This imaging tool provides more precision in lung cancer

The left CT image (A) shows the direction (red arrow) in which the left lung mass was biopsied and came back negative for cancer. This was because only dead tissue (blue) was at the site of the biopsy as can be seen in the 18F-FDG PET-CT scan (B). The cancer tissues (red with a yellow-green border) are present in other parts of the mass. — Photos: Dr ALEX KHOO CHEEN HOE

Since the start of the Covid-19 pandemic, anyone complaining of cough or breathlessness would be routinely investigated for the infectious disease.

Although many people would have been diagnosed with Covid-19 itself, there are also a handful of patients who were found to have lung cancer.

According to the latest cancer registries, lung cancer is the third most common cancer in Malaysia, and also in the world.

Most patients with lung cancer tend to present with breathlessness, cough, haemoptysis (the coughing of blood), or a combination of those symptoms.

Some patients will initially present with what appears to be unrelated symptoms like headache, bone pain or reduced effort tolerance (inability to do as much physical activity as you should be able to).

The assumption that only smokers get lung cancer is incorrect, especially among females.

Non-smokers are also at risk of lung cancer and recent observations have shown that the frequency of non-smokers getting lung cancer is growing.

So, the next question is: who is at risk of getting lung cancer?

Accurate diagnosis

The left PET-CT image (C) shows a metabolically-active left lung mass (red arrow). However, the mediastinal node (seen in D, green arrow) is not metabolically active, thus downstaging the patient and confirming their suitability for curative lung surgery. The maximum intensity projection of the PET scan (E) makes staging of lung cancer easier for clinicians.

In general, cigarette smokers are at higher risk of lung cancer, followed by secondhand smokers.

Patients who are exposed to radon and asbestos, or have family history of lung cancer or history of radiation to the chest are also at risk of lung cancer.

Is there any way to know if one has lung cancer?

Regular health examinations for everyone and low-dose computed tomography (CT) of the lung for those at high risk of lung cancer is now advocated.

Prevention is definitely better than cure, but what happens if one is already diagnosed with lung cancer?

According to the latest Malaysian Cancer Registry, over 90% of lung cancer cases are diagnosed when they are already in the advanced stages of the disease (stages III and IV).

In the past, the prognosis of a patient with newly-diagnosed lung cancer was poor.

Historically, the median survival for patients with advanced lung cancer was only about one year after diagnosis despite treatment.

The five-year survival rate was dismal at less than 10%.

With the advent of newer treatment options such as targeted therapy and immunotherapy, there have been significant improvements not only in survival rates, but also in quality of life.

First and foremost, it is important for patients to be correctly diagnosed with lung cancer, and subsequently, to be optimally staged.

There are times when clinicians detect abnormalities in the lung that are suspicious of cancer, but they are unable to obtain a satisfactory tissue sample for diagnosis.

This can be attributed to the fact that some parts of the lung “lesion” are either just necrotic (dead) or collapsed.

This can be circumvented by using 18F-FDG-based PET (positron emission tomography) imaging (usually in combination with CT, hence PET-CT).

Guiding treatment

A patient with lung cancer had 18F-FDG PET-CT scans done six months apart - before (F and H) and after (G and I) undergoing chemotherapy, radiotherapy and immunotherapy. The right lung cancer (red arrows) had reduced significantly in size and activity, whereas the mediastinal lymph nodes (green arrows) were no longer seen after treatment. A CT scan before treatment would have overestimated the size of the lung cancer and led to unnecessary radiation of normal, but collapsed lung (white arrow in H). Oesophagitis (blue arrows in G and I), which is a treatable side effect of immunotherapy, was also picked up post-treatment.

In the event that curative surgery of the lung cancer is not possible, clinicians would need to consider other options, such as chemotherapy, radiotherapy, targeted therapy, immunotherapy or combinations of these.

Advances in radiotherapy have led to more successful treatment of lung cancers, but such treatment would be pointless if the target is not accurately identified and the normal surrounding tissues are exposed to unnecessary radiation, as this may lead to permanent collateral damage.

Oncologists are now using PET-CT to guide radiotherapy as it leads to better delineation of the tumours and assessment of response to therapy.

Meanwhile, targeted therapies include tyrosine kinase inhibitors and monoclonal antibodies.

These target the underlying abnormal proteins, receptors or pathways that occur as a result of gene mutations, which, in turn, lead to the development and growth of cancer.

The state-of-the-art treatment nowadays is immunotherapy.

Immunotherapy has been widely integrated into clinical practice for cases of lung cancer with PD-L1 expression.

PD-L1 is a type of protein on the cancer cell surface that acts as a “shield”, protecting cancer cells from being detected by our immune cells.

The use of immunotherapy targetting this protein has significantly improved treatment response rates, progression-free survival (where the tumour is pre-sent, but does not grow) and overall survival.

In fact, the data has shown that one-third of advanced lung cancer patients with high PD-L1 expression who received immunotherapy remain alive after five years!

Unfortunately, these treatments are not cheap.

While patients are on treatment, the oncologist must carefully monitor their well-being and response to treatment.

This is important as the timing as to when to start, stop or switch these therapies is crucial.

How would clinicians know if their patients have responded to treatment?

Conventional imaging such as CT and MRI (magnetic resonance imaging) basically looks at sequential anatomical differences, particularly in terms of size, to see if there is progression, improvement or no significant changes.

Nonetheless, anatomical assessment alone may not be as accurate, and may cause unnecessary changes to successful therapies or delayed changes in failed therapies.

This is where PET imaging becomes crucial in cancer imaging, as illustrated in the photo above.

In short, PET imaging should be fully utilised in the management of lung cancer, and not just as a nice-to-have imaging modality.

PET imaging is the “key” to precision medicine, arming clinicians in their fight against lung cancer.

Just like with any tool, you have to pick right tool for the job!

Dr Alex Khoo Cheen Hoe is a consultant nuclear medicine physician and Dr Ang Soo Fan is a consultant oncologist. For more information, email [e-mail]. The information provided is for educational and communication purposes only, and should not be considered as medical advice. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this article. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.