tbuckley/cabot-search huggingface dataset:
Cognitive outcomes in meningioma patients undergoing surgery: individual changes over time and predictors of late cognitive functioning
Authors: Sophie J M Rijnen, Ikram Meskal, Marjan Bakker, Wouter De Baene, Geert-Jan M Rutten, Karin Gehring, Margriet M Sitskoorn
Journal: Neuro-Oncology (2019)

Meningioma patients are known to face cognitive deficits before and after surgery. We examined individual changes in cognitive performance over time and identified preoperative predictors of cognitive functioning 12 months after surgery in a large sample of meningioma patients.Patients underwent neuropsychological assessment (NPA) using CNS Vital Signs 1 day before (T0) and 3 (T3) and 12 (T12) months after surgery. Patients' sociodemographically corrected scores on 7 cognitive domains were compared with performance of a normative sample using one-sample z tests and chi-square tests of independence. Reliable change indices with correction for practice effects were calculated for individual patients. Linear mixed effects models were used to identify preoperative predictors of performance at T12.At T0, 261 patients were assessed, and 229 and 82 patients were retested at T3 and T12, respectively. Patients showed impaired cognitive performance before and after surgery, and although performance improved on the group level, cognitive scores remained significantly lower than in the normative sample up to T12. On the individual level, performance remained stable in the majority of patients. Better preoperative performance, younger age, male sex, and higher educational level predicted better late cognitive performance.Meningioma patients face serious and persistent pre- and postsurgical cognitive deficits. A preoperative NPA together with sociodemographic characteristics may provide valuable information on the late cognitive outcome of individual meningioma patients. These results can help to inform patients and clinicians on late cognitive outcomes at an early stage, and emphasizes the importance of presurgical NPA and timely cognitive rehabilitation.
Evaluation of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) tool: Acceptability, feasibility and potential role in enhancing clinical care of men with early-stage prostate cancer.
Authors: Doris Howell, Sarah Stevens, Farzana Haji, Zahra Ismail, Michael Donald Brundage
Journal: Journal of Clinical Oncology (2016)

e21631 Background: The purpose of this multi-site study was to test feasibility of implementing the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) symptom tool in routine ambulatory care and evaluate its acceptability and role in customizing care from the perspective of patients and clinicians. Methods: This feasibility study recruited prostate cancer patients from four cancer centres between November 2014 and June 2015. Eligible patients were those attending radiation or surgical oncology consultation, follow-up, or on-treatment review. Patient participants completed the EPIC-CP symptom reporting tool, results of which were reviewed as part of the clinical encounter with nurse and/or physician. Experience with the tool was evaluated from the patient perspective through a 9-item Patient Exit Survey; and from the provider perspective, through semi-structured qualitative interviews. Results from the patient and provider perspectives were analyzed and compared to identify common themes. Results: A total of 287 Patient Exit Surveys were completed. Patients averaged 2.8 EPIC-CP screens during the study. Missing data across all 16 items ranging from 0.5% (bowel function) to 9.5% (orgasm quality). Eighty-two percent (82%) of patients were willing to complete similar questionnaires at future clinic visits. Only a few patients (3.5%) felt that the EPIC-CP tool did not help with their clinical encounter, and only 4% felt that the content should not include questions about sexual functioning. Thematic analysis from provider interviews revealed that the EPIC-CP tool captures essential prostate-specific effects that facilitated person-centered communication and customization of interventions. Conclusions: EPIC-CP is highly endorsed by healthcare practitioners and by prostate patients across consultation and follow-up visits, and across four diverse cancer centres. The EPIC-CP tool captures prostate-specific symptom information that assists in enhancing clinical care and symptom management. Provincial roll-out of this tool as a standard of care is recommended.
Phase II study of hepatic artery chemotherapy for advanced adenocarcinoma of the pancreas.
Authors: Robert D. Levin, Pakorn Sirijintakarn
Journal: Journal of Clinical Oncology (2016)

e15733 Background: Cure of metastatic pancreatic cancer is not previously described.. Methods: Chemotherapy via intra-arterial perfusions are more intense than with intravenous chemotherapy. We gave a monthly 5 hour perfusion of the hepatic artery perfusion using DDP (50 mg/m2) and MIC (8 mg/m2). Also given is monthly intravenous (IV) therapy with four hours of Leucovorin (LV) (1000mg/m2/day), with an injection of FUDR, 800 mg/m2, during the last hour of LV, daily x 5 days. This combination defines LVDRPMIC. Doses or FUDR and MIC are increased 10% monthly if grade II toxicity did not occur in the prior cycle. Patients with Stage IIIB disease received 2 cycles of LVDRPMIC prior to radiotherapy. Ninety six patients with adenocarcinoma of the pancreas in stage IIIB or 4 since 1991 were given chemotherapy every four weeks. All patients had no prior chemotherapy. Eighty six patients with stage IV disease received the therapy for up to 6 months depending tolerance of the mitomycin C, but afterwards only IV LVFUDR therapy was given until progressive diseasedeveloped. Thirteen patients with stage IIIB disease received two cycles of LVDRPMIC followed by radiotherapy.. Unusual toxicities observed included duodenal ulceration in the week after infusion. Mitomycin toxicity had a nadir 10-14 days after injection. Since 1991, there was one patient had hemolysis related to the mitomycin, but no other hemolysis was seen. Results: Of the 13 patients with IIIB disease, none were cured, and most had terminal relapse of tumor into the duodenum; Conclusions: Toxicity of LVDRPMIC was generally acceptable. We describe 7 patients who had Stage IV initially, who achieved a CR, and of these 7, 4 are now > 7 years after therapy and probably cured. Best Responsein IV Disease # Mean Survival ± SD (mos) # without relapse CR 7 98.6 ± 72.8 (Median 90.7) 4 PR 10 30.1 ± 41.6(Median 13.3) 0 SD 18 10.5 ± 6.8 (Median 7.5) 0 PD 10 6.6 ± 3.0 (Median 6.7) 0 # Patients with Early Septic Death: 4 # Patients with early death unrelated to therapy: 1 (Auto accident) # Patients with >Gr 2 toxicity: 8(1 Liver abscess and varix bleed, 3 hematemesis due to necrosis in stomach, and 4 had pancreatitis) # Patients only received 1 cycle of LVDRPMIC and chose not to return for further therapy: 5
Early mortality with immune checkpoint inhibitors (IOs) in solid tumors: An inconvenient truth?
Authors: Eric Winquist, Sara Kuruvilla, Anthony Charles Nichols, John Gordon Lenehan, S. Danielle Macneil, David A. Palma
Journal: Journal of Clinical Oncology (2018)

12121 Background: Overall survival (OS) benefit with IOs has been demonstrated in several solid tumor types leading to their rapid adoption and use in practice. We noticed IO randomized controlled trials (RCTs) with early crossover of OS Kaplan-Meier (KM) curves favoring control therapy but with overall benefit favoring IO therapy. This suggests a subpopulation of patients at a higher risk of death on IO therapy compared to control therapy early in treatment. We performed a systematic review to examine the frequency and characteristics of IO RCTs showing this negative discordant crossover (NDC). Methods: RCTs studying IOs and non-IOs in solid tumors with published OS KM curves were identified by electronic database search and FDA approvals 2015-17. Early OS divergence was identified by blinded reviewers. NDC of OS KM curves was defined as early divergence discordant with an overall beneficial survival trend. RCT characteristics were compared using Fisher’s exact test. Results: 29 IO RCTs providing 33 comparisons and 24 non-IO RCTs providing 25 comparisons were identified. Nine IO RCTs (27%) and 1 non-IO RCT (4%) demonstrated NDC (p = 0.03). NDC occurred in NSCLC (3/9), urothelial cancer (2/2), melanoma (2/9), SCLC (1/2) and CRPC (1/2) RCTs. RCTs with NDC trended to less often study melanoma (22% v 46%) and squamous cancer (0% v 13%), and less often report OS benefit (22% v 71%). They trended to more often study urothelial cancer (22% v 0%) and 2nd-line treatment (56% v 38%), and more often have active treatment control arms (89% v 75%). Conclusions: Early NDC of overall survival curves occurs commonly in IO RCTs. This suggests a subpopulation of patients at higher risk of early death with IO therapy. Causes of this mortality are unclear but could include toxicity of IO therapy, superior antitumor effects of control therapy, and/or tumor growth promoting effects of IO therapy. We are quantitating this risk. Such crossover complicates proportional hazards modeling. Further research to identify the causes of and patients at risk for early mortality with IO therapy should be a priority and patients should be informed of this potential risk.
Perioperative outcomes in elderly patients undergoing pancreatic resection for pancreatic adenocarcinoma: A systematic review and meta-analysis.
Authors: Elinor Tan, Charbel Sandroussi
Journal: Journal of Clinical Oncology (2018)

e16227 Background: Pancreatic cancer is most frequently diagnosed among people aged 65-74. Pancreatic resection in the elderly with pancreatic tumour is controversial however surgery is one of a therapeutic option that offers a potential cure. As the demographics continue to shift towards an aged population, the incidence of pancreatic cancer is expected to rise. This study aims to compare postoperative outcomes of pancreatic resection for pancreatic adenocarcinoma among the elderly (≥70yr, ≥75yr, ≥80yr) and their respective younger counterparts ( < 70yr, < 75yr, < 80yr). Methods: MEDLINE, EMBASE, PubMed and Cochrane Library, were searched. Quality of studies was assessed using the NOS. Primary end-point was 30-day mortality. Secondary endpoints were postoperative complications, length of stay (LOS), postoperative pancreatic fistula. MH-method was used to combine odds ratios and IV-method to combine mean differences. A random-effects model was applied where applicable. Publication bias was evaluated using funnel plots. Results: Ten studies [n = 4351] were included in this review. Elderly patients were associated with higher ASA grade (p < 0.001) and cardiovascular comorbidities (p < 0.001). Older patient had significantly larger tumours (p < 0.001). Nonetheless, they were less likely to undergo portal vein resection (p = 0.005) and had lesser intraoperative blood loss volume (WMD [95%CI], -197.1 [-417, 22.8], p = 0.010) as compared to their younger counterparts. There was no difference in the depth of tumour or nodal stage between both groups (p > 0.05). Postoperative complications were higher in the older group (OR [95%CI], 1.48 [1.12, 1.95], p = 0.006, I2 = 31%) nonetheless, there was no difference in postoperative pancreatic fistula (OR [95%CI], 1.05 [0.80, 1.39], p = 0.71, I2 = 0%) length of hospital stay (WMD [95%CI], 0.75 [-0.50, 2.00], p = 0.24, I2 = 37%) and postoperative mortality (OR [95%CI], 1.41 [0.89, 2.25], p = 0.15, O2 = 0%). Conclusions: Pancreatic resection of pancreatic adenocarcinoma can be performed safely on elderly patients with acceptable risks in experienced centres by expert surgeons. Age alone is not a reliable predictor of poor surgical outcomes.
Trajectories of Nevus Development From Age 3 to 16 Years in the Colorado Kids Sun Care Program Cohort
Authors: Nancy L. Asdigian, Anna E. Barón, Joseph G. Morelli, Stefan T. Mokrohisky, Jenny Aalborg, Robert P. Dellavalle, Matthew F. Daley, Marianne Berwick, Keith E. Muller, Neil F. Box, Lori A. Crane
Journal: JAMA Dermatology (2018)

Nevi are a risk factor for melanoma and other forms of skin cancer, and many of the same factors confer risk for both. Understanding childhood nevus development may provide clues to possible causes and prevention of melanoma.To describe nevus acquisition from the ages of 3 to 16 years among white youths and evaluate variation by sex, Hispanic ethnicity, and body sites that are chronically vs intermittently exposed to the sun.This annual longitudinal observational cohort study of nevus development was conducted between June 1, 2001, and October 31, 2014, among 1085 Colorado youths. Data analysis was conducted between February 1, 2015, and August 31, 2017.Total nevus counts on all body sites and on sites chronically and intermittently exposed to the sun separately.A total of 557 girls and 528 boys (150 [13.8%] Hispanic participants) born in 1998 were included in this study. Median total body nevus counts increased linearly among non-Hispanic white boys and girls between the age of 3 years (boys, 6.31; 95% CI, 5.66-7.03; and girls, 6.61; 95% CI, 5.96-7.33) and the age of 16 years (boys, 81.30; 95% CI, 75.95-87.03; and girls, 77.58; 95% CI, 72.68-82.81). Median total body nevus counts were lower among Hispanic white children (boys aged 16 years, 51.45; 95% CI, 44.01-60.15; and girls aged 16 years, 53.75; 95% CI, 45.40-63.62) compared with non-Hispanic white children, but they followed a largely linear trend that varied by sex. Nevus counts on body sites chronically exposed to the sun increased over time but leveled off by the age of 16 years. Nevus counts on sites intermittently exposed to the sun followed a strong linear pattern through the age of 16 years. Hispanic white boys and girls had similar nevus counts on sites intermittently exposed to the sun through the age of 10 years, but increases thereafter were steeper for girls, with nevus counts surpassing those of boys aged 11 to 16 years.Youths are at risk for nevus development beginning in early childhood and continuing through midadolescence. Patterns of nevus acquisition differ between boys and girls, Hispanic and non-Hispanic white youths, and body sites that are chronically exposed to the sun and body sites that are intermittently exposed to the sun. Exposure to UV light during this period should be reduced, particularly on body sites intermittently exposed to the sun, where nevi accumulate through midadolescence in all children. Increased attention to sun protection appears to be merited for boys, in general, because they accumulated more nevi overall, and for girls, specifically, during the adolescent years.
TCT-39 Functional Assessment of In-stent Restenosis With Quantitative Flow Ratio (QFR). A Comparison With De Novo Coronary Stenoses.
Authors: Catherine Liontou, Hernan Mejia-Renteria, Sonoka Goto, hyunjong lee, Francesco Lauri, Fernando Macaya, Nieves Gonzalo, Maria Del Trigo, Pilar Jimenez-Quevedo, Pablo Salinas, Luis Nombela Franco, Ivan Nuñez-Gil, Antonio Fernandez-Ortiz, Javier Escaned
Journal: Journal of the American College of Cardiology (2018)
Evaluation of the risk of relapse of patients with stage III cutaneous melanoma at event-free survival time points.
Authors: Alison M. Weppler, Derrick G Lee, Dirk van Niekerk, Kerry J. Savage
Journal: Journal of Clinical Oncology (2017)

e21074 Background: The prognosis of patients (pts) with stage III cutaneous melanoma is typically estimated at the time of diagnosis. Recent studies in other malignancies have reported the utility of estimating outcome using a conditional survival approach. Herein, we evaluated the risk of melanoma relapse at event-free survival (EFS) time points in pts with stage III cutaneous melanoma in British Columbia (BC). Methods: The Cancer Surveillance &amp; Outcomes Database and Co Path Database were screened to identify pts diagnosed between 1998 and 2013 in BC with completely resected stage III cutaneous melanoma. A competing risk model was used to estimate 5-year (y) risk of recurrence at pre-specified EFS time points, with non-melanoma related deaths considered competing risks. Results: In total, 513 patients were identified: 329 males (64%); median age at diagnosis 58 y (16-99); median follow-up 5.6 y (0.2-17.5) for living pts. In total, 330 pts (64%) had a melanoma recurrence and most were distant metastases (n=194, 59% v regional n=79, 24% v local n= 57, 17%). The median time to first recurrence of any type was 11.6 months. The 5-y risk of any relapse was 63.8% at EFS 0, which decreased to 11.4% by EFS 5 y (Table 1). Full staging information was available for 423 pts (83%); the risk of relapse was lower for stage IIIA compared to IIIB and IIIC at EFS 0 (48%, 68% and 77%, respectively, p&lt;0.001). By EFS 2 y, there was no difference between the groups; however, the 5-y risk of relapse was still moderate (IIIA 40%, IIIB 41%, IIIC 36%, p=0.46). Conclusions: While the risk of melanoma relapse decreases over time, it remains moderate up until 5 y, with distant recurrence as the most frequent event. This data can help inform surveillance guidelines and serves as a benchmark to compare the impact of novel therapies in the adjuvant setting. [Table: see text]
Quality of life in patients undergoing pleurectomy and decortication for malignant pleural mesothelioma.
Authors: Wickii T. Vigneswaran, Diana Kircheva, Diego Patino, Sydeaka Watson, Hedy L. Kindler, Aliya Noor Husain
Journal: Journal of Clinical Oncology (2016)

8556 Background: Pleurectomy and decortication (PD), a maximal cyto-reductive surgery for malignant pleural mesothelioma (MPM) improves survival in selected patients. In others the survival benefit is modest. We report QoL following PD in a large cohort of patients. Methods: Patients undergoing PD were prospectively enrolled . EORTC QLQ-C30 was utilized to assess the QOL at baseline, 1, 4 -5, 7- 8, and 10-11 months (m) postoperatively. Global health, variables in functional domain and symptoms domains were investigated. Sub-group analysis were performed for pre-operative performance status (PS, 0 vs 1&2), histology (epithelioid vs non-epithelioid) and pathological tumor volume (PV, < 600 ml vs > 600mls). Survival was summarized using Kaplan-Meier estimates; Log-rank tests were used to compare subgroups. Results: 114 patients were enrolled. Median age: 70 years (range: 50-88). PS0: 35 (30.7%), PS1: 74 (64.9%), PS2: 5 (4.4%). Epithelioid histology: 61 (53.5%), volume < 600ml: 58 (50.9%). Overall global health worsened at the first post-operative month (p = 0.0005) returning to baseline at 3-4 months with subsequent improvement. Non-epithelioid histology, PS 1&2 and PV > 600mls did not show deterioration at 1 month, and remained unchanged. Functional domain, physical functioning, role functioning and social functioning deteriorated at 1 month. Cognitive function was not altered whereas emotional functioning significantly improved. All measures continued to improve during follow-up. In the symptoms domain: pain, fatigue and insomnia were worse at 1 month in all groups. Dyspnea was worse only in PS 0, epithelioid and in patients with volume < 600 ml. The overall survival was significantly better among patients with epithelioid histology (19.9m p < 0.0001), PS 0 (19.1m, p = 0.031), and volume < 600ml (19.1m, p < 0.001). Conclusions: Improvement in QoL was observed after the first month and maintained at late follow-up. QoL was not adversely affected by PD at any time in patients with PS 1&2, non-epithelioid histology and tumor volume > 600 ml. A trend towards improvement at late follow-up was observed. The net benefit of PD justifies the procedure in the majority of patients with MPM.
Identification of potentially actionable molecular alterations in advanced hepatocellular carcinoma (HCC).
Authors: James J. Harding, Zachary J. Heins, Louise Catherine Connell, Tara Soumerai, Nancy E. Kemeny, William R. Jarnagin, Eileen Mary O'Reilly, Ronald P. DeMatteo, Michael Ian D'Angelica, Maeve Aine Lowery, T. Peter Kingham, Maya Gambarin, David Michael Hyman, Michele LY, Casey R. Hamilton, Michael F. Berger, David B. Solit, Leonard Saltz, Nikolaus Schultz, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2016)

e15635 Background: Next-generation sequencing (NGS) technologies have been applied to early stage HCCs; however, it is unclear if NGS is feasible or clinically meaningful for advanced HCC patients (pts). Methods: We prospectively identified unresectable/metastatic HCC pts seen at our Center from 2013 to 2015. Tumors and matched normal samples underwent testing by NGS of 410 cancer-associated genes. We correlated genomic alterations (alts) by Fisher’s exact test with clinical parameters and defined actionable molecular alts as those for which there are FDA approved biomarkers and drugs in another indication. Results: 53 advanced HCC pts underwent NGS. Male/female: (68%/22%), ethnicity: Asian/non-asian (28%/72%), Extrahepatic spread/none: (70%/30%), Etiology: Viral/non-viral (50%/50%). 40/53 (75%) pts received sorafenib. Median alts per sample: 5, median sample coverage: 605X, median sample purity 60%. Recurrent alts in > 5% of cases were in TERT (42%), CTNNB1 (27%), TP53 (27%), RECQL4 (13%), TSC2 (12%), NFE2L2 (10%), FGF4 (8%), CDND1 (8%), MYC (8%), KIT (8%), JAK1 (8%), APC (6%), AXIN1 (6%), KDM5A (6%) and SETD2 (6%). Wnt-beta pathway alts trended towards mutual exclusivity with TP53 alts (odds ratio 0.4, p = 0.07). Viral mediated HCCs were more likely to harbor alts in TP53 (p = 0.02). Oncogenic drivers were not detected in 11% of cases. Actionable alts were quite rare and found in only 7% cases (3 TSC truncating and 1 KIT mutation). All JAK1 alts occurred in the kinase domains, are predicted to convey cytokine–independent signaling, and are unique to HCC when compared to 169 other solid tumors that harbor JAK1alts. Serial tumor sampling in 3 pts revealed discordance of alts across separate tumors. Genomic alts did not correlate with sorafenib response or overall survival. Conclusions: Advanced HCC tumors exhibit similar genomic alts when compared to published data enriched with early stage cases. NGS of advanced HCCs does not inform routine clinical practice due to low rates of actionable alts; however, remains a powerful tool to explore genomic differences in HCC etiologic factor. Future studies will focus on genomic profiling on larger cohorts of pts with discrete ethnicity and HCC-etiology.