Yoga as a non-pharmacologic therapy to reduce dinutuximab-induced pain in patients with neuroblastoma.

BACKGROUND: Anti-GD2 antibodies are key components of treatment for high-risk neuroblastoma; however, they cause neuropathic pain. Yoga therapy may help reduce pain and distress associated with anti-GD2 therapy. PROCEDURE: Children 3 years of age or older with neuroblastoma participated in individualized yoga therapy while receiving the anti-GD2 antibody dinutuximab (DIN). Yoga therapy was deemed feasible if patients participated during 60% or more of DIN admissions. Patients and caregivers assessed pain/distress before and after yoga therapy with a distress thermometer (DT) and Wong-Baker FACES pain rating scale and completed questionnaires regarding satisfaction with yoga therapy. Therapy was deemed efficacious if there was a ≥1 point pain score change and reduction in distress after yoga. RESULTS: Eighteen patients were enrolled; 52 encounters (admissions for DIN) were evaluable. Ten of 18 were female, three of 18 were Hispanic, and 10/18 were White. Median age at enrollment was 5.5 years (range: 3-11). Yoga therapy was feasible in 39/52 (75%) encounters. Significant reductions in caregiver-reported pain and distress and reductions in patient-reported pain and distress after yoga therapy were reported. Twelve of 18 caregivers completed questionnaires: seven agreed/strongly agreed that yoga was valuable, and nine agreed/strongly agreed to continued participation in yoga. Thirty-four of 36 clinicians reported that they would recommend yoga therapy for other patients receiving DIN. CONCLUSIONS: Yoga therapy was feasible during DIN therapy and may be effective in reducing DIN-associated pain and distress. Future studies are needed to evaluate changes in opioid usage with the addition of yoga therapy during anti-GD2 antibody therapy.

Progression-Free Survival and Patterns of Response in Patients With Relapsed High-Risk Neuroblastoma Treated With Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor.

PURPOSE: Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy. PATIENTS AND METHODS: Patients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded. Responses were evaluated using the International Neuroblastoma Response Criteria. RESULTS: One hundred forty-six patients were included. Tumors were MYCN-amplified in 50 of 134 (37%). Seventy-one patients (49%) had an objective response to I/T/DIN/GM-CSF (objective response; 29% complete response, 14% partial response [PR], 5% minor response [MR], 21% stable disease [SD], and 30% progressive disease). Of patients with SD or better at first post-I/T/DIN/GM-CSF disease evaluation, 22% had an improved response per International Neuroblastoma Response Criteria on subsequent evaluation (13% of patients with initial SD, 33% with MR, and 41% with PR). Patients received a median of 4.5 (range, 1-31) cycles. The median progression-free survival (PFS) was 13.1 months, and the 1-year PFS and 2-year PFS were 50% and 28%, respectively. The median duration of response was 15.9 months; the median PFS off all anticancer therapy was 10.4 months after discontinuation of I/T/DIN/GM-CSF. CONCLUSION: Approximately half of patients receiving I/T/DIN/GM-CSF for relapsed HRNB had objective responses. Patients with initial SD were unlikely to have an objective response, but > 1 of 3 patients with MR/PR on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended PFS in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed HRNB.

Detection and Interpretation of Impossible and Improbable Coma Recovery Scale-Revised Scores.

OBJECTIVE: To determine the frequency with which specific Coma Recovery Scale-Revised (CRS-R) subscale scores co-occur as a means of providing clinicians and researchers with an empirical method of assessing CRS-R data quality. DESIGN: We retrospectively analyzed CRS-R subscale scores in hospital inpatients diagnosed with disorders of consciousness (DOCs) to identify impossible and improbable subscore combinations as a means of detecting inaccurate and unusual scores. Impossible subscore combinations were based on violations of CRS-R scoring guidelines. To determine improbable subscore combinations, we relied on the Mahalanobis distance, which detects outliers within a distribution of scores. Subscore pairs that were not observed at all in the database (ie, frequency of occurrence=0%) were also considered improbable. SETTING: Specialized DOC program and university hospital. PARTICIPANTS: Patients diagnosed with DOCs (N=1190; coma: n=76, vegetative state: n=464, minimally conscious state: n=586, emerged from minimally conscious state: n=64; 794 men; mean age, 43±20y; traumatic etiology: n=747; time postinjury, 162±568d). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Impossible and improbable CRS-R subscore combinations. RESULTS: Of the 1190 CRS-R profiles analyzed, 4.7% were excluded because they met scoring criteria for impossible co-occurrence. Among the 1137 remaining profiles, 12.2% (41/336) of possible subscore combinations were classified as improbable. CONCLUSIONS: Clinicians and researchers should take steps to ensure the accuracy of CRS-R scores. To minimize the risk of diagnostic error and erroneous research findings, we have identified 9 impossible and 36 improbable CRS-R subscore combinations. The presence of any one of these subscore combinations should trigger additional data quality review.

Sensitivity and Specificity of the Coma Recovery Scale--Revised Total Score in Detection of Conscious Awareness.

OBJECTIVE: To describe the sensitivity and specificity of Coma Recovery Scale-Revised (CRS-R) total scores in detecting conscious awareness. DESIGN: Data were retrospectively extracted from the medical records of patients enrolled in a specialized disorders of consciousness (DOC) program. Sensitivity and specificity analyses were completed using CRS-R-derived diagnoses of minimally conscious state (MCS) or emerged from minimally conscious state (EMCS) as the reference standard for conscious awareness and the total CRS-R score as the test criterion. A receiver operating characteristic curve was constructed to demonstrate the optimal CRS-R total cutoff score for maximizing sensitivity and specificity. SETTING: Specialized DOC program. PARTICIPANTS: Patients enrolled in the DOC program (N=252, 157 men; mean age, 49y; mean time from injury, 48d; traumatic etiology, n=127; nontraumatic etiology, n=125; diagnosis of coma or vegetative state, n=70; diagnosis of MCS or EMCS, n=182). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sensitivity and specificity of CRS-R total scores in detecting conscious awareness. RESULTS: A CRS-R total score of 10 or higher yielded a sensitivity of .78 for correct identification of patients in MCS or EMCS, and a specificity of 1.00 for correct identification of patients who did not meet criteria for either of these diagnoses (ie, were diagnosed with vegetative state or coma). The area under the curve in the receiver operating characteristic curve analysis is .98. CONCLUSIONS: A total CRS-R score of 10 or higher provides strong evidence of conscious awareness but resulted in a false-negative diagnostic error in 22% of patients who demonstrated conscious awareness based on CRS-R diagnostic criteria. A cutoff score of 8 provides the best balance between sensitivity and specificity, accurately classifying 93% of cases. The optimal total score cutoff will vary depending on the user's objective.