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Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.
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Objective:To evaluate the safety and tolerance of sequential thoracic radiotherapy combined with PD-1/PD-L1 inhibitors in patients with extensive-stage small cell lung cancer (ES-SCLC) after induction systemic therapy.Methods:ES-SCLC patients from a phase I trial and a real-world study were enrolled for those who received thoracic radiotherapy after induction systemic treatment (chemotherapy/chemotherapy combined with PD-1/PD-L1 inhibitors) and consolidated with PD-1/PD-L1 inhibitors. These two studies were both approved by the Ethics Committee of Chinese Academy of Medical Sciences Cancer Hospital (Clinical Trials.gov number, NCT03971214, NCT04947774).Results:Between January 2019 and March 2021, a total of 11 patients with ES-SCLC were analyzed, aged 52-73 years, with a median age of 62 years. Among them, five patients (45.5%) received induction chemotherapy and six patients (54.5%) received chemotherapy combined with PD-1/PD-L1 inhibitor, and then all received intensity-modulated thoracic radiotherapy after evaluation of systemic treatment efficacy. Two patients developed treatment-related grade G3-5 toxicity (18.2%, 1 treatment-related pneumonitis and 1 radiation esophagitis). G 1-G 2 hematologic toxicity, pneumonia, and anorexia were common mild toxicities. Only one patient (9.1%) terminated immunotherapy due to immune-related pneumonitis. During a median follow-up time of 12.5 months (range: 3.5-16.4 months), the median disease progression-free survival and overall survival was 7.4 months (95% CI: 6.9-8.0 months) and 14.6 months (95% CI: 9.0-20.2 months), respectively. Conclusions:Sequential thoracic radiotherapy followed by PD-1/PD-L1 inhibitor is safe and feasible in patients with ES-SCLC after induction therapy. Given that both thoracic radiotherapy and immunotherapy benefits the ES-SCLC in survival, this comprehensive treatment modality warrants further investigation.
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Radiotherapy is one of the most important components of cancer treatment. Image-guided radiotherapy (IGRT) is the mainstream tool in the precision radiation oncology. Magnetic resonance (MR) accelerator can perform MRI for tumors during radiotherapy, deliver real-time tracing and monitoring of tumors and thus realize the MRI-guided adaptive radiotherapy. Here, the latest research status and clinical application of MR accelerator in lung cancer were reviewed.
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Objective:To compare magnetic resonance imaging (MRI)-based and computed tomography (CT)-based target volume delineation and dose coverage in partial breast irradiation (PBI) for patients with breast cancer, aiming to explore the application value of MRI localization in PBI after breast-conserving surgery.Methods:Twenty-nine patients with early breast cancer underwent simulating CT and MRI scans in a supine position. The cavity visualization score (CVS) of tumor bed (TB) was evaluated. The TB, clinical target volume (CTV), planning target volume (PTV) were delineated on CT and MRI images, and then statistically compared. Conformity indices (CI) between CT- and MRI-defined target volumes were calculated. PBI treatment plan of 40 Gy in 10 fractions was designed based on PTV-CT, and the dose coverage for PTV-MRI was evaluated.Results:The CVS on CT and MRI images was 2.97±1.40 vs. 3.10±1.40( P=0.408). The volumes of TB, CTV, PTV on MRI were significantly larger than those on CT, (24.48±16.60) cm 3vs. (38.00±19.77) cm 3, (126.76±56.81) cm 3vs. (168.42±70.54) cm 3, (216.63±81.99) cm 3vs. (279.24±101.55) cm 3, respectively, whereas the increasing percentage of CTV and PTV were significantly smaller than those of TB. The CI between CT-based and MRI-based TB, CTV, PTV were 0.43±0.13, 0.66±0.11, 0.70±0.09( P<0.001), respectively. The median percentage of PTV-MRI receiving 40 Gy dose was 81.9%(62.3% to 92.4%), significantly lower than 95.6%(95.0%~97.5%) of PTV-CT. Conclusions:The CVS between CT and MRI is not significantly different, but the MRI-based TB, CTV, PTV are significantly larger than CT-based values. The PTV-MRI is of underdose if PBI treatment plan is designed for PTV-CT. As a supplement of CT scan, MRI can enhance the accuracy of TB delineation after breast-onserving surgery.
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Objective@#To analyze the failure patterns of locoregional recurrence (LRR) and investigate the range of radiotherapy in T1-2N1 breast cancer patients undergoing modified radical mastectomy.@*Methods@#From September 1997 to April 2015, 2472 women with T1-2N1 breast cancer after modified radical mastectomy without neoadjuvant systemic therapy were treated in our hospital. 1898 patients who did not undergo adjuvant radiotherapy were included in this study. The distribution of accumulated LRR was analyzed. The LR and RR rates were estimated by the Kaplan-Meier method, and the prognostic factors were identified in univariate analyses with Log-rank test. Multivariate analysis was performed using Cox logistic regression analysis.@*Results@#With a median follow-up of 71.3 months (range 1.1-194.6), 164 patients had LRR, including supraclavicular/infraclavicular lymph nodes in 106(65%), chest wall in 69(42%), axilla in 39(24%) and internal mammary lymph nodes (IMNs) in 19 patients (12%). In multivariate analysis, age (>45 years vs.≤45 years), tumor location (other quadrants vs. inner quadrant), T stage (T1 vs. T2), the number of positive axillary lymph nodes (1 vs. 2-3), hormone receptor status (positive vs. negative) were significant prognostic factors for both LR and RR.@*Conclusions@#In patients with T1-2N1 breast cancer after modified radical mastectomy, the most common LRR site is supraclavicular/infraclavicular nodal region, followed by chest wall. The axillary or IMN recurrence is rare. The prognostic factors for LR and RR are similar, which indicates that supraclavicular/infraclavicular and chest wall irradiation should be considered for postmastectomy radiotherapy.
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Objective:To analyze the efficacy of chest wall boost radiotherapy in stage T 4 breast cancer patients after modified radical mastectomy. Methods:A retrospective analysis was performed on the data of 148 stage T 4 breast cancer patients who were admitted from 2000 to 2016 and received radiotherapy after modified radical mastectomy. There were 57 cases in the chest wall boost radiotherapy group and 91 cases in the conventional dose group. Radiotherapy was performed by conventional+ chest wall electron beam, three-dimensional conformal+ chest wall electron beam, intensity modulated radiotherapy+ chest wall electron beam irradiation. EQD 2 at the boost group was >50Gy. All patients received neoadjuvant chemotherapy. Kaplan-Meier method was used to analyze survival; Logrank was used to test differences; and Cox model was used to do multivariate prognostic analysis. Results:The median follow-up time was 67.2 months. The 5-year rates of chest wall recurrence (CWR), locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) were 9.9%, 16.2%, 58.0%, and 71.4%, respectively. The 5-year rates of CWR, LRR, DFS, and OS with and without chest wall boost radiotherapy were 14% vs. 7%, 18% vs. 15%, 57% vs. 58%, 82% vs. 65%( P>0.05), respectively. Multivariate analysis showed that chest wall boost radiotherapy had no significant effect on prognosis ( P>0.05). Among 45 patients in the recurrent high-risk group, boost radiotherapy seemed to have higher OS rate ( P=0.058), DFS rate ( P=0.084), and lower LRR rate ( P=0.059). Conclusions:Stage T 4 breast cancer patients had strong heterogeneity. Chest wall boost radiotherapy did not apparently benefit all patients. For patients with 2-3 high risk factors including positive vascular tumor embolus, pN 2-N 3, and hormone receptor negative, chest wall boost radiotherapy showed a trend of improving efficacy.
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Objective To analyze the differences in the treatment patterns,clinical characteristics,treatment outcomes and prognostic factors between breast cancer patients with ductal carcinoma in situ (DCIS) and ductal carcinoma in situ with microinvasion (DCIS-MI).Methods Clinical data of 866 female patients including 631 DCIS cases and 235 DCIS-MI cases treated in our institution between 1999 and 2013 were retrospectively analyzed.The local control (LC),disease-free survival (DFS) and overall survival (OS) rates were calculated by Kaplan-Meier survival analysis.The prognostic factors were identified by Log-rank test.Results Similar LC,DFS and OS rates were obtained between two groups (all P＞ O.05).The univariate analysis demonstrated that Her-2-positive patients had worse OS and DFS than Her-2-negative counterparts.Patients undergoing breast-conserving surgery without radiotherapy had lower LC and DFS rates compared with those receiving radical mastectomy.Conclusions DCIS and DCIS-MI patients have similar clinical prognosis in terms of OS,LC and DFS.Her-2 positive is an unfavorable prognostic factor for DFS and OS.The LC and DFS rates in the breast-conserving surgery alone group are worse than those in the mastectomy group.
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Objective To analyze the failure patterns of locoregional recurrence (LRR) and investigate the range of radiotherapy in T1-2N1 breast cancer patients undergoing modified radical mastectomy.Methods From September 1997 to April 2015,2472 women with T1-2N1 breast cancer after modified radical mastectomy without neoadjuvant systemic therapy were treated in our hospital.1898 patients who did not undergo adjuvant radiotherapy were included in this study.The distribution of accumulated LRR was analyzed.The LR and RR rates were estimated by the Kaplan-Meier method,and the prognostic factors were identified in univariate analyses with Log-rank test.Multivariate analysis was performed using Cox logistic regression analysis.Results With a median follow-up of 71.3 months (range 1.1-194.6),164 patients had LRR,including supraclavicular/infraclavicular lymph nodes in 106(65％),chest wall in 69(42％),axilla in 39(24％) and internal mammary lymph nodes (IMNs) in 19 patients (12％).In multivariate analysis,age (＞45 years vs.≤45 years),tumor location (other quadrants vs.inner quadrant),T stage (T1 vs.T2),the number of positive axillary lymph nodes (1 vs.2-3),hormone receptor status (positive vs.negative) were significant prognostic factors for both LR and RR.Conclusions In patients with T1-2N1 breast cancer after modified radical mastectomy,the most common LRR site is supraclavicular/infraclavicular nodal region,followed by chest wall.The axillary or IMN recurrence is rare.The prognostic factors for LR and RR are similar,which indicates that supraclavicular/infraclavicular and chest wall irradiation should be considered for postmastectomy radiotherapy.
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Objective To compare the clinical efficacy between breast-conserving surgery (BCS) plus radiotherapy (RT) and modified mastectomy in patients with stage Ⅰ breast cancer in clinical setting.Methods Clinical data of 6 137 patients diagnosed with pT1-2N0 breast cancer from 1999 to 2014 were retrospectively reviewed.Among them,1 296 patients received BCS plus RT (BCS group) and 4 841 cases underwent modified mastectomy alone (modified mastectomy group).Kaplan-Meier analysis was used for survival analysis.Log-rank test,single factor analysis and Cox's proportional hazards regression model were performed.The results were further confirmed with the propensity score-matching (PSM) method.Results Within a median follow-up period of 55.2 months (range,1-222 months),the 5-year locoregional recurrence-free survival (LRFS),distant metastasis-free survival (DMFS),disease-free survival (DFS) and overall survival (OS) were 96.3％,93.7％,91.9％ and 96.9％,respectively.In the BCS plus RT group,the 5-year DMFS (96.9％ vs.92.9％,P＜0.001),DFS (94.9％ vs.91.2％,P=0.005) and OS (99.1％ vs.96.4％,P=0.001) were significantly higher than those in the mastectomy group.Multivariate analysis revealed that postoperative RT was an influencing factor of DMFS (P=0.003,HR=0.621;95％CI:0.455-0.849) and OS (P=0.036;HR=0.623;95％CI:0.401-0.969).For 1 252 pairs of patients matched by PSM,the 5-year OS (99.1％ vs.96.1％,P=0.001),DMFS (97.0％ vs.92.2％,P＜0.001) and DFS (95.3％ vs.90.2％,P=0.001) in the BCS plus RT group were significantly higher compared with those in the mastectomy group.Conclusion The long-term clinical prognosis of patients with stage Ⅰ breast cancer in the BCS plus RT group is better than that in the mastectomy group.BCS plus RT should be recommended for patients with stage Ⅰ breast cancer.
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Objective To evaluate the risk factors of non-sentinel lymph node (NSLN) metastasis in breast cancer patients with 1-2 positive sentinel lymph nodes and to establish a new Nomogram prediction model.Methods Clinicopathological data of breast cancer patients who were diagnosed with 1-2 positive lymph nodes and underwent axillary lymph node dissection (ALND) without neoadjuvant chemotherapy from January 2008 to December 2014 were retrospectively analyzed.Measurement data between two groups were analyzed by chi-square test.Multivariate analysis was performed by logistic regression model.The prediction accuracy of the Nomogram model was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves.Results A total of 270 patients were recruited in this study.Among them,87(32.2％) patients had NSLN metastases.The median age was 46 years old (21-80 years),the median number of SLNs was 4 (1-10) and the median number of axillary lymph nodes was 20(10-41).Univariate analysis demonstrated that the pathological grade,the size of SLN metastasis,the number of negative and positive SLNs were the risk factors of NSLN metastasis (P=0.001-0.045).Multivariate analysis showed that pathological grade,the number of negative and positive SLNs were independent risk factors of NSLN metastasis (P=0.000-0.041).The AUC value of Nomogram prediction model for NSLN metastasis was 0.70.The false negative rate of Nomogram was 10.5％ when the cut-off point of predictive probability was ≤ 15％.Conclusions The Nomogram is a useful prediction model for evaluating NSLN metastasis.ALND or axillary radiotherapy can be avoided for patients with a low probability of NSLN metastasis.
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Objective To analyze the changes in treatment patterns,clinical characteristics,treatment outcomes and prognostic factors of ductal carcinoma in situ (DCIS).Methods Clinical data of 617 female patients admitted to our institution between 2000 and 2013 were retrospectively analyzed.KaplanMeier survival analysis was adopted to calculate the local control (LC),disease-free survival (DFS) and overall survival (OS) rates.Log-rank test was utilized to identify the prognostic factors.Results Along the number of DCIS patients was gradually increased year by year,the proportion of breast conservative surgery was also elevated.However,mastectomy remained the primary surgical method.A total of 374 patients underwent mastectomy,160 cases received breast conservative surgery plus radiotherapy and 83 underwent breast conservative surgery alone.Postoperatively,366 patients (83.6％) with positive hormone receptor received hormone therapy and 45 patients (7.3％) underwent chemotherapy.The median follow-up time was 47 months.The 5-year LC,DFS and OS rates were 98.4％,97.5％ and 98.9％,respectively.Univariate analysis demonstrated that Her-2-positive patients obtained worse OS (P=0.019).Although mastectomy group had more adverse factors compared with breast conservative surgery with or without radiotherapy groups,similar survival results were obtained among three groups.Mastectomy yielded better LC and DFS compared with breast conservative surgery alone.Conclusions DCIS patients obtain favorable clinical prognosis between the breast conservative surgery and mastectomy groups.The LC rate in the mastectomy group is better than that in the breast conservative surgery group.
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Objective To investigate the clinical efficacy and prognostic factors of breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM) receiving neoadjuvant chemotherapy,surgery combined with radiotherapy at diagnosis.Methods Therapeutic outcomes of 65 breast cancer patients with ISLNM treated in our hospital between 1999 and 2013 were retrospectively analyzed.All patients were pathologically diagnosed with breast cancer.They were complicated with ISLNM,without distant metastasis confirmed by pathological or imaging examinations.All patients received multi-modality therapy consisting of neoadjuvant chemotherapy,surgery and postoperative radiotherapy.KaplanMeier method was adopted to calculate the overall survival (OS),progression-free survival (PFS) and supraclavicular lymph node recurrence (SCFR).The differences between two groups were statistically analyzed by the log-rank test.Results The median follow-up time was 66 months (range:6-137 months).Five patients had SCFR after corresponding treatment.The overall 5-year SCFR,OS and PFS rates were 9.2％,71.5％ and 49.5％,respectively.Following preoperative chemotherapy,the complete response (CR) of supraclavicular lymph node was a prognostic factor affecting OS.The 5-year OS rates in patients with and without CR were 81.4％ and 53.9％ (P=O.035).The size of supraclavicular lymph node (≤ 1 cm vs.＞ 1 cm at diagnosis was a risk factor of the SCFR (0％ vs.21.0％,P=0.037) and OS rates (≤1 cm vs.＞1 cm:86.1％ vs.55.6％,P =0.001).Conclusions Breast cancer patients with ISLM at diagnosis can obtain high OS rate and excellent tumor control after undergoing multi-modality therapy consisting of preoperative chemotherapy,surgery and postoperative radiotherapy.
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Objective@#To investigate the locoregional benefit from adjuvant anti-HER-2 target therapy and the possibility of omitting postmastectomy radiation therapy (PMRT) in HER-2 positive breast cancer patients.@*Methods@#Clinical data of 1398 patients diagnosed with HER-2+ breast cancer admitted to our hospital who underwent mastectomy without PMRT from 2009 to 2014 were retrospectively analyzed, and 370 of them received adjuvant anti-HER-2 target therapy mainly with trastuzumab.@*Results@#Anti-HER-2 target therapy significantly improved the disease-free survival (DFS) and overall survival (OS), whereas reduced the locoregional recurrence (LRR) insignificantly. Multivariate analysis demonstrated that anti-HER-2 target therapy improved the locoregional recurrence-free survival (LRRFS)(P=0.06). After propensity score matching, the 5-year LRR rate was 4.4% vs. 6.4%(P=0.070) for those treated with and without anti-HER-2 target therapy. Subgroup analysis revealed that the locoregional control benefit was only significant in patients with pathological Grade Ⅰ-Ⅱtumors (2.5% vs. 5.9%, P=0.046). For patients with pN1 tumors with and without anti-HER-2 target therapy, the 5-year LRR rate was 8.2% vs. 12.3%(P=0.150). Patients with hormone receptor-positive tumors obtained significant benefit from anti-HER-2 target therapy. The 5-year LRR rate could be less than 5% in patients with favorable risk factors who received anti-HER-2 target therapy.@*Conclusions@#Anti-HER-2 target therapy with trastuzumab can improve the LRRFS of patients with HER-2+ breast cancer after mastectomy. Nevertheless, patients with radiotherapy indications have to receive radiotherapy due to relatively high recurrence rate. Newly approved dual HER-2 blockade is a promising approach to further reduce LRR. Subgroup analysis is required to identify the low-risk patients.
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Objective@#To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients compared to 7th edition.@*Methods@#a total of 1 823 female patients with T1-2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log-rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic (ROC) analyses and the concordance index (C-index).@*Results@#5-year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5-year distant metastasis (DM) rate was 11.5%, 5-year disease-free survival (DFS) was 85.0%, and 5-year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS (P<0.05). Compared with stage by 7th edition, 1 278(70.1%) were assigned to a different prognostic stage group: 1 088 (85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stage ⅠA, ⅠB, ⅡA, ⅡB and ⅢA according to 8th edition of the AJCC staging system(P<0.001). Prognostic stage had significantly higher C-indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system (P<0.001).@*Conclusion@#The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1-2N1M0 breast cancer, and has better clinical therapeutic guidance value.
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Objective@#To investigate the overall efficacy of early breast cancer after breast-conserving treatment. To analyze risk factors affecting local regional recurrence (LRR), distant metastasis (DM) and survival.@*Methods@#1 791 breast cancer patients treated with breast-conserving surgery were retrospectively analyzed. The inclusion criteria were pathologic diagnosis of invasive breast cancer without supraclavicular and internal mammary node metastasis, T1-2N0-3M0, and no neoadjuvant therapy. Univariate analysis of survival was performed by Kaplan-Meier method and log rank test. Cox regression model was used for multivariate analysis.@*Results@#The median follow-up time was 4.2 years. For all patients, the 5-year LRR, DM, disease-free survival(DFS) and overall survival(OS) rates were 3.6%, 4.6%, 93.0% and 97.4%, respectively. The LRR rates of patients with Luminal A, Luminal B1, Luminal B2, HER-2 over-expressed and triple-negative breast cancer were 2.0%, 6.1%, 5.9%, 0 and 10.0%, while the DM rates were 3.2%, 6.7%, 8.3%, 4.8% and 7.3%, respectively. Among the N0 patients, axillary dissection was performed in 689 cases and sentinel lymph node biopsy in 652 cases. The 5-year LRR rates were 3.3% and 3.2% (P=0.859), and the OS rates were 98.2% and 98.3% (P=0.311) respectively, which showed no statistically significant. There were 1 576 patients that underwent postoperative radiotherapy. Postoperative radiotherapy significantly reduced the 5-year LRR compared with surgery alone (2.5% vs 12.9%). The 5-year LRR rates of patients who received conventional fractionated radiotherapy and hypo-fractionated radiotherapy were 2.7% and 3.1%, respectively. But the difference was not statistically significant (P=0.870). Multivariate analysis showed that age, lymphovascular invasion, pathological T staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors of LRR in breast cancer patients (all P<0.05). Histological grade and pathological N staging were independent factors of DM (all P<0.05). The age, lymphovascular invasion, pathological T and N staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors for DFS (all P<0.05). Histological grade, pathological N staging, ER/PR status and endocrine therapy were factors for OS (all P<0.05).@*Conclusions@#With contemporary standard treatment, the recurrence rate of early breast cancer after breast conserving treatment is less than 10%. Node-negative patients after sentinel lymph node biopsy did not need axillary dissection. The overall utilization of radiotherapy after breast conserving surgery is satisfactory. Hypofractionated radiotherapy is as effective as conventional fractionated radiotherapy. Local regional recurrence and distant metastasis have different risk factors.
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<p><b>OBJECTIVE</b>To evaluate the outcome of radical surgery combined with adjuvant radiotherapy for patients aged over 75 years with stage II( or III( rectal cancer.</p><p><b>METHODS</b>From 2000 to 2010, 178 patients aged over 75 years at diagnosis who underwent radical surgery in National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were selected from 3995 patients with stage II( or III( rectal cancer in the database of the above center and enrolled into this retrospective cohort study, which was approved by ethics committee of the above hospital (ClinicalTrials.gov number, NCT02312284).</p><p><b>RESULTS</b>Median age of patients was 77 years (range 75-87). There were 37 (20.8%), 69 (38.8%), and 72 (40.4%) patients with tumors locating in the high, middle and low rectum respectively; 89(50%) patients of pathological stages II( and III( respectively; 21(11.8%), 137(77%), 19(10.7%), and 1(0.6%) patients with poorly, moderately, well differentiated adenocarcinoma, and mucinous adenocarcinoma respectively. The Charlson/Deyo comorbidity index (CCI) score was 0 in the majority (73.6%) of patients. Fifty-three patients underwent abdominoperineal resection, 116 underwent low anterior resection and 9 underwent Hartmann resection. All the patients received computed tomography-based simulation and treatment planning using an anal marker in a prone or supine position. Patients were treated with linear accelerator by megavoltage photons (6MV), with 2D technique in early years and 3D conformal or simplified intensity-modulated radiotherapy technique later, at a dose of 50 Gy in 25 fractions to the pelvis within an overall treatment time of 35 days. Sixty-one patients (34.3%) received surgery combined with radiation (ART group), in whom 16 received radiation alone 117 patients did not receive radiation(NORT group). The baseline data between ART and NORT group were not significantly different(all P>0.05). There was no significant difference in 5-year overall survival between ART and NORT groups (61.0% vs. 63.0%, P=0.586). The cumulative local relapse was 10.9% and 25.4% in ART and NORT group respectively (P=0.032). Cox multivariate analysis revealed that surgery combined with radiation improved local control significantly(HR=0.27, 95%CI:0.11-0.68, P=0.005).</p><p><b>CONCLUSIONS</b>For elderly patients aged over 75 years with stage II( or III( rectal cancer, radical surgery combined with radiation does not increase the overall survival, but can improve local control rate. It is reasonable to selectively apply adjuvant radiotherapy to the elderly patients in the setting of radical surgery.</p>
Subject(s)
Adenocarcinoma , Radiotherapy , General Surgery , Aged , Aged, 80 and over , Humans , Neoplasm Recurrence, Local , Neoplasm Staging , Radiotherapy, Adjuvant , Rectal Neoplasms , Radiotherapy , General Surgery , Retrospective StudiesABSTRACT
Objective To explore the effect of oxaliplatin ( OXA) on enhancing radiosensitivity in human hepatocellular carcinoma cell line HepG2 . Methods 50% inhibition concentration ( IC50 ) of HepG2 cells treated with OXA was measured by using MTT method at 6, 12, 24, 48 hours. Then clone formation assay was applied to obtain sensitizing enhancement ratio ( SER) of OXA combing IR, according to the survival fraction of three groups 10?14 days after treatments:placebo?treated group ( C) ,radiation group ( IR, single dose of 1 Gy,2 Gy,4 Gy,6 Gy,8 Gy,10 Gy) and IR synchronizing OXA group ( IR+3 mg/L OXA) . The proportions of cell apoptosis were analyzed using flow cytometry at 24 hours after treatment. At last, we semi?quantitative tested the expression of extracellular regulated protein kinase 1/2 ( ERK 1/2 ) and DNA damage repair protein Ku?70 of the C,IR and IR+OXA groups. Statistical analysis was performed by T test. Results The IC50 of OXA on HepG2 cells is 54?4 mg/L at 6 hours,29?1 mg/L at 12 hours,17?8 mg/L at 24 hours and 10?5 mg/L at 48 hours.3 mg/L was selected in clone formation assay at which 80?90% HepG2 cells survived at 24 hours. The SER ( SF2 ) is calculated as 1?59. Flow cytometry showed the proportion of survival cells in IR+OXA group is significantly lower than those of IR group ( P=0?005) ,OXA group ( P=0?008) and C group ( P=0?001) . The expressions of ERK 1/2 were inhibited in IR and IR+OXA groups compared by that of control group. But the expression of ERK 1/2 in IR group showed increasing after 48 hours which was higher than that of IR+OXA group. For Ku?70,the changes of expression were similar with that of ERK 1/2. Conclusion Oxaliplatin presented enhancing radiosensitivity in human hepatocellular carcinoma cell line HepG2 in vitro.
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Objective To reduce the radiation dose to the hematopoietic bone marrow (hBM) and acute hematologic toxicity (HT) in patients with rectal cancer undergoing intensity-modulated radiotherapy (IMRT).Methods The previously untreated patients with rectal cancer were enrolled in a prospective study.Pelvic magnetic resonance imaging ( MRI) was used to determine and delineate the distribution of hBM,and dose limitations were set (V5<95%,V10<90%,V20<80%,V30<65%).The neoadjuvant therapeutic regimen included concurrent IMRT (95% PTV 50 Gy/25 fractions,2 Gy/fractions),oxaliplatin 50 mg/m2 , qw,and capecitabine 1650 mg/m2 ,1 fractions/d (twice a day during radiotherapy).Results A total of 35 patients were enrolled and completed the therapeutic regimen.The incidence of grade 2-4 HT was 31.4%;among these patients, 9 ( 26%) experienced leucopenia, 6 ( 17%) experienced neutropenia, 1 ( 3%) experienced erythropenia,and 1(3%) experienced thrombocytopenia.No patients experienced grade ≥3 anemia.The multivariate logistic linear regression analysis showed that hBM-V5 was significantly correlated with the lowest counts of leukocytes ( P=0.005),neutrophils ( P=0.002),and platelets ( P=0.017).Conclusions The radiation dose to the hBM in the pelvis on MRI is significantly correlated with the incidence and severity of acute HT in patients with rectal cancer undergoing neoadjuvant concurrent chemoradiotherapy.Clinical Trial Registry ClinicalTrials.gov,registration number:NCT01863420.
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AIM: To investigate the effects of human umbilical cord-derived mesenchymal stem cells ( hUC-MSCs) on the proliferation and migration of osteosarcoma cells ( Saos-2 ) and the underlying molecular mechanism. METHODS:hUC-MSCs were isolated and cultured by tissue explants adherent method.The cell surface markers on hUC-MSCs were identified by flow cytometry.The effects of conditioned medium ( CM) from hUC-MSCs ( hUC-MSCs-CM) , re-combinant human interleukin-6 (rhIL-6) and IL-6 neutralizing antibody on the proliferation of Saos-2 cells were detected by CCK-8 assay and cell counting.IL-6 secretion of hUC-MSCs was assayed by ELISA.RT-PCR was used to assess the tran-scription level of proliferation-related genes proliferating cell nuclear antigen ( PCNA) , cyclin D1 and survivin.The migra-tion potential of hUC-MSCs and Saos-2 cells was measured by Transwell assay.RESULTS:hUC-MSCs migrated to Saos-2 cells.hUC-MSCs-CM contained a high concentration of IL-6, up to (1 835.5 ±134.1) ng/L.hUC-MSCs-CM and rhIL-6 promoted the proliferation and migration of Saos-2 cells.Addition of neutralizing antibody against IL-6 in the hUC-MSCs-CM impaired this proliferation and migration of Saos-2 cells.The mRNA expression of PCNA, cyclin D1 and survivin was up-regulated by hUC-MSCs-CM and rhIL-6, while this effect was dramatically attenuated by treatment with IL-6 neutralizing antibody.CONCLUSION:hUC-MSCs migrate to osteosarcoma cells and promote the proliferation and migration of osteo-sarcoma cells through secreting IL-6 in vitro.
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Aim To investigate the effect and mecha-nism of quercetin combined with cisplatin on prolifera-tion and apoptosis of human osteosarcoma cell line MG-63 . Methods MG-63 cells were treated with quercetin alone or combined with cisplatin. Cellular morphologic changes were observed under inverted phase contrast microscope. The effects of proliferation inhibition were assayed by CCK-8 method. The combination effect was judged through Chou-Talaly analysis. The apoptosis ra-tios of cells were analyzed by flow cytometry. The gene expression of Bcl-2 and caspase-3 was detected by RT-PCR assay. The protein expression of Bcl-2 and caspase-3 was measured by Western blot assay. Re-sults Quercetin alone or combined with cisplatin could inhibit the proliferation, but induce the apoptosis of MG-63 cells. Combination of quercetin and cisplatin revealed a synergistic effect on cell proliferation and apoptosis as it reduced the expression of Bcl-2 but en-hanced that of caspase-3 at both gene and protein lev-els. Conclusion Synergistic effect of quercetin com-bined with cisplatin on cell proliferation and apoptosis of MG-63 cells is possibly due to reduction of Bcl-2 and enhancement of caspase-3 expression.