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Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.
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The adjacency or invasion to great vessels such as superior mesenteric artery/vein and celiac axis increase the difficulties to achieve R 0 resection and evoked high local recurrence for patients with borderline resectable pancreatic cancer. Intraoperative radiation therapy refers to a single high-dose irradiation during the surgery, which achieved the purpose of precise target treatment and protected normal tissues. In borderline resectable pancreatic cancer, preoperative radiotherapy and chemotherapy combined with surgery and intraoperative radiotherapy has a better effect, and compared with surgery alone, the addition of intraoperative radiotherapy does not increase the risk of serious postoperative complications. Here, we summarized the application of intraoperative radiation therapy in borderline resectable pancreatic carcinoma.
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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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Objective:To analyze and compare the dosimetric differences based on volumetric-modulated arc therapy (VMAT), fixed field intensity-modulated radiotherapy (F_IMRT), and electron irradiation combined with VMAT (E&VMAT) in radiotherapy for breast cancer after modified mastectomy, aiming to provide reference for clinical selection of treatment plan.Methods:Ten patients with the left breast cancer who received radiotherapy after modified mastectomy were randomly selected. The target areas included chest wall and supraclavicular region, and the prescribed dose was 43.5 Gy in 15 fractions (2.9 Gy/F). Based on the Pinnacle 3 planning system, the VMAT, F_IMRT and E&VMAT plans (electron beam for chest wall, VMAT for supraclavicular area) were designed for each patient. The conformity and homogeneity of the target areas, the dose of organs at risk and treatment time were compared. Results:The VMAT plan could improve the dose distribution of the target areas. The conformity index and homogeneity index of the target dose were significantly better than those of the F_IMRT and E&VMAT plans (all P<0.05). The average dose, V 30Gy, V 20Gy, V 10Gy of the left lung in the VMAT plan were significantly better than those in the F_IMRT and E&VMAT plans (all P<0.05). The V 5Gy of the left lung in the VMAT plan was significantly better than that in the F_IMRT plan ( P<0.05). There was no statistical difference in the V 5Gy of the left lung between the VMAT and E&VMAT plans ( P>0.05). The heart, right breast and right lung of the VMAT plan could meet the clinical dose limit requirements. The treatment time of the VMAT, F_IMRT and E&VMAT plans was (326±27) s, (1 082±169) s, and (562±48) s, respectively. Conclusions:Compared with the F_IMRT and E&VMAT plans, the VMAT plan has better quality and shorter treatment time. VMAT plan has higher value in clinical application compared with the F_IMRT and E&VMAT plans.
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Objective:To evaluate the 5-year survival outcome of patients with unresectable locally advanced non-small cell lung cancer (NSCLC) treated with Endostar in combination with platinum-based concurrent chemoradiotherapy.Methods:From March 2009 to June 2015, 115 patients with the unresectable locally advanced NSCLC from two prospective studies[Clinical trials 2009-2012(ClinicalTrials.gov NCT01894) and 2012-2015(ClinicalTrials.gov, NCT01733589)] were treated with Endostar in combination with platinum-based concurrent chemoradiotherapy. A total dose of 60-66 Gy was delivered in 30-33 fractions. Endostar was given 1 week prior to the beginning of radiotherapy, and repeated fortnightly during the concurrent chemoradiotherapy. After long-term follow up, survival outcome was evaluated in 104 patients treated with radiation dose of ≥60 Gy. Kaplan-Meier method was used for survival analysis. Univariate survival analysis was performed using the log-rank test.Results:Of 104 eligible patients, 60.6% of them had squamous carcinoma and 65.4% were classified in stage Ⅲ B. All the patients received ≥2 cycles of Endostar and 93.3% of them received 4 cycles of Endostar. The median follow-up time was 68.3 months. The median overall survival (OS) and median progression-free survival (PFS) were 31.3 and 13.9 months, respectively. The 3-year and 5-year OS were 45.6% and 35.7%, respectively. The 3-year and 5-year PFS were 27.1% and 24.9%, respectively. Univariate analysis indicated that sex, ECOG, pathological type, clinical stage, radiotherapy technique, chemotherapy regimen, chemotherapy cycle and cycle of Endostar use were not associated with OS. Late radiation injury occurred in 14.4% of patients, and no grade 4-5 late injury was observed. Conclusion:Patients with unresectable locally advanced NSCLC treated with Endostar fortnightly in combination with platinum-based concurrent chemoradiotherapy achieve better OS than historical data with tolerable toxicities.
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Surgical resection is the most important treatment of thymoma. However, the role of postoperative adjuvant radiotherapy (PORT) has been controversial. The survival benefits of two-dimensional radiotherapy are not significant. However, precision radiotherapy has significantly changed tumor radiotherapy. The value of PORT for thymoma may also be altered. At present, the effect of radiotherapy in patients with positive surgical margins or inoperable resection is confirmed. For patients with complete surgical resection, Masaoka-Koga stage Ⅰ patients do not require PORT. Whether PORT should be given for stage Ⅱ patients remains debated if stage Ⅱ b, large volume and B2/B3 type were considered during radiotherapy. The role of PORT for stage Ⅲ patients is also in disputed, whereas a majority of findings support the application of PORT. Precision technology is recommended during PORT. The clinical target volume suggests that the three-dimensional expansion of the tumor bed is 0.5 cm, including the mediastinal pleura involved by the tumor and 0.5-1.0 cm along the anterior and posterior direction of the mediastinal pleura, the cranial and caudal direction, the lung side is expanded within the 0.5 cm, and the vascular wall around the tumor and part of the vascular space, so as to avoid including too much normal tissue. The dose for complete resection is 45-50 Gy and 54-60 Gy or slightly higher for incomplete resection, which may increase the benefits and reduce the risk of PORT.The application of new radiotherapy techniques such as particle therapy can gain the advantage of dosimetric distribution, and whether it can be transformed into clinical benefits needs to be further explored.
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Objective@#To investigate the dosimetric characteristics of conventional two-dimensional radiotherapy of the chest wall, supra-and infra-clavicular regions, and the incidental irradiation dosage of the internal mammary region after modified mastectomy in breast cancer patients.@*Methods@#Clinical data of 20 breast cancer patients including 10 left and 10 right cases who received radiotherapy after modified mastectomy between 2015 and 2016 were retrospectively analyzed. All patients received irradiation to the chest wall, supra-and infraclavicular regions at a prescription dose of 43.5 Gy in 15 fractions with conventional technique. One anterior-posterior (AP) photon field irradiation was delivered for the supra-and infra-clavicular regions, and one electron field for the chest wall. The supra-and infraclavicular regions were re-planned by using two AP/PA fields and the doses of organ at risk were evaluated.@*Results@#With conventional radiotherapy, the D90 of the supra-and infra-clavicular regions were more than 39.15 Gy (EQD2≥45 Gy) in 17 patients (85%), and the median D90 of the chest wall was 35.38 Gy. The median dose of incidental internal mammary region was 13.65 Gy. Patients with lower body mass index (BMI) received higher D90 in both supra-and infra-clavicular and chest wall irradiation (P=0.039, 0.347).@*Conclusions@#Irradiation at D90 of 39.15 Gy to the supra-and infra-clavicular regions with AP/PA fields can meet the prescription dose requirement of ≥90% in most cases and does not increase the irradiation dose to normal tissues. The dose distribution of one electron field of the chest wall is poor. Incidental internal mammary region can be irradiated at a limited dosage. BMI is an influencing factor for dose distribution.
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Objective To investigate the dosimetric characteristics of conventional two-dimensional radiotherapy of the chest wall,supra-and infra-clavicular regions,and the incidental irradiation dosage of the internal mammary region after modified mastectomy in breast cancer patients.Methods Clinical data of 20 breast cancer patients including 10 left and 10 right cases who received radiotherapy after modified mastectomy between 2015 and 2016 were retrospectively analyzed.All patients received irradiation to the chest wall,supra-and infraclavicular regions at a prescription dose of 43.5 Gy in 15 fractions with conventional technique.One anterior-posterior (AP) photon field irradiation was delivered for the supra-and infra-clavicular regions,and one electron field for the chest wall.The supra-and infraclavicular regions were re-planned by using two AP/PA fields and the doses of organ at risk were evaluated.Results With conventional radiotherapy,the D90 of the supra-and infra-clavicular regions were more than 39.15 Gy (EQD2 ≥45 Gy) in 17 patients (85％),and the median D90 of the chest wall was 35.38 Gy.The median dose of incidental internal mammary region was 13.65 Gy.Patients with lower body mass index (BMI) received higher D90 in both supra-and infra-clavicular and chest wall irradiation (P=0.039,0.347).Conclusions Irradiation at D90 of 39.15 Gy to the supra-and infra-clavicular regions with AP/PA fields can meet the prescription dose requirement of ≥90％ in most cases and does not increase the irradiation dose to normal tissues.The dose distribution of one electron field of the chest wall is poor.Incidental internal mammary region can be irradiated at a limited dosage.BMI is an influencing factor for dose distribution.
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Objective To evaluate the dose distribution and clinical efficacy of hippocampal-sparing prophylactic cranial irradiation ( HS-PCI ) in patients with small cell lung cancer by using helical tomotherapy. Methods Clinical data of 49 patients with small cell lung cancer receiving HS-PCI using helical tomotherapy in Cancer Hospital between 2014 and 2017 were retrospectively analyzed. All patients received brain MRI to exclude the possibility of brain metastasis within 1 month after standard surgery or radio-and chemo-therapy. The prescription dose was 95% PTV,25 Gy in 10 fractions. The adverse reactions and cognitive functions of patients were observed before,6 months and 1 year after treatment,and the dose distribution in the hippocampal gyrus,survival rate and brain metastasis rate were analyzed. Results The median follow-up time was 16 months. The average dose in the hippocampal gyrus was 7. 23 Gy and 8. 46 Gy in the reduction region,which was reduced by 71. 88% and 66. 16% compared with the prescription dose. The maximum dose in the hippocampal gyrus was 10. 66 Gy and 15. 43 Gy in the reduction region. Among 49 patients,8 died,the 1-year survival rate was 85. 1% and the 2-year survival rate was 70. 3%.Nine patients (18. 3%) had brain metastases,and one of them with extensive multiple brain metastases (n＝13) presented with metastasis adjacent to the hippocampal gyrus. The main adverse reactions included mild headache, dizziness and brain edema,whereas no ≥ grade 2 adverse reactions occurred. At 6 months after treatment, the HVLT-R score was significantly decreased,and declined by 6. 78% at 12 months after treatment. The HVLT-R scores did not significantly differ in patients without brain metastasis before and 12 months after treatment ( P＞0. 05 ). Conclusion Application of HS-PCI using helical tomotherapy meets the dose requirement,effectively protects the cognitive function and yields slight adverse reactions.
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Objective To assess the prognostic benefits of intraoperative radiotherapy (IORT) with electron beam among patients with unresectable locally advanced pancreatic cancer.Methods Between January 2009 and December 2014,167 patients with unresectable locally advanced pancreatic cancer received IORT with electron beam (10-20 Gy) in our hospital.After surgery,12 patients were treated with external beam radiotherapy,56 patients with chemoradiotherapy (CRT),and 17 patients with chemotherapy.Overall survival (OS),local recurrence,and toxicities were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,the log-rank test was used for survival difference analysis and univariate prognostic analysis,and the Cox model was used for multivariate prognostic analysis.Results The follow-up rate was 100％.The median OS time was 10.3 months,and the 2-year OS rate was 22％.The median progression-fiee survival (PFS) time was 6.3 months,and the 2-year PFS rate was 9.9％.The cancer-specific survival (CSS) time was 11.2 months,and the 2-year CSS rate was 23.6％.In the patients treated with IORT alone at doses of＜15 Gy,15 Gy and＞15 Gy,the median OS times were 6.2 months vs.9.1 months vs.22.2 months,and the 1-year OS rates were 10.0％ vs.39.6％ vs.74.4％ (P=0.000).Among the patients receiving postoperative adjuvant therapy,those treated with IORT+CRT had the best survival,with a median OS time of 11.6 months (P=0.033).The univariate analysis showed that IORT dose (P =0.000),tumor size (P =0.006),and IORT applicator diameter (P =0.007) were prognostic factors.The multivariate analysis showed that IORT dose (P=0.000) and IORT combined with CRT (P=0.006) were independent prognostic factors.Conclusions IORT with electron beam is an effective and safe treatment strategy for unresectable locally advanced pancreatic cancer.After protecting surrounding organs,increasing the IORT dose can improve the survival.IORT combined with CRT should be recommended because it improves survival for unresectable locally advanced pancreatic cancer without increasing toxicities.
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Objective To analyze survival and recurrence rates of patients with Masaoka stage Ⅲ thymoma and to explore the prognostic factors.Methods Between September 1965 and December 2010,a total of 111 patients with stage Ⅲ thymoma treated in our hospital were retrospectively analyzed.Sixty-eight patientsreceived comple te rescction ± radiotherapy,whilc 23 patients received incomplete resection ±radiotherapy and 20 patients received biopsy ± radiotherapy.Eighty-seven patients received postoperative radiotherapy (12 patients received preoperative radiotherapy) while 24 patients received surgery alone.Results The median follow-up time was 66 months (5-540) with a follow-up rate of 92.5％ (111/120).Compared with incomplete resection ± radiotherapy and biopsy ± radiotherapy,the 5-year overall survival (OS) (88％ vs.59％ and 57％,x2 =12.11,P =0.002),disease free survival (DFS) (74％ vs.40％ and 41％,x2 =11.49,P =0.003) and disease specific survival (DSS) (94％ vs.69％ and 60％,x2 =10.95,P =0.004) could be improved with complete resected ± radiotherapy.Compared with surgery alone,postoperative radiotherapy did not improve OS,DFS and DSS (55％ vs.77％ (x2 =1.01,P =0.316),61％vs.61％ (x2 =0.12,P =0.729) and 72％ vs.85％ (x2 =0.27,P =0.601),respectively).For the 68 patients received complete resection,radiotherapy after complete resection (56 patients) did not improve OS,DFS and DSS (82％ vs.89％ (x2 =0.31,P =0.576),72％ vs.81％ (x2 =0.05,P=0.819) and 89％vs.95 ％ (x2 =0.05,P =0.825),respectively) compared with surgery alone (8 patients).Conclusions Stage Ⅲ thymoma patients received complete resection had better outcome than patients received incomplete resection or biopsied only.The role of postoperative radiotherapy is still controversial for stage Ⅲ thymoma,randomized clinical trial is needed
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Objective To investigate the safety and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors.Methods From May 2008 to August 2009, 52 patients with abdominal tumors were treated with intraoperative electron radiotherapy,including 14 patients with breast cancer,19 with pancreatic cancer,3 with cervical cancer, 4 with ovarian cancer, 6 with sarcoma, and 6 with other tumors.Fifteen patients were with recurrent tumors.The intraoperative radiotherapy was performed using Mobetron mobile electron accelerator, with total dose of 9 - 18 Gy.In all, 29, 4 and 19 patients received complete resection, palliative resection and surgical exploration, respectively.The complications during the operations and within 6 months after operations were graded according to Common Terminology Criteria for Adverse Events v3.0 (CTC 3.0).Results The median duration of surgery was 190 minutes.Intraoperative complications were observed in 5 patients, including 3 with hemorrhage, 1 with hypotension,and 1 with hypoxemia, all of which were treated conservatively.The median hospitalization time and time to take out stitches was 12 and 13 days, respectively.And the in-hospital mortality was 4% (2/52).Twentyfour patients suffered post-operative adverse events, including 3 postoperative infections.With a median follow-up time of 183 days, 20% of patients sufferred from grade 3 to 5 adverse events, with hematological toxicities being the most common complication, followed by bellyache.Grade 1 and 2 toxicities which were definitely associated with intraoperative radiotherapy was 28% and 4%, respectively.None of grade 3 to 5 complications were proved to be caused by intraoperative radiotherapy.Conclusions Intraoperative electron radiotherapy is well tolerable and could be widely used for patients with abdominal tumors, with a little longer time to take out stitches but without more morbidities and toxicities compared surgery alone.