Table 2.
Studies of potential tissue biomarker for PDAC patients considering radiotherapy
| Study | Study type | Pt no. | PDAC stage | Tissue Origin | Treatment | biomarker | Endpoint | Conclusion | Significance |
|---|---|---|---|---|---|---|---|---|---|
| 2011 Crane CH [52] | Pro-spective phase II | 69 | LA | Cytology | GEMOX + cetuximab + capecitabine-CRT | Smad4 | Failure pattern | Pattern of progression may be predictable on the basis of Smad4 expression |
intact Smad4 in 11/15 (73.3%) of local dominant recurrence. Smad4 loss in 10/14 (71.4%) distant dominant recurrence P = 0.016 |
|
2017 Shin SH [53] |
Retro-spective | 641 | resectable | IHC |
Adjuvant 5-FU/LV or GEM; 5-FU-CRT for R1 resection |
Smad4 | OS, recurrence |
1.Inactivation Smad4 indicate metastasis 2.In expressed Smad4, local therapy contributes to improved survival |
1. HR: 4.28 2. p = 0.002 |
| 2015 Whittle MC [54] | Retro-spective | 88 | resectable | IHC /ICGC | Chemotherapy with or without radiotherapy | Runx3 | OS, relapse pattern | Low Runx3 benefit from radiotherapy | p < 0.018 |
|
2021 Pen SL [58] |
Pro-spective phase III | 111 | resectable | IHC | Adjuvant GEM +/- GEM-CRT | Smad4, KLF10, Runx3 | OS, RFS | Combining KLF10 and Smad4 may predict the benefits of adjuvant CRT in resected PDAC | High KLF10 or Smad4 (n = 55) had better local RFS (p = 0.026) and longer OS (p = 0.12) receiving adjuvant CRT than GEM alone. |
| 2019 Nevler A [59] | Retro-spective | 129 | resected | DNA/ TCGA | With or without radiotherapy | Indoleamine 2,3 dioxygenase 2 (IDO2) | RFS | IDO2 inactivation associated with improved RFS in response to RT | p = 0.023 |
| 2022 Wada Y [60] | Retro-spective | 88 | resected | Frozen tissue | Resected with or without Neoadjuvant CRT | Choline metabolites | RFS | Reduced choline metabolites correlate with better RFS especially in NA-CRT group |
Choline: P = 0.0022 (in NA-CRT: p = 0.028) Phospho-choline: p = 0.0086 (in NA-CRT p = 0.0037) |
| 2015 Strom T [62] | Retro-spective | 73 | resectable | DNA |
Adjuvant GEM/5FU ± RT(n = 61) No adjuvant therapy (n = 12) |
10 specific genes (RSI score) | OS | Among clinical high risk irradiated patients, RSI low (radiosensitive) had significantly improved survival | High risk patient (R1, N1, postop CA19-9 > 90, n = 31) RSI low vs. RSI high OS:31.2 vs. 13.2 months, p = 0.04 |
Pt: patient; LA: locally advanced; GEMOX: gemcitabine + oxaliplatin; CRT: chemoradiotherapy; IHC: immunohistochemistry;5-FU/LV: 5-fluorouracil/leucovorin; ICGC: International Cancer Genome Consortium; RFS: recurrence-free survival; OS: overall survival; TCGA: the cancer genome atlas; NAT: neoadjuvant therapy; RSI: radiation sensitivity index