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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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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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Objective: To evaluate the primary outcomes and adverse reactions of patients with hepatocellular carcinoma treated by stereotactic body radiation therapy (SBRT) using tomotherapy. Methods: From December 2012 to December 2015, Forty-six patients with hepatocellular carcinoma who received SBRT in Zhongshan Hospital Affiliated to Fudan University were enrolled. The clinical and pathological data and follow-up data of all cases were collected. The median diameter of tumors was 2.5 cm, ranging from 0.9 to 5.8 cm. All cases were performed by four-dimensional CT (4-DCT) scan and image-guided matching calibration before SBRT. Total irradiation dose ranged from 48 to 50 Gy in 5 to 10 fractions. The supportive treatments of liver protection and nutritional support were administrated during SBRT. The curative tumor response was evaluated using the modifed Response Evaluation and Criteria in Solid Tumors (mRECIST) 6 months after SBRT. The adverse reactions were evaluated using National Cancer Institute- Common Terminology Criteria for Adverse Events 3.0 (NCI-CTC 3.0). The cumulative probability of survival was calculated according to Kaplan-Meier method. Results: All cases completed SBRT. They were followed up every 3 months after treatment. Based on mRECIST, 58.7% of patients achieved complete response (CR), 32.6% achieved partial response (PR), and there were 4.3% patients with stable disease, and 2.61% patients with tumor progression. The total effective rate (CR+PR) was 91.3%. The overall survival (OS) rates at 1, 2 and 3 years were 95.4%, 75.7% and 69.9%, respectively. For the adverse reaction, only 5 cases of grade? bone marrow suppression, 2 cases of gradeII bone marrow suppression and 2 cases of grade? transaminase increase were found; no radiation-induced liver disease (RILD) occurred. Conclusion: Tomotherapy is a safe and effective treatment for the patients with unresectable hepatocellular carcinoma. So SBRT using tomotherapy is worth promoting as an alternative treatment for unresectable hepatocellular carcinoma unsuitable for standard treatment.
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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.