Komal Shah

Impact of intraoperative high-field magnetic resonance imaging guidance on glioma surgery: a prospective volumetric analysis.

OBJECTIVETo determine the impact of intraoperative magnetic resonance imaging (iMRI) on the decision to proceed with additional glioma resection during surgery and to maximize extent of resection (EOR). METHODSPatients who underwent craniotomy for glioma resection with high-field iMRI guidance were prospectively evaluated between September 2006 and August 2007. Volumetric analysis and EOR were assessed with iMRI, using postcontrast T1-weighted images for tumors showing contrast enhancement and T2-weighted images for nonenhancing tumors. RESULTSForty-six patients underwent resection using iMRI guidance, with iMRI being used to evaluate the EOR in 44 patients and for reregistration in 2 patients. Surgery was terminated after iMRI in 23 patients (52%) because gross total resection was achieved or because of residual tumor infiltration in an eloquent brain region. Twenty-one patients (47%) underwent additional resection of residual tumor after iMRI. For enhancing gliomas, the median EOR increased significantly from 84% (range, 59%–97%) to 99% (range, 85%–100%) with additional tumor removal after iMRI (P < 0.001). For nonenhancing gliomas, the median EOR increased (from 63% to 80%) with additional tumor removal after iMRI, but not significantly, owing to the small sample size (7 patients). Overall, the EOR increased from 76% (range, 35%–97%) to 96% (range, 48%–100%) (P < 0.001). Gross total resection was achieved after additional tumor removal after iMRI in 15 of 21 patients (71%). Overall, 29 patients (65%) experienced gross total resection, and in 15 (52%), this was achieved with the contribution of iMRI. CONCLUSIONHigh-field iMRI is a safe and reliable technique, and its use optimizes the extent of glioma resection.

Efficacy and Tolerability of Vemurafenib in Patients with BRAFV600E -Positive Papillary Thyroid Cancer: M.D. Anderson Cancer Center Off Label Experience

CONTEXT Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation. OBJECTIVE To determine the efficacy and safety of vemurafenib when used outside of a clinical trial. DESIGN A retrospective review at MD Anderson Cancer Center. METHODS The best responses were evaluated using RECIST v1.1. A single radiologist reviewed all images. Adverse events (AEs) were evaluated using CTCAE v.4.0. RESULTS We identified 17 patients with advanced PTC harboring the BRAF(V600E) mutation who were treated with vemurafenib outside of a clinical trial. Median age at diagnosis was 63 years, and 53% were male. At vemurafenib start, 3 (18%) patients had disease confined to the neck, and 14 (72%) had distant metastases. Tyrosine kinase inhibitors had been previously administered to 4 (24%) patients. Two (12%) patients discontinued vemurafenib because of AEs before restaging. Best response: partial response (PR) in 7/15 (47%) and stable disease (SD) in 8/15(53%) patients. The rate of durable response (PR plus SD ≥ 6 months) was 67%. Median time to treatment failure was 13 months. There was no association between change in thyroglobulin and tumor size. Drug discontinuation, drug interruptions, and dose reductions were needed in 5 (29%), 13 (76%), and 10 (59%) patients, respectively. Most common AEs were fatigue (71%), weight loss (71%), anorexia (65%), arthralgias (59%), hair loss (59%), rash (59%), hand-foot syndrome (53%), calluses (47%), diarrhea (47%), fever (41%), dry mouth (35%), nausea (35%), and verrucous keratosis (35%). Grade ≥ 3 AEs were present in 8 (47%) patients. CONCLUSIONS Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation. Our results are similar to those reported in a phase II clinical trial and support the potential role of vemurafenib in this patient population.

Subcortical injury is an independent predictor of worsening neurological deficits following awake craniotomy procedures.

BACKGROUND Tailored craniotomies for awake procedures limit cortical exposure. Recently we demonstrated that the identification of eloquent areas increased the risk of postoperative deficits. However, it was not clear whether the observed neurological deficits were caused by proximity of functional cortex to the tumor [cortical injury] or subcortical injury. OBJECTIVE We hypothesize that subcortical injury during tumor resection is an important predictor of postoperative neurological deficits compared to cortical injury. METHODS A retrospective review of 214 patients undergoing awake craniotomy was carried out in whom preoperative functional magnetic resonance imaging (fMRI) and cortical mapping (CM) were performed. A radiologist blinded to the clinical data reviewed and graded the postoperative changes on diffusion-weighted MR-imaging (DWI). RESULTS Of the 40 cases who developed new intraoperative neurological deficit, 36 (90%) occurred during subcortical dissection, 3 (7.5%) during both subcortical and cortical dissection, and 1 (2.5%) during cortical dissection. Neurological dysfunction acquired during subcortical dissection was an independent predictor of postoperative deficits both in the immediate postoperative period (P < .001) and at the 3-month follow-up (P < .001). Significant DWI restriction in the subcortical white matter was predictive of neurological deficits both immediately and at 3 months, P = .011 and P < .001, respectively. New or worsening deficits were seen in 38% of patients; however, at 3 months 13% had a mild persistent neurological deficit. CONCLUSION Subcortical injury with significant DWI changes result in postoperative neurological decline despite our efforts to preserve cortical areas of function. This underscores the importance of preserving subcortical fiber tracts during awake craniotomy procedures.

Spontaneous involution of Rathke cleft cysts: Is it rare or just underreported? Report of 9 cases

Rathke cleft cysts (RCCs) are benign cystic lesions of the sella that arise from the remnants of Rathke pouch. Although most are asymptomatic, symptoms can result from mass effect and commonly include headache, endocrinopathy, or visual field disturbance. Although asymptomatic patients undergo conservative treatment, patients with symptoms are typically treated surgically. The authors report 9 patients with symptomatic cystic sellar lesions and imaging characteristics consistent with an RCC; in all cases there was spontaneous involution of the lesions, and in 5 of 7 patients presenting with headache the symptom resolved. Spontaneous involution of an RCC may be more common than the paucity of prior reports would suggest, especially because the natural history of both symptomatic and asymptomatic RCCs is poorly understood. The potential for spontaneous involution, together with the clinical course of the patients reported here, supports a conservative approach for patients with symptomatic RCCs presenting solely with headache.

Impact of preoperative functional magnetic resonance imaging during awake craniotomy procedures for intraoperative guidance and complication avoidance

Background: We wanted to study the role of functional MRI (fMRI) in preventing neurological injury in awake craniotomy patients as this has not been previously studied. Objectives: To examine the role of fMRI as an intraoperative adjunct during awake craniotomy procedures. Methods: Preoperative fMRI was carried out routinely in 214 patients undergoing awake craniotomy with direct cortical stimulation (DCS). Results: In 40% of our cases (n = 85) fMRI was utilized for the intraoperative localization of the eloquent cortex. In the other 129 cases significant noise distortion, poor task performance and nonspecific BOLD activation precluded the surgeon from using the fMRI data. Compared with DCS, fMRI had a sensitivity and specificity, respectively, of 91 and 64% in Brocas area, 93 and 18% in Wernickes area and 100 and 100% in motor areas. A new intraoperative neurological deficit during subcortical dissection was predictive of a worsened deficit following surgery (p < 0.001). The use of fMRI for intraoperative localization was, however, not significant in preventing worsened neurological deficits, both in the immediate postoperative period (p = 1.00) and at the 3-month follow-up (p = 0.42). Conclusions: The routine use of fMRI was not useful in identifying language sites as performed and, more importantly, practiced tasks failed to prevent neurological deficits following awake craniotomy procedures.

The role of imaging in the management of patients with nonmelanoma skin cancer: When is imaging necessary?

&NA; When treating aggressive skin cancers, pre‐ and postoperative imaging provides important information for treatment planning and multidisciplinary cooperation of care. It is important for dermatologists to recognize the clinical scenarios where imaging is indicated in the management of skin cancer. We here address the most common indications for imaging in cutaneous oncology and how to best utilize the modalities available.

The role of imaging in the management of patients with nonmelanoma skin cancer: Diagnostic modalities and applications

While uncomplicated cases of nonmelanoma skin cancer can be treated with surgery, destruction, or topical therapy alone, advanced or neglected cases require more complex management decisions. Dermatologists and dermatologic surgeons should be familiar with the imaging techniques relevant to cutaneous oncology and their value in different clinical scenarios. Herein we review imaging modalities used in management of nonmelanoma skin cancer.

Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

Comparison of gadolinium-enhanced fat-saturated T1-weighted FLAIR and fast spin-echo MRI of the spine at 3 T for evaluation of extradural lesions

OBJECTIVE Inversion recovery has been used to correct the loss of CSF and tissue contrast at 3 T versus 1.5 T but has not been formally investigated in the spine after IV administration of gadolinium-based contrast agent. The purpose of this study is to compare two sequences for gadolinium-enhanced spine imaging at 3 T--fat-saturated T1-weighted FLAIR and fat-saturated T1-weighted fast spin-echo (FSE)--for evaluation of extradural lesions and CSF-cord contrast. MATERIALS AND METHODS After IV administration of gadolinium-based contrast agent, fat-saturated T1-weighted FSE and FLAIR sequences were obtained in 156 MRI scans of 143 patients at 3 T. Three experienced radiologists compared these sequences for conspicuity differences in bone lesions, disk lesions, other epidural lesions, and cord-CSF contrast. A 7-point visual rating scale was used, with lower numbers indicating increased conspicuity on gadolinium-enhanced fat-saturated T1-weighted FLAIR and higher numbers indicating increased conspicuity on gadolinium-enhanced fat-saturated T1-weighted FSE. RESULTS A slight increase in the conspicuity of gadolinium-enhancing bone lesions (mean score, 3.6; p < 0.0001), disk lesions (mean score, 3.5; p < 0.0001), and epidural lesions (mean score, 3.4; p < 0.0001) was seen on fat-saturated T1-weighted FLAIR compared with fat-saturated T1-weighted FSE. A higher degree of contrast between the spinal cord and CSF was seen on fat-saturated T1-weighted FLAIR, by a large margin (mean score, 1.8; p < 0.0001). All enhancing lesions seen on fat-saturated T1-weighted FSE images were also seen on fat-saturated T1-weighted FLAIR images. CONCLUSION Decreased CSF-cord contrast at 3 T, as seen on T1-weighted FSE, can be regained by using T1-weighted FLAIR. Fat-saturated T1-weighted FLAIR may increase conspicuity of gadolinium-enhancing extradural lesions compared with fat-saturated T1-weighted FSE.

Spinal Anaplastic Oligodendroglioma With Oligodendrogliomatosis: Molecular Markers and Management: Case Report

BACKGROUND AND IMPORTANCE Spinal cord oligodendrogliomas are rare tumors, with a reported incidence varying between 0.8% and 4.7% of all spinal cord tumors and just over 50 cases reported in the literature. Of these, only 9 cases are histologically defined as anaplastic oligodendrogliomas, with few having complete molecular characterization. The diffuse tumor spread that can occur along the subarachnoid space with secondary invasion of the leptomeninges is called oligodendrogliomatosis and is associated with poor outcome. CLINICAL PRESENTATION A 68-year-old man with a history of lumbar stenosis status after lumbar decompression presented with new-onset right lower-extremity weakness. Magnetic resonance imaging demonstrated an intramedullary lesion from T9 to T12. During an attempted diagnostic biopsy, numerous intradural intramedullary lesions not present on magnetic resonance imaging were observed. Tissue biopsy demonstrated a 1p/19q-codeleted anaplastic oligodendroglioma with diffuse oligodendrogliomatosis. Postoperative treatment included 39.2-Gy radiation over 22 fractions from T1 to the bottom of the thecal sac with a boost to the T9-T12 area, the primary site of disease, to a total dose of 43.2 Gy in 24 fractions, followed by adjuvant temozolomide at a dose of 200 mg/m on days 1 to 5 in a 28-day cycle. At the 1-year follow-up, the patient demonstrated moderate neurological improvement. CONCLUSION Management, prognosis, and use of molecular data in the decision-making algorithm for these patients are discussed, together with a review of all cases of primary intradural intramedullary spinal anaplastic oligodendrogliomas reported to date. Our study indicates that the combination of sequential treatment with radiation and temozolomide might provide a favorable outcome in the case of 1p/19q-codeleted spinal anaplastic oligodendrogliomas and that molecular analysis can be beneficial in guiding treatment strategies, although the impact of IDH mutations on these tumors is still unclear.