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Objective:To evaluate the efficacy and safety of quadruple therapy involving radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX (oxaliplatin and gemcitabine) chemotherapy (quadruple therapy) in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The patients with recurrent, metastatic, or unresectable ICC underwent quadruple therapy at Zhongshan Hospital, Fudan University between September 2018 and May 2022 were selected. The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until December 31, 2022. The efficacy, prognosis, and toxicity data were collected and analyzed.Results:A total of 41 patients were included in the analysis. After a median follow-up period of 15 months, disease progression was diagnosed in 36 patients (18 patients died), while 3 patients were lost to follow-up. The causes of death included liver failure induced by intrahepatic tumor progression ( n=6), distant metastases (lungs or brain, n=6), abdominal lymph node metastases ( n=3), cancer cachexia ( n=2), and unknown cause ( n=1). The median progression-free survival (PFS) was 11 months (95% CI: 9.2-12.8), and the median overall survival (OS) was 35 months (95% CI: 17.0-52.0). All patients experienced treatment-related adverse events (AEs) during the study treatment period. Of the 41 patients, 13 patients experienced at least once grade 3 or worse treatment-related AE, but all were manageable with symptomatic treatment. No treatment-related deaths were reported during the follow-up period. Conclusions:Radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety, which is worthy of clinical application.
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Objective:To explore the effect of a new teaching mode, which includes bridge-in, outcome, pre-test, participation, post-test and summary (BOPPPS), on the online teaching of radiobiology related knowledge for cancer radiotherapy practitioners.Methods:Taking the cell survival curve, cell cycle and radiosensitivity as examples, the radiotherapy practitioners in multiple university-affiliated hospitals were organized to carry out a multicenter prospective randomized control study. All practitioners were randomly divided into BOPPPS group and control group. The courses for BOPPPS group were designed as an online classroom, consisting of pre-class preparation, online teaching and post-class stages. The online teaching stage included video viewing, basic knowledge learning, literature discussion, group discussion and others. The control group employed the traditional teaching mode. The χ2 test was used to compare the consistency of general conditions between the two groups, and nonparametric test was used to compare the differences in scores between two or more groups. Results:The score of the pre-class test was 58.56 ± 0.99. Post-class average score for BOPPPS group was 85.48±0.85 and for control group 77.79±1.10, with the former being higher 7.69 ( Z=5.31, P<0.001) than the latter. The average answer time was (296.62±15.40) s for BOPPPS group and (386.41±21.27) s for control group, with the former being shorter 89.79 s ( Z=3.34, P=0.001) than latter. Subgroup analysis shown that the scores of BOPPPS group were significantly rising, regardless of whether or not the students had studied radiobiology courses. Among the students who have not studied these courses, the scores were rising greatly. Moreover, From the analysis of different positions, it was found that both the scores of BOPPPS group and control group have risen, especially for doctors, deputy chief doctors, physicists and technicians. There were also statistically differences between different degrees, with significantly rise in scores for undergraduate and doctoral students ( Z=3.64, 4.18, P<0.001). Conclusions:The flexible application of BOPPPS teaching mode to the online education of such boring disciplines, like radiobiology, is of great significance to raise the theoretical basis of radiotherapy practitioners.
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The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.
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Objective:To study the effects of radiotherapy and the prognostic factors in hepatocellular cancer (HCC) patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis (LNM).Methods:We retrospectively analyzed 56 HCC patients with cardiophrenic angle or superior diaphragmatic LNM who were treated with or without external beam radiation therapy (EBRT) in Zhongshan Hospital of Fudan University from Jan 2010 to Aug 2020. Patients were divided into two groups according to whether they received radiotherapy, EBRT group and non-EBRT group, and each group had 28 patients. Radiation fields included or excluded primary tumor in EBRT group, and the cardiophrenic angle or superior diaphragmatic LNM did not receive any local treatment in non-EBRT group. The response rate, survival rate, local control rate, prognostic risk factors of the two groups were studied.Results:After EBRT, the partial response rate and complete response rate were 32.1%(9/28) and 32.1%(9/28). The median survival rate of EBRT group was 16.1 months (95% CI 9.00-23.21, RR=3.63) vs. 6.9 months (95% CI 4.63-8.77, RR=1.06) for the non-EBRT group, with statistically significant difference ( χ2=15.53, P<0.05). Cardiophrenic angle or superior diaphragmatic lymph nodes 1-year local control rate for EBRT group and non-EBRT group were 37.0% vs. 10.7%, with statistically significant difference ( χ2=5.28, P<0.05). Since diagnosis of cardiophrenic angle or superior diaphragmatic LNM, 4 patients (14.3%) in the EBRT group vs. 13 patients (46.4%) in the non-EBRT group had higher alpha-fetoprotein (AFP) level after 3 months compared with the AFP before EBRT ( χ2=6.84, P<0.05). Multivariate analysis showed that multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L, no EBRT were poor prognostic factors. Conclusions:EBRT can prolong overall survival and improve the control rate of lymph node of HCC patients with cardiophrenic angle or superior diaphragmatic LNM. Patients with multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L and no EBRT have poor prognosis.
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The purpose of tumor staging is to guide treatment, and the treatment for a certain stage should be adjusted based on the changes in disease condition, in order to facilitate better control of tumor. Therefore, the treatment of liver cancer requires follow-up and re-staging to develop better treatment regimens for patients, especially the opportunity for cure. Surgical resection is not suitable for large hepatocellular carcinoma confined to the liver, and after embolization chemotherapy combined with radiotherapy for tumor regression and downstaging, some patients may undergo surgical resection, and the incurable tumor can thus be cured. For liver cancer patients with portal vein tumor thrombus, surgical resection can be performed after tumor thrombus is reduced by neoadjuvant radiotherapy, and the patients undergoing neoadjuvant radiotherapy have a significant increase in survival time than those not undergoing neoadjuvant radiotherapy. Large hepatocellular carcinoma can be downstaged to small hepatocellular carcinoma after multimodality therapy, and then stereotactic radiotherapy or radiofrequency ablation can help to achieve radical treatment. There is an increasing number of clinical reports of radiotherapy for liver cancer downstaging, with a gradual increase in evidence-based level, and thus it holds promise for clinical application.
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Objective To explore the efficacy of renal transplantation plus hematopoietic stem cell transplantation on inducing immune tolerance and summarize its long-term follow-up outcomes . Methods From 2009 to 2018 ,a total of 11 cases of living related donor kidney transplantation plus hematopoietic stem cell transplantation were performed .Two of them were HLA-matched and the remainder were mismatched for one HLA haplotype . The donor hematopoietic stem cells were mobilized using granulocyte colony-stimulating factor at 5 days pre-transplantation and collected at 1 day pre-operation .The recipients received total lymphoid irradiation for 3 days pre-transplantation and received anti-thymocyte globulin induction during transplantation .The donor hematopoietic stem cells were infused at 2 ,4 and 6 postoperative day .Postoperative regulatory T cells ,chimerism ,B cell activating factor and mixed lymphocyte culture and other parameters were detected and long-term follow-up outcomes tracked .Results The immune tolerance-inducible recipients had a significant increase in activated Treg .One HLA-matched recipient achieved 30％-50％ of chimerism and lost after 6 months .However ,other recipients did not achieve mixed chimerism .The BAFF of recipient spiked sharply after transplantation .Mixed lymphocyte culture indicated that a donor-specific low response was induced .The recipients were followed up for 717 to 3612 days .The first recipient lost renal function and another ten recipients had stable renal function . None of the recipients had myelosuppression or graft-versus-host disease .Allograft biopsy confirmed only one case of mild acute rejection . The dose of immunosuppressive agents was lowered in 5 patients .Conclusions Hematopoietic stem cell transplantation for inducing tolerance is safe during renal transplantation . And chimerism is essential for inducing immune tolerance .
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Objective@#To evaluate left ventricular (LV) dysfunction in patients with esophageal cancer (EC) during concurrent chemoradiotherapy (CCRT) using real-time three-dimensional speckle tracking echocardiography (3D-STE) and analyze its influence factors.@*Methods@#Thirty-one patients with EC who received CCRT were enrolled in the study.Conventional echocardiography and 3D-STE were performed pre-CCRT and during CCRT (radiotherapy dose reached 40Gy). Three-dimensional parameters including LV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) as well as global circumferential strain (GCS) were compared between pre-CCRT and during CCRT. The independent factors on left ventricular function parameters were analyzed.@*Results@#There was no change on LV diameters, LV volumes and LVEF during CCRT (all P>0.05), while LV diastolic function indexes were impaired compared with those of pre-CCRT, demonstrated by the decreased E/A, Em/Am, and increased E/Em(all P<0.05). 3DGLS was also significantly decreased during CCRT compared with that of pre-CCRT (P<0.05), but no significant difference was found in 3DGCS (P>0.05). Multivariate linear regression analysis manifested that cardiac V40(the percentage of cardiac volume as radiotherapy dose reached 40Gy) was an independent determinant of LV 3DGLS in patients with esophageal cancer during CCRT (P<0.05).@*Conclusions@#LV GLS provided by real-time 3D-STE could sensitively detect CCRT-induced myocardial injury. Cardiac V40 is independently associated with LV 3DGLS during CCRT, representing the impact of radiotherapy on the subclinical LV function change.
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Objective To evaluate the safety of helical tomotherapy (HT) for hepatocellular carcinoma confined to the liver,and to investigate the efficacy of HT by comparison with three-dimensional conformal radiotherapy (3DCRT).Methods In June 2011,hypofractionated HT was performed in 35 patients with unresectable hepatocellular carcinoma confined to the liver who had no distant metastasis or tumor thrombosis.The dose in each fraction increased from 2.4 Gy to 5.0 Gy with a median dose of 3.2 Gy.The median dose for the total treatment was 50.0 Gy.Within the same period,45 patients received conventionally fractionated 3DCRT with a median dose of 54.0 Gy.The adverse reactions,clinical outcomes,and survival time were compared between the two groups.The survival rate was calculated with Kaplan-Meier method,and log-rank test was used to estimate statistical significance of survival differences.Multivariate analysis of survival was carried out with Cox' s regression model.Results There were no significant differences in adversc reactions between the two groups.The objective response rate was significantly higher in the HT group than in the 3DCRT group (60％ vs.33％,P=0.024).There was no significant difference in the disease control rate between the two groups (94％ vs.89％,P=0.459).The HT group showed significantly higher 1-,2-,and 3-year overall survival rates than the 3DCRT group (97％ vs.80％,P=0.025;81％ vs.55％,P =0.008;67％ vs.50％,P =0.048).The multivariate analysis indicated that tumor smaller than 8 cm,transarterial chemoembolization before radiotherapy,and HT were associated with improved survival (P=0.005;P =0.000;P=0.002).Conclusions HT shows an advantage in precise treatment of hepatocellular carcinoma confined to the liver.With acceptable toxicity,hypofractionated HT shortens the treatment duration and improves the survival in patients.
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Objective To investigate the efficacy and toxicity of conventional fractionated three-dimensional conformal radiotherapy (3D-CRT) on unresectable hepatocelluar carcinoma(HCC).Methods Fifty two patients with unresectable HCC,all without extrahepatic metastases,were treated by 3D-CRT conducted 5 times a week with the total radiation dose of 36-66 Gy and a daily dose of 2 Gy.The curative effect was evaluated by CT scan to observe the maximum tumor size.Survival rates,survival time,and adverse responses were recorded.Results The total effective rate of the 52 patients was 69.2％ with complete response (CR) in 2 patients and partial response (PR) in 34 patients.The incidence rate of radioactive hepatitis was 1.92％.The 1-,2-,3-,and 4-year survival rates were 57.7％,34.6％,23.1％,and 9.61％ respectively,and the median survival time was 10.5 months.The 1-,2-,3-,and 4-year local control rates were 67％,51.5％,32.3％,and 2.24％,and the 1-,2-,3-,and 4-year distant metastasis rate were 17.2％,23.5％,36.7％,and 76.9％ respectively.The intrahepatic metastases rate was 62.5％ and 37.5％ of the patients suffered from extrahepatic metastasis,including metastases of lung,bone,and retroperitoneal lymph nodes.The remission rate of the≥50 Gy group was 76.9％,significantly higher than that of the ≤50 Gy group (46.2％,x2 =10.72,P ＜ 0.05 ).There was no grade 3 or 4 acute toxicity,and two patients (3.84％) developed gastric or duodenal ulcer.Conclusions Conventional fractionaled 3D-CRT evokes a rather effective response for unresectable HCC with acceptable toxicity.Radiation dose seems to be a significant prognostic factor in RT response for HCC.
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Objective To investigate the role and mechanism of TMPRSS4 in radiation induced metastasis of hepatocellular carcinoma (HCC).Methods Metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude mice.Mice bearing xenografts in liver were killed after radiation and the residual tumors were resected and reimplanted into the liver of normal nude mice.At the end of sixth week,the mice were killed and the histopathological features,tumor volume,intrahepatic and lung metastasis were evaluated.Expression of epithelial-mesenchymal transition (EMT) related genes including N-cadherin,Vimentin,SIP1 and TMPRSS4 were measured by Western blotting and RT-PCR.Results The tumor volume and frequency of lung metastasis of control group was 2.25±0.52 cm3 and 66.7％,respectively.Compared to control group,tumor diameter (1.61±0.51 cm3,P＜0.05) and lung metastasis (12.5％,P＜0.05) were significantly inhibited 2 days after radiation.Whereas,30 days after radiation,tumor growth recovered (2.60±0.61 cm3,P＞0.05) and lung metastasis was enhanced (100％,P＜0.05).There were no intrahepatic metastasis in the control group and in the group of reimplantation of HCC 2 days after radiation,while the tumors from those 30 days after radiation showed enhanced intrahepatic metastasis (18 ± 8.05,P＜ 0.01 ),with overexpression of SIP1,N-cadherin,Vimentin and TMPRSS4,and reduced expression of E-cadherin.Conclusion The metastasis potential of residual HCC after radiation was first inhibited and then promoted.Overexpression of TMPRSS4 plays a critical role in radiation induced long-term metastasis of HCC by facilitating EMT.
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Objective To evaluate the feasibility of active breathing control (ABC) in conformal radiotherapy (CRT) for patients with non-small cell lung cancer (NSCLC). Methods From Feb 2005 to Mar 2008, 29 patients with inoperable NSCLC (stage Ⅱ-Ⅳ) were evaluated. For each patient, two series of CT scans were obtained with free breathing (FB) and ABC system during simulation, respectively. Then two confonnal radiotherapy (CRT) plans were finished based on the two sets of reconstructed images. The pattern of post-inspiratory breath-hold was triggered at 80% of the peak of inspiration curve. The margin of clinical target volume (CTV) to planning target volume (PTV) was 0. 6 cm for lesions of the superior lobe, and 1.0 cm for the lesions of middle and inferior lobes. Three to five coplanar fields were performed in conformal radiotherapy. The gross tumor volume (GTV), CTV, PTV, volume of the bilateral lungs (Volume_(lung)), V_(20) and mean lung dose (MLD) of two plans were evaluated by dose-volume histogram (DVH). The World Health Organization criteria and National Cancer Institute Common Toxicity Criteria 3.0 (NCI-CTC3.0) scale were used to assess the immediate response and acute side-effect, respectively. Results Significant differences of GTV, CTV, FIN, Volum_(lung), V_(20) and MDL were observed between the two plans (36. 35 cm~3 vs. 31.40 cm~3, t = 9. 70, P <0. 001 ;82. 33 cm~3 vs. 70. 83 cm~3, t = 8. 19, P < 0. 001 ; 230. 73 cm~3 vs. 197.59 cm~3 ,t=5.72,P <0. 001 ;21.66% vs. 18. 76% ,t = 11.16,P <0. 001 ;1329. 07 Gy vs. 1143. 14 Gy, t = 13. 24, P < 0. 001). With ABC, all patients completed their treatment successfully except one patient for financial problems. The median radiation dose to the GTV was 64 Gy (60 -64 Gy). The overall immediate response rate was 64% (18/28). According to the NCI-CTC 3.0, grade 1 and 2 acute radiation-related toxicities occurred in 68% (19/28) and 18% (5/28) of patients for esophagitis, 82% (23/28) and 7% (2/28) for pneumonitis, respectively. Grade 1, 2 and 3 bone marrow suppression occurred in 57% (16/28), 25% (7/28) and 14% (4/28) of patients, respectively. Grade 1 and 2 acute cardiac injuries occurred in 86% (24/28) and 14% (4/28) of patients. Conclusions During CRT for patients with NSCLC, the use of ABC can decrease the radiation dose and acute complications of normal tissues.
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Objective To analyze the results and prognosis for patients with inoperable pancreatic carcinoma treated by interventional chemotherapy (IC) ,three-dimensional radiotherapy (RT), or IC + RT.Methods From 2003 to 2008,139 patients with locally advanced (82 patients, stage Ⅲ) or metastatic (57 patients, stage Ⅳ) pancreatic cancer were retrospectively analyzed, including 74 with pancreatic head carcinoma (53.2%).Three patients with ductal adenocarcinoma were diagnosed with fine-needle aspiration, all other patients were clinically diagnosed with imagings (CT, MRI and/or ultrasonosraphy),clinical symptoms and tumor markers, There were 71,34 and 34 patients receiving IC alone, 3DCRT alone and 3DCRT plus IC, respectively.Log-rank univariate and Cox model multivariate analyses were used to determine prognostic factors.Results The follow-up rate was 92.1%.115 and 98 patients were followedup longer than 1 and 2 years, respectively.The 1-and 2-year overall survival rates were 37.1% and 16.3%for all patients, 44% and 20% for patients with locally advanced disease.The corresponding rates were 18% and 5%, 61% and 29% ,48% and 25% (χ2= 14.65,P=0.001) for patients receiving IC alone, RT alone, and IC + RT, respectively.In univariate analysis, staging (χ2= 44.49, P = 0.035), radiotherapy (χ2= 15.32, P = 0.000) and tumor location (χ2= 10.741, P = 0.002) were prognostic factors.In multivariate analysis, tumor location (χ2= 5.00, P = 0.025) and radiotherapy (χ2= 7.93, P = 0.005) were prognostic factors.Conclusions Radiotherapy can improve overall survival among patients with inoperable pancreatic cancer.The effect of RT + IC should be further investigated.
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Objective To evaluate the microscopic characteristics of hepatocellular carcinoma (HCC) invasion,and to provide the reference for GTV-to-CTV expansion. Methods From January 2002 to January 2006,149 HCC patients treated by surgical resection were included. The pathologic slices and clinical data were reviewed, including the tumor size, capsule status, tumor edge, portal vein invasion, TNM stage, histology grade, serum alpha-fetoprotein (AFP), platelet count and the degree of liver cirrhosis. The distance between the tumor capsule and the invasion was measured by 2 senior pathologists. Results of the 149 patients evaluated,79(53.0%) patients presented micro-invasion ranged between 0.5-4.0 mm. The recurrence rate was higher in patients with micro-invasion than those without (44% vs 29%, P=0.047). The invasion extent was positively relative to the tumor size, capsule status, tumor edge, portal vein invasion, TNM stage,histology grade and AFP,while negatively relative to the platelet count. A score system was established according to five predictors of tumor size, capsule status, portal vein invasion, AFP and platelet count. The invasion distance below 2 mm was in 96.6% patients who had≤2 points and only 83.3% for those with 2 points. Conclusions For HCC patients,the invasion extent is relative to the tumor size,cap sule status,portal vein invasion, AFP and platelet count. These 5 predictors could be potentially used as a score system for GTV-to-CTV expansion.
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Objective To retrospectively analyze the role of 3-dimensioual conformal radiotherapy (3-DCRT) after percutaneous transhepatic portal vein stenting and transcatheter arterial chemoembolization (PTPVS-TACE) in the treatment of patients with hepatocellular carcinoma (HCC) complicated by main portal vein tumor throw.bus (MPVTT).Methods Between July 2002 and July 2007,45 patients with HCC complicated by MPVTT were treated by PTPVS-TACE.Among them,3-DCRT were undertaken for MPVTT in 16 patients (group A),the other 29 patients were not treated with 3-DCRT(group B).The clinical effects,complication,stent patency rates,cumulative survival rates were evaluated among groups.The Kaplan-Meier method and log-rank test were used for survival analysis.Results No patient died during stent placement or within the preceding first 24 hours.No severe procedure-related complications were observed.The 60--,180--,360--day cumulative stent patency rates were 100.0%,62.2% and 34.6% in group A,and 58.6%,21.7% and 10.8% in group B,respectively,showing significant difference between the two groups (X2 =9.672,P <0.01).The mean patency time was(475±137) and (200±61)days,respectively.The 60--,180--,and 360--day cumulative survival rates were 93.8%,81.3% and 32.5% for group A,86.2%,13.8% and 6.9% for group B,respectively.There were significant statistical differences between the two groups(X2=9.672,14.596,P < 0.01).Conclusion Treatment with PTPVS-TACE-3-DCRT is a more effective modality than PTPVS-TACE for HCC complicated by MPVTT.
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Purpose:To evaluate the acute side effects an d efficacy of three-dimensional conformal radiotherapy(3-DCRT)combined with hype rthermia for locally advanced non-small-cell lung cancer(LANSCLC). Methods:From Jan.2001 to April.2003,35 patients with LANSCLC we re treated with three-dimensional conformal radiotherapy(3-DCRT) combined with hyperthermia. Results:The overall response rate(CR+PR)was 91.4%for the primar y tumor. Acute radiation esophagistis occurred in 48.6%of patients(Grades Ⅰ,Ⅱ ). Acute radiation pneumonitis was observed in 8.6% of patients (Grades Ⅰ,Ⅱ). Grade Ⅰ-Ⅱ bone marrow suppression occurred in 8.6%(3/35)of patients and Grade Ⅰ-Ⅱ myocardical injury was present in 14.3%(5/35) of patients. The median fo llow-up duration was 24(6-28) months. Conclusions:Hyperthermia combined with 3-DCRT is well tolerate d in most patients with LANSCLC. Its early responses are milder than the convent ional radiotherapy. Remote results await futher follow-up.
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The purpose of tumor staging is to guide treatment, and the treatment for a certain stage should be adjusted based on the changes in disease condition, in order to facilitate better control of tumor. Therefore, the treatment of liver cancer requires follow-up and re-staging to develop better treatment regimens for patients, especially the opportunity for cure. Surgical resection is not suitable for large hepatocellular carcinoma confined to the liver, and after embolization chemotherapy combined with radiotherapy for tumor regression and downstaging, some patients may undergo surgical resection, and the incurable tumor can thus be cured. For liver cancer patients with portal vein tumor thrombus, surgical resection can be performed after tumor thrombus is reduced by neoadjuvant radiotherapy, and the patients undergoing neoadjuvant radiotherapy have a significant increase in survival time than those not undergoing neoadjuvant radiotherapy. Large hepatocellular carcinoma can be downstaged to small hepatocellular carcinoma after multimodality therapy, and then stereotactic radiotherapy or radiofrequency ablation can help to achieve radical treatment. There is an increasing number of clinical reports of radiotherapy for liver cancer downstaging, with a gradual increase in evidence-based level, and thus it holds promise for clinical application.