intensity-modulated radiotherapy with simultaneous integrated boost (iMRt-SiB) reduces overall treatment duration and results in less radiotherapy (RT)-induced dermatitis. However, the use of traditional sequential approach or iMRt-SiB is still under debate since there is not enough evidence of long-term clinical outcomes. The present study investigated 216 patients who underwent breast conserving surgery (BCS) between 2010 and 2013. The median age was 51 years (range, 21-81 years). All patients received IMRT-SIB, 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Among 216 patients, 175 patients received post-operative RT with forward IMRT and 41 patients had Tomotherapy. The median follow-up was 6.4 years. Forty patients (97.6%) in the Tomotherapy arm and 147 patients (84%) in the IMRT arm developed grade 0-1 skin toxicity (P = 0.021). For the entire cohort, the 5-year and 7-year overall survival (OS) rates were 94.4% and 93.1% respectively. The 7-year distant metastasis-free survival rates were 100% vs 89.1% in the tomotherapy and iMRt arm respectively (P = 0.028). In conclusion, Tomotherapy improved acute skin toxicity compared with forward IMRT-SIB. Chronic skin complication was 1.9%. IMRT-SIB resulted in good long-term survival.
Serine peptidase inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, is known to be associated with inflammation and pathogenesis. The aim in this study was to demonstrate the clinicopathological role and progression of SPINK1 in rectal cancer (RC) patients undergoing concurrent chemoradiotherapy (CCRT). Immunohistochemical staining for SPINK1 protein expression in 111 RC cases revealed high SPINK1 expression was significantly associated with perineural invasion and poor CCRT response in pre-CCRT specimens. In addition, multivariable analyses showed that pre-CCRT SPINK1 expression was a significant prognostic marker of both overall and disease-free survival in RC patients receiving pre-operative CCRT; furthermore, in vitro studies demonstrated SPINK1 interacted with EGFR to promote the abilities of proliferation, migration and invasion attenuated by SPINK1 si-RNA via ERK, p38, and JNK pathways. SPINK1 was also found to regulate radio-resistance in CRC cell lines. In conclusion, SPINK1 expression is an independent prognostic marker in patients receiving pre-operative CCRT, and SPINK1 regulates proliferation, migration and invasion via EGFR-downstream ERK, p38 and JNK pathways. The phenotypes of radiosensitivity that could be reversed with attenuation of SPINK1 levels suggest that targeting SPINK1 might offer a strategy for optimal precision medicine.
Preoperative concurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced rectal cancer patients, but 20–30% do not benefit from the desired therapeutic effects. Previous reports indicate that high levels of ERCC1 reduce the effectiveness of cisplatin-based CCRT; however, it remains unclear as to whether ERCC1 overexpression increases radiation resistance. To clarify the correlation between ERCC1 levels and radiation (RT) resistance, we established two cell lines (HCT116-Tet-on and COLO205-Tet-on), induced them to overexpress ERCC1, detected cell survival following exposure to radiation, established HCT116-Tet-on and COLO205-Tet-on heterotopic cancer animal models, and detected tumor volume following exposure to radiation. We found that ERCC1 overexpression increased radiation resistance. After regulating ERCC1 levels and radiation exposure to verify the correlation, we noted that increased radiation resistance was dependent on ERCC1 upregulation in both cell lines. For further verification, we exposed HCT116-Tet-on and COLO205-Tet-on heterotopic cancer animal models to radiation and observed that ERCC1 overexpression increased colorectal cancer tumor radioresistance in both. Combined, our results suggest that ERCC1 overexpression may serve as a suitable CCRT prognostic marker for colorectal cancer patients.
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