Proton beam therapy as a promising option for high-risk limited stage small cell lung cancer: revealing potential of future novel agents

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Radiat Oncol J. 2023;41(4):223-224
Publication date (electronic) : 2023 December 29
doi :
Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan, Republic of Korea
Correspondence: Chai Hong Rim Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, 123 Jeokgeum-ro, Danwon-gu, Ansan 15355, Republic of Korea. Tel: +82-31-412-6850 Email:
Received 2023 November 30; Revised 2023 December 11; Accepted 2023 December 12.

Radiotherapy (RT) is the main local treatment for limited-stage small-cell lung cancer (LS-SCLC). Notably, SCLC is extremely sensitive to radiotherapy. Turrisi et al. [1] demonstrated the oncological benefit of high radiation doses by showing the survival benefit of a 45 Gy/1.5 Gy bid protocol compared to the conventional 45 Gy in 25 fractions treatment. Recently, Faivre-Finn et al. [2] reported that treatment with 66 Gy in 33 fractions could achieve a survival similar to that of the bid regimen. Referencing the literature on non-small cell lung cancer (NSCLC), dose-escalation beyond 60–66 Gy is not always successful and has the potential to increase toxicity [3].

Despite high radiosensitivity, SCLC is prone to systemic recurrence. Considering the studies on NSCLC, whether further escalation of the RT dose can improve the prognosis of SCLC, requires further study. Many patients with SCLC have concomitant diseases and reduced lung function. Therefore, reducing lung exposure using proton beam therapy (PBT) may be a valid option for high-risk patients. In this issue of the Radiation Oncology Journal, although Seo et al. [4] applied PBT to a group with significantly poorer lung function, oncological outcomes and toxicity profiles were similar to those of the control group. While the literature on PBT for LS-SCLC is limited, this study is valuable in clinical and research terms.

Welsh et al. [5] conducted a phase I/II study, applying chemoradiation and pembrolizumab for LS-SCLC. Grade ≥2 pneumonia occurred in 15%, and median progression-free and overall survival were favorable at 19.75 months and 39.5 months, respectively. Unfortunately, a recent phase II randomized study (STIMULI trial) adding nivolumab and ipilimumab to standard treatment for LS-SCLC failed to demonstrate its benefit, resulting in an increase in grade ≥3 toxicities (62% vs. 25%) [6]. Nonetheless, the efficacy of various immunotherapeutic agents is being evaluated for LS-SCLC [7], hopefully achieving encouraging results as in NSCLC. If potential toxicities can be reduced using PBT, the effectiveness of immunotherapy in treating LS-SCLC may be revealed in the future.

Seo et al [4]. reported the safety and efficacy of PBT in patients with high-risk LS-SCLC. These results may expand the role of RT in high-risk groups of LS-SCLC and help demonstrate the effectiveness of novel agents.


Conflict of Interest

No potential conflict of interest relevant to this article was reported.


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