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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.
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Objective:To compare the efficacy of stereotactic body radiotherapy(SBRT) and surgery in treating intrapulmonary recurrence of non-small cell lung cancer (NSCLC) after radical surgery.Methods:A retrospective analysis was conducted on NSCLC patients, who underwent radical surgery at the Cancer Hospital Affiliated to University of Chinese Academy of Sciences from November 2012 to December 2018 and then received SBRT or secondary surgery because of postoperative intrapulmonary recurrence. The survival rates of these patients were calculated using the Kaplan-Meier method. The comparison between the two groups was made using the Log-rank method, and the univariate and multivariate analysis was made using the Cox regression method.Results:Among 62 eligible patients, 33 received SBRT and 29 received secondary surgery, and they were divided into the SBRT group and the surgery group accordingly. For the SBRT and surgery groups, the median follow-up time was 45.8 months and 37.4 months, the 3-year locoregional control rate (LRCR) 79.8% and 90.2%, respectively ( P > 0.05), the progression-free-survival (PFS) 58.5% and 42.3%, respectively ( P >0.05), and the overall survival (OS) 78.0% and 85.5%, respectively ( P >0.05). The multivariate analysis suggested that treatment method, Charlson comorbidity index (CCI), and adjuvant drug therapy were independent prognostic factors for PFS ( P = 0.027, 0.013, 0.001). Conclusions:The efficacy of SBRT and surgery is comparable for patients with intrapulmonary recurrence of NSCLC after radical surgery.
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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.
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Objective:To make comparisons of treatment outcomes between video-assisted thoracoscopic surgery (VATS) lobectomy and stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC).Methods:Overall survival (OS), cancer specific survival (CSS), locoregional control (LRC), and disease-free survival (DFS) were retrospectively compared between early stage NSCLC patients who underwent VATS lobectomy and SBRT at our institution from January 2012 to December 2016. Propensity score matching (PSM) was carried out to reduce selection bias between two groups based on age, gender, Karnofsky performance score (KPS), Charlson comorbidity index (CCI), pulmonary function, and tumor diameter.Results:A total of 567 patients treated with VATS lobectomy ( n=458) or SBRT ( n=109) were included. 104 patients were matched for further analysis (52 in VATS lobectomy group and 52 in SBRT group). The median follow-up time was 44 months. the 3- and 5-year OS were 94.2% and 91.6% for VATS lobectomy and 88.6% and 79.9% for SBRT ( P=0.097), respectively. No statistically significant differences were noted in 5-year CSS (91.6% vs. 83.7%, P=0.270). The cumulative incidence of LRC was comparable between two group (94.0% and 85.9% vs. 93.5% and 93.5% at 3, 5 years, P=0.621). Differences in the DFS were not statistically significant (80.5% and 79.0% at 5 years, P=0.624). In the VATS lobectomy group, 10% patients ( n=5) experienced ≥ grade 3 CTCAE toxicity. One patient died of septicemia due to severe lung infection within 30 d after VATS lobectomy. In the SBRT group, one patient suffered from grade 3 radiation pneumonitis. There were no grade 4 or 5 toxicities in SBRT group. Conclusions:This propensity matched analysis suggests that SBRT can be an alternative option to VATS lobectomy for stage I-II NSCLC. Randomized trials are needed to evaluate the outcomes.
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Objective@#To compare the overall survival (OS), progression-free survival (PFS) and brain metastasis free survival (BMFS) between the chemo-radiotherapy and surgical treatment for patients with limited stage small cell lung cancer (LS-SCLC).@*Methods@#Clinical data of 69 patients diagnosed with LS-SCLC undergoing surgery in Zhejiang Cancer Hospital between 2000 and 2016 were collected. According to T, N stage, treatment duration, age, gender and whether or not prophylactic cranial irradiation (PCI), 69 patients of 503 LS-SCLC patients who underwent standard radiochemotherapy were assigned into the radiochemotherapy group by using the pair-matched case-control method.@*Results@#Among 138 patients, 69 cases were allocated into the surgery group (24 cases of stage Ⅰ, 14 cases of stage Ⅱ and 31 cases of stage Ⅲ) and 69 cases in the radiochemotherapy group (24 cases of stage Ⅰ, 14 cases of stage Ⅱ and 31 cases of stage Ⅲ). The median OS time was 37.1 months (95%CI: 24.1-50.2 months) in surgery group and 45.0 months (95%CI: 15.8-74.2 months) in the radiochemotherapy group. The 2-and 5-year OS rates were 60% and 45% in the surgery group, and 64% and 45% in the radiochemotherapy group (P=0.846). The median PFS time was 27.1 months (95%CI: 0.00-60.3 months) in the surgery group and 36.2 months (95%CI: 20.9-51.4 months) in the radiochemotherapy group. The 2-and 5-year PFS rates were 52%, and 38% in the surgery group, and 56% and 40% in the chemo-radiotherapy group (P=0.610). The 2-and 5-year BMFS rates were 81% and 76% in the surgery group, and 84% and 80% in the radiochemotherapy group (P=0.774). The 5-year OS rate (62% vs. 40%, P=0.038) and 5-year PFS rate (80% vs.40%, P=0.048) for patients with stage Ⅰ LS-SCLC in the surgery group were significantly higher than those in the radiochemotherapy group. However, the 5-year BMFS rate in patients with stage Ⅰ LS-SCLC did not significantly differ between two groups (92% vs.95%, P=0.816). The 5-year OS rate (41% vs.51%, P=0.946), 5-year PFS rate (65% vs.42%, P=0.280) and 5-year BMFS rate (75% vs.78%, P=0.720) for stage Ⅱ SCLC did not significantly differ between two groups. As for stage Ⅲ SCLC patients, the OS rate (25% vs.48%, P=0.220), 5-year PFS rate (28% vs.36%, P=0.333) and 5-year BMFS rate (76% vs. 74%, P=0.84) did not significantly differ between two groups.@*Conclusions@#Surgical treatment can bring survival benefits to patients with stage Ⅰ LS-SCLC. The survival prognosis of stage Ⅱ patients is equivalent between two groups. Patients with stage Ⅲ LS-SCLC receiving radiochemotherapy obtain better survival trend compared with those undergoing surgery. The conclusion remains to be validated by studies with larger sample size or prospective investigations.
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Objective In view of the controversy over radiotherapy target volume for patients with limited-stage small cell lung cancer ( SCLC), a prospective randomized controlled trial was conducted to compare the impact of different radiotherapy target volumes on prognosis. Methods After 2 cycles of EP chemotherapy,patients without progressive disease were randomly assigned to receive thoracic radiotherapy (TRT) to either the post-or pre-chemotherapy primary tumour extent as study arm or control. Involved field radiotherapy (IFRT) to the entire metastatic lymph node regions was applied for both arms. TRT consisted of 45 Gy/30Fx/19 d administered concurrently with cycle 3 chemotherapy. Prophylactic cranial irradiation was administered to patients achieved complete or partial remission. Kaplan-Meier method was used for survival analysis. Results Between June 2002 and December 2017,159 and 150 patients were randomly assigned to study arm and control respectively. The 1-,2-,and 5-year local/regional control rates were 79. 4%,61. 5% and 60. 1% respectively in the study arm versus 79. 8%,66. 5%,and 57. 3% in the control arm (P=0. 73). The median OS time was 22. 1 months in the study arm (95%CI,18. 2-26. 0 months) and 26. 9 months (95%CI,23. 5-30. 3 months) in the control arm,the 1-,3-,5-,and 7-year OS rates were 81. 1%,31. 6%, 23. 9% and 22. 2% respectively in the study arm versus 85. 3%,36. 6%,26. 1% and 20. 0% in the control arm (P=0. 51).Grade 2-3 acute esophagitis was developed in 32. 9% and 43. 2% of patients respectively in study arm and control arm (P=0. 01),while grade 2-3 pulmonary fibrosis was observed in 2. 0% and 10. 9% of patients ( P= 0. 01 ) respectively. Conclusions For patients with limited-stage SCLC who received induction chemotherapy,thoracic radiotherapy can be limited to post-chemotherapy tumour extent and IFRT can be routinely applied.
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Objective To evaluate the clinical efficacy between stereotactic body radiotherapy (SBRT) and surgical treatment for stage Ⅰ-Ⅱ non-small cell lung cancer (NSCLC).Methods Clinical data of 120 patients with early-stage NSCLC who underwent SBRT or surgical treatment in Zhejiang Cancer Hospital from 2012 to 2015 were retrospectively analyzed.Propensity score matching was carried out between two groups.Sixty eligible patients were enrolled in each group.In the SBRT group,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 5-15 Gy and the median biologically equivalent dose was 100 Gy (range:57.6-150.0 Gy).In the operation group,32 patients underwent video-assisted thoracoscopic lobectomy and 9 patients underwent wedge resection or segmentectomy.Results All patients successfully completed corresponding treatment and were followed up.The median follow-up was 32.3 months (range:8.6-68.4 months).In the operation group,3 patients died from infection within postoperative 90 d,whereas no case died in the SBRT group (P=0.079).In the SBRT group,3 patients died of other factors besides tumor (cerebral infarction,heart disease,etc.) during follow-up.Local-regional recurrence occurred in 12 patients including 5 cases in the operation group and 7 in the SBRT group (P=0.543).In the operation group,11 patients experienced distant metastases with a median disease-free survival (DFS) of 33.5 months.In the SBRT group,6 patients had distant metastases and the median DFS was 38.4 months (P=0.835,P=0.178).In the SBRT group,the 1-and 3-year overall survival rates were 93％ and 83％,and 95％ and 83％ in the operation group (P=0.993).Conclusions The 1-and 3-year overall survival rates and local control rate do not significantly differ between SBRT and operation for patients with early-stage NSCLC.
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Objective To detect the frequency of BRAF/ KRAS and PIK3CA mutations in the small cell lung cancer (SCLC) specimens from a large population of Chinese patients and to analyze the gene mutation and clinical characteristics. Methods A total of 557 samples were collected from SCLC patients from 2009 to 2014.BRAF,KRAS,PIK3CA,NRAS and MEK1 gene mutations were detected by the dideoxy sequencing. Chi-square test was adopted to analyze the correlation between clinical factors and gene mutation. Kaplan-Meier method was utilized for survival analysis. Cox model was used for multivariate prognostic analysis. Results BRAF mutations were detected in 13 out of 557 specimens. The mutation types included V600E (n= 5) ,V600A (n= 2) ,V600M (n= 1) ,D594G (n= 1),G464E (n= 1),K601R (n= 2) and S605N (n= 1).KRAS mutation was detected in 6 cases including G12C (n= 3),G12A (n= 1),G12D (n=1) andG13D (n= 1).PIK3CA mutation was observed in 4 samples including E545G (n= 2) and H1047R (n= 2).Besides,NRAS mutation (Q61R) was detected in 1 case and MEK1 mutation (D61Y) was noted in 1 case. These gene mutations were not significantly correlated with the age, gender, smoking status and clinical staging of the patients. Univariate survival analysis demonstrated the median survival time of patients with gene mutation was (10.30±0. 751) months (95％CI:8. 829-11. 771 months),significantly shorter than (12.80±0. 543) months (95％CI:11. 736-13. 864 months) of their counterparts without gene mutation (P=0. 011). Conclusions BRAF/ KRAS and PIK3CA gene mutation is detected in a small proportion of SCLC patients. These gene mutations are not significantly correlated with the clinical characteristics. Univariate survival analysis demonstrates that negative these gene mutations are negatively correlated with the clinical prognosis of SCLC patients.
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Objective To investigate the effects of hyperfractionated radiotherapy versus hypofractionated radiotherapy combined with concurrent chemotherapy on the prognosis of limited-stage small-cell lung cancer (SCLC).Methods A total of 188 patients with limited-stage SCLC were enrolled in this study and divided into hyperfractionated group (n=92) and hypofractionated group (n=96).The hyperfractionated group received thoracic radiotherapy at 45 Gy in 30 fractions twice a day, while the hypofractionated group received 55 Gy in 22 fractions once a day.The Kaplan-Meier method was used to calculate survival rates, and the Cox model was used for multivariate prognostic analysis.Results There were not significant differences in 1-, 2-, and 5-year progression-free survival (PFS) rates and 1-, 2-, and 5-year overall survival (OS) rates between the hyperfractionated group and the hypofractionated group (82% vs.85%, 61% vs.69%, 59% vs.69%, P=0.27;85% vs.77%, 41% vs.34%, 27% vs.27%, P=0.37).The multivariate analysis showed that the time from the initiation of chemotherapy to the initiation of thoracic radiotherapy ≤43 days was favorable prognostic factor for PFS (P=0.005).The time from the initiation of chemotherapy to the end of thoracic radiotherapy ≤63 days and prophylactic cranial irradiation were favorable prognostic factors for OS (P=0.044;P=0.000).There were significant differences in incidence rates of grade 2 and 3 acute radiation esophagitis between the two groups (28% vs.16%, 9% vs.2%, P=0.009).Conclusions Both hyperfractionated radiotherapy and hypofractionated radiotherapy combined with chemotherapy can improve the PFS and OS of patients with limited-stage SCLC.The time from the initiation of chemotherapy to the initiation of thoracic radiotherapy ≤43 days and the time from the initiation of chemotherapy to the end of thoracic radiotherapy ≤63 days are favorable prognostic factors for PFS and OS, respectively.However, the hyperfractionated group has significantly higher incidence rates of grade 2 and 3 acute radiation esophagitis than the hypofractionated group.
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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.
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Stereotactic body radiotherapy (SBRT) is a treatment of high dose radiation in a single or small number fractions to the target areas.Compared with conventional radiotherapy,SBRT has the features of higher dose and better precision.The application in lung cancer can be summarized as the following three points:① SBRT has established the status of standard treatment for early (T1-2 N0 M0) nonsmall cell lung cancer (NSCLC) patients who unable or unwilling to undergo surgery.② The resuhs of preliminary application of SBRT in the operable NSCLC are not inferior to surgery.③ As for isolated metastases (1-3),the combination of systemic treatment and SBRT has been gradually accepted.This article makes a summary of this.