Article Figures & Data
Figures
- Figure 1.
Clinical presentation of patient ADO-06 (A) before treatment; B, at 3 months of imatinib showing marked tumor shrinkage (PR); C, at 6 months of imatinib showing ongoing tumor shrinkage, but also secondary resistance with outgrowth of new tumor lesions (arrows); D, at 13.5 months after onset of imatinib, 7 months after imatinib discontinuation, and definitive surgery with tumor-free margins, showing a good result of skin graft reconstruction but also local tumor recurrence at the left neck (arrow). This recurrent tumor was resistant to imatinib, but sensitive to sunitinib.
- Figure 2.
Patient ADO-06. A, FDG (2[18F]fluoro-2-deoxy-d-glucose)-positron emission tomography scans showing a decrease of FDG uptake in the tumor area (arrows), (left) before treatment compared with (right) 10 days of imatinib. B, FISH analysis on tumor cells obtained (left) before treatment and (right) at 3 months of imatinib showing colocalization and amplification of COL1A1 (green) and PDGFB (red). C, phosphorylation analysis of 42 RTKs in tumor tissue obtained (top) before treatment and (bottom) at 3 months of imatinib: 1, EGFR; 2, PDGFRA; 3, PDGFRB; 4, MCSFR; 5, insulin receptor; 6, IGF-1R. D, immunohistochemical staining of CD34 in tumor tissue obtained (from top to bottom) before treatment, at 3 months of imatinib showing decreased cellularity and hyalinic fibrosis, from local recurrence at 7 months after stop of imatinib, and from tumor mass infiltrating the lung at 35 months after stop of imatinib; magnification 1:100.
Tables
- Table 1.
Patient characteristics at enrollment (per protocol)
Patient ID Age y Gender History of histologically confirmed DFSP (mo) Disease stage Location Longest tumor diameter (method of assessment) ECOG performance state Previous therapy of DFSP ADO-01 52 F 177 Local recurrence Trunk (presternal) 3.4 cm (ultrasound) 0 Surgery ADO-02 50 M 1 Primary Trunk (presternal) 9.5 cm (ultrasound) 0 None ADO-03 66 M 2 Primary Extremities (upper arm) 3.6 cm (MRI) 0 None ADO-04 74 F 1 Primary Trunk (inframammary) 5.0 cm (MRI) 0 None ADO-05 37 F 1 Primary Extremities (upper leg) 5.9 cm (MRI) 0 None ADO-06 69 F 10 Primary Trunk (upper back) 18.3 cm (MRI) 1 None ADO-07 51 F 1 Primary Trunk 9.2 cm (ultrasound) 0 None ADO-09 27 F 27 Local recurrence Trunk (shoulder/upper back) 1.7 cm (ultrasound) 0 Surgery ADO-10 56 F 1 Primary Trunk (lower abdomen) 2.7 cm (ultrasound) 0 None ADO-11 43 F 1 Primary Trunk (presternal) 4.0 cm (MRI) 0 None ADO-12 57 M 294 Local recurrence Trunk (shoulder/upper back) 6.0 cm (CT) 2 Surgery, radiation ADO-13 39 F 1 Primary Trunk (presternal) 4.5 cm (MRI) 0 None ADO-15 72 F 17 Primary Trunk (upper abdomen) 6.8 cm (MRI) 2 None ADO-16 37 F 3 Primary Trunk (lower abdomen) 4.0 cm (MRI) 0 None NOTE: Characteristics of the per protocol patient population at study enrollment.
- Table 2.
Treatment characteristics, response, and follow-up (per protocol)
Patient ID Longest tumor diameter at enrollment (method) Longest tumor diameter at 6 weeks (method) response Longest tumor diameter at 12 weeks (method) response Duration of imatinib therapy (months) Best overall response (diameter change by RECIST) Progression during ongoing imatinib therapy (subsequent treatment) Definitive surgery (months from onset of imatinib) Safety margins at definitive surgery Relapse after end of imatinib therapy (subsequent treatment) Follow-up from onset of imatinib (months) ADO-01 34 mm (Ultrasound) 25 mm (Ultrasound) SD 19 mm (Ultrasound) PR 3.0 PR (−42%) None Yes (3.1) Unknown None 97.3+ ADO-02 95 mm (Ultrasound) 92 mm (Ultrasound) SD 33 mm (Ultrasound) PR 2.8 PR (−65%) None Yes (3.2) 1.5 cm None 29.9+ ADO-03 36 mm (MRI) 28 mm (Ultrasound) SD 22 mm (Ultrasound) PR 1.5 PR (−40%) None Yes (2.8) 0.5 cm None 89.3+ ADO-04 50 mm (MRI) 35 mm (MRI) PR 29 mm (MRI) PR 2.8 PR (−42%) None Yes (2.9) 1.0 cm None 82.9+ ADO-05 59 mm (MRI) 57 mm (MRI) SD 48 mm (MRI) SD 7.0 PR (−33%) None Yes (7.0) 1.0 cm None 84.2+ ADO-06 183 mm (MRI) 165 mm (MRI) SD 125 mm (MRI) PR 6.3 PR (−45%) Progression and new lesions in primary location at 5.7 months (surgery: CR) Yes (6.5) 0.5 cm Local recurrence at 7 months (imatinib: PD, sunitinib: PR, surgery: CR); distant metastasis at 35 months (radiation: PD) 48.3; Death by DFSP ADO-07 92 mm (Ultrasound) 115 mm (Ultrasound) PD NE (tumor excised) 1.5 PD (+25%) Progression at 1.5 months (surgery: CR) Yes (1.5) Unknown None 23.2+ ADO-09 17 mm (Ultrasound) 17 mm (Ultrasound) SD 15 mm (Ultrasound) SD 2.8 SD (−12%) None Yes (2.8) 1.0 cm None 57.2+ ADO-10 27 mm (Ultrasound) 25 mm (Ultrasound) SD 40 mm (Ultrasound) PD 2.9 SD (−7%) Progression at 2.9 months (surgery: CR) Yes (2.9) 2.0 cm None 79.5+ ADO-11 40 mm (MRI) 36 mm (MRI) SD 32 mm (MRI) SD 2.8 SD (−20%) None Yes (3.1) 1.0 cm None 67.5+ ADO-12 60 mm (CT) 58 mm (CT) SD 62 mm (CT) SD 5.2 SD (±0%) None Yes (6.5) Wide (limb amputation) None 76.9+ ADO-13 45 mm (MRI) 45 mm (MRI) SD 45 mm (MRI) SD 3.3 SD (±0%) None Yes (3.3) Unknown None 76.7+ ADO-15 68 mm (MRI) 59 mm (MRI) SD 48 mm (MRI) PR 16.7 CR (clinical evaluation) None No (imatinib continued until CR) NA None 46.7; Death by other reason ADO-16 40 mm (MRI) ND 28 mm (MRI) PR 3.3 PR (−30%) None Yes (3.7) 2.0 cm None 70.2+ NOTE: Course of treatment, outcome and follow-up of the (per protocol) patient population.
Abbreviations: NA, not applicable; ND, not done; NE, not evaluable; SD, stable disease.
- Table 3.
Morphologic and molecular tumor characteristics before imatinib therapy (per protocol)
Patient ID Tumor type COL1A1–PDGFB Localization (tissue layers involved) CD34 S100 Vascularization Hemorrhages Cellular/nuclear pleomorphism Ki67 Mitoses ADO-01 DFSP NE Dermis + subcutis Positive (homogeneous) Negative Moderate Several None/none 5% None ADO-02 DFSP NE Dermis + subcutis + sceletal muscles Positive (homogeneous) Negative High None None/moderate ND None ADO-03 DFSP ND Subcutis Positive (heterogeneous) Negative Low None None/moderate–high ND Several ADO-04 DFSP-FS Positive (RT-PCR + sequencing, FISH) Dermis + subcutis Positive (homogeneous) Negative Moderate None Low–moderate/none 6% Sporadic ADO-05 DFSP Positive (RT-PCR + sequencing) Dermis + subcutis Positive (homogeneous) Negative Moderate None None/none 2% None ADO-06 DFSP, myxoid type Positive (RT-PCR + sequencing, FISH) Dermis + subcutis Positive (homogeneous) Negative Moderate None Low/none 3% None ADO-07 DFSP-FS, pigmented type Positive (RT-PCR + sequencing, FISH) Dermis + subcutis Positive (heterogeneous) Positive (heterogeneous) High None Moderate/moderate–high ND Sporadic ADO-09 DFSP, pigmented-type ND Dermis + subcutis Positive (homogeneous) Negative Low None None/none ND None ADO-10 DFSP Negative (RT-PCR + sequencing) Dermis + subcutis Positive (homogeneous) ND Moderate None None/none 4% None ADO-11 DFSP Positive (RT-PCR + sequencing) Dermis + subcutis Positive (homogeneous) Negative Moderate None None/none 4% None ADO-12 DFSP ND Dermis + subcutis + deep soft tissue + bone Positive–negative (heterogeneous) Negative High Numerous None/none 5% None ADO-13 DFSP Negative (FISH) Dermis + subcutis Positive (homogeneous) Negative Moderate None Low/none 8% Sporadic ADO-15 DFSP NE Dermis + subcutis Positive (homogeneous) Negative Low None Moderate/none 2% None ADO-16 DFSP Negative (RT-PCR + sequencing) Dermis + subcutis Positive (homogeneous) ND Moderate None Low/none 2% Several NOTE: Morphologic and molecular tumor characteristics as analyzed in the per protocol population, for details see Patients and Methods.
Abbreviations: ND, not done; NE, not evaluable.
- Table 4.
Clinical trials of imatinib in DFSP
Clinical trial Regimen/imatinib dose Patients (total) Patients with DFSP only (tumor type) Median therapy duration (months) Grade 3 and 4 toxicity Best response (DFSP only) Secondary resistance to imatinib Relapse after definitive surgery Biomarkers of responsea Median follow-up time (years) ITECS B2225 (McArthur and colleagues 2005) Imatinib in nonresectable DFSP, 800 mg/d 10 (8 Locally advanced, 2 metastatic) 10 (8 DFSP Classic, 2 DFSP-FS) 7.0 ND 4 CR 2/10 (1 PD After 2 years, 1 PD after 7 months) 0/6 Decrease of cellularity (+), formation of hyalinic fibrosis (+) 1.1 5 PR 1 SD (90% CR/PR) SWOG S0345 (Rutkowski and colleagues 2010) Imatinib in nonresectable DFSP, 400 mg/d 8 (7 Locally advanced, 1 metastatic) 7 (5 DFSP Classic, 2 DFSP-FS) 10.8 7 Events/8 patients (87.5%) 4 PR ND ND ND 2.6 2 SD 1 PD (57% CR/PR) EORTC 62027 (Rutkowski and colleagues 2010) Imatinib in nonresectable DFSP, 800 mg/d 16 (10 Locally advanced, 6 metastatic) 16 (8 DFSP Classic, 7 DFSP-FS, 1 DFSP pigmented-type) 8.1 13 Events/16 patients (81.3%) 7 PR ND ND ND 2.6 4 SD 3 PD 2 NE (44% CR/PR) French trial (Kerob and colleagues 2010) Neoadjuvant imatinib in resectable DFSP, 600 mg/d 25 (All locally advanced) 25 (25 DFSP Classic) 2.0 5 Events/25 patients (20%) 9 CR/PR NA (Obligatory tumor excision after 2 months of imatinib) ND Decrease of cellularity (+), formation of hyalinic fibrosis (+) No follow-up 15 SD/PD 1 NE (36% CR/PR) ADO DFSP-001 (Ugurel and colleagues) Neoadjuvant imatinib in resectable DFSP, 600 mg/d 16 (All locally advanced) 14 (10 DFSP Classic, 2 DFSP-FS, 1 DFSP pigmented-type, 1 DFSP myxoid) 3.1 4 Events/16 patients (25%) 1 CR 1/14 (PD After 6 months) 1/13 (Local recurrence, metastasis and death) Low PDGFRB phosphorylation (−), pigmented-type DFSP (−), decrease of cellularity (+), formation of strong hyalinic fibrosis (+) 6.4 7 PR 5 SD 1 PD (57% CR/PR) NOTE: Overview on clinical trials of imatinib in DFSP.
Abbreviations: SD, stable disease; NE, not evaluable; NA, not applicable; ND, not done.
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↵a(+), favorable prognosis; (−), unfavorable prognosis.
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Supplementary Data
Files in this Data Supplement:
- Supplementary Methods, Tables 1 - 2 - PDF file - 98K, Table 1. Toxicity of the intention to treat (ITT) population, classified and graded according to CTC 2.0 (http://ctep.cancer.gov/reporting/ctc.html). Data represent the worst CTC grade experienced by each patient. Table 2. Morphological and molecular tumor characteristics as analyzed in the per protocol (PP) population, for details see Patients and Methods. PDGFRB, platelet-derived growth factor receptor beta; EGFR, epidermal growth factor receptor; IR, insulin receptor; NA, not applicable.
Volume 20, Issue 2
