Response to preoperative chemotherapy in patients undergoing resection of pulmonary metastasis from soft tissue sarcoma – a predictor of outcome?

Figures & data

Figure 1. Flow chart demonstrating the subgroups of patients chosen for analysis (study population in filled boxes). *Not included in this study.

Table I. Comparison of clinicopathologic and treatment characteristics in study population.

	Preoperative chemotherapy	Surgery alone
Characteristics	N = 52	N = 41	p
Gender
Male	27	13
Female	25	28	0.05
Median age at diagnosis (range), years	48 (14–72)	51 (10–81)	0.49
Primary site
Lower extremity	17	17
Upper extremity	11	8
Thoracic wall	10	7
Intraabdominal	10	7
Other	4	2	0.92
Histology
FS	6	3
LMS	8	6
LS	4	2
MFH	16	13
MPNST	2	2
SS	7	6
Other	9	9	0.99
Grade
Low	5	8
High	43	29
Unknown	4	4	0.32
Depth
Superficial	9	6
Deep	40	34
Unknown	3	1	0.77
Primary tumor size
< 5 cm	15	12
5–10 cm	22	11
> 10 cm	14	13
Unknown	1	5	0.15
Local recurrence
Yes	10	8
No	42	32
Unknown	0	1	0.68
Median DFI (range), m	17.5 (6–108)	35 (6–219)	0.02
Median no. of met * (range)	3 (1–50)	1 (1–52)	0.56
Pulmonary sides involved
Unilateral	27	35
Bilateral^$	25	6	0.001
Additional pleural met
Yes	14	8
No	38	33	0.47
Additional extrapulm met
Yes	10	6
No	42	34
Unknown	0	1	0.57
Radiotherapy to primary tumor
Yes	17	19
No	35	22	0.20
Chemotherapy to primary tumor
Yes	10	11
No	42	30	0.46

DFI, disease-free interval; FS, fibrosarcoma; LMS, leiomyosarcoma; LS, liposarcoma; MFH, malignant fibrous histiocytoma; MPNST, malignant peripheral nerve sheath tumor; SS, synovial sarcoma. Other (histology): phyllodes tumor, alveolar soft tissue sarcoma, clear cell sarcoma, Ewing's sarcoma, primitive neuroectodermal tumor, rhabdomyosarcoma, other small cell tumor, angiosarcoma, extraskeletal chondrosarcoma or unclassified. *Median number of metastasis at first event. ^$When handled sequentially, no more than three months between thoracotomies. Statistical significance in italic characters.

Table II. Distribution of patients among histological and radiological response to preoperative chemotherapy.

Radiological response (WHO)	Histological response (Huvos)
	I	II	III	IV	na	Total
CR	0	0	0	1^7	0	1
PR	8^2,4–7	5^3,7	1^1	2^3,7,$	0	16
SD	15^1–4,6,7,$	3^2,3,7	1^3,*	1^2,*	1^2,*	21
PD	4^3,6,$	3^3,6,$	0	0	0	7
na	3^3,$	1^5,$,*	0	0	3^1–3	7
Total	30	12	2	4	4	52

CR, complete response (the disappearance of all known disease, determined by two observations not less than four weeks apart); na, not applicable; PD, progressive disease (25% or more increase in the size of one or more measurable lesions or the appearance of new lesions); PR, partial response (50% or more decrease in total tumor load of the lesions that have been measured to determine the effect of therapy by two observations not less than four weeks apart); SD, stable disease (a 50% decrease in tumor size cannot be established nor has a 25% increase in the size of one or more measurable lesions been demonstrated). ¹Synovial sarcoma; ²Fibrosarcoma; ³Malignant fibrous histiocytoma; ⁴Malignant peripheral nerve sheath tumor; ⁵Liposarcoma; ⁶Leiomyosarcoma; ⁷Other histotypes; ^$1–5 patients with adjuvant chemotherapy in primary setting; *No postoperative chemotherapy. In bold characters, Adriamycin-based chemotherapy to all patients.

Figure 2. Kaplan-Meier curves depicting (a) DSS and PFS for the two cohorts in study population; preoperative chemotherapy and surgery alone. (b) PFS comparing various histopathologic responses to chemotherapy assessed by Huvos grading system and (c) DSS and PFS for various radiological responses; partial response (PR), stable disease (SD) and progressive disease (PD).

Table III. A. Uni- and multivariate analysis in histological response groups. Progression-free survival.

Univariate				Multivariate
Variables	Hazard ratio	95% CI	p	Variables	Hazard ratio	95% CI	p
Huvos IV	0.17	(0.02–1.21)	0.08	Huvos IV	0.08	(0.01–0.66)	0.02
MPNST	26.2	(4.31–159)	< 0.001	MPNST	24.6	(3.78–160)	0.001
Unilateral disease	0.51	(0.27–0.98)	0.04	Unilateral disease	0.48	(0.23–0.99)	0.05
No pleural metastasis	0.51	(0.25–1.05)	0.07	No pleural metastasis	0.39	(0.18–0.86)	0.02

B. Uni- and multivariate analysis in radiological response groups. Disease-specific survival.
PR	0.27	(0.10–0.75)	0.01	PR	0.19	(0.06–0.58)	0.003
SD	0.42	(0.17–1.04)	0.06	SD	0.27	(0.10–0.73)	0.01
FS	2.44	(0.90–6.61)	0.08
Unilateral disease	0.5	(0.24–1.03)	0.06
1–3 pulmonary nodules	0.31	(0.09–1.09)	0.07
No pleural metastasis	0.36	(0.17–0.80)	0.01
No extrapulmonary metastasis	0.49	(0.21–1.16)	0.10

C. Uni- and multivariate analysis in radiological response groups. Progression-free survival.
PR	0.27	(0.10–0.75)	0.01	PR	0.19	(0.06–0.55)	0.002
MPNST	35	(4.83–254)	< 0.001	MPNST	28.9	(3.67–227)	0.001
FS	2.40	(0.89–6.47)	0.08	FS	3.60	(1.18–10.9)	0.02
LR	2.24	(0.92–5.45)	0.08	LR	3.52	(1.32–9.41)	0.01
Unilateral disease	0.48	(0.24–0.94)	0.03	Unilateral disease	0.45	(0.21–0.93)	0.03
1–3 pulmonary nodules	0.33	(0.09–1.14)	0.08
No pleural metastasis	0.38	(0.17–0.83)	0.02

Multivariate Cox regression model with strategy ‘Backward LR’. CI, confidence interval; FS, fibrosarcoma; HR, hazard ratio; LR, local relapse; MPNST, malignant peripheral nerve sheath tumor; PR, radiological partial response; SD, radiological stable disease. Age, gender, performance status, primary tumor site, -size, -depth and -grade, other histological subtypes, disease-free interval, number of chemotherapy cycles, presence/absence of postoperative chemotherapy and other histological or radiological chemotherapy responses were not significant in univariate analysis (0.10 significance level), thus not included in multivariate analysis.

Statistical significance in italic characters.