Michael Wahl1, Joanna J Phillips2,3, Annette M Molinaro3,4, Yi Lin3,5, Arie Perry2,3, Daphne A Haas-Kogan6, Joseph F Costello3, Manisha Dayal7, Nicholas Butowski3, Jennifer L Clarke3,8, Michael Prados3, Sarah Nelson7,8,9, Mitchel S Berger3, Susan M Chang3. 1. Department of Radiation Oncology, University of California, San Francisco, USA. 2. Department of Pathology, University of California, San Francisco, USA. 3. Department of Neurosurgery, University of California, San Francisco, USA. 4. Department of Epidemiology and Biostatistics, University of California, San Francisco , USA. 5. Department of Neurosurgery, First Affiliated Hospital of China Medical University, China. 6. Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 7. Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA. 8. Department of Neurology, University of California, San Francisco, USA. 9. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, USA.
Abstract
Background: Optimal adjuvant management of adult low-grade gliomas is controversial. Recently described tumor classification based on molecular subtype has the potential to individualize adjuvant therapy but has not yet been evaluated as part of a prospective trial. Methods: Patients aged 18 or older with newly diagnosed World Health Organization grade II low-grade gliomas and gross residual disease after surgical resection were enrolled in the study. Patients received monthly cycles of temozolomide for up to 1 year or until disease progression. For patients with available tissue, molecular subtype was assessed based upon 1p/19q codeletion and isocitrate dehydrogenase-1 R132H mutation status. The primary outcome was radiographic response rate; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Results: One hundred twenty patients were enrolled with median follow-up of 7.5 years. Overall response rate was 6%, with median PFS and OS of 4.2 and 9.7 years, respectively. Molecular subtype was associated with rate of disease progression during treatment (P<.001), PFS (P=.007), and OS (P<.001). Patients with 1p/19q codeletion demonstrated a 0% risk of progression during treatment. In an exploratory analysis, pretreatment lesion volume was associated with both PFS (P<.001) and OS (P<.001). Conclusions: While our study failed to meet the primary endpoint for objective radiographic response, patients with high-risk low-grade glioma receiving adjuvant temozolomide demonstrated a high rate of radiographic stability and favorable survival outcomes while meaningfully delaying radiotherapy. Patients with 1p/19q codeletion are potential candidates for omission of adjuvant radiotherapy, but further work is needed to directly compare chemotherapy with combined modality therapy.
Background: Optimal adjuvant management of adult low-grade gliomas is controversial. Recently described tumor classification based on molecular subtype has the potential to individualize adjuvant therapy but has not yet been evaluated as part of a prospective trial. Methods:Patients aged 18 or older with newly diagnosed World Health Organization grade II low-grade gliomas and gross residual disease after surgical resection were enrolled in the study. Patients received monthly cycles of temozolomide for up to 1 year or until disease progression. For patients with available tissue, molecular subtype was assessed based upon 1p/19q codeletion and isocitrate dehydrogenase-1 R132H mutation status. The primary outcome was radiographic response rate; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Results: One hundred twenty patients were enrolled with median follow-up of 7.5 years. Overall response rate was 6%, with median PFS and OS of 4.2 and 9.7 years, respectively. Molecular subtype was associated with rate of disease progression during treatment (P<.001), PFS (P=.007), and OS (P<.001). Patients with 1p/19q codeletion demonstrated a 0% risk of progression during treatment. In an exploratory analysis, pretreatment lesion volume was associated with both PFS (P<.001) and OS (P<.001). Conclusions: While our study failed to meet the primary endpoint for objective radiographic response, patients with high-risk low-grade glioma receiving adjuvant temozolomide demonstrated a high rate of radiographic stability and favorable survival outcomes while meaningfully delaying radiotherapy. Patients with 1p/19q codeletion are potential candidates for omission of adjuvant radiotherapy, but further work is needed to directly compare chemotherapy with combined modality therapy.
Authors: M Klein; J J Heimans; N K Aaronson; H M van der Ploeg; J Grit; M Muller; T J Postma; J J Mooij; R H Boerman; G N Beute; G J Ossenkoppele; G W van Imhoff; A W Dekker; J Jolles; B J Slotman; H Struikmans; M J B Taphoorn Journal: Lancet Date: 2002-11-02 Impact factor: 79.321
Authors: David E Reuss; Felix Sahm; Daniel Schrimpf; Benedikt Wiestler; David Capper; Christian Koelsche; Leonille Schweizer; Andrey Korshunov; David T W Jones; Volker Hovestadt; Michel Mittelbronn; Jens Schittenhelm; Christel Herold-Mende; Andreas Unterberg; Michael Platten; Michael Weller; Wolfgang Wick; Stefan M Pfister; Andreas von Deimling Journal: Acta Neuropathol Date: 2014-11-27 Impact factor: 17.088
Authors: M J van den Bent; J S Wefel; D Schiff; M J B Taphoorn; K Jaeckle; L Junck; T Armstrong; A Choucair; A D Waldman; T Gorlia; M Chamberlain; B G Baumert; M A Vogelbaum; D R Macdonald; D A Reardon; P Y Wen; S M Chang; A H Jacobs Journal: Lancet Oncol Date: 2011-04-05 Impact factor: 41.316
Authors: Matthew J McGirt; Kaisorn L Chaichana; Frank J Attenello; Jon D Weingart; Khoi Than; Peter C Burger; Alessandro Olivi; Henry Brem; Alfredo Quinoñes-Hinojosa Journal: Neurosurgery Date: 2008-10 Impact factor: 4.654
Authors: Roger Stupp; Monika E Hegi; Warren P Mason; Martin J van den Bent; Martin J B Taphoorn; Robert C Janzer; Samuel K Ludwin; Anouk Allgeier; Barbara Fisher; Karl Belanger; Peter Hau; Alba A Brandes; Johanna Gijtenbeek; Christine Marosi; Charles J Vecht; Karima Mokhtari; Pieter Wesseling; Salvador Villa; Elizabeth Eisenhauer; Thierry Gorlia; Michael Weller; Denis Lacombe; J Gregory Cairncross; René-Olivier Mirimanoff Journal: Lancet Oncol Date: 2009-03-09 Impact factor: 41.316
Authors: K Hoang-Xuan; L Capelle; M Kujas; S Taillibert; H Duffau; J Lejeune; M Polivka; E Crinière; Y Marie; K Mokhtari; A F Carpentier; F Laigle; J M Simon; P Cornu; P Broët; M Sanson; J Y Delattre Journal: J Clin Oncol Date: 2004-08-01 Impact factor: 44.544
Authors: Fumi Higuchi; Alexandria L Fink; Juri Kiyokawa; Julie J Miller; Mara V A Koerner; Daniel P Cahill; Hiroaki Wakimoto Journal: Mol Cancer Ther Date: 2018-09-14 Impact factor: 6.261
Authors: Felipe J Núñez; Flor M Mendez; Padma Kadiyala; Mahmoud S Alghamri; Masha G Savelieff; Maria B Garcia-Fabiani; Santiago Haase; Carl Koschmann; Anda-Alexandra Calinescu; Neha Kamran; Meghna Saxena; Rohin Patel; Stephen Carney; Marissa Z Guo; Marta Edwards; Mats Ljungman; Tingting Qin; Maureen A Sartor; Rebecca Tagett; Sriram Venneti; Jacqueline Brosnan-Cashman; Alan Meeker; Vera Gorbunova; Lili Zhao; Daniel M Kremer; Li Zhang; Costas A Lyssiotis; Lindsey Jones; Cameron J Herting; James L Ross; Dolores Hambardzumyan; Shawn Hervey-Jumper; Maria E Figueroa; Pedro R Lowenstein; Maria G Castro Journal: Sci Transl Med Date: 2019-02-13 Impact factor: 17.956
Authors: Michael Wahl; Susan M Chang; Joanna J Phillips; Annette M Molinaro; Joseph F Costello; Tali Mazor; Sanda Alexandrescu; Janine M Lupo; Sarah J Nelson; Mitchel Berger; Michael Prados; Jennie W Taylor; Nicholas Butowski; Jennifer L Clarke; Daphne Haas-Kogan Journal: Cancer Date: 2017-07-31 Impact factor: 6.860
Authors: C Izquierdo; A Alentorn; A Idbaih; M Simó; G Kaloshi; D Ricard; M Barritault; D Meyronet; J Bruna; J Honnorat; J Y Delattre; F Ducray Journal: J Neurooncol Date: 2017-11-15 Impact factor: 4.130