Brain metastases from an unknown primary tumour: which diagnostic procedures are indicated?

Pol, M. van de; Aalst, V C van; Wilmink, J. T.; Twijnstra, A.

doi:10.1136/jnnp.61.3.321

Cited by 56 publications

(34 citation statements)

References 4 publications

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“…Therefore a costly extensive evaluation for the undetected primary during the follow-up is not appropriate until more effective cancer therapies are available [106,126]: in this regard the clinical relevance of FDG-PET for detecting the primary tumor in addition to conventional procedures [62] is limited.…”

Section: Diagnosismentioning

confidence: 99%

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Management of brain metastases

Soffietti¹,

Rudà²,

Mutani³

2002

Journal of Neurology

319

215

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Brain metastases occur in 20-40% of patients with cancer and their frequency has increased over time. Lung, breast and skin (melanoma) are the commonest sources of brain metastases, and in up to 15% of patients the primary site remains unknown. After the introduction of MRI, multiple lesions have outnumbered single lesions. Contrast-enhanced MRI is the gold standard for the diagnosis. There are no pathognomonic features on CT or MRI that distinguish brain metastases from primary malignant brain tumors or nonneoplastic conditions: therefore a tissue diagnosis by biopsy should be always obtained in patients with unknown primary tumor before undergoing radiotherapy and/or chemotherapy. Some factors are prognostically important: a high Performance Status, a solitary brain metastasis, an absence of systemic metastases, a controlled primary tumor and a younger age. Based on these factors, subgroups of patients with different prognosis have been identified (RPA class I, II, III). Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures. In patients with newly diagnosed brain metastases prophylactic anticonvulsants should not be used routinely. The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition. Complete surgical resection allows a relief of intracranial hypertension, seizures and focal neurological deficits. Radiosurgery, alone or in conjunction with WBRT, yields results which are comparable to those reported after surgery followed by WBRT, provided that lesion's diameter does not exceed 3-3.5 cm. Radiosurgery offers the potential of treating patients with surgically inaccessible metastases. Still controversial is the need for WBRT after surgery or radiosurgery: local control seems better with the combined approach, but overall survival does not improve. Late neurotoxicity in long surviving patients after WBRT is not negligible; to avoid this complication patients with favorable prognostic factors must be treated with conventional schedules of RT, and monitoring of cognitive functions is important. WBRT alone is the treatment of choice in patients with single brain metastasis not amenable to surgery or radiosurgery, and with an active systemic disease, and in patients with multiple brain metastases. A small subgroup of these latter may benefit from surgery. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumor and extracranial metastases, some tumor types being more chemosensitive (small cell lung carcinoma, breast carcinoma, germ cell tumors). New radiosensitizers and cytotoxic or cytostatic agents, and innovative technique of drug delivery are being investigated.

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Section: Diagnosismentioning

confidence: 99%

“…CT of the abdomen occasionally shows an unsuspected cancer. Further search for a primary tumor is almost never fruitful without positive features in the patient's history or localizing signs on the physical examination to suggest a specific primary tumor [126].…”

Section: Diagnosismentioning

confidence: 99%

Management of brain metastases

Soffietti¹,

Rudà²,

Mutani³

2002

Journal of Neurology

319

215

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“…With improved imaging technology, it is now possible to find even small primary tumors, minimizing the number of patients with primary tumors of an unknown origin. Tumors that are small enough to elude high-resolution imaging, endoscopy, or serologic tests should have a smaller extracranial tumor burden despite the presence of a brain metastasis [18,28]. Thus, better local control of the brain metastasis may lead to a better outcome.…”

Section: Discussionmentioning

confidence: 99%

Brain Metastasis: Experience of the Xi-Jing Hospital

Wang

Guo

Zhang

et al. 2002

Stereotact Funct Neurosurg

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Background: The management of metastatic brain tumors is an important issue in patients with malignant tumors or cancer. The authors summarize the results of patients with brain metastases treated at the Xi-Jing Hospital during a 10-year period, in order to assess the best modality of treatment for patients with brain metastases. Methods: Between 1990 and 2000, 463 patients with brain-metastatic tumors were treated at the Xi-Jing Hospital of the Fourth Military Medical University, Xian, China. In most patients, the pathologic diagnosis of primary cancer was obtained before they were referred for their brain metastasis. There were 34 (8.42%) cases with an unknown primary cancer site at the time of initial presentation. Patients were grouped according to treatment methods, which included neurosurgical craniotomy (NS; 130 patients), whole-brain radiotherapy (WBRT; 120 patients). Linac XKnife radiosurgery (RS; 130 patients) and Linac XKnife radiosurgery plus WBRT (RT; 83 cases). Survival was measured from the time of treatment and was analyzed by the Kaplan-Meier product-limit method and then plotted. Differences between curves were evaluated using the log-rank test. Multivariate factors associated with survival were analyzed using the Cox proportional hazards model. Results: The survival time was 68.4 ± 7.20 weeks after NS, 51.3 ± 5.04 weeks after WBRT, 67.9 ± 3.68 weeks after RS and 89.7 ± 4.50 weeks after RT. The presence of active systemic cancer in a larger number of metastatic tumors was associated with a poor survival (p = 0.0003 and 0.0000). The female patients showed better survival rates over the male ones (p = 0.0000). Patients treated with RT had a better survival than those treated with NS, WBRT and RS (p = 0.0048, 0.0000 and 0.1222, respectively), although the latter did not show statistical significance. Conclusions: RS was an effective modality for patients with brain metastases, and if combined with WBRT, survival was better. Progression of systemic cancer and the number of metastatic tumors were the most significant factors for a poor survival after treatment of the brain metastases.

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“…Tumor cells should also be able to invade through basement membranes and escape immune detection with the aid of MMPs and through the loss of surface adhesion molecules, respectively. 17,47 A change in the expression of integrin and adheren molecules in cancer cells seems to signal the initiation of invasion. Cadherins play an important role in cellto-cell interaction.…”

Section: Mobilization Processmentioning

confidence: 99%

Molecular events of brain metastasis

Santarelli¹,

Sarkissian²,

Hou³

et al. 2007

FOC

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✓The brain is a privileged site of systemic cancer metastasis. The stages of the metastatic journey from the periphery to the brain are driven by molecular events that tie the original site of disease to the distant host tissue. This preference is not arbitrary but rather a directed phenomenon that includes such critical steps as angiogenesis and the preparation of the premetastatic niche. It appears that the connection between naïve brain and cancer cells is made in advance of any metastatic breach of the blood–brain barrier. This contributes to the preferential homing of cancer cells to the brain. Delineation of the guidance mechanisms and elements that influence cancer cell motility and dormancy are important for the advancement of treatment modalities aimed at the remediation of this devastating disease.

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Brain metastases from an unknown primary tumour: which diagnostic procedures are indicated?

Cited by 56 publications

References 4 publications

Management of brain metastases

Management of brain metastases

Brain Metastasis: Experience of the Xi-Jing Hospital

Molecular events of brain metastasis

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