World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 15, Number 4, August 2024, pages 711-721

Results of Stereotactic Body Radiotherapy With CyberKnife-M6 for Primary and Metastatic Lung Cancer

Figure 2. A case with lymph node (4L) metastasis treated with 39 Gy/6 fx. (a) PET/CT image before treatment. (b) Complete response with PET/CT at 4 months after treatment. PET/CT: positron emission tomography/computed tomography.

**Table 1.** Clinical Characteristics
Features	Median (range) (%)
SBRT: stereotactic body radiotherapy; BED: biologically effective dose.
Median age (years)	68 (47 - 82)
Male-to-female ratio	29 to 6
Karnofsky performance status	90 (70 - 100)
Histology (n = 35)
Adenocarcinoma	15 (43%)
Squamous cell carcinoma	10 (28.5%)
Adenosquamous cell carcinoma	1 (3%)
Large cell neuroendocrine carcinoma (LCNEC)	2 (5.5%)
LCNEC + small cell lung carcinoma (SCLC)	2 (5.5%)
SCLC	1 (3%)
Non-small cell lung carcinoma	2 (5.5%)
Histological diagnosis absent	2 (5.5%)
Stage before SBRT (AJCC 2018) (n = 35)
I	20 (57%)
II	0 (0%)
III	5 (14%)
IV	10 (29%)
Tumor size (mm) (n = 42)	15 (6 - 36) (mean 22.5 ± 1.88)
Primary lung lesion (n = 23)	17 (10 - 36) (mean 26 ± 2.44)
Metastatic lung lesion (n = 12)	12 (6 - 30) (mean 15 ± 1.90)
Lymph node metastasis (n = 7)	13 (10 - 20) (mean 18 ± 1.36)
Lung lesion (n = 35)
Right	20 (57%)
Left	15 (43%)
Lymph nodes (n = 7)
4R	3 (43%)
4L	1 (14%)
5	1 (14%)
6	1 (14%)
7	1 (14%)
Prescription dose (Gy/fx) (n = 42)	48 Gy/4 fx (28 - 55 Gy/1- 7 fx)
Primary lung lesion (n = 23)	50 Gy/5 fx (40 - 55 Gy/4 - 7 fx)
Metastatic lung lesion (n = 12)	48 Gy/4 fx (28 - 55 Gy/1 - 7 fx)
Lymph node metastases (n = 7)	36 Gy/6 fx (30 - 42 Gy/5 - 6 fx)
BED₁₀ (Gy) (n = 42)	105.6 (48 - 151.2) (mean 118 ± 5.63)
Primary lung lesion (n = 23)	105.6 (80 - 151.2) (mean 131 ± 10.19)
Metastatic lung lesion (n = 12)	105.6 (48 - 151.2) (mean 97 ± 10.19)
Lymph node metastases (n = 7)	57.6 (48 - 72) (mean 71 ± 0.21)
Response at a median 2 month (1 - 6) (n = 42)
Complete	11 (26%)
Partial	26 (62%)
Stable	4 (9.5%)
Unevaluated	1 (2.5%)
Response at 12th month (n = 42)
Complete	15 (35.5%)
Partial	20 (47.5%)
Stable	2 (5%)
Progression	5 (12%)

Table 1. Clinical Characteristics

Features

Median (range) (%)

SBRT: stereotactic body radiotherapy; BED: biologically effective dose.

Median age (years)

68 (47 - 82)

Male-to-female ratio

29 to 6

Karnofsky performance status

90 (70 - 100)

Histology (n = 35)

Adenocarcinoma

15 (43%)

Squamous cell carcinoma

10 (28.5%)

Adenosquamous cell carcinoma

1 (3%)

Large cell neuroendocrine carcinoma (LCNEC)

2 (5.5%)

LCNEC + small cell lung carcinoma (SCLC)

2 (5.5%)

SCLC

1 (3%)

Non-small cell lung carcinoma

2 (5.5%)

Histological diagnosis absent

2 (5.5%)

Stage before SBRT (AJCC 2018) (n = 35)

20 (57%)

0 (0%)

III

5 (14%)

10 (29%)

Tumor size (mm) (n = 42)

15 (6 - 36) (mean 22.5 ± 1.88)

Primary lung lesion (n = 23)

17 (10 - 36) (mean 26 ± 2.44)

Metastatic lung lesion (n = 12)

12 (6 - 30) (mean 15 ± 1.90)

Lymph node metastasis (n = 7)

13 (10 - 20) (mean 18 ± 1.36)

Lung lesion (n = 35)

Right

20 (57%)

Left

15 (43%)

Lymph nodes (n = 7)

3 (43%)

1 (14%)

Prescription dose (Gy/fx) (n = 42)

48 Gy/4 fx (28 - 55 Gy/1- 7 fx)

Primary lung lesion (n = 23)

50 Gy/5 fx (40 - 55 Gy/4 - 7 fx)

Metastatic lung lesion (n = 12)

48 Gy/4 fx (28 - 55 Gy/1 - 7 fx)

Lymph node metastases (n = 7)

36 Gy/6 fx (30 - 42 Gy/5 - 6 fx)

BED₁₀ (Gy) (n = 42)

105.6 (48 - 151.2) (mean 118 ± 5.63)

Primary lung lesion (n = 23)

105.6 (80 - 151.2) (mean 131 ± 10.19)

Metastatic lung lesion (n = 12)

105.6 (48 - 151.2) (mean 97 ± 10.19)

Lymph node metastases (n = 7)

57.6 (48 - 72) (mean 71 ± 0.21)

Response at a median 2 month (1 - 6) (n = 42)

Complete

11 (26%)

Partial

26 (62%)

Stable

4 (9.5%)

Unevaluated

1 (2.5%)

Response at 12th month (n = 42)

Complete

15 (35.5%)

Partial

20 (47.5%)

Stable

2 (5%)

Progression

5 (12%)

**Table 2.** Dosimetric Features
Features (n = 42)	Median (range, %)
ITV: internal target volume; PTV: planning target volume.
Tracking method
Two-view	5 (12%)
One-view	13 (31%)
Zero-view	24 (57%)
Node number	37 (4 - 60)
Beam number	38 (22 - 128)
Segment number	47 (25 - 82)
Beam on time (min)	25 (12 - 42)
Duration of treatment (day)	7 (1 - 14)
Dose (Gy)	48 (30 - 55)
Fraction number	4 (1 - 7)
ITV volume (cc)	9.64 (1.89 - 52.34)
PTV volume (cc)	21.27 (5.57 - 82.70)
PTV isodose (%)	82.75% (74.50-99.00%)
PTV 95% (cGy)	4,801 (2,800 - 5,842)
PTV coverage (%)	95% (94-100%)
Conformity index	1.13 (1.01 - 1.77)
New conformity index	1.19 (1.07 - 1.47)
Homogeneity index	1.21 (1.10 - 1.32)
Monitor units	16,924.5 (6,223.7 - 35,236.4)
Total lung volume (cc)	2,777.85 (1,402.00 - 6,345.44)
Lung 1500cc (Gy)	1.31 (0.00 - 4.72)
Lung 1000 cc (Gy)	2.22 (0.19 - 7.24)
Mean lung dose (Gy)	2.74 (0.70 - 7.20)
Lung V5 (%)	16.55% (0.00-49.40%)
Lung V20 (%)	2.55% (0.00-7.50%)
Ipsilateral mean lung dose (Gy)	5.74 (0.98 - 13.50)
Heart max dose (Gy)	4.88 (0.09 - 41.50)
Esophagus max dose (Gy)	11.69 (0.00 - 41.06)
For central lesions (n = 8)	21.67 (9.99 - 41.06)
For peripheral lesions (n = 34)	7.91 (0.00 - 3,103)
Spinal cord max dose (Gy)	7.37 (0.97 - 20.46)

Table 2. Dosimetric Features

Features (n = 42)

Median (range, %)

ITV: internal target volume; PTV: planning target volume.

Tracking method

Two-view

5 (12%)

One-view

13 (31%)

Zero-view

24 (57%)

Node number

37 (4 - 60)

Beam number

38 (22 - 128)

Segment number

47 (25 - 82)

Beam on time (min)

25 (12 - 42)

Duration of treatment (day)

7 (1 - 14)

Dose (Gy)

48 (30 - 55)

Fraction number

4 (1 - 7)

ITV volume (cc)

9.64 (1.89 - 52.34)

PTV volume (cc)

21.27 (5.57 - 82.70)

PTV isodose (%)

82.75% (74.50-99.00%)

PTV 95% (cGy)

4,801 (2,800 - 5,842)

PTV coverage (%)

95% (94-100%)

Conformity index

1.13 (1.01 - 1.77)

New conformity index

1.19 (1.07 - 1.47)

Homogeneity index

1.21 (1.10 - 1.32)

Monitor units

16,924.5 (6,223.7 - 35,236.4)

Total lung volume (cc)

2,777.85 (1,402.00 - 6,345.44)

Lung 1500cc (Gy)

1.31 (0.00 - 4.72)

Lung 1000 cc (Gy)

2.22 (0.19 - 7.24)

Mean lung dose (Gy)

2.74 (0.70 - 7.20)

Lung V5 (%)

16.55% (0.00-49.40%)

Lung V20 (%)

2.55% (0.00-7.50%)

Ipsilateral mean lung dose (Gy)

5.74 (0.98 - 13.50)

Heart max dose (Gy)

4.88 (0.09 - 41.50)

Esophagus max dose (Gy)

11.69 (0.00 - 41.06)

For central lesions (n = 8)

21.67 (9.99 - 41.06)

For peripheral lesions (n = 34)

7.91 (0.00 - 3,103)

Spinal cord max dose (Gy)

7.37 (0.97 - 20.46)

**Table 3.** Univariate and Multivariate Analysis of Factors Influencing Overall Survival
Significance in univariate analysis	OS (mean, months, 95% CI)	P value	LRFS (mean, months, 95% CI)	P value
*P < 0.05. SUVmax: maximum standard uptake value; CI: confidence interval; SBRT: stereotactic body radiotherapy; OS: overall survival; LRFS: local recurrence-free survival.
Patients (n = 35)	31.55 (26.01 - 3708)		29.67 (23.52 – 35.82)
	85.7% (1-year)		76.7% (1-year)
	54.1% (2-year)		51.4% (2-year)
Smoking pack-year (case)		0.026*		0.057
≥ 40 (n = 20)	35.52 (29.00 - 42.03)		34.62 (27.57 - 41.66)
< 40 (n = 12)	23.10 (15.09 - 31.10)		21.83 (12.83 - 30.83)
Target lesion		< 0.001*		< 0.001*
Primary lung (n = 23)	31.95 (25.89 - 38.01)		30.90 (24.37 - 37.44)
Metastatic lung (n = 12)	14.00 (9.77 - 18.22)		9.02 (5.64 - 12.40)
Lymph node (n = 7)	42.57 (36.35 - 48.79)		40.42 (30.31 - 50.53)
Response (2nd month)		0.044*		0.043*
Complete (n = 11)	40.18 (32.92 - 47.44)		39.02 (30.29 - 47.74)
Partial (n = 26)	27.02 (20.96 - 33.08)		25.46 (18.92 - 32.00)
Stable (n = 4)	19.50 (5.39 - 35.57)		14.00 (0.00 - 31.07)
Response (12th month)		0.002*		0.034*
Complete (n = 15)	43.73 (39.41 - 30.43)		36.88 (29.28 - 44.49)
Partial (n = 20)	21.54 (15.21 - 27.87)		23.12 (15.59 - 30.65)
Stable (n = 2)	14.50 (0.00 - 29.20)		16.00 (3.52 - 28.47)
Progression (n = 5)	22 (13.41 - 30.58)		8.20 (3.19 - 13.20)
Esophagus max (Gy)		0.044*		0.020*
< 11.69 (n = 19)	23.63 (16.82 - 30.43)		17.64 (11.33 - 23.95)
≥ 11.69 (n = 23)	34.45 (28.06 - 40.85)		33.67 (26.86 - 40.48)
SUVmax before SBRT		0.018*		0.027*
< 5 (n = 17)	25.00 (17.32 - 32.67)		21.66 (12.76 - 30.56)
≥ 5 (n = 18)	37.60 (31.43 - 43.77)		36.01 (28.75 - 43.26)
Significance in Cox regression analysis	Hazard ratio (95% CI)
Response (12th month)	8.602 (1.05 - 70.01)	0.044*

Table 3. Univariate and Multivariate Analysis of Factors Influencing Overall Survival

Significance in univariate analysis

OS (mean, months, 95% CI)

P value

LRFS (mean, months, 95% CI)

P value

*P < 0.05. SUVmax: maximum standard uptake value; CI: confidence interval; SBRT: stereotactic body radiotherapy; OS: overall survival; LRFS: local recurrence-free survival.

Patients (n = 35)

31.55 (26.01 - 3708)

29.67 (23.52 – 35.82)

85.7% (1-year)

76.7% (1-year)

54.1% (2-year)

51.4% (2-year)

Smoking pack-year (case)

0.026*

0.057

≥ 40 (n = 20)

35.52 (29.00 - 42.03)

34.62 (27.57 - 41.66)

< 40 (n = 12)

23.10 (15.09 - 31.10)

21.83 (12.83 - 30.83)

Target lesion

< 0.001*

Primary lung (n = 23)

31.95 (25.89 - 38.01)

30.90 (24.37 - 37.44)

Metastatic lung (n = 12)

14.00 (9.77 - 18.22)

9.02 (5.64 - 12.40)

Lymph node (n = 7)

42.57 (36.35 - 48.79)

40.42 (30.31 - 50.53)

Response (2nd month)

0.044*

0.043*

Complete (n = 11)

40.18 (32.92 - 47.44)

39.02 (30.29 - 47.74)

Partial (n = 26)

27.02 (20.96 - 33.08)

25.46 (18.92 - 32.00)

Stable (n = 4)

19.50 (5.39 - 35.57)

14.00 (0.00 - 31.07)

Response (12th month)

0.002*

0.034*

Complete (n = 15)

43.73 (39.41 - 30.43)

36.88 (29.28 - 44.49)

Partial (n = 20)

21.54 (15.21 - 27.87)

23.12 (15.59 - 30.65)

Stable (n = 2)

14.50 (0.00 - 29.20)

16.00 (3.52 - 28.47)

Progression (n = 5)

22 (13.41 - 30.58)

8.20 (3.19 - 13.20)

Esophagus max (Gy)

0.044*

0.020*

< 11.69 (n = 19)

23.63 (16.82 - 30.43)

17.64 (11.33 - 23.95)

≥ 11.69 (n = 23)

34.45 (28.06 - 40.85)

33.67 (26.86 - 40.48)

SUVmax before SBRT

0.018*

0.027*

< 5 (n = 17)

25.00 (17.32 - 32.67)

21.66 (12.76 - 30.56)

≥ 5 (n = 18)

37.60 (31.43 - 43.77)

36.01 (28.75 - 43.26)

Significance in Cox regression analysis

Hazard ratio (95% CI)

Response (12th month)

8.602 (1.05 - 70.01)

0.044*

**Table 4.** Correlation Coefficients Among Dosimetric Variables (Spearman’s Rank-Order Correlation)
Parameters	Node number	Beam number	Segment number	Monitor units	Beam on time	ITV med (cc)	PTV (cc)
r: Spearman’s correlation coefficient; ITV: internal target volume; PTV: planning target volume; CI: conformity index; nCI: new conformity index; MLD: mean lung dose; Vx: lung volume receiving x Gy.
Beam number	P < 0.001		P < 0.001	P < 0.001	P < 0.001
	r = 0.940		r = 0.896	r = 0.547	r = 0.495
Segment number	P < 0.001	P < 0.001		P < 0.001	P = 0.026
	r = 0.860	r = 0.896		r = 0.663	r = 0.356
Monitor units	P < 0.001	P < 0.001	P < 0.001		P = 0.002
	r = 0.582	r = 0.547	r = 0.663		r = 0.456
Beam on time	P < 0.001	P < 0.001	P = 0.026
	r = 0.506	r = 0.495	r = 0.356
CI median		P = 0.022
		r = -0.353
nCI median		P = 0.032
		r = -0.332
Heart 15 cc	P < 0.001	P < 0.001	P < 0.001	P = 0.008
	r = 0.490	r = 0.516	r = 0.679	r = 0.401
Heart max	P = 0.025	P = 0.023	P < 0.001	P = 0.046
	r = 0.368	r = 0.373	r = 0.577	r = 0.330
Lung 1500 cc	P = 0.009	P = 0.006	P < 0.001	P = 0.002	P < 0.001	P < 0.001	P < 0.001
	r = 0.398	r = 0.415	r = 0.559	r = 0.456	r = 0.525	r = 0.497	r = 0.585
Lung 1000 cc	P = 0.006	P = 0.002	P < 0.001	P = 0.002	P < 0.001	P < 0.001	P < 0.001
	r = 0.417	r = 0.459	r = 0.626	r = 0.456	r = 0.512	r = 0.510	r = 0.596
MLD	P = 0.001	P < 0.001	P < 0.001	P = 0.004	P < 0.001	P = 0.002	P < 0.001
	r = 0.482	r = 0.533	r = 0.624	r = 0.438	r = 0.576	r = 0.471	r = 0.565
Lung V5	P < 0.001	P < 0.001	P < 0.001	P < 0.001		P = 0.006	P = 0.001
	r = 0.549	r = 0.578	r = 0.781	r = 0.503		r = 0.415	r = 0.486
Lung V10	P = 0.001	P < 0.001	P < 0.001	P < 0.001	P = 0.004	P = 0.006	P < 0.001
	r = 0.475	r = 0.523	r = 0.754	r = 0.501	r = 0.431	r = 0.419	r = 0.494
Lung V20	P = 0.014	P = 0.007	P < 0.001	P < 0.001	P < 0. 001	P < 0.001	P < 0.001
	r = 0.376	r = 0.411	r = 0.701	r = 0.546	r = 0.538	r = 0.563	r = 0.588
Lung V30	P = 0.013	P = 0.009	P < 0.001	P < 0.001	P < 0.001	P < 0.001	P < 0.001
	r = 0.381	r = 0.397	r = 0.651	r = 0.515	r = 0.586	r = 0.559	r = 0.578
Ipsilateral lung MLD	P < 0.001	P < 0.001	P < 0.001	P = 0.004	P = 0.008	P < 0.001	P < 0.001
	r = 0.529	r = 0.578	r = 0.776	r = 0.431	r = 0.405	r = 0.502	r = 0.593
Ipsilateral lung V10	P = 0.007	P = 0.002	P < 0.001	P = 0.046	P = 0.018	P = 0.022	P = 0.003
	r = 0.409	r = 0.462	r = 0.617	r = 0.309	r = 0.363	r = 0.354	r = 0.443
Ipsilateral lung V20	P = 0.007	P = 0.004	P < 0.001	P = 0.041	P = 0.002	P = 0.006	P < 0.001
	r = 0.408	r = 0.430	r = 0.583	r = 0.316	r = 0.457	r = 0.415	r = 0.501
Ipsilateral lung V30	P = 0.019	P = 0.016	P < 0.001	P = 0.048	P < 0.001	P = 0.004	P < 0.001
	r = 0.360	r = 0.369	r = 0.517	r = 0.307	r = 0.538	r = 0.430	r = 0.524

Table 4. Correlation Coefficients Among Dosimetric Variables (Spearman’s Rank-Order Correlation)

Parameters

Node number

Beam number

Segment number

Monitor units

Beam on time

ITV med (cc)

PTV (cc)

r: Spearman’s correlation coefficient; ITV: internal target volume; PTV: planning target volume; CI: conformity index; nCI: new conformity index; MLD: mean lung dose; Vx: lung volume receiving x Gy.

Beam number

P < 0.001

r = 0.940

r = 0.896

r = 0.547

r = 0.495

Segment number

P < 0.001

P = 0.026

r = 0.860

r = 0.896

r = 0.663

r = 0.356

Monitor units

P < 0.001

P = 0.002

r = 0.582

r = 0.547

r = 0.663

r = 0.456

Beam on time

P < 0.001

P = 0.026

r = 0.506

r = 0.495

r = 0.356

CI median

P = 0.022

r = -0.353

nCI median

P = 0.032

r = -0.332

Heart 15 cc

P < 0.001

P = 0.008

r = 0.490

r = 0.516

r = 0.679

r = 0.401

Heart max

P = 0.025

P = 0.023

P < 0.001

P = 0.046

r = 0.368

r = 0.373

r = 0.577

r = 0.330

Lung 1500 cc

P = 0.009

P = 0.006

P < 0.001

P = 0.002

P < 0.001

r = 0.398

r = 0.415

r = 0.559

r = 0.456

r = 0.525

r = 0.497

r = 0.585

Lung 1000 cc

P = 0.006

P = 0.002

P < 0.001

P = 0.002

P < 0.001

r = 0.417

r = 0.459

r = 0.626

r = 0.456

r = 0.512

r = 0.510

r = 0.596

MLD

P = 0.001

P < 0.001

P = 0.004

P < 0.001

P = 0.002

P < 0.001

r = 0.482

r = 0.533

r = 0.624

r = 0.438

r = 0.576

r = 0.471

r = 0.565

Lung V5

P < 0.001

P = 0.006

P = 0.001

r = 0.549

r = 0.578

r = 0.781

r = 0.503

r = 0.415

r = 0.486

Lung V10

P = 0.001

P < 0.001

P = 0.004

P = 0.006

P < 0.001

r = 0.475

r = 0.523

r = 0.754

r = 0.501

r = 0.431

r = 0.419

r = 0.494

Lung V20

P = 0.014

P = 0.007

P < 0.001

P < 0. 001

P < 0.001

r = 0.376

r = 0.411

r = 0.701

r = 0.546

r = 0.538

r = 0.563

r = 0.588

Lung V30

P = 0.013

P = 0.009

P < 0.001

r = 0.381

r = 0.397

r = 0.651

r = 0.515

r = 0.586

r = 0.559

r = 0.578

Ipsilateral lung MLD

P < 0.001

P = 0.004

P = 0.008

P < 0.001

r = 0.529

r = 0.578

r = 0.776

r = 0.431

r = 0.405

r = 0.502

r = 0.593

Ipsilateral lung V10

P = 0.007

P = 0.002

P < 0.001

P = 0.046

P = 0.018

P = 0.022

P = 0.003

r = 0.409

r = 0.462

r = 0.617

r = 0.309

r = 0.363

r = 0.354

r = 0.443

Ipsilateral lung V20

P = 0.007

P = 0.004

P < 0.001

P = 0.041

P = 0.002

P = 0.006

P < 0.001

r = 0.408

r = 0.430

r = 0.583

r = 0.316

r = 0.457

r = 0.415

r = 0.501

Ipsilateral lung V30

P = 0.019

P = 0.016

P < 0.001

P = 0.048

P < 0.001

P = 0.004

P < 0.001

r = 0.360

r = 0.369

r = 0.517

r = 0.307

r = 0.538

r = 0.430

r = 0.524