Initial and cumulative recurrence patterns of glioblastoma after temozolomide-based chemoradiotherapy and salvage treatment: a retrospective cohort study in a single institution.
OBJECTIVE
To analyze initial recurrence patterns in patients with newly diagnosed glioblastoma after radiotherapy plus concurrent and adjuvant temozolomide, and to investigate cumulative recurrence patterns after salvage treatment, including surgery, stereotactic radiotherapy, and chemotherapy.


METHODS
Twenty-one patients with glioblastoma that recurred after concurrent temozolomide and localized radiotherapy were retrospectively analyzed (11 male, 10 female; median age, 57 years; range, 27-74). Disease progression was assessed by new response criteria proposed by the Response Assessment in Neuro-Oncology Working Group of the American Society of Clinical Oncology. The pattern of recurrence was determined by relationships between locations of recurrent tumors and irradiated doses. Central, in-field, marginal, and out-field recurrences were defined relative to the prescribed isodose line. Distant recurrence was operationally defined as subependymal or disseminated disease. Initial and cumulative patterns of recurrence were evaluated in each patient.


RESULTS
The median follow-up of the recurrent patients was 501 (range, 217-1815) days after initial surgery. Initial recurrences were central in 14 patients (66.7%), in-field in four patients (19.0%), marginal in no patient (0%), out-field in two patients (9.5%), and distant in four patients (19.0%). One patient had both central and in-field recurrences simultaneously, and two had both central and distant recurrences. In the analysis of cumulative recurrence patterns, five patients, who had no scans after initial recurrences, were excluded and the remaining 16 were included. Cumulative recurrences were central in 11 patients (68.8%), in-field in five patients (31.3%), marginal in three patients (18.8%), out-field in five patients (31.3%), and distant in 14 patients (87.5%). Regarding salvage treatments, 11 (52.4%), 11 (52.4%) and 17 (81.0%) patients underwent surgery, stereotactic radiotherapy and chemotherapy, respectively. Eighteen (85.7%) patients had died at the time of analysis, and 16 of them (88.9%) had suffered distant recurrences, which could have been the immediate causes of death.


CONCLUSIONS
Recurrence patterns of glioblastoma after radiotherapy plus concomitant and adjuvant temozolomide were mainly central at first, and distant recurrences were often detected during the clinical course. Much better local control and prevention of distant recurrence, including effective salvage treatment, seem to be important.
Kengo
K
Ogura
Departments of Radiation Oncology and Image-applied Therapy, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto 606-8507, Japan. mizo@kuhp.kyoto-u.ac.jp.
Takashi
T
Mizowaki
Yoshiki
Y
Arakawa
Masakazu
M
Ogura
Katsuyuki
K
Sakanaka
Susumu
S
Miyamoto
Masahiro
M
Hiraoka
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D059248:Chemoradiotherapy; D015331:Cohort Studies; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies; D016879:Salvage Therapy; D000077204:Temozolomide
D000970:Antineoplastic Agents; D003606:Dacarbazine; D000077204:Temozolomide