Discriminating uninfected surgical bed cysts from bacterial brain abscesses after Carmustine wafer implantation in newly diagnosed IDH-wildtype glioblastomas

PurposeCarmustine wafers can be implanted in the surgical bed of high-grade gliomas, which can induce surgical bed cyst formation, leading to clinically relevant mass effect.MethodsAn observational retrospective monocentric study was conducted including 122 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent a surgical resection with Carmustine wafer implantation as first line treatment (2005–2018).FindingsTwenty-two patients (18.0%) developed a postoperative contrast-enhancing cyst within the surgical bed: 16 uninfected cysts and six bacterial abscesses. All patients with an uninfected surgical bed cyst were managed conservatively, all resolved on imaging follow-up, and no patient stopped the radiochemotherapy. Independent risk factors of formation of a postoperative uninfected surgical bed cyst were age ≥ 60 years (p = 0.019), number of Carmustine wafers implanted ≥ 8 (p = 0.040), and partial resection (p = 0.025). Compared to uninfected surgical bed cysts, the occurrence of a postoperative bacterial abscess requiring surgical management was associated more frequently with a shorter time to diagnosis from surgery (p = 0.009), new neurological deficit (p < 0.001), fever (p < 0.001), residual air in the cyst (p = 0.018), a cyst diameter greater than that of the initial tumor (p = 0.027), and increased mass effect and brain edema compared to early postoperative MRI (p = 0.024). Contrast enhancement (p = 0.473) and diffusion signal abnormalities (p = 0.471) did not differ between postoperative bacterial abscesses and uninfected surgical bed cysts.ConclusionsClinical and imaging findings help discriminate between uninfected surgical bed cysts and bacterial abscesses following Carmustine wafer implantation. Surgical bed cysts can be managed conservatively. Individual risk factors will help tailor their steroid therapy and imaging follow-up.

Symptomatic cerebral vasospasm in the setting of carmustine wafer placement for glioblastoma: A case presentation and review of literature

Background: Gliadel placement in glioblastoma resection, particularly with concurrent chemoradiation, has demonstrated an improvement in survival. There have been several reported adverse effects, some of which lend to significantly increased morbidity and mortality. With only two other cases described in literature, cerebral vasospasm secondary to carmustine-impregnated wafers is an extremely rare side effect. Case Description: We report the case of a 51-year-old female who presented with the left lower limb paresis 8 days after high-grade glioma resection provoked by carmustine wafer placement. Conclusion: We urge surgeons to reconsider placement of carmustine wafers in nations where the surgical resection cavity includes exposed large cerebral vasculature. We also propose the early identification of this devastating complication in the postoperative period by maintaining a high clinical suspicion and prompt utilization of computed tomography and digital subtraction angiography in the management and treatment of these patients accordingly.

ACT-25 CLINICAL TRIALS BY THE JCOG BRAIN TUMOR STUDY GROUP

Ongoing brain tumor clinical trials by the Japan Clinical Oncology Group (JCOG) are:JCOG1016, phase III randomized study in patients with anaplastic glioma of radiotherapy with temozolomide versus nimustine hydrochloride (ACNU) followed by temozolomide, is to prove superiority of post-operative radiotherapy with ACNU. JCOG1114, phase III study of high-dose methotrexate and whole brain radiotherapy with or without concomitant and adjuvant temozolomide in patients with primacy CNS lymphoma, is to prove usefulness and get insurance approval of TMZ for primary CNS lymphoma. JCOG1303, randomized phase III study for unresectable WHO Grade II diffuse astrocytoma with radiotherapy alone or chemoradiotherapy with temozolomide, is to prove superiority of STUPP regimen over simple radiotherapy for newly diagnosed and unresectable diffuse astrocytoma. JCOG1308, a multicenter randomized phase III study for recurrent glioblastoma comparing bevacizumab alone with dose-dense temozolomide followed by bevacizumab, is to prove usefulness of dose-dense, 7 days on/7 days off, TMZ, and to approve insurance coverage for recurrent GBM. JCOG1703, a multicenter randomized phase III study for newly-diagnosed maximally resected glioblastoma comparing carmustine wafer implantation followed by Stupp regimen with Stupp regimen alone, is to prove the survival advantage of surgery of GBM using carmustine wafer.

A multicenter randomized phase III study for newly diagnosed maximally resected glioblastoma comparing carmustine wafer implantation followed by chemoradiotherapy with temozolomide with chemoradiotherapy alone; Japan Clinical Oncology Group Study JCOG1703 (MACS study)

A randomized phase III trial in Japan commenced in June 2019. The present standard treatment for newly diagnosed glioblastoma is maximal resection followed by chemoradiotherapy with temozolomide. The purpose of this study is to confirm the superiority of maximal resection with carmustine wafer implantation followed by chemoradiotherapy with temozolomide over the standard maximal resection followed by chemoradiotherapy with temozolomide in terms of overall survival for newly diagnosed glioblastoma. A total of 250 patients will be accrued from 35 Japanese institutions in 5.5 years. Patients with &gt;90% surgical resection will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is overall survival and the secondary endpoints are progression-free survival, loco-regional progression-free survival and incidence of adverse events. This trial has been registered in the Japan Registry of Clinical Trial, as jRCT1031190035 [https://jrct.niph.go.jp/en-latest-detail/jRCT1031190035].