CNS Necrosis vs Progression?

[Haybrant]

Im covering on a patient so I don't know the patient well but he was treated SRS to a high left parietal lesion 16 months ago for NSCLC metastasis. 1.5 months ago developed right hemiparetic symptoms and MRI revealed 1.5 cm nodular enhancing lesion in the area of prior SRS. He was started on steroids and responded well and followed. The enhancing component is now 3.5 cm and he represented to Neurosurgeon with dense right hemiparesis while he was tapering steroids. Surgeon says he could remove it but it would be high risk of permanent hemiparesis.

Whats the appropriate step here? Biopsy to get tissue confirmation? If that biopsy is positive or negative what would you do?

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[evilbooyaa]

What dose of SRS? GTV to PTV planning margin? Treated at your facility? Can you look at the plan, with fusion of the MRI from 1.5 months ago (and help determine if it's truly 100% in-field or some sort of marginal recurrence of tumor)? How long was patient on steroids after initial 1.5cm imaging eval? Seems like he was on it for a while as he was tapering them down over a 1.5 month period.

Do you have access to MR-SPECT? I'm not 100% familiar with that literature, but I know that certain peak analyses can help differentiate?

Assuming you have no other info and no other means to obtain info, I'd lean towards biopsy at least, maybe awake crani and resect out as much as possible?

However, if you CAN review the plan and do see that this is a marginal miss then I'm not sure it's worth doing a biopsy.

 

[Haybrant]

What dose of SRS? GTV to PTV planning margin? Treated at your facility? Can you look at the plan, with fusion of the MRI from 1.5 months ago (and help determine if it's truly 100% in-field or some sort of marginal recurrence of tumor)? How long was patient on steroids after initial 1.5cm imaging eval? Seems like he was on it for a while as he was tapering them down over a 1.5 month period.

Do you have access to MR-SPECT? I'm not 100% familiar with that literature, but I know that certain peak analyses can help differentiate?

Assuming you have no other info and no other means to obtain info, I'd lean towards biopsy at least, maybe awake crani and resect out as much as possible?

However, if you CAN review the plan and do see that this is a marginal miss then I'm not sure it's worth doing a biopsy.

I don't think it was a marginal miss, was a pretty small lesion also it was 16 months ago. What would we do if the biopsy is negative now though?

 

[Neuronix]

Agree with evilbooya--look at old plan. I fuse and overlay the old scans / plans in MIM with the new MRI to see for sure if it's in field, marginal, or out of field.

Assuming this is in field or marginal:

Biopsy

If negative, back on steroids + add avastin if possible

If positive, whole brain


If biopsy is too risky or pt refuses, could consider brain PET, MR spectroscopy, or DSC-MRI. None are definitive, but would help guide your decision to try one of the above options.

 

[nkmiami]

Wouldnt be surprising if she was on a checkpoint inhibitor. I just had a case like this recently that went for resection and it was radiation effect (not necrosis) with increased cd4 cells present. Personally, I havent found much help from mri in this situation, although others have. Sometimes PET is helpful.

 

[radiaterMike]

Wouldnt be surprising if she was on a checkpoint inhibitor. I just had a case like this recently that went for resection and it was radiation effect (not necrosis) with increased cd4 cells present. Personally, I havent found much help from mri in this situation, although others have. Sometimes PET is helpful.

Reviewing the plan is helpful but unlikely to be that helpful in distinguishing necrosis from progression especially if the radiographic changes are circumferential around the target. Special imaging - PET, MR spectroscopy, MR perfusion - can be helpful. I don’t think a biopsy really helps you. A negative biopsy (which is highly likely unless there is a definite solid component) doesn’t rule out progression. A craniotomy and resection can be considered whether there is progression or steroid dependent necrosis and to some extent would be diagnostic although the likely path of mixed necrosis and tumor cells might not really tell you what the etiology is. Either way - reducing the mass effect can help.

 

[mavrik13]

A wise neurosurgeon once told me... when you're wondering about radionecrosis vs recurrent tumor, the findings after resection often find both being present.

Sounds like it is progressing relatively quickly. You could order biopsy and MRI-spect and MRI-perfusion (we don't have easy access to brain PET). Biopsy is also reasonable if patient is well and you have time. As you rightly pointed out, will it change your management?

If patient continues to progress, what you've described sounds reasonable for resection. It's tough to say when we don't know original tumor size, PTV expansion, dose/fraction (you mention SRS so I assume Gammaknife, but would want to be certain). Does he have disease elsewhere? Stable or progressing elsewhere? On systemic therapy? Performance status? Many factors that would influence my approach...

 

[evilbooyaa]

I don't think it was a marginal miss, was a pretty small lesion also it was 16 months ago. What would we do if the biopsy is negative now though?

Sorry, shouldn't say marginal miss (no Rad Onc wants to hear that). I meant marginal recurrence. Sometimes you look at the prescription dose cloud and see the new tumor just at the edge of 50 or 80% of the prescription dose. That leans you more towards recurrence, versus a symmetric expansion around the entirety of your highest dose region leans you more towards necrosis.

I think if biopsy is negative you consider going with steroids +/- Avastin versus symptomatic decompressive resection given patient's acute symptoms. At 16 months out, I wouldn't expect significant clumps of tumor cells if patient is truly having radionecrosis (rather than recurrence).

Wouldnt be surprising if she was on a checkpoint inhibitor. I just had a case like this recently that went for resection and it was radiation effect (not necrosis) with increased cd4 cells present. Personally, I havent found much help from mri in this situation, although others have. Sometimes PET is helpful.

Something to consider if patient was recently started on immunotherapy (without history of having been on it before). I've anecdotally seen 'recall' RT reaction to previous SRS that strongly mimics necrosis that normalized by 6 months later. I think likelihood of that is low, but not impossible.

 

[nkmiami]

Sorry, shouldn't say marginal miss (no Rad Onc wants to hear that). I meant marginal recurrence. Sometimes you look at the prescription dose cloud and see the new tumor just at the edge of 50 or 80% of the prescription dose. That leans you more towards recurrence, versus a symmetric expansion around the entirety of your highest dose region leans you more towards necrosis.

I think if biopsy is negative you consider going with steroids +/- Avastin versus symptomatic decompressive resection given patient's acute symptoms. At 16 months out, I wouldn't expect significant clumps of tumor cells if patient is truly having radionecrosis (rather than recurrence).



Something to consider if patient was recently started on immunotherapy (without history of having been on it before). I've anecdotally seen 'recall' RT reaction to previous SRS that strongly mimics necrosis that normalized by 6 months later. I think likelihood of that is low, but not impossible.

In theory, fusing with the original plan is helpful, but if there is edema and some shift, which there often is,it really complicates this and often find it unsatisfying , even with mim deformations (which i really like). if original radiosurgery was fractionated (8gy x3 etc) radionecrosis is less likely. Ultimately for this size tumor, pt would benefit from debulking/biopsy unless progressing rapidly systemically.

 

[RSAOaky]

Consider the overall picture. The patient has survived almost 1.5 years with brain mets, they've already beat the odds. Whether it is radionecrosis or progression (I suspect the latter), the overall prognosis is poor and particularly so if they are not a candidate for resection. Do they have any other brain mets/indications for whole brain? If so, may be reasonable to start there and see how it responds and if it responds favorably you can say it was probably tumor and justify an SRS/SRT boost to the residual.

I don't really see a need to put the patient through a biopsy. If it is negative what do you tell them? Good news, it's just dead tissue. Bad news, there's nothing we can do about it because neurosurgery doesn't want to operate. If the biopsy is positive what really changes? Control rates for a 3.5cm lesion are poor, probably moreso in the reirradiation setting, and you're probably not doing much anyways.

If neurosurgery is willing to remove or even maximally debulk the "mass" you could have path, immediate symptomatic relief, and justify a resection cavity boost with some possible hope of long term control.

 

[evilbooyaa]

In an area that's already gotten SRS once and is concerning for necrosis right now, you want to do whole brain (and the patient will be on high-dose steroids given his symptoms), followed by additional SRS (if it responds, which it should regardless if it's tumor or necrosis given you're treating both issues simultaneously), with no additional evaluation? I disagree with that.

If the biopsy is negative you keep them on high dose long-term steroids with Avastin and don't have to put them through RT, especially not WBRT.
Debulking of the mass at biopsy for symptom control is reasonable and what I would push for. I'm not sure that with radionecrosis you have to do a GTR or it's worthless.

How much edema is on the current MRI? You can consider looking at edema/contrast enhancing ratio if you can't do SPECT - Extent of perilesional edema differentiates radionecrosis from tumor recurrence following stereotactic radiosurgery for brain metastases. - PubMed - NCBI

 

[nkmiami]

If this is 100% radio necrosis, the worst thing you can do is give additional radiation. I can tell you from experience that safe debulking without GTR can improve symptoms and will give you an idea about what is going on.

 

[Mandelin Rain]

I have found perfusion MRIs more helpful than SPECT in this setting. At the size you've indicated, I think an FDG PET could also be useful. If it's solid and enhancing, I'd bet on tumor. If it's more cystic, I'd think necrosis is more likely.

When in doubt, start Avastin and hope for the best whether it's progression or necrosis. Follow with MR in 6 weeks or worsening of symptoms.

 

[Palex80]

As other have said: Review the plan and fuse with current imaging.
If the lesion was underdosed (for whatever reason), progression is more probable. If the lesion was adequately dosed (or overdosed), then necrosis may be an issue.

I still think it's rather progression than necrosis. Rates of truly evident and symptomatic necrosis after SRS are lower than rates of local recurrence. I'd say odds about 1:3?