bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone H3 modifying genes may serve as a predictive marker for metastasis in synovial sarcoma.
Authors: Awasthi Achal , Seligson Nathan David , Millis Sherri Z. , Hays John L. , Chen James Lin
Published: March 2020

11058

Background: Synovial sarcomas (SS) are rare, mesenchymal tumors that exhibit heterogeneous clinical behavior. SS is characterized molecularly by a fusion of the SS18 and one of three SSX genes. While fusion type has been shown to play a role in prognosis, little is known regarding the role of secondary genomic variants in SS. We hypothesized that frequently mutated secondary mutations corresponded to altered molecular pathways associated with accelerated disease progression. Here we present further analysis of the largest study of secondary SS genomic alterations and their potential clinical implications particularly in regard to Histone H3 modifying genes. Methods: Comprehensive Genomic Profiling (CGP) from 203 SS18-SSX fusion positive SS subjects were obtained from Foundation Medicine (FMI). Correlation between gene expression and survival endpoints were assessed in two independent datasets (GSE40018, n = 34; GSE40021, n = 58). A histone H3 score (HH3Score) was calculated through summation of expression values of MLL2, MLL3, SETD2. Altered expression was assessed for genes mutated in > 5% of SS in the FMI dataset. Datasets were also combined with appropriate adjustments for multivariate analysis. Cox proportional hazard, and Chi-squared test were used as appropriate. Results: In CGP profiling of SS, only 4 genes were seen in > 5% of subjects ( MLL3 9%, SETD2 7%, MYO18A 6%, MLL2 6%). 3 of these variants are known to regulate histone H3 activity and are collectively altered in 22% (44 of 203) of the FMI SS subjects. Notably, these H3 targeted gene alterations were found to be mutually exclusive of one another (p < 0.001). In 2 independent SS datasets, subjects with high histone H3 modifying gene RNA expression levels (HH3Score) demonstrated worsened outcomes with earlier tumor metastasis (GSE40018: HR = 0.41, 95%CI 0.15-1.07, p = 0.07; GSE40021: HR = 0.22, 95%CI 0.09-0.52, p < 0.001). Multivariate analysis demonstrated that HH3Score remained significantly correlated to metastasis-free survival (HR = 0.41, 95%CI 0.22-0.77, p < 0.01) when subjects’ age (p < 0.001) and fusion type (p = 0.60) were taken into consideration. Conclusions: Altered expression of histone H3 modifying genes may serve as a key driver for SS progression. Further prospective research is necessary to confirm its prognostic importance.
Pathologic response rates after neoadjuvant therapy for sarcoma.
Authors: Shrivastava Gautam A. , Jarboe John Stewart , Ahmed Awad , Conway Sheila Ann , Pretell Juan , Freedman Laura M. , Wolfson Aaron Howard , Rosenberg Andrew , Trent Jonathan C. , Yechieli Raphael
Published: March 2020

11060

Background: Treatment approaches for soft-tissue sarcomas (STS) vary across sarcoma centers of excellence. A multi-institutional study showed neoadjuvant doxorubicin and ifosfamide (AI) surpassed other agents in recurrence-free survival of several sarcoma subtypes. Our institution manages high-grade STS of the extremity and trunk with neoadjuvant chemotherapy (NA-CTX), neoadjuvant radiation (NA-XRT), or neoadjuvant sequential chemoradiation (NA-CRT) followed by oncologic resection and adjuvant chemotherapy. We report the pathologic (%) necrosis in 48 patients comparing NA-XRT, NA-CTX, and NA-CRT. We also investigated initial clinical outcomes correlated with % necrosis. Methods: We reviewed records of patients who received neoadjuvant therapy for sarcoma over the last four years at our center. We required a pathology report that detailed % necrosis in the specimen. We excluded the same histologies according to RTOG 9514 and RTOG 0630 protocols. There were 48 patients evaluable. The primary regimens compared were NA-CTX, NA-XRT, and NA-CRT before oncologic resection. After determining the mean % necrosis and SE for each group, we determined statistical significance through one-way ANOVA with post-hoc Tukey HSD Test. Kaplan-Meier Analysis was used to compare rates of % necrosis with OS, LC, and DF. Radiation therapy was 50Gy in 25 fractions over 5 weeks. The most common preoperative chemotherapy regimen was 3-4 cycles of AI. Results: Whole cohort evaluation found significant improvement in % necrosis with sequential NA-CRT (78%) compared to NA-CTX (51%, p = 0.049), but a trend when compared to NA-XRT (45%, p = 0.075). Evaluation of patients only receiving neoadjuvant AI revealed significantly improved % necrosis with NA-CRT (83%) compared to either NA-CTX (44%, p = 0.011) or NA-XRT (45%, p = 0.031). At a MFU of 1.6 years we found a non-significant trend toward improved outcomes with higher % necrosis [at 70%, OS (HR = 0.11), LC (HR = 0.34), and DF (HR = 0.61)]. Conclusions: In patients diagnosed with high-grade STS of the extremity or trunk, sequential NA-CRT followed by surgery yields greater % necrosis in tumors when compared to NA-CTX or NA-XRT alone. Longer follow up is required to determine if pathologic response correlates with improved outcomes.
A single-center retrospective study of patients treated with trabectedin (TRB) with long-term follow up.
Authors: Schroeder Brett A. , He Chad , Zhang Yuzheng , Wagner Michael , Jones Robin Lewis , Cranmer Lee D. , Pollack Seth
Published: March 2020

11061

Background: TRB is FDA approved drug for the treatment of liposarcoma (Lipo) and leiomyosarcoma (LMS). The aim of this study was to evaluate potential biomarkers associated with prolonged benefit in patients treated with TRB at our center prior to 2016. Methods: We performed a retrospective search of UW/FHCRC CASIS database to identify patients treated with TRB prior to 2016. Demographic variables and clinical variables (such as histology and treatment) were retrieved. Statistics were performed with R 3.4.1 software. Pairwise Pearson’s correlation was calculated for the # of prior chemotherapy regimens with # of TRB cycles. The Kaplan-Meir method was used to evaluate overall survival (OS). Log-rank test was conducted to compare groups in terms of OS. Results: 145 sarcoma patients treated with TRB were identified with a mean follow up of 5 years (generally on NCT01427582 or NCT01343277). Patients averaged 1.9 prior chemotherapy regimens prior to TRB (range 0-7 regimens) and received an average of 5.6 TRB doses (range 1-25 doses). Subtypes are listed on table. The # of prior regimens was negatively correlated with the # of TRB cycles that patients received (pairwise correlation coefficient = -1.77; p=0.034), suggesting that multiple prior treatment lines either made TRB less tolerable or made sarcoma less sensitive to TRB. The median OS for this heavily treated metastatic population was 0.5 years. However, patients who were able to stay on TRB for more than 5 cycles had a significantly higher OS (p=0.001). While only 23% of patients who received less than 5 cycles of TRB were alive at 5 years (95% CI: 0.15, 0.32), 53% of those who received 5 or more cycles of (95% CI: 0.39, 0.65) were alive at 5 years. Conclusions: TRB may be more effective when administered as an earlier line of therapy. Patients who are able to stay on TRB for a longer duration had a significant improvement in OS. Detailed subset analysis will be presented as will initial findings of our biomarker work. These retrospective data warrant further evaluation. Clinical trial information: NCT01427582 or NCT01343277. [Table: see text]
Prognostic factors and therapeutic options for epithelioid hemangioendothelioma (EHE): A multicenter analysis of a series of fifty-seven cases.
Authors: Vozy Aurore , Simonaggio Audrey , Terrier Philippe , Paradis Valerie , Penel Nicolas , Mir Olivier , Honoré Charles , Dumont Sarah Naomie , Spano Jean-Philippe , Le Cesne Axel
Published: March 2020

11062

Background: EHE is a rare vascular mesenchymal tumor for which there is currently no standard for treatment particularly for metastatic disease. EHE often present metastatic evolution but metastases are not a poor prognostic factor. The aim of this study was to improve knowledge of outcome of EHE patients and see the impact of active surveillance on outcome for metastatic EHE patients. Methods: Patients with EHE treated at three centers in France were included in this retrospective cohort. Univariate analysis of prognostic factors was performed using the Cox model. Survival was estimated using the Kaplan-Meier method and long rank analysis. Results: Fifty-seven patients with EHE were collected in this analysis: 27 (47%) women and 30 (53%) men, with a median age at diagnosis of 39 years (range, 12-83). At diagnosis, 17 (29.8%) patients had a localized tumor, while 40 (70.2%) patients had synchronous metastases. The most commonly affected organs were liver (29.8%), bones (14.0%), skin, lungs and soft tissues (10.5% each). For the 17 patients with localized EHE, the median distant recurrence-free survival after resection of primary was 64.6 months, 95% CI [29.4, NA], (median follow-up of 62.7 months, range, 12.5-234.8). For the 40 patients with metastatic EHE, the median progression-free survival (PFS) was 59.0 months, 95% CI [21.3, NA], (median follow-up of 121.1 months, range, 1.0-202.0). No prognostic factor was identified for localized EHE. For metastatic EHE, age was associated with progression (p = 0.019), and presence of pleural/ascites/pericarditis effusion adversely affected overall survival (OS) (p = 0.002). An initial “wait and see” attitude was proposed to 23 patients (57.5%) while 17 patients (42.5%) were treated at diagnosis with local or systemic treatment (monotherapy or combination of chemotherapy with anthracyclin, taxane, cyclophosphamide). OS were similar in both groups of patients, 174months and 121months for chemotherapy treated patients and active surveillance patients respectively (p = 0.56). Conclusions: Presence of effusion was a significant poor prognostic factor in metastatic EHE patients. Active surveillance could be proposed for asymptomatic patients without effusion but this strategy need to be confirmed in largest or prospective randomized trials.
Activity of sirolimus in advanced epithelioid hemangioendothelioma (EHE): A retrospective analysis within the Italian Rare Tumor Network (RTR).
Authors: Simeone Noemi , Baldi Giacomo Giulio , Frezza Anna Maria , Palassini Elena , David Bruna Bianca Lopes , Vincenzi Bruno , Brunello Antonella , Dagrada Gianpaolo , Collini Paola , Morosi Carlo , Dei Tos Angelo Paolo , Casali Paolo Giovanni , Stacchiotti Silvia
Published: March 2020

11065

Background: EHE is an exceedingly rare soft tissue sarcoma (STS) with no active standard treatment available in advanced patients (pts). We already reported on the activity of sirolimus in a retrospective series of 18 EHE treated within the RTR. We herein update this series on a longer follow-up in a larger number of pts. Methods: Adult pts affected by an advanced, progressive and centrally confirmed EHE treated with sirolimus within the RTR from 2006 to 2018 were retrospectively reviewed. Sirolimus was administered at the starting dose of 5 mg/day, until toxicity or progression. Sirolimus dose was adjusted according to plasma levels (target: 15–20 ng/dL). Response was assessed by RECIST 1.1. Survival was estimated by Kaplan-Meier method. Results: 33 patients were retrospectively identified (median age = 47 years, female = 20 (60%), male = 13 (40%); pretreated = 8, naïve = 25; presence of pleural effusion at baseline = 6). All patients had metastatic disease and evidence of disease progression before starting sirolimus. Mean sirolimus daily dose was 5 mg (range 2-10). 9 pts are still on therapy, 24 stopped sirolimus (13 progression, 5 toxicity, 6 other). 31 pts were evaluable for response (2 pts too early). Best RECIST response was: 1 (3.2%), PR, 26 (83.8%) SD, 4 (12.9%) progression. At a 14-mo median FU, median PFS (m-PFS) was 12.3 mos (range 8–15) and median OS (m-OS) was 19 mos (range 1–40). Pleural effusion correlated with a short m-PFS (3.4 vs 14.3 mos in patients without pleural effusion, p = 0.006) and m-OS (10.6 vs 40 mos in patients without pleural effusion, p <0.0001). Amongst those without pleural effusion, the proportion of pts being progression free at > 24 mos was 23%, with 54 % being alive. Conclusions: We selected pts with advanced EHE with clear evidence of disease progression. This singles out a subgroup of EHE pts with a bad prognosis. Prognosis was shown to be exceedingly bad when there was evidence of serosal effusion, and sirolimus was not effective. Though in an uncontrolled setting, apparently sirolimus is able to slightly prolong PFS and, above all, to allow mid-term freedom of progression in roughly 25% of pts.
A randomized trial comparing four-weekly versus 12-weekly administration of bone-targeted agents (denosumab, zoledronate, or pamidronate) in patients with bone metastases from either breast or castration-resistant prostate cancer.
Authors: Clemons Mark J. , Ong Michael , Stober Carol , Ernst D. Scott , Booth Christopher M. , Canil Christina M. , Mates Mihaela , Robinson Andrew George , Blanchette Phillip S. , Joy Anil Abraham , Hilton John Frederick , Aseyev Olexiy , Pond Gregory Russell , Hutton Brian , Jeong Ahwon , Vandermeer Lisa , Fergusson Dean
Published: March 2020

11501

Background: Defining the optimal dosing interval of commonly used bone-targeted agents (BTAs), such as denosumab and bisphosphonates, for patients with bone metastases remains an important clinical question. We performed a pragmatic randomised trial comparing the non-inferiority of 12- versus 4-weekly BTAs in patients with bone metastases from breast and prostate cancer. Methods: Patients with bone metastases, who were either BTA-naïve, or already receiving, denosumab, pamidronate or zoledronate were eligible. They were randomised to receive their chosen BTA every 12- or 4-weeks for one year. The primary endpoint was Health related quality of life (HRQL) (EORTC-QLQ-C30 Functional Domain - Physical Subdomain). Secondary endpoints included: pain (EORTC-QLQ-BM22 - pain domain), Global Health Status (EORTC-QLQ-C30), symptomatic skeletal events (SSE) rates and time to SSEs. Adverse events and toxicity profiles were also compared. Results: Of 263 patients (60.8% breast and 39.2% prostate), 130 (49.4%) were randomised to 12-weekly and 133 (50.6%) to 4-weekly therapy. 138 (52.5%) were bone-agent naïve. The BTAs included; denosumab (n=148, 56.3%), zoledronate (n=63, 24.0%) and pamidronate (n=52, 19.8%). Study-reported outcomes showed no significant difference in; HRQL-physical domain (median [range]: 0 [-86, 40] vs. 0 [-66, 53.3]), pain (median [range]: 0 [-66, 72] vs. 0 [-100, 88]), Global Health Status (median [range]: 0 [-100, 66.7] vs. 0 [-83, 33.3]), SSE rates (N [%]: 24 [18.5%] vs. 22 [16.5%]), 1-year SSE-free rate (median, range; 73.2% [63.6, 80.7] vs. 77.9% [69.1, 84.4]) between the 12- and 4-weekly arms, respectively. Subgroup analyses for BTA naïve and pre-treated patients, and for patients receiving denosumab, zoledronate and pamidronate, showed no significant difference between the 12- and 4-weekly arms. There was no significant difference in reported rates of renal impairment (2.3% vs. 3.0%), symptomatic hypocalcaemia (1.5% vs. 1.5%) or osteonecrosis of the jaw (0.8% vs. 0.8%). Conclusion: The findings of this trial are consistent with those previously reported for de-escalating zoledronate. This trial also included patients receiving de-escalated denosumab and pamidronate. While the results of the Swiss REDUSE trial are awaited, the data presented would suggest that de-escalation of all commonly used BTAs is a reasonable treatment option. Clinical trial information: NCT02721433.
Association of baseline cardiovascular risk factors and health care utilization and costs in elderly breast cancer patients enrolled in SWOG clinical trials.
Authors: Hershman Dawn L. , Till Cathee , Wright Jason Dennis , Accordino Melissa Kate , Vaidya Riha , Barlow William E. , Ramsey Scott , Unger Joseph M.
Published: March 2020

11508

Background: Cardiovascular-disease risk factors (CVD-RFs) increase the risk of cardiac events in women undergoing chemotherapy. Less is known about the impact of CVD-RFs on healthcare utilization and costs. Methods: We examined breast cancer patients treated uniformly on SWOG clinical trials from 1999-2011. We identified baseline diabetes, hypertension, hypercholesterolemia, and coronary artery disease (CAD) by linking trial records to Medicare claims; obesity was identified using clinical records. The outcomes were emergency room visits (ER), hospitalizations and costs. Multivariable logistic and linear regression were used. Results: Among the 708 patients included in the analysis, 160 (22.6%) experienced 234 separate hospitalizations, and 193 (27.3%) experienced 311 separate ER visits. Diabetes, hypertension, hypercholesterolemia, and CAD were all associated with increased risk of hospitalizations and ER visit. Hypertension had the strongest association, with more than a threefold risk of hospitalization for those with hypertension compared to those without (OR [95% CI], 3.16 [1.85-5.40], p<0.001). For those with ≥3 CVD-RFs, the risk of hospitalization was greater compared to 0 or 1 CVD-RFs (OR [95% CI], 2.74 [1.71-4.38], p<0.001). Similar results were seen for ER visits. In the first 12 months after trial registration, patients with diabetes ($38,324 vs $30,923, 23.9% increase, p=0.05), hypercholesterolemia ($34,168 vs $30,661, 11.4% increase, p=0.02), and CAD ($37,781 vs $31,698, 19.2% increase, p=0.04) had statistically significantly higher total healthcare costs. Additionally, those with 2 significant CVD-RFs ($35,353 vs. $28,899, 22.3% increase, p=.005) had higher total healthcare costs. Conclusions: Our study demonstrates that the presence of both CVD-RFs and ER visits and hospitalizations are frequent among elderly BC patients. The risk of ER visits and hospitalizations is higher among patients with CVD-RFs, and increases with the number of RFs. Better management of CVD-RFs and more aggressive symptom management may be required to reduce both physical and financial toxicities to elderly patients undergoing BC therapy.
Randomized trial of a hospice video decision aid for patients with advanced cancer and their caregivers.
Authors: El-Jawahri Areej , Vanbenschoten Olivia , Fenech Alyssa L. , Jankowski Amanda L. , Markovitz Netana , Traeger Lara , Greer Joseph , Volandes Angelo E. , Temel Jennifer S.
Published: March 2020

11513

Background: Although hospice provides high-quality end-of-life (EOL) care for patients with advanced cancer and their family caregivers, the service remains underutilized in part due to lack of adequate information provided to patients and families about hospice care. Methods: We conducted a single-site randomized clinical trial of a hospice video decision aid versus a verbal description in 150 hospitalized patients with advanced cancer and their caregivers. Patients without an available caregiver were still eligible to participate. Intervention participants (75 patients; 18 caregivers) received a verbal description about hospice plus a six-minute video depicting hospice care. Control participants (75 patients; 26 caregivers) received only the verbal description. The primary endpoint was patient preference for hospice care immediately after the intervention, adjusting for baseline preferences. Secondary outcomes included patient and caregiver knowledge and perceptions of hospice (Hospice Perception and Knowledge Questionnaire). Results: Between 2/2017 and 1/2019, we enrolled 55.7% (150/269) of potentially eligible patients and 44 caregivers. Post-intervention, patients assigned to the video group were more likely to prefer hospice care at the EOL (86.7% vs. 82.7%, OR = 2.85, P = 0.08), but this was not statistically significant. Patients in the video group reported greater knowledge about hospice (B = 0.50, P = 0.024) and were less likely to endorse that hospice care is only about death (6.7% vs. 21.6%, OR = 0.28, P = 0.035). Post-intervention, caregivers assigned to the video were more likely to prefer hospice care for their loved ones (94.4% vs. 65.4%, P = 0.031), reported greater knowledge about hospice (B = 1.94, P < 0.001), and were less likely to endorse that hospice care is only about death (0.0% vs. 23.1%, P = 0.066). Conclusions: Patients with advanced cancer and their caregivers who viewed a hospice video decision support tool were more informed about hospice care and reported more favorable perceptions of hospice. Future work should examine the impact of the video on hospice utilization and length-of-stay among patients with advanced cancer. Clinical trial information: NCT03040102.
Effects of a structured intervention program to improve physical activity (PA) of adolescents and young adult cancer survivors (AYAs): Final results of the randomized Motivate AYA–MAYA trial.
Authors: Salchow Jannike Lisa , Jensen Wiebke , Koch Barbara , von Grundherr Julia , Elmers Simon , Escherich Gabriele , Reer Rüdiger , Bokemeyer Carsten , Mann Julia , Stein Alexander
Published: March 2020

11518

Background: Major cardiovascular (CV) events are the most common late toxicities among AYAs. Although regular PA of vigorous intensity (≥ 9 metabolic equivalent [MET]-hours/week) lowers the risk for CV events and mortality, no larger randomized controlled trials on interventions are available. Our aim was to assess whether a 12-week structured intervention increases the vigorous PA of AYAs. Methods: AYAs aged 15 to 39 years, after curative intent cancer treatment with at least one CV risk factor, were randomized to usual-care control group (CG) and to intervention group (IG). The CG received standard recommendations, and the IG participated at a semi-structured interview and phone consulting focusing on PA and behavioral change. At baseline, post-intervention (12 wks), and at follow-up (52 wks), participants completed the International Physical Activity Questionnaire (IPAQ) and quality of life assessment (EORTC QLQ-C30). Primary endpoint was the rate of AYAs with ≥ 9 MET-hours/week of vigorous activity (IPAQ) at 12 weeks. This single center trial was registered (DRKS00009453). Results: Among 115 screened AYA 89 eligible patients were randomized; 69 (77.5%) completed the intervention and the endpoint assessment; 36 (52.2%) were in the IG and 33 (47.8%) in the CG. Median age was 24.3 years (range, 18 to 39). CV risk factors were use of anthracyclines (94.2%), chest radiation (47.8%), or both (44.9%). At baseline 49.2% of all AYAs reported to perform vigorous PA with at least 9 MET-hours/week, although reporting was individually biased. Post-intervention this rate significantly increased in the IG from 45.7% to 69.7% (p = 0.007), whereas in the CG only a modest non-significant increase was noted (53.3% to 65.6%, p = 0.134). Notably, upon long-term follow up (52 wks) AYAs did not keep their increased vigorous PA, whereas improved moderate PA was achieved (MET score in IG p = 0,044). Also, both groups reduced significantly the time they spent sitting from 6.5 (SD, 2.9) to 5.4 (SD, 2.7) hours/day (p = 0.001). Conclusions: Intensified PA counseling improves short term vigorous PA and long term moderate PA of AYAs and, should thus be part of survivorship programs. Further studies with AYAs will be required to establish reliable PA screening methods and to confirm the results in larger cohorts. Clinical trial information: DRKS00009453.
Goals of care designation associated with improved survival and indicators of quality end-of-life care in pancreatic cancer (PC) patients (pts) undergoing palliative chemotherapy.
Authors: Anaka Matthew , Spratlin Jennifer L. , Cheung Winson Y. , Ghosh Sunita , Lee Minji
Published: March 2020

11532

Background: Discussion of goals of care (GoC) is a key part of quality care for pts with palliative cancer. Numerous studies have shown that documentation of GoC in this population remains low. Here we describe changes in GoC documentation and other indicators of quality end-of-life care in PC pts undergoing palliative chemotherapy during a health-system wide initiative to improve advanced care planning (ACP). Methods: This is a retrospective cohort analysis of 106 pts with locally advanced or metastatic PC treated with palliative chemotherapy from 2012-2015 in Northern Alberta (Canada). In 2014, an initiative was launched to provide pts with hard copies of their GoC designation intended to be available at all health-system interactions. Data were obtained from outpatient medical oncology (MO) and palliative care (PAL) notes and the provincial cancer registry. Survival analysis used a multivariate Cox-regression. All other tests were Chi-squared. Results: 50% (53/106) of pts had a documented GoC discussion, with 45% (48/106) receiving a specific GoC designation. In 2012, 31% (6/19) of pts had a GoC designation, which increased to 61% (20/33) in 2015. Of 84 individual GoC discussions documented, 34% (29/84) were by MO, 62% (52/84) were by PAL, and at least 8% (7/84) referenced prior discussions with a family physician or discussion while admitted to hospital. Pts with a GoC designation had increased median overall survival (287 vs 216 days; HR = 0.62; p = 0.041), and were less likely to receive chemotherapy in the last two weeks of life (p = 0.016). Conclusions: Rates of GoC discussions for PC pts undergoing palliative chemotherapy increased during a health-system wide ACP initiative. Having a GoC designation was associated with greater overall survival and indicators of higher quality end-of-life care.
Economics of using telehospice to supplement hospice care in rural areas.
Authors: Lomenick Adam , Kuhlman Sandy , Gurley-Calvez Tami , Barnes Joe , Krebill Hope , Spaulding Ashley , Doolittle Gary C.
Published: March 2020

11535

Background: Hospice care in rural areas is often characterized by provider shortages and vast geographical service areas to cover, making access to quality end-of-life care challenging. Telehospice, the utilization of interactive video (ITV) technology to provide health services over a distance for hospice patients, has been proposed as a solution to address access issues. In 2017, the University of Kansas Medical Center (Kansas City, Kansas) partnered with Hospice Services, Inc. (HSI) (Phillipsburg, Kansas) to augment traditional, in-person hospice care with hospice care delivered via mobile tablets.This work examines the costs of Telehospice when compared with the costs of in-person hospice services. Methods: Detailed administrative data from July 1, 2018 to December 31, 2018 was analyzed to estimate the costs of service after Telehospice use was inculcated into routine practice. Results: Hospice Services, Inc., which averages a daily census of 34 patients, conducted 257 calls, averaging 28 hours a month. The average time for a Telehospice call was 21 and 18 minutes for nursing and medical director calls, respectively. Through various hospice functions, including administrative, patient, and non-patient related connections, HSI saved over $115,000 in staff travel time and mileage reimbursement. Administratively, by hosting their weekly 14-member interdisciplinary meeting via ITV, HSI saved $29,869 of staff travel time and mileage reimbursement. Conclusions: Our estimates indicate substantial cost saving potential with the use of Telehospice services. Further research is needed to assess the effects of Telehospice utilization on the experiences and subsequent cost of hospice care. Additional cost data specifics will be presented in poster form. [Table: see text]
Variation in the intensity of end-of-life care, hospice enrollment, and the cost of care by cancer site.
Authors: Uppal Shitanshu , Pleasant Versha , Bell Sarah , Reynolds R. Kevin , Rice Laurel , Spencer Ryan J.
Published: March 2020

11539

Background: To compare end-of-life (EOL) care intensity across multiple cancer sites and its impact on the cost of care during the last 30-days of life. Methods: Cross-sectional retrospective study using Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked database from 2008-2013. Utilization of the following in the EOL period (last 30 days of life prior to death) was examined: 2 or more visits to the Emergency Department (ED), hospitalizations, receipt of any life-extending procedures, admission to intensive care unit, any hospice use, hospice used ≤3 days, death in hospital, or receipt of chemotherapy (last 14 days). We tallied the claims made during the EOL period for each patient. Median expenditures during the EOL period were tabulated by cancer site and stratified by receipt of hospice care. Results: EOL care utilization varied widely between cancer sites. The rates of any hospice utilization were the highest for breast cancer (48.2%) compared to ovarian (17.4%) (p < 0.001). Chemotherapy during the last two weeks of life was the highest for ovarian cancer (1.7%) and the lowest for colorectal cancer (0.5%). The median cost of care during the EOL period for patients who received hospice care was $7,547.84 (Interquartile range [IQR] $5,422-$17,293) compared to $17,179 (IQR $10,323 - $30,824) for those never received hospice care (p < .0001). There was no significant variation in median cost by cancer site for those who received hospice services (range $7,317 - $9,816). However, the cost of care varied for those who did not receive hospice care. Median costs for this subgroup was the lowest for pancreatic cancer ($14,635) and the highest for colorectal cancer ($24,324) (p < 0.001). Conclusions: Despite increasing acceptance of palliative care services and hospice in cancer care, there continues to be intensive and costly care administered during the EOL period. These costs vary considerably across cancer sites when patients do not receive hospice care, but costs are relatively similar when patient are enrolled in hospice Further research to investigate the causes of this variation should be undertaken to design interventions aimed at improving timely hospice enrollment at the EOL and reducing costly care in the EOL period.
Guided geriatric interventions (GI) in older adults with cancer: What, how, and for whom? The French PACA EST Cohort Experience.
Authors: Boulahssass Rabia , Gonfrier Sebastien , Ferrero Jean-Marc , Champigny Noemie , Rambaud Cyrielle , Largillier Remy , Chauviere Damien , Barranger Emmanuel , Bereder Jean Marc , Benizri Emmanuel , Borchiellini Delphine , Durand Matthieu , Baque Patrick , Delotte Jerome , Barriere Jerome , Hannoun-Levi Jean-Michel , Guigay Joel , Piche Thierry , FRANCOIS Eric , Guerin Olivier
Published: March 2020

11548

Background: Some previous studies in geriatric oncology have described the GI and their adherence. Today’s challenge is to screen patients needing specific GI and repeated Comprehensive Geriatric Assessments (CGA). We recently analyzed a phenotype of patients requiring more GI (Boulahssass et al, Cancers 2019). The main purpose of the present study is to compare types of GI implemented, according to patient frailty levels, in order to better understand the necessary care plan. Methods: Between April 2012 and May 2018, 3530 consecutive patients with solid tumors were enrolled in this multicentric, prospective cohort. 3140 patients (mean age:82y) were finally included and a CGA was performed at Baseline. Twelve GI were standardized, individualized or based on experience if no guidelines were available. Within 1 month, geriatricians including patients in the cohort received standardized training. Logistic regression was performed to compare types of GI in the 3 groups using the Balducci Score (B1/B2/B3). Results: 8819 GI were implemented for the 3140 patients. On average, fit patients had 1.5 GI (n = 146), vulnerable patients 2.4 GI (n = 1568) and frail patients 3.3 GI (n = 1426). We observed no significant differences between the 3 groups concerning specific pain management (Fit vs B2: p = 0.19; Fit vs B3: p = 0.57) and psychological care (Fit vs B2:p = 0.03; Fit vs B3:p = 0.24). In vulnerable and frail patients, we recorded more significant GI for nutritional care, delirium prevention, comorbidity management, nursing interventions, social worker interventions, treatment modifications for optimization or iatrogenic disorders and physiotherapy, with the highest Odds Ratio for nursing interventions (Fit vs B2 OR:2.9 p = 0.011; Fit vs B3 OR:9 P < 0.001) and physiotherapy (Fit vs B2:OR 4.3 p < 0.001; Fit vs B3:OR:9 p < 0.001). B3 patients had significantly more GI on care pathways modifications (OR:3.1, p = 0.002) and caregiver care (OR:2, p = 0.049). Conclusions: Fit patients also needed GI. We observed differences in types of GI between the groups. However, the aims and levels also seemed to differ and need further studies to analyze their impact.
Predicting severe toxicity of targeted therapies in elderly patients with cancer (PreToxE): A multicenter, prospective, and retrospective study.
Authors: Lebreton Coriolan , Cantarel Coralie , Toulza Emilie , Desgrippes Romain , Bozec Lemoal Laurence , Saada Esma , Ducoulombier Agnes , Tardy Magalie Pascale , Paillaud Elena , Lalet Caroline , Mathoulin-Pélissier Simone , Italiano Antoine
Published: March 2020

11550

Background: It is crucial that targeted therapies are also studied in senior patients to establish predictive factors of severe toxicity. Methods: The PRETOXE study includes 3 multicentric independent cohorts of patients ≥70 years old with advanced solid tumor (2 retrospectives and one prospective) and treated with a tyrosine/threonine kinase inhibitor (TKI) as per drug label. Data on clinical and biological characteristics of the patient, disease and treatment were centrally collected at the beginning of the treatment. Primary endpoint is severe toxicity defined as treatment-related death, persistant or significant disability/incapacity, hospitalization or discontinuation of treatment for more than three weeks. Predictive factors of severe toxicity were first identified in a training retrospective cohort by multivariate analysis. Two independent cohorts ( retrospective and prospective) will be used for external validation. Results: 371 patients entered the study (training retrospective cohort n = 171, 46.1 %; validation retrospective cohort: n = 160, 43.1%, validation prospective cohort: n = 40, 10.8%). Median age was 74.0 (range 70.0-88.0) in the training retrospective cohort. 73 patients (42.7%) were male. The most frequent solid tumors were lung 64 (37.4%), breast 50 (29.2%), sarcomas 27 (15.8%), colon 10 (5.8%) and kidney 8 (4.7%). The five most frequent prescribed TKIs were everolimus 51 (29.8%), erlotinib 43 (25.1%), pazopanib 18 (10.5%), gefitinib 17 (9.9%) and regorafenib 14 (8.2%). The prescribed dose was lower than that recommended in the drug label in 32.1% of cases. 46 (26.9%) patients had a severe toxicity as per protocol definition in retrospective cohort: hospitalization 5 (10.9%), discontinuation of treatment more than 3 weeks 4 (8.7%), definitive discontinuation of treatment 38 (82.6%), persistent or significant disability/incapacity 14 (30.4%). On multivariate analysis, female gender, ≥3 concomitant medications and anti-angiogenic activity of TKI were independent predictive factors of severe toxicity. External validation on the other two independent cohorts (retrospective and prospective) will be presented at the meeting. Conclusions: One in four cancer patient ≥ 70 years old and treated with a TKI has severe toxicity impacting treatment outcome. The role of geriatric intervention to prevent such toxicities should be considered particularly in female patients, patients with ≥3 concomitant medications or when the TKI targets the VEGF receptors family. Clinical trial information: NCT02751827.
Prognostic value of routine biomarkers in older patients with cancer: Pooled analysis of three prospective cohorts.
Authors: Paillaud Elena , Soubeyran Pierre , Oubaya Nadia , Brain Etienne , Fonck Marianne , Reinald Nicoleta , Heitz Damien , Allain Mylene , Zebachi Sonia , Rousselot Hubert , Laurent Marie , Dauba Jérôme , Caillet Philippe , Bastuji-Garin Sylvie , Rainfray Muriel , Bringuier Michael , Grellety Thomas , Bellera Carine A. , Mathoulin-Pélissier Simone , Canoui-Poitrine Florence
Published: March 2020

11551

Background: To assess prognostic value of routine biomarkers in older patients with cancer. Methods: A pooled analysis of three prospective multicentre cohorts, ELCAPA, PHRC Aquitaine and ONCODAGE was conducted. Patients aged 70 years or older, with cancer were included. Biomarkers collected were plasmatic C-reactive protein, albumin and a combined score: Glasgow Prognostic Score (GPS). The GPS comprised three categories (0: CRP≤10 mg/L, albumin≥35 g/L; 1: CRP≤10 mg/L and albumin < 35 g/L, or CRP > 10 mg/L and albumin≥35 g/L; 2: CRP > 10 mg/L and albumin < 35 g/L).The primary endpoint was overall survival at 12 months. Multivariable Cox models were used, adjusting for age, sex, localisation, metastatic status, performance status, frailty screening index, the G8. Discriminative properties were assessed using Harrell C index and NRI (Net Reclassification Improvement). Results: Overall 1800 patients were analyzed (ELCAPA: N = 543, PHRC Aquitaine: N = 253, ONCODAGE: N = 1004; mean age: 78.5±5.5 years; 61.7% of men; 37% metastatic; most frequent localisations: breast (34.9%) and colon-rectum (17.7%); 70.7% of patients screened at risk of frailty with G8). Overall survival was 71.1%. GPS was independently associated with death (among normal G8: GPS 1: Hazard Ratio (HR) = 4.48; 95% Confidence Interval (95% CI) = [2.03; 9.89], GPS 2: 11.64 [4.54; 29.81], among abnormal G8: GPS 1: 2.45 [1.79; 3.34], GPS 2: 3.97 [2.93; 5.37]. The addition of GPS to the clinical model (Harell C: 0.82 [0.80; 0.83]) improved discrimination (Harell C: 0.84 [0.82; 0.85], NRI: 11% [5; 19]). Conclusions: GPS could be used in older patients with cancer to help decision-making and prognosis assessment.
Role of the oncological-multidimensional prognostic index in older patients with metastatic colorectal cancer treated in a real-world setting.
Authors: Procaccio Letizia , Brunello Antonella , Fiduccia Pasquale , Lettiero Annunziata , Tierno Giuseppina , Pusole Grazia , Bergamo Francesca , Schirripa Marta , Manai Chiara , Zagonel Vittorina , Lonardi Sara
Published: March 2020

11552

Background: About 50% of diagnoses of colorectal cancer (CRC) occur in patients (pts) older than 70 years. Though a comprehensive geriatric assessment (CGA) is recommended for proper management of older cancer pts, there is still no consensus on the best form of geriatric assessment. We investigated possible prognostic factors in elderly metastatic (m)CRC pts in a real-world setting, focusing on the role of the oncological-multidimensional prognostic index (onco-MPI). Methods: Pts aged ≥ 70 years with mCRC referred to the Medical Oncology 1 Unit from May 2010 to May 2017 were assessed by a multidisciplinary team and received a basal CGA. Onco-MPI was calculated by a validated algorithm as a weighted linear combination of the CGA domains, as previously described. The following 3 different prognostic groups were identified: low (scores 0.0-0.46), medium (scores 0.47-0.63) and high risk (scores 0.64-1.0). Results: A total of 206 mCRC pts were included, 123 males. Mean age was 76.1 years (69.2-90.8). ECOG PS was < 2 in 90% and mini-mental state examination was ≥ 24 in 85% of pts. Primary tumor was located in rectum, left and right side in 18%, 42% and 40% of pts, respectively. RAS and BRAF mutations were detected in 44% and 9% of pts, respectively. According to onco-MPI score, 32%, 39% and 28% of cases were low, medium and high risk, respectively. According to CGA as per Balducci’s criteria, 56% of pts were classified as fit, 31% vulnerable and 13% frail. Median overall survival (OS) was 26 months (95% CI 19.7-32.4). The following factors were significantly associated with OS: ECOG PS (0-1 vs > 1, 31% vs 15%, p = 0.004); onco-MPI score (low vs medium vs high risk, 29% vs 38% vs 19%, p = 0.005), treatment (monotherapy vs doublet vs triplet, 20% vs 31% vs 30%, p = 0.01). No significant difference in OS was observed in CGA-based groups (p = 0.15). In high onco-MPI score, doublet-regimen correlated with higher OS compared to monotherapy (79% vs 51%, p = 0,03). Conclusions: Onco-MPI emerged as a significant prognosticator in mCRC elderly pts. It may be useful in daily clinical practice for driving decision-making in this age group. Thanks to its marked standardization it may be also applied in clinical trials.
Physiological and psychosocial effects of a highly structured exercise program on breast cancer survivorship.
Authors: Tjoe Judy A. , Piacentine Linda B. , Yin Jun , Papanek Paula , Ng Alexander V.
Published: March 2020

11558

Background: Exercise after breast cancer treatment improves cancer-related outcomes, although the mechanism of action is unclear. Engagement in healthy active lifestyles after cancer treatment may also impact overall survival. We aimed to determine effectiveness of a highly structured, clinically overseen, goal oriented, group triathlon training program on improving physiological and psychosocial outcomes in female breast cancer survivors (BCS). Methods: After stage appropriate local and systemic breast cancer treatment, 53 female BCS were recruited to participate in this study. The 14-week group triathlon training program was individually adjusted for treatment side effects. 28 similar BCS who did not participate in the training served as controls. Pre- and post-exercise training measures included: Functional endurance (Timed 6MWT), quality of life (QOL, FACT-B), cancer-related fatigue (CRF, FACIT-F), exercise self-efficacy (ESE) via questionnaires, estradiol, and inflammatory biomarkers (C-reactive protein, TNFr1, leptin and adiponectin). Results: Complete data were obtained from 41 [mean age 51 (7) yr, mean BMI 29.5 (6.2)] triathlon finishers and 16 [mean age 56 (10) yr, mean BMI 31.5 (8.0)] controls. 6MWT improved (26 m) more in the triathlon group (p < 0.05). FACT-B, FACIT-F, and ESE all improved compared to controls (all p < 0.05). Body mass and BMI decreased in the training group compared to controls (p = 0.01, p = 0.04 respectively). Arm circumference decreased in the trained group but increased in controls (p < 0.05). Estradiol and leptin positively correlated with initial body weight in both groups but did not change after training. Adiponectin significantly decreased in the triathlon group (p = 0.01), perhaps due to selection bias of controls. No significant changes were seen in other serological markers. Conclusions: A highly structured, clinically overseen, moderate intensity exercise program can improve endurance, QOL, CRF, body mass, and possibly improve survival after breast cancer treatment. Furthermore, improvements in ESE may provide tools for patients to continue adherence to regular exercise guidelines that may lower obesity and its related comorbidities, including arm lymphedema.
The CAROLE (CArdiac Related Oncologic Late Effects) Study: A Phase II, single-arm feasibility trial.
Authors: Puckett Lindsay , Saba Shahryar , Henry Sonia , Rosen Stacey , Rooney Elise , Laxer Alison , Gilbo Philip , Pappas Karalyn , Eacobacci Katherine , Kapyur Amitha , Robeny Justin , Filosa Samaria , Musial Samantha , Chaudhry Anisha , Chaudhry Rahul , Lesser Martin , Riegel Adam , Charlton Jessica , Ramoutarpersaud Sariah , Lee Lucille
Published: March 2020

11569

Background: Long-term breast cancer survivors are at risk of late effects from cardiotoxic (tox) radiation (RT) and chemotherapy (chemo). However, there is a paucity of data to recommend appropriate cardiac screening for those ~10 years (yrs) after diagnosis (dx). This phase II, single arm study assessed multimodality screening in a heterogeneous cohort of long-term survivors. Methods: Our prospective, single center pilot study enrolled 201 (of 200 planned) eligible patients (pts): age 18-65 at dx, with treatment (tx) for breast cancer (any stage/tx) in 2004-2011 (≥6 yrs prior), with no cardiac disease (dz) at dx. The primary endpoint was presence of any cardiac dz (preclinical or clinical) on electrocardiogram (EKG), echocardiogram (echo), or coronary artery calcium CT (CAC CT); secondary endpoint included clinical (clin) dz alone. Subgroups assessed were: no tox chemo or RT (no tox), tox RT (left-sided) alone, tox chemo (anthracycline) alone, and both tox chemo and tox RT (tox chemoRT). Results: After enrollment (6/2017-7/2018), 200 pts had sufficient data for analysis. Median age was 50 (29-65) at dx, 63 (37-77) at imaging, and interval (dx to imaging) was 11.5 (6.7-14.5) yrs. There were 44% no tox, 31.5% tox RT, 16% tox chemo, and 8.5% tox chemoRT pts. Among all pts, 77.6% displayed evidence of any cardiac dz, 51.5% had clin dz. Per modality, rates of any and clin dz were: 27.1%/10% EKG, 50.0%/25.3% echo, and 50.8%/45.8% CAC CT. Among subgroups, these rates were: 73.9%/53.4% no tox, 82.5%/58% tox RT, 75%/38.7% tox chemo, and 82.4%/35.3% tox chemoRT (NS on χ2 test, p = .58/p = .15). Multivariable logistic regression with tox RT, tox chemo, and age as covariates, showed no significant tox RT (NS) or tox chemo effect (NS), however, increasing age was significantly associated with higher incidence of cardiac dz (p < 0.01; OR = 1.12 per yr, 95% CI: 1.07-1.18). Conclusions: Among pts with a median of > 10 yrs post breast cancer tx, multimodality CAROLE screening was feasible and showed high rates of cardiac dz (any/clin = 77.6%/51.5%) among all subgroups, including those without tox tx. This study provides evidence for long-term cardiac screening in a diverse group of breast cancer survivors and provides a novel pathway for evaluation. Clinical trial information: NCT03235427.
Cardiorespiratory fitness and cardiovascular mortality after prolonged androgen deprivation therapy for prostate cancer.
Authors: Gong Jingyi , Payne David , Caron Jesse Pittard , Bay Camden , McGregor Bradley Alexander , Hainer Jon , Partridge Ann H. , Neilan Tomas G. , Di Carli Marcelo , Nohria Anju , Groarke John
Published: March 2020

11576

Background: Androgen deprivation therapy (ADT) plays a pivotal role in management of prostate cancer (PC), with prolonged ADT favored over short-term use in the definitive treatment of high risk PC with radiation. Objectives: To compare cardiorespiratory fitness (CRF) and cardiovascular (CV) mortality among patients with PC with and without ADT exposure, and to explore how duration of ADT exposure influences CRF and CV mortality risk. Methods: This is a retrospective study of patients referred for exercise treadmill testing (ETT) after a diagnosis of PC. PC risk classification was based on Gleason score (GS) at diagnosis: high risk GS ≥ 8, intermediate risk GS= 7, and low risk GS ≤ 6. CRF was categorized according to metabolic equivalents (METs): METs ≥ 8 defined as good CRF and METs < 8 as reduced CRF. ADT exposure was grouped as short-term (≤ 6 months) versus prolonged (> 6 months). Results: 616 patients underwent an ETT a median of 4.8 years (interquartile range: 2.0-7.9) after diagnosis of PC. 150 patients (24.3%) received ADT prior to ETT; 51 with short-term versus 99 with prolonged exposure. 524 (85.1%) patients had ≥ 2 CV risk factors, and 28 CV deaths occurred over 4.2 (interquartile range: 2.3-7.1) years following the ETT. Reduced CRF was more frequent among ADT-exposed versus ADT-naive patients (48.7 versus 32.6%, p< 0.001). Prolonged ADT was associated with reduced CRF (odds ratio (OR): 2.71; 95% confidence interval (CI): 1.31-5.61; p=0.007) and increased CV mortality (hazard ratio (HR): 3.87; 95% CI: 1.16-12.96; p=0.03) in adjusted analyses. In contrast, short-term ADT exposure was not independently associated with either reduced CRF (OR 1.71; 95% CI: 1.00-2.94); p=0.05) or CV mortality (HR: 1.60; 95% CI: 0.51-5.01; p=0.42). Conclusions: Among patients with PC and high baseline CV risk, > 6 months ADT exposure but not less was associated with reduced CRF and increased CV mortality. Reduced CRF may in part mediate increased CV mortality risk. Exercise interventions concurrent with prolonged ADT warrants investigation to potentially offset risk.