There is no cure available for neuroendocrine tumors available yet but as usual, there is treatment. The prognosis of the patient can be decided on the basis of stage and grade of cancer and certain other factors like age, the general condition of the patient. All these factors are looked at collectively to determine the prognosis of the tumor.
Brain metastases are rarely reported in patients with neuroendocrine carcinoma (NEC) of non-lung origin and neuroendocrine tumors (NETs) of the gastroenteropancreatic or bronchopulmonary system. Symptomatic brain metastases are associated with a dismal prognosis, so early detection and treatment could be advisable.
The incidence of brain metastases for neuroendocrine tumors (NET) is reportedly 1.5~5%, and the origin is usually pulmonary.
NETs are considered to be the origin of brain metastases in 1.5~5% of all patients with brain metastases, and in 45–71% of these patients, the primary tumor was located in the bronchi or lungs. If brain metastases are present, lymph node metastases are found in 75% and liver metastases are found in 50% of these patients. Primary unknown NET represents just 13% of these tumors. It is difficult to detect the primary focus, especially for functional NETs, because patients have specific symptoms when the tumor size is small. Somatostatin receptor scintigraphy (SRS) is useful to detect the primary focus, especially for NET G1 and NET G2, whereas PET is more sensitive. The most widely used tracer is F18-deoxyglucose (FDG), but well-differentiated NETs do not uptake the FDG very well; therefore, 68 Ga-DOTA-TOC PET could be better for detecting pulmonary NETs. Somatostatin receptor imaging, by 111In-pentetreotide scintigraphy or PET with 68 Ga-DOTA-TOC PET, frequently identifies lesions that are not visible on other radiographic images. Currently, somatostatin receptor scintigraphy with 111In-pentetreotide is frequently available technique to determine somatostatin receptor expression. In the future, because of its higher sensitivity, 68 Ga-DOTA-TOC PET is expected to replace somatostatin receptor scintigraphy. However, 68 Ga-DOTA-TOC PET is not available in any place. So FDG-PET is easier to be performed. FDP-PET is usually sufficient for the detection of the tumor if the patient has a long-term follow-up even if the tumor is not high-grade NET.
Brain metastases are the most common intracranial neoplasm in adults. They often originate from lung cancer, breast cancer, or melanoma, but also other malignancies like renal cancer, colorectal cancer, and ovarian cancer are increasingly associated with brain metastases. Nearly 20% of the patients with small-cell lung carcinoma (SCLC) demonstrate brain metastases at initial diagnosis and about half of the patients develop brain metastases during follow-up. In contrast, brain metastases are rarely reported in patients with neuroendocrine carcinoma of non-lung origin and neuroendocrine tumors (NETs) of the gastroenteropancreatic or broncho-pulmonary system. In the Spanish and German NET Registries, 4 of 837 (0.5%) and 12 of 2358 (0.5%) patients with brain metastases are documented. The estimated incidence in NETs is 1.5–5%.
Somatostatin and other neuropeptides are expressed in tumors originating from neuronal precursors and paraganglia, namely meduloblastoma, central Primitive Neuro-Ectodermal Tumors (cPNETs), neurocytoma, gangliocytoma, olfactory neuroblastoma, paraganglioma. In meduloblastoma, the most common malignant tumor in childhood, there is an extensive expression of somatostatin in addition to somatostatin receptors (SSTR) type 2. Although the density of SSTR-2 and intensity of expression
General screening for brain metastases is not recommended in NET and non-lung NEC patients. Whether or not prophylactic brain irradiation in limited disease NEC of gastroenteropancreatic origin could result in better prognosis like in SCLC is unknown. Symptomatic brain metastases are often associated with a dismal prognosis, so early detection and treatment could be advisable.
Somatostatin and other neuropeptides are expressed in tumors
originating from neuronal precursors and paraganglia, namely meduUoblastoma, central Primitive Neuro-Ectodermal Tumors (cPNETs), neurocytoma, gangliocytoma, olfactory neuroblastoma, paraganglioma. In meduUoblastoma, the most common
malignant tumor in childhood, there is an extensive expression of somatostatin in addition to somatostatin receptors (SSTR) type 2. Although the density of SSTR-2 and intensity of expression of somatostatin genes have no prognostic significance in medulloblastoma, their presence may bring along important information on oncogenesis and relate medulloblastoma to
cPNETs. Radio-labeled octreotide scintigraphy may be useful in the follow-up of these patients, allowing differentiation. between scar and tumoral tissue. Moreover, on the basis of octreotide-induced inhibition of cell proliferation in meduUoblastoma, a trial with octreotide in patients with recurrent or. high-risk tumour is warranted. Meningiomas and low-grade astrocytic gliomas, even if not displaying a clear neuroendocrine phenotype, have high levels of SSTR-2. In meningiomas,
Meningiomas express SSTRs in nearly 100% of cases,
both in scintigraphy and in cell culture studies. By an
in situ hybridization technique, meningiomas have been
confirmed to express only intense and homogeneous
SSTR-2.
SSTR-2A was demonstrated by immunohistochemistry
and Western blot analysis.
SSTR-2A was demonstrated by immunohistochemistry
and Western blot analysis
However, somatostatin receptor scintigraphy is not
part of the routine pre-operative work-up of a patient
suspected to have meningioma. This is partly explained
by discrepancies among different groups. While some
authors reported positive in octreotide scintigraphy in 100% meningiomas, others claimed that a low percentage of smaller meningiomas (<2.7 cm in diameter) were negative by scintigraphy.
Unexpectedly, in cultured meningiomas, somatosta-
tin and octreotide do not inhibit cell proliferation, but
rather slightly increase it, and this was accomplished
through the inhibition of adenylate cyclase. How-
ever, it cannot be excluded that somatostatin-analogues
in vivo may have antisecretory effects on para/autocrine
growth factors, such as FGF, which in turn stimulates
tumor growth . Furthermore, somatostatin-analogues, even if inactive in inhibiting proliferation, could
still play a role in meningioma therapy, contrasting
secretory phenomena associated with the formation of
edema around the tumour. In conclusion, therapeutic
trials in patients with recurrent or inoperable menin-
giomas with somatostatin analogues have to be carried
out with great caution.
Astrocytic gliomas
The majority of low-grade gliomas (WHO grade 2) and
a smaller fraction of anaplastic astrocytomas (WHO
grade 3) have been reported to contain SSTRs, as
assessed with various receptor binding techniques. Recent gene expression studies (RT-PCR ) have
shown that low-grade astrocytomas highly express
SSTR-2, alone or in combination with SSTR-1 .
while high-grade gliomas scarcely express, or do not
express, SSTR-2. Therefore, it has been supposed
that SSTRs are important only in programming cell
differentiation, and lose this significance with progressive differentiation.
Non-neoplastic cultured astrocytes express only low
levels of SSTR-1,2,4, whereas low-grade gliomas are
believed to overexpress SSTR-2, in accordance with the
overexpression of SSTRs seen in different tumours.
However, the overexpressed SSTR-2 in human glioma
cells was found to be intact (SSTR-2A splice variant is
predominantly expressed) and functional]. In fact,
no gene mutation was detected and the receptor showed
functional properties similar to those of non-neoplastic
astrocytes.
Unfortunately, use of the different expression of
SSTR-2 in low- vs. high-grade gliomas in radiolabeled-
octreotide scintigraphy is not useful in the differential
diagnosis of gliomas . Discrepancies between in vivo
scintigraphy with labelled-octreotide and the SSTRs sta-
tus in vitro were repeatedly observed. They can be
explained by the fact that in vivo uptake of radiolabeled
octreotide in gliomas is due to the disruption of the
blood brain barrier (BBB) rather than to the presence of
SSTRs [18,19]; therefore, radiolabeled octreotide cannot
reach SSTRs in astrocytoma WHO grade 2, where the
BBB is intact, while in high-grade gliomas, where the
BBB is disrupted, there is a non-specific accumulation
of the tracer. In conclusion, radiolabeled-octreo-
tide scintigraphy does not add information to routine
CTand MRI scans in the differential diagnosis of intra-
cranial lesions .
For the same reasons, radionuclide-labelled long-act-
ing somatostatin analogues also do not seem to be useful
in low-grade glioma, because the intact BBB would
prevent the therapeutic agent from reaching the target
SSTR-2.
Recently, a pilot study has proposed the use of a
radio-labelled, diffusible somatostostatin analogue in a
loco-regional approach to overcome the intact BBB. The vector, a somatostatin analogue conjugated
with the radiometal chelator DOTA (DOTATOC or
90Y-labeled DOTA°-d-Phe'-Tyr3-octreotide) was in-
serted in one to four fractions into a stereotactically
inserted Port-a-cath; the total cumulative activity was
up to 550 Gy. Selected patients had low-grade glioma
(five astrocytoma and two oligodendroglioma WHO
grade 2) or high-grade glioma (one oligodendroglioma
WHO grade 3 and three glioblastomas) with documented
disease progression, despite previous surgery, external
beam radiotherapy, brachytherapy and/or chemotherapy.
The authors did not observe any vector diffusion into
the adjacent normal brain, and reported the shrinking
of a cystic low-grade astrocytoma in addition to six dis-
ease stabilizations. Accordingly, the activity: dose ratio
(MBq:Gy) was a measure for the stability of peptide
retention in receptor-positive tissue and might predict
the clinical course. A trend toward longer progression-
free survival in low-grade glioma patients with an activi-
ty: dose ratio < 5 was observed
The neuroendocrine system comprises a complex architecture of cells that are capable of producing NETs throughout the body. While NETs are known to develop throughout the gastrointestinal and respiratory tracts, there are only a few reports to suggest NETs originating primarily from the brain. NETs can be well-differentiated or poorly differentiated, and in the high grade poorly differentiated types, they can be a large cell
or small cell variants. The incidence of NETs has been prominently increasing over the past two decades. This is believed to be secondary to increased detection rates. Generally, the majority of NET metastases occur in the liver, lungs, and bone.Involvement of other sites is much rarer. NETs are considered to be the origin of brain metastases in 1.5-5% of all patients that.have brain metastases. In 70% of these patients, the primary
tumour was located in the bronchi or the lungs. If brain metastases are present, lymph node metastases are found in 75%, and.liver metastases are found in 50% of these patients. Primary unknown NET represents just 13% of these tumours.
Because the leading cause of death in patients with brain
NETs is secondary to systemic disease progression, the prognosis may be substantially different from metastatic brain NETs.Primary brain NETs appear to be more similar to non-metastaticNETs in which the ten-year overall survival rate is 47%
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