Radiotherapy with concurrent temozolomide for the management of extraneural metastases in pituitary carcinoma.

BACKGROUND: Pituitary carcinomas (PC) are uncommon neuroendocrine tumors, accounting for 0.1 % of all pituitary tumors. The diagnosis of PC is based on the presence of metastases from a pituitary adenoma, and not by local invasion or pathological features alone. PC is typically resistant to therapy, with a median overall survival of only 31 months. There is no standard treatment for PC, but maximal safe resection and radiation are performed when possible. Encouraging preliminary data on the use of temozolomide (TMZ)-based therapy has been previously reported. METHODS: We report the response to therapy and safety of radiation with concurrent temozolomide (RT/TMZ) in 2 adult patients with heavily pretreated PC and extraneural metastases. RESULTS: Both patients had prior history of pituitary macroadenoma. At the time of diagnosis of PC, Ki-67 % was 24.2 and 10 %, with positive p53 staining in one case. Metastatic sites included lymph nodes, liver and bone. Case-1 received RT/TMZ to the tumor bed in the skull base and to the metastases in the cervical lymph nodes. Case-2 received RT/TMZ to recurrent tumor involving portacaval lymph nodes. Both patients achieved excellent long-term control of the sites of treated extraneural metastases, with no significant acute or delayed toxicity. CONCLUSIONS: RT/TMZ was safely delivered and might provide sustained control of extraneural metastases in PC. Although this retrospective report has limitations, RT/TMZ can be considered as a therapeutic option for the management of extraneural metastases in PC.

Pineal parenchymal tumor of intermediate differentiation: a single-institution experience.

BACKGROUND: Pineal parenchymal tumors are exceedingly rare brain tumors responsible for less than 1% of all adult primary intracranial malignancies in the United States. In this study, we describe the clinicopathologic features, management, and outcomes of patients with pineal parenchymal tumor of intermediate differentiation (PPTID). METHODS: We describe a single-center, multidisciplinary team experience in managing PPTID patients over a 15-year period (January 2000 to January 2015) at The University of Texas MD Anderson Cancer Center (MDACC). Pathology was reviewed by the pathology collaborators (A.G. and G.N.F.) and retrospective chart review was performed for treatment and clinical outcomes. RESULTS: We identified 17 patients (9 male) with diagnosis of PPTID. Median age at diagnosis of PPTID was 37 years (range, 15-57 years). Follow-up ranged from 0.1 to 162.8 months with 6 reported deaths. Most patients presented with headaches and diplopia. Three patients had neuroaxial dissemination at initial diagnosis, and recurrence of tumor was common (7/16) despite treatment. CONCLUSIONS: No clear prognostic factors were identified in this series. Extension of resection showed a trend toward improved survival. PPTID with neuroaxial dissemination benefits from aggressive initial treatment including craniospinal irradiation and adjuvant chemotherapy, whereas localized disease may be treated traditionally with maximum debulking followed by adjuvant radiotherapy alone. Long-term monitoring is recommended for neurotoxicity and/or late recurrence.

Quantitative ultrasound of muscle can detect corticosteroid effects.

OBJECTIVES: In this study, we sought to determine whether quantitative ultrasound (QUS) could detect the impact of corticosteroids on muscle in the absence of frank weakness. METHODS: QUS was performed on selected limb muscles of 20 brain tumor patients treated with dexamethasone and 30 healthy controls. Echointensity was quantified using gray scale level (GSL) analysis and compared between groups; correlation to corticosteroid exposure was also performed. RESULTS: Average 4-muscle GSL (±standard deviation) was greater in patients compared to controls (35.5 ±â€¯5.61 arbitrary units (AU) versus 30.4 ±â€¯4.17 AU, p = 0.001), with the greatest differences in tibialis anterior. Average muscle GSL also correlated to length of corticosteroid therapy (rho = 0.52, p = 0.01). CONCLUSIONS: These findings suggest that QUS may be able to quantify skeletal muscle alterations associated with chronic corticosteroid use. Further study of this approach is warranted. SIGNIFICANCE: The findings of this study may provide a tool to evaluate corticosteroid myopathy.

Intracranial dural, calvarial, and skull base metastases.

Metastatic disease to the intracranial dura, the calvarium, and the skull base is relatively uncommon but presents unique diagnostic and management challenges in the patient with cancer. Modern imaging techniques have facilitated the detection of intracranial tumor deposits, leading to increased incidence. While dural and calvarial metastases often present with nonspecific symptoms, skull base metastases present with distinct clinical syndromes dependent on the local neurovascular structures affected. Intracranial dural metastases can often be confused with meningioma and pose a diagnostic challenge, as well as significant neurologic morbidity, especially in the setting of hemorrhage. Surgical intervention may be helpful in selected patients for symptomatic relief as well as survival benefit. Management paradigms need to take into account the relative risks, benefits, and likely outcomes for each possible modality of treatment. Surgical excision is useful in many patients and in combination with radiation therapy can provide significant palliation. While medical therapy is rarely an initial therapy in these entities, it may be of added benefit dependent on the underlying tumor histology and prior treatment history. Occasionally treatment with curative intent is justified.

Treatment of Glioblastoma.

Glioblastoma is the most common and most aggressive form of primary brain tumor in adults and contributes to high social and medical burden as a result of its incurable nature and significant neurologic morbidity. Despite ongoing research, there has not been improvement in survival in glioblastoma. This review discusses recent advances in clinically significant molecular profiling, including IDH mutation status and O6-methylguanine-DNA methyltransferase ( MGMT) promoter methylation. We review updates in management of newly diagnosed and recurrent glioblastoma, as well as common difficulties in management, such as pseudoprogression and pseudoresponse. Ongoing translational research in targeted therapy and immunotherapy is briefly discussed.

Current chemotherapeutic regimens for brain metastases treatment.

Brain metastasis is a common complication in advanced systemic cancer, with an increasing incidence. The diagnosis of brain metastasis historically portended a dismal prognosis. The successful development of effective treatments for patients with brain metastasis is complicated by the differences among cancer subtypes, the limited understanding of the underlying pathophysiology of BM, the impact of the blood-brain barrier, and other factors. There is now renewed interest in treating this often devastating complication of cancer, and in understanding the underlying mechanisms of disease in this "sanctuary" site. Promising treatment strategies include brain-penetrant targeted therapies and immunotherapy, and strategies for enhanced delivery of therapy. This review highlights a selection of these approaches.