title: Upfront chemotherapy and subsequent resection for molecularly defined gliomas.
abstract: Functional preservation is critical in glioma surgery, and the extent of resection influences survival outcome. Neoadjuvant chemotherapy is a promising option because of its potential to facilitate tumor shrinkage and maximum tumor resection. The object of this study was to assess the utility of the neoadjuvant strategy in a prospective series of gliomas with favorable molecular status. Twenty-six consecutive cases of diffuse gliomas of WHO grade II or III with either 1p19q codeletion or MGMT methylation were treated with upfront chemotherapy following maximal safe removal. In cases of incomplete initial surgery, second-look resection was intended after tumor volume decrease by chemotherapy. Among 22 evaluable cases, chemotherapy led to a median change in the sum of the product of perpendicular diameters of -35 %, and 14 out of the 22 cases (64 %) showed objective response. Second-look resection after tumor volume decrease was performed in 12 out of 19 cases of incomplete initial surgery (GTR/STR 9, removal of residual methionine PET uptake 3). The median progression-free survival among the 22 patients with grade II tumors was 57 months, with some cases showing durable progression-free survival after second-look resection. MIB-1 indices of the second-look resected tumors were lower than those of the initial tumors, and the methylation status of the MGMT gene was unchanged. Neoadjuvant chemotherapy based on molecular guidance often produces significant volume decrease of incompletely resected gliomas. Radical second-look resection is an optional advantage of upfront chemotherapy for chemosensitive gliomas compared with initial radiotherapy.
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan, hsasaki@keio.jp.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sasaki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hirose
authors.forename: Takahito
authors.initials: T
authors.lastname: Yazaki
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Katayama
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Toda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohira
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery*; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000627:therapeutic use; D011446:Prospective Studies; D000077204:Temozolomide; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide