Clinical trial of proton craniospinal irradiation for leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. METHODS: We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). RESULTS: We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment-related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5-13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months. CONCLUSION: Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients.

Effective methods to improve recruitment and retention in school-based substance use prevention studies.

BACKGROUND: Poor recruitment and high attrition may invalidate results of research studies. This paper describes successful recruitment and retention strategies in a school-based substance use prevention trial and explores factors associated with intervention attendance and retention. METHODS: A total of 384 parent-child dyads from 15 schools in the New York Metropolitan area participated in a control trial, testing the efficacy of parent-training to prevent youth substance use. Assessments were completed immediately post-intervention and 6-, 12-, and 24-month postintervention. Logistic regression analyses were used to determine which familial and study characteristics predicted attendance in the intervention and retention by parents and youth. RESULTS: 84% of intervention parents attended 4 of the 5 workshops; 83% of control parents attended their single workshop. Intervention attendance was predicted by parent job status, but this was not significant after controlling for other family factors. Retention rates ranged from 87% to 91% over the 2 years. No family characteristics predicted retention, but time since baseline and attendance at treatment workshops and the control workshop did. For children, age at baseline and ethnicity predicted retention, but this did not remain significant in the adjusted model. CONCLUSION: Intervention attendance was high and retention rates far exceeded the minimum standard of 70% retention in behavioral studies. Recruitment and retention strategies were effective for different family constellations. Efforts to maximize participation in both treatment and control interventions are critical to retention in longitudinal trials.