PURPOSE: Nodular desmoplastic medulloblastoma (ND) and medulloblastoma with extensive nodularity (MBEN) have been associated with a more favorable outcome in younger children. However, treatment-related neurotoxicity remains a significant concern in this vulnerable group of patients. PATIENTS AND METHODS: ACNS1221 was a prospective single-arm trial of conventional chemotherapy for nonmetastatic ND and MBEN based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate, aiming to achieve similar outcome (2-year progression-free survival [PFS] ≥ 90%) with reduced treatment-related neurotoxicity. Secondary objectives included feasibility of timely central pathology review and evaluation of tumor molecular profile. RESULTS: Twenty-five eligible patients (15 males and 10 females; median age, 18.7 months) were enrolled. Eighteen patients had ND and 7 had MBEN histology. Three patients had residual disease at baseline. The study closed early because of a higher than expected relapse rate. Twelve patients experienced relapse-local (n= 6), distant (n = 3), and combined (n = 3)-at a median of 9.8 months from diagnosis (range, 8.9-13.7 months), and 2 patients died of disease. Two-year PFS and overall survival rates were 52% (95% CI, 32.4% to 71.6%) and 92% (95% CI, 80.8% to 100.0%) respectively. Patients older than 12 months of age (P = .036) and ND histology (P = .005) were associated with worse PFS. No patients with MBEN histology experienced relapse. All tumor samples clustered within the sonic hedgehog (SHH) group. Methylation analysis delineated 2 subgroups, SHH-I and SHH-II, which were associated with 2-year PFS rates of 30.0% (95% CI, 1.6% to 58.4%) and 66.7% (95% CI, 44.0% to 89.4%), respectively (P = .099). CONCLUSION: The proposed modified regimen of conventional systemic chemotherapy without serial intraventricular methotrexate injection failed to achieve the targeted 2-year PFS of 90%. With this cohort, we prospectively confirmed the existence of two SHH subgroups and observed a trend toward worse outcome for SHH-I patients.
PURPOSE:Nodular desmoplastic medulloblastoma (ND) and medulloblastoma with extensive nodularity (MBEN) have been associated with a more favorable outcome in younger children. However, treatment-related neurotoxicity remains a significant concern in this vulnerable group of patients. PATIENTS AND METHODS: ACNS1221 was a prospective single-arm trial of conventional chemotherapy for nonmetastatic ND and MBEN based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate, aiming to achieve similar outcome (2-year progression-free survival [PFS] ≥ 90%) with reduced treatment-related neurotoxicity. Secondary objectives included feasibility of timely central pathology review and evaluation of tumor molecular profile. RESULTS: Twenty-five eligible patients (15 males and 10 females; median age, 18.7 months) were enrolled. Eighteen patients had ND and 7 had MBEN histology. Three patients had residual disease at baseline. The study closed early because of a higher than expected relapse rate. Twelve patients experienced relapse-local (n= 6), distant (n = 3), and combined (n = 3)-at a median of 9.8 months from diagnosis (range, 8.9-13.7 months), and 2 patients died of disease. Two-year PFS and overall survival rates were 52% (95% CI, 32.4% to 71.6%) and 92% (95% CI, 80.8% to 100.0%) respectively. Patients older than 12 months of age (P = .036) and ND histology (P = .005) were associated with worse PFS. No patients with MBEN histology experienced relapse. All tumor samples clustered within the sonic hedgehog (SHH) group. Methylation analysis delineated 2 subgroups, SHH-I and SHH-II, which were associated with 2-year PFS rates of 30.0% (95% CI, 1.6% to 58.4%) and 66.7% (95% CI, 44.0% to 89.4%), respectively (P = .099). CONCLUSION: The proposed modified regimen of conventional systemic chemotherapy without serial intraventricular methotrexate injection failed to achieve the targeted 2-year PFS of 90%. With this cohort, we prospectively confirmed the existence of two SHH subgroups and observed a trend toward worse outcome for SHH-I patients.
Authors: Stefan Rutkowski; Bruce Cohen; Jonathan Finlay; Roberto Luksch; Vita Ridola; Dominique Valteau-Couanet; Junichi Hara; Maria-Luisa Garre; Jacques Grill Journal: Pediatr Blood Cancer Date: 2010-04 Impact factor: 3.167
Authors: Florence M G Cavalli; Marc Remke; Ladislav Rampasek; John Peacock; David J H Shih; Betty Luu; Livia Garzia; Jonathon Torchia; Carolina Nor; A Sorana Morrissy; Sameer Agnihotri; Yuan Yao Thompson; Claudia M Kuzan-Fischer; Hamza Farooq; Keren Isaev; Craig Daniels; Byung-Kyu Cho; Seung-Ki Kim; Kyu-Chang Wang; Ji Yeoun Lee; Wieslawa A Grajkowska; Marta Perek-Polnik; Alexandre Vasiljevic; Cecile Faure-Conter; Anne Jouvet; Caterina Giannini; Amulya A Nageswara Rao; Kay Ka Wai Li; Ho-Keung Ng; Charles G Eberhart; Ian F Pollack; Ronald L Hamilton; G Yancey Gillespie; James M Olson; Sarah Leary; William A Weiss; Boleslaw Lach; Lola B Chambless; Reid C Thompson; Michael K Cooper; Rajeev Vibhakar; Peter Hauser; Marie-Lise C van Veelen; Johan M Kros; Pim J French; Young Shin Ra; Toshihiro Kumabe; Enrique López-Aguilar; Karel Zitterbart; Jaroslav Sterba; Gaetano Finocchiaro; Maura Massimino; Erwin G Van Meir; Satoru Osuka; Tomoko Shofuda; Almos Klekner; Massimo Zollo; Jeffrey R Leonard; Joshua B Rubin; Nada Jabado; Steffen Albrecht; Jaume Mora; Timothy E Van Meter; Shin Jung; Andrew S Moore; Andrew R Hallahan; Jennifer A Chan; Daniela P C Tirapelli; Carlos G Carlotti; Maryam Fouladi; José Pimentel; Claudia C Faria; Ali G Saad; Luca Massimi; Linda M Liau; Helen Wheeler; Hideo Nakamura; Samer K Elbabaa; Mario Perezpeña-Diazconti; Fernando Chico Ponce de León; Shenandoah Robinson; Michal Zapotocky; Alvaro Lassaletta; Annie Huang; Cynthia E Hawkins; Uri Tabori; Eric Bouffet; Ute Bartels; Peter B Dirks; James T Rutka; Gary D Bader; Jüri Reimand; Anna Goldenberg; Vijay Ramaswamy; Michael D Taylor Journal: Cancer Cell Date: 2017-06-12 Impact factor: 31.743
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Authors: J Russell Geyer; Richard Sposto; Mark Jennings; James M Boyett; Richard A Axtell; David Breiger; Emmett Broxson; Bernadine Donahue; Jonathan L Finlay; Joel W Goldwein; Linda A Heier; Dennis Johnson; Claire Mazewski; Douglas C Miller; Roger Packer; Diane Puccetti; Jerilynn Radcliffe; May Lin Tao; Tania Shiminski-Maher Journal: J Clin Oncol Date: 2005-10-20 Impact factor: 44.544
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Authors: David M Ashley; Thomas E Merchant; Douglas Strother; Tianni Zhou; Patricia Duffner; Peter C Burger; Douglas C Miller; Nancy Lyon; Melanie J Bonner; Michael Msall; Allen Buxton; Russell Geyer; Larry E Kun; Lee Coleman; Ian F Pollack Journal: J Clin Oncol Date: 2012-07-30 Impact factor: 44.544
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Authors: David Capper; David T W Jones; Martin Sill; Volker Hovestadt; Daniel Schrimpf; Dominik Sturm; Christian Koelsche; Felix Sahm; Lukas Chavez; David E Reuss; Annekathrin Kratz; Annika K Wefers; Kristin Huang; Kristian W Pajtler; Leonille Schweizer; Damian Stichel; Adriana Olar; Nils W Engel; Kerstin Lindenberg; Patrick N Harter; Anne K Braczynski; Karl H Plate; Hildegard Dohmen; Boyan K Garvalov; Roland Coras; Annett Hölsken; Ekkehard Hewer; Melanie Bewerunge-Hudler; Matthias Schick; Roger Fischer; Rudi Beschorner; Jens Schittenhelm; Ori Staszewski; Khalida Wani; Pascale Varlet; Melanie Pages; Petra Temming; Dietmar Lohmann; Florian Selt; Hendrik Witt; Till Milde; Olaf Witt; Eleonora Aronica; Felice Giangaspero; Elisabeth Rushing; Wolfram Scheurlen; Christoph Geisenberger; Fausto J Rodriguez; Albert Becker; Matthias Preusser; Christine Haberler; Rolf Bjerkvig; Jane Cryan; Michael Farrell; Martina Deckert; Jürgen Hench; Stephan Frank; Jonathan Serrano; Kasthuri Kannan; Aristotelis Tsirigos; Wolfgang Brück; Silvia Hofer; Stefanie Brehmer; Marcel Seiz-Rosenhagen; Daniel Hänggi; Volkmar Hans; Stephanie Rozsnoki; Jordan R Hansford; Patricia Kohlhof; Bjarne W Kristensen; Matt Lechner; Beatriz Lopes; Christian Mawrin; Ralf Ketter; Andreas Kulozik; Ziad Khatib; Frank Heppner; Arend Koch; Anne Jouvet; Catherine Keohane; Helmut Mühleisen; Wolf Mueller; Ute Pohl; Marco Prinz; Axel Benner; Marc Zapatka; Nicholas G Gottardo; Pablo Hernáiz Driever; Christof M Kramm; Hermann L Müller; Stefan Rutkowski; Katja von Hoff; Michael C Frühwald; Astrid Gnekow; Gudrun Fleischhack; Stephan Tippelt; Gabriele Calaminus; Camelia-Maria Monoranu; Arie Perry; Chris Jones; Thomas S Jacques; Bernhard Radlwimmer; Marco Gessi; Torsten Pietsch; Johannes Schramm; Gabriele Schackert; Manfred Westphal; Guido Reifenberger; Pieter Wesseling; Michael Weller; Vincent Peter Collins; Ingmar Blümcke; Martin Bendszus; Jürgen Debus; Annie Huang; Nada Jabado; Paul A Northcott; Werner Paulus; Amar Gajjar; Giles W Robinson; Michael D Taylor; Zane Jaunmuktane; Marina Ryzhova; Michael Platten; Andreas Unterberg; Wolfgang Wick; Matthias A Karajannis; Michel Mittelbronn; Till Acker; Christian Hartmann; Kenneth Aldape; Ulrich Schüller; Rolf Buslei; Peter Lichter; Marcel Kool; Christel Herold-Mende; David W Ellison; Martin Hasselblatt; Matija Snuderl; Sebastian Brandner; Andrey Korshunov; Andreas von Deimling; Stefan M Pfister Journal: Nature Date: 2018-03-14 Impact factor: 49.962
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