Paolo Palmisciano1, Gina Watanabe2, Andie Conching2, Christian Ogasawara3, Morana Vojnic4, Randy S D'Amico5. 1. Department of Neurosurgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45229, USA. paolo.palmisciano94@gmail.com. 2. John A. Burns School of Medicine, University Oh Hawai'i, Honolulu, HI, USA. 3. Department of Neurosurgery, University of Texas Medical Branch, Galveston, TX, USA. 4. Donald and Barbara Zucker School of Medicine at Hofstra, Northwell Health Cancer Institute, Lenox Hill Hospital, New York, NY, USA. 5. Department of Neurological Surgery, Donald and Barbara Zucker School of Medicine at Hofstra, Lenox Hill Hospital, New York, NY, USA.
Abstract
PURPOSE: Leptomeningeal metastatic disease (LMD) from advanced malignancies has poor prognoses and limited treatments. Intrathecal therapy (ITT) protocols are available, showing variable outcomes. We reviewed the therapeutic and toxicity profiles of ITT in LMD. METHODS: PubMed, EMBASE, Web-of-Science, and Scopus were searched following the PRISMA-ScR guidelines to include studies reporting ITT for LMD. CLINICALTRIAL: gov and Cochrane were searched to identify ongoing clinical trials. RESULTS: We included 27 published studies encompassing 2161 patients and 4 ongoing trials. LMD originated from brain metastases (85.5%), lymphomas (5.4%), high-grade gliomas (4.6%), medulloblastomas (2.3%), and leukemias (2.1%). LMD was mostly diagnosed with the co-presence of neurological-related symptoms and positive imaging and/or cerebrospinal fluid cytology (60.8%). The most common ITT agents were methotrexate (35.9%), cytarabine (21.9%), and thiotepa (8.2%), standalone or combined. Patients received a median of 6.5 ITT cycles (range, 1.0-71.0) via intraventricular (58.8%) or lumbar intrathecal (41.2%) routes. The Ommaya reservoir was implanted in 38.5% cases. Concurrent systemic chemotherapy (45.2%) and/or radiotherapy (30.6%) were used. After 1-3 cycles, 44.7% patients had improved clinical status and 29.9% converted into negative cerebrospinal fluid cytology. The most common ITT-related severe adverse events were neutropenia (6.5%), meningitis (5.2%) and encephalopathy (4.5%). Median freedom from progression was 2.4 months (range, 0.1-59.5) and median overall survival 5.5 months (range, 0.1-148.0). CONCLUSION: Current ITT protocols are variable but effective and well-tolerated in LMD. Ongoing trials are investigating dose-limiting toxicity profiles and long-term overall survival. Future studies should analyze the therapeutic and safety profiles of ITT compared to newer systemic therapies.
PURPOSE: Leptomeningeal metastatic disease (LMD) from advanced malignancies has poor prognoses and limited treatments. Intrathecal therapy (ITT) protocols are available, showing variable outcomes. We reviewed the therapeutic and toxicity profiles of ITT in LMD. METHODS: PubMed, EMBASE, Web-of-Science, and Scopus were searched following the PRISMA-ScR guidelines to include studies reporting ITT for LMD. CLINICALTRIAL: gov and Cochrane were searched to identify ongoing clinical trials. RESULTS: We included 27 published studies encompassing 2161 patients and 4 ongoing trials. LMD originated from brain metastases (85.5%), lymphomas (5.4%), high-grade gliomas (4.6%), medulloblastomas (2.3%), and leukemias (2.1%). LMD was mostly diagnosed with the co-presence of neurological-related symptoms and positive imaging and/or cerebrospinal fluid cytology (60.8%). The most common ITT agents were methotrexate (35.9%), cytarabine (21.9%), and thiotepa (8.2%), standalone or combined. Patients received a median of 6.5 ITT cycles (range, 1.0-71.0) via intraventricular (58.8%) or lumbar intrathecal (41.2%) routes. The Ommaya reservoir was implanted in 38.5% cases. Concurrent systemic chemotherapy (45.2%) and/or radiotherapy (30.6%) were used. After 1-3 cycles, 44.7% patients had improved clinical status and 29.9% converted into negative cerebrospinal fluid cytology. The most common ITT-related severe adverse events were neutropenia (6.5%), meningitis (5.2%) and encephalopathy (4.5%). Median freedom from progression was 2.4 months (range, 0.1-59.5) and median overall survival 5.5 months (range, 0.1-148.0). CONCLUSION: Current ITT protocols are variable but effective and well-tolerated in LMD. Ongoing trials are investigating dose-limiting toxicity profiles and long-term overall survival. Future studies should analyze the therapeutic and safety profiles of ITT compared to newer systemic therapies.
Authors: M Carausu; M Carton; A Darlix; D Pasquier; M Leheurteur; M Debled; M A Mouret-Reynier; A Goncalves; F Dalenc; B Verret; M Campone; P Augereau; J M Ferrero; C Levy; J-D Fumet; C Lefeuvre-Plesse; T Petit; L Uwer; C Jouannaud; L Larrouquere; M Chevrot; C Courtinard; L Cabel Journal: ESMO Open Date: 2021-05-10
Authors: Isabella C Glitza; Michelle Rohlfs; Nandita Guha-Thakurta; Roland L Bassett; Chantale Bernatchez; Adi Diab; Scott E Woodman; Cassian Yee; Rodabe N Amaria; Sapna P Patel; Hussein Tawbi; Michael Wong; Wen-Jen Hwu; Patrick Hwu; Amy Heimberger; Ian E McCutcheon; Nicholas Papadopoulos; Michael A Davies Journal: ESMO Open Date: 2018-01-24