What to Know About Stage 3 Non-Small Cell Lung Cancer

Lung Cancer Test Predicts Survival In Early Stages Better Than Current Methods

Researchers at the Francis Crick Institute, the UCL Cancer Institute and UCLH have shown that a test called ORACLE can predict lung cancer survival at the point of diagnosis better than currently used clinical risk factors. This could help doctors make more informed treatment decisions for people with stage 1 lung cancer, potentially reducing the risk of the cancer returning or spreading.

In research published in Nature Cancer, the team tested ORACLE in 158 people with lung cancer as part of the Cancer Research UK-funded TRACERx study. They found that ORACLE could better predict patient survival than currently used clinical standards like tumour stage.

ORACLE was developed in 2019 to overcome the lack of biological markers in lung cancer, which can indicate to doctors who might be at a greater risk of their cancer coming back or spreading to another part of the body1.

This is particularly important for people with stage 1 lung cancer, who are normally given surgery without chemotherapy. For a quarter of stage 1 patients, their cancer returns, suggesting they may have benefitted from more frequent monitoring or chemotherapy.

When doctors take a sample from a tumour, they typically only capture less than 1% of the tumour, and the genetics can vary massively from region to region within the same tumour. ORACLE overcomes this by looking at genes expressed at a high or low level in every part in the tumour.

The new findings show that ORACLE could predict which patients with stage 1 lung cancer had a lower chance of survival, and might benefit from chemotherapy as well as surgery. Currently used clinical standards weren't able to give this information for stage 1 patients.

The researchers also found that high ORACLE risk scores were linked to regions of the tumour that were more likely to spread to another part of the body.

Finally, by looking at 359 current and potential lung cancer drugs, they found that a high ORACLE risk score predicted better response to some types of chemotherapy, particularly platinum drugs like cisplatin

This is because tumour regions with high ORACLE scores are associated with unstable DNA (called 'chromosomal instability'), which is particularly targeted by platinum drugs. The same lab has recently found that changes in a key gene called FAT1 drive chromosomal instability, which is also one of the genetic variations ORACLE looks for.

The next steps for the researchers are to compare people with high ORACLE scores receiving standard care and those receiving more surveillance or chemotherapy to determine if the test improves survival, even for people diagnosed at the earliest stage.

Dhruva Biswas, Translation Fellow at the Crick, Postdoctoral Fellow at the UCL Cancer Institute, Associate Research Scientist at Yale School of Medicine, and co-first author, said: "ORACLE can now predict survival rates in patients diagnosed at the earliest stage. If validated in larger cohorts of patients with lung cancer, doctors could one day use ORACLE to help make informed treatment decisions, bringing lessons from cancer evolution into the clinic."

Yun-Hsin Liu, Research Assistant at the UCL Cancer Institute, and co-first author, said: "We wanted to build on the previous work developing ORACLE and show that it can predict survival at the point of a lung cancer diagnosis. We've also shown that it can predict who would benefit from certain types of chemotherapy drugs or if someone's cancer is likely to spread, giving a holistic measure of how a patient's cancer might progress and respond."

Charles Swanton, Deputy Clinical Director and Head of the Cancer Evolution and Genome Instability Laboratory at the Crick, medical oncologist at University College London Hospitals, Chair in Personalised Cancer Medicine at the UCL Cancer Institute, Chief Investigator for TRACERx, and co-senior author of the study, said: "Lung cancer is the leading cause of cancer-related death throughout the world, so it's clear we need better markers to accurately classify tumours and predict who is at high risk. We're now working with the Translation team at the Crick and industry partners to progress ORACLE into a test which could hopefully be used in the clinic as soon as possible."

Paul Mercer, Head of Industry Partnerships in the Crick Translation team, said: "This is an important step forward, translating our understanding of the infinite complexities of lung cancer mutation into a diagnostic tool, prioritising patients for the most effective therapies. We look forward to working with partners to take this work forward and maximise patient benefit from ORACLE."

Dani Edmunds, Science Engagement Manager at Cancer Research UK, said:"In the last 50 years, cancer survival has doubled in the UK. However, progress has not been equal across all types of cancer. Although survival for lung cancer has improved since the 1970s, it's still one of the most challenging cancers to treat.

"New tests to predict lung cancer's behaviour could help doctors tailor treatment strategies to each person's condition, giving the best chance of a successful outcome.

"This research reflects Cancer Research UK's commitment to tackle this hard-to-treat cancer. While ORACLE still needs testing in larger-scale trials, these initial results show it could take us a step closer to more personalised approaches to treating lung cancer, so more people live longer, better lives."

The study is supported by the National Institute for Health and Care Research UCLH Biomedical Research Centre.

Why Lung Cancer Hits Black Communities Hardest

Lung cancer continues to have a profound impact on many communities, but the disparity is especially notable within Black populations. In these communities, lung cancer incidence and mortality rates are higher, underscoring the urgent need for targeted prevention and intervention strategies. Understanding the causes of lung cancer and addressing the factors contributing to its prevalence in Black communities can help reduce health disparities and improve outcomes.

Understanding cancer development mechanisms

Lung cancer develops through a combination of environmental exposures and cellular changes. Over time, the accumulation of DNA damage, mutations, and disrupted cell division can lead to the formation of cancerous growths. One of the key processes in cancer development is the alteration of the immune response, which prevents the body from effectively identifying and fighting abnormal cells.

Certain risk factors further contribute to these cellular changes, including oxidative stress, which accelerates cellular damage, and inflammation, which can disrupt normal tissue repair processes. These factors, when combined, create an environment conducive to cancer development, particularly when the body's mechanisms for repairing damaged cells are compromised.

Primary cause

Tobacco smoking remains the leading preventable cause of lung cancer. Smoking directly impacts the cells in the lungs by damaging their DNA and triggering inflammatory responses that impair the immune system. The mutagenic compounds in tobacco smoke further accelerate cellular damage, increasing the likelihood of cancerous growth.

For many Black communities, smoking rates are higher due to factors such as economic stress, cultural influences, and limited access to smoking cessation resources. The disproportionate burden of smoking-related diseases in these communities highlights the need for comprehensive prevention programs. Increased access to smoking cessation resources and community-based education can help reduce tobacco use and ultimately lower the incidence of lung cancer.

Environmental factor

Secondhand smoke is another major environmental risk factor for lung cancer. Exposure to secondhand smoke occurs in various settings, such as households, workplaces, public spaces, and multi-unit housing. Passive smoke inhalation, especially over prolonged periods, significantly raises the risk of developing lung cancer. Cumulative exposure is particularly harmful to children, affecting their respiratory development and overall health.

In Black communities, where multi-unit housing and urban environments are more common, secondhand smoke exposure is a pervasive issue. Addressing this risk requires both public health outreach and stricter regulations to limit exposure in both public and private spaces.

Environmental hazard

Radon gas, a naturally occurring but invisible and odorless hazard, is a significant environmental factor in lung cancer development. Radon exposure is particularly problematic in certain geographic areas, where the gas seeps from the ground into homes and buildings. The construction and ventilation of buildings can also influence the amount of radon exposure.

Though radon exposure is a silent threat, its risks can be mitigated through home testing programs and the installation of mitigation systems. Increased community awareness of radon and public health campaigns are crucial to reducing this hidden risk.

Occupational exposure risks

Occupational exposure to hazardous substances is another important contributor to lung cancer risk. Workers in industries such as construction, manufacturing, and chemical processing are often exposed to harmful substances like asbestos, industrial chemicals, and urban pollution. These exposures can increase the likelihood of developing lung cancer, especially in individuals who work in high-risk environments without adequate protection.

To protect workers, safety measures such as the use of protective equipment, regular workplace monitoring, and health screenings are essential. Legal protections for workers exposed to these hazards can further reduce the risks of lung cancer and other related diseases.

Genetic predisposition factors

Genetic predisposition plays a crucial role in lung cancer risk. People with a family history of lung cancer or those carrying specific genetic mutations are at a heightened risk. Mutations that affect DNA repair capacity or metabolism can predispose individuals to cancer. The presence of certain genetic markers can also make individuals more susceptible to environmental carcinogens, such as tobacco smoke or industrial chemicals.

Early genetic screening and counseling can help identify individuals at increased risk, allowing for proactive prevention strategies. Understanding genetic influences on lung cancer can aid in creating personalized interventions and improve early detection efforts.

Healthcare access considerations

Addressing healthcare disparities remains a critical component of reducing lung cancer incidence in Black communities. Barriers to healthcare, such as insurance coverage limitations, the distribution of healthcare facilities, and cultural competency within medical practice, prevent many from receiving timely care. In communities with limited access to healthcare services, cancer is often diagnosed at later stages, reducing the chances of successful treatment.

Improvement strategies include expanding access to healthcare services through community health programs, mobile screening units, and patient navigation services. Building cultural competency within healthcare teams is equally important, as it fosters trust and ensures that medical providers can effectively communicate with diverse populations.

Prevention and screening protocols

Lung cancer prevention and early detection programs are essential for reducing its impact. Comprehensive prevention strategies include smoking cessation programs, environmental protection efforts, workplace safety enhancements, and improving healthcare access. Screening programs play a vital role in identifying lung cancer in its early stages, when treatment is more effective.

By coordinating regular health assessments and risk factor evaluations, healthcare systems can ensure that individuals at higher risk are closely monitored. Follow-up care is just as important, as it ensures that any signs of cancer are detected early and that individuals receive the appropriate treatments.

Community engagement strategies

The involvement of communities in lung cancer prevention is crucial. Outreach programs that provide education, support groups, and resources can significantly reduce risk factors. Engaging community leaders and integrating cultural considerations into these programs ensures that they resonate with the population they aim to serve.

Public health campaigns that incorporate language-appropriate materials, traditional practices, and leadership involvement can build trust and motivate individuals to take action in reducing lung cancer risks. Community engagement can help empower individuals to make healthier choices and advocate for better healthcare access and environmental protections.

Innovative Biopsy Technique Leads To Early Lung Cancer Detection And Recovery

Twelve years after losing her husband David to lung cancer, Bev Brookshire faced her own health scare. When she began to experience shortness of breath and wheezing, a CT scan at Washington state-based MultiCare revealed a nodule on her lung. And when the usual approach to evaluate further wasn't possible due to a health condition, doctors got creative.

"Bev has significant kyphoscoliosis (curvature of the spine that's both sideways and forward/backward), which made the biopsy challenging," MultiCare Interventional Pulmonologist Abhishek Biswas, M.D., explained in a MultiCare blog post. "The only way to do the biopsy was with robotic-navigation bronchoscopy with cone-beam, real-time imaging."

Bronchoscopy, or transbronchial biopsy, is a minimally invasive procedure where a thin tube is guided down the throat to the lungs. Using this unique method, Brookshire's care team was able to determine that she had stage 1 non-small cell lung cancer and acted quickly to get her into treatment. Following a successful surgery, Brookshire recovered quickly and enjoyed an Alaskan cruise with her daughter two weeks later. Since then, she hasn't had to undergo radiation or chemotherapy and her last CT scan was clear. And now she's a major proponent of early CT scans.

"I tell everybody I know, 'If you're a smoker or former smoker, get a CT scan,'" Brookshire said. "Better safe than sorry."

Resources on the Role of Hospitals

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