United States Acculturation and Cancer Patients' End-of-Life Care

Background: Culture shapes how people understand illness and death, but few studies examine whether acculturation influences patients' end-of-life treatment preferences and medical care. Methods and Findings: In this multi-site, prospective, longitudinal cohort study of terminally-ill cancer patients and their caregivers (n = 171 dyads), trained interviewers administered the United States Acculturation Scale (USAS). The USAS is a 19-item scale developed to assess the degree of "Americanization" in first generation or non-US born caregivers of terminally-ill cancer patients. We evaluated the internal consistency, concurrent, criterion, and content validity of the USAS. We also examined whether caregivers' USAS scores predicted patients' communication, treatment preferences, and end-of-life medical care in multivariable models that corrected for significant confounding influences (e.g. education, country of origin, English proficiency). The USAS measure was internally consistent (Cronbach α = 0.98); and significantly associated with US birthplace (r = 0.66, P<0.0001). USAS scores were predictive of patients' preferences for prognostic information (AOR = 1.31, 95% CI:1.00-1.72), but not comfort asking physicians' questions about care (AOR 1.23, 95% CI:0.87-1.73). They predicted patients' preferences for feeding tubes (AOR = 0.68, 95% CI:0.49-0.99) and wish to avoid dying in an intensive care unit (AOR = 1.36, 95% CI:1.05-1.76). Scores indicating greater acculturation were also associated with increased odds of patient participation in clinical trials (AOR = 2.20, 95% CI:1.28-3.78), compared with lower USAS scores, and greater odds of patients receiving chemotherapy (AOR = 1.59, 95% CI:1.20-2.12). Conclusion: The USAS is a reliable and valid measure of "Americanization" associated with advanced cancer patients' end-of-life preferences and care. USAS scores indicating greater caregiver acculturation were associated with increased odds of patient participation in cancer treatment (chemotherapy, clinical trials) compared with lower scores. Future studies should examine the effects of acculturation on end-of-life care to identify patient and provider factors that explain these effects and targets for future interventions to improve care (e.g., by designing more culturally-competent health education materials). © 2013 Wright et al

Pazopanib in the management of advanced soft tissue sarcomas

Lee D Cranmer,1 Elizabeth T Loggers,2 Seth M Pollack2 1Division of Medical Oncology, University of Washington, Seattle, WA, USA; 2Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Abstract: Therapy of soft tissue sarcomas represents an area of significant unmet need in oncology. Angiogenesis has been explored as a potential target both preclinically and clinically, with suggestions of activity. Pazopanib is a multitargeted tyrosine kinase inhibitor with prominent antiangiogenic effects. In a Phase II study, pazopanib demonstrated activity in strata enrolling patients with leiomyosarcomas, synovial sarcomas, or other sarcomas but not those enrolling adipocytic sarcomas. PALETTE, the pivotal Phase III trial, demonstrated improved progression-free survival versus placebo in pazopanib-treated patients previously treated for advanced soft tissue sarcomas. No survival benefit was observed, and adipocytic sarcomas were excluded. Health-related quality-of-life assessments indicated significant decrements in several areas affected by pazopanib toxicities, but no global deterioration. Cost-effectiveness analyses indicate that pazopanib therapy may or may not be cost-effective in different geographic settings. Pazopanib provides important proof-of-concept for antiangiogenic therapy in soft tissue sarcomas. Its use can be improved by further biological studies of its activity profile in sarcomas, studies of biological rational combinations, and clinicopathologic/biological correlative studies of activity to allow better drug targeting. Keywords: pazopanib, soft tissue sarcoma, cost-effectiveness, PALETTE, angiogenesis, tyrosine kinase inhibito

Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma.

Chondrosarcoma is the most common bone sarcoma in adults. Conventional chondrosarcoma, the commonest histological subtype, is largely resistant to anthracycline-based chemotherapy. There have been anecdotal reports of durable clinical benefit with antiangiogenic agents in this disease. A retrospective search of patients treated at three sarcoma referral centers was performed to identify patients with advanced chondrosarcoma treated with antiangiogenic agents. The aim of this study was to evaluate the efficacy and safety of antiangiogenic agents in advanced chondrosarcoma. Ten patients were identified; seven with conventional, one each with clear cell, extraskeletal mesenchymal chondrosarcoma and extraskeletal myxoid chondrosarcoma. The median progression-free survival for patients with conventional and clear cell sarcoma was 22.6 months. Median overall survival has not been met. Antiangiogenic therapy was well tolerated in this series of patients. Our retrospective data suggest that antiangiogenic therapy can provide prolonged clinical benefit in advanced chondrosarcoma patients. Further prospective trials are required to precisely define the role of this class of agent in advanced chondrosarcoma

Safety and Efficacy Outcomes of Embolization in Hepatic Sarcomas.

OBJECTIVE:The outcome for patients with unresectable hepatic sarcoma is poor with a median survival period of 12-16 months. The purpose of this study was to evaluate liver-directed transcatheter therapies for the treatment of hepatic sarcomas. MATERIALS AND METHODS:In a retrospective study, the cases of patients with primary and metastatic hepatic sarcoma treated by transcatheter embolization, chemoembolization, and 90Y radioembolization between 2004 and 2015 were identified. Response Evaluation Criteria in Solid Tumors version 1.1 response was assessed for the target tumor. Survival was assessed by means of Kaplan-Meier analysis. RESULTS:Twenty-eight patients (17 [61%] men, 11 [39%] women; median age, 47 years) were included. Eighteen patients were treated electively. Two of the electively treated patients underwent embolization; eight, chemoembolization; six, radioembolization; and two, a combination of transcatheter treatments. Treatment was well tolerated; only one patient had grade 3 hepatic toxicity. The objective response rate of the index tumor was 61%, and the median overall survival period was 26.7 months. Ten patients underwent emergency embolization to control acute hemorrhage from tumor rupture. The median overall survival periods were 611 days for the patients with ruptured gastrointestinal stromal tumors (GIST) (n = 3) and 19 days for the patients with ruptured angiosarcoma (n = 7). CONCLUSION:Liver-directed transcatheter therapies are safe and may have a role in the elective management of unresectable primary and metastatic liver sarcomas. Emergency embolization for ruptured GIST may be effective for stabilizing the patient's condition and allowing more definitive therapy in the future. However, emergency embolization has limited efficacy in treating patients with ruptured angiosarcoma, likely because of substantial venous bleeding at rupture and the aggressive behavior of this lesion

Assessment of Doxorubicin and Pembrolizumab in Patients With Advanced Anthracycline-Naive Sarcoma: A Phase 1/2 Nonrandomized Clinical Trial.

IMPORTANCE: Anthracycline-based therapy is standard first-line treatment for most patients with advanced and metastatic sarcomas. Although multiple trials have attempted to show improved outcomes in patients with soft-tissue sarcoma over doxorubicin monotherapy, each has fallen short of demonstrating improved outcomes. OBJECTIVE: To evaluate the safety and efficacy of doxorubicin in combination with pembrolizumab in patients with advanced, anthracycline-naive sarcomas. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized clinical trial used a 2-stage phase 2 design and was performed at a single, academic sarcoma specialty center. Patients were adults with good performance status and end-organ function. Patients with all sarcoma subtypes were allowed to enroll with the exception of osteosarcoma, Ewing sarcoma, and alveolar and embryonal rhabdomyosarcoma. INTERVENTIONS: Two dose levels of doxorubicin (45 and 75 mg/m2) were tested for safety in combination with pembrolizumab. MAIN OUTCOMES AND MEASURES: Objective response rate (ORR) was the primary end point. Overall survival (OS) and progression-free survival (PFS) were secondary end points. Correlative studies included immunohistochemistry, gene expression, and serum cytokines. RESULTS: A total of 37 patients (22 men; 15 women) were treated in the combined phase 1/2 trial. The median (range) patient age was 58.4 (25-80) years. The most common histologic subtype was leiomyosarcoma (11 patients). Doxorubicin plus pembrolizumab was well tolerated without significant unexpected toxic effects. The ORR was 13% for phase 2 patients and 19% overall. Median PFS was 8.1 (95% CI, 7.6-10.8) months. Median OS was 27.6 (95% CI, 18.7-not reached) months at the time of this analysis. Two of 3 patients with undifferentiated pleomorphic sarcoma and 2 of 4 patients with dedifferentiated liposarcoma had durable partial responses. Tumor-infiltrating lymphocytes were present in 21% of evaluable tumors and associated with inferior PFS (log-rank P = .03). No dose-limiting toxic effects were observed. CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial, doxorubicin plus pembrolizumab was well tolerated. Although the primary end point for ORR was not reached, the PFS and OS observed compared favorably with prior published studies. Further studies are warranted, especially those focusing on undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02888665

A phase II, multicenter study of the EZH2 inhibitor tazemetostat in adults: Epithelioid sarcoma cohort (NCT02601950)

status: publishe

Use of the Physician Orders for Life-Sustaining Treatment among California Nursing Home Residents

BACKGROUND: Physician Orders for Life-Sustaining Treatment (POLST) is a tool that facilitates the elicitation and continuity of life-sustaining care preferences. POLST was implemented in California in 2009, but how well it disseminated across a large, racially diverse population is not known and has implications for end-of-life care. OBJECTIVE: To evaluate the use of POLST among California nursing home residents, including variation by resident characteristics and by nursing home facility. DESIGN: Observational study using California Minimum Data Set Section S. PARTICIPANTS: A total of 296,276 people with a stay in 1,220 California nursing homes in 2011. MAIN MEASURES: The proportion of residents with a completed POLST (containing a resuscitation status order and resident/proxy and physician signatures) and relationship to resident characteristics; change in POLST use during 2011; and POLST completion and unsigned forms within nursing homes. KEY RESULTS: During 2011, POLST completion increased from 33 to 49 % of California nursing home residents. Adjusting for age and gender using a mixed-effects logistic model, long-stay residents were more likely than short-stay residents to have a completed POLST [OR = 2.36 (95 % CI 2.30, 2.42)]; severely cognitively impaired residents were less likely than unimpaired to have a completed POLST [OR = 0.89 (95 % CI 0.87, 0.92)]; and there was little difference by functional status. There was no difference in POLST completion among White non-Hispanic, Black, and Hispanic residents. Variation in POLST completion among nursing homes far exceeded that attributable to resident characteristics with 40 % of facilities having ≥80 % of long-stay residents with a completed POLST, while 20 % of facilities had ≤10 % of long-stay residents with a completed POLST. Thirteen percent of nursing home residents had a POLST containing a resuscitation preference but lacked a signature, rendering the POLST invalid. CONCLUSIONS: Statewide nursing home data show broad uptake of POLST in California without racial disparity. However, variation in POLST completion among nursing homes identifies potential areas for quality improvement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-016-3728-9) contains supplementary material, which is available to authorized users

Molecular characterization of epithelioid sarcoma (ES) tumors derived from patients enrolled in a phase II study of tazemetostat (NCT02601950)

status: publishe