Bevacizumab for critical brain metastases in a patient with pulmonary pleomorphic carcinoma.

Bevacizumab was initially contraindicated in patients with brain metastases, but several reports have shown the efficacy and safety of bevacizumab for brain metastases. We herein report the case of a patient with pulmonary pleomorphic carcinoma for which bevacizumab plus weekly paclitaxel following whole-brain radiotherapy (WBRT) was effectively and safely administered for critical and refractory brain metastases. Although the 50-year-old male patient received WBRT with anti-edema therapies for progressive brain metastases, his clinical symptoms deteriorated rapidly. After the completion of WBRT, we administered bevacizumab plus weekly paclitaxel, and his neurological symptoms improved dramatically. Brain magnetic resonance imaging demonstrated a marked response by the brain metastases and improved brain edema. This case suggested both synergism between WBRT and bevacizumab, and an anti-edema effect of bevacizumab. Bevacizumab may be therefore a potent therapeutic option for patients with refractory brain metastases.

Oedema-based model for diffuse low-grade gliomas: application to clinical cases under radiotherapy.

OBJECTIVES: Diffuse low-grade gliomas are characterized by slow growth. Despite appropriate treatment, they change inexorably into more aggressive forms, jeopardizing the patient's life. Optimizing treatments, for example with the use of mathematical modelling, could help to prevent tumour regrowth and anaplastic transformation. Here, we present a model of the effect of radiotherapy on such tumours. Our objective is to explain observed delay of tumour regrowth following radiotherapy and to predict its duration. MATERIALS AND METHODS: We have used a migration-proliferation model complemented by an equation describing appearance and draining of oedema. The model has been applied to clinical data of tumour radius over time, for a population of 28 patients. RESULTS: We were able to show that draining of oedema accounts for regrowth delay after radiotherapy and have been able to fit the clinical data in a robust way. The model predicts strong correlation between high proliferation coefficient and low progression-free gain of lifetime, due to radiotherapy among the patients, in agreement with clinical studies. We argue that, with reasonable assumptions, it is possible to predict (precision ~20%) regrowth delay after radiotherapy and the gain of lifetime due to radiotherapy. CONCLUSIONS: Our oedema-based model provides an early estimation of individual duration of tumour response to radiotherapy and thus, opens the door to the possibility of personalized medicine.

Urgent radiotherapy is effective in the treatment of metastatic medulloblastoma causing symptomatic brainstem edema.

A 3-year-old male who presented with hydrocephalus symptoms was found to have metastatic medulloblastoma with diffuse spinal disease. Thirteen days following surgical resection of his primary tumor, he clinically deteriorated due to worsening brainstem edema. Following intubation, stress-dose steroids, and mannitol, urgent radiotherapy was initiated to the whole brain and cervical cord. The patient improved clinically with a repeat MRI showing decreased leptomeningeal enhancement in the radiation fields. In the literature, there are no reports of successful urgent radiotherapy in medulloblastoma, but in this instance, it proved to be a viable option.

Brain irradiation improves focal cerebral ischemia recovery in aged rats.

BACKGROUND: Studies have shown that aging is a significant factor in worsening stroke outcomes. While many mechanisms may aggravate brain injury in the elderly, one such potential system may involve increased glial proliferation in the aged stroke patient that could result in increased scar formation. We hypothesized that in aged rats a single brain-only exposure to a low radiation dose prior to focal brain ischemia would reduce glial proliferation and confer a long-term neuroprotective effect. METHODS: Brain-only proton irradiation (8 Gy) was performed ten days prior to middle cerebral artery occlusion (MCAO) in aged male rats. Magnetic resonance imaging (MRI) was undertaken in naive, radiation-only (Rad), MCAO, and MCAO+Rad groups at 2, 14 and 28 days post-stroke followed by immunohistochemistry (day 28). RESULTS: Ischemic lesion volume in MCAO+Rad group was decreased by 50.7% with an accelerated temporal reduction in peri-lesional brain edema and increased water mobility within the ischemic core (39.8%) compared to MCAO-only rats. In the peri-lesional brain region of MCAO+Rad rats there was a decreased scar formation (49%, glial fibrillary acidic protein), brain tissue sclerosis (30%, aquaporin-4) and necrosis/apoptosis (58%, TUNEL positive cells) compared to those in MCAO animals. CONCLUSION: In aged animals a single exposure to brain-only radiation prior to focal cerebral ischemia is neuroprotective as it prevents glial hyperproliferation, progressive brain tissue sclerosis and reduces the apoptosis/necrosis in the peri-lesional region. Decreased lesion volume is in agreement with accelerated reduction of brain edema in these animals.

Evaluation of peritumoral edema in the delineation of radiotherapy clinical target volumes for glioblastoma.

PURPOSE: To evaluate the spatial relationship between peritumoral edema and recurrence pattern in patients with glioblastoma (GBM). METHODS AND MATERIALS: Forty-eight primary GBM patients received three-dimensional conformal radiotherapy that did not intentionally include peritumoral edema within the clinical target volume between July 2000 and June 2001. All 48 patients have subsequently recurred, and their original treatment planning parameters were used for this study. New theoretical radiation treatment plans were created for the same 48 patients, based on Radiation Therapy Oncology Group (RTOG) target delineation guidelines that specify inclusion of peritumoral edema. Target volume and recurrent tumor coverage, as well as percent volume of normal brain irradiated, were assessed for both methods of target delineation using dose-volume histograms. RESULTS: A comparison between the location of recurrent tumor and peritumoral edema volumes from all 48 cases failed to show correlation by linear regression modeling (r(2) = 0.0007; p = 0.3). For patients with edema >75 cm(3), the percent volume of brain irradiated to 46 Gy was significantly greater in treatment plans that intentionally included peritumoral edema compared with those that did not (38% vs. 31%; p = 0.003). The pattern of failure was identical between the two sets of plans (40 central, 3 in-field, 3 marginal, and 2 distant recurrence). CONCLUSION: Clinical target volume delineation based on a 2-cm margin rather than on peritumoral edema did not seem to alter the central pattern of failure for patients with GBM. For patients with peritumoral edema >75 cm(3), using a constant 2-cm margin resulted in a smaller median percent volume of brain being irradiated to 30 Gy, 46 Gy, and 50 Gy compared with corresponding theoretical RTOG plans that deliberately included peritumoral edema.

Response of radiochemotherapy-associated cerebral edema to a phytotherapeutic agent, H15.

Twelve patients with brain tumors and progressive edema caused by tumor progression or radiochemotherapy-related leukoencephalopathy were treated with H15, a phytotherapeutic anti-inflammatory agent. Edema was reduced in two of seven patients with glioblastoma with tumor progression and in three of five patients with treatment-related leukoencephalopathy. All patients with leukoencephalopathy improved clinically for several months.

[Brain metastases of bronchial and breast carcinoma. Differences in metastatic behavior and prognosis]. / Hirnmetastasen des Bronchial- und Mammakarzinoms. Unterschiede in Metastasierungsverhalten und Prognose.

Evaluation of 135 cases with brain metastases from non-small-cell lung cancer (group 1) compared with 51 cases from small-cell lung cancer (group 2) and 56 cases from breast cancer (group 3) showed that the frequency of solitary metastases was significantly higher in group 1 and 3. However, in group 2 lesions without surrounding edema occurred more frequently. The rate of patients with extracerebral metastases was significantly higher in groups 2 and 3. The longest median interval between primary tumor and brain metastases was observed in breast cancer patients. The highest local remission rate was seen in small-cell lung cancer if patients who received whole-brain irradiation of 30 Gy alone were compared (63% vs 45% in group 1 and 52% in group 3). However, with regard to clinical course no significant differences were recorded. Survival of lung cancer cases was similar, whereas breast cancer cases survived significantly longer, both after radiotherapy alone and after surgery plus radiotherapy. This might be caused by differences in the natural course of the two diseases as well as adjuvant treatment modalities like hormone and chemotherapy. In conclusion, because long-term survivors were observed only in the breast cancer group, these patients probably have the highest chance of profiting from a locally aggressive treatment approach.