how do you treat isolated adrenal mets?

[Raygun77]

Hey guys,

In your hospitals/practices, is SBRT or interventional radiology (RFA) becoming a viable alternative to surgery for isolated adrenal mets?

Just wanting to gauge practice

Thanks!

Ray

---

Members don't see this ad.

 

[Palex80]

We don't do RFA.

I've done SBRT several times. The dose constraints to the gastric wall can be a problem sometimes (for the left-sided ones).
I usually give 5x5 Gy to the 60% isodose which covers the PTV, resulting into something like 5x8 Gy to the met itself.

 

[seper]

Lap adrenalectomy or SBRT (6-7 Gy X 5).
However, one always has to mention, there is no evidence that it improves outcomes in NSCLC and I personally doubt that it does.

 

[napoleondynamite]

Here's a series of 34 patients treated with decent results:

http://www.ncbi.nlm.nih.gov/pubmed/22263925

 

[medgator]

Chemotherapy














I kidd, I kidd (sort of)

Seriously, as seper alluded to, It's not clear that it helps in NSCLC. The adrenal gland is very much a hematogenous source for accumulating and disseminating mets. Even if nothing else lights up on a PET, it's hard to imagine there isn't microscopic disease elsewhere. I think surgery has the most data to back it up, but in total, it's a pretty tough scenario.

 

[Reaganite]

Little surprised about the nihilism here! The retrospective data on metastasectomy for solitary adrenal and brain mets (particularly in the setting of early T-stage N0 disease) are apparently robust enough to lead to a recommendation for definitve treatment in the NCCN guidelines for NSCLCa. I think this is one of the few scenarios where the NCCN panel has actually recommended definitive treatment in the metastatic setting! This being said, if you do subscribe to the camp that these patients are potentially curable, are the commonly used schemes like 6 Gy x 5 really enough?

 

[RadRadRad]

I'd favor local treatment. This is the best paper I've found on the topic. Over 100 pts pooled together. 5 yr OS of 25% for NSCLC with isolated adrenal metastases. This is similar to resection of hepatic mets from colorectal cancer, albeit with smaller n. NCCN also lists local therapy to adrenal + treatment of lung primary in the setting of solitary adrenal met....although they also list chemo alone as a choice.

Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis.
Tanvetyanon T, Robinson LA, Schell MJ, Strong VE, Kapoor R, Coit DG, Bepler G.
J Clin Oncol. 2008 Mar 1;26(7):1142-7. Review.
PMID: 18309950

 

[RadRadRad]

sorry reaganite...didn't see your NCCN post come through....and agree about dose limitations. I'd prefer adrenalectomy if medically operable.

 

[deleted4401]

Not that I don't think it's reasonable to treat, but that number is sort of high to report (25% at 5Y) because stage III 5YOS ranges from 5-20% in literature. Maybe oligometastatic disease is better prognostically compared to locally advanced disease, or maybe there is strong selection bias in these reports. I think the latter, but totally agree with treating them fairly aggressively. Don't really need the gland, so cut it out!

 

[Palex80]

The problem with giving out solid (NCCN-like) recommendations for treating adrenal mets, is the evidence level at hand.
Most (if not all data) from surgical series are based on retrospective reviews of patients.
This leads to major bias, since (as we have often seen before) people tend to publish only:
a) if their results are good
b) by making their results look good

Which more or less means, that (as far as we know) only the "good" patients may have been published, basically those staying in remission. Given the rather limited extent of data, its also different to give out detailed recommendations, based on prognostic factors, for example:
a) only operate patients, which presented in a Stage <IIIA intrathoracic disease
b) only operate patients, with favorable histology (not G3-adeno, which tends to be metastatic all over the place)
etc...
We have such recommendations formulated for metastasectomy in other settings, for example for liver mets in colon cancer or lung mets in sarcoma. We don't have them for adrenal mets in NSCLC.

Other than that, I see no reason, why not to perform SBRT and go for surgery. Local control seems to be quite high with SBRT. Actually most SBRT-data may actually be even that surgical data, since some of the series seem to have been created in the context of a Phase I/II trial.

A young NSCLC patient with two different primaries in the right and left lobe (different histology) and IIIB disease in the mediastinum + one adrenal met.
He got 60 Gy to all the intrathoracic disease and an SBRT for the adrenal met. Concurrent chemo with Cisplatin/Etoposide.
Toxicity was ok, I am anxious to see his first follow up imaging.

I know, I know, it's a very ambitious therapy scheme and his prognosis is probably miserable, but I thought: "Why not just do it?"

 

[napoleondynamite]

I know, I know, it's a very ambitious therapy scheme and his prognosis is probably miserable, but I thought: "Why not just do it?"

I say strong work, personally. I think that if anyone is going to challenge the oligometastatic theory, it should be our field. With the limited toxicity of SBRT, I think it is worth investigating. Who knows, we may actually improve outcomes

 

[Cancerdancer]

I agree with lap adrenalectomy or SBRT in this situation. However, for the new guys out there, a few points. I've heard attendings quote these kind of studies above to patients with synchronous, metastatic NSCLC...

Way too many people in our field extrapolate data from studies of metachronous oligometastatic patients to patients with synchronous metastatic patients. The median OS for synchronous metastatic NSCLC in the JCO paper above? 12 months, which is what we see in studies of chemo for stage IV disease...

In my opinion, the following 2 papers are must-reads for anyone considering doing SBRT for 'oligometastatic' disease.

PMID: 16564447 Solitary metastases: illusion versus reality
PMID: 16564443
Key quote: If improvement in survival is the goal, the treatment would likely be most beneficial in patients with controlled primaries; limited metastatic disease; metachronous appearance of primary and metastatic disease; histologies including colorectal, sarcoma, and renal carcinoma; younger age; and higher performance status.

A case of NSCLC with N2 chest disease, and synchronous mets is an entirely different ballgame. I know Palex as a seasoned vet knows this, but there is a difference between oligometastatic (where a few clonogens get past upfront treatment and are detected years later) and upfront metastatic disease that we can currently only clinically detect a low volume of...and we too often confuse these in our excitement to 'cure oligometastatic disease.'

 

[seper]

I am genuinely surprised to see NCCN guidelines for treating adrenal mets. By inserting this kind of stuff, the lung expert panel and NCCN organization discredit themselves as world leaders in cancer care.

 

[medgator]

I am genuinely surprised to see NCCN guidelines for treating adrenal mets. By inserting this kind of stuff, the lung expert panel and NCCN organization discredit themselves as world leaders in cancer care.

Yeah the evidence is sparse. I'm surprised it got a Category 2B rec. Would have expected Category 3

 

[Raygun77]

Thanks for the interest and posts everyone. Very interesting discussion!

What's clear from the recent paper by Scorsetti et al. Is that there's very little consensus as to the fractionation schedule/dosing for adrenal mets. I guess this is because we're not yet sure what the treatment intention should be with all the prog factors (histo, synch vs. metachronous, other active disease, etc). Although there is a lot of heterogeneity in schedules in the data nicely summarized by Scorsetti et al., the local control rates (which i suppose is the best value to compare) are very heartening! I'll do a bit of a search and see if RFA rates are similar though I expect they would be given it's another local ablation therapy.

I've read anecdotally that a BED of >=100Gy is being seen as the necessary dose for SABR to lung primaries...I'm not sure though, is this an arbitrary figure or is there much data behind this? If anyone could enlighten me as to how this figure was come to id be grateful!

 

[Palex80]

A case of NSCLC with N2 chest disease, and synchronous mets is an entirely different ballgame. I know Palex as a seasoned vet knows this, but there is a difference between oligometastatic (where a few clonogens get past upfront treatment and are detected years later) and upfront metastatic disease that we can currently only clinically detect a low volume of...and we too often confuse these in our excitement to 'cure oligometastatic disease.'

I fully agree with you.
Time will tell. I hope, I won't have to post images of the WBRT-planning we may have to do for the patient I mentioned.

What's clear from the recent paper by Scorsetti et al. Is that there's very little consensus as to the fractionation schedule/dosing for adrenal mets. I guess this is because we're not yet sure what the treatment intention should be with all the prog factors (histo, synch vs. metachronous, other active disease, etc).

True. The next point is chemo, which you may do in some of these patients, before or after SBRT. In my patient, we actually did it concurrently (that means, he got the SBRT immediately following his thoracic RT course).

 

[bix]

While I am not opposed to SBRT for oligometastatic disease such as an adrenal met, it is important to be careful in patient selection. The NCCN guidelines also list systemic chemo as an option for isolated adrenal mets. One footnote states "patients with N2 disease have a poor prognosis and systemic therapy may be considered." In the discussion section when talking about adrenalectomy they note that "some panel members feel that resection of adrenal metastases only makes sense if the synchronous lung disease is stage I or maybe stage II (ie resectable). Systemic therapy is also another option."

Patients with adrenal oligomets tend to be more likely to progress systemically than other sites of oligometastatic disease. PMID: 18072260

In this SABR adrenal met study all patients failed distantly and 91% did so in the first year. PMID: 21300473

It will be interesting to see how the literature evolves and hopefully clinical trial will give us more data.

I've read anecdotally that a BED of >=100Gy is being seen as the necessary dose for SABR to lung primaries...I'm not sure though, is this an arbitrary figure or is there much data behind this? If anyone could enlighten me as to how this figure was come to id be grateful!

I believe the following study from Onishi is where the BED of at least 100 Gy comes from: PMID:15378503

 

[Raygun77]

...
A case of NSCLC with N2 chest disease, and synchronous mets is an entirely different ballgame. I know Palex as a seasoned vet knows this, but there is a difference between oligometastatic (where a few clonogens get past upfront treatment and are detected years later) and upfront metastatic disease that we can currently only clinically detect a low volume of...and we too often confuse these in our excitement to 'cure oligometastatic disease.'

This may be a bit of a pie-in-the-sky thought, but is there any marker on pathology that can determine if a cancer cell/clonogen collection has been irradiated in a past-life? To distinguish the two types of metachronous mets- one which was microscopic/latent at treatment of the primary but subsequently grew, and the other that represents the 'clonogens that got past' upfront treatment?

I vaguely remember a consultant mentioning a marker for this. Still very much in the realm of lab research. RAD51 maybe? Has anyone else heard of such a marker?

 

[Cancerdancer]

This may be a bit of a pie-in-the-sky thought, but is there any marker on pathology that can determine if a cancer cell/clonogen collection has been irradiated in a past-life? To distinguish the two types of metachronous mets- one which was microscopic/latent at treatment of the primary but subsequently grew, and the other that represents the 'clonogens that got past' upfront treatment?

I vaguely remember a consultant mentioning a marker for this. Still very much in the realm of lab research. RAD51 maybe? Has anyone else heard of such a marker?

I think you're misunderstanding. 'Clonogens that got past upfront treatment' would be a tumor cell that metastasized, grew to some subclinical volume (say 10,000 cells) and then was log reduced by chemo (say down to 2 cells) that subsequently grew. This would be a common scenario whereby mets present metachronously following, for example, surgery plus adjuvant chemo for early stage lung CA or stage III colorectal cancer.

You are suggesting that a tumor cell would get by upfront RT...if so, it would result in locoregional failure, not a met.

 

[Palex80]

You are suggesting that a tumor cell would get by upfront RT...if so, it would result in locoregional failure, not a met.

But this locoregional failure could then create new metastatic lesions, I think that's what he was talking about.

 

[StIGMA]

This may be a bit of a pie-in-the-sky thought, but is there any marker on pathology that can determine if a cancer cell/clonogen collection has been irradiated in a past-life? To distinguish the two types of metachronous mets- one which was microscopic/latent at treatment of the primary but subsequently grew, and the other that represents the 'clonogens that got past' upfront treatment?

I vaguely remember a consultant mentioning a marker for this. Still very much in the realm of lab research. RAD51 maybe? Has anyone else heard of such a marker?

If you had a tissue sample from the original tumor, a spectral karyotype should differentiate a latent primary met from an irradiated but remaining (or subsequently metastasized) 'clonogen'. Obviously, the latent primary met would be more similar to the original tumor. Whole genome sequencing would be able to differentiate as well, probably without even the control sample.

http://www.ncbi.nlm.nih.gov/pubmed/16546907

 

[Cancerdancer]

But this locoregional failure could then create new metastatic lesions, I think that's what he was talking about.

Sure, that's possible, but a local failure (especially after RT, which he was questioning about) that subsequently seeds mets is entirely different than metachronous mets which may be considered for SBRT. Again, SBRT should only be considered when the primary is controlled. I was just trying to highlight the fact that metachronous mets that 'get by upfront treatment' should not include the situation where a local failure is a component of the pattern of failure, as he was suggesting by the question.

That's why we don't see series describing SBRT for H&N CA that's failed locally and subsequently met'd out...

 

[Palex80]

Sure, that's possible, but a local failure (especially after RT, which he was questioning about) that subsequently seeds mets is entirely different than metachronous mets which may be considered for SBRT. Again, SBRT should only be considered when the primary is controlled.

1. There is always the chance of having isolated failures in the primary tumor region/mediastinum, which can be controlled by either surgery or reirradiation. It's not very common, but we may see it more often, especially with involved node RT becoming standard of care, rather than elective irradiation in NSCLC.
2. There are patients, who may develop mets during neodjuvant treatment with RCT before surgery in stage IIIA. For these patients, it would be interesting to see, if those metastatic cells originate from the irradiated primary tumor and bear some radioresistance characteristics. There are some reports about a higher incidence of brain metastasis in NSCLC patients who received neoadjuvant CT and not RCT before surgery.

That's why we don't see series describing SBRT for H&N CA that's failed locally and subsequently met'd out...

I think that's a bit more complicated than that. A recurrent and metastatic H&N CA is a whole different ball game IMHO, due to several different reasons.
I've done SBRT for metastatic H&N in patients, where the med oncs did not want to start palliative chemo for one or two lung metatases. It worked well for about 6 months, until a whole group of new metastases grew.