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How To Interpret Lung Nodules On A Chest X-Ray: Can They Be Cancerous?

Chest X-rays are an effective method to assess your lungs and heart. It is often considered when a patient complains of symptoms like chest pain, shortness of breath, and persistent cough. Often incidentally, medical professionals detect small, abnormal growths in the lungs, which might cause some worry. These are also known as lung nodules. In an interaction with the OnlyMyHealth team, Dr Shriram Shenoy, Consultant Pulmonologist, Manipal Hospital, Kharadi, explains ways to interpret, assess, and monitor lung nodules.

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What Are Lung Nodules?

"Lung nodules are tiny growths in the lung tissue that are round or oval in shape and generally have a diameter of less than three centimetres," describes Dr Shenoy, adding that they tend to be found by chance during a chest X-ray or CT scan that is done for unrelated purposes.

According to a 2022 study published in the JAMA, lung, or pulmonary, nodules are identified in approximately 10.6 lakh people per year in the US and are detected on about 30% of chest CT scans.

The majority of lung nodules don't cause any symptoms and could indicate either benign or cancerous.

While a chest X-ray gives a first look, a CT scan gives a more comprehensive assessment that helps identify the nodule's size, form, and features.

To differentiate benign nodules from those that need more assessment, additional imaging or follow-up procedures are sometimes required. Further treatment is influenced by variables such as the nodule's appearance, smoking status, and patient history.

Can Lung Nodules Be Cancerous?

Most lung nodules are benign and are caused by inflammation, infections, or non-cancerous growths like hamartomas or granulomas. According to Dr Shenoy, the percentage of malignant lung nodules is lower, and those who have a history of smoking, exposure to chemicals, or a family history of lung cancer are at higher risk.

Size, form, and growth rate are some of the variables that affect the chance of malignancy. While larger or irregularly shaped nodules need closer examination, nodules smaller than 6 mm have a lower chance of being malignant. The type of nodule and the necessity of additional treatment are ascertained with the aid of follow-up imaging and other testing.

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Follow-Up Tests To Assess Lung Nodules

While most lung nodules are harmless and benign, it is always advised to assess them and keep them under close observation.

Multiple types of additional tests are usually used to evaluate lung nodules based on their size, appearance, and risk factors. "To evaluate changes over time, high-resolution CT scans offer thorough imaging. PET scans can be used to evaluate metabolic activity, particularly in nodules that are bigger or appear suspicious. Before any invasive operation, pulmonary function testing aids in determining lung capacity," says Dr Shenoy.

He adds, "When cancer is suspected, a biopsy may be done for histological study using bronchoscopy, needle aspiration, or surgical excision. In certain situations, molecular profiling and blood testing are employed. Regular imaging follow-up over several months or years helps in tracking the development of nodules."

When Is A Biopsy Required?

According to the doctor, monitoring of solitary lung nodules is often guided by the Fleischner Society pulmonary nodule recommendations. The Fleischner Society Guidelines provide recommendations for managing incidental pulmonary nodules detected on CT scans in adults less than or equal to 35 years old.

"After six to twelve months, follow-up imaging is often required for low-risk individuals with small nodules (less than 6 mm). Repeat CT scans may be required more frequently for larger nodules or those with questionable characteristics. If a nodule exhibits strong metabolic activity on a PET scan, has uneven or spiculated boundaries, or shows considerable growth, a biopsy is required. Patients with a high-risk profile or those who exhibit symptoms are also advised to undergo invasive testing. A multidisciplinary team approach ensures the best possible diagnosis and treatment choices," shared Dr Shenoy in detail.

Conclusion

Lung nodules are usually harmless; however, it is always necessary to monitor them. Size, growth pattern, and related risk factors are some of the variables that affect when lung nodules need to be monitored, says Dr Shenoy. For more information or clarification, it is best to consult a doctor and understand individual risk and circumstances

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Using Precision Diagnostics For Early Detection Of Lung Cancer

A key focus of R&D for Sanmed Biotech is precisely detecting and profiling lung nodules as a means to better diagnose lung cancer.Credit: Kateryna Kon/Science Photo Library/Getty

Lung cancer is the second most common type of cancer and the leading cause of cancer deaths worldwide. Early-stage lung cancer is often asymptomatic, meaning patients are typically diagnosed at an advanced stage, where tumours are growing rapidly and the prognosis is grave. A cross-disciplinary team at Sanmed Biotech, a precision medicine innovation firm founded in 2016, is hoping to improve the outlook for lung cancer through new solutions for early diagnosis.

"The survival rate of stage 1A lung cancer at 10 years is over 90%. Yet for late-stage lung cancer patients, the survival drops significantly and only the 5-year survival rate is calculated," says Frank Shi, CEO of Sanmed Biotech. "Early diagnosis of lung cancer is critical in reducing the mortality rate and prolonging survival."

Credit: Sanmed Biotech

Credit: Sanmed Biotech

Credit: Sanmed Biotech

As Shi explains, the company has its roots in Cynvenio Biosystems, a global pioneer in liquid biopsy technology founded in 2008 by Nobel-winning physicist and chemist, Alan J. Heeger, and company Zhuhai Livzon Diagnostics, one of China's first in vitro diagnostic products manufacturing enterprises.

Differentiating cancerous nodules

The research and development priority at Sanmed Biotech is to precisely detect and profile lung nodules — small lumps of tissue that can be benign, precancerous or metastatic tumours. Low dose computed tomography (LDCT) screening is the recommended test to detect and measure nodules, but it's fraught with challenges.

"Where nodules are found to be 15 or even 20 millimeters, clinicians may propose further testing, such as a positron emission tomography scan, bronchoscopy or tissue biopsy," says Xin Ye, product development director of Sanmed Biotech. "However, LDCT has proven difficult to accurately profile smaller suspect nodules, presenting a major diagnostic challenge for clinicians to determine whether the nodule is malignant or benign, or whether an invasive biopsy or immediate surgical resection is necessary."

An effective, non-invasive, early detection test is needed to improve the diagnostic efficacy of LDCT, and Sanmed Biotech's proprietary liquid biopsy technology, fits the bill, says Ye.

Sanmed's liquid biopsy assay uses a novel multiplex fluorescence in-situ hybridization (FISH) test to detect chromosomal aberrant cells (CACs) in peripheral blood: a technique developed in 2010 by Ruth Katz. In 2020, refinements of this technique by Katz's team led to improved diagnosis of benign and malignant lung nodules by detecting chromosomal abnormalities in the peripheral blood genome through a simple, safe, effective, non-invasive test.

Sanmed's test contrasts with other liquid biopsy technologies that detect 'antigen-dependent' circulating tumour cells (CTC): these may lose sensitivity if the tumour cells alter the antigen profile by leaking into the bloodstream. Sanmed's liquid biopsy assay can distinguish between benign and malignant lung nodules by identifying individual cells bearing gains and/or loss of specific chromosomal loci that are labeled with distinct fluorophores.

Towards greater diagnostic certainty

Early lung cancer diagnosis is also impeded by the absence of standardized methods for interpreting LDCT images. Due to imaging anomalies and human error, doctors may reach different diagnostic conclusions on the same scan. So, Sanmed Biotech has invested globally in specialized high-throughput computation and image recognition algorithms to automate the LDCT image and data analysis.

One outcome is the SANMED Target Call Lung Nodule Analysis Platform, which is built on deep convolutional neural networks and machine learning algorithms trained on a massive dataset of around 300,000 annotated pulmonary nodules. This platform can automatically reconstruct, segment, and analyse the LDCT images and label the lung nodules with the relevant parameter values indicating malignancy risks.

In 2022, Sanmed Biotech published its preliminary findings in Frontiers in Oncology. This study proposed a machine-learning-based prediction model, which integrates clinical characteristics (age and smoking history) and radiological profiles of nodules with the artificial intelligence (AI) analysis of LDCT data and Sanmed's liquid biopsy assay results. In a sample of 728 subjects, the model achieved optimal diagnostic performance, outperforming any approaches conducted alone.

Ramping up with applications

Sanmed has established a sound intellectual property protection system and its technological advantage has stretched to far-reaching applications and collaborations. At present, the products are in clinical use in more than 20 leading hospitals in China.

Furthermore, the company's comprehensive solution in early detection of lung cancer attracted a specialist in respiratory diseases. Chunxue Bai, chair of the Chinese Alliance against Lung Cancer and vice president of the Chinese Respiratory Association, plans to partner with the company to conduct a multi-center clinical study of AI-assisted Sanmed's liquid biopsy assay diagnosis of benign and malignant lung nodules in China, enrolling more than 10 hospitals and 100,000 participants.

"We strive to offer cutting-edge products to maximize benefits for both patients and physicians," says Ye. "We believe our non-invasive option will be a useful complementary tool for clinicians in assessing early lung cancer. It could help to improve early lung cancer diagnosis and treatment in patients with malignant nodules while sparing those with benign entities from unnecessary and potentially harmful surgery."

Contact Info

Phone: +86-0756-6931621

Email: info@sanmedbio.Com

Website: www.Sanmedbio.Com

This advertisement appears in Nature Spotlight 2022 Precision medicine, an editorially independent supplement. Advertisers have no influence over the content.

Improving Survival Rates With High-tech Lung Cancer Detection And Treatment

Human lung tissue under the microscope. Researchers are developing liquid biopsies which detect lung cancer markers in blood.Credit: Choksawatdikorn/Shutterstock

The five-year survival rate for lung cancer is around 56% when it is detected while the cancer is still localized. But few cancers are caught at this early stage.

To improve survival rates and patient experience, screening and treatment of early-stage lung cancer is shifting toward less invasive techniques.

Chang Chen leads Tongji University-affiliated Shanghai Pulmonary Hospital in China, the world's largest minimally invasive thoracic surgery centre by patient volume.

In this Q&A, Chen discusses some of the challenges of treating and detecting early-stage lung cancers, and how he and his colleagues have developed advanced approaches to overcome them.

What are the challenges with early detection?

Conventional diagnostic tools for identifying early-stage lung cancer include low-dose CT (computed tomography) scans and tissue biopsies. CT scans, while sensitive, can trigger false alarms, leading to unnecessary procedures. Interpreting biopsy results is less error-prone, but obtaining tissue samples is invasive and may cause pain, bleeding and infection.

To minimize the side effects, liquid biopsies that use blood have been developed. For example, lung cancer can be diagnosed by measuring DNA from the tumour in blood samples. But getting a reliable diagnosis has proved tricky because the amount of tumour DNA released into the blood is highly variable.

Vice-president of Shanghai Pulmonary Hospital in China, which is affiliated with Tongji University.Credit: Shanghai Pulmonary Hospital

How can we improve early detection?

We worked with researchers at the Chinese Academy of Sciences in Shanghai to develop a high-throughput liquid biopsy. This technology identifies long non-coding RNA from extracellular vesicles (EV-lncRNA). The vesicles are secreted by tumour cells and find their way into the blood. To increase sensitivity, we combined PCR with a microfluidic chip to detect low levels of different EV-lncRNA biomarkers. We called the technology miDER for multi-colour fluorescence digital PCR EV-lncRNA analysis chip. We published it in 20191.

Although miDER is currently less sensitive than standard tissue biopsy, it requires a smaller amount of blood than many other liquid biopsy methods. When miDER is used to target two lncRNA biomarkers, it is almost as accurate as tissue biopsy, and potentially more suitable for screening large numbers of people for early-stage lung cancer because it is less invasive. The miDER test is currently being developed for clinical use.

The test could also be used beyond diagnosis. Doctors could adjust treatment based on EV-lncRNA. Monitoring of EV-lncRNA could help spot small residue disease or early relapses.

How do you treat early-stage lung cancer?

We mainly use video-assisted thoracoscopic surgery or VATS — in which a thoracoscope, a thin flexible tube with a light and camera, is introduced into the chest through an incision.

The world's first VATS lobectomy — surgery to remove one of the lobes of the lungs — using a single incision was reported in 2011. At the Shanghai Pulmonary Hospital, we performed the first single-port VATS in 2012.

Compared with multi-port VATS, a single-port procedure further reduces trauma and post-surgery pain for patients, and the surgeon still gets a traditional open view via video.

By April 2023, our facility had completed more than 75,000 single-port VATS, the most in the world for a single hospital. Today, nearly 90% of our early lung cancer surgeries are done using this technique.

To help doctors better perform this procedure, we developed proprietary single-port VATS tool kits, containing specialised surgical equipment. They have been adopted globally.

How else has VATS improved lung cancer care?

Our team has solved the key challenge of rebuilding, under single-port VATS, the pulmonary artery and trachea, which can be damaged by invasive lung cancer. This has established single-port VATS as a safe approach for complex thoracic surgeries. As we continue to perfect the method at Shanghai Pulmonary Hospital, our cure rate for locally advanced lung cancer under minimally invasive procedures has increased from 5% to 42%.

Our team also published 21 papers on single-port VATS in three of the world's leading thoracic surgery journals, making up 31% of the papers in this field.

Computed topography (CT) scans, artificial intelligence software, and 3D printing are used to create a model of the chest to guide lung surgery at Shanghai Pulmonary Hospital in China.Credit: Shanghai Pulmonary Hospital

How could more surgeons learn single-port VATS?

Our mission is not limited to improving care for our own patients. We also want to introduce these advanced techniques to our peers. So we have been hosting training courses since 2014, and have so far welcomed 842 doctors. We have a training centre with about 200 people enrolling annually.

We also established a minimally invasive thoracic surgery knowledge-sharing platform, online, aimed at a global audience.

Single-port VATS is still mostly performed at large healthcare facilities. Our analysis found that on average it takes a doctor 90 surgeries to become proficient using VATS for a complex procedure for lung cancer called a 'sleeve lobectomy'2.

We hope with our new training centre and high patient throughput, we'll be able to standardize minimally invasive surgery education, shorten the learning curve and bring the technique to community hospitals in China.

What other technologies have you developed to assist in lung surgery?

Trying to pinpoint lung nodules to take a biopsy, or to operate on them, is like trying to locate a submarine in the ocean depths from above the water. So, we designed a 3D printing-based navigation system to help doctors locate the nodules.

With the standard protocol, surgeons use multiple 2D CT scans to guide them. We use CT images, computer software and 3D printing to create a 3D reconstruction of a patient's chest structures, which we use as a navigational template. The template is fixed to the patient's chest cavity to guide the surgeon. One key challenge is matching the 3D model with the patient's breathing pattern because breathing changes the shape of the lungs.

The 3D printing-based navigation system is currently as accurate as traditional CT-assisted nodule localization3. Our model can now help the surgeon limit deviation from the actual nodule site to around 6 mm. With the help of AI, we aim to bring this level down to below 1 mm, which is a lot better than traditional CT methods.

What is the future focus of your research?

We have built a database of two million patients, including information on radiology, pathology, genomics, metabolomics and clinical phenotypes. We plan to use AI to extract information from these data to assist in accurate diagnosis and to guide surgery or other precision treatment.

There is also room to refine miDER in multiple ways. For example, the expression of EV-lncRNA is affected by several factors that we are working to better understand. There is also no gold standard for purifying EVs, and we plan to develop one. Lowering costs for mass adoption is also a focus for developing next-generation miDER.

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