Late delayed radiation toxicity or side effects from SRS on excision site? - 1261390

btlaw123
Posts:45

My wife is on Tarceva 100mg since oct 2011. Tarceva side effects has been difficult but tolerable. She has been NED for over 2 yr and 3 months since SR irradiation of the excision bed (site) of the right occipital lobe in 2011. SRS of the surgical site was given instead of WBR because we were reluctant to consent to whole brain radiation since overall she has practically no cancer burden anywhere else. Her situation matches closely to the single "precocious solitary brain mets" case I have read somewhere on this site.

She has about a fifth of her left vision field on both eyes not able to see clearly since the occipital lobe surgery from 2011. However over time since the SRS, her eyes has developed hyper-sensitivy to light and she has been having frequent visual migraine with multi-color ora but no headache since Sept 2012. Orpthalmologist ruled out specific eye defects but stated symptoms likely neurological.

Q1: Are visual migraine known to be side effect of radiation toxicity or narcosis from the SRS?

Q2: Is there any treatment known that will reverse or retard progression of possibly radiation toxicity resulting from high single fraction of SRS?

Forums

Dr West
Posts: 4735

I'm sorry to hear of her complications.

We can forward your questions to Dr. Loiselle, a radiation oncologist who does SRS.

I'm pretty sure the answer to the question of visual migraines will be a function of the location and very specific parameters of radiation, so there is nothing that could be anticipated as a general side effect of SRS in terms of migraines.

Also, to my knowledge there is no intervention currently known to reverse or retard progression of radiation toxicity/necrosis from SRS.

-Dr. West

dr loiselle
Posts: 37

Hi -

Visual migranines are not a common side effect after stereotactic radiation in the occipital region, but seems possibly related.

In such a case as you described, if an MRI and/or other imaging studies (like a brain PET/CT since you are years out from treatment) strongly suggest radionecrosis, treatment with bevacizumab (Avastin) can in many cases dramatically reverse symptoms related to radiation necrosis.

Ruling out recurrent disease vs. radionecrosis this kind of situation can be a challenge.

I hope that helps and that you are receiving good guidance from your physician team.

Regards,

Dr Loiselle

btlaw123
Posts: 45

Many thanks to both Dr West and Dr Loiselle for rendering their expert observations. At this point there is no definitive conclusion that my wife is suffering from radiation narcosis or even toxicity or recurrence.

So far, from the multiple MRI's since the SRS given in Sept 2011 the radiologists who read the scans consistently indicated no new lesion noted in the excision site nor any surrounding white matter edema.

All the reports indicated that "There are postsurgical changes with gliosis and amorphous enhancement at the operative site within the right occipital lobe"... and that " there are multiple foci of T2 signal hyperintensities identified within the white matter of both cerebral hemispheres. In this age group, they are most likely from small vessel ischemic changes"....

There are simply too much information for a lay person to understand or too little that is really known in medical science (or is it an art?)

Since wife had the one and only lesion detected in her brain, we decline WBR and she was given the SRS "1800 cGy delivered to 80% line" at the occipital surgical site as a "mop up" measure to assure that all the cancer cells are destroyed.

Q1: What are gliosis and amorphous enhancements?

Q2: Are these post surgical changes and T2 signal hyperintensities the results from too many MRI's or are they results from possibly radiation injuries?

Q3: Is there any new research recommendation on how best to treat a solitary brain met?

Thanks for helping to understand more how to render support to my wife.

btlaw123
Posts: 45

Sorry, my last question Q3 should read: Is there any new recommendations for how best to monitor the after care for a patient with a "precocious solitary brain mets"?

I am very concern that the frequent MRI's would cause other potential problems such as toxicities and residual ill effects from the dye used for the MRI contrast. I realized that she is in some uncharted territory. When I asked the few questions, her physician team and oncologists almost always have no definitive answers.

Unfortunately despite her low to no cancer load condition and that she is EGFR positive and responding well to Tarceva, medical statistics has already written her off just because she has outlived the average life expectancy of a typical stage IV lung cancer survivor!!

Dr West
Posts: 4735

The radiologist is really just describing what is characterized as likely vague post-treatment scarring, I think.

It is exceptionally unlikely, even bordering on unfathomable, that her brain imaging is a cause of any of what is being described.

The approach of stereotactic radiosurgery (e.g., gamma knife, cyber knife) really represents the best technology, which is becoming more precise with every hardware and software iteration.

Good luck.

-Dr. West

btlaw123
Posts: 45

Dr West,

I am in total agreement and respectful of your position in terms of not being able to provide medical opinion. Regardless, I appreciate much the existence of this website allowing patients and caregivers to share information and gain insight to make sense of life and how to deal with this "C" monster.

So far, her oncologist, radiologists, ophthalmologist and neurologists have not been able to make any sense of the shimmering in her left vision field "blind spot" and the visual migraine that she recently have experienced. I was hoping that the vast membership of this forum and the faculties may shed some light to her condition.

Thank you for taking time to follow her saga in her battle with cancer.

btlaw123
Posts: 45

Hello Dear Doctors/Faculty of Grace,

I am very much in distress. We are at a crossroad with the symptoms and condition of my wife. Its seems like medical science is at a standstill when it comes to my wife's treatment. She has been on Tarceva since Sept 2011 (3 yrs & 9 months). Currently she is still considered NED other than the recent finding in her MRI.

On July 2013 she first detected left vision field simmering and eye flashes (with visual migraines and aura) once or twice per week. Now her eye sight and occasional visual migraines has progressively getting worse (24/7 left vision field light shimmering and visual migraines 3 or 4 times a week each with duration of 20 to 30 minutes) MRI's since May 2014 detected light shadows of enhancement at the original surgical site where SRS was done.

The oncology team has not officially ruled out cancer recurrence. But based on the course and the timeline of her medical condition, they think its more likely radiation necrosis She had not been offered any form of treatment. The proposed intervention is to wait till the symptoms are totally intolerable then she will be offered steroid and possibly surgical or chemo with Avastin Just wondering if "wait until your back is against the wall" is the only approach in her situation or if there is any proactive treatment intervention that she should be on now before she is at a point of no return? Is hyperbaric oxygen treatment a possible choice of early intervention?

Any insight from anyone?

catdander
Posts:

Hi advocate,

I'm so sorry your wife is having these progressive symptoms. I've read through all 3 of your latest posts and adjoining threads and have come to conclusion that the question is whether or not to wait for treating your wife's symptoms. Is that correct? I don't want Dr. Loiselle to rehash what has already been said. Let me know and I imagine we can get an answer tomorrow.

Dr. Loiselle covered this topic a couple of years ago including this passage, "As far as treatment, this is challenging as well. Surgical resection can offer relief of some symptoms, but also can be a direct threat to function. Other strategies such as hyperbaric oxygen and avastin have been examined and reported in specific situations, with mixed results. Hyperbaric oxygen has been most studied in necrosis of the jaw following radiation for head and neck cancer. Avastin has less extensively been reported to potentially help renormalize brain vascularity after treatment with radiation and chemotherapy for primary brain tumors. How effective it is at treating or reversing any actual radionecrosis is yet to be seen, though there does seem to be some improvement according to MRI… but then again, we don’t even know how good MRI is at characterizing radionecrosis (see previous paragraph!)." http://cancergrace.org/radiation/topic/radiation-necrosis/

There are also these posts with a bit of info on the subject. Unfortunately there doesn't seem to be anything new since Dr. Loiselle last posted. http://cancergrace.org/forums/index.php?topic=9693.0
http://cancergrace.org/forums/index.php?topic=5576.0

All best to you and your wife,
Janine

btlaw123
Posts: 45

Thank you Janine for do some of the leg work in summarizing ahead of the faculty on all the pertinent posts on the subject of treatments for radiation necrosis. However all the embedded reference postings were at least 2 or 3 years old. Just wondering if there are any new data that point to preference of one method over the other when it comes to actually treating radiation necrosis? I have read this 2014 publication in Translational Cancer Research with a few of the co-authors happened to be from Swedish Radiosurgery Center, Swedish Medical Center, Seattle, WA, USA

http://www.thetcr.org/article/view/2950/html

My question is since Hyperbaric Oxygen seems to be pretty safe why is it not recommended as treatment of choice instead of the more invasive or damaging treatment like surgery and chemo with avastine?

dr loiselle
Posts: 37

It is hard to say without looking at the scan.
We would generally look at the size of the enhancing area, the extent of any edema, and how this maps exactly to the area of prior treatment. If the prior metastasis was resected and a cavity was treated with radiosurgery, how does the rest of the cavity margin look? Is the enhancement in a high dose area, intermediate dose area, or low/marginal dose area? If the area was treated to 18 Gy to the 80% line, than a small volume received 20 Gy or more. How does this specific area look? Not to imply any specific rules about interpreting radionecrosis vs. recurrent tumor, but a careful analysis of these aspects of the scan can be quite helpful.

In terms of new treatments, not much new is available, though our experience with Avastin is very good. I have not seen hyperbaric oxygen be helpful in this situation.

In terms of new diagnostic tools, our recent experience with PET/CT has shown it to be quite helpful in a few patients... may patients have intermediate results however, which are difficulty to interpret.

Best of luck to you and your spouse,

Dr Loiselle

btlaw123
Posts: 45

Dear Dr. Loiselle and other esteemed faculties,

My wife's most recent monitoring MRI (12/1/15) shows further enlargement of the enhancing area in her right occipital lobe now measuring 3.2 x 2.4 x3.1. In Aug 2015, based on a number of scans including MRI's, perfusion MRI, and PET/CAT scan, the oncology treatment team concluded that my wife is suffering more from radiation necrosis and not recurrence. She was put on a 3 months MRI monitoring schedule.

But now the enhanced area has increased to almost double the size in all three dimensions since first discovered in May of 2014 (1cm AP x 1.8cm transverse x 1.2cm cranio-caudal), not sure the meaning of these units.

In addition to the 24/7 flashing of lights in a third of her left vision field in both eyes (since day one in May 2014) and occasional 2-3 times a week of 10-15 minutes duration of visual migraines, she now experiencing daily, a dull headaches at her right temple area that radiates to her right eye socket that necessitates her taking an extended release extra strength Tylenol.

The 12/1/15 report also suggests surrounding white matter edema and possible internal hemorrhage.

Is there any medical intervention at this point to control the edema and hemorrhage or do we just sit and wait for the symptoms to run its course and hope and pray that her body will take care of the necrosis?

Ben

btlaw123
Posts: 45

Sorry I was remiss not including the following. Since July she was put on Trental and vitamin E for helping with the necrosis healing and Depakote for controlling the visual migraines.

I understood that Trental is supposedly to help with blood circulation. Should she stop Trental immediately in case it is causing the hemorrhage?

The treatment team members are each so specialized, that they may not have a good integrative picture! God have mercy.

catdander
Posts:

Hi Ben, I'm so sorry your wife has been through so much.

The standard of care for swelling in the brain are steroids. If hemorrhaging is an issue stopping blood thinners if possible is very appropriate.

As Dr. Loiselle mentioned in several of his post on the subject of necrosis, "treatment with bevacizumab (Avastin) can in many cases dramatically reverse symptoms related to radiation necrosis."

I wish there was more information and help to offer. You are a great advocate for your wife!
Janine

carrigallen
Posts: 194

In my limited experience, it seems uncommon to have a pronounced inflammatory process become progressively worse more than 4 years after stereotactic radiation. Of the downsides to radiation is that there is little we can do to 'reverse' it once it is given. The side effects can appear late. Nonetheless, as someone mentioned above, one wonders if something else is provoking this condition. Neurologists are often the best equipped to help with this. She requires a detailed assessment of all her medications, vital signs, imaging, and history. We are neither equipped nor allowed to provide medical advice to the level of detail she requires on an internet forum.
If the Trental and Vitamin E have been unsuccessful in controlling the symptoms of radionecrosis, then cessation seems reasonable. Trental is a blood thinner. In general, for situations like this, I would advocate for talking to her doctors promptly about stopping the Trental and possibly starting corticosteroids. Remember we can't give medical advice on this forum, only education.

dr loiselle
Posts: 37

Ben -
Have you seen a neurosurgeon? Has your team contemplated surgical excision of this lesion in the brain? If things outside of the brain remain without evidence of disease, and this area continues to evolve and be problematic, it is a reasonable consideration. This has risks, including a somewhat worse permanent visual field cut, but would yield a diagnosis and in some manner also be therapeutic whether this is recurrent tumor or radionecrosis. The specific details of the brain issue and your wife's health are paramount to a good decision here. I encourage you to bring this idea to your treatment team and seek consultation with a recommended neurosurgeon and radiation oncologist to jointly consider all such options and their potential good or bad repercussions.

Kind regards,
Dr Loiselle

btlaw123
Posts: 45

Surgical excision of this "Necrosis" was done. Surgical notes stated "removed obviously necrotic tissue" for biopsy.

Biopsy report however stated "By immunohistochemistry, the tumor is positive for TTF-1 and Napsin: The morphology and immunophenotype are compatible with lung cancer origin"

My wife is now scheduled for repeat radiation of the "necrotic" site.(she had SRS back in 2011 of the same site where the original solidary cancer met was removed)

Question:

1) Could this positive pathology result is from simply a histological footprints of the original cancer met and not a real recurrence?

2) Now they are treating it as if its a recurrence with 10 fractionized IMRT (something they called Intensity modified radiation treatment?? not sure if I understood correctly) late February. We have to go there 10 consecutive days.

3)Is this second radiation going to cause more necrosis? They said 10 fractions will cause less problem.

.

cards7up
Posts: 636

I'd just like to mention something I read recently on another post on another site. This person had one brain met treated with GK along with treatment for lung cancer. Somewhat similar in following your posts. Headaches that wouldn't go away and finally a new biopsy done. What happened is there was a new tumor that growing behind the one that had GK and it couldn't be seen due to scar tissue on the scans. It was just such a way that it was hidden. So this is most likely a new recurrence after original had been treated. I think they'd know if this was from the original. It could be a combo of necrosis and a recurrence. She's done well if this is positive going back 4 years or so and hopefully she'll do well this time.
Take care, Judy

Dr Pennell
Posts: 139

Hi, I can understand why this would be confusing. Cancer can often contain necrotic (dead) material and may even be mostly dead, especially after treatment such as radiation. However, if the pathologist was able to find intact cancer cells in the specimen amongst the necrotic cells, which it sounds like was seen in your wife's case, then there is living cancer there and this would mean a recurrence. You would not expect there to be residual intact but dead cells many months after a treatment (you can see this in the days and weeks after radiation). The IMRT is a form of radiation that allows very precise targeting of the tumor to spare the normal brain as much as possible.

Yes the tumor probably will become necrotic (or more necrotic) after radiation, but doing it in smaller doses over more fractions rather than one single very high dose reduces the chances that this will cause problems.

btlaw123
Posts: 45

Dr. Pennell, Thank you so very much for the explanation. Indeed the field of medicine is often times is like an art form. It takes the medical practitioners lots of dedication and effort to provide an individualized care to the patient. That is why this GRACE site is such a "God send" when I first discovered it.

In the case of my wife, she is on a daily 100mg of Tarceva, and she is considered NED with the exception of this recent discovery of radiation necrosis.

Is Tarceva considered a systemic chemo treatment?

Should she be off the Tarceva for the two weeks of pending radiation treatment?

I have read somewhere that a person should not have chemo concurrent with radiation treatment in fear that it would increase the dosage effect of the drug or the radiation and producing greater undesirable side effect of both.

Are there any do's or don'ts for this upcoming treatment?

Dr Pennell
Posts: 139

Ah, that is a good question without a good answer. Yes Tarceva is a systemic treatment but it is different than chemotherapy. We do try and avoid giving chemotherapy and brain radiation at the same time if we can because it can increase the side effects. Whether to stop Tarceva during brain radiation is unknown. It can be safely given at the same time for many people, but I also have seen patients who get severe skin rash in the scalp from the radiation while on Tarceva (and many who did not). I would say some doctors hold it and some do not, and I don't know what the right answer is.

The specific dos and don't would probably be best answered by the her oncologists there since they can be very specific to the patient and exact treatment.

I know that isn't very helpful but each case ends up being decided individually in a situation like this where there is no clear right or wrong.

btlaw123
Posts: 45

I also read in GRACE somewhere that stopping Tarceva for whatever good reasons might trigger a flare up of the EGFR mutation with a vengeance. Is this true? What a catch 22 situation!

catdander
Posts:

Advo, this flare up is turning out to be pretty rare and thought to be enough so not to keep someone from stopping if it's thought needed. Dr. West still mentions this from time to time. You can probably find one if you search tarceva flare.

Hope she AND you are feeling alright.
Janine

btlaw123
Posts: 45

To all esteemed radiation oncology faculty,

I have some questions in how an external beam radiation of the brain or for that matter any part of the body, can focus on the cancer without damaging everything along the path? Case in point is with SRS or IMRT.

I understood that in IMRT, as many as up to 8 beams are used to avoid or spare certain structures of the brain or vital parts of the brain that might be more susceptible to injury to preclude unnecessary damages and preserve vital brain function.

I read and understood only vaguely and simplistically that with multiple beams and the fractionized delivery concept, only the focused point where all the beams meet would receive the most radiation dose while minimizing the collateral damage of the beams along the way.

However can someone please explain if in real practice, would the multiple beams’ individual pathways need to shift and change with each of the fractions delivered to attain the maximum benefit of structures and vital organ avoidance?

From an anxious husband

Ben

catdander
Posts:

Hi Ben, I know how it feels to be an anxious spouse. I'll try to get our radiation oncology faculty to comment.
Hopes for the best for her and you,
Janine

dr loiselle
Posts: 37

HI Ben -

You are right - IMRT typcially involves multiple beams, crossfiring irregular patterns to paint higher prescription radiation dose across at-risk areas, while other areas in the path of the beam (entrance and exit) receive a fraction of that prescription radiation dose.

The beams are usually fixed per fraction with IMRT, although increasingly, multiple arcs of radiation (beam moving during treatment) are used to deliver radiation in desired dose profiles.

There are lots of ways to deliver safe and effective radiation in this scenario.

I would ask your radiation oncologist to show you the isodose plan from the initial stereotactic treatment and the current isodose plan.

Best regards,
Dr Loiselle

btlaw123
Posts: 45

If the beams are fixed then each of the 10 or 12 fractions beam all passing through the same pathway. Would it not injure all the live cells along the way just the same?

Again I know very little if not nothing how this works. I can only imagine the radiation beams like a bunch of kids gathering around in circle each with a magnifying glass trying to aim the beam of light from the sun at a single match just to try to light it up on fire. Though the heat from each beam coming through the magnifying glass is relatively weak, but with all the beams concentrating on the same match, it catches up on fire in no time.

Is this pictorial analogy somewhat correct? Or am I all wet?

I am just too busy to worry about my wife's IMRT to come up with this question. Thanks for reading.

dr loiselle
Posts: 37

yes and no...

again, ask your radiation oncologist to review the "isodose plan" with you. this should help.

Dr Loiselle

btlaw123
Posts: 45

Dear Dr. Loiselle,

Thank you for your patience in explaining what I was asking. This is exactly why I love this site so much. Information presented patiently in layman's term is what brings people back to this site time and time again.

We are with a large HMO in Southern California. Most of the time we do not have such luck and luxury to communicate with our provider team. Thank you once again for the information you have given.

btlaw123
Posts: 45

My wife has just completed (on March 9th) a 12 fractions IMRT on her right occipital lobe of her brain. This was a follow-up on the second brain resection done on Dec 12 2015.

The neurosurgeon found some viable cancer cell in the midst of a massive necrotic tissue, supposedly built up from 2011 after surgery removal of a solitary mets followed with SRS.

For some unexplained reasons, in this past week after the IMRT treatment, the hair on her entire left side of her head started falling off. The hair on her right side of her head is still intact.

Is this normally expected or did they zap the wrong side of her head?

dr. weiss
Posts: 206

Radiation follows a mostly straight line, so in addition to hitting tumor, there's some entrance dose to healthy tissue "in the way" on the way in and some exit dose to healthy tissue on the way out. These can certainly cause side effects. If you ask, the radiation oncologist should be able to give you an idea of how much entrance and exit doses there were to see if it fits with the hair loss.

btlaw123
Posts: 45

Thank you Dr Weiss for attempting to answer my question.

That was exactly why I posted the earlier question in this thread. Radiation treatments, be it SRS or IMRT or for that matter WBRT are so brutal, scary and damaging that I wish there is a better alternative treatment.

One would think that if they can send a man to the moon and back they could have design a better form of treatment for brain cancer.

What I posted begs the question as to why in each consecutive fractionized multiple-beam radiation treatments would we not intentionally alter or change the entry and exit points (or the pathways) so as to minimize the repeat and cumulative damaging effect of the fixed beams passing the same set of healthy tissues or skin surfaces along the way? This procedure is so barbaric! God have mercy on us.

dr. weiss
Posts: 206

The quick answer to your question is likely already obvious to you: we keep using radiation for the brain because barbaric as it is, lung cancer in the brain is even more barbaric. But, your question is a very good one that deserves a more detailed answer regarding attempts to do better.

First, radiation oncologists are exploring new methods to try to do what you're describing. Some of the more promising approaches to improved targeting are cyberknife for small tumors, partial brain irradiation in select cases, and attempts to spare key areas of the brain when they're not involved with cancer. Medications such as memantine are being attempted to lower the cognitive side effects of brain radiation. Second, medical oncologists are working hard on newer drugs that in addition to controlling cancer in the body (south of the brain) can also cross the blood brain barrier and control cancer in the brain.