Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors

Gurney, James G.; Kadan‐Lottick, Nina S.; Packer, Roger J.; Neglia, Joseph P.; Sklar, Charles A.; Punyko, Judy; Stovall, Marilyn; Yasui, Yutaka; Nicholson, MA; Wolden, Suzanne L.; McNeil, D. Elizabeth; Mertens, Ann C.; Robison, Leslie L.

doi:10.1002/cncr.11095

Cited by 330 publications

(235 citation statements)

References 26 publications

(9 reference statements)

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“…This study is the first population-based survey focussing on self-reported potential endocrine late effects in adult cancer survivors. When comparing results from this registry based study to currently available epidemiological data on the frequency of endocrine disorders in Germany (23,24,25,26), an increased prevalence of these diseases in adult long-term cancer survivors is obvious and similar to that observed in patients diagnosed with cancer during childhood and adolescence (13,17).…”

Section: Discussionsupporting

confidence: 54%

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Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

Gebauer

Fick

Waldmann

et al. 2015

European Journal of Endocrinology

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Objective: Due to the increasing success and survival rates in the primary treatment of malignancies derived from the CNS as well as the hematopoietic system, endocrine late effects of cancer and its therapy are of growing importance. Despite evaluation of these late effects in patients treated for cancer in childhood, the impact on adults remains largely unclear. Methods: 1035 adult patients primarily diagnosed with a CNS malignancy, a Hodgkin (HL) or non-Hodgkin lymphoma (NHL) between 1998 and 2008 were recruited via the regional epidemiological cancer registry covering w2.8 million inhabitants in the federal state of Schleswig-Holstein, Northern Germany. The prevalence of endocrine disorders and current psychosocial impairment was assessed employing several questionnaires (SF-36v1, WHO-5). Results: Fully completed questionnaires of 558 patients were available for subsequent analysis showing markedly reduced overall performance and psychological status when compared to German reference data. Thyroid disorders were reported in 16.3% of patients with 10.4% suffering from hypo-and 5.9% from hyperthyroidism. Overall, 17.6% stated to be affected by diabetes mellitus with an increased rate of 21.1% among NHL patients and 11.5% of participants were affected by osteoporosis. Conclusion: Compared to German population based studies on the prevalence of diabetes mellitus, osteoporosis and thyroid disorders the frequency of all these endocrine problems was significantly increased in CNS, HL, and NHL cancer survivors. These data confirm that not only children and adolescents but also adult cancer patients are at risk for therapy associated endocrine late effects.

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Section: Discussionsupporting

confidence: 54%

“…As data from children and adolescents suggested that the highest frequency of endocrine late effects are observed in patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and CNS tumours (CNS-T) we restricted our analysis to these patients (15,16,17,18,19).…”

Section: Introductionmentioning

confidence: 99%

Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

Gebauer

Fick

Waldmann

et al. 2015

European Journal of Endocrinology

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“…Modern multifaceted treatment regimens for childhood brain tumors have resulted in improved five-year survival rates (Ries, 2004) and a growing number of longterm survivors such that the majority of children diagnosed with brain tumors are now surviving into adulthood (Gurney et al, 2003). However, the risks for poor long-term outcomes are substantial, especially in those survivors treated aggressively and at a young age (Ellenberg et al, 2009;Mulhern, Merchant, Gajjar, Reddick, & Kun, 2004).…”

Section: Introductionmentioning

confidence: 99%

Cumulative neurological factors associated with long-term outcomes in adult survivors of childhood brain tumors

King

2015

Child Neuropsychology

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“…First, patients with high-risk features, such as metastatic disease, unfavorable biologic features, or relapsed disease have poor to dismal clinical outcomes (2-6). Second, radiotherapy, which is the mainstay of current treatment regimens, results in substantial long-term morbidities including endocrinopathies, impaired cognition, vasculopathies, and the risk of second malignant brain tumors (7). While the addition of chemotherapy to treatment regimens has allowed for reductions in radiation doses for lower risk patients, attempts to eliminate radiation therapy have resulted in inferior outcomes (8).…”

Section: Introductionmentioning

confidence: 99%

Targeting the Inhibitor of Apoptosis Proteins as a Novel Therapeutic Strategy in Medulloblastoma

Keating

Tsoli

Hallahan

et al. 2012

Molecular Cancer Therapeutics

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Medulloblastoma is the most common malignant brain tumor of childhood. Novel therapeutic strategies are urgently needed to overcome cytotoxic resistance. We hypothesized that antiapoptotic signals contribute to resistance and that treatment with proapoptotic agents could increase the efficacy of conventional therapies. A PCR array was used to assess the status of the apoptotic signaling pathway in medulloblastoma cells after treatment with cytotoxic chemotherapy. Treatment with cisplatin led to the upregulation of antiapoptotic signals, including inhibitor of apoptosis proteins (IAP), in medulloblastoma cells. We subsequently investigated the synergistic effect of a small-molecule IAP inhibitor, LBW242, in combination with cisplatin and/or radiotherapy in three human medulloblastoma cell lines and 5 short term primary patient medulloblastoma cultures. The addition of LBW242 to chemotherapy resulted in significantly increased antitumor activity with a similar effect observed in combination with radiotherapy. Measurement of caspase-8 and -9 activity indicated that the synergy resulted from induction of both the intrinsic and extrinsic apoptotic pathways. Apoptosis was confirmed by Annexin V staining and activation of caspases 3/7. Xenograft models were used to evaluate the mechanism of action and efficacy in vivo. The combination therapy significantly reduced the tumor burden in a medulloblastoma xenograft model and TUNEL analysis in a medulloblastoma orthograft confirmed in vivo induction of apoptosis. These findings support the strategy of targeting IAPs in combination with cytotoxic therapy as a novel treatment strategy for patients with medulloblastoma.

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Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors

Cited by 330 publications

References 26 publications

Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

Cumulative neurological factors associated with long-term outcomes in adult survivors of childhood brain tumors

Targeting the Inhibitor of Apoptosis Proteins as a Novel Therapeutic Strategy in Medulloblastoma

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