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What Does A Combination Treatment Of Lung Cancer Look Like?
Lung cancer is the commonest killer among all cancers worldwide. Historically, the patients with lung cancer presented at an advanced stage, and the treatment options were limited. With rapid strides in the knowledge of the biology of this disease coupled with advancements in treatment modalities, this disease has a far better outcome now.
Almost all wings of oncology contribute to a multidisciplinary approach to the treatment of lung cancer. The patient's story generally starts with seeing by a physician or a pulmonary medicine specialist who would ask for an X-ray chest and other investigations. The pulmonary physician plays a very important role in differentiating a lung cancer from tuberculosis and other lung infections that are quite common in our country. Imaging techniques like CT scan and PET scan along with a CT-guided or a bronchoscopic biopsy would confirm the diagnosis and stage of the disease.
Broadly, lung cancer can be classified pathologically as small cell and non-small cell cancers. Small cell cancers are extremely aggressive cancers, and are usually treated with chemotherapy, sometimes with radiotherapy when the disease is limited to one side of the chest, and very occasionally with surgery for a really early disease. Non-small cell lung cancers are far more common, and can be either a squamous cell carcinoma or an adenocarcinoma. The pathologist will give additional information on the targetable genetic mutations (especially in case of adenocarcinoma), and about the potential immunotherapy markers like PDL-1.
Lung cancer is generally staged based on the size and extent of the tumor in the lung, the presence of lymph nodes in the mediastinum (the space between the two lungs), and spread of disease to other sites of the body like liver, brain, bones, adrenals etc. This staging information is given by a combination of PET-CT scan and often MRI of the brain. Invasive staging for the mediastinal nodes is sometimes required, and is done by endo-bronchial ultrasound (EBUS) or by a surgical procedure called mediastinoscopy.
In early stages (Stage 1 and 2), when the disease is limited to the lung or one of its lobes, surgical removal by removal of a lobe (lobectomy) or sometimes the whole lung (pneumonectomy) is the treatment of choice. Such patients need to have further evaluation of their lung function (Pulmonary Function Test) and their cardiac function (usually by a stress Echocardiogram or a treadmill test) in order to ascertain their fitness for surgery. Traditionally, the patients would have a long cut on the side of the chest for approaching the tumor through the muscles and ribs. Today, technical developments like muscle-sparing thoracotomy, video-assisted thoracoscopic surgery (VATS), and robotic-assisted thoracoscopic surgery (RATS) have made the surgery much easier to endure for the patients. The developments of stapler technology to seal and divide the blood vessels and bronchus have made the surgery much faster and safer. The advances in anesthesiology and pain management have added to the safety of surgery.
The specimen that is removed on surgery undergoes a detailed analysis by a pathologist, and the final stage of the disease and other risk factors are ascertained. Most patients will undergo adjuvant chemotherapy after surgery, unless the cancer was less than 4 cm without any other risk factor and without involvement of any lymph nodes.
The management of a patient with a locally advanced (Stage 3) disease is far more complex and nuanced. Multidisciplinary treatment has had its maximum impact in this group of patients. In Stage 3A disease (when the mediastinal nodes are limited to the side of the tumor), the patients are generally treated with chemotherapy first and then with surgery (lobectomy or pneumonectomy). Sometimes a patient with Stage 3A lung cancer may not be suitable for this approach when the mediastinal nodes are large or at multiple sites. In such patients, a combination of chemotherapy and radiotherapy is preferred. The outcome of patient who can have surgery in addition to chemotherapy with/without radiotherapy has been seen to be better than those who cannot have surgery. Careful selection of patients for different treatment modalities is thus of paramount importance.
A patient with Stage 3B lung cancer (when the mediastinal nodes are also on opposite side, or if the tumor is involving the vital vascular structures) is usually treated by non-operative options. A combination of chemotherapy and radiotherapy is the standard of care in a fit individual. However, other options like chemotherapy or immunotherapy can also be considered on a case to case basis. The planning of radiotherapy and its execution is vitally important in Stage 3 patients. With the advent and growing popularity of the modern radiotherapy techniques like IMRT and IGRT, the treatment has become more focused resulting in fewer complications and improved outcome.
When the lung cancer has spread to other organs (Stage 4), the aim of treatment changes from cure to improvement in survival and control of symptoms. Very occasionally, an oligometastatic disease can be treated with curative intent including surgery when the metastasis is limited to a single site in brain or adrenal gland. In all other patients, systemic therapy is the treatment of choice. The choice of chemotherapy would depend on the type of cancer (histology), the molecular markers, the general condition of the patient, and other factors.
The outcome of such Stage 4 disease was historically quite dismal with an average survival of 9-12 months. This has undergone a paradigm shift with the understanding of new molecular mechanisms and the development of targeted drugs and immunotherapy. Especially in adenocarcinoma of the lung, if a molecular target is detected (EGFR, ALK-1, ROS-1), there are oral medications that can act on such targets. With these targeted drugs, the outcome of lung cancer has improved significantly from a dismal figure of a median survival of about 9 months to nearly 3 years.
Immunotherapy is a relatively new kid in the block, and has also had a great impact on the outcome of lung cancer. In a properly selected patient the responses to immunotherapy are sometimes quite dramatic and durable. Seeing such encouraging results of targeted therapy and immunotherapy in Stage 4 disease, these drugs are also being tested in patients with early disease in conjunction with surgery and sometimes as a replacement of conventional chemotherapy.
Most patients with lung cancer and especially those with advanced disease are often riddled with symptoms like pain and shortness of breath, and symptoms related to the site of metastasis. While the cancer-directed treatment continues, it is also vitally important to take care of these symptoms. The Pain and Palliative Medicine specialist plays a vital role in providing comfort and care to these patients.
Treatment of any cancer today is multidisciplinary, and lung cancer perfectly showcases this collaborative effort of several specialists in order to give an optimal outcome to the patient. Surgical, Medical & Radiation Oncologists work hand in hand towards the care of the patient. Specialists in Pulmonary Medicine, Nuclear Medicine, Anesthesiology & Critical Care, Pain and Palliative Care also contribute to the care of such patients. Finally, all advances in science and technology have their roots in basic research. These researchers have identified newer molecular mechanisms and targets which are employed by oncologists for use in patients with lung cancer.
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DisclaimerViews expressed above are the author's own.
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Lung Cancer Deaths Cut In Half With AstraZeneca Pill, Large Trial Finds
A once-daily pill from drugmaker AstraZeneca cut deaths in half among a subset of early-stage lung cancer patients who had undergone surgery, according to new clinical trial results.
The findings were presented Sunday at the American Society of Clinical Oncology's annual meeting in Chicago and simultaneously published in the New England Journal of Medicine.
The data is the first to show how a targeted treatment for early-stage lung cancer impacts survival, said Dr. Roy Herbst, the trial's principal investigator and deputy director at Yale Cancer Center. The drug, called osimertinib and sold under the name Tagrisso, is directed at a specific receptor that helps cancer cells grow.
"I think we're curing some patients," Herbst said. "We're really showing progress in lung cancer like never before."
The trial results were "about twice as good as we expected," Herbst added.
In an international study of 682 lung cancer patients, roughly half of the participants were given the daily pill for three years, while the other half received a placebo. Five years after their diagnosis, 88% of those who took the pill were still alive, compared with 78% of the placebo group. The study was funded by AstraZeneca and included people from more than 20 countries across the U.S., Europe, South America, Asia and the Middle East.
The researchers found that the drug lowered the overall risk of death from lung cancer by 51%.
Last year, the Biden administration set a moonshot goal of reducing the cancer death rate in the U.S. By at least 50% over 25 years.
"At least in this one area, we've hit the mark," Herbst said.
Tagrisso is already approved in more than 100 countries, including the U.S. The Food and Drug Administration approved the drug in 2015 for people with more advanced lung cancer who saw their disease get worse during or after taking other treatments. Then in 2020, the agency approved Tagrisso for early-stage versions of the disease.
Herbst's research team showed three years ago that Tagrisso kept tumors from coming back and prevented cancer from spreading to the brain, liver and bone.
"We already knew that this drug was effective. However, what we are seeing now is that patients will also live longer," said Dr. Charu Aggarwal, an associate professor of medicine at the University of Pennsylvania's Perelman School of Medicine, who wasn't involved in the research.
The trial included people with stages 1, 2 and 3 non-small cell lung cancer, the most common type of lung cancer.
Participants also had a mutation in a receptor called EGFR. The receptor normally helps cells grow, but the mutation can make cells excessively divide and multiply, which may cause cancer. The pill functions as an "off" switch for that mutated receptor, Herbst said.
Around 10 to 15% of lung cancer cases in the U.S. Have an EGFR mutation, though it's more common in Asia and Australia. The mutation is usually detected in people with little to no smoking history.
Herbst said the new survival data could encourage more doctors to prescribe the drug. The data might also prompt wider insurance coverage of the pill, he said, since the treatment is expensive and insurers prefer to see a survival benefit before deciding to reimburse a costly drug.
Patrick Forde, an associate oncology professor at Johns Hopkins Medicine, said that before targeted treatments like Tagrisso were available, patients with stage 1 to 3 lung cancer would normally receive chemotherapy after surgery. That might improve their odds of survival by about about 5% compared to those who didn't receive chemo, he estimated. (Forde wasn't involved in the new research, but he has consulted for AstraZeneca and obtained research funding from the company in the past.)
"If you go back 15 years, for this patient population we would have expected maybe a survival of 50% at five years," he said. "But because of the advances both for stage 4 cancer, and now this advance in earlier stage cancer, we're up to 88%."
Doctors may still recommend both chemotherapy and Tagrisso after surgery, Forde said.
Compared to chemo, Tagrisso comes with fewer major side effects. According to Herbst, some people on the pill experience skin rashes and mild diarrhea, but overall the drug is "quite well tolerated."
Jill Feldman, a lung cancer patient who has been taking Tagrisso for more than four years, said that her cancer has stopped progressing on the drug and noted that it was easy to take at home as a pill. But she added that side effects that aren't life-threatening can still be life-altering to patients. Since she started on the drug, said Feldman, 53, of Deerfield, Illinois, she has experienced diarrhea, mouth sores, fatigue and a skin infection in her nail beds.
One lingering question, Forde said, is whether survival rates would stay the same if patients were given the pill after their cancer relapsed versus immediately after surgery. However, doctors generally recognize that treating cancer early improves survival rates.
Early screening is still a challenge, though: In most cases, Forde said, doctors don't screen broadly enough to detect lung cancer before it spreads to other parts of the body. The U.S. Preventive Services Task Force recommends annual lung cancer screenings for certain adults ages 50 to 80 with a history of smoking.
"Only about 5% of patients are being appropriately screened, and that's in contrast to things like breast cancer mammograms or cervical screening," Forde said.
Aggarwal said many lung cancer patients aren't tested for EGFR mutations, either. The new data could be a "call to action" to increase those screenings, she said.
Small Cell Vs. Non-small Cell Lung Cancer
Small cell and non-small cell are the two main types of lung cancer. There are several key differences, including the outlook for each.
In a person with small cell lung cancer, the cancerous cells appear small and round under a microscope. The cells of non-small cell lung cancer are larger.
Smoking is a major risk factor for both types. Of those who receive a diagnosis of small cell lung cancer, 95% have a history of smoking.
There are several subtypes of both small and non-small cell lung cancer. Non-small cell lung cancers include adenocarcinoma, squamous cell, and large cell carcinoma.
Small cell lung cancers vary depending on the expression of specific genes.
Some types are more aggressive than others, but generally, small cell lung cancer is more aggressive than non-small cell lung cancer.
Lung cancer — including both small and non-small cell types — is the third most common form of cancer among adults in the United States. Lung cancers account for 13% of new cancer diagnoses.
Small and non-small cell lung cancers cause similar symptoms. Sometimes, symptoms do not appear until the cancer reaches a later stage.
Symptoms include:
The symptoms of small and non-small cell lung cancers are similar, but small cell lung cancer spreads more rapidly.
A person may be more likely to experience symptoms after lung cancer has reached a later stage.
Does lung cancer affect women differently? Learn more here.
Can shoulder pain be a sign of lung cancer? Find out more.
Causes and risk factors for small and non-small cell lung cancer tend to be similar.
Smoking is the main risk factor. Cigarette smoke and the chemicals it contains can damage the lungs. This can lead to cellular changes that may result in cancer.
Additional risk factors include:
Smoking is a major risk factor for lung cancer. Find some ideas about how to quit here.
If a person sees a doctor about a persistent cough and other possible symptoms of lung cancer, the doctor will ask questions and take a medical history. They will also perform a physical examination.
If lung cancer may be present, the doctor will also request imaging scans, such as an X-ray or CT scan, and look for signs of a tumor, scarring, or a buildup of fluid.
They may also request samples of phlegm in order to perform a sputum test. This can help indicate whether cancer is present. The doctor will probably ask the person to provide a sample every morning for 3 days in a row.
Doctors may also perform a biopsy. This involves using a needle to take a sample of cells from the lungs for examination under a microscope. They may do this during surgery.
A biopsy can show:
Sometimes, the doctor requests a bronchoscopy. This procedure involves inserting a tool with a built-in camera through the mouth or nose and into the lungs. This helps them see the area and take tissue samples.
They may also carry out other tests to determine whether the cancer has spread beyond the lungs.
What does lung cancer look like? Find out here.
StagingThe stage of cancer describes how far it has spread within the body.
There are different ways to describe the stages. One simple way is:
However, each type of lung cancer has its own specific method of staging.
Non-small cell lung cancerFor this type of cancer, doctors typically use a 5-stage system.
Doctors generally categorize small cell lung cancer with one of two stages:
Some doctors use further staging for small cell lung cancer.
Can a person have both types?Around 5–28% of small cell lung cancer cases are "mixed." This means that the person has small and non-small cell lung cancers. Research suggests that it may be easier to treat mixed cancer than small cell lung cancer alone.
After making a diagnosis, a doctor will describe the treatment options and develop a treatment plan.
Factors that affect the plan will include:
As each person's situation is different, treatment will vary accordingly.
Non-small cell lung cancerTreatment options for non-small cell lung cancer include:
For small cell lung cancer, treatment mainly aims to manage the disease.
Options include:
Doctors may use a combination of treatments for lung cancer, depending upon an individual's needs, the stage of the cancer, and the location of the tumor.
Experts use past statistics to estimate the percentage of people who are likely to live for 5 or more years after a diagnosis of cancer. These estimations are called survival rates.
They represent averages and do not take into account factors such as a person's age or overall health.
Non-small cell lung cancerFor non-small cell lung cancer, the American Cancer Society (ACS) reports the following relative 5-year survival rates:
The overall average likelihood of living for at least another 5 years is 26%.
Small cell lung cancerThe ACS estimates the following 5-year survival rates for people with small cell lung cancer:
The overall average likelihood of living for at least another 5 years after a diagnosis of small cell lung cancer is 7%.
Other factors that may affect survival rates include whether the cancer has come back after treatment and a person's age. Recurring cancer and advanced age can have a negative effect on survival rates.
There are two main types of lung cancer: small cell and non-small cell. Small cell lung cancer is less common and more aggressive.
Quitting smoking — or never smoking — can significantly reduce the risk of developing any type of lung cancer.
Read this article in Spanish.
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