Non-Small Cell Lung Cancer (NSCLC)

RET rearrangement positive NSCLC can affect different parts of the body depending on the location and extent of the disease. Many patients with RET-positive NSCLC have no symptoms until the cancer has grown to a certain size or has spread to other areas of the body. In lung cancer that has spread to other areas of the body, patients may experience bone pain in the back or hip, headache, weakness, dizziness, yellowing of the eyes and skin, and swelling of lymph nodes.

Other common symptoms of RET-positive NSCLC include cough that progressively gets worse, coughing up blood or blood-stained mucus, shortness of breath, hoarseness, new onset wheezing, loss of appetite, and unexplained weight loss. In some cases, swelling in the face, swelling of the veins in the neck, and chest pain also can occur.

Doctors utilize many different techniques to find and diagnose cancer. Procedures such as a physical exam, imaging, sputum cytology, biopsy of abnormal lung tissue, and RET genetic testing may be used to detect and stage RET-positive NSCLC.

• Imaging: used to diagnose and monitor NSCLC. Imaging used in NSCLC includes chest X-ray and computed tomography.
  • Chest X-ray: a quick and easy test that uses X-rays to capture 2D images of the structures in and around the chest. A chest X-ray can be used to diagnose and monitor treatment.
  • Computed tomography (CT): takes pictures from inside of the body using X-rays taken from different angles. Images are combined to a detailed, 3D image to show abnormalities or tumors. A CT scan can be used to measure tumor size or to help determine if cancer has spread to other parts of the body.
• Sputum cytology: if patients are coughing up mucus, sputum cytology can be completed. A sample of mucus is taken and placed under a microscope to identify possible cancer cells. These samples are usually taken early in the morning for several days. If the results are positive for cancer, a biopsy is required to determine the type of cancer a patient has.
• Biopsy: if cancer is suspected, the doctor will order a biopsy of the abnormal area. This is done because even if something abnormal is seen on imaging, there is no way to tell if the abnormal area is lung cancer, another type of tumor, or another condition. The only way to know for sure is to remove cells from the area and examine them under a microscope.
  • Once obtained by biopsy, a pathologist will look at the abnormal area under a microscope. Oftentimes, additional tests are ordered to diagnose RET-positive NSCLC. An additional test that can help to confirm a RET-positive NSCLC diagnosis is RET genetic testing.
• RET Genetic Testing- these tests are done to look for mutations in the RET gene itself and to detect RET gene fusions. Testing for changes in RET requires doctors to take a biopsy of your cancer for the purposes of genetic analysis. There are several available tests to analyze for genetic changes in RET. Common tests used to determine if you have RET-positive NSCLC are break-apart fluorescence in situ hybridization (FISH), reverse-transcriptase polymerase chain reaction (RT-PCR), and next-generation sequencing (NGS).

Treatment options depend on several factors, including tumor size, where the cancer is located, if the cancer has spread to other parts of the body, and the presence of any genetic mutations. Treatment options include surgery, radiation, systemic chemotherapy, immunotherapy, and targeted therapy

• Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. For patients with cancer that has not spread to other parts of the body, surgery is the standard treatment and should be performed when possible.
• Radiation therapy uses radiation to shrink tumors or kill cancer cells. Radiation can be used in combination with surgery and/or chemotherapy. This option can be used to treat patients with cancer localized to one part of the body, or cancer that has spread to other areas. Radiation can be used with both palliative and curative intent.
• Systemic chemotherapy and/or immunotherapy can also be used to treat RET rearrangement positive NSCLC. Systemic chemotherapy often includes platinum doublet therapy, such as the combination of carboplatin and paclitaxel. Other agents that may be commonly used to treat NSCLC include gemcitabine, docetaxel, pemetrexed, etoposide, and bevacizumab. Immunotherapy is a class of treatments that helps a person’s own immune system eliminate or control cancer. Immunotherapy may be prescribed as a single agent or may be combined with systemic chemotherapy. Immunotherapy that may be used to treat NSCLC includes Tecentriq®, Imfinzi®, Keytruda®, Opdivo®, and Yervoy®. While systemic therapy and immunotherapy can be considered, patients with RET-positive NSCLC typically do not respond as well to this option.
• Targeted therapy, such as tyrosine kinase inhibitors. Targeted therapy is treatment that specifically targets the RET rearrangements that cause the cancer to grow and survive. The goal of targeted therapy is to block the growth and spread of the cancer while trying to limit damage to normal, healthy cells. FDA approved tyrosine kinase inhibitors to treat RET rearrangement positive NSCLC include GavretoTM and RetevmoTM.