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Objective:To explore the method of constructing automatic delineation model for clinical target volume (CTV) and partially organs at risk (OAR) of postoperative radiotherapy for prostate cancer based on convolutional neural network, aiming to improve the clinical work efficiency and the unity of target area delineation.Methods:Postoperative CT data of 117 prostate cancer patients manually delineated by one experienced clinician were retrospectively analyzed. A multi-class auto-delineation model was designed based on 3D UNet. Dice similarity coefficient (DSC), 95% Hausdorf distance (95%HD), and average surface distance (ASD) were used to evaluate the segmentation ability of the model. In addition, the segmentation results in the test set were evaluated by two senior physicians. And the CT data of 78 patients treated by other physicians were also collected for external validation of the model. The automatic segmentation of these 78 patients by CTV-UNet model was also evaluated by two physicians.Results:The mean DSC for tumor bed area (CTV1), pelvic lymph node drainage area (CTV2), bladder and rectum of CVT-UNet auto-segmentation model in the test set were 0.74, 0.82, 0.94 and 0.79, respectively. Both physicians' scoring results of the test set and the external validation showed more consensus on the delineation of CTV2 and OAR. However, the consensus of CTV1 delineation was less.Conclusions:The automatic delineation model based on convolutional neural network is feasible for CTV and related OAR of postoperative radiotherapy for prostate cancer. The automatic segmentation ability of tumor bed area still needs to be improved.
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Objective:To investigate the prognosis after salvage radiotherapy with or without hormone therapy for prostate cancer.Methods:From May 2014 to December 2020, 248 patients undergoing salvage radiotherapy due to prostate-specific antigen (PSA)persistence or biochemical progression after radical prostatectomy at Sun Yat-sen University Cancer Center (n=157) and West China Hospital, Sichuan University (n=91) were analyzed. Median age was 66 (45-78) years old. Median PSA was 23.50 (0.18-845.00) ng/ml. The number of PSA persistence and biochemical progression were 143 (59%) and 105 (42%). The number of pT 2, pT 3a, pT 3b, pT 4, and unknown T stage was 99, 49, 78, 15 and 7 cases.The number of N 0, N 1 and unknown N stage was 153, 44 and 51 cases. 165 cases had positive surgical margin. Gleason score of 6, 7, 8, >8 score and unknown was in 12, 104, 34, 90 and 8 patients. Early and late salvage radiotherapy was performed in 117 and 131 patients, and 70 patients (28%) were CRPC. Hormone therapy was used combined with radiotherapy in 182 patients (73%). PSA decline after radiotherapy was compared with Chi-squre test. Kaplan-Meier method and log-rank test were used to compare progression free-survival (PFS)after radiotherapy. Univariate and multivariate analyses of PFS were performed using Cox proportional hazards model. Early salvage radiotherapy was defined as PSA≤0.5 ng/ml before radiotherapy, and late salvage radiotherapy was defined as PSA>0.5ng/ml. Results:PSA response (PSA decline ≥50%) rate was 94% (233/248), and 82% (203/248) patients had PSA decline ≥ 90%. Twelve (5%) patients had rising PSA after completing radiotherapy, but only 4 (2%) had real progression. The median PFS was 69 months (95% CI 68-70), and 3-year and 5-year PFS rate were 80% and 67%. PFS of PSA persistence and biochemical progression were similar ( HR =0.71, 95% CI 0.37-1.37, P=0.311). Compared with late salvage radiotherapy, early salvage radiotherapy had better PFS [69 (95% CI 68-70) vs. 59 (95% CI 44-74) months, P<0.001]. Compared with hormone sensitive, castration-resistant was associated with worse PFS (5-year PFS rate 74% vs. 51%, P<0.001). In multivariate analysis, Gleason score>8, castration-resistant and late salvage radiotherapy were unfavorable prognostic factors. Conclusions:In patients receiving salvage radiotherapy with or without hormone therapy for PSA persistence and biochemical progression after radical prostatectomy, high PSA level before radiotherapy and castration resistant is associated with poor prognosis.
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Objective@#To explore the recovery time and risk factors of coagulopathy caused by rodenticide poisoning through analyzing and following up the confirmed cases, and to provide more useful guidance information for the clinic practice.@*Methods@#A total of 96 cases with coagulation dysfunction caused by anticoagulant rodenticide poiso-ning in Children′s Hospital, Chongqing Medical University from January 2014 to December 2016, were analyzed retrospectively.The recovery time of coagulation function and the relationship between recovery time and drug involved way, dysfunction organs and poison concentration were studied respectively.@*Results@#(1) A total of 96 patients were hospitalized because of severe coagulopathy caused by the poisoning of second generation anticoagulant rodenticide.Brodifacoum was detected from 33 blood samples and the median concentration was 364 μg/L (55-4 654 μg/L). Bromadiolone was detected from 7 blood samples and the median concentration was 130 μg/L (18-652 μg/L). Brodifacoum and Bromadiolone were both detected from 8 cases and the median concentration was 741 μg/L (63-6 000 μg/L) and 11 μg/L (3-3 694 μg/L), respectively.(2) A total of 57 cases of the patients were successfully followed up.A total of 18 cases were confirmed with oral poisoning, 16 cases with dermal poisoning, while 23 cases denied any involved ways of poisoning, and 7 cases had organs dysfunction.The follow-up time was 12-54 months.All the hospitalized patients were given specific antidote Vitamin K treatment and recovered successfully without any sequelae.(3) The median recovery time of coagulopathy caused by rodenticide poisoning was 2.5 months.(4) The recovery time of coagulation function was positively correlated with the plasma concentration of Brodifacoum(r=0.619, P<0.01). (5) There was no significant correlation between recovery time and organ dysfunction or drug involved ways of poisoning involvement (all P>0.05).@*Conclusions@#The recovery time of coagulation dysfunction caused by anticoagulant rodenticide in children is much longer.The higher the concentration of Brodifacoum poison is, the longer the recovery time.Enough supplementation course of Vitamin K should be given according to the follow-up of coagulation function.
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Objective@#To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) with high risk factors.@*Methods@#Data of 101 patients who were diagnosed with stage II-III rectal cancer with high risk factors and received TNT between March 2015 and January 2018 at West China Hospital of Sichuan University were analyzed retrospectively. Inclusion criteria: (1) patients were diagnosed with stage II-III rectal cancer by high-resolution MRI combined with CT and endorectal ultrasound; (2) at least one high risk factor: cT4a, cT4b, cN2, EMVI+, CRM+ and lateral lymph node+; (3) distance from tumor to anal verge was within 15 cm; (4) Eastern Collaborative Oncology Group (ECOG) performance status score was 0-1; bone marrow function, liver function and kidney function were suitable for chemoradiotherapy; (5) patients were treated with TNT strategy; (6) the follow-up data and postoperative pathological data were complete. Patients with previous rectal cancer surgery (except prophylactic colostomy), pelvic radiotherapy, and systemic chemotherapy, those with distant metastases, those without neoadjuvant radiotherapy, those receiving less than 4 cycles of neoadjuvant chemotherapy were excluded. The regimen of TNT: 3 cycles of induction CAPOX (oxaliplatin plus capecitabine) were followed by pelvic radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after radiotherapy. Total mesorectal resection (TME) or watch-and-wait strategy was selected according to the therapeutic effect and patients' wishes. Short-term efficacy, including tumor regression grade (TRG), pathological complete response (pCR), clinical complete response (cCR), postoperative complications within 30 days of surgery, and adverse events (AE) to radiotherapy and chemotherapy (measured using CTCAE 4.0) was analyzed.@*Results@#The 101 patients included 68 males (67.3%) and 33 females (32.7%) with a median age of 54 years. The proportion of patients with cT4a, cT4b, cN2 and enlarged lateral lymph node was 13.9%, 29.7%, 56.4% and 43.6%, respectively. The mean cycle of neoadjuvant chemotherapy was 6.0±1.3. Seventy-five patients (74.3%) received at least 6 cycles of neoadjuvant chemotherapy and 100 (99.0%) completed radiotherapy. The mean cycle of induction and consolidation chemotherapy was 2.0±0.9 and 2.8±1.0 respectively. Most common grade 3 AE was leucopenia (n=13, 12.9%) and thrombocytopenia (n=7, 6.9%). Grade 3 diarrhea and radiation dermatitis were observed in 5 cases (5.0%) respectively. Grade 3 anemia and rectal pain were observed in 4 cases (4.0%) respectively. And rectal mucositis was observed in 2 cases (2.0%). Most of the AE was observed during concurrent chemoradiotherapy. No grade 4 or higher AE was observed. After TNT, 32 patients (31.7%) achieved pCR or cCR, and 62 patients (60.4%) achieved partial response (PR). Only 2 patients (2.0%) developed distant metastasis after chemoradiotherapy, while the other patients did not show disease progression. Seven patients (6.9%) with cCR refused surgery and selected watch-and-wait, while 7 patients without cCR still refused surgery. The other 87 patients (86.1%) underwent TME successfully. The mean interval from the completion of chemoradiotherapy to surgery was (20.1±8.5) weeks. The R0 resection rate was 97.7% (85/87).The morbidity of surgical complication was 16.1% (14/87), including pelvic infection or abscess in 6 cases (6.9%), anastomotic leakage in 3 (3.4%), hemorrhage in 2 (2.3%), and gastrointestinal dysfunction in 3 (3.4%). Pathological findings revealed that 24 cases (27.6%) had TRG 0, 20 (23.0%) had TRG 1, 30 (34.5%) TRG 2, and 13 (14.9%) TRG 3.@*Conclusion@#TNT is safe and has good short-term efficacy for locally advanced rectal cancer patients with high risk factors.
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Stereotactic body radiation therapy (SBRT) can effectively kill renal cancer cells by biological molecules such as hypoxia-inducible factor-1α and acid sphingomyelinase. SBRT regimen with higher biological dose and single irradiation can achieve more effective local control of primary and metastatic lesion of advanced renal cancer, and adverse reactions can be tolerated. Combination of SBRT and targeted drugs can increase the sensitivity of renal cancer to radiotherapy, and the combination of SBRT and immune drugs can enhance the immune response through the abscopal effect. The efficacy of SBRT in the treatment of advanced renal cancer remains to be explored.
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Stereotactic body radiation therapy (SBRT)can effectively kill renal cancer cells by biologi-cal molecules such as hypoxia-inducible factor-1α and acid sphingomyelinase. SBRT regimen with higher biological dose and single irradiation can achieve more effective local control of primary and metastatic lesion of advanced renal cancer,and adverse reactions can be tolerated. Combination of SBRT and targeted drugs can increase the sensitivity of renal cancer to radiotherapy,and the combination of SBRT and immune drugs can enhance the immune response through the abscopal effect. The efficacy of SBRT in the treatment of advanced renal cancer remains to be explored.
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Objective To explore the mechanism by which liraglutide modulated the differentiation of monocyte subsets in high glucose (HG) conditions.Methods Primary mouse splenocyte suspensions were cultured in HG conditions induced by IFN-γ in the presence or absence of liraglutide.The cells were harvested,co-incubated with antibodies,and analyzed on a BD FACS Calibur.Mononuclear cells (MNCs) were gated according to lower granularity and larger size by SSC and FSC.Monocytes (MCs) were defined as CD11b+MNC and divided into three subsets based on Ly6C expression:Ly6Clow,Ly6Cmid,and Ly6Chi.ROS production in Ly6C+ and Ly6C-MCs was detected by 2',7'-dichlorofluorescein-diacetate (DCFH-DA) staining and ROS-containing MCs were identified as DCF+ cells in both Ly6C+ and Ly6C-MCs.Results HG (15 mmol/L,25 mmol/L,35 mmol/L) dose-dependently increased Ly6Chi and Ly6Cmid MC differentiation and also enhanced the production of ROS in Ly6C+MCs.Liraglutide (100 U,200 U) dose-dependently inhibited HG-induced Ly6Chi and Ly6Cmid MC differentiation and also promoted the differentiation of Ly6Clow MCs.Moreover,liraglutide significantly inhibited HG-induced ROS production in Ly6C+ MCs.Conclusion Liraglutide treatment significantly inhibited inflammatory MC diferentiation induced by HG and also reduced ROS production in inflammatory MCs.
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<p><b>BACKGROUND</b>Image guided radiotherapy (IGRT) is a new precise radiotherapy applied in clinic. The aim of this study is to evaluate the impact of using active breath control (ABC) and stereotactic body frame on reducing the positioning error and increasing treatment precision during radiotherapy for pulmonary cancer.</p><p><b>METHODS</b>Seven patients with pulmonary recurrences or metastasis after prior treatment were enrolled. A total number of 13 tumor targets received irradiation, with a fraction dose of 7Gy treated every other day to a total of 7 fractions. X-ray beam volume CT was done at every fraction for correction of positioning error at 3 dimensions.</p><p><b>RESULTS</b>The errors between pre-treatment positioning and treatment planning at left-right, anterior-posterior and cephalic-caudal directions were 0.30cm±0.14cm, 0.22cm±0.15cm and 0.28cm ±0.21cm, respectively. The positioning error was reduced after correction by volume CT and after treatment but the errors between pre-correction, post-correction and post-treatment had no statistical significance at all 3 directions. Eight targets had complete response, 4 targets had partial response, and 1 had no change.</p><p><b>CONCLUSIONS</b>Image guided hypofractionation radiotherapy with ABC and stereotactic body frame has the advantage of increasing radiation dose and reducing overall treatment time and radiation toxicity.</p>
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<p><b>BACKGROUND</b>Recent studies have showed that combination of chemotherapy and radiotherapy might result in better outcome for locally advanced non-small cell lung cancer (NSCLC). The aim of this study is to determine the maximal tolerance dose (MTD) and efficacy of full-dose gemcitabine and oxaliplatin when given concurrently with 3-dimentional radiation therapy (3D-RT) for locally advanced NSCLC.</p><p><b>METHODS</b>Oxaliplatin was administered at a fixed dose of 130mg/m², and gemcitabine was administered at a starting dose of 800mg/m² with an incremental dose gradient of 200mg/m² for 3 dose levels. MTD was defined as the immediate dose level lower than the dose at which dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered at 3-week cycle. The RT was given as 3-D conformal manner at a single daily dose of 2Gy for 5 days per week.</p><p><b>RESULTS</b>Twenty-two patients were evaluable and distributed to three different dose levels: 6 at level 1, 8 at level 2 and 8 at level 3. Pulmonary toxicity, esophageal and hematologic toxicity were the main DLT. Grade III acute pulmonary toxicity occurred in one patient each at level 2 and level 3, both with V20 > 20%, and grade III esophagitis in two patients at level 3. The MTD of gemcitabine in this study was 1000mg/m². The overall response rate was 75.0% (9/12). The 1- and 2-year survival rate was 70.0% and 30.5% respectively. The median time to progression was 8.7 months (range 5-11.8 months).</p><p><b>CONCLUSIONS</b>With reduced radiation volume, gemcitabine of 1000mg/m² in combination with oxaliplatin of 130mg/m² was effective and could be safely administered for NSCLC.</p>