Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation

Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.

Chemotherapy-free radiotherapy combined with immune checkpoint inhibitors:a new regimen for locally advanced non-small cell lung cancer?

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.

Hypofractionated Radiotherapy for Stage I Non-small Cell Lung Carcinoma in Patients Aged 75 Years and Older

Purpose: We report our single-institution experience using hypofractionated radiotherapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) Non-Small Cell Lung Carcinoma. Materials and methods: This is a single-institution, retrospective analysis examining disease free and overall survival and toxicity after hypofractionated radiation therapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) NSCLC. Between 1991 and 2005, a total of 33 such patients were identified with a median age of 79 years. Patients were treated with a median total dose of 7000 cGy using median daily dose fractions of 250 cGy. Analysis of competing risks (local failure, distal failure or death as the first event) was performed and cumulative incidence functions (CIF) were estimated. Results: The median length of follow-up was 19.8 months (range: 4.3 - 103.8 months). Of the 33 patients treated, 21 (63.6% of total) had no evidence of disease recurrence on follow-up imaging over the course of the study. Of the 12 patients with disease recurrence, 6 (18.2% of total) had local failure as the first event and 6 (18.2% of total) had distant metastasis as the first event. Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 19.5% (95%CI: 7.6%, 35.6%);the probability of distal failure as the first detected event was 21.5% (95%CI: 7.9%,39.4%);and the probability of death without recording a failure was 44.1% (95%CI: 26.1%, 60.7%). There were no treatment related deaths reported. Conclusions: Elderly patients diagnosed with stage I non-small cell lung cancer may safely be offered hypofractionated radiotherapy as an effective option with curative intent.

Intraoperative photodynamic therapy for tracheal mass in non-small cell lung cancer:A case report

BACKGROUND Tracheal neoplasms represent less than 0.1%of all malignancies and have no established treatment guidelines.Surgical resection with reconstruction is the primary treatment.This study demonstrates successful treatment of concurrent lung and tracheal tumors using surgical excision and intraoperative photodynamic therapy(PDT),highlighting the effectiveness and safety of this approach.CASE SUMMARY A 74-year-old male with a history of smoking and chronic obstructive pulmonary disease was diagnosed with tracheal squamous cell carcinoma and right lower lobe adenocarcinoma.A multidisciplinary team created a treatment plan involving tumor resection and PDT.The tracheal tumor was removed through a tracheal incision and this was followed by intraluminal PDT.The trachea was repaired and a right lower lobectomy was performed.The patient received a second PDT treatment postoperatively and was discharged 10 d after the tracheal surgery,without complications.He then underwent platinum-based chemotherapy for lymphovascular invasion of lung cancer.Three-month postoperative bronchoscopy revealed normal tracheal mucosa with a scar at the resection site and no evidence of tumor recurrence in the trachea or lung.CONCLUSION Our case of concurrent tracheal and lung cancers was successfully treated with surgical excision and intraoperative PDT which proved safe and effective in this patient.

Survival and prognostic factors of non-small cell lung cancer patients with postoperative locoregional recurrence treated with radical radiotherapy

Background: Locoregional recurrence remains the challenge for long-term survival of non-small cell lung cancer(NSCLC) patients after radical surgery, and curative-intent radiotherapy could be a treatment choice. This study aimed to assess the survival and prognostic factors of patients with postoperative locoregionally recurrent NSCLC treated with radical radiotherapy.Methods: We reviewed medical records of 74 NSCLC patients with postoperative locoregional recurrence who received radical radiotherapy between April 2012 and February 2016 at Sun Yat-sen University Cancer Center(Guangzhou, China). The efficacy and safety of radical radiotherapy were analyzed. The probability of survival was estimated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to identify prognostic factors.Results: Grade 3/4 adverse events included neutropenia(8 cases, 10.8%), esophagitis(7 cases, 9.5%), pneumonitis(1 case, 1.4%), and vomiting(1 case, 1.4%).The 2-year overall survival, progression-free survival, local recurrencefree survival(LRFS), and distant metastasis-free survival(DMFS) rates of all patients were 84.2,42.5,70.0, and 50.9%,respectively. Univariate and multivariate analyses showed that a higher biological effective dose(BED) of radiation was associated with longer LRFS [hazard ratios(HR)=0.317,95% confidence interval(CI) = 0.112-0.899, P = 0.016] and that wild-type epidermal growth factor receptor(EGFR) was associated with longer DMFS compared with EGFR mutation(HR = 0.383,95% CI=0.171-0.855, P = 0.019).Conclusions: Radical radiotherapy is effective and well-tolerated in NSCLC patients with postoperative locoregional recurrence. High BED is a predictor for long LRFS, and the presence of wild-type EGFR is a predictor for long DMFS.

Progress in image-guided radiotherapy for the treatment of non-small cell lung cancer

Lung cancer is one of the most common malignant tumors. It has the highest incidence and mortality rate of all cancers worldwide. Late diagnosis of nonsmall cell lung cancer(NSCLC) is very common in clinical practice, and most patients miss the chance for radical surgery. Thus, radiotherapy plays an indispensable role in the treatment of NSCLC. Radiotherapy technology has evolved from the classic two-dimensional approach to three-dimensional conformal and intensity-modulated radiotherapy. However, how to ensure delivery of an accurate dose to the tumor while minimizing the irradiation of normal tissues remains a huge challenge for radiation oncologists, especially due to the positioning error between fractions and the autonomous movement of organs. In recent years, image-guided radiotherapy(IGRT) has greatly increased the accuracy of tumor irradiation while reducing the irradiation dose delivered to healthy tissues and organs. This paper presents a brief review of the definition of IGRT and the various technologies and applications of IGRT. IGRT can help ensure accurate dosing of the target area and reduce radiation damage to the surrounding normal tissue. IGRT may increase the local control rate of tumors and reduce the incidence of radio-therapeutic complications.

Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer:A Case Report

Skin reaction or dermatological toxicities induced by immunotherapy is common.It usually manifests skin rash or erythema and can be cured by skin lotion or steroid.Nivolumab,a human IgG4 programmed cell death protein 1(PD-1)inhibitor,blocks T cells activation preventing signal and allows the immune system to clear cancer cells.Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA,with less than 10%unusual skin reaction,like sensory neuropathy,peeling skin,erythema multiforme,vitiligo,and psoriasis.Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity.The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies,but the risk of side effects may be high.We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy.The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events.Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.

Clinical analysis of concurrent chemoradiotherapy in 83 patients with locally advanced non-small cell lung cancer

Objective:The purpose of this study was to evaluate the efficacy and safety of concurrent chemoradiotherapy (CCRT) in patients with locally advanced non-small cell lung cancer (LANSCLC). Methods:83 cases of patients who have been diagnosed for locally advanced NSCLC by determined cytology or pathology were divided into two groups randomly, 42 patients in NP group and 41 patients in EP group. All patients accepted thoracic three-dimensional conformal radiotherapy (3D-CRT) and concurrent either NP chemotherapy in NP group or EP chemotherapy in EP group. 3D-CRT were started on day 1 in the first cycle of chemotherapy. Chemotherapy were carried out for 4 cycles, every cycle was 21 days. Thoracic radiotherapy adopted conventional fractionated irradiation with 15 MeV-X ray, a total dose of 60 Gy. Results: In 83 patients were evaluable, there were 5 cases complete regression to be observed, 29 cases had partial regression (PR), 7 cases with stable disease (SD) and 1 case with progression disease (PD) in NP group. CR 3 cases, PR 27 cases, SD 9 cases and PD 2 cases in EP group. The overall response rate (RR) both NP group and EP group were 80.9%, 73.2%, respectively (P = 0.785).1-, 2-, 3-year survival rate were 90.5%, 69.0%, 28.6% and 82.9%, 51.2%, 21.9%, respectively (P = 0.393). The incidence of leukopenia and thrombocytopenia in NP group was higher than that in the EP group (P < 0.05). Conclusion:CCRT in patients with locally advanced non-small cell lung cancer, 3D-CRT with concurrent NP or EP chemotherapy. 1-, 2-, 3-year overall survival (OS) and average survival time (AST) were not statistically differences, a higher incidence of toxicities were observed in NP group but can be tolerable.

Accuracy of endoscopic ultrasound-guided needle aspiration specimens for molecular diagnosis of non-small-cell lung carcinoma

BACKGROUND Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)are highly sensitive for diagnosing and staging lung cancer.In recent years,targeted therapy has shown great significance in the treatment of non-small cell lung carcinoma(NSCLC).Using these minimally invasive techniques to obtain specimens for molecular testing will provide patients with a more convenient diagnostic approach.AIM To evaluate the feasibility and accuracy of tissue samples obtained using EUSFNA and EBUS-TBNA for molecular diagnosis of NSCLC.METHODS A total of 83 patients with NSCLC underwent molecular testing using tissues obtained from EUS-FNA or EBUS-TBNA at the Tianjin Medical University Cancer Hospital from January 2017 to June 2019.All enrolled patients underwent chest computed tomography or positron emission tomography/computed tomography prior to puncture.We detected abnormal expression of EGFR,KRAS,MET,HER2,ROS1 and anaplastic lymphoma kinase protein.Two patients failed to complete molecular testing due to insufficient tumor tissue.The clinical features,puncture records,molecular testing results and targeted treatment in the remaining 81 patients were summarized.RESULTS In a total of 99 tissue samples obtained from 83 patients,molecular testing was successfully completed in 93 samples with a sample adequacy ratio of 93.9%(93/99).Biopsy samples from two patients failed to provide test results due to insufficient tumor tissue.In the remaining 81 patients,62 cases(76.5%)were found to have adenocarcinoma,11 cases(13.6%)had squamous cell carcinoma,3 cases(3.7%)had adenosquamous carcinoma and 5 cases(6.2%)had NSCLC-not otherwise specified.The results of molecular testing showed EGFR mutations in 21 cases(25.9%),KRAS mutations in 9 cases(11.1%),ROS-1 rearrangement in 1 case(1.2%)and anaplastic lymphoma kinase-positive in 5 cases(6.2%).Twentyfour patients with positive results received targeted therapy.The total effectiveness rate of targeted therapy was 66.7%(16/24),and the disease control rate was 83.3%(20/24).CONCLUSION Tissue samples obtained by EUS-FNA or EBUS-TBNA are feasible for the molecular diagnosis of NSCLC and can provide reliable evidence for clinical diagnosis and treatment.

Concurrent gemcitabine and cisplatin combined with 3D conformal radiotherapy for stage III non-small cell lung cancer

Objective： To study the toxicities and efficacy of concurrent gemcitabine plus cisplatin combined with three-dimensional conformal radiotherapy for stage Ⅲ non-small cell lung cancer （NSCLC）. Methods： Thirty-six patients with pathologically diagnosed NSCLC received radiotherapy and concurrent chemotherapy. There were 22 patients with stage Ilia and 14 patients with IIIb. Radiotherapy was given a total of 60-70 Gy in conventional fractionation. Chemotherapy included gemcitabine （600 mg/m^2） and cisplatin （20 mg/m^2）, once per week. Results： Thirty-two patients received a total dose of 60-72 Gy. Two patients received 56 Gy and another two patients received 58 Gy. Thirty-four patients received 4-6 weeks of chemotherapy, while two patients received only 2 weeks of chemotherapy. The overall response rate （CR ＋ PR）, complete response rate （CR）, partially response rate （PR） were 83.3% （30/36）, 11.1% （4/36） and 72.2% （26/36） respectively. The median follow-up duration was 18.4 months. The 1- and 2-year overall survival rates were 77.8% （28/36） and 55.6% （20/36）, respectively. Conclusion： Concurrent gemcitabine and cisplatin combined with three-dimensional conformal radiotherapy for stage III non-small cell lung cancer is effective and well tolerated. Lone-term results need further study.

Clinical Research on Three-Dimensional Conformal Radiotherapy of Non-Small Cell Lung Cancer

OBJECTIVE To investigate the clinical efficacy and toxic effect of the 3-dimensional conformal radiation therapy （3DCRT） for non- small cell lung cancer （NSCLC）. METHODS Fifty-two patients with the Stage-I and IV NSCLC were treated with 3DCRT. Cross analysis of the clinical data was conducted in the comparison between the 52 cases with 3DCRT and the other 50 cases with the conventional radiation therapy （CRT）. In the 3DCRT group, only the primary tumor and positive lymph-node draining area were included in the clinical target area, setting 4 to 6 coplanar or non-coplanar irradiation fields, with 2 Gy or 3 Gy/fraction, 1 fraction a day and 5 fractions per week. The total dose ranged from a test dose （DT） of 66 Gy to 72 Gy. In the CRT group, the field area contained the primary tumor plus the homolateral hilum of the lung, the mediastinum superior or hol-mediastinum, and opposed anteroposterior irradiation. When the dosage reached DT 36-40 Gy, an oblique portal administered radiation was conducted in order to avoid injuring the spinal cord. The DT was 1.8-2.0 Gy/fraction, 1 fraction a day, 5 fractions per week, with a total dose of 60 Gy to 70 Gy. RESULTS The therapeutic effect （CR ＋ PR） was 90.4% in the 3DCRT group, and was 72% in the CRT group. There was statistically significant difference between the two groups, P 〈 0.01. There was a clinical symptom improvement attained by 96.5% and 86.4% respectively in the two groups, and there was a statistically significant difference between the groups, P 〈 0.01. The 6-month, 1 and 2-year overall survival rates were 92.3%, 75.0% and 42.3% in the 3DCRT group, and 76%, 60% and 30% in the CRT group, respectively. There was a significant difference in the 6-month overall survival rate between the groups, P 〈 0.05. There was no obvious significant difference in the 1 and 2-year overall survival rates between the two groups, P 〉 0.05. The toxic reaction was 12.5% and 23.7% respectively in the 3DCRT and CRT groups. Acute radioactive esophagitis and leucopenia were markedly lower in the 3DCRT group than in the CRT group. There was a statistically significant difference between the groups, P 〈 0.05. No toxic reaction of Stage-III and over was found in the 3DCRT group during radiation therapy. CONCLUSION The 3DCRT method has a satisfactory shortterm efficacy and improvement of clinical symptoms in treating NSCLC, with a mild toxic reaction and good tolerance in patients. It can be used for enhancing the tumor-control rate and bettering the quality of life.

Glabridin and Anti-Non-Muscle Myosin IIA Therapy Disrupts Non-Small Cell Lung Carcinoma Motility

Lung cancer is the leading cause of cancer related death in the United States killing over 130,000 people each year. While a combination of chemo and radiation therapy may be effective, surgery is still required for many patients. Without surgery, the disease may progress and lead to metastases. We sought to determine if treatment with anti-non-muscle myosin IIA antibody would inhibit movement of the cells in the presence and absence of glabridin (an isoflavonoid compound shown to inhibit cell migration by inhibiting myosin). We compared inhibition by glabridin to that of an anti-non-muscle myosin IIA antibody and a combination therapy of both at 12 and 24 hours post wound creation. Cells that took up the anti-non-muscle myosin IIA antibody were greatly inhibited in motility and exhibited no significant change in wound healing. Glabridin treatment resulted in a dramatic increase in wound size within 12 hours and regeneration within 24 hours. The greatest decrease in motility was observed in cells treated with the combination of both glabridin and anti-non-muscle myosin IIA antibody. By 24 hrs, cell migration had halted due to death of the cells resulting from this combination. Further testing needs to be done to determine a safe mode of delivery of the combination therapy to ensure only local distribution. Controlled release drug delivery depot systems have been used as a means to provide local release of drugs intra-tumorally or adjacent to the cancerous tissue after surgical resection and have great potential.

Initial outcome of induction chemotherapy followed by radiotherapy and concurrent weekly paclitaxel for stage Ⅲ non-small cell lung cancer

Objective： The aim of our study was to evaluate the toxicity and efficacy of induction chemotherapy （ICT） followed by three-dimensional conformal radiotherapy （3D CRT） and concurrent weekly paclitaxel on unresectable non-small cell lung cancer （NSCLC）. Methods： Stage III NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin （AUC = 5-6, dl） combined with paclitaxel （175 mg/m〈 dl）, then followed by weekly paclitaxel （40 mg/m2） and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 〈 31% and spinal cord dose 〈 50 Gy. Results： Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild （16/31）： all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious （29/31, grade 3 in 21）. Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grades 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grades 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months. Conclusion： The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage III NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting.

Induction chemotherapy followed by weekly paclitaxel and carboplatin with concurrent radiotherapy in inoperable stage Ⅲ non-small cell lung cancers: results of a phase Ⅱ trial

Objective： several trials have suggested the superiority of concurrent chemoradiotherapy. It has been hypothesized that the addition of systemic dose sequential chemotherapy to concurrent chemoradiotherapy, as induction or as consolidation, might further improve survival rates. So we sought to evaluate the safety and efficacy of induction paclitaxel and carboplatin followed by weekly paclitaxel and carboplatin with concurrent radiotherapy in inoperable stage III non-small cell lung cancer （NSCLC）. Methods： Fifty-six patients with stage III inoperable NSCLC received induction chemotherapy with 2 cycles of paclitaxel 200 mg/m2 and carboplatin AUC-6 every 3 weeks then patients were assigned to concurrent chemoradiotherapy with paclitaxel 45 mg/m2 and carboplatin AUC-2 weekly along with concurrent radiotherapy at dose of 60 Gy （1.8 Gy/d x 5 d/week）. Results： Median age of the 56 eligible patients was 61 years, most of them were males （87.5%）. Squamous cell carcinoma was the most common pathological type （55.4%） and 85.7% had a performance status of 1. The majority of patients were presented with stage IIIB （62.5%）. Neutropenia was the most common toxicity during induction therapy （12.5% expressed grade 3） whereas esophagitis was the most common non hematologic adverse reaction during concurrent chemoradiotherapy （14.3% of grade 3）. The overall response rate was 71.6% with complete response in 19.6%. After median follow up of 20 months, the median survival time was 13 months （95% CI： 10.917-15.083） and 1 year overall survival rate was 53.6%. Conclusion： This regimen has demonstrated an acceptable toxicity profile and encouraging response to treatment. Evaluation of this regimen in larger number and a phase III trial are recommended.

Palliative chemotherapy followed by consolidation radiotherapy in patients with advanced and metastatic non-small cell lung cancer not suitable for radical treatment

Objective:This is a retrospective study to assess the effectiveness of consolidation radiotherapy (CRT) following palliative chemotherapy in patients with metastatic or locally advanced non-small cell lung cancer (NSCLC) who are not suitable for radical treatment.Methods:This study involved retrospective analysis of a prospective database of Northampton Oncology Centre from January 2005 to December 2010,63 patients with advanced/metastatic NSCLC treated at the oncology centre were enrolled.Patients were either treated with high dose (39/36 Gy /13-12 fractions,group 1) or low dose (20 Gy /5 fractions,group 2) CRT or those were not offered any CRT (group 3).Results:There was no significant difference between the three groups as regard age,sex,performance status,comorbidities or chemotherapy given.However there was a statistically significant difference as regard the stage P=0.009 with more stage IV patients at group II and III compared to group I.The mean survival for the three groups was 27 months,14 months &15 months,respectively.There was a statistically significant improvement of survival in patients treated with high dose palliative CRT compared to the other two groups (P=0.006).In multivariate analysis only the radiotherapy dose remains as the only statistical significant factor affecting the survival with hazard ratio 0.372 and confidence interval (0.147-0.726).Conclusion:Despite the limitation of our retrospective study,it is worth considering CRT approach for patients with advanced and metastatic NSCLC-not suitable for radical treatment-who have not progressed on chemotherapy.

Postoperative UFT-/Tegafur-based Chemotherapy Versus Postoperative Radiotherapy for Early-stage Non-small Cell Lung Cancer:A Systematic Review and Network Meta-analysis

Background:Both of UFT-/Tegafur-based postoperative chemotherapy and postoperative radiotherapy have made large progress in treatment of early-stage non-small cell lung cancer.While it is unclear that,whether UFT-/Tegafur-based postoperative chemotherapy is superior to postoperative radiotherapy for early-stage non-small cell lung cancer with no direct evidence.Methods:Electronic databases(Pubmed,embase,cochrane library and clinicaltrials.gov)were searched to obtain relevant studies.This systematic review and meta-analysis is reported in accordance with the Preferred Items for Systematic Reviews and Meta-analysis(PRISMA)Statement and was registered at International Prospective Register of Systematic Reviews(number CRD42018095979).Sensitive analysis was conducted by excluding overweight studies.Funnel plot and egger’s test were performed to conduct publication bias.Results:Twenty-one randomized control trials were included.Our results suggested UFT-/Tegafur-based postoperative chemotherapy could improve overall survival over postoperative radiotherapy[HR=0.69(0.59-0.80),p=0.000].But subgroup analysis about stage showed there was no significant difference between them,no matter of stage I,II and III.As to chemotherapy regime,both UFT-/Tegafur+platinum+vinca alkaloid[HR=0.68(0.56-0.82),p=0.000]and UFT-/Tegafur only[HR=0.66(0.54-0.79),p=0.000]were superior to radiotherapy.Subgroup analysis about radiotherapy delivery method and dose showed,significant improvement of chemotherapy over radiotherapy for Cobalt-60 only[HR=0.54(0.39-0.75),p=0.000],Cobalt-60 and linac[HR=0.69(0.59-0.81),p=0.000]and≥45 Gy[HR=0.64(0.54-0.75),p=0.000],but not for linac only[HR=0.78(0.60-1.03),p=0.081]and≥45 Gy[HR=0.86(0.67-1.11),p=0.241].Conclusion:UFT-/Tegafur-based postoperative chemotherapy was superior to postoperative radiotherapy for improving overall survival of early-stage non-small cell lung cancer,but it is not always so under certain circumstance,such as RT delivery method and radiation dose.Of course,it is imperative to further explore differences in specific stage,such as I A and I B.

Postoperative Radiotherapy and N2 Non-small Cell Lung Cancer Prognosis: A Retrospective Study Based on Surveillance, Epidemiology, and End Results Database

The purpose of this study is to clarify the significance of postoperative radiotherapy for N2 lung cancer.This study aimed to investigate the effect of postoperative radiotherapy on the survival and prognosis of patients with N2 lung cancer.Data from 12,000 patients with N2 lung cancer were extracted from the Surveillance,Epidemiology,and End Results database(2004-2012).Age at disease onset and 5-year survival rates were calculated.Survival curves were plotted using the Kaplan-Meier method.The univariate log-rank test was performed.Multivariate Cox regression were used to examine factors affecting survival.Patients’median age was 67 years(mean 66.46±10.03).The 5-year survival rate was 12.55%.Univariate analysis revealed age,sex,pathology,and treatment regimen as factors affecting prognosis.In multivariate analysis,when compared to postoperative chemotherapy,postoperative chemoradiotherapy was better associated with survival benefits(hazard ratio[HR]=0.85,95%confidence interval[CI]:0.813-0.898,P<0.001).Propensity score matching revealed that patients who had received postoperative chemoradiotherapy had a better prognosis than did patients who had received postoperative chemotherapy(HR=0.869,95%CI:0.817-0.925,P<0.001).Female patients and patients aged<65 years had a better prognosis than did their counterparts.Patients with adenocarcinoma had a better prognosis than did patients with squamous cell carcinoma.Moreover,prognosis worsened with increasing disease T stage.Patients who had received postoperative chemoradiotherapy had a better prognosis than did patients who had received postoperative chemotherapy.Postoperative radiotherapy was an independent prognostic factor in this patient group.

Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

Stereotactic body radiation therapy for non-small cell lung cancer:A review

Stereotactic body radiation therapy(SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer(NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility,prescription dose and delivery, and follow up duration varied widely. Threeyears overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.

Management of oligometastatic non-small cell lung cancer patients:Current controversies and future directions

Oligometastatic non-small cell lung cancer(NSCLC)describes an intermediate stage of NSCLC between localized and widely-disseminated disease.This stage of NSCLC is characterized by a limited number of metastases and a more indolent tumor biology.Currently,the management of oligometastatic NSCLC involves radical treatment(radiotherapy or surgery)that targets the metastatic lesions and the primary tumor to achieve disease control.This approach offers the potential to achieve prolonged survival in patients who,in the past,would have only received palliative measures.The optimal therapeutic strategies for the different scenarios of oligometastatic disease(intracranial vs extracranial disease,synchronous vs metachronous)remain undefined.Given the lack of head-to-head studies comparing radiotherapy to surgery in these patients,the decision to apply surgery or radiotherapy(with or without systemic treatment)must be based on prognostic factors that allow us to classify patients.This classification will allow us to select the most appropriate therapeutic strategy on an individualized basis.In the future,the molecular or microRNA profiles will likely improve the treatment selection process.The objective of the present article is to review the most relevant scientific evidence on the management of patients with oligometastatic NSCLC,focusing on the role of radiotherapy and surgery.We also discuss areas of controversy and future directions.