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Objective:To analyze the clinical characteristics of long-term survival patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy combined with primary tumor radiotherapy, and to establish a Nomogram prognostic model, aiming to provide a certain reference for making a decision about the treatment of advanced NSCLC.Methods:A retrospective analysis was made on the data of 260 NSCLC patients who participated in two prospective clinical studies from January 2003 to May 2012 and the data of 138 NSCLC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from January 2014 to August 2020. The former 260 cases were used as a training set and the latter 138 cases were used as the validation set. The overall survival (OS) of ≥ 18 months was defined as long-term survival (LTS). The clinical characteristics of LTS patients were compared with those with OS less than 18 months. The clinical characteristics and treatment-related parameters between the two types of patients were compared using the χ2 test. A multivariate analysis was made using logistic regression, and a nomogram model was built using RStudio. Results:The median OS of the training set was 13.4 months (95% CI: 11.9-14.9), with 1-, 2-, and 3-year OS rates of 55.4%, 19.1%, and 11.9%, respectively. In the training set, 87 cases had LTS and were classified as the LTS group, while 173 cases had OS less than 18 months and were classified as the non-LTS group. The univariate analysis showed that the prognostic factors affecting LST included the KPS score, T status, the number of metastatic organs, the number of metastatic lesions, brain metastasis, bone metastasis, the number of chemotherapy cycles, the biologically effective dose (BED) to the primary tumor, hemoglobin level, platelet count, plasma D-dimer, fibrinogen level, lactate dehydrogenase, and lung immune prognostic index (LIPI; χ2=4.72-12.63, P < 0.05). The multivariable analysis showed that the independent prognostic factors of LTS included a number of chemotherapy cycles ≥ 4, BED ≥ 70 Gy, platelets ≤ 220×10 9/L, D-dimer ≤ 0.5 mg/L, and a good LIPI score ( P= 0.002, 0.036, 0.005, 0.008, and 0.002). A nomogram model was established using the meaningful parameters obtained in the multivariable analysis, determining that the training and validation sets had a consistency index (C-index) of 0.750 and 0.727, respectively. As shown by the analytical result of the corrected curves, for the advanced NSCLC patients treated with thoracic radiotherapy, their LTS probability predicted using the nomogram prognostic model was highly consistent with their actual LTS probability. Both the analytical result of the receiver operating characteristic (ROC) curves and the decision curve analysis (DCA) result showed that the composite prediction model was more beneficial than a single prediction model. Conclusions:For patients with advanced NSCLC treated with thoracic radiotherapy, the independent prognostic factors of LTS included the number of chemotherapy cycles, BED, platelet count, pre-chemotherapy D-dimer, and LIPI score. The Nomogram prognostic model built based on these prognostic factors is a convenient, intuitive, and personalized prediction model used to screen patients who can benefit from thoracic radiotherapy.
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Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.
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Objective:To study the effects of gantry acceleration limitations of a linear accelerator (linac) on the dosimetry of volumetric modulated arc therapy (VMAT) plans, machine efficiency, and dose verification result of VMAT plans and to explore the optimal selection of gantry motion models in the Pinnacle treatment planning system.Methods:Ten cases of nasopharyngeal carcinoma, non-small cell lung cancer, sigmoid adenocarcinoma with retroperitoneal lymph node metastasis, and invasive ductal carcinoma of the breast were each selected for this study. Then two models were set up in the Pinnacle v9.10 treatment planning system, namely the one allowing gantry acceleration and the one limiting gantry acceleration. The same field arrangement, optimized target parameters, and optimized weights of VMAT plans were adopted in the two models, in order to analyze the dosimetric variations in targets and organs at risk (OARs) and compare the differences in treatment time and gamma passing rates.Results:The treatment time of the enrolled patients under the model allowing gantry acceleration was significantly lower than that of the patients under the model limiting gantry acceleration was adopted ( t=-6.751, -0.209, -19.523, -28.999; P< 0.05) and decreased by 15.27%, 18.07%, 19.71%, and 28.75%, respectively. Meanwhile, the conformity and uniformity of target areas were affected, while there was no statistical significance in the gamma passing rates in the validation of VMAT plans ( P>0.05). For the cases of nasopharyngeal carcinoma (NPC), the maximum dose to brainstem PRV increased by 1.25%. For the cases of lung cancer, the maximum dose to the spinal cord and lung V20 increased by 1.19% and 1.21%, respectively, while lung V5 decreased by 1.21%. For the cases of sigmoid adenocarcinoma with retroperitoneal lymph node metastasis, the mean doses to bilateral kidneys, livers, small intestine, and colon all increased. For the cases of breast cancer, lung V10 on the opposite side of cancer increased by 1.66% and the mean dose to the lungs on the same side of cancer decreased by 7.45%. Conclusions:The model allowing gantry acceleration allows the treatment time to be significantly shortened and the treatment efficiency improved. Although this model had the shortcomings such as affecting the conformity and uniformity of target areas to a certain extent and increasing the doses to some OARs, clinical requirements for dosimetry were still met. Therefore, it is recommended to use the model allowing gantry acceleration in the Pinnacle planning system.
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Objective:To analyze the radiotherapy-related factors affecting the survival of non-small cell lung cancer (NSCLC) patients complicated with malignant pleural effusion (MPE)(MPE-NSCLC).Methods:From 2007 to 2019, 256 patients pathologically diagnosed with MPE-NSCLC received primary treatment. Among them, 117 cases were enrolled in this study. All patients were divided into two groups according to the radiation dose (<63 Gy and≥63 Gy). Propensity score matching (PSM) was performed to further adjust the confounding factors (Calipers value=0.1). The impact of radiotherapy-related factors on the overall survival (OS) was analyzed by Kaplan—Meier method, log-rank test and Cox’s regression model. Results:Primary tumor radiotherapy significantly prolonged the OS ( P<0.001). The radiation dose escalation (36.0-44.1 Gy, 45.0-62.1 Gy, 63.0-71.1 Gy) of primary tumor significantly prolonged the OS ( P<0.001). The corresponding median OS were 5, 13 and 18 months, respectively. Before the PSM, univariate analysis suggested that radiation dose ≥63 Gy, gross tumor volume (GTV)<157.7 cm 3 and stations of metastatic lymph node (S-mlN)≤5 were significantly associated with better OS (all P<0.05) and T 4N 3 was significantly associated with worse OS ( P=0.018). After the PSM, univariate analysis indicated that radiation dose ≥63 Gy was significantly associated with better OS ( P=0.013) and S-mlN ≤5 had a tendency to prolong the OS ( P=0.098). Prior to the PSM, multivariate analysis showed that radiation dose ≥63 Gy was an independent favorable factor of OS ( HR=0.566, 95% CI 0.368-0.871, P=0.010) and GTV<157.7 cm 3 had a tendency to prolong the OS ( HR=0.679, 95% CI 0.450-1.024, P=0.065). After the PSM, multivariate analysis revealed that radiation dose ≥63 Gy was still an independent favorable factor of OS ( HR=0.547, 95% CI 0.333~0.899, P=0.017). No ≥grade 4 radiation toxicity occurred. The incidence rates of grade 3 radiation esophagitis and pneumonitis were 9.4% and 5.1%, respectively. Conclusion:For MPE-NSCLC, radiotherapy dose of primary tumor may play a key role in improving OS on the basis of controllable MPE.
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Objective:To investigate the primary tumor volume change and timing of radiotherapy for patients with stage Ⅳ non-small cell lung cancer with EGFR mutation during molecular targeted therapy.Methods:Simulated CT scanning measurement and analysis were performed to observe the volume changes of primary tumors before and after treatment with a time interval of 10 days in this prospective study. Positioning and volume measurement were terminated when the volume change was 5% or less between two time points before and after treatment or 90 days after treatment. Primary tumor radiation therapy was then performed, acute radiation-induced injury was recorded, and the implementation and simulation of related parameters of radiotherapy plans were compared.Results:Twenty-nine of 30 cases were included in the analysis (1 case dropped off). After EGFR-TKIs treatment, the volume of all primary tumors was decreased, but the shrinking rate was inconsistent with the speed. Until the last simulated CT scanning, the maximum and minimum shrinking rates were 90% and 28%, respectively. There was no case of termination within 30 days of treatment, and the average tumor volume was significantly decreased within 40 days and the average tumor volume significantly differed every 10 days ( P<0.001). After 40 days, the volume shrinking rate of primary tumors ≤5% gradually appeared, and one patient presented with a volume shrinking rate of >5% on 90 days. During this time, the average volume shrinking rate slowed down and became stable, ranging from 49.15% to 54.77%. Moreover, the average volume continued to gradually shrink after slight increase at 70 days. There was no significant difference in the average volume every 10 days ( P>0.05). After the termination of simulated CT scanning, the dose of primary tumor was (69±7) Gy for patients receiving radiotherapy. Two patients had grade 2 acute radiation-induced pneumonitis and 3 patients had grade 3 acute radiation-induced pneumonitis. In addition, 1 patient had grade 2 radiation-induced esophagitis. According to the technology and dose parameters of radiotherapy plan, simulated radiotherapy plans before and 40 days after EGFR-TKIs treatment were designed. The timing of implementation plan was significantly better than that before EGFR-TKIs treatment (all P<0.05), whereas it was similar to that at 40 days after EGFR-TKI treatment ( P>0.05). Conclusions:The primary tumor shrinking rate is gradually slowed down over time after EGFR-TKIs treatment in patients with stage Ⅳ non-small cell lung cancer. The average tumor volume is significantly decreased within 40 days and then the shrinking rate becomes slow. The tumor shrinking rate of each case is inconsistent. Radiotherapy at 40 days after treatment is probably the optimal timing to obtain high dose and control radiation-induced injury.
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Objective:To retrospectively analyze the clinical efficacy and safety of three-dimensional radiotherapy for the primary tumors in patients with stage Ⅳ non-small cell lung cancer complicated with malignant pleural effusion (MPE-NSCLC).Methods:A total of 198 patients who were initially pathologically diagnosed with MPE-NSCLC from January 2007 to April 2018 were enrolled and divided into the untreated group ( n=45), drug group ( n=57) and radiotherapy group ( n=96), respectively. The short-term efficacy, overall survival (OS) and adverse events in the drug and radiotherapy groups were analyzed. The OS rate was analyzed by Kaplan-Meier method and log-rank test. Clinical prognosis was evaluated by multivariate Cox′s regression model. Results:In the radiotherapy group, the objective response rate and non-response rate was 54% and 46%, significantly better than 25% and 75% in the drug group ( P=0.007). In the radiotherapy group, the 1-, 2-, 3-, 5-year OS and median survival was 47%, 18%, 6%, 1% and 12 months, remarkably higher than 15%, 3%, 2%, 0% and 5 months in the drug group, respectively (all P<0.001). Multivariate Cox′s regression analysis showed that radiotherapy for the primary tumors was an independent prognostic factor to prolong the OS ( P<0.001). Radiotherapy at a dose of ≥63 Gy and 4-6 cycles of chemotherapy tended to prolong the OS ( P=0.063 and 0.071). The OS of patients with EGFR mutation receiving radiotherapy combined with molecular target therapy was significantly better than that of those with unknown EGFR status treated with radiotherapy and chemotherapy ( P=0.007). Addition of radiotherapy for the primary tumors did not significantly increase the incidence of adverse events ( P>0.05). Conclusion:Addition of three-dimensional radiotherapy for the primary tumors in MPE-NSCLC patients may prolong the OS and yield tolerable adverse events.
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Objective To investigate the impact of the changes of posttreatment karnofsky performance status (KPSpost) on the overall survival (OS) for patients with stage Ⅳ non-small cell lung cancer (NSCLC) underwent concurrent chemoradiation.Methods A total of 279 patients (male 198 and female 81) with histological confirmed stage Ⅳ NSCLC were enrolled in this study with a median age of 58 years old (range 22 to 80 years old).There were 166 cases of squamous carcinoma,87 cases of adenocarcinoma,and 22 cases of unclassified carcinoma,respectively.All enrolled patients received more than 2 cycles of chemotherapy and more than 36 Gy of concurrent radiotherapy.Kaplan-Meier method and Log-rank test were applied to evaluate OS.Multivariate analyses were carried out by the Cox proportionalhazard model.Chi-square test and logistic regression analysis were used to explore the related factors of KPSpost.Results There were 198 patients with improved KPSpost and 81 patients with decreased KPSpost,respectively.Univariate and multivariate analyses indicated that the improvement of KPSpost was associated with longer OS.Logistic regression analysis showed that the improvement of KPSpost was positively related with treatment of more than 4-6 cycles chemotherapy concurrent with over 63 Gy radiation to primary tumor.The improvement of KPSpost also correlated positively with disease control rate (DCR),but negatively with PLT toxicity and radiation esophagitis.Conclusions KPSpost was an independent prognostic factor of OS for patients with stage Ⅳ NSCLC underwent concurrent chemoradiation.Chemotherapy of 4-6 cycles and concurrent over 63 Gy radiotherapy dose to primary tumor,as well as DCR were positive factors for KPSpost improvement.However,stage 3-4 PLT toxicities and radiation esophagitis decreased the KPSpost.
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Objective To analyze the survival and toxicity after concurrent chemoradiotherapy in patients of different ages with stage Ⅳ non-small cell lung cancer (NSCLC).Methods Clinical data of 282 NSCLC patients in two prospective studies were retrospectively analyzed,who completed the protocol (at least 2 cycles of chemotherapy and thoracic radiation doses of ≥36 Gy).Among them,44 patients were assigned into in the young group (≤ 45 years old),161 patients in the middle-age group (46-64 years old) and 77 patients in the elderly group (≥ 65 years old).The clinical characteristics of patients among different groups were analyzed by x2 test.The overall survival (OS) was calculated by Kaplan-Meier method.Stratified analysis was performed by Log-rank test.Multi-factor prognosis analysis was conducted by Cox's proportional hazards regression model.Results The incidence of NSCLC in the male patients in the elderly group was higher than that in the middle-age and young groups.The 1-,2-,3-and 5-year OS did not significantly differ among different groups (P=0.810).The OS did not significantly differ among patients of the same gender,pathological type,T stage,N stage,metastasis status,same chemotherapy cycle,primary tumor dose and comprehensive treatment and short-term response (all P＞0.05).The incidence of adverse events did not considerably differ among different groups.Multivariate analysis demonstrated that age was not an independent factor for survival (P＞ O.05).Conclusion Patients of different ages with stage Ⅳ NSCLC obtain similar survival benefits and adverse events after concurrent chemoradiotherapy.
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Objective To evaluate the clinical efficacy and toxicity of concurrent pemetrexed-cisplatin (PP) or docetaxel-cisplatin (DP) with intensity-modulated radiation therapy (IMRT) in patients with stageⅠV lung adenocarcinoma. Methods Stage IV lung adenocarcinoma patients with unknown EGFR mutation status or wild-type admitted to Guizhou Cancer Hospital from 2011 to 2016 were randomly assigned into the PP (n=50) and DP groups (n=51).All patients received concurrent IMRT of the chest at a prescription dose of 60-70 Gy. Primary endpoint was 1-year survival rate, and secondary endpoint was acute toxicity. Results The overall response rate was 68. 0％ and 72. 5％ in the PP and DP groups (χ2=0. 250, P=0. 617) . The median survival time was 19. 6 months ( 95％CI 13. 9-25. 3) versus 12. 1 months ( 95％CI 10. 7-13. 5) in the PP and DP groups. The 1-, 2-and 3-year overall survival rates were 72. 0％ versus 52. 9％, 28. 0％ versus 17. 6％, and 16. 0％ versus 13. 7％, respectively in the PP and DP groups ( P=0. 049) . In the PP and DP groups, the incidence of grade 3-4 leukopenia was declined by 48％ and 63％( P=0. 098) , and the incidence of grade 3-4 neutropenia was decreased by 34％ and 65％( P=0. 002) , the incidence of grade 3-4 anemia was reduced by 38％ and 10％(P=0. 024), and the incidence of grade 3-4 thrombocytopenia was declined by 40％ and 14％( P=0. 003) . The incidence rate of grade 2 pneumonitis ( P=0. 625) and grade 3 esophagitis ( P=0. 484) were similar in both groups. No patients experienced ≥grade 3 pneumonitis or ≥ grade 4 radiation esophagitis. Conclusions Pemetrexed-cisplatin combined with chemoradiotherapy yields higher clinical efficacy compared with docetaxel-cisplatin plus concurrent chemoradiation in the treatment of stageⅠV lung adenocarcinoma. The incidence of radiation pneumonitis and esophagitis is similar. The incidence and severity of hematological toxicity does not significantly differ between two groups.Treatment-related toxicity is tolerable in both groups. Clinical Trial Registration Chinese Clinical Trial Registry ( ChiCTR-TRC-13004184) .
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Objective To retrospectively analyze the effect of three-dimensional radiotherapy on the survival of patients with stage Ⅳ squamous cell lung cancer.Methods Of the 101 patients collected from two prospective phase Ⅱ studies, 88 were part of the per-protocol set.All patients received platinum-doublet chemotherapy with concurrent radiation to the primary tumor.Primary endpoints were overall survival (OS) and progression-free survival (PFS).Survival was calculated using the Kaplan-Meier estimator, and univariate and multivariate analyses were performed using the log-rank test and Cox model, respectively.Results The 1-, 2-, 3-, and 5-year OS rates of the 88 patients were 42.2%, 13.6%, 8.7%, and 3.1%, respectively, and the median survival time (MST) was 10 months.The 1-, 2-, 3-, and 5-year OS and MST at PTV dose ≥63 Gy were 45.7%, 25.7%, 17.1%, 7.1%, and 11 months, respectively, whereas the 1-, 2-, 3-, and 5-year OS and MST at PTV dose<63 Gy were 39.6%, 4.5%, 2.8%, 0%, and 10 months, respectively (P=0.007).The median PFS at ≥63 Gy and<63 Gy were 9 months and 7 months, respectively (P=0.032).The 1-, 2-, 3-, and 5-year OS and PFS of patients who received 4 cycles of chemotherapy at a PTV dose of ≥63 Gy were 51.9%, 29.6%, 18.5%, 9.9%, and 9 months, respectively (P=0.001 and P=0.012), which were significantly prolonged compared with other treatment modalities.Multivariate analysis showed that PTV ≥63 Gy may be influence the OS of patients (P=0.080).Conclusions Three-dimensional radiotherapy can prolong the survival of patients with stage ⅠV squamous cell lung cancer, as demonstrated by the gradual improvement in OS and PFS following the increase in the intensity of concurrent chemotherapy and radiation therapy.A PTV dose of ≥63 Gy may be influence the OS.
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Objective To evaluate the efficacy and safety of adding neoadjuvant chemotherapy following neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.Methods A total of 80 patients confirmed with locally advanced rectal cancer were enrolled during January 2012 and December 2015 in Guizhou Medical University Affiliated Cancer Hospital and were randomized with the method of lottery into the experimental group and the control group.In the experimental group,40 patients received 4 cycles of FOLFOX4 after chemoradiotherapy and then had total mesorectal excision (TME).Another 4 cycles of FOLFOX4 were administered after surgery.In the control group,40 patients had TME surgery 6-8 weeks after chemoradiotherapy and received 8 cycles of FOLFOX4 as adjuvant chemotherapy.Pelvic radiotherapy dose was 50 Gy in 25 fractions,5 days per week for 5 weeks.5-Fu continuous infusion was administered throughout radiotherapy.The pCR rate,downstaging rate,R0 resection rate,local recurrence rate,distant metastasis rate,survival rate,incidence of toxicities,surgical complications and completion of treatment were observed.Results The pCR rate was 20.0％ in the experimental group and 5.0％ in the control group (x2 =4.114,P ＜ 0.05).The downstaging rate was 77.4％ in the experimental group and 55.6％ in the control group(P ＞ 0.05).No statistically significant difference was observed in R0 resection rate,3-year local recurrence rate,3-year distant metastasis rate and 3-year survival rate between the two groups (P ＞ 0.05).Patients in the experimental group had higher completion rate of 8 cycles of systemic chemotherapy (87.1％ vs.61.5％,x2 =4.985,P ＜0.05).No statistically significant difference was observed in acute toxicities and postoperative complications.Conclusions Adding systemic chemotherapy after neoadjuvant chemoradiotherapy for locally advanced rectal cancer has significantly higher pCR rate and lower toxicities and side events compared with chemoradiotherapy alone.Longer follow-up and larger scale of clinical research are needed.Trial registration Chinese clinical trial registry,ChiCTR-IPR-17010454.
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Objective To investigate the impact of clinical factors on survival in patients receiving concurrent chemotherapy and three?dimensional radiotherapy ( 3DRT) for stage IV non?small cell lung cancer ( NSCLC) . Methods A total of 203 patients were enrolled in a prospective clincial study from 2008 to 2012, and among these patients, 178 patients were eligible for analysis of clinical factors. All patients were treated with platinum?based doublets chemotherapy, with a median number of chemotherapy cycles of 4( 2?6 cycles) and a median dose of 3DRT of 60?3 Gy (36?0?76?5 Gy).The Kaplan?Meier method was used to calculate overall survival ( OS) rates, the log?rank test was used to compare survival rates between groups, and the Cox regression model were used for multivariate analysis. Results The 1?, 2?, and 3?year overall survival rates were 56%, 16%, and 10%, respectively, and the median survival time was 13 months (95% CI=11?500?14?500). The univariate analysis showed that platelet count ≤221×109/L, neutrophil count ≤5.2×109/L, white blood cell count<7×109/L, and improvement in Karnofsky Performance Scale ( KPS) after treatment significantly prolonged OS ( P=0?000,0?022,0?003, and 0?029) , and metastasis to a single organ and hemoglobin≥120 g/L tended to prolong OS (P=0?058 and 0?075). The multivariate analysis showed that white blood cell count<7×109/L, platelet count ≤221×109/L, and improvement in KPS after treatment were beneficial to OS ( all P<0?05) . Conclusions White blood cell count and platelet count before treatment and KPS after treatment are prognostic factors for patients with stage IV NSCLC receiving concurrent chemotherapy and 3DRT. Clinical Trial Registry ClinicalTrials. gov, registration number:ChiCTRTNC10001026.
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Objective To investigate the efficacy and safety of three?dimensional radiotherapy (3DRT) with concurrent chemotherapy for stage IV non?small?cell lung cancer ( NSCLC). Methods A total of 198 eligible patients from 2008 to 2012 were enrolled as subjects. With an age ranging between 18 and 80 years and a Karnofsky Performance Status ( KPS) score of 70 or more, those patients had no contraindication for radiotherapy and chemotherapy, and were newly diagnosed with stage IV NSCLC confirmed by histology or cytology, as well as limited metastatic disease (≤3 organs). Survival rates and acute toxicities in those patients were evaluated. Results The 3?year follow?up rate was 98?? 5% and the 3?year sample size was 165. The median overall survival (OS) and progression?free survival (PFS) were 13?? 0 months (95% CI,11?? 7 ?14?? 3 months) and 9?? 0 months (95% CI,7?? 7 ?10?? 3 months), respectively, while the 1?, 2?, and 3?year OS rates were 53?? 5%, 15?? 8%, and 9?? 2%, respectively. Multivariate analysis showed that a primary tumor volume smaller than 134 cm3 , a stable or increased KPS score after treatment, and a radiation dose of 63 Gy or more were independent prognostic factors for longer survival time ( P=0?? 008;P= 0?? 010;P= 0?? 014). The incidence rates of grade 3?4 neutropenia, thrombocytopenia, anemia, grade 3 radiation esophagitis, and grade 3 radiation pneumonitis were 37?? 9%, 10?? 1%, 6?? 9%, 2?? 5%, and 6?? 6%, respectively. The main cause of death was distant metastasis, and only 10% of the patients died of recurrence alone. Conclusions 3DRT with concurrent chemotherapy achieves satisfactory treatment outcomes with tolerable toxicities for stage IV NSCLC. Primary tumor volume, change in the KPS score after treatment, and radiation dose are independent prognostic factors for OS.Clinical Trial Registry Chinese Clinical Reistry,registration number:ChiCTRC10001026.
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Objective To investigate the role of three-dimensional (3D) radiotherapy to the thoracic primary tumor in non-small cell lung cancer (NSCLC) patients with bone metastases during chemotherapy with concurrent 3D radiotherapy.Methods From 2003 to 2010,the clinical data of 95 stage Ⅳ NSCLC patients with bone metastases were collected.All patients received 3D radiotherapy to the thoracic primary tumor and at least 2 cycles of chemotherapy.Of the 95 patients,47 had only bone metastases,and 48 had metastases to bones and other organs.The Kaplan-Meier method was used to calculate overall survival (OS) rates.The log-rank test was used for survival difference analysis and univariate prognostic analysis.The Cox regression model was used for multivariate prognostic analysis.Results The follow-up rate was 95％.The 1-,2-,and 3-year OS rates were 44％,17％,and 9％,respectively.The univariate analysis showed that radiation dose to the planning target volume (PTV) of primary tumor of ≥ 63 Gy,response to treatment of primary tumor,and at least 4 cycles of chemotherapy were favorable prognostic factors for OS in all patients (P =0.001,0.037,and 0.009).Radiation dose to the PTV of primary tumor of ≥ 63 Gy remained the favorable prognostic factor for OS in patients with only bone metastases and those with metastases to bones and other organs (P =0.045 and 0.012).Among patients with only bone metastases,those with T1 + T2 primary tumors had longer OS than those with T3 + T4 primary tumors (P =0.048).The multivariate analysis showed that radiation dose to the PTV of primary tumor of ≥ 63 Gy and metastases to bones only were independent favorable prognostic factors for OS in all patients (P =0.036 and 0.035).Conclusions For NSCLC patients with bone metastases,3D radiotherapy to the thoracic primary tumor and its dose play an important role in improving OS during chemotherapy with concurrent 3D radiotherapy.
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ObjectiveThis study evaluates the feasibility of intensity-modulated radiation therapy (IMRT) to treat patients with 1 -5 brain metastases from non-small cell lung cancer (NSCLC).Methods 30 IMRT patients with brain metastases for NSCLC studied retrospectively.Whole brain radiotherapy plus three-dimensional conformal radiotherapy (WBRT + 3DCRT) and WBRT plus stereotactic radiotherapy ( WBRT + SRT) plans were generated.Planning target volume ( PTV ) and organs at risk dose were measured and compared by dose volume histogram.Differences were analyzed in the three techniques by Wilcoxon Z -test.Results D99％ of the shoulder ( D99％-D90％ ) from IMRT were higher than from WBRT +3DCRT and WBRT+SRT in all cases.From D15％ of slope (D90％-D10％) to D5％ of tail (D10％ -D1％ ),IMRT were lower than WBRT + 3DCRT and WBRT + SRT ( Z =- 4.72,P =0.000 and Z =- 4.72,P =0.000).D10％ and D5％ of IMRT were (35.1 ±1.42) Gy and (37.7 ±2.91) Gy,WBRT +3DCRT were (36.5±2.86) Gy and ( 39.1 ± 3.56) Gy ;WBRT + SRT were (36.2 ± 2.57) Gy and ( 38.7 ± 3.67) Gy.IMRT vs WBRT+ 3DCRT and WBRT + SRT were significant ( Z=-3.18,-3.18,P=0.001,0.001 and Z=- 4.11,- 3.02,P =0.000,0.002) in 13 patients with 3 - 5 brain metastases.The total mean monitor units were 14756.3,9614.8 and 9043.2 for IMRT,WBRT +3DCRT and WBRT + SRT plans,respectively,with a 38.7％ reduction from IMRT to WBRT + SRT (Z =-4.78,-4.78,P =0.000,0.000).The brain doses around metastases were similar in the three techniques with 1 -2 metastases,but IMRT was the best with 3 -5 metastases.ConclusionsIMRT can advance brain metastases dose and improve the planning target minimum dose and spare the dose around brain metastases.Only IMRT is the best choice for just sparing the dose around brain metastases among 3 -5 brain metastases.
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Objective To investigate the dosimetric influence of pure carbon fiber treatment tabletop of Elekta Precise new linear accelerator in radiotherapy.Methods Surface-axis distance (SAD) technology was employed for the measurement.Two groups of fields were set and both of them were SAD opposed portals ( one of them went through the tabletop,while the other did not).A PTW electrometer and a 0.6 cm3 Farmer ionization chamber were utilized for comparison measurement.Then dose attenuation of the main table board,extended body board,the extended board for head,neck and shoulders,and the joints of these boards were calculated.Results Under the energy of 6 MV,the dose attenuations of the following locations were:1.4％ - 7.2％ at the main treatment table board; 2.8％ - 38.7％,1.4％ -30.1％,1.5％ -20.8％ and 1.4％ - 11.2％,respectively at distances of 1,4,7 and 8 cm from the joint of the main table board ;0.5％ - 5.0％ at the extended body board; 4.7％ - 15.4％ at distance of 1cm from the joint of the extended body board; 0.5％ -3.3％ at the neck position of the extended board for head,neck and shoulders; 5.3％ - 16.7％ at the shoulder positions; and 6.8％ -30.4％ at the joint between the extended boards and the main table board.Conclusions The dose attenuations of the new linear accelerator pure carbon fiber treatment tabletop vary at different locations. Considerable higher attenuations are observed at the table board joints than other locations.
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ObjectiveTo prospectively investigate the impact of short-time response on survival of concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC). Methods From Jan.2003 to Oct.2010,201 patients with pathologically or cytologically proven stage Ⅳ NSCLC were included.All patients received platinum-based chemotherapy.Of the 167 patients eligible for analysis,the median number of chemotherapy were 4 cycles.The median dose for planning target volume (PTV) of thoracic primary tumor was 63 Gy.Response was scored according to WHO criteria. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression model were used to examine the effect of response on overall survival.ResultsThe follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up.For the 167 patients eligible for analysis,the CR,PR,NC and PD rate of primary tumor was 5.4％,65.9％,21.0％ and 7.7％,respectively.The effective group ( CR + PR) and ineffective group ( NC + PD) was 71.3％ and 28.7％,respectively.The median survival time (MST) for patients with CR,PR,NC and PD was 22.6,13.4,8.8 and 4.8 months,respectively ( χ2 =44.79,P =0.000).The MST for effective and ineffective group was 13.9 and 7.6 months,respectively in the whole group ( χ2 =8.3 0,P =0.004 ),12.1months and 7.3 months in those treated with 2 - 3 cycles chemotherapy ( χ2 =7.71,P =0.007 ),and 13.9months and 7.9 months in those treated with 2 -5 cycles chemotherapy and radiation dose to PTV ≥36 Gy ( χ2 =4.00,P =0.045 ).No significant MST difference was detected between patients of effective group and ineffective group treated with 4 -5 cycles chemotherapy ( χ2 =0.67,P =0.413),or those treated with 4 -5 cycles of chemotherapy and radiation dose to primary lesion ≥36 Gy (χ2 =0.00,P =0.956).Multivariate analysis showed that 4-5 cycles of chemotherapy and CR and PR achieved in primary tumor (β =0.182,P=0.041 ) were independent favorable factors for survival. Conclusion CCTTRT can improve local control,and prolong the survival time for Stage Ⅳ NSCLC.
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ObjectiveTo explore the effect of radiation dose on survival for stage Ⅳ non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT).Methods From Jan.2003 to Jul.2010,201 Stage Ⅳ NSCLC patients were enrolled.Nineteen patients who received only one cycle chemotherapy were not included in survival analysis.Of the 182 patients eligible for survival analysis,all patients received platinum-based chemotherapy of two drugs.The median number of cycles was 4.The median dose to planning target volume of primary tumor ( DTPTV )was 63 Gy. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression models were used to examine the effect of DTPTV on overall survival.ResultsThe follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up.The 1-,2-,3-year overall survival rate and median survival time was 20％,14％,0％ and 7.1 months;27％,10％,3％ and 9.6 months;and 59％,22％,16％ and 14.9 months,respectively for patients treated with DTPTV ＜ 45.0 Gy,45.0 - 62.1 Gy and ≥63.0 Gy,respectively ( χ2 =27.88,P =0.000 ) ;43％,19％,0％and 1 1 months and 2 0 ％,1 1％,5 ％ and 8 months,respectively for those received 2 - 3 cycles of chemotherapy and radiation dose ≥63 Gy and ＜ 63 Gy,respectively (χ2 =2.99,P =0.084) ;66％,23％,19％ and 16 months and 29％,12％,0％ and 8.8 months,respectively for those received 4 - 5 cycles chemotherapy and radiation dose ≥ 63 Gy and ＜ 63 Gy,respectively (χ2=15.87,P=0.000).No significant difference was found for patients received 2 - 3 cycles chemotherapy concurrently with DTP,Tv ≥63 Gy and 4 -5 cycles chemotherapy concurrently with DTPTV ＜63 Gy,respectively (χ2 =1.93,P =0.165).Multivariate analysis showed that 4 -5 cycles chemotherapy concurrently with DTPTv ≥63 Gy ( β =0.243,P =0.019),and improved KPS after treatment ( β =1.268,P =0.000) were independent favorable factors for survival.ConclusionChemotherapy concurrent with CCTTRT can prolong survival time of patients with stage Ⅳ NSCLC,especially for those treated with DTPTV ≥63 Gy.
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Objective To evaluate the importance of three-dimensional radiotherapy for elderly patients of stage Ⅳ non-small cell lung cancer (NSCLC).Methods Comparing with treatment outcome of ≥65 years 67 patients and ＜ 65 years 134 patients using concurrent chemotherapy and thoracic threedimensional radiotherapy during 2003 to 2010 years.Survival analysis was taken by Kaplan-Meier method.The multivariate prognosis was analyzed by Cox model.Results The follow-up was 97.8％.The percentage of ≥65 years and ＜ 65 years patients accepted with concurrent 4-5 cycles chemotherapy were 30％ and 55％,and with 42％ and 49％ patients with radiotherapy ≥63 Gy.The median survival time (MST) were 17 months and 14 months (x2 =0.76,P =0.384) for ≥65 years and ＜ 65 years patients accepted with concurrent 4-5 cycles chemotherapy concurrent ≥63 Gy radiotherapy respectively.The MST and 1-,2-,3year overall survival rate were 17 months and 8 months,65％ and 23％,30％ and 13％,24％ and 9％(x2 =7.90,P =0.005) for whole groups patients treated with chemotherapy concurrent ≥63 Gy and ＜ 63 Gy radiotherapy.And the MST of patients ≥ 63 Gy was significantly longer than those with ＜ 63 Gy either concurrent chemotherapy any cycles (x2 =9.54,P =0.023).The MST were 14 months and 8 months (x2 =1.82,P=0.178),17 months and 17 months (x2 =0.47,P=0.492) for ≥ 65 years and ≥ 63 Gy radiotherapy patients accepted with concurrent 4-5 cycles and 2-3 cycles chemotherapy concurrent respectively.Multivariate analysis showed local response (β =0.600,P =0.003) and numbers of tumor metastasis (β =0.670,P =0.040) were independent factors for survival.Conclusions For a part of elderly patients of stage Ⅳ NSCLC,concurrent chemotherapy and thoracic three-dimensional radiotherapy can prolong survival time with acceptable toxicity.Perhaps radiotherapy is more important.
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Objective To evaluate clinical factors as predictors of radiation pneumonitis(RP)in advanced stage non-small cell lung cancer(NSCLC)patients treated with concurrent radiochemotherapy when gross tumor volume is 70 Gy. Methods Data of 84 patients with histologically proved NSCLC treated with 3DCRT or IMRT were collected. To evaluate the correlation between clinical parameters and radiation pneumonitis(RP). The clinical parameters were considered: pathological type, therapy agents, age,gender, stage, karnofsky performance status(KPS), smoking status, diabetes, chronic obstructive pulmonary disease(COPD). Results The occurrence of grade 1,2 RP was 63%, 33%, respectively. In univariate analysis, diabetes was significantly associated with RP of ≥ grade 1(x2 =4.03, P = 0.045)and ≥grade 2(x2 = 15.59 ,P =0.000). KPS was significantly associated with RP of ≥grade 1(x2 =3.98 ,P = 0.046)and ≥grade 2(x2 = 5.21, P = 0.023). In logistic multivariate analysis, diabetes was significantly associated with RP of ≥grade 1(x2 =5.50,P =0.019)and ≥grade 2(x2 = 12.92,P =0.000). KPS was significantly associated with RP of ≥ grade 1(x2 = 6.29, P = 0.012)and ≥ grade 2(x2 = 6.61, P =0.010). Conclusion The definite statistical significant risk factors of RP are diabetes and KPS.