tbuckley/cabot-search huggingface dataset:
Comprehensive molecular and genomic characterization of pancreatic tropism in metastatic renal cell carcinoma.
Authors: Nirmish Singla, Jacob Choi, Oreoluwa Onabolu, Layton Woolford, Christina Stevens, Vanina Tcheuyap, Tiffani McKenzie, Zhiqun Xie, Tao Wang, Renee McKay, Alana Christie, Payal Kapur, Brian I. Rini, James Brugarolas
Journal: Journal of Clinical Oncology (2019)

633 Background: Patients with metastatic renal cell carcinoma (mRCC) involving the pancreas have been shown to exhibit a relatively indolent course, yet the biologic explanation is unclear. We sought to characterize the genomic landscape of patients with mRCC harboring pancreatic metastases to identify molecular drivers of pancreatic tropism. Methods: mRCC patients harboring pancreatic metastases from UTSW and Cleveland Clinic were identified. Clinicopathologic data and oncologic outcomes were analyzed. Samples were obtained from primary tumors, metastatic sites (including pancreatic or other distant metastases), and matched normal tissue. Whole exome (WES) and RNA sequencing of tumors was conducted. Patient-derived xenograft (PDX) models were generated from a subset of patients, and the engrafted tumors were analyzed. Results: 31 mRCC patients with pancreatic metastases were included with 54 tumor samples derived from the primary tumor or thrombus (24), pancreatic metastasis (21), or other metastatic sites (9). Median follow-up was 101 months. Clinicopathologic characteristics were similar between the two institutional cohorts, and all but one patient were favorable or intermediate IMDC risk. All patients had clear cell histology. 8 patients (26%) were metastatic at diagnosis, and median time to metastasis in the remaining patients was 74 months (IQR 32-120). Overall (OS) and cancer-specific (CSS) survival did not vary by IMDC risk group. Morphologically, tumors largely displayed low-grade acinar patterns. WES with matched normal tissue and RNAseq were completed with adequate quality for 48 and 30 samples, respectively. 14 PDX lines were generated, of which 5 (36%) engrafted stably (≥2 passages). WES from 2 tumorgraft specimens revealed preservation of specific mutations in the corresponding human samples. Conclusions: mRCC patients with pancreatic metastases exhibit remarkably favorable survival outcomes. The relatively indolent biology of these tumors is reflected histologically and genomically and can be recapitulated in PDX models. Understanding tumor heterogeneity may help refine prognostic models for mRCC and hold implications for improved personalization of therapy.
Programmed death-ligand 1 (PD-L1) expression in pheochromocytoma.
Authors: Yasuhiro Hashimoto, Hayato Yamamoto, Shingo Hatakeyama, Takahiro Yoneyama, Chikara Ohyama
Journal: Journal of Clinical Oncology (2019)

537 Background: Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy that is frequently overexpressed in several neoplasms. But there were few reports about PD-L1 expression of pheochromocytoma. In the present study, we examined PD-L1 expression in pheochromocytoma. Methods: PD-L1 mRNA expression was compared across 184 pheochromocytoma, 492 prostate cancer cases and 404 bladder cancer cases based on The Cancer Genome Atlas (TCGA). Furthermore, we enrolled 32 pheochromocytoma patients treated with surgery at our hospital between June 2005 and February 2016. We conducted an immunohistochemistry (IHC) of PD-L1 using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0/1/2). Results: Comparison of PD-L1 mRNA expression based on the TCGA revealed that PD-L1 expression was significantly higher in pheochromocytoma than in bladder cancer and in prostate cancer (p &lt; 0.001). In the SP 142 assay of our 32 pheochromocytoma, the prevalence of positive PD-L1 expression (IHC score 1 or 2 (1/2)) in tumor-infiltrating immune cells (TICs) was 8 patients (25%). The prevalence of positive PD-L1 expression in tumor cells (TCs) was 9 patients (28.1%). Tumor diameter of PD-L1 (+) in TICs patients was 3.36±0.35 cm and that of PD-L1 (-) in TCs patients was 5.37±0.50cm, there was statistically significance between two groups. (unpaired t test: p=0.044) In our cohort, there were two malignant pheochromocytoma. But there were not PD-L1 positive cases in malignant pheochromocytoma. Conclusions: PD-L1 expression is relatively high in pheochromocytoma compared to bladder cancer and prostate cancer based on TCGA. In the SP142 assay of our 32 pheochromocytoma cases, tumor diameter of PD-L1 (-) in TICs cases was larger than that of PD-L1 (+) cases. In our cohort, there were not PD-L1 (+) cases in malignant pheochromocytoma. These findings suggest that PD-L1 expression of pheochromocytoma was comparatively common and PD-L1 positive expression of pheochromocytoma may not be associated with tumor aggressiveness.
Safety and efficacy of restarting immune checkpoint inhibitors (CPI) after immune-related adverse events (irAEs) in metastatic renal cell carcinoma (mRCC).
Authors: Sarah Abou Alaiwi, Dylan J Martini, Wanling Xie, Amin Nassar, Ziad Bakouny, John A. Steinharter, Pier Vitale Nuzzo, Ronan Flippot, Nieves M. Chanza, Xiao X. Wei, Bradley Alexander McGregor, Mehmet Asim Bilen, Toni K. Choueiri, Lauren Christine Harshman
Journal: Journal of Clinical Oncology (2019)

652 Background: CPI can induce a range of irAEs with various degrees of severity. Clinical experience with retreatment following clinically significant irAEs is growing. Methods: We retrospectively reviewed mRCC patients treated with CPI-based regimens who had &gt;1 week therapy delay for irAEs at Dana Farber and Emory to characterize the safety and outcomes of retreatment. Toxicity was graded by CTCAEv5. Patients were divided into retreatment (R) and discontinuation (D) cohorts. Patient characteristics were compared by Fisher’s exact test or Wilcoxon’s rank sum test. ORR, OS and PFS were assessed descriptively. Results: Of 339 treated with CPI, 53 (16%) had irAEs warranting treatment interruption: 24 (45%) in R and 29 (55%) in D. Median (med) time to drug interruption was 2.0 (&lt;0.1-74) months (mos) in D and 3.2 (&lt;0.1-21) mos in R (p=0.89). Prior to irAE onset, 8 (28%) of cohort D and 5 (21%) of cohort R experienced partial responses (PR). While type of irAEs were balanced across D and R, initial irAEs were less severe in R vs D (all p&lt;0.05) with fewer grade (gr) 3-4 events (29% vs 66%), less hospitalizations (25% vs 69%), and lower steroid requirements (&gt;40 mg: 29% vs 79%). The most common irAEs in R were transaminitis, pancreatitis and dermatitis with 7 gr 3/4 events (pancreatitis, colitis, adrenal insufficiency and dermatitis). Median drug break before retreatment was 1.2 (0.3-4.8) mo. Subsequent irAEs occurred in 42% (n=10) after restarting (8 new, 2 recurrent) with 2 discontinuations; 6/10 were gr 3 with no gr 4/5 events. Median interval to irAE recurrence after retreatment was 2.1 (0.5-3.3) mos. Retreatment resulted in 4 (17%) PRs in patients whose disease had not responded prior to irAE (med time to PR from R = 2 mos). Conclusions: Despite a significant rate of irAE recurrence, most patients with prior clinically significant irAEs can be safely retreated. Retreatment can induce responses in an appreciable proportion of patients with no response prior to irAE. Larger studies are warranted to confirm these findings. [Table: see text]
The impact of the time to start radiotherapy (TRT) on overall survival in newly diagnosed glioblastoma.
Authors: Vanessa Montes Santos, Marcella Coelho Mesquita, Maria Del Pilar Estevez-Diz, Gustavo N Marta, Olavo Feher
Journal: Journal of Clinical Oncology (2015)

2040 Background: Glioblastoma (GB) is the most common malignant primary brain tumor in adults. The standard therapy for newly diagnosed glioblastoma is surgical resection followed by radiotherapy (RT) and temozolomide (TMZ). In some institutions it is difficult to start radiotherapy within 2 to 4 weeks following surgery, mostly due to logistic limitations. On the other hand it is unclear how TRT impacts OS in GB. This study aims to evaluate the impact of the time to start radiotherapy (TRT) on overall survival of GB treated with TMZ and RT. Methods: In this retrospective study we included all consecutive patients with GB treated at the Instituto do Cancer do Estado de São Paulo (ICESP) with TMZ and RT from 2008 to 2014. Patients with recurrent or secondary GB were excluded. TRT was defined as the time between surgery and the first day of RT, measured in days. The primary end point was overall survival (OS) with regard to TRT. Categorical data was showed as frequencies and percentiles. Survival analysis was performed using Kaplan-Meier curves and log-rank test for comparison between survival curves. Univariate and multiple Cox regression model were performed for overall survival, and stepwise forward method was used for selection variables. We considered 5% of level of significance for all hypotheses tests. All statistical analysis was performed using SPSS for Windows v.18. Results: A total of 89 patients were included in this study. The median OS was 27 months for the whole group. Median TRT was 70 days. In the multivariate analysis we identified age was the only significant independent predictor for OS. TRT analyzed as a continuous variable did not impact negatively on OS. When considering TRT at cutoff points of 45 and 60 days, again no negative impact on OS was observed, although a trend was observed for a TRT > 60 days. (HR = 1.93 (95% CI 0.99 – 3.75); p = 0.053). The same adverse trend is observed when considering only younger patients (age < 65 y.o.), for a TRT > 60 days (HR = 2.14 (95% CI 0.99-4.67); p = 0.055). Conclusions: Within the limitations of this retrospective analysis, we could not show a clear statistical significant adverse impact of TRT on OS in glioblastoma up to 60 days. However it is a possible that a TRT > 60 days adversely affects OS.
Hospitalization after prostate biopsy in Iceland: Results from a nationwide study.
Authors: Birgitta Ã“lafsdÃ³ttir, Rafn Hilmarsson, Jon Orn Fridriksson, Sigurdur Gudmundsson, Sigurdur Gudjonsson
Journal: Journal of Clinical Oncology (2019)

113 Background: The best method to confirm prostate cancer diagnosis is by performing a transrectal ultrasound guided biopsy. This procedure does not come without risks as international reports suggest that frequency of hospitalization after biopsy are increasing. This study aimed to estimate incidence and risk factors for hospitalization after prostate biopsy in Iceland. Methods: Every patient in Iceland who had undergone a prostate biopsy during the years 2013-2017 was included in the study. Primary outcome measure was hospitalization within fifteen days from the biopsy. We also studied the type of infectious agents and resistance to ciprofloxacin or trimethoprim. Multivariable logistic regression model was used to identify risk factors for hospitalization. Results: Of 2076 men who had prostate biopsies 59 (2.8%) were hospitalized within fifteen days. Of these men 45 (76.3%) were hospitalized because of infection, 6 (10.2%) were hospitalized because of bleeding and 8 (13.5%) were hospitalized for other reasons. Risk factor for hospitalization was higher age (OR 1.06 p &lt; 0.001). An antibiotic prescription within 6 months of biopsy was a protecting factor (OR 0.57 p = 0.04). E.coli was the most common infectious agent (73.3%). Pseudomonas, Staphylococcus and Streptococcus dysgalactiae where other agents. Of those admitted to hospital with infection 57.1% of the agents were resistant to ciprofloxacin and 54% to trimethoprim. 31.4% of the infectious agents were resistant to both antibiotics. Conclusions: Despite the invasive nature of the procedure and increasing bacterial antibiotic resistance the rate of hospitalization was relatively low (2.8%). Antibiotic resistance to ciprofloxacin or trimethoprim might prompt a change in common prophylactic practice and a need for new clinical practice guidelines in Iceland.
Pulmonary physiology is poorly associated with radiological extent of disease in systemic sclerosis-associated interstitial lung disease
Authors: Amrit Jhajj, Harinder Pal Gill, Cameron J. Hague, Darra Murphy, Brett Elicker, Jeanette Soon, Nada Sulaiman, Daniela Castillo-Saldana, Pearce G. Wilcox, James Dunne, Joyce S. Lee, Paul J. Wolters, Brett Ley, Kirk D. Jones, Julie Morisset, Christopher J. Ryerson
Journal: European Respiratory Journal (2019)

Trials in systemic sclerosis-associated interstitial lung disease (SSc-ILD) typically use forced vital capacity (FVC) as the primary end-point [1, 2]; however, pulmonary function tests have limitations in SSc-ILD, notably being influenced by non-ILD factors such as pulmonary hypertension and diseases of the chest wall. High-resolution computed tomography (HRCT) may provide a more direct assessment of ILD severity, but HRCT-derived visual and quantitative scores also have limitations. The objective of this study was to determine the correlation of visual HRCT findings with severity, progression and mortality of SSc-ILD, and specifically whether HRCT findings and lung function measurements provide redundant or complementary measures of SSc-ILD severity and prognosis. Pulmonary physiology is poorly associated with radiological extent of disease in systemic sclerosis-associated interstitial lung disease <http://ow.ly/Bx0X30o92aV>
Decreasing ureteral stent duration following radical cystectomy decreases readmissions and urinary infectious complications.
Authors: Hamza Mustafa Beano, Jiaxian He, Caitlin Hensel, William Mills Worrilow, Kris E Gaston, Peter E Clark, Stephen Boyd Riggs
Journal: Journal of Clinical Oncology (2019)

366 Background: Readmission following Radical Cystectomy with Urinary Diversion (RCUD) is often related to Urinary Tract Infection (UTI). We hypothesized that decreasing the duration of ureteral stenting postoperatively would decrease UTI-related complications without affecting ureteroenteric stenosis (UES) rates. Methods: We analyzed a prospectively and retrospectively collected dataset for cystectomy patients at our tertiary center. Adult patient who underwent RCUD for malignancy from January 2013-January 2018 were included. Patients with a history of abdominal/pelvic radiation and continent diversions were excluded. The patient population was divided to Late stent removal group (LSR- POD 14) and early stent removal group (ESR- POD 4). Statistical methods included t-test, chi-square test and multivariate logistic regression. Results: 177 patients were included in the final analysis after inclusion/exclusion criteria were applied. The LSR (n=75) and ESR (n=102) groups were similar in preoperative characteristics except higher intracorporeal ileal conduit formation in ESR. The LSR had higher 90-day overall readmission rates (OR=2.26, 95% CI;1.13,4.51, p-value=0.021), UTI-related readmissions (OR=3.05, 95% CI:1.32,7.04, p-value=0.010) and UAE (OR=3.02, 95%CI;1.47,6.18, p-value=0.003). Conclusions: Shorter ureteral stent duration following RCUD is associated with decreased readmissions and urinary infections complications without concurrent increase in UES. Strong consideration should be directed towards early stent removal. [Table: see text]
Synchronous delivery of hydroxyapatite and connective tissue growth factor derived osteoinductive peptide enhanced osteogenesis
Authors: Ruodan Xu, Zhongyang Zhang, Mette Steen Toftdal, Anne Christine Møller, Frederik Dagnaes-Hansen, Mingdong Dong, Jesper Skovhus Thomsen, Annemarie Brüel, Menglin Chen
Journal: Journal of Controlled Release (2019)
The role of robot-assisted adrenalectomy for large pheochromocytoma pressing inferior vena cava or extending to retrovena cava space.
Authors: Zhoujun Shen, Xiaojing Wang, Wei He
Journal: Journal of Clinical Oncology (2015)

e15637 Background: To evaluate the efficacy and safety of robot-assisted laparoscopic adrenalectomy(RALA) for large pheochromocytoma pressing inferior vena cava or extending to retrovena cava space. Methods: From September 2009 to December 2014, 15 RALA were performed on patients with pheochromocytoma pressing inferior vena cava or extending to retrovena cava space. The mean tumor size was 7.6cm (range: 5-11). The preoperative Imaging data suggested that all the tumors compressed the inferior vena cava. The mean age of the patients was 32 yr, and the mean body mass index was 26.5. Positioning and port placement is designed for adequate reach and visualization of the upper retroperitoneum. The tumor is dissected away carefully from both the inferior vena cava and normal adrenal cortex, preserving normal adrenal tissue. Results: All the 15 cases were completed robotically. The mean operative time was 65 min (range: 60-130), the median estimated blood loss was 95 ml (range: 50-250), There was no conversion to an open procedure. At a median follow-up of 12.3 mo (range: 6–38), there were no recurrences or metastatic events. Conclusions: RALA for the treatment of large pheochromocytoma pressing vena cava or extending to retrovena cava space is feasible and safe and provides encouraging functional and oncologic outcomes. However, if local invasion is detected by the preoperative imaging studies, robotic surgery is no longer a preferred option.
Prognostic significance of history of nonmuscle invasive bladder cancer in patients with muscle invasive bladder cancer treated with neoadjuvant chemotherapy followed by surgery.
Authors: Yongjune Lee, Young Seok Kim, Bumsik Hong, Yong Mee Cho, Jae-Lyun Lee
Journal: Journal of Clinical Oncology (2019)

375 Background: Efficacy of cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) for T2-4aN1M0 muscle-invasive bladder cancer (MIBC) was proved by randomize controlled trials. Recent retrospective studies suggested that MIBC patients who had a history of non-muscle invasive bladder cancer (NMIBC) had lower pathologic complete response and worse overall survival rate to NAC and RC. This study aimed to compare clinical outcomes between MIBC that progressed from NMIBC (secondary MIBC) and primary MIBC. Methods: A retrospective analysis of patients with urothelial carcinoma (cT2-4aN0-1M0) who received neoadjuvant chemotherapy from January 2011 and December 2017 in Asan Medical Center was conducted. Clinicopathologic outcomes were compared between 187 patients with primary MIBC and 38 patients with secondary MIBC. Results: Baseline characteristics are well balanced between the groups. Downstaging rate ( &lt; ypT2 and no N upstaging) are 46.7% for secondary MIBC group, 55.6% for primary MIBC group (p = 0.390), and positive pathologic metastatic nodes (ypN1+) are observed in 23.3% for secondary MIBC group, 18.3% for primary MIBC group (p = 0.523). There were no differences in overall survival (OS) (3 year OS 69.3% for secondary MIBC, 70.3% for primary MIBC, p = 0.420), disease-free survival (DFS) (3 year DFS 57.7% vs 56.6%, p = 0.880) between the groups. History of NMIBC is not independent prognostic factor for OS on multivariable analysis. Conclusions: Patients with secondary MIBC treated with NAC showed no differences in NAC response, pathologic downstaging rate, OS, DFS compared to patients with primary MIBC. Prospective or larger cohort study are required in the future. Genomic analysis is ongoing to identify genetic differences between two groups.
Prospective Observation on the Use of Von Willebrand Factor (VWF) Concentrates in a Large Cohort of Type 3 Von Willebrand Disease (VWD): Interim (18-months) Analyses on 149 Cases Enrolled into the 3Winters-Ips Project
Authors: Augusto B Federici, Zahra Badiee, Mohammad-Reza Baghaipour, Giancarlo Castaman, Peyman Eshghi, Jenny Goudemand, Charles RM Hay, Hamid Hoorfar, Mehran Karimi, Bijan Keikhaei, Riitta Lassila, Frank Leebeek, Maria Fernanda Lopez Fernandez, Renato Marino, Ian Peake, Rafael Parra Lòpez, Flora Peyvandi, Cristina Santoro, Simona Maria Siboni, Alberto Tosetto, Marc Trossaert, Jeroen C.J. Eikenboom
Journal: Blood (2018)
Evaluating an Intervention to Improve Communication Between Oncology Clinicians and Patients With Life-Limiting Cancer
Authors: Joanna Paladino, Rachelle Bernacki, Bridget A. Neville, Jane Kavanagh, Stephen P. Miranda, Marissa Palmor, Joshua Lakin, Meghna Desai, Daniela Lamas, Justin J. Sanders, Jonathon Gass, Natalie Henrich, Stuart Lipsitz, Erik Fromme, Atul A. Gawande, Susan D. Block
Journal: JAMA Oncology (2019)

Earlier clinician-patient conversations about patients' values, goals, and preferences in serious illness (ie, serious illness conversations) are associated with better outcomes but occur inconsistently in cancer care.To evaluate the efficacy of a communication quality-improvement intervention in improving the occurrence, timing, quality, and accessibility of documented serious illness conversations between oncology clinicians and patients with advanced cancer.This cluster randomized clinical trial in outpatient oncology was conducted at the Dana-Farber Cancer Institute and included physicians, advanced-practice clinicians, and patients with cancer who were at high risk of death.The primary outcomes (goal-concordant care and peacefulness at the end of life) are published elsewhere. Secondary outcomes are reported herein, including (1) documentation of at least 1 serious illness conversation before death, (2) timing of the initial conversation before death, (3) quality of conversations, and (4) their accessibility in the electronic medical record (EMR).We enrolled 91 clinicians (48 intervention, 43 control) and 278 patients (134 intervention, 144 control). Of enrolled patients, 58% died during the study (n=161); mean age was 62.3 years (95% CI, 58.9-65.6 years); 55% were women (n=88). These patients were cared for by 76 of the 91 enrolled clinicians (37 intervention, 39 control); years in practice, 11.5 (95% CI, 9.2-13.8); 57% female (n=43). Medical record review after patients' death demonstrated that a significantly higher proportion of intervention patients had a documented discussion compared with controls (96% vs 79%, P = .005) and intervention conversations occurred a median of 2.4 months earlier (median, 143 days vs 71 days, P < .001). Conversation documentation for intervention patients was significantly more comprehensive and patient centered, with a greater focus on values or goals (89% vs 44%, P < .001), prognosis or illness understanding (91% vs 48%, P < .001), and life-sustaining treatment preferences (63% vs 32%, P = .004). Documentation about end-of-life care planning did not differ between arms (80% intervention vs 68% control, P = .08). Significantly more intervention patients had documentation that was accessible in the EMR (61% vs 11%, P < .001).This communication quality-improvement intervention resulted in more, earlier, better, and more accessible serious illness conversations documented in the EMR. To our knowledge, this is the first such study to demonstrate improvement in all 4 of these outcomes.ClinicalTrials.gov identifier: NCT01786811.