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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS10072-TPS10072
    Abstract: 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/m 2 /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 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Cancer Medicine, Wiley, Vol. 10, No. 8 ( 2021-04), p. 2714-2722
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2659751-2
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  • 3
    In: Journal of Pain and Symptom Management, Elsevier BV, Vol. 61, No. 3 ( 2021-03), p. 686-
    Type of Medium: Online Resource
    ISSN: 0885-3924
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1500639-6
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  • 4
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 25-25
    Abstract: Background: Due to relatively more favorable survival rates, parents and providers of children with hematologic malignancies maintain high hopes for cure, resulting in more cure-directed therapy and hospitalizations at the end-of-life (EOL), as well as delayed palliative care (PC) involvement. Pediatric patients with hematologic malignancies are less likely to receive PC and die at home versus patients with solid tumors, and often undergo intensive EOL care. Despite favorable prognoses, patients still relapse and experience other challenging events throughout their disease. A "palliative opportunity" is an event during a patient's disease course at which time subspecialty PC, or care provided by clinicians with subspecialty training or board certification in PC, could be provided to improve the overall care of the patient or family. It is important to explore palliative opportunities to better understand the disease course, as well as how and when to introduce PC to patients and families. Objectives: Examine the palliative opportunities present during a patient's course with a hematologic malignancy and relevant demographic, disease, or EOL associations. Methods: A single-center retrospective review was conducted on patients aged 0-18 years with leukemia or lymphoma who died from 1/1/12-11/30/17. Demographic, disease, and treatment data were collected. A priori, nine palliative opportunity categories were defined: (1) relapse of disease, (2) disease progression, (3) receipt of bone marrow transplant (BMT) or chimeric antigen receptor T-cell (CAR-T) therapy, (4) Phase 1 trial enrollment, (5) admission for symptoms (pain or dyspnea requiring IV opioids, nausea/vomiting requiring IV anti-emetics, fatigue, neurologic symptoms, or social concerns), (6) intensive care unit (ICU) admission, (7) admission for EOL care, (8) hospice enrollment, (9) do-not-resuscitate (DNR) status. Opportunities were evaluated overall and temporally over quartiles from diagnosis to death, independent of PC consultation. Descriptive and inferential statistics were performed using SAS Enterprise Guide 7.1. Results: During the study period, 92 patients with hematologic malignancies died, including 55 with B or T-cell lymphoid leukemia/lymphoma, 33 with acute/chronic myeloid leukemia, and 4 with Hodgkin/Non-Hodgkin lymphoma. These patients incurred 522 total opportunities with a median of 5.0 (Interquartile Range (IQR)=6.0) palliative opportunities per patient throughout their disease course. The majority of opportunities occurred in the last quartile of the disease course. Of the 522 opportunities, 64.9% occurred prior to or without PC support. Except for religion (p=0.0002), number and type of opportunities did not differ by demographics. 44 patients (47.9%) received PC consultation, occurring a median of 1.8 months (IQR=4.1) prior to death. PC consultation was most common in patients with lymphoid leukemia (63.6%) vs myeloid leukemia (36.4%) or Hodgkin/Non-Hodgkin lymphoma (0%, p=0.14). Receipt of PC was associated with BMT status and a higher number of palliative opportunities (p=0.0018 and p=0.0005, respectively). The most common documented reason for PC consultation was disease-related relapse or progression (30, 68.2%), followed by EOL (7, 15.9%), and symptom management (7, 15.9%). The palliative opportunities that immediately preceded PC consultation were most commonly ICU admission (15, 34.1%), relapse (8, 18.2%), disease progression (6, 13.6%), and DNR order placement (5, 11.4%). Patients who received PC consultation were more likely to have also enrolled in hospice (19/44, 43.2%) compared to those that did not receive PC consultation (6/48, 12.5%, p=0.001). Conclusion: Patients with hematologic malignancies experience many events warranting PC support, which increase toward the EOL. However, less than half of patients in this cohort received PC consultation, and often late in their disease course. This demonstrates potential missed opportunities for discussion of goals of care or improving quality of life through relief of physical, psychological, and psychosocial symptoms. The integration of PC into cancer care improves symptom management, emotional and psychosocial wellbeing, and EOL decisions. Defining palliative opportunities together with the disease program helps identify ideal timing and candidates for PC involvement. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Pediatric Blood & Cancer, Wiley, Vol. 70, No. 1 ( 2023-01)
    Abstract: Childhood cancer causes significant physical and emotional stress. Patients and families benefit from palliative care (PC) to reduce symptom burden, improve quality of life, and enhance family‐centered care. We evaluated palliative opportunities across leukemia/lymphoma (LL), solid tumors (ST), and central nervous system (CNS) tumor groups. Procedure A priori, nine palliative opportunities were defined: disease progression/relapse, hematopoietic stem cell transplant, phase 1 trial enrollment, admission for severe symptoms, social concerns or end‐of‐life (EOL) care, intensive care admission, do‐not‐resuscitate (DNR) status, and hospice enrollment. A single‐center retrospective review was completed on 0–18‐year olds with cancer who died from January 1, 2012 to November 30, 2017. Demographic, disease, and treatment data were collected. Descriptive statistics were performed. Opportunities were evaluated from diagnosis to death and across disease groups. Results Included patients ( n  = 296) had LL ( n  = 87), ST ( n  = 114), or CNS tumors ( n  = 95). Palliative opportunities were more frequent in patients with ST (median 8) and CNS tumors (median 7) versus LL (median 5, p  = .0005). While patients with ST had more progression/relapse opportunities ( p   〈  .0001), patients with CNS tumors had more EOL opportunities ( p   〈  .0001), earlier PC consultation, DNR status, and hospice enrollment. Palliative opportunities increased toward the EOL in all diseases ( p   〈  .0001). PC was consulted in 108 (36%) patients: LL (48%), ST (30%), and CNS (34%, p  = .02). Conclusions All children with cancer incur many events warranting PC support. Patients with ST and CNS tumors had more palliative opportunities than LL, yet received less subspecialty PC. Understanding palliative opportunities within each disease group can guide PC utilization to ease patient and family stress.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2130978-4
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Neuro-Oncology Practice Vol. 8, No. 4 ( 2021-07-14), p. 451-459
    In: Neuro-Oncology Practice, Oxford University Press (OUP), Vol. 8, No. 4 ( 2021-07-14), p. 451-459
    Abstract: 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 January 1, 2012 and November 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 = .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.
    Type of Medium: Online Resource
    ISSN: 2054-2577 , 2054-2585
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2768945-1
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  • 7
    In: Journal of Adolescent and Young Adult Oncology, Mary Ann Liebert Inc, Vol. 11, No. 4 ( 2022-08-01), p. 402-409
    Type of Medium: Online Resource
    ISSN: 2156-5333 , 2156-535X
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2022
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Current Oncology Reports Vol. 24, No. 2 ( 2022-02), p. 161-174
    In: Current Oncology Reports, Springer Science and Business Media LLC, Vol. 24, No. 2 ( 2022-02), p. 161-174
    Type of Medium: Online Resource
    ISSN: 1523-3790 , 1534-6269
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2054295-1
    detail.hit.zdb_id: 2057359-5
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  • 9
    Online Resource
    Online Resource
    Elsevier BV ; 2019
    In:  Journal of Pain and Symptom Management Vol. 57, No. 2 ( 2019-02), p. 493-494
    In: Journal of Pain and Symptom Management, Elsevier BV, Vol. 57, No. 2 ( 2019-02), p. 493-494
    Type of Medium: Online Resource
    ISSN: 0885-3924
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 1500639-6
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  • 10
    In: Pediatric Blood & Cancer, Wiley, Vol. 67, No. 10 ( 2020-10)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2130978-4
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