Invasive pulmonary aspergillosis in patients with solid tumours: risk factors and predictors of clinical outcomes

Figures & data

Figure 1. Screening, exclusion and inclusion criteria.

Table 1. Characteristics and treatment of IPA in patients with IPA and solid tumours (N = 101).

Variable	Value
Median age at IPA (IQR), yr	63 (58–70)
Sex, %
Male	47
Female	53
Race, %
White	89
African American	7
Asian	4
Underlying solid tumour, %^a
Lung cancer	51
Head and neck cancer	19
Gastrointestinal cancer	13
Breast cancer	11
Other cancer	15
Host factors, %
Diabetes mellitus	16
ESRD	3
COPD	33
Underlying lung disease^b	76
HIV	2
Other risk factors, %
Prednisone therapy in the 30 days before IPA diagnosis	31
Chemotherapy in the 30 days before IPA diagnosis	30
Immunotherapy in the 30 days before IPA diagnosis	10
ANC <500 cells/µL at time of IPA diagnosis	2
Radiation therapy to the chest before IPA diagnosis	47
Source of fungal culture
Sputum	14
BAL	76
Endotracheal tube	3
Pleural fluid	3
Biopsy	5
Clinical presentation, %
Respiratory symptoms (cough and/or dyspnea)	81
Fever	20
Hemoptysis	16
Pleuritic chest pain	11
Serum galactomannan positive, %^c	40
Calcofluor fungal stain positive by microscopy for aspergillosis, %	21
CT scan findings, %
Nodular lesions	41
Cavitary lesions	14
Nodular and cavitary lesions	11
Consolidative lesions	17
First-line antifungal therapy, %
Voriconazole monotherapy	70
Voriconazole plus either echinocandin or liposomal amphotericin B	9
Posaconazole monotherapy	6
Itraconazole monotherapy	5
Echinocandin monotherapy	4
Other antifungal combination therapy	5
Median duration of primary antifungal therapy (IQR), weeks	8 (3–16)

^a 13 patients (12%) had multiple cancers.

^b primary lung cancer or lung metastasis, radiation pneumonitis, and other structural lung diseases.

^c Galactomannan test was available for 57 cases; the percentage was calculated based on available tests.

ANC: absolute neutrophil count; COPD: chronic obstructive pulmonary disease; BAL: bronchoalveolar lavage; CT: computed tomography; ESRD: end-stage renal disease; IPA: invasive pulmonary aspergillosis; IQR: interquartile range.

Figure 2. (A) Kaplan–Meier survival curves among patients with invasive aspergillosis classified per underlying malignancy status. (p < .01). (B) Kaplan–Meier survival curves among patients with invasive aspergillosis classified per steroid intake. (p = .04). (C) Kaplan–Meier survival curves among patients with invasive aspergillosis classified per prior radiation therapy (p = .02).

Table 2. Univariate and multivariate analysis of predictors of overall survival at 12-week follow-up (N = 101)^a.

				Multivariate cox regression analysis
Predictor	Alive at 12 Weeks (n = 70)	Died Before 12 Weeks (n = 31)	p Value	Hazard Ratio (95% CI)	p Value
Median age (IQR), yr	62 (57–70)	63 (58–71)	.45
Sex, male	26 (37)	21 (68)	<.01
Race, white	63 (90)	27 (87)	.86
Type of solid tumour
Lung cancer	34 (49)	17 (55)	.56
Head and neck cancer	12 (17)	5 (16)	.90
Breast cancer	11 (16)	0	.02
Gastrointestinal cancer	8 (11)	4 (13)	>.99
Status of solid tumour
Remission/stable	38 (54)	5 (16)	<.01	1.0 (reference)	–
Progressive	32 (46)	26 (84)		4.7 (1.8–12.4)	.02
Chemotherapy^b	20 (29)	10 (32)	.71
Prior history of chest radiation therapy	28 (40)	19/30 (63)	.03	2.6 (1.2–5.5)	.01
Steroids^b	17 (24)	14 (45)	.04	2.2 (1.1–4.6)	.03
Steroid dose >600 mg^c	10 (14)	9 (29)	.08
Diabetes mellitus	10 (14)	6 (19)	.56
COPD	24 (34)	9 (29)	.60
Underlying lung disease^d	49 (70)	28 (90)	.03
Serum GM positive at diagnosis	12/38 (32)	11/19 (58)	.06
Fungal stain positive for aspergillosis	11 (16)	10 (32)	.06
Bacterial co-infection	33 (47)	12 (39)	.43
CT findings
Nodular lesions	31/67 (46)	6/23 (26)	.09
Cavitary lesions	10/67 (15)	3/23 (13)	>.99
Nodular and cavitary lesions	7/67 (10)	3/23 (13)	.71
Consolidative lesions	10/67 (15)	5/23 (22)	.52
Therapy^e			.09
Voriconazole-containing therapy	57/69 (83)	18/27 (67)
Other therapy	12/69 (17)	9/27 (33)

^a Values in table are number of patients (percentage) unless otherwise indicated.

^b Chemotherapy or steroid therapy within 30 days before IPA diagnosis.

^c Cumulative steroid dose equivalent to >600 mg prednisone in the last 30 days before IPA diagnosis.

^d Underlying lung disease included primary lung cancer or lung metastasis, radiation pneumonitis, and other structural lung diseases.

^e Five patients died before receiving antifungal therapy and were excluded from analysis.

CI: confidence interval; IPA: invasive aspergillosis; COPD: chronic obstructive pulmonary disease; CT: computed tomography; GM: galactomannan.

Table 3. Univariate and multivariate analysis of predictors of success vs. Failure of antifungal therapy (n = 77)^a.

				Multivariate logistic regression analysis
Predictor	Success (n = 47)	Failure (n = 30)	p Value	Odds ratio (95% CI)	p Value
Median age (IQR)-yr	61 (57–70)	63 (57–67)	.83
Sex, male	14 (30)	18 (60)	.01
Race, white	42 (89)	26 (87)	>.99
Type of solid tumour
Lung cancer	19 (40)	18 (60)	.09
Head and neck cancer	10 (21)	4 (13)	.38
Breast cancer	10 (21)	1 (3)	.04
Gastrointestinal cancer	4 (9)	5 (17)	.30
Status of solid tumour
Remission/stable	30 (64)	8 (27)	<.01	1.0 (reference)	–
Progressive	17 (36)	22 (73)		0.1 (0.03–0.38)	<.01
Chemotherapy^b	10 (21)	12 (40)	.08
Prior history of chest radiation therapy	18 (38)	19/30 (66)	.02
Steroids^b	10 (21)	10 (33)	.24
Steroid dose >600 mg^c	6 (13)	6 (20)	.52
Diabetes mellitus	7 (15)	7 (23)	.35
COPD	17 (36)	8 (27)	.39
Underlying lung disease^d	32 (68)	25 (83)	.14
Serum GM positive at diagnosis	11/25 (44)	9/22 (41)	.83
Fungal stain positive for aspergillosis	7 (15)	12 (40)	.01	0.2 (0.05–0.75)	.02
Bacterial co-infection	21 (45)	13 (43)	.91
CT findings
Nodular lesions	19/45 (42)	14/25 (56)	.27
Cavitary lesions	6/45 (13)	2/25 (8)	.70
Nodular and cavitary lesions	5/45 (11)	4/25 (16)	.71
Consolidative lesions	7/45 (16)	2/25 (8)	.47
Therapy
Voriconazole-containing therapy	42 (89)	19 (63)	<.01	10.1 (2.1–48.5)	<.01
Other therapy	5 (11)	11 (37)		1.0 (reference)	–

^a Only patients who received primary antifungal therapy and had known end-of-therapy outcome were included in this analysis. Success was defined as complete response or partial response to therapy and patient alive at 12 weeks follow-up. Failure was defined as stable disease, progression of disease, or death at 12 weeks follow-up. Values in table are number of patients (percentage) unless otherwise indicated.

^b Chemotherapy or steroid therapy within 30 days before IPA diagnosis.

^c Cumulative steroid dose equivalent to >600 mg prednisone in the last 30 days before IPA diagnosis.

^d Underlying lung disease including tumour involvement as primary lung cancer or metastasis, radiation pneumonitis, and other structural lung diseases.

CI: confidence interval; COPD: chronic obstructive pulmonary disease; CT: computed tomography; GM: galactomannan; IPA: invasive aspergillosis.