Delayed Effects of Whole Brain Radiotherapy in Germ Cell Tumor Patients With Central Nervous System Metastases

Doyle, Danielle; Einhorn, Lawrence H.

doi:10.1016/j.ijrobp.2007.11.005

Cited by 37 publications

(19 citation statements)

References 17 publications

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“…For patients with brain metastasis at initial diagnosis, 2-year survival rates range from around 30 to 54% and median survival from 15 to 56 months in the different series [8,9,10,11,12]. In these series, most of the patients were treated with upfront chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Doyle and Einhorn [9] recently reported 5 cases of severe neurotoxicity among 30 patients with GCT treated with radiotherapy for brain metastases; 3 died from these complications. Four patients developed multifocal progressive leukoencephalopathy.…”

Section: Discussionmentioning

confidence: 99%

“…In most series, patients were treated with radiotherapy with or without chemotherapy [8,9,10,11,12]. …”

Section: Discussionmentioning

confidence: 99%

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Management of Brain Metastases from Germ Cell Tumors: A Single Center Experience

Jouanneau¹,

Droz²,

Fléchon³

2013

Oncology

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Background: Brain metastases from germ cell tumors (GCT) are rare and treatment has not yet been standardized. Methods: The clinical data of men with brain metastases from GCT treated in a single cancer hospital from January 1993 to September 2007 were reviewed. Patients with primary central nervous system GCT were excluded. Results: Thirteen patients had brain metastases at initial diagnosis. All patients received cisplatin-based chemotherapy. Three also received radiotherapy and 1 underwent surgery. Eight of the patients died. Median survival was 19 months (95% CI 0.84-not reached). Twenty-two patients developed brain metastases at recurrence. Median time from initial diagnosis to brain metastases was 8.25 months (3-17.5 months). Five patients received radiotherapy alone, 3 received chemotherapy alone and 3 received supportive care only. Nine patients were operated on: 6 received postoperative chemotherapy and 1 received postoperative radiotherapy. Only 1 patient is still alive. Median survival was 5.1 months (95% CI: 2.2-10.5 months). Conclusions: Patients with GCT who present with brain metastases at diagnosis tend to do better than patients who develop them at relapse. Chemotherapy can be adequate treatment for initial brain metastases. Treatment for patients with brain metastases at relapse is still not optimal.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Management of Brain Metastases from Germ Cell Tumors: A Single Center Experience

Jouanneau¹,

Droz²,

Fléchon³

2013

Oncology

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“…68 Following intracranial irradiation astrocytes proliferate and form scar tissue, referred to as reactive gliosis. 69 Hwang et al reported that a single dose of 15 Gy radiation to the rat brain increased immunostaining of GFAP in astrocytes at 6 hours with increased staining at 24 hours, which the authors interpreted as the onset of gliosis. 70,71 Identifying features of reactive gliosis are hypertrophy of astrocytic processes, upregulation of intermediate filaments, and increased glial fibrillary acidic protein (GFAP) expression.…”

Section: Early Radiation Induced Cns Abnormalities In Preclinicalmentioning

confidence: 99%

Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours

et al. 2016

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Standard treatment of primary and metastatic brain tumors includes high dose megavoltage radiation to the cranial vault. About half of patients survive >6 months, many attain long term control or cure, but 50-90% of survivors overall exhibit disabling cognitive dysfunction. The radiation cognitive syndrome is poorly understood and there is no effective prevention or long-term treatment. Attention has primarily focused on mechanisms of disability appearing at six months to one year after radiotherapy. However, a range of studies have revealed that CNS alterations and dysfunction develop much earlier than 6 months following radiation exposure. This has prompted the recent hypothesis that relatively subtle early forms of radiation induced CNS damage may drive chronic pathophysiology leading to permanent cognitive decline. Within this perspective, the present review presents evidence of acute CNS irradiation triggered inflammation, and injury to neuronal lineages, accessory cells and their progenitors, and loss of supporting structure integrity. Moreover, injury related processes set in motion soon after intracranial irradiation may interact and synergize to alter the neuronal and supporting cell progenitor signaling environment in stem cell niches in the brain, and specifically in the hippocampus, a structure critical to memory and cognition. Changed niche conditions may cause a sustained decline in neurons and progressive deterioration of cognition. The concluding discussion addresses, (1) what further data is needed, and (2) potential treatment interventions, identified via recent findings on acute CNS radiation injury, that may reverse degenerative processes before they can cause permanent cognitive disability.

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“…Radiation studies to date examining cognitive function have demonstrated profound functional and structural effects on the brain, ranging from progressive cognitive impairment (2, 3) and dementia (4) to white matter lesions and degradation (5) in patients treated for cancer. However, these clinical studies have largely utilized fractionated radiation schemes involving repeated small-fraction doses, and are often confounded by concurrent chemotherapy treatment (6) and/or the presence of neoplasms (7).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Cognitive Functioning in Single-Dose Total-Body Gamma-Irradiated Rhesus Monkeys (Macaca mulatta)

et al. 2016

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In this study, the effects of a potentially lethal radiation exposure on the brain for long-term cognitive sequelae were investigated using Rhesus macaques (Macaca mulatta) adopted from other facilities after analysis of acute radiation response via the Centers for Medical Countermeasures against Radiation (CMCR) network. Fifty-nine animals were given the opportunity to participate in cognitive cage-side testing. The animals that received single-dose gamma irradiation were significantly less likely to engage in cognitive testing than the controls, suggesting that irradiated animals may have differences in cognitive ability. Five irradiated (6.75–8.05 Gy) and three naïve control animals self-selected, were extensively trained and administered a simple visual discrimination with reversal (SVD+R) task 2–3 times per week for 11–18 months. Each session consisted of 30 trials in which the animals were required to choose the correct visual stimulus for a food reward. After the initial presentation, the stimulus that signaled the presence of food was twice reversed once the animal reached criterion (90% accuracy across four consecutive sessions). While the limited sample size precluded definitive statistical analysis, irradiated animals took longer to reach the criterion subsequent to reversal than did control animals, suggesting a relative deficiency in cognitive flexibility. These results provide preliminary data supporting the potential use of a nonhuman primate model to study radiation-induced, late-delayed cognitive deficits.

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Delayed Effects of Whole Brain Radiotherapy in Germ Cell Tumor Patients With Central Nervous System Metastases

Cited by 37 publications

References 17 publications

Management of Brain Metastases from Germ Cell Tumors: A Single Center Experience

Management of Brain Metastases from Germ Cell Tumors: A Single Center Experience

Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours

Long-Term Cognitive Functioning in Single-Dose Total-Body Gamma-Irradiated Rhesus Monkeys (Macaca mulatta)

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