Preliminary analysis of the risk factors for radiation pneumonitis in patients with non-small-cell lung cancer treated with concurrent erlotinib and thoracic radiotherapy

Figures & data

Table 1 Patient characteristics and treatment modalities

Factors	Value
Sex, n (%) of cases
Male	9 (38%)
Female	15 (62%)
Age (years)
Median	64
Range	33–85
Location, n (%)
Upper lobe	14 (58%)
Middle and lower lobe	10 (42%)
Clinical stage, n (%)
IIIA	11 (46%)
IIIB	7 (29%)
IV	6 (25%)
ECOG PS, n (%)
0	6 (25%)
1	18 (75%)
Smoking history, n (%)
Yes	8 (33%)
No	16 (67%)
FVCa (L)
Median	2.46
Range	1.4–4.2
FVC1a (L)
Median	1.90
Range	0.9–3.2
DLcoa (L)
Median	2.05
Range	1.2–4.7
Pathology, n (%)
Squamous	5 (21%)
Adenocarcinoma	17 (71%)
Adenosquamous carcinoma	1 (4%)
Sarcomatoid carcinoma	1 (4%)
Intention of the radiotherapy, n (%)
Radical	14 (58%)
Palliative	10 (42%)
Radiotherapy dose (Gy)
Median	57
Range	46–66
Dose per fraction (Gy)
Median	2
Range	1.8–2.1
GTV size (mL)
Median	35.50
Range	8.6–454.4
PTV size (mL)
Median	279.70
Range	32.9–794.1
Neoadjuvant chemotherapy, n (%)
Yesb	13 (54%)
No	11 (46%)
Adjuvant chemotherapy, n (%)
Yesb	12 (50%)
No	12 (50%)
Taking time of erlotinib concurrent with RT (days)
Median	41.5
Range	30–45
Total taking time of erlotinib (months)
Median	3.2
Range	1.2–27
Time onset of radiation pneumonitis (weeks)c
Median	9.5
Range	4–15.5

Notes:

a An AS-507 lung function tester (Autospiro-507; Minato Medical Science, Osaka, Japan) was used in the research

b the most frequently used regimen for chemotherapy was cisplatin-based doublet

c the time was from the beginning of radiotherapy to the onset of pneumonitis in the patients who had radiation pneumonitis.

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; FVC, forced vital capacity; FVC1, forced vital capacity in 1 second; DLco, diffusing capacity of the lung; GTV, gross tumor volume; PTV, planning target volume, RT, radiation therapy.

Table 2 Univariate analysis of factors related to radiation pneumonitis (≥ grade 2)

Factors	RR value	95% CI	P-value
Female versus male	0.327	0.050–2.120	0.241
Age	0.438	0.079–2.437	0.345
Smoking history	2.200	0.385–12.573	0.375
Location	1.200	0.225–6.388	0.831
Pre-RT FVC	1.429	0.271–7.518	0.674
Pre-RT FEV1	0.914	0.174–4.811	0.916
Pre-RT DLco	0.750	0.133–4.224	0.744
Whole lung volume	2.500	0.458–13.629	0.290
RT dose	0.429	0.271–7.518	0.377
GTV size	5.000	0.806–31.002	0.084
PTV size	1.007	1.001–1.013	0.025
Taking time of erlotinib concurrent with radiotherapy	0.533	0.100–2.839	0.461
Total taking time of erlotinib	0.333	0.059–1.877	0.213
With versus without neoadjuvant chemotherapy	1.904	0.208–5.756	0.916
With versus without adjuvant chemotherapy	2.909	0.271–31.904	0.378

Abbreviations: RR, relative risk; CI, confidence interval; RT, radiation therapy; FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; DLco, diffusing capacity of the lung; GTV, gross tumor volume; PTV, planning target volume.

Table 3 Lung dosimetric parameters

Variable	Radiation pneumonitis	Non-radiation pneumonitis	P-value
MLD (cGy)	1,334.6±236.3	919.6±221.9	0.001
V5 (%)	45.4±9.6	34.5±8.2	0.012
V10 (%)	35.9±7.4	27.3±6.8	0.012
V15 (%)	28.1±5.8	21.2±5.2	0.010
V20 (%)	24.7±4.4	16.9±4.1	0.001
V30 (%)	19.0±4.0	13.0±3.1	0.002

Notes: Parameters in patients with radiation pneumonitis and in patients without radiation pneumonitis (mean ± standard deviation).

Abbreviation: MLD, mean lung dose.

Figure 1 The receiver operating characteristic (ROC) curves of lung dosimetric parameters.

Abbreviation: MLD, mean lung dose.

Table 4 Lung dosimetric parameters to predict radiation peneumonitis with an ROC curve

	AUC	95% CI	Z-statistic	P-value (area =0.5)	Youden index J	Associated criterion	Sensitivity	Specificity
MLD (cGy)	0.878±0.0829	0.680–0.975	4.559	<0.0001	0.6889	>1,027	88.9	80.0
V5 (%)	0.815±0.113	0.605–0.942	2.782	0.0054	0.7111	>44	77.8	93.3
V10 (%)	0.819±0.104	0.609–0.944	3.055	0.0022	0.6222	>29	88.9	73.3
V15 (%)	0.822±0.0985	0.613–0.947	3.270	0.0011	0.6000	>27	66.7	93.3
V20 (%)	0.889±0.0771	0.694–0.979	5.044	<0.0001	0.7111	>22	77.8	93.3
V30 (%)	0.881±0.0692	0.684–0.976	5.514	<0.0001	0.6000	>17	66.7	93.3

Abbreviations: ROC, receiver operating characteristic; AUC, area under the curve; CI, confidence interval; MLD, mean lung dose.