Clinical Outcomes and Prognostic Factors of Salvage Stereotactic Body Radiotherapy for Post-Surgical Thoracic Oligo-Recurrence/Metastasis of Non-Small-Cell Lung Cancer

Figures & data

Figure 1 The CONSORT diagram for the study.

Table 1 CyberKnife Radiosurgery Treatment

Characteristics	No. (%)
Age(years) at CK: median (range)	68 years (39–85 years)
Gender
Male	35(79.5%)
Female	9 (20.5%)
Smoking status
Past smoker and current smoker	22(50%)
Never smoker	22(50%)
Disease free interval Median (range)	22.43 months (3.93–161.3 months)
Symptoms at recurrence (yes/no)	8(18.2%):36(81.8%)
Therapy Pre-CK
Chemotherapy	12(27.3%)
Targeted therapy	2(5.1%)
Both	1(2.7%)
None	29(65.9%)
EGFR mutation positive	19(43%)
Location of oligo-recurrent lesions relative to prior tumor
Ipsilateral lung	26(59.1%)
Contralateral lung	12(27.3%)
Regional nodes (mediastinum)	4(9.1%)
Chest wall	2(4.5%)
Tumor location
Central	13(29.5%)
Peripheral	31(70.5%)
Number of initial recurrent lesions
1 lesion	41(93.2%)
2–3 lesions	3(6.8%)
Median tumor size, cm (range)	2.83cm (1.9 to 8.1cm)
<3 cm	21(47.7%)
3–7 cm	20(45.5%)
>7 cm	3(6.8%)
ECOG score Pre-CK
0	26(59.1%)
1	18(40.9%)
Hemoglobin Levels, median (min, max)	133(90–168)
WBC counts, median (min, max)	5.50(3.5–10.6)
Neutrophil counts, median (min, max)	3.23(1.82–7.10)
Lymphocyte counts, median (min, max)	1.54 (0.56–3.24)
Platelet counts median (min, max)	185.5(103–475)
NLR median (min, max)	1.90 (1.11–5.9)
PLR median (min, max)	118.39 (56.78–456.24)
BED (Gy) Median (range)	124.8 Gy (60–180 Gy)
CCI Median (range)	9 (7–12)
Therapy Post-SBRT
Absent	8(18.2%)
Present	36(81.8%)

Abbreviations: CK, CyberKnife radiosurgery; ECOG score, Eastern Cooperation Oncology Group score; SBRT, stereotactic body radiotherapy; BED₁₀, biologically effective dose (using the LQ model with the α/β=10 Gy); NLR, Neutrophil-to-lymphocyte ratio; PLR, Platelet-to-lymphocyte ratio; CCI, Charlson comorbidity index, EGFR-TKI, Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.

Table 2 CyberKnife Radiosurgery Treatment

	Item	CI	nCI	HI	Coverage (%)	Prescription Dose (Gy)	PTV (cm^3)	Fx	BED10 (Gy)	Isodose (%)
All patients	Range	1.01–3.32	1.15–3.47	1.12–1.52	67.31–99.68	30–60	3.55–157	2–6	60–180	66–89
	Mean	1.28	1.4	1.25	91.28	50.73	34.20	4.1	121.5	80
	Median	1.18	1.28	1.24	94.45	50	14.20	4.5	124.8	80
Central	Range	1.01–1.16	1.18–2.05	1.18–1.41	67.31–95.61	40–60	4.23–157	3–6	80–133.3	71–85
	Mean	1.19	1.41	1.26	85.63	50.15	46.12	4.77	105.3	79.5
	Median	1.66	1.29	1.25	90.68	50	26.17	5	100	80
Peripheral	Range	1.03–3.32	1.15–3.47	1.12–1.52	70.49–99.68	30–60	3.55–142.84	2–5	60–180	66–89
	Mean	1.31	1.41	1.24	93.45	51.77	29.21	3.77	128.27	81
	Median	1.18	1.27	1.23	95.4	51	12.71	3	132	81

Abbreviations: Coverage: the coverage is volume of the tumor receiving greater than or equal to the prescription dose divided by the total volume of the tumor times 100; CI, conformity index; nCI, new conformity index; HI, homogeneity index; Fx, fraction.

Figure 2 Prognosis of patients underwent slave SBRT. Kaplan–Meier estimates of (A) LC, (B) PFS and (C) OS for patients who underwent SBRT.

Abbreviations: OS, overall survival; PFS, progression-free survival; LC, local control; SBRT, stereotactic body radiotherapy.

Table 3 Univariate Analysis for LC, OS

Variables	LC		OS
	Univariate		Univariate
	HR (95% CI)	P-value	HR (95% CI)	P-value
Sex (female vs male)	0.58(0.07–4.97)	0.617	1.47(0.34–6.38)	0.093
Age at CK (≥74:<74)	3.59(0.72–17.93)	0.119	1.88(0.72–4.91)	0.199
Smoking history (yes vs no)	1.60(0.32–8.12)	0.571	2.15(0.82–5.6)	0.112
Histology (adenocarcinoma vs alternative subtypes)	1.43(0.26–8.01)	0.678	2.15(0.82–5.63)	0.110
pN classification (pN0: pN≥1)	29.13(0.01–1297)	0.432	1.63(0.46–0.57)	0.441
Disease-free interval, years (≥2 years vs <2years)	119 (0.12–122700)	0.177	0.91(0.29–2.83)	0.302
Disease-free interval, years(≥1year vs.<1year)	31.93(0.01–79136)	0.385	1.62(0.64–4.11)	0.869
Symptoms at Recurrence (yes vs no)	0.96(0.112–8.239)	0.097	1.13(0.32–4.01)	0.850
ECOG score Pre-SBRT (0 vs 1)	1.87(0.375–9.29)	0.446	3.25(1.22–8.65)	0.013
Hemoglobin Levels (≥110 vs <110)	0.79(0.09–6.77)	0.828	0.73(0.21–2.60)	0.629
CCI (>9 vs ≤9)	4.37(0.78–24.34)	0.093	3.97(1.46–10.78)	0.007
NLR (<2.68 vs ≥2.68)	5.79(0.95–35.25)	0.056	8.64(2.43–30.77)	0.001
PLR (<117.66 vs ≥ 117.66)	3.57(0.62–20.54)	0.154	2.12(0.82–5.65)	0.111
EGFR-TKI (present vs absent)	5.74(0.67–49.28)	0.111	1.25(0.46–3.36)	0.662
Number of initial recurrent lesions(1lesion vs 2–3 lesions)	1.66(0.19–14.45)	0.647	0.73(0.21–2.60)	0.629
Tumor diameter  ≥34 mm  < 34 mm	1.54(0.27–8.71)	0.627	2.50(0.27–22.87)	0.012
Tumor location (central vs peripheral)	2.06(0.24–17.72)	0.509	1.27(0.46–3.48)	0.641
BED (Gy)
≥100 vs <100 Gy	26.79(0.03–28130)	0.486	0.84(0.24–2.99)	0.790
≥120 vs <120 Gy	1.37(0.25–7.47)	0.719	0.91(0.34–2.45)	0.849
Post-SBRT therapy (absent vs present)			4.13(0.52 to 32.94)	0.071

Abbreviations: HR, hazard ratios; CK, CyberKnife radiosurgery; ECOG, Eastern Cooperation Oncology Group score; SBRT, stereotactic body radiotherapy; BED10, biologically effective dose (using the LQ model with the α/β=10 Gy); pN, pathological N classification; NLR, Neutrophil-to-lymphocyte ratio; PLR, Platelet-to-lymphocyte ratio, CCI, Charlson comorbidity index.

Table 4 Multivariate Analyses for OS After CK

Variables	Multivariate	P-value
	HR (95% CI)	P-value
ECOG score Pre-SBRT (0 vs 1)	2.905(0.852–9.908)	0.088
CCI (≤9 vs >9)	0.281(0.102–0.777)	0.014
NLR (<2.68 vs ≥2.68)	0.135(0.038–0.473)	0.002
Tumor diameter  ≥34 mm  < 34 mm	0.319(0.063–1.610)	0.167

Abbreviations: HR, hazard ratios; CK, CyberKnife radiosurgery; ECOG, Eastern Cooperation Oncology Group score; SBRT, stereotactic body radiotherapy; NLR: Neutrophil-to-lymphocyte ratio; NLR, Neutrophil-to-lymphocyte ratio; CCI, Charlson comorbidity index.

Figure 3 Kaplan–Meier survival curves of overall survival in postsurgical thoracic oligo-recurrence of non-small-cell lung cancer patients. (A) OS according to the NLR (B) OS according to CCI.

Abbreviations: NLR, neutrophil-to-lymphocyte ratio; OS, overall survival; CCI, Charlson comorbidity index.

Table 5 Study Outcomes of SBRT for the Treatment of Post-Surgical Recurrence of NSCLC

Study	NO	Median FU (mo)	LC (%)	OS(%)	PFS(%)	Dose (Gy/fx)	Adverse Events(>Grade2)
Takeda et al^Citation16	23	17	1y:94.7%; 2ys: 86.8%	1y:84%; 2ys:76.4%	1y:89.5%; 2ys:62.5%	40–60Gy/5-10fx	4 patients
AGOLLI et al^Citation17	28	18	1y:96.6%; 2ys: 84.7%	1y:92.4%; 2ys: 57.5%	1y:74.4%; 2ys: 36.6%	23–454Gy/1-3fx	1 patient
Aoki et al^Citation18	52	25	1y:97.9%; 3ys: 94.9%	1y:84.4%; 3ys: 67.8%	1y:80.8%; 3ys: 58.7%	50–56Gy/4-10fx	4 patients
Our study	44	48.5	1y:97.7%; 3ys:85.1%; 5ys:80.1%;	1y:97.7%; 3ys:65.3%; 5ys:47.7%;	1y:77.1%; 3ys:28.8%; 5ys:5.3%;	30–60Gy/2-6 fx	none

Abbreviations: SBRT, stereotactic body radiotherapy; FU, follow-up; OS, overall survival; LC, local control; PFS, progression free survival; y, year; fx, fraction; mo, month.

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