Introduction: Recently, the "Expert Consensus on Radiotherapy Combined with Immunotherapy for Unresectable Lung Cancer (2024 Edition)" was published, co-authored by Academician Jinming Yu of Shandong Cancer Hospital, Professor Ying Cheng of Jilin Cancer Hospital, and Professor Liangan Chen of the Chinese People’s Liberation Army General Hospital. This publication marks a new level of scientific standardization in the multidisciplinary management of radiotherapy and immunotherapy.Oncology Frontier invited Dr. Yong Song from the Department of Respiratory Medicine, Jinling Hospital, Nanjing University Medical School, one of the core reviewers of the consensus expert group, to share his insights on the consensus guidelines for managing adverse reactions from a respiratory perspective.

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Oncology Frontier: From a respiratory perspective, how can we leverage multidisciplinary strengths to achieve better survival benefits for patients receiving radiotherapy and immunotherapy for unresectable lung cancer?

Dr. Yong Song: As a respiratory physician, I have extensive experience with the diagnosis and treatment of respiratory diseases, and I deeply understand the role of respiratory medicine in the multidisciplinary treatment of lung cancer.

Firstly, lung cancer, as a major respiratory disease, has shown an increase in incidence in recent years. Most lung cancer patients are older and may have unfavorable lifestyle habits, which often lead to comorbidities such as COPD, interstitial lung disease, and cardiovascular disease. Treating lung cancer scientifically requires managing these comorbidities, hence our “dual treatment of cancer and lung” approach—not only treating the cancer but also addressing comorbid conditions.

Secondly, common treatments like radiotherapy, chemotherapy, and immunotherapy can all lead to respiratory complications, such as radiation pneumonitis and immune-related pneumonitis. Immune checkpoint inhibitors can also cause adverse reactions in multiple systems. Respiratory physicians play a crucial role in managing lung complications due to their extensive clinical experience with such cases.

Lastly, respiratory departments are often the primary diagnostic centers for lung cancer. Under the primary physician responsibility system, most lung cancer patients are managed from diagnosis to treatment and follow-up by respiratory physicians. In MDT (multidisciplinary team) settings, the respiratory department frequently gathers experts from various disciplines for case discussions.

In summary, in the era of MDT, the role of respiratory medicine in lung cancer diagnosis and treatment is indispensable.

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Oncology Frontier: Radiotherapy combined with immunotherapy can bring more side effects and complications. What are the current challenges in managing these side effects? How do you balance treatment benefits with the risk of adverse effects in clinical practice?

Dr. Yong Song: For patients with locally advanced NSCLC or limited-stage SCLC, the standard treatment currently involves concurrent or sequential chemoradiotherapy followed by consolidation with immunotherapy or targeted agents. These treatments can lead to lung damage, with some patients developing radiation pneumonitis or immune-related pneumonitis, especially when combining radiotherapy and immunotherapy, which further increases the risk of pneumonitis. For clinicians, balancing efficacy and safety to help patients complete treatment smoothly is a critical task.

In cases where severe lung reactions occur during concurrent chemoradiotherapy, it’s essential to promptly adjust treatment. For example, when grade 2 or higher pneumonitis occurs, radiotherapy or immune checkpoint inhibitors should be paused, and the patient’s symptoms should be monitored. If necessary, interventions with corticosteroids or immunosuppressants can be considered. We have guidelines and expert consensus for managing adverse effects like pneumonitis in radiotherapy and immunotherapy, but there’s still room for improvement in the implementation of standardized management in clinical practice. This consensus emphasizes the importance of assessing toxicities such as pneumonitis and cardiovascular risks to improve clinical management.

In balancing efficacy and adverse effects, the contributions of respiratory physicians and the wisdom of the entire MDT, through team discussions, are invaluable for optimizing radiotherapy and immunotherapy.

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Oncology Frontier: Before initiating combined radiotherapy and immunotherapy, should patients undergo risk assessment for adverse reactions? If radiation pneumonitis is reduced to below grade 1, can immunotherapy be restarted?

Dr. Yong Song: Before beginning radiotherapy and immunotherapy, a comprehensive evaluation of the patient is essential, including organ function and preexisting diseases, as conditions like autoimmune diseases and cardiovascular disease are significant factors affecting the success of radiotherapy and immunotherapy. This consensus recommends actively assessing patients’ risk factors and optimizing radiotherapy plans to minimize damage to normal lung tissue.

Although combined radiotherapy and immunotherapy carry higher risks of adverse effects, comprehensive risk-benefit assessment can help achieve a safe and effective balance. Prior to treatment, assessing lung function and the risk of treatment-related pneumonitis allows for effective management within a controllable range. At this year’s ASCO Annual Meeting, a phase II study led by Academician Jinming Yu investigated atezolizumab with sequential thoracic radiotherapy for first-line treatment in ES-SCLC. The study showed a median OS of 21.4 months in the ITT population, a new breakthrough for ES-SCLC, with only a 6% incidence of grade 3 or higher pneumonitis, demonstrating good, controllable safety.

Pneumonitis during radiotherapy and immunotherapy can sometimes be challenging to diagnose. After a pause or intervention, if pneumonitis severity reduces to below grade 1, symptoms improve, and lung inflammation subsides, the question of whether immunotherapy can be resumed becomes critical. If treatment has shown good efficacy and both patient and doctor are eager to continue, we generally consider restarting treatment, but with closer monitoring to maximize safety and efficacy. Before resuming treatment, using the MDT model to bring together specialists from radiology, respiratory medicine, oncology, radiology, and pathology helps ensure optimal decision-making.

Dr. Yong Song

• Chief Physician, PhD Supervisor
• Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University Medical School
• Chest Tumor Center, Nanjing Tianyinshan Hospital, China Pharmaceutical University
• Director, Nanjing University Respiratory Research Institute
• Committee Member, Respiratory Disease Section, Chinese Medical Association
• Chairman, Respiratory Disease Section, Jiangsu Medical Association
• President-Elect, Respiratory Section, Jiangsu Medical Doctor Association
• Council Member, Chinese Society of Clinical Oncology (CSCO)
• Editor-in-Chief, Translational Lung Cancer Research, Editorial Board Member, Chinese Medical Journal