Faculty Bibliography

PURPOSE: To retrospectively correlate various diffusion tensor imaging (DTI) metrics in patients with glioblastoma multiforme (GBM) with patient survival analysis and also degree of tumor proliferation index determined histologically. MATERIALS AND METHODS: Thirty-four patients with histologically confirmed treatment naive GBMs underwent DTI on a 3.0 Tesla (T) scanner. Region-of-interest was placed on the whole lesion including the enhancing as well as nonenhancing component of the lesion to determine the various DTI metrics. Kaplan-Meier estimates and Cox proportional hazards regression methods were used to assess the relationship of DTI metrics (minimum and mean values) and Ki-67 with progression free survival (PFS). To study the relationship between DTI metrics and Ki-67, Pearson's correlation coefficient was computed. RESULTS: Univariate analysis showed that patients with fractional anisotropy (FA)(mean) 0.68 and Ki-67 > 0.3 had lower PFS rate. The multivariate analysis demonstrated that only CP(min) was the best predictor of survival in these patients, after adjusting for age, Karnofsky performance scale and extent of resection. No significant correlation between DTI metrics and Ki-67 were observed. CONCLUSION: DTI metrics can be used as a sensitive and early indicator for PFS in patients with glioblastomas. This could be useful for treatment planning as high-grade gliomas with lower ADC(min), FA(mean), CP(min), and higher CS(mean) values may be treated more aggressively.

Brain tumor patients undergo various combinations therapies, leading to very complex and confusing imaging appearances on follow up MR imaging and hence, differentiating recurrent or progressing tumors from treatment induced necrosis or effects has always been a challenge in neuro-oncologic imaging. This particular topic has become more relevant these days because of the advent of newer anti-angiogenic and anti-neoplastic chemotherapeutic agents as well as use of salvage radiation therapy. Various clinically available functional imaging modalities can provide additional physiologic and metabolic information about the tumors which could be useful in identifying viable tumor from treatment induced necrosis and hence, can guide treatment planning. In this review we will discuss various functional neuro-imaging modalities, their advantages and limitations and also their utility in treatment planning.

After withdrawal of bevacizumab in patients with recurrent high-grade glioma, we have observed a rapid tumour re-growth or "rebound" radiographic phenomenon with accelerated clinical decline. We retrospectively reviewed 11 patients treated at the Henry Ford Hermelin Brain Tumor Center with recurrent high-grade glioma who demonstrated a rebound progression pattern after the discontinuation of bevacizumab. The original tumour area-of-enhancement increased by a mean of 158%, when compared to the rebound magnetic resonance imaging. After rebound, no patients (0/8) showed a response to next-line treatments that did not include bevacizumab. The median survival of those re-treated with bevacizumab was 149 and 32 days for those who received other regimens. Abrupt discontinuation of bevacizumab after recurrence often leads to a dramatic rebound phenomenon and rapid clinical decline. Slow tapering of the bevacizumab dose after tumour progression may prevent this from occurring and improve responsiveness to next-line therapies.

Stereotactic Radiotherapy (SRT) is more commonly used for skull base tumors in conjunction with the technical development of radiation intensity modulation. Purpose of this study is to correlate clinical and radiographic characteristics of delayed radiation injury (RI) occurring around central skull base following SRT with SRT dosimetric data. Total of six patients were identified to have developed RI in the vicinity of SRT target volume out of 141 patients who received SRT in he center or near-center of the skull base. The images and medical records were retrospectively reviewed. The analysis was performed for RI location, time of development, imaging and clinical characteristics and evolution of RI and correlated with SRT dosimetric analysis using image fusion with follow-up MRI scans. Mean follow-up time was 24 +/- 9 months. During the follow-up period, twelve sites of RI were found in 6 patients. They were clinically symptomatic in 4/6 patients (66.6%) at median 12.5 months after SRT. Mean time interval between SRT and detection of RI was 9 +/- 3, 18.5 +/- 5, and 13.5 months for brainstem, temporal lobe, and cerebellum/labyrinth lesions, respectively. All RI lesions were included in the region of high SRT doses. After steroid and symptomatic treatment, 50% of RI lesions showed complete response, and 40% showed partial response. RI can occur around the skull base because of irregular shape of target tumor, its close proximity to normal brain parenchyma, and inhomogeneity of dose distribution. Brainstem lesions occurred earlier than temporal lobe RI. The majority of the RI lesions, not mixed with the tumor in this study, showed radiographic and clinical improvement with steroid and symptomatic treatments.

BACKGROUND: Surgical decompression of metastatic epidural compression (MEC) improved ambulatory function. Spine radiosurgery can accurately target the epidural tumor and deliver high radiation doses for tumor control. Therefore, a clinical trial was performed to quantitatively determine the degree of epidural decompression by radiosurgery of metastatic epidural compression. METHODS: Sixty-two patients with a total of 85 lesions of metastatic epidural compression were treated. Epidural compression was diagnosed by magnetic resonance imaging (MRI) scans. Main criteria of inclusion were neurological status with muscle power 4 of 5 or better. Radiosurgery was performed to the involved spine segment, including the epidural mass with median dose of 16 Gy (range 12-20 Gy) in a single session. All patients had prospective clinical follow-up, ranging from 1-48 months (median 11.5 months), and 36 patients had pretreatment and post-treatment imaging, ranging from 2-33 months (median 9.3 months). Primary endpoints were epidural tumor control and thecal sac decompression. RESULTS: The mean epidural tumor volume reduction was 65 +/- 14% at 2 months after radiosurgery. The epidural tumor area at the level of the most severe spinal cord compression was 0.82 +/- 0.08 cm(2) before radiosurgery and 0.41 +/- 0.06 cm(2) after radiosurgery (P < .001). Thecal sac patency improved from 55 +/- 4% to 76 +/- 3% (P < .001). Overall, neurological function improved in 81%. CONCLUSIONS: This study demonstrated a radiosurgical decompression of epidural tumor. Although neurosurgical decompression and radiotherapy is the standard treatment in patients with good performance, radiosurgical decompression can be a viable noninvasive treatment option for malignant epidural compression.

Bevacizumab and irinotecan are effective against recurrent malignant gliomas. However, at subsequent progression, patients rarely respond to a second bevacizumab-containing chemotherapeutic regimen. Salvage re-irradiation with bevacizumab for recurrent but bevacizumab naive malignant gliomas showed encouraging results. We performed a retrospective review of the medical records of 23 patients treated with either fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS) after progression on an initial bevacizumab regimen. Patients were treated after re-irradiation with bevacizumab but combined with a different chemotherapy. We then compared them to another 23 patients who progressed on an initial bevacizumab + chemotherapy regimen. These patients did not receive re-irradiation but bevacizumab was continued combined with a different chemotherapy. Patients treated with FSRT/SRS/bevacizumab had a longer median progression-free period (2.6 vs. 1. 7 months, P = 0.009), longer median post FSRT/SRS treatment survival (7.2 vs. 3.3 months, P = 0.03) and higher radiographic response rate (22 vs. 0%, P = 0.049). FSRT or SRS followed by bevacizumab + chemotherapy may have a role for patients who progress on bevacizumab.

Tumefactive demyelinating lesions (TDLs) can mimic a neoplasm on conventional imaging and may necessitate biopsy for diagnosis. The purpose of this study was to differentiate TDLs from high grade gliomas based on physiologic (permeability) and hemodynamic (blood volume) parameters using perfusion CT. Five patients who presented with tumefactive enhancing lesions on initial MRI that mimicked a neoplasm underwent perfusion CT. We compared the perfusion CT parameters of these patients with those of 24 patients with high grade gliomas. TDLs showed lower permeability surface area product (PS) (0.8 +/- 0.2 vs 2.4 +/- 1.4 ml/100 g/min, P-value 0.014) and lower cerebral blood volume (CBV) (1.0 +/- 0.2 vs 2.8 +/- 1.2 ml/100 g, P-value 0.006) as compared to high grade gliomas. TDLs show lower PS and CBV as compared to high grade gliomas, to which they can mimic on conventional MR imaging, due to lack of neoangiogenesis and vascular endothelial proliferation and hence perfusion CT can be used to differentiate the two entities.

The purpose of this study was to assess the usefulness of diffusion weighted imaging as an additional imaging biomarker for treatment response in recurrent/progressive malignant gliomas treated with bevacizumab alone or in combination with other chemotherapeutic agents. Twenty patients treated with bevacizumab alone or concurrent chemotherapy were followed up with serial MR imaging. Volume and ADC values of contrast enhancing lesion (CEL(vol), CEL(ADC)) and also of non-enhancing lesion (NEL(vol), NEL(ADC)) were obtained. CEL(vol) showed a progressive decrease in non-progressors with a median percentage change of -73.2% (P = 0.001) as compared to -33.4% for progressors by 1 year/last imaging (P = 0.382). NEL(vol) also showed a decrease in non-progressors on follow up imaging though only significant for 3 months follow up (P = 0.042). In progressors, CEL(vol) and NEL(vol) showed initial decrease followed by slight increase by 1 year/last imaging though not significant (P value of 0.382 and 0.46, respectively). CEL(ADC) and NEL(ADC) in non-progressors did not show any statistically significant change though there was slight trend for positive percent change especially for CEL(ADC) by 1 year/last imaging follow up study (P value of 0.077 and 0.339, respectively). Progressors showed a progressive negative percent change of CEL(ADC) and NEL(ADC). In progressors, NEL(ADC) decreased at 6 weeks (P = 0.054), 3 months (P = 0.023) and 1 year/last (P = 0.078) as compared to baseline study and was also statistically significant as compared to non-progressors at 6 weeks (P = 0.047) and 3 months (P = 0.025). CEL(ADC) and NEL(ADC) appear to follow different trends over time for non-progressors and progressors with a stable to slightly progressive increase in non-progressors and a progressive decrease in progressors, especially early on. These findings suggest that DWI may be used as an additional imaging biomarker for early treatment response.