bluuebunny/crossref_metadata_2025 huggingface dataset:
Epitheliod sarcoma: Molecular insights into proximal versus classic variant.
Authors: Frezza Anna Maria , Sigalotti Luca , Del Savio Elisa , Baldazzi Davide , Sbaraglia Marta , Righi Alberto , Gambarotti Marco , Barisella Marta , Brich Silvia , Dei Tos Angelo Paolo , Stacchiotti Silvia , Maestro Roberta
Published: May 2020

e23552

Background: Epithelioid sarcoma (ES) is an ultra-rare sarcoma with distinctive pathologic and clinical features, marked by the loss of the expression of the SWI/SNF chromatin remodeling complex subunit SMARCB1. The current WHO classification recognizes two ES subtypes, different by morphology, clinical behavior and outcome: the “classic-type” and “proximal-type” ES. This study is aimed to better understand the molecular grounds sustaining this difference, and to identify new potential treatment targets to personalize therapy in this rare disease. Methods: RNA sequencing profiling was conducted on FFPE samples. Functional annotation enrichment was evaluated through over representation and gene set enrichment analyses (GSEA). Inference of immune contexture was obtained through deconvolution and single sample GSEA (ssGSEA) approaches. Results: Twelve samples from 5 proximal-type ES and 7 classic-type ES were profiled, 10 naïve and 2 pre-treated with chemotherapy. Proximal variant samples featured an overepresentation of MYC activity signatures and of other signatures impacting on cell cycle, protein synthesis and chromatin metabolism. Pathways enriched in the classic variant included NOTCH/HEDGEHOG and immune system regulation (e.g. inflammatory, interferon alpha and interferon gamma). Accordingly, deconvolution and ssGSEA approaches predicted an increased immune infiltration in classic subtype samples, essentially involving T cells, as well as increased expression of HLA class I molecules. Conclusions: Different regulatory networks seem to contribute to the different biologic and clinical behavior of proximal and classic ES. These preliminary data suggest a potential greater sensitivity of proximal type ES to drugs targeting the cell cycle, whilst immune checkpoint inhibitors might have some activity in classic variant ES. Further studies are ongoing to validate these preliminary observations.
Patient and diagnostic intervals of sarcoma patients: Results from a survivorship study in the Netherlands.
Authors: Soomers Vicky L.M.N. , Husson Olga , Desar Ingrid M.E. , van de Sande Michiel , De Haan Jacco , Verhoef Cornelis , Vriens Ingeborg , van Houdt Winan J. , van de Poll-Franse Lonneke V , Van Der Graaf Winette T.A.
Published: May 2020

e23553

Background: Sarcoma patients are hypothesised to experience long intervals to cancer diagnosis, due to the rarity of the disease, heterogeneous presentation, and complexity of histological diagnosis. Comprehensive assessment of patient interval (time between first symptom and presentation to a doctor), diagnostic interval (time between presentation to a doctor and diagnosis ), and their associated factors is needed to improve referral pathways and outcomes for sarcoma patients. We investigated patient and diagnostic intervals and identified factors associated with prolonged intervals in order to identify risk groups. Methods: We conducted a cross-sectional cohort study among adult sarcoma survivors, diagnosed between 2008-2016. After informed consent, patient-reported interval length was collected via (online) questionnaires. This data was linked to the Netherlands Cancer Registry, which collects clinical data from patients at diagnosis. Descriptive statistics were used to describe interval lengths. Logistic regression analyses were conducted to investigate associations of patient and tumour characteristics (gender, age at diagnosis, time since diagnosis, histology, presence of metastases, grade, and localisation), with patient and diagnostic interval length. Results: 1099 survivors completed questionnaires (response rate 58%); 53% had a patient interval ≥1 month. Risk factors for a patient interval ≥1 month were bone or breast sarcoma, and being young(18-39 years). An interval ≥3 months (33%) was associated with dermatofibrosarcoma protuberans, bone sarcoma, low grade, and location in skin or pelvis. Diagnostic interval length was ≥1 month in 53%; risk groups were bone sarcomas, females, and young (18-39) or middle-aged (40-69) patients. In 27% the diagnostic interval lasted ≥3 months; risk groups were synovial sarcoma, chordoma, bone sarcomas in general, females, and being young (18-39) or middle aged (40-69). Conclusions: Over half of sarcoma survivors had a patient interval ≥1 month; a third ≥3 months. More than half of them reported a diagnostic interval ≥1 month; a quarter ≥3 months. Females and young patients were more at risk for a long diagnostic interval. Although limited by its retrospective nature, this study is the largest that studied the interval in a sarcoma survivorship group. Our current QUEST study (NTR-7253) will study the diagnostic trajectory prospectively to confirm these findings and find reasons for these results.
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.
Does age contribute to distress in new geriatric oncology patients?
Authors: Saiganesh Harish , Khurshid Humera , Raza Sakeena , Dizon Don S.
Published: May 2020

e24023

Background: As part of routine practice at the Lifespan Cancer Institute (LCI), all new patients are screened with the NCCN Distress Thermometer (DT). There is little to no data comparing initial distress levels among patients 65 and older recently diagnosed with cancer and how this might change with increasing age. This study sought to describe distress at initial presentation among two cohorts: patients 65 to 74 years and those 75 years and over. Methods: We have retrospectively reviewed 1800 patients at Lifespan Cancer Institute so far, all of whom were initially seen between the years 2014-2017. Data related to demographics, tumor type, initial distress score, and sources of distress were gathered using our electronic medical records. Categorical data were analyzed using Fisher’s Exact Test or Chi-Square. Multinomial logistic regression was performed for multivariate analysis. All analyses were performed in STATA 15.0. Results: At time of diagnosis, 898 (49.9%) patients were over 65 years. Of those, 577 (64%) had distress thermometers and were included in this analysis. The median age was 72 (range 65 to 92), 66.9% were female, and 42.5% were married or partnered; 393 (68.1%) were under 75 years and 184 (31.9%) were 75 or older. The major cancers represented included breast (44%), lung (19.6%), and prostate (17%) cancers. The presence of severe distress (DT score of 4 or higher) did not significantly differ by age cohort (45.3 versus 45.7%, respectively, p > 0.5) but differed by tumor group (p < 0.001). Compared to people under 75 years, more of those 75 and older reported sadness (27 versus 20%, respectively, p < 0.05), issues with memory and concentration (12 versus 7.6%, p < 0.1) and trouble with getting around (14.7 versus 8.4%, p < 0.05). On multinomial logistic regression, only tumor group and reporting sadness on the DT remained significant factors for severe distress, whereas age did not. Conclusions: There is no significant difference in distress reporting among geriatric patients with cancer who are under 75 compared to those 75 and older. Tumor type and sadness at the initial presentation were associated with severe distress in this group of people.
Outcomes for geriatric patients evaluated in a same-day multidisciplinary central nervous system clinic for radiation oncology and neurosurgery in a community hospital setting.
Authors: Paez Wencesley A. , Gheewala Rohi , Jaboin Jerry J. , Thomas Charles R. , Ciporen Jeremy N. , Mitin Timur
Published: May 2020

e24034

Background: The geriatric cancer population is rapidly increasing in the United States. Management of geriatric patients with central nervous system (CNS) disease requires a patient-centric, multidisciplinary approach together with meticulous assessment of their outcomes, as clinical studies guiding treatment recommendations are lacking in this patient population. We have previously reported the outcomes of our multidisciplinary community hospital-based CNS clinic, RADIANS, where both radiation oncology and neurosurgery specialists simultaneously evaluate patients in a same-day, single-setting clinic. We have sought to analyze the outcomes of the geriatric patient population of our RADIANS clinic. Methods: We identified patients 65 years and older in our IRB-approved RADIANS Prospective Patient Registry for CNS Disease. Descriptive statistics were used to report patient characteristics, diagnoses, treatments and outcomes, and patient satisfaction scores. Results: Between August 2016 and February 2020, 56 patients 65 years and older (mean age 74.6, range: 65-94; 32 women and 24 men) were evaluated in the RADIANS clinic. Mean distanced traveled by patients to clinic was 43.4 miles (med = 8.3; range = 0.6-341). Patient-reported Satisfaction Score was 4.81 (0-5 Scale, 5-very satisfied). The most common referral source was medical oncology. Forty-two patients had malignant CNS disease (brain mets-18; spine mets-12; both-4; primary brain-6; primary spine-2), 14 had benign CNS disease. Post-evaluation treatment: radiation therapy (RT) only (n = 20), neurosurgery (NS) only (n = 6), both RT and NS (n = 14), and no RT/NS intervention (n = 16). Fractionated stereotactic radiosurgery was most common RT delivered; craniotomy with tumor resection was most common NS performed. Treatment outcomes: local tumor control = 39/40 (97.5%); radiation necrosis/radiation-induced myelitis = 0/34 (0.0%). Conclusions: This is the first report of outcomes in geriatric patients with CNS malignancies treated in a community hospital-based multidisciplinary clinic. We show excellent outcomes comparable to younger patients with CNS malignancies, as well as patient satisfaction and ability to travel great distances to receive multidisciplinary care.
Impact of cancer related stress on illness beliefs and glycemic control in breast cancer survivors with comorbid diabetes.
Authors: Lin Jenny J. , James Janey , Goel Mita , Harris Yael T
Published: May 2020

e24053

Background: Cancer and diabetes mellitus (DM) are leading causes of death in the US and survivors with comorbid DM have a significantly higher mortality. Furthermore, posttraumatic stress disorder (PTSD) can be triggered by life-threatening illnesses such as cancer; however, little is known about the impact of cancer-related PTSD (Ca-PTSD) on illness beliefs and glycemic control. We undertook this study to assess factors associated with DM management in breast cancer survivors with DM. Methods: We recruited women with Stage 0-IIIA breast cancer diagnosed in the past 10 years, who had completed chemotherapy and/or hormonal therapy and had pre-existing DM on ≥1 oral DM medication. The Impact of Event Scale-Revised (IES-R) was used to assess distress caused by cancer. A total IES-R score of ≥33 identified those with probable Ca-PTSD. Cancer and DM related beliefs were assessed using the Illness Perception Questionnaire. Objective adherence to DM medication was assessed using electronic caps that record bottle openings. Wilcoxon rank-sum tests were used to examine the relationship between Ca-PTSD and illness beliefs. Pearson correlation tests were used to assess the relationship between cancer related stress, DM medication adherence, and glycemic control. Results: Of 111 women recruited to date, mean age was 65.4 years and 37% were black, 31% white, 14% Hispanic, 6% Asian, and 8% other. Of these, 15% had probable Ca-PTSD. Survivors with Ca-PTSD were more likely to believe the consequences of cancer and DM were more severe (median score 23.5 vs. 19.0 [p < 0.001] and 24.0 vs. 16.0 [p < 0.001], respectively), that cancer and DM were more cyclical or recurrent (15.0 vs. 9.0 [p = 0.002] and 13.0 vs. 8.5 [p = 0.002], respectively), and there was greater emotional impact due to cancer and DM (24.0 vs. 16.5 [p < 0.001] and 23.0 vs. 14.0 [p < 0.001], respectively). Additionally, those with Ca-PTSD were less likely to understand their cancer (14.0 vs. 20.0, p = 0.004). Furthermore, as cancer-related stress scores increased, glycemic control worsened (r = 0.23, p = 0.03) and DM medication adherence decreased (r = -0.23, p = 0.04). Conclusions: Breast cancer survivors with comorbid DM who have Ca-PTSD are more likely to have negative beliefs about both cancer and DM. Cancer-related stress is also associated with poorer glycemic control and DM medication adherence. Providers should be aware of the impact of cancer related stress on beliefs about comorbid illnesses and increase interventions that support cancer survivors to better manage their comorbidities.
Prospective investigation of immunotherapy-induced fatigue by rest and stress echocardiography.
Authors: Zingarelli Roman , Aras Mandar A , Bibby Dwight , Fang Qizhi , Daud Adil , Schiller Nelson B , Tsai Katy K.
Published: May 2020

e24060

Background: Immune checkpoint inhibitors (ICI) effect durable responses in cancer patients (pts). Myocarditis is rare but fatigue is commonly reported, and whether ICI-induced fatigue is due to subclinical cardiac toxicity is unknown. We hypothesized that pts on ICI develop changes on rest and stress echocardiogram (echo) that correlate with fatigue. Methods: A prospective observational study was performed to monitor cardiac function in pts receiving ICI. Our cohort consisted of pts (n = 10) with stage III/IV melanoma, ECOG 0-1, deemed safe to exercise, without unstable cardiac symptoms. ICI-naïve pts received anti-PD1 alone or in combination with anti-CTLA-4, in adjuvant or metastatic setting. Rest transthoracic echo and dynamic staged exercise stress echo testing was conducted at baseline (prior to ICI) and at 3 and 6 months (mo) following ICI. Various echo parameters at rest and stress were compared. irAEs were detailed and surveys administered at baseline and post-follow up. Results: 10 pts (9 men, mean age 56 yrs) completed baseline cardiac testing of whom 7 completed follow up testing at 6 mo (6 anti-PD1 monotherapy, 1 metastatic combination therapy). Of these 7 pts, 5 (71%) reported increased fatigue per CTCAE at 3 or 6 mo follow up and all 7 had irAEs (3 rash, 1 colitis, 1 diarrhea, 1 hypophysitis, 1 arthralgia, 1 xerostomia). Among resting echo parameters, left ventricular outflow tract velocity time integral (LVOT VTI) was significantly reduced at 6 mo compared to baseline (22.6 ± 3.4 vs 20.0 ± 2.5, p = 0.0047), albeit still within normal range. No other resting echo parameters changed. Among exercise echo parameters, there was no difference in METs achieved, time of exercise, blood pressure or heart rate between time points. Of note, of 7 subjects who completed 6 mo testing, 2 (29%) were unable to achieve previous peak stage of exercise during testing. Conclusions: Though no echo parameter significantly correlating with fatigue was reported, nearly one-third of a small cohort of pts were unable to achieve peak exercise 6 mo after starting ICI. This combined with the statistical reduction in LVOT VTI suggests functional limitation and warrants further study. Post-follow up surveys are pending and may further inform issues important in ICI survivorship. [Table: see text]
Quantitative assessment of proprioceptive dysfunction in cancer survivors post oxaliplatin-containing chemotherapy.
Authors: Wang Allison B. , Housley Stephen Nick , Cope Timothy C. , Flores Ann Marie , Perreault Eric J.
Published: May 2020

e24071

Background: Oxaliplatin (OX) is commonly used for gastrointestinal cancers but can cause chronic neurotoxicity with long-term motor impairments (e.g. dexterity loss, poor balance, and falls). These impairments are often attributed to OX-induced sensory neuropathy that disrupts touch, vibration, and proprioception in distal limbs. However, some cancer survivors report motor impairments even in the absence of sensory neuropathy. Recent animal studies suggest OX induces global signaling dysfunction in muscle proprioceptors that may account for the motor impairments in the absence of sensory neuropathy. However, this mechanism has yet to be investigated in cancer survivors. We hypothesize that cancer survivors will display impaired proprioceptive function compared to age-matched healthy controls using quantitative techniques that are more sensitive than current clinical measures. Methods: We assessed use of proprioception for controlling upper extremity position, force, and posture using target reaching, force matching, and postural stability tasks, respectively. A haptic robot quantified motor performance in all tasks, performed with and without visual feedback to disambiguate proprioceptive from vision. The dominant hand and wrist were fixed in an orthosis emphasizing elbow and shoulder use since these joints are less likely to have sensory neuropathy. Self-reported symptoms and functional limitations were measured with the QLQ-CIPN20 questionnaire. Accuracy and trial-to-trial variability for each task were compared between cancer survivors and controls using linear mixed effect models. Results: Thirteen cancer survivors (0 – 20 months post OX-treatment) and 7 controls completed the study. Without visual feedback, cancer survivors had significantly decreased accuracy (p < 0.001) and increased trial-to-trial variability (p < 0.05) in all tasks compared to controls. Deficits in force matching were correlated with self-reported motor dysfunction on the QLQ-CIPN20 (r = 0.87, p < 0.001). Conclusions: Proprioceptive deficits occur in cancer survivors who received OX-treatment and are associated with motor dysfunction. This identified mechanism of motor impairment may present opportunities for targeted interventions.
Efficacy and toxicity of extending bone modifying agents beyond two years for bone metastases in breast or castrate-resistant prostate cancer patients: A systematic review.
Authors: Ng Terry L. , Tu Megan M. , Ibrahim Mohammed FK , Basulaiman Bassam Mohammed , McGee Sharon , Srikanthan Amirrtha , Fernandes Ricardo , Vandermeer Lisa , Stober Carol , Sienkiewicz Marta , Jeong Ahwon , Saunders Deanna , Awan Arif Ali , Hutton Brian , Clemons Mark J.
Published: May 2020

e24083

Background: Randomized clinical trials evaluated bone modifying agents (BMAs) such as bisphosphonates and denosumab for bone metastases for 1-2 years in duration even though BMA therapy is commonly administered for much longer. A systematic review on the risk-benefit of continuing BMAs for longer than 2 years in breast cancer or castrate-resistant prostate cancer was conducted. Methods: Medline, Embase and Cochrane Register of Controlled Trials were searched (1970 - February 2019) for randomized studies, observational studies, and case series reporting on BMA efficacy and toxicity beyond 2 years. Efficacy was assessed by skeletal-related event (SRE) rates and quality of life metrics. Toxicity was assessed by rates of osteonecrosis of the jaw (ONJ), renal impairment, hypocalcemia, and atypical femoral fractures (AFF). Results: Of 2107 citations, 64 studies were identified. A total of 3 prospective and 9 retrospective studies were eligible. Data beyond 2 years was limited to subgroup analyses in all studies. Three studies [zoledronate (ZOL) (n = 481), pamidronate (PAM) (n = 87), PAM-ZOL (n = 43) ibandronate (n = 30)] reported on SRE-related endpoints. Only one study reported SRE rates based on duration of BMA exposure and showed reduced SRE rates from 27.6% (0-24 months) to 15.5% ( > 24 months) over time. None reported on quality of life. All 12 studies [denosumab (n = 948), ZOL (n = 1036), PAM (n = 163), PAM-ZOL (n = 522), ibandronate (n = 118)] reported on at least one toxicity outcome. Data from 7 bisphosphonate studies (n = 1077) and 1 denosumab study (n = 948) reported on ONJ incidence. In 3 studies (n = 67, n = 221, n = 948), ONJ incidence ranged from 1-4% in the first 2 years and from 3.8-18% beyond 2 years. In another study (n = 252), the cumulative hazard of ONJ was 0% (1% ZOL), 3% (7% ZOL), 7% (21% ZOL) and 11% (21% ZOL) at 12, 24, 36, and 48 months, respectively (p = 0.005); 4 remaining studies reported 1 (n = 181), 3 (n = 57), 7 (n = 99) and 2 (n = 200) cases of ONJ, all after 24 months. Incidence of clinically significant hypocalcemia ranged from 1-2%. Incidence of severe renal function decline was ≤ 3%. AFF occurred in two subjects in one of two studies after 37 and 79 months of BMA exposure. Conclusions: Although the evidence informing the use of BMA is heterogeneous and based on retrospective analysis, BMA exposure beyond 2 years is associated with reduced SRE risk and increased ONJ incidence. Prospective randomized studies addressing the use of BMA for more than 2 years is needed with greater emphasis on quality of life.
Nasal vestibulitis: An MNCCTN natural history trial—Nasal vestibulitis symptoms associated with paclitaxel, docetaxel, and other chemotherapy agents.
Authors: Cathcart-Rake Elizabeth Jane , Zahrieh David , Smith Deanne s. , Young Susan , Wolfe Eric G. , O'Connor Amanda , Thome Stephan , Lacouture Mario E. , Register Terra , Piens Jill , McCue Shaylene , Loprinzi Charles L.
Published: May 2020

e24086

Background: Nasal vestibulitis has been infrequently described as a side effect of cancer-directed therapy; however, a preliminary study reported that 71% of patients undergoing taxane chemotherapy experienced nasal vestibulitis symptoms. This natural history trial describes the incidence, characteristics, and severity of nasal vestibulitis symptoms among patients undergoing paclitaxel, docetaxel, and non-taxane chemotherapy. Methods: Eligible participants who reported baseline (prior to starting chemotherapy) nasal symptoms ≤ 2 on a 10-point scale were enrolled in this trial upon initiation of a new treatment regimen, involving paclitaxel or docetaxel, or non-taxane chemotherapy. Participants completed nasal symptom logs each time they received a dose of therapy until either the regimen was stopped or four months had passed. The proportion of patients reporting new nasal symptoms was estimated within each cohort with the 95% exact confidence interval (CI). A cumulative incidence model was utilized to quantify the incidence of treatment-emergent nasal symptoms within each cohort, while controlling for age, sex, smoking history, and history of asthma or allergies. Results: Thirty-five participants received paclitaxel, 21 received docetaxel, and 25 received other types of chemotherapy. 86.4% of participants were female, mean age was 60.2 ± 11.2 years; 93.8% of participants completed 2 or more surveys. A higher percentage of participants in the paclitaxel cohort experienced new nasal vestibulitis symptoms than participants in the other two cohorts. The percentage (95% CI) of participants with nasal symptoms, for patients receiving paclitaxel, docetaxel, and non-taxane chemotherapy were 74.3% (56.7%, 87.5%), 47.6% (25.7%, 70.2%), and 44.0% (24.4%, 65.1%), respectively. Epistaxis was reported by 60% of participants in the paclitaxel cohort. Paclitaxel-receiving participants also reported nasal dryness (48.6%), scabbing (40.0%), and pain (20.0%). Nearly half of participants reported moderate symptoms (4-7 out of a 10-point scale), with 8.6% reporting symptoms as severe (8-10 on a 10-point scale). Conclusions: Nasal vestibulitis is a common side effect of chemotherapy, especially paclitaxel chemotherapy.
Excessive mortality in 1,353 five-year survivors of nasopharyngeal cancer.
Authors: Chiang Chi Leung , Cheung Ching Lung , Hingley James Philip , Sing Chor Wing , Fong Ka Shun , Lam Tai Chung , Lee Victor Ho-Fun , Au Kwok Hung , Chow James Chung-Hang , Cheung Yin Ting , Ngan Roger Kai-Cheong , Choi Cheuk-Wai , Lee Anne WM , Wong Ian Chi Kei
Published: May 2020

e24090

Background: Survival of NPC patients has improved in past decades. Yet, survivors continue to face elevated risks of life-threatening late effects. Their impact on late mortality remains poorly quantified. Methods: 1353 five-year NPC survivors diagnosed between 1997 and 2013 at Queen Mary Hospital were reviewed. Their demographics and treatment data were taken from electronic medical records. Survival probability, standardized mortality ratios (SMRs) and absolute excessive risk were calculated for overall and cause-specific deaths. Results: At median follow-up time of 12.4 years, 412 (30.5%) five-year survivors had died at the time of analysis. 66.2% of deaths attributed to non-recurrence death. Estimated 10-, 15-, and 20-year survival probability were 81.4%, 67.6%, and 57.3% respectively. Compared to Hong Kong general population, absolute excessive risk of death from any causes was 17 deaths per 1000 person-years; overall SMR was 3.52 (95% CI: 3.19 to 3.87, p<0.001). Increases in cause-specific mortality were seen for death due to pulmonary (SMR: 6.75; 95% CI: 5.67 to 7.98) and secondary malignancy (SMR: 1.41; 95% CI: 1.06 to 1.83). Conclusions: Five-year NPC survivors still face excessive mortality long after diagnosis, and majority of death was from non-recurrence death. Further analyses are needed to determine predictive factors of excessive mortality. [Table: see text]