Lung Cancer / Mesothelioma
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Loading ...We’ll cover the general management principles for the more typical situation of patients with multiple brain metastases from lung cancer soon, but today we’ll cover the special situation of the patient who has a brain metastasis identified as the ONLY area of metastatic disease (generally referring to NSCLC, since SCLC has such a high tendency to spread distantly early in its history). Recall that metastatic, or stage IV, lung cancer, is treated with a palliative approach, due to the inability to achieve prolonged survival except in very rare cases. These patients are generally treated as a unique category for whom an aggressive treatment is often considered, not only for the brain metastasis but also for disease in the chest.
One important point is that finding an area of metastatic disease in the brain only represents the concept of a “precocious metastasis”, a metastatic deposit that somehow slipped out before the rest of the disease was readily shedding metastatic disease (not all of the discussion of this concept requires just a single brain metastasis – some consider this idea to also apply to up to three brain lesions that can be treated aggressively). A thorough staging workup, including a PET scan, is very important in this setting. If there is a brain metastasis and one liver metastasis or a second tumor in the lung opposite the main tumor, the brain lesion isn’t “precocious”: it’s now a cancer that has at least a couple of areas of distant spread. This doesn’t mean that the brain metastasis shouldn’t be treated aggressively, but the situation isn’t as favorable as having a stage I or II NSCLC cancer in the chest and a single brain metastasis. For that matter, many people also make the distinction between early stage NSCLC, especially stage I, in the chest and locally advanced NSCLC aside from the brain metastasis. The idea of the precocious metastasis doesn’t apply as well if the staging outside of the brain is IIIB. The most encouraging results have been in the patients with an early stage NSCLC tumor aside from a single brain metastasis. These are patients in whom surgery is often considered both for the lung disease and the brain metastasis.
There are two primary means of aggressive treatment for a solitary brain metastasis: surgery or stereotactic radiosurgery (SRS, also known as gamma knife, which is a brand name for the technique). The latter entails focusing a radiation beam very precisely on the target area, using a stereotactic frame to keep the skull in place, so the radiation obliterates the tumor in the brain but delivers very little radiation outside of the target area. There has never been a randomized controlled trial that directly compares neurosurgery to SRS, but the results of the two techniques have appeared to be quite comparable in terms of survival, local control in the brain, side effects, and treatment-related mortality (deaths). Because of this, they’ll be discussed as more or less interchangeable approaches in terms of providing local control of a single brain metastasis.
While there isn’t any suggestion that an aggressive approach for precocious brain metastasis should applies to any particular NSCLC subtype, outcomes have tended to be more favorable in younger patients and women, as well as those who develop a metastatic brain lesion some period of time after the lung tumor has been treated. The results also have a tendence to be more favorable in patients with a brain lesion less than 3 cm, compared with a larger tumor, and in those with lesions in the larger cerebral hemispheres compared with the cerebellum (the latter about 15%).
For patients in these situations, treated aggressively and with curative intent, survival far exceeds the general numbers for metastatic NSCLC. The five-year survival in many of these case series, which has involved a delay between lung tumor treatment and brain tumor treatment in about 2/3 of cases, hovers around 21%, with a range of around 16-30%. There is an approximately 2% mortality risk from aggressive, curative treatment, which historically has usually been surgery for both chest and brain.
One of the key questions is whether people should undergo whole brain irradiation after definitive treatment, whether neurosurgery or SRS, on a brain metastasis. This remains completely unclear, with one study showing no benefit (abstract here), and another showing a significant improvement in survival (abstract here). One study of 95 patients who underwent resection of a single brain metastases were randomized to receive post-operative WBI or observation (full article provided free here) and reported that WBI quite significantly reduced the rate of brain relapses (18% vs. 70%). Patients who received WBI were less likely to die of neurologic symptoms/complications (14% vs. 44%), but this didn’t translate into a significantly higher overall survival for recipients of WBI.
These trials have been conducted in a time in which adjuvant chemotherapy was not routinely administered for patients with early stage, resected chest disease. Now that post-operative chemotherapy is commonly recommended to reduce the risk of recurrence and death from lung cancer. This should only improve the long-term outcome for patients with a “precocious metastasis”, a high-risk situation but one in which we can see more and more patients surviving year after year to provide hope, another example of the benefit of tailoring treatment plans for different patients. This doesn’t apply for enough patients with advanced lung cancer, but it can certainly make a difference for the minority in whom it does apply.
We’ll break from the subject of brain metastases and cover a few other issues, then get back to general management of brain metastases again very soon.
Posted in: General Lung Cancer Issues, Lung Cancer, Management of Brain Metastases, Radiation therapy, Surgery Issues, Treatment
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[…] Solitary Brain Mets and the Concept of the… […]
Solitary Brain Mets and the Concept of the…
Wow! I have never heard of this being a special subset of patients. I have two family members that fit in this category! My Dad was diagnosed in 1996 at the age of 51. Seizures were his presenting symptom and he was found to have a 1cm tumor in his lung and a 4cm tumor in his frontal lobe. Classified at stage IV no one would operate but I kept pushing until I found someone to take out the brain tumor since it was in such a operable area. He received whole brain radiation and then carboplatin/taxol/radiation for the lung tumor. The lung tumor remained stable for 18 months and then began growing again. By then he was strong enough to endure lung surgery. He has been NED ever since- ten years and counting. My Dad’s sister in law was diagnosed one year after him with a lung tumor and then a brain tumor and has enjoyed the same longterm survival. I still think that my Dad and Aunt are walking miracles but now I know that their survival is not of winning the lottery statistical proportions.
You mention the use of whole brain radiation in these cases. Something to consider is the long term effects of the whole brain radiation . When in the throws of treatment you do not even consider ten years out b/c you are thinking in terms of gaining a few months or maybe a couple of years. Both my aunt and father developed some post radiation effects in the last couple of years resulting in a significant worsening of their cognitve problems.
I learn so much every time I visit this site. Thank you so much for such an important service!
deniseo
Denise,
Thanks for the supportive, kind words. I’m happy to provide useful information.
Your father and aunt are still very impressive, remarkably encouraging cases for people to know about, and perhaps it’s better to know that the odds aren’t astronomically against people. However, I have just a single patient I follow who has done that well, so every case should be congratulated and celebrated.
Your point about whole brain radiation is very well taken. I haven’t really gotten to the broader issues of treating the more common situation of brain metastases in the palliative setting (often multiple areas of metastatic disease inside and outside of the brain), but I’ve watched as stereotactic radiosurgery (SRS) has become increasingly popular not only for single lesions (where just about everyone agrees it’s a very appealing approach) to 4, or 6, or even 8 or more brain metastases (where many people would consider SRS to not have a role because there are so many mets you can see and very likely more you can’t see). But you’re right that much of the impetus behind SRS is a concern about neurologic deterioration from whole brain radiation. Historically, survival even with treatment for brain metastases and metastatic lung cancer in general wasn’t long enough to worry much about any long-term side effects of treatment. But now we are seeing so many more patients, even with multiple brain metastases, living longer and longer, so we have the new problem of worrying about side effects of treatment. It’s bad to have the potential for such significant side effects, but it’s good to be in a position to worry about them. It’s possible that the whole brain radiation made the difference between later brain metastases down the line and never having a brain recurrence. These are the kind of questions we are now struggling with.
Very, very interesting. Congrats to your family, and thanks for sharing stories that can provide hope for other people who may be facing similar challenges.
-Dr. West
My father 77-years old has suffered since Aug 2006 from lung cancer (squamus NSLC) with tumours 4.5 cm, 1.5 cm in right lung and a single brain metastasis of 2.5 cm. He had gamma-knife SRS and brain tumour shrunk to 0.4 cm - no progression and lung tumours shrunk to 3 cm and 0.5 cm with platinum chemo. During the last 4 months he’s had no progression and has been with Tarceva for the last 2 months. I would be very much like for him to be in the special case that you mentioned. The problem is that his condition (age, cardiac malfunction) does not allow for any lung surgery. So we are considering about Cyberknife. Of course we feel grateful to our doctor and God that we reach a point of no further progression. I hope this continues. Looking forward to your comments.
Regards,
Demetrios.
demetrios
Demetrios,
I’m afraid I can’t really offer any specific suggestions, as this is a unique situation that requires a detailed knowledge of your father’s overall health as well as the exact location of his disease. You mentioned that there are two tumors in the right lung, which makes me concerned that this may be more advanced, even if there is not a large disease burden. Radiating the areas involved certainly seems appropriate to me in this setting, and it will give him a fighting chance, since he’ll now have received both local therapy (radiation) and systemic (whole body) therapy with chemo to try to give him the best outcome possible. Obviously, we don’t want to give either too much or too little treatment for anyone, but that’s particularly important to be mindful of in older patinets who have other medical issues, like heart disease. There is a real potential for doing harm if patients receive more treatment than they can safely handle.
-Dr. West
Dr West,
thank you for your wise approach and remarks on my father’s case. My father is a fighter and keeps on going out, does the shopping, walks 1 hour every day and visits his friends. He complains about some difficulty in breathing after walking but that is a known problem of his heart disease. He takes 1,5 hour rest 2-3 times a day. He had more than 70% severe rash from Tarceva (taken for 2 months) with a leaking nose, many pimples, red spots and fatigue that gone away after stopping it. He still has anorexia though, but he eats with a little persistence. He will have a thoracic scan after a month’s stop of Tarceva and I guess that he ‘ll have to continue with a lower dose of 100 mg. His doctor is rather skeptical on going for radiation at this point in time. Do you think that Cyberknife in the long term is better than radiation ? Is it safer for his case ? The location of his tumours are : The big tumour is in the middle of the upper lobe and the smaller is in the center of the middle lobe in right lung.
Thank you for your help. Looking forward to any comments.
Regards,
Demetrios
demetrios
Demetrios,
I would say that in the setting of known metastastatic disease there really is no clear role for radiation outside of treating a specific symptom like bony pain, risk of a fracture, brain met causing seizure or headache, etc. At the same time, radiation covers not just the cancer but some surrounding tissue, so there would be a real risk that if he lost a significant amount of good lung from the radiation, he may feel and do worse rather than better, especially in combination with his heart disease. I have had some patients with a small amount of disease, but enough to be metastatic, who did quite well with less rather than more treatment. Sometimes, the progression can be quite slow, and many lung experts tend to see this more often in older patients. With a rather indolent progression, and a very real of overtreatment, we may recommend treatment only intermittently, as needed.
Cyberknife is a form of very focal radiation, but it does require placement of markers into the target tumor so that the tumor can be tracked precisely by the cyberknife machine (that’s the requirement at our center, and I believe it’s the case everywhere this technique is used). This is an invasive technique, so there is some risk involved with placing this markers into the target tumor. For your father’s case, it seems this would need to be done twice. Frankly, while the role of cyberknife is still evolving, I would consider it to be a much more appealing option in someone with a single area of viable cancer, rather than two or more. Again, it’s hard to give specific recommendations without really knowing all of the details, so I would still defer to his oncologists on these matters.
-Dr. West
Dr West,
Unfortunately my father had progression.
The last CT - after 3 months - revealed a less than 2 cm new brain tumour in parencephalitis. His main lung tumour also increased by 0.5-1 cm. My father behaves normally apart from the fact that he walks slowly with caution. Although he had been on Tarceva for 2 months and stopped 22 days ago it seems that progression could not be prevented. I am afraid that in his case Tarceva might had caused a kind of bad reaction. What is your opinion about that ? He has started WBRT (with a mask). Is it recommended or GKS would be more appropriate? Is there anything else e.g. medication that could be tried ? I would appreciate your comments.
Many thanks,
Demetrios
demetrios
Demetrios,
Sorry for the delay in responding; the site software was confused and thought your comment was spam for some reason, although I don’t have a clue why.
I know that your father certainly had a lot of toxicity troubles with tarceva, but I know of no way that it would have led to progression of cancer. There are arguments to be made for WBRT, gamma knife, or the combination, which I cover in my other posts on the topic of brain metastases (not “precocious mets”). That topic is still quite controversial even among very smart radiation oncologists. Otherwise, the medication temodar (temozolomide) has also looked favorable but is not yet considered the standard of care to add to radiation yet. I also wrote about that in one of my posts, here:
http://onctalk.com/2007/04/30/temodar-for-brain-mets/
I hope he does well with his next treatment.
-Dr. West
Dr. West,
I just stumbled across your article, and wonder if this situation applies to me.
I starting having severe headaches in early January 2007. I also started loosing my ability to think and talk. I’d go to work and couldn’t figure out how to do my job. A brain MRI showed 2 tumors, one on top of the other, that were removed by an emergency craniotomy on 1/20. The largest tumor was < 2 cm. Prior to surgery, I had a head to toe CT scan to look for other tumors to biopsy, showed enlarged lymph nodes near heart, a 3mm nodule in lateral right middle lobe, 2mm nodule in lateral basal left lower lobe, and a bump on liver, nothing definitive.
Pathology of the brain tumors indicated poorly differentiated metastatic carcinoma consistent with metastatic pulmonary adenocarcinoma - Stage IV NSCLC.
Met radiation onc - no WBR will monitor brain monthly, do gamma knife on any new tumors.
Met with medical onc; chemo to be given every 3 weeks for a maximum of 6 treatments. Taxol & Carboplatin. Not a candidate for Avastin because of recent brain surgery.
PET scan lit 2 left hilar lymph nodes (SUV 4.6) and one lymph node in the inferior left hilum between the heart and descending aorta (SUV 3.7), lung nodules did not light, spots may be to small. Liver bump is definitely not cancer.
Have had 2 more CT scans, which show the nodes have shrunk, and are now at almost normal size. Regular brain MRIs are still clear (little panic over 2 small dots, which later MRI showed beginning to dissipate).
I have confirmed with my ONC that the primary tumor is unknown and lung nodules are probably not cancer, he thinks (now) they may be
scars from previous infection. The best guess for the primary is somewhere near the node near my aorta.
I am wondering if I may fall into this unique subcategory?
stephf1958
Steph,
It is quite favorable that you have a very minimal tumor burden (total volume of viable cancer) and also that you have had a very good response to chemo. Both of those factors are favorable prognostic signs, and that’s really the key in cases like this: are the people who undergo more aggressive treatment doing better because of that, or are the selected population of patients who are treated this way already destined to do much better than other people because they’ve already shown that they don’t have a significant amount of viable cancer.
Aside from having brain metastases at all, the only negative prognostic factor I can foresee is the fact that your pathology shows poorly differentiated carcinoma, which is often associated with a more aggressive disease. Still, the clinical behavior of your cancer counts more than what it looked like under a microscope, in my book.
I think it would be very attractive to consider consolidation radiation in the area of the primary disease. However, I would not be inclined to do this in a patient of mine if there is any evidence of disease elsewhere on a re-staging PET scan (I would be inclined to do a very careful re-staging procedure before diverging from standard approaches). Also, since WBR can reduce the risk of CNS recurrence pretty convincingly over surgery alone, I think it would only make sense to consider a more aggressive approach outside of the brain if a similarly aggressive approach is pursued for controlling disease in the brain as well. Otherwise, I would consider it to be too high risk to have relapse in the brain that would obviate any value of more aggressive therapy.
-Dr. West
I am not sure what you mean by consolidation radiation.
I have considered insisting upon WBR, but didn’t want to persue that option until after all my chemo cycles have been completed (last one 6/11/07). I know that WBR was put on hold so that I could recieve chemo. Now that it is almost over, no reason to hold off.
The onc’s didn’t want to do WBR because of long range side effects (I work in a very technical field), but if I don’t survive, whats the point?
Are you also suggesting I ask to have another PET? And what is CNS?
stephf1958
All good questions. I try to remember not to use jargon, but we all suffer from the “curse of knowledge”, having a hard time thinking from the perspective of someone who doesn’t use these terms. I can guarantee that many other readers would wonder the same things you asked.
The idea of “Consolidation radiation” is kind of “icing on the cake”, treatment after what is clearly needed to control the disease that is meant to reduce the risk of recurrence. It’s basically the same idea as “adjuvant therapy”, but adjuvant therapy is the term most commonly used after surgery (so I suppose it would be a very appropriate alternate term for radiation after neurosurgery). Consolidation therapy could be radiation or chemo, depending on the situation.
I share the concern about doing concurrent whole brain radiation (WBR, since we’re trying to ensure everyone knows the terms) with chemo and would not be inclined to add any potential risk in the absence of an urgent need. And while I don’t want to minimize the potential for long term cognitive problems, that risk is quite hard to really know, and it needs to be weighed against the risk of reducing your overall chance for long-term survival. There isn’t a right or wrong answer, though.
I must say that I don’t routinely do follow-up PET scans in the setting of metastatic disease. PET scans have their clearest role in initial staging, and they really aren’t well validated in measuring response, even though they’re used sometimes in that setting. However, I would be inclined to do as careful a restaging as possible, which I would say would ideally include a PET scan, before pursuing a more aggressive treatment plan than is considered the standard of care. Local treatment such as radiation isn’t of obvious value in metastatic disease in general, except to treat local symptoms like pain in a bony met or bulky compressive disease in the chest. Because of that, if that’s being considered, I’d want to be as sure as possible that there isn’t evidence of disease in the liver or an adrenal gland, etc. If there were, more aggressive treatment of the residual chest disease really wouldn’t make sense to me.
Finally, CNS stands for central nervous system, basically just another term for brain.
-Dr. West
Dr West,
my father has completed 10 sessions of wbrt and unfortunately his general condition is getting worse i.e. trouble walking, staying in bed most of the time, anorexia, sore throat etc. He takes 8 mg/day of dexamethasone for the last 14 days and he is going to take 16 mg for the next 3 days in order to have some general improvement. I am afraid that there is either a progression of the disease (the last scan showed an increase of the lung tumour by 0.5 cm) or the radiation is not enough to treat the new brain tumour and I guess he ‘ll have to take a GKS too. Do you have any thoughts about that ? If finally decided, is there any recommended time lag between the two procedures ?
Thanks for your help !
demetrios
Demetrios,
I think all of those considerations sound reasonable, including a trial of a higher dose of steroids. I have had some patients who actually demonstrated new lesions and progression of some existing ones after WBR, and that’s obviously a bad sign. We did try gamma knife after that in one patient I’m thinking of, and that helped in the brain, but then problems emerged elsewhere. You’re right that the battle is on two fronts, in the brain (intracranial) and the rest of the body (extracranial). I would say that as sick as your father is now, there would be real danger in trying any more aggressive anti-cancer treatment like chemo, so it may be that the most that can be done is to try to support him and give him a chance to improve. If he’s progressing through all of this, I don’t know of anything that could reverse the process, and the best approach may be to try to focus on making things as easy for him as possible.
Dr West,
we have completed 11 sessions of WBRT and my father’s condition is getting worse in terms of walking and directing his walk. We have to treat the parencephalous tumour 2 cm with either Gamma knife or 3D conformal. What could be the favourable ?
If the choice is gamma-knife can it start right after WBRT ?
Thanks for your help.
demetrios
Demetrios,
I’m afraid your questions are details best answered by a radiation oncologist. That’s a little too specific and outside of what I do. I’m sorry it’s been so rough.
-Dr. West
Dr West,
Following up on your comment to my response on May 24th.
I recieved my 6th and final chemo (Taxol/Carbo) treatment on the 11th of June. I had my 6 week brain MRI yesterday, and I am still tumor free. I talked with my radiation oncologist about the “Precocious Metastasis” theory, and he is familiar with the concept, and agrees that I fall into this category.
My hospital (Providence Portland) is planning on doing a study of this when the new cancer certer opens in 2008, but for Melanoma and Liver cancer. So not good for me.
But, he is willing to go outside the standard of care, and radiate (5x week for 6 wks) my lymph nodes - the only area of cancer in my body. I get my regular CT scan on Monday (the follow up to chemo), but will get a more throrough scan to prepare for radiation sometime in the next couple weeks (I don’t know if is a PET or just more detailed CT). As my general health is good (he views me as a strong woman), and the amount of disease is so small, that taking a more agressive (curative) approach may be benefitial in my case. He warned me that it may have no long term benefit, but it will have no adverse affect. I am willing to give it a try, as I know what the affect of doing nothing is.
He also thinks that we are doing the right thing in not doing WBR. He said that WBR is typically done imediatly after surgery, and as it is a little over 5 months since mine, that starting it now has no value. However, I will continue recieving MRIs every 2-3 months. If something does arrive, then it will be removed by Gamma Knife. At that point I may do WBR as a follow up.
I want to thank you for this article. I now have a small amount of hope as I will be treated as if I can be cured. I will stay realistic, but hope is a powerful thing.
stephf1958
I agree that real life has a lot of people and situations that don’t fit neatly into categories with lots of data. Because of that, we’re left using our judgment and sometimes deviating from the most common practices, and I think that’s particularly appropriate for patients who are well informed about the risks and benefits of various approaches.
I also agree that the value of post-surgical WBR is really established in the setting of more immediate treatment after surgery, rather than months later, where the value would be much more questionable/doubtful.
Good luck with treatment, both in terms of tolerating it, and in terms of how you do beyond that (let’s hope for a long time beyond that!).
-Dr. West
Dr. West,
I just wanted to give you a follow-up after our “chat” 6 months ago. I went through the radiation therapy, 17 treatments total (less than the original 30 becuase of increased dose). I had virtually no side effects, just a small amount of pain on the left side towards the end.
The CT at the end of August showed “no evidence of disease”, the brain MRI was clear as well. Since that time I’ve had 2 brain MRIs and on chest CT (both done last week), and remain clear. A little radiation fibrosis in the left lung, but nothing else.
It has been 1 year since my brain surgery, with no reoccurannce, so will now get MRIs every 4 months at the same time as the chest CT.
I have been told that this is as good as it gets, and my doctors are cautiously optomistic. I have been living life as a “normal” person for the past 5 months.
I can’t thank you enough for this article and for the treatment I recieved because of it.
stephf1958
Just to give everyone a story of hope, I saw one of the most delightful patients I’ve ever known today, and she’s more than 9 years out from her surgery for stage I disease, 7 years out from her recurrene in the mediastinum that was treated with chemo and radiation, and 6 years out from her whole brain radiation and stereotactic radiation boost to the solitary brain lesion she developed. Her scans have been stable for years and she’s living her life.
The general rule for advanced lung cancer may be far more dire than we’d like, but there are exceptions to every rule.
I just wish I saw more patients with suh a history.
-Dr. West
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