Analysis of failure patterns and survival after SBRT for 147 cases of T 1-2N 0M 0 stage non-small cell lung cancer / 中华放射肿瘤学杂志

Objective:To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T 1-2N 0M 0 non-small cell lung carcinoma (NSCLC). Methods:Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model.Results:A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95% CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion:Distant metastasis is the main failure pattern in patients with T 1-2N 0M 0 NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.

Clinical application and prospect of SBRT in treatment of oligo-metastatic NSCLC / 中华放射肿瘤学杂志

The rapid progress on immunotherapy and targeted therapy has brought long-term survival benefits for locally advanced non-small cell lung cancer (NSCLC). The oncology community has also paid more attention to the local treatment for advanced NSCLC, especially for patients with limited metastatic lesions, also known as oligo-metastasis. Many studies have reported that oligo-metastatic NSCLC patients could benefit from the combination of local and systematic treatment, and even to be cured. In recent years, with the advances in radiation technology, stereotactic body radiation therapy (SBRT) has achieved precise high-dose radiotherapy for small target tumors. Currently, SBRT has been widely applied in the treatment of inoperable early lung cancer, and its application value and safety in patients with advanced lung cancer are also being actively explored. In this article, the research status, progress and future development direction of SBRT in the treatment of oligo-metastatic NSCLC were discussed.

Prediction model of radiation pneumonitis after chemoradiotherapy for esophageal cancer based on dosiomics / 中华放射肿瘤学杂志

Objective:To study the risk factors and prediction model of radiation pneumonitis (RP) after radical chemoradiotherapy for locally advanced esophageal cancer based on dosiomics.Methods:Clinical data of 105 patients with esophageal cancer undergoing radical chemoradiotherapy at Zhejiang Cancer Hospital between January 2020 and August 2021 were retrospectively analyzed. RP was scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0). Clinical factors, traditional dosimetric features and dosiomics features were collected, respectively. The features for predicting PR were analyzed by limma package. Support vector machine, k-nearest neighbor, decision tree, random forest and extreme gradient boosting were used to establish the prediction model, and the ten-fold cross-validation method was employed to evaluate the performance of the model. The differences of this model when different features were chosen were analyzed by delong test.Results:The incidence of RP in the whole group was 21.9%. One clinical factor, 6 traditional dosimetric features and 42 dosiomics features were significantly correlated with the occurrence of RP (all P<0.05). Support vector machine using linear kernel function yielded the optimal prediction performance, and the area under the receiver operating characteristic (ROC) without and with dosiomics features was 0.72 and 0.75, respectively. The models established by support vector machine, random forest and extreme gradient boosting were significantly different with and without dosiomics features (all P<0.05). Conclusion:The addition of dosiomics features can effectively improve the performance of the prediction model of RP after radiotherapy for esophageal cancer.

Failure mode and long-term survival after neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

Analysis of prognostic factors in 135 patients with pulmonary metastasis from esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To investigate the prognostic factors of patients with esophageal squamous cell carcinoma with pulmonary metastasis.Methods:Clinical characteristics of 135 esophageal squamous cell carcinoma patients presenting with pulmonary metastasis after treatment in Zhejiang Cancer Hospital from 2008 to 2018 were retrospectively analyzed. Thesurvival rate was calculated by Kaplan-Meier method. Univariate analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by Cox models.Results:The median follow-up time of 135 patients with esophageal squamous cell carcinoma was 94.2 months (19.5-258.9 months), and 109 patients died (80.7%). The 1-and 2-year overall survival rates were 47.4% and 25.1%, with the median survival time was 11.1 months (7.3-14.9 months). Univariate prognostic analysis showed that age, number of lung metastases, treatment of lung metastases, lymph node metastasis, distant organ metastasis, and the interval between the first treatment and lung metastasis were the prognostic factors of esophageal squamous cell carcinoma with lung metastasis (all P<0.05). Multivariate analysis demonstrated that age and number of lung metastases were the independent prognostic factors for patients with esophageal squamous cell carcinoma with lung metastases (all P<0.05). Conclusions:Age and number of lung metastases are the independent prognostic factors for patients with esophageal squamous cell carcinoma with lung metastases. Surgery or radiotherapy-based regional therapy can enhance clinical prognosis.

Risk analysis of brain metastases in limited-stage small cell lung cancer (LS-SCLC)achieving complete remission after thoracic radio-chemotherapy / 中华放射肿瘤学杂志

Objective:Small cell lung cancer (SCLC) is a highly malignant tumor with a high risk of brain metastasis (BMs). The purpose of this study was to evaluate the clinical factors affecting the occurrence of BMs in patients with stage IIB-IIIB SCLC who achieved complete remission (CR) after thoracic radio-chemotherapy.Methods:Clinical data of 191 patients with stage IIB-IIIB SCLC who achieved CR after thoracic radio-chemotherapy in Zhejiang Cancer Hospital from January 2009 to April 2016 were retrospectively analyzed. Common clinical factors related to the risk of BMs, including gender, age, thoracic radiotherapy dose, combined mode of radiotherapy and chemotherapy, pretreatment serum NSE and LDH, whether PCI was performed, TMN stage and PS score, were analyzed using log-rank method for univariate analysis, COX regression method for multivariate analysis and Kaplan-Meier method to plot the survival curve.Results:Univariate analysis showed that pretreatment LDH level≥240IU, pretreatment NSE ≥17 ng/ml and no PCI were positively correlated with the risk of BMs (all P＜0.05). Multivariate analysis showed that the risk of BMs was only positively correlated with pretreatment LDH≥240IU [HR: 1.90, 95%CI(1.07-3.37), P=0.029], and no PCI [HR:2.08, 95%CI(1.17-3.72), P=0.013]. Conclusion:Pretreatment serum LDH levels provide important value for predicting the risk of BMs in patients with stage IIB-IIIB SCLC who achieve CR after thoracic radio-chemotherapy.

Research progress on hippocampal-avoidance whole brain radiotherapy / 中华放射肿瘤学杂志

With the advancement of imaging diagnosis and the development of modern radiotherapy, the survival of cancer patients has been prolonged and the incidence rate of brain metastases (BM) has been significantly increased. The quality of life of patients and potential radiotherapy-induced neurocognitive impairment have gradually captivated widespread attention. Whole brain radiotherapy (WBRT) is one of the common local therapies for BM patients. However, the application of WBRT is controversial because it may lead to neurocognitive impairment. The incidence of metastatic tumors in hippocampus and radiation-induced neurocognitive impairment can accelerate the implementation of hippocampal-avoidance WBRT (HA-WBRT). In this article, the feasibility of HA-WBRT was discussed and research progress in recent years was reviewed.

Risk factors and dosimetric limitations for acute radiation pneumonitis after gemcitabine induction chemotherapy for non-small cell lung cancer / 中华放射肿瘤学杂志

Objective:To summarize the incidence of acute radiation pneumonitis (ARP) after gemcitabine induction chemotherapy for non-small cell lung cancer (NSCLC) and identify the high risk factors and dosimetric limitations of ARP after gemcitabine induction chemotherapy.Methods:We retrospectively analyzed 191 NSCLC cases who were received gemcitabine induction chemotherapy and chest radiotherapy in radiotherapy department of Zhejiang Cancer Hospital between January 2010 and December 2010. Base line data, treatment information and the incidence of ARP after treatment were collected. The risk factors of ARP were analyzed with univariate and multivariate Logistic regression method.Results:A total of 49 patients developed ≥ grade Ⅱ ARP, accounting for 25.7% of all cases. Univariate analysis indicated that the probability of ARP in patients who received the cumulative dose of gemcitabine ≥ 9.0 g was 3.45 times higher than that in those treated at a dose of < 9.0 g ( P=0.015). Radiation dose ≥ 50 Gy was significantly correlated with the occurrence of ARP ( P=0.008). The risk of ARP was increased by 7.69 times if the time interval between radiotherapy and chemotherapy was within 10 weeks ( P=0.047). Among the dosimetric parameters, V 5Gy, V 20Gy, V 30Gy and mean lung dose (MLD) of bilateral lungs were 45%, 22%, 16%, and 1 200 cGy respectively. All of them could effectively predict the occurrence of ARP (all P≤0.001). Multivariate analysis indicated that only radiotherapy dose ( P=0.044) and V 5Gy( P=0.02) were the independent predictors of ARP. Conclusions:For NSCLC patients who receive gemcitabine induction chemotherapy, the cumulative dose of gemcitabine, the interval time between chemotherapy and radiotherapy and the radiation dose are associated with the occurrence of ARP. We should strictly limit the total lung dosimetric parameters, such as V 5Gy, V 20Gy, V 30Gy and MLD to reduce the incidence of ARP.

Experience and efficacy of SBRT for lung cancer: an analysis of 142 patients / 中华放射肿瘤学杂志

Objective:To evaluate the clinical efficacy and safety of stereotactic body radiation therapy (SBRT) for stage Ⅰ-Ⅱ non-small cell lung cancer.Methods:Retrospective analysis of patients with early stage lung cancer who received SBRT in Zhejiang Cancer Hospital from 2012 to 2018 was conducted. The Kaplan-Meier method was used for survival analysis. The main endpoints of the study were locoregional control (LRC) and cancer specific survival (CSS).Results:A total of 142 eligible cases were included, with a median BED10100Gy (100-132Gy). The median age was 75.6 years (47.2-89.0 years), among which 75 patients were aged (greater than or equal to 75 years old). The median follow-up time was 31.0 months, for patients< 75 years old and patients ≥ 75 years old. The 5-year LRC were 84.5% and 95.8% respectively, 5-year CSS were 72.4% and 78.6% respectively, for patients< 75 years old and elderly patients. The systemic response was mild during treatment, no grade 4-5 adverse events occurred in all patients. The main acute side effect was radiation pneumonitis (RP) below grade 3. Grade 2 RP appeared in 14 patients (9.9%) after SBRT where grade 3 RP occurred in 2(1.4%). There was no treatment-related mortality in the SBRT group.Conclusions:SBRT is a safe and effective treatment for early primary lung cancer with satisfactory rates of LRC and CSS in 5 years and mild complication, which is similar to previous reports.

Investigation and analysis of the reasons for omission of adjuvant radiotherapy after breast-conserving surgery for early-stage breast cancer / 中华放射肿瘤学杂志

Objective To investigate and analyze the reasons for the omission of adjuvant radiotherapy after breast-conserving surgery (BCS) in patients with breast cancer.Methods The clinicopathologial characteristics and socioeconomic data of 55 breast cancer patients undergoing BCS without postoperative adjuvant radiotherapy in our hospital from 2012 to 2016 were retrospectively analyzed.Results Among the 55 patients who did not receive radiotherapy,25 patients were due to low local recurrence risk,12 patients were due to economic or family reasons,12 patients were due to fear of adverse reactions of radiotherapy,and 5 patients were not recommended by primary physicians for radiotherapy.In addition,3 cases with multiple distant metastases and 3 cases with concomitant thyroid cancer didn't received radiotherapy.Conclnsions Low risk local recurrence is the main reason for the omission of adjuvant radiotherapy,followed by the fear of radiation-induced toxicity and poor financial support.Patient education and medical insurance may improve the adjuvant radiotherapy compliance.

Experience and efficacy of SBRT for lung cancer:an analysis of 200 patients / 中华放射肿瘤学杂志

Objective To evaluate the safety and clinical efficacy of stereotactic body radiation therapy (SBRT) for lung cancer.Methods A retrospective analysis was performed on 200 patients with primary non-small cell lung cancer (NSCLC)(118 patients) or solitary pulmonary metastasis (82 patients) who underwent SBRT in Zhejiang Cancer Hospital from January 2012 to September 2015.The 80% isodose line covered 95% of the planning target volume,and the 100% isodose line covered 100% of the internal gross tumor volume.The fractional dose was 4.0-18.0 Gy daily or every other day,and the biologically equivalent dose ranged from 40.0 to 151.2 Gy (median 100 Gy).Results All patients completed treatment.The follow-up rate was 96.0%.The complete response and partial response rates were 14.8%(17/115) and 65.2%(75/115) for the primary tumor group,versus 25%(19/77) and 38%(29/77) for the metastasis group.The incidence rates of grade Ⅱ and Ⅲ acute radiation pneumonitis were 4.7% and 3.1%,respectively.The median follow-up was 14.9 months.The 1-and 2-year local control rates were 95.7% and 84.3% for the primary tumor group,versus 92% and 73% for the metastasis group.The 1-and 2-year overall survival rates were 94.5% and 92.0% for the primary tumor group,versus 85% and 62% for the metastasis group.Conclusions SBRT is a safe and effective treatment for early primary NSCLC and solitary pulmonary metastasis,resulting in high 1-and 2-year local control and overall survival rates and low rate of complications.

An analysis of risk factors for brain metastases after prophylactic cranial irradiation for limited-stage small-cell lung cancer / 中华放射肿瘤学杂志

Objective To evaluate the high?risk factors for brain metastases after prophylactic cranial irradiation ( PCI), and to provide a basis for personalized treatment. Methods A retrospective analysis was performed in 188 patients with limited?stage small?cell lung cancer who received PCI in our hospital from 2005 to 2010. The Kaplan?Meier method was used to calculate the cumulative rate of brain metastases. The log?rank test and the Cox model were used for the univariate and multivariate analyses of the potential factors for the cumulative incidence of brain metastases, respectively. Results In the 188 patients, 31 ( 16?5%) had brain metastases. The 1?, 2?, and 3?year cumulative incidence rates of brain metastases were 4%, 15%, and 20%, respectively. The univariate analysis showed that staged Ⅲ disease before treatment, elevated levels of tumor markers, incomplete remission after chemoradiotherapy, and local?regional relapse were risk factors for high incidence of brain metastases ( P= 0?044, 0?037, 0?005, 0?007) . The multivariate analysis revealed that incomplete remission after chemoradiotherapy and local?regional relapse after chemoradiotherapy were risk factors for high incidence of brain metastases after PCI ( P= 0?003, 0?040 ) . Conclusions Patients with incomplete remission or local?regional relapse after chemoradiotherapy have high incidence of brain metastases after PCI. For those patients, a frequent follow?up of the central nervous system plus salvage cranial irradiation might provide an alternative to PCI.

Endoscopic ultrasonography for defining primary tumor in esophageal radiotherapy / 中华消化内镜杂志

Objective To investigate the differences of measurement of gross target volume (GTV)between endoscopic ultrasonography ( EUS )-based ( GTVEUS ) and computed tomography ( CT ) -based (GTVCT) method for thoracic esophageal squamous cell carcinoma. Methods EUS was performed on 36consecutive patients with thoracic squamous cell carcinoma, and the superior and inferior boarders of the tumor defined by EUS were marked with hemoclips. The CT planning scan was then performed with the patient in supine position, and the GTVCT and GTVEUS were contoured respectively. The lengths ( LCT and LEUS) and spatial locations of longitudinal GTVCT and GTVEUS were compared. Results The mean LCT and LEUS were (7. 79 ± 3. 15 ) cm and (7. 42 ± 2. 72) cm, respectively ( t = 0. 82, P ＞ 0. 05 ), with a correlation coefficient of 0. 61 (P ＜0. 001 ). Locations of longitudinal GTVCT and GTVEUS were compared in 34cases, with 2 excluded for invisualization on CT. The mean conformal index (CI) was (0. 79 ± 0. 18 ), and spatial variations were found in 71% patients, with 8 patients at proximal end and 21 others at distal end.There was no clip placement associated complication. Conclusion Endoscopic hemoclips placement is safe and reliable. EUS can provide additional information to CT in defining longitudinal GTV in thoracic esophageal squamous cell carcinoma, especially in superficial and submucosal carcinomas.

A dosimetric comparison of three plans in simultaneous integrated boost intensity-modulated radiotherapy in cervical esophageal carcinoma undergoing prophylactic lymphatic irradiation / 中华放射医学与防护杂志

Objective To evaluate the optimized simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) plans in cervical esophageal carcinoma underwent prophylactic lymphatic irradiation.MethodsSix patients with cervical esophageal carcinoma were studied.The gross tumor volume (GTV) and clinical target volume (CTV) (including bilateral mid-lower neck and supraclavicular lymph drainage regions,upper mediastinal lymph drainage regions) were delineated on sim-CT images,GTV and CTV were uniformly expanded by 5 mm to create PGTV and PTV.Five fields(5F) ,7F and 9F SIB-IMRT plans were designed.The prescribed doses to PGTV and PTV were 66 Gy and 60 Gy in 30 fractions respectively.The parameters of dose-volume histograms in three groups planning were compared.Results The values of conformity index(CI) of PGTV were 0.56,0.62 and 0.69 (F =6.22,P ＜0.01 ),the V66 with 88.24% ,95.03% and 94.91% ( F = 4.39,P ＜ 0.05 ) and D95 with 6539.67,6601.83 and 6602.00 cGy (F=4.46,P ＜0.05) in 5F,7F and 9F SIB-IMRT plans.The values of CI,V66 and D95 of PTV were 0.80,0.85 and 0.87 (F=11.29,P＜0.01),with 91.64%,94.05% and 95.06% (F=4.10,P＜0.05) and with 5934.00,5987.17 and 6006.33 cGy (F =4.01,P ＜0.05).The values of maximal dose of spinal cord were 4707.17,4497.83 and 4357.00 cGy( F = 11.26 ,P ＜0.011 ) in 5F ,7F and 9F SIB-IMRT plans.The values of all dosimetic parameters about PGTV and PTV were same in 7F and 9F SIB-IMRT plans ( all P ＞ 0.05 ).Conclusion 7F-SIB-IMRT plan is best one scheme for cervical esophageal carcinoma underwent prophylactic lymphatic irradiation.

Survey on changes of breast cancer radiotherapy in four hospitals within southeast coastal region of China / 中华放射医学与防护杂志

Objective To explore the changes and the tendency of breast cancer radiotherapy in China within the past decade.Methods A survey on breast cancer radiotherapy in 1 999 and 2006 was conducted in 4 hospitals located within the southeast coastal region of China,including patients'clinical characteristics,the purpose of radiotherapy and its techniques.Results The percentage of breast conservative treatment(BCT)increased from 3%in 1999 to 13%in 2006.For radiotherapy techniques in 2006 compared with 1999,the growth trend was found in use of breast immobilization devices(80% vs.46%),treatment planning system(70% vs.23%),and CT simulation(14%vs.0).The frequency was increased in the chest wall irradiation after masteetomy(90%vs.67%),but decreased in internal mammary region(30%vs.76%)and axilla(37%vs.69%)treatment.There were no differences in total dose and fractionation prescription.Conclusions BCT was performed more frequently,but postmastectomy radiotherapy was still essential option in China at present.Although some advanced techniques were applied frequently in clinical practice.Simulation,treatment planning,and irradiation target design were urgent for improvement and standardization.