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Discussion of Clinical Trials, Including Novel Therapies and Approaches, in Lung Cancer

GRACE Video

Overall Management for Stage IIIA Disease

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GRACE Cancer Video Library - Lung

GCVL_LU-E03_Mark_Socinski_WCLC_3

 

Dr. Mark Socinski, University of Pittsburgh Medical Center, describes the primary treatment options for stage IIIA NSCLC, including chemoradiation and surgery, and discusses trial evidence for each approach.

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The overall management for stage IIIA disease really boils down to essentially two different strategies. One is chemoradiation, and the second is a surgical approach in which you would either use chemotherapy or chemoradiation prior to surgery, and maybe in some cases, following surgery. There is not an agreed-upon standard in this regard — we’ve had several trials looking at the role of surgery in stage IIIA disease, specifically in those patients who have N2, or lymph nodes that are positive on the same side of the tumor that reside in the mediastinum.

From these two experiences, one of which employed preoperative chemoradiation, the other employed preoperative chemotherapy alone, this surgical arm, relative to the radiotherapy arm, did not show a long-term survival advantage as a result of surgery. So surgery remains controversial in this setting — not to say that there are not selected patients in which surgery should be considered, but I think they have to be very highly selected in this particular setting.

Now, getting back to one of the points we discussed earlier — that’s the heterogeneity of the disease. Often, we’ll find that patients undergo preoperative staging, which is very important. One must define the pathologic contents of the mediastinal lymph nodes prior to deciding about taking that patient to the operating room. I would say that if you can document N2, or certainly N3 disease, that the initial maneuver should not be surgical resection of that patient. However, there are patients in whom preoperative assessment of the mediastinal lymph nodes does not detect mediastinal disease, but while in the operating room at the time of resection, microscopic N2 disease or unsuspected N2 disease is found.
I think most surgeons, if possible, if they could do a complete resection, and resect all the involved lymph nodes, I would agree that would be the right thing to do, and in that case I think there is a clear role for postoperative adjuvant chemotherapy in resected N2 disease, in consideration of postoperative radiotherapy, depending upon the nature and the extent of the N2 disease.


GRACE Video

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

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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.


GRACE Video

The Lung Cancer Master Protocol/SWOG 1400 as a Clinical Trial for a New Era of Molecular Oncology

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LCAM 2015

 

Dr. Jack West reviews the Lung Cancer Master Protocol for second line treatment of patients with advanced squamous NSCLC, an “umbrella protocol” in which all patients undergo molecular testing and have treatment assigned by the results.

November is Lung Cancer Awareness Month. What are you grateful for?

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Get more information about the Lung-MAP Trial.

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GRACE Video

Clinical Trial Spotlight: Targeting Brain Mets in EGFR Lung Cancer Patients

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LCAM 2015

 

Dr. Ross Camidge talks about a clinical trial that will test to see if the drug tesevatinib will work to kill cancer that has progressed in the brains of EGFR-mutant lung cancer patients. The trial is scheduled to begin in late 2015 or early 2016.

November is Lung Cancer Awareness Month. What are you grateful for?

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GRACE Video

Clinical Trial Spotlight: Can Epigenetic Priming Improve Efficacy of Immunotherapy in NSCLC?

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LCAM 2015

 

Dr. Jack West reviews the concept of epigenetics, epigenetic priming, and whether oral azacytidine can improve outcomes in patients who receive immunotherapy for advanced lung cancer.

November is Lung Cancer Awareness Month. What are you grateful for?

Watch, read, and then share your own stories of empowerment in our online forum. Your story may inspire others.

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