Dr Hales on the Use of Post-Operative Radiotherapy in NSCLC

“Right now, based on the randomized data we have, we have insufficient [information] to guide the routine use of PORT in [patients with resected stage III NSCLC]. That being said, there are subsets of patients that probably benefit from radiation.”

Russell Hales, MD, director, Thoracic Oncology Multidisciplinary Program, associate professor, clinical radiation oncology and molecular radiation sciences, and director, thoracic multidisciplinary clinic, John Hopkins University School of Medicine, discusses clinical data that challenge the use of post-operative radiotherapy (PORT) in patients with non–small cell lung cancer (NSCLC).

The phase 3 Lung ART (NCT00410683) and PORT-C (NCT00880971) trials both investigated the role of adjuvant radiotherapy in patients with resected stage III NSCLC, Hales begins. Lung ART did not demonstrate a significant improvement in disease-free survival or overall survival with PORT, he says. However, the study primarily used 3-dimensional conformal radiation therapy, a technique that is largely outdated in contemporary clinical practice, he explains. This approach likely resulted in increased radiation exposure to healthy tissues, including in the heart and lungs, which may have contributed to a higher incidence of cardiovascular events and ultimately negated the potential benefit derived with radiotherapy, he emphasizes.

In contrast, the PORT-C trial used more advanced intensity-modulated radiation therapy, which allows for greater precision in radiation delivery and reduces toxicity to surrounding organs, Hales notes. However, a significant limitation of the PORT-C trial was that 23.9% of patients who were randomly assigned to receive radiation did not undergo the study treatment, thereby introducing a significant protocol adherence issue that complicates data interpretation, he reports. When analyzing outcomes based on treatment assignment, investigators observed no clear benefit with adjuvant radiotherapy, according to Hales. However, an analysis based on actual treatment received suggested a potential advantage with PORT, he states.

Given the conflicting results with PORT in the literature, the extrapolation of data from these trials into clinical practice remains challenging, Hales says. Although the randomized trial data do not provide sufficient evidence to support the routine use of PORT in all patients with resected stage III NSCLC, certain patient subsets might still derive benefit from this treatment approach, he concludes.

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Russell Hales, MD, discusses clinical data that challenge the use of post-operative radiotherapy in patients with non–small cell lung cancer.

Russell Kenneth Hales, MD, director, Thoracic Oncology Multidisciplinary Program, assistant professor of radiation oncology and molecular radiation sciences, Sidney Kimmel Cancer Center, Johns Hopkins Medicine, discusses the role of multidisciplinary care in locally advanced lung cancer.

Locally advanced lung cancer is managed by medical oncologists, radiation oncologists, surgical oncologists, and other health care professionals from pulmonary medicine, Hales says. Therefore, it is perhaps one of the most nuanced disease states to treat, Hales explains.

As such, facilitating good communication between the disciplines is critical, particularly as new data emerge underscoring the importance of multidisciplinary care for optimal patient outcomes, Hales says. Ultimately, weighing insights from several specialties appears to be the optimal way to serve this patient population, Hales concludes. 

Russell Kenneth Hales, MD, discusses the role of multidisciplinary care in locally advanced lung cancer.  



Dr. Hales on the Role of Multidisciplinary Care in Locally Advanced Lung Cancer 

Russell Kenneth Hales, MD, director, Thoracic Oncology Multidisciplinary Program, assistant professor of radiation oncology and molecular radiation sciences, Sidney Kimmel Cancer Center, Johns Hopkins Medicine, discusses investigational treatment strategies that have the potential to build upon the positive results of the phase 3 PACIFIC trial (NCT02125461) in stage III non–small cell lung cancer (NSCLC). 

On February 16, 2018, the FDA approved durvalumab (Imfinzi) for the treatment of patients with unresectable stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. Findings from the randomized PACIFIC trial, which led to the regulatory decision, demonstrated significant overall survival and progression-free survival improvement with durvalumab compared with placebo in this patient population.

These results changed practice for patients with stage III NSCLC; however, the field is continuing to develop novel therapies that could improve responses further, Hales explains. For example, many of these patients are over the age of 70 years, have a history of smoking, and have comorbidities, which makes tolerating concurrent chemoradiation difficult. Therefore, research strategies are evaluating the efficacy of consolidative immunotherapy following radiation therapy alone. Although this likely wouldn’t be the standard for patients with stage III NSCLC, it could be useful for patients who are not candidates for chemotherapy.

Another strategy includes incorporating immunotherapy with concurrent chemoradiation to synergize their effects, Hales says. Additionally, giving patients neoadjuvant immunotherapy prior to chemoradiation or adding an adjuvant therapy like a PARP inhibitor with immunotherapy following chemoradiation may be useful strategies as well, Hales concludes.

Russell Kenneth Hales, MD, discusses investigational treatment strategies that have the potential to build upon the positive results of the phase 3 PACIFIC trial in stage III non–small cell lung cancer.  



Russell Kenneth Hales, MD

Articles

Dr Hales on the Use of Post-Operative Radiotherapy in NSCLC

Dr. Hales on the Role of Multidisciplinary Care in Locally Advanced Lung Cancer

Dr. Hales on Investigational Treatment Strategies to Build Upon the PACIFIC Trial Results in Stage III NSCLC