tbuckley/cabot-search huggingface dataset:
Changing patterns of hospice and end of life care.
Authors: Jolyn Sharpe Taylor, Ning Zhang, Larissa Meyer, Lois M. Ramondetta, Diane C. Bodurka, Suja Rajan, Sharon Hermes Giordano
Journal: Journal of Clinical Oncology (2016)

e21516 Background: The number of hospice providers has increased in recent years. We assessed how hospice and end of life care has changed among ovarian cancer (OC) patients in Texas 2000-2012. Methods: Using Texas Cancer Registry-Medicare data, we selected OC patients who died 2000-2012, had > = 30 days from diagnosis to death and > = 13 months of continuous Medicare coverage before death. Descriptive statistics and multivariate logistic regressions were conducted to evaluate the following hospice outcomes: enrollment in hospice, death while in hospice, > 1 hospice enrollment before death, enrollment during last 3 days of life (DoL) and enrollment as an inpatient v. outpatient. Results: A total of 4,003 patients were included with 3,009 (75%) white, 637 (16%) Hispanic, 307 (8%) black and 50 (1%) other. Median age at death was 76, 74% had Charlson Comorbidity Index (CCI) < 2 and 79% lived in urban settings. 2,869 (72%) patients enrolled in hospice with a median enrollment of 19 days. Of those who enrolled in hospice, 326 (11%) did not die in hospice. Furthermore, 530 (23%) patients unenrolled from hospice at least once and 1403 (49%) enrolled in hospice as an inpatient. Of those who died in hospice, 398 (14%) enrolled in the last 3 DoL. Trends in hospice and end of life care were examined with 2000 as a reference. Over time, patients were more likely to enroll in hospice (2012 OR 2.20 [1.48-3.27]; p < 0.001), die in hospice (2012 OR 2.75 [1.88-4.01]; p < 0.001), remain in hospice once enrolled (2012 OR 2.28 [1.33-3.92];p = 0.002) and enroll as an inpatient (2012 OR 1.62 [1.04-2.51]; p = 0.03). Despite more patients enrolling in hospice, patients were more likely to receive invasive care in the last 30 DoL (2011 OR 1.68 [1.05- 2.69]; p = 0.03) and have > 1 ER visit in the final 30 DoL (2012 OR 3.12 [1.58-6.25]; p < 0.001). Outcomes which did not consistently change over time included enrolling in hospice during the last 3 DoL, receipt of chemotherapy or life-saving procedures and having any ICU or > 1 hospital admission in the last 30 DoL. Conclusions: In recent years, OC patients were more likely to enroll, remain enrolled and die in hospice. However, patients were also more likely to receive invasive care and visit the ER multiple times in the last 30 DoL. Other outcomes remained stagnant.
Phase I study of muscadine grape extract in advanced malignancy.
Authors: Rhonda L. Bitting, Janet A. Tooze, William J. Petty, Stefan C. Grant, Rodwige J. Desnoyers, Alexandra Thomas, Christopher Y. Thomas, Angela Tatiana Alistar, Shannon Golden, Katherine Pleasant, E Ann Tallant, Patricia E. Gallagher, Heidi D. Klepin
Journal: Journal of Clinical Oncology (2018)

e14548 Background: Preclinical studies with muscadine grape extract (MGE) show anti-tumor activity and decreased systemic inflammation. This phase I study (NCT02583269) assessed safety and tolerability of a proprietary MGE in patients (pts) with advanced solid tumors. Methods: Adult pts with metastatic or unresectable malignancy progressing on standard therapies were assigned to MGE (~160 mg total phenolics/capsule, Piedmont R&D) in a standard 3 + 3 design. Five dose levels were tested (320 to 1600 mg total phenolics/day). Safety and maximum tolerated dose (MTD) were assessed after 4 weeks. Pts were evaluated for response at 8 weeks and continued on MGE if clinically stable. Secondary outcomes were adherence, quality of life (QOL) by Functional Assessment of Cancer Therapy-General [FACT-G] and PROMIS-fatigue, and overall survival (OS). Median time on therapy and OS were estimated using the Kaplan-Meier method. Change in QOL outcomes were compared to zero using a one-sample t-test, and correlated with dose using Pearson correlation. Results: 23 pts (lung n = 7 ; gastrointestinal n = 7; genitourinary n = 6; other n = 3) received MGE in 5 dose levels: 1 (n = 3), 2 (n = 7), 3 (n = 3), 4 (n = 4), 5 (maximum administered dose, n = 6) capsules by mouth twice daily. Two pts were inevaluable at 4 weeks (1 withdrew, 1 noncompliant). The evaluable cohort (median age 72 y [range 43-86], 48% female, 95% white) was heavily pre-treated. After 4 weeks on MGE, possibly-attributable grade 2-3 adverse events (AEs) were decreased lymphocytes (4.7%), fatigue (4.7%), and constipation (9.5%), including one dose limiting toxicity for grade 3 constipation requiring hospitalization. Dose level 2 was expanded accordingly. There were no > grade 3 AEs. MTD was not reached. 93% of pts took ≥ 80% of pills prescribed. Median time on therapy was 8.1 weeks (95% CI 7.7, 20.3) with a 7.1 month median OS (95% CI 4.3, 12.2). QOL and fatigue levels were stable from baseline to 4 and 8 weeks (p values > 0.2). Higher MGE dose was correlated with improvement in self-reported physical function at 8 weeks (r = 0.56, p = 0.04). Conclusions: MGE is safe and well-tolerated in heavily pretreated and elderly cancer pts. The relationship between MGE and improved physical function warrants further study. Clinical trial information: NCT02583269.
Impact of the pediatric central institutional review board (PedCIRB) in Children's Oncology Group Phase 1 Consortium dose escalation studies.
Authors: Charles G. Minard, Nita Seibel, Stacey L. Berg, Elizabeth Fox, Brenda Weigel
Journal: Journal of Clinical Oncology (2016)

e18050 Background: The Pediatric Central Institutional Review Board (PedCIRB) was initiated by the National Cancer Institute (NCI) in November 2004 in order to improve efficiency and to increase the availability of clinical trials in pediatric oncology. The Children’s Oncology Group (COG) Phase 1 Consortium began utilizing the PedCIRB for dose escalation studies in 2014. The objectives of this study are to compare the time required for IRB approval between PedCIRB review and local IRB (siteIRB) review in COG Phase 1 dose escalation studies. Methods: A total of 13 COG Phase 1 consortium studies (3 PedCIRB and 10 siteIRB) across 38 research sites were included in this retrospective, observational study. IRB approval time was calculated as the time between submission to the PedCIRB and the approval date for PedCIRB studies. For siteIRB studies, the median of the approval times across all local IRB sites was calculated for each study. Kaplan-Meier curves and log-rank tests were used to compare IRB approval time between siteIRB and PedCIRB studies. Results: The PedCIRB significantly reduced the time to IRB approval compared with siteIRB reviews (P = 0.008). The median time to approval for PedCIRB studies was 5.0 weeks (95% CI: 2.9, 7.4) and the median approval time for siteIRB studies was 11.3 weeks (95% CI: 7.2, 13.9). Conclusions: Use of the PedCIRB significantly reduced the time to IRB approval for Phase 1 dose escalation studies in the Children’s Oncology Group Phase 1 Consortium.
Cooperative effect of polyvinylpyrrolidone and HPMC E5 on dissolution and bioavailability of nimodipine solid dispersions and tablets
Authors: Zhisu Sun, Huicong Zhang, Huiyang He, Lingling Sun, Xiaorui Zhang, Qun Wang, Kexin Li, Zhonggui He
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Solid dispersion (SD) systems have been extensively used to increase the dissolution and bioavailability of poorly water-soluble drugs. To circumvent the limitations of polyvinylpyrrolidone (PVP) dispersions, HPMC E5 was applied in the formulation process and scaling-up techniques, simultaneously. In this study, SD of nimodipine (NMP) and corresponding tablets were prepared through solvent method and fluid bed granulating one step technique, respectively. Discriminatory dissolution media were used to obtain reliable dissolution results. Meanwhile, the stability study of SDs was investigated with storage under high temperature and humidity conditions. Moreover, the solubility of SDs was measured to explore the effect of carriers. The preparations were characterized by DSC, PXRD, and FTIR. Dramatical improvements in the dissolution rate of NMP were achieved by the ingenious combination of the two polymers. Binary NMP/PVP/HPMC-SDs released steadily, while the dissolution of single NMP/PVP-SDs decreased rapidly in water. The fluid-bed tablets (FB-T) possessed a similar dissolution behavior to the commercial Nimotop™ tablets. The characterization patterns implied that NMP existed in an amorphous state in our SDs. Furthermore, the results of stability tests suggested a better stability of the binary SDs. A special cooperative effect of PVP and HPMC was discovered on dissolution characteristics of NMP SDs and tablets, which could be extended to other drugs henceforth. Finally, the bioavailability of FB-T was evaluated in beagle dogs with Nimotop™ as the reference, and the results showed a higher AUC0-12hvalue for FB-T.
<i>RASA1</i> and <i>NF1</i> co-mutated non-small cell lung carcinomas: Cancer genomic data and evaluation of sensitivity to MEK inhibition.
Authors: Takuo Hayashi, Patrice Desmeules, Roger Smith, Alexander E. Drilon, Romel Somwar, Marc Ladanyi
Journal: Journal of Clinical Oncology (2017)

11600 Background: Ras-GTPase activating proteins (RasGAPs), notably NF1 and RASA1, mediate negative control of the RAS/MAPK pathway. While NF1 mutations are enriched in non-small cell lung carcinomas (NSCLC) lacking KRAS alterations, they are not completely mutually exclusive. We evaluated clinical and molecular characteristics of NSCLC with RASA1 mutations in comparison with NF1-mutated cases. Methods: Large genomic datasets of NSCLC [MSK-IMPACT™ dataset at MSKCC (n = 2004), TCGA combined lung cancer dataset (n = 1144)] were analyzed to define concurrent mutations and clinical features of RASA1-mutated NSCLCs. Functional studies were performed using immortalized human bronchial epithelial cells (HBECs) and NSCLC lines with RasGAP truncating mutations, in RASA1 (RERFLCKJ), NF1 (LCLC103H and H1838), or both (EPLC272H). Results: Overall, approximately 2% of NSCLCs had RASA1 truncating mutations, and this alteration was statistically, but not completely, mutually exclusive with known activating EGFR (p = .02) and KRAS (p = .02) mutations. Unexpectedly, RASA1 truncating mutations had a strong tendency to co-occur with NF1 truncating mutations (p &lt; .001), suggesting selection for loss of more than one RasGAP. Furthermore, all patients (16/16) with concurrent RASA1/NF1 truncating mutations lacked other known lung cancer drivers, including KRAS. Knockdown of RASA1 in HBECs activated signaling downstream of RAS and promoted cell growth. Conversely, restoration of RASA1 expression in RERFLCKJ cells reduced MAPK and PI3K signaling. While growth of cell lines with inactivation of only one of these two RasGAPs showed moderate and variable sensitivity to inhibitors of MEK (trametinib) or PI3K (GDC0941, PI103), EPLC272H cells (with concurrent RASA1/NF1 mutations) showed notably more profound sensitivity (IC 50 : 0.040µM trametinib). Finally, simultaneous silencing of RASA1 and NF1 sensitized both HBECs and NSCLC cells to MEK inhibition. Conclusions: Cancer genomic and functional data nominate concurrent RASA1/NF1 loss of function mutations as a strong mitogenic driver in NSCLC. Patients whose tumors show this distinctive genotype should be considered for trials of MEK inhibitors.
Abstract 19793: Relationship Between Self-care, Functional Health, and Health Resource Use in Adults With Congenital Heart Defects
Authors: Nancy McCabe, Wendy Book, Melinda Higgins, Javed Butler, Carolyn Reilly, Sandra Dunbar
Journal: Circulation (2015)

Introduction: Many adults with congenital heart disease (ACHD) face progressive functional decline and increasing health resource use (HRU) related to long-term complications. The ability of ACHD self-care to influence functional decline is relatively unknown. The purpose of this study was to determine the relationship between self-care (maintenance, monitoring, and management behaviors), functional health (exercise capacity, symptom burden) and HRU. Methods: Adults with moderate or severe ACHD (mean age 36 ± 11 years, 55% female, 81% Caucasian) were recruited from a single ACHD center (N=132). Participants completed baseline surveys on self-care, symptom burden, and sociodemographics, and a six-minute walk test (6MWT). Clinical data were collected by chart review. Self-reported HRU was collected prospectively for 3 months. Bivariate correlations, linear and logistic regression analyses were used. Results: Mean total distance walked on the 6MWT was 1365 ± 275 feet. Participants experienced 7.4 ± 4.8 symptoms in the previous month. A total of 101 (80.8%) participants experienced 310 healthcare encounters (275 office visits, 21 hospitalizations, 20 ED visits); 73 persons (58.4%) had &gt; 1 HRU encounter. In multivariate analysis, self-care management (β=-44.20, p=.001) and monitoring (β=-14.59, p=.03) were independently associated with the 6MWT; self-care maintenance and monitoring were independently associated with symptom burden (β=-.39, p&lt;.001; β=1.52, p&lt;.001); higher self-care monitoring was an independent predictor of ≥ 1 HRU encounter (OR=1.21, 95% CI [1.09, 1.35], p&lt;.001). Conclusions: Self-care may be an important, modifiable predictor of functional health and HRU in the ACHD population. The development of interventions to improve self-care should be pursued in future studies.
Impact of adjuvant treatment in elderly patients with locally advanced rectal cancer: A population-based retrospective study.
Authors: Shiru Lucy Liu, Pierre O'Brien, Yizhou Zhao, Wilma M Hopman, Nathan William Dana Lamond, Ravi Ramjeesingh
Journal: Journal of Clinical Oncology (2017)

3613 Background: Little is known about the benefit and use of adjuvant chemotherapy (ADJ) in the elderly population (age ≥ 65) with locally advanced rectal cancer (LARC). We undertook a provincial review of LARC patients to evaluate the potential benefits, including survival and time to relapse (TTR), of ADJ in elderly patients. Methods: We performed a retrospective analysis of 286 LARC patients (stage 2 and 3) diagnosed between January 2010 and December 2013 from Nova Scotia, Canada, who underwent curative-intent surgery. Baseline patient, tumor and treatment characteristics were collected. Survival and TTR analysis were performed using Kaplan-Meier and Cox-regression statistics. Results: 152 patients were age ≥65, and 92 age ≥70. Median follow-up was 46 months. 178 patients (62%) received neoadjuvant chemo-radiation (NEOADJ). While 109 patients (81%) age &lt; 65 received ADJ, only 68 patients (45%) age ≥ 65 received ADJ. Kaplan-Meier analysis revealed a significant survival and TTR advantage for ADJ irrespective of age (table). In cox-regression multivariate analysis, ECOG status, T stage, and ADJ were significant predictors of survival (p &lt; 0.04), while age was not. Similarly, N stage, NEOADJ, and ADJ were significant predictors of TTR (p &lt; 0.007). Poor ECOG status was the most common cause of ADJ omission. There was a significantly higher amount of grade≥ 1 chemotherapy-related toxicity experienced by patients age ≥ 65 treated with ADJ compared to no ADJ (77% vs 32%, p &lt; 0.0001), which consisted mostly of diarrhea and mucositis. Toxicity was the main reason for non-completion of ADJ in the elderly. Conclusions: Elderly patients with LARC have significantly improved overall survival with ADJ, but the use of ADJ is lower than in patients age &lt; 65. However, elderly patients experience more chemotherapy-related toxicities, leading to higher rates of early treatment discontinuation. [Table: see text]
Portal hypertension and ascites in pancreatic cancer.
Authors: Varun Yadav Roy, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2018)

e16242 Background: Ascites is a recognized complication of pancreatic cancer. There are no guidelines for a standardized approach to its treatment but commonly used therapies include diuretics, paracenteses, and drains. SMAD4, a gene that encodes a signal transducer that plays a role in pancreatic cell proliferation and apoptosis, is mutated in a number of pancreatic cancers. The mutation has been associated with a locally aggressive subset of cancer but these findings have not led to appreciable changes in management. Objective: The objective of this study is to gather information on the incidence and treatment of portal hypertension leading to ascites in a cohort of pancreatic cancer patients. Our hypothesis is that factors such as SMAD4 genetic mutation and prior radiation therapy are associated with an increased risk of developing portal hypertension and ascites in pancreatic cancer. Methods: We conducted a retrospective review of a cohort of 325 pancreatic cancer patients treated at Cedars Sinai Medical Center. We analyzed clinical variables including presence of ascites, serum ascites albumin gradient (SAAG), treatment modalities for ascites, genetic mutations with focus on SMAD4, and administration of radiation therapy. Results: 186 of 325 patients developed ascites at some point in pancreatic cancer progression. 119 of these patients were on diuretics, 73 underwent paracentesis, and 19 had placement of Pleurx catheters. Of 54 patients who had ascitic fluid analysis, 52 had SAAG > 1.1 g/dL. 80/123 (65%) patients without SMAD4 mutation and 22/33 (67%) SMAD4+ patients developed ascites (RR 1.02, 95% CI 0.78 – 1.35, p 0.86). A higher incidence of ascites was found in patients who had received any form of radiation therapy compared to those who had not (RR 1.19, 95% CI 1.00 – 1.42, p 0.05). Conclusions: Ascites due to portal hypertension is a significant complication of pancreatic cancer. SMAD4 mutation was not found to have an association with the development of ascites in pancreatic cancer. An association was identified between radiation therapy and development of ascites. A variety of methods are employed empirically for palliation of ascites and further investigation is warranted to develop an evidence-based approach to management of ascites in pancreatic cancer.
Unusual Wide Complex Tachycardia During Rhythm Control for Atrial Fibrillation
Authors: Bharatraj Banavalikar, Jayaprakash Shenthar, Deepak Padmanabhan
Journal: Circulation (2018)

ECG CHALLENGEA 72-year-old woman with paroxysmal atrial fibrillation on oral metoprolol 5 mg twice a day, flecainide 150 mg twice a day for rhythm control, and acenocoumarol 2 mg daily presented with vomiting, presyncope, and fatigue of 3 days duration.Examination revealed a heart rate of 110 bpm, blood pressure of 106/78 mm Hg, and systemic oxygen saturation of 98% at room air.The serum potassium was 3.76 mEq/L, serum magnesium was 1.8 mg/L, serum sodium was 124 mEq/L, and serum creatinine was 1.1 mg/dL.ECG at presentation is shown in Figure 1.What is the rhythm and how should it be treated?Please turn the page to read the diagnosis.
Dimethyl sulfoxide (DMSO) cryopreserved stem cell infusion-related seizures: A single institution experience.
Authors: Shirin Attarian, Murali Janakiram, Ali Ezzati, Rasim A. Gucalp
Journal: Journal of Clinical Oncology (2017)

e19002 Background: An essential step in hematopoietic stem cell transplantation (HSCT) is the cryopreservation of stem cells in DMSO. Neurologic complications related to DMSO are well known and include strokes, seizures, encephalopathy and coma, but risk factors have not been identified. We focused on seizures as a DMSO-related neurologic adverse event. Methods: From 1/2006 to 4/2016, 982 cases of HSCT were reviewed. We identified neurologic adverse events within 24h of stem cell infusion (SCI). Results: 16 cases of neurologic adverse events occurred, including transient paresthesias (2), altered mental status (5), syncope (3), stroke (1), and 5 seizures. The mean age of the patients (pt) was 64.2 years (range 52-79), with 2 females and 3 males. All 5 pts developed seizures during SCI. 4 pts had conditioning: 2 Melphalan, 1 BEAM and 1 Bu/Cy. One pt received SCI without conditioning as a last resort to treat severe neutropenia and overwhelming sepsis. Of these 5 cases, one had a prior history of seizures in the setting of primary CNS lymphoma and 1 had a prior history of stroke, and 1 pt had an acute stroke during SCI. These 3 cases had abnormal EEG with a potential focus for seizure. Conclusions: Understanding the predisposing factors for developing seizures with SCI will improve patient safety and outcomes. History of structural brain lesions or seizure may be a risk factor for development of seizures. Applying prophylactic strategies, such as DMSO removal or prophylactic antiepileptic medications prior to SCI may decrease the risk of seizures. [Table: see text]
A phase I study of anti-GPC3 chimeric antigen receptor modified T cells (GPC3 CAR-T) in Chinese patients with refractory or relapsed GPC3+ hepatocellular carcinoma (r/r GPC3+ HCC).
Authors: Bo Zhai, Donghua Shi, Huiping Gao, Xingxing Qi, Hua Jiang, Yuan Zhang, Jiachang Chi, Huaying Ruan, Huamao Wang, Qinhua Cindy Ru, Zonghai Li
Journal: Journal of Clinical Oncology (2017)

3049 Background: HCC was commonly diagnosed and identified as leading causes of cancer death in China. Using a 10% cutoff score, GPC3 was detected in 63.6% of HCCs. Safety and preliminary efficacy of a GPC3 CAR-T was evaluated in 13 Chinese patients (pts) with r/r GPC3+ HCC in a Phase I trial. Methods: Pts between 18 and 70 yrs old with histopathological confirmed r/r GPC3+ HCC, Child-Pugh score≤B7, ECOG≤1, lymphocyte ≥ □0.7 x10 9 , post-transduction positive T cells □ ≥30%, amplification by α CD3/CD28 ≥5 □, and without ascites and HIV infection were enrolled. Eligible pts undergo leukapheresis or whole blood colletion, which further developed into GPC3 CAR-T via lentiviral transduction. Standard release tests were conducted before administering GPC3 CAR-T in pts. Adverse events were graded per NCI CTCAE v.4.03. Efficacy was evaluated per modified RECIST (mRECIST). Results: All 13 pts, who received at least one infusion of GPC3 CAR-T, tolerated the treatment well. No dose-limiting toxicity (DLT) was identified, and only one SAE of grade 3 fever was reported. Preliminary analysis compared the clinical outcomes in pts who received GPC3 CAR-T without lymphodepleting conditioning (LDC) (Group A) vs. with LDC (Group B) at baseline. In Group A (N = 5), all pts developed progressive disease (PD) shortly after received a total infusion of GPC3 CAR-T ranging from 0.92x10 7 to 8.72 x10 7 cells/kg. In Group B (N = 8), following the LDC with fludarabine and cyclophosphamide, pts received a total infusion of GPC3 CAR-T ranging from 0.013x10 7 to 14.68 x10 7 cells/kg. Except two non-evaluable pts, the best response for the rest 6 pts are 1 PR, 3 SD, 2 PD. As of Feb 1, 2017, the PR pt remains alive for 385 days; 2 SD pts remain alive for 384 and 562 days, respectively; and one SD deceased at 108 days. Also worth to mention, one pt in Group A decided to remain on the study after PD, further received a total of 6.23 x10 7 cells/kg infusions following a LDC given around Day 150, remains stable for 571 days as of Feb 1, 2017. Conclusions: Phase I trial shows GPC3 CAR-T is feasible and safe for Chinese pts with r/r GPC3+ HCC, and holds promising antitumor potential when LDC is applied along with GPC3 CAR-T. Clinical trial information: NCT02395250.