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Review
. 2021 Apr 28;13(9):2132.
doi: 10.3390/cancers13092132.

Radiation for Oligometastatic Lung Cancer in the Era of Immunotherapy: What Do We (Need to) Know?

Stephanie T H Peeters  1 , Evert J Van Limbergen  1 , Lizza E L Hendriks  2 , Dirk De Ruysscher  1
Affiliations
Review

Radiation for Oligometastatic Lung Cancer in the Era of Immunotherapy: What Do We (Need to) Know?

Stephanie T H Peeters et al. Cancers (Basel). .

Abstract

Oligometastatic cancer is recognized as a separate entity within the spectrum of metastatic disease. It was suggested that patients with oligometastatic disease can obtain long-term survival by giving local ablative therapy (LAT) to all visible disease locations. However, the true extent from which metastatic cancer should be called "oligometastatic" is unknown, although a consensus definition for oligometastatic disease is proposed by research organizations, such as the EORTC (maximum of five metastases in three organs). Different states of the oligometastatic disease are defined, such as synchronous vs. metachronous, oligopersistent vs. oligoprogressive disease. All clinical trials including patients with non-small cell lung cancer (NSCLC) are small and most are not randomized. Two small randomized phase II trials on synchronous disease showed an improvement in progression free survival, with the addition of LAT, and one also demonstrated an overall survival benefit. Immune checkpoint inhibitors (ICI) were not part of the treatment in these trials, while ICI significantly improved long-term outcomes of patients with metastatic NSCLC. Radiotherapy might improve the prognosis of patients treated with ICI because of its immunostimulatory effects and the possibility to eradicate metastatic deposits. Here, we summarize the data for adding ablative radiotherapy to the treatment of oligometastatic NSCLC, especially in the ICI era, and discuss the challenges of combined treatment.

Keywords: immune checkpoint inhibitor; immunotherapy; non-small cell lung cancer; oligometastatic; radiotherapy.

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Conflict of interest statement

Stephanie Peeters declares no conflict of interest. Evert van Limbergen declares no conflict of interest. Lizza Hendriks declares no conflict of interest related to the current manuscript; (outside of current manuscript: research funding Roche Genentech, Boehringer Ingelheim, AstraZeneca (all institution); advisory board: Boehringer, BMS, Eli Lilly, Roche Genentech, Pfizer, Takeda, MSD, Boehringer Ingelheim, Amgen, AstraZeneca (all institution); speaker–MSD (institution); travel/conference reimbursement: Roche Genentech (self); mentorship program with key opinion leaders–funded by AstraZeneca; fees for educational webinars–Quadia (self); interview sessions funded by Roche Genentech (institution); local PI of clinical trials–AstraZeneca, Novartis, BMS, MSD/Merck, GSK, Takeda, Blueprint Medicines, Roche Genentech, Janssen Pharmaceuticals, Mirati). Dirk De Ruysscher declares no conflict of interest related to the current manuscript.

Figures

Figure 1
Figure 1
Trials from Table 1 classified according to the classification of the ESTRO/EORTC recommendation [9], except for the Collen trial, which could not be classified because of missing information. Reprinted from [9] with permission from Elsevier and adapted.
Figure 2
Figure 2
Overall survival (OS) (a) and progression-free survival (PFS) (b) at different time-points (1–6 years). Data points were obtained from the original papers in the text or derived from the graphs. The data points connected with full lines represent (mainly) synchronous, and with striped lines (mainly) metachronous oligometastatic disease. For comparison, in Figure 2a, the 1y and 2y OS results are shown from the Keynote-024 RCT (KN024) on metastatic disease treated with chemo (blue diamonds) or ICI (red diamonds), without LAT. Bauml: PFS-L is reported. Only ‘Bauml’ and ‘KN024 pembro’ show patients with ICI treatment.
See this image and copyright information in PMC

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