Prospective Evaluation of Radiation Dose Escalation in Patients With High-Risk Neuroblastoma and Gross Residual Disease After Surgery: A Report From the Children’s Oncology Group ANBL0532 Study

Liu, Kevin X.; Naranjo, Arlene; Zhang, Fan F.; DuBois, Steven G.; Braunstein, Steve; Voss, Stephan D.; Khanna, Geetika; London, Wendy B.; Doski, John J.; Geiger, James D.; Kreissman, Susan G.; Grupp, Stephan A.; Diller, Lisa; Park, Julie R.; Haas‐Kogan, Daphne A.

doi:10.1200/jco.19.03316

Cited by 41 publications

(47 citation statements)

References 34 publications

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“…Our study complements the existing literature on children undergoing RT for NB confirming high LC and acceptable OS. Local control and survival rates were similar to other studies, which demonstrated a 3-to 5-year LC and OS of 64.7-97% and 35-94% (13,(19)(20)(21)(22)(23)(24)(25)(26)(27). In the literature, the most common late effects associated with RT were musculoskeletal abnormalities, gastrointestinal dysfunctions, metabolic disorders, vascular changes, and secondary malignancies (22,(28)(29)(30)(31).…”

Section: Discussionsupporting

confidence: 84%

Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry

et al. 2021

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ObjectiveRadiotherapy (RT) is an integral part of the interdisciplinary treatment of patients with high-risk neuroblastoma (NB). With the continuous improvements of outcome, the interest in local treatment strategies that reduce treatment-related side effects while achieving optimal oncological results is growing. Proton beam therapy (PBT) represents a promising alternative to conventional photon irradiation with regard to the reduction of treatment burden.MethodRetrospective analysis of children with high or intermediate risk NB receiving PBT of the primary tumor site during first-line therapy between 2015 and 2020 was performed. Data from the prospective in-house registry Standard Protonentherapie WPE – Kinder- (KiProReg) with respect to tumor control and treatment toxicity were analyzed. Adverse events were classified according to CTCAE Version 4 (V4.0) before, during, and after PBT.ResultsIn total, 44 patients (24 male, 20 female) with high (n = 39) or intermediate risk NB (n = 5) were included in the analysis. Median age was 3.4 years (range, 1.4–9.9 years). PBT doses ranged from 21.0 to 39.6 Gray (Gy) (median 36.0 Gy). Five patients received PBT to the MIBG-avid residual at the primary tumor site at time of PBT according to the NB-2004 protocol. In 39 patients radiation was given to the pre-operative tumor bed with or without an additional boost in case of residual tumor. After a median follow-up (FU) of 27.6 months, eight patients developed progression, either local recurrence (n = 1) or distant metastases (n = 7). Four patients died due to tumor progression. At three years, the estimated local control, distant metastatic free survival, progression free survival, and overall survival was 97.7, 84.1, 81.8, and 90.9%, respectively. During radiation, seven patients experienced higher-grade (CTCAE ≥ °3) hematologic toxicity. No other higher grade acute toxicity occurred. After PBT, one patient developed transient myelitis while receiving immunotherapy. No higher grade long-term toxicity was observed up to date.ConclusionPBT was a well tolerated and effective local treatment in children with high and intermediate risk NB. The role of RT in an intensive multidisciplinary treatment regimen remains to be studied in the future in order to better define timing, doses, target volumes, and general need for RT in a particularly sensitive cohort of patients.

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Section: Discussionsupporting

confidence: 84%

Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry

et al. 2021

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“…With response-adjusted chemotherapy and resection, intermediate-risk patients have excellent survival rates of >90% at 5-years ( 3 , 5 , 12 , 13 ). Approximately 40–50% of patients are diagnosed with high-risk disease, which requires multimodality treatment, including chemotherapy, surgery, myeloablative chemotherapy with autologous stem cell transplant, radiation therapy, and anti-disialoganglioside (GD2)-based immunotherapy ( 10 , 14 – 17 ). For patients with high-risk disease, 5-year OS remains ~50% despite these aggressive strategies ( 8 , 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

“Re-educating” Tumor Associated Macrophages as a Novel Immunotherapy Strategy for Neuroblastoma

Liu

Joshi

2020

Front. Immunol.

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Neuroblastoma is the most common extracranial pediatric tumor and often presents with metastatic disease, and patients with high-risk neuroblastoma have survival rates of ~50%. Neuroblastoma tumorigenesis is associated with the infiltration of various types of immune cells, including myeloid derived suppressor cells, tumor associated macrophages (TAMs), and regulatory T cells, which foster tumor growth and harbor immunosuppressive functions. In particular, TAMs predict poor clinical outcomes in neuroblastoma, and among these immune cells, TAMs with an M2 phenotype comprise an immune cell population that promotes tumor metastasis, contributes to immunosuppression, and leads to failure of radiation or checkpoint inhibitor therapy. This review article summarizes the role of macrophages in tumor angiogenesis, metastasis, and immunosuppression in neuroblastoma and discusses the recent advances in “macrophage-targeting strategies” in neuroblastoma with a focus on three aspects: (1) inhibition of macrophage recruitment, (2) targeting macrophage survival, and (3) reprogramming of macrophages into an immunostimulatory phenotype.

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“…At MSK, a radiotherapy dose of 2100 cGy is used for the prevention of soft tissue relapse at the primary site and at sites of bulky (>3 cm diameter) disease 20,21 . Although the optimal dose for radiotherapy of measurable disease has not been determined for the treatment of persistent MIBG‐avid skeletal metastases after completion of induction therapy or at recurrence, a dose of 3000‐3600 cGy is typically used 22,23 . Other investigators have also reported on the benefit of radiotherapy to metastatic sites at relapse 24 .…”

Section: Discussionmentioning

confidence: 99%

Mandibular metastases in neuroblastoma: Outcomes and dental sequelae

Singh

Modak

Solano

et al. 2021

Pediatric Blood & Cancer

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Background Although metastatic involvement of bony sites including cranial bones is common in neuroblastoma (NB), mandibular metastases (MM) are uncommon, and specific outcomes have not been reported upon in the modern therapeutic era. Methods In this retrospective study, medical records on patients with MM from NB were reviewed. Statistical analysis was performed using the Kaplan‐Meier method. Results Of 29 patients, nine (31%) had MM at diagnosis, whereas in 20 (69%) MM were first detected at NB relapse at a median time of 26 (6‐89) months from diagnosis. Median maximal diameter of lesions was 3 (range 0.8‐4.9) cm. MM were unilateral in 83% of patients, with ascending ramus (55%) and mandibular body (38%) being the two most common sites. All patients received systemic chemotherapy, and 26 (93%) patients received radiotherapy to MM. At a median follow‐up of 37.3 (24.2‐219.5) months, eight of nine patients with MM at diagnosis did not experience mandibular progressive disease. Eighteen of 20 patients with MM at relapse received therapeutic radiotherapy; objective responses were noted in 78%. Seventy‐two percent (5/18) had not experienced relapse within the radiation field at a median of 12 (2‐276) months postradiotherapy. Dental findings at follow‐up after completion of NB therapy included hypodontia, hypocalcification of enamel, and trismus. Median 3‐year overall survival in patients with relapsed MM was 51 ± 12% months from relapse. Conclusion MM when detected at diagnosis is associated with a prognosis similar to that for other skeletal metastases of NB. Radiotherapy is effective for control of MM detected both at diagnosis and relapse. Significant dental abnormalities posttherapy warrant regular dental evaluations and appropriate intervention.

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Prospective Evaluation of Radiation Dose Escalation in Patients With High-Risk Neuroblastoma and Gross Residual Disease After Surgery: A Report From the Children’s Oncology Group ANBL0532 Study

Cited by 41 publications

References 34 publications

Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry

Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry

“Re-educating” Tumor Associated Macrophages as a Novel Immunotherapy Strategy for Neuroblastoma

Mandibular metastases in neuroblastoma: Outcomes and dental sequelae

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