Background Pediatric patients with sarcomas experience significant morbidity and compromised quality of life throughout their course. These times could be viewed as opportunities for increased subspecialty palliative care (PC). Systematically defining opportunities for additional PC support has not occurred in pediatric oncology. The frequency, timing, and associated factors for palliative opportunities in pediatric patients with sarcomas are unknown. Methods A priori, nine palliative opportunities were defined (disease progression or relapse, admission for symptoms, social concerns or end‐of‐life, intensive care or bone marrow transplant admission, phase 1 trial or hospice enrollment, do‐not‐resuscitate status). A single‐center retrospective review was conducted on patients aged 0‐18 years with bone/soft tissue sarcomas who died from January 1, 2012 to November 30, 2017. Demographic, disease, and treatment data were collected. Descriptive statistics were performed. Opportunities were evaluated over quartiles from diagnosis to death. Results Patients (n = 60) had a mean of nine (SD = 4) palliative opportunities with the majority occurring in the last quartile of the disease course. Number and type of opportunities did not differ by demographics or diagnosis. Eighteen patients (30%) received PC consultation a median of 2.2 months (interquartile range [IQR] 11.5) prior to death. Consultation was unrelated to diagnosis or total opportunities. Conclusions Patients with sarcomas incur repeated events warranting subspecialty PC, which increase toward the end‐of‐life. Increased PC utilization may help decrease suffering and bolster family coping during these episodes. Additional work should further refine if opportunities differ across cancers, and how to incorporate this framework into clinical oncology care to prevent missed opportunities for PC.
Background Despite favorable prognoses, pediatric patients with hematologic malignancies experience significant challenges that may lead to diminished quality of life or family stress. They are less likely to receive subspecialty palliative care (PC) consultation and often undergo intensive end‐of‐life (EOL) care. We examined “palliative opportunities,” or events when the integration of PC would have the greatest impact, present during a patient's hematologic malignancy course and relevant associations. Methods A single‐center retrospective review was conducted on patients aged 0–18 years with a hematologic malignancy who died between 1/1/12 and 11/30/17. Demographic, disease, and treatment data were collected. A priori, nine palliative opportunity categories were defined. Descriptive statistics were performed. Palliative opportunities were evaluated over temporal quartiles from diagnosis to death. Timing and rationale of pediatric PC consultation were evaluated. Results Patients (n = 92) had a median of 5.0 (interquartile range [IQR] 6.0) palliative opportunities, incurring 522 total opportunities, increasing toward the EOL. Number and type of opportunities did not differ by demographics. PC consultation was most common in patients with lymphoid leukemia (50.9%, 28/55) and myeloid leukemia (48.5%, 16/33) versus lymphoma (0%, 0/4, p = 0.14). Forty‐four of ninety‐two patients (47.8%) received PC consultation a median of 1.8 months (IQR 4.1) prior to death. Receipt of PC was associated with transplant status (p = 0.0018) and a higher number of prior palliative opportunities (p = 0.0005); 70.3% (367/522) of palliative opportunities occurred without PC. Conclusion Patients with hematologic malignancies experience many opportunities warranting PC support. Identifying opportunities for ideal timing of PC involvement may benefit patients with hematologic cancers and their caregivers.
Background Children with brain and central nervous system (CNS) tumors experience substantial challenges to their quality of life during their disease course. These challenges are opportunities for increased subspecialty palliative care (PC) involvement. Palliative opportunities have been defined in the pediatric oncology population, but the frequency, timing, and factors associated with palliative opportunities in pediatric patients with CNS tumors are unknown. Methods A single-institution retrospective review was performed on children ages 0-18 diagnosed with a CNS tumor who died between 01/01/2012-11/30/2017. Nine palliative opportunities were defined prior to data collection (progression; relapse; admission for severe symptoms; intensive care admission; bone marrow transplant; phase 1 trial; hospice; do-not-resuscitate (DNR) order). Demographic, disease, treatment, palliative opportunity, and end-of-life data were collected. Opportunities were evaluated over quartiles from diagnosis to death. Results Amongst 101 patients with a median age at death of eight years (Interquartile range, IQR=8.0, range 0-22), there was a median of seven (IQR=6) palliative opportunities per patient, which increased closer to death. PC consultation occurred in 34 (33.7%) patients, at a median of 2.2 months before death, and was associated with having a DNR order (p=0.0028). Hospice was involved for 72 (71.3%) patients. Conclusion Children with CNS tumors suffered repeated events warranting PC yet received PC support only one-third of the time. Mapping palliative opportunities over the cancer course promotes earlier timing of PC consultation which can decrease suffering and resuscitation attempts at the end-of-life.
TPS10072 Background: Risk of relapse for children with high-risk solid tumors (ST) remains unacceptably high despite aggressive multimodal therapy. Maintenance therapy is an emerging option to improve outcomes. Sirolimus, an inhibitor of mammalian target of rapamycin, is a potent immunosuppressant with antiproliferative and antiangiogenic effects. Low-dose metronomic chemotherapy along with the cyclooxygenase-2 inhibitor celecoxib also decreases neovascularization in in vitro and in vivo systems. The maximum tolerated dose (MTD) of sirolimus in combination with celecoxib and etoposide alternating with cyclophosphamide was determined in a phase I study in pediatric patients with relapsed/refractory ST. The regimen was well-tolerated and showed best response of stable disease in 8/18 subjects and partial response in 1/18. The efficacy of this regimen in relapsed/refractory ST is being tested in a Phase II study (NCT02574728). We hypothesize that patients with high-risk ST administered a 12-month course of this maintenance regimen will have improved 2-year progression-free survival (PFS) when compared to matched historical patients who were observed following completion of upfront therapy. Methods: This is a phase II study of sirolimus in combination with celecoxib and alternating low-dose etoposide and cyclophosphamide delivered as maintenance therapy. Sirolimus will be given at the MTD of 2mg/m2/day with celecoxib 100mg twice daily and oral etoposide 50mg/m2/day (max 100mg) alternating every 21 days with oral cyclophosphamide 2.5mg/kg/day (max 100mg). This study includes: 1) a prospective cohort of patients with high-risk ST in first complete remission (CR), 2) a prospective cohort of patients with recurrent ST in second CR, and 3) a historical cohort matched 2:1 with cohort 1 on diagnosis, age, metastatic sites, and date of diagnosis treated with observation following upfront therapy. The study will enroll up to 38 patients in cohort 1. Eligible subjects are children (1-30 years) with a diagnosis of high-risk extracranial ST (metastatic sarcoma, desmoplastic small round cell tumor, malignant rhabdoid tumor) in first CR or any ST in second CR. Patients enrolled in upfront clinical trials are excluded. Primary endpoint is 2-year PFS of cohort 1 compared to the historical cohort. Secondary endpoints are median PFS of cohort 1, 2-year PFS and overall survival of cohorts 1 and 2, incidence of severe toxicities, and feasibility of completing the 12-month course following standard upfront therapy. Exploratory objectives include evaluation of circulating tumor DNA (ctDNA) in this population of patients in CR or with minimal disease burden and correlation of clinically obtained tumor molecular profiling with outcomes. As of January 2023, 12 subjects are enrolled, 9 in cohort 1 and 3 in cohort 2. Clinical trial information: NCT04469530 .
Previous presentations: Differences in palliative opportunities across diagnosis groups in children with cancer.
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