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Objective:To investigate the regulatory effect of deoxycytidine kinase (dCK) on ionizing radiation (IR) induced ferroptosis in triple-negative breast cancer (TNBC).Methods:TNBC cell line MDA-MB-231 was used to establish dCK knockdown and different phosphorylation phenotypes cell models, and were treated with ferroptosis activator Erastin and / or ferroptosis inhibitor ferrostatin-1 (Fer-1) combined with / without X-ray irradiation. Cell viability was detected by MTT assay. The level of reactive oxygen species (ROS) was measured by 2′,7′-dichlorofluorescin diacetate (DCFH-DA) staining. The expression levels of dCK, transferrin, transferrin receptor (TfR1), ferroportin (FPN) and ferritin heavy chain 1 (FTH1) were detected by Western blot. Statistical analysis was performed by SPSS 17.0 and Origin 2021 software. Measurement data with normal distribution were expressed by Mean ±SD. The comparison between two groups was conducted by Student t-test. The comparison among three or more groups was performed by one-way analysis of variance. Results:In MDA-MB-231 cells, IR induced cell death was observed and Erastin significantly promoted radiation induced cell death, while Fer-1 was able to reverse radiation induced cell death. Compared with the control group, IR induced cell death was increased, the level of ROS was suppressed in the dCK knockdown group. Erastin combined with IR induced reduced cell death and weakened ROS level. Fer-1 reduced the degree of IR induced cell death, and it could not inhibit the induction of ROS by IR.Compared with the control cells, the rate of cell death was decreased induced by IR, the level of ROS was decreased, the expression of FTH1 was down-regulated after IR in the dCK wild-type (dCK-WT ) or dCK hyperphosphorylated (dCK-S74E) MDA-MB-231 cells. In addition, Erastin promotes IR induced cell death and increased ROS levels, while Fer-1 significantly enhances the degree of reversal of IR induced ROS and cell death in these cells. Conclusions:dCK phosphorylation increases ferroptosis induced by IR in TNBC cells. Targeting dCK may be a novel therapeutic approach to overcome radioresistance in TNBC treatment.
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Objective To evaluate the efficacy of accelerated partial breast irradiation ( APBI ) and whole breast irradiation ( WBI ) with simultaneous integrated boost ( SIB ) from the perspective of economics, and provide a reference for postoperative adjuvant therapy mode selection for early-stage breast cancer after breast-conserving surgery. Methods A total of 355 early-stage breast cancer patients who underwent APBI or WBI-SIB after breast-conserving surgery were evaluated on efficacy and cost-effectiveness, of which 177 patients received APBI, and 178 patients received WBI-SIB. Survival analysis was done according to treatment received. NCI-CTC 3.0 was used to score the toxicities. Breast aesthetic outcome were evaluated with Harris standards. Results Median follow-up was 42 months ( 5.8 -92.7 months) . The 3-year locoregional recurrence free survival( LRFS) rates in APBI group and WBI-SIB group were 98.2％ and 97.6％, distant metastasis free survival( DMFS) were 94.3％ and 93.7％, disease-free survival ( DFS) were 93.1％ and 91.6％, and overall survival 95.5％ and 94.3％, respectively, without statistically significant differences(P>0.05). Compared with WBI-SIB group, the acute reaction rates in APBI group decreased from 5. 6％ to 3.4％(χ2 =6.044, P <0. 05), and late reactions from 5.6％ to 2.3％ (χ2 =6.149, P<0. 05), while the cosmetic outcome improved from 88.8％ to 93.8％(χ2 =5.22, P<0. 05). Moreover, the processing average time was shortened by 26.5 d (χ2 =40.76, P<0. 05). Conclusions After breast-conserving surgery, the efficacy of APBI showed no difference from WBI-SIB with respect to 3-year local control, disease-free survival, and overall survival, but displayed a significantly better toxicity profile and cost-effectiveness ratio for early breast cancer patients. It can be used as a good radiotherapy model after breast-conserving surgery in early-stage breast cancer.
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Objective To investigate the consensus and controversies on the delineation of radiotherapy target volume for patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods Questionnaires including 15 questions on the delineation of radiotherapy target volume of NSCLC were sent to 12 radiation departments in China in November 2015.A patient with LA-NSCLC was selected by Fudan University Shanghai Cancer Center, and simulation CT images and medical history data were sent to the 12 radiation departments.Twelve radiation oncologists from the 12 radiation departments showed and explained the delineation of radiotherapy target volume of their own, and the patient was discussed by all experts in the sixth multidisciplinary summit forum of precise radiotherapy and chemotherapy for tumor and lung cancer.Results All receivers of the questionnaire answered the questions.The standard lung window width/level for the delineation of lung cancer was 800-1600/-600 to-750 HU, and the mediastinum window was 350-400/20-40 HU.Respiratory movement was measured by stimulator, 4D-CT, and stimulator+4D-CT with 2-5 mm expansion based on experience.The primary clinical target volume (CTV) was defined as gross target volume (GTV) plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma.The metastatic lesion of mediastinal lymph nodes was delineated as 5 mm plus primary lesion in 6 departments and as primary lesion in another 6 departments.Of the 12 departments, 10 applied 5 mm of set-up error, 1 applied 3 mm, and 1 applied 4-6 mm.For V20 of the lungs, 10 departments defined it as<30%, 1 as<35%, and 1 as 28%.Nine departments defined the radiation dose of concurrent chemoradiotherapy (CCRT) for LA-NSCLC as 60 Gy in 30 fractions, 62.7 Gy in 33 fractions in 1 department, 50-60 Gy in 25-30 fractions in 1 department, and 60-70 Gy in 25-30 fractions in 1 department.For the delineation of target volume for the LA-NSCLC patient treated with CCRT, the primary planning target volume (PTV) was defined as GTV plus organ movement (IGTV) and set-up error (GTV→IGTV→PTV) in 3 departments, as CTV plus organ movement (ITV) and set-up error (GTV→CTV→ITV→PTV) in 8 departments, and as CTV plus set-up error/IGTV plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma (CTV) and set-up error (GTV→CTV→PTV/GTV→IGTV→CTV→PTV) in 1 department.For the delineation of PTV in the mediastinal lymph node, GTV→IGTV→PTV was performed in 3 departments, GTV→CTV→ITV→PTV in 8 departments, and GTV→CTV→PTV in 1 department.For 10%-100% patients with LA-NSCLC, the radiation field needed to be replanned when 38-50 Gy was completed.There was no unified standard for the optimal standardized uptake value (SUV) of positron emission tomography (PET)-computed tomography (CT) simulation and delineation.Seven departments had applied magnetic resonance imaging (MRI) simulation and 10 departments had applied stereotactic body radiation therapy (SBRT) for the treatment of early-stage NSCLC.For the delineation of PTV for early-stage NSCLC (T1-2N0M0), GTV→IGTV→PTV was performed in 5 departments, IGTV→PTV in 3 departments, and GTV→CTV→ITV→PTV in 2 departments.In all the 12 departments, peripheral early-stage NSCLC was given 6.0-12.5 Gy/fraction, 3-12 fractions and central early-stage NSCLC was given 4.6-10.0 Gy/fraction, 5-10 fractions.The results of discussion on the delineation of target volume for the patient were as follows:respiratory movements should be measured by 4D-CT or simulator;the lung window width/level is 1600/-600 HU and the mediastinal window width/level is 400/20 HU;the primary controversy is whether the involved-field irradiation or elective nodal irradiation should be used for the delineation of CTVnd in the mediastinal lymph node.Conclusions Basic consensus is reached for the delineation of target volume in LANSCLC in these aspects:lung window width/level, respiratory movements and set-up error, primary lesion delineation, the radiation dose in CCRT, and the optimal time for replanning the radiation field.There are controversies on the optimal SUV in the delineation of target volume based on PET-CT simulation, the optimal dose fractionation in SBRT for early-stage NSCLC, and the delineation of CTVnd.