Objective The aim of this report is 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 Minimal Conscious State (EMCS) as the reference standard for conscious awareness and the total CRS-R score as the “test criterion”. A receiver operating curve (ROC) was constructed to demonstrate the optimal CRS-R total cut-off score for maximizing sensitivity and specificity. Setting Specialized DoC program Participants 252 patients enrolled in the DoC program (157 male; mean age = 49 years; mean time from injury =48 days; traumatic etiology=127, non-traumatic etiology=125; diagnosis of coma or VS=72, diagnosis of MCS or EMCS=182) Interventions Not applicable. Main Outcome Measure(s) 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 0.78 for correct identification of patients in MCS or EMCS, and specificity of 1.00 for correct identification of patients who did not meet criteria for either of these diagnoses (i.e., were diagnosed with VS or coma). The area under the curve (AUC) in the ROC analysis is 0.98. Conclusion(s) 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 cut-off score of 8 provides the best balance between sensitivity and specificity, accurately classifying 93% of cases. The “optimal” total score cut-off will vary depending on the user's objective.

Objectives 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 DoC 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 (i.e., frequency of occurrence = 0%) were also considered improbable. Setting Specialized DOC program and University hospital. Participants 1190 patients diagnosed with DoC (coma= 76, VS= 464, MCS= 586, EMCS= 64; 794 males; mean age= 43±20 years; traumatic etiology= 747; time post injury= 162±568 days). Interventions Not applicable. Main Outcome Measure(s) 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.

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.