In recent years, there have been very promising developments in the treatment of lung cancer. Advances in molecular pathology and especially imaging techniques have enabled us to better understand lung cancer and its course. Especially in the last 15 years, new chemotherapy drugs, targeted smart molecules, improvement in surgical techniques, modernization of radiotherapy devices, radiotherapy applications focusing on 3-4 dimensional tumor tissue, and cyber-knife for small-sized tumors that are not suitable for surgery. Technologies, and dazzling methods that burn and freeze the tumor in interventional radiology, and deliver intensive treatment from the artery directly to the tumor, have made lung cancer much more manageable. While all these developments provide extremely positive contributions to the patient, they will also eliminate the confusion in the treatment sequences with the right treatment planning and management organization. When planning treatment, we consider a number of factors related to your disease and your characteristics.
-The type of your lung cancer
-The location of the tumor in the lung
-The general health status of the patient
-The level of spread of the cancer and its relationship with critical organs (stage of the cancer) )
-Results of imaging and blood tests
-After getting comprehensive information about treatment alternatives, your choice is very important in treatment planning.
Is the type of cancer important in the treatment of lung cancer?
Lung cancer is mainly examined in two groups and the choice of treatment is evaluated separately in two subgroups. Lung cancers are divided into small cell lung cancer and non-small cell lung cancer. The treatment for non-small cell lung cancer is different from the treatment for small cell lung cancer.
Small cell lung cancer is most often treated with chemotherapy and radiotherapy. Surgery may be preferred in rare cases where the cancer has not spread to the lymph nodes in the center of the chest (mediastinal lymph nodes) and is very small in size. When small cell lung cancer is diagnosed, it is usually observed that the cancer has spread. For this reason, chemotherapy is often used as the main treatment. In the treatment of this type of lung cancer, radiotherapy is also used as an adjunct to chemotherapy.
Treatment of non-small cell lung cancer is performed by sequential or simultaneous administration of surgery, chemotherapy, radiotherapy depending on the stage of the disease when diagnosed. In some patients with advanced lung cancer, biologic therapy may also be administered. One of the important misconceptions in society is that only large cell lung cancer comes to mind when non-small cell lung cancer is mentioned. The expression of non-small cell lung cancer includes 4 main groups that differ from small cell and are treated with a similar treatment strategy, especially in the early stage (stages 1-3). They are subdivided in order of frequency as adenocarcinomas, squamous cell cancers, large cell and mixed type cancers. In the treatment of these groups in advanced stage, that is, metastatic (prolapsed) patients, they differ in both the choice of chemotherapy and the choice of targeted smart therapies.
Small cell lung cancer treatment according to stages
Patients diagnosed with early stage small cell lung cancer usually receive radiotherapy to the lung simultaneously or after chemotherapy. Chemotherapy and radiotherapy can be given at the same time (chemoradiotherapy) to patients whose health conditions, spread, stage and test results of the cancer are suitable. In this type of cancer, spread to the brain is quite common. For this reason, radiotherapy is usually recommended to the lung area where the main tumor is located and to the brain in patients whose tumor is reduced by chemotherapy treatment. This radiotherapy is usually given after chemotherapy treatment is completed and is aimed at killing potential cancer cells that have spread to the brain and are too small to be seen on imaging tests. This method is called prophylactic cranial irradiation or PKI.
In very early stage small cell lung cancer that has not spread to the lymph nodes in the middle of the chest (mediastinal lymph nodes), part of the lung can be removed together with the tumor (lobectomy). Following the surgery, the patient is given chemotherapy and occasionally radiotherapy. However, when small cell lung cancer is diagnosed, it has usually spread and surgery is unlikely to be used as a treatment.
Small cell lung cancer that has spread to the lymph nodes or other parts of the body may be treated with chemotherapy, radiotherapy, or palliative therapy to relieve symptoms. If chemotherapy succeeds in shrinking the tumor in the lung, it is likely that radiotherapy can be applied to the brain to kill cancer cells that have spread to the brain.
For more than 30 years, significant improvements in the survival and treatment options of small cell lung cancer have not been achieved. Although many smart molecules have been investigated in this disease, they have not contributed to life expectancy. The treatment strategies presented at the American (ASCO) and European Oncology (ESMO) congresses this year have led to slight changes in our preferred treatment strategies in this type. In particular, new generation immunotherapy drugs (pembrolizumab) have shown hope for patients with small cell lung cancer, but have not yet been used in clinical practice. In addition, while protective irradiation was applied to the brain only after chemotherapy and good response in metastasized small cell lung cancer before, applying radiation to the area where the cancer originated in patients who responded well to chemotherapy after new studies has extended the life span of these patients. The benefit of radiation therapy applied to the brain has been questioned and closely examined in recent years. We will be following new developments in this regard and will continue to keep you informed.
Treatment of non-small cell lung cancer by stages
Stage I
Stage I is rare in non-small cell lung cancer. At this stage, surgical intervention is performed by removing part (lobectomy) or all of the lung (pneumonectomy). Targeted radiotherapy may be offered to patients who cannot undergo surgery due to other health problems, rather than trying to cure the cancer. Another option for patients with small tumors that cannot be operated on is radiofrequency ablation (RFA).
Stage II
In stage II non-small cell lung cancer, surgery may be recommended. Depending on the location of the tumor, part of the lung (lobectomy) or all (pneumonectomy) can be removed. If the cancer is completely removed, the patient may be offered preventive chemotherapy. Chemotherapy aims to reduce the risk of cancer recurrence. This chemotherapy application is called adjuvant chemotherapy. Before treatment, it is important for the doctor to inform the patient about the side effects and benefits of chemotherapy. If the entire tumor cannot be removed, it is possible for the patient to receive radiotherapy after surgery.
Radiotherapy or a combined treatment of chemotherapy and radiotherapy (chemoradiotherapy) may be recommended for patients who cannot be operated due to other health problems. This treatment aims to completely destroy the cancer.
Stage III
The staging of the third stage disease is examined in two groups. While they are divided into two groups as 3A and 3B, these two groups are divided into two subgroups that are extremely vital and determine the treatment strategy. Stage 3A is divided into two groups as minimal involvement (minimal N2) and severe involvement (bulky N2) according to the type of involvement of the chest cavity lymph node, which is referred to as the mediastinum. While minimal involvement in the thoracic cavity lymph nodes is not detected on the films, it means that it is detected by random sampling. At this stage, multiple metastases are not detected in the thoracic cavity lymph nodes. Surgery after chemotherapy is an important option in suitable patients with stage 3A minimal involvement. However, radiotherapy concurrent chemotherapy is the most effective method in patients who are not suitable for surgery. At this stage, intra-arterial chemotherapy, which is one of the innovative treatment applications in our clinic, is offered to our patients. Intensive chemotherapy can be applied to the tumor with the treatment applied through the artery, and the treatment response rate is significantly increased, while the chance of surgical success increases in parallel. In the IIIA stage, in the group we call Bulky N2, multiple metastases to the chest cavity lymph nodes have occurred. In this group, surgery is not a preferred method in the world. Radiotherapy concurrent chemotherapy is the only method to be preferred in fit patients whose general condition is suitable.
Stage IIIB is examined in two groups within itself. In the first of these, the tumor has made serious contact with critical organs, but there is no aggressive mediastinal lymph node involvement (opposite lymph nodes involvement); Some of the patients in this group can be operated directly by competent surgeons, and sometimes, if a reasonable level of regression is achieved in the tumor with chemotherapy, the chance of surgery can be offered. However, if the 3B group has extensive, that is, aggressive, thoracic cavity lymph node involvement, surgery is not possible and the most accurate treatment is radiotherapy and simultaneous chemotherapy if the patient’s general condition is good.
Stage IV
Surgical method is rarely preferred in the fourth stage. In rare cases that are suitable for surgery, patients are examined extensively to try to minimize the error rate. Surgery may be preferred in three cases in stage 4 lung cancer. In lung cancer, if the main tumor is not very large and has not involved critical organs, however, if it has not spread to the lymph nodes of the chest cavity, and has metastasized to a single lung, a single brain or a single adrenal gland, surgery for both tumors can be performed. Decisions to be taken in this group of patients should be made after detailed examination by competent multidisciplinary oncology groups. Such decisions require serious and different perspectives that cannot be made by a single physician alone.
Treatment of stage IV non-small cell lung cancer aims to shrink the tumor to control the cancer for as long as possible and reduce symptoms. In many studies, chemotherapy was used in this situation and it was observed that the patient’s life expectancy was prolonged and the symptoms were alleviated.
Patients with cancer cells with certain proteins (receptors) may be treated with biologic drugs called erlotinib (Tarceva), gefitinib (Iressa), or crizotinib (Xalkori).
Patients undergoing chemotherapy treatment and the spread of cancer cannot be controlled, if their condition is deemed appropriate, they are taken to chemotherapy again. If there is a mutation (change) in the EGFR receptor in cancer, erlotinib treatment may be recommended. If there is a change in the ALK gene, a targeted drug called Xalkori is preferred.
Radiotherapy can be used to control some symptoms such as cough or pain. If the tumor is in one of the main airways (right or left bronchus), other treatments as well as radiotherapy can relieve or prevent symptoms. These treatments can be listed as follows:
-Internal radiotherapy (brachytherapy)
-Freezing the tumor (cryotherapy)
-Using a rigid tube (stent) to keep the airway open
-Light therapy (photodynamic therapy)
Immunotherapy in lung cancer
Opdivo (nivolumab)
on 4 March 2014 in patients with advanced squamous cell lung cancer, 9 October In 2015, it received FDA approval as a second-line therapy for non-small cell lung cancer in adenocarcinoma. Opdivo prevents the activity of the PD-1 protein, which suppresses our immune system cells, so that our immune system cells can continue to work. Opdivo is an immunotherapy drug that was previously approved for the treatment of melanoma. The most important side effect has been shown as rash.
Keytruda (pembrolizumab)
Pembrolizumab active ingredient Keytruda was approved for use in non-small cell lung cancer on October 2, 2015. It has not yet been approved in our country. We will be following the developments closely and sharing them with you.
