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Neoplastic meningitis in solid tumors: from diagnosis to personalized treatments.

ABSTRACT: Neoplastic meningitis (NM) is a devastating complication of solid tumors with poor outcome. Some randomized clinical trials have been conducted with heterogeneous inclusion criteria, diagnostic parameters, response evaluation and primary endpoints. Recently, the Leptomeningeal Assessment in Neuro-Oncology (LANO) Group and the European Society for Medical Oncology/European Association for Neuro-Oncology have proposed some recommendations in order to provide diagnostic criteria and response evaluation scores for NM. The aim of these guidelines is to integrate the neurological examination with magnetic resonance imaging and cerebrospinal fluid findings as well as to provide a framework for use in clinical trials. However, this composite assessment needs further validation. Since intrathecal therapy represents a treatment with limited efficacy in NM, many studies have been conducted on systemic therapies, including target therapies, with some encouraging results in terms of disease control. In this review, we have analyzed the clinical aspects and the most recent diagnostic tools and therapeutic options in NM.

SUBMITTER: Pellerino A

PROVIDER: S-EPMC5844521 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Neoplastic meningitis in solid tumors: from diagnosis to personalized treatments.

Pellerino Alessia A Bertero Luca L Rudà Roberta R Soffietti Riccardo R

Therapeutic advances in neurological disorders 20180307

Neoplastic meningitis (NM) is a devastating complication of solid tumors with poor outcome. Some randomized clinical trials have been conducted with heterogeneous inclusion criteria, diagnostic parameters, response evaluation and primary endpoints. Recently, the Leptomeningeal Assessment in Neuro-Oncology (LANO) Group and the European Society for Medical Oncology/European Association for Neuro-Oncology have proposed some recommendations in order to provide diagnostic criteria and response evalua ...[more]

PMID: 29535794

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Project description:BackgroundRecent genomic and bioinformatic technological advances have made it possible to dissect the immune response to personalized neoantigens encoded by tumor-specific mutations. However, timely and efficient identification of neoantigens is still one of the major obstacles to using personalized neoantigen-based cancer immunotherapy.MethodsTwo different pipelines of neoantigens identification were established in this study: (1) Clinical grade targeted sequencing was performed in patients with refractory solid tumor, and mutant peptides with high variant allele frequency and predicted high HLA-binding affinity were de novo synthesized. (2) An inventory-shared neoantigen peptide library of common solid tumors was constructed, and patients' hotspot mutations were matched to the neoantigen peptide library. The candidate neoepitopes were identified by recalling memory T-cell responses in vitro. Subsequently, neoantigen-loaded dendritic cell vaccines and neoantigen-reactive T cells were generated for personalized immunotherapy in six patients.ResultsImmunogenic neo-epitopes were recognized by autologous T cells in 3 of 4 patients who utilized the de novo synthesis mode and in 6 of 13 patients who performed shared neoantigen peptide library, respectively. A metastatic thymoma patient achieved a complete and durable response beyond 29 months after treatment. Immune-related partial response was observed in another patient with metastatic pancreatic cancer. The remaining four patients achieved the prolonged stabilization of disease with a median PFS of 8.6 months.ConclusionsThe current study provided feasible pipelines for neoantigen identification. Implementing these strategies to individually tailor neoantigens could facilitate the neoantigen-based translational immunotherapy research.TRIAL REGSITRATION. ChiCTR.org ChiCTR-OIC-16010092, ChiCTR-OIC-17011275, ChiCTR-OIC-17011913; ClinicalTrials.gov NCT03171220.FundingThis work was funded by grants from the National Key Research and Development Program of China (Grant No. 2017YFC1308900), the National Major Projects for "Major New Drugs Innovation and Development" (Grant No.2018ZX09301048-003), the National Natural Science Foundation of China (Grant No. 81672367, 81572329, 81572601), and the Key Research and Development Program of Jiangsu Province (No. BE2017607).

Dataset Information

Neoplastic meningitis in solid tumors: from diagnosis to personalized treatments.

Publications

Neoplastic meningitis in solid tumors: from diagnosis to personalized treatments.

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