Delayed Neurotoxicity in Primary Central Nervous System Lymphoma

Omuro, Antonio; Ben-Porat, Leah; Panageas, Katherine S.; Kim, Amy K.; Correa, Denise D.; Yahalom, Joachim; DeAngelis, Lisa M.; Abrey, Lauren E.

doi:10.1001/archneur.62.10.1595

Cited by 247 publications

(136 citation statements)

References 33 publications

(20 reference statements)

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“…Omuro et al (4) reported that age ≥60 years was a statistically significant risk factor for developing neurotoxicity. Kiewe et al (19) evaluated surviving patients without evidence of lymphoma or late neurotoxicity, and reported a positive correlation between radiological and clinical abnormalities.…”

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confidence: 99%

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Health-related quality of life in outpatients with primary central nervous system lymphoma after radiotherapy and high-dose methotrexate chemotherapy

Okita

Narita²,

Miyakita³

et al. 2016

Molecular and Clinical Oncology

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Abstract. Chemoradiotherapy for primary central nervous system lymphoma (PCNSL) is associated with a considerable risk of long-term neurotoxicity. The present study aimed to assess the health-related quality of life (HRQOL) of outpatients with PCNSL who have received radiotherapy and high-dose methotrexate (HDMTX) chemotherapy, and to determine the factors that cause a decline in HRQOL and interfere with home living. A total of 37 patients were surveyed 0.9-14.2 years after their initial diagnosis and treatment. Each patient completed a multi-part HRQOL questionnaire that was used to examine the associations of HRQOL scores with leukoencephalopathy, Karnofsky performance status (KPS) scores, age, history of recurrence and HDMTX-based chemoradiotherapy. The results demonstrated that the history of recurrence, number of cycles of MTX chemotherapy and age affected the development of leukoencephalopathy. Reductions in KPS score were associated with a history of recurrence (P=0.03), but not with leukoencephalopathy (P=0.8). KPS score, leukoencephalopathy and age were significantly associated with a decline in HRQOL score. A decline in the HRQOL associated with a reduction in KPS score was also observed by multivariate analyses. Deterioration of the HRQOL among outpatients with PCNSL post-chemoradiotherapy was significantly associated with older age (≥66 years) and decreased KPS score. Older patients with a history of recurrence had a higher risk for deteriorated QOL due to development of leukoencephalopathy. Therefore, it is recommended that clinicians monitor the KPS score among outpatients with PCNSL. QOL examination for older patients

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confidence: 99%

“…However, leukoencephalopathy is associated with a risk of neurotoxicity and may severely interfere with cognitive function (2,3). Progressive leukoencephalopathy with cognitive deterioration is associated with a significant decrease in the quality of life (QOL) (4).…”

Section: Introductionmentioning

confidence: 99%

Health-related quality of life in outpatients with primary central nervous system lymphoma after radiotherapy and high-dose methotrexate chemotherapy

Okita

Narita²,

Miyakita³

et al. 2016

Molecular and Clinical Oncology

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“…Some 50% of long-term survivors develop latedelayed cognitive deficits due to radiation-induced injury of normal brain tissue (1,2). Age is an important risk factor for the development and severity of cognitive dysfunction following WBI, with pediatric and elderly patients appearing to be more vulnerable to WBI-induced brain injury than young adults (3)(4)(5)(6). There is a paucity of experimental data regarding the effects of old age on the radiation response in the brain despite evidence that the average age for developing the cancers that require treatment with WBI is > 50 years old, making middle-aged and older adults a commonly treated patient population (7).…”

Section: Introductionmentioning

confidence: 99%

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

Schindler¹,

Forbes²,

Robbins³

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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Purpose-To assess the impact of aging on the radiation response in the adult rat brain.Methods and Materials-Male rats 8, 18, or 28 months of age received a single 10Gy dose of whole brain irradiation (WBI). The hippocampal dentate gyrus (DG) was analyzed one and ten weeks later for sensitive neurobiological markers associated with radiation-induced damage: changes in the density of proliferating cells, immature neurons, total microglia, and activated microglia.Results-A significant reduction in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased following WBI in young rats but not in old rats. Total microglial number decreased following WBI at all ages but microglial activation increased markedly, particularly in older animals.Conclusions-Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in the number of immature neurons following WBI but have a greater inflammatory response. The latter may play an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

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“…Their confirmation of some long-term survivors emphasizes the need to consider the potential longterm neurotoxicity of treatment, as has become widely recognized in immunocompetent patients with primary central nervous system lymphoma. 3,4 …”

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confidence: 99%