Publications by authors named "April Sykes"

37 Publications

Cytoneme delivery of Sonic Hedgehog from ligand-producing cells requires Myosin 10 and a Dispatched-BOC/CDON co-receptor complex.

Elife 2021 Feb 11;10. Epub 2021 Feb 11.

Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, United States.

Morphogens function in concentration-dependent manners to instruct cell fate during tissue patterning. The cytoneme morphogen transport model posits that specialized filopodia extend between morphogen-sending and responding cells to ensure that appropriate signaling thresholds are achieved. How morphogens are transported along and deployed from cytonemes, how quickly a cytoneme-delivered, receptor-dependent signal is initiated, and whether these processes are conserved across phyla are not known. Herein, we reveal that the actin motor Myosin 10 promotes vesicular transport of Sonic Hedgehog (SHH) morphogen in mouse cell cytonemes, and that SHH morphogen gradient organization is altered in neural tubes of mice. We demonstrate that cytoneme-mediated deposition of SHH onto receiving cells induces a rapid, receptor-dependent signal response that occurs within seconds of ligand delivery. This activity is dependent upon a novel Dispatched (DISP)-BOC/CDON co-receptor complex that functions in ligand-producing cells to promote cytoneme occurrence and facilitate ligand delivery for signal activation.
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http://dx.doi.org/10.7554/eLife.61432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968926PMC
February 2021

Chemoreduction with topotecan and vincristine: Quantifying tumor response in bilateral retinoblastoma patients.

Pediatr Blood Cancer 2021 Apr 28;68(4):e28882. Epub 2021 Jan 28.

Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee.

Background: Evaluate the efficacy of two courses of vincristine and topotecan (VT) neoadjuvant intravenous chemotherapy in reducing retinoblastoma tumor volumes.

Methods: Twenty-seven patients with previously untreated, bilateral advanced retinoblastoma who were enrolled on a prospective treatment protocol (NCT00186888). Patients underwent high-resolution ophthalmic imaging at diagnosis and were reimaged following treatment with two cycles of VT. Tumor height and diameter were measured before and after treatment, and tumor volumes were calculated. Statistical methods for dependent samples were used.

Results: Imaging was completed for 75 tumors in 23 patients (43 eyes). After two cycles of VT, median decrease in tumor height was 47% and median decrease in tumor diameter was 22%. Median decrease in estimated tumor volume was 74%. Sixty-one of 75 tumors demonstrated >50% reduction in tumor volume. Distance from the optic nerve (=0 vs >0), age (<4 vs >4 months), macular location (within vs outside), and time (pre- and posttreatment) were found significantly associated with log-transformed tumor volume adjusting for the repeated effect of patient eye using generalized estimating equations to estimate the parameters of a generalized linear model (P < .0001 [ : 1.95, CI: 1.53-2.36], P = .0031 [ : 1.49, CI: 0.57-2.41], P < .0001 [ : .94, CI: 0.54-1.35], and P < .0001 [ : 1.43, CI: 1.15-1.71]).

Conclusion: Chemoreduction was achieved in all patients and most retinoblastoma tumors following two cycles of VT. Reduction in tumor dimensions was comparable to that reported with platinum-based chemotherapy. Tumor location, distance from the optic nerve, and age at diagnosis were significant predictors of treatment response.
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http://dx.doi.org/10.1002/pbc.28882DOI Listing
April 2021

The impact of tumor excision on American Society of Anesthesiology-Physical Status scoring among pediatric anesthesiologists: A retrospective review.

Paediatr Anaesth 2021 Apr 21;31(4):491-493. Epub 2021 Jan 21.

Division of Anesthesiology, St. Jude Children's Research Hospital, Memphis, TN, USA.

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http://dx.doi.org/10.1111/pan.14110DOI Listing
April 2021

A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies.

Eur J Cancer 2020 09 11;137:204-213. Epub 2020 Aug 11.

Departments of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Departments of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; The Departments of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38103, USA.

Background: Talazoparib combined with irinotecan and temozolomide demonstrated efficacy in a murine Ewing sarcoma model. Based on these data, we conducted a phase I trial of talazoparib and irinotecan with/without temozolomide in paediatric patients with recurrent/refractory solid malignancies.

Patients And Methods: Cohorts of 3-6 patients with recurrent/refractory solid malignancies received escalating doses of oral talazoparib and intravenous irinotecan (arm A) and oral talazoparib, oral temozolomide and intravenous irinotecan (arm B) in a 3 + 3 design. Talazoparib was administered on days 1-6, and intravenous irinotecan and oral temozolomide were administered on days 2-6, of a 21-day course. Serum for talazoparib and irinotecan pharmacokinetics was obtained during course 1. UGT1A1 polymorphism and Schlafen family member 11 (SLFN11) immunohistochemical staining were performed.

Results: Forty-one patients (20 males; median age, 14.6 years; 24 with recurrent disease) were evaluable for dose escalation. Twenty-nine and 12 patients were treated on arm A and arm B, respectively, for a total of 208 courses. The most common diagnosis was Ewing sarcoma (53%). The most common ≥grade III haematologic toxicities in arms A and B included neutropenia (78% and 31%, respectively) and thrombocytopenia (42% and 31%, respectively). In arms A and B, febrile neutropenia (24% and 14%, respectively) and diarrhoea (21% and 7%, respectively) were the most common ≥grade III non-hematologic toxicities. Six patients (Ewing sarcoma [5 patients] and synovial sarcoma [1 patient]) had a response (1 with a complete response, 5 with a partial response). The objective response rates were 10.3% (arm A) and 25% (arm B). Pharmacokinetic testing demonstrated no evidence of drug-drug interaction between talazoparib and irinotecan. UGT1A1 was not related to response. SLFN11 positivity was associated with best response to therapy.

Conclusions: The combination of talazoparib and irinotecan with/without temozolomide is feasible and active in Ewing sarcoma, and further investigation is warranted.
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http://dx.doi.org/10.1016/j.ejca.2020.06.014DOI Listing
September 2020

The Art and Science of Selecting a CD123-Specific Chimeric Antigen Receptor for Clinical Testing.

Mol Ther Methods Clin Dev 2020 Sep 30;18:571-581. Epub 2020 Jun 30.

Department of Bone Marrow Transplant and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Chimeric antigen receptor (CAR) T cells targeting CD123, an acute myeloid leukemia (AML) antigen, hold the promise of improving outcomes for patients with refractory/recurrent disease. We generated five lentiviral vectors encoding CD20, which may serve as a target for CAR T cell depletion, and 2 or 3 generation CD123-CARs since the benefit of two costimulatory domains is model dependent. Four CARs were based on the CD123-specific single-chain variable fragment (scFv) 26292 (292) and one CAR on the CD123-specific scFv 26716 (716), respectively. We designed CARs with different hinge/transmembrane (H/TM) domains and costimulatory domains, in combination with the zeta (z) signaling domain: 292.CD8aH/TM.41BBz (8.41BBz), 292.CD8aH/TM.CD28z (8.28z), 716.CD8aH/TM.CD28z (716.8.28z), 292.CD28H/TM. CD28z (28.28z), and 292.CD28H/TM.CD28.41BBz (28.28.41BBz). Transduction efficiency, expansion, phenotype, and target cell recognition of the generated CD123-CAR T cells did not significantly differ. CAR constructs were eliminated for the following reasons: (1) 8.41BBz CARs induced significant baseline signaling, (2) 716.8.28z CAR T cells had decreased anti-AML activity, and (3) CD28.41BBz CAR T cells had no improved effector function in comparison to CD28z CAR T cells. We selected the 28.28z CAR since CAR expression on the cell surface of transduced T cells was higher in comparison to 8.28z CARs. The clinical study (NCT04318678) evaluating 28.28z CAR T cells is now open for patient accrual.
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http://dx.doi.org/10.1016/j.omtm.2020.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393323PMC
September 2020

Predictors of narcolepsy and hypersomnia due to medical disorder in pediatric craniopharyngioma.

J Neurooncol 2020 Jun 28;148(2):307-316. Epub 2020 Apr 28.

Department of Psychology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.

Purpose: Several studies describe sleep-wake disturbances in pediatric craniopharyngioma, but none have determined the prevalence or associated predictors of excessive sleepiness in this group after diagnosis and prior to post-operative observation or adjuvant radiotherapy. In this study, we report sleep-wake disturbances in children and adolescents with craniopharyngioma and associated clinical and treatment variables.

Methods: After surgery and prior to radiotherapy or observation, pediatric patients (n = 110) with craniopharyngioma ≥ 3 years old completed a baseline sleep clinic evaluation by a pediatric sleep specialist, polysomnography (PSG) and next-day multiple sleep latency test (MSLT). MSLT was limited to those ≥ 6 years old. Logistic regression models were used to determine the relationship between patient characteristics and the presence and type of hypersomnia.

Results: Amongst patients completing PSG and MSLT, 80% had polygraphic evidence of excessive daytime sleepiness. Hypersomnia due to medical condition was diagnosed in 45% and narcolepsy in 35%. Overweight or obese patients were more likely to be diagnosed with hypersomnia (P = 0.012) or narcolepsy (P = 0.009). Grade 2 hypothalamic involvement (HI) at diagnosis was associated with the diagnosis of narcolepsy (P = 0.0008).

Conclusions: This study describes the prevalence and associated predictors of hypersomnia for patients with craniopharyngioma after surgical resection. HI was predictive of narcolepsy diagnosis, and a higher body mass index z-score was associated with hypersomnia due to medical condition and narcolepsy. We recommend that sleep assessment and intervention begin after surgical resection, especially in overweight or obese patients and those with extensive tumors.
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http://dx.doi.org/10.1007/s11060-020-03519-3DOI Listing
June 2020

Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial.

J Immunother Cancer 2020 03;8(1)

Oncology Department, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

Background: Natural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics, phenotype, and function is understudied.

Methods: We prospectively examined NK cell properties from 63 children with newly diagnosed neuroblastoma enrolled in a phase II trial (NCT01857934) and correlated our findings with tumor volume reduction after 2 courses of chemoimmunotherapy. NK cell studies were conducted longitudinally during chemoimmunotherapy and autologous hematopoietic cell transplantation (autoHCT) with optional haploidentical NK cell infusion and additional immunotherapy.

Results: Chemoimmunotherapy led to significant NK cytopenia, but complete NK cell recovery reliably occurred by day 21 of each therapy course as well as after autoHCT. Haploidentical NK cell infusion elevated the NK cell count transiently during autoHCT. NK cell cytotoxicity increased significantly during treatment compared with diagnosis. In addition, NK cells maintained their ability to respond to cytokine stimulation in culture longitudinally. Unsupervised cluster analysis of CD56 NK cell count and tumor volume at diagnosis and after two courses of chemoimmunotherapy identified two patient groups with distinct primary tumor sizes and therapy responses.

Conclusion: After profound NK cytopenia due to chemoimmunotherapy, endogenously reconstituted NK cells exhibit enhanced NK cytotoxicity compared with pretherapy measurements. Our data suggest a relationship between CD56 expression and tumor size before and after two courses of chemoimmunotherapy; however, future studies are necessary to confirm this relationship and its predictive significance.

Trial Registration Number: NCT01857934.
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http://dx.doi.org/10.1136/jitc-2019-000176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206969PMC
March 2020

A phase 1 trial of everolimus and bevacizumab in children with recurrent solid tumors.

Cancer 2020 04 22;126(8):1749-1757. Epub 2020 Jan 22.

Department of Pediatrics, Penn State University College of Medicine, Hershey, Pennsylvania.

Background: The prognosis for children with recurrent solid tumors generally is poor. Targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor A with everolimus and bevacizumab, respectively, synergistically improves progression-free survival and is well tolerated in adults with solid tumors.

Methods: In the current phase 1 study, a total of 15 children with recurrent or refractory solid tumors were treated with bevacizumab and everolimus to establish the maximum tolerated dose, toxicity, and preliminary antitumor response (ClinicalTrials.gov identifier NCT00756340). The authors also evaluated everolimus-mediated inhibition of the mTOR pathway in the peripheral blood mononuclear cells of treated patients.

Results: Tumors predominantly were soft tissue and/or bone sarcomas (8 cases) and brain tumors (5 cases). The first 2 patients enrolled at dose level 1 (10 mg/kg of bevacizumab and 4 mg/m of everolimus) experienced dose-limiting toxicities (DLTs). The next 5 patients were enrolled at dose level 0 (8 mg/kg of bevacizumab and 4 mg/m of everolimus), and DLTs occurred in 2 patients. The authors then modified the protocol to permit expansion of dose 0, and 8 additional patients were added, with no DLTs reported. Of all the patients, stable disease occurred in 4 patients (30.8%; median, 2 courses), and progressive disease occurred in 9 patients (69.2%). Overall survival was 0.59 years (95% CI, 0.24-1.05 years). The mTOR biomarker phospho-4EBP1 Thr/37/46 significantly decreased from baseline to day 27 in peripheral blood mononuclear cells (P = .045). Phospho-AKT levels also decreased from those at baseline.

Conclusions: The maximum tolerated dose of cotreatment with bevacizumab and everolimus was 8 mg/kg of bevacizumab and 4 mg/m of everolimus in a 4-week cycle for children with recurrent solid tumors.
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http://dx.doi.org/10.1002/cncr.32722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103504PMC
April 2020

Clinical impact of post-induction resolution of pulmonary lesions in metastatic Ewing sarcoma.

Pediatr Blood Cancer 2020 04 15;67(4):e28150. Epub 2020 Jan 15.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Patients with metastatic Ewing sarcoma experience poor outcomes despite intensive systemic and local therapy. Early chemotherapy response of pulmonary metastases has been associated with prognosis in other pediatric malignancies. We reviewed the outcomes of patients with Ewing sarcoma and pulmonary metastases treated at our institution based on therapy received and early pulmonary response.

Materials And Methods: We retrospectively reviewed patients with newly diagnosed Ewing sarcoma and pulmonary metastases at St. Jude Children's Research Hospital between 1979 and 2015. Data obtained included demographic and treatment characteristics including chemotherapy, local control measures, whole lung irradiation (WLI) administration, autologous stem cell transplantation, and outcomes. Patients were evaluated for radiographic post-induction pulmonary complete response (CR). We estimated event-free survival (EFS) and overall survival (OS) and used Cox proportional hazards regression to examine the effects of clinical and treatment factors on outcomes.

Results: Fifty-four patients (median age, 12.9 years) were evaluated. Post-induction pulmonary CR was observed in 33 (61%) patients. WLI was delivered to 16 patients (4/33 with pulmonary CR and 12/21 with non-CR). At median 3.6 years follow-up, five-year EFS and OS were 30.8% ± 6.4% and 49.6% ± 7.1%, respectively. Post-induction pulmonary CR was associated with prolonged EFS (P < 0.001) but not improved OS (P = 0.065). Post-induction pulmonary CR was associated with a lower incidence of lung failure (P = 0.031).

Conclusions: Post-induction pulmonary CR is associated with improved EFS in patients with Ewing sarcoma who present with pulmonary metastases.
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http://dx.doi.org/10.1002/pbc.28150DOI Listing
April 2020

A Phase II Trial of Hu14.18K322A in Combination with Induction Chemotherapy in Children with Newly Diagnosed High-Risk Neuroblastoma.

Clin Cancer Res 2019 11 10;25(21):6320-6328. Epub 2019 Oct 10.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Purpose: We sought to evaluate whether combining a humanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma.

Patients And Methods: We conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoin were then administered. Secondary outcomes included reduced tumor volume and semiquantitative I-metaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction.

Results: Forty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6-88.0]. This was accompanied by primary tumor volume reductions (median, -76%; range, -100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9-93.3).

Conclusions: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-1452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825564PMC
November 2019

Sensitivity and Specificity of the Modified Epworth Sleepiness Scale in Children With Craniopharyngioma.

J Clin Sleep Med 2019 10;15(10):1487-1493

Department of Pediatric Medicine, Division of Nursing Research, St. Jude Children's Research Hospital, Memphis, Tennessee.

Study Objectives: Children with craniopharyngioma are at risk for excessive daytime sleepiness (EDS). Multiple Sleep Latency Testing (MSLT) is the gold standard for objective evaluation of EDS; however, it is time and resource intensive. We compared the reliability, sensitivity, and specificity of the modified Epworth Sleepiness Scale (M-ESS) and MSLT in monitoring EDS in children with craniopharyngioma.

Methods: Seventy patients (ages 6 to 20 years) with craniopharyngioma completed the M-ESS and were evaluated by polysomnography and MSLT. Evaluations were made after surgery, if performed, and before proton therapy.

Results: MSLT revealed that 66 participants (81.8%) had EDS, as defined by a mean sleep latency (MSL) < 10 minutes, with only 28.8% reporting EDS on the M-ESS by using a cutoff score of 10. The M-ESS demonstrated adequate internal consistency and specificity (91.7%) but poor sensitivity (33.3%) with the established cutoff score of 10. A cutoff score of 6 improved the sensitivity to 64.8% but decreased the specificity to 66.7%.

Conclusions: Patients with craniopharyngioma are at high risk for EDS, as documented objectively on the MSLT, but they frequently do not recognize or accurately report their sleepiness. Future sleep studies should investigate whether specific items or alternative self- and parent-reported measures of sleepiness may have greater clinical utility in monitoring sleepiness in this population.
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http://dx.doi.org/10.5664/jcsm.7982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778340PMC
October 2019

Reducing Compassion Fatigue in Inpatient Pediatric Oncology Nurses.

Oncol Nurs Forum 2019 05;46(3):338-347

St. Jude Children's Research Hospital.

Objectives: To develop an evidence-based compassion fatigue program and evaluate its impact on nurse-reported burnout, secondary traumatic stress, and compassion satisfaction, as well as correlated factors of resilience and coping behaviors.

Sample & Setting: The quality improvement pilot program was conducted with 59 nurses on a 20-bed subspecialty pediatric oncology unit at the St. Jude Children's Research Hospital in Memphis, Tennessee.

Methods & Variables: Validated measures of compassion fatigue and satisfaction (Professional Quality of Life Scale V [ProQOLV]), coping (Brief COPE), and resilience (Connor-Davidson Resilience Scale-2) were evaluated preprogram and at two, four, and six months postprogram, with resilience and coping style measured at baseline and at six months postprogram.

Results: Secondary traumatic stress scores significantly improved from baseline to four months. Select coping characteristics were significantly correlated with ProQOLV subscale scores.

Implications For Nursing: Ongoing organizational support and intervention can reduce compassion fatigue and foster compassion satisfaction among pediatric oncology nurses.
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http://dx.doi.org/10.1188/19.ONF.338-347DOI Listing
May 2019

Speaking genomics to parents offered germline testing for cancer predisposition: Use of a 2-visit consent model.

Cancer 2019 07 22;125(14):2455-2464. Epub 2019 Mar 22.

Division of Cancer Predisposition, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Patients with cancer are increasingly offered genomic sequencing, including germline testing for cancer predisposition or other disorders. Such testing is unfamiliar to patients and families, and clear communication is needed to introduce genomic concepts and convey risk and benefit information.

Methods: Parents of children with cancer were offered the opportunity to have their children's tumor and germline examined with clinical genomic sequencing. Families were introduced to the study with a 2-visit informed consent model. Baseline genetic knowledge and self-reported literacy/numeracy were collected before a study introduction visit, during which basic concepts related to genomic sequencing were discussed. Information was reinforced during a second visit, during which informed consent was obtained and a posttest was administered.

Results: As reflected by the percentage of correct answers on the pretest and posttest assessments, this model increased genetic knowledge by 11.1% (from 77.8% to 88.9%; P < .0001) in 121 parents participating in both the study introduction and consent visits. The percentage of parents correctly identifying the meaning of somatic and germline mutations increased significantly (from 18% to 59% [somatic] and from 31% to 64% [germline]; P < .0001). Nevertheless, these concepts remained unfamiliar to one-third of the parents. No relation was identified between the change in the overall percentage of correct answers and self-reported literacy, numeracy, or demographics.

Conclusions: The use of a 2-visit communication model improved knowledge of concepts relevant to genomic sequencing, particularly differences between somatic and germline testing; however, these areas remained confusing to many participants, and reinforcement may be necessary to achieve complete understanding.
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http://dx.doi.org/10.1002/cncr.32071DOI Listing
July 2019

Are we meeting the informational needs of cancer patients and families? Perception of physician communication in pediatric oncology.

Cancer 2019 05 2;125(9):1518-1526. Epub 2019 Jan 2.

Division of Quality-of-life and Palliative Care, Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: High-quality oncology care is marked by skillful communication, yet little is known about patient and family communication perceptions or content preferences. Our study sought to elicit pediatric oncology patient and parent perceptions of early cancer communication to establish whether informational needs were met and identify opportunities for enhanced communication throughout cancer care.

Method: An original survey instrument was developed, pretested, and administered to 129 patients, age 10-18 years, and their parents at 3 cancer centers between 2011 and 2015. Statistical analysis of survey items about perceived communication, related associations, and patient/parent concordance was performed.

Results: A greater percentage of participants reported "a lot" of discussion about the physical impact of cancer (patients, 58.1% [n = 75]; parents, 69.8% [n = 90]) compared with impact on quality of life (QOL) (patients, 44.2% [n = 57]; parents, 55.8% [n = 72]) or emotional impact (patients, 31.8% [n = 41]; parents, 43.4% [n = 56]). One fifth of patients (20.9% [n = 27]) reported they had no up-front discussion about the emotional impact of cancer treatment. Parents indicated a desire for increased discussion regarding impact on family life (27.9% [n = 36]), long-term QOL (27.9% [n = 36]), and daily activities (20.2% [n = 26]). Patients more frequently than parents indicated a desire for increased physician/patient discussion around the impact on daily activities (patients, 40.3% [n = 52]; parents, 21.7% [n = 28]; P < .001), long-term QOL (patients, 34.9% [n = 45]; parents, 16.3% [n = 21]; P < .001), pain management (patients, 23.3% [n = 30]; parents, 7% [n = 9]; P < .001), physical symptom management (patients, 24% [n = 31]; parents, 7.8% [n = 10]; P < .001), short-term QOL (patients, 23.3% [n = 30]; parents, 9.3% [n = 12]; P = .001), and curative potential (patients, 21.7% [n = 28]; parents, 8.5% [n = 11]; P = .002, P values calculated using McNemar's test).

Conclusion: Oncologists may not be meeting the informational needs of many patients and some parents/caregivers. Communication could be enhanced through increased direct physician-patient communication, as well as proactive discussion of emotional symptoms and impact of cancer on QOL.
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http://dx.doi.org/10.1002/cncr.31937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945977PMC
May 2019

Incorporating Bereaved Parents as Faculty Facilitators and Educators in Teaching Principles of Palliative and End-of-Life Care.

Am J Hosp Palliat Care 2018 Dec 16;35(12):1518-1525. Epub 2018 Jul 16.

2 Division of Quality of Life and Palliative Care, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Background:: Education and training for interdisciplinary pediatric providers requires training in principles of palliative and end-of-life (EOL) care. The experiences of bereaved parents can inform and enhance palliative care educational curricula in uniquely powerful and valuable ways. The objective of this study is to present an innovative palliative care educational program facilitated by trained bereaved parents who serve as volunteer educators in local and national palliative care educational forums and to describe how incorporation of bereaved parents in these educational forums affects participant comfort with communication and management of children at the EOL.

Methods:: Parent educators underwent both general and session-specific training and participated in debriefings following each session. Survey tools were developed or adapted to determine how bereaved parent educators affected participant experiences in 3 different educational forums. Pre- and postsession surveys with incorporation of retrospective preprogram assessment items to control for response shift were used in the evaluation of institutional seminars on pediatric palliative and EOL care and role-play-based communication training sessions. Results from feedback surveys sent to attendees were used to appraise the participants' experience at the international oncology symposium.

Results:: Involvement of trained parent educators across diverse, interdisciplinary educational forums improved attendee comfort in communicating with, and caring for, patients and families with serious illness. Importantly, parent educators also derive benefit from involvement in educational sessions with interdisciplinary clinicians.

Conclusions:: Integration of bereaved parents into palliative and EOL care education is an innovative and effective model that benefits both interdisciplinary clinicians and bereaved parents.
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http://dx.doi.org/10.1177/1049909118786875DOI Listing
December 2018

Clinical Characteristics of Children and Adolescents Undergoing Hematopoietic Cell Transplantation Who Develop Oral Mucositis.

Oncol Nurs Forum 2018 07;45(4):457-462

St. Jude Children's Research Hospital.

Objectives: To describe the clinical characteristics of children and adolescents undergoing hematopoietic cell transplantation (HCT) who develop oral mucositis.

Sample & Setting: 45 patients who underwent HCT from July 2015 to May 2016 at St. Jude Children's Research Hospital in Memphis, Tennessee.

Methods & Variables: Clinical factors were described as transplantation type, mucositis severity or grade, mucositis duration, days to engraftment, total parenteral nutrition (TPN) support, IV opioid pain management use during mucositis, positive blood or oral cultures, and length of hospitalization, then compared across mucositis grade.

Results: 24 patients had grade 3 or greater mucositis onset from day -3 to day 9 of transplantation; of these, 23 required IV opioid medication to treat mucosal pain. Patients with mucositis grade 3 or greater were more likely to have undergone an allogeneic transplantation, receive TPN, have documented positive blood or oral cultures, and have longer hospitalizations than those with low-grade mucositis.

Implications For Nursing: Nurses are in a unique position to propose and administer interventions to prevent and alleviate symptoms of mucositis.
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http://dx.doi.org/10.1188/18.ONF.457-462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152915PMC
July 2018

Rapid decrease of serum alpha-fetoprotein and tumor volume predicts outcome in children with hepatoblastoma treated with neoadjuvant chemotherapy.

Int J Clin Oncol 2018 Oct 9;23(5):900-907. Epub 2018 May 9.

Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.

Background: Neoadjuvant chemotherapy is given to children with unresectable hepatoblastoma to increase the rate and safety of curative complete surgical resection. Elevated levels of serum alpha-fetoprotein (sAFP) decline with tumor shrinkage. In this single-institution retrospective study, we determined early dynamic changes of sAFP levels and tumor volume in children during therapy for unresectable hepatoblastoma.

Methods: We correlated early dynamic changes of sAFP levels and tumor volume and the sum of the longest primary tumor and measurable metastatic disease diameters as per RECIST 1.1 criteria with patient outcome.

Results: There were 34 patients, 7 of whom died of disease. Patients with ≥ 90% (≥ 1 log) decrease in sAFP levels after two chemotherapy courses had a better event-free survival (P = 0.039) and overall survival (OS; P = 0.045) than those with < 90% decrease. During this treatment interval, average tumor volume decreased from 481 mL (± 254 mL) to 268 mL (± 258 mL; P < 0.001) which was associated with OS (P = 0.029). Relative change in sAFP levels or tumor volume in between course 2 and pre-surgery or response as per RECIST 1.1 was not associated with OS.

Conclusion: Early decline of sAFP levels and tumor volume, but not response as per RECIST 1.1 may predict survival in children with unresectable hepatoblastoma. This finding could be useful to identify therapy non-responders for whom alternative interventions may be required for cure. Confirmation of the finding using larger patient cohorts will be necessary before this strategy is incorporated into prospective trials.
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http://dx.doi.org/10.1007/s10147-018-1285-4DOI Listing
October 2018

Predictors of Location of Death for Children with Cancer Enrolled on a Palliative Care Service.

Oncologist 2018 12 4;23(12):1525-1532. Epub 2018 May 4.

St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Background: In the U.S., more children die from cancer than from any other disease, and more than one third die in the hospital setting. These data have been replicated even in subpopulations of children with cancer enrolled on a palliative care service. Children with cancer who die in high-acuity inpatient settings often experience suffering at the end of life, with increased psychosocial morbidities seen in their bereaved parents. Strategies to preemptively identify children with cancer who are more likely to die in high-acuity inpatient settings have not been explored.

Materials And Methods: A standardized tool was used to gather demographic, disease, treatment, and end-of-life variables for 321 pediatric palliative oncology (PPO) patients treated at an academic pediatric cancer center who died between 2011 and 2015. Multinomial logistic regression was used to predict patient subgroups at increased risk for pediatric intensive care unit (PICU) death.

Results: Higher odds of dying in the PICU were found in patients with Hispanic ethnicity (odds ratio [OR], 4.02;  = .002), hematologic malignancy (OR, 7.42;  < .0001), history of hematopoietic stem cell transplant (OR, 4.52;  < .0001), total number of PICU hospitalizations (OR, 1.98;  < .0001), receipt of cancer-directed therapy during the last month of life (OR, 2.96;  = .002), and palliative care involvement occurring less than 30 days before death (OR, 4.7;  < .0001). Conversely, lower odds of dying in the PICU were found in patients with hospice involvement (OR, 0.02;  < .0001) and documentation of advance directives at the time of death (OR, 0.37;  = .033).

Conclusion: Certain variables may predict PICU death for PPO patients, including delayed palliative care involvement. Preemptive identification of patients at risk for PICU death affords opportunities to study the effects of earlier palliative care integration and increased discussions around preferred location of death on end-of-life outcomes for children with cancer and their families.

Implications For Practice: Children with cancer who die in high-acuity inpatient settings often experience a high burden of intensive therapy at the end of life. Strategies to identify patients at higher risk of dying in the pediatric intensive care unit (PICU) have not been explored previously. This study finds that certain variables may predict PICU death for pediatric palliative oncology patients, including delayed palliative care involvement. Preemptive identification of patients at risk for PICU death affords opportunities to study the effects of earlier palliative care integration and increased discussions around preferred location of death on end-of-life outcomes for children with cancer and their families.
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http://dx.doi.org/10.1634/theoncologist.2017-0650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292533PMC
December 2018

Predictors of Late Palliative Care Referral in Children With Cancer.

J Pain Symptom Manage 2018 06 8;55(6):1550-1556. Epub 2018 Feb 8.

St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Context: Early integration of palliative care (PC) in the management of children with high-risk cancer is widely endorsed by patients, families, clinicians, and national organizations. However, optimal timing for PC consultation is not standardized, and variables that influence timing of PC integration for children with cancer remain unknown.

Objectives: To investigate associations between demographic, disease, treatment, and end-of-life attributes and timing of PC consultation for children with high-risk cancer enrolled on a PC service.

Methods: A comprehensive standardized tool was used to abstract data from the medical records of 321 patients treated at a large academic pediatric cancer center, who died between 2011 and 2015.

Results: Gender, race, ethnicity, enrollment on a Phase I protocol, number of high-acuity hospitalizations, and receipt of cardiopulmonary resuscitation were not associated with timing of PC involvement. Patients with hematologic malignancy, those who received cancer-directed therapy during the last month of life, and those with advance directives documented one week or less before death had higher odds of late PC referral (malignancy: odds ratio [OR] 3.24, P = 0.001; therapy: OR 4.65, P < 0.001; directive: OR 4.81, P < 0.0001). Patients who received hospice services had lower odds of late PC referral <30 days before death (OR 0.31, P < 0.001).

Conclusion: Hematologic malignancy, cancer-directed therapy at the end of life, and delayed documentation of advance directives are associated with late PC involvement in children who died of cancer. Identification of these variables affords opportunities to study targeted interventions to enhance access to earlier PC resources and services for children with high-risk cancer and their families.
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http://dx.doi.org/10.1016/j.jpainsymman.2018.01.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223026PMC
June 2018

Comparison of Resting Energy Expenditure Assessment in Pediatric Oncology Patients.

Nutr Clin Pract 2018 Apr 2;33(2):224-231. Epub 2018 Feb 2.

Department of Pediatric Medicine, Division of Nursing Research, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Background: Evaluation of energy requirements is an important part of the nutrition assessment of pediatric oncology patients. Adequate provision of energy in this population is of extreme importance because of the prevalence of malnutrition and its effect on growth, development, quality of life, morbidity, and mortality. Numerous methods are used in clinical practice for estimating the resting energy expenditures (REE), specifically indirect calorimetry and predictive equations. A relatively new instrument used to assess REE is the hand-held indirect calorimeter. The purpose of this quality improvement project was to compare the accuracy of REE measurements taken by a hand-held indirect calorimeter and predictive equations to that of a standard indirect calorimeter metabolic cart.

Methods: Patients receiving therapy for pediatric cancer, aged 7-18 years, and having a weight ≥15 kg and scheduled for a REE nutrition assessment were eligible. Sequentially, the patient's REE was assessed with the cart and the hand-held indirect calorimeter along with the predictive equation calculation.

Results: Post hoc pairwise comparisons revealed that all 3 methods were significantly different from one another (P < .0001). When compared with the cart, the portable hand-held calorimeter was found to underestimate REE by 11.9%, whereas predictive equations overestimated REE by 12.4%.

Conclusion: Our quality improvement project suggests that the hand-held indirect calorimeter underestimated REE, and predictive equations overestimated REE in pediatric oncology nutrition assessment. Therefore, we recommend that these limitations in assessment be considered when assessing REE using a hand-held indirect calorimeter or predictive equations.
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http://dx.doi.org/10.1002/ncp.10002DOI Listing
April 2018

Illness and end-of-life experiences of children with cancer who receive palliative care.

Pediatr Blood Cancer 2018 04 8;65(4). Epub 2017 Dec 8.

Department of Oncology, Division of Quality of Life and Palliative Care, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: The field of pediatric palliative oncology is newly emerging. Little is known about the characteristics and illness experiences of children with cancer who receive palliative care (PC).

Methods: A retrospective cohort study of 321 pediatric oncology patients enrolled in PC who died between 2011 and 2015 was conducted at a large academic pediatric cancer center using a comprehensive standardized data extraction tool.

Results: The majority of pediatric palliative oncology patients received experimental therapy (79.4%), with 40.5% enrolled on a phase I trial. Approximately one-third received cancer-directed therapy during the last month of life (35.5%). More than half had at least one intensive care unit hospitalization (51.4%), with this subset demonstrating considerable exposure to mechanical ventilation (44.8%), invasive procedures (20%), and cardiopulmonary resuscitation (12.1%). Of the 122 patients who died in the hospital, 44.3% died in the intensive care unit. Patients with late PC involvement occurring less than 30 days before death had higher odds of dying in the intensive care unit over the home/hospice setting compared to those with earlier PC involvement (OR: 4.7, 95% CI: 2.47-8.97, P < 0.0001).

Conclusions: Children with cancer who receive PC experience a high burden of intensive treatments and often die in inpatient intensive care settings. Delayed PC involvement is associated with increased odds of dying in the intensive care unit. Prospective investigation of early PC involvement in children with high-risk cancer is needed to better understand potential impacts on cost-effectiveness, quality of life, and delivery of goal concordant care.
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http://dx.doi.org/10.1002/pbc.26895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159948PMC
April 2018

The Effectiveness of Trivalent Inactivated Influenza Vaccine in Children with Acute Leukemia.

J Pediatr 2017 12;191:218-224.e1

Department of Infectious Diseases, St. Jude Children's Research Hospital, Carmel, IN; Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN. Electronic address:

Objective: The objective of this study was to determine the effectiveness of trivalent inactivated influenza vaccine (TIV) for the prevention of laboratory-confirmed influenza and influenza-like illnesses (ILI) among children and adolescents receiving therapy for acute leukemia.

Study Design: A retrospective review of the demographic and clinical characteristics of 498 patients at a pediatric cancer center who received therapy for acute leukemia during 3 successive influenza seasons (2010-2011 through 2012-2013).

Results: In 498 patient seasons with a known immunization history (median age, 6 years; range, 1-21), 354 patients (71.1%) were immunized with TIV and 98 (19.7%) received a booster dose of vaccine. Vaccinated and unvaccinated patients had generally similar demographic characteristics. There were no differences in the overall rates of influenza or ILI between vaccinated and unvaccinated patients overall, or in any individual season. There was no difference in the rates of influenza or ILI between patients who received 1 dose of vaccine and those who received 2 doses. Time to first influenza infection and time to first ILI in vaccinated and unvaccinated patients were not different.

Conclusion: TIV did not protect children and adolescents with acute leukemia against laboratory-confirmed influenza or ILI. Future prospective studies should assess TIV effectiveness in high-risk subpopulations and alternative strategies to prevent influenza should be considered in this population.
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http://dx.doi.org/10.1016/j.jpeds.2017.08.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726795PMC
December 2017

Clinical Characteristics of Intravenous PEG-Asparaginase Hypersensitivity Reactions in Patients Undergoing Treatment for Acute Lymphoblastic Leukemia [Formula: see text].

J Pediatr Oncol Nurs 2018 Mar/Apr;35(2):103-109. Epub 2017 Nov 21.

1 St. Jude Children's Research Hospital, Memphis, TN, USA.

Background: Asparaginase poses a substantial risk for hypersensitivity reactions during and after administration; however, these reactions vary by asparaginase formulation and administration route. It is imperative that nurses be knowledgeable of clinical symptoms associated with intravenous (IV) monomethoxypolyethylene glycol (PEG)-asparaginase reactions, as well as potential reaction timing.

Purpose: This single institution retrospective study describes the clinical factors among patients with IV PEG-asparaginase hypersensitivity reactions.

Methods: Reaction frequency and severity, dose, phase of treatment, and time between infusion initiation and reaction were collected on patients identified as having an IV PEG-asparaginase hypersensitivity reaction while undergoing acute lymphoblastic leukemia treatment.

Results: Sixty-three patients (12.8%) developed a hypersensitivity reaction to IV PEG-asparaginase, with the reaction occurring during a median of 3 doses in both risk arms. Reactions were noted ≤60 minutes after infusion initiation in 98% of patients, and no reactions were fatal.

Conclusion: Nurses should carefully observe patients throughout the infusion and anticipate adverse reactions, particularly during the first 3 doses and first 10 minutes of each infusion. Patient and family education should include the rare risk of delayed reactions.
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http://dx.doi.org/10.1177/1043454217741868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803366PMC
September 2019

Prevalence, risk factors, and response to treatment for hypersomnia of central origin in survivors of childhood brain tumors.

J Neurooncol 2018 Jan 8;136(2):379-384. Epub 2017 Nov 8.

Division of Nursing Research, Department of Pediatrics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.

Daytime sleepiness is recognized in childhood brain tumor survivors. Our objective was to determine prevalence, risk factors for PSG/MLST proven hypersomnia/narcolepsy, and response to stimulants in childhood brain tumor survivors. Standard PSG/MSLT criteria were used to diagnose hypersomnia/narcolepsy. Medical records of brain tumor survivors having undergone a PSG/MSLT were reviewed for the diagnostic code of hypersomnia/narcolepsy. Survivors with hypersomnia/narcolepsy were matched with 2-3 survivors without reported hypersomnia/narcolepsy by age at tumor diagnosis, gender, and time from tumor diagnosis. Between January 2000 to April 2015, 39 of the 2336 brain tumor patients treated at our institution were diagnosed with hypersomnia/narcolepsy for a prevalence rate of 1670/100,000. Hypersomnia/narcolepsy was diagnosed at a median of 6.1 years (range 0.4-13.2) from tumor diagnosis and 4.7 years (range - 1.5 to 10.4) from cranial radiation. Midline tumor location (OR 4.6, CI 1.7-12.2, p = 0.002) and anti-epilepsy drug (AED) use (OR 11, CI 2.4-54) correlated with hypersomnia/narcolepsy while radiation dose > 30 Gray trended towards significance (OR 1.8, CI 0.9-3.6); posterior fossa tumor location reduced the risk (OR 0.1, CI 0.04-0.5, p = 0.002). AED use also correlated with midline tumor location. Thirty-seven survivors were treated with stimulants and reported improved wakefulness and school performance [response rate CI 0.97 (0.86-0.99) and 0.83 (0.65-0.94)]. Prevalence of hypersomnia/narcolepsy among childhood brain tumor survivors was higher than the general population. Tumor location and radiation dose were possible risk factors, and stimulants were reported to be beneficial.
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http://dx.doi.org/10.1007/s11060-017-2662-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814140PMC
January 2018

Evaluation of a fever-management algorithm in a pediatric cancer center in a low-resource setting.

Pediatr Blood Cancer 2018 Feb 12;65(2). Epub 2017 Sep 12.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: In low- and middle-income countries (LMICs), inconsistent or delayed management of fever contributes to poor outcomes among pediatric patients with cancer. We hypothesized that standardizing practice with a clinical algorithm adapted to local resources would improve outcomes. Therefore, we developed a resource-specific algorithm for fever management in Davao City, Philippines. The primary objective of this study was to evaluate adherence to the algorithm.

Procedure: This was a prospective cohort study of algorithm adherence to assess the types of deviation, reasons for deviation, and pathogens isolated. All pediatric oncology patients who were admitted with fever (defined as an axillary temperature  >37.7°C on one occasion or ≥37.4°C on two occasions 1 hr apart) or who developed fever within 48 hr of admission were included. Univariate and multiple linear regression analyses were used to determine the relation between clinical predictors and length of hospitalization.

Results: During the study, 93 patients had 141 qualifying febrile episodes. Even though the algorithm was designed locally, deviations occurred in 70 (50%) of 141 febrile episodes on day 0, reflecting implementation barriers at the patient, provider, and institutional levels. There were 259 deviations during the first 7 days of admission in 92 (65%) of 141 patient episodes. Failure to identify high-risk patients, missed antimicrobial doses, and pathogen isolation were associated with prolonged hospitalization.

Conclusions: Monitoring algorithm adherence helps in assessing the quality of pediatric oncology care in LMICs and identifying opportunities for improvement. Measures that decrease high-frequency/high-impact algorithm deviations may shorten hospitalizations and improve healthcare use in LMICs.
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http://dx.doi.org/10.1002/pbc.26790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051353PMC
February 2018

The bereavement experience of adolescents and early young adults with cancer: Peer and parental loss due to death is associated with increased risk of adverse psychological outcomes.

PLoS One 2017 23;12(8):e0181024. Epub 2017 Aug 23.

Division of Quality of Life and Palliative Care, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.

Background: Adolescents commonly experience loss due to death, and perceived closeness to the deceased can often increase the intensity of bereavement. Adolescents and early young adult (AeYA) oncology patients may recall previous losses or experience new losses, possibly of other children with cancer, while coping with their own increased risk of mortality. The bereavement experiences of AeYA patients are not well described in the literature.

Methods And Findings: This analysis of bereavement sought to describe the prevalence and types of losses, the support following a death, and the impact of loss on AeYAs aged 13-21 years with malignant disease (or a hematologic disorder requiring allogeneic transplant). Participants were receiving active oncologic therapy or had completed therapy within the past 3 years. Participants completed a bereavement questionnaire and inventories on depression, anxiety, and somatization. The cross-sectional study enrolled 153 AeYAs (95% participation), most (88%) of whom had experienced a loss due to death. The most commonly reported losses were of a grandparent (58%) or friend (37%). Peer deaths were predominantly cancer related (66%). Many participants (39%) self-identified a loss as "very significant." As loss significance increased, AeYAs were more likely to report that it had changed their life "a lot/enormously" (P<0.0001), that they were grieving "slowly or never got over it" (P<0.0001), and that they felt a need for more professional help (P = 0.026). Peer loss was associated with increased risk of adverse psychological outcomes (P = 0.029), as was parental loss (P = 0.018).

Conclusions: Most AeYAs with serious illness experience the grief process as slow or ongoing. Peer or parental loss was associated with increased risk of negative mental health outcomes. Given the high prevalence of peer loss, screening for bereavement problems is warranted in AeYAs with cancer, and further research on grief and bereavement is needed in AeYAs with serious illness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181024PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568383PMC
October 2017

Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult patients: Results from a prospective study using limited-margin radiotherapy.

Cancer 2017 Nov 31;123(22):4419-4429. Epub 2017 Jul 31.

Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy.

Methods: Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0.

Results: At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%).

Conclusions: The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673566PMC
November 2017

Patients' and Parents' Needs, Attitudes, and Perceptions About Early Palliative Care Integration in Pediatric Oncology.

JAMA Oncol 2017 Sep;3(9):1214-1220

Division of Quality of Life and Palliative Care, Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.

Importance: Early palliative care integration for cancer patients is now touted as the optimal care model, yet significant barriers often prevent its implementation. A perceived barrier, especially for pediatric oncology patients, is the notion that patients and their families may not need or want palliative care involvement early in the disease trajectory.

Objective: To determine the perception of symptom burden early in treatment and assess attitudes toward early integration of palliative care in pediatric oncology patient-parent pairs.

Design, Setting, And Participants: Novel but pretested survey tools were administered to 129 patient-parent dyads of hospital-based pediatric oncology ambulatory clinics and inpatient units between September 2011 and January 2015. All patient participants were aged between 10 and 17 years and were diagnosed as having an oncologic condition 1 month to 1 year before enrollment. Both the patient and the parent in the dyad spoke English, and all participating parents provided written informed consent. A convenience sample was used for selection, with participants screened when otherwise presenting at a participating site. A total of 280 eligible participants were approached for study inclusion, 258 of whom were enrolled in the study (92.1% positive response-rate).

Main Outcomes And Measures: Degree of perceived suffering from early symptom-related causes, attitudes toward early palliative care integration, and patient-parent concordance. Statistical analysis included descriptive statistics, calculation of concordance, McNemar test results, and Cochran-Armitage trend test results.

Results: Of the 129 patients in the dyads, 68 were boys, and 61 girls; of the 129 parents, 15 were men, and 114 women. Patients reported the following symptoms in the first month of cancer therapy: nausea (n = 109; 84.5%), loss of appetite (n = 97; 75.2%), pain (n = 96; 74.4%), anxiety (n = 77; 59.7%), constipation (n = 69; 53.5%), depression (n = 64; 49.6%), and diarrhea (n = 52; 40.3%). A large proportion of those reporting suffering indicated substantial suffering severity from specific symptoms (ie, a great deal or a lot) including nausea, 52.3% (57 of 109), loss of appetite, 50.5% (49 of 97), constipation 30.4% (21 of 69), pain 30.2% (29 of 96), anxiety 28.6% (22 of 77), depression 28.1% (18 of 64), and diarrhea 23.1% (12 of 52). Few children and parents expressed opposition to early palliative care involvement (2 [1.6%] and 8 [6.2%]) or perceived any detrimental effects on their relationship with their oncologist (6 [4.7%] and 5 [3.9%]), loss of hope (3 [2.3%] and 10 [7.8%]), or therapy interference (3 [2.3%] and 2 [1.6%], respectively). Intradyad concordance was low overall: 26% to 29% for exact concordance and 40% to 69% for agreement within 1 response category. Significant differences in patient-parent attitudes toward aspects of early palliative care included child participants being more likely than their parents (40.3% [n = 52] vs 17.8% [n = 23]) to indicate that palliative care would have been helpful for treating their symptoms (P < .001).

Conclusions And Relevance: Pediatric oncology patients experience a high degree of symptom-related suffering early in cancer therapy, and very few patients or parents in this study expressed negative attitudes toward early palliative care. Our findings suggest that pediatric oncology patients and families might benefit from, and are not a barrier to, early palliative care integration in oncology.
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http://dx.doi.org/10.1001/jamaoncol.2017.0368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824292PMC
September 2017

Integrating next-generation sequencing into pediatric oncology practice: An assessment of physician confidence and understanding of clinical genomics.

Cancer 2017 Jun 13;123(12):2352-2359. Epub 2017 Feb 13.

Division of Nursing Research, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: The incorporation of genomic testing to identify targetable somatic alterations and predisposing germline mutations into the clinical setting is becoming increasingly more common. Despite its potential usefulness, to the authors' knowledge physician confidence with regard to understanding and applying genomic testing remains unclear, particularly within the realm of pediatric oncology.

Methods: Before initiating an institutional feasibility study regarding the integration of clinical genomic testing, the authors surveyed pediatric oncologists regarding their confidence around understanding of genomic testing, perceived usefulness of test results, preferences around the disclosure of germline test results, and possible risks and benefits of testing.

Results: Among survey respondents (52 of 88 contacted; response rate of 59%), only a minority were confident in interpreting, using, and discussing somatic (35%) or germline (27%) genomic test results. Providers who were confident in interpreting somatic results were significantly more likely to anticipate using the results to plan the treatment of patients with relapsed or refractory cancers (P = .009). Similarly, providers who reported confidence in interpreting germline results were significantly more likely to discuss and use these results as part of clinical care (P<.0001). The majority of physicians (93%), regardless of their level of confidence, wanted to speak to a genetic counselor before disclosing germline test results.

Conclusions: Among physicians at a comprehensive pediatric cancer center, confidence in the interpretation, use, and discussion of oncology-based genomic test results appears to be low, both in terms of somatic and germline testing. To optimize the integration of genomic sequencing into cancer care, methods must be developed to improve basic competencies around cancer-based genomic testing. Given the complexities surrounding variant interpretation and genotype-phenotype relationships, interdisciplinary collaborations are warranted. Cancer 2017;123:2352-2359. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710798PMC
June 2017

Palliative Care Involvement Is Associated with Less Intensive End-of-Life Care in Adolescent and Young Adult Oncology Patients.

J Palliat Med 2017 05 18;20(5):509-516. Epub 2017 Jan 18.

4 Division of Quality of Life and Palliative Care, Department of Oncology, St. Jude Children's Research Hospital , Memphis, Tennessee.

Background: Adolescent and young adult oncology (AYAO) patients often receive intensive medical care and experience significant symptoms at the end of life (EOL).

Objective: This study aimed to describe the characteristics of AYAO patients aged 15-26 years who died as inpatients in a hospital and to compare the illness and EOL experiences of AYAO patients who did and did not receive palliative care (PC).

Design And Setting: A standardized data extraction tool was used to collect information about demographics, treatment, terminal characteristics, and symptoms during the last month of life (LMOL) for 69 AYAO patients who died while hospitalized between 2008 and 2014.

Measurements And Results: AYAO patients who died in the hospital required considerable medical and psychosocial care and experienced numerous symptoms during the LMOL. Compared to those patients who received no formal PC services, patients followed by the PC team were less likely to die in the intensive care unit (ICU) (38% vs. 68%, p = 0.024) and less likely to have been on a ventilator (34% vs. 63%, p = 0.028) during the LMOL. They also received fewer invasive medical procedures during the LMOL (median, 1 vs. 3 procedures, p = 0.009) and had a do not resuscitate order in place for a longer time before death (median, 6 vs. two days, p = 0.008).

Conclusions: Involvement of the PC team was associated with the receipt of less intensive treatments and fewer deaths in the ICU.
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http://dx.doi.org/10.1089/jpm.2016.0451DOI Listing
May 2017