Survival benefit of prophylactic cranial irradiation in limited-stage small-cell lung cancer in modern magnetic resonance imaging staging: a systematic review and meta-analysis

Figures & data

Figure 1. Flow chart of literature search in the meta-analysis.

Table 1. Characteristics of the included trials in the meta-analysis.

Study, y	Median age, y	Patients, n		Male, %		Complete response (%)		Proportion of stage III (%)	Primary therapy	PCI schedule (Gy/fraction)	Restaging brain scan	Median FU (months)
		PCI	No PCI	PCI	No PCI	PCI	No PCI
Farris, 2019 [8]	NR	39	53	10 (26.0)	28 (53.0)	12 (30.8)	17 (32.1)	67.0	TRT	25Gy/10F	no routine	NR
Lim, 2022 [16]	68	26	81	22 (84.6)	69 (85.2)	NR	NR	NR	Both	25–37.5 Gy in 1.5‒3Gy	NR	NR
Pezzi, 2020 [10]	66	84	84	49 (58.3)	47 (56.0)	27 (71.1)	35 (53.8)	NR	TRT	25–30Gy/10–15F	yes	84
Qi, 2022 [15]	<65	75	75	11 (14.7)	59 (78.7)	16 (21.3)	8 (10.7)	68.0	TRT	25Gy/10F	yes	25
Li, 2021 [11]	<70	69	69	50 (75.3)	51(65.5)	29 (42.0)	21(30.4)	76.1	TRT	25Gy/10F	yes	17.8
Ghanta, 2021 [13]	66	83	83	32 (38.6)	31 (37.3)	23 (27.7)	22 (26.5)	75.1	TRT	25–36Gy/10–18F	yes	21.3
Eze, 2017 [14]	63	71	113	36 (50.7)	75 (66.4)	NR	NR	NR	TRT	30Gy/15F	yes	NR
Zhu, 2014 [23]	55	67	126	49(73.1)	101 (80.2)	NR	NR	52.3	Surgery	25Gy/10F	no routine	39.4
Farooqi, 2017 [25]	62	364	294	187(51.4)	155 (52.7)	NR	NR	NR	TRT	25Gy/10F	NR	21
Korczynska, 2018 [21]	60	167	104	103(61.7)	71 (68.3)	Total, 172 (63.5)		NR	TRT	30Gy/15F	yes	33.2
Yin, 2018 [24]	<60	88	52	Total, 81(57.9)		NR	NR	72.9	Both	30–40Gy in 2–3Gy	NR	30
Kim, 2019 [26]	61	139	95	123(88.5)	81 (85.3)	Total, 126 (53.8)		77.2	TRT	25Gy/10F	NR	22
Jeong, 2020 [20]	64	45	56	Total, 88(87.1)		Total, 62 (61.4)		84.2	TRT	25Gy/10F	NR	27
Lou, 2020 [22]	63	46	100	40 (87.0)	88 (88.0)	NR	NR	NR	Surgery	NR	NR	28
Held, 2021 [12]	63 ∼ 65	28	21	12 (43)	11 (52)	NR	NR	NR	TRT	25Gy/10F	no routine	26–33

PCI: prophylactic cranial irradiation; FU: follow-up; TRT: thoracic radiotherapy; NR: not reported.

Figure 2. Forest plot of HR for OS in the era of pretreatment Magnetic Resonance Imaging (MRI) staging for patients with limited-stage small-cell lung cancer (LS-SCLC) with and without PCI.

Table 2. Overall survival (OS) outcomes and adjusted hazard ratios (HR) of included studies.

Study, year	2-year OS PCI (%)	2-year OS No-PCI (%)	Median OS PCI (M)	Median OS No-PCI (M)	Adjusted HR (95% CI)
Farris, 2019 [08]	74.0*	52.7*	37.9	30.5	0.61 (0.36–1.05)
Lim, 2022 [16]	50.0	29.0	23.4	13.9	0.41 (0.22–0.77)
Pezzi, 2020 [10]	56.7*	52.8*	30.5*	25.0*	0.79 (0.56–1.11)
Qi, 2022 [15]	66.7*	57.4*	35.0	28.0	0.76 (0.53–1.08)
Li, 2021 [11]	69.1*	44.2*	35.3*	20.1*	0.42 (0.25–0.70)
Ghanta, 2021 [13]	62.3	50.0	35.0	25.0	0.74 (0.49–1.11)
Eze, 2017 [14]	53.0*	18.7*	26.0	14.0	0.53 (0.38–0.73)
Zhu, 2014 [23]	92.5	63.2	NR	NR	0.43 (0.26–0.71)
Farooqi, 2017 [25]	56.9	43.8	27.0*	20.3*	0.76 (0.63–0.91)
Korczynska, 2018 [21]	49.2*	23.3*	26.0	14.0	0.56 (0.42–0.74)
Yin, 2018 [24]	NR	NR	NR	NR	0.64 (0.43–0.95)
Kim, 2019 [26]	59.1	35.9	29.8*	14.7*	0.54 (0.38–0.77)
Jeong, 2020 [20]	NR	NR	NR	NR	0.53 (0.33–0.84)
Lou, 2020 [22]	71.4*	71.2*	49.7*	43.9	0.95 (0.52–1.75)
Held, 2021 [12]	74.6*	47.6*	55.0	24.0	0.51 (0.21–1.28)
Weighted mean	59.8	42.0	30.1	20.7	–

CI: confidence interval; M: months. *Extract data from Kaplan-Meier survival curves by data extraction software.

Figure 3. Subgroup analysis for OS according to the male proportion.

Table 3. Subgroup analyses of the overall survival.

Subgroups	N studies	Pooled HR (95% CI)	P value (Heterogeneity between subgroups)	I ^2
Primary tumor treatment			0.680	24.9%
Surgery	2	0.59 (0.40–0.87)
TRT	11	0.62 (0.59–0.72)
Both	2	0.56 (0.40–0.79)
Proportion of CR			0.545	7.8%
≥50%	5	0.60 (0.51–0.71)
<50%	4	0.65 (0.53–0.81)
Median age (years)			0.520	24.6%
≥65	3	0.70 (0.55–0.89)
<65	10	0.64 (0.57–0.71)
Publication years			0.931	24.9%
>2018	10	0.64 (0.55–0.73)
≤2018	5	0.64 (0.56–0.73)
Restaging brain scan			0.726	24.9%
Yes	6	0.63 (0.54–0.72)
No routine or NR	9	0.65 (0.57–0.74)
PCI dose (EQD2α/β10)			0.257	22.3%
26Gy	8	0.65 (0.57–0.73)
>26Gy	3	0.57 (0.47–0.68)
Proportion of male			0.002	33.0%
≥60%	7	0.53 (0.45–0.62)
<60%	5	0.74 (0.64–0.85)
Proportion of smoking history			0.113	28.6%
<80%	4	0.53 (0.42–0.67)
≥80%	4	0.70 (0.54–0.91)
Proportion of stage III			0.453	0%
<75.0%	4	0.63 (0.51–0.78)
≥75.0%	4	0.56 (0.45–0.69)

N: number; HR: hazard radio; CI: confidence interval; TRT: thoracic radiation therapy; CR: complete response; NR: not reported; EQD2: Equivalent Dose in 2 Gy/f.

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Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.