The overall survival impact of prophylactic cranial irradiation in limited-stage small-cell lung cancer: A systematic review and meta-analysis

Mathijs L Tomassen; Jacquelien Pomp; Janneke van der Stap; Anne S R van Lindert; Max Peters; José S.A. Belderbos; Dirk K M De Ruysscher; Steven H Lin; Joost J C Verhoeff; Peter S N van Rossum

doi:10.1016/j.ctro.2022.02.002

The overall survival impact of prophylactic cranial irradiation in limited-stage small-cell lung cancer: A systematic review and meta-analysis

Mathijs L Tomassen, Jacquelien Pomp, Janneke van der Stap, Anne S R van Lindert, Max Peters, José S.A. Belderbos, Dirk K M De Ruysscher, Steven H Lin, Joost J C Verhoeff^*, Peter S N van Rossum^*

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

Background: Prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) patients has become more controversial. Since the publication of the systematic review by Aupérin et al. in 1999, no randomized controlled trials regarding PCI in LS-SCLC have been completed. The aim of this study was to systematically review and meta-analyze the effect of PCI on overall survival (OS) in patients with LS-SCLC.

Methods: A systematic search was conducted in the databases of MEDLINE (PubMed), Embase and the Cochrane library. Only studies that reported an adjusted hazard ratio (aHR), indicating the effect of PCI versus no PCI on OS (adjusted for confounders) in patients with LS-SCLC were included for critical appraisal and meta-analysis. A pooled aHR estimate was calculated using a random-effects model.

Results: Pooling of 28 retrospective studies including a total of 18,575 patients demonstrated a significant beneficial effect of PCI versus no PCI on OS with a pooled aHR of 0.62 (95% CI: 0.57-0.69). Substantial heterogeneity of reported aHRs among studies was observed (I2 = 65.9%). Subgroup analyses revealed that this heterogeneity could partly be explained by study sample size. The pooled aHR among 7 versus 21 studies with a sample size of > 300 versus ≤ 300 patients was 0.79 (95% CI: 0.64-0.97) versus 0.56 (95% CI: 0.46-0.69; p < 0.001), respectively.

Conclusions: This meta-analysis demonstrates a significant beneficial effect of PCI on OS in patients with LS-SCLC. Larger studies reported a milder beneficial effect, possibly due to a decreased risk of model overfitting. Serious risk of selection and confounding bias were of concern due to the lack of prospective trials. These results support the role of PCI in standard clinical practice in patients with LS-SCLC while awaiting results of prospective trials on alternative strategies.

Original language	English
Pages (from-to)	145-152
Number of pages	8
Journal	Clinical and Translational Radiation Oncology
Volume	33
DOIs	https://doi.org/10.1016/j.ctro.2022.02.002
Publication status	Published - Mar 2022

Keywords

CHEMORADIOTHERAPY
ELDERLY-PATIENTS
ONCOLOGY
OUTCOMES
QUALITY-OF-LIFE
RANDOMIZED-TRIAL
RESECTION
SCHEDULES
THERAPY
TNM STAGE

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Tomassen, M. L., Pomp, J., van der Stap, J., van Lindert, A. S. R., Peters, M., Belderbos, J. S. A., De Ruysscher, D. K. M., Lin, S. H., Verhoeff, J. J. C., & van Rossum, P. S. N. (2022). The overall survival impact of prophylactic cranial irradiation in limited-stage small-cell lung cancer: A systematic review and meta-analysis. Clinical and Translational Radiation Oncology, 33, 145-152. https://doi.org/10.1016/j.ctro.2022.02.002

@article{7e62631969f945fe91726f783d1b0e16,

title = "The overall survival impact of prophylactic cranial irradiation in limited-stage small-cell lung cancer: A systematic review and meta-analysis",

abstract = "Background: Prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) patients has become more controversial. Since the publication of the systematic review by Aup{\'e}rin et al. in 1999, no randomized controlled trials regarding PCI in LS-SCLC have been completed. The aim of this study was to systematically review and meta-analyze the effect of PCI on overall survival (OS) in patients with LS-SCLC.Methods: A systematic search was conducted in the databases of MEDLINE (PubMed), Embase and the Cochrane library. Only studies that reported an adjusted hazard ratio (aHR), indicating the effect of PCI versus no PCI on OS (adjusted for confounders) in patients with LS-SCLC were included for critical appraisal and meta-analysis. A pooled aHR estimate was calculated using a random-effects model.Results: Pooling of 28 retrospective studies including a total of 18,575 patients demonstrated a significant beneficial effect of PCI versus no PCI on OS with a pooled aHR of 0.62 (95% CI: 0.57-0.69). Substantial heterogeneity of reported aHRs among studies was observed (I2 = 65.9%). Subgroup analyses revealed that this heterogeneity could partly be explained by study sample size. The pooled aHR among 7 versus 21 studies with a sample size of > 300 versus ≤ 300 patients was 0.79 (95% CI: 0.64-0.97) versus 0.56 (95% CI: 0.46-0.69; p < 0.001), respectively.Conclusions: This meta-analysis demonstrates a significant beneficial effect of PCI on OS in patients with LS-SCLC. Larger studies reported a milder beneficial effect, possibly due to a decreased risk of model overfitting. Serious risk of selection and confounding bias were of concern due to the lack of prospective trials. These results support the role of PCI in standard clinical practice in patients with LS-SCLC while awaiting results of prospective trials on alternative strategies.",

keywords = "CHEMORADIOTHERAPY, ELDERLY-PATIENTS, ONCOLOGY, OUTCOMES, QUALITY-OF-LIFE, RANDOMIZED-TRIAL, RESECTION, SCHEDULES, THERAPY, TNM STAGE",

author = "Tomassen, {Mathijs L} and Jacquelien Pomp and {van der Stap}, Janneke and {van Lindert}, {Anne S R} and Max Peters and Belderbos, {Jos{\'e} S.A.} and {De Ruysscher}, {Dirk K M} and Lin, {Steven H} and Verhoeff, {Joost J C} and {van Rossum}, {Peter S N}",

note = "{\textcopyright} 2022 The Author(s).",

year = "2022",

month = mar,

doi = "10.1016/j.ctro.2022.02.002",

language = "English",

volume = "33",

pages = "145--152",

journal = "Clinical and Translational Radiation Oncology",

issn = "2405-6308",

publisher = "Elsevier Ireland Ltd",

}

Tomassen, ML, Pomp, J, van der Stap, J, van Lindert, ASR, Peters, M, Belderbos, JSA, De Ruysscher, DKM, Lin, SH, Verhoeff, JJC & van Rossum, PSN 2022, 'The overall survival impact of prophylactic cranial irradiation in limited-stage small-cell lung cancer: A systematic review and meta-analysis', Clinical and Translational Radiation Oncology, vol. 33, pp. 145-152. https://doi.org/10.1016/j.ctro.2022.02.002

The overall survival impact of prophylactic cranial irradiation in limited-stage small-cell lung cancer: A systematic review and meta-analysis. / Tomassen, Mathijs L; Pomp, Jacquelien; van der Stap, Janneke et al.
In: Clinical and Translational Radiation Oncology, Vol. 33, 03.2022, p. 145-152.

Research output: Contribution to journal › (Systematic) Review article › peer-review

TY - JOUR

T1 - The overall survival impact of prophylactic cranial irradiation in limited-stage small-cell lung cancer

T2 - A systematic review and meta-analysis

AU - Tomassen, Mathijs L

AU - Pomp, Jacquelien

AU - van der Stap, Janneke

AU - van Lindert, Anne S R

AU - Peters, Max

AU - Belderbos, José S.A.

AU - De Ruysscher, Dirk K M

AU - Lin, Steven H

AU - Verhoeff, Joost J C

AU - van Rossum, Peter S N

PY - 2022/3

Y1 - 2022/3

N2 - Background: Prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) patients has become more controversial. Since the publication of the systematic review by Aupérin et al. in 1999, no randomized controlled trials regarding PCI in LS-SCLC have been completed. The aim of this study was to systematically review and meta-analyze the effect of PCI on overall survival (OS) in patients with LS-SCLC.Methods: A systematic search was conducted in the databases of MEDLINE (PubMed), Embase and the Cochrane library. Only studies that reported an adjusted hazard ratio (aHR), indicating the effect of PCI versus no PCI on OS (adjusted for confounders) in patients with LS-SCLC were included for critical appraisal and meta-analysis. A pooled aHR estimate was calculated using a random-effects model.Results: Pooling of 28 retrospective studies including a total of 18,575 patients demonstrated a significant beneficial effect of PCI versus no PCI on OS with a pooled aHR of 0.62 (95% CI: 0.57-0.69). Substantial heterogeneity of reported aHRs among studies was observed (I2 = 65.9%). Subgroup analyses revealed that this heterogeneity could partly be explained by study sample size. The pooled aHR among 7 versus 21 studies with a sample size of > 300 versus ≤ 300 patients was 0.79 (95% CI: 0.64-0.97) versus 0.56 (95% CI: 0.46-0.69; p < 0.001), respectively.Conclusions: This meta-analysis demonstrates a significant beneficial effect of PCI on OS in patients with LS-SCLC. Larger studies reported a milder beneficial effect, possibly due to a decreased risk of model overfitting. Serious risk of selection and confounding bias were of concern due to the lack of prospective trials. These results support the role of PCI in standard clinical practice in patients with LS-SCLC while awaiting results of prospective trials on alternative strategies.

AB - Background: Prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) patients has become more controversial. Since the publication of the systematic review by Aupérin et al. in 1999, no randomized controlled trials regarding PCI in LS-SCLC have been completed. The aim of this study was to systematically review and meta-analyze the effect of PCI on overall survival (OS) in patients with LS-SCLC.Methods: A systematic search was conducted in the databases of MEDLINE (PubMed), Embase and the Cochrane library. Only studies that reported an adjusted hazard ratio (aHR), indicating the effect of PCI versus no PCI on OS (adjusted for confounders) in patients with LS-SCLC were included for critical appraisal and meta-analysis. A pooled aHR estimate was calculated using a random-effects model.Results: Pooling of 28 retrospective studies including a total of 18,575 patients demonstrated a significant beneficial effect of PCI versus no PCI on OS with a pooled aHR of 0.62 (95% CI: 0.57-0.69). Substantial heterogeneity of reported aHRs among studies was observed (I2 = 65.9%). Subgroup analyses revealed that this heterogeneity could partly be explained by study sample size. The pooled aHR among 7 versus 21 studies with a sample size of > 300 versus ≤ 300 patients was 0.79 (95% CI: 0.64-0.97) versus 0.56 (95% CI: 0.46-0.69; p < 0.001), respectively.Conclusions: This meta-analysis demonstrates a significant beneficial effect of PCI on OS in patients with LS-SCLC. Larger studies reported a milder beneficial effect, possibly due to a decreased risk of model overfitting. Serious risk of selection and confounding bias were of concern due to the lack of prospective trials. These results support the role of PCI in standard clinical practice in patients with LS-SCLC while awaiting results of prospective trials on alternative strategies.

KW - CHEMORADIOTHERAPY

KW - ELDERLY-PATIENTS

KW - ONCOLOGY

KW - OUTCOMES

KW - QUALITY-OF-LIFE

KW - RANDOMIZED-TRIAL

KW - RESECTION

KW - SCHEDULES

KW - THERAPY

KW - TNM STAGE

U2 - 10.1016/j.ctro.2022.02.002

DO - 10.1016/j.ctro.2022.02.002

M3 - (Systematic) Review article

C2 - 35243025

SN - 2405-6308

VL - 33

SP - 145

EP - 152

JO - Clinical and Translational Radiation Oncology

JF - Clinical and Translational Radiation Oncology

ER -