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What is the role of radiotherapy for extensive-stage small cell lung cancer in the immunotherapy era?

ABSTRACT: Small cell lung cancer has been a difficult disease to treat with poor survival and few significant improvements in outcomes in the last three decades. Most recently the addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) resulted in improved overall survival and progression-free survival compared to chemotherapy alone. Recent randomized studies examining both consolidative thoracic radiotherapy and prophylactic cranial irradiation (PCI) in ES-SCLC have impacted the utilization of these interventions. The approval of immune checkpoint inhibitors (ICIs) to platinum/etoposide chemotherapy for the treatment of ES-SCLC in the front-line setting may also further impact the role of radiotherapy in this disease. In this article, we review the current evidence supporting thoracic radiotherapy in ES-SCLC and discuss the promising therapeutic implications of thoracic radiation in light of the inclusion of ICIs. We also address how the increasing routine use of surveillance brain magnetic resonance imaging (MRI) and ICIs may diminish the use of PCI in ES-SCLC.

SUBMITTER: Nesbit EG

PROVIDER: S-EPMC6795575 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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What is the role of radiotherapy for extensive-stage small cell lung cancer in the immunotherapy era?

Nesbit Eric G EG Leal Ticiana A TA Kruser Tim J TJ

Translational lung cancer research 20190901 Suppl 2

Small cell lung cancer has been a difficult disease to treat with poor survival and few significant improvements in outcomes in the last three decades. Most recently the addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) resulted in improved overall survival and progression-free survival compared to chemotherapy alone. Recent randomized studies examining both consolidative thoracic radiotherapy and prophylactic cranial irradia ...[more]

PMID: 31673520

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Project description:Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%-2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients' survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.

Project description:Background: Rechallenge of immunotherapy beyond progression (RIBP) has been demonstrably effective in a variety of cancers. Our study aims to investigate the efficacy of RIBP in small-cell lung cancer (SCLC) patients under real-world conditions. Methods: SCLC patients who experienced progressive disease after receiving programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors combined with chemotherapy from January 2017 to October 2021 were enrolled. The study population was divided into two groups: the RIBP group and the discontinuation of immunotherapy beyond progression (DIBP) group. Inverse propensity score weighting (IPSW) method was used to balance the clinical baseline characteristics. The short-term and long-term efficacy of the two groups was compared. Results: 100 SCLC patients were included in this study. There were 45 patients in the RIBP group and 55 patients in the DIBP group. The disease control rate (DCR) and the proportion of durable clinical benefit (DCB) were significantly higher in the RIBP group (DCR: 79.7% vs. 55.7%, p = 0.027; DCB: 40.7 vs. 20.7%, p = 0.025) after weighting. The median progressive-free survival (PFS) in the RIBP group was significantly longer than the DIBP group in the total population (mPFS: 4.8 vs. 2.4 months, p = 0.002), while there was no significant difference in overall survival (OS) of the two groups (mOS: 17.4 vs. 8.0 months, p = 0.098). In the weighted first-line initial immunotherapy subgroup, PFS and OS were significantly improved in the RIBP group (mPFS: 4.5 vs. 2.8 months, p = 0.017; mOS: 11.6 vs. 5.4 months, p = 0.028). After weighting, the RIBP group had a significantly longer PFS than the DIBP group in the SD/PD response to the initial immunotherapy subgroup (mPFS: 6.8 vs. 1.8 months, p = 0.026). Conclusion: Rechallenge of PD-1/PD-L1 inhibitors could bring benefits to SCLC patients, especially in the first-line initial immunotherapy subgroup or SD/PD response to the initial immunotherapy subgroup.

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What is the role of radiotherapy for extensive-stage small cell lung cancer in the immunotherapy era?

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What is the role of radiotherapy for extensive-stage small cell lung cancer in the immunotherapy era?

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