Optimization of Metabolic Tumor Volume as a Prognostic Marker in CAR T-Cell Therapy for Aggressive Large B-cell NHL.

BACKGROUND: CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become a standard of care in relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphomas (B-NHL) though the majority of recipients do not receive durable disease benefit, prompting the need to better define risk factors for relapse/progression. OBJECTIVES: We performed a single-center, retrospective analysis of patients treated with commercial CAR T-cell therapy to evaluate the impact of tumor burden, as measured by whole-body metabolic tumor volume (MTV) from 18F fluorodeoxyglucose PET imaging, on treatment outcomes. STUDY DESIGN: Sixty-one patients treated with CAR T-cell therapy for R/R B-NHL between May 2016 and November 2021 were included. RESULTS: Using a receiver operating characteristic curve-based MTV optimization cutoff of 450 mL, 1-year progression-free survival (PFS) was 22% for high MTV versus 54% for low MTV (P < .01), and 1-year overall survival (OS) was 37% and 73%, respectively (P = .01). In a subset of 46 patients, residual MTV of less than 106 mL at the day 30 (D30) disease assessment was associated with significantly improved outcomes (1-year OS 85% vs. 13%, P < .01). Incorporation of pretreatment MTV to the International Prognostic Index (IPI) scoring system significantly distinguished 2-year PFS and OS outcomes by 3 risk groups. CONCLUSIONS: Our findings suggest that both pretreatment and D30 MTV are predictive of outcomes among R/R B-NHL patients treated with CAR T-cell therapy. These data indicate that efforts to reduce pretreatment tumor burden may improve longitudinal clinical outcomes. Furthermore, D30 postinfusion MTV quantification may aid clinicians in optimally identifying patients at high-risk for progression, and in whom closer disease monitoring should be considered. MTV also adds prognostic value to patients with high-risk IPI and holds promise for incorporation in novel risk scoring systems which can identify patients prior to CAR T-cell therapy at highest risk of adverse outcomes.

Predicting Response to Chemotherapy in Patients With Newly Diagnosed High-Risk Neuroblastoma: A Report From the International Neuroblastoma Risk Group.

PURPOSE: Metaiodobenzylguanidine (MIBG) scans are a radionucleotide imaging modality that undergo Curie scoring to semiquantitatively assess neuroblastoma burden, which can be used as a marker of therapy response. We hypothesized that a convolutional neural network (CNN) could be developed that uses diagnostic MIBG scans to predict response to induction chemotherapy. METHODS: We analyzed MIBG scans housed in the International Neuroblastoma Risk Group Data Commons from patients enrolled in the Children's Oncology Group high-risk neuroblastoma study ANBL12P1. The primary outcome was response to upfront chemotherapy, defined as a Curie score ≤ 2 after four cycles of induction chemotherapy. We derived and validated a CNN using two-dimensional whole-body MIBG scans from diagnosis and evaluated model performance using area under the receiver operating characteristic curve (AUC). We also developed a clinical classification model to predict response on the basis of age, stage, and MYCN amplification. RESULTS: Among 103 patients with high-risk neuroblastoma included in the final cohort, 67 (65%) were responders. Performance in predicting response to upfront chemotherapy was equivalent using the CNN and the clinical model. Class-activation heatmaps verified that the CNN used areas of disease within the MIBG scans to make predictions. Furthermore, integrating predictions using a geometric mean approach improved detection of responders to upfront chemotherapy (geometric mean AUC 0.73 v CNN AUC 0.63, P < .05; v clinical model AUC 0.65, P < .05). CONCLUSION: We demonstrate feasibility in using machine learning of diagnostic MIBG scans to predict response to induction chemotherapy for patients with high-risk neuroblastoma. We highlight improvements when clinical risk factors are also integrated, laying the foundation for using a multimodal approach to guiding treatment decisions for patients with high-risk neuroblastoma.

Implementation of a hybrid angiography-CT system: increased short-term revenue at an academic radiology department.

PURPOSE: To analyze the financial impact following implementation of a hybrid Angio-CT system at a tertiary care academic medical center. METHODS: Aggregate case types and volumes were compared 24 months before and 12 months after a hybrid Angio-CT system replaced a traditional interventional C-arm angiography suite at an academic medical center. Procedure revenues from this 36-month study period were derived from five payors mixes (Medicare, Medicaid, commercial insurance, out-of-pocket and managed care program) and Medicare-rate adjusted to each individual payor types. RESULTS: Average case volume per month increased 12% in the hybrid Angio-CT suite when compared to the previous traditional angiography suite (P < 0.05). The variety of IR procedures in the hybrid Angio-CT suite also expanded to include more complex interventional radiology and interventional oncology procedures; the breadth of cases performed in the hybrid Angio-CT suite were associated with CPT codes of higher rates (average CPT value/case increased from $2,334.61 to $2,567.25). The estimated average annual revenue of the hybrid Angio-CT suite increased 23% as compared to previous traditional angiography suite. CONCLUSION: A hybrid Angio-CT system is a financially feasible endeavor at a tertiary care academic medical center that facilitated higher complexity procedure codes and increased procedure-related revenue.

Improved Utilization Following Conversion of a Fluoroscopy Suite to Hybrid CT/Angiography System.

PURPOSE: To assess changes in operational utilization following conversion of a single IR suite to a hybrid CT/angiography (Angio-CT) system at an academic tertiary care center. MATERIALS AND METHODS: The total number of interventional procedures and diagnostic CT examinations performed in 29 rooms (20 diagnostic radiology, 7 IR, 2 shared between divisions) was calculated in the 24 months before conversion of an IR suite to Angio-CT and 12 months after conversion. The total number of IR procedures (global IR/month) and diagnostic CT scans per month (global CT/month) in both before and after conversion periods was calculated and defined as baseline institutional growth. This was compared against the change in the number of IR procedures performed in the before and after periods in the converted room (Angio-CT/month) as well as the number of diagnostic CT scans performed in the shared rooms (shared CT/month). RESULTS: The percent change in global CT and global IR from the before to the after periods was 39.2% and 3.1%, respectively. Shared CT per month and Angio-CT per month increased by 46.7% and 12.0% across the same time periods, respectively. The ratio of the percent increase in Angio-CT per month to percent increase in global IR per month was 3.87. The ratio of the percent increase in shared CT per month to percent increase in global CT per month was 1.19. CONCLUSIONS: Operational utilization improved in both diagnostic radiology and IR sections following conversion of a conventional fluoroscopic IR suite to an Angio-CT room.

Interventional Techniques for the Ablation and Augmentation of Extraspinal Lytic Bone Metastases.

In addition to being a major source of cancer-related pain, metastatic osseous lesions are frequently at risk for pathologic fracture and its accompanying morbidity. While bony metastases are commonly thought of as occurring within the vertebral column, over 80% are found outside the spine. Percutaneous interventional treatment options for nonspinal metastases offer a broad array of minimally invasive, image-guided procedures that are rapidly effective, reduce the need for opioids, and often work in complementary fashion with adjunct treatments in radiation oncology, orthopaedic surgery, and/or medical oncology. This article presents an approach to assess extraspinal metastases, reviews available interventional techniques in use today, and offers example cases as an introductory primer to the thought process used for selecting the appropriate interventional treatment.

Expert Consensus and Equipoise: Planning a Randomized Controlled Trial of Magnetically Controlled Growing Rods.

STUDY DESIGN: Expert consensus building using combined Delphi method and Nominal group technique. OBJECTIVES: To identify the current state of equipoise surrounding the use of magnetically controlled growing rods (MCGRs) and to determine consensus for planning a randomized controlled trial (RCT) with MCGRs. BACKGROUND: The use of MCGRs for the treatment of early-onset scoliosis (EOS) is a new technology. Optimal use has not been thoroughly investigated and much uncertainty exists. Areas of uncertainty include construct architecture, timing of lengthenings, and amount of distraction per lengthening. Expert discussion and consensus is useful at this early juncture and necessary when designing an RCT. METHODS: Two rounds of surveys were administered to a group of experienced pediatric spine surgeons, followed by a 2-hour, face-to-face meeting in November 2015 and a 1-hour, face-to-face meeting in February 2016. The first survey used example cases to establish agreement around the proper use of MCGRs and identified areas of equipoise and disagreement. The second survey again used example cases-this time selected for their equipoise status-to solicit trial arms for a potential RCT of MCGRs and identified important open questions in the use of MCGRs. Lastly, the face-to-face meetings employed iterative voting to preliminarily plan an RCT of MCGRs. RESULTS: Following the Delphi survey rounds and the two Nominal face-to-face meetings, the group of experts decided on an MCGR RCT design that standardized all patients to bidirectional constructs, and randomized to a lengthening interval of 6 versus 16 weeks with a standardized equation for calculating the total yearly lengthening that approximates normal spine growth. CONCLUSION: This endeavor indicates expert support for the use of MCGR in children older than 6 years, with curves greater than 60°. The uncertainty surrounding frequency of lengthening justifies an RCT of MCGRs. LEVEL OF EVIDENCE: Level V.

Raising Mean Arterial Pressure Alone Restores 20% of Intraoperative Neuromonitoring Losses.

STUDY DESIGN: Multicenter prospective. OBJECTIVE: To assess the effect of intraoperative interventions in restoring intraoperative neuromonitoring (IONM) signals in pediatric spine surgery. SUMMARY OF BACKGROUND DATA: No prior studies have prospectively examined the rate of return of IONM signals by increasing blood pressure (BP) alone. METHODS: Patients undergoing posterior spinal deformity surgery were enrolled at their preoperative appointment. Surgeons completed an intraoperative data form on patients who experienced an IONM change defined as a 50% or greater decrease in either transcranial motor evoked potentials or somatosensory evoked potentials. RESULTS: Four hundred fifty two patients were enrolled with 30 (7%) having IONM change. Thirty patients met inclusion criteria (mean age, 12 yrs, range, 5-19) and had the following diagnoses: idiopathic scoliosis (43%), neuromuscular scoliosis (13%), congenital scoliosis (10%), early onset scoliosis (7%), and other (27%). 20% (6/30) had return of signals due to an increase in BP alone with no other interventions (mean arterial pressure [MAP] increased from mean of 68 [range, 58-76] to 86 mmHg [range, 75-95]). Signals returned to baseline after mean of 16 minutes (range, 2-45). In 60% of patients (18/30), MAP was raised from a mean of 72 mmHg (range, 55-84) to 86 mmHg (range, 75-100) in conjunction with other interventions and had mean return of signals in 37 minutes (range, 8-210). Six (20%) of patients had signals return to baseline after a mean of 6 minutes (range, 3-13) in which MAP did not change appreciably. All patients had return of signals at the conclusion of the procedure with one patient having postoperative neurological sequale. CONCLUSION: In this prospective study of 452 pediatric spinal deformity surgeries, raising MAPs above 85 mmHg should be considered the first step in response to IONM signal changes, as this alone was successful in 20% of patients without sacrificing deformity correction. LEVEL OF EVIDENCE: 2.

The Classification for Early-onset Scoliosis (C-EOS) Correlates With the Speed of Vertical Expandable Prosthetic Titanium Rib (VEPTR) Proximal Anchor Failure.

BACKGROUND: The Classification for Early-onset Scoliosis (C-EOS) was developed by a consortium of early-onset scoliosis (EOS) surgeons. This study aims to examine if the C-EOS classification correlates with the speed (failure/unit time) of proximal anchor failure in EOS surgery patients. METHODS: A total of 106 EOS patients were retrospectively queried from an EOS database. All patients were treated with vertical expandable prosthetic titanium rib and experienced proximal anchor failure. Patients were classified by the C-EOS, which includes a term for etiology [C: Congenital (54.2%), M: Neuromuscular (32.3%), S: Syndromic (8.3%), I: Idiopathic (5.2%)], major curve angle [1: ≤20 degrees (0%), 2: 21 to 50 degrees (15.6%), 3: 51 to 90 degrees (66.7%), 4: >90 degrees (17.7%)], and kyphosis ["-": ≤20 (13.5%), "N": 21 to 50 (42.7%), "+": >50 (43.8%)]. Outcome was measured by time and number of lengthenings to failure. RESULTS: Analyzing C-EOS classes with >3 subjects, survival analysis demonstrates that the C-EOS discriminates low, medium, and high speed of failure. The low speed of failure group consisted of congenital/51-90/hypokyphosis (C3-) class. The medium-speed group consisted of congenital/51-90/normal and hyperkyphosis (C3N, C3+), and neuromuscular/51-90/hyperkyphosis (M3+) classes. The high-speed group consisted of neuromuscular/51-90/normal kyphosis (M3N), and neuromuscular/>90/normal and hyperkyphosis (M4N, M4+) classes. Significant differences were found in time (P<0.05) and number of expansions (P<0.05) before failure between congenital and neuromuscular classes.As isolated variables, neuromuscular etiology experienced a significantly faster time to failure compared with patients with idiopathic (P<0.001) and congenital (P=0.026) etiology. Patients with a major curve angle >90 degrees demonstrated significantly faster speed of failure compared with patients with major curve angle 21 to 50 degrees (P=0.011). CONCLUSIONS: The ability of the C-EOS to discriminate the speeds of failure of the various classification subgroups supports its validity and demonstrates its potential use in guiding decision making. Further experience with the C-EOS may allow more tailored treatment, and perhaps better outcomes of patients with EOS. LEVEL OF EVIDENCE: Level III.