Table 3 (supplement)

Studies assessing TS as biomarker in locally advanced rectal cancer by immunhistochemical staining
Author / No. of patients / Method / RCT regimen / Endpoints / Notes
Okonkwo et al. Onkol Rep. 2001 / n = 25 / IHC staining was assessed for positivity (>10% of tumor cells with cytoplasmatic staining) / 45Gy + 5-FU / Responder (pCR or only minimal residual tumor in mucosa or submucosa) vs Non-responders (invasion into muscularis propria and or lymph node metastases) / 8 tumors + for TS, 1 positive tumor in the responding group, 7 Non-responders (no statistical significance).
Negri et al. 200825 / n = 19 / IHC staining and categorizing according to visual grading system:
0 and 1 = low intensity
2 and 3 = high intensitiy / 40-45Gy + 5-FU + oxaliplatin / Responders (pCR or residual microfoci 0.3 to 0.9 cm) vs. Nonresponders (large residual carcinoma) in pathology specimens / Patients with high TS expression had higher rate of response to RCT.
Saw et al. Dis Colon Rectum 2003 / n = 35 / IHC staining, positivity if any tumor cell showed positive staining for TS / 45-50.4Gy + 5-FU/LV / TRG/CSS/LR/T-stage downstaging / Lack of TS expression correlatated with T-stage downsizing.
Bertolini et al.
Int J Radiation Oncol Biol Phys 2007 / n = 91 / IHC staining; positive if > 15% of tumor cells stained positive / 50.4Gy +5-FU / TRG, T-downstaging, DFS/CSS / No correlation.
Kikuchi et al. 200923 / n = 60 / IHC assessment of positivity by intensity and percentage score from tumor biopsies. / 45Gy +S-1 + Irinotecan / TRG / High TS levels correlated with response to RCT.
Conradi et al. 2011 / n = 208 / IHC staining of pretherapeutical biopsy and residual tumor. Assessment after modified Remmele score. / 50.4Gy +
5-FU or oxapliplatin / TRG, pCR rate, DFS and CSS / - Low TS in pre-treatment biopsy →
↓CSS (p=0.015).
- Low TS in residual tumor in ypN+
patients → ↓ DFS (p=0.040).

RCT (radiochemotherapy), IHC (Immunohistochemistry), pCR (pathological complete response), TRG (tumor regression grading), CSS (cancer specific overall survival), LR (local recurrence), DFS (disease free survival)