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Denise Brock

Lung Cancer Video Library – Spanish Language: Video #44 Treatment of Stage III Unresectable Non-Small Cell Lung Cancer

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We are pleased to continue this series of informational videos for our Spanish speaking community.  GRACE is pleased to welcome Dr. Rafael Santana-Davila, Assistant Professor with the University of Washington School of Medicine and Seattle Cancer Care Alliance.  In this 44th video for the Spanish lung cancer video library, Dr. Santana-Davila joined GRACE to discuss the treatment of stage 3 unresectable non-small cell lung cancer.


 

 

 

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TRANSCRIPTS – Spanish and English
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Tratamiento de Cancer de Pulmón de Células no Pequeñas en Estadio Tres no Resecable

Treatment of Stage III Nonresectable Non-Small Cell Lung Cancer

 

Rafael Santana-Davila, MD
Assistant Professor of Medicine
University of Washington Seattle Cancer Care Alliance
Seattle, Washington

 

Spanish TRANSCRIPT

Cuando el paciente se encuentra en estadio tres y no es candidato a cirugía porque el cancer está en varios ganglios del mediastino o por otras razones, lo que hacemos es quimioterapia con radiación al mismo tiempo. La radiación se da todos los días por cuatro a seis semanas y la quimioterapia dependiendo de qué régimen se escoge puede ser una vez por semana o dos ciclos de quimioterapia durante la radiación.

Para saber cuál quimioterapia es mejor es un poco controversial, pero depende mucho de la plática que se tiene con el paciente para conocer el tiempo que se tiene, los beneficios y riesgos. Los regímenes que son más comunes en Estados Unidos son carboplatino con paclitaxel una vez por semana. Una vez que se acaban las cuatro a seis semanas de radiación, se dan otros dos ciclos que se llaman ciclos de consolidación. El otro régimen que es muy común es cisplatino con etopósido y esto se da dos ciclos de quimioterapia durante la radiación sin hacer quimioterapias adicionales.


  

English TRANSCRIPT

When the patient is in stage three and is not a candidate to surgery because the cancer is in some lymph nodes of the mediastinum or other reasons, the best option is chemotherapy with radiation at the same time. The radiation is given every day for four to six weeks and the chemotherapy, depending on the regimen chosen, can be once per week or two cycles of chemotherapy during the entire treatment of radiation.

The types of chemotherapies are controversial because to choose which one is better depends on the discussion you have with your doctor to know the time they have, the risks and benefits. The most common regimens in United States are carboplatin and paclitaxel once per week. Once the four to six weeks are over, two more cycles of radiation are given to consolidate. The other common regimen is cisplatin with etoposide, they are given in two cycles of chemotherapy during the radiation with no additional chemotherapies.


Denise Brock

Lung Cancer Video Library – Spanish Language: Video #22 Treating Stage III Unresectable NSCLC

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GRACE Cancer Video Library - Lung

 

We continue to provide informational videos for our Spanish speaking community and welcome Dr. Luis Raez, MD FACP FCCP, Chief of Hematology/Oncology and Medical Director at Memorial Cancer Institute, and Clinical Associate Professor of Medicine at Florida International University.  Dr. Raez joined GRACE to discuss the basics of lung cancer.  In this 22nd video for the Spanish lung cancer video library, Dr. Raez discusses treating stage III unresectable NSCLC.


 

 

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TRANSCRIPTS – Spanish and English
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Tratamiento para el cáncer de pulmón en estadio III no operable

En el caso de estadio IIIB no se pueden resecar, porque tienen un tumor que está invadiendo el mediastino y los grandes vasos. Normalmente ese tumor se podía sacar porque no hay metástasis, pero ya que la localización no es adecuada, no se puede sacar.

El tratamiento para un tumor en estadio IIIB cuando el tumor es inoperable, es dar quimioterapia con radioterapia al mismo tiempo. Como ustedes saben por un estudio famoso del grupo HOG, sabemos que el estándar es quimioterapia con cisplatino- etopósido y radiación, pero cisplatino-etopósido es una quimioterapia un poco antigua y tóxica. Por lo que hoy en día a pesar de que ese es el estándar de los grupos cooperativos americanos que usamos de referencia, preferimos dar carboplatino y paclitaxel, que es una quimioterapia fácil de manejar y que se da semanalmente.

Incluso en Estados Unidos, tenemos pacientes de edad mayor de 80-85 años que no van a tolerar el cisplatino ni etopósido, por eso el régimen de carboplatino-paclitaxel semanal es la quimioterapia de elección en estos estadios. Así que es muy importante tener estos criterios en cuenta cuando abordamos a los pacientes.


Treatment for lung cancer in stage III unresectable

In the case of stage III, is unresectable because they have a tumor invading the mediastinum or the great vessels. Usually this tumor would have been able to be resectable because it didn’t have metastasis, but the location is not adequate so that’s why it’s unresectable.

Treatment for a stage IIIB unresectable tumor is chemotherapy and radiotherapy at the same time. As you know, based in a famous trial by the group HOG, we know that the standard treatment is with cisplatin- etoposide and radiation, but cisplatin-etoposide is an old and toxic chemotherapy. So today, despite the standard American cooperative groups treatment, we prefer to use carboplatin and paclitaxel, which is a chemotherapy easy to handle and it’s given weekly.

Even in United States, we have elderly patients of 80-85 years old that will not tolerate cisplatin nor etoposide, so the weekly regimen of carboplatin- paclitaxel is the go therapy in these stages. So, it is very important to have these criteria when we are approaching the patients.


GRACE Video

Is There a Role for Induction or Consolidation Chemotherapy Before/After Chemo/Radiation?

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GCVL_LU-E10c_Induction_Consolidation_Chemotherapy_Role

 

Dr. Nasser Hanna, Indiana University Health, considers the use of induction or consolidation chemotherapy for unresectable stage III NSCLC.

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Transcript

Can we do better than what we demonstrated in the 90s and early 2000s with concurrent chemoradiation? We know that we improved outcomes, that people were having more tumor shrinkage and control of their tumors was a little bit better. We were actually even able to cure more patients but we still were not curing enough patients. These were modest gains and they came at the consequence of having a number of side effects.

So we hypothesized that perhaps patients just needed more systemic therapy. The major reason for death from lung cancer is systemic recurrences, and so while we were doing pretty good with radiation and in some cases surgery, patients still had poor control over the disease over time because it would pop up in the liver, or in the brain, or in the bones, or elsewhere.

So throughout the 2000s there were two basic strategies that were tested. One strategy was to give a couple of courses of chemotherapy first, and then give patients chemotherapy and radiation concurrently. The other approach was to give chemotherapy and radiation concurrently from the get-go, but when folks were done with treatment, give them additional chemotherapy.

Both of these strategies were studied in multiple groups on multiple continents over about a five to ten year period of time. Unfortunately the bottom line to all of this type of treatment is that neither giving chemotherapy first, prior to concurrent chemoradiation, nor giving chemotherapy after concurrent chemoradiation was able to cure more people than simply giving chemotherapy and radiation at the same time.

So while we have tested a number of drugs in a number of different strategies, the bottom line is we’ve never been able to demonstrate further improvement in outcomes compared to just giving chemotherapy and radiation concurrently, alone.


GRACE Video

Chemoradiation as a Standard of Care for Unresectable NSCLC

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GCVL_LU-E09_Chemoradiation_Standard_Care_Unresectable_NSCLC

 

Dr. Nasser Hanna, Indiana University Health, discusses the development of chemoradiation as a standard of care for unresectable stage III NSCLC.

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Transcript

So what is the standard of care treatment for those who are not going to have surgery for stage III disease that are either medically inoperable or they are surgically unresectable? Well for decades radiation therapy has formed the backbone of treatment. If you can’t surgically remove a tumor, you can certainly apply radiation to that tumor; you radiate the tumor, the lymph nodes, and some surrounding tissue where microscopic disease may be. That form of therapy can be effective but by itself oftentimes is not curative. It will shrink tumors and oftentimes patients will have a reduction in symptoms, maybe a tumor was compressing an airway or maybe it was causing them to cough up blood or something like that where the radiation therapy can be effective at relieving some of those symptoms.

Historically radiation therapy alone for stage III disease has resulted in about a 5% cure rate — the vast majority of patients will develop growth shortly thereafter, either outside the radiated field, occasionally in the radiated field, but most commonly distant metastatic disease. That’s because even though the disease appears to be confined to the chest, we know that the majority of patients already have microscopic spread of their cancer to other parts of their body. That’s not something that you can see on a CT scan, it’s not something that you can see on a PET scan, it’s certainly not something you can feel on a physical exam, but we know that’s the case because historically when you’ve done surgery alone for this group of patients and successfully removed all the disease you can see, the vast majority of people will still develop distant, recurrent disease usually within about a year’s time. Radiation therapy alone can have some effectiveness for patients, but by and large it’s a short term effect and it oftentimes doesn’t cure patients.

Starting really about three or four decades ago, chemotherapy was beginning to be incorporated in the treatment of patients with stage III disease. In the 1970s it was demonstrated that chemotherapy could shrink cancers that had already metastasized, and perhaps if it could shrink cancers that were large enough to see on x-rays, maybe it would be effective enough to treat that microscopic disease that patients have with stage III lung cancer.

So beginning in the 1970s and really going in full force in the 1980s, chemotherapy was incorporated with radiation strategies and a whole host of different strategies were tried. The most common strategy was to give a couple of courses of chemotherapy first, try to shrink the cancer, try to treat that microscopic metastatic disease early on, and then follow that with radiation therapy. Early efforts into that approach were not terribly successful, and that’s for several reasons. Number one, our staging tools weren’t very good, so oftentimes even though we thought patients have stage III disease, they oftentimes already had stage IV disease and they weren’t going to be cured with that type of strategy. Secondly, many patients who participated in those clinical trials were already not doing well. They had what we call a low performance status, in other words, they had already become very debilitated by their disease and their ability to tolerate therapy wasn’t very good. Thirdly, our radiation techniques were fairly crude at the time, radiation planning was very crude at the time as well. Fourth, our chemotherapy actually was not terribly active; although it was modestly active, it probably wasn’t the most effective therapy that patients could receive. Lastly, it really wasn’t recognized, the clinical significance of having weight loss. So oftentimes patients will have suffered a lot of weight loss which is really a signal that they truly have systemic disease, and when you include all those types of patients on clinical trials, you’re really setting yourself up for failure.

The initial attempts at trying to treat patients with both chemotherapy and radiation therapy really would be considered failures. Outcomes were not very good, we really didn’t seem to improve cure rates over radiation therapy alone, and this was in an era in which chemotherapy was not very well tolerated. That really started to change in the mid-1980s, and really a landmark trial was conducted by a United States cooperative group. In this trial, patients were excluded if they had a really poor functional status, if they had significant weight loss, and so it really narrowed the group of patients who could potentially benefit from this therapy. In this study, patients received two courses of chemotherapy, and then that was followed by six weeks of radiation therapy. For the first time, we were able to demonstrate an improvement in cure rates. It was fairly modest, we went from about a 5% cure rate to about a 15% cure rate.

Because that was the first time that was really ever demonstrated, a second trial was required to really make sure that this was a real finding. So a second trial was done in the United States by other cooperative groups; this was a much larger trial and they essentially replicated that data.

Well in the 1980s and in the 1990s, this strategy of giving chemotherapy and radiation therapy at the same time was becoming a standard approach in many different cancers. This included cancers of the pancreas, of the esophagus, of the head and neck, of the rectum, and so that sort of idea was attempted in lung cancer. Now we weren’t sure if we could actually give chemotherapy and radiation at the same time to somebody who had lung cancer. It’s a bit different radiating the mid-chest area where the heart is going to get radiation, the lungs are exposed to a lot of toxicity from radiation, the esophagus would oftentimes be in the field of radiation. So the first thing we had to do was prove that it was safe and feasible to do, and indeed investigators did demonstrate that. The next step was to determine whether that strategy of giving chemotherapy and radiation at the same time would truly be more effective than giving them separately – there were a lot of theoretical advantages to doing that. First, you would not delay the radiation therapy. Secondly, you might be able to give both therapies at the same time which would work to kill cancer cells in different ways simultaneously, but we knew that it would come at a risk.

We knew that it would come at a risk of increased side effects when you give the treatments together versus giving them separately. Several randomized trials were conducted in the United States, in Japan, in Europe, that looked at comparing the concurrent administration of chemotherapy and radiation to the sequential administration of those two. Those trials by and large demonstrated that while it was more difficult on patients and there were certainly more side effects, you could improve cure rates by giving the treatment concurrently.

So really through the 1990s and into the early 2000s, the standard of care treatment for those who were well enough and fit enough for this type of therapy was to give concurrent chemotherapy and radiation therapy.


GRACE Video

What is Stage III Unresectable NSCLC?

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GCVL_LU-E08_Defining_Stage_III_Unresectable_NSCLC

 

Dr. Nasser Hanna, Indiana University Health, describes the factors which determine whether stage III NSCLC is resectable.

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Transcript

So what defines stage III, unresectable non-small cell lung cancer? Well first it’s important to distinguish patients who have potentially resectable stage III disease, versus those who have unresectable stage III disease. In general, stage III disease is defined by disease that involves the mediastinum. The mediastinum is this compartment in the midsection of your chest that lies between the two lungs — the heart, lymph nodes, the esophagus, the trachea, various blood vessels reside in that region. When disease involves the mediastinum, that section between the two lungs, oftentimes it is difficult for a surgeon to surgically resect it and to get all the disease out that they can see. So the vast majority of people who have disease involving the mediastinum will be considered to have unresectable disease.

There are some exceptions to this — there are some patients who we think may have stage I or stage II disease that does not involve the mediastinum. The surgeon will routinely do surgery and will remove lymph nodes in that portion of the chest, and will incidentally find that there is cancer in the lymph nodes. In that case those patients also have stage III disease, but they were able to undergo a surgical resection.

There are also a small subset of patients who have clinically known disease in the mediastinum that’s low volume that may require a lesser surgical resection. Occasionally patients will be able to undergo surgery in that group. However the vast majority of people are going to have pretty advanced disease in the midsection. They’re going to have multiple lymph nodes that are enlarged, they’re going to have tumors that involve major structures, they’re going to require large operative procedures. For those patients, we consider them to be unresectable.

I would estimate that probably 3/4, maybe 80% of people who are diagnosed with stage III disease would be considered unresectable, and some patients may be technically resectable, but they may be medically inoperable. In other words, removing the lung or doing that sort of operative intervention might be too difficult for them, they may not have the heart reserve or the lung reserve to be able to survive a procedure like that. So that group of patients oftentimes is also not treated with surgery.


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