Surgery enhances the effectiveness of peptide receptor radionuclide therapy in metastatic gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: With the advent of peptide receptor radionuclide therapy, the timing and sequence of surgery in the treatment of metastatic gastroenteropancreatic neuroendocrine tumors merits further study. We hypothesized that surgery before peptide receptor radionuclide therapy might enhance its effectiveness in patients with metastatic gastroenteropancreatic neuroendocrine tumors. METHODS: Eighty-nine patients with metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors treated with 177Lutetium-dotatate peptide receptor radionuclide therapy between 2018 and 2023 were included. Fifty-six patients underwent surgery (primary tumor resection and/or liver debulking) before peptide receptor radionuclide therapy and 33 patients did not. Primary outcome was progression-free survival according to Response Evaluation Criteria in Solid Tumors. Pretreatment dotatate positron emission tomography/computed tomography was used to calculate tumor volumes. RESULTS: The surgery and no-surgery groups were well-matched. Median progression-free survival after peptide receptor radionuclide therapy was 15.6 months (interquartile range, 9.1-22.7 months) in the no-surgery group compared with 26.1 months (interquartile range, 12.7-38.1 months) in the surgery group (P = .04). On subgroup analysis, median progression-free survival was 18.1 months (interquartile range, 11.9-38.4 months) in patients who underwent primary tumor resection only compared with 26.2 months (interquartile range, 14.0-38.1 months) in patients who underwent liver debulking (P = .04). Tumor volume was lowest in patients who underwent liver debulking (median 146.07 mL3) compared with no surgery (median 626.42 mL3) (P = .001). On univariable analysis, a tumor volume <138.8 mL3 was associated with longer progression-free survival (hazard ratio, 2.03; 95% confidence interval, 0.95-4.34, P = .05), with a median progression-free survival of 38.1 months (interquartile range, 16.9-41.3 months) compared with 17.8 months (interquartile range, 10.8-28.7 months). CONCLUSION: Surgery may enhance the effectiveness of 177Lutetium-dotatate in the treatment of metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors. This positive effect may be the result of a lower tumor volume in patients after surgery. Our findings fortify the concept of using surgical debulking to improve systemic therapies such as peptide receptor radionuclide therapy.

MEN1/DAXX/ATRX mutations enhance progression-free survival in gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy.

Pre-clinical data suggest that mutations in the MEN1, DAXX, and/or ATRX genes may potentially increase radiation efficacy in cancer cells. Herein, we explore the association between response to peptide receptor radionuclide therapy (PRRT) and those mutations in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We analyzed tissue-based next generation sequencing (NGS) assay results and clinicopathologic data from 28 patients with GEP-NETs treated with PRRT. Findings were correlated with progression-free survival (PFS) and objective response rate (ORR). Patients with mutations in MEN1, DAXX, and/or ATRX (n = 13) had a longer median PFS (26.47 vs 12.13 months; P = 0.014) than wild-type (n = 15) patients when adjusted for surgery prior to PRRT, tumor grade, and presence of TP53 mutation. Alterations in MEN1 along with a concurrent mutation in either DAXX or ATRX (n = 6) trended toward longer PFS compared to patients without concurrent mutations (31.53 vs 17.97 months; P = 0.09). ORR was higher in patients with a mutation in MEN1, DAXX, or ATRX (41.67% vs 15.38%). In pancreatic NET patients, these target mutations also showed a longer PFS (28.43 vs 9.83 months; P = 0.04). TP53 alterations showed a shorter PFS than wild-type cases (11.17 vs 20.47 months; P = 0.009). Mutations in MEN1/DAXX/ATRX are associated with improved PFS in patients with GEP-NETs receiving PRRT and might be used as a biomarker for treatment response.

Comparison of Measurement and Prognostic Power of SUV Between High-Definition and Standard PET Imaging in Non-Small Cell Lung Cancer Patients.

This study aimed to evaluate the measurement and prognostic ability of the SUVmax of whole-body tumors (SUVmaxwb) in non-small cell lung cancer (NSCLC) patients, comparing high-definition (HD) PET imaging with standard-definition (SD) PET imaging. Methods: The study included 242 consecutive NSCLC patients who underwent baseline 18F-FDG PET/CT from April 2018 to January 2021. Two imaging techniques were used: HD PET (using ordered-subsets expectation maximization with point-spread function modeling and time-of-flight techniques and smaller voxels) and SD PET (with ordered-subsets expectation maximization and time-of-flight techniques). SUVmaxwb was determined by measuring all the tumor lesions in the whole body, and tumor-to-background ratio (TBR) was calculated using the background SUVmean of various body parts. Results: The patient cohort had an average age of 68.3 y, with 59.1% being female. During a median follow-up of 29.6 mo, 83 deaths occurred. SUVmaxwb was significantly higher in HD PET than SD PET, with respective medians of 17.4 and 11.8. The TBR of 1,125 tumoral lesions was also higher in HD PET. Univariate Cox regression analysis showed that SUVmaxwb from both HD and SD PET were significantly associated with overall survival. However, after adjusting for TNM (tumor, node, metastasis) stage, only SUVmaxwb from SD PET remained significantly associated with survival. Conclusion: HD PET imaging in NSCLC patients yields higher SUVmaxwb and TBR, enhancing tumor visibility. Despite this, its prognostic value is less significant than SD PET after adjusting clinical TNM stage. Thus, consideration should be given to using HD PET reconstruction to increase tumor visibility, and SD PET is recommended for NSCLC patient prognostication and therapeutic evaluation, as well as for the classification of lung nodules.

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.

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.