In Part 1, Maria Werner-Wasik, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, discussed the rapidly changing standards of care for patients with stage III non-small cell lung cancer with the advent of preoperative combination chemotherapy and immunotherapy.

In this video, Dr Werner-Wasik explains that with this new modality, more patients may be considered for inclusion of surgery and notes which patients may be better suited to remain with definitive chemoradiation. She also discusses the possibility of combining stereotactic body radiotherapy with chemoimmunotherapy, followed by surgery.

Watch Part 1

Transcript:

We as radiation oncologists are seeing in our practices and in the multidisciplinary tumor boards where patients with lung cancer being discussed, that the recommendations are changing rapidly. More and more patients are being considered for inclusion of surgery in their management while having chemoimmunotherapy as a standard, especially as this was approved by the FDA a few months ago.

It is not fully clear which patients are considered resectable or not. That standard is evolving and may differ between different institutions and different surgeons depending on their personal experience in surgery. However, what is unusual patients who do well after chemoimmunotherapy followed by surgery these days seem to be not only those who had single nodal level involvement, but also patients who have multiple nodal levels involved in mediastinum and some patients with T4 lesions or T4N1 lesions. This creates a completely novel landscape of treatment and leaves us radiation oncologists wondering which patients will continue to receive chemoradiation with a definitive intention without surgery.

Some examples which come to mind may include those who have contraindications to immunotherapy. There is a small subgroup of patients, maybe 10%, who have autoimmune diseases such as lupus, active rheumatoid arthritis, multiple sclerosis, who per virtue of some other coexisting disease are on chronic steroids. And those patients will be excluded from the approach of chemoimmunotherapy for all by surgery and per default, I would imagine they will continue to get definitive chemoradiation.

Also, patients with specific situations, for example, a pancoast tumor which involves brachial plexus and is associated with severe pain and where local tumor control is of paramount importance. That patient may be more likely to be considered for definitive chemoradiation or preoperative chemoradiation followed by surgery since it is unclear whether lack of response in those tumors to chemoimmunotherapy may result in higher risk of local tumor progression or recurrence if surgery is performed, there may be other scenarios where radiation may be still useful.

Another very interesting approach is the consideration of using radiation not in this 6 or 7 week daily regimen standard fractionated, but instead using a short regimen of stereotactic body radiotherapy, SBRT, for example, 8 gray times 3 or 6 gray times 5, the doses which are considered in preclinical data to be more of immunostimulatory or immunomodulating radiation rather than cytocidal radiation. This can be combined easily with chemoimmunotherapy and then followed by surgery. One such study comes from first author, [Nasser] Altorki [, MD, Weill Cornell Medicine, New York, NY] in which patients received neoadjuvant durvalumab with or without stereotactic body radiotherapy, a short course of radiotherapy 8 Gray times 3 was used, which is considered to be more immunomodulatory and immunostimulating rather than the standard course of 5 or 6 weeks of daily radiation treatments. This was a single center randomized phase 2 trial and it showed a very impressive difference in pathologic complete response rate being 31% in the experimental arm of SBRT and durvalumab immunotherapy versus essentially no pathologic complete responses in the durvalumab arm. This is one of the potential approaches of radiotherapy used in the future and definitely it's intriguing enough that it needs to be studied further.

In summary, it is very exciting time to observe that patients can have wonderful outcomes with introduction of immunotherapy in earlier stage lung cancer and in earlier phases of the treatment rather than only as consolidation therapy per PACIFIC trial. There are many ongoing other large clinical trials which are looking at various combinations of immunotherapy with chemotherapy or immunotherapy alone, and we're awaiting the results of those trials. Thank you for attention.

Source:

Werner-Wasik M. “Preoperative Therapy for Stage III Non-Small Cell Lung Cancer: The Big Revival.” Presented at: Radiation Oncology Summit: ACRO 2023; March 15-18, 2023; Lake Buena Vista, FL.