Table of ContentsView AllTable of ContentsSymptomsCausesDiagnosisTreatmentPrognosis

Table of ContentsView All

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Table of Contents

Symptoms

Causes

Diagnosis

Treatment

Prognosis

ROS1 positive lung cancer is an aggressive form of lung cancer that often spreads quickly. New, targeted medications can help keep this type of lung cancer from progressing for a period of time, providing a better prognosis today compared to previous generations.

A ROS1 rearrangement is a type of chromosome abnormality that may affect cells ofnon-small cell lung cancer(NSCLC). This genetic mutation occurs in about 1% to 2% of people diagnosed with NSCLC.

Symptoms of ROS1-Positive Lung Cancer

ROS1 mutation is most often seen inadenocarcinomatumors that are negative for other driver mutations. Adenocarcinoma, the most common type of NSCLC,usually begins near the outer portion of the lungs and typically does not produce symptoms in the early stages.

When adenocarcinoma progresses to the point that tumors interfere with breathing, signs are often less obvious than with other forms of lung cancer, but may include:

Because these signs usually begin only after the cancer has spread, adenocarcinoma and ROS1 variations of adenocarcinoma are usually diagnosed at anadvanced stage of cancer.

Symptoms of Non-Small Cell Lung Cancer

Cell genes act as a blueprint for proteins that regulate the growth and division of cells. When one of these genes is damaged, mutated, or rearranged, it directs the production of an abnormal protein, which may then function abnormally.

The ROS1 gene is one in a subfamily of tyrosine-kinase insulin-receptor genes. The ROS1 gene mutation seen in NSCLC is really a fusion between ROS1 and another gene. This fusion produces a defective gene that acts as a chance driver, causing cancer cells to multiply excessively.

Mutations like the ROS1 rearrangement are often acquired, which means that they are not inherited or present at birth.

Studies have found that certain factors are associated with ROS1-positive lung cancer:

Why Is Lung Cancer Increasing in Non-Smokers?

There are a few ways in which people with lung cancer can be tested to see if they have a ROS1 rearrangement. This genetic defect is only present in the cancer cells, and not in any other cells in the body.

Genetic testingis usually done on a tissue sample from alung biopsyor from tissue removed during lung cancer surgery. Increasingly, healthcare providers are usingliquid biopsyto help diagnose ROS1 rearrangement. This blood test checks for cancer cells circulating in the blood and can be used to identify genetic mutations in cancer cells.

Testing methods include usingimmunohistochemistryandfluorescence in situ hybridization(FISH) to analyze the samples and determine genetic abnormalities.

Part of the testing involves ruling out other genetic abnormalities includingKRAS mutations,EGFR mutations, andALK rearrangements.

Testing will also help identify the stage of your lung cancer, which is important for determining the best course of treatment for your particular type of NSCLC.

If your lung cancer is caught in theearly stages—1, 2 or 3A—local treatments may be recommended. These include treatments that work on cancer tumors that are still small and located in one place. They include:

For more advanced cancer or tumors that are inoperable or not able to be irradiated,chemotherapyhas been the standard treatment of decades.

Chemotherapy drugs, which kill cancer cells but also damage healthy cells, are still widely used for lung cancer, but with ROS1 rearrangement, these drugs may not be the first course of treatment. Instead, healthcare providers are now using targeted medications, which offer many advantages.

Some chemotherapy agents are also effective in ROS1-positive tumors. ROS1-positive lung cancer appears to respond well to the chemotherapy drug Alimta (pemetrexed), for instance.

Common Chemotherapy Side Effects

Targeted Treatment

Targeted therapymedications are oral medications that act on specific genetic mutations to prevent cancer from growing, shrink tumors, or manage cancer symptoms.

Currently, three oral medications have U.S. Food and Drug Administration (FDA) approval for patients withmetastaticNSCLC who have ROS1-positive lung cancer:

Each medication is meant to be taken long-term. You would only stop taking the medications if the cancer starts to spread (which indicates the drug is no longer working) or if you cannot tolerate the medication. Never stop any medication without first consulting your healthcare provider.

Zykadia (ceritinib), a kinase inhibitor indicated for the treatment of ALK-positive (NSCLC), has also been used to treat ROS1-positive lung cancer.

Studies suggest that a component of vitamin E called a-tocopherol may greatly reduce the effectiveness of crizotinib.

Treatment of Brain Metastases

Brain metastasesare a common complication associated with NSCLC, with an estimated 15% of patients being diagnosed with brain metastases within a year of their lung cancer diagnosis.ROS1-positive lung cancer, like all NSCLC, commonly spreads to the brain, leading to lung cancer metastatic to the brain.

Xalkori doesn’t work very well for brain metastases because it does notcross the blood-brain barrierwell. The blood-brain barrier is a control system of specialized membranes that work to prevent toxins (as well as chemotherapy drugs) from entering the sensitive environment of the brain.

Rozlytrek appears to have better brain penetration and has shown success in small trials.

Radiation therapy may also offer some hope for ROS1-positive lung cancer that has spread to the brain. Radiation may be given in a couple of different ways:

The choice between these two treatments is an area of debate. Stereotactic radiotherapy—since it only treats a small portion of the brain—has fewer side effects. But whole-brain radiotherapy may offer better outcomes.

At least 75% of people undergoing whole-brain radiotherapy report some improvement in symptoms, and it has been shown to improve overall survival—from one month with no treatment—to two to seven months with treatment.

Drug Resistance

Most cancers eventually become resistant to targeted therapy medications. Your healthcare provider will prescribe a new treatment once your cancer show signs of resistance. But that treatment, too, might become ineffective.

New drugs are being investigated withclinical trials, and there is hope that new treatments will be available in the future.

ROS1-positive lung cancer tends to be aggressive, growing, and spreading fairly rapidly. But it does respond to targeted therapy.

Studies of Xalkori show that the drug offers a disease-control rate of 90%, and those taking the drugs have no progression of the disease for an average of 19.2 months.

Understanding Survival Rate for Each Stage of Lung Cancer

A Word From Verywell

ROS1 is such an uncommon form of cancer that it can be difficult to navigate the “normal” cancer channels. Finding a support group comprised of those who share your diagnosis can help you connect with people who better understand your emotions in relation to your disease and who can help point you towards resources and research.

15 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

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Davare M, Saborowski A, Eide C, et al.Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins.Proceedings of the National Academy of Sciences of the United States of America. 2013;(48)110:19519-24. doi:10.1073/pnas.1319583110

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Lukas R, Hasan Y, Nicholas M, Salgia R.ROS1 rearranged non-small cell lung cancer brain metastases respond to low dose radiotherapy.J Clin Neurosci. 2015;(12)22:1978-9. doi:10.1016/j.jocn.2015.04.009

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Solomon B.Validating ROS1 rearrangements as a therapeutic target in non-small-cell lung cancer.J Clin Oncol. 2015;33(9):972-4. doi:10.1200/JCO.2014.59.8334

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