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FL: Monitoring to Initiate Therapy and Gauge Response

Insights From: Carla Casulo, MD, University of Rochester Medical Center; Nathan H. Fowler, MD, University of Texas MD Anderson Cancer Center
Published: Wednesday, Feb 21, 2018



Transcript: 

Nathan H. Fowler, MD: In addition to determining patients’ pretreatment risk by using one of the scoring systems such as FLIPI, I do think it’s important to look at or determine what we call a “risk assessment,” and that would be looking at the bulk of their tumor. It often includes how the patient presents, looking at their LDH [lactate dehydrogenase], and looking at their grade. There are different factors that we use to determine patients who have a high tumor burden, and this is often a modified GELF criteria. These are criteria that we use to determine whether patients have high bulk. This includes things like large nodes—3 nodes of more than 3 cm or 1 node of more than 7 cm—the presence of circulating tumor cells, splenomegaly, threatened organ function, or symptoms from their disease. Now, looking at those factors if patients have one of these criterium for high tumor burden, then we do use that to determine treatment. This is often a decision between watching a patient or initiating chemotherapy with something like rituximab.

Carla Casulo, MD: The GELF criteria are a set of clinical factors that we use to decide whether a patient requires therapy for follicular lymphoma or not. Those include different things like the number of lymph nodes, whether or not the patient has B symptoms, whether they have cytopenias, whether they have a large lymph node mass, and several other things. The British National Lymphoma Investigation criteria include some of those as well, but it also includes whether a patient is at disease progression within the first 3 months and whether they have certain organ involvement, like kidney involvement or bone involvement.

What those 2 things really do is give us a set of guidelines that help us understand when the right time to treat someone with follicular lymphoma is. The reason that’s important is that this is a disease that has a very long natural history. You want to make sure that the patients who are getting treated actually need to be treated, because most of them do very well. So, these are tools that help us understand, what are the factors that are most likely to cause symptoms in a patient or are most likely to cause accelerated growth of disease? That’s the reason that we use the GELF criteria to initiate therapy in patients with follicular lymphoma.
 
Nathan H. Fowler, MD: I think that a PET scan is a great tool for staging patients and for monitoring response to therapy. PET scans are very, very sensitive at detecting the presence of active follicular lymphoma. In fact, if you look at several studies, they suggest that the PET sensitivity for a patient with active follicular lymphoma is around 95%. The majority of time, if a patient has active follicular lymphoma, it will be picked up on PET scans.

A large percentage of patients, when you see them in clinic, are initially observed. But many of these patients will eventually develop a reason to initiate treatment. And so, we have fairly well-defined parameters or criteria of when to start an asymptomatic patient on therapy. In other words, when does the disease get to a point that you should initiate therapy? This really revolves around 2 main factors. The first is when patients start to develop bulky disease, and that can be defined as splenomegaly; large nodes, meaning there are 3 nodes of more than 3 cm or 1 node of more than 7 cm; circulating lymphoma cells; or if they have symptoms from their disease, and that can be night sweats, fever, weight loss, or pain.

Finally, if this disease is pressing on a critical organ—and I like to use this analogy for my patients: It’s like a rock in your shoe—regardless of the size, if it’s in the wrong place, you really should take care of it. The most common organ that becomes threatened would be the kidney. There are many nodes in retroperitoneum that can sometimes press on the ureter. Regardless of the size of the node, if there are threatened ureters, I often will initiate therapy.

I think that it is important to monitor response to therapy. When patients finish induction therapy, they should clearly have imaging. If the PET scan was positive at induction, I think they should get a repeat PET scan to make sure they’re in complete remission. At minimum, they should have a CT scan at the end of induction to determine their response to therapy. I think there’s a lot of controversy now about how to monitor these patients after they finished therapy, especially patients who attain a complete remission.

In my practice, I often look at CT scans every 3 to 6 months in the first year. In the second year, I often go to every 6 months. After that, if patients remain in remission, it’s really up to the patient and the physician. Many times, I’ll quickly move to annual monitoring in patients with low-grade lymphomas who are asymptomatic and in remission. Since this is an area that is evolving, there are some folks who are recommending not doing any surveillance imaging. Many of us are in-between, where we’re slowly extending the duration between imaging studies as patients achieve longer and longer remissions.

Transcript Edited for Clarity 
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Transcript: 

Nathan H. Fowler, MD: In addition to determining patients’ pretreatment risk by using one of the scoring systems such as FLIPI, I do think it’s important to look at or determine what we call a “risk assessment,” and that would be looking at the bulk of their tumor. It often includes how the patient presents, looking at their LDH [lactate dehydrogenase], and looking at their grade. There are different factors that we use to determine patients who have a high tumor burden, and this is often a modified GELF criteria. These are criteria that we use to determine whether patients have high bulk. This includes things like large nodes—3 nodes of more than 3 cm or 1 node of more than 7 cm—the presence of circulating tumor cells, splenomegaly, threatened organ function, or symptoms from their disease. Now, looking at those factors if patients have one of these criterium for high tumor burden, then we do use that to determine treatment. This is often a decision between watching a patient or initiating chemotherapy with something like rituximab.

Carla Casulo, MD: The GELF criteria are a set of clinical factors that we use to decide whether a patient requires therapy for follicular lymphoma or not. Those include different things like the number of lymph nodes, whether or not the patient has B symptoms, whether they have cytopenias, whether they have a large lymph node mass, and several other things. The British National Lymphoma Investigation criteria include some of those as well, but it also includes whether a patient is at disease progression within the first 3 months and whether they have certain organ involvement, like kidney involvement or bone involvement.

What those 2 things really do is give us a set of guidelines that help us understand when the right time to treat someone with follicular lymphoma is. The reason that’s important is that this is a disease that has a very long natural history. You want to make sure that the patients who are getting treated actually need to be treated, because most of them do very well. So, these are tools that help us understand, what are the factors that are most likely to cause symptoms in a patient or are most likely to cause accelerated growth of disease? That’s the reason that we use the GELF criteria to initiate therapy in patients with follicular lymphoma.
 
Nathan H. Fowler, MD: I think that a PET scan is a great tool for staging patients and for monitoring response to therapy. PET scans are very, very sensitive at detecting the presence of active follicular lymphoma. In fact, if you look at several studies, they suggest that the PET sensitivity for a patient with active follicular lymphoma is around 95%. The majority of time, if a patient has active follicular lymphoma, it will be picked up on PET scans.

A large percentage of patients, when you see them in clinic, are initially observed. But many of these patients will eventually develop a reason to initiate treatment. And so, we have fairly well-defined parameters or criteria of when to start an asymptomatic patient on therapy. In other words, when does the disease get to a point that you should initiate therapy? This really revolves around 2 main factors. The first is when patients start to develop bulky disease, and that can be defined as splenomegaly; large nodes, meaning there are 3 nodes of more than 3 cm or 1 node of more than 7 cm; circulating lymphoma cells; or if they have symptoms from their disease, and that can be night sweats, fever, weight loss, or pain.

Finally, if this disease is pressing on a critical organ—and I like to use this analogy for my patients: It’s like a rock in your shoe—regardless of the size, if it’s in the wrong place, you really should take care of it. The most common organ that becomes threatened would be the kidney. There are many nodes in retroperitoneum that can sometimes press on the ureter. Regardless of the size of the node, if there are threatened ureters, I often will initiate therapy.

I think that it is important to monitor response to therapy. When patients finish induction therapy, they should clearly have imaging. If the PET scan was positive at induction, I think they should get a repeat PET scan to make sure they’re in complete remission. At minimum, they should have a CT scan at the end of induction to determine their response to therapy. I think there’s a lot of controversy now about how to monitor these patients after they finished therapy, especially patients who attain a complete remission.

In my practice, I often look at CT scans every 3 to 6 months in the first year. In the second year, I often go to every 6 months. After that, if patients remain in remission, it’s really up to the patient and the physician. Many times, I’ll quickly move to annual monitoring in patients with low-grade lymphomas who are asymptomatic and in remission. Since this is an area that is evolving, there are some folks who are recommending not doing any surveillance imaging. Many of us are in-between, where we’re slowly extending the duration between imaging studies as patients achieve longer and longer remissions.

Transcript Edited for Clarity 
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