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Background: Surgical resection is a mainstay of treatment in high-risk neuroblastoma (HR-NB), but there exists wide variability in perioperative management practices. The aim of this study was to evaluate two standardized adult perioperative enhanced recovery practices (ERPs) in pediatric patients undergoing open resection of abdominal HR-NB., Methods: All patients with abdominal HR-NB surgically resected at a free-standing children's hospital between 12/2010 and 7/2020 were retrospectively reviewed. Perioperative ERPs of interest included avoidance of routine nasogastric tube (NGT) use and the use of neuraxial anesthesia. Primary outcomes included time to enteral intake, urinary catheter use, opioid utilization, and length of stay (LOS)., Results: Overall, 37 children, median age 33 months (IQR: 20-48 months), were identified. Avoidance of an NGT allowed for earlier feeding after surgery ( P = .03). Neuraxial anesthesia use more frequently required an indwelling urinary catheter ( P < .01) for a longer duration ( P = .02), with no difference in total opioid utilization ( P = .77) compared to patients without neuraxial anesthesia. Postoperative LOS was unaffected by avoidance of routine NGT use ( P = .68) or use of neuraxial anesthesia ( P = .89)., Conclusion: Children undergoing open resection of abdominal HR-NB initiated diet sooner when an NGT was not left postoperatively, and the need for a urinary catheter was significantly higher in patients who received neuraxial anesthesia. However, these two ERP components did not decrease postoperative LOS. To optimize the postoperative management of NB patients, postoperative NGTs should be avoided, while the benefit of neuraxial anesthesia is less clear as it necessitates the placement of a urinary catheter without decreasing opioid utilization., Competing Interests: Declaration of Conflicting InterestsThe author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

C-C motif chemokine ligand 2 (CCL2) is a monocyte chemoattractant that promotes metastatic disease and portends a poor prognosis in many cancers. To determine the potential of anti-CCL2 inhibition as a therapy for recurrent metastatic disease in neuroblastoma, a mouse model of minimal residual disease was utilized in which residual disease was treated with anti-CCL2 monoclonal antibody with etoposide. The effect of anti-CCL2 antibody on neuroblastoma cells was determined in vitro with cell proliferation, transwell migration, and 2-dimensional chemotaxis migration assays. The in vivo efficacy of anti-CCL2 antibody and etoposide against neuroblastoma was assessed following resection of primary tumors formed by two cell lines or a patient-derived xenograft (PDX) in immunodeficient NOD-scid gamma mice. In vitro, anti-CCL2 antibody did not affect cell proliferation but significantly inhibited neuroblastoma cell and monocyte migration towards an increasing CCL2 concentration gradient. Treatment of mice with anti-CCL2 antibody combined with etoposide significantly increased survival of mice after resection of primary tumors, compared to untreated mice., (© 2023. The Author(s).)

Background: Immunotherapy with anti-disialoganglioside dinutuximab has improved survival for children with high-risk neuroblastoma (NB) when given after induction chemotherapy and surgery. However, disease recurrence and resistance persist. Dinutuximab efficacy has not been evaluated when initiated before primary tumor removal. Using a surgical mouse model of human NB, we examined if initiating dinutuximab plus ex vivo-activated natural killer (aNK) cells before resection of the primary tumor improves survival., Methods: In vitro, human NB cells (SMS-KCNR-Fluc, CHLA-255-Fluc) were treated with dinutuximab and/or aNK cells and cytotoxicity was measured. In vivo, NB cells (SMS-KCNR-Fluc, CHLA-255-Fluc, or COG-N-415x PDX) were injected into the kidney of NOD-scid gamma mice. Mice received eight intravenous infusions of aNK cells plus dinutuximab beginning either 12 days before or 2 days after resection of primary tumors. Tumors in control mice were treated by resection alone or with immunotherapy alone. Disease was quantified by bioluminescent imaging and survival was monitored. aNK cell infiltration into primary tumors was quantified by flow cytometry and immunohistochemistry at varying timepoints., Results: In vitro, aNK cells and dinutuximab were more cytotoxic than either treatment alone. In vivo, treatment with aNK cells plus dinutuximab prior to resection of the primary tumor was most effective in limiting metastatic disease and prolonging survival. aNK cell infiltration into xenograft tumors was observed after 1 day and peaked at 5 days following injection., Conclusion: Dinutuximab plus aNK cell immunotherapy initiated before resection of primary tumors decreases disease burden and prolongs survival in an experimental mouse model of NB. These findings support the clinical investigation of this treatment strategy during induction therapy in patients with high-risk NB., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)