The results from these aforementioned studies highlight that many experimental therapies for the treatment of LMC are currently on the horizon. Further investigation is required to determine which emerging experimental therapies, if any, will provide significant improvements to LMC treatment.
LMC is a rapidly fatal consequence of systemic cancer spread. Current therapeutic options are predominantly palliative and do not significantly prolong patient survival. It is likely that the dismal response to current treatments among patients with LMC may be due to a variety of factors, such as limited delivery of therapeutic drugs to the CNS due to the BBB, the inherently aggressive biology of the subset of tumors cells predisposed to metastasize to the leptomeninges, shared intrinsic properties of LMC tumor cells that drive therapy resistance, and the LMC microenvironment, including normal leptomeningeal cells and infiltrating immune cells.
Contemporary experimental techniques, including analysis of CSF ctDNA, scRNA-seq, and animal models, have provided a means for deeper understanding of the biology underlying formation, outgrowth, and maintenance of leptomeningeal metastasis.
Continued efforts to understand the basic pathophysiology of LMC will also be necessary to guide the development of more efficacious treatments. Despite advances in the cellular and genetic characterization of primary cancers, the underlying molecular alterations that enable leptomeningeal spread are poorly understood. However, recent work has begun to elucidate several factors that may play a role in leptomeningeal carcinomatosis LMC pathogenesis.
Liquid biopsy of cerebrospinal fluid CSF is a promising tool in both the genetic characterization and diagnosis of LMC. CSF-derived circulating tumor DNA more accurately represents the genomic landscape of leptomeningeal metastasis compared with circulating tumor DNA derived from blood plasma. There exists a high degree of genetic divergence between a primary tumor and its leptomeningeal metastasis, suggesting the existence of premetastatic, subclonal populations of cancer cells within the primary tumor that are predisposed to leptomeningeal colonization.
Thus far, studies of immunotherapy and novel experimental methods to treat LMC have been limited, with low-grade evidence of treatment efficacy.
Further research with rigorous, randomized controlled studies is necessary. The authors have no conflicts of interest to report.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. National Center for Biotechnology Information , U. Neurosurg Clin N Am. Author manuscript; available in PMC Aug Hriday P. Bhambhvani , BS, a Adrian J. Rodrigues , BS, a Maxine C. Adrian J. Maxine C. Author information Article notes Copyright and License information Disclaimer.
Copyright notice. The publisher's final edited version of this article is available at Neurosurg Clin N Am. Open in a separate window. Novel Scientific Techniques to Characterize Leptomeningeal Carcinomatosis In recent years, exponential advances have been seen in the understanding of biology and pathology at single-cell resolution, and technological advances to suggest cell-free nucleic acid tests may act as surrogates for solid tissue biopsy.
Animal Models of Leptomeningeal Carcinomatosis Rodent models of LMC are most commonly established through injection of cancer cells directly into the cisterna magna, or into the subarachnoid space of the spinal cord. Radiation Although radiation has failed to prolong overall survival OS in LMC patients, it can result in dramatic symptom relief and improved quality of life for patients with symptomatic disease.
Systemic Chemotherapy Systemic chemotherapy has the obvious advantage of simultaneously treating extra-CNS disease and LMC; numerous studies have identified this treatment strategy as providing a survival benefit, although modest.
Intrathecal Chemotherapy In theory, IT chemotherapy delivers cytotoxic agents directly to the site of ventricular disease and to tumor cells present throughout the CSF. Table 2 Summary of studies involving immunotherapy in leptomeningeal carcinomatosis. Leptomeningeal disease: current diagnostic and therapeutic strategies.
Oncotarget ; 8 42 : — Leptomeningeal disease and the evolving role of molecular targeted therapy and immunotherapy. Ochsner J ; 17 4 : — Leptomeningeal metastasis: survival and prognostic factors in patients. J Neurol Sci ; 2 — Beauchesne P Intrathecal chemotherapy for treatment of leptomeningeal dissemination of metastatic tumours. Lancet Oncol ; 11 9 —9. Groves MD. Leptomeningeal disease. Neurosurg Clin N Am ; 22 1 —78, vii. Carcinomatous meningitis: leptomeningeal metastases in solid tumors.
Surg Neurol Int ; 4 Suppl 4 : S— Leptomeningeal metastasis from systemic cancer: review and update on management. Cancer ; 1 : 21— Leptomeningeal metastasis: challenges in diagnosis and treatment. Curr Cancer Ther Rev ; 7 4 — Balm M, Hammack J. Leptomeningeal carcinomatosis: presenting features and prognostic factors.
Arch Neurol ; 53 7 — Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival.
Cancer ; 42 2 —8. Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the National Cancer Institute experience. Medicine ; 61 1 : 45— Meningeal carcinomatosis in breast cancer.
Cancer ; 42 1 —6. Neurologic complications of cancer Contemporary neurology series. New York: Oxford University Press; Central nervous system metastasis from breast carcinoma. Autopsy study.
Cancer ; 52 12 — Meningeal carcinomatosis in small cell carcinoma of the lung. Am J Med ; 71 1 — Breast cancer leptomeningeal metastasis: propensity of breast cancer subtypes for leptomeninges and the analysis of factors influencing survival.
Med Oncol ; 30 1 Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome.
Breast Cancer Res ; 6 3 :R— Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry. Lancet Oncol ; 15 13 :e— J Neurooncol ; — Neurology ; 29 10 : — J Thorac Oncol ; 11 11 —9. Leptomeningeal metastases in the MRI era. Neurology ; 74 18 — Prognostic factors and clinical outcomes in patients with leptomeningeal metastasis from solid tumors.
J Neurooncol ; 93 2 — Diffuse involvement of the leptomeninges by tumour—a clinical and pathological study of 63 cases. Postgrad Med J ; 56 — Comparative risk of leptomeningeal disease after resection or stereotactic radiosurgery for solid tumor metastasis to the posterior fossa.
J Neurosurg ; 2 — Comparative risk of leptomeningeal dissemination of cancer after surgery or stereotactic radiosurgery for a single supratentorial solid tumor metastasis. Neurosurgery ; 64 4 — A balanced view of the cerebrospinal fluid composition and functions: focus on adult humans.
Exp Neurol ; — Molecular basis of metastasis. N Engl J Med ; 26 — Cell-cycle and DNA-damage response pathway is involved in leptomeningeal metastasis of non-small cell lung cancer.
Clin Cancer Res ; 24 1 — Biomarkers of disease: cerebrospinal fluid vascular endothelial growth factor VEGF and stromal cell derived factor SDF -1 levels in patients with neoplastic meningitis NM due to breast cancer, lung cancer and melanoma. J Neurooncol ; 94 2 — Vascular endothelial growth factor VEGF in leptomeningeal metastasis: diagnostic and prognostic value. Br J Cancer ; 91 2 — CSF levels of angiogenesis-related proteins in patients with leptomeningeal metastases.
Neurology ; 65 7 —2. Complement component 3 adapts the cerebrospinal fluid for leptomeningeal metastasis. Cell ; 6 — Proteomic analysis of CSF from patients with leptomeningeal melanoma metastases identifies signatures associated with disease progression and therapeutic resistance. Clin Cancer Res Tumour heterogeneity: the key advantages of single-cell analysis. Int J Mol Sci ; 17 12 Tumour heterogeneity and metastasis at single-cell resolution. Nat Cell Biol ; 20 12 — Liquid biopsies come of age: towards implementation of circulating tumour DNA.
Nat Rev Cancer ; 17 4 — Brain tumor mutations detected in cerebral spinal fluid. Clin Chem ; 61 3 — Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun ; 6 Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy. Ann Oncol ; 29 4 — J Thorac Oncol ; 14 5 — Obermeier B.
Development, maintenance and disruption of the blood-brain barrier. Pardridge W. CSF, blood-brain barrier, and brain drug delivery.
Expert Opin. Drug Deliv. Liu Y. Characteristics and Significance of the Pre-metastatic Niche. Cancer Cell. Olson E. Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab.
Patil T. Schinkel A. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Sanchez-Covarrubias L. Transporters at CNS barrier sites: Obstacles or opportunities for drug delivery? Wijaya J. Soffietti R. Management of brain metastases according to molecular subtypes. Lyle L. Cancer Res. Tiwary S. Gril B. Reactive astrocytic S1P3 signaling modulates the blood-tumor barrier in brain metastases.
Yonemori K. Taskar K. Lapatinib distribution in HER2 overexpressing experimental brain metastases of breast cancer. Zou H. Henry M. In-vivo longitudinal MRI study: An assessment of melanoma brain metastases in a clinically relevant mouse model.
Melanoma Res. Kienast Y. Real-time imaging reveals the single steps of brain metastasis formation. Murrell D. Arvanitis C.
Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption. Kodack D. Wyatt E. Method of establishing breast cancer brain metastases affects brain uptake and efficacy of targeted, therapeutic nanoparticles. Morikawa A. Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: A prospective study.
Neuro Oncol. Saleem A. Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer. Lewis Phillips G. Trastuzumab uptake and its relation to efficacy in an animal model of HER2-positive breast cancer brain metastasis.
Breast Cancer Res. Askoxylakis V. Cancer Inst. Kummar S. Phase 0 clinical trials: Conceptions and misconceptions. Cancer J. Pellerino A. Neoplastic meningitis in solid tumors: From diagnosis to personalized treatments. Chang P. Perineural spread of malignant melanoma of the head and neck: Clinical and imaging features.
AJNR Am. Ahn J. Risk for leptomeningeal seeding after resection for brain metastases: Implication of tumor location with mode of resection. Mahajan A. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: A single-centre, randomised, controlled, phase 3 trial. Foreman P. Postoperative radiosurgery for the treatment of metastatic brain tumor: Evaluation of local failure and leptomeningeal disease.
Boire A. Conrad C. Profiling of metalloprotease activities in cerebrospinal fluids of patients with neoplastic meningitis. Fluids Barriers CNS. Chi Y. Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis. Remsik J. Leptomeningeal metastatic cells adopt two phenotypic states. Cancer Rep. Palmieri D. Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Allen J. COX-2 drives metastatic breast cells from brain lesions into the cerebrospinal fluid and systemic circulation.
Dankner M. Invasive growth associated with Cold-Inducible RNA-Binding Protein expression drives recurrence of surgically resected brain metastases.
Nanjo S. Cancer Ther. Balak M. Novel DY and common secondary TM mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Fan Y. Jiang B. NGS to reveal heterogeneity between cerebrospinal fluid and plasma ctDNA among non-small cell lung cancer patients with leptomeningeal carcinomatosis. Oxnard G. Brastianos P. Cancer Discov. Shih D. Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma.
Hohensee I. Wikman H. Relevance of PTEN loss in brain metastasis formation in breast cancer patients. Chamberlain M. Prabhu R. A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases. Turner B. Nguyen T. Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases. Breast Cancer. Role of flow cytometry immunophenotyping in the diagnosis of leptomeningeal carcinomatosis.
Nayak L. Rare cell capture technology for the diagnosis of leptomeningeal metastasis in solid tumors. Diagnostic and prognostic significance of flow cytometry immunophenotyping in patients with leptomeningeal carcinomatosis.
Lee J. Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer. CellSearch technology applied to the detection and quantification of tumor cells in CSF of patients with lung cancer leptomeningeal metastasis.
Lung Cancer. Milojkovic Kerklaan B. EpCAM-based flow cytometry in cerebrospinal fluid greatly improves diagnostic accuracy of leptomeningeal metastases from epithelial tumors. Glantz M. Cerebrospinal fluid cytology in patients with cancer: Minimizing false-negative results.
EpCAM-based assays for epithelial tumor cell detection in cerebrospinal fluid. Campoli M. Detection and quantification of CSF malignant cells by the CellSearch technology in patients with melanoma leptomeningeal metastasis. Hyun K. Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer. Patel A.
Identification and enumeration of circulating tumor cells in the cerebrospinal fluid of breast cancer patients with central nervous system metastases. Nevel K. A retrospective, quantitative assessment of disease burden in patients with leptomeningeal metastases from non-small-cell lung cancer. Magbanua M. Molecular profiling of tumor cells in cerebrospinal fluid and matched primary tumors from metastatic breast cancer patients with leptomeningeal carcinomatosis.
Clinical significance of detecting CSF-derived tumor cells in breast cancer patients with leptomeningeal metastasis. Cordone I. Overexpression of syndecan-1, MUC-1, and putative stem cell markers in breast cancer leptomeningeal metastasis: A cerebrospinal fluid flow cytometry study.
Development of a new method for identification and quantification in cerebrospinal fluid of malignant cells from breast carcinoma leptomeningeal metastasis. BMC Clin. Acosta M. Screening of carcinoma metastasis by flow cytometry: A study of cases.
B Clin. Novel method for the detection and quantification of malignant cells in the CSF of patients with leptomeningeal metastasis of lung cancer. Lin X. Cerebrospinal fluid circulating tumor cells: A novel tool to diagnose leptomeningeal metastases from epithelial tumors.
Circulating epithelial tumor cell analysis in CSF in patients with leptomeningeal metastases. Malani R. Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer.
De Mattos-Arruda L. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Momtaz P. Pentsova E. Liquoral liquid biopsy in neoplastic meningitis enables molecular diagnosis and mutation tracking: A proof of concept.
Swinkels D. Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: A new medium of liquid biopsy. Liquid biopsy in central nervous system metastases: A RANO review and proposals for clinical applications. Huang R. Detection of circulating tumor DNA from non-small cell lung cancer brain metastasis in cerebrospinal fluid samples.
Zheng M. Carausu M. Angus L. Detection of aneuploidy in cerebrospinal fluid from patients with breast cancer can improve diagnosis of leptomeningeal metastases. Ballester L. Smalley I. Gani C. Outcome after whole brain radiotherapy alone in intracranial leptomeningeal carcinomatosis from solid tumors.
Brower J. Management of leptomeningeal metastases: Prognostic factors and associated outcomes. El Shafie R. Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis. Cancer Manag. Devecka M. Craniospinal irradiation CSI in patients with leptomeningeal metastases: Risk-benefit-profile and development of a prognostic score for decision making in the palliative setting.
BMC Cancer. Yang T. Clinical trial of proton craniospinal irradiation for leptomeningeal metastases. Kuiper J. Treatment and survival of patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastasis: A retrospective cohort analysis. Grommes C. Lee E. Erlotinib versus gefitinib for control of leptomeningeal carcinomatosis in non-small-cell lung cancer.
Yang H. Kawamura T. Cancer Chemother. Jackman D. A phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer. Tamiya A. Yang J. Standard-dose osimertinib for refractory leptomeningeal metastases in TM-positive EGFR-mutant non-small cell lung cancer. Saboundji K. Ahn M. Park S. Okuno T. OncoTargets Ther. Soria J. Choi M. Jing W. Great efficacy of bevacizumab plus erlotinib for leptomeningeal metastases from non-small cell lung cancer with initially positive EGFR mutation: A case report.
Cancer Biol. Jiang T. Lung Cancer Res. Liao B. Lancet Respir. Cho B. Costa D. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. Ahn H. ALK inhibitor crizotinib combined with intrathecal methotrexate treatment for non-small cell lung cancer with leptomeningeal carcinomatosis.
Arrondeau J. LDK compassionate use for treating carcinomatous meningitis in an ALK translocated non-small-cell lung cancer. Leptomeningeal metastases; pp. Chamberlain MC.
Neoplastic meningitis. J Clin Oncol. Gleissner B, Chamberlain MC. Lancet Neurol. Groves M. Diagnosis and treatment of leptomeningeal metastases from solid tumors: Experience with 90 patients.
Leptomeningeal carcinomatosis. Cancer Treat Rev. Kokkoris CP. How does cancer reach the pia-arachnoid? Prophylaxis and treatment of leukemia in the central nervous system and other sanctuaries. Sem Oncol. Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol.
Cerebrospinal fluid tumor markers for the diagnosis and management of leptomeningeal metastases. Eur J Cancer Clin Oncol. High incidence of occult leptomeningeal disease detected by flow cytometty in newly diagnosed aggressive b-cell lymphomas at risk for central nervous system involvement: The role of flow cytometry versus cytology. Biomarkers of disease: Cerebrospinal fluid vascular endothelial growth factor vegf and stromal cell derived factor sdf -1 levels in patients with neoplastic meningitis nm due to breast cancer, lung cancer and melanoma.
J Neurooncol. Davson H, Segal ME. Physiology of the csf and blood-brain barriers. New York: CRC; Measurements of blood-brain barrier permeability in patients undergoing radiotherapy and chemotherapy for primary cerebrallymphoma. Eur J Cancer. Activity of rituximab in primary central nervous system nervous system lyniphoma pcnsl ASCO Proceedings. Rituximab therapy for CNS lymphomas: Targeting the leptomeningeal compartment.
Leptomeningeal metastasis: A comparison of gadolinium-enhanced mri and contrast-enhanced ct of the brain. Chamberlain Me.
Radioisotope CSF flow studies in leptomeningeal metastases. Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Retrospective analysis of patients with leptomeningeal disease lmd in the mri era 1. Clin Onc. DeAngelis LM. Current diagnosis and treatment of leptomeningeal metastasis. Chamberlain M. A phase ii trial of intra-cerebrospinal fluid alpha interferon in the treatment of neoplastic meningitis. Mehta M, Bradley K.
Radiation therapy for leptomeningeal cancer. Cancer Treatment and Research. Posner JB. Philadelphia: FA Davis; Radiotherapy of the neuroaxis for palliative treatment of leptomeningeal carcinomatosis. Strahlenther Onkol. Chamberlain MC, Kormanik P. Carcinoma meningitis secondary to non-small cell lung cancer: Combined modality therapy. Arch Neurol. High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: Is intrathecal chemotherapy necessary?
Systemic high-dose intravenous methotrexate for central nervous system metastases. Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary cns lymphoma. Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate.
Primary cns lymphoma treated with osmotic blood-brain barrier disruption: Prolonged survival and preservation of cognitive function. Methotrexate: Distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. Ommaya reservoirs for the treatment of leptomeningeal metastases. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis.
Evidence-based review of intrathecal chemotherapy in outcome of patients with leptomeningeal metastasis. J Clin Onc. Cerebrospinal fluid flow abnonnalities in patients with neoplastic meningitis. An evaluation using indium-dtpa ventriculography. AmJ Med. Leptomeningeal metastases: indium-dtpa csf flow studies. Leukoencephalopathy following combined therapy of central nervous system leukemia and lymphoma.
Acta Neuropathol Suppl. Survival of patients with high grade glioma treated with intrathecal thiotriethylene-phosphoramide for ependymal or leptomeningeal gliomatosis. Cytosine arabinoside cerebrospinal fluid kinetics.
Clin Pharmacol Ther. A randomized controlled trial comparing intrathecal sustained-release cytarabine depocyt to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res. Quality-of-life-adjusted survival comparison of sustained-release cytosine arabinoside versus intrathecal methotrexate for treatment of solid tumor neoplastic meningitis.
Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern cooperative oncology group. A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: A randomised study.
Durable response of breast cancer leptomeningeal metastasis to capecitabine monotherapy. Neuro Oncol. Capecitabine therapy of central nervous system metastases from breast cancer.
Lapatinib plus capecitabine for her2-positive advanced breast cancer. Pilot phase ii trial of temozolomide for leptomeningeal metastases: Preliminary report.
Temozolomidemediated radiation enhancement in glioblastoma: A report on underlying mechanisms. A multicenter phase 2 trial of intrathecal topotecan in patients with meningeal malignancies. Phase ii trial of intracerebrospinal fluid etoposide in the treatment of neoplastic meningitis.
Pestalozzi BC, Brignoli S. Trastuzumab in csf. Trastuzumab for breast cancer-related carcinomatous meningitis. Clin Breast Cancer. Application of intrathecal trastuzumab herceptin,trade mark for treatment of meningeal carcinomatosis in her2-overexpressing metastatic breast cancer.
Oncol Rep. Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab. Lancet Oncol. High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to her-2 overexpressing breast cancer. Ann Oncol. Intra-csf trastuzumab in patients with neoplastic meningitis from breast cancer or primary brain tumors. Burris HA. Phase I study of intraventricular administration of rituximab in patients with recurrent cns and intraocular lymphoma.
Recurrent lymphomatous meningitis treated with intra-csf rituximab and liposomal ara-c. J Neuro-oncoI. Response of leptomeningeal metastases from breast cancer to hormonal therapy. Durable clinical benefit with exemestane in leptomeningeal metastasis of breast cancer.
Clin Transl Oncol. Durable remission of leptomeningeal metastasis of breast cancer with letrozole: A case report and implications of biomarkers On treatment selection. Jpn J Clin Oncol. Phase 1 study of targeted radioimmunotherapy for leptomeningeal cancers using intra-ommaya i-3f8. Anti-g d2 antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. Radioimmunodetection of neuroblastoma with iodinef8: Correlation with biopsy, iodinemetaiodobenzylguanidine and standard diagnostic modalities.
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