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BACKGROUND: There are two main choices of administration route of recombinant human endostatin (Endostar) available and the treatment options of concurrent chemoradiotherapy (CCRT) have changed over time. The aim of this study was to observe the long-term efficacy and safety of different administration routes of Endostar combined with CCRT. METHODS: Patients with unresectable stage III non-small cell lung cancer (NSCLC) from two phase II trials were included as two cohorts. Both were treated with Endostar combined with CCRT. Endostar was administrated by intravenous injection (7.5 mg/m2 /day, seven days) in the IV arm and by continuous intravenous pumping (7.5 mg/m2 /24 hours, 120 hours) in the CIV arm. RESULTS: A total of 48 patients were included in the IV arm and 67 patients in the CIV arm. The median progression-free survival (PFS), overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) in the IV arm and CIV arm were 9.9 months versus 15.4 months (HR = 0.751, 95% CI 0.487-1.160, P = 0.200), 24.0 months versus 38.5 months (HR = 0.746, 95% CI 0.473-1.178, P = 0.209), 32.3 months versus 27.1 months (HR = 1.193, 95% CI 0.673-2.115, P = 0.546), 20.1 months versus 49.7 months (HR = 0.603, 95% CI 0.351-1.036, P = 0.067). The one, three, five-year PFS in the IV arm and CIV arm was 45.8% versus 52.9%, 18.3% versus 31.4%, and 18.3% versus 27.7% and the one, three, five-year OS was 81.2% versus 82.1%, 31.1% versus 50.3%, and 31.1% versus 41%, respectively. Incidence of hematological adverse reactions were numerically lower in the CIV arm than the IV arm. CONCLUSIONS: Endostar delivered by CIV with CCRT may be a better option than IV in terms of potential survival and safety for unresectable stage III NSCLC. KEY POINTS: Significant findings of the study Endostar delivered by continuous intravenous pumping might achieve more favorable survival over intravenous injection and reduce adverse hematological reactions in patients with unresectable stage III NSCLC treated with Endostar combined with CCRT.What this study adds The administration route of recombinant human endostatin is also one key factor for survival and safety to consider when treating patients with unresectable stage III NSCLC.
Subject(s)
Adenocarcinoma of Lung/therapy , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/mortality , Endostatins/administration & dosage , Lung Neoplasms/therapy , Adenocarcinoma of Lung/pathology , Administration, Intravenous , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Patient Safety , Prognosis , Survival RateABSTRACT
RTOG 0617 trial has indicated that no benefit can be obtained in the overall survival of locally advanced non-small cell lung cancer patients by improving the prescribed dose,which promotes the adjustments to the strategies of dose escalation.Currently,multiple studies have been designed to explore more effective approaches to boost dose,such as dose boosts based on increased 18FDG-uptake regions,simultaneous integrated boost intensity-modulated radiotherapy and modulation of dose fractions,which have achieved a series of progress.The widespread application of PET-CT and intensity-modulated radiotherapy offers broad space for the dose escalation and optimization.
ABSTRACT
RTOG 0617 trial has indicated that no benefit can be obtained in the overall survival of locally advanced non-small cell lung cancer patients by improving the prescribed dose, which promotes the adjustments to the strategies of dose escalation. Currently, multiple studies have been designed to explore more effective approaches to boost dose, such as dose boosts based on increased 18FDG-uptake regions, simultaneous integrated boost intensity-modulated radiotherapy and modulation of dose fractions, which have achieved a series of progress. The widespread application of PET-CT and intensity-modulated radiotherapy offers broad space for the dose escalation and optimization.
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Objective To evaluate the dose distribution and clinical efficacy of hippocampal-sparing prophylactic cranial irradiation ( HS-PCI ) in patients with small cell lung cancer by using helical tomotherapy. Methods Clinical data of 49 patients with small cell lung cancer receiving HS-PCI using helical tomotherapy in Cancer Hospital between 2014 and 2017 were retrospectively analyzed. All patients received brain MRI to exclude the possibility of brain metastasis within 1 month after standard surgery or radio-and chemo-therapy. The prescription dose was 95% PTV,25 Gy in 10 fractions. The adverse reactions and cognitive functions of patients were observed before,6 months and 1 year after treatment,and the dose distribution in the hippocampal gyrus,survival rate and brain metastasis rate were analyzed. Results The median follow-up time was 16 months. The average dose in the hippocampal gyrus was 7. 23 Gy and 8. 46 Gy in the reduction region,which was reduced by 71. 88% and 66. 16% compared with the prescription dose. The maximum dose in the hippocampal gyrus was 10. 66 Gy and 15. 43 Gy in the reduction region. Among 49 patients,8 died,the 1-year survival rate was 85. 1% and the 2-year survival rate was 70. 3%.Nine patients (18. 3%) had brain metastases,and one of them with extensive multiple brain metastases (n=13) presented with metastasis adjacent to the hippocampal gyrus. The main adverse reactions included mild headache, dizziness and brain edema,whereas no ≥ grade 2 adverse reactions occurred. At 6 months after treatment, the HVLT-R score was significantly decreased,and declined by 6. 78% at 12 months after treatment. The HVLT-R scores did not significantly differ in patients without brain metastasis before and 12 months after treatment ( P>0. 05 ). Conclusion Application of HS-PCI using helical tomotherapy meets the dose requirement,effectively protects the cognitive function and yields slight adverse reactions.
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Along with the development of modern medical modality and health awareness, the maintenance of favorable quality of life ( QoL) has become one of the most important goals for cancer survivors. Non-small-cell lung cancer ( NSCLC) survivors may suffer from substantial impairment on the overall QoL due to surgical treatment, radiotherapy and chemotherapy, etc. Evaluating the effect of NSCLC treatment upon the QoL of NSCLC patients contributes to understanding and enhancing the QoL through relevant interventions, improving life-cycle surveillance and subsequently obtaining the optimal therapeutic option. In this paper, recent researches on the QoL of NSCLC patients were summarized and reviewed.
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Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4%,48. 9%,39. 3%,and 30. 9%,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5%,41.5%,35.2%,and 30%,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.
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Objective To investigate the consensus and controversies on delineation of radiotherapy target volume for patients with non-small cell lung cancer(NSCLC). Methods Study questionnaires were designed by radiation oncologists in Peking University School of Oncology. The forms were sent through email to radiation oncologists in 10 radiation departments in China and 2 departments in US in November,2007. The brief introduction and PET/CT digital data of one patient with NSCLC were sent to radiation oncologists in 10 departments in Beijing. On Jan. 12,2008,the case discussion was held by more than 300 radiation oncologists from Beijing,Tianjin, Hebei, Liaoning Province and Inner Mongolia Autonomous Region. Results All receivers of the questionnaire responded . The set up error was 5-7 mm . For patients with locally advanced NSCLC treated with radiotherapy concurrently with near full dose chemotherapy,ll out ot 12 responding departments defined planning target volume(PTV) of primary tumor as gross tumor volume(GTV) plus 6-8 nun plus set-up error and respiratory movements ,and only one defined PTV as GTV plus set-up error and respiratory movements. For PTV of the mediastinal lymph nodes in the same patient,9 out of 12 responding departments defined PTV as GTV plus 6-8 mm plus set-up error and respiratory movements,and 3( of China) out of 12 defined PTV as GTV plus set-up error and respiratory movements. Stereotactic body .radiotherapy with high fraction dose was used in 11 out of 12 responding departments with fraction dose varying from 6 to 20 Gy,including 6 of which defined PTV of primary tumor as GTV plus 6-8 mm plus respiratory movements and set-up error, and 5 defined PTV of early stage lung cancer as GTV plus respiratory movements and set-up error. The consensus on delineation of primary tumor of the case discussion was that the appropriate window width and window level were 1600 Houasfield Units(HU) and -600 HU for lung window,and 400 HU and 20 HU for mediastinal window. The controversies was focused on whether the CTV for metastatic lymph nodes should be restricted as GTV plus 6-8 mm or enlarged to enclose all the involved lymph node region. Conclusions PIT of primary tumor and mediastinal metastatic lymph nodes should be GTV plus 6-8 mm plus respiratory movements plus set-up error. The basic controversies of target delineation are focused on the fraction dose and PIT range for early stage NSCLC, and on the possibility of defining the PIT as GTV plus respiratory movements and set-up error when treated with concurrent radiotherapy and full dose chemotherapy for locally advanced NSCLC.
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Objective To retrospectively analyze treatment results of radiotherapy for medically inoperable stage Ⅰ/Ⅱ non-small cell lung cancer. Methods Between Jan.2000 and Dec.2005,fifty-eight such patients were enrolled into the database analysis,including 37 with clinical stage Ⅰ and 21 with stage Ⅱ disease.Fifty patients received radiotherapy alone and eight with radiotherapy and chemotherapy.Fortythree patients were treated with 3-D conformal radiotherapy(3D-CRT)and 15 with conventional radiotherapy.Results The 1-,2-and 3- year overall survival rates were 85%,54%and 30%,and the median survival time was 26.2 months for the whole group.The corresponding figures were 88%,60%,36%and 30.8 months for cancer-specific survival:84%,64%,31%and 30.8 months for Stage Ⅰ disease;81%,47%,28%and 18.8 months for Stage Ⅱ disease;95%,57%,33%and 30.8 months for 3D-CRT group and 53%,44%,24%and 15.3 months for conventional radiotherapy group.By logrank test,tumor volume,pneumonitis of Grade Ⅱ or higher and weight loSS more than 5%showed statistically significant impact on overall survival.Tumor volume was the only independent prognostic factor in Cox muhivariable regression.Pneumonitis and esophagitis of Grade Ⅱ or higher were 16%and 2%,respectively.Age and lung function before treatment had a significant relationship with pneumonitis.Failure included the local recurrence(33%)and distant metastasis(21%).There was no difference between the treatment modalities and failure sites. Conclusions For medically inoperable early stage non-small cell lung cancer patients,tumor volume is the most important prognostic factor for overall survival.The conformal radiotherapy marginally improves the survival.The age and pulmonary function are related to the incidence of treatment induced pneumonitis.
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Objective To evaluate the treatment effects of chemotherapy comparing with chemotherapy and radiotherapy in the limited-stage small cell lung cancer (SCLC). Methods 234 patients were cyto-pathologically diagnosed and staged as limited small cell lung cancer. The patients were treated with combined chemotherapy and radiotherapy,in which 22 cases were treated by alone chemotherapy (C),39 patients by chemotherapy plus radiotherapy(C+R),and 173 cases by combined chemotherapy and radiotherapy + chemotherapy (C+R+C). The chemotherapy regimen included CE (or PE),CAP or CAV for 4~6 cycles. Irradiation treatment covering the primary tumor,the ipsilateral hilar nodes and mediastinum was delivered once daily with 6 megavoltage X-ray beam to a median irradiation does of 56 Gy being given in 5~6 weeks. Results The 1-,2-,3-,and 5-year overall survival rates were 76.5%,38.2%,25.3%,15.6% respectively,and the median survival time (MST) was 19 months. There was a significantly difference on the survival rate between C+R+C group and C+R group or C group (P
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<p><b>BACKGROUND</b>Angiotensin-converting enzyme (ACE), the key enzyme of RAS, is expressed in abundance in lung. Recent studies show that it plays various biological roles and even contributes importantly to the carcinogenesis of malignant tumors. The aim of this study is to investigate whether the insertion (I)/deletion (D) polymorphism of ACE is related to the susceptibility, pathological type or staging of lung cancer.</p><p><b>METHODS</b>DNA was extracted from the peripheral veinous blood derived from 47 lung cancer patients and 54 normal persons. The ACE genotype of each sample was amplified with PCR.</p><p><b>RESULTS</b>The frequencies of II, ID and DD genotype of ACE in lung cancer group were 0.447, 0.447 and 0.106 respectively, and the frequencies of I and D allele were 0.670 and 0.330 respectively. The frequencies of II, ID and DD geno-(type) of ACE in control group were 0.370, 0.556 and 0.074 respectively, and the frequencies of I and D allele were 0.648 and 0.352 respectively. There was no significant difference of ACE genotypes or alleles frequencies between the lung cancer and control groups. No significant difference of ACE genotypes or alleles frequencies was found between small cell lung cancer and non-small cell lung cancer groups or between the different staging groups of lung cancer patients.</p><p><b>CONCLUSIONS</b>No association is found between the polymorphism of ACE gene and the susceptibility, pathological type or clinical staging of lung cancer.</p>
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<p><b>BACKGROUND</b>The lung and esophagus are always damaged during radiation on thoracic tumors to a certain extent. This study is to report the incidence of radiation pneumonitis and radiation esophagitis and to analyze the factors as predictors of radiation toxicity in the treatment of three-dimensional conformal radiotherapy (3DCRT) for lung cancer.</p><p><b>METHODS</b>Between March 1999 and September 2003, 112 lung cancer patients treated with 3DCRT were reviewed at this Hospital. This population consisted of 87 men and 25 women, including 97 cases of non-small cell lung cancer and 15 of small cell lung cancer. The median age was 64 years old. Radiotherapy was delivered at 2Gy fraction, 5 fractions per week. The median total dose was 60Gy.</p><p><b>RESULTS</b>Grade 2 or more acute radiation pneumonitis developed in 7.1% (8/112) of patients while grade 2 or more late radiation pneumonitis appeared in 1.8% (2/112) of patients. Acute radiation esophagitis was observed in 8.9% (10/112) of patients with grade 2. No clinical and physical factor was relative to acute radiation pneumonitis by univariate and multivariate analysis. In the entire population, the univariate analysis revealed that many parameters (pre-treatment weight loss more than 5%, chemotherapy and concurrent chemotherapy) were significantly associated with acute radiation esophagitis. Multivariate analysis revealed that pre-treatment weight loss more than 5% was the most important risk factor for acute radiation esophagitis (P= 0.016).</p><p><b>CONCLUSIONS</b>No clinical and physical factor is relative to acute radiation pneumonitis and pre-treatment weight loss more than 5% is the most important risk factor for acute radiation esophagitis in this study.</p>
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Muti-modality therapy is the principle of cancer treatment.Concurrent chemoradiotherapy has been becoming one of the common used therapy models in cancer treatment practice.This article discussed the establishment of concurrent chemoradiotherapy,the possible biological interaction mechanisms and clinical practice.The mechanisms and future of combined bio-target therapy and radiation were also discussed.