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Objective:To systematically evaluate the efficacy and safety of precision thoracic radiotherapy (TRT) in the limited-stage small cell lung cancer (LS-SCLC) patients by network meta-analysis.Methods:Randomized controlled trials (RCTs) of TRT regimes in the LS-SCLC were electronically searched from PubMed, Web of Science, The Cochrane Library, CNKI and Wanfang Data from inception to September 1 st, 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Statistical analysis was performed by Stata 17 and R 4.1.1 software. Results:A total of 6 RCTs involving 1730 patients with six radiation regimens including hyperfractionated radiotherapy (HFRT): HFRT 45(45 Gy/30 F) and HFRT 60(60 Gy/40 F); conventional fractionated radiotherapy (CFRT): CFRT 70(70 Gy/35 F) and CFRT 66(66 Gy/33 F); moderately hypofractionated radiotherapy (MHFRT): MHFRT 65(65 Gy/26 F) and MHFRT 42(42 Gy/15 F) were included. The network meta-analysis showed that: in terms of improving progression-free survival and overall survival, there was no statistically significant difference among the six radiotherapy regimens. The probabilistic ranking results were: MHFRT 65> HFRT 60>CFRT 66>CFRT 70>MHFRT 42>HFRT 45, and HFRT 60>MHFRT 65>CFRT 66>CFRT 70>HFRT 45>MHFRT 42, respectively. The HFRT 60 regimen was superior to other regimens in reducing the incidence of grade ≥3 pneumonia, and there was no difference between the regimens in causing grade ≥3 radiation esophagitis, and the results of ranking probability were: HFRT 60> MHFRT 42>CFRT 66>CFRT 70>HFRT 45>MHFRT 65, and HFRT 60>CFRT 70>CFRT 66>HFRT 45>MHFRT 42>MHFRT 65, respectively. Conclusions:HFRT 60 radiotherapy regimen may be more effective and safer in the treatment of LS-SCLC patients as a priority choice for LS-SCLC TRT. Limited by the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
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Objective:To evaluate the efficacy and safety of thoracic radiotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) with different metastatic sites.Methods:A retrospective analysis was performed among 830 ES-SCLC patients who were admitted to our hospital from 2010 to 2019. They all received the first-line chemotherapy and had no progression after chemotherapy. 341 patients of them received thoracic radiotherapy after chemotherapy. The main endpoint was overall survival. The Chi-square test was used to compare the categorical data including gender and age, etc. Univariate survival analysis was estimated by Kaplan-Meier method and the log-rank test was used to compare the survival curves between two groups. A multivariate prognostic analysis was made by the Cox proportional hazard model.Results:In all the patients, the overall survival (OS) was 12.4 months. The patients with thoracic radiotherapy had significantly higher OS than the patients without thoracic radiotherapy (15.2 months vs.10.8 months, P<0.001). Thoracic radiotherapy significantly improved the OS in patients without liver metastasis (16.0 months vs.11.4 months, P<0.001) in the oligometastatic patients. But for the oligometastatic patients with liver metastasis, the OS benefit was not significant (14.2 months vs. 10.6 months, P=0.072). For polymetastatic patients without liver metastasis, thoracic radiotherapy offered significant OS benefits (14.5 months vs.10.9 months, P<0.001), but for the polymetastatic patients with liver metastasis, the OS was not improved with thoracic radiotherapy (10.2 months vs.9.2 months, P=0.715). Conclusions:In ES-SCLC patients, thoracic radiotherapy provides significant OS benefits in patients with oligometastases ES-SCLC without liver metastasis and for the liver metastatic patients may also benefit from thoracic radiotherapy based on the effectiveness of chemotherapy. In patients with multiple metastases, thoracic radiotherapy only improves the OS in patients without liver metastasis, but does not improve the prognosis in patients with liver metastasis.
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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 evaluate the risk and prognostic factors of brain metastasis (BM) after prophylactic cranial irradiation (PCI) in limited stage small cell lung cancer (LS-SCLC) patients with complete and partial remission (CR/PR) after radiochemotherapy.Methods:Baseline data of 550 patients with LS-SCLC who obtained CR/PR after chemoradiotherapy and received PCI in Zhejiang Cancer Hospital between 2002 and 2017 were collected. The risk of BM and clinical prognosis were retrospectively analyzed. The survival analysis was performed by Kaplan-Meier method. Multivariate prognostic analysis was conducted byCox models.Results:The overall BM rate after PCI was 15.6%(86/550), with 9%(4/43), 13%(7/52), and 16.5%(75/455) for stage Ⅰ, Ⅱ and Ⅲ patients, respectively. The median overall survival (OS) for the entire cohort was 27.9 months, and the 5-year OS rate was 31.0%. The OS was 24.9 and 30.2 months for patients with or without BM, and the 5-year OS rates were 8.9% and 36.1%( P<0.001). BM was an independent factor of OS ( P<0.001). Clinical staging remained the influencing factor of OS and BM-free survival ( P<0.001, P=0.027). Having tumors of ≥5 cm in diameter significantly increased the risk of BM ( P=0.034) rather than the OS ( P=0.182). The median OS of patients aged<60 years was significantly longer than those aged ≥60 years (34.9 months vs. 24.6 months, P=0.001). The median OS of patients irradiated with 2 times/d was 29.8 months, significantly longer than 24.5 months of those irradiated with 1 time/d ( P=0.013). Age, sex, radiotherapy fraction and efficacy of radiochemotherapy (CR/PR) were not associated with the incidence rate of BM (all P>0.05). Conclusions:SCLC patients with tumors of ≥5 cm in diameter may have a higher risk of developing BM after PCI. Patients aged<60 years achieve better OS compared with their counterparts aged ≥60 years.
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Objective:To investigate the role of concurrent chemoradiotherapy in the treatment of limited-stage small cell lung cancer (LS-SCLC) and the impact of the number of chemotherapy cycle during radiotherapy (RT) on clinical prognosis.Methods:Patients with LS-SCLC treated with definitive radiotherapy from May, 2008 to September, 2016 were included in the study. The primary endpoint was overall survival (OS), which was calculated from the start of treatment to the date of death or last follow-up. The effect of the number of concurrent chemotherapy cycle and other clinical factors on clinical efficacy was analyzed. Survival analysis was performed with Kaplan- Meier method, and multivariate analysis was performed with Cox regression model. Results:Three hundred and seventeen patients were eligible for the analysis. Among them, 129 patients received sequential chemoradiotherapy and 188 patients received concurrent chemoradiotherapy. Among patients receiving concurrent chemoradiotherapy, 86 patients received 1 cycle of concurrent chemotherapy and 102 cases of 2 cycles of concurrent chemotherapy. The median follow-up time was 22.47 months. Multivariate survival analysis showed that only clinical stage, timing of RT administration and prophylactic cranial irradiation (PCI) were the independent prognostic factor for OS. The median OS in patients who received 1 cycle and 2 cycles of concurrent chemotherapy during RT were 33.8 months and 30.4 months ( P=0.400). No matter in elder patients or in younger patients, in early RT group or in late RT group and application of PCI or not, the number of concurrent chemotherapy cycle exerted no significant impact on OS. The incidence of grade 3 or above adverse events was 20% in the 1-cycle concurrent chemotherapy group, and 13.7% in the 2-cycle concurrent chemotherapy group. Conclusions:Concurrent chemoradiotherapy is the standard treatment of LS-SCLC. Two cycles of concurrent chemotherapy during RT is not necessarily superior to 1 cycle of concurrent chemotherapy. The optimal number of concurrent chemotherapy cycle during RT need to be studied in a large prospective randomized clinical trial.
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Objective@#To explore the effect of nutritional status pre-and during chemoradiotherapy on the prognosis of patients with limited- stage small cell lung cancer (LS-SCLC).@*Methods@#We retrospectively collected medical records of 172 LS-SCLC patients undergoing concurrent chemoradiotherapy in our hospital from 2000 to 2014, with 126 males and 46 females. The data of complete blood count and hepatic and renal function were collected before initial treatment, before radiotherapy, 4 weeks during radiotherapy, and 1 month after complete of treatment. The prognostic nutritional index(PNI)was calculated. Kaplan-Meier method was used to calculate the survival rate. Log-rank test was performed used to compare the survival differences between groups. Multivariate prognostic analysis was performed using Cox regression model.@*Results@#The median overall survival (OS) was 21 months, with median progression-free survival (PFS) of 11 months. At the beginning of treatment, patients with pre-treatment PNI ≥ 53 had significantly superior OS (median 37 vs 15 months, P=0.001) and PFS (median 16 vs 10 months, P=0.017). Patients with pre-treatment hemoglobin ≥140 g/L and <140 g/L had an median OS of 32 months and 17 months (P=0.019), and median PFS of 16 months and 9 months (P=0.040), respectively. During chemoradiation, patients with elevated hemoglobin had similar median OS compared with those had decreased hemoglobin (27 vs 18 months, P=0.063, but superior median PFS (15 vs 9 months, P=0.017). Multivariate analysis revealed that prophylactic cranial irradiation, pre-treatment hemoglobin ≥140 g/L, and pretreatment PNI ≥53 were independent predictors of OS and PFS in patients with LS-SCLC.@*Conclusion@#Pre-treatment nutritional status and the changes of nutritional status during chemoradiotherapy is significantly associated with the prognosis of patients with limited-stage small cell lung cancer. The patients with better pre-treatment nutritional status have a better prognosis.
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Objective To investigate the association between the timing of brain metastases and the prognosis of patients with small cell lung cancer (SCLC).Methods A retrospective analysis was performed in 131 patients with limited-stage SCLC firstly metastasized to the brain were admitted to our hospital from 2007 to 2015.According to the median bone metastasis-free survival (BMFS),all patients were divided into A group (BMFS ≤ 10 months,n =61) and B group (BMFS＞ 10 months,n=70).The survival rates were analyzed using the Kaplan-Meier method.Between-group comparison was performed by log-rank test.The Cox regression model was used for multivariate prognostic analysis.Results In all 131 patients,the median overall survival (OS) and 1-,2-,and 3-year OS rates were 22.5 months,87.3％,44.7％,and 20.8％,respectively.The median OS after brain metastases and 1-and 2-year OS rates were 9.3 months,39.3％ and 14.8％,respectively.No statistical significance was observed in the median OS after brain metastases between the A and B groups (8.6 vs.9.3 months,P=0.695).Moreover,the OS after brain metastases did not significantly differ in patients without PCI or those receiving different therapies after brain metastases between two groups (P=0.240-0.731).Conclusions The timing of SCLC with brain metastases is significantly correlated with the OS rather than the OS after brain metastases.Therefore,prevention of brain metastases may be an effective approach to prolong the OS of patients with SCLC.
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Objective To evaluate the effect of thoracic radiotherapy (TRT) on the prognosis of elderly patients with extensive-stage small cell lung cancer (ES-SCLC).Methods Clinical data of 83 patients aged ≥65 years diagnosed with metastatic ES-SCLC admitted to our hospital from 2010 to 2016 were retrospectively analyzed.All enrolled patients received etoposide plus cisplatin or carboplatin as the standard regimen for chemotherapy.After the propensity score matching (PSM),70 cases were either assigned into the TRT (n=35) or non-TRT groups (n=35).Among them,56 patients were male and 14 female.The median age was 69 years (range:65-85 years).The median chemotherapy cycle was 4 cycles (range:1-11 cycles).The median chest irradiation dose was 50 Gy (range:30-60 Gy).Overall survival (OS),progression-free survival (PFS) and local recurrence-free survival (LRFS) were regarded as end-point of observation.The survival rate was calculated by using Kaplan-Meier method and statistically compared between two groups by using Log-rank test.Multivariate prognostic analysis was performed using Cox regression model.Results For all patients,the 1-year OS,PFS and LRFS rates were 40％,16％ and 21％,respectively.Patients undergoing TRT obtained better survival outcomes than their counterparts without TRT:the 1-year OS,PFS and LRFS were 52％ vs.29％(P=0.005),30％ vs.3％(P＜0.001),38％ vs.6％ (P＜0.001),respectively.Furthermore,TRT did not increase the incidence of adverse reactions in elderly patients (P=0.690).Conclusion The addition of TRT for elder ES-SCLC patients can significantly improve the rate of chest tumor control and prolong the survival time,which is worthy of further validation by prospective studies with large sample size.
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Small cell lung cancer (SCLC) is a kind of highly invasive malignant neoplasm, which is characterized by short survival and high-risk cranial metastasis. Therefore, application of prophylactic cranial irradiation(PCI) is of clinical significance to reduce the incidence of brain metastasis and prolong the patients' survival on the basis of radio-and chemo-therapy. Nevertheless, the indications and clinical value of PCI have been controversial in recent years. These controversies mainly include the significance of PCI for extensive-stage SCLC,the indications of PCI for limited-stage SCLC and the alternative approaches for PCI. In this paper, the controversies and progresses of PCI applied in clinical practice are investigated and reviewed.
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Objective To evaluate the clinical efficacy of prophylactic cranial irradiation (PCI) in the treatment of surgically resected small cell lung cancer (SCLC).Methods Clinical data of SCLC patients undergoing radical resection surgery in Zhejiang Cancer Hospital from 2003 to 2015 were retrospectively analyzed.According to the treatment modality,all patients were allocated into the PCI and non-PCI groups.A total of 52 patients were finally included,including 19 patients in the PCI group (5 cases of stage Ⅰ,5 stage Ⅱ and 9 stage Ⅲ) and 33 in the non-PCI group (12 cases of stage Ⅰ,5 stage Ⅱ and 16 stage Ⅲ).Kaplan-Meier method was utilized for survival analysis.Cox proportional hazards model was adopted to analyze clinical prognosis.Results The median survival time was 32.9 months in the PCI group,and 20.4 months in the non-PCI group.The 2-year overall survival rate was 72％ in the PCI group,significantly higher than 38％ in the non-PCI group (P=0.023).The median brain metastasis-free survival (BMFS) was 32.5 months in the PCI group,and 17.1 months in the non-PCI group.In the PCI group,the 2-year BMFS rate was 89％,significantly better than 53％ in the non-PCI group (P=0.026).Subgroup analysis demonstrated that PCI could confer survival benefit to patients with p-stage Ⅲ (p=0.031) rather than p-stage Ⅰ (P=0.924) and Ⅱ (P=0.094) counterparts.Multivariate analysis revealed that PCI (HR=0.330,P=0.041) was an independent prognostic factor of the overall survival.Conclusions PCI can reduce thr risk of brain metastasis rate and improve the overall survival of patients with surgically resected SCLC.
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Objective To investigate the relationships of neuron-specific enolase (NSE) and progastrin-releasing peptide (ProGRP) with the initial chemotherapeutic effect and survival of patients with small-cell lung cancer (SCLC).Methods A total of 197 patients with SCLC diagnosed pathologically from January 2011 to September 2013 in Shanxi Provincial Cancer Hospital were selected.x 2 test and logistic regression analysis were used to analyze the factors affecting the initial chemotherapeutic response;KaplanMeier method,log-rank test and Cox regression analysis were used to analyze the factors affecting survival of patients.Results Among the 197 patients,NSE was negative in 64 cases and positive in 133 cases;ProGRP was negative in 51 cases and positive in 146 cases;41 cases with hyponatremia and 156 cases without hyponatremia.152 cases (77.2 ％) had well response to initial treatment and 45 cases (22.8 ％) had no reaction.Univariate analysis showed that stage of disease (x2 =4.456,P =0.033) and ProGRP (x2 =13.424,P ＜ 0.001) were associated with initial therapeutic response.Logistic regression analysis showed that stage of disease (OR =0.404,95 ％ CI 0.197-0.828％,P =0.013) and ProGRP (OR =4.058,95 ％ CI 1.939-8.491,P =0.000) were the independent predictors of initial therapeutic response.Kaplan-Meier survival analysis showed that sex,age,smoking,with or without hyponatremia,stage of disease,NSE,ProGRP and number of chemotherapy cycles were all associated with 2-year survival rate (x2 values were 4.319,6.811,4.264,4.687,32.631,41.045,11.379,33.466,respectively,all P ＜ 0.05).Multivariate analysis showed that stage of disease (RR =2.110,95 ％ CI 1.491-2.985,P ＜ 0.001),number of chemotherapy cycles (RR =0.398,95 ％ CI 0.283-0.588,P ＜ 0.001) and NSE (RR =1.422,95 ％ CI 1.113-1.784,P =0.002) were independent predictors of survival.However,ProGRP was not associated with survival of patients (RR =1.065,95 ％ CI 0.854-1.328,P =0.587).Conclusions ProGRP is associated with the initial chemotherapeutic response in patients with SCLC,and it has certain clinical significance in predicting the initial chemotherapeutic effect.NSE is associated with the survival prognosis of SCLC,and it is a prognostic factor of poor survival.
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Objective@#To explore the associations between genetic variations of glutathione synthetase gene (GSS) and response to platinum-based chemotherapy of small cell lung cancer(SCLC), and to analyze the influencing factors on survival.@*Methods@#Four haplotype-tagging single nucleotide polymorphisms (htSNPs) of GSS were genotyped by Sequenom MassARRAY methods in 903 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between genotypes and platinum-based chemotherapy response were measured by odds ratios (OR) and 95% confidence intervals (CI), adjusted for sex, age, smoking, KPS, staging and chemotherapy regiments, by unconditional logistic regression model. The hazard ratios (HR) were estimated by Cox proportional hazards regression model.@*Results@#Among the 903 patients, 462(51.2%) cases received cis-platinum and etoposide treatment while others were treated with carboplatin and etoposide. 656 patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time (MST) of these patients was 25.0 months.We found that rs725521 located in the 3′ near gene region of GSS was significantly associated with chemotherapy response. Compared with the T allele, patients with C allele had a worse chemotherapy response and an increased risk of no-responders (P=0.027). Rs7265992 and rs725521 of GSS were associated with the overall survival (OS) of SCLC patients who received platinum-based chemotherapy (HR=1.16, 95% CI=1.02-1.33, P=0.027; HR=1.17, 95% CI=1.05-1.31, P=0.006, respectively). The patients carrying 1 or 2 risk alleles and the patients carrying 3 or 4 risk alleles had worse MST than the patients without the rs7265992A and rs725521C risk alleles (24.0 and 22.0 versus 30.0 months), with the HR for death being 1.26 (95% CI=1.04-1.54) and with the HR of 1.52 (95%CI=1.18-1.97, P=0.001). Rs2025096 and rs2273684 were not associated with the OS of SCLC patients who received platinum-based chemotherapy. Age ≤ 56, KPS> 80, limited-stage, chemotherapy response and radiation therapy had a remarkably prolonged OS (all P<0.05).@*Conclusions@#These results suggest that GSS genetic polymorphism rs725521 plays an important role in the response to platinum-based chemotherapy, while rs7265992 and rs725521 have important effect on the prognosis of SCLC patients, which may be potential genetic biomarkers for personalized treatment of SCLC.
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Objective To investigate the effects of different metastatic sites on the prognosis of extensive?stage small cell lung cancer ( SCLC ) . Methods A retrospective analysis was performed among 322 patients pathologically or cytologically diagnosed with extensive?stage SCLC ( stage ⅠV defined by the seventh edition of the American Joint Committee on Cancer) who were admitted to our hospital from 2011 to 2015. In those patients, 246 had primary lesions with distant metastasis and 76 primary lesions with non?regional lymph node metastasis;261 had single?organ metastasis and 61 multi?organ metastases. Survival rates were calculated using the Kaplan?Meier method. Between?group comparison of the survival was made by the log?rank test. A multivariate prognostic analysis was made by the Cox proportional hazard model. Results In all the patients, the median survival time ( MST) was 11. 7 months;1?and 2?year overall survival ( OS) rates were 47. 9% and 19. 5%, respectively. The patients with single?organ metastasis had significantly longer MST and significantly higher 1?and 2?year OS rates than the patients with multi?organ metastases ( 12. 4 vs. 8. 9 months;52. 5% vs. 30. 5%;21. 9% vs. 11. 2%;P=0. 014) . In the patients with single?organ metastasis, those with liver metastasis had the worst prognosis with a MST of 8. 5 months, while those with non?regional lymph node metastasis had the best prognosis with a MST of 14. 5 months ( P= 0. 001 );there was no significant difference in the prognosis between patients with metastasis to different organs other than the liver ( P=0. 139) . In the patients with multi?organ metastases, those with liver metastasis and bone metastasis had the worst prognosis ( P=0. 016,0. 006);there was no significant relationship between brain metastasis and the prognosis of extensive?stage SCLC with multi?organ metastases ( P=0. 995) . There was no significantdifference in the prognosis between those with liver metastasis only and multi?organ metastases ( P=0. 862) . Conclusions Liver metastasis predicts the worst prognosis in patients initially diagnosed with extensive?stage SCLC and single?organ metastasis. Liver metastasis and bone metastasis predict the worst prognosis in patients with multi?organ metastases. Brain metastasis has no significant effect on the prognosis. There is no significant difference in the prognosis of extensive?stage SCLC between patients with single?and multi?organ metastases once liver metastasis occurs.
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Small cell lung cancer ( SCLC ) is one common type of lung cancer in China. No remarkable progress has been made in systemic therapy for SCLC since the 90’ s. However, there are some advances in radiotherapy ( RT) for SCLC, which make it possible to improve treatment outcomes of SCLC. Those advances are mainly made in thoracic RT and prophylactic cranial irradiation for extensive?stage SCLC, radiation dose and technology of thoracic RT for limited?stage SCLC, and significance of prophylactic cranial irradiation for early?stage SCLC. The paper reviews the research advances in the East and West to provide some help and references for readers.
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Objective To prepare nanobubbles and analysis its application for enhanced ultrasound imaging of small-cell lung cancer (SCLC). Methods Nanobubbles were prepared using a thin-film hydration-sonication method. MTT assay was used to evaluate the cytotoxicity of the nanobubbles for SCLC H446 cell line. The contrast-enhanced ultrasound (CEUS) of xenografted SCLC tumors in 10 nude mice was performed using nanobubbles and micro-scale microbubbles, and compared with livers. The time-intensity curve (TIC) was obtained using the Gamma variate and the following parameters were calculated, including area under the curve, time to peak, arrival time, peak intensity, and half-peak time. Results Nanobubbles with spherical shape distributed homogeneously, without obvious aggregation, the mean diameters was (392.1 ±48.6) nm and average zeta potential was (-16.8 ±2.9) mV. The MTT results indicated that the nanobubbles had no obvious cytotoxicity toward H446 cell line within the concentrations used for in vivo ultrasound imaging with nanobubbles (5 μg/ml). CEUS with the nanobubbles showed significantly higher peak intensity, and half-peak time [(18.14 ±0.62) s, (141.55 ±8.21) s] in comparison with the micro-scale microbubbles [(14.82 ±0.51) s, (120.43 ±8.73) s] (P= 0.033, 0.040). There was no significant difference in time to arrival, area under the curve and time to peak (all P>0.05). Compared with livers, the nanobubbles in xenografted SCLC tumors showed significantly shorter time to peak, lower peak intensity and area under the curve, and higher half-peak time (all P 0.05). Conclusion Nanobubbles ultrasound enhanced contrast agent shows good stability and contrast-enhancement effect in vitro, and provides an experimental basis for targeting ultrasound imaging and therapeutics of SCLC.
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Objective To investigate the effects of different chemoradiotherapy ( CRT) schemes on the prognosis of extensive?stage small?cell lung cancer ( SCLC ) . Methods A retrospective analysis was performed in 322 patients with extensive?stage SCLC who were admitted to our hospital from 2011 to 2015.All patients received standard EP/CE ( etoposide+cisplatin/carboplatin) chemotherapy. According to RECIST criteria, the efficacy of chemotherapy was divided into complete response, partial response, stable disease, and progressive disease ( PD). A total of 232 patients without PD after chemotherapy were enrolled as subjects and divided into radiotherapy group (n=187) and non?radiotherapy group (n=45).The patients undergoing radiotherapy were further divided into early radiotherapy group ( before 3 cycles of chemotherapy, n=65) and late radiotherapy group (after 3 cycles of chemotherapy, n=122),or concurrent CRT group ( n=45 ) and sequential CRT group ( n=142 ) . The survival rates were analyzed using the Kaplan?Meier method. Between?group comparison was made by log?rank test. The Cox regression model was used for multivariate prognostic analysis. Results In all the patients, the median overall survival ( OS ) , progression?free survival (PFS),and local recurrence?free survival (LRFS) time was 13?2,8?7,and 14?6 months, respectively. The non?radiotherapy group had significantly shorter median OS, PFS, and LRFS time than the radiotherapy group ( 8?7 vs. 15?0 months, P=0?00;5?6 vs. 9?8 months, P=0?00;5?9 vs. 19?2 months, P=0?00).There were no significant differences in median OS, PFS, or LRFS time between the early radiotherapy group and the late radiotherapy group ( 15?4 vs. 14?6 months, P=0?720;8?0 vs. 10?8 months, P=0?426;19?2 vs. 18?1 months, P=0?981) . The concurrent CRT group had significantly longer median OS time than the sequential CRT group (19?4 vs. 13?8 months, P=0?036),while there were no significant differences in median PFS or LRFS time between the two groups ( 10?8 vs. 9?8 months, P=0?656;19?8 vs. 17?8 months, P= 0?768 ) . Generally, patients undergoing radiotherapy had increased incidence rates of adverse reactions than those without radiotherapy (P=0?038).However, the incidence rates of grade ≥3 adverse reactions were similar between the two groups ( P=0?126) . Conclusions In the treatment of extensive?stage SCLC, thoracic radiotherapy improves the treatment outcomes without increasing the incidence rates of severe adverse reactions. When to receive radiotherapy has nothing to do with the prognosis. Concurrent CRT may further improve the treatment outcomes, which still needs further studies.
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Objective To preliminarily observe the clinical efficacy of hippocampal-sparing prophylactic cranial irradiation (HS-PCI) using helical tomotherapy (HT) in patients with limited-stage small-cell lung cancer (LS-SCLC) after chemoradiotherapy,and compare HT with intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in dose distribution.Methods From April to June,2014,six patients with LS-SCLC who had achieved a complete remission after chemoradiotherapy were assigned to HS-PCI using HT within a month after brain metastasis was ruled out using brain magnetic resonance imaging (MRI).After fusing CT images and MRI images,the hippocampus was contoured in the fusion images and hippocampal avoidance regions were created using a volumetric expansion of 3 mm around the hippocampus.A dose of 25 Gy in 10 fractions to 95％ of planning target volume (PTV) was prescribed in HT,IMRT,and VMAT.The clinical efficacy,adverse reactions,neurocognitive function,and brain metastasis were evaluated for HT.The dose distribution in PTV and hippocampus were compared between HT,IMRT,and VMAT.Results There were one patient with abdominal wall and abdominal lymph node metastases,one patient with local recurrence,and no patient with brain metastasis during the observation period.The numbers of patients with grade 1 and grade 2 headache,dizziness,and hair loss reactions were 3 and 1,3 and 1,and 4 and 2,respectively.There were no significant differences in the average score of the Mini-Mental State Examination before treatment and at 3 and 6 months after treatment (29.7,29.2,and 29.3 ; P =0.083,0.317,and 0.157).The mean dose to the hippocampus was 16.85 Gy for IMRT and 17.59 Gy for VMAT.For HT,the mean doses to the hippocampus and avoidance regions were reduced to 5.26 Gy and 6.21 Gy,respectively.The prescribed dose for HT was reduced by 79％ and 71％ compared with IMRT and VMAT,respectively.The average coverage rate of the prescribed dose was 94.48％ for HT.Conclusions HT achieves promising dose distribution and target coverage in sparing of the hippocampus.Moreover,HT dose not increase the incidence of adverse reactions.The change in neurocognitive function needs to be further studied with longterm observation and large-scale sampling.
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Objective To evaluate the correlation of different fractionation schedules in radiotherapy with the local control ( LC) and overall survival ( OS) rates in patients with extensive?stage small cell lung cancer ( ES?SCLC ) , and to figure out the relationship between different fractionation schedules in radiotherapy and the prognosis of ES?SCLC. Methods One hundred and ten patients newly diagnosed with ES?SCLC from February 2010 to March 2015 received chemoradiotherapy. According to the radiation dose, all patients were divided into hypo?fractionation group ( 30?45 Gy/3 Gy/10?15 f, n=31) and conventional fractionation group ( 54?60 Gy/1?8?2?0 Gy/27?30 f, n=79) . In all patients, 90?9% had stageⅣSCLC;21 patients had brain metastasis;39 patients were treated with prophylactic cranial irradiation ( PCI ) . The Kaplan?Meier method was used to calculate the survival time and log?rank test was used for between?group comparison. Between?group comparison of categorical data was made by χ2 test. Results The number of patients followed?up were 85 at 2?years. In all patients, the 2?year OS, progression?free survival ( PFS) , and LC rates were 27?7%, 17?5%, and 38?9%, respectively. The hypo?fractionation group had similar prognosis to the conventional fractionation group. There were no significant differences in the 2?year OS, PFS, and LC rates between the two groups ( 35% vs. 26%, P=0?886;18% vs. 16%, P=0?560;67% vs. 36%, P=0?159) . There was also no significant difference in the 2?year OS rate between patients treated with and without PCI (44% vs. 18%, P=0?044). In 84 patients with treatment failure, 11 had local recurrence, 41 had distant metastasis, and 32 had local recurrence plus distant metastasis. Conclusions The hypofractionated radiotherapy has similar efficacy but substantially shortened radiation time compared with conventionally fractionated radiotherapy. The palliative hypofractionated radiotherapy requires further study for ES?SCLC.
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Objective The aim of this retrospective study was to analyze the role of surgery in the management of limited-stage-Ⅱ small cell lung cancer.Methods A retrospective review of 82 patients with limited-stage Ⅱ small cell lung cancer between January 2001 and December 2009 was performed.The prognostic impact of different therapy and the clinicopathologic factors were analyzed.Using SPSS 16.0 statistical software for data analysis.Log-rank test for the difference of survivale rate.Using the Cox model for muliti-factor survival analysis.Chi-square test for local recurrence and distant metastasis rate.Results The overall median survival time and the 1-,3-,and 5-year overall survival rates were 27.0 months,62.1％,35.9％,and 21.0％,respectively.Median survival was 34.0 months in surgical patients vs 16.0 months in nonsurgical patients (P =0.000).Median survival after lobectomy or pneumonectomy was significantly longer than after wedge resection (P =0.048).However,survival after wedge resection was still significantly longer than survival in nonsurgical patients(P =0.024).Survival analysis confirmed that the operation,chemotherapy and radiotherapy were showed to be independent prognostic factors.The local-regional recurrencer rates of lobectomy or pneumonectomy group was lower than wedge resection group(P =0.030).The distant metastasis rates of lobectomy or pneumonectomy group was lower than nonsurgical grou (P =0.021).Conclusion This study suggests that lobectomy or pneumonectomy combined with adjuvant radio-chemotherapy should be recommended for patients with limited-stage Ⅱ small cell lung cancer.
ABSTRACT
Objective: To investigate the influences of vascular endothelial growth factor C (VEGF-C) on cell proliferation, invasion and apoptosis of NCI-H446 human small-cell lung cancer (SCLC) cells in vitro . Methods: The plasmids for VEGF-C overexpression (pHRi-VEGF-C) and small RNA interference targeting VEGF -C (pHRi-siVEGF-C) were constructed. Then the NCI-H446 cells were infected with the lentiviral packaging plasmids pHRi (an empty vector), pHRi-VEGF-C and pHRi-siVEGF-C, respectively. The expression of VEGF-C was examined by Western blotting; the cell proliferation was detected by MTT method; the invasive ability was detected by Transwell assay; and the apoptosis rate was determined by flow cytometry (FCM). Results: The expression level of VEGF-C protein in the NCI-H446 cells was significantly increased after lentiviral packaging plasmid pHRi-VEGF-C infection while it was significantly decreased after lentiviral packaging plasmid pHRi-siVEGF-C infection. The cell proliferation was significantly increased after the NCI-H446 cells were infected with pHRi-VEGF-C for five days as compared with that of the NCI-H446 cells infected with pHRi-siVEGF-C or pHRi (1.481±0.056, 0.838±0.035 and 1.146±0.07; P < 0.05). The average number of invasive cells in each visual field was significantly reduced in the pHRi-siVEGF-C-infected NCI-H446 cells as compared with that of the pHRi-VEGF-Cor pHRi-infected NCI-H446 cells (39.78±0.77, 84.87±1.27 and 60.82±1.05; P < 0.01). The number of apoptotic cells was also reduced by 90% in the pHRi-VEGF-C-infected NCI-H446 cells as compared with that of the pHRi-infected NCI-H446 cells (P < 0.01). Conclusion: The overexpression of VEGF-C can obviously promote the proliferative and invasive abilities of NCI-H446 cells, and it also can reduce the apoptosis. Meanwhile, these effects can be inhibited by small RNA interference targeting VEGF -C . The results suggest that VEGF -C may become a target of gene treatment for small-cell lung cancer. Copyright © 2012 by TUMOR.