Role of prophylactic cranial irradiation in patients with limited disease small cell lung cancer: A Danish single institution cohort
DOI:
https://doi.org/10.2340/1651-226X.2025.43935Keywords:
Prophylactic cranial irradiation, Small cell lung cancer, Limited disease, cancer survival, cohort studyAbstract
Background and purpose: Prophylactic cranial irradiation (PCI) is part of standard treatment for patients with limited disease small cell lung cancer (LD-SCLC), treated with curative intent. However, doubt has been raised about the efficacy of PCI in a modern clinical setting. Therefore, we examined factors impacting PCI receival, the cumulative incidence of symptomatic brain metastases, and overall survival (OS) with and without PCI.
Patient/material and methods: Records of 190 patients with LD-SCLC consecutively treated between 2012 and 2021 at our institution were reviewed. Patients were grouped based on whether they received PCI (PCI, n = 119) or not (no PCI, n = 71). Baseline characteristics, Kaplan-Meier estimates of OS, and cumulative incidence of symptomatic brain metastases were compared for the two groups.
Results: PCI no patients were older, had a poorer performance status, were more often treated in 2018–2021 and had more frequently a brain magnetic resonance imaging (MRI) at the time of diagnosis. No PCI median OS was 19 months compared to 24 months for PCI, not significantly different (p = 0.40). During follow-up 54 patients (28.4%) developed symptomatic brain metastases, with no statistically significant difference in the numbers of patients with, and cumulative incidence of, symptomatic brain metastases between the two groups (p = 0.35 and p = 0.21, respectively).
Interpretation: Despite patients not receiving PCI being older and in poorer performance status, no statistically significant difference in OS or cumulative incidence of brain metastasis were observed compared to patients who received PCI. This supports uncertainty regarding the role of PCI.
Downloads
References
Dingemans AMC, Früh M, Ardizzoni A, Besse B, Faivre-Finn C, Hendriks LE, et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(7):839–53.
https://doi.org/10.1016/j.annonc.2021.03.207 DOI: https://doi.org/10.1016/j.annonc.2021.03.207
Turrisi AT, 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999;340(4):265–71.
https://doi.org/10.1056/NEJM199901283400403 DOI: https://doi.org/10.1056/NEJM199901283400403
Higgins KA, Gorgens S, Sudmeier LJ, Faivre-Finn C. Recent developments in limited stage small cell lung cancer. Transl Lung Cancer Res. 2019;8(Suppl 2):S147–52.
https://doi.org/10.21037/tlcr.2019.05.13 DOI: https://doi.org/10.21037/tlcr.2019.05.13
Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017;18(8):1116–25.
https://doi.org/10.1016/S1470-2045(17)30318-2 DOI: https://doi.org/10.1016/S1470-2045(17)30318-2
Gronberg BH, Killingberg KT, Flotten O, Brustugun OT, Hornslien K, Madebo T, et al. High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial. Lancet Oncol. 2021;22(3):321–31.
https://doi.org/10.1016/S1470-2045(20)30742-7 DOI: https://doi.org/10.1016/S1470-2045(20)30742-7
Winther-Larsen A, Hoffmann L, Moeller DS, Khalil AA, Knap MM. Evaluation of factors associated with loco-regional failure and survival in limited disease small cell lung cancer patients treated with chemoradiotherapy. Acta Oncol. 2015;54(9):1574–81.
10.3109/0284186X.2015.1062135 DOI: https://doi.org/10.3109/0284186X.2015.1062135
Seute T, Leffers P, ten Velde GP, Twijnstra A. Neurologic disorders in 432 consecutive patients with small cell lung carcinoma. Cancer. 2004;100(4):801–6.
https://doi.org/10.1002/cncr.20043 DOI: https://doi.org/10.1002/cncr.20043
Auperin A, Arriagada R, Pignon JP, Le Pechoux C, Gregor A, Stephens RJ, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999;341(7):476–84.
https://doi.org/10.1056/NEJM199908123410703 DOI: https://doi.org/10.1056/NEJM199908123410703
Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357(7):664–72.
https://doi.org/10.1056/NEJMoa071780 DOI: https://doi.org/10.1056/NEJMoa071780
Hochstenbag MM, Twijnstra A, Wilmink JT, Wouters EF, ten Velde GP. Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis. J Neurooncol. 2000;48(3):243–8.
https://doi.org/10.1023/a:1006427407281 DOI: https://doi.org/10.1023/A:1006427407281
Seute T, Leffers P, ten Velde GP, Twijnstra A. Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI). Cancer. 2008;112(8):1827–34.
https://doi.org/10.1002/cncr.23361 DOI: https://doi.org/10.1002/cncr.23361
Gaebe K, Erickson AW, Li AY, Youssef AN, Sharma B, Chan KKW, et al. Re-examining prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis. EClinicalMedicine. 2024;67:102396.
https://doi.org/10.1016/j.eclinm.2023.102396 DOI: https://doi.org/10.1016/j.eclinm.2023.102396
Takahashi T, Yamanaka T, Seto T, Harada H, Nokihara H, Saka H, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(5):663–71.
https://doi.org/10.1016/S1470-2045(17)30230-9 DOI: https://doi.org/10.1016/S1470-2045(17)30230-9
Wolfson AH, Bae K, Komaki R, Meyers C, Movsas B, Le Pechoux C, et al. Primary analysis of a phase II randomized trial Radiation Therapy Oncology Group (RTOG) 0212: impact of different total doses and schedules of prophylactic cranial irradiation on chronic neurotoxicity and quality of life for patients with limited-disease small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;81(1):77–84.
https://doi.org/10.1016/j.ijrobp.2010.05.013 DOI: https://doi.org/10.1016/j.ijrobp.2010.05.013
Belderbos JSA, De Ruysscher DKM, De Jaeger K, Koppe F, Lambrecht MLF, Lievens YN, et al. Phase 3 randomized trial of prophylactic cranial irradiation with or without hippocampus avoidance in SCLC (NCT01780675). J Thorac Oncol. 2021;16(5):840–9.
https://doi.org/10.1016/j.jtho.2020.12.024 DOI: https://doi.org/10.1016/j.jtho.2020.12.024
de Ruiter MB, Groot PFC, Deprez S, Pullens P, Sunaert S, de Ruysscher D, et al. Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small cell lung cancer reduces hippocampal atrophy compared to conventional PCI. Neuro Oncol. 2023;25(1):167–76.
https://doi.org/10.1093/neuonc/noac148 DOI: https://doi.org/10.1093/neuonc/noac148
Rodriguez de Dios N, Counago F, Murcia-Mejia M, Rico-Oses M, Calvo-Crespo P, Samper P, et al. Randomized phase III trial of prophylactic cranial irradiation with or without hippocampal avoidance for small-cell lung cancer (PREMER): a GICOR-GOECP-SEOR study. J Clin Oncol. 2021;39(28):3118–27.
https://doi.org/10.1200/JCO.21.00639 DOI: https://doi.org/10.1200/JCO.21.00639
Daly ME, Ismaila N, Decker RH, Higgins K, Owen D, Saxena A, et al. Radiation therapy for small-cell lung cancer: ASCO guideline endorsement of an ASTRO guideline. J Clin Oncol. 2021;39(8):931–9.
https://doi.org/10.1200/JCO.20.03364 DOI: https://doi.org/10.1200/JCO.20.03364
Qiu B, Li Q, Liu J, Huang Y, Pang Q, Zhu Z, et al. Moderately hypofractionated once-daily compared with twice-daily thoracic radiation therapy concurrently with etoposide and cisplatin in limited-stage small cell lung cancer: a multicenter, Phase II, randomized trial. Int J Radiat Oncol Biol Phys. 2021;111(2):424–35.
https://doi.org/https://doi.org/10.1016/j.ijrobp.2021.05.003 DOI: https://doi.org/10.1016/j.ijrobp.2021.05.003
Cheng Y, Spigel DR, Cho BC, Laktionov KK, Fang J, Chen Y, et al. Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer. N Engl J Med. 2024;391(14):1313–27.
https://doi.org/10.1056/NEJMoa2404873 DOI: https://doi.org/10.1056/NEJMoa2404873
Møller DS, Holt MI, Alber M, Tvilum M, Khalil AA, Knap MM, et al. Adaptive radiotherapy for advanced lung cancer ensures target coverage and decreases lung dose. Radiother Oncol. 2016;121(1):32–8.
https://doi.org/10.1016/j.radonc.2016.08.019 DOI: https://doi.org/10.1016/j.radonc.2016.08.019
Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjögren M,
et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke. 2001;32(6):1318–22.
https://doi.org/10.1161/01.STR.32.6.1318 DOI: https://doi.org/10.1161/01.STR.32.6.1318
Longstreth WT, Jr, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA, et al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke. 1996;27(8):1274–82.
https://doi.org/10.1161/01.str.27.8.1274 DOI: https://doi.org/10.1161/01.STR.27.8.1274
Andreatta Maduro P, Guimarães MP, de Sousa Rodrigues M, Pereira Rolim Coimbra Pinto AP, da Mota Junior AA, Lima Rocha AS, et al. Comparing the efficacy of two cognitive screening tools in identifying gray and white matter brain damage among older adults. J Aging Res. 2024;2024:5527225.
https://doi.org/10.1155/2024/5527225 DOI: https://doi.org/10.1155/2024/5527225
Noh T, Walbert T. Brain metastasis: clinical manifestations, symptom management, and palliative care. Handb Clin Neurol. 2018;149:75–88.
https://doi.org/10.1016/B978-0-12-811161-1.00006-2 DOI: https://doi.org/10.1016/B978-0-12-811161-1.00006-2
Jena A, Taneja S, Talwar V, Sharma JB. Magnetic resonance (MR) patterns of brain metastasis in lung cancer patients: correlation of imaging findings with symptom. J Thorac Oncol. 2008;3(2):140–4.
https://doi.org/10.1097/JTO.0b013e318161d775 DOI: https://doi.org/10.1097/JTO.0b013e318161d775
Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379(23):2220–9.
https://doi.org/10.1056/NEJMoa1809064 DOI: https://doi.org/10.1056/NEJMoa1809064
Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929–39.
https://doi.org/10.1016/s0140-6736(19)32222-6 DOI: https://doi.org/10.1016/S0140-6736(19)32222-6
Varlotto J, Voland R, DeCamp M, Khatri J, Shweihat Y, Nwanwene K, et al. Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era. Radiother Oncol. 2025;202.
https://doi.org/10.1016/j.radonc.2024.110619 DOI: https://doi.org/10.1016/j.radonc.2024.110619
Additional Files
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2025 Sara Linde, Marianne Maquard Knap, Lone Hoffmann, Azza Ahmed Kahlil, Christina Maria Lutz, Maria Kandi, Lise Saksø Mortensen, Ditte Sloth Møller, Hjørdis Hjalting Schmidt
This work is licensed under a Creative Commons Attribution 4.0 International License.
