tbuckley/cabot-search huggingface dataset:
Selective killing of circulating tumor cells prevents metastasis and extends survival
Authors: Yi Rang Kim, Jung Ki Yoo, Chang Wook Jeong, Jin Woo Choi
Journal: Journal of Hematology & Oncology (2018)

Distant metastasis is initiated by circulating tumor cells (CTCs), which are considered to be a determining factor for the degree of metastasis and the survival of cancer patients. Although CTC-based diagnostic approaches are being rapidly developed, limited studies have proven the benefits of CTC elimination, with most studies providing only hypothetical inference because of the technical difficulty in examining the effects of CTC elimination in vivo. We modified photodynamic therapy to specifically eliminate green fluorescent protein (GFP)-expressing CTCs and evaluated the therapeutic efficacy of CTC elimination. When circulating blood is illuminated with a blue laser (λ = 473 nm), the combination of GFP and photosensitizers induces a selective elimination of GFP-expressing CTCs, with limited effect on normal cells. In GFP-expressing cancer cell-infused or transplanted mice models, the treatment suppressed distant metastasis and extended the survival of the tumor-bearing mice. Taken together, CTCs are a core seed to be metastasized into secondary organs and elimination of CTCs may improve the survival of cancer patients.
Treating the elderly with immune checkpoint inhibitors: Real life experience from a large Brazilian center.
Authors: Clarissa Cavalin Silva, Daniel Herchenhorn
Journal: Journal of Clinical Oncology (2018)

e15077 Background: Immune checkpoint inhibitors (ICI) have shown good efficacy and favorable safety profiles in clinical trials, but due to lack of representation of the elderly population in those studies, we currently rely on real-life data and cohorts. Treatment tolerance is a major issue in this population. Methods: Retrospective, observational study, including patients with solid malignancies above age 65, treated with FDA-approved ICI from 2015 to 2017 in our clinics in Rio de Janeiro, Brazil. Our goal was to document outcomes and identify individuals at higher risk for developing toxicities. Subjects were selected by convenience, side effects graded according Common Terminology Criteria for Adverse Events (CTCAE) v.4.0, comorbidities graded using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Results: 106 subjects were included, average age of 74,4 (65 -90), all Stage IV, with common primary sites: Lung, Melanoma, Urologic and Colorectal. Performance Status (PS) 1 in 64%, 2 in 16%, cachexia was present in 20 cases, frailty in 52, polypharmacy in 64. Mean CIRS-G was 5,76 (4-12), Nivolumab was given to 77, Pembrolizumab to 23, Ipilimumab to 4 and Atezolizumab to 2. All-grade Adverse Events (AE) occurred in 55%. 13 AE led to treatment discontinuation. There were 21 Immune-related adverse events (irAEs), most common and mild: thyroiditis, rash, pruritus. 5 severe irAEs occurred: colitis, antibody-enhanced anemia, fulminant hepatitis and polymyositis. The only predictive variable for risk to AE was frailty, OR 3,03 (95%CI 1,36 – 6,74; p 0,006). 4 patients died during treatment. Mean follow-up time was 28 weeks (4-148). 57 subjects are still on follow-up: 3 with complete response, 5 stable disease, 12 progressed and are now on chemotherapy. Conclusions: Our profile of AE’s and irAE’s is similar than reported in Literature. Frailty was the only statistically significant variable associated with development of AE. When dealing with elderly patients in the real world, having a comprehensive geriatric assessment and multidisciplinar care may indicate whether a patient develops severe AE, irAE or even dies from treatment and the value of such tools should be further investigated in prospective studies.
Value of EGD for gastric cancer surveillance in patients with hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome (LS).
Authors: Swetlana Ladigan, Deepak B. Vangala, Judith Kuhlkamp, Christian Pox, Christoph Engel, Robert Hueneburg, Claudia Perne, Jacob Nattermann, Verena Steinke-Lange, Nils Rahner, Hans K. Schackert, Matthias Kloor, Christian Strassburg, Monika Morak, Elke Holinski-Feder, Reinhard Büttner, Stefan Aretz, Markus Loeffler, Wolff H. Schmiegel, Karsten Schulmann
Journal: Journal of Clinical Oncology (2018)

1522 Background: Gastric cancer (GC) is the second most common non-gynecologic malignancy in patients with LS. Due to an absence of prospective randomized data, the value of esophago-gastro-duodenoscopy (EGD) for GC surveillance in LS patients remains a controversial issue. According to German guidelines regular EGDs beginning at the age of 35 are recommended for LS patients. The focus of this study was to evaluate the effectiveness of EGD as an instrument for early GC detection. Methods: Data of HNPCC and LS patients diagnosed with GC was retrieved from the German Consortium for Familial Intestinal Cancer Registry. Individuals from 3 groups were included: pathogenic germline mismatch repair gene mutation carriers (n = 47), untested patients from families with known germline mutations (putative carriers; n = 8) and individuals fulfilling at least the revised Bethesda criteria without a mutation but with microsatellite instability (MSI group; n = 47). Statistics were calculated using Fisher's exact test. Results: Overall a total number of 107 GCs were observed in 102 patients (male/female: 60/42) with 71 (69%) having a negative family history of GC. Among germline mutation carriers, MLH1 (n = 21) and MSH2 (n = 24) mutations were the most prevalent; EPCAM and MSH6 mutations were rare with only one case each. The median age at diagnosis was 54.4 years (28.9-81.4) for the whole cohort, with mutation carriers being diagnosed at a younger age (51.8 years) than individuals from the MSI group (63.1 years). Of all GC patients, two were diagnosed at an age younger than 35 years and 7 patients were younger than 40 years. The GCs in patients undergoing surveillance were diagnosed significantly more often with an early stage disease (UICC I) than GCs detected through symptoms (77.8% vs. 23.5%; p = 0.0046). Conclusions: To our knowledge this is the largest study investigating the effectiveness of EGD surveillance for early GC detection in HNPCC or LS patients. This study indicates a benefit for patients undergoing regular EGDs and supports the recommendation of regular gastroscopic surveillance for HNPCC and LS syndrome patients beginning not later than at the age of 35.
Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly
Authors: John J. McNeil, Rory Wolfe, Robyn L. Woods, Andrew M. Tonkin, Geoffrey A. Donnan, Mark R. Nelson, Christopher M. Reid, Jessica E. Lockery, Brenda Kirpach, Elsdon Storey, Raj C. Shah, Jeff D. Williamson, Karen L. Margolis, Michael E. Ernst, Walter P. Abhayaratna, Nigel Stocks, Sharyn M. Fitzgerald, Suzanne G. Orchard, Ruth E. Trevaks, Lawrence J. Beilin, Colin I. Johnston, Joanne Ryan, Barbara Radziszewska, Michael Jelinek, Mobin Malik, Charles B. Eaton, Donna Brauer, Geoff Cloud, Erica M. Wood, Suzanne E. Mahady, Suzanne Satterfield, Richard Grimm, Anne M. Murray
Journal: New England Journal of Medicine (2018)

Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk.
Does the old-fashioned sofosbuvir plus ribavirin treatment in genotype 2 chronic hepatitis C patients still works for Koreans?
Authors: Jong Eun Yeon
Journal: Clinical and Molecular Hepatology (2018)

See the Original "Efficacy and safety of sofosbuvir plus ribavirin for Korean patients with hepatitis C virus genotype 2 infection: A retrospective multi-institutional study" on page 311.
Circulating tumor (ct)-DNA alterations in urothelial/bladder cancer (UC/BC): Updates on a dynamic genomic landscape.
Authors: Petros Grivas, Rebecca J Nagy, Gregory Russell Pond, Sumati Gupta, Jue Wang, Ulka N. Vaishampayan, Sumanta K. Pal, Mehmet Asim Bilen, Gurudatta Naik, Pooja Ghatalia, Christopher J. Hoimes, Dharmesh Gopalakrishnan, Pedro Barata, Richard B. Lanman, AmirAli Talasaz, Guru Sonpavde
Journal: Journal of Clinical Oncology (2017)

4534 Background: Cell-free ctDNA may be potentially actionable, may have prognostic/predictive role and evolve after therapy. We updated our analysis of our retrospective study to shed light on UC/BC biology. Methods: Patients (pts) with UC/BC with ctDNA analysis for potentially actionable alterations using Guardant360 were identified. A 70-gene ctDNA next generation sequencing panel from a CLIA-licensed, CAP-accredited laboratory (Guardant Health, Inc.) offers complete exon sequencing for 29 cancer genes, critical exons in 39 genes and amplifications (16 genes), fusions (6 genes) and indels (3 genes) harvested from 10 mL of peripheral blood. Descriptive statistics were used. Results: There were 246 pts with 276 samples. At least 1 alteration was detected in 249 (90%) samples. Median age at time of ctDNA collection was 67 years (39-85), 78% men, median number of alterations per sample was 3.5 (1-35) most pts had MIBC. In MIBC pts, the most common alterations at the 1st ctDNA sample were in TP53 (52%), PI3KCA (18%) ARID1A (17%), FGFR2 (15%), MET &amp; NF1 (14%), EGFR (13%), BRAF (12%), FGFR3 (11%), RAF1 (10%), BRCA1 &amp; CCNE1 (9%). In MIBC pts, the most common genes with increased copy number were RAF1 &amp; CCNE1 (8%), ERBB2 &amp; PI3KCA (7%), EGFR, BRAF, FGFR1, MYC (each 5%), MET (4%), KRAS (3%). Most common altered pathways included TP53 signaling (56%), RAS/RAF/MEK/ERK (51%), RTK (48%), cell cycle (38%), FGFR family (34%), DNA damage response (25%), PI3KCA/AKT/mTOR (23%) and chromatin remodeling (17%). Interestingly, FGFR3 and RAS alterations were mutually exclusive in most cases, but each may co-occur with TP53alterations. 54 serial ctDNA samples from 24 pts (18 pts with 2 samples; 6 pts with 3 samples) revealed persistent, lost and new gene alterations. Conclusions: ctDNA was detected in 90% of pts and alterations were similar to those previously seen in UC tumor tissue. Tumor heterogeneity, interim therapy, genomic instability and clonal evolution can explain differences in serial samples. Correlation assessment with prior therapies and outcomes is being pursued to inform trial designs. Prospective validation, assessment of ctDNA concordance with tumor tissue DNA, and evaluation of clinical utility is warranted.
KEYNOTE-564: A phase 3, randomized, double blind, trial of pembrolizumab in the adjuvant treatment of renal cell carcinoma.
Authors: Toni K. Choueiri, David I. Quinn, Tian Zhang, Howard Gurney, Gurjyot K. Doshi, Patrick Wayne Cobb, Francis Parnis, Jae-Lyun Lee, Se Hoon Park, Andrey Semenov, Wayne Yen-Hwa Chang, Shuyan M. Wan, Christian Heinrich Poehlein, Thomas Powles
Journal: Journal of Clinical Oncology (2018)

TPS4599 Background: The typical management for renal cell carcinoma (RCC) is nephrectomy. Despite this, patients with intermediate- to high-risk advanced disease can experience relapse with metastatic, usually incurable, disease. Adjuvant therapies are needed for patients at risk for recurrence after nephrectomy. Upregulation of the programmed death 1 (PD-1) pathway is associated with poor prognosis in RCC, and drugs to target the PD-1 pathway have shown efficacy and reasonable safety in metastatic RCC. Therefore, the PD-1 pathway may represent a novel target to prevent disease recurrence. The randomized, double-blind, placebo-controlled phase 3 KEYNOTE-564 trial (NCT03142334) is designed to evaluate the efficacy and safety of pembrolizumab in the adjuvant treatment of RCC after nephrectomy. Methods: Key inclusion criteria include age ≥18 years, histologically confirmed clear cell RCC of intermediate-high risk (pT2, grade 4 or sarcomatoid, N0 M0; or pT3, any grade, N0 M0), high risk (pT4, any grade, N0 M0; or pT any stage, any grade, N+ M0), or M1 NED; no prior systemic therapy for advanced RCC; negative surgical margins; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; and tumor sample available for biomarker analyses. Patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo every 3 weeks by intravenous infusion. Treatment will continue until disease recurrence, treatment discontinuation, or the completion of 17 cycles. Imaging will be performed every 12 weeks. The primary end point is disease-free survival (DFS) per investigator assessment. The secondary end point is overall survival (OS). Additional secondary analyses include safety and tolerability, pharmacokinetic parameters, antidrug antibodies, and DFS and OS per PD-L1 expression status. Biomarkers that may be associated with response will be evaluated as an exploratory objective. Recruitment will continue until ~950 patients are enrolled. Clinical trial information: NCT03142334.
Post-discharge transitions of care for hospitalized patients with advanced cancer.
Authors: Daniel E Lage, Ryan David Nipp, Sara D'Arpino, Samantha M.C. Moran, Ephraim P. Hochberg, Lara Traeger, Vicki A. Jackson, Barbara J. Cashavelly, Holly S Martinson, David P. Ryan, Joseph A. Greer, Jennifer S. Temel, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2017)

6504 Background: Patients with advanced cancer experience frequent hospitalizations and burdensome transitions of care post-discharge. We examined predictors of discharge location for patients with advanced cancer. Methods: We prospectively enrolled patients with advanced cancer with unplanned hospitalizations from 9/14 to 3/16. Upon admission, we used the Edmonton Symptom Assessment Scale and Patient Health Questionnaire-4 to assess physical and psychological symptoms, respectively. We used logistic regression models to identify predictors of discharge to location other than home, including post-acute care (PAC) [skilled nursing facility or long term acute care hospital] or hospice [any setting]. We used Cox regression models adjusted for clinical variables to assess the relationship between discharge location and survival. Results: Out of 932 patients, 726 (77.9%) were discharged home, 118 (12.7%) to PAC and 88 (9.4%) to hospice. Compared with patients discharged home, those discharged to PAC or hospice had higher symptom burden, including dyspnea, constipation, low appetite, drowsiness, fatigue, depression, and anxiety (all p &lt; 0.05). Patients discharged to PAC or hospice vs. home were more likely to be older (OR 1.03, p &lt; 0.0001), live alone (OR 1.95, 95% CI: 1.25-3.02, p &lt; 0.003), have impaired mobility (OR 5.08, 95% CI: 3.46-7.45, p &lt; 0.0001), longer length of stay (OR 1.15, 95% CI: 1.11-1.20, p &lt; 0.0001), higher ESAS physical symptoms (OR 1.02, 95% CI: 1.003-1.032, p &lt; 0.017), and higher PHQ-2 depression symptoms (OR 1.13, 95% CI: 1.01-1.25, p &lt; 0.027). Patients discharged to hospice vs. PAC were more likely to receive palliative care consultation (OR 4.44, 95% CI: 2.12 to 9.29, p &lt; 0.0001) and have shorter length of stay (OR 0.84, 95% CI: 0.77 to 0.91, p &lt; 0.0001). Compared with patients discharged home, those discharged to PAC had lower survival (HR 1.53, 95% CI 1.22-1.93, p &lt; 0.0001). Conclusions: Patients with advanced cancer discharged to PAC or hospice have substantial physical and psychological symptom burden and poor physical function. Patients discharged to PAC also have inferior survival compared with those discharged home. They may benefit from targeted interventions to improve their quality of life and care.
Feasibility of a geriatric chemotherapy toxicity prediction tool in adults with advanced cancer: A pilot study at the University of Pittsburgh Medical Center (UPMC).
Authors: Christine Ann Garcia, Ellen Ormond, G J. Van Londen, Edward Chu, Melissa Amber Burgess
Journal: Journal of Clinical Oncology (2017)

e18179 Background: Adults with advanced cancer vary considerably in health status and functional reserve. Given the substantial risk of toxicity from systemic therapy, the challenge for medical oncologists is to objectively evaluate the risk of treatment complications prior to starting treatment. The Hurria Prediction Tool for Chemotherapy Toxicity in older adults was developed to aid medical oncologists in predicting which patients are at the highest risk of toxicity. This validated tool stratified geriatric patients with advanced cancer into low, medium, and high risk for toxicity from chemotherapy. In line with UPMC’s mission to “ensure that every patient gets the right care, in the right way, at the right time, every time,” we investigated the feasibility and usefulness of the tool to predict toxicity in adults with advanced cancer, and assist in shared decision making when undergoing treatment decisions. Methods: Adults ≥ 18 years old with advanced cancer whom were being considered for systemic therapy were identified. Patients completed a brief health assessment form prior to their physician visit. Lab values and treatment characteristics were combined with the patient’s subjective health assessment to calculate a toxicity score. Karnofsky and ECOG performance statuses, toxicities, treatment details, hospitalizations, and length of stay were collected. This project was approved by UPMC’s Quality Improvement Committee. Results: Initial pilot testing in sarcoma and genitourinary cancer clinics demonstrated that the implementation of a toxicity prediction tool is feasible in busy academic oncology clinics. We will present results of staff surveys related to the ease of use and utility of this tool. Conclusions: Preliminary results suggest the use of this chemotherapy toxicity tool, previously validated in the geriatric population, to be feasible and useful in adults with advanced cancer. Further data analysis and studies are planned to expand this validated tool in other oncology clinic settings, and evaluate how well predicted toxicity correlates with actual toxicity for patients of all ages and treatment types.
Patient recruitment in an oligometastases trial: experience from a phase II study of 5 fraction stereotactic body radiation therapy (SBRT).
Authors: Rebecca Barbara Goody, Patricia Lindsay, Dhivya Murthy Paravasthu, Anthony M. Brade, Laura A. Dawson, Peter W. M. Chung, Andrea Bezjak, James D. Brierley, John Kim, Jolie Ringash, Alexander Sun, Meredith Elana Giuliani, Andrew J. Hope, Sarika Gill, Rebecca Wong
Journal: Journal of Clinical Oncology (2016)

e14050 Background: The challenges of recruitment of patients (pts) to clinical studies are well recognized. Assessment of the recruitment process is important in planning for adequate accrual and when considering the generalizability of trial outcomes, but is inadequately reported. We evaluated patient accrual at the planned first interim analysis in our single arm phase II study. Methods: Key study eligibility criteria were pts with ≤ 5 sites of metastatic disease, plan for ablative therapy to all sites and ≥ 1 lesions suitable for SBRT. Potential candidates were identified by clinical investigators and eligibility reviewed by a research coordinator. All cases were reviewed at monthly study-specific tumor board. Reasons for screen failure were assessed from study database, and confirmed by review of pt records. Results: Since March 2013, 130 pts were screened; 56 (43%) were ineligible for enrolment. Reasons for failure to enroll were: progressive disease on repeat imaging (n = 18, with progression identified on CT sim in 2), pt declined (n = 11), lesion not suitable for study SBRT (tumor growth n = 2, unable to meet dose constraints n = 2, lesion within prior radiotherapy field n = 2, alternate dose/fractionation more appropriate n = 5), alternative treatment selected (palliative radiotherapy = 1, surgery = 5, systemic therapy = 3), lack of complete response in primary disease (n = 5), no evidence of active disease on restaging (n = 1), ablative therapy not planned to all disease (n = 1). In at least 15 cases tumor board influenced decision. 15 primary malignancies were represented in both screened and enrolled patient cohorts; most commonly colorectal, lung and breast. No clear association was observed between primary disease and failure to enroll. Conclusions: Despite ready access to imaging, one third of patients considered to have oligometastatic disease at referral were ineligible due to disease progression beyond 5 metastatic sites. Tumor board discussions had an important role in considering treatment alternatives and interpretation of diagnostic imaging. These factors have implications for future trial design in this patient population. Clinical trial information: NCT01761929.
Hypofractionated accelerated radiotherapy (HART) with concurrent and maintenance temozolomide in newly diagnosed glioblastoma: a phase II randomized trial (HART-GBM).
Authors: Supriya Mallick, KP Haresh, Subhash Gupta, Seema Sharma, M. A Laviraj, Ashish Dutt Upadhyay, Dayanand Sharma, Pramod Kumar Julka, Goura Kishor Rath
Journal: Journal of Clinical Oncology (2018)

e14090 Background: To compare Overall Survival (OS) between Hypofractioanted accelerated radiotherapy (HART) and Conventional fractionated radiotherapy (CRT) in newly diagnosed GBM. Methods: Patients (Pts) randomly assigned by computer generated randomization chart. Inclusion criteria: Age 16 - 65 years, KPS ≥70, Undergone Surgery, referred for radiation within 4 weeks (wks.), adequate hematological parameter. Primary endpoint OS and secondary endpoint Progression free survival (PFS), toxicity and compliance. Radiotherapy was delivered by 3DCRT technique in CRT arm (60 Gy/30#/6 wks) or SIB-IMRT in HART arm (60 Gy/ 20 #4 wks) with concurrent (75mg/m2) and maintenance Temozolomide (150-200 mg/m2 D1-D5 4 weekly for six cycles). Univariate analysis was performed using log rank test to find the impact of age, extent of surgery, IDH-1 mutation, anti-epileptic use, fractionation scheme. Cox regression model was used for multivariate analysis. STATA version 12 software was used for statistical analysis. Results: After a median follow up of 11.4 months (Range: 2.9-42.5) median OS 23.4 months; CRT and HART arm median OS 18.07 [95% CI: 14.52-NR] and 25.18 months [95% CI: 12.89-NR]; p = 0.3. Median PFS 13.5 months (Range: 11.7-15.7), median PFS for CRT and HART arm 14.1 [95% CI: 10.5-15.9] and 13.1months (95% CI: 10-NR]. Pts ≤40 years had a significantly better OS, HR: 5.32, [95% CI: 1.93-14.65]; p = 0.001. Pts with STR had worse OS and PFS HR 2.07 [95% CI: 0.92- 4.66] for STR compared to GTR [p = 0.07] and [HR: 2.06, 95% CI: 1.07- 3.95, p = 0.02]. Pts with IDH-1 mutation had better OS and PFS than IDH wild type tumor, [HR: 0.23, 95% CI: 0.05-1.02, p = 0.02] and [HR: 0.35, 95% CI: 0.12-1.01, p = 0.03]. Use of AED had no impact on PFS and OS. All pts completed planned radiation and two Pts required hospitalization for raised intracranial tension. Another two required hospitalization after completion of radiation of for Deep venous thrombosis. Two pts in the HART arm required a prolonged course of steroids. Conclusions: HART is non-inferior to CRT in terms of survival outcome without any excess treatment interruption and minimal toxicity.