Lung cancer still difficult to treat
SPRINGFIELD – Lung cancer, especially in its advanced stages, is still very difficult to treat. The good news is that advances in molecular genetics are resulting in new "designer therapies" which are offering greater hope for lung cancer patients who are told they have an incurable disease.
"The advances in combating lung cancer that we are seeing now are a direct result of the Human Genome Project. The key to the future is going to be these personalized, directed therapies, where we look at a patient's tumor, or the words I use among colleagues is interrogating or investigating tissue taken during biopsy, to identify already known gene mutations that alter the basic backbone of cellular life," Dr. Christopher Otis, director, Surgical Pathology at Baystate Medical Center, said.
It is precisely these molecular mutations which are the target of these new designer therapies that are offering some patients a chance at a longer life expectancy after diagnosis. And it is the pathologist in the laboratory looking at tissue taken by radiologists during a core biopsy, who are key to identifying specific cell types and any molecular or genetic changes in them that will help oncologists to make important decisions regarding the most effective treatment for their patients. It's what some doctors are now referring to as "personalized medicine."
The three common gene mutations that have been identified in lung cancers so far are EGFR, KRAS, and ALK.
"We have custom-designed, molecular therapies for two of these mutations that target the altered proteins that come off this altered DNA, effectively shutting them down for a time and stopping the cancer cells from multiplying," Otis said.
While promising for those who have mutations in the EGFR and ALK genes – there is no drug yet designed for KRAS – only a small fraction of patients with lung cancer have these mutations that can be effectively targeted with new therapies. However, the Baystate pathologist said he expects treatment for simply the three main mutations to expand by a much greater magnitude over the years.
"The way I see this happening is that those three main mutations we have identified will expand slowly to 12, then over the course of time will expand again to 100, then 1,000 and even 10,000 and more in the future. Along with that expansion will come an increase in therapies to benefit our patients. Some will be drugs that are already approved for use in other cancers, while other new designer therapies, some already in experimental use now, will have to be developed," Otis said.
"Our next challenge will be to learn why the cells we are attacking eventually develop a resistance to these new designer drugs and how we can counteract that process," he added.
Ninety percent of lung cancers occur in smokers. Still 10 percent diagnosed with lung cancer have never smoked. However, a very small number of people have no risk factors. The majority of people in that 10 percent category have been exposed to second-hand smoke, radon gas, asbestos or other chemicals or pollution.
A big proponent against smoking who has actively worked in prevention efforts with teenagers, Dr. Gary Hochheiser, chief of thoracic surgery at Baystate Medical Center, said treatment of lung cancer remains difficult due to a number of factors including the relative aggressiveness of most lung cancers.
"The mainstay of treatment continues to be surgery, but is only possible if the disease is found at an early stage," Hochheiser said.
"We have learned over the last 10 years that we can combine treatment to include surgery with chemotherapy and radiation to improve cure rates for those with early stage lung cancer, those whose tumors have grown larger, and others whose lung cancer has spread locally, but not to other areas of the body," Dr. John McCann, an oncologist in the Baystate Regional Cancer Program, said.
According to Hochheiser, minimally invasive surgical techniques have helped to reduce risk by decreasing complication rates, speeding recovery, and offering less post-operative pain for the patient. These newer methods, which Hochheiser performs, include thoracoscopic or VATS (Video Assisted Thoracoscopic Surgery), as well as more recently introduced robotic surgical technology.
Perhaps the most important aspect of lung cancer care is the availability of a multidisciplinary team for evaluation and treatment, Hochheiser noted.
Baystate brings together a team that includes members of many different disciplines, including surgeons, medical oncologists, radiation oncologists, pathologists, pulmonologists and radiologists who meet and review all aspects of a patient with lung cancer. The end result is the development of a plan of action that follows accepted guidelines and that allows for personalization of available treatments to benefit the patient's individual scenario.
"The bottom line is that we are getting better at controlling advanced lung cancer which had a life-expectancy of four to six months back in the 1990s. It is still very short, but today we can extend that to greater than one year for some patients. More importantly, a growing but still small group of patients are getting substantially longer benefits from these treatments. Our hope is that these newer treatments for advanced cancer will also translate into improved cure rates for patients with earlier stage lung cancers," McCann said.