GRACE :: Lung Cancer

Heterogeneity of Stage III NSCLC/Defining Resectability for Locally Advanced NSCLC

GRACE Cancer Video Library - Lung

GCVL_LU-E01_Mark_Socinski_WCLC_1

 

Dr. Mark Socinski, University of Pittsburgh Medical Center, describes the different types of stage III (locally advanced) NSCLC, and states which of these types tend to be resectable.

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Let’s start by defining, or explaining, the heterogeneity of stage III disease. In my mind, the two major types of stage III patients are those that have lesions that start to invade structures, and certainly T3 lesions that may invade the chest wall, the pericardium, the diaphragm — associated with N1 disease, are stage III disease but they are generally considered resectable. Then, we have those lesions that are more invasive and invade vital structures and are so-called T4 lesions, which for the most part, are not resectable, with some rare exceptions with regard to resection of vital structures and reconstruction and those sorts of issues.

The second major group is the development of mediastinal lymph node involvement by the cancer. The mediastinum is full of lymph nodes, they’re obviously the major draining site for many cancers. We divide the mediastinal nodes into N2 nodes, or nodes that are on the same side as the cancer, versus N3 nodes that are on the opposite side of the cancer.

You can think of the range of patients that you would see, either with larger invasive disease, or disease involving mediastinal lymph nodes. Another area is where patients have multiple nodules in either the same lobe, or a different lobe on the same side, and those would be the difference between T3 and T4 lesions, which would also be categorized within stage III disease.

So, you can see that this patient population encompasses a wide range of patients, each of which demands, really, a different approach and an individualized approach based on what type of subset you’re in, with regard to stage III disease.


What is V20 and Why Do Radiation Dose & Field Size Matter?

GRACE Cancer Video Library - Lung

GCVL_LU-E11b_Jeff_Bradley_V20_Radiation_Dose_Field_Size

 

Dr. Jeffrey Bradley, Radiation Oncologist at Washington University in St. Louis, defines the V20 standard for lung radiation and outlines the advantages of limiting dose and field size in lung radiation therapy.

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These are specific questions for radiation oncology — we do tend to think about these things quite a bit. V20 is a metric we use for the normal lung tissue dose, so when we generate a radiation therapy plan, we typically contour out what normal lungs are, right and left, we subtract the tumor volume, and we call that total lung minus tumor volume, and we look at how much of that lung volume receives 20 Gy, and we like for that percentage to be less than 35% or so, because that’s been shown in patients who have a V20 below 35% have a much lower rate of radiation pneumonitis; so, that’s a metric we use. There are other metrics for that, one could look at V25 Gy, one can look at mean lung dose — there are various parameters, but V20 tends to be a good thing to look at, and that’s what we’ve used in our trials.

Now, naturally, the larger the tumor, the harder it is to achieve a V20 below 35%. Likewise, the more central a tumor, the closer it is to the hilum, the harder it is to achieve a V20 of 35%. We showed a paper yesterday, from the RTOG 0617 manuscript, where IMRT reduced lung V20 and reduced the rate of radiation pneumonitis complications in that patient population. In 0617, approximately half of the patients received IMRT, and half the patients received 3D conformal radiation therapy, and that was a stratified variable, so it was a good venue to compare the two. IMRT looks like it reduces normal lung dose, is able to deliver dose to the tumor, and reduce normal tissue toxicity.

Why does radiation dose matter? Well, this is a curative patient population, patients with Stage III or node positive disease. You can achieve a cure rate in about 25% of these patients, and one can’t achieve a cure if you don’t eradicate the local tumor. Systemic therapy is unable to do that, radiation therapy is able to do that. Studies have shown that higher doses of radiation therapy matter — the higher the dose, the greater your cell kill.

The problem comes into play when your high dose exceeds normal tissue toxicity effects. That can be a bad thing, and has shown to be a bad thing in 0617. More conformal techniques – we’re testing protons today, because protons can avoid normal tissue toxicity. We’re trying to escalate radiation dose with protons in a current phase three trial randomized called RTOG 1308. Patients are able to receive 70 Gy of chemoradiation therapy with proton beam, versus IMRT, to see if proton beam reduces normal tissue dose and perhaps improves survival.

Why does field size matter? Field size matters because you’re trying to limit your normal tissue toxicities, so you don’t want to over-treat the lung tissue, or the heart tissue, and so, the smaller the field size, the better. That correlates with how small the tumor is — the smaller the tumor, the better. That’s a pretty standard thought process.

What do you do with large tumors? You do the best you can. You treat at least to 60 Gy, use the most sophisticated techniques you can. IMRT is a good venue to try to reduce normal lung tissue doses by choosing the beam angles and beam weights to try to achieve a V20 less than 35%, and try to limit your heart V40 as much as possible.


High vs. Standard Dose Chest Radiation in Stage III Lung Cancer

GRACE Cancer Video Library - Lung

GCVL_LU-E11_High_Standard_Dose_Chest_Radiation_Stage_III_Lung_Cancer

 

Dr. Jeffrey Bradley, Radiation Oncologist at Washington University in St. Louis, provides trial evidence showing that patients may not benefit from high dose chest radiation therapy vs. standard dose therapy.

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This is a topic I’ve been a little passionate about over the past ten years or so. We published a paper in Lancet Oncology this past February, it was RTOG 0617, and it was a comparison of high dose radiation therapy, 74 Gy, versus standard dose radiation, 60 Gy, in patients with stage III non-small cell lung cancer. They were unresectable, they received either the high dose or standard dose of radiation, and they were further randomized to receive cetuximab or not; cetuximab is an EGFR antibody.

The trial was published — it didn’t show an advantage to high dose radiation therapy, in fact, it shows a disadvantage to high dose radiation therapy. The median survival of the patients that were treated with 60 Gy without cetuximab was 28 months, compared to 20 months for patients receiving high dose radiation therapy. It turns out, even though we used the most sophisticated treatment techniques at the time, perhaps normal tissue doses were the cause of the high dose arm failing to achieve a better outcome, and a poor outcome in fact. We look at this as the heart dose — it turned out to be very important. We didn’t place heart dose constraints because, at the time, no one was placing heart dose constraints, and now we find out that’s very important. So, our subsequent trials have included heart dose constraints going forward, within, at least, the Energy Oncology Cooperative Group.

Likewise, there was no advantage to cetuximab in this patient population. These patients were unselected for EGFR status, and there’s an indication from the paper that if you look for EGFR status, people who had a high H-score may have benefitted from that drug. Nevertheless, there was no distinct survival advantage to receive cetuximab.

So the standard of care nowadays is 60 Gy with concurrent chemotherapy  — in that trial we used weekly paclitaxel and carboplatinum. We also used two cycles of consolidative chemotherapy in that study.


SBRT for Oligometastatic Lung Cancer

GRACE Cancer Video Library - Lung

GCVL_LU-F10_SBRT_Oligometastatic_Lung_Cancer

 

Dr. Jeffrey Bradley, Radiation Oncologist at Washington University in St. Louis, defines oligometastatic lung cancer and describes the recent trend toward the use of stereotactic body radiation therapy to treat it.

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First, let’s define the term “oligometastatic disease.” Oligometastatic disease typically means patients who have metastatic disease, but have a few metastases that, if they could be eradicated, their life could be prolonged. There are some good examples of the literature where patients have been resected, let’s say for metastatic colorectal cancer, or metastatic renal cancer, let’s say they had a brain metastasis that was resected and given curative therapy for their primary cancer, and there is about a 20-25% overall survival rate in that situation.

That, broadened out with the development of stereotactic body radiation therapy, has brought into play SBRT for patients with oligometastases for a variety of tumors. There is some recent literature in lung cancer, let’s say, that show that if you have patients with a few metastases that are receiving systemic therapy, that you can achieve median survivals approaching 20 months in metastatic lung cancer, and that’s previously unseen. That data was a trial from UT Southwestern and the University of Colorado groups, published this past year in the JCO — one of the most cited papers in the JCO this past year.

I think the oligometastatic patient population is a good patient population for focused radiation therapy. People ask, “what is oligometastasis?” It has classically been defined as patients with three or fewer metastases who have their remainder of the disease or the disease burden is under control with  systemic therapy; some have expanded that to five or six metastases. It typically doesn’t matter where they are. The classic example, of course, is a metastasis to the brain. We’ve applied this to patients in the lung, liver, spine, various places that are able to receive this focused radiation dose, and I think it’s a good tool, if chosen for the right patients, to extend their survival — perhaps we could even cure a few.


SBRT for Medically Inoperable Stage I Lung Cancer

GRACE Cancer Video Library - Lung

GCVL_LU-D08_SBRT_Medically_Inoperable_Stage_I_Lung_Cancer

 

Dr. Jeffrey Bradley, Radiation Oncologist at Washington University in St. Louis, describes the history and current use of stereotactic radiation therapy for inoperable lung lesions.

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The classic example of the use of stereotactic radiation therapy in the body is for lesions of the lung. This technology started in the 1990s in Japan and in Germany where they were giving five or fewer fractions of radiation therapy to a solitary nodule in the lung in a patient who couldn’t have surgery because they had underlying problems like heart disease or lung disease that wouldn’t allow the patient to have surgery. So they were giving, let’s say 15 gray doses, up to 20 gray doses, in three fractions, to eradicate these tumors in the lung.

That spread to the United States in the 2000s, and it’s a very common treatment today for patients who have been evaluated for surgery but can’t have surgery, usually because their pulmonary function is too low. This technique is very effective, the local control of eradicating that lesion is better than 90%, and 95% in some series. It’s stood the test of time, results are available at five years, giving a good indication that it’s probably equivalent to surgery in the population that’s high risk.

A very controversial area today, are patients who are operable candidates for stereotactic body radiation therapy, and that’s the next topic.


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