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Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma

  • Clinical Study - Patient Study
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Abstract

Innovation in the management of brain metastases is needed. We evaluated the addition of compartmental intrathecal antibody-based radioimmunotherapy (cRIT) in patients with recurrent metastatic central nervous system (CNS) neuroblastoma following surgery, craniospinal irradiation, and chemotherapy. Twenty one patients treated for recurrent neuroblastoma metastatic to the CNS, received a cRIT-containing salvage regimen incorporating intrathecal 131I-monoclonal antibodies (MoAbs) targeting GD2 or B7H3 following surgery and radiation. Most patients also received outpatient craniospinal irradiation, 3F8/GMCSF immunotherapy, 13-cis-retinoic acid and oral temozolomide for systemic control. Seventeen of 21 cRIT-salvage patients are alive 7–74 months (median 33 months) since CNS relapse, with all 17 remaining free of CNS neuroblastoma. One patient died of infection at 22 months with no evidence of disease at autopsy, and one of lung and bone marrow metastases at 15 months, and one of progressive bone marrow disease at 30 months. The cRIT-salvage regimen was well tolerated, notable for myelosuppression minimized by stem cell support (n = 5), and biochemical hypothyroidism (n = 5). One patient with a 7-year history of metastatic neuroblastoma is in remission from MLL-associated secondary leukemia. This is significantly improved to published results with non-cRIT based where relapsed CNS NB has a median time to death of approximately 6 months. The cRIT-salvage regimen for CNS metastases was well tolerated by young patients, despite their prior history of intensive cytotoxic therapies. It has the potential to increase survival with better than expected quality of life.

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References

  1. Choi HS, Koh SH, Park ES, Shin HY, Ahn HS (2005) CNS recurrence following CD34+ peripheral blood stem cell transplantation in stage 4 neuroblastoma. Pediatr Blood Cancer 45:68–71

    Article  CAS  PubMed  Google Scholar 

  2. Kramer K, Kushner B, Heller G, Cheung NK (2001) Neuroblastoma metastatic to the central nervous system. The Memorial Sloan-kettering Cancer Center experience and a literature review. Cancer 91:1510–1519

    Article  CAS  PubMed  Google Scholar 

  3. Matthay KK, Brisse H, Couanet D, Couturier J, Benard J, Mosseri V, Edeline V, Lumbroso J, Valteau-Couanet D, Michon J (2003) Central nervous system metastases in neuroblastoma: radiologic, clinical, and biologic features in 23 patients. Cancer 98:155–165

    Article  PubMed  Google Scholar 

  4. Moseley RP, Davies AG, Richardson RB, Zalutsky M, Carrell S, Fabre J, Slack N, Bullimore J, Pizer B, Papanastassiou V et al (1990) Intrathecal administration of 131I radiolabelled monoclonal antibody as a treatment for neoplastic meningitis. Br J Cancer 62:637–642

    CAS  PubMed  Google Scholar 

  5. Kemshead JT, Papanastassiou V, Coakham HB, Pizer BL (1992) Monoclonal antibodies in the treatment of central nervous system malignancies. Eur J Cancer 28:511–513

    Article  CAS  PubMed  Google Scholar 

  6. Brown MT, Coleman RE, Friedman AH, Friedman HS, McLendon RE, Reiman R, Felsberg GJ, Tien RD, Bigner SH, Zalutsky MR, Zhao XG, Wikstrand CJ, Pegram CN, Herndon JE II, Vick NA, Paleologos N, Fredericks RK, Schold SC Jr, Bigner DD (1996) Intrathecal 131I-labeled antitenascin monoclonal antibody 81C6 treatment of patients with leptomeningeal neoplasms or primary brain tumor resection cavities with subarachnoid communication: phase I trial results. Clin Cancer Res 2:963–972

    CAS  PubMed  Google Scholar 

  7. Riva P, Franceschi G, Frattarelli M, Lazzari S, Riva N, Giuliani G, Casi M, Sarti G, Guiducci G, Giorgetti G, Gentile R, Santimaria M, Jermann E, Maeke HR (1999) Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with 90Y: a phase I study. Clin Cancer Res 5:3275s–3280s

    CAS  PubMed  Google Scholar 

  8. Bigner DD, Brown MT, Friedman AH, Coleman RE, Akabani G, Friedman HS, Thorstad WL, McLendon RE, Bigner SH, Zhao XG, Pegram CN, Wikstrand CJ, Herndon JE II, Vick NA, Paleologos N, Cokgor I, Provenzale JM, Zalutsky MR (1998) Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results. J Clin Oncol 16:2202–2212

    CAS  PubMed  Google Scholar 

  9. Reardon DA, Zalutsky MR, Akabani G, Coleman RE, Friedman AH, Herndon JE II, McLendon RE, Pegram CN, Quinn JA, Rich JN, Vredenburgh JJ, Desjardins A, Guruangan S, Boulton S, Raynor RH, Dowell JM, Wong TZ, Zhao XG, Friedman HS, Bigner DD (2008) A pilot study: 131I-antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost. Neuro Oncol 10:182–189

    Article  CAS  PubMed  Google Scholar 

  10. Kramer K, Humm JL, Souweidane MM, Zanzonico PB, Dunkel IJ, Gerald WL, Khakoo Y, Yeh SD, Yeung HW, Finn RD, Wolden SL, Larson SM, Cheung NK (2007) Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. J Clin Oncol 25:5465–5470

    Article  PubMed  Google Scholar 

  11. Modak S, Kramer K, Gultekin SH, Guo HF, Cheung NK (2001) Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors. Cancer Res 61:4048–4054

    CAS  PubMed  Google Scholar 

  12. Modak S, Guo HF, Humm JL, Smith-Jones PM, Larson SM, Cheung NK (2005) Radioimmunotargeting of human rhabdomyosarcoma using monoclonal antibody 8H9. Cancer Biother Radiopharm 20:534–546

    Article  CAS  PubMed  Google Scholar 

  13. Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, De Bernardi B, Evans AE, Favrot M, Hedborg F et al (1993) Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 11:1466–1477

    CAS  PubMed  Google Scholar 

  14. Kushner BH, Kramer K, Modak S, Cheung NK (2006) Irinotecan plus temozolomide for relapsed or refractory neuroblastoma. J Clin Oncol 24:5271–5276

    Article  CAS  PubMed  Google Scholar 

  15. Kushner BH, Kramer K, LaQuaglia MP, Cheung NK (2003) Curability of recurrent disseminated disease after surgery alone for local-regional neuroblastoma using intensive chemotherapy and anti-G(D2) immunotherapy. J Pediatr Hematol Oncol 25:515–519

    Article  PubMed  Google Scholar 

  16. Cheung NK, Kushner BH, Cheung IY, Kramer K, Canete A, Gerald W, Bonilla MA, Finn R, Yeh SJ, Larson SM (1998) Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. J Clin Oncol 16:3053–3060

    CAS  PubMed  Google Scholar 

  17. Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, Swift P, Shimada H, Black CT, Brodeur GM, Gerbing RB, Reynolds CP (1999) Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children’s Cancer Group. N Engl J Med 341:1165–1173

    Article  CAS  PubMed  Google Scholar 

  18. Brock CS, Newlands ES, Wedge SR, Bower M, Evans H, Colquhoun I, Roddie M, Glaser M, Brampton MH, Rustin GJ (1998) Phase I trial of temozolomide using an extended continuous oral schedule. Cancer Res 58:4363–4367

    CAS  PubMed  Google Scholar 

  19. Kramer K, Gerald WL, Kushner BH, Cheung NKV (2001) Disialoganglioside GD2 loss following mononclonal antibody therapy is rare in neuroblastoma. Med Pediatr Oncol 36:194–196

    Article  CAS  PubMed  Google Scholar 

  20. Cheung NK, Landmeier B, Neely J, Nelson AD, Abramowsky C, Ellery S, Adams RB, Miraldi F (1986) Complete tumor ablation with iodine 131-radiolabeled disialoganglioside GD2-specific monoclonal antibody against human neuroblastoma xenografted in nude mice. J Natl Cancer Inst 77:739–745

    CAS  PubMed  Google Scholar 

  21. Program CTE: Common Terminology Criteria for Adverse Events Version 3.0. In: DCTD, NCI, NIH, DHHS (eds)

  22. Kushner BH, Kramer K, Modak S, Kernan NA, Reich LM, Danis K, Cheung NK (2006) Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system. Bone Marrow Transplant 37:271–276

    Article  CAS  PubMed  Google Scholar 

  23. Kramer K, Cheung NK, Humm J, DiResta G, Arbit E, Larson S, Finn R, Rosenblum M, Nguyen H, Gonzalez G, Liu C, Yang YF, Mendelsohn ME, Gillio AP (1997) Pharmacokinetics and acute toxicology of intraventricular 131I-monoclonal antibody targeting disialoganglioside in non-human primates. J Neurooncol 35:101–111

    Article  CAS  PubMed  Google Scholar 

  24. DuBois SG, Kalika Y, Lukens JN, Brodeur GM, Seeger RC, Atkinson JB, Haase GM, Black CT, Perez C, Shimada H, Gerbing R, Stram DO, Matthay KK (1999) Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival. J Pediatr Hematol Oncol 21:181–189

    Article  CAS  PubMed  Google Scholar 

  25. Eriksson D, Joniani HM, Sheikholvaezin A, Lofroth PO, Johansson L, Riklund Ahlstrom K, Stigbrand T (2003) Combined low dose radio- and radioimmunotherapy of experimental HeLa Hep 2 tumours. Eur J Nucl Med Mol Imaging 30:895–906

    CAS  PubMed  Google Scholar 

  26. Buchegger F, Roth A, Allal A, Dupertuis YM, Slosman DO, Delaloye AB, Mach JP (2000) Radioimmunotherapy of colorectal cancer liver metastases: combination with radiotherapy. Ann N Y Acad Sci 910:263–269; discussion 269–270

    Article  CAS  PubMed  Google Scholar 

  27. Larson SM, Pentlow KS, Volkow ND, Wolf AP, Finn RD, Lambrecht RM, Graham MC, Di Resta G, Bendriem B, Daghighian F et al (1992) PET scanning of iodine-124-3F9 as an approach to tumor dosimetry during treatment planning for radioimmunotherapy in a child with neuroblastoma. J Nucl Med 33:2020–2023

    CAS  PubMed  Google Scholar 

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Acknowledgments

We wish to thank the Cyclotron-Radiochemistry Core of MSKCC and Yiauchung Sheh for production and supply of the I-124. This study was supported in part by the FDA-KK-01A2, CA89935, CA89936, CA106450, CA117076, FD003089, PO1 CA033049, Robert Steel Foundation, Katie’s Find A Cure Fund, Pediatric Cancer Foundation, Aubrey Fund, Hope Street Kids, Major Fund, Leptomeningeal Research Fund, the MSKCC Experimental Therapeutics Center and the Ludwig Center for Cancer Immunotherapy.

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Authors and Affiliations

  1. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 429, New York, NY, 10065, USA

    Kim Kramer, Brian H. Kushner, Shakeel Modak, Hong Xu & Nai-Kong V. Cheung

  2. Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

    Neeta Pandit-Taskar, Peter Smith-Jones & Steven M. Larson

  3. Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

    Pat Zanzonico & John L. Humm

  4. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

    Suzanne L. Wolden

  5. Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

    Mark M. Souweidane

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  1. Kim Kramer
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  2. Brian H. Kushner
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  3. Shakeel Modak
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  4. Neeta Pandit-Taskar
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  7. John L. Humm
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  9. Suzanne L. Wolden
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  12. Nai-Kong V. Cheung
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Correspondence to Kim Kramer.

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Kramer, K., Kushner, B.H., Modak, S. et al. Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma. J Neurooncol 97, 409–418 (2010). https://doi.org/10.1007/s11060-009-0038-7

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  • DOI: https://doi.org/10.1007/s11060-009-0038-7

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