tbuckley/cabot-search huggingface dataset:
Early discontinuation of combination therapy in multiple myeloma: A pilot analysis.
Authors: Jay Lin, Melissa Lingohr-Smith, Mohamed Omar, Clara Chen
Journal: Journal of Clinical Oncology (2016)

e18099 Background: Combination therapy (CT) with proteasome inhibitors and immunomodulatory drugs is effective in improving progression-free survival (PFS) in patients (pts) with multiple myeloma (MM) with a trend toward improving overall survival (OS). In 2 recent trials, pts received CT for ≥ eight 21-day cycles, and ≥ six 28-day cycles. The length of time that pts in the real world remain on CT has not been evaluated. The aims of this study were to examine duration of CT (DoCT) and the clinical and cost outcomes associated with early discontinuation of CT. Methods: A retrospective cohort study was conducted of pts with 12 months (mo) of continuous enrollment in Medicare before MM diagnosis in 2007-2011 who received CT for MM. Pts were selected from the SEER-Medicare linked database and followed until 12/31/2012. Exclusion criteria included stem cell transplantation. Median DoCT (mDoCT) was assessed. Cohort 1 included pts with DoCT ≥ mDoCT. Cohort 2 included pts with DoCT < mDoCT. Statistical analysis included descriptive and Kaplan-Meier analyses of OS and PFS from initiation of CT. Per-patient-per-month (PPPM) costs were measured from the CT start date until the end of follow-up between cohorts using a phase-of-care approach. Results: A total of 185 MM pts with mDoCT of 4 mo were included. Mean follow-up was 19 mo for Cohort 1 (n = 95) and 16 mo for Cohort 2 (n = 90). No significant difference was found in age at CT start date, sex, region, comorbidity, or frailty between the 2 cohorts. Pts with DoCT ≥ mDoCT had longer OS and PFS, fewer MM-related hospitalizations, and lower inpatient costs (Table). Conclusions: Pts with longer DoCT may have better clinical and cost outcomes than those with shorter DoCT. Because of the small sample size, future research with a larger population may be needed to further validate the benefits of longer-term use of CT. Total Duration of CT P value ≥ mDoCT < mDoCT No. of pts 185 95 90 Median OS (mo) 48.6 Not reached 25.9 0.011 Median PFS (mo) 22.6 27.2 17.0 0.009 PPPM MM-related inpatient services and medical costs* No. of admissions 0.15 0.11 0.19 0.007 Reimbursement $1,319 $848 $1,817 0.009 Charges $5,515 $3,354 $7,797 0.011 * Reimbursement = amount covered by Medicare; Charges = amount billed to Medicare.
Burdensome end-of-life (EOL) transitions among frail older adults with advanced cancer.
Authors: Daniel E Lage, Yoojin Lee, Susan L. Mitchell, Jennifer S. Temel, Sarah Berry, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2018)

6534 Background: Older adults with advanced cancer residing in nursing homes (NHs) are a vulnerable population that has not been well studied in terms of clinical needs and health care utilization. We sought to describe the clinical characteristics of these patients and examine their burdensome care transitions at the EOL. Methods: We conducted a retrospective analysis of deceased older adults (> 65 yrs) with advanced solid tumors (defined using Medicare claims, per prior literature) who resided in U.S. NHs and enrolled in Medicare fee-for-service (2008-2009). Medicare claims data were linked with geriatric assessments as part of the Minimum Data Set. Clinical characteristics, including comorbidities, pain scores, activities of daily living (ADLs) and cognition, were measured within 90 days of death. Using Medicare claims and per prior studies on end of life health care utilization, we defined a burdensome transition as two or more hospitalizations or an intensive care unit (ICU) admission in the last 90 days of life. Results: We included 34,670 patients with advanced solid tumors. Many residents had comorbid congestive heart failure (CHF) (29.3%), chronic obstructive pulmonary disease (COPD) (34.1%), and diabetes (35.0%). Over half (53.8%) had moderate or severe cognitive impairment; 66.5% were dependent in all ADLs, and 21.1% experienced daily pain. Only 55.4% of patients used hospice. 36.0% of patients experienced a burdensome transition at the EOL, and burdensome transitions were more common for patients who did not receive hospice (45.3% vs. 28.6%, p < 0.01). In adjusted analyses, the following characteristics were associated with a higher risk of a burdensome transition at the EOL: female sex (OR 1.2, P < 0.001), CHF (OR 1.56, P < 0.001), COPD (OR 1.3, P < 0.001), diabetes (OR 1.3, P < 0.001), full dependence in ADLs (OR 1.9, P < 0.001), and receipt of chemotherapy in the last 90 days of life (OR 1.7, P < 0.001). Conclusions: Although NH residents with advanced cancer have substantial comorbidities, cognitive deficits, and functional impairments, over a third experienced a burdensome care transition at the EOL. Interventions are critically needed to reduce burdensome transitions at EOL in this vulnerable population.
Machine learning and medical education
Authors: Vijaya B. Kolachalama, Priya S. Garg
Journal: npj Digital Medicine (2018)

Artificial intelligence (AI) driven by machine learning (ML) algorithms is a branch in computer science that is rapidly gaining popularity within the healthcare sector. Recent regulatory approvals of AI-driven companion diagnostics and other products are glimmers of a future in which these tools could play a key role by defining the way medicine will be practiced. Educating the next generation of medical professionals with the right ML techniques will enable them to become part of this emerging data science revolution.
PD-L1 expression profile and immunotherapy (IO) experience in African American (AA) and Hispanic (H) lung cancer (LC) patients: Addressing disparities at a minority-based academic cancer center.
Authors: Elaine Shum, Christopher Su, Changcheng Zhu, Rasim A. Gucalp, Missak Haigentz, Stuart H. Packer, Cheryl Baker, Yoko Eng, Elizabeth Ravera, Royston Browne, Roman Perez-Soler, Balazs Halmos, Haiying Cheng
Journal: Journal of Clinical Oncology (2017)

e18073 Background: Immune checkpoint inhibitors have changed the treatment paradigm for metastatic LC. Minority populations are under-represented in large IO clinical trials. Among 989 pts with newly diagnosed LC at Montefiore Medical Center - a community-based academic center from 2014-2015, 330 (33%) were AA and 195 (20%) were H. In line with practice-changing clinical studies, PD-L1 expression testing and IO have been incorporated into LC treatment. Methods: Pts receiving IO and/or had PD-L1 testing between 1/1/14-12/31/16 were identified from records obtained from pathology, pharmacy, oncology clinics and Clinical Looking Glass. Retrospective chart review was conducted. PD-L1 testing was performed using 22C3pharmDx IHC. Results: We identified 111 pts with LC who received IO and/or had PD-L1 testing, with a median age of 66. 55% were female. Based on race, 52 (47%) were AA, 24 (22%) were White, 26 (24%) were Other, and 9 (8%) were race unknown. Based on ethnicity, 30 (27%) were H, 73 (66%) were non-H and 8 (7%) were ethnicity unknown. 82% were former/current smokers. Adenocarcinoma was the dominant histology (60%). The majority were EGFR WT (91%) and ALK neg (98%). PD-L1 testing was performed in 67 (60%), including 32 (29%) AAs and 20 (18%) Hs. Archival tissue was used in 63%. PD-L1 TPS &gt; 50% was found in 30%, 1-49% in 24%, &lt; 1% in 37%. 62 pts received IO, including 26 (42%) AAs and 18 (29%) Hs. Nivolumab was the most commonly used agent (77%). In AAs, 8 (31%) received IO as 1st line, 13 (50%) as 2nd line, 5 (19%) as 3rd line and above. In Hs, 1 (5%) received IO as 1st line, 10 (56%) as 2nd line, 7 (39%) as 3rd line and above. Immune-related adverse events (IRAEs) were reported in 31% of AAs and 39% of Hs. Data analysis on survival is ongoing. Conclusions: Unlike the low numbers of minority pts in large clinical trials, we found no significant difference in PD-L1 testing and IO across racial and ethnic groups treated at our center. Compared to large clinical trials, we observed lower rates of IRAEs in our cohort. Our current and ongoing observations in these populations may have future implications in narrowing health disparities based on race/ethnicity.
NANT 2012-01: Phase 1 study of DFMO and celecoxib with cyclophosphamide and topotecan for relapsed or refractory high-risk neuroblastoma.
Authors: Araz Marachelian, Michael D. Hogarty, Andrea Flynn, Kangning Liu, Eugene W. Gerner, Elizabeth Bruckheimer, Anasheh Shamirian, Charlotte Hasenauer, Murray Norris, Michelle Haber, Susan G. Groshen, David Simon Ziegler, Katherine K. Matthay
Journal: Journal of Clinical Oncology (2018)

10558 Background: MYC drives polyamine expansion to support its oncogenic functions. Ornithine decarboxylase (Odc) is a direct MYC target that is rate-limiting for polyamine synthesis, and is itself amplified in a poor-outcome subset of NB. Difluoromethylornithine (DFMO) is an Odc inhibitor with preclinical activity via protein translation and immunomodulatory effects. We studied dose-escalated DFMO added to celecoxib (polyamine export inducer), Cyclo/Topo. Methods: Patients 2-30 years with RR HR NB were eligible. DFMO was studied at four dose levels (DL1-3,000; DL2/2A-4,500; DL3A-6,750; and DL4A-9,000mg/m2/day po daily) with celecoxib (500mg/m2/daily), Cyclo (250mg/m2/day) and Topo (0.75mg/m2/day) IV for 5 days, with G-CSF. DFMO pharmacokinetics and biomarkers of ODC regulation (promoter SNP) and polyamine depletion were performed. Results: Twenty-four patients enrolled; median age 6.8 years. Patients received 124 total cycles (range, 1-17). DL1 and 2 used 21d cycles (DFMO given 14/21d). Due to delayed platelet recovery, DL 2A-4A used 28d cycles (DFMO given 21/28d). Toxicities were predominantly hematologic/fever-related. There were three cycle-1 DLTs (hematologic; anorexia; transaminitis) and two DLTs in later cycles (cycle-2 hematuria; cycle-11 hypotension). Eight patients stopped therapy by choice; two due to DLT; 9 due to PD; 3 completed therapy (CR = 1, PR = 2; all at dose-levels ≥4500 mg/m2/day DFMO); and 2 remain on therapy. Median time-to-progression was 19.8 months. Dose-level 4A exceeded tolerability (2/6 with DLT). Dose-level 3A (6,750mg/m2/day) is the RP2D. Steady-state Cmin for DFMO increased by dose-level with median Cmin of 125mM at DL3A, equivalent to DFMO concentrations achieved in preclinical murine studies in water, and above the exposure needed to inhibit protein translation. Conclusions: DFMO and celecoxib added to Cyclo/Topo is tolerable in heavily pretreated NB patients, with a RP2D of 6,750mg/m2/day. Achievable DFMO concentrations at this dose have demonstrable bioactivity using in vitro and in vivo preclinical models. Further testing with DFMO in combination with chemotherapy in this population is warranted. Clinical trial information: NCT02030964.
Final phase II trial results of Sorafenib plus Capecitabine (SorCape) in previously treated metastatic colorectal cancer.
Authors: Thomas J. George, Alison Marguerite Ivey, Karen Colleen Daily, Long H. Dang, Scott Watson, Margaret A. McEwan, Xiaomin Lu, Sanda Tan, Atif Iqbal, Jennifer Michelle Duff, Carmen Joseph Allegra
Journal: Journal of Clinical Oncology (2016)

e15035 Background: Inhibition of the MEK/ERK pathway through Raf has been shown to sensitize tumor cells resistant to chemotherapy. Sorafenib (Sor) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation and angiogenesis through inhibition of the Ras/Raf/MEK/ERK, VEGF, and PDGF pathways. Fluoropyrimidines and similar TKIs have each demonstrated efficacy as monotherapy in advanced mCRC. Documenting clinical activity and manageable toxicity of these antineoplastic class combinations is a clinical unmet need. Methods: Eligible pts had progressive mCRC after prior oxaliplatin and irinotecan, at least 1 measurable target lesion by RECIST, ECOG PS 0-1, and adequate organ function. Pts received Cape (1000mg/m2 PO BID D1-14) and Sor (400mg PO BID max via dose escalation per cycle). Cycles were q21d with tumor assessments q9w until progression. Primary endpoint was PFS with secondary endpoints including objective and biochemical response rates, OS, toxicity and quality of life. Sample size was based on a 50% improved median PFS from 3 (historical) to 4.5 months (mo) using Woolson’s one-sample one-sided logrank test. Results: 42 pts were treated with median f/u of 4.6 mo. Patient demographics are shown in table. Median number of cycles was 5.6 (range 1-39). Compared to historical controls, median PFS and OS were 4.1 vs. 3mo (p < 0.039) and 8.7 vs. 6mo, respectively. Clinical benefit rate (CR+PR+SD) was 52%. 31 pts (74%) had a grade 3 AE (16/31 were HFS). There was one grade 4 (sepsis) and no g5 toxicities. Four pts (9%) discontinued due to toxicity. Conclusions: The combination of SorCape in this heavily pre-treated population significantly improved PFS with manageable, but notable toxicity. Molecular predictors of response are being analyzed. Further studies involving the combination of fluoropyrimidines with multi-targeted TKIs are indicated. Clinical trial information: NCT01471353.Baseline patient demographics. Variable (n = 42) Median value (%) Race Caucasian n = 31 (74%) Gender Male n = 33 (78%) Age 57 (36-79) K-Ras mutation 23 (55%) Prior lines of therapy for mCRC 3.5 (2-7) Baseline LDH (U/L) 379 (96-2450) Baseline CEA (ng/mL) 254 (4.3-1804)
A multicenter phase II study of pazopanib in patients with unresectable or recurrent dermatofibrosarcoma protuberans (DFSP).
Authors: Julie Delyon, Raphael Porcher, Maxime Battistella, Nicolas Meyer, Henri Adamski, François Bertucci, Bernard Guillot, Thomas Jouary, Marie Thérèse Leccia, Sophie Dalac, Laurent Mortier, Laetitia Da Meda, Eric Vicaut, Florence Pedeutour, Samia Mourah, Celeste Lebbe
Journal: Journal of Clinical Oncology (2018)

11557 Background: DFSP is a tumor accounting for 6% of soft-tissue sarcoma, with a high risk of local infiltrative dissemination. Wide local excision is the standard treatment. The identification of the COL1A1-PDGFB translocation activating the PDGF pathway in > 90% of DFSP had led to the use of the kinase inhibitor imatinib in locally advanced or metastatic DFSP, with a response rate of 36-57%. Pazopanib (pazo) is a multitargeted tyrosine kinase inhibitor (VEGF, PDGF, KIT) approved in severe pretreated soft-tissue sarcomas. We sought to evaluate the efficacy and safety of pazo in the treatment of DFSP. Methods: We conducted an open-label phase II trial in patients with histologically proven unresectable primary, recurrent or metastatic DFSP. Patients received pazo 800 mg qd. The primary study endpoint was the objective response rate defined as the reduction of the biggest diameter of the tumor ≥ 30%(RECIST) at 6 months(mo) or at surgery if performed before 6 mo. Pharmacodynamics analyses were performed on tumor biopsies and blood samples at baseline, month 1-3-6 and progression (PDGF, PDGFR, VEGF, VEGFR mRNA and downstream signaling pathway components). Results: 23 patients were included from Jul 2010 to Feb 2014 (9 centers, France). 18 had primary, 4 recurrent and 1 metastatic DFSP. The median follow up was 6.2 mo (interquartile range 5.6-7.8). 5 patients (22%, 95% CI: 7-22%) among 23 evaluable had response according to the primary endpoint. The best objective response rate was 30% (7/23, 95%CI 13-53%). 18 patients had surgery, including 12 with free margins. One patient with metastatic DFSP died. Median treatment duration was 3.8 mo (2.1-6.0); 9/23 patients discontinued for AEs; 11(48%) patients had dose reduction. Grade 3-4 AEs were transaminitis(5), cholestasis(3), hemolytic and uremic syndrome(1), nephrotic syndrome(1). No drug-related death occurred. Using FISH the COL1A1-PDGFB translocation was identified in 18 patients(5 not evaluable). High plasma level of soluble VEGFR2 was associated with tumor response (p = 0.01). Conclusions: Our results suggest that pazo is a therapeutic option in DFSP. As compared to previous studies with imatinib, we did not observe an improved response rate. Clinical trial information: NCT01059656.
Thrombus Aspiration in Patients With High Thrombus Burden in the TOTAL Trial
Authors: Sanjit S. Jolly, John A. Cairns, Shahar Lavi, Warren J. Cantor, Ivo Bernat, Asim N. Cheema, Raul Moreno, Sasko Kedev, Goran Stankovic, Sunil V. Rao, Brandi Meeks, Saqib Chowdhary, Peggy Gao, Matthew Sibbald, James L. Velianou, Shamir R. Mehta, Michael Tsang, Tej Sheth, Vladimír Džavík
Journal: Journal of the American College of Cardiology (2018)
Double lumen esophagus due to false submucosal path induced by nasogastric tube: endoscopic treatment with marsupialization
Authors: Jean-Philippe Le Mouel, Paul Basile, Jean-Michel Gonzalez, Rodrigo Irarrazaval, Mélanie Serrero, Marc Barthet
Journal: Endoscopy (2018)

A 39-year-old man with a medical history of vertebrobasilar stroke 1 year previously, associated with tobacco and cocaine use, presented with dysphagia. During his hospitalization, the patient developed swallowing disorders. An attempt to insert a nasogastric tube (NGT) was unsuccessful owing to unusual resistance. A percutaneous endoscopic gastrostomy was therefore performed. During upper gastrointestinal endoscopy (UGE), a false submucosal path, secondary to NGT impaction was observed, with upper and lower orifices located at 33 cm and 38 cm, respectively, from the dental arches ([Fig. 1]). Enteral nutrition and proton pump inhibitors were initiated but no endoscopic surveillance was proposed.
Venous thromboembolism is associated with advanced cancer stage, hypertension and cardiovascular disease regardless of latency from surgery in patients with uterine serous carcinoma.
Authors: Gregory M. Gressel, Lauren Turker, Shayan M Dioun, Aileen P. McGinn, Nicole Suzanne Nevadunsky
Journal: Journal of Clinical Oncology (2018)

e17568 Background: Although gynecologic cancer patients are known to be at increased risk of venous thromboembolism (VTE) after surgical staging, it remains unclear how long that risk persists. This study seeks to characterize risk factors and timing of VTE in women with uterine serous carcinoma (USC). Methods: A retrospective study was performed of all women diagnosed with USC from 1999- 2016 at our institution. Data analysis was performed using Stata 14.2. Clinical data was collected including patient age, stage, and diagnosis of medical co-morbidities (diabetes, hypertension, cardiovascular disease, prior VTE, smoking history, chronic obstructive pulmonary disease, chronic kidney disease, obesity). Timing of VTE was calculated from cancer diagnosis until clot diagnosis and was characterized according to cancer treatment status (presenting symptom, postoperatively, during or after adjuvant chemo-radiotherapy). Logistic regression and Cox proportional hazards modeling were used to examine the association between covariates and risk and timing of clot. Results: Seventy of the 413 included patients (17%) developed VTE with a median time from cancer diagnosis to VTE of 9.9 months (IQR 1.5, 26.2). Most patients who developed VTE were not post-operative (64.3%) and many developed clots while on chemotherapy (35.7%). There was a strong association between both stage and hypertension with VTE diagnosis in logistic regression. Cox modeling revealed that only cancer stages III and IV (HR 3.48, 95% CI 1.67-7.25 and HR 8.90, 95% CI 4.61-17.22 respectively), and hypertensive or cardiovascular diseases (HR 2.15, 95% CI 1.02- 4.54 and HR 1.81, 95% CI 1.05- 3.12) were associated with time to VTE. Conclusions: Patients with USC are at high risk of developing VTE even many months after their cancer diagnosis. This risk is highest for those patients with hypertension, cardiovascular disease and advanced cancer. This study generates the hypothesis that extended VTE prophylaxis may be beneficial in USC patients with these high-risk features, however large randomized trials are needed to test this theory.
Abstract 13639: Comparison of the Flexible Tip Irrigated Catheter to the Rigid Tip Irrigated Catheter in a Porcine Thigh Muscle Preparation.
Authors: Carlos Oberti, Jami A Hegrenes, John A Sral, Ayman Hussein, William Kowalewski, John Lopez, Jacqueline Kattar, Bruce Lindsay, Oussama M Wazni, Walid Saliba
Journal: Circulation (2011)

Introduction: The flexible fully irrigated catheter has been introduced to reduce formation of char and coagulum at the catheter tissue interface and also to conform to the endocardial surface for ...
Inpatient burden of neoplasm related pain in the United States: An analysis of national trends in the United States from 2007 to 2013.
Authors: Supreet Kaur, Dhruv Mehta, Shanti Patel, Abhishek Kumar, Mahendar Kumar, Chandra Chandran, Michael Maroules
Journal: Journal of Clinical Oncology (2016)

10138 Background: Despite increasing interest in and efforts to improve its management, pain remains poorly controlled in nearly half of all patients with cancer. Pain is among the most distressing and disabling sequelae of cancer and its related treatments and remains poorly managed. The prevalence of cancer-related pain has ranged from 14% to 100% in surveys. We aim to determine the incidence and costs of hospital admission associated with Neoplasm related pain (NRP) using a nationally representative database. Methods: National Inpatient Sample (NIS) accounts for 20% of all U.S hospitalizations. We reviewed the NIS for all hospitalizations in which NRP (ICD9 code 338.3) was the principal discharge diagnosis during the period from 2007-2013 .We then analyzed changes in temporal trends of incidence, length of stay, costs and in-hospital mortality utilizing Cochrane-Armitage test. Results: There were 140,999 primary admissions for NRP during the study period. In-hospital mortality for the cohort was 8.5% (n= 12,040). Hospitalization with NRP (primary diagnosis) increased significantly from 12,765 cases to 23,025 (p < 0.01). This trend was similar but much significant when the same ICD code was used for both primary and secondary discharge diagnosis(48,473 cases in 2007 to 107,345 cases in 2013 (p < 0.0001)).There was a significant reduction in in-hospital mortality over a period of 6 years from 9.65% in 2007 to 7.62% in 2013 (p < 0.01). In addition, during this period the mean hospital charges increased significantly from $27,227 (after adjusting for inflation) per admission in 2007 to $33,835 per admission in 2013(p < 0.001), whereas the “national burden” increased from $308 million to $777 million during the study period (P < 0.01) without any significant change in length of hospitalization during the same period. Conclusions: There is significant increase in the hospitalization and cost for cancer related pain. This could be partly because of previous under-reporting, increased awareness, healthcare seeking behavior and increasing use of procedural techniques to alleviate pain. More studies are needed to assess factors associated with increased hospitalization.