Hi everyone, I'm Em Gootee, a research fellow at Cincinnati Children's Hospital Medical
Center.
Today, we will hear from Dr. Meera Kodagal, a pediatric surgeon at Cincinnati Children's,
about neuroblastoma diagnosis, staging, and management with three cases.
Neuroblastoma makes up about 8 to 10 percent of all pediatric cancers and about 15 percent
of cancer-related deaths.
That is basically made up of low-risk, intermediate-risk, and high-risk disease.
When we think about low-risk disease, those patients often have a fairly benign course.
The high-risk patients often have metastatic disease or the disseminated disease and it's
often fatal.
So high-risk disease and low-risk disease are very different.
And we are going to walk through some cases.
This is a three-year-old girl.
She has no past medical history.
She has some recent intermittent abdominal pain, no fever, weight loss, no subcutaneous
nodules, no proptosis.
And we get the ultrasound that shows an abdominal mass and we order a CT.
CT shows a lobulated soft tissue mass just below the diaphragm, 5.8 by 4.9 by 7.9 centimeters,
and has some calcifications.
It encases the abdominal aorta proximal to the level of the renal arteries and includes
the celiac and its branches as well as the SMA.
It pushes the IVC laterally and it elevates the portahepitis.
What do you want to do when you get a cancer patient?
Name it, stage it, treat it, right?
So we're going to start with diagnosis and staging.
What labs do you want?
We'll start with a simple blood panel, including blood cell counts, liver and kidney function,
coagulation panel, and electrolytes.
For this patient, we'll move to the specific labs.
Neuroblastoma cells often make catecholamines like epinephrine and norepinephrine.
So you're going to get the urine spot catacolamine serum levels.
And then we can check for epinephrine and norepinephrine metabolites, which are homovenilic
acid, HVA, and vanilla mandelic acid, VMA.
So this patient's HVMA and VMA are normal.
How many neuroblastomas have elevated HVA and VMA?
10% chance.
90% of them do have elevated.
But for the neuroblastomas, we don't think of them as causing blood pressure.
And after diagnosis, the next step is staging.
What imaging would you want to get for staging?
So CD of the chest, abdomen, pelvis, and maybe an MRI to rule out retroperitoneal liposarcoma.
So you got abdominal imaging, you get a chest imaging that's negative, anything else.
So in our institution, we tend to get both MIVG and PET.
It also to help you understand the metastatic disease.
How much bony disease do they have?
Do they have calvarian lesions?
And then you can track that with a CURE score over time in order to be able to see whether
or not they have regression with treatment.
The CURE score is specifically used to assess the extent of metastasis in neuroblastoma
patients based on MIVG scans.
The body is divided into 10 regions.
Each region is scored from 0 to 3 based on the degree of cancer involvement.
0, no involvement, to 3, extensive involvement.
The scores from each region are summed to produce a total CURE score.
The maximum possible score is 30.
This score helps determine the extent of metastatic disease in neuroblastoma, which is critical
for staging the disease, evaluating treatment response, and guiding therapeutic decisions.
So this is this patient that went on to get a biopsy.
And the biopsy showed ganglion neuroblastoma intermixed with favorable histology, non-amplified
and then they got bone marrow aspirates.
The bone marrow was negative for metastatic tumor and the biopsy was also negative.
So no evidence of disease in the bone marrow.
When thinking about neuroblastomas, there are two staging systems that are the most
common ones people talk about.
There's the INSS.
INSS stands for International Neuroblastoma Staging System.
The INSS takes into account the results of surgery to remove the tumor.
It cannot help doctors determine a stage before any treatment has started.
So it doesn't work as well for children who don't need or can't have surgery.
This is obviously not so useful for us in thinking about patients preoperatively.
So there has been a sort of progression in staging to think about INRG, which stands
for the International Neuroblastoma Risk Group, which is a preoperative staging system.
And it's designed to allow you to think about how difficult patients may be to resect and
how we can compare patients preoperatively across.
Of course, INRG does not replace INSS.
Providers generally use both, but INRG is often used pre-op.
The INRG staging system includes L1, which are local tumors, L2, which are local tumors
that also have an IDRF.
Or an image-defined risk factor.
M for metastatic tumors and MS for metastatic special, which is similar to 4S.
There are lots and lots of IDRFs.
The best way to think about IDRFs are things that touch things that are important.
Touching the vessels, touching the brachial plexus, touching the trachea, all of those
things count as IDRFs.
Radiologists and Cincinnati Children's use a standard template to go through and be able
to tell you this is IDRF positive or not.
And that helps determine whether it's L1 or L2, unless it's in more than one body
cavity, in which case it automatically becomes an disease.
We then put patients into risk groups based on their INRG status and a bunch of other
things.
H, NMIC status, Ploidi, and 11Q aberrations are factors considered for the staging.
Also, we have a tree that we use with INRG for staging.
You can find the illustrations in the description below.
Neuroblastoma tends to fall into aggressive neuroblastoma, benign neuroblastoma, and then
that intermediate risk is in the middle.
Aggressive neuroblastoma is high-stage, and benign neuroblastoma is low-stage disease.
High-stage disease has very poor survival.
And so our goals are to intensify therapy.
Low-stage disease has really good survival rates.
And our goals with that are really to reduce their therapy and try to avoid late effects
from therapy.
Because we know that for many cancer patients, two-thirds of them will have some long-term
morbidity from their chemo.
Let's go back to our patient.
The biopsy came, ganglion neuroblastoma, favorable histology, not amplified NMIC.
We'll start at the bottom of the tree.
The tumor was localized to the abdomen, but encasing SMA.
Does that make her an L2?
Any IDRF.
You can come in L2.
And you know that she has no bone marrow disease.
So that helps you to know that she doesn't have M disease.
Age is greater than 18 months.
She did not have loss of heterozygosity.
And she had differentiating neuroblastoma.
So she's actually at age.
And now we're looking at the table for grouping patients according to their INRG3 result.
Again, you can find this table attached in the description below.
She's eight.
She's intermediate risk.
In general, the intermediate risk patients are getting chemo.
My experience is that the neuroblastoma patients, they will get neoadjuvant chemotherapy.
Depending on the degree of the chromosomal factors, they'll get two, four, six, or eight
cycles.
After that, you then make a plan to go to the OR.
What is your approach?
We have a couple of things to think about with neuroblastoma resections.
They're different from other tumors because we divide them into tiny, tiny pieces while
we're taking them out.
The biggest thing to do with neuroblastoma is stay on the vessels.
So find yourself a normal vessel and work from normal to abnormal.
So if you're on the left side, find yourself the aorta and walk your way up the aorta.
Because you want to stay on vessel and walk up.
The closer you are to the vessels, the safer you are.
You could use a drip ultrasound.
We don't generally.
Usually you start on the vessels and you just work your way from known to unknown.
In this case, they went through and carefully separated the mass from all the vessels.
And here Dr. Kodagal shares the pathology findings from this case.
Neuroblastic tumor status post treatment, predominantly viable tumor with minimal therapy
related to this.
So this was a kid that had not had a substantial response to chemo.
So classic presentation for this case, right?
Management of intermediate risk, which is going to include upfront and then eventual
resection and then IDRFs really are associated with risk of complications.
Let's move on to the second case.
14 month old male with no past medical history who presented with a cough and a respiratory
viral illness.
And then the patient underwent a chest CT, which revealed a hypo intense heterogeneous
mass with calcifications originating from the mediastinum.
This mass appears to be extending towards the right side, exerting pressure on the right
lung and is located adjacent to the aorta.
Additional imaging like CT abdomen and pelvis, MIBG and PET scan didn't show any metastatic
disease.
And here Dr. Kodagal brought us a paper which shows that when corneal biopsies are performed
by experienced practitioners who ensure to obtain multiple cores, the adequacy of these
biopsies significantly improves.
We as our standard here will get percutaneous corneal biopsies for patients unless there
is no window.
Our radiologists usually get 25 cores from different parts of the tumor.
All this to say percutaneous biopsy is not inferior to open surgical biopsy.
So when you can, spare the patient an open surgical procedure and give them their percutaneous
biopsy so that they can get on with their treatment.
Let's get back to our case.
We did the biopsy and what did the results show?
Now we're back to our 3.
You can check this 3 illustration attached in the description below.
Here we're starting from the trunk and following branches until we reach the end and see which
group the patient is in.
Since the tumor is encasing the aorta, for IDRF classification we can tell it's L2.
Tumor is N-Mc- and the patient is younger than 18 months old.
So we are at G, intermediate risk.
So we have another intermediate risk here.
What do you want to do?
We would start off with neoadjuvant chemotherapy, follow up the patient and then decide on operative
resection.
Do neuroblastoma resections have to be done open?
Well, not necessarily.
For neuroblastoma, unlike most tumors that we resect, we would like to get as much as
of it we can.
But we would expect that we're not possibly getting every single ounce of tumor.
So basically your goal is to get as much of tumor as you can without causing harm.
This was an intermediate risk kid with the right chest mass.
We called it a subtotal resection because it was extending down beyond the diaphragm.
So we chased it a little ways down into the abdomen behind the diaphragm.
But then there was a point where it was right on the renal vein and Dr. Kottigal and her
team chose to stay there.
This patient responded very well to the chemo before the operation and there was a great
treatment response for the remaining tumor.
So percutaneous biopsy can be safely used for the diagnosis of neuroblastoma and minimally
invasive approaches can be used when you pick the patients.
And here's our third and final case of the day.
On the chest CT, this mass looks like it's behind the diaphragm.
And it's a very common place for these tumors.
We see them sneaking into the space right behind the diaphragm.
We know that the patient had no IDRFs.
There's no evidence of metastatic disease.
All we have is a four-month-old with an L1 tumor.
You get a biopsy and it says it's neuroblastoma.
So this patient is going to get an observation as their treatment.
Dr. Kottigal brought us a study from the Children's Oncology Group, or COG, that looked at expected
observations for young infants.
So it was 87 patients less than six months of age with a small adrenal mass and no evidence.
And they observed these patients with serial ultrasounds, intermittent CT, MRI, and then
labs.
In the study, there were four patients that had immediate surgery based on the qualifications.
Sixteen patients were in the observation arm and eventually had surgery, and the remainder
did not.
The four-year event-free survival for patients with neuroblastoma was 97%.
This was obviously studied primary adrenal, but we've expanded that and used that really
for L1 tumors in kids under six months.
So infants with small masses that are not metastatic can be safely observed.
Well that was all for today.
In summary, neuroblastoma is divided into low, intermediate, and high-risk groups, with
high-risk cases having poor survival rates, especially after relapse.
Diagnosis involves imaging and specific blood and urine tests, while staging uses CT, MRI,
MIBG, and PET scans to determine disease extent.
INSS is used postoperatively and INRG preoperatively to assess surgical risks and classify neuroblastoma
stages.
Intermediate-risk patients receive neoadjuvant chemotherapy and careful surgical resection
to maximize tumor removal and minimize harm.
Percutaneous biopsy is effective for diagnosis, and infants with small, non-metastatic tumors
can often be safely observed without immediate surgery.
Thank you for listening to this episode.