Shana Jacobs

Family-Centered Advance Care Planning for Teens With Cancer

IMPORTANCEnAdvance care planning (ACP) prepares patients and their families for future health care decisions; however, the needs of adolescent oncology patients for participation in ACP have not been well studied.nnnOBJECTIVEnTo examine the efficacy of family-centered ACP.nnnDESIGN AND SETTINGnTwo-group randomized controlled trial in a pediatric oncology program.nnnPARTICIPANTSnSixty adolescents aged 14 to 21 years with cancer and their surrogates or families were enrolled in the study between January 17, 2011, and March 29, 2012.nnnINTERVENTIONnThirty dyads received 3- to 60-minute sessions 1 week apart. Intervention dyads completed (1) the Lyon Family-Centered ACP Survey, (2) the Respecting Choices interview, and (3) Five Wishes. Control subjects received standard care plus information.nnnMAIN OUTCOME MEASURESnStatement of treatment preferences and Decisional Conflict Scale score.nnnRESULTSnThe mean age of the adolescents was 16 years; 36 (60%) were male, 30 (50%) white, 26 (43%) black, and 4 (7%) Asian. Diagnoses were as follows: leukemia (14 patients [47%]), brain tumor (8 [27%]), solid tumor (6 [20%]), and lymphoma (2 [7%]). Significantly increased congruence was observed for intervention dyads compared with controls for 4 of the 6 disease-specific scenarios; for example, for situation 2 (treatment would extend my life by not more than 2 to 3 months), intervention dyads demonstrated higher congruence (κ = 0.660; P < .001) vs control dyads (κ = -0.0636; P = .70). Intervention adolescents (100%) wanted their families to do what is best at the time, whereas fewer control adolescents (62%) gave families this leeway. Intervention adolescents were significantly better informed about end-of-life decisions (t = 2.93; effect size, 0.961; 95% CI, 0.742-1.180; P = .007). Intervention families were more likely to concur on limiting treatments than controls. An ethnic difference was found in only one situation.nnnCONCLUSIONSnAdvance care planning enabled families to understand and honor their adolescents wishes. Intervention dyads were more likely than controls to limit treatments. Underserved African American families were willing to participate.

PROMIS Pediatric Measures in Pediatric Oncology: Valid and Clinically Feasible Indicators of Patient-Reported Outcomes

Establishing the ability of children and adolescents with cancer to complete the NIH‐sponsored PROMIS pediatric measures electronically and the preliminary validity estimates of the measures (both full item banks and short forms) in pediatric oncology will contribute to our knowledge of the impact of cancer treatment on these young patients.

A Longitudinal, Randomized, Controlled Trial of Advance Care Planning for Teens With Cancer: Anxiety, Depression, Quality of Life, Advance Directives, Spirituality

PURPOSEnTo test the feasibility, acceptability and safety of a pediatric advance care planning intervention, Family-Centered Advance Care Planning for Teens With Cancer (FACE-TC).nnnMETHODSnAdolescent (age 14-20 years)/family dyads (N = 30) with a cancer diagnosis participated in a two-armed, randomized, controlled trial. Exclusion criteria included severe depression and impaired mental status. Acceptability was measured by the Satisfaction Questionnaire. General Estimating Equations models assessed the impact of FACE-TC on 3-month post-intervention outcomes as measured by the Pediatric Quality of Life Inventory 4.0 Generic Core Scale, the Pediatric Quality of Life Inventory 4.0 Cancer-Specific Module, the Beck Depression and Anxiety Inventories, the Spiritual Well-Being Scale of the Functional Assessment of Chronic Illness Therapy-IV, and advance directive completion.nnnRESULTSnAcceptability was demonstrated with enrollment of 72% of eligible families, 100% attendance at all three sessions, 93% retention at 3-month post-intervention, and 100% data completion. Intervention families rated FACE-TC worthwhile (100%), whereas adolescents ratings increased over time (65%-82%). Adolescents anxiety decreased significantly from baseline to 3 months post-intervention in both groups (β = -5.6; p = .0212). Low depressive symptom scores and high quality of life scores were maintained by adolescents in both groups. Advance directives were located easily in medical records (100% of FACE-TC adolescents vs. no controls). Oncologists received electronic copies. Total Spirituality scores (β = 8.1; p = .0296) were significantly higher among FACE-TC adolescents versus controls. The FACE-TC adolescents endorsed the best time to bring up end-of-life decisions: 19% before being sick, 19% at diagnosis, none when first ill or hospitalized, 25% when dying, and 38% for all of the above.nnnCONCLUSIONSnFamily-Centered Advance Care Planning for Teens With Cancer demonstrated feasibility and acceptability. Courageous adolescents willingly participated in highly structured, in-depth pediatric advance care planning conversations safely.

Plasma and cerebrospinal fluid pharmacokinetics of intravenous oxaliplatin, cisplatin, and carboplatin in nonhuman primates

Purpose: Describe and compare the central nervous system pharmacology of the platinum analogues, cisplatin, carboplatin, and oxaliplatin and develop a pharmacokinetic model to distinguish the disposition of active drug from inert platinum species. Experimental Design: Oxaliplatin (7 or 5 mg/kg), cisplatin (2 mg/kg), or carboplatin (10 mg/kg) was given i.v. Serial plasma and cerebrospinal fluid (CSF) samples were collected over 24 hours. Plasma ultrafiltrates were prepared immediately. Platinum concentrations were measured using atomic absorption spectrometry. Areas under the concentration × time curve were derived using the linear trapezoidal method. CSF penetration was defined as the CSF AUC0-24/plasma ultrafiltrate AUC0-24 ratio. A four-compartment model with first-order rate constants was fit to the data to distinguish active drug from inactive metabolites. Results: The mean ± SD AUCs in plasma ultrafiltrate for oxaliplatin, cisplatin, and carboplatin were 61 ± 22, 18 ± 6, and 211 ± 64 μmol/L hour, respectively. The AUCs in CSF were 1.2 ± 0.4 μmol/L hour for oxaliplatin, 0.56 ± 0.08 μmol/L hour for cisplatin, and 8 ± 2.2 μmol/L hour for carboplatin, and CSF penetration was 2.0%, 3.6%, and 3.8%, respectively. For oxaliplatin, cisplatin, and carboplatin, the pharmacokinetic model estimated that active drug accounted for 29%, 79%, and 81% of platinum in plasma ultrafiltrate, respectively, and 25%, 89%, and 56% of platinum in CSF, respectively. The CSF penetration of active drug was 1.6% for oxaliplatin, 3.7% for cisplatin, and 2.6% for carboplatin. Conclusions: The CSF penetration of the platinum analogues is limited. The pharmacokinetic model distinguished between active drug and their inactive (inert) metabolites in plasma and CSF.

Extracellular fluid concentrations of cisplatin, carboplatin, and oxaliplatin in brain, muscle, and blood measured using microdialysis in nonhuman primates

PurposeCisplatin, carboplatin, and oxaliplatin are chemically reactive anticancer drugs with modest activity in brain tumors. Previously, we have demonstrated that drug exposure in cerebrospinal fluid (CSF) for these platinum analogs is <5% of the plasma ultrafiltrate (UF) drug exposure in nonhuman primates. Microdialysis is a minimally invasive in vivo method for sampling small molecules in the blood and tissue extracellular fluid (ECF). The purpose of this study was to estimate the penetration of platinum analogs into the brain ECF.MethodsWe measured free concentrations of cisplatin, carboplatin, and oxaliplatin in ECF of brain, muscle, and blood of nonhuman primates using microdialysis and compared ECF platinum concentrations in blood and brain to plasma UF and CSF concentrations obtained using conventional sampling methods.ResultsFor all three platinum analogs, AUC0-4h for microdialysis sampling from the vein was similar to standard plasma UF sampling. The median AUC0-4h ratio for vein to plasma UF was 1.1 (range, 0.9–1.4). The platinum analogs had limited distribution (<5%) to the CSF and brain ECF. CSF penetration predicts for the limited penetration of the platinum analogs into brain ECF, but concordance between CSF and brain ECF measurements was poor. CSF oxaliplatin concentrations (AUC0-4h, 0.4–0.9xa0μMxa0h) were substantially lower than brain ECF concentrations (AUC0-4h, 2.0–8.6xa0μMxa0h).ConclusionsThe penetration of platinum analogs into CSF and brain is limited. The differences in the CNS penetrations among the three platinum analogs are not clinically significant. For cisplatin and carboplatin, CSF penetration appears to be a surrogate for brain extracellular free drug exposure.

Adolescent end of life preferences and congruence with their parents' preferences: Results of a survey of adolescents with cancer

Little is known about how well family members accurately represent adolescents when making EOL decisions on their behalf. This study reports on surveys given to adolescents with cancer and their parents as part of a larger study facilitating advanced care discussions, as well as the results of a survey for health care providers.

Phase II Trial of Ixabepilone Administered Daily for Five Days in Children and Young Adults with Refractory Solid Tumors: A Report from the Children's Oncology Group

Purpose: Ixabepilone is a microtubule-stabilizing agent with activity in adult solid tumors and in pediatric tumor xenograft models that are resistant to paclitaxel. The maximum tolerated dose on the daily-for-5-days i.v. schedule was 6 mg/m2/dose in adults and 8 mg/m2/dose in children, and the primary dose-limiting toxicity (DLT) was neutropenia. This study aimed to determine the response rate to ixabepilone in six solid tumor strata in children and young adults. Experimental Design: We conducted a phase II trial of ixabepilone (8 mg/m2/dose for 5 days every 21 days) using a two-stage design in taxane-naïve children and young adults with treatment-refractory, measurable rhabdomyosarcoma, Ewing sarcoma family tumors, osteosarcoma, synovial sarcoma, or malignant peripheral nerve sheath tumor, neuroblastoma, and Wilms tumor. Results: Sixty-one eligible patients (36 male) were enrolled. Median (range) age was 13 years (range, 3-36). Fifty-nine patients were fully evaluable for toxicity and response. DLTs, most commonly myelosuppression, occurred in 11 patients (15% incidence in 3-18 years old and 33% in 19-36 years old; P = 0.2) during cycle 1. The median (range) number of cycles was 2 (range, 1-38). No partial or complete responses (response evaluation criteria in solid tumors) were observed. Seven patients received ≥3 cycles, and two had prolonged stable disease (Wilms tumor, 38 cycles; synovial sarcoma, 8 cycles). Conclusions: Ixabepilone at 8 mg/m2/dose daily for 5 days was tolerable in children and adolescents, but did not show evidence of clinical activity in the childhood solid tumors studied. Clin Cancer Res; 16(2); 750–4

Patterns of symptoms and functional impairments in children with cancer

Children with cancer experience multiple symptoms due to their disease and as a result of treatment. The purpose of this study was to demonstrate the feasibility and potential utility of using latent profile analysis (LPA), a type of cluster analysis, in children with cancer to identify groups of patients who experience similar levels of symptom severity and impairment of physical function.

Feasibility and acceptability of the patient-reported outcomes measurement information system measures in children and adolescents in active cancer treatment and survivorship

Background: Patient-reported outcomes related to symptoms, function, and quality of life during and following cancer treatment can guide care for pediatric cancer patients. To advance the science of patient-reported outcomes, the National Institutes of Health funded the Patient-Reported Outcomes Measurement Information System (PROMIS). Objective: The objective of this study was to assess feasibility and acceptability of the PROMIS pediatric measures, as defined by enrollment and attrition rates as well as missingness by measure, item, participant, and assessment time point. Methods: Eight- to18-year-olds participated in 2 studies: PROMIS I, a cross-sectional study of children in active cancer treatment or survivorship, and PROMIS II, a longitudinal study with 3 assessment time points for children receiving curative treatment. Results: PROMIS I (n = 200) and PROMIS II (n = 94) had enrollment rates of 92.5% and 89.7%, respectively. For PROMIS I, measure missingness was acceptable (8% missed any measures) and was not related to other study variables. For PROMIS II, measure missingness was minimal (0.8%), and item-level missingness was relatively low. In general, items that were skipped asked about experiences that participants had not encountered in the past 7 days. Conclusions: In both studies, the PROMIS instruments demonstrated good feasibility and acceptability among pediatric cancer patients. Overall, we had high enrollment, low attrition, and acceptable rates of measure and item missingness. Implications for Practice: Our results demonstrate that PROMIS measures are acceptable to 8- to 18-year-olds in different points of cancer care and feasible for use in pediatric cancer inpatient and outpatient settings.

Substitution of oral and intravenous thioguanine for mercaptopurine in a treatment regimen for children with standard risk acute lymphoblastic leukemia: A collaborative Children's Oncology Group/National Cancer Institute pilot trial (CCG‐1942)

Although mercaptopurine (MP) is conventionally used to treat childhood acute lymphoblastic leukemia (ALL), thioguanine (TG) is a more potent thiopurine in vitro and, when administered orally to patients, achieves cytotoxic drug concentrations in the cerebrospinal fluid (CSF). We performed a pilot study incorporating oral and 24‐hr continuous IV infusion (CIVI) TG in children with newly diagnosed standard‐risk ALL.