tbuckley/cabot-search huggingface dataset:
Cumulative burden of severe chronic health conditions (CHC) and health related quality of life (HRQoL) among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort study (SJLIFE).
Authors: Nickhill Bhakta, Tara M. Brinkman, Matthew J. Ehrhardt, Qi Liu, Kirsten K. Ness, Kevin R. Krull, Deo Kumar Srivastava, Deo Kumar Srivastava, James L. Klosky, Patricia A. Ganz, Melissa M. Hudson, Yutaka Yasui, Leslie L. Robison, I-Chan Huang
Journal: Journal of Clinical Oncology (2018)

10078 Background: Childhood cancer survivors have high cumulative burden of severe and life-threatening CHC. The impact of CHC burden on self-reported HRQoL, however, has not been extensively assessed. Methods: Participants included 2666 survivors (mean age at study 34 years [range 18-66]) enrolled in the SJLIFE cohort; eligibility: survived ≥10 years and ≥18 years of age. Survivors were clinically assessed for the presence of a severe/life-threatening condition for 78 CHC using the SJLIFE modified CTCAE. HRQoL was assessed with the Short Form 36 and categorized into suboptimal ( < -0.5 SD) or optimal (≥ -0.5 SD) based on the physical and mental component summaries (PCS, MCS). A latent class analysis approach was used to generate CHC classes, identify socio-demographic and exposure determinants and estimate associations with HRQoL. Results: Unique HRQoL profiles corresponded with the three CHC latent classes identified: optimal PCS and MCS (81% of survivors), suboptimal PCS/optimal MCS (4%) and suboptimal PCS & MCS (15%). Component scores and the prevalence of a subset of CHCs by HRQoL profiles are presented in the Table. Survivors who received ≥30Gy cranial radiation were more likely to have suboptimal PCS/MCS while those who received ≥250mg/m2 anthracyclines clustered in the suboptimal PCS/optimal MCS class (p < 0.01, respectively). Conclusions: Despite a high cumulative burden of CHC, most adult survivors of childhood cancer report a HRQoL similar to the general population. Results suggest that most survivors adjust well to the excess disease burden, but also identified profiles of subgroups with suboptimal HRQoL who may benefit from targeted interventions. Class 1: Suboptimal PCS and MCS Class 2: Suboptimal PCS/optimal MCS Class 3: Optimal PCS and MCS HRQoL Mean PCS 39* 43* 53 Mean MCS 41* 54 48 % Prevalence** CHC Stroke 6 0 1 Myocardial infarction 9 27 1 Heart valve disease 5 24 1 Cardiovascular dysfunction 7 73 2 Arrhythmias 7 27 1 Pulmonary disorder 39 37 2 Chronic renal disease 4 9 1 Hypogonadism 11 23 2 Diabetes 14 14 4 Peripheral neuropathy 20 13 1 Hearing loss 16 23 6 Second neoplasm 19 18 4 *SD < -0.5; **p < 0.01 across 3 classes
Clinical outcome in patients who did not accept complementary surgery after neoadjuvant chemoradiotherapy (QT-RT) in locally advanced rectal cancer (LARC).
Authors: German Caderillo-Ruiz, Dr. Consuelo Diaz, Horacio Noe López-Basave, MaryTere Herrera, Erika Ruiz Garcia, Javier Melchor, Guadalupe Trejo, Jose Luis Aguilar, Angel Herrera Gomez, Abelardo Meneses-Garcia
Journal: Journal of Clinical Oncology (2016)

e15144 Background: In patients with LARC the neoadjuvant concurrent chemoradiotherapy (CRT) follow by radical surgery is the standard approach. Approximately 15-20% achieve pathologic complete remission (pCR) after CRT. The morbidity, mortality, risk of permanent colostomy and other factors are the main reasons to refuse the surgical procedure. The evolution of these patients is uncertain. The aim of the present analysis is to determinate the benefit of observation in these patients. Methods: This is a retrospective study of patients with LARC who completed neoadjuvant CRT and refused radical surgery. Results: Between 2000 and 2014, 413 patients with LARC adenocarcinoma were treated with neoadjuvant CRT, of these, 248 were men and 165 women. All patients received 45-50.4 Gys concurrent with fluoropyrimidine based chemotherapy and only 14 patients received fluoropyrimidine with oxaliplatin. After clinical, tomographic, endoscopic and histological evaluation the patients were candidates for radical surgery. In 89 patients the radical surgery was refused. Of these group, 77 were male and 12 women. The level of rectal cancer in these patients was: 8 patients in upper third (9%), 21 patients in middle third (24%) and 60 patients in the lower third (67%). We defined response to the neadjuvant CRT as a pCR (Clinic-tomographic, Endoscopic and Pathological -no residual viable tumor cells in the primary rectal mass-) and No-pCR. Ten patients who had refused radical surgery post CRT, accepted the procedure during the surveillance period, median of 16.3 months. The median overall survival in the patients who achieved pRC was 41.1 months with clinic-tomographic evaluation, 41.7 months with endoscopic evaluation and 38.5 months pathologic evaluation. vs 14.5, 23.7 and 11.2 months, respectively in the No-pCR group. Of the 10 patients also treated with surgery, median survival was 51.8 months vs 16.4 months for the rest of the group. Conclusions: Male refuse commonly the radical surgery. The pCR may need complementary methods to settle if the patient decides to initiate surveillance instead of radical surgery. Radical surgery is essential to increase perspective of life:
Impact of pre-existing cardiovascular disease (CVD) on patterns of care and outcomes in breast cancer (BC).
Authors: Winson Y. Cheung, Joseph C. Dort, Yuan Xu, Shiying Kong, Safiya Karim, Antoine Bouchard-Fortier, May Lynn Quan
Journal: Journal of Clinical Oncology (2018)

e18723 Background: Cancer and CVD are the two leading causes of death. As the population ages, more patients will be affected with both conditions. Cardio-oncology research has largely focused on characterizing the cardiac toxicities of cancer therapies, but it has not addressed if and how the presence of one comorbidity influences the management and outcomes of the other. We hypothesized that BC patients with pre-existing CVD disease are undertreated for their cancer. Methods: We assembled a population based cohort of women diagnosed with BC between 2004 and 2015 from 17 centers in a large Canadian province. Using provincially linked administrative data, variations from standard guidelines in the receipt of cancer treatments, including surgery, radiation (RT) and systemic therapy (ST) were examined and compared between BC patients with and without a prior diagnosis of CVD. Overall (OS) and cancer-specific (CSS) were evaluated. Results: We identified 25,594 women. In this cohort, the majority (94%) had early stage BC. CVD was present in 2,053 (8%) patients of whom 303 (15%), 613 (30%), and 754 (37%) had preceding myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular accident (CVA), respectively. Compared to those without prior CVD, patients with any past CVD were less likely to receive ST (p < 0.001) and RT (p < 0.001), but more likely to undergo surgery (p = 0.002) for their BC, after adjusting for cancer stage and other confounders. Patients in the CVD group also had worse OS (p < 0.001) and CSS (p = 0.028) than those in the non-CVD group. In analyses stratified by treatment, inferior OS persisted among CVD patients regardless of cancer therapy, but inferior CSS was only seen among CVD patients who did not receive ST (Table). Conclusions: The presence of CVD resulted in less use of ST and RT in BC patients. The former was associated with worse cancer-related outcomes. Appropriate and early engagement of cardiologists may ensure that cancer care of CVD patients are comparable to that of their non-CVD counterparts. Table: Hazard Ratio for Cancer-Specific Death CSS (all) p value CSS (no ST) p value CSS (yes ST) p value No CVD 1.0 0.028 1.0 0.036 1.0 0.111 MI 1.11 1.39 1.02 CHF 1.42 1.85 1.36 CVA 1.18 1.24 1.05
Quality and cost comparison of powered versus manual bone marrow biopsy devices at a large U.S. cancer center.
Authors: Abhishek Maiti, Srdan Verstovsek, Cynthia A Powers, Cheryl P Fullmer, Steven R Reyes, Carlos E. Bueso-Ramos, Nicholas James Short
Journal: Journal of Clinical Oncology (2016)

e18283 Background: Although powered bone marrow biopsy devices (PBM) have been shown to yield longer biopsy samples than manual bone marrow biopsy devices (MBM), the relative quality and cost-effectiveness of these two methods has not been established. Methods: We retrospectively reviewed 569 bone marrow (BM) biopsy samples obtained between 9/2010 to 5/2015 from 293 patients with myelofibrosis. Length and adequacy of PBM and MBM biopsy samples were compared. In a separate cohort of treatment-naïve patients (N = 126) we evaluated biopsy specimens for length of evaluable marrow (by retrospective pathologist review) and aspirate samples for adequate yield of diagnostic information. Results: PBM yielded longer BM samples compared to MBM (p < 0.001) and longer length of evaluable marrow elements (p = 0.05). Despite these advantages of PBM, no differences were observed in adequacy of biopsy or aspirate samples that impacted the determination of relevant morphologic or other clinical information (Table). Accounting for necessary supplies for each procedure, the cost to our institution for the PBM system was $130 per BM biopsy vs. $56 per BM biopsy for MBM, yielding an average excess cost of approximately $74 per BM biopsy performed with PBM. Given ~17,000 BM biopsies are performed annually at our institution, the projected cost for universal adoption of PBM was estimated at $1,258,000 more than that for MBM (annual cost of materials: $2,210,000 vs. $952,000 respectively). Conclusions: Although PBM yielded longer core biopsies and more evaluable marrow than did MBM, this did not translate to discernable improvement in the quality of specimens obtained. Given the increased cost of PBM, these data do not support the universal adoption of PBM. PBM (N = 73) MBM (N = 496) P Mean biopsy length ± SD (cm) 1.65 ± 0.48 1.40 ± 0.41 < 0.001 Mean length of evaluable marrow ± SD (cm)* 0.96 ± 0.34 (n = 12) 0.80 ± 0.41 (n = 92) 0.05 Inadequate biopsy, n (%) 12 (16) 105 (21) 0.35 Not evaluable for cellularity assessment, n (%) 5 (7) 17 (3) 0.29 Not evaluable for special staining, n (%) 2 (3) 15 (3) 0.89 Inadequate cytogenetic assessment, n/N (%)* 1/10 (10) 16/108 (15) 0.68 Inadequate for cell differential, n/N (%)* 8/13 (62) 70/113 (62) 0.98 * Treatment naïve patients
Long-term survival in chronic lymphocytic leukemia after first primary malignancy in the United States.
Authors: Amir Bista, Dipesh Uprety, Subash Ghimire, Megha Giri, Binay Kumar Shah
Journal: Journal of Clinical Oncology (2017)

e18090 Background: There has been significant improvement in survival among patients with primary Chronic Lymphocytic Leukemia (CLL) in recent years but, not much is known about survival among CLL developed after a first primary malignancy. Methods: SEER 18 database, 2015 submission, was used to calculate 5 and 10 year relative survival (RS) by period survival modeling method for 1993 to 2012, with division of the period into 4 cohorts of 5 years each. SEER*Stat software from National Cancer Institute was used to calculate relative survival (RS) for 4 different periods of 5 years duration. The trend in survival for cases with CLL as second primary cancer (CLLSPC) was evaluated using COX proportional hazard method using Cansurv software and also compared with that of primary CLL cases. Results: A total of 8731 patients with CLLSPC were included in the study, which represents 14.5% of all cases of CLL. The median age at diagnosis was 75 years. Median time to diagnosis of CLL was 50 months after diagnosis of first primary malignancy. Prostate cancer, breast cancer and colorectal cancer were 3most common primary cancers. 5-year and 10-year RS improved significantly in the year 2008-2012 compared to 1993-1997 (59.3% to 70.2%,P 0.044 and 40.1% to 50.6%, p 0.045). In subgroup analysis, significant improvement in 5-year and 10-year RS was seen in females and ≥ 80 years age group but no significant improvement was observed in males and age group 60-79 years. Survival among CLLSPC was significant worse compared to first primary CLL in all periods, even after adjusting for age and sex. Conclusions: CLLSPC represents about 14.5% of all CLL cases. Relative survival among patients with CLLSPC is gradually improving but still lags behind that of CLL as first primary cancer.
A phase II clinical study evaluating the efficacy and safety of neoadjuvant and adjuvant sunitinib in previously untreated patients with metastatic renal cell carcinoma (mRCC)(NeoSun).
Authors: Sarah Welsh, Kate Fife, Athena Matakidou, Jean Mullin, Andrea Machin, Wendi Qian, Victoria Ingleson, Katy Marie Dalchau, Pamela Whittaker, Anne Warren, Andrew N Priest, Fulvio Zaccagna, Tristan Barrett, Ferdia Aidan Gallagher, Antony Riddick, James Neil Armitage, Timothy George Quentin Eisen
Journal: Journal of Clinical Oncology (2017)

e16087 Background: Sunitinib improves clinical outcomes in patients (pts) with mRCC. The single arm phase II NeoSun trial was designed to investigate its added value to nephrectomy, and to explore translational biological and imaging biomarkers. Methods: Pts with mRCC, scheduled for nephrectomy, no prior systemic therapy were recruited to receive 50mg OD sunitinib for 12 days, then post-surgery on a 4 week-on, 2 week-off, repeating 6 week cycle until disease progression. Diffusion-weighted, BOLD and dynamic contrast enhanced MR imaging (DW-MRI, DCE-MRI) and research blood sample collection were performed at baseline and end of 12 days. CT Imaging was performed at baseline, pre- and post-surgery, and then every 2 cycles. The primary endpoint was objective response rate (RECIST). Secondary endpoints included changes in diffusion DW-MRI, DCE- MRI of the tumour following 12 days suntinib, overall survival (OS), progression-free survival (PFS), response duration, surgical morbidity/mortality, and toxicity. Results: 14 pts received pre-surgery sunitinib, 71% (10/14) took the planned 12 doses. All 14 underwent total nephrectomy, and 13 recommenced sunitinib post-operatively. The mean number of post-surgery cycles was 11 (range 2 – 22). 58.3% (7/12) of pts achieved confirmed response (95% CI: 27.7 - 84.8%).91.7% (11/12) achieved objective clinical benefit (95% CI: 61.5 - 99.8%). Median OS is 33.7m and median PFS is 15.7m. Amongst those achieving PR/CR, median response duration is 8.7m. No unexpected surgical or sunitinib-related toxicities or complications were observed and the mean number of days from surgery to hospital discharge was 5.9 (range 3.0 – 17.0).There was a trend forOS to be better in pts with high baseline plasma VEGF-A (p = 0.06) or VEGF-C (p = 0.02) expression. A larger % tumour volume reduction after 12 days treatment is correlated with a smaller baseline % necrosis (coefficient = -0.51, p = 0.03). Conclusions: Sunitinib is effective and safe when given before and after nephrectomy to previously untreated pts with mRCC. Neoadjuvant studies such as NeoSun can safely explore translational biological and imaging endpoints. Clinical trial information: 2005-004502-82.
TCT-253 Placement of Axillary Intraaortic Balloon Pump Leads to Higher Adverse Event Rate When Compared to Placement of Femoral Intraaortic Balloon Pump
Authors: Baldeep Dhaliwal, Vinod Chainani, Russell Riehl, Sapna Desai, Aditya Bansal, John Reilly
Journal: Journal of the American College of Cardiology (2018)
Reflectance confocal microscopy and melanocytic lesions: The road to saving a biopsy.
Authors: Ann Mary John, Attiya Haroon, Gina Francisco, Babar K Rao
Journal: Journal of Clinical Oncology (2018)

e21614 Background: Melanocytic lesions can be difficult to evaluate, even with the advent of dermoscopy. Reflectance confocal microscopy (RCM) is an FDA-approved device to supplement clinical examination in determining the need for skin biopsy. RCM non-invasively provides images with details similar to histological images in under 10 minutes. The purpose of our study is to determine the accuracy of RCM in determining the need for biopsy in equivocal melanocytic lesions. Methods: Clinically suspicious melanocytic lesions from 2011 to 2017 were retrospectively reviewed. Patient age, location of lesion, confocal microscopy diagnosis by a trained confocal specialist, and histology diagnosis were recorded. Lesions determined as benign on RCM were followed for at least 1 year to determine if any clinical changes necessitating biopsy were found. Results: In total, 823 clinically suspicious melanocytic lesions were analyzed. Of these, 95 lesions were determined to be positive for atypia on RCM and 728 lesions were determined to be benign. Of the 95 lesions that showed atypia, 66 lesions were biopsy-proven atypical melanocytic lesions. The remaining 29 lesions were benign nevi. Moreover, 42 of the 66 lesions showing atypia were moderately to severely atypical or melanoma, while the remaining 24 lesions were mildly atypical. The 728 lesions determined to be benign on RCM remained unchanged on clinical examination for at least 1 year. Conclusions: RCM provides a convenient supplement to clinical and dermoscopy examination to determine the need for biopsy. As melanocytic lesions often require excisional biopsies, minimizing the removal of benign lesions decreases patient complications, such as scarring and infection, particularly in clinically sensitive sites, including faces and acral surfaces. Moreover, RCM can be used to guide where a biopsy should be performed in larger lesions, such as lentigo maligna.
Abstract 17629: A Novel Specific Risk Stratification Score Improves Stroke Prediction in Dialysis Patients with Atrial Fibrillation
Authors: William Maddox, Jennifer Waller, Avirup Guha, Matthew Diamond, Michele Murphy, Sheldon Litwin, Stan Nahman, Mufaddal Kheda, Robert A Sorrentino
Journal: Circulation (2014)

Introduction: In dialysis (ESRD) patients with atrial fibrillation (AF), we have previously shown that CHADS2 and CHA2DS2VASc (CHF, Hypertension (HTN), Age, Diabetes, Stroke (CVA), Vascular disease) score predicted risk of CVA. However, multivariate analysis showed that CHF, HTN, and PVD individually were not predictive. We theorized that a risk stratification scoring scheme tailored to unique ESRD co-morbidities may improve CVA prediction in this population. Methods: All incident adult ESRD cases from the US Renal Data System (2005-2008), were queried for CVA, AF or flutter and selected conditions using ICD-9 diagnosis codes and CMS form 2728. Logistic regression was used to estimate the odds ratio (OR) of individual co-morbidities for CVA. The area under the receiver operator curves (AROC) for CHADS2 and CHA2DS2VASc scores were compared to the ARCHSS2 (Age, Race, Cause of ESRD is HTN, Sex (female) and previous Stroke) score. Results: Of 443,890 incident ESRD patients, 35,147 had a diagnosis of AF or flu...
Early detection of post-transplant lymphoproliferative disorder using circulating tumor DNA.
Authors: Joanne Soo, Joseph Schroers-Martin, Andrea Garofalo, David Matthew Kurtz, Nathan D'Emilio, David Robert Grimm, Helen Luikart, Matt Van De Rijn, Maximilian Diehn, Kiran K Khush, Ash A. Alizadeh
Journal: Journal of Clinical Oncology (2018)

7572 Background: Diffuse large B cell (DLBCL)-like post-transplant lymphoproliferative disorder (PTLD) affects 2-5% of transplant recipients. Although 50% of PTLDs can be related to Epstein-Barr virus (EBV) infection (Luskin et al., 2015) and high or increasing EBV viral load may precede EBV+ PTLD (Tsai et al., 2008), preemptive monitoring of EBV titers does not reliably predict development of PTLD (Dierickx et al., 2018). We aimed to assess the utility of circulating tumor DNA (ctDNA) for early detection of PTLD. Methods: We applied CAPP-Seq (Newman et al., 2014) to diagnostic tumor and plasma samples and matched germline in a cohort of 9 transplant recipients who developed PTLD to identify somatic alterations. We compared mutational patterns in PTLD to 149 de novo DLBCL cases sequenced by the same method as well 1112 published whole exome sequences (Pasqualucci et al, 2011; Reddy et al, 2017). We additionally sequenced serial post-transplant plasma samples preceding diagnosis in 5 patients and during or after treatment in 8 patients to determine the dynamics of ctDNA and compared these patterns to clinical outcome and EBV titers. Results: There was no significant difference in mutational burden between patients with PTLD and de novo DLBCL (median PTLD variants: 216, IQR = 79 – 321; median de novo DLBCL variants: 143.5, IQR = 45 – 243.8; p = 0.35), though there was a trend toward greater variant count in EBV- compared to EBV+ PTLD (p = 0.064). The prevalence of alterations in known driver genes including CREBBP, CARD11, MYD88, and EZH2 was similar between PTLD and de novo DLBCL. Prediagnostic plasma samples were available for 5 cases, including two EBV- PTLD, and we detected ctDNA in all patients prior to clinical diagnosis (mean lead time = 114 days). In the 3 EBV+ cases, EBV titers were concordant with ctDNA levels in EBV+ cases at all time points. In addition, ctDNA levels during and after treatment were concordant with clinical response in all patients. Conclusions: PTLD patients have detectable ctDNA prior to clinical diagnosis. Development of screening tools utilizing both ctDNA and EBV titers could facilitate early detection of PTLD in the transplant population.
A phase 1 study of TTI-621, a novel immune checkpoint inhibitor targeting CD47, in subjects with relapsed or refractory hematologic malignancies.
Authors: Stephen Maxted Ansell, Robert W. Chen, Ian Flinn, Michael B. Maris, Owen A. O'Connor, Elizabeth Wieland, Eric L. Sievers
Journal: Journal of Clinical Oncology (2016)

TPS7585 Background: TTI-621 (SIRPαFc) is a soluble recombinant fusion protein designed to bind human CD47 and prevent it from delivering an inhibitory signal to macrophages. TTI-621 is created by combining the sequences encoding the N-terminal portion of human SIRPα with the Fc region of human IgG1. The SIRPα region interacts with its ligand CD47, while the Fc region binds to macrophage Fcγ receptors. High levels of CD47 expression are observed on many different tumor types, where its expression is often associated with poor prognosis. It is hypothesized that tumor cells exploit the suppressive CD47-SIRPα axis to evade macrophage-mediated destruction. TTI-621 is thought to function as a decoy receptor, binding CD47 on tumor cells and blocking its anti-phagocytic signal, allowing macrophages to ingest malignant cells. In vitro studies have shown that TTI-621 promotes macrophage-mediated phagocytosis of a range of hematologic tumor cells and selectively induces phagocytosis of malignant cells over normal cells. TTI-621 has also shown potent antitumor activity in preclinical AML and B-cell lymphoma xenograft models. Methods: The objective of this phase 1, open label, multicenter study (TTI-621-01) is to evaluate the safety and tolerability, and to identify the maximum tolerated dose of intravenously-delivered TTI-621 in subjects with relapsed/refractory lymphoma using a 3+3 dose-escalation study design. Once the optimal dose has been determined in the dose-escalation phase, multiple expansion cohorts of subjects with a wide variety of relapsed/refractory hematologic malignancies will be enrolled. Pharmacokinetics, immunogenicity, and antitumor activity will also be evaluated. Eligible subjects are adults with advanced, measurable, hematologic malignancies, which have progressed on standard anticancer therapy or for which no other approved therapy exists. Subjects with cutaneous T-cell lymphoma, high grade lymphoma, and AML M3 are excluded. TTI-621 will be administered IV once weekly at protocol-defined doses starting at 0.05 mg/kg. Treatment may continue until disease progression, unacceptable toxicity, or other reason for discontinuation (NCT02663518). Clinical trial information: NCT02663518.