Diagnostic value of 18F-fluordesoxyglucose positron emission tomography for patients with brain metastasis from unknown primary site

Wolpert, Fabian; Weller, Michael; Berghoff, Anna Sophie; Füreder, Lisa; Petyt, G.; Leske, Henning; Andratschke, Nicolaus; Regli, Luca; Neidert, Marian C.; Stupp, Roger; Stahel, Rolf A.; Dummer, Reinhard; Frauenfelder, Thomas; Reyns, Nicolas; Kaufmann, Philipp A.; Rhun, Émilie Le

doi:10.1016/j.ejca.2018.03.010

Cited by 17 publications

(14 citation statements)

References 19 publications

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“…This represents a considerable smaller fraction than in previous studies postulating that no primary tumor can be identified in 25–37% of BM patients [1–3, 13–15]. As these studies investigated patients in the time period before 2000, this difference may be accounted for by improvement in diagnostic process as well as implementation of FDG-PET in extended diagnostic assessment in recent years [16]. Splitting up our cohort in patients with BM diagnosis before and after 2000, we observed a significantly smaller amount of only 10% remaining with the diagnosis CUP in the latter group, supporting this hypothesis.…”

Section: Discussionmentioning

confidence: 94%

“…Splitting up our cohort in patients with BM diagnosis before and after 2000, we observed a significantly smaller amount of only 10% remaining with the diagnosis CUP in the latter group, supporting this hypothesis. Indeed, a recently published series, including BM patients with unknown primary diagnosed between 2004 and 2014, suggested that primary tumor detection as well as prognostic assessment was improved by adding FDG-PET to the diagnostic work flow [16]. Of note, in 17.6% of CUP patients the primary tumor could finally be identified after > 3 months during subsequent checkup and staging.…”

Section: Discussionmentioning

confidence: 99%

“…These patients presented with significantly enhanced survival estimation compared to other CUP patients, probably due to both the benefits from late systemic manifestation and the later applicability of tumor adapted chemotherapy. As in two-thirds of these cases the diagnosis was made by CT or PET-CT scan, it appears that continuation of diagnostic follow-up using these techniques may be beneficial even if initial investigations were inconclusive [16].…”

Section: Discussionmentioning

confidence: 99%

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Brain metastases as first manifestation of advanced cancer: exploratory analysis of 459 patients at a tertiary care center

Füreder

Widhalm

Gatterbauer

et al. 2018

Clin Exp Metastasis

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Symptomatic brain metastases (BM) are a frequent and late complication in cancer patients. However, a subgroup of cancer patients presents with BM as the first symptom of metastatic cancer. Here we aimed to analyze the clinical course and prognostic factors of this particular BM patient population. Patients presenting with newly diagnosed BM without a history of metastatic cancer were identified from the Vienna Brain Metastasis Registry. Clinical characteristics and overall survival were retrieved by chart review. 459/2419 (19.0%) BM patients presented with BM as first symptom of advanced cancer. In 374/459 (81.5%) patients, an extracranial primary tumor, most commonly lung cancer, could be identified within 3 months after BM diagnosis. In 85/459 (18.5%) patients no extracranial primary tumor could be identified despite comprehensive diagnostic workup within the first 3 months after diagnosis of BM. Survival of patients with identified extracranial tumor differed only numerically from patients with cancer of unknown primary (CUP), however patients receiving targeted therapy after molecular workup showed significantly enhanced survival (20 months vs. 7 months; p = 0.003; log rank test). The GPA score showed a statistically significant association with median overall survival times in the CUP BM patients (class I: 46 months; class II: 7 months; class III: 4 months; class IV: 2 months; p < 0.001; log rank test). The GPA score has a strong prognostic value in patients with CUP BM and may be useful for patient stratification in the clinical setting. Comprehensive diagnostic workup including advanced imaging techniques and molecular tissue analyses appears to benefit patients by directing specific molecular targeted therapies.Electronic supplementary materialThe online version of this article (10.1007/s10585-018-9947-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Brain metastases as first manifestation of advanced cancer: exploratory analysis of 459 patients at a tertiary care center

Füreder

Widhalm

Gatterbauer

et al. 2018

Clin Exp Metastasis

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“…The first step in the diagnosis of a metastatic brain lesion is to exclude a primary CNS tumor, followed by identification of tumor origin. In the clinic, the characteristics of brain tumor lesions (e.g., number, location) [26–28], advanced imaging techniques like PET-CT [29], and pathological exams may provide possible indications for distinguishing primary and metastatic brain tumors. However, when the metastatic brain tumor is poorly differentiated, morphology and IHC often fail to identify its anatomical origin and histological type [30].…”

Section: Discussionmentioning

confidence: 99%

90-gene signature assay for tissue origin diagnosis of brain metastases

et al. 2019

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Background Brain metastases (BM) are the most common intracranial tumors. 2–14% of BM patients present with unknown primary site despite intensive evaluations. This study aims to evaluate the performance of a 90-gene expression signature in determining the primary sites for BM samples. Methods The sequence-based gene expression profiles of 708 primary brain tumors (PBT) collected from The Cancer Genome Atlas (TCGA) database were analyzed by the 90-gene expression signature, with a similarity score for each of 21 common tumor types. We then used Optimal Binning algorithm to generate a threshold for separating PBT from BM. Eighteen PBT samples were analyzed to substantiate the reliability of the threshold. In addition, the performance of the 90-gene expression signature for molecular classification of metastatic brain tumors was validated in a cohort of 48 BM samples with the known origin. For each BM sample, the tumor type with the highest similarity score was considered tissue of origin. When a sample was diagnosed as PBT, but the similarity score below the threshold, the second prediction was considered as the primary site. Results A threshold of the similarity score, 70, was identified to discriminate PBT from BM (PBT: > 70, BM: ≤ 70) with an accuracy of 99% (703/708, 95% CI 98–100%). The 90-gene expression signature was further validated with 18 PBT and 44 BM samples. The results of 18 PBT samples matched reference diagnosis with a concordance rate of 100%, and all similarity scores were above the threshold. Of 44 BM samples, the 90-gene expression signature accurately predicted primary sites in 89% (39/44, 95% CI 75–96%) of the cases. Conclusions Our findings demonstrated the potential that the 90-gene expression signature could serve as a powerful tool for accurately identifying the primary sites of metastatic brain tumors.

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“…The situation is different for patients with brain metastases from solid tumours. For brain metastases from unknown primary tumours, either rapid neurosurgical intervention as clinically needed or initial work-up by chest abdomen CT or FDG-PET are standard procedures [78] whereas liquid biopsies have so far not assumed a role. However, patients with new brain lesions detected by neuroimaging who are known to suffer from a malignancy are not routinely sent for neurosurgical resection unless this is thought to be in the best interest of the patient, e.g.…”

Section: Road To Clinical Practicementioning

confidence: 99%

Cerebrospinal fluid cell-free tumour DNA as a liquid biopsy for primary brain tumours and central nervous system metastases

et al. 2019

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Challenges in obtaining tissue specimens from patients with brain tumours limit the diagnosis and molecular characterisation and impair the development of better therapeutic approaches. The analysis of cell-free tumour DNA in plasma (considered a liquid biopsy) has facilitated the characterisation of extra-cranial tumours. However, cell-free tumour DNA in plasma is limited in quantity and may not reliably capture the landscape of genomic alterations of brain tumours. Here, we review recent work assessing the relevance of cell-free tumour DNA from cerebrospinal fluid in the characterisation of brain cancer. We focus on the advances in the use of the cerebrospinal fluid as a source of cell-free tumour DNA to facilitate diagnosis, reveal actionable genomic alterations, monitor responses to therapy, and capture tumour heterogeneity in patients with primary brain tumours and brain and leptomeningeal metastases. Profiling cerebrospinal fluid cell-free tumour DNA provides the opportunity to precisely acquire and monitor genomic information in real time and guide precision therapies.

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Diagnostic value of 18F-fluordesoxyglucose positron emission tomography for patients with brain metastasis from unknown primary site

Cited by 17 publications

References 19 publications

Brain metastases as first manifestation of advanced cancer: exploratory analysis of 459 patients at a tertiary care center

Brain metastases as first manifestation of advanced cancer: exploratory analysis of 459 patients at a tertiary care center

90-gene signature assay for tissue origin diagnosis of brain metastases

Cerebrospinal fluid cell-free tumour DNA as a liquid biopsy for primary brain tumours and central nervous system metastases

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