Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in Non-Small Cell Lung Cancer.

INTRODUCTION: Intracranial metastases are a common cause of morbidity and mortality in patients with advanced NSCLC, and are frequently managed with radiation therapy (RT). The safety of cranial RT in the setting of treatment with immune checkpoint inhibitors (ICIs) has not been established. METHODS: We identified patients with advanced NSCLC with brain metastases who received cranial RT and were treated with or without programmed cell death 1/programmed death ligand 1 inhibitors between August 2013 and September 2016. RT-related adverse events (AEs) were retrospectively evaluated and analyzed according to ICI treatment status, cranial RT type, and timing of RT with respect to ICI. RESULTS: Of 163 patients, 50 (31%) received ICIs, whereas 113 (69%) were ICI naive. Overall, 94 (58%), 28 (17%), and 101 (62%) patients received stereotactic radiosurgery, partial brain irradiation, and/or whole brain RT, respectively. Fifty percent of patients received more than one radiation course. We observed no significant difference in rates of all-grade AEs and grade 3 or higher AEs between the ICI-naive and ICI-treated patients across different cranial RT types (grade ≥3 AEs in 8% of ICI-naive patients versus in 9% of ICI-treated patients for stereotactic radiosurgery [p = 1.00] and in 8% of ICI-naive patients versus in 10% of ICI-treated patients for whole brain RT [p = 0.71]). Additionally, there was no difference in AE rates on the basis of timing of ICI administration with respect to RT. CONCLUSIONS: Treatment with an ICI and cranial RT was not associated with a significant increase in RT-related AEs, suggesting that use of programmed cell death 1/programmed death ligand 1 inhibitors in patients receiving cranial RT may have an acceptable safety profile. Nonetheless, additional studies are needed to validate this approach.

Rewards of parenting children and adolescents with spinal cord injuries.

STUDY DESIGN: Mixed-method study. OBJECTIVES: Describe caregiver perspectives on the rewards of parenting youth with spinal cord injury (SCI) and explore the relationships between rewards and child/caregiver demographic characteristics and child psychosocial outcomes. SETTING: Data collection occurred at three pediatric specialty hospitals within a single hospital system in the United States. METHODS: Self-identified primary caregivers (n=178) of children aged 1-18 years answered the question: 'What has been most rewarding in parenting a child with SCI'? and completed a questionnaire about their child's health-related quality of life (HRQOL). Participants aged 7-18 years (n=134) also completed tools assessing their community participation, anxiety, depression and HRQOL. RESULTS: Four reward themes emerged: Enhanced Resilience (for example, resilience in my child, self and family), Caregiver-Child Relationship, Connecting with Others, and Learning. Caregivers of children with lower self-reported school and overall psychosocial HRQOL were more likely to report Enhanced Resilience in their child. Caregivers whose children had fewer depressive symptoms, lower levels of participation and who were older at injury and interview felt rewarded by an enhanced Caregiver-Child Relationship. Caregivers of children with a broader context of participation and higher school and psychosocial HRQOL reported Connecting with Others. Finally, unemployed caregivers and those with less education were more likely to report Learning. CONCLUSIONS: Caregivers reported a variety of rewards from parenting their children with SCI, and several relationships emerged between rewards and demographics and child psychosocial outcomes. Future research should further examine the positive experiences of caregivers and whether focusing on strengths might yield better long-term outcomes for children with SCI.

The spinal cord independence measure (SCIM)-III self report for youth.

STUDY DESIGN: The items and response scales of the Spinal Cord Independence Measure (SCIM-III) self report (SR) were exposed to formal cognitive testing with children with SCI, and in parallel a survey using the modified Delphi Technique was conducted to engage content experts in an iterative critical review of the SCIM-III SR. OBJECTIVES: To evaluate the validity of the SCIM-III SR for pediatric utilization. SETTING: United States of America. METHODS: Formal cognitive testing was conducted with 17 youths with SCI and required them to read and answer each SCIM-III SR item aloud. Think aloud methodology was used to record details about how youths understood and interpreted items and why they selected a given response. The interviews were audiotaped and transcribed verbatim. Content analysis focused on identifying words that children could not read or understand. In parallel, the Modified Delphi Technique engaged expert therapists to critically review the SCIM-III SR for pediatric utilization. RESULTS: Every SCIM-III SR item and response scale required modification before children were able to read, understand and respond to them. Youth encountered difficulties because of vague terms, medical jargon and complex words and phrases. Three iterative Delphi rounds were required before achieving 80% agreement that items and response scales were written well for children. CONCLUSION: Our findings informed modifications to every SCIM-III SR item and response scale, producing a pediatric version of the tool that we formally refer to as the SCIM-III SR-Youth (SCIM-III SR-Y). SPONSORSHIP: The study was funded by the Craig H Neilsen Foundation, Spinal Cord Injury Research on the Translation Spectrum, Senior Research Award #282592 (Mulcahey, PI).

Examination and measurement of coping among adolescents with spinal cord injury.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To describe coping strategy use in adolescents with spinal cord injury (SCI), to explore the underlying factor structure of a measure of coping among adolescents with SCI and to assess relationships between coping and psychosocial outcomes. SETTING: Multiple pediatric SCI centers in the United States. METHODS: One hundred and eighty-two participants aged 13-17 years who experienced an SCI completed measures including the Kidcope, Children's Depression Inventory, Revised Children's Manifest Anxiety Scale and the Pediatric Quality of Life Inventory. RESULTS: Participants reported that cognitive restructuring and resignation are the most used coping strategies, whereas social support, emotional regulation (calming) and cognitive restructuring are the most effective coping strategies. An exploratory factor analysis revealed that a three-factor solution provided the most parsimonious model for the relationships between the different coping strategies. However, only one of the three factors had acceptable internal consistency. This factor comprised escape-oriented coping strategies or an avoidant approach to coping with the sequelae of SCI. After controlling for demographic/injury-related factors, higher scores on the escape-oriented factor were associated with the lower quality of life and higher levels of depression and anxiety symptomatology. CONCLUSION: Escape-oriented coping is associated with maladaptive psychosocial outcomes in adolescents with SCI. These adolescents report that active coping strategies are most effective in reducing SCI-related distress. Coping strategy use may mediate psychosocial outcomes in adolescents with SCI and represent an intervention target in adolescents who overly rely on escape-oriented coping.

Relationships between the psychological characteristics of youth with spinal cord injury and their primary caregivers.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To describe anxiety and depression among caregivers of youth with spinal cord injury (SCI), examine predictors of caregiver psychological functioning and evaluate relationships between caregiver and child psychological outcomes. The protective factor of youth social relationships was also included to examine its impact on relationships between caregiver and child psychological functioning. SETTING: Families received services at one of three pediatric specialty hospitals within a single hospital system in the United States. METHODS: The study included English-speaking youth with SCI, aged between 7 and 17 years, who had been injured at least one year before, and their self-identified primary caregivers. Participants completed surveys assessing their anxiety, depression and youth's perceived social relationships. RESULTS: The study included 203 youth with an average age of 12.70 years (s.d.=3.15), and among them 70% had paraplegia. Seventy-eight percent of caregivers were mothers, 14% fathers and 8% other family members. In all, 16 and 21% of caregivers scored in the range of moderate/severe anxiety and depression, respectively. Being female and having a child with mental health problems predicted caregiver anxiety and depression. In addition, having a child who was older at the time of injury predicted caregiver depression. Poor social relationships, having a caregiver with mental health problems and having a caregiver with less education predicted both child anxiety and depression. CONCLUSION: Caregiver sex, child age at injury and child mental health were related to caregiver outcomes; caregiver education, marital status and child age were not. Caregiver mental health and education and child social relationships predicted child outcomes. Neither injury level nor injury severity was related to caregiver or child outcomes.

Rehabilitation and future participation of youth following spinal cord injury: caregiver perspectives.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To examine caregivers' perspectives on the effectiveness of rehabilitative support experienced by youth with spinal cord injury (SCI) during acute rehabilitation and after community reintegration in terms of their community participation. SETTING: Data collection took place at the three Shriners SCI hospitals: Chicago, Philadelphia, and Northern California. METHODS: A total of 132 primary caregivers of youth with SCI completed a survey on what their child had experienced during and after rehabilitation to enhance their community participation. RESULTS: Caregivers found technical support from staff (41%), motivation and encouragement from staff (25%), and education (17%) to be the most important factors during rehabilitation for encouraging their child's future participation in school or community activities. Caregivers found involvement in activities (30%), personal resilience (22%) and interactions with others with disabilities (13%) to be important experiences since rehabilitation in terms of their child's participation in school and community activities. Caregivers who responded that something they experienced during rehabilitation was helpful to participation had children who had been injured longer and who were older at time of injury. In addition, caregivers who reported that something they have experienced since their child's rehabilitation has been helpful in terms of participation also had children who were older at time of injury. CONCLUSIONS: Findings from this study can be used to help professionals tailor rehabilitation programs to better meet the needs of youth with SCI and their families, thereby increasing chances of successful reintegration back into their communities.