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Clinical Indications for Treatment of Brain Tumors
Maryam Rahman, MD, discusses the clinical indications for treatment of brain tumors with laser interstitial thermotherapy (LITT) and she examines the expected outcomes of LITT treated brain tumors. She shares how the development of complementary technologies, such as intraoperative magnetic resonance imaging (MRI) and real-time MRI thermometry have enabled LITT to enter the fields of neurosurgery and neuro-oncology.
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Learn more about Maryam Rahman, MD, MS
Maryam Rahman, MD, MS
Maryam Rahman, MD, MS, is an assistant professor in the department of neurosurgery at the University of Florida. Working within the Preston A. Wells Jr. Center for Brain Tumor Therapy at UF, she specializes in the treatment of patients with brain or spinal tumors.Learn more about Maryam Rahman, MD, MS
Transcription:
Male Speaker: The University of Florida College of Medicine is accredited by the Accreditation Counsel for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of .25 AMA PRA Category 1 credit. Physician’s should claim only the credit commencer with the extent of their participation in this activity.
Melanie Cole, MS (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole, and I invite you to listen as we discuss the clinical indications for treatment of brain tumors with laser interstitial thermal therapy. Joining me is Dr. Maryam Rahman. She’s an assistant professor of neurosurgery in the department of neurosurgery at the University of Florida College of Medicine. Dr. Rahman, it’s a pleasure to have you join us today. This is a fascinating topic. Tell us the prevalence before we get into LITT, tell us the prevalence of metastatic brain tumors. Tell us a little bit about this condition, how it comes about, and what’s generally the primary cause.
Maryam Rahman, MD (Guest): The nice thing about LITT, or laser interstitial thermal therapy, is that much like surgery you can use it for multiple indications. Malignant brain tumors is just one of many indications which include epilepsy, benign conditions, even things like radiation necrosis. My specialty is the in area of brain tumors. Brain tumors are a major cause of morbidity and mortality from childhood all the way through adulthood. Metastatic brain tumors—which are tumors that have spread from cancer somewhere in the body—are much more common than primary brain cancer. We have about 100,000 new cases of metastatic brain tumors reported each year in the United States. There are about 10,000 cases of new primary brain cancers reported each year in the United States. Of course, those numbers do not include the patients who survive for greater than a year and continue to struggle with their disease.
Host: Since virtually any systemic malignancy that can metastasize to the brain, are there some that have a greater proclivity to do so? Tell other providers some of the most common reasons for metastases that you see.
Dr. Rahman: Absolutely. The question you're asking is very relevant. Primary cancers that have a predisposition to metastasizing to the brain include lung cancers—both non-small cell and small cell—breast carcinomas. Those two are the most common. Melanoma, renal cell carcinoma, colon cancer, and then the other things that are less common can go to the brain, but we see them less commonly.
Host: So then tell us some of the challenges of treating these types of brain metastases and was it previously due to the inability to monitor tissue temperature during laser treatment or thus the control of the extent of the ablation. Tell us some of the challenges that you’ve run into when treating these, and then we’ll get into LITT.
Dr. Rahman: Patients who present with brain metastases, each patient is different. This is much more true for patients with brain metastases in other conditions because we have to look at multiple factors, including the type of cancer they have, the control of the cancer elsewhere in their body—is the cancer elsewhere in their body controlled or is it also growing or metastasizing elsewhere? The functional status of the patient. How well do they look? Can they do their activities of daily living? What current treatments have they received? Have they received chemotherapy? Radiation? Prior surgeries for their cancer? All of those are factors that we take into consideration. Treatment options for patients with brain metastases traditionally include surgical resection, fractionated radiotherapy, and then stereotactic radio surgery, which is a high dose typically one time treatment for tumors. All of these therapies have pretty good response rates of the tumors and local control rates, and they each have their pros and cons. The nice thing about LITT is that it provides an alternative treatment, it’s minimally invasive, and oftentimes is an option when patients have failed one or multiple of the prior treatments that I just mentioned.
Host: Well then as treatment approaches for metastatic brain tumors continue to evolve as we’re talking about today with increasing emphasis on focal therapies, tell us a little bit about LITT. Describe the clinical indications for it, and really how have the development of complementary technologies—such as interoperative MRI—how have they contributed to your ability to do this procedure?
Dr. Rahman: Basically, what you say is correct. So LITT is now possible—So we’ve had the ability to place a fiber optic or laser probe within the brain and deliver a heat based treatment for decades. That has always been possible. The limitations of that treatment previously were that we had no way of knowing how much heat we were delivering and how that heat was spreading through the tissue. So with the advent of interoperative MRI and with software that now gives us thermal data about the tissue heating process real time during treatment, it allows us to do this safely. So the way the procedure works—and it’s a little bit different depending on what center you go to—but the basic framework is the same which is that you have to very accurately choose a trajectory that will get the laser probe safely into the lesion to allow you to perform a biopsy and to then place the laser probe down the center of the lesion so that you can get most of the lesion with the laser ablation. We use stereotaxis to obtain that level of accuracy within a millimeter. Then the patient is typically placed in the MRI scanner or an intraoperative MRI scanner is brought into the operating room.
You first obtain an anatomic scan that will show you what you traditionally think off—the data that you see with an MRI scan where you can see the brain structures. Then you advance the laser probe to the part of the tumor that you want to burn. At that point, the MRI scanner goes on and the data that we’re receiving from the MRI is no longer anatomic data where we see those structures of the brain but actually thermal data, so we actually see the heat that we’re generating. That gets on laid onto the map of the anatomic brain of the patient. So as we turn the laser on, we can see the heat that we’re generating. There's complex formulas used to determine how much heat for how long you need to actually cause that portion to the tissue to die. Then you move the laser probe back along the tumor until you have the entire tumor covered with the appropriate heat. Once you're done, you take the laser out. Usually it’s a long incision half a centimeter long that gets closed with a single stitch. For us, most of those patients go home the following day.
Host: Wow. Isn’t that so interesting? So as this procedure enters the fields of neurosurgery and neurooncology, Dr. Rahman, speak about patient selection and why proper patient selection for the appropriate indication is of utmost important to ensure success of LITT.
Dr. Rahman: Because LITT is minimally invasive, it does give us the opportunity to treat patients who otherwise may be high risk for surgery and may not be able to tolerate a big craniotomy or general anesthesia. Depending on the center that you go to, LITT is performed a little bit differently from an anesthetic side, but here at University of Florida oftentimes we do these without any anesthesia or just some mild sedation as long as the patient isn’t claustrophobic for the MRI. The limitation is size of tumor, which is the same limitation we have for radiosurgery. So we can treat tumors up to about the two to three centimeter range. As they get larger than that, it is hard to get enough coverage from the laser probe to cover the entire tumor with the heat. Sometimes we do use multiple trajectories. So sometimes we’ll actually place two lasers from different trajectories from lesions that are a little bit larger that have a funny shape and aren’t perfectly circular or oval in shape. Size is one limitation. The other thing is that after treatment—this is actually a pro and a con of the treatment—is that you will get this pretty robust inflammatory response within the tumor as the tumor cells are dying. So your brain and your immune system detect that, and a lot of the immune cells infiltrate that area to take up those dead and dying tumor cells. The benefit of that is that you get this immune response that you can then further augment with immunotherapy, which is one of the things that we’re investigating pretty intently here at the University of Florida. The downside of that is that you do get some brain swelling after treatment. So if you're in smaller lesions, that’s not a problem. In larger lesions, sometimes that’s something that would require us to treat with steroids or other therapies to reduce the brain swelling.
Host: So how well tolerated is this procedure from the patient’s perspective?
Dr. Rahman: From the patient’s perspective, the actual procedure if they're awake for it does require some patience because they are awake and sitting in an MRI scan for longer than you would for a normal regular scan. From the standpoint of pain and recovery, it’s much better than undergoing a craniotomy or anything else invasive that we do. In fact, all of our patients go home the next day. Most of them are feeling back to themselves within a week or two.
Host: Before we wrap up, give us your view of the expected outcomes of LITT treated brain tumors and what you’ve seen and what you’d like other providers to take away from this episode as far as the importance of referral and what you would like them to know about this type of therapy.
Dr. Rahman: What I would say is expected outcomes from LITT depends a little bit of the tumor type. I’ll say response rates with LITT for brain metastases, radiation necrosis, other conditions, the long term control rates are similar to surgical resection and radiosurgery. So they range between 80 to 90% local control rates. The local control rates with high grade glioma—which is primary brain cancer—are lower than that, but that is also true with all the other therapies that we have for high grade glioma. What I would say is that I think LITT is a good option for patients who have either deep lesions that are not accessible from a surgical resection standpoint or lesions that have failed other treatments such as surgery, fractionated radiation, or radiosurgery and you need an option. Or patients who you don’t think would tolerate general anesthesia and a craniotomy, LITT is a good option for that. We do have two clinical trials here now testing LITT with immunotherapy either for brain metastases or for high grade glioma. We have some interesting preliminary data demonstrating that the type of cell death that cells undergo with LITT provides an advantage when you augment with immunotherapy. You also, obviously, get breakdown on the blood brain barrier with LITT treatment which allows therapies that otherwise wouldn’t penetrate the brain to penetrate the brain for up to four weeks after treatment. We’re trying to take advantage and leverage those qualities of LITT with some of these other novel therapies that we’re testing.
Host: Wow, thank you so much Dr. Rahman. What an interesting segment. Thank you for coming on and sharing your expertise with us today. To refer your patient or to learn more about this and other healthcare topics at UF Health Shands Hospital, please visit ufhealth.org/medmatters to get connected with one of our providers. That concludes today’s episode of UF Health MedEd Cast with UF Health Shands Hospital. Please remember to subscribe, rate, and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. s
Male Speaker: The University of Florida College of Medicine is accredited by the Accreditation Counsel for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of .25 AMA PRA Category 1 credit. Physician’s should claim only the credit commencer with the extent of their participation in this activity.
Melanie Cole, MS (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole, and I invite you to listen as we discuss the clinical indications for treatment of brain tumors with laser interstitial thermal therapy. Joining me is Dr. Maryam Rahman. She’s an assistant professor of neurosurgery in the department of neurosurgery at the University of Florida College of Medicine. Dr. Rahman, it’s a pleasure to have you join us today. This is a fascinating topic. Tell us the prevalence before we get into LITT, tell us the prevalence of metastatic brain tumors. Tell us a little bit about this condition, how it comes about, and what’s generally the primary cause.
Maryam Rahman, MD (Guest): The nice thing about LITT, or laser interstitial thermal therapy, is that much like surgery you can use it for multiple indications. Malignant brain tumors is just one of many indications which include epilepsy, benign conditions, even things like radiation necrosis. My specialty is the in area of brain tumors. Brain tumors are a major cause of morbidity and mortality from childhood all the way through adulthood. Metastatic brain tumors—which are tumors that have spread from cancer somewhere in the body—are much more common than primary brain cancer. We have about 100,000 new cases of metastatic brain tumors reported each year in the United States. There are about 10,000 cases of new primary brain cancers reported each year in the United States. Of course, those numbers do not include the patients who survive for greater than a year and continue to struggle with their disease.
Host: Since virtually any systemic malignancy that can metastasize to the brain, are there some that have a greater proclivity to do so? Tell other providers some of the most common reasons for metastases that you see.
Dr. Rahman: Absolutely. The question you're asking is very relevant. Primary cancers that have a predisposition to metastasizing to the brain include lung cancers—both non-small cell and small cell—breast carcinomas. Those two are the most common. Melanoma, renal cell carcinoma, colon cancer, and then the other things that are less common can go to the brain, but we see them less commonly.
Host: So then tell us some of the challenges of treating these types of brain metastases and was it previously due to the inability to monitor tissue temperature during laser treatment or thus the control of the extent of the ablation. Tell us some of the challenges that you’ve run into when treating these, and then we’ll get into LITT.
Dr. Rahman: Patients who present with brain metastases, each patient is different. This is much more true for patients with brain metastases in other conditions because we have to look at multiple factors, including the type of cancer they have, the control of the cancer elsewhere in their body—is the cancer elsewhere in their body controlled or is it also growing or metastasizing elsewhere? The functional status of the patient. How well do they look? Can they do their activities of daily living? What current treatments have they received? Have they received chemotherapy? Radiation? Prior surgeries for their cancer? All of those are factors that we take into consideration. Treatment options for patients with brain metastases traditionally include surgical resection, fractionated radiotherapy, and then stereotactic radio surgery, which is a high dose typically one time treatment for tumors. All of these therapies have pretty good response rates of the tumors and local control rates, and they each have their pros and cons. The nice thing about LITT is that it provides an alternative treatment, it’s minimally invasive, and oftentimes is an option when patients have failed one or multiple of the prior treatments that I just mentioned.
Host: Well then as treatment approaches for metastatic brain tumors continue to evolve as we’re talking about today with increasing emphasis on focal therapies, tell us a little bit about LITT. Describe the clinical indications for it, and really how have the development of complementary technologies—such as interoperative MRI—how have they contributed to your ability to do this procedure?
Dr. Rahman: Basically, what you say is correct. So LITT is now possible—So we’ve had the ability to place a fiber optic or laser probe within the brain and deliver a heat based treatment for decades. That has always been possible. The limitations of that treatment previously were that we had no way of knowing how much heat we were delivering and how that heat was spreading through the tissue. So with the advent of interoperative MRI and with software that now gives us thermal data about the tissue heating process real time during treatment, it allows us to do this safely. So the way the procedure works—and it’s a little bit different depending on what center you go to—but the basic framework is the same which is that you have to very accurately choose a trajectory that will get the laser probe safely into the lesion to allow you to perform a biopsy and to then place the laser probe down the center of the lesion so that you can get most of the lesion with the laser ablation. We use stereotaxis to obtain that level of accuracy within a millimeter. Then the patient is typically placed in the MRI scanner or an intraoperative MRI scanner is brought into the operating room.
You first obtain an anatomic scan that will show you what you traditionally think off—the data that you see with an MRI scan where you can see the brain structures. Then you advance the laser probe to the part of the tumor that you want to burn. At that point, the MRI scanner goes on and the data that we’re receiving from the MRI is no longer anatomic data where we see those structures of the brain but actually thermal data, so we actually see the heat that we’re generating. That gets on laid onto the map of the anatomic brain of the patient. So as we turn the laser on, we can see the heat that we’re generating. There's complex formulas used to determine how much heat for how long you need to actually cause that portion to the tissue to die. Then you move the laser probe back along the tumor until you have the entire tumor covered with the appropriate heat. Once you're done, you take the laser out. Usually it’s a long incision half a centimeter long that gets closed with a single stitch. For us, most of those patients go home the following day.
Host: Wow. Isn’t that so interesting? So as this procedure enters the fields of neurosurgery and neurooncology, Dr. Rahman, speak about patient selection and why proper patient selection for the appropriate indication is of utmost important to ensure success of LITT.
Dr. Rahman: Because LITT is minimally invasive, it does give us the opportunity to treat patients who otherwise may be high risk for surgery and may not be able to tolerate a big craniotomy or general anesthesia. Depending on the center that you go to, LITT is performed a little bit differently from an anesthetic side, but here at University of Florida oftentimes we do these without any anesthesia or just some mild sedation as long as the patient isn’t claustrophobic for the MRI. The limitation is size of tumor, which is the same limitation we have for radiosurgery. So we can treat tumors up to about the two to three centimeter range. As they get larger than that, it is hard to get enough coverage from the laser probe to cover the entire tumor with the heat. Sometimes we do use multiple trajectories. So sometimes we’ll actually place two lasers from different trajectories from lesions that are a little bit larger that have a funny shape and aren’t perfectly circular or oval in shape. Size is one limitation. The other thing is that after treatment—this is actually a pro and a con of the treatment—is that you will get this pretty robust inflammatory response within the tumor as the tumor cells are dying. So your brain and your immune system detect that, and a lot of the immune cells infiltrate that area to take up those dead and dying tumor cells. The benefit of that is that you get this immune response that you can then further augment with immunotherapy, which is one of the things that we’re investigating pretty intently here at the University of Florida. The downside of that is that you do get some brain swelling after treatment. So if you're in smaller lesions, that’s not a problem. In larger lesions, sometimes that’s something that would require us to treat with steroids or other therapies to reduce the brain swelling.
Host: So how well tolerated is this procedure from the patient’s perspective?
Dr. Rahman: From the patient’s perspective, the actual procedure if they're awake for it does require some patience because they are awake and sitting in an MRI scan for longer than you would for a normal regular scan. From the standpoint of pain and recovery, it’s much better than undergoing a craniotomy or anything else invasive that we do. In fact, all of our patients go home the next day. Most of them are feeling back to themselves within a week or two.
Host: Before we wrap up, give us your view of the expected outcomes of LITT treated brain tumors and what you’ve seen and what you’d like other providers to take away from this episode as far as the importance of referral and what you would like them to know about this type of therapy.
Dr. Rahman: What I would say is expected outcomes from LITT depends a little bit of the tumor type. I’ll say response rates with LITT for brain metastases, radiation necrosis, other conditions, the long term control rates are similar to surgical resection and radiosurgery. So they range between 80 to 90% local control rates. The local control rates with high grade glioma—which is primary brain cancer—are lower than that, but that is also true with all the other therapies that we have for high grade glioma. What I would say is that I think LITT is a good option for patients who have either deep lesions that are not accessible from a surgical resection standpoint or lesions that have failed other treatments such as surgery, fractionated radiation, or radiosurgery and you need an option. Or patients who you don’t think would tolerate general anesthesia and a craniotomy, LITT is a good option for that. We do have two clinical trials here now testing LITT with immunotherapy either for brain metastases or for high grade glioma. We have some interesting preliminary data demonstrating that the type of cell death that cells undergo with LITT provides an advantage when you augment with immunotherapy. You also, obviously, get breakdown on the blood brain barrier with LITT treatment which allows therapies that otherwise wouldn’t penetrate the brain to penetrate the brain for up to four weeks after treatment. We’re trying to take advantage and leverage those qualities of LITT with some of these other novel therapies that we’re testing.
Host: Wow, thank you so much Dr. Rahman. What an interesting segment. Thank you for coming on and sharing your expertise with us today. To refer your patient or to learn more about this and other healthcare topics at UF Health Shands Hospital, please visit ufhealth.org/medmatters to get connected with one of our providers. That concludes today’s episode of UF Health MedEd Cast with UF Health Shands Hospital. Please remember to subscribe, rate, and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. s