Diagnosis and treatment of non-small cell lung cancer in the US

Modern methods of diagnosis and treatment of non-small cell lung cancer in the US give patients a real chance to defeat this deadly disease and preserve a high quality of life.

In developing countries, about 2/3 of lung cancers are diagnosed in stages III and IV, when the 5-year survival rate does not reach even 5%.

According to statistics, malignant neoplasms of the lungs are the leading cause of death of men and the second biggest killer of women. Annually more than 270,000 Europeans and about 1.8 million people around the world hear this devastating diagnosis.

Scientists predict that 1 out of 15 people will eventually develop lung cancer. This risk is much higher for smokers. About 85% of cases are non-small cell lung cancer (also known as NSCLC).

Risk Factors and Symptoms of Lung Cancer

Among the most common symptoms of NSCLC are:

- dyspnea
- chest pain
- persistent cough
- hoarseness
- difficulty swallowing
- frequent pulmonary infections
- hemoptysis
- unexplained weight loss
- weakness and fatigue
- bones and joint pain
- unexplained fractures
- headache
- memory impairment
- bleeding
- thrombosis

Unfortunately, about 25% of people with lung cancer have no symptoms. Most often these patients seek medical help too late. Sometimes tumors diagnosed accidentally during medical tests.

Important risk factors for NSCLC:

- exposure to radon
- active or passive smoking
- chronic obstructive pulmonary disease
- genetic predisposition
- heavy air pollution
- industrial chemicals

Despite well established and proven relationship between pulmonary neoplasms and smoking, even non-smokers can develop cancer due to passive smoking or other factors.

Lung cancer screening: low-dose spiral computed tomography

Lung tumors may develop in young people who actively engaged in sports and never smoke. No one can feel safe. That's why American oncologists strongly recommend CT lung cancer screening. Low-dose spiral computed tomography (CT) is extensively used to detect small tumors.

Cleveland Clinic proved that CT screening is useful for current and former smokers, as well as for people over 55 years of age. Early diagnosis of the most fatal cancer is definitely worth the theoretical risks associated with computed tomography or X-ray.

10 best cancer treatment centers in the US 2018

High-tech molecular and genetic tests are important elements of the diagnostic process. New technologies allow doctors to identify patients who are suitable for a particular type of treatment.

US oncologists have achieved tremendous progress in molecular diagnosis, surgical treatment and targeted cancer therapy. By choosing the right treatment to the right patients, our leading cancer centers successfully increased the 5-year survival rate for stage IA1 NSCLC to about 92-95%, stage IIA – 65%.

According to the latest US News & World Report 2018, the MD Anderson Cancer Center (Houston) is recognized as the best cancer treatment hospital in the United States.

The legendary clinic is located on Texas Medical Center’s campus. There is a well known department of thoracic surgery and a lot of research facilities working in the field of lung cancer diagnosis and treatment. It is one of the largest scientific and clinical institutions in the world. MD Anderson serves more than 120,000 patients every year, and the center's staff is now exceeding 20,000. Adults and children from all over the world can get professional care and second opinion there.

Top 10 cancer treatment centers and hospitals in America

1. MD Anderson Cancer Center
2. Memorial Sloan Kettering Cancer Center
3. Mayo Clinic in Rochester
4. Dana-Farber / Brigham and Women's Cancer Center
5. Seattle Cancer Alliance / University of Washington Medical Center
6. Johns Hopkins Hospital in Baltimore
7. Cleveland Clinic, Ohio
8. Hospitals of the University of Pennsylvania-Penn Presbyterian
9. Moffitt Cancer Center and Research Institute
10. UCSF Medical Center

Lung cancer: early diagnosis and treatment

One of the most common malignant neoplasms, lung cancer is divided into several types. Each type is special and requires unique clinical approach. That is why innovative diagnostic methods are critically important for achieving optimal therapeutic results and prolonging the life of patients.

The main varieties of the disease:

1. Non-small cell carcinoma occurs in the vast majority of cases. It is classified into large cell, squamous cell carcinoma and adenocarcinoma.

2. Small cell carcinoma: about 10-20% of all cases. Aggressive, with a poor prognosis.

3. Carcinoid tumors: up to 1-2% of all cases. Slow development, lower incidence of metastasis.

Diagnosis of non-small cell lung cancer in the United States

Early diagnosis maximizes the chances of curing the disease. Sometimes malignant neoplasm is manifested by cough, dyspnea and hemoptysis, but in some cases NSCLC is asymptomatic. In such cases innovative diagnostic technologies come into play.

Cancer care in the US is the responsibility of professional team, including a thoracic surgeon, a medical oncologist, an oncoradiologist, a pulmonologist, a psychologist and rehabilitation specialists. Each member of the team plays an important role. For example, medical oncologist is responsible for pharmacological treatment including chemotherapy and immunotherapy.

Medical history and physical examination

Despite the development of cutting-edge technologies of medical imaging and laboratory diagnostics, the physical examination and medical history continue to play an important role in diagnosis of NSCLC.

Before moving on to more complicated, costly or painful tests, the doctor must check your symptoms and risk factors. The consultation of a qualified oncologist is an important step towards a correct diagnosis.

If your doctor suspects a lung tumor, additional tests are prescribed:

- computed tomography
- plain X-rays
- blood tests
- biopsy etc.

Diagnostic imaging in non-small cell lung cancer

This extensive diagnostic area includes ultrasonic, radiographic (CT) studies, the use of magnetic fields (MRI) and radioactive isotopes to visualize organs and tissues.

Radiation diagnosis allows to detect the primary tumor and metastases, but also to monitor treatment response.

Diagnostic imaging tests in NSCLC:

1. Radiography of the chest (plain X-ray)

2. Computed tomography of the lungs and mediastinum: allows estimating the localization, size and shape of neoplasms. In advanced cancer CT scan shows metastases in the brain, liver or other internal organs. CT guided biopsy is designed to take tissue samples.

3. Magnetic resonance imaging: MRI scan provides high-quality images of soft tissues. Using gadolinium (contrast), your doctor can better see details. MRI is a safe method with no radiation.

4. Positron emission Tomography: radioactive sugar (FDG) is used for this test. Drug is injected into the bloodstream before scanning. Due to rapid metabolism, malignant cells quickly absorb this carbohydrate, and glucose highlights them on the screen.

5. PET / CT: this hybrid method is based on the simultaneous use of computer and positron emission tomography. In this case, the doctor compares the image of CT with zones of increased radioactivity. PET / CT is the most popular technology in the diagnosis of NSCLC.

6. Bone scintigraphy: the radioactive material is injected into the patient's blood. This drug is distributed throughout the skeleton. Areas of increased radioactivity can be seen with a special scanner. These are the most likely sites of metastases. 

Laboratory methods for diagnosis of non-small cell lung cancer

Even if CT or MRI results suggest a tumor, doctors should determine the type of the disease using laboratory tests. The treatment approach and prognosis depend on the type of tumor and specific cell mutations. Tissue sample for the study is obtained from sputum and taken taken during a biopsy. Sputum cytology in suspected cases can help to detect tumors in the large bronchi, especially squamous cell NSCLC.

Methods of obtaining tissue samples:

1. Pleural puncture: a procedure also called thoracentesis allows removing fluid from the pleural space. Lab test show the cause of the effusion including tumor, infection or other diseases.

2. Pericardiocentesis (PPC): a similar procedure that involves fluid removal from the pericardial space (sac surrounding the heart). The presence of malignant cells in pericardial effusion may be a sign of metastases of NSCLC in the heart.

3. Needle biopsy: this method is divided into fine needle aspiration biopsy (FNA) and so-called core biopsy. With a needle biopsy, there is no need for a surgical incision. The main disadvantage is a small amount of tissue. Biopsy is more often performed with CT.

4. Bronchoscopy: The doctor uses a flexible optical tube (bronchoscope), which is inserted into the respiratory tract through the nose and reaches directly to the tumor. There special equipment allows inspecting the bronchi and taking a sample.

Obtained tissue samples are sent to the pathology laboratory where they are studied by immunohistochemical and molecular genetic methods:

1. Immunohistochemistry: for this test, thin tissue slices are treated with specific proteins (antibodies). They bind only to a specific type of tumor cells, so the diagnosis becomes obvious.

2. Molecular analysis: this test reveals genetic changes in malignant cells and allows predicting response to treatment. In lung tumors, the epidermal growth factor (EGFR) gene, the KRAS oncogene, ALK kinase gene (5% of NSCLC cases), the ROS1 gene (1-2%) and BRAF may change.

Other diagnostic tests:

1. Blood tests: CBC and biochemical test

2. Pulmonary function tests (PFT)

Determining the clinical stage of NSCLC

Once the tumor is detected, it is important to determine the stage. Has the tumor spread to lymph nodes or internal organs? The stage of cancer largely determines the tactics of further treatment and prognosis.

1. Endobronchial ultrasonography: high frequency sound waves is a safe tool for studying internal organs. With endobronchial ultrasonography (EBUS), a bronchoscope with a transducer is inserted directly into the respiratory tract, showing tiny changes in the tissues and lymph nodes.

2. Transesophageal ultrasonography: a similar method in which an endoscope with an ultrasound transducer at the end is inserted into the esophagus. Requires anesthesia and sedation of the patient.

3. Mediastinoscopy and mediastinotomy: invasive procedures, in which the surgeon makes cuts for direct access to the lymph nodes of the mediastinum, bronchi and vessels.

4. Thoracoscopy: sometimes surgeon needs to carefully examine the space between the chest wall and lungs, to assess the condition of the lymph nodes and take tissue samples. For this purpose, thoracoscopy (medical and diagnostic operation) may be ordered.

Treatment of non-small cell lung cancer in the US

Depending on the patient's condition, stage of the disease and other factors, the treatment may include surgical resection, radiation therapy, radiofrequency ablation, chemotherapy, immunotherapy and targeted drugs. Usually, several methods are used in combination. For example, surgical resection with subsequent (adjuvant) chemotherapy. Immunotherapy combined with chemotherapy.

Surgical treatment of NSCLC

American thoracic surgeons have made significant progress in surgical resection techniques. Leading cancer clinics in the United States operate not only young and healthy patients, but also elderly people. Good example is the story of successful treatment of Ken Settlemire (76 y.o.), who was rescued by the Mayo Clinic surgeons in Florida, who performed a sleeve resection of the lung.



In the early stages of disease surgery gives a chance to completely heal cancer. With advanced disease, surgical methods can alleviate symptoms and prolong life.

Main surgical techniques in NSCLC:

1. Lobectomy: resection of the lobe that is affected by the tumor

2. Pneuromectomy: removal of the entire affected lung with tumor

3. Segmentectomy: partial resection of the affected lobe

4. Sleeve resection: ensures maximum preservation of pulmonary tissue

Any kind of surgery involves the removal of nearby lymph nodes. After the intervention, an additional course of therapy is usually required to prevent relapse. The duration of hospitalization is about 1 week.

Video-assisted Thoracic Surgery (VATS)

US surgeons widely use video-assisted thoracic surgery, which is less traumatic than thoracotomy. During the operation, doctor makes several miniature incisions and inserts a thin tube with a camera. VATS can perform a wide range of tasks, from biopsy to lobectomy or even removal of the entire lung.

VATS is a technically complex procedure that requires costly special equipment and qualified surgeons. Advantages of the method are obvious: small incisions, less bleeding, shorter recovery period.

Radiofrequency ablation (RFA) for non-small cell lung cancer

RFA uses high energy waves that destroy the neoplasm from the inside. Under the control of a computer tomography, the surgeon inserts a catheter to the tumor and heats the cancer cells. This procedure is performed under local anesthesia and does not require prolonged stay in the hospital. Serious complications are rare. Radiofrequency ablation is recommended for patients with small tumors that can not be candidates for routine surgical intervention.

Radiation therapy for non-small cell lung cancer in the US

Radiotherapy for NSCLC can be used as the main treatment (alone or in combination with chemo). It is given before or after the operation, to reduce the size of the neoplasm or to alleviate the symptoms of the disease.

Types of radiation therapy:

• External: 3D-CRT, IMRT, VMAT, SBRT, SRS
• Internal radiation or brachytherapy

External radiotherapy for NSCLC

This procedure resembles radiography. The patient lies on the table, and the computer directs beams exactly to the tumor. This procedure is painless, and lasts for several minutes. Usually the course of external radiotherapy for NSCLC includes five sessions per week for 4-7 weeks in a row.

Modern methods of radiotherapy:

1. Three-dimensional conformal radiation therapy, or 3D-CRT: the method is based on the use of a computer that calculates the position and size of the lesion.

Radiation is delivered as accurately and efficiently as possible.

2. Modulated intensity radiation therapy (IMRT): an improved version of 3D-CRT is designed to preserve healthy tissues. The beams are not only sent from different angles, but are also regulated by intensity.

3. Stereotactic ablative radiotherapy (SABR, or SBRT): the method involves the high-precision delivery of large doses of radiation for fewer sessions. To increase the accuracy of radiotherapy, the patient is placed in a special frame that immobilizes the body for the procedure.

4. Stereotactic radiosurgery (SRS): a single procedure that can replace surgical intervention in some cases. Among other things, SRS is prescribed for metastases in the brain. Option widely used in America, Gamma Knife focuses 200 beams on the tumor from different angles.

Brachytherapy for NSCLC

Brachytherapy is widely used for metastases of lung cancer. Method is called internal radiation because the source of beams is placed directly in the patient's body. During surgical procedure or bronchoscopy, doctor inserts radioactive particles into the tumor. This material is removed later or left to "dissolve".

Side effects of radiotherapy:

• weakness and fatigue
• exhaustion and weight loss
• nausea, vomiting, decreased appetite
• radiation burns of the skin
• hair loss

Proton therapy for lung cancer in the Anderson Cancer Center (USA)

MD Anderson is the home of the world's best Proton Therapy Center specializes on lung, prostate, liver, brain, head and neck cancers. Here children and adults from different countries are received.

Proton therapy uses accelerated particles (protons), which bombard tumor tissue and destroy the genetic material of cells. Modern technology has made this procedure very accurate and safe for healthy tissues. Proton therapy provides promising results even for inoperable malignant neoplasms.

Chemotherapy for non-small cell lung cancer

The so-called "chemo" is aimed to destroy rapidly dividing cells. Chemotherapeutic agents circulate through the body, targeting tumors and single abnormal cells regardless of their location.

Chemotherapy for lung cancer is usually combined with other options, including surgical resection and radiation. Before the surgery, chemo can reduce the size of the neoplasm (neoadjuvant therapy), after the intervention it destroys the remaining cancer cells (adjuvant therapy).

Because of the high toxicity, American oncologists do not recommend chemo to patients with poor health. Nevertheless, the old age itself is not a contraindication. Everything depends on the patient's condition.

Chemotherapy agents for NSCLC:

• Vinblastine
• Vinorelbine
• Etoposide
• Docetaxel
• Paclitaxel
• Cisplatin
• Carboplatin
• Irinotecan
• Pemetrexed
• Gemcitabine

Most often a combination of two drugs is prescribed. According to recent studies, the addition of a third drug to the treatment regimen is not useful because of excessive risks and minimal additional benefits. Chemotherapy is often combined with targeted therapy (for example, necitumumab or bevacizumab).

Possible side effects:

• fatigue
• weakness
• hair loss
• mouth sores
• decreased appetite
• nausea, diarrhea, constipation
• peripheral neuropathy
• frequent infections
• bleeding
• anemia

Targeted therapy for non-small cell lung cancer in the United States

A new generation of targeted drugs is different from traditional chemo:

1. Anti-angiogenesis agents: So-called angiogenesis inhibitors stop the growth of the vasculature, forcing the tumors to starve. This group includes bevacizumab (Avastin), ramucirumab (Cyramza).

2. EGFR-inhibitors: epidermal growth factor receptor mutations allow cancer cells to grow quickly. There are three main EGFR inhibitors: erlotinib (Tarceva), gefitinib (Iressa), ozimertinib (Tagrisso).

3. ALK-inhibitors: in adenocarcinoma, tumors secrete a mutant ALK protein that stimulates their growth. Crizotinib (Xalcorie), Alectinib (Alecensa), Ceritinib (Zicardia), and brigatinib (Alunbrig) may be useful even after the development of resistance to chemotherapy.

4. BRAF-inhibitors: modern BRAF-inhibitor dabrafenib (Tafinlar) and the related MEK-inhibitor trametinib (Mekinist) deprive the tumor of proteins necessary for rapid progression.

Immunotherapy for non-small cell lung cancer  

This therapy stimulates the patient's own immune system to recognize and fight against tumor cells.
 
Immune control checkpoint inhibitors of are extensively prescribed for the treatment of non-small cell lung cancer in the United States. Nivolumab (Opdivo), pembrolizumab (Keytruda), durvalumab (Imphinzi) and atezolizumab (Tecentric) are among the most effective drugs. Immune control checkpoint inhibitors uncover tumor cells "camouflage" - special molecules that help to avoid an immune response. After such therapy, the patient's organism easily recognizes and fights cancer.
 
Immunotherapy may be used as a first-line therapy, but sometimes may be prescribed for relapse after previous chemotherapy or radiation. All agents of this group are administered intravenously (IV). Despite numerous side effects, immunotherapy showed excellent results for metastatic lung cancer. 

Targeted therapy for lung cancer at the Dana-Farber Institute (USA) 

One of the best plavces in America for the treatment of NSCLC is the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute (DF / BWCC). This center is famous for historical discoveries in the field of targeted therapy, including the discovery of EGFR mutations.
 
Oncologists of DF / BWCC demonstrated for the first time the real impact of genetic tests on treatment outcomes. They were true pioneers in the use of targeted drugs against the mutant genes EGFR (erlotinib, gefitinib), MET and RET, NTRK1, FGFR 2 and 3 and other cancer targets. The development of a unique laboratory panel allowed practicing oncologists to detect vulnerable NSCLC target genes and select the most effective drugs for each patient.
 
Why Dana-Farber Institute is the best?

Read numerous patient stories and find out how the achievements of oncology save people’s lifes. Among DF patients were people with advanced stages of disease. People sentenced to death by cancer. Many of them are still alive.



Treatment of non-small cell lung cancer in the US means advanced technology and high professionalism. For thousands of medical tourists, who come to the United States from all over the world, this is the only chance to heal and return to normal life.

© Analytical reviews and oncology news by K. Mokanov: clinical pharmacist and professional medical translator