Simultaneous integrated boost intensity-modulated radiotherapy post breast-conserving surgery: clinical efficacy, adverse effects, and cosmetic outcomes in breast cancer patients.

BACKGROUND: Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) is an innovative technique delivering a higher dose to the tumor bed while irradiating the entire breast. This study aims to assess the clinical outcomes, adverse effects, and cosmetic results of SIB-IMRT following breast-conserving surgery in breast cancer patients. METHODS: We conducted a retrospective analysis of 308 patients with stage 0-III breast cancer who underwent breast-conserving surgery and SIB-IMRT from January 2016 to December 2020. The prescribed doses included 1.85 Gy/27 fractions to the whole breast and 2.22 Gy/27 fractions or 2.20 Gy/27 fractions to the tumor bed. Primary endpoints included overall survival (OS), local-regional control (LRC), distant metastasis-free survival (DMFS), acute and late toxicities, and cosmetic outcomes. RESULTS: The median follow-up time was 36 months. The 3-year OS, LRC, and DMFS rates were 100%, 99.6%, and 99.2%, respectively. Five patients (1.8%) experienced local recurrence or distant metastasis, and one patient succumbed to distant metastasis. The most common acute toxicity was grade 1-2 skin reactions (91.6%). The most common late toxicity was grade 0-1 skin and subcutaneous tissue reactions (96.7%). Five patients (1.8%) developed grade 1-2 upper limb lymphedema, and three patients (1.1%) had grade 1 radiation pneumonitis. Among the 262 patients evaluated for cosmetic outcomes at least 2 years post-radiotherapy, 96.9% achieved excellent or good results, while 3.1% had fair or poor outcomes. CONCLUSIONS: SIB-IMRT after breast-conserving surgery in breast cancer patients demonstrated excellent clinical efficacy, mild acute and late toxicities, and satisfactory cosmetic outcomes in our study. SIB-IMRT appears to be a feasible and effective option for breast cancer patients suitable for breast-conserving surgery.

Cardiac valve calcification prevalence and association with neutrophil-to-lymphocyte ratio in newly diagnosed patients with non-dialysis chronic kidney disease stage 3-5.

OBJECTIVE: Cardiac valvular calcification (CVC) is the main cause of cardiovascular disease and all-cause death in patients with chronic kidney disease (CKD). However, the relationship between Neutrophil lymphocyte ratio (NLR) and CVC in patients with CKD is not clear. In this study, we aimed to investigate the prevalence of CVC in newly diagnosed patients with non-dialysis CKD stage 3-5 and evaluate the correlation between NLR and CVC. METHODS: A total of 483 newly diagnosed patients with non-dialysis CKD stage 3-5 were included. According to the presence of CVC, these patients were retrospectively divided into two groups: CVC group and non-CVC group. RESULTS: CVC was found in 80 patients (16.56 %), 53 (10.97 %) of whom had only aortic valve calcification (AVC), 18 (3.73 %) had mitral valve calcification (MVC), and 9 (1.86 %) had both AVC and MVC. The level of NLR in the CVC group was significantly higher than that in the non-CVC group (p=0.002). Multivariate logistic regression analysis showed that NLR was an independent risk factor for CVC (95% CI 1.017~1.225, p=0.020). ROC curve analysis showed that the area under the curve of NLR for predicting CVC was 0.610 (95% CI 0.543-0.676, p=0.002). The best cut-off point of NLR was 3.340, with a sensitivity of 49.4 % and a specificity of 70.0 %. CONCLUSION: CVC is not uncommon in newly diagnosed patients with non-dialysis CKD stage 3-5, and NLR is an independent risk factor for CVC (Tab. 4, Fig. 1, Ref. 34).

Expressing MLH1 in HCT116 cells increases cellular resistance to radiation by activating the PRKAC.

Mut L homolog-1 (MLH1) is a key DNA mismatch repair protein which participates in the sensitivity to DNA damaging agents. However, its role in the radiosensitivity of tumor cells is less well characterized. In this study, we investigated the role of MLH1 in cellular responses to ionizing radiation (IR) and explored the signaling molecules involved. The isogenic pair of MLH1 proficient (MLH1+) and deficient (MLH1-) human colorectal cancer HCT116 cells was exposed to IR for 24 h at the dose of 3 cGy. The clonogenic survival was examined by the colony formation assay. Cell cycle distribution was analyzed with flow cytometry. Changes in the protein level of MLH1, DNA damage marker γH2AX, and protein kinase A catalytic subunit (PRKAC), a common target for anti-tumor drugs, were examined with Western blotting. The results showed that the HCT116 (MLH1+) cells demonstrated increased radio-resistance with increased S population, decreased G2 population, a low level of γH2AX, a reduced ratio of phosphorylated PRKACαß to total PRKAC, and an elevated level of total PRKAC and phosphorylated PRKACßII following IR compared with the HCT116 (MLH1-) cells. Importantly, silencing PRKAC in HCT116 (MLH1+) cells increased the cellular radiosensitivity. In conclusion, MLH1 may increase cellular resistance to IR by activating PRKAC. Our finding is the first to demonstrate the important role of PRKAC in MLH1-mediated radiosensitivity, suggesting that PRKAC has potential as a biomarker and a therapeutic target for increasing radio-sensitization.