Feasibility pilot trial of a tailored medication adherence-promotion intervention for adolescents and young adults with cancer: Study design and protocol.

BACKGROUND: Medication non-adherence is common among adolescents and young adults (AYAs) with cancer and associated with poor health outcomes. AYAs with cancer endorse multiple barriers to adherence that differ across individuals, suggesting that tailoring intervention content to an AYA's specific barriers may have the potential to improve adherence. The purpose of this manuscript is to report on ORBIT-guided Phase I design efforts to create the first tailored adherence-promotion intervention for AYAs with cancer and the study protocol for the ongoing Phase II pilot feasibility trial. METHODS: Phase I design included qualitative interviews (n = 15 AYAs) to understand patient preferences for adherence-promotion care, development and refinement of a best-worst scaling exercise barriers tool (n = 5 AYAs), and development of intervention modules and a tailoring algorithm. In the ongoing Phase II pilot feasibility trial, AYAs (ages 15-24 years) with cancer currently taking oral chemotherapy or prophylactic medication will be recruited from three children's hospitals. Feasibility, acceptability, and usability will be assessed and these outcomes along with data on medication adherence will be used to inform the next phases of intervention development and testing. CONCLUSIONS: If promising, this program of research ultimately has the potential to equip clinicians with additional strategies for supporting adherence among AYAs with cancer. NCT05706610.

MRD at the end of induction and EFS in T-cell lymphoblastic lymphoma: Children's Oncology Group trial AALL1231.

ABSTRACT: Defining prognostic variables in T-lymphoblastic lymphoma (T-LL) remains a challenge. AALL1231 was a Children's Oncology Group phase 3 clinical trial for newly diagnosed patients with T acute lymphoblastic leukemia or T-LL, randomizing children and young adults to a modified augmented Berlin-Frankfurt-Münster backbone to receive standard therapy (arm A) or with addition of bortezomib (arm B). Optional bone marrow samples to assess minimal residual disease (MRD) at the end of induction (EOI) were collected in T-LL analyzed to assess the correlation of MRD at the EOI to event-free survival (EFS). Eighty-six (41%) of the 209 patients with T-LL accrued to this trial submitted samples for MRD assessment. Patients with MRD <0.1% (n = 75) at EOI had a superior 4-year EFS vs those with MRD ≥0.1% (n = 11) (89.0% ± 4.4% vs 63.6% ± 17.2%; P = .025). Overall survival did not significantly differ between the 2 groups. Cox regression for EFS using arm A as a reference demonstrated that MRD EOI ≥0.1% was associated with a greater risk of inferior outcome (hazard ratio, 3.73; 95% confidence interval, 1.12-12.40; P = .032), which was independent of treatment arm assignment. Consideration to incorporate MRD at EOI into future trials will help establish its value in defining risk groups. CT# NCT02112916.

Checking IN: Development, Acceptability, and Feasibility of a Pediatric Electronic Distress Screener.

Objective: Chronic illness in children and adolescents is associated with significant stress and risk of psychosocial problems. In busy pediatric clinics, limited time and resources are significant barriers to providing mental health assessment for every child. A brief, real-time self-report measure of psychosocial problems is needed. Methods: An electronic distress screening tool, Checking IN, for ages 8-21 was developed in 3 phases. Phase I used semi-structured cognitive interviews (N = 47) to test the wording of items assessing emotional, physical, social, practical, and spiritual concerns of pediatric patients. Findings informed the development of the final measure and an electronic platform (Phase II). Phase III used semi-structured interviews (N = 134) to assess child, caregiver and researcher perception of the feasibility, acceptability, and barriers of administering Checking IN in the outpatient setting at 4 sites. Results: Most patients and caregivers rated Checking IN as "easy" or "very easy" to complete, "feasible" or "somewhat feasible," and the time to complete the measure as acceptable. Most providers (n = 68) reported Checking IN elicited clinically useful and novel information. Fifty-four percent changed care for their patient based on the results. Conclusions: Checking IN is a versatile and brief distress screener that is acceptable to youth with chronic illness and feasible to administer. The summary report provides immediate clinically meaningful data. Electronic tools like Checking IN can capture a child's current psychosocial wellbeing in a standardized, consistent, and useful way, while allowing for the automation of triaging referrals and psychosocial documentation during outpatient visits.

Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma.

PURPOSE: To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS: Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS: AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS (P = .412) and OS (P = .600). CONCLUSION: Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.

Psychosocial Interventions and Therapeutic Support as a Standard of Care in Pediatric Oncology.

Research indicates that a subset of youths with childhood cancer and their parents will experience significant psychological distress throughout the course of their illness. Importantly, the existing literature indicates that psychosocial support is beneficial in decreasing symptoms of distress in these families. The aim of the current review is to determine the extent of the evidence to support a standard of psychosocial care for children and their families throughout the cancer trajectory; thus, we examined the research related to psychosocial outcomes in youth with cancer and their parents.

Factors affecting recruitment and participation of bereaved parents and siblings in grief research.

This study examined participation factors in a study of families (N = 84) within 1 year of a child's cancer-related death. Specific aims were to examine associations between: (a) recruitment variables (number of phone calls made to eligible families, number of calls answered by eligible families) and participation rates (study agreement and refusal) and (b) characteristics of deceased children (gender, age, length of illness, time since death) and participation rates. Characteristics of deceased children did not differ between participating and non-participating families. Researchers made significantly fewer calls to participating versus refusing families. Participating families most often agreed during the first successful call connection, and more calls did not mean more recruitment success. Thus, it is reasonable to limit the number of calls made to bereaved families. Despite recruitment challenges, many bereaved parents and siblings are willing and interested to participate in grief research.

Bereaved parents and siblings offer advice to health care providers and researchers.

OBJECTIVE: To determine how to improve care for families by obtaining their advice to health care providers and researchers after a child's death from cancer. DESIGN: Families with a surviving sibling (age, 8 to 17 y) were recruited from cancer registries at 3 hospitals in the United States and Canada 3 to 12 months (M=10.4, SD=3.5) after the child's death. SETTING: Data were collected in the home. PARTICIPANTS: Participants (N=99) included 36 mothers, 24 fathers, and 39 siblings from 40 families. OUTCOME MEASURES: Each participant completed a qualitative interview that was audio recorded, transcribed, and coded for thematic content. FINDINGS: Five major themes included the need for: (a) improved communication with the medical team, (b) more compassionate care, (c) increased access to resources, (d) ongoing research, and (e) offering praise. Interwoven within the 5 themes was a subtheme of continuity of care. CONCLUSIONS: Many participants were pleased with the care the child with cancer received, but others noted areas in need of improvement, particularly medical communication and continuity of care. Additional research is needed to inform interventions to improve services for families of children with life-limiting conditions.