bluuebunny/crossref_metadata_2025_split huggingface dataset:
We couldn’t resist comparing central with local RECIST1.1 and with Choi assessment: Exploratory analysis of tumor imaging in EORTC STBSG Phase 2 trial 1317 “CaboGIST.
Authors: Kyriazoglou Anastasios , Jespers Pieter , Vandecaveye Vincent , Mir Olivier , Kasper Bernd , Papai Zsuzsanna , Blay Jean-Yves , Italiano Antoine , Zaffaroni Facundo , Litiere Saskia , Nzokirantevye Axelle , Schoffski Patrick 
Published: May 2020

e23563 Background: Gastrointestinal stromal tumor (GIST) is commonly driven by activating mutations in KIT or PDGFRA. Advanced GIST is treated with tyrosine kinase inhibitors (TKIs) but develops resistance over time. EORTC 1317 assessed the safety and activity of cabozantinib, a multi-TKI targeting KIT, MET, AXL and proangiogenic pathways, in GIST patients who had progressed on imatinib and sunitinib. The efficacy analysis of the trial, which met its primary endpoint, was based on local assessment of RECIST1.1 response. RECIST neglects myxoid degeneration, necrosis and vascular remodeling induced by TKIs without major volumetric changes. Density changes on CT scans can predict clinical benefit and can be assessed by Choi criteria. Methods: We describe results of a post hoc exploratory analysis of CT scans performed centrally using RECIST 1.1 and Choi criteria. Results: Week 12 scans were available and evaluable by central review in 43 pts, Choi in 42 cases. Comparisons between local and central RECIST1.1 outcome revealed discrepancies in 17/43 evaluable cases (39.5%). When comparing Choi with local and central RECIST1.1 at week 12, discrepancies were observed in 27/42 (64.3%) and 21/42 (50%) evaluable cases, respectively. In summary, 70% of evaluable patients were progression-free and alive at week 12 based on local assessment, 86% and 83% according to central RECIST1.1 and Choi criteria, respectively. The main difference was the rate of objective response with cabozantinib in week 12: 5 PR (12%) with local RECIST1.1, 3 PR (7%) with central assessment, and 21 PR (50%) with Choi criteria. Conclusions: RECIST1.1 remains an unsatisfactory tool for response assessment in GIST, illustrated by the high inter-rater variability of response outcome comparing local versus central analysis. RECIST1.1 clearly underestimates the anti-tumor activity of TKIs in GIST. Cabozantinib did not only meet the primary endpoint of this trial when applying RECIST1.1 per protocol, but achieved objective responses in 50% of evaluable patients in week 12 when using Choi criteria. [Table: see text]
Hyperthermia combined with nanoparticles to enhance cytotoxic effects of fresh human soft tissue sarcoma.
Authors: Raj Shailaja KS , Raj Shailaja KS , Triozzi Pierre , Staley Stephanie , Emory Cynthia , Wilson Scott , Shen Perry , Levine Edward Allen , Savage Paul David , Levi-Polychenko Nicole 
Published: May 2020

e23570 Background: Sarcomas represent 1% of all adult cancers and 20% of all pediatric cancers worldwide.Sarcomas are heterogeneous with more than 50 histologic subtypes involving the mesenchyme including bones, muscle, fat, blood vessels, and nerves. Patients with high-risk localized or advanced disease are treated with the combination of neoadjuvant or adjuvant chemotherapy, radiation, and surgical resection have all failed to substantially improve overall survival (OS).4 Novel treatments are desperately needed in the management of soft tissue sarcoma. Thermal ablation of sarcoma may offer a novel method for eradicating the disease. Polymer based nanoparticles that can be stimulated with light to generate heat (photothermal nanoparticles) have been developed previously and used to induce. The goal of the current work is to utilize these nanoparticles for selected ablation of sarcoma. Methods: Polymer nanoparticles were first prepared in the in our lab through the synthesis of 2‐ethylhexyl cyclopentadithiophene 2,1,3‐benzoselenadiazole (PCPDTBSe). Nanoparticles of this polymer were prepared using an oil-water emulsion technique, with FITC labeled polyethylene glycol as the stabilizing agent, to create an aqueous suspension. The nanoparticles were characterized for their size and ability to generate heat when stimulated with 800 nm laser light (180J/cm2). Fresh Soft tissue sarcoma samples are obtained through informed consent and approval of the institutional IRB. Nanoparticles were injected into sarcoma in a volume of 100ul, at a concentration of 250ug/ml. The tissues were then exposed to the laser source to generate heat. Controls included the injection of the sarcoma with the nanoparticles and no laser exposure, as well as the injection of water, plus laser exposure. Results: Sarcomas vary in their ability to take up and response to nanoparticles. We have found that liposarcoma samples are extremely leaky and do not hold the injection of nanoparticles, which leach out of the tumor. Conclusions: Future directions include studies that would involve targeted, immunotherapy and chemotherapy given with nanoparticles that facilitate combinatory and unique individual cytotoxic effects of the soft tissue sarcoma subtypes.
Integrated genomic and functional analysis of patient-derived sarcoma cell lines validates their use for candidate treatment discovery including knockdown of a novel BCOR fusion gene.
Authors: Swierczek Sabina , Pandya Deep , Billaud Jean-Noel , Vigil Dominguez Irma , Farisello Sara , Sieber Steven , Chen Ying , Chuang Linus T. , Andikyan Vaagn , Martignetti John 
Published: May 2020

e23572 Background: Malignant peripheral nerve sheath tumors (MPNST) are rare, biologically-aggressive soft tissue sarcomas of neural origin, characterized by high risk of recurrence, metastases, treatment resistance and lethality. Preclinical models accurately reflecting underlying genetics are needed for exploring the tumor’s biology and developing novel therapeutic approaches. Using genomic, biochemical and bioinformatic approaches we generated and deeply characterized a patient-derived MPNST cell-line model (PDCL) and functionally validated identified therapeutic targets including a novel BCOR fusion gene. Methods: Under IRB consent, two geographically distinct metastatic tumor samples were obtained from a right peritoneal nodule (PN) and the pelvis (P) of a 63-year-old woman, with recurrent uterine MPNST to generate PDCL. Whole exome (WES) and RNA sequencing was performed on all samples. Data and bioinformatic analysis was performed using the QIAGEN software suite (CLC Genomic Workbench, Ingenuity Variant and Pathway Analysis, OmicSoft-ArrayStudio). Results: To define the degree of shared genomic diversity, WES and RNAseq of tumors and PDCL was performed. WES of metastatic samples identified both shared (n = 39) and novel (98 and 116, respectively) cancer driver variants, which were also present in the paired PDCL (38% and 39%, respectively). Furthermore, somatic copy number alterations (SCNAs) were also shared between tissue and paired PDCL. These SCNAs are present in the MPNST TCGA dataset suggesting broad biologic significance. Finally, a novel and expressed BCOR-CREBRF fusion was present in all samples. With the potential to identify and validate candidate therapies, bioinformatic analysis was used to identify shared canonical signaling pathways (Ephrin receptor signaling) and upstream regulators (HBEGF, VEGFA, and ERBB2) between tumors and PDCL. Based upon this analysis, the inhibitory effects of a targeted list of candidate drugs was performed: Dasatinib, Pazopanib, PD153035, and Lapatinib all selectively resulted in tumor cell death. Moreover, siRNA-mediated BCOR-CREBRF knockdown significantly inhibited PDCL growth. Conclusions: We demonstrate that MPNST PDCL capture the genomic diversity inherent in their founder tumor tissues and potentially other MPNST. Moreover, using a bioinformatic approach for therapeutic discovery, demonstrate the use of these PDCL for testing treatment candidates for possible use in MPNST patients.
Combined surgeries for retroperitoneal tumors.
Authors: Kit Oleg I. , Katelnitskaya Oksana V. , Maslov Andrey A. , Gevorkyan Yuriy A. , Kolesnikov Evgeniy N. , Trifanov Vladimir S. , Kozhushko Mikhail A , Lysenko Irina B. 
Published: May 2020

e23579 Background: Retroperitoneal tumors are rare heterogeneous malignant tumors. Due to their poor response to chemoradiotherapy, surgery is the main treatment option. Currently, there is little data on treatment outcomes in patients who underwent en block resection of retroperitoneal tumors and major vessels. Our purpose was to analyze surgical and oncological results in patients with retroperitoneal tumors and major blood vessel involvement. Methods: 27 patients received surgery for retroperitoneal tumors with major vessel resection in 2015-2019. Results: The mean tumor diameter was 17 cm (11-39 cm). The most frequent histological types were moderately differentiated liposarcoma (33.4%), well differentiated (18.5%), poorly differentiated sarcoma (18.5%), pleomorphic liposarcoma (22.2%), leiomyosarcoma (7.4%). Resection of the suprarenal inferior vena cava (IVC) with prosthetics was performed in 4 cases, resection of its renal segment with renal vein reimplantation - 1, resection of the infrarenal IVC with prosthetics - 8. PTFE prostheses were used as a conduit in all cases. Marginal excision of the suprarenal IVC was performed in one patient, that of the infrarenal IVC - in 5 patients; resection of the infrarenal IVC without the reconstruction - in one case. The iliac venous segment resection was required in 6 patients, in one case – with the iliac arterial segment resection and prosthetics. Macroscopic complete resection (R0-R1) was achieved in 92.6%. The postoperative morbidity was 25.9%, with no fatal outcomes. Despite the anticoagulant therapy, the frequency of thrombosis of the venous reconstruction area in the early postoperative period (1 month) was 7.4%. The median relapse-free survival was 14 months; the median overall survival was not achieved. Conclusions: Combined surgeries with simultaneous removal of retroperitoneal tumor and angioplasty demonstrate an acceptable level of morbidity and mortality. Radical removal of tumors with major blood vessel involvement allows increasing the survival in patients often considered inoperable.
End-of-life characteristics associated with short hospice length of service for patients with solid tumors enrolled on phase I clinical trials.
Authors: Sedhom Ramy , Turnbull Alison , Blackford Amanda L. , Gupta Arjun , Heussner Janet , Griffiths Kelly , Carducci Michael Anthony 
Published: May 2020

e24005 Background: Patients participating in phase I trials represent a population with advanced cancer and symptoms, with QOL implications from both disease and treatment. Transitions to end of life for these patients has received little attention. Good empirical data is needed to better understand the role of advanced care planning (ACP) and palliative care (PC) during phase I trial transitions. We investigated how physician-patient communication at time of progression, patient characteristics, and patterns of care were associated with EOL care. Methods: Retrospective chart review of all patients with solid tumors enrolled in phase I trials at a comprehensive cancer center from Jan 2015 to Dec 2017. We captured physician-patient communication during disease progression, and for all patient deaths, assessed PC referral, ACP, place of death, health care utilization in the final month of life, hospice enrollment and LOS. Factors independently associated with a short hospice LOS (defined as ≤3 days) were estimated from a multivariable model building approach. Results: Among 207 participants, median age was 61 (range 31-91), 48% were female and 20% were ethnic minorities. Predominant diagnoses were GI (40%), GU (14%), and lung cancer (15%). 40% of patients were referred from an outside institution. At the time of disease progression, 64% had goals of care documented, 57% were referred to PC, and 54% discussed hospice with their oncologist. Overall, 82% of patients died within 1 year of study enrollment. Of all patients who died, 85% enrolled in hospice and 76% died at home. In the last 30 days of life, 37% were hospitalized, 21% received chemotherapy, and 8% were admitted to the ICU. 15% had a short hospice LOS. The multivariable model revealed that increased age > 65 was positively associated with short hospice length of service (odds ratio (OR) 1.12 [95% CI 1.01, 1.24], p = 0.03), while remaining at the same institution (OR 0.72 [95% CI 0.65, 0.8], p < 0.001), and referral to PC before progression (OR 0.83 [95% CI 0.75, 0.92], p < 0.001) were associated with a decreased risk of short hospice LOS. Conclusions: This data supports the benefit of PC for patients on phase I trials and the danger of transitions for all patients, with particular attention needed for older adults, regardless of care received. Leaving a clinical trial is a time when clear communication is paramount. Phase 1 studies will continue to be vital in advancing cancer treatment. It is equally important to advance the support provided to patients who transition off these trials.
End-of-life (EOL) trajectories among older adults dying with lung cancer (LC).
Authors: Davidoff Amy J. , Canavan Maureen , Wang Shi-Yi , Prsic Elizabeth Horn , Saphire Maureen , Presley Carolyn J 
Published: May 2020

e24008 Background: Medicare decedents often receive intensive care during the last month (mth) of life. There is little information on longer (6-mth) EOL trajectories of care intensity. Area hospice use rates may reflect supply and/or patient and physician preferences, and may influence patterns for individual decedents. Methods: Using SEER-Medicare linked registry and claims data, we selected decedents diagnosed with LC between 2008-2013 who survived ≥6-mths and died between 2008-2014. We linked Dartmouth Atlas data on hospital referral region (HRR) % cancer decedents with hospice use. Each mth we assessed claims to identify cancer-directed (CD) care (chemotherapy or radiation) and pharmacologic or other palliative care services (PCS) and assigned decedents to either CD only, PCS only, concurrent CD & PCS, full-mth inpatient (IP) or full-mth hospice. We ordered monthly care intensity from high to low (IP > CD only > concurrent CD & PCS > PCS only > hospice). Using the indicators arrayed by calendar mth, we assigned each decedent to 1 of 6 trajectories: stable (6-mth continuous) hospice, stable PCS only, stable CD only or concurrent CD & PCS, decreasing intensity, increasing intensity, and mixed (multiple directional shifts). Multinomial logistic regression estimated associations between area hospice rates, socio-demographics, and comorbidity with EOL trajectory, controlling for 1st line therapy, and diagnosis stage. Results: Our sample (N = 24,342) was predominantly male (53.7%), age ≥75 years (59.4%), and non-Hispanic white (80.5%); 19.1% lived in HRRs where ≤50% of cancer decedents received any hospice care. Trajectories were 7% stable hospice, 26% stable PCS only, 4% stable CD; 29% decreasing intensity, 9% increasing intensity, and 26% mixed. Relative to stable hospice, higher HRR-level hospice rates were associated with decreasing EOL intensity; higher age, female, and married were associated with increased probability of stable hospice enrollment); Black, non-Hispanic decedents had higher risk of increasing intensity (aRRR: 1.39, 95% confidence interval: 1.09-1.76, p < .01) and mixed patterns. Conclusions: Among older decedents with LC, only 62% had 6-mth EOL trajectories indicating low- (stable hospice or PCS only) or decreasing intensity, but few received persistent CD care. Area hospice use patterns, demographic characteristics and health status were associated with EOL trajectory. Additional research is needed to identify subgroups at risk of high or increasing intensity trajectories, and interventions that may shift trajectories towards lower intensity at EOL.
The association between initial chemotherapy treatment timing, intensity, and end-of-life (EOL) care trajectory among older adults with advanced stage lung cancer (aLC).
Authors: Presley Carolyn J , Shahzad Haseeba , Canavan Maureen , Prsic Elizabeth Horn , Saphire Maureen , Wang Shi-Yi , Davidoff Amy J. 
Published: May 2020

e24009 Background: The use of chemotherapy regimens with varying intensities at specific time points may have an effect on EOL care trajectories among older adults with aLC (IIIB & IV). Methods: Using the Surveillance, Epidemiology, and End Results (SEER)–Medicare registry and claims data, we selected decedents diagnosed with aLC (small cell: SCLC and non-small cell: NSCLC) between 2008 and 2013 who survived ≥6 months (death between 2008 and 2014). Main outcome measures were EOL care trajectories in the 6 months prior to death among patients receiving chemotherapy characterized by intensity levels. A multinomial logit model was used to determine the association between intensity of initial chemotherapy regimen and EOL care trajectory. Results: Our sample (N = 10,594) was mostly NSCLC (77%) of whom only 63% received chemotherapy. Patients receiving chemotherapy were predominantly males (70.4%), age 66-69 years (80%), non-Hispanic white (68.1%) and 78.4% were married. 41 % received treatment prior to EOL-6 and 10.4 % first initiated treatment during EOL-6. The majority of patients received a platinum-based doublet as a first line therapy. Compared to non-cisplatin platinum doublet chemotherapy, patients receiving cisplatin were least likely to be in the decreasing intensity EOL group and most likely to be in increasing intensity EOL group (see table). Conclusions: Among aLC decedents, patients who received cisplatin chemotherapy as compared to non-cisplatin doublet chemotherapy were least likely to be in the decreasing EOL intensity group and most likely to be in the increasing EOL intensity group. EOL care preferences may need to be considered when choosing initial chemotherapy treatment regimens. [Table: see text]
Immune checkpoint inhibitor toxicity and associated outcomes in a geriatric population.
Authors: Polewski Peter James , Hayashi-Tanner Yacki , Gaddam Mamatha , Fisher Nancy R , Kovacs Attila J , Marinier David E. 
Published: May 2020

e24014 Background: Increased use of immune checkpoint inhibitor (ICI) therapy over various cancer types has resulted in a parallel rise in immune-related adverse events (irAEs). There is limited data with regards to understanding irAEs in the elderly population despite its widespread use. We aimed to investigate irAEs in elderly patients receiving checkpoint inhibitor immunotherapy in a community oncology practice setting. Methods: Our retrospective study included patients ≥65 years old treated at a community oncology practice setting from January 1, 2011 through September 30, 2019 who received at least one treatment of a PD-1 or PDL-1 inhibitor (PDI) and/or CTLA-4 checkpoint inhibitor. We evaluated the prevalence of irAEs, determined if age, class of ICI, or oncologic response (clinical and radiographic) was associated with higher grades of irAE. The impact of irAEs on progression-free survival (PFS) and overall survival (OS) was also analyzed. Results: A total of 210 patients were identified, of which 76 developed irAEs. The overall mean age was 75.0 ± 7.2 years. Males accounted for 58% and the overall majority were Caucasian. The most common cancers were lung (56.7%), melanoma (20.0%) and genitourinary (14.8%). The prevalence of irAEs was 36.2% with a distribution of grades 1-2-3-4-5 being 31.6% - 43.4% - 17.1% - 6.6% and 1.3%, respectively. Hazard ratio adjusted for number of cycles for OS was 1.47 (95% CI, 0.98 to 2.19; p = 0.058) and PFS was 1.11 (95% CI, 0.72 to 1.71). Conclusions: To our knowledge, this is one of the few studies that has explored irAEs in the geriatric population. There was no association between ICI-associated higher-grade toxicities and oncologic response in our elderly population. Although there was a trend in OS, we found no statistical differences between elderly patients with irAEs and those without for OS and PFS. Further study is needed to explore the occurrence irAEs in the elderly to improve management of these patients.
Treatment trends with immune checkpoint inhibitor (ICI) therapy in older adults with lung cancer.
Authors: Walko Christine Marie , Dickey Allison , Motsinger-Reif Alison A. , Scholl Elizabeth , McLeod Howard L. , Hauser Robert Sean , Van Londen G J. , Singh Harpreet , Simon Jody 
Published: May 2020

e24016 Background: ICI therapy has become the standard of care for the treatment of most types of advanced lung cancer with an average age at diagnosis of 70 years old (yo). The objectives of this study were to describe the demographics and practice patterns of real-world ICI usage in lung cancer patients > 70 yo. Methods: We conducted a retrospective, observational cohort study utilizing statistically deidentified data sourced from CancerLinQ Discovery® ( www.cancerlinq.org/solutions/researchers ): Lung Cancer (2014-2019), October, 2018 data set release, American Society of Clinical Oncology’s (ASCO’s) CancerLinQ LLC. Of the 1632 patients in this data release, only those patients who received a single agent ICI of nivolumab, pembrolizumab or atezolizumab and had a known birthdate were included in the analyses. Results: The majority of the 1632 patients in the data set were male (46.9%) and Caucasian (43.4%), although a substantial percentage of patient Gender and Race data was not known (14.5% and 43.1% respectively). The majority of the patients were treated in the southern part of the United States (52.6%) and the median ages for adenocarcinoma and squamous cell carcinoma histologies were 66 and 70, respectively, with interquartile ranges of 59-74 and 63-76. In the analyses, the major delineator was age at 70 yo, where age is based on when a patient received their first ICI dose. For patients < 70 yo, the mean (max) number of cycles in patients who received atezolizumab, nivolumab and pembrolizumab was 5.4 (24), 8.7 (62) and 7.7 (32), respectively and for patients > 70 yo was 4.6 (30), 8.1 (64) and 6.5 (23), respectively. The median overall survival for patients < 70 yo who received atezolizumab, nivolumab and pembrolizumab was 24, 12 and 24 months, respectively and for patients > 70 yo was 24, 12 and 18 months, respectively. Conclusions: The number of cycles and overall survival reported in this real-world dataset were similar between patients older and younger than 70 yo with lung cancer treated with ICI. Limitations included decreased power for multivariate analysis due to suppressed data elements which has been improved in more recent data releases.