Thoracic Surgeon

Midsouth Regional Thoracic Center

Memphis, Tennessee.

Surgery, especially minimally invasive (‘key-hole’) surgery, is an effective and safe treatment for patients with early stage lung cancer. However, between 20 to 30 percent of patients relapse in the first five years following surgical treatment alone in Stage 1 non-small cell lung cancer. In Stage 2, this percentage rises 40 to 50%. There have been many recent attempts to decrease this rate of relapse. Chemotherapy after surgery has been investigated thoroughly. Latest pooled data from the best studies have shown that chemotherapy after surgery improves survival approximately 4% more than surgery alone at five years. Because of these modest results, there has been at least one major study looking at targeted therapy using the drug erlotinib after surgery. Results of this trial are awaited. One other strategy would be to use vaccines (immunotherapy) against lung cancer.

Using the body’s own immune system to fight cancer has long been considered a possible elegant anti-cancer strategy. However vaccine therapy for cancer suffers from potential difficulties. One difficulty was that the vaccine should be targeted against the tumor alone, and not normal tissue. In other words, the genetic makeup of the tumor should contain specific targets that the vaccine would act against, leaving normal tissues unaffected.

In the early 1990s, researchers began to look more closely at the genetic makeup of cancers. It was noticed that many cancers contained a specific family of genes, named the ‘cancer-testis antigens’. These genes were most pronounced in non-small cell lung cancer. One class of these genes was called the Melanoma Associated Antigen (MAGE).  In the following years many teams investigated the details of the MAGE family. Amongst the many MAGE antigens found in lung cancer, the MAGE 3 antigen was considered a good target for development of a vaccine against the lung cancer that contained this particular antigen. However, only 30% of non-small cell lung cancers contained  (‘expressed’, in medical parlance) the MAGE 3 antigen.

Scientists at GlaxoSmithKline, the pharmaceutical company, then developed a specific vaccine against the MAGE 3 expressing non-small cell lung cancer. The vaccine would induce specific white blood cells to attack the tumor. In addition, the vaccine would contain a non-specific immune boosting mechanism to enhance the effect of these specific white blood cells. Early studies of this vaccine in patients with non-small cell lung cancer have shown encouraging results. This led to the establishment of a major clinical trial testing this vaccine (called the Phase III  MAGRIT trial). Many centers around the world are participating in this trial. There are also smaller trials of various immunotherapy approaches going on at specific institutions in the U.S, however the MAGRIT Trial is the only vaccine trial for post-surgical patients being conducted worldwide at this time.

Patients are consented to participate in the trial following surgery. As a first step, the patient consents for the tumor that was removed at surgery to be tested for the MAGE 3 antigen. If their tumor contains the antigen it means two things – one, that the patients who are MAGE 3 positive do somewhat worse (in the long term) than people who are MAGE 3 negative and two, they are eligible for the trial. MAGE 3 positive patients are then randomized to receive the vaccine over a period of the next two years in 13 injections. The injection is given into the arm or buttock muscle, similar to a flu shot. Recent experience has shown the vaccine to be safe with very few minor side effects. The patients are randomized on a 2:1 ratio, meaning every 3^rd patient receives a placebo and the other two patients receive the vaccine. This is done in a blinded fashion, meaning neither the research staff or the patient knows who is receiving the vaccine versus the placebo. I would encourage all patients who have surgery for lung cancer to discuss with their surgeon or oncologist for possible enrollment in the MAGRIT Trial.

Further lung cancer vaccines are in development, thus potentially benefiting patients that are MAGE 3 negative.

After trastuzumab, genotypebased patient selection in trials was ignored as a strategy for common cancers. “Ten years go by, and then there aren’t any other examples of anybody actually doing that,” said Ross Camidge, M.D., Ph.D., a medical oncologist at the University of Colorado in Denver.

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p.s. sorry its been so long since the last update, WE HAVE BEEN LIVING LIFE. ; )

A week later, just about the time I had accepted that we could go a full year without looking again, I had a phone call from the oncologist.  His voice was slow and deliberate, sincere. I knew the tone.  Somehow I felt sorry for him-his job must be so difficult. A week earlier he had shared my joy at the thought that everything was stable and now he had to break the new that the cancer was actually growing. I knew this phone call was difficult for him, too. With as much reassurance as he could, he told me that the radiologist had read the scans with growth, and that as he reviewed them, he agreed.  He recommended I start thinking of a new treatment in the near future.  He reassured me that it was slow growing, minimal growth and we had plenty of time to make a wise decision.

Even though it is small growth, it is such a disappointment.  I had thought we had a year-and then we didn’t.  I had somehow let myself think that maybe it was truly gone.  That somehow it wouldn’t come back– that the cancer had faded away and life might go on as normal.  I had let myself think that maybe we had beat this for good.  Deep down, I guess, I knew better.  Its lung cancer. Unrelenting lung cancer.

So, I’ve known now for several days and its time to get over the disappointment and start thinking about what to do next.  At this point, treatment decisions are sometimes a matter of elimination.  I don’t want chemo- it’s too slow growing. I don’t want surgery again- I’m already missing too much lung tissue.  I’m worried about doing anything that would diminish anymore lung function.  Carbone said he wasn’t in favor of the RFA again, but I’m not sure why.  I thought it was a pretty good treatment choice.  He said he wanted me to think about stereotactic radiation, however, I’m scared, terrified, of radiation to my lungs.  I am not worried about the treatment itself- but the long term effects to the lungs.

So, I have lots to think about.  I have lots to figure out. Next week, I’ll talk to Dr. Carbone again. It’s time to make a plan.

It all started when I developed an upper respiratory illness—unrelenting cough, congested, body aches, and fever that has hung on through lots of rest, orange juice and two rounds of antibiotics.  Even when I can rationalize that I have a cough because I have an infection, somewhere in the deep wrinkles of my brain something whispers, “or maybe it’s cancer growing in your lungs”.

And tomorrow is scan day. It’s been scheduled for 5 months. It’s routine. I have them often. I’ve always had CT scans frequently since 2001 when I first learned I had lung cancer. So this is routine. Its what I do.

Still, I never quite get used to it.  Sometimes are better than others.  This one has been hard and I can feel the overwhelming anxiety overtaking me. Yesterday, seemed worse than today has been. Yesterday, I was even tearful for short intervals without due cause. Today is not that bad, yet I am still not myself.

Surely, there are better ways to handle this. I am the first to admit that I don’t do scans very well. And I can understand why this one is especially hard– it’s still wintery out- no sunshine, I haven’t felt well lately, I have a cough and fatigue too easily, and I already know there is something there and we are just waiting for it to grow.

So until tomorrow, I’ll be anxious, I’ll be uptight, I might be tearful, I’ll be sick and tired of hearing and talking about cancer; and I’ll have to take an ambien to sleep.

This is routine. Its what I do.

We received amazing news March 3, 2010. My PET scan showed dramatic improvement when compared with my prior PET scan just 2 months before. I am a stage 4 NSCLC never smoker diagnosed almost 3 ½ years ago.
My Mom is a TVaholic who was watching ABC news one night as they detailed a remarkable man, whose doctor’s had nothing left to offer him to treat his stage 4 lung cancer. His last chance was to have his tissue biopsied to look for the presence of a genetic mutation in his cancer cells called the ALK mutation. It turned out he was positive for this mutation and after taking an oral drug targeted specifically for this mutation a miracle happened. His cancer disappeared. The story went on to detail another man with this mutation who had significant reduction of his lung mass.

As a physician and lung cancer advocate, I had never heard of this mutation. I asked my own oncologist about having my tumor tissue tested. It took a few weeks to get the results. Shockingly my result was + for the ALK mutation and after a one month wash out period off chemo, I began taking this same Pfizer drug 1066. I am now 7 weeks after beginning this drug and the PET scan result brought tears to our family’s eyes. Findings consistent with marked improvement of neoplastic process. “Non visualization of the previously seen intensely metabolically active enlarged lymph nodes.” Remaining lymph nodes were reduced by greater than 50%. My bone metastasis also was gone. No new lymph nodes. My remaining right lung showed no evidence for previously seen metabolically active nodules. Simply amazing!

For the past 3+ years I have had problems with long range planning along the lines of ‘don’t buy any long playing records. Planning a trip even in the near future is problematic. I now feel like I’ve been given a longer leash. I feel like I can go out and buy something as simple as a shirt without feeling quilty about how many times I might actually wear it.

After just attending the IASLC (International Association for the Study of Lung Cancer) meeting, it is clear to me we need to shout it out to the lung cancer community and bring awareness to the masses of the importance of asking their doctors to test their cancer tissue for genetic mutations. There are treatments evolving for so many of these genetic mutations. This is what is so exciting about translational research (bench to bedside). This ALK mutation from discovery, testing to treatment just evolved over the past 3 years! New targeted therapies are emerging as we speak. Personalized medicine is the hot topic. The goal of managing lung cancer and prolonging lives is within sight. So remember, testing lung cancer tissue is nothing to sneeze at!

By Michael Weitz

The fact that this meeting is called “targeted therapies” is simply wonderful because that title speaks volumes. It means that this disease is recognized on an individual level and treated as so. There may be two people with stage four lung cancer sitting next to one another and each have a completely different type of cancer. We have known for several years that certain gene mutations are present in certain types of lung cancer, (now the “ah-ha” factor) but what we are learning now is which medications will successfully “target” certain types of gene mutations.  This is so important because if someone is diagnosed with lung cancer and has gene mutation testing done as soon as possible following the diagnosis, the chances of being matched with the most effective medications (as first line therapy) are much higher and this could make all the difference.  This could potentially save the patient from harsh unnecessary treatments.  There are several recognized mutations that can be tested for, the problem is, this is NOT a standard of care at every single oncology office. So, this is why BEING YOUR OWN ADVOCATE is crucial.

I would love to share a few tips that I have learned on our journey through cancer land.

1. There is nothing wrong with seeking a first, second or even third opinion about your treatment options.

2. If you have found something, heard of something, or read something that sounds promising in the treatment of your lung cancer, ASK YOUR DOCTOR ABOUT IT. Your doctor should be able to expound upon what you have presented to him/her giving you an even better understanding of it.  (if the doctor is consistently not receptive to you, use tip number one and seek out the second and third opinions).

3.  Nobody has set your future in stone; you are making your own, so FIGHT FOR IT!

Ok enough of the “tiffisms”.

The targeted therapies meeting also provided the opportunity for me to meet with the Lung Cancer Foundation of Americas founders and other patient advocates. This was so awesome to see all of these passionate minds collaborate and make big plans for the future of lung cancer outcomes. To actually be part of a foundation that literally turns every penny given to them into research dollars that lead to future promising treatments is extraordinary.  So, everyone that has donated to this foundation, please know that I am so grateful to you and please know that it is making a difference. I wish I had better, bigger verbiage for that, but it really is MAKING A DIFFERENCE.  Thank you. Even more promising treatments are on the horizon and the funding is desperately needed to make them happen.

I almost forgot to tell you, my husband is doing WONDERFUL. He continues on the avastin as maintenance, which he receives intravenously every twenty-one days. He recently had scans that even showed improvement in certain areas. We are blessed! Even in the midst of this disease, we have been shown so many blessings and now ~life just tastes sweeter~

Tiff

Experimental Drug Could Help One In 20 Lung Cancer Patients

“I’d only been on the drug for six weeks and went in for the PET scan,” said Pulhamus.

And when compared to her PET/CT scan from the beginning of the study, doctors saw dramatic shrinkage of a tumor on her kidney. 

“There were four other tumors, and some of them we couldn’t even see anymore,” said Pulhamus. 

“It’s really a dramatic shrinkage of the tumor that we are seeing, and for an experimental drug it’s quite exciting to see that,” said Dr. Robert Doebele, assistant professor medical oncology at UC Denver. 

The ALK Inhibitor works by blocking the activity of a specific abnormal gene found in about 5 percent of lung cancer patients. 

“And because this gene is so important for the growth and spread of the lung cancer, and its dependence on that gene, it actually shrinks the tumor,” said Doebele. 

Technology developed at UC Denver allows doctors to genetically test a biopsy to identify those patients who are likely to benefit from the ALK Inhibitor. This leads to personalized medicine and therapies for patients. 

For Pulhamus, the targeted therapy resulted in the 60 percent reduction of an egg-sized tumor, with just two pills a day. 

“No chemo, no radiation. I’ve done that,” Pulhamus said with a giggle. 

“If we are able to tailor our therapy to the individual patient based on what we see on molecular tests, then it will be very beneficial to the patients because we won’t spend time using very toxic drugs that may not work,” said Doebele. 

With fewer and less significant side effects, the ALK Inhibitor can be administered for months, if not years longer than chemotherapy. This means that right now, Pulhamus’ wish for more time to spend with her children and grandchildren has come true. 

“It changes everything, it gives me hope,” said Pulhamus. “It makes me realize that maybe there is a future for me.” 

In fact, her third PET/CT scan revealed another 50 percent reduction in the size of her tumor. 

Doctors at the University of Colorado Cancer Center recommend that everyone in Colorado with lung cancer be evaluated for eligibility in this clinical trial. For more information about free genetic tumor screenings and enrollment in the UCCC clinical trial, call Tiffiany Caudill, 720-848-0392. 

The free lung cancer tumor testing is also taking place at: 

*The Brigham and Women’s Hospital *Dana Farber Cancer Institute *Emory University/Winship Cancer Center *Moffitt Cancer Center *Johns Hopkins/Sidney Kimmel Cancer Center *MD Anderson Cancer Center *Mass General Hospital Cancer Center *Memorial-Sloan Kettering Cancer Institute *National Cancer Institute *UCLA/Jonssen Cancer Center *University of Pittsburgh Cancer Institute *University of Texas-Southwestern Cancer Center *Vanderbilt-Ingraham Cancer Center.

So, lets back up.  How do we know which mutation our own tumors possess? It is not done routinely and is not part of what the pathologists looks at when examining the cells to make a diagnosis of adenocarcinoma or squamous cell lung cancer.  It is not the same test as gene amplification–that just tell us if the gene has reproduced excessively; however it doesn’t tell us if it has actually mutated.  The actually gene mutation test is specific, and takes up to two weeks to perform. It doesn’t take a lot of tissue– and can be done on paraffin block tumors. The gene mutation testing needs to be done at a certified lab specific for gene mutation testing.

They are finding out different things about different tumors.  For example, the EGF mutations have a part that is actually deleted. exxon 19 and exxon 21.  ALK gene fuses with another gene.

What does all this mean for patients?  One thing that I heard over and over was that the gene mutation testing does not eliminate treatment, but it help prioritize treatments.  For example: Many people who are EGF gene mutation negative still may have benefit from taking Tarceva. However if a patient’s tumor has the exxon 19 deletion that patient most likely will respond to Tarceva.  There is still alot we don’t know, but we can use the knowledge we have to help guide us to know what therapies might work best for us.

So who should have their tumors tested??  EVERYBODY WHO HAS LUNG CANCER. This is something all the doctors were saying- we have enough information now that we can design treatment based on gene biology of the cancer.

That’s amazing.