Stereotactic body radiation therapy for mediastinal lymph node metastases: how do we fly in a ‘no-fly zone’?

Figures & data

Table 1. Patient and treatment characteristics.

Parameter		No. (%)
Age at the SBRT	Median (range) [years]	62.3 (43–84)
Gender	Male	17 (40)
	Female	25 (60)
Primary tumor	Lung adenocarcinoma	18
	Lung SCLC	3
	Lung squamous cell carcinoma	2
	Lung adenoid cystic carcinoma	1
	Lung atypical carcinoid	1
	Breast cancer	5
	Ovarian cancer	3
	Gynecological squamous cell carcinoma	2
	Gynecological adenocarcinoma	2
	Head and neck squamous cell carcinoma	1
	Nasopharyngeal carcinoma	1
	Neuroendocrine tumor	1
	Squamous cell carcinoma of anal canal	1
	Rectal cancer	1
Synchronous metastases	Yes	24 (57)
	No	18 (43)
Previous RT	Yes	11 (26)
	No	31 (74)
Other treatments	Chemotherapy	24
	Hormonotherapy	6
	None	12
RT technique	Dynamic Arc	28
	IMRT	14
Treatment schedules	Nfr = 5, Dfr = 5 Gy, BEDα/β=10Gy = 37.5 Gy	14
	Nfr = 5, Dfr = 8 Gy, BEDα/β=10Gy = 72 Gy	6
	Nfr = 3, Dfr = 8 Gy, BEDα/β=10Gy = 43.2 Gy	5
	Nfr = 5, Dfr = 7 Gy, BEDα/β=10Gy = 59.5 Gy	4
	Nfr = 3, Dfr = 10 Gy, BEDα/β=10Gy = 60 Gy	4
	Nfr = 5, Dfr = 6 Gy, BEDα/β=10Gy = 48 Gy	3
	Nfr = 3, Dfr = 7 Gy, BEDα/β=10Gy = 35.7 Gy	2
	Nfr = 4, Dfr = 12 Gy, BEDα/β=10Gy = 105.6 Gy	2
	Nfr = 3, Dfr = 12 Gy, BEDα/β=10Gy = 79.2 Gy	1
	Nfr = 5, Dfr = 10 Gy, BEDα/β=10Gy = 100 Gy	1
GTV-heart distance (mm)	Median (IQR)	6.0 (27.7)
	Min–max	0.0–76.6
GTV-esophagus distance (mm)	Median (IQR)	18.7 (19.1)
	Min–max	0.0–55.7
GTV-trachea distance (mm)	Median (IQR)	5.0 (25.4)
	Min–max	0.0–64.0

SBRT: stereotactic body radiation therapy; SCLC: small-cell lung cancer; RT: radiation therapy; IMRT: intensity modulated radiation therapy; Nfr: number of fractions; Dfr: dose per fraction; BED_{α/β = 10 Gy}: biologically effective dose considering α/β equal to 10 Gy; IQR: interquartile range; Min: minimum; Max: maximum.

Figure 1. Cox proportional-hazard regression of lung toxicity, considering G ≥ 1, for different irradiation techniques.

Table 2. Statistical analysis of pulmonary toxicity.

Parameter	Characteristic	G ≤ 1	G ≥ 2	Test	p value
Technique	IMRT	12	2	Chi-squared	1
	Dynamic Arc	24	4
Systemic treatment	None	8	3	Chi-squared	.53
	Pre-radiotherapy chemotherapy only	7	1
	Concomitant chemotherapy	0	0
	Post-radiotherapy chemotherapy only	1	0
	Hormonotherapy	0	0
	Various combinations of pre/concomitant/post-radiotherapy chemotherapy	20	2
Re-irradiation	No	26	5	Chi-squared	.57
	Yes	10	1
BED α/β = 10 Gy	<40 Gy	14	2	Chi-squared	.42
	40–60 Gy	9	3
	>60 Gy	13	1
Treatment site	Supraclavicular zone	0	0	Chi-squared	.04
	Upper zone (superior mediastinal nodes)	12	4
	Aortopulmonary zone	7	2
	Subcarinal zone	2	0
	Lower zone (inferior mediastinal nodes)	3	0
	Hilar and interlobar zone (pulmonary nodes)	12	0
	Peripheral zone (pulmonary nodes)	0	0
Total dose	–			LR	.61
GTV max diameter	–			LR	.79
GTV dose max	–			LR	.57
GTV volume	–			LR	.83
PTV volume	–			LR	.75
Lung max dose	–			LR	.88
Lung mean dose	–			LR	.39
Lung V10%	–			LR	.33
Lung V5%	–			LR	.09
Trachea Dmax	–			LR	.16
Trachea D4cc	–			LR	.50
GTV-trachea distance	–			LR	.40
	<1 mm	15	1	Chi-squared	.43
	1–20 mm	11	2
	>20 mm	10	3

IMRT: intensity modulated radiation therapy; BED: biologically effective dose; GTV: gross tumor volume; PTV: planning target volume; LR: logistic regression; Vx%: volume receiving X% of prescribed dose.

Figure 2. Histogram of local control distribution at increasing BED. Three subpopulations were identified, corresponding to patients treated with BED ≤40 Gy, 40 Gy < BED <60 Gy and BED ≥60 Gy. Local control is defined as 0 (there is not local disease progression, black columns). Otherwise, local control is defined as one if local disease progression was found (grey columns).

Table 3. Cox proportional-hazard regression analysis of the effect of dosimetric parameters upon local control.

Dosimetric parameter	HR	95% CI	p value
Mean dose to GTV	0.89	0.81–0.98	.006
Mean dose to PTV	0.90	0.82–0.99	.009
Maximum dose to GTV	0.89	0.83–0.99	.012
Dose to 98% of GTV	0.89	0.81–0.98	.007
Dose to 95% of GTV	0.89	0.81–0.98	.007
Dose to 50% of GTV	0.90	0.82–0.99	.010
Dose to 2% of GTV	0.90	0.83–0.99	.011

HR: hazard ratio; CI: confidence interval; GTV: gross tumor volume; PTV: planning target volume.

Table 4. Radiologic response evaluated according to RECIST criteria [21] at 6 months.

Radiologic response	Number of patients	Median (range) BED α/β = 10
Complete response	11	60 (37.5–79.2)
Partial response	7	43.2 (29.7–105.6)
Stable disease	9	59.5 (37.5–100)
Progression disease	9	43.2 (37.5–105.6)

BED: biologically effective dose.