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Published in: World Journal of Surgical Oncology 1/2024

Open Access 01-12-2024 | Systemic Therapy | Research

The therapeutic effect of radiotherapy combined with systemic therapy compared to radiotherapy alone in patients with simple brain metastasis after first-line treatment of limited-stage small cell lung cancer: a retrospective study

Authors: Xinyu Gao, Tingting Liu, Min Fan, Hongfu Sun, Shixuan Zhou, Yuxin Zhou, Haolin Zhu, Ru Zhang, Zhanyuan Li, Wei Huang

Published in: World Journal of Surgical Oncology | Issue 1/2024

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Abstract

Purpose

We aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC).

Methods

The patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS).

Results

133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6–19.8) in combined therapy and 8.2 months (95% CI, 5.7–10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1–5 BMs (HR = 1.808, P = 0.012).

Conclusions

Compared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1–5 BMs reduce the risk of extracranial recurrence.
Literature
1.
go back to reference Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. Cancer J Clin. 2023;73(1):17–48. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. Cancer J Clin. 2023;73(1):17–48.
2.
go back to reference Petty WJ, Paz-Ares L. Emerging strategies for the treatment of small cell lung Cancer: a review. JAMA Oncol. 2023;9(3):419–29.CrossRefPubMed Petty WJ, Paz-Ares L. Emerging strategies for the treatment of small cell lung Cancer: a review. JAMA Oncol. 2023;9(3):419–29.CrossRefPubMed
3.
go back to reference Rossi A, Di Maio M, Chiodini P, Rudd RM, Okamoto H, Skarlos DV, et al. Carboplatin- or cisplatin-based chemotherapy in First-Line treatment of small-cell Lung Cancer: the COCIS Meta-Analysis of Individual Patient Data. J Clin Oncol. 2012;30(14):1692–8.CrossRefPubMed Rossi A, Di Maio M, Chiodini P, Rudd RM, Okamoto H, Skarlos DV, et al. Carboplatin- or cisplatin-based chemotherapy in First-Line treatment of small-cell Lung Cancer: the COCIS Meta-Analysis of Individual Patient Data. J Clin Oncol. 2012;30(14):1692–8.CrossRefPubMed
4.
go back to reference Lukas RV, Gondi V, Kamson DO, Kumthekar P, Salgia R. State-of-the-art considerations in small cell lung cancer brain metastases. Oncotarget. 2017;8(41):71223–33.CrossRefPubMedPubMedCentral Lukas RV, Gondi V, Kamson DO, Kumthekar P, Salgia R. State-of-the-art considerations in small cell lung cancer brain metastases. Oncotarget. 2017;8(41):71223–33.CrossRefPubMedPubMedCentral
5.
go back to reference Kristjansen PE, Soelberg Sørensen P, Skov Hansen M, Hansen HH. Prospective evaluation of the effect on initial brain metastases from small cell lung cancer of platinum-etoposide based induction chemotherapy followed by an alternating multidrug regimen. Ann Oncol. 1993;4(7):579–83.CrossRefPubMed Kristjansen PE, Soelberg Sørensen P, Skov Hansen M, Hansen HH. Prospective evaluation of the effect on initial brain metastases from small cell lung cancer of platinum-etoposide based induction chemotherapy followed by an alternating multidrug regimen. Ann Oncol. 1993;4(7):579–83.CrossRefPubMed
6.
go back to reference Lee JS, Murphy WK, Glisson BS, Dhingra HM, Holoye PY, Hong WK. Primary chemotherapy of Brain Metastasis in Small-Cell Lung Cancer. J Clin Oncol. 1989;7(7):916–22.CrossRefPubMed Lee JS, Murphy WK, Glisson BS, Dhingra HM, Holoye PY, Hong WK. Primary chemotherapy of Brain Metastasis in Small-Cell Lung Cancer. J Clin Oncol. 1989;7(7):916–22.CrossRefPubMed
7.
go back to reference Yomo S, Hayashi M. Is stereotactic radiosurgery a rational treatment option for brain metastases from small cell lung cancer? A retrospective analysis of 70 consecutive patients. BMC Cancer. 2015;15(1):95–102.CrossRefPubMedPubMedCentral Yomo S, Hayashi M. Is stereotactic radiosurgery a rational treatment option for brain metastases from small cell lung cancer? A retrospective analysis of 70 consecutive patients. BMC Cancer. 2015;15(1):95–102.CrossRefPubMedPubMedCentral
8.
go back to reference Putora PM, Fischer GF, Früh M, Califano R, Faivre-Finn C, Van Houtte P, et al. Treatment of brain metastases in small cell lung cancer: decision-making amongst a multidisciplinary panel of European experts. Radiother Oncol. 2020;149:84–8.CrossRefPubMed Putora PM, Fischer GF, Früh M, Califano R, Faivre-Finn C, Van Houtte P, et al. Treatment of brain metastases in small cell lung cancer: decision-making amongst a multidisciplinary panel of European experts. Radiother Oncol. 2020;149:84–8.CrossRefPubMed
9.
go back to reference Zhu Y, Cui Y, Zheng X, Zhao Y, Sun G. Small-cell lung cancer brain metastasis: from molecular mechanisms to diagnosis and treatment. Biochimica et Biophysica Acta (BBA) -. Mol Basis Disease. 2022;1868(12):166557.CrossRef Zhu Y, Cui Y, Zheng X, Zhao Y, Sun G. Small-cell lung cancer brain metastasis: from molecular mechanisms to diagnosis and treatment. Biochimica et Biophysica Acta (BBA) -. Mol Basis Disease. 2022;1868(12):166557.CrossRef
10.
go back to reference Rittberg R, Banerji S, Kim JO, Rathod S, Dawe DE. Treatment and Prevention of Brain metastases in Small Cell Lung Cancer. Am J Clin Oncol. 2021;44(12):629–38.CrossRefPubMed Rittberg R, Banerji S, Kim JO, Rathod S, Dawe DE. Treatment and Prevention of Brain metastases in Small Cell Lung Cancer. Am J Clin Oncol. 2021;44(12):629–38.CrossRefPubMed
11.
go back to reference Li B, Dai ZX, Chen YD, Liu YW, Liu S, Gu XN, et al. Systemic therapy after Radiotherapy significantly reduces the risk of mortality of patients with 1–3 brain metastases: a retrospective study of 250 patients. Chin Med J. 2017;130(24):2916–21.CrossRefPubMedPubMedCentral Li B, Dai ZX, Chen YD, Liu YW, Liu S, Gu XN, et al. Systemic therapy after Radiotherapy significantly reduces the risk of mortality of patients with 1–3 brain metastases: a retrospective study of 250 patients. Chin Med J. 2017;130(24):2916–21.CrossRefPubMedPubMedCentral
12.
go back to reference Tsui DCC, Camidge DR, Rusthoven CG. Managing Central Nervous System Spread of Lung Cancer: the state of the art. J Clin Oncol. 2022;40(6):642–60.CrossRefPubMed Tsui DCC, Camidge DR, Rusthoven CG. Managing Central Nervous System Spread of Lung Cancer: the state of the art. J Clin Oncol. 2022;40(6):642–60.CrossRefPubMed
13.
go back to reference Lin NU, Lee EQ, Aoyama H, Barani IJ, Barboriak DP, Baumert BG, et al. Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 2015;16(6):e270–8.CrossRefPubMed Lin NU, Lee EQ, Aoyama H, Barani IJ, Barboriak DP, Baumert BG, et al. Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 2015;16(6):e270–8.CrossRefPubMed
14.
go back to reference Gamboa-Vignolle C, Ferrari-Carballo T, Arrieta Ó, Mohar A. Whole-brain irradiation with concomitant daily fixed-dose Temozolomide for brain metastases treatment: a randomised phase II trial. Radiother Oncol. 2012;102(2):187–91.CrossRefPubMed Gamboa-Vignolle C, Ferrari-Carballo T, Arrieta Ó, Mohar A. Whole-brain irradiation with concomitant daily fixed-dose Temozolomide for brain metastases treatment: a randomised phase II trial. Radiother Oncol. 2012;102(2):187–91.CrossRefPubMed
15.
go back to reference Zhuang H, Yuan Z, Wang J, Zhao L, Pang Q, Wang P. Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma. Drug Des Devel Ther. 2013;7:1179–86.CrossRefPubMedPubMedCentral Zhuang H, Yuan Z, Wang J, Zhao L, Pang Q, Wang P. Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma. Drug Des Devel Ther. 2013;7:1179–86.CrossRefPubMedPubMedCentral
16.
go back to reference Liu Y, Liu XH, Wang Y, Zhu J, Xin Y, Niu K, et al. A study on different therapies and prognosis-related factors for 101 patients with SCLC and brain metastases. Cancer Biol Ther. 2017;18(9):670–5.CrossRefPubMedPubMedCentral Liu Y, Liu XH, Wang Y, Zhu J, Xin Y, Niu K, et al. A study on different therapies and prognosis-related factors for 101 patients with SCLC and brain metastases. Cancer Biol Ther. 2017;18(9):670–5.CrossRefPubMedPubMedCentral
17.
go back to reference Koide Y, Nagai N, Miyauchi R, Kitagawa T, Aoyama T, Shimizu H, et al. Radiotherapy or systemic therapy versus combined therapy in patients with brain metastases: a propensity-score matched study. J Neurooncol. 2022;160(1):191–200.CrossRefPubMed Koide Y, Nagai N, Miyauchi R, Kitagawa T, Aoyama T, Shimizu H, et al. Radiotherapy or systemic therapy versus combined therapy in patients with brain metastases: a propensity-score matched study. J Neurooncol. 2022;160(1):191–200.CrossRefPubMed
18.
go back to reference Neuhaus T, Ko Y, Muller RP, Grabenbauer GG, Hedde JP, Schueller H, et al. A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer. Br J Cancer. 2009;100(2):291–7.CrossRefPubMedPubMedCentral Neuhaus T, Ko Y, Muller RP, Grabenbauer GG, Hedde JP, Schueller H, et al. A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer. Br J Cancer. 2009;100(2):291–7.CrossRefPubMedPubMedCentral
19.
go back to reference Ge XH, Lin Q, Ren XC, Liu YE, Chen XJ, Wang DY, et al. Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer. Radiat Oncol. 2013;8(1):238.CrossRefPubMedPubMedCentral Ge XH, Lin Q, Ren XC, Liu YE, Chen XJ, Wang DY, et al. Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer. Radiat Oncol. 2013;8(1):238.CrossRefPubMedPubMedCentral
20.
go back to reference Postmus PE, Haaxma-Reiche H, Gregor A, Groen HJ, Lewinski T, Scolard T, et al. Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study. Radiother Oncol. 1998;46(1):29–32.CrossRefPubMed Postmus PE, Haaxma-Reiche H, Gregor A, Groen HJ, Lewinski T, Scolard T, et al. Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study. Radiother Oncol. 1998;46(1):29–32.CrossRefPubMed
21.
go back to reference Böttger F, Semenova EA, Song JY, Ferone G, van der Vliet J, Cozijnsen M, et al. Tumor heterogeneity underlies Differential Cisplatin Sensitivity in Mouse models of Small-Cell Lung Cancer. Cell Rep. 2019;27(11):3345–e33584.CrossRefPubMedPubMedCentral Böttger F, Semenova EA, Song JY, Ferone G, van der Vliet J, Cozijnsen M, et al. Tumor heterogeneity underlies Differential Cisplatin Sensitivity in Mouse models of Small-Cell Lung Cancer. Cell Rep. 2019;27(11):3345–e33584.CrossRefPubMedPubMedCentral
22.
go back to reference Li H, Xue R, Yang X, Han S, Yang W, Song X, et al. Best supportive care Versus whole-brain irradiation, chemotherapy alone, or WBRT Plus Chemotherapy in patients with brain metastases from small-cell lung Cancer: a case-controlled analysis. Front Oncol. 2021;11:568568.CrossRefPubMedPubMedCentral Li H, Xue R, Yang X, Han S, Yang W, Song X, et al. Best supportive care Versus whole-brain irradiation, chemotherapy alone, or WBRT Plus Chemotherapy in patients with brain metastases from small-cell lung Cancer: a case-controlled analysis. Front Oncol. 2021;11:568568.CrossRefPubMedPubMedCentral
23.
go back to reference Deeken JF, Löscher W. The blood-brain barrier and Cancer: transporters, treatment, and Trojan horses. Clin Cancer Res. 2007;13(6):1663–74.CrossRefPubMed Deeken JF, Löscher W. The blood-brain barrier and Cancer: transporters, treatment, and Trojan horses. Clin Cancer Res. 2007;13(6):1663–74.CrossRefPubMed
24.
go back to reference Seute T, Leffers P, Wilmink JT, ten Velde GP, Twijnstra A. Response of asymptomatic brain metastases from small-cell lung Cancer to systemic first-line chemotherapy. J Clin Oncol. 2006;24(13):2079–83.CrossRefPubMed Seute T, Leffers P, Wilmink JT, ten Velde GP, Twijnstra A. Response of asymptomatic brain metastases from small-cell lung Cancer to systemic first-line chemotherapy. J Clin Oncol. 2006;24(13):2079–83.CrossRefPubMed
25.
go back to reference Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus Docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65.CrossRefPubMed Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus Docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65.CrossRefPubMed
26.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
27.
go back to reference Chen Y, Paz-Ares L, Reinmuth N, Garassino MC, Statsenko G, Hochmair MJ, et al. Impact of brain metastases on treatment patterns and outcomes with First-Line Durvalumab Plus Platinum-Etoposide in extensive-stage SCLC (CASPIAN): a brief report. JTO Clin Res Rep. 2022;3(6):100330.PubMedPubMedCentral Chen Y, Paz-Ares L, Reinmuth N, Garassino MC, Statsenko G, Hochmair MJ, et al. Impact of brain metastases on treatment patterns and outcomes with First-Line Durvalumab Plus Platinum-Etoposide in extensive-stage SCLC (CASPIAN): a brief report. JTO Clin Res Rep. 2022;3(6):100330.PubMedPubMedCentral
28.
go back to reference Aupérin A, Arriagada R, Pignon JP, Le Péchoux 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.CrossRefPubMed Aupérin A, Arriagada R, Pignon JP, Le Péchoux 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.CrossRefPubMed
29.
go back to reference Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, et al. Summary Report on the graded Prognostic Assessment: an Accurate and Facile diagnosis-specific Tool to Estimate Survival for patients with brain metastases. J Clin Oncol. 2012;30(4):419–25.CrossRefPubMed Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, et al. Summary Report on the graded Prognostic Assessment: an Accurate and Facile diagnosis-specific Tool to Estimate Survival for patients with brain metastases. J Clin Oncol. 2012;30(4):419–25.CrossRefPubMed
30.
go back to reference Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010;77(3):655–61.CrossRefPubMed Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010;77(3):655–61.CrossRefPubMed
31.
go back to reference Bernhardt D, Adeberg S, Bozorgmehr F, Opfermann N, Hoerner-Rieber J, König L, et al. Outcome and prognostic factors in patients with brain metastases from small-cell lung cancer treated with whole brain radiotherapy. J Neuro Oncol. 2017;134(1):205–12.CrossRefPubMed Bernhardt D, Adeberg S, Bozorgmehr F, Opfermann N, Hoerner-Rieber J, König L, et al. Outcome and prognostic factors in patients with brain metastases from small-cell lung cancer treated with whole brain radiotherapy. J Neuro Oncol. 2017;134(1):205–12.CrossRefPubMed
32.
go back to reference Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37(4):745–51.CrossRefPubMed Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37(4):745–51.CrossRefPubMed
Metadata
Title
The therapeutic effect of radiotherapy combined with systemic therapy compared to radiotherapy alone in patients with simple brain metastasis after first-line treatment of limited-stage small cell lung cancer: a retrospective study
Authors
Xinyu Gao
Tingting Liu
Min Fan
Hongfu Sun
Shixuan Zhou
Yuxin Zhou
Haolin Zhu
Ru Zhang
Zhanyuan Li
Wei Huang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2024
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-024-03372-y

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