Lung cancer treatment in France: diagnosis, therapy and surgery

Leading oncology centers such as the Institute Curie have made lung cancer treatment in France well-known among doctors and patients from all over the world.

Lung cancer affects almost 40,000 people in France every year.

Up to 90% of these tumors are associated with smoking.

Despite the decline in incidence among men, it has steadily increased among women since 1980; the number of new cases diagnosed each year over the past three decades has increased sevenfold.

The prevalence of lung cancer and high mortality force the French authorities to invest tens of millions of euros in research on this disease and the search for new treatments.

Best lung cancer centers in France

There are such scientific centers as the Institute Curie in Paris, the Institute Gustave Roussi in Villejuif and the Institute of Oncology ICO in Angers and Nantes. There are dozens of national and international cancer studies conducted simultaneously in these centers.

Gustave Roussy Institute is a “center for the fight against cancer” (CLCC), located in Villejuif in the Val-de-Marne. It was found by Professor Gustave Roussy in 1926. Gustave Roussy Institute is the leading center for cancer care, research and education in France.

Some facts about the Institute:

• 34 research teams
• More than 3,100 professionals
• 3,000 students and doctors trained each year
• 247,000 consultations provided to 48,000 patients last year
• 74 million euros spent on research each year

The Institute Curie Hospital (Paris) is one of the largest oncology centers in France, where all the technical opportunities for diagnosis and treatment are combined. The “Curie Model” means the continuity between basic research and clinical practice. Its uniqueness lies in uniting researchers, doctors, and patients to make new methods of cancer diagnosis and treatment more accessible. This model has inspired many research institutions including 20 “centers for the fight against cancer” in France.

The Western Cancer Institute (L'Institut de cancérologie de l'Ouest, ICO) is a regional center for the fight against cancer in western France. It is located in Angers (headquarters) and Saint-Herblain. The former provincial hospital, ICO is now considered the third largest cancer center in France. In terms of radiotherapy, it becomes the largest center in the country, with 80,000 sessions per year.

ICO's research interests include immunotherapy for lung cancer, development of anticancer vaccines, proton cancer therapy, biopathology and sequencing of the tumor cell genome, proteomic studies, etc..

Staging of lung cancer and approach to the treatment

There are two fundamentally different types of the disease: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The approach to therapy in each case depends on the type and stage of disease.

Non-small cell lung cancer

The evolution of NSCLC can be divided into four stages:

• The first stage is a very localized cancer that has not penetrated the lymph nodes;
• In the second stage, the cancer has spread to nearby lymph nodes;
• At the third stage, the cancer has spread to the organs nearby from its original location;
• The fourth stage is the spread of cancer to distant organs (metastasis).

Small cell lung cancer

French oncologists distinguish two stages of SCLC evolution:

• The localized stage when the cancer remains within the tissues of the chest;
• Cancer spreads when tumors are found in distant organs outside the chest.

Since surgical intervention is very rarely used in the treatment of small cell lung cancer, the stage of development of the disease is not so important for the choice of therapy as in the case of NSCLC. It is very likely that doctor will recommend chemotherapy alone or in combination with radiation therapy. Finally, regardless of the type of cancer, the choice of treatment is made by a multidisciplinary team of specialists, which includes oncologists, surgeons, radiologists, pulmonologists, and rehabilitation specialists.

The earlier the diagnosis is made, the higher the chance of successful treatment; this is especially true in the case of non-small cell lung cancer, which can sometimes be surgically removed.

Age standardized 5-year survival in France is 17% (16% in men, 20% in women); 10-year survival is 10% (9% for men, 13% for women). Median age at death: 68 years for men, 67 years for women.

Lung cancer treatment in France: options and prices

French clinics can offer three options for treating lung cancer: surgery, radiation therapy, and drug therapy (chemotherapy, targeted therapy, and immunotherapy). They can be used alone or in combination, depending on the stage of the disease, the location of the tumor and the patient's condition.

The diagnostic process will require consultations of oncologist, surgeon, and pulmonologist ($ 500-800), laboratory blood tests ($ 600-1000), MRI ($ 1800-2000), PET / CT ($ 2000-2500), computed tomography, chest radiography, bone scintigraphy and other tests. Tumor biopsy with histological examination is crucial.

Surgery

Surgery, when possible, remains the leading treatment for lung cancer. It is aimed at complete removal of the tumor. For this purpose, the affected area is removed, the whole lobe (lobectomy) or the whole lung (pneumonectomy). Sometimes it is also necessary to intervene in neighboring structures (for example, removal of a rib or a large blood vessel).

Surgery can be “minimally invasive”: the surgeon inserts a camera and miniature instruments through small incisions on the body, limiting the effects on surrounding tissues and minimizing blood loss.

During the operation, the lymph nodes located around the tumor are removed for histological examination. The presence of tumor cells in the lymph nodes indicates that the disease has begun to spread. This information is necessary for making decisions about additional methods of treatment after surgery.

Surgical treatment is associated with complications: pain, respiratory failure (persistent dyspnea), infection of the lungs (pneumonia), pleurisy (fluid accumulation), weakness, heart problems, voice changes, etc.

Removal of a lung tumor in France can cost $ 20000-40000, depending on the type of procedure.

Some tumors use less invasive ablative methods. Such treatment is carried out only by experienced teams and requires special equipment, which is available at large private hospitals and institutes. This may include radiofrequency ablation, which involves the use of a heating electrode to destroy a tumor. Cryotherapy is based on the same principle, but there is liquid nitrogen of very low temperature is used to destroy tumors. Currently, cryotherapy for lung cancer is undergoing clinical trials in France.

Radiation therapy

Radiation therapy involves the irradiation of a tumor with high-energy rays that destabilize the genetic material and destroy rapidly dividing cancer cells. This treatment can be used alone or in combination with other methods, such as chemotherapy.

The cost of radiation therapy in France is $ 8,000-10,000 per course or more.

3D conformal radiation therapy is the most widely used method of radiation therapy for lung cancer. 3D-CRT is designed for maximum accurate irradiation of tumors of complex shape, bending around the surrounding tissue. Thus, it is possible to significantly reduce damage to healthy lung tissue, esophagus, etc.

Stereotactic radiation therapy (SRT) has become the gold standard for small tumors or brain metastases in disseminated lung cancer. It is assigned to patients who are not candidates for surgical removal of the tumor due to respiratory failure, as well as local recurrence of the disease.

Radiation therapy is painless, but it can lead to a number of side effects that gradually appear during the sessions. They usually go away after a few days or a few weeks after stopping treatment. Patients may experience fatigue, painful swallowing, cough, and skin reactions (redness, dryness).

Chemotherapy

Chemotherapy involves the administration of one or more drugs that are toxic to tumor cells. The advantage of chemotherapy is that it destroys these cells throughout the body (systemic therapy). Unlike surgical procedures and radiation, which act locally, chemotherapy affect metastases, even if they are not detectable.



French oncologists mainly use the following drugs:

• Platinum (cisplatin, carboplatin)
• Taxanes (docetaxel, paclitaxel)
• Vinorelbine
• Etoposide
• Gemcitabine
• Pemetrexed.

Thanks to numerous combinations, doctors choose protocols that are adapted to each type of tumor and each patient. The cost of chemotherapy varies greatly depending on the drugs used. During treatment, specialists can change the drug or dose to increase the response to treatment. Most often, chemotherapy is administered by intravenous infusion, sometimes orally (vinorelbine or etoposide tablets).

Chemotherapy destroys cancer cells as well as healthy cells that divide rapidly (for example, hematopoietic cells, hair follicles and mucous membranes). That is why chemotherapy is often associated with hair loss, leukopenia, anemia, loss of appetite, changes in taste, nausea and vomiting, stomatitis and weakness.

Today, French doctors can offer highly effective drugs and non-drug methods to prevent or alleviate these side effects. When chemotherapy is stopped, these unpleasant effects gradually decrease and go away.

Targeted therapy

Targeted therapy uses innovative molecules that specifically affect cancer cells or their microenvironment. Recommended for lung cancer with metastases, targeted therapy cannot completely cure the disease. In some patients this treatment effectively controls cancer in the long term.

Erlotinib, afatinib, osimertinib and gefitinib are targeted therapies commonly used in lung cancer treatment. They prevent tumor growth by inhibiting EGFR, a protein that sends a stimulating signal to the tumor cells. These agents are prescribed when a mutation of the EGFR gene has been confirmed during a molecular analysis of the tumor. Crizotinib, ceritinib and alectinib are prescribed for lung cancer when the ALK gene mutation is confirmed (ROS1 and MET for crizotinib). Currently, several targeted agents can be administered sequentially.

Angiogenesis inhibitors represent another category of targeted therapy. They inhibit the growth of blood vessels that supply the tumor with oxygen and nutrients. In lung cancer, bevacizumab remains the main angiogenesis inhibitor. These drugs are usually combined with traditional chemotherapy (cytostatics).

In the case of cancer recurrence or insufficient effect of previous therapy, the doctor may recommend a repeat biopsy of the tumor. The purpose of this procedure is to study the molecular profile of the tumor and identify other mutations. Numerous clinical studies that are conducted in leading French hospitals, give hope to patients, even in cases where the standard treatment options are exhausted.

In recent years, the identification of new targets (ROS1, MET, BRAF) has led to the development of new targeted therapies. While continuing this work, French researchers are also testing targeted therapy combinations that have yielded promising early results.

In 2017, European Medicines Agency granted a marketing authorization for the combination of dabrafenib + trametinib, which is particularly useful for rare form of non-metastatic NSCLC (BRAF V600 mutation).

Lung cancer immunotherapy

Immunotherapy is a thriving therapeutic strategy that involves using the patient's natural defenses to fight cancer. The immune system is modified so that it effectively recognizes the specific tumor cells and destroys them. This option is recommended in advanced forms of non-small cell lung cancer and preferentially for patients who smoke. Unfortunately, it is effective only in a limited number of patients. The results of comparative studies are beginning to demonstrate a higher efficacy of immunotherapy (nivolumab, atezolizumab or pembrolizumab) compared with cytotoxic chemotherapy.

In some situations, it is advisable to use first line immunotherapy before chemotherapy. Moreover, immunotherapy drugs usually cause fewer side effects than chemotherapy. Only a small percentage of patients may experience severe reactions that make further treatment impossible.

The European experience of lung cancer immunotherapy showed a paradoxical effect: in some patients, treatment causes hyperprogression of the disease. In other words, the tumor grows faster. Doctors cannot yet identify patients in whom immunotherapy can cause hyperprogression of cancer.

Cancer immunotherapy research in France

Personalization of lung cancer treatment in accordance with the "molecular identification card" of each tumor is an important area of research for French oncology. The goal is to be able to choose the right approach (chemotherapy, targeted therapy or immunotherapy) based on the presence or absence of specific abnormalities in the tumor cells. For example, recent studies have shown that tumors with many mutations respond better to immunotherapy.

Other studies are aimed at characterizing the immune system of each patient and factors that may affect the effectiveness of cancer treatment. It has been found that certain bacteria of the intestinal flora determine the ability of a patient's leukocytes to respond to immunotherapy.

Combinations of immunotherapy and other systemic treatments (other immunotherapy, chemotherapy, targeted therapy) are becoming increasingly important. These combinations provide higher clinical efficacy than each of the methods separately.

A French clinical trial, SABR-PD-L1, evaluates the effectiveness of immunotherapy (atezolizumab) in combination with stereotactic radiation therapy for metastatic lung cancer. This new strategy is based on the assumption that the destruction of a tumor by radiotherapy leads to the release of signaling molecules that stimulate the immune response. Therapeutic vaccination (specific immunotherapy) stimulates the immune response when the disease progresses. Research in this area is aimed at developing components of the so-called "immunogenic" cancer cells for administration to patients. These compounds cause a specific immune response against the tumor.

In the near future, patients with lung cancer will receive immunotherapy after surgery or radiation therapy. This method will complement or replace chemotherapy with cytostatics.

Choice of treatment depending on the type of lung cancer

Small cell lung cancer

Small cell lung cancer spreads rapidly to distant regions of the lung. It is common that metastases are not detected by routine examinations (clinical examination, chest x-ray, CT scan, etc.). This is why the treatment is most often based on chemotherapy that can act on tumors throughout the body. Chest radiotherapy is sometimes proposed, depending on the extent of disease at diagnosis. Whole brain radiotherapy is often indicated even in the absence of visible brain metastases on CT or MRI.

The duration of treatment is up to six months. Early phases of clinical trials demonstrate that the use of immunotherapy is promising.

There is no targeted therapy for this type of lung cancer.

Non-small cell lung cancer

When a tumor is operable, it must be surgically removed if there are no other contraindications. The type of intervention depends on the size and location of the tumor. Adjuvant chemotherapy and / or radiation therapy may be suggested in some cases to improve results. If surgery is not possible, radiation therapy or thermoablation may be offered. When a tumor is considered inoperable, but remains localized in the chest, radiation therapy is indicated. Sometimes radiation is combined with chemotherapy, depending on the general condition of the patient.

In cases where the tumor has penetrated into distant organs, systemic therapy is suggested; most often this is chemotherapy with cytostatics, and in some cases targeted therapy or immunotherapy.

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