tbuckley/cabot-search huggingface dataset:
Diversity of first-line palliative systemic treatments for esophagogastric cancer patients with synchronous metastases: A real world evidence study.
Authors: Willemieke P.M. Dijksterhuis, Martijn G.H. van Oijen, Rob H.A. Verhoeven, Hanneke W.M. Van Laarhoven
Journal: Journal of Clinical Oncology (2018)

4064 Background: Optimal palliative systemic treatment for metastatic esophagogastric cancer is not well defined, causing variation in treatment. Aim of this study was to explore diversity in first-line systemic treatment in metastatic esophagogastric cancer patients in a real world setting and assess the effect on overall survival (OS) and progression-free survival (PFS). Methods: In a retrospective cohort study (2010-2016), esophagogastric cancer patients (n= 2295) with synchronous metastases treated with systemic therapy were included. Systemic therapy was divided in monotherapy, doublets, triplets (all without trastuzumab), and regimens with trastuzumab. Kaplan-Meier curves and Cox proportional hazards regression, with adjustment for age, gender, tumor and metastatic locations, year of diagnosis and performance status, was used to analyze OS and PFS (PFS only available for 2010-2014 patients, n= 1392). Results: Up to 69 different systemic treatment regimens were administered, with a median OS of 8.7 and PFS of 4.8 months. Nearly half of patients (48.2%) were treated with doublet therapy, while 752 patients (32.5%) received triplet and 230 (10.0%) monotherapy (Table 1). Median survival was highest in patients with trastuzumab. For patients not treated with trastuzumab, triplet therapy did not show difference in survival compared to doublet therapy. Conclusions: Esophagogastric cancer patients with synchronous metastases are treated with a wide variety of palliative systemic treatment. In our cohort we found that patients treated with a trastuzumab regimen had the best survival, and that doublet therapy provided similar overall and progression-free survival compared to triplet chemotherapy. First-line palliative treatment Overall survival (n= 2295) Progression-free survival (n= 1392) % Median OS (months) Adjusted HR 95% HR CI % Median PFS (months) Adjusted HR 95% HR CI Monotherapy 10.0% 5.8 1.51 1.29-1.77 12.4% 2.8 1.37 1.14-1.65 Doublet 48.2% 9.2 1.00 - 42.2% 4.7 1.00 - Triplet 32.5% 8.7 0.98 0.89-1.12 39.4% 5.3 0.89 0.77-1.02 Trastuzumab 7.0% 12.5 0.60 0.49-0.73 4.7% 7.6 0.58 0.44-0.77 Not specified 2.3% 9.0 1.22 0.86-1.73 1.4% 7.3 0.83 0.47-1.45
Association of distinct baseline tissue biomarkers with response to nivolumab (NIVO) and ipilimumab (IPI) in melanoma: CheckMate 064.
Authors: Scott Rodig, Daniel Gusenleitner, Donald Jackson, Evisa Gjini, Anita Giobbie-Hurder, Chelsea Jin, Han Chang, Scott Lovitch, Christine Horak, Jeffrey S. Weber, Margaret Ann Shipp, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2017)

9515 Background: CheckMate 064 (open label, phase 2) randomized advanced melanoma pts to NIVO 3 mg/kg Q2W for 6 doses then IPI 3 mg/kg Q3W for 4 doses (n = 70; cohort A), or the reverse (IPI then NIVO; n = 70; cohort B). More cohort A than cohort B pts had complete or partial response (54% and 31%, respectively). We sought to determine whether common or distinct baseline biomarkers were associated with response for each cohort. Methods: Protein expression of biomarkers identifying a broad array of cell lineages and immunoregulatory factors was determined by IHC and evaluated by 2 pathologists, with concordance. Global transcript expression was determined by RNAseq from frozen tissue. An elastic net predictor was trained on cohort A (α = 0.1, λ = 0.05) using leave-one-out cross-validation. RECIST v1.1 was used to assess tumor response. Results: Patients with tumors showing a pro-inflammatory transcriptional signature at baseline had superior overall response in cohort A, but not cohort B. Consistent with this observation, a parsimonious classifier of 10 immune/IFNγ-related genes predicted BOR (AUC 0.87) and OS (CPH log-likelihood P= 0.0003) for patients in cohort A, but not cohort B. In contrast, low baseline expression of MHC class I protein by malignant cells ( &lt; 50% positive) was associated with disease progression (MHCI &lt; 50% vs ≥50%: 12/13 vs 16/28 progressed) and inferior OS for patients in cohort B (MHCI &lt; 50%: 6.42 mo [2.20, 9.66]; MHCI ≥50%: mOS 18.02 mo [7.98, not reached]: P= 0.0021, log-rank test), but not cohort A. Conclusions: Different pre-treatment biological characteristics of melanoma are associated with clinical response to NIVO followed by a planned switch to IPI (cohort A) and clinical response to IPI followed by NIVO (cohort B). Improved outcome with initial NIVO is strongly associated with a pro-inflammatory signature enriched for IFNγ targets. Inferior outcome with initial IPI is associated with reduction/loss of MHC I antigen presentation machinery. These data imply that NIVO broadly activates innate and adaptive immunity, whereas IPI is reliant upon CD8/MHC class I mediated adaptive immunity to effect clinical response. Clinical trial information: NCT01783938.
Correlations between the EGFR mutation status and clinicopathological features of surgically resected non-small cell lung cancer.
Authors: Ying Jin, Xinmin Yu, Ming Chen, Yiping Zhang
Journal: Journal of Clinical Oncology (2016)

e20043 Background: The clinical behavior of patients with advanced non-small cell lung cancer (NSCLC) differ between epidermal growth factor receptor (EGFR) exon 19 deletion (Ex19) and EGFR exon 21 L858R mutation (Ex21). This study aimed to evaluate whether these differences exist in surgically resected NSCLC. Methods: Patients received surgery for primary lung tumors in Zhejiang Cancer Hospital from Jan 1, 2011 to Dec 30, 2013 were screened retrospectively. A total of 198 patients with surgically resected NSCLC harbouring Ex19 (n = 53), Ex21 (n = 51), and EGFR wild-type (Wt) (n = 94) were analyzed. The clinicopathological features, laboratory parameters, recurrent sites and disease-free survival (DFS) were compared according to mutational EGFR status. Results: Ex21 lesions occurred more frequently in female (p<0.001), never-smokers (p<0.001), adenocarcinoma (p<0.001), low grade (p=0.011) and had a higher pleural invasion rate (p=0.029) and lower vessel invasion rate (p=0.029) than Wt lesions. Ex19 lesions occurred more frequently in female (p=0.013), never-smokers (p=0.006), adenocarcinoma (p<0.001), low grade (p=0.023) than Wt lesions. Ex21 lesions occurred more frequently in never-smokers (p=0.034) than Ex19 lesions. Both Ex19 (0.013) and Ex 21 (0.041) had smaller mucinous variant components than Wt. Ex 21 (0.016) had larger lepidic growth components than Wt. Ex21 lesions were associated with lower pretreatment neutrophil: lymphocyte ratio (NLR) than Wt lesions (p=0.017). The recurrent sites and DFS were similar among patients with Wt, Ex19 and Ex21. Conclusions: While no significant difference in DFS was observed, the clinicopathological features were different among Wt, Ex19 and Ex21 in surgically resected NSCLC.
The clinical impact of sarcopaenia on chemotherapy delivery for gastric and oesophageal cancers.
Authors: Katherine Geddes, Hannah Rouse, Vijaya Sundararajan, Sue-Anne McLachlan, Melissa M. Moore
Journal: Journal of Clinical Oncology (2016)

e15564 Background: Sarcopaenia (low muscle mass) in cancers with a high incidence of weight-loss is associated with treatment toxicity and poor prognosis. We aimed to determine the clinical impact of sarcopaenia on chemotherapy delivery in a population with gastric and oesophageal cancers receiving neoadjuvant and palliative treatments. Methods: Patients diagnosed with gastric or oesophageal cancers with digital imaging that received chemotherapy between 2010 and 2014 at St Vincent’s Hospital were included. Our primary aim was to determine whether sarcopaenia affected treatment by assessing the reason for cessation of chemotherapy, treatment tolerability and toxicity end-points. Baseline and three month post-chemotherapy body composition analysis calculated CT muscle cross-sectional area using Slice-O-Matic software. A lumbar-skeletal muscle index (LSMI) ≤ 38.5cm2/m2 in females and ≤ 52.4cm2/m2in males defines sarcopaenia. Results: Primary analysis included 32 patients. 72%(N = 23) were sarcopaenic at diagnosis, 75% of those patients lost further muscle mass throughout chemotherapy (2.6-30.6% loss). 63% of those with baseline normal muscle mass became sarcopaenic at three months. Median body mass index (BMI) at diagnosis was 24 kg/m2 (range 17.6-34.4). 44% (N = 14) were within normal range of BMI, 25% (N = 8) underweight, 25% (N = 8) overweight and 6% (N = 2) obese. 100% of those underweight were also sarcopaenic, 72% of normal and 63% of overweight. 70% required dose reductions, delays or cessation due to toxicity; 35% in the sarcopaenic group, 89% in non-sarcopaenic group. Baseline sarcopaenia was associated with worse survival; adjusted for age and amount of chemotherapy received. For every 10cm2/m2decrease in LSMI, there was a 90% increased risk of death (p = 0.05, HR 1.88). Conclusions: Most patients with gastric or oesophageal cancers are sarcopaenic at diagnosis regardless of stage. For those with normal body composition, most will become sarcopaenic during treatment. Sarcopaenia does not correlate with BMI. The majority of sarcopaenic patients completed chemotherapy without delay or dose adjustment for toxicity. Despite this, sarcopaenia is an independent negative predictor of survival in this group.
Age as a decision factor for doing autologous stem cell transplantation in fit patients with myeloma and lymphoma.
Authors: Osman Ilhan, Erden Atilla, Pinar Ataca, Sinem Civriz Bozdag, Selami Kocak Toprak, Meltem Kurt Yuksel, Pervin Topcuoglu, Onder Arslan, Muhit Ozcan, Taner Demirer, Hamdi Akan, Meral Beksac, Gunhan Gurman
Journal: Journal of Clinical Oncology (2016)

e19001 Background: Although there are many elderly patients who are eligible for high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) rescue, the evidence is inadequate. Methods: Between Jan 2003 and Oct 2015, 146 patients (91 M; 55F) admitted to Ankara University Department of Hematology were included in the study. We retrospectively evaluated the early toxicity and outcome of the ASCT following HDT. Results: Patient characteristics are shown in table. In comparison of the toxicities including oral mucositis, diarrhea, renal failure, liver and cardiac toxicity and the incidences of overall infections, we found only oral mucositis and diarrhea that were more frequent in patients with myeloma than lymphoma (p=0.02 and 0.03, respectively). When similar comparisons were repeated according to age (<65 ys vs ≥65 ys), Sorror CI (low vs intermediate and high), the intensity of conditioning regimen for melphalane (standard vs low dose), the rates of toxicities and infection did not change. In addition, engraftment kinetics were not affected by the diagnosis, and age. However, faster neutrophil recovery was observed in low and intermediate Sorror CI compared to high index (median 11 days vs 12 days, p=0.03). Early-transplant related mortality (TRM) was seen only in 6 patients. The diagnosis, age and Sorror CI were not found to have any impacts on both TRM and overall survival. Conclusions: Although the oral and gastrointestinal mucositis were more frequent in myeloma patients, TRM and OS did not differ. Therefore, HDT with ASC rescue was demonstrated to be a safe option in the treatment of myeloma and lymphoma patient in advanced age in our cohort. Patient Characteristics Median age (years) 64 (60-74 years) Median time from diagnosis to transplantation (months) 18.4 months (3.1-188.7 months) Diagnosis 127 Multiple Myeloma,10 Diffuse Large B cell, 6 Mantle cell Lymphoma, 1 Plas mositoma, 1 Primary Amyloidosis, 1 Fol licular Lymphoma Sorror Comorbidity index Low 69.2%,Intermediate 24.6%,High 6.2% Pretransplant disease status 40% active disease, 60% remission Conditioning regimen 95% (BEAM: BCNU+Etoposide+ARAC +Melphalan), 5% (ICE: Ifosfamide+Car boplatin+Etoposide)
Use of Intracardiac Echocardiography in Interventional Cardiology
Authors: Andres Enriquez, Luis C. Saenz, Raphael Rosso, Frank E. Silvestry, David Callans, Francis E. Marchlinski, Fermin Garcia
Journal: Circulation (2018)

The indications for catheter-based structural and electrophysiological procedures have recently expanded to more complex scenarios, in which an accurate definition of the variable individual cardiac anatomy is key to obtain optimal results. Intracardiac echocardiography (ICE) is a unique imaging modality able to provide high-resolution real-time visualization of cardiac structures, continuous monitoring of catheter location within the heart, and early recognition of procedural complications, such as pericardial effusion or thrombus formation. Additional benefits are excellent patient tolerance, reduction of fluoroscopy time, and lack of need for general anesthesia or a second operator. For these reasons, ICE has largely replaced transesophageal echocardiography as ideal imaging modality for guiding certain procedures, such as atrial septal defect closure and catheter ablation of cardiac arrhythmias, and has an emerging role in others, including mitral valvuloplasty, transcatheter aortic valve replacement, and left atrial appendage closure. In electrophysiology procedures, ICE allows integration of real-time images with electroanatomic maps; it has a role in assessment of arrhythmogenic substrate, and it is particularly useful for mapping structures that are not visualized by fluoroscopy, such as the interatrial or interventricular septum, papillary muscles, and intracavitary muscular ridges. Most recently, a three-dimensional (3D) volumetric ICE system has also been developed, with potential for greater anatomic information and a promising role in structural interventions. In this state-of-the-art review, we provide guidance on how to conduct a comprehensive ICE survey and summarize the main applications of ICE in a variety of structural and electrophysiology procedures.
Comprehensive tumor genomic testing in the community oncology setting in the United States.
Authors: John Marshall, Arden Buettner, Maria L. Lankford, Mitch Scharf, Joanne P. Willey, Susan Lynne Britton
Journal: Journal of Clinical Oncology (2018)

e24304 Background: Next-generation sequencing (NGS) is increasingly performed to provide personalized care for patients with cancer. 2017 was a historic year for precision medicine in oncology: In May, the FDA approved pembrolizumab for MSI-H or dMMR solid tumors, the first approval based on a biomarker rather than tumor location Over the course of 2017, the FDA approved Thermo Fisher Oncomine Target Test, MSKCC IMPACT, and FoundationOne CDx Also in Nov, the Center for Medicare and Medicaid Services issued a preliminary National Coverage Determination for NGS testing, which would provide coverage for FDA-approved companion diagnostic claims Methods: In 2017, we assessed practices, preferences, and barriers related to NGS testing among 143 practicing US-based community medical oncologists (USMO) using Xcenda’s live, market research tool with blinded audience response technology. Research support sources were double blinded. Results: USMO believe NGS testing will continue to grow in importance to their practice and to treatment decisions for their patients. USMO are most likely to order NGS testing for pts with NSCLC, CRC, and melanoma, and for tumors with fewer treatment options, whose 1st line decision depends on marker results, or if all lines of standard therapy have been used. Insurance coverage/reimbursement, insufficient tissue, and patient cost are the biggest obstacles to using NGS profiling. Conclusions: Excitement and interest in NGS profiling and tumor agnostic/genetically-defined cancers is high, but challenges and barriers exist in the community oncology setting. The recent FDA approvals of NGS tests, and preliminary CMS NCD should increase awareness of and access to NGS profiling. Challenges to ordering NGS profiling Rank order Insurance coverage/reimbursement 1 Insufficient tissue 2 Cost to the patient 3 Utility of the results to impact clinical decision-making 4 Difficulty interpreting reports 5 Lack of clinical evidence to support the testing 6 Lack of guideline support 7 Cost to the practice/institution/system 8 Resistance from pathologists or other specialists 9 Turn-around time for results 10
INNOVATE-3: Phase 3 randomized, international study of tumor treating fields (200 kHz) concomitant with weekly paclitaxel for the treatment of platinum-resistant ovarian cancer.
Authors: Eilon David Kirson, Moshe Giladi, Zeev Bomzon, Uri Weinberg, Ori Farber
Journal: Journal of Clinical Oncology (2018)

TPS5614 Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality FDA-approved for glioblastoma. TTFields act by disrupting mitotic spindle formation during metaphase. In multiple preclinical models of ovarian cancer, TTFields (200 kHz) reduced viability of cell lines via apoptosis. TTFields has demonstrated synergistic effects with taxanes in vitro and in vivo. The Phase 2 INNOVATE clinical study [NCT02244502] demonstrated the safety of TTFields combined with weekly paclitaxel in 31 PROC (platinum-resistant ovarian cancer) patients. Patients had a median of 4.1 prior chemotherapy regimens (range: 1-11). Most patients had CTCAE grade 1-2 TTFields-related dermatitis; 6.4% had grade 3 toxicity. Median progression-free survival was 8.9 months. The INNOVATE-3 is a phase 3 study in PROC of TTFields combined with weekly paclitaxel. Methods: Patients with PROC (progression per RECIST V1.1) within 6 months of last platinum therapy with a maximum of two lines following the diagnosis of PROC and maximum total of five prior lines of systemic therapy will be enrolled. Patients (ECOG score 0-1) will have no peripheral neuropathy. Patients with primary refractory disease (progression during first line therapy) will be excluded. Patients will be randomized in a ratio of 1:1 to receive either weekly paclitaxel alone or weekly paclitaxel in combination with TTFields (200 kHz). Weekly paclitaxel will be administered at standard starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for each subsequent 28-day cycle. TTFields will be applied in the experimental arm for at least 18 hours/day on average, and maybe continued as long as there is no progression in the abdominal or pelvic regions ("in-field region") per RECIST V1.1. Clinical follow up will be performed q4w, with radiological follow up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint will be overall survival. Main secondary endpoints include progression-free survival, objective response rate, severity and frequency of adverse events and quality of life based on EORTC QLQ-C30 with the QLQ-OV28 questionnaire.
Relationship of healthcare costs and disease progression in patients with HER2+ breast cancer.
Authors: Hans-Peter Goertz, Daniel Sheinson, Ning Wu
Journal: Journal of Clinical Oncology (2018)

e13013 Background: Reducing disease recurrence with better treatments in the adjuvant setting may alleviate the economic burden associated with metastatic disease in HER2 positive breast cancer (BC). Analyses were performed to complement existing literature on the cost of metastatic HER2+ breast cancer given the introduction of new treatment options since 2012. Methods: We performed a retrospective cohort study using Truven Marketscan 2011-2016 commercial and Medicare administrative claims data. Metastatic BC patients were followed for up to three years and healthcare costs (hospital stays, prescription costs, outpatient services) were analyzed. An additional matched cohort analysis was performed for recurrent patients, selecting adjuvant treated patients who did not progress with similar age, year of initial anti-HER2 treatment, anti-HER2 treatment duration and follow-up duration. Results: Three year costs following a diagnosis of metastatic BC cancer were $470,240. The matched cohort analysis showed patients with metastatic BC incurred costs greater than $240,000 vs. less than $20,000 for a cohort of adjuvant treated patients who did not progress in the first year post-index date. Average Healthcare Costs After Metastasis in HER2+ Breast Cancer Conclusions: Total healthcare costs in the first year after metastatic diagnosis was high in HER2+ breast cancer patients. Relative to healthcare costs in patients treated in the early BC setting who did not progress, metastatic BC costs were over $240,000 vs less than $20,000 for a comparable cohort of patients. Reducing recurrences with better treatment in the adjuvant setting may be important in alleviating the economic burden associated with HER2 positive metastatic breast cancer Sample Costs in the 1st year after metastasis Mean (SE) Costs in 2 years after metastasis Mean (SE) Costs in 3 years after metastasis Mean (SE) Pts with at least 1yr follow-up (N = 1,799) 267,485 (3,737) Pts with at least 2yr follow-up (N = 910) 257,316 (5,257) 382,115 (8,704) Pts with at least 3yr follow-up (N = 391) 248,759 (7,904) 366,811 (13,383) 470,240 (18,672)
Theranostics based on AIEgens
Authors: Dong Wang, Michelle Mei Suet Lee, Wenhan Xu, Ryan Tsz Kin Kwok, Jacky Wing Yip Lam, Ben Zhong Tang
Journal: Theranostics (2018)

The utilization of luminogens with aggregation-induced emission (AIE) characteristics has recently been developed at a tremendous pace in the area of theranostics, mainly because AIE luminogens (AIEgens) hold various distinct advantages, such as good biocompatibility, excellent fluorescence properties, simple preparation and modification, perfect size of nano-aggregation for enhanced permeability and retention effect, promoted efficiencies of photodynamic and photothermal therapies, efficient photoacoustic imaging, and ready constructions of multimodal imaging and therapy. Significant breakthroughs and developments of theranostics based on AIEgens have been achieved in the past few years, and great progress has been witnessed in many theranostic modalities, indicating that AIEgens remarkably complement conventional theranostic materials and promote the development of theranostics. This review provides theoretical insights into the advantages of AIEgens in theranostics, and systematically summarizes the basic concepts, seminal studies, recent trends and perspectives in theranostics based on AIEgens. We believe that AIEgens would be promising multifunctional theranostic platforms in clinical fields and facilitate significant advancements in this research-active area.