Antonio Dono1,2, Kristin Alfaro-Munoz3, Yuanqing Yan1, Carlos A Lopez-Garcia2, Zaid Soomro3, Garret Williford3, Takeshi Takayasu2, Lindsay Robell3, Nazanin K Majd3, John de Groot3, Yoshua Esquenazi1,4,5, Carlos Kamiya-Matsuoka3, Leomar Y Ballester1,2,5. 1. Vivian L. Smith Department of Neurosurgery, School of Biomedical Informatics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA. 2. Department of Pathology and Laboratory Medicine, School of Biomedical Informatics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA. 3. Department of Neuro-Oncology, MD Anderson Cancer Center, Houston, Texas, USA. 4. Center of Precision Health, School of Biomedical Informatics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA. 5. Memorial Hermann Hospital, Houston, Texas, USA.
Abstract
BACKGROUND: Reports suggest that phosphatidylinositol 3-kinase pathway alterations confer increased risk of progression and poor prognosis in oligodendroglioma, IDH-mutant, and 1p/19q-codeleted molecular oligodendrogliomas (mODG). However, factors that affect prognosis in mODG have not been thoroughly studied. In addition, the benefits of adjuvant radiation and temozolomide (TMZ) in mODGs remain to be determined. OBJECTIVE: To evaluate the role of PIK3CA mutations in mODGs. METHODS: One hundred seven mODGs (2008-2019) diagnosed at 2 institutions were included. A retrospective review of clinical characteristics, molecular alterations, treatments, and outcomes was performed. RESULTS: The median age was 37 years, and 61 patients (57%) were male. There were 64 (60%) World Health Organization (WHO) grade 2 and 43 (40%) WHO grade 3 tumors. Eighty-two patients (77%) were stratified as high risk (age 40 years or older and/or subtotal resection per Radiation Treatment Oncology Group-9802). Gross-total resection was achieved in 47 patients (45%). Treatment strategies included observation (n = 15), TMZ (n = 11), radiation (n = 13), radiation/TMZ (n = 62), and others (n = 6). Our results show a benefit of TMZ vs observation in progression-free survival (PFS). No difference in PFS or overall survival (OS) was observed between radiation and radiation/TMZ. PIK3CA mutations were detected in 15 (14%) mODG, and shorter OS was observed in PIK3CA-mutant compared with PIK3CA wild-type mODGs (10.7 years vs 15.1 years, P = .009). WHO grade 3 tumors showed a shorter PFS, but no significant difference in OS was observed between WHO grades. CONCLUSION: Our findings suggest that mODGs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS with TMZ treatment, adjuvant TMZ, radiation, or a combination of the two showed no significant improvement in OS.
BACKGROUND: Reports suggest that phosphatidylinositol 3-kinase pathway alterations confer increased risk of progression and poor prognosis in oligodendroglioma, IDH-mutant, and 1p/19q-codeleted molecular oligodendrogliomas (mODG). However, factors that affect prognosis in mODG have not been thoroughly studied. In addition, the benefits of adjuvant radiation and temozolomide (TMZ) in mODGs remain to be determined. OBJECTIVE: To evaluate the role of PIK3CA mutations in mODGs. METHODS: One hundred seven mODGs (2008-2019) diagnosed at 2 institutions were included. A retrospective review of clinical characteristics, molecular alterations, treatments, and outcomes was performed. RESULTS: The median age was 37 years, and 61 patients (57%) were male. There were 64 (60%) World Health Organization (WHO) grade 2 and 43 (40%) WHO grade 3 tumors. Eighty-two patients (77%) were stratified as high risk (age 40 years or older and/or subtotal resection per Radiation Treatment Oncology Group-9802). Gross-total resection was achieved in 47 patients (45%). Treatment strategies included observation (n = 15), TMZ (n = 11), radiation (n = 13), radiation/TMZ (n = 62), and others (n = 6). Our results show a benefit of TMZ vs observation in progression-free survival (PFS). No difference in PFS or overall survival (OS) was observed between radiation and radiation/TMZ. PIK3CA mutations were detected in 15 (14%) mODG, and shorter OS was observed in PIK3CA-mutant compared with PIK3CA wild-type mODGs (10.7 years vs 15.1 years, P = .009). WHO grade 3 tumors showed a shorter PFS, but no significant difference in OS was observed between WHO grades. CONCLUSION: Our findings suggest that mODGs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS with TMZ treatment, adjuvant TMZ, radiation, or a combination of the two showed no significant improvement in OS.
Authors: Barbara J Fisher; Stephanie L Pugh; David R Macdonald; Arnab Chakravatri; Glenn J Lesser; Sherry Fox; C Leland Rogers; Maria Werner-Wasik; Thomas Doyle; Jean-Paul Bahary; John B Fiveash; Joseph A Bovi; Steven P Howard; Hsiang-Hsuan Michael Yu; David D'Souza; Nadia N Laack; Igor J Barani; Young Kwok; Daniel R Wahl; Jon F Strasser; Minhee Won; Minesh P Mehta Journal: Int J Radiat Oncol Biol Phys Date: 2020-04-03 Impact factor: 7.038
Authors: Linda Douw; Martin Klein; Selene Saa Fagel; Josje van den Heuvel; Martin Jb Taphoorn; Neil K Aaronson; Tjeerd J Postma; W Peter Vandertop; Jacob J Mooij; Rudolf H Boerman; Guus N Beute; Jasper D Sluimer; Ben J Slotman; Jaap C Reijneveld; Jan J Heimans Journal: Lancet Neurol Date: 2009-08-07 Impact factor: 44.182
Authors: Paul A Harris; Robert Taylor; Brenda L Minor; Veida Elliott; Michelle Fernandez; Lindsay O'Neal; Laura McLeod; Giovanni Delacqua; Francesco Delacqua; Jacqueline Kirby; Stephany N Duda Journal: J Biomed Inform Date: 2019-05-09 Impact factor: 6.317
Authors: Daniel J Brat; Kenneth Aldape; Howard Colman; Eric C Holland; David N Louis; Robert B Jenkins; B K Kleinschmidt-DeMasters; Arie Perry; Guido Reifenberger; Roger Stupp; Andreas von Deimling; Michael Weller Journal: Acta Neuropathol Date: 2018-09-26 Impact factor: 17.088
Authors: Wolfgang Wick; Patrick Roth; Christian Hartmann; Peter Hau; Makoto Nakamura; Florian Stockhammer; Michael C Sabel; Antje Wick; Susanne Koeppen; Ralf Ketter; Peter Vajkoczy; Ilker Eyupoglu; Rolf Kalff; Torsten Pietsch; Caroline Happold; Norbert Galldiks; Friederike Schmidt-Graf; Michael Bamberg; Guido Reifenberger; Michael Platten; Andreas von Deimling; Christoph Meisner; Benedikt Wiestler; Michael Weller Journal: Neuro Oncol Date: 2016-07-01 Impact factor: 12.300
Authors: Ahmet Zehir; Ryma Benayed; Ronak H Shah; Aijazuddin Syed; Sumit Middha; Hyunjae R Kim; Preethi Srinivasan; Jianjiong Gao; Debyani Chakravarty; Sean M Devlin; Matthew D Hellmann; David A Barron; Alison M Schram; Meera Hameed; Snjezana Dogan; Dara S Ross; Jaclyn F Hechtman; Deborah F DeLair; JinJuan Yao; Diana L Mandelker; Donavan T Cheng; Raghu Chandramohan; Abhinita S Mohanty; Ryan N Ptashkin; Gowtham Jayakumaran; Meera Prasad; Mustafa H Syed; Anoop Balakrishnan Rema; Zhen Y Liu; Khedoudja Nafa; Laetitia Borsu; Justyna Sadowska; Jacklyn Casanova; Ruben Bacares; Iwona J Kiecka; Anna Razumova; Julie B Son; Lisa Stewart; Tessara Baldi; Kerry A Mullaney; Hikmat Al-Ahmadie; Efsevia Vakiani; Adam A Abeshouse; Alexander V Penson; Philip Jonsson; Niedzica Camacho; Matthew T Chang; Helen H Won; Benjamin E Gross; Ritika Kundra; Zachary J Heins; Hsiao-Wei Chen; Sarah Phillips; Hongxin Zhang; Jiaojiao Wang; Angelica Ochoa; Jonathan Wills; Michael Eubank; Stacy B Thomas; Stuart M Gardos; Dalicia N Reales; Jesse Galle; Robert Durany; Roy Cambria; Wassim Abida; Andrea Cercek; Darren R Feldman; Mrinal M Gounder; A Ari Hakimi; James J Harding; Gopa Iyer; Yelena Y Janjigian; Emmet J Jordan; Ciara M Kelly; Maeve A Lowery; Luc G T Morris; Antonio M Omuro; Nitya Raj; Pedram Razavi; Alexander N Shoushtari; Neerav Shukla; Tara E Soumerai; Anna M Varghese; Rona Yaeger; Jonathan Coleman; Bernard Bochner; Gregory J Riely; Leonard B Saltz; Howard I Scher; Paul J Sabbatini; Mark E Robson; David S Klimstra; Barry S Taylor; Jose Baselga; Nikolaus Schultz; David M Hyman; Maria E Arcila; David B Solit; Marc Ladanyi; Michael F Berger Journal: Nat Med Date: 2017-05-08 Impact factor: 53.440
Authors: Mehdi Touat; Yvonne Y Li; Adam N Boynton; Liam F Spurr; J Bryan Iorgulescu; Craig L Bohrson; Isidro Cortes-Ciriano; Cristina Birzu; Jack E Geduldig; Kristine Pelton; Mary Jane Lim-Fat; Sangita Pal; Ruben Ferrer-Luna; Shakti H Ramkissoon; Frank Dubois; Charlotte Bellamy; Naomi Currimjee; Juliana Bonardi; Kenin Qian; Patricia Ho; Seth Malinowski; Leon Taquet; Robert E Jones; Aniket Shetty; Kin-Hoe Chow; Radwa Sharaf; Dean Pavlick; Lee A Albacker; Nadia Younan; Capucine Baldini; Maïté Verreault; Marine Giry; Erell Guillerm; Samy Ammari; Frédéric Beuvon; Karima Mokhtari; Agusti Alentorn; Caroline Dehais; Caroline Houillier; Florence Laigle-Donadey; Dimitri Psimaras; Eudocia Q Lee; Lakshmi Nayak; J Ricardo McFaline-Figueroa; Alexandre Carpentier; Philippe Cornu; Laurent Capelle; Bertrand Mathon; Jill S Barnholtz-Sloan; Arnab Chakravarti; Wenya Linda Bi; E Antonio Chiocca; Katie Pricola Fehnel; Sanda Alexandrescu; Susan N Chi; Daphne Haas-Kogan; Tracy T Batchelor; Garrett M Frampton; Brian M Alexander; Raymond Y Huang; Azra H Ligon; Florence Coulet; Jean-Yves Delattre; Khê Hoang-Xuan; David M Meredith; Sandro Santagata; Alex Duval; Marc Sanson; Andrew D Cherniack; Patrick Y Wen; David A Reardon; Aurélien Marabelle; Peter J Park; Ahmed Idbaih; Rameen Beroukhim; Pratiti Bandopadhayay; Franck Bielle; Keith L Ligon Journal: Nature Date: 2020-04-15 Impact factor: 49.962