Why Pancreatic Cancer is known as Morbid Malady?
Despite its low rate of occurrence, pancreatic cancer is distinguished in having exceptionally high mortality rates, with the 5-year
survival rate of some types being only 3 to 15%, depending on the stage at the time
of diagnosis. The cause is largely unknown and it develops rapidly, showing symptoms
of abdominal pain with weight loss and jaundice. Since these symptoms are vague,
delay in diagnosis can lead to its detection in later stages, at which point it has lower
prognosis due to the tumor having spread to the rest of the body. In addition to this,
the presence of the organ in a remote location in the body, difficulty in establishment
of diagnosis, lack of specific diagnostic markers and aggressive nature of the cancer
makes it respond poorly to chemo- and radiotherapies. All of these factors contribute
to the high mortality in pancreatic cancer. Among the risk factors of pancreatic cancer
are family history, tobacco consumption, ethnicity, and obesity
. In addition to these,
there are suspected links of pancreatic cancer to ABO blood group (more common in
people with blood group A and B) and infection with
cancer-causing viruses such as Hepatitis C virus.
What are the 4 types of pancreatic cancer?
Pancreatic cancers are mainly of two types based on the site of origin:
more commonly pancreatic adenocarcinoma, arising in exocrine glands
of the pancreas, and pancreatic neuroendocrine tumor, which is less
common and occurs in the endocrine tissue of the pancreas. Staging
of pancreatic cancers is similar to other cancers, with Stage 1 being
localized tumor and Stage IV cancer being metastasized to distant
parts of the body. Compared to other pancreatic cancers, adenocarcinoma
is most commonly detected at stage Ill or IV, and as a result has a poorer
prognosis. This could be due to the fact that the available Diagnostic tests are
nonspecific and can miss many patients at early stage of the disease. Surgical
resection is the only treatment for pancreatic cancer which is curative.
At the advanced stages, pancreatic cancer has no definitive cure,
although radiotherapy and chemotherapy
may be done to extend the life of the patient.
How to Diagnose Pancreatic Cancer?
Accurate diagnosis of pancretic cancer is essential,
with focus on staging of the disease, assessment of resectability
(how well the tumor can be surgically excised), and managing of symptoms.
In many cases, asymptomatic pancreatic cancer is detected due to an
abdominal scan carried out for other reasons. Imaging has thus increased
the number of pancreatic cancers detected. Mostly, initial evaluation is done
using Computed Tomography (CT) with intravenous administration of contrast dye.
This allows visualization of the tumor in context of surrounding structures
as well as distant organs and gives a fairly good assessment of the resectability
of the tumor. In addition, Endoscopic Ultrasonography can be done in patients
who do not show visible mass in CT scan. Tissue samples for tumor biopsy can
be obtained using endoscopic means such as Endoscopy with fine-needle
aspiration and Endoscopic Retrograde Cholangiopancreatography (ERCP).
Certain serum biomarkers are currently under study for diagnosis,
estimating prognosis, and monitoring therapy in pancreatic cancers,
an example of which is Carbohydrate antigen (CA 19.9). Recently,
PET-CT is emerging to play a promising role in pancreatic cancer.
F-Fluorodeoxyglucose Positron Emission Tomography
Computed Tomography (F-FDG PET-CT)
The F-FDG PET-CT scan is a type of nuclear medicine imaging technique that can
measure metabolic functions in the body such as blood flow, oxygen
usage and glucose metabolism. Cancer cells are distinguished from other
cells in their ability to breakdown slucose much more rapidly, which can
be detected by "F-FDG PET. "F. FDG is a tracer used in PET scans that gets
taken up by the cancer cells wherein it accumulates and its location can
be detected. CT scans provide an accurate image of the internal structures
of the body, thus PET-CT combined, allows the precise localization of the
abnormal region in the body.
Whole body PET-CT Scan
Can PET-CT scan detect pancreatic cancer?
PET-CT is reported to be highly sensitive and accurate for detection of
pancreatic cancer, with sensitivity being as high as 85% to 97% and accuracy
85% to 95%. This modality is also able to evaluate tumor response to therapy
after surgery, and can be used to monitor recurrence patterns during or after
chemoradiotherapy. Lesions (tumors) that are less dense and which may not
appear on conventional imaging techniques can be detected with PET-CT.
Such lesions can be detected earlier by PET-CT as compared to CT or MRI alone,
since at this point, the lesion is not visible as a physical abnormality. Most malignant pancreatic tumors are hypermetabolic as compared
to normal pancreatic tissue, this causes them to take-up much higher
quantities of F-FDG than normal cells, with the uptake being directly
proportional to the size of the tumor (especially those larger than 1 cm).
PET-CT has been used for differentiating pancreatic carcinoma from other
pancreatic diseases like Chronic
pancreatitis. However, differentiating
mass-forming pancreatitis from pancreatic adenocarcinoma remains controversial,
even with PET-CT, although as per some reports PET-CT offers better characterization
of mass-forming pancreatitis arising due to adenocarcinoma. Lastly, PET-CT has
played an important role in differentiating between benign and malignant cystic
neoplasms. The information obtained through PET-CT can also be used for precise
targeting in imaging-guided biopsies.
Applications of F-FDG PET-CT in Pancreatic Cancer Management and Diagnosis
Recent data highlight the importance of PET-CT in the including characterization of the tumor, staging of the cancer, and presurgical
and preradiotherapy planning. It also has a greater ability of distinguishing
between benign and malignant tumors.
Staging and Presurgical planning staging-
Staging of pancreatic cancer is done using the TNM system,
for which PET-CT is highly effective
as it allows better detection of distant metastases. PET.
CT has been found to have high accuracy in detecting peritoneal
metastases, primary pancreatic lesions, loco-regional staging,
and restaging of pancreatic cancer.
For pancreatic cancers, it is essential to determine the resectability
of the tumor to plan further treatment. PET-CT has shown far superior
performance as compared to other modalities in initial staging of disease
as well as detection of nodal and distant metastases. Pancreatic cancer
most commonly metastasizes to the liver and peritoneum.
PET-CT has been reported to show greater sensitivity than
conventional scans in identifying distant metastases. This is especially useful for initial staging of pancreatic
adenocarcinoma as it detects small and distant metastases,
thus showing greater sensitivity in diagnosis of adenocarcinoma.
Staging of pancreatic cancers using imaging techniques helps
prevent unnecessary surgical procedures like Laparotomy.
It is important to accurately identify the gross tumor
volume in pancreatic cancers that cannot be resected, to avoid irradiation of
healthy tissue in the surroundings during radiotherapy. PET-CT can help in
estimating (delineating) gross tumor volume and planning the conformal
radiation field in pancreatic cancer patients who are candidates for radiotherapy.
Since PET-CT can detect additional metastatic lymph node lesions,
its use has resulted in around 30% increase in gross tumor volume
as compared to that obtained by CT scan alone.
Predicting Prognosis, Therapy Response,
Recurrence of Pancreatic Cancer
It has been shown that readings obtained from PETCT before
treatment gave good indication of prognosis,
overall survival and progression-free survival in patients with
unresectable pancreatic cancer. Higher the baseline
SUVmax (which indicates the amount of tracer taken-up by tissue of interest),
the greater the likelihood of recurrence after surgery.
SUVmax can also predict overall survival in patients with locally
advanced pancreatic cancer However, results are varied between different
studies and some suggest that correlation between metabolic
response on FDG-PET and prognosis is still controversial."
Detection of recurrence through PET-CT is possible since actual
changes in morphology are preceded by a reduction in F-FDG uptake.
As a result, PET-CT Scan can detect the metabolic change before morphological
changes appear in in vivo studies. Evidence suggests that PET-CT can
distinguish between residual malignancy and fibrosis which commonly
occurs after surgery, as well as characterize the metabolic behavior of
hepatic lesions that are not accessible for biopsy.
Treatment response after chemotherapy can also be assessed
by running PET-CT scan before and after the treatment.
PET-CT has been useful in restaging of cases presenting with rising
tumor marker levels, but which show negative CT evaluation,
as well as for assessment of the tumor response to chemotherapy.
Following surgery, F-FDG uptake is normally expected to resolve after 3 months,
any remaining uptake after this time is usually indicative of residual tumor or recurrence.
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How is PET-CT scan Cost Effective?
In addition to the above mentioned applications,
PETCT has the advantage of being more cost-effective in the management of
pancreatic cancer, which is one of the deciding factors in selection of the
optimal imaging modality. This is because, although PET-CT may have high
initial cost, it has potential to reduce the total number of scans required
due to its superior detection of distant metastases, thus, helping in
preventing surgery and reducing total imaging cost.
PET-CT is not without limitations- its sensitivity and specificity is still insufficient for detection of
tumors 2-3 mm cm in size (at the point where they are resectable and curable).
Further, F-FDG also accumulates in inflammatory tissue, hence there is a need
for development of more sensitive and specific radiotracers for PET. At present,
studies are underway for the development of novel radiotracers
such as 3'-deoxy-3'-'F-Fluorothymidine.