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Personalised and targeted cancer therapies for improved outcomes

Article-Personalised and targeted cancer therapies for improved outcomes

Shutterstock cancer therapies
Shedding light on how surgery and medical therapies can be combined.

Lung cancer places a heavy burden on patients’ lives and healthcare systems, as the number one cause of death in the world among both men and women. Unfortunately, most cases are diagnosed when metastatic and only about 20 per cent of the disease is responsive to curative-intent surgery. Thus, there is an urgent need to improve early detection strategies to increase the fraction of cancers diagnosed in early stages when they are most curable.

According to Dr. David Carbone, Professor of Internal Medicine and Director of the James Thoracic Oncology Center at The Ohio State University Comprehensive Cancer Center, it is always better to prevent lung cancer than to treat it, considering the high number of relapses in half of the patients despite having tumours surgically removed at an early stage. Healthcare providers are diverting their attention to reversing changes in the airway epithelium early and prevent the development of the lung disease.

At Arab Health, Dr. Carbone highlighted the advances in surgery combined with medical therapies such as chemotherapy and immunotherapy. These have recently undergone revolutionary changes, thanks to large-scale clinical trials, and will continue to develop over the next few years.

Dr. Carbone has over 30 years of experience as a specialist in lung cancer and operates a research lab dedicated to the study of different components related to the disease.

“We have witnessed dramatic improvement in our treatments and the outcomes, however, there remains huge room for improvement as we still lose many patients from lung cancer. We are looking for better approaches to personalise therapies to better understand why some patients respond while others do not,” he said.

Understanding these patterns enable the selection of the optimal current therapy for individual patients, as well as the development of new therapies that overcome resistance mechanisms, which can be administered to patients whose tumours would not otherwise respond.

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Dr. David Carbone

Improving and personalising therapies

Dr. Carbone’s research over the years has focused on answering these questions, studying tumours before and after surgery, and the application of different approaches such as genetics and proteomics.

“We recently published a paper in Nature Medicine, looking at patients treated with immunotherapy before surgery, and these patients have significantly improved survival outcomes. By studying blood and tumour samples before and after therapy, we can try to discover some of the new features of patients and their cancers to personalise therapies (called “biomarker”) and discover the mechanisms of resistance,” said Dr. Carbone.

The discovery of specific biomarkers in lung cancers has transformed the way the disease is treated. Now, multiple subsets of cancers can be recognised and diagnosed, and have specific, personalised treatment approaches. “In the past, we treated all patients with the same approach and saw quite poor outcomes with lung cancer,” he added.

With biomarkers and molecular testing, specific treatments can be matched to specific patients. This has resulted in improved outcomes for patients with unresectable diseases.

“We are just learning how to best combine targeted and immunotherapies with surgery. A targeted therapy has now been approved for patients that have a specific genetic alteration in the EGFR gene, and many patients with tumours without these gene alterations are now approved to get immunotherapy in addition to surgery. Looking ahead, we are hoping that the biomarker-directed personalisation of therapies for lung cancer patients will improve outcomes,” said Dr. Carbone.

Lung cancer surgery over the years

Considered a complex surgery, lung cancer surgery in the past involved large incisions and long hospital stays. Recently, minimally invasive approaches have been developed, including robotic surgeries that involve very small incisions in the skin with faster recovery, less pain, decreased hospital stays, and a good sampling of lymph nodes.

“The other major advance in surgery is surgeons working more closely with medical and radiation oncologists to do multi-modality management of these patients. This can dramatically improve chances of survival by combining medical therapies with the surgery,” he said.

Dr. Carbone explained that chemotherapy contributed around five per cent of the five-year survival rate among patients. Now, early data demonstrate almost 80 per cent survival at three years with immunotherapies, which is almost twice of what would be expected. “This multi-speciality approach to lung cancer has transformed the way we treat patients. Selection of the appropriate medical therapy combinations requires gene sequencing and other biomarker testing of the patient's tumour. Presently, the standard of care is to conduct gene sequencing and marker testing in every patient,” he said.

The role of technology

Robotic surgery is recognised as an extraordinary innovation where a surgeon leads with a controller while a robot does the surgeries. This gives surgeons the opportunity to examine patients at angles that were previously impossible. In the case of cancers, they have a stereoscopic vision for much better visualisation of the tumour and its surroundings.

“Robots give surgeons the ability to move surgical instruments in a way that is not possible with human hands. In addition, we can now perform a genetic assessment of the tumour using only a drop of blood from a sample, instead of a tumour biopsy. The technology behind current imaging, bronchoscopy and staging with a bronchoscope by endoscopic ultrasound have all dramatically improved. All of these technologies did not exist decades ago, and are now significantly improving how we manage these patients,” said Dr. Carbone.

Looking ahead

To improve and better tune therapies to individual patients, the team at James Thoracic Center at The Ohio State University is always vigilant in identifying new features of cancers.

“In our latest research study, we discovered patterns of distinct types of immune cells in the blood of patients before treatment that were associated with whether or not they responded to immunotherapy. We also identified some markers that could be used as additional therapy targets, where rational combinations could convert non-responders to responders. This is done by selecting patients for different types of immunotherapy based on these markers. I believe this should be a priority for future research,” he added.

When asked about the importance of collaborations, Dr. Carbone commented that conferences such as Arab Health engage physicians from all over the world and help them work towards optimising care everywhere in the world.

“The latest findings and optimisation of patient multi-speciality care are a few of many topics discussed at conferences like Arab Health. While it is important that prominent universities discover cutting-edge approaches, disseminating that technology and implementing it around the world to benefit all patients is also critical. I believe that is the true goal of such a conference: to disseminate information and provide patients all over the world with access to state-of-the-art technologies.”

This article appears in the Daily Dose 2023. Read the full issue online today.

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