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  • 1
    Online Resource
    Online Resource
    Brain metastasis from squamous cell carcinoma of the head and neck: a review of the literature in the genomic era
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2018
    In:  Neurosurgical Focus Vol. 44, No. 6 ( 2018-06), p. E11-
    Details
    In: Neurosurgical Focus, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 44, No. 6 ( 2018-06), p. E11-
    Abstract: Squamous cell carcinoma of the head and neck (HNSCC) affects nearly 500,000 individuals globally each year. With the rise of human papillomavirus (HPV) in the general population, clinicians are seeing a concomitant rise in HPV-related HNSCC. Notably, a hallmark of HPV-related HNSCC is a predilection for unique biological and clinical features, which portend a tendency for hematogenous metastasis to distant locations, such as the brain. Despite the classic belief that HNSCC is restricted to local spread via passive lymphatic drainage, brain metastases (BMs) are a rare complication that occurs in less than 1% of all HNSCC cases. Time between initial diagnosis of HNSCC and BM development can vary considerably. Some patients experience more than a decade of disease-free survival, whereas others present with definitive neurological symptoms that precede primary tumor detection. The authors systematically review the current literature on HNSCC BMs and discuss the current understanding of the effect of HPV status on the risk of developing BMs in the modern genomic era.
    Type of Medium: Online Resource
    ISSN: 1092-0684
    URL: Article
    DOI: 10.3171/2018.2.FOCUS17761
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2018
    detail.hit.zdb_id: 2026589-X
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  • 2
    Online Resource
    Online Resource
    ENDOCRINE TUMORS: BRAF V600E mutations in papillary craniopharyngioma
    Oxford University Press (OUP) ; 2016
    In:  European Journal of Endocrinology Vol. 174, No. 4 ( 2016-04), p. R139-R144
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 174, No. 4 ( 2016-04), p. R139-R144
    Abstract: Papillary craniopharyngioma (PCP) is an intracranial tumor that results in high levels of morbidity. We recently demonstrated that the vast majority of these tumors harbor the oncogenic BRAF V600E mutation. The pathologic diagnosis of PCP can now be confirmed using mutation specific immunohistochemistry and targeted genetic testing. Treatment with targeted agents is now also a possibility in select situations. We recently reported a patient with a multiply recurrent PCP in whom targeting both BRAF and MEK resulted in a dramatic therapeutic response with a marked anti-tumor immune response. This work shows that activation of the MAPK pathway is the likely principal oncogenic driver of these tumors. We will now investigate the efficacy of this approach in a multicenter phase II clinical trial. Post-treatment resection samples will be monitored for the emergence of resistance mechanisms. Further advances in the non-invasive diagnosis of PCP by radiologic criteria and by cell-free DNA testing could someday allow neo-adjuvant therapy for this disease in select patient populations.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-15-0957
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1183856-5
    detail.hit.zdb_id: 1485160-X
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  • 3
    Online Resource
    Online Resource
    Ipilimumab and craniotomy in patients with melanoma and brain metastases: a case series
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2015
    In:  Neurosurgical Focus Vol. 38, No. 3 ( 2015-03), p. E5-
    Details
    In: Neurosurgical Focus, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 38, No. 3 ( 2015-03), p. E5-
    Abstract: In patients with large or symptomatic brain lesions from metastatic melanoma, the value of resection of metastases to facilitate administration of systemic ipilimumab therapy has not yet been described. The authors undertook this study to investigate whether craniotomy creates the opportunity for patients to receive and benefit from ipilimumab who would otherwise succumb to brain metastasis prior to the onset of regression. METHODS All patients with metastatic melanoma who received ipilimumab and underwent craniotomy for metastasis resection between 2008 and 2014 at the Massachusetts General Hospital were identified through retrospective chart review. The final analysis included cases involving patients who underwent craniotomy within 3 months prior to initiation of therapy or up to 6 months after cessation of ipilimumab administration. RESULTS Twelve patients met the inclusion criteria based on timing of therapy (median age 59.2). The median number of metastases at the time of craniotomy was 2. The median number of ipilimumab doses received was 4. Eleven of 12 courses of ipilimumab were stopped for disease progression, and 1 was stopped for treatment-induced colitis. Eight of 12 patients had improvement in their performance status following craniotomy. Of the 6 patients requiring corticosteroids prior to craniotomy, 3 tolerated corticosteroid dose reduction after surgery. Ten of 12 patients had died by the time of data collection, with 1 patient lost to follow-up. The median survival after the start of ipilimumab treatment was 7 months. CONCLUSIONS In this series, patients who underwent resection of brain metastases in temporal proximity to receiving ipilimumab had qualitatively improved performance status following surgery in most cases. Surgery facilitated corticosteroid reduction in select patients. Larger analyses are required to better understand possible synergies between craniotomy for melanoma metastases and ipilimumab treatment.
    Type of Medium: Online Resource
    ISSN: 1092-0684
    URL: Article
    DOI: 10.3171/2014.12.FOCUS14698
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2015
    detail.hit.zdb_id: 2026589-X
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  • 4
    Online Resource
    Online Resource
    Genetic Characterization of Brain Metastases in the Era of Targeted Therapy
    Frontiers Media SA ; 2017
    In:  Frontiers in Oncology Vol. 7 ( 2017-09-25)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 7 ( 2017-09-25)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2017.00230
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2017
    detail.hit.zdb_id: 2649216-7
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  • 5
    Online Resource
    Online Resource
    Targeting Molecular Pathways in Intracranial Metastatic Disease
    Frontiers Media SA ; 2019
    In:  Frontiers in Oncology Vol. 9 ( 2019-3-4)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 9 ( 2019-3-4)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2019.00099
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2649216-7
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  • 6
    Online Resource
    Online Resource
    Diagnosis and management of craniopharyngiomas in the era of genomics and targeted therapy
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2016
    In:  Neurosurgical Focus Vol. 41, No. 6 ( 2016-12), p. E2-
    Details
    In: Neurosurgical Focus, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 41, No. 6 ( 2016-12), p. E2-
    Abstract: Craniopharyngiomas are rare intracranial neoplasms that pose clinical challenges due to their location adjacent to vital structures. The authors have previously shown high mutation rates of BRAF V600E in papillary craniopharyngioma and of CTNNB1 in adamantinomatous craniopharyngioma. These activating driver mutations are potential therapeutic targets, and the authors have recently reported a significant response to BRAF/MEK inhibition in a patient with multiply recurrent PCP. As these targetable mutations warrant prospective research, the authors will be conducting a national National Cancer Institute–sponsored multicenter clinical trial to investigate BRAF/MEK inhibition in the treatment of craniopharyngioma. In this new era of genomic discovery, the treatment paradigm of craniopharyngioma is likely to change.
    Type of Medium: Online Resource
    ISSN: 1092-0684
    URL: Article
    DOI: 10.3171/2016.9.FOCUS16325
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2016
    detail.hit.zdb_id: 2026589-X
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  • 7
    Online Resource
    Online Resource
    Targeted sequencing of SMO and AKT1 in anterior skull base meningiomas
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2017
    In:  Journal of Neurosurgery Vol. 127, No. 2 ( 2017-08), p. 438-444
    Details
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 127, No. 2 ( 2017-08), p. 438-444
    Abstract: Meningiomas located in the skull base are surgically challenging. Recent genomic research has identified oncogenic SMO and AKT1 mutations in a small subset of meningiomas. METHODS The authors performed targeted sequencing in a large cohort of patients with anterior skull base meningiomas (n = 62) to better define the frequency of SMO and AKT1 mutations in these tumors. RESULTS The authors found SMO mutations in 7 of 62 (11%) and AKT1 mutations in 12 of 62 (19%) of their cohort. Of the 7 meningiomas with SMO mutations, 6 (86%) occurred in the olfactory groove. Meningiomas with an SMO mutation presented with significantly larger tumor volume (70.6 ± 36.3 cm 3 ) compared with AKT1 -mutated (18.2 ± 26.8 cm 3 ) and wild-type (22.7 ± 23.9 cm 3 ) meningiomas, respectively. CONCLUSIONS Combined, these data demonstrate clinically actionable mutations in 30% of anterior skull base meningiomas and suggest an association between SMO mutation status and tumor volume. Genotyping of SMO and AKT1 is likely to be high yield in anterior skull base meningiomas with available surgical tissue.
    Type of Medium: Online Resource
    ISSN: 0022-3085 , 1933-0693
    URL: Article
    DOI: 10.3171/2016.8.JNS161076
    RVK:
    XA 10000
    RVK:
    XA 55270
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2017
    detail.hit.zdb_id: 3089-2
    detail.hit.zdb_id: 2026156-1
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