Initial and cumulative recurrence patterns of glioblastoma after temozolomide-based chemoradiotherapy and salvage treatment: a retrospective cohort study in a single institution

Kengo Ogura, Takashi Mizowaki, Yoshiki Arakawa, Masakazu Ogura, Katsuyuki Sakanaka, Susumu Miyamoto, Masahiro Hiraoka, Kengo Ogura, Takashi Mizowaki, Yoshiki Arakawa, Masakazu Ogura, Katsuyuki Sakanaka, Susumu Miyamoto, Masahiro Hiraoka

Abstract

Purpose: 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.

Figures

Figure 1
Figure 1
The target delineation method used in our hospital. GTV = gross target volume, CTV = clinical target volume, FLAIR = fluid-attenuated inversion recovery, HIA = high intensity area.
Figure 2
Figure 2
Overall survival and progression-free survival. Overall survival (OS) and progression-free survival (PFS) of 21 recurrent patients were estimated using the Kaplan-Meier method.
Figure 3
Figure 3
Summary of initial and cumulative recurrence patterns. Initial and cumulative recurrence patterns in 21 and 16 recurrent patients, respectively. The red bars indicate initial recurrences and the blue bars cumulative recurrences.
Figure 4
Figure 4
Examples of recurrence patterns. Examples of recurrence patterns on T1-weighted magnetic resonance imaging with contrast: central (a), in-field (b), marginal (c), out-field (d), and distant recurrences (e). Red contours indicate recurrent tumors. Green and yellow lines indicate 95% isodose lines of 60 Gy and 50 Gy, respectively.

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