Histopathological correlates with survival in reoperated glioblastomas

Abstract

The addition of concomitant and adjuvant chemotherapy to radiation therapy after surgical resection has increased significantly the survival of patients with glioblastoma (GB). In conjunction, there has been an increasing fraction of patients who present with new enlarged areas of contrast enhancement and edema on post-treatment imaging that improve without further treatment. It remains to be established how this phenomenon, commonly termed pseudoprogression, can be distinguished from true tumor recurrence defined as the histological presence of active high-grade tumor, as well as its prognostic significance. Data for over 500 patients undergoing surgery for recurrent GB were reviewed. Pathological specimens were categorized as those that contained active high-grade glioma in any amount, and those that did not. Patient survival was compared between these two groups, and independent associations were assessed using Cox proportionate hazards regression analysis. 59 patients met the study criteria including complete pathological and follow-up data. Mean age was 53 ± 11 years. Median survival from suspected recurrence and initial diagnosis were 8 [5–14] and 20 [12–30] months. Seventeen patients (29 %) had no evidence of active high-grade tumor and 42 (71 %) had at least focal active high-grade glioma. Pathologic pseudoprogression at re-operation (p = 0.03) and gross total resection (p = 0.01) were independently associated with survival. The histopathological features defined here and used to assess the tumor at reoperation were independently associated with survival. These findings may be important in designing treatment strategies and clinical trial endpoints for patients with GB.

5-ALA-induced fluorescence behavior of reactive tissue changes following glioblastoma treatment with radiation and chemotherapy

“…It cannot be excluded, that some of these MIB1-or p53-positive cells were interspersed residual glioma cells. However, in line with the study by Woodworth et al [22], these findings were not regarded as recurrent cellular glioma. None of the investigated tissue samples immunostained for the IDH1-R132H mutant protein contained positive tumor cells.…”

“…Although reliable preoperative differentiation between true tumor progression/recurrence and reactive changes in response to the previous treatment is not yet possible by standard imaging, intraoperative differentiation is important for surgical outcome; 5-AIF is considered to enable reliable differentiation of vital tumor tissue and regressive tissue such as scars, necrosis or gliosis [12]. However, there are only few studies about pseudoprogression that have included histopathological analysis, with the majority of these studies not clearly defining histopathological criteria for distinguishing treatment effects and reactive changes from active recurrent tumor [22]. The behavior of 5-AIF in reactive and regressive lesions without active tumor recurrence has yet to be investigated.…”

Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

“…In cancer patients, there is no reliable way of parsing out treatment effects from tumor recurrence, causing many patients to undergo unnecessary repeat surgeries. For example, in ∼30% of patients with glioblastoma who undergo a repeat resection for presumptive recurrence, pathologic examination of the resected specimen reveals necrosis, scarring, or other treatment-related effects rather than recurrent disease (20). Conversely, while patients are waiting for or recovering from surgery for suspicious lesions, chemotherapy or radiation therapy cannot be administered, providing time for unabated tumor growth.…”

Amide proton transfer-weighted magnetic resonance image-guided stereotactic biopsy in patients with newly diagnosed gliomas

“…In clinical practice, pathologic tissue analysis is required for diagnosis, and the results dictate the treatment strategy [2]. However, the heterogeneous characteristics of gliomas and their capacity for diffuse infiltration complicate the ability to accurately sample the highest-grade portion of tumor during diagnostic neurosurgical procedures.…”