Lung cancer is the fifth most commonly diagnosed form of cancer and is responsible for almost one in five cancer deaths worldwide. ^[1] Factors that can increase your risk of lung cancer include smoking tobacco, second-hand smoke exposure, exposure to asbestos and other occupational substances and a family history of lung cancer or lung disease. ^[1]

Lung Cancer Subtypes

Lung cancer starts when abnormal cells grow and multiply in an uncontrolled way. Lung cancer is comprised of two main histological subtypes – non-small cell lung cancer and small cell lung cancer

Non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Approximately 85% of newly diagnosed lung cancers are NSCLC. The most common NSCLC subtypes include:

• Adenocarcinomas– begin in mucus-producing cells and make up roughly 40% of lung cancers. While this type of lung cancer is most commonly diagnosed in current or former smokers, it is also the most common lung cancer in non-smokers. ^[1]
• Squamous cell (epidermoid) carcinomas– commonly develop in the larger airways of the lung.
• Large cell undifferentiated carcinomas– can appear in any part of the lung and are not clearly squamous cell or adenocarcinoma.

Small Cell Lung Cancer

Small cell lung cancer (SCLC) usually begins in the middle of the lungs and spreads more quickly than NSCLC. It accounts for around 15% of lung cancers.^[1]

Common Treatment Options

For most early stage Lung Cancers, treatment typically entails surgery to remove as much of the tumour as possible, followed by chemotherapy. The chemotherapy treatment plan for lung cancer often consists of a combination of drugs. Among the drugs most commonly used are cisplatin (Platinol) or carboplatin (Paraplatin) plus docetaxel (Taxotere), gemcitabine (Gemzar), paclitaxel (Taxol), vinorelbine (Navelbine and others), or pemetrexed (Alimta). ^[2]

Targeted therapies, that specifically target cancer cells, can also be used such as:

• EGFRTKIs (Erlotinib – Tarceva®, Afatinib – Gilotrif® and Gefitinib – Iressa®)
• Bevacizumab (Avastin)
• ALK – Crizotinib (Xalkori) Ceritinib (Zykadia)

These treatments may not always work, or despite initial positive responses to treatment, the cancer may develop resistance or come back over time. The 5-year survival rate of people diagnosed with lung cancer is ~18%. ^[3] In cases where cancer is detected when it is still localised within the lungs, the 5-year survival rate is ~56%. ^[3] However, only 16% of lung cancers are diagnosed at an early stage. Therefore, it is important that lung cancer patients receive personalised, targeted treatment from the beginning of their diagnosis. This is where Genomic Testing can help.

How can Genomic Testing benefit me?

Although all Lung Cancers all arise from cells within the lungs, there are many different genetic drivers of cancer, meaning that a detailed genetic analysis is important for choosing the most effective treatment plan. Among patients with NSCLC adenocarcinoma the most common mutations occur in EGFR, KRAS and TP53. ^[4] Lung Squamous cell carcinomas (SQCC) are characterized by a high overall mutation rate and marked genetic complexity. Up to 90% of Lung SQCCs have TP53 mutations, and other mutated genes commonly found in Lung SQCCs include GRM8, BAI3, ERBB4, RUNX1T1, KEAP1, FBXW7 and KRAS. ^[5]

Genomic testing looks at the DNA of your tumour and identifies mutations that are unique to each person’s cancer. Once we have identified the specific mutations causing your cancer, we can find targeted solutions to treat them. Genomic testing provides a personalized approach to your cancer treatment, giving you the best chance of survival. Clinical trials of over 70,000 patients have shown that personalized therapy, based on genomic profiling of tumors, is the most effective way to improve treatment outcomes, with higher response rates, longer progression free and overall survival, and fewer deaths related to toxic effects across cancers. ^[6-8]

The cost of investing in genomic testing to obtain a complete diagnosis and select targeted therapy, is small compared with the time and money that may be wasted on ill-chosen therapies. Genomic testing provides a powerful diagnostic tool, and every patient with cancer deserves an accurate diagnosis.

The power of Genomic Testing in Lung Cancer

A comprehensive genomic analysis of your tumor may provide information on potential therapeutics, likelihood of resistance to therapeutics, clinical trials and new treatments you may be able to access, prognosis and disease progression tracking. Lung cancer genome sequencing may identify:

• EGFRmutations other than the two most common mutations – in-frame deletions in exon 19 and L858R point mutations in exon 21 – which account for 90% of all EGFR mutations, and are routinely screened for. ^[9.10]
• Resistance mutations such as EGFRT790M, which impairs binding of First Generation TKIs (e.g erlotinib and gefitinib) resulting in primary resistance, providing answers when treatments have stop working and guiding further treatment
• KRASmutations, which are associated with resistance to EGFR TKIs, helping to guide treatment choices. ^[11]
• STK11mutations, which are associated with resistance to immune checkpoint inhibitors in NSCLC.
• TP53mutations, which are a significant marker of poor prognosis in pulmonary adenocarcinoma, helping to guide treatment choices. ^[12-14]
• Many other mutations in >120 genes* that will help guide your treatment by highlighting potential drug targets or drug resistance and prognosis, as a small percentage of tumors will have rare mutations that may be targetable with specific treatment options.
  
  

Potential therapeutics and resistance

Genetic alterations are identified in about 50% of NSCLCs. ^[15] Among patients with NSCLC adenocarcinoma the most common mutations occur in EGFR, KRAS, TP53 and ALK ^[15,16] all of which are covered on our Codex Pro  Solid Tumour Analysis. If these mutations are identified in your tumour, it may highlight a number of potential targeted therapy options, such as:

Clinical Trials and New Treatments

Given the breakneck pace of new drug discovery, new options may become available after your initial presentation or diagnosis. A comprehensive genomic analysis can be referred to as new trials and treatments become available, to determine if your cancer is likely to respond to the treatment being trialed in specific clinical trials.

What testing options are available?

 Lung & Bowel Cancer Targeted Testing

• Our Lung & Bowel Cancer Targeted Testing Panel assay is a targeted panel designed for colon cancers, lung cancers and melanoma. It assesses 23 cancer genes commonly implicated in these tumour types, including the most common genes implicated in lung cancer – EGFR, KRAS, TP53and ALK – along with 19 other commonly mutated genes found in these cancer types – BRAF, PIK3CA, AKT1, ERBB2, PTEN, NRAS, STK11, MAP2K1, DDR2, CTNNB1, MET, SMAD4, FBXW7, FGFR3, NOTCH1, ERBB4, FGFR1, FGFR2 and KIT
• Your personalized report will highlight potential targeted therapies and treatments you may be able to access based on the mutations identified in your cancer.

Codex Pro Solid Tumour Analysis

• The Comprehensive PlusSolid Tumour Analysis is a comprehensive cancer panel that may detect DNA mutations and RNA fusions across >121 genes that are commonly indicated in a range of cancer types.
• The analysis covers some of the most commonly mutated genes found in lung cancers including EGFR, KRAS, TP53and ALK
• Your personalized report will provide you with the genetic characteristics of your tumour, which may provide information on potential therapeutics, resistance to therapeutics, prognosis and clinical trialsor new treatments you may be able to access.

Cell-Free Tumour DNA (ctDNA) Testing and Tracking

• Tumours may release small fragments of DNA (ctDNA) into the bloodstream, which may contain identical mutations to those identified in the primary tumor.
• As ctDNA is released into the bloodstream, this allows for a liquid biopsy to be performed from a blood draw. This may eliminate the need for invasive procedures to obtain samples, such as biopsies, which can be painful for patients or may not be possible due to the size or location of the tumour.
• ctDNA can be tracked over time to monitor your response to treatment and the development of resistance to treatment. ctDNA testing can also be used to check for residual cancer following treatment and can reflect tumour size and burden more accurately than other diagnostic techniques.

Ready to take control of your treatment plan?

Codex Genetics Center aims to educate patients and their families on their cancer types and empower them with the knowledge to take control of their treatment plans. As each patient’s case is unique, there is no “one size fits all” when it comes to testing. We encourage you to contact Codex centerfe, and we can work with you and your oncologist/specialist, to determine what tests would benefit you.

References

1. Cancer Council. (2019). Lung Cancer. Retrieved from: https://www.cancer.org.au/about-cancer/types-of-cancer/lung-cancer.html
2. (2019). Lung Cancer 101 – Non-Small Cell Lung Cancer Treatment. Retrieved from: https://www.lungcancer.org/find_information/publications/163-lung_cancer_101/269-non-small_cell_lung_cancer_treatment
3. S. National Institute Of Health, National Cancer Institute. SEER Cancer Statistics Review, 1975–2015.
4. Krawczyk, P., T. Kucharczyk and K. Wojas-Krawczyk (2012). Screening of Gene Mutations in Lung Cancer for Qualification to Molecularly Targeted Therapies. Mutations in Human Genetic Disease. Intec: 201-216.
5. Heist, R. S., Sequist, L. V., & Engelman, J. A. (2012). Genetic changes in squamous cell lung cancer: a review. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 7(5), 924–933. doi:10.1097/JTO.0b013e31824cc334
6. Jardim, D. L., M. Schwaederle, C. Wei, J. J. Lee, D. S. Hong, A. M. Eggermont, R. L. Schilsky, J. Mendelsohn, V. Lazar and R. Kurzrock (2015). “Impact of a Biomarker-Based Strategy on Oncology Drug Development: A Meta-analysis of Clinical Trials Leading to FDA Approval.” J Natl Cancer Inst 107(11).
7. Schwaederle, M., M. Zhao, J. J. Lee, A. M. Eggermont, R. L. Schilsky, J. Mendelsohn, V. Lazar and R. Kurzrock (2015). “Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials.” J Clin Oncol 33(32): 3817-3825
8. Subbiah, V. and R. Kurzrock (2016). “Universal genomic testing needed to win the war against cancer: Genomics is the diagnosis.” JAMA Oncology 2(6): 719-720
9. Lai, Y., Z. Zhang, et al. (2013). “EGFR mutations in surgically resected fresh specimens from 697 consecutive Chinese patients with non-small cell lung cancer and their relationships with clinical features.” Int J Mol Sci14(12): 24549-24559.
10. Roengvoraphoj, M., G. J. Tsongalis, et al. (2013). “Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non-small cell lung cancer: focus on epidermal growth factor receptor mutation testing and mutation-positive patients.” Cancer Treat Rev39(8): 839-850.
11. Wang, H. L., J. Lopategui, M. B. Amin and S. D. Patterson (2010). “KRAS mutation testing in human cancers: The pathologist’s role in the era of personalized medicine.” Adv Anat Pathol17(1): 23-32.
12. Mogi, A. and H. Kuwano (2011). “TP53 mutations in nonsmall cell lung cancer.” J Biomed Biotechnol2011: 583929.
13. Govindan, R. and J. Weber (2014). “TP53 mutations and lung cancer: not all mutations are created equal.” Clin Cancer Res20(17): 4419-4421.
14. Barlesi, F., J. Mazieres, et al. (2016). “Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT).” Lancet387(10026): 1415-1426.
15. Krawczyk, P., T. Kucharczyk, et al. (2012). Screening of Gene Mutations in Lung Cancer for Qualification to Molecularly Targeted Therapies. Mutations in Human Genetic Disease. Intec: 201-216.
16. Petitjean, A., M. I. Achatz, et al. (2007). “TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes.” Oncogene26(15): 2157-2165.