR or PR. Limited observed efficacy in LNs was noted. Low-dose Cy monotherapy may be insufficient for lymphodepletion. CAR T cell expansion and antitumor efficacy may be limited by a hostile CLL microenvironment. Strategies to enhance CAR T cell expansion and efficacy in pts with CLL are in preparation. Clinical trial information: NCT01416974.