Pediatric Blood & Cancer最新文献

Background: Cisplatin is used to treat solid tumors but causes irreversible hearing loss. Pedmark, a formulation of sodium thiosulfate (STS), is approved to prevent cisplatin-induced hearing loss (CIHL). Prior to approval, non-Pedmark formulations of STS pentahydrate (STS-P) were prescribed off-label for otoprotection and continue to be used in the absence of data.

Procedure: This multicenter retrospective study examined tolerability, toxicity, and hearing outcomes of STS-P used off-label for otoprotection. Exploratory analyses compared toxicity and hearing data in patients receiving STS-P versus the pre-Pedmark investigational formulation (STS-inv) tested in trials.

Results: Fifty-nine patients received STS-P (16 or 20 g/m²). Infusion-related reactions (IRR) occurred in 14% (8/59), more commonly in patients receiving 20 g/m². No severe adverse events occurred. One patient (2%) discontinued STS-P for IRR. The prevalence of CIHL (International Society of Paediatric Oncology [SIOP] Grade ≥2) at the end of therapy and at the most recent hearing assessment was 30% at both timepoints (12/40 and 8/27, respectively). In exploratory analyses comparing STS-P with STS-inv (n = 14), there was no difference in tolerance or toxicity. In multivariable analysis, a lower risk for CIHL at the end of therapy was found for age ≥5 years, higher dosing of 20 g/m², and received STS-inv (odds ratio 0.02, 95% confidence interval: 0.0003-0.691, p < 0.01). No difference was present at the most recent exam.

Conclusions: STS-P off-label for otoprotection following cisplatin was tolerable in a real-world setting across age groups and cancer types. Formal testing in larger studies of different STS formulations is needed to explore possible differences in toxicity and CIHL prevention.

Background: Rehabilitation (i.e., physical, occupational, speech therapy) aims to optimize function and quality of life (QOL) but is not consistently integrated into oncology care. This study aimed to develop a rehabilitation information sheet informed by the rehabilitation experiences of children diagnosed with cancer before age 19 and their parents/caregivers.

Procedure: This mixed methods, primarily qualitative study was conducted at two US children's hospitals. Eligible participants included childhood cancer survivors (CCS) aged 12-25 years who were referred to one or more rehabilitation therapies following diagnosis. Parents/Caregivers were eligible if their child was diagnosed with cancer before age 19 and referred to rehabilitation. Participants completed a semi-structured interview in English. Qualitative findings guided the development of a rehabilitation information sheet. CCS and caregiver participants and oncology and rehabilitation clinicians at the study sites provided feedback on the information sheet through an electronic survey.

Results: Thirteen CCS, 33 parents/caregivers, and 36 clinicians participated. Participants described how engaging in rehabilitation promoted normalcy following a new pediatric cancer diagnosis and supported self-confidence and mental health. Participants wanted information about rehabilitation soon after the child's diagnosis and emphasized that they prioritized rehabilitation during cancer care. Common barriers to rehabilitation included treatment side effects, insurance, and outpatient scheduling, whereas clear communication and working with consistent providers supported engagement. Almost all individuals (99%) reported the information sheet was easy to understand and the amount of information was just right (86%).

Conclusions: Rehabilitation is highly valued by CCS and parents/caregivers, necessitating its integration into pediatric cancer care.

Background: Diffuse intrinsic pontine glioma (DIPG) carries a poor prognosis with a median survival of less than 12 months. Key molecular features include histone H3 mutation (K27M) and AKT pathway dysregulation. There is currently no curative treatment.

Methods: This is a Phase I study of vorinostat and temsirolimus in newly diagnosed (Stratum 1) and progressive (Stratum 2) DIPG (NCT02420613). The primary aims are to determine the safety, maximum tolerated dose (MTD), and toxicities. A modified 3 + 3 design was used to establish the MTD, where the first three patients were assigned the first dose level regardless of stratum. Stratum 1 received radiotherapy with vorinostat, followed by up to 10 cycles of vorinostat and temsirolimus. Stratum 2 received up to 12 cycles of vorinostat and temsirolimus. Vorinostat was administered at a fixed dose of 230 mg/m² daily on Days 1-8, and temsirolimus was administered on Days 1 and 8 at 25 mg/m² (Dose level 1) or 35 mg/m² (Dose level 2).

Results: Six patients were enrolled, three in each stratum. No dose-limiting toxicity was observed, and most adverse effects were limited to Grades 1 or 2, including fatigue, myelosuppression, hyperlipidemia, hyperglycemia, elevated creatinine, nausea, vomiting, and headache. One patient experienced Grade 3 leukopenia. In the study, the MTD with acceptable toxicity was vorinostat 230 mg/m² and temsirolimus 35 mg/m².

Conclusions: Overall, the combination of temsirolimus and vorinostat is well-tolerated and safe, prompting the need for larger studies to investigate its efficacy.

Introduction: Survivors of childhood cancer exhibit variable humoral immunity to vaccine-preventable diseases (VPDs) following cancer treatment. An increasing number of children are surviving a cancer diagnosis, making it imperative to document the extent to which survivors are at risk for VPDs and their response to vaccinations.

Methods: This Phase II prospective study included 65 pediatric patients diagnosed with cancer and treated with intensive chemotherapy without transplantation. Serum vaccine antibody concentrations were determined for 12 VPDs: tetanus, diphtheria, pertussis, polio, Haemophilus influenzae, pneumococcus, hepatitis B, meningococcus A, measles, mumps, rubella, and varicella following completion of cancer treatment and after vaccination.

Results: Many patients lacked protective antibody levels to VPDs at the end of treatment. After vaccination, 87%-100% of patients had protective antibody titers against inactivated vaccines. The percentage of patients protected against the live attenuated vaccines was lower: measles (79%), mumps (83%), rubella (85%), and varicella (82%). Differences in response rates to vaccinations were not statistically significant for age (<7 vs. ≥7 years of age), diagnosis (hematologic disease vs. solid tumor), the time between the end of treatment and vaccination (3-6 vs. >6 months for inactivated vaccines), or between absolute lymphocyte count or CD4⁺ T-cell count at baseline.

Conclusion: For pediatric cancer survivors, a single dose of inactivated vaccines given 3 months following the end of treatment protects against these VPDs without the need for assessment of serostatus after inoculation. For live attenuated vaccines, patients require two inoculations for protection, and we recommend an assessment of serostatus to inform patients and providers of their risk for acquiring one of these communicable VPDs.

Purpose: Treatment decision-making in adolescents and young adults (AYAs) requires preference consideration and tradeoffs. Using MyPref, an adaptive conjoint analysis tool, we examined and compared the decision-making and treatment preferences of both AYAs and their parent or other trusted person (PTP).

Patients and methods: AYAs aged 15-30 with advanced cancer independently completed MyPref, including demographic questions, the Control Preference Scale, and the adaptive conjoint analysis survey. AYAs could invite a PTP to participate. Participants received a personalized MyPref Summary Report quantifying their preference for nine treatment attributes. Preference scores were summarized and compared by participant group, AYA age, sex, cancer diagnosis, and distance from the hospital.

Results: We enrolled 50 AYAs, 15 of whom selected a PTP to participate. Most AYAs identified as male (64%), White, non-Hispanic (84%), and had solid tumors (48%). The majority (80%) of PTPs identified as the AYA's mother. AYAs favored participant-led decision-making, while PTPs preferred a shared approach. Treatment attributes with the highest preference scores included time until cancer grows, quality of life, and side effects. Compared to PTPs, AYAs had lower preference scores for quality of life. Older AYAs ( $\ge 24$  years) placed more emphasis on the time until cancer grows, whereas younger AYAs prioritized clinic visit frequency.

Conclusion: AYAs with advanced cancer exhibit diverse preferences for decision-making roles and treatment factors. Despite differences, participants valued longer time until cancer progression and quality of life. Future research should explore how preferences of AYAs and their PTPs change over time and optimal strategies for initiating preference discussions earlier in the illness course.

Bone and soft tissue pediatric sarcomas metastasize to the lungs, and computed tomography (CT) represents the diagnostic gold standard. We aimed to investigate the diagnostic accuracy of turbo inversion recovery magnitude (TIRM), inverted TIRM (inverted turbo inversion recovery magnitude [iTIRM]), and T1-weighted (T1w) controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) DIXON with water contrast for the diagnosis of lung metastases in children who underwent 18F-fluorydexoxyglucose-positron emission tomography/magnetic resonance ([18F]-FDG-PET/MR) for staging. TIRM showed the highest sensitivity (84.62%), whereas iTIRM and T1w had higher specificity (89.13% and 100%, respectively). Magnetic resonance imaging provides a good diagnostic performance for pulmonary metastases in children with sarcomas using both fluid sensitive and T1w sequences.