tbuckley/cabot-search huggingface dataset:
Retrospective analysis of prognostic factors influencing very late onset PTLD.
Authors: Ravneet Bajwa, Rohit Bishnoi, William Paul Skelton, Yu Wang, Aaron J Franke, Chintan Shah, Niraj Patel, Susan P. McGorray, Nam H. Dang
Journal: Journal of Clinical Oncology (2018)

e19561 Background: Post-transplant lymphoproliferative disorder (PTLD), is a very rare complication following transplant (solid organ or allogeneic) due to proliferation of lymphoid cells in immunosuppresed state. The incidence of PTLD follows a bimodal distribution, with high incidence immediately after transplant (early-onset PTLD), followed by a decline and then a high-incidence again 5 years after transplantation (late-onset PTLD). This study, exclusively aims to identify prognostic factors for the subgroup of PTLD, described as very late onset PTLD, occurring after 10 years of transplant. Methods: This study was conducted at University of Florida after IRB approval and study population was identified through cancer registry. Data was collected by individual chart review and analyzed. Survival estimates, univariate and multivariate analysis was performed to measure effects of each variable on overall survival. Results: Total of 33 patients were identified with median age at transplant was 42.3 years, while median age at PTLD diagnosis was 54.7 years. Median time from transplant to PTLD diagnosis was 13.3 years. Kidney (30.3%), liver (27.3%) and heart (24.2%) transplant were the most common allografts associated with very late PTLD development. Most common pathology was DLBCL in 45.5% patients. CHOP+/-R was the most common chemo regimen used as initial choice in 36.4% patients. Median survival was 5.4 years. Univariate analysis showed age at diagnosis above 65, gender, bone marrow involvement, PMH of malignancy, immunosuppression regimen at PTLD diagnosis and initial and final best response to treatment were significant (p < 0.05). On multivariate analysis bone marrow involvement was statistically significant with poor survival (p = 0.008). Surprisingly performance status, EBV status, pathology type, Ann-arbor stage and chemotherapy regimen were not significantly associated with survival. At the end of study 48.5% patients achieved complete remission and allograft survived in 84.8%. Conclusions: In this retrospective single institution study, first ever on very-late onset PTLD identified factors different from early and late PTLD. These factors should be considered during treatment of this sub-group of PTLD patients.
TCT-598 Prediabetes and its Impact on Clinical Outcome After Coronary Intervention in Chinese Patients
Authors: Huan-Huan Wang, Ying Song, Lin Jiang, Ping Jiang, Ru Liu, Xueyan Zhao, Zhan Gao, Shubin Qiao, Yuejin Yang, Runlin Gao, Bo Xu, Jinqing Yuan
Journal: Journal of the American College of Cardiology (2018)
Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.
Authors: Tristan Alexandra Barnes, Eitan Amir, Arnoud J. Templeton, Susana Gomez Garcia, Beatriz Navarro, Bostjan Seruga, Alberto Ocana
Journal: Journal of Clinical Oncology (2017)

e18336 Background: New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. Methods: Drugs approved for the treatment of solid tumors between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes or dysregulated pathways (group 1), anti-angiogenic drugs (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the reports of randomized trials supporting registration and pooled in a meta-analysis. Odds ratios (ORs) for rates of toxic death, treatment discontinuation and grade 3-4 toxicity were compared relative to control groups. The Micromedex Red Book was used to calculate the monthly price of each agent. Results: Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a lesser degree with groups 3 and 4 than with groups 1 and 2, (pooled HR:0.54, 0.56, 0.63, and 0.76 for groups 1–4 respectively, p for difference &lt; 0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR:0.77, 0.78, 0.68, and 0.83 for groups 1–4 respectively, p for difference = 0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no statistically significant difference between groups. There was limited to no correlation between drug pricing and efficacy. Conclusions: Compared to control groups, chemotherapy improves efficacy to a lesser degree than the other groups. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy.
Real-time circulating tumor DNA profiling of advanced cholangiocarcinoma (CCA).
Authors: Kabir Mody, Mitesh J. Borad, Tanios S. Bekaii-Saab, Ju Dong Yang, Ramesh K. Ramanathan, Daniel H. Ahn, Amit Mahipal, Ali Roberts, Rebecca J Nagy, Pashtoon Murtaza Kasi
Journal: Journal of Clinical Oncology (2018)

4089 Background: Cholangiocarcinoma (CCA) has limited treatment options. Genomic analyses have led to development of targeted therapies now in several clinical trials, and may enable the discovery of new treatment options. However, biopsy often yields limited tissue, thus hampering tissue-based profiling opportunities. Data regarding circulating tumor DNA (ctDNA) plasma analysis in CCA during real time clinical practice is limited. Methods: We performed ctDNA NGS analysis in patients with advanced CCA (January 2015 – December 2017). ctDNA analysis was performed using Guardant 360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in up to 73 different genes. Seventeen samples were performed on previous panel versions (3 on a 54-gene, 1 on a 68-gene, and 13 on a 70-gene panel) The mutant allele fraction (MAF) for detected alterations was calculated relative to wild type in ctDNA. Actionability was defined as possible treatments within OncoKB levels I-IV and R1. The study was conducted in accordance with Mayo Clinic Institutional Review Board requirements. Results: Among 104 patients and 115 total samples, ctDNA NGS revealed at least one genomic alteration (excluding variants of uncertain significance (VUS) and synonymous mutations) in 80 patients (77%). Median number of alterations per patient was 3 [range, 1-15], with a median mutant allele fraction of 0.42% (range, 0.1% - 94.2%). The total number of unique alterations was 389, with the most commonly altered genes being: TP53 (84 alterations, 22%), followed by KRAS (34 alterations, 9%), FGFR2 (31 alterations, 8%), ARID1A (20 alterations, 5%), APC and PIK3CA (16 alterations each, 4%). Amplifications were noted in 14 genes, including BRAF, CCND1, CCND2, CCNE1, CDK4, CDK6, EGFR, ERBB2, FGFR1, FGFR2, MET, MYC, PDGFRA, and PIK3CA. Fusions of FGFR2 were seen in 3 cases. Potentially actionable alterations were seen in 63 of the 104 patients (61%). Conclusions: ctDNA plasma profiling of patients with advanced CCA is a feasible alternative method to gather comprehensive genomic data. Further study of responses to ctDNA NGS-guided over tissue-guided targeted therapy is needed to define the best means to optimize outcomes in CCA.
David Oliver: “Why did they put her on a geriatric ward?”
Authors: David Oliver
Journal: BMJ (2018)

Geriatricians sometimes field formal complaints and informal calls for concern. Patients’ families can be unhappy that their loved one has been admitted or transferred to a geriatric medicine ward, whatever the quality of care or communication.

Sometimes it isn’t even a geriatric medicine ward. Fellow patients in 21st century acute medical units or wards are often older, frailer, or more cognitively impaired than the public might expect. I’ve seen this misunderstanding often in my work as an independent expert reviewer for courts, regulators, or complaint resolution.

For doctors who have devoted their professional career to the care of the oldest and most medically complex patients, and for the skilled multidisciplinary teams of nurses and allied health professionals we work closely with, such complaints can be unsettling.

Why are relatives, and …
Interim baseline characteristics from RIFTOS MKI, a global non-interventional study assessing the use of multikinase inhibitors (MKIs) in the treatment of patients with asymptomatic radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC).
Authors: Marcia S. Brose, Fabian Pitoia, Johannes WA Smit, Chia-Chi Lin, Marc Mardoche Fellous, Yoriko De Sanctis, Iwao Sugitani, Martin Schlumberger
Journal: Journal of Clinical Oncology (2017)

6084 Background: RIFTOS MKI was designed to compare the time to symptomatic progression from study entry in patients with RAI-R DTC for whom there was a decision to treat or not to treat with an MKI in the real-life setting. Here, we report interim baseline characteristics for the first 274 patients enrolled in the study. Methods: RIFTOS MKI is a non-interventional study enrolling patients with asymptomatic RAI-R DTC. The decision to initiate MKIs at study entry was at the discretion of the treating physician. Final analysis will be performed once 700 patients have been enrolled and the last enrolled patient has been followed for 24 months. Results: Of 274 patients, the median duration of observation was 169.5 days. Patients have been enrolled from USA (n = 74), Japan (n = 55), Europe (n = 80), and rest of the world (n = 65); 54% were female and the median age was 68 years. Most patients had an ECOG performance status of 0 or 1 (97%) and distant metastases (81%). The most frequent histology was papillary (73%). The median time from initial diagnosis of DTC to study entry was 7 years. RAI refractoriness was mainly due to lack of RAI uptake (60%), primarily in Japan (80%). Japan also had the shortest median time from RAI classification to initial visit (2 months) vs other regions, and the average dose per RAI treatment and median cumulative activity of RAI were lower in Japanese patients (3.4 and 3.7 GBq, respectively) (Table). Conclusions: The RIFTOS MKI study is the largest non-interventional study in RAI-R DTC. The regional differences in treatment history observed in the RIFTOS MKI study reflect differences in accessibility and treatment practice. The study is ongoing. Clinical trial information: NCT02303444. [Table: see text]
P01.129 Cost-effectiveness of [18F] FET for therapy assessment of temozolomide for patients with glioblastoma in a Belgian healthcare setting
Authors: T Baguet, J Verhoeven, F de Vos, I Goethals
Journal: Neuro-Oncology (2018)

Temozolomide has been approved for the treatment of glioblastoma by the FDA in 2005 and became the standard of care very fast. However, more than 50% of the patients treated with temozolomide do not show any clinical response. MRI forms the main imaging modality to assess the therapy effectiveness. Galldiks et al. reported in 2012 that PET with ([18F] FET) was a better imaging tool to predict the clinical outcome of the therapy than standard MRI. Techniques such as MRI and PET deliver tremendous information albeit at a high cost. With increasing healthcare costs being a huge burden on society, cost-effectiveness becomes an important parameter in medical interventions. Therefore, the cost-effectiveness of [18F] FET for therapy assessment of temozolomide after surgery is calculated here. Clinical data derived from the paper reported by Galldiks et al. was used to set up a decision tree to assess the effectiveness of PET and MRI. In this paper the authors describe the comparison of [18F] FET and gadolinium enhanced T2 for the prediction of clinical outcome after surgery and radiotherapy/temozolomide in glioblastoma patients. They report the TBRmax for PET and volume of gadolinium uptake directly after surgery and after the first session of radiotherapy and temozolomide. After the second scan the patients received another 4 weeks of temozolomide. For the two imaging modalities responders and non-responders were identified based on TBRmax and gadolinium volume difference between scan one and two. Clinical response was assessed on overall survival and progression free survival. Costs were calculated from a Belgian healthcare perspective including all costs done by the government and by social security. Cost-effectiveness was calculated as incremental cost-effectiveness ratio for one extra correct prognosis (ICER 1) and for one non-responder identified (ICER 2). Sensitivity analysis was done by means of one-way deterministic analysis and Monte Carlo analysis. Chances on right prediction of clinical outcome rose with 20.70% for PET in comparison with MRI based on overall survival of the patient and with 22.76% based on progression free survival. Chances on recognition of a non-responder rose with 57.14% based on overall survival and with 58.35% based on progression free survival. Total costs of [18F] FET-scan is 390.25 euro and a total of 780.50 euro for the two scans combined. These results give an ICER 1 value of 3769.77 euro and 3427.07 euro based on respectively overall survival and progression free survival. The results for ICER 2 are 1365.86 euro and 1357.38 euro. Sensitivity analysis show very robust values with low variability. [18F] FET reports a cost-effectiveness of around 1360 euro per non-responder recognized. Sensitivity analysis show these are robust calculations with low variability.
Clinical and dosimetric predictors of acute hematologic toxicity in rectal cancer patients treated with concurrent chemotherapy and intensity-modulated pelvic radiotherapy.
Authors: XiangBo Wan, Yikan Cheng
Journal: Journal of Clinical Oncology (2016)

e15088 Background: To identify clinical and dosimetric factors associated with acute hematologic toxicity (HT) in rectal cancer patients undergoing neoadjuvant intensity-modulated pelvic radiotherapy with concurrent chemotherapy. Methods: We analyzed 130 rectal cancer patients in single institution who were treated with concurrent chemotherapy and neoadjuvant intensity-modulated pelvic radiotherapy. Pelvic bone marrow (BM) was contoured for each patient and divided into three subsites: lumbosacral spine (LSSP), ilium, and lower pelvis (LP) and dose-volume parameters were extracted. HT was graded according to the Common Terminology Criteria for Adverse Events V4.0. Logistic regression was used to test associations between HT and dosimetric/clinical parameters on HT. Receiver operating characteristic (ROC) curves were used to assess the dose tolerances for the significant dosimetric factors with respect to severe ( ≥ grade 3) HT. Results: Of 130 patients, 17 (13.1%), 15 (11.5%), 5 (3.8%), 1(0.8%) experienced acute Grade 3–4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. Patients with BMI ≤ 25 had higher rates of Grade 3 or worse leukopenia (P = 0.006). Increased iliac BM V15 was associated with an increased Grade 3 or worse leukopenia (P = 0.047). Patients with increased iliac BM V20 were more likely to have Grade 3 or worse leukopenia (P = 0.049).ROC curve indicated a V15 of 89.71% (area under ROC curves, 0.680; P = 0.017) and V20 of 86.15% (area under ROC curves, 0.672; P = 0.022) were the tolerated doses for Grade 3 or worse leukopenia. Conclusions: The volume of iliac BM receiving low-dose radiation is associated with severe acute HT. Our study suggest a limit of 89.71% for V15 and 86.15% for V20 to optimize rectal cancer radiation planning, whilst minimizing the risk of Grade 3 or worse acute HT.
Cediranib phase II study in children with metastatic alveolar soft part sarcoma (ASPS).
Authors: John Glod, Julia Wanda Cohen, Brigitte C. Widemann, Anne Goodwin, Joanne Derdak, Eva Dombi, Oxana Borisovna Kapustina, Seth M. Steinberg, Geraldine O'Sullivan, Shivaani Kummar, Alice P. Chen
Journal: Journal of Clinical Oncology (2018)

10540 Background: ASPS, a rare, highly vascular sarcoma with a clinically indolent course, frequently presents with metastases at diagnosis. Standard sarcoma chemotherapy is ineffective. Vascular endothelial growth factor (VEGF) is a promising therapeutic target. In a phase II trial of the VEGF receptor inhibitor cediranib for adults with ASPS, the partial response (PR) rate (RECIST v1.0) was 35% (15/43;95% CI:21-51%); (Kummar S,et al. J Clin Oncol 2013; 31(18): 2296-302). We evaluated the objective-response rate [PR + complete response] of cediranib in the pediatric population (NCT00942877). Methods: Patients (pts) ≤16 years old (yo) with metastatic, unresectable ASPS received cediranib at the pediatric maximum tolerated dose of 12 mg/m2 (≅70% of the fixed adult phase II dose of 30 mg) orally daily [1 cycle (cy) = 28 days]. Response was assessed every 2 cy (RECIST v1.0). A Simon two-stage optimal design (target response rate 35%, rule out 5%, alpha = 0.1, beta = 0.1) was used. With ≥ 1 response in 6 pts, enrollment would expand to 12 pts; with responses in ≥2/12pts, cediranib would be considered active. Results: 7 pts (4 female), median age 13 yo, (range 9-15), all with pulmonary metastases, enrolled on stage 1. Best response was stable disease (SD) (median cy number = 18). 2 pts were removed from study for disease progression (cy 4 and 5), and one pt for surgical resection of primary tumor (cy 16) per pt and local oncologist choice. 5 of 7 pts had SD for ≥14 months. 4 pts with SD remain on study after 18-44+ cy. Each of these pts had 1 (n = 3) or 2 (n = 1) cediranib dose reductions for grade 2 hypertension (n = 1, cy 2), fatigue (n = 2, cy 2), and proteinuria (n = 1, cy 38), and grade 3 ALT elevation (n = 1, cy 1). No growth plate toxicity was detected on MRI. Conclusions: Cediranib did not reach the target response rate in this small pediatric cohort; thus, no additional pts were enrolled. This is in contrast to the adult 35% PR rate. Pediatric dosing was 30% lower compared to adult dosing, which may have contributed to response differences. Prolonged SD was observed in 5 pts, but given the indolent nature of ASPS, SD cannot be clearly attributed to cediranib. Cediranib has an acceptable safety profile, with no growth plate toxicity, with several pts experiencing prolonged SD. Clinical trial information: NCT00942877.
A database of tissue-specific rhythmically expressed human genes has potential applications in circadian medicine
Authors: Marc D. Ruben, Gang Wu, David F. Smith, Robert E. Schmidt, Lauren J. Francey, Yin Yeng Lee, Ron C. Anafi, John B. Hogenesch
Journal: Science Translational Medicine (2018)

Bioinformatic analyses of human tissue samples were used to build a database of rhythmically expressed genes across the body.
Is hospital patient safety culture relevant?
Authors: James N Masciale, Patrick Samedy, Scott Ogden, Steve Brauer, Kent Sepkowitz, Svetlana Granovsky
Journal: Journal of Clinical Oncology (2018)

e18775 Background: Hospital culture is the product of multiple factors such as management directives and mission statements which, in turn, can influence individual attitudes and perceptions (Ryan & Deci, 2000). Patient safety culture is important in order to minimize risks to patients and improve outcomes, and can be thought of as containing 3 main factors: psychological, behavioral, and situational. Each affects patient outcomes (Meddings, et al., 2017) and adverse events (Burlison, et al., 2016). To that end, the Agency for Healthcare Research & Quality developed their Patient Safety Culture Survey (PSCS; Nieva & Sorra, 2003) to assess 12 different factors making up safety culture. Our aim was to examine how each of these uniquely relates to reported adverse events in a tertiary academic cancer hospital setting. Methods: Eligible participants were recruited among staff having direct or indirect contact with patients by way of email and hospital home page announcements. The survey itself was administered by the New York State Partnership for Patients. A total of 3,567 staff participated, representing a variety of roles (e.g. physician, nurse, pharmacist) and services (e.g. medicine, surgery, pediatrics). Adverse events in the three months prior to survey administration were recorded to an online reporting system. Staff can record events that cause actual harm ranging from level 0 (a near miss) to level 4 (death). Results: Multiple regressions analyses, including all 12 subscales controlling for each other, suggest that within inpatient floors, higher levels of Organizational Learning (β = -.30) and Overall Perceptions of Safety (β = -.28) were associated with reported adverse events of lowered severity. Greater perceived levels of Teamwork (β = .46) were associated with more severe reported adverse events. Conclusions: Among the 12 subscales of the PSCS, three emerged as uniquely predictive of severity of reported adverse events, with moderate effect sizes. Therefore, assessing and analyzing safety culture may have tangible, beneficial effects for patients. Potential interventions to maintain and improve culture are discussed.
Tumor sidedness and intrinsic subtypes in patients with stage II/III colon cancer: Analysis of NSABP C-07 (NRG Oncology).
Authors: S. Rim Kim, Nan Song, Greg Yothers, Patrick Gavin, Carmen Joseph Allegra, Soonmyung Paik, Katherine L. Pogue-Geile
Journal: Journal of Clinical Oncology (2017)

3514 Background: The predictive value of tumor sidedness in colorectal cancer is currently of interest especially in metastatic setting for anti-EGFR therapy response. We tested whether intrinsic molecular subtype classification predictive of treatment benefit in stage II/III colon cancer is an independent novel marker in association with tumor sidedness. Methods: All available cases included in the NSABP/NRG C-07 trial for which we had both gene expression data and anatomical data (n=1603) were used to determine the molecular subtypes using the following classifiers; the Colorectal Cancer Assigner (CRCA), the Colon Cancer Subtypes (CCS) and the Consensus Molecular Subtypes (CMS). Frequency of tumor sidedness in each subtype and recurrence-free survival were analyzed. Results: Intrinsic subtypes were differentially distributed in right- and left-colon tumors with the exception of the stem-like or CMS4 (mesenchymal) subtype (Table 1). Sidedness was not associated with prognosis (p=0.82, HR: 1.022 [CI: 0.851-1.227]) or prediction of patients with greater benefit from oxaliplatin when combined with 5-Fu+LV (interaction p=0.484). Conclusions: Although tumor sidedness is associated with distribution of intrinsic subtypes in stage II/III colon cancer, it is not predictive of survival benefit from oxaliplatin in C-07. Support: -180868, -180822, U24-CA196067; HI13C2162; PA DOH; Sanofi-Synthelabo Clinical trial information: NCT00004931. [Table: see text]