Trial Information

1. Treatment protocol

- Patients with limited-stage (stage I/II) are treated with CHOP/CHOP-like
chemotherapy [cyclophosphamide 750 mg/m2 i.v. on D1, vincristine 1.4 mg/m2 i.v. on
D1, doxorubicin 50 mg/m2 i.v. on D1, and prednisolone 60 mg/m2 p.o. on D1-5] in
standard doses every three weeks and three to four cycles of CHOP/CHOP-like
chemotherapy followed by involved field radiation therapy (IFRT, 30 Gy). Patients
with advanced-stage (stage III/IV) are treated with eight cycles of primary
chemotherapy and patients greater than 65 years and/or those with a frail general
condition were treated with only six cycles of primary chemotherapy if they
achieved a complete response (CR) for the interim response.

2. Response evaluation based on three parameters of visual, standard uptake
value(SUV)-based and metabolic tumor volume (MTV)-based assessments

- We firstly classify patients with five-point scale (5-PS) by the interim PET/CT
analysis based on the Deauville criteria12: 1, No uptake; 2, uptake ≤ mediastinum;
3, uptake > mediastinum but ≤ liver; 4, uptake moderately increased compared to
the liver uptake at any site; 5, markedly increased uptake compared to the liver
at any site and new sites or/and new sites of disease. Interim PET/CT image are
graded as negative or positive by comparison of initial PET/CT and grade 1-3
considered as negative and grade 4-5 considered for positive.19 This grading
process is independent of the size of the residual tumor.

Secondly, we classify the patients with the quantitative analysis of 18F-FDG uptake
changes based on the percentage of SUVmax reduction between initial and interim PET/CT.
On axial, coronal, or sagittal coregistered PET/CT slices, simple circular regions of
interest (ROIs) were placed so as to cover the lesion or background. SUV measurements
are corrected for body weight according to the following standard formula: Mean ROI
activity (MBq/ml)

- [Injected dose (MBq)/Body weight (kg)].20 For each PET dataset, the maximum SUV
(SUVmax) is defined as the highest SUV among all hypermetabolic tumor foci. SUVmax
reduction rate (ΔSUVmax) is calculated as following:

ΔSUVmax (%) = 100 x [SUVmax (initial) - SUVmax (interim)]/SUVmax (initial)

If all lesions had disappeared on interim PET, ROI were drawn in the same area on
interim PET as on baseline PET.

We finally classify the patients with the quantitative analysis of metabolic volume
changes based on the percentage of MTV reduction (ΔMTV) between initial and interim
PET/CT. To define the exact tumor margins around the target lesions, SUV2.5 is used as
following previous reports, which means that the tumor volume area in PET/CT is
delineated by a circle encompassing regions with SUV cutoff value of 2.5.16,21 The
MTV2.5 is measured using AW Volume ShareTM workstation (GE Healthcare) on the fused
PET/CT images.17 AW Volume ShareTM allows automatic registration and fusion between two
volumetric acquisitions, which come from different acquisition modalities. The active
MTV2.5 are measured in a 3-D manner by selecting volume of interest (VOI) on the axial
image, and the size of VOI is manually regulated on the corresponding coronal and
sagittal images to include entire active tumors in the VOI. The SUVmax and the sum of
the tumor volumes in all hypermetabolic tumor foci were computed automatically by the
program. The MTV2.5 reduction rate (ΔMTV2.5) is calculated as same formula as SUVmax
reduction rate.

3. The response assessments of interim PET/CT scans

- will be assessed based on the combination with three parameters of the Deauville
five-point scale (5-PS), the reduction rate of maximal standardized uptake value
(ΔSUVmax), and the reduction rate of metabolic tumor volume (ΔMTV2.5) in PTCLs