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.

Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

The prognostic value of radiomics based on ^(18)F-FDG PET/CT imaging in advanced non-small cell lung cancer

Objective:To investigate the prognostic value of radiomics features based on ^(18)F-FDG PET/CT imaging for advanced non-small cell lung cancer(NSCLC)treated with chemotherapy.Methods:A sample of 146 NSCLC patients stagedⅢor stageⅣwere included in this retrospective study who received ^(18)F-FDG PET/CT before treatment.All patients were treated with standardized chemotherapy after PET/CT examination and were divided into training group and validation group in an 8:2 ratio randomly.Radiomics features were extracted.In the training group,the minimum absolute contraction and selection operator(LASSO)algorithm and Cox risk proportional regression model were used to screen radiomics and clinical prognostic factors of progression-free survival(PFS).The radiomic model,clinical model and complex model were established respectively.The corresponding scores were calculated,then verified in the validation group.Results:The LASSO algorithm finally screened four radiomics features.ROC results showed that in the training group,the AUC of PFS predicted by the radiomics model was 0.746,and that in the verification group was 0.622.COX multivariate analysis finally included three clinical features related to PFS in NSCLC patients,namely pathological type,clinical stage and MTV30.The AUC for predicting PFS by clinical model,radiomics model and composite model were 0.746,0.753 and 0.716,respectively.The radiomics model had the highest diagnostic efficacy,and its sensitivity and specificity were 0.663 and 0.833,respectively.Delong test verified that there was no statistical difference in the predictive efficacy between the radiomics model and the composite model(Z=1.777,P=0.076)and the clinical imaging model(Z=0.323,P=0.747).Conclusion:The radiomics model based on PET/CT has a good predictive value for the prognosis of advanced NSCLC treated with chemotherapy,but it needs further validation before it can be widely used in clinical practice.

CLINICAL STUDY IN ACCELERATED HYPERFRACTIONATED IRRADIATION IN THE TREATMENT OF LOCAL ADVANCED NON-SMALL CELL LUNG CANCER

Objective To evaluate the effect of accelerated hyperfractionated irradiation (AHFJ) and conventional fractionated irradiation (CFI) for local advanced non- small cell lung cancer (NSCLC). Methods The patients of AI-IFJ group were irradiated to large-field target volume by a daily fraction of 2Gy, and small-field target volume by a daily fraction of 1Gy with more than 6h interval. The total dose of large-field target volume was SOGy/25Fx/SW and of small-field target volume was 7SGy/SOFx/5W. The patients in CFI group were irradiated by a daily fraction of 2Gy to the total dose of 66Gy/33Fx/6. 6W. After 3 months of radiotherapy, the tumor response rates of complete recovery (CR), partial recovery (PR), and no change (NC) and 1- and 2- year survival rate in the two groups were observed. Results The tumor response rates of CR,PR,NC in AHFI group and CFI group were 22.9%(8/35), 60.0%(21/35), 17.1%(6/35) and 11.4% (4/35), 51.4% (18/35), 37.2% (13/35) respectively (P>0. 05). All patients were followed up 2 years or more. The 1- and 2- year survival rates in AHFI group and CFI group were 62.9% (22/35), 31 .4% (11/35) and 42.9% (15/35) , 17.1% (6/35) respectively (P< 0.05). The incidences of esophagitis and pneumonitis in AHFI group and CFI group were 34.3% (12/35), 22. 9% (8/35) and 40.0% (14/35), 17.1% (6/35)(P>0. 05). Conclusion In comparison with CFI, AHFI may increase 1- and 2- year sur-vival rate after treatment of local advanced non-small cell lung cancer, while the radio-reactions, either early or late, did not increase significantly.

Effect of Astragalus Injection Combined with Chemotherapy on Qual ity of Life in Patients with Advanced Non-small Cell Lung Cancer

Objective: To observe the effect of Astragalus injection (AI) combined with chemotherapy on quality of life (QOF) in patients with advanced non-small cell lung caner (NSCLC). Methods: Sixty NSCLC patients were randomly divided into the treated group (n=30,treated with AI combined with chemotherapy) and the control group (n=30, treated with chemotherapy alone). Chemotherapy of MVP protocol was applied to both groups. AI was supplemented to the treated group by intravenous dripping 60 ml per day. Treatment of 21-28 days consisted one treatment cycle, and 2-3 cycles were applied. WResults: The effective rate in the treated group was 40.0% and in the control group was 36.7%, the mean remission rate in them being 5.4 month s and 3.3 months, the median survival period 11 month and 7 month and the 1-year survival rate 46.75% and 30.0%, respectively, the difference of these indexes between the two groups were all significant (P<0 05). Moreover, the clinical improving rate and QOF elevation rate in the treated group was 80.4% and 43.3%, as compared with those in the control group (50.0% and 23.3% respectively), the different was also significant (P<0 01). Conclusion: AI combined with chemotherapy can significantly improve the QOF in NSCLC patients of advanced stage.

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.

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer

Objective： To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer （NSCLC）. Methods： A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results： A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate （RR） was 36.0% （32/89）, and the disease control rate （DCR） was 69.7% （62/89）. RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma （P〈0.05）. The symptom improvement rate was 57.3% （51/89）, and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 （33.7%）] and diarrhea [15/89 （16.9%）]. The level of toxicity was typically low. Conclusions： The use of icofinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

TT genotype of GNAS1 T393C polymorphism predicts better outcome of advanced non-small cell lung cancer patients

AIM: To evaluate the potential prognostic value of GNAS1 T393 C polymorphism in advanced non-small cell lung cancer.METHODS: We extracted genomic DNA from the peripheral blood leucocytes of 94 patients with advanced non-small cell lung cancer. Quantitative real-time polymerase chain reaction was used to determine the allelic discrimination. The correlation between genotype and overall survival was evaluated using the multivariate analysis and Kaplan-Meier approach.RESULTS: Thirty-eight out of 94(40%) patients displayed a TT genotype, 29 out of 94(31%) a CT genotype and 27 out of 94(29%) a CC genotype. The median survival of TT(25 mo) genotype carriers was longer than CT(12 mo) or CC(8 mo) genotype carriers. The favorable TT genotype predicted better overall survival(OS)(2-year OS: 48%; P =0.01) compared with CT(2-year OS: 18%) or CC(2-year OS: 15%) genotype. However, dichotomization between C-genotypes(CC + CT) and T-genotypes(TT) revealed significantly lower survival rates(2-year OS: 16%; P = 0.01) for C allele carriers.CONCLUSION: Our data provided strong evidence that the GNAS1 T393 C genetic polymorphism influenced the prognosis in advanced non-small lung cancer with a worse outcome for C allele carriers.

A phaseⅠtrial of an oral subtype-selective histone deacetylase inhibitor,chidamide,in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer

Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer （NSCLC）. Methods： Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel （175 mg/m2） and carboplatin [area under the curve （AUC） 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacoldnetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results： Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response （PR）. Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions： Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.

Efficacy and safety of anlotinib plus S-1as thirdly-line or later-line treatmentin advanced non-small cell lung cancer

Objective Anlotinib,an oral vascular endothelial growth factor receptor 2(VEGFR2)inhibitor,has confirmed antitumor activity in lung cancer in both in vitro and in vivo assays,and has been recommended as third-line treatment agent in non-oncogene driven non-small cell lung cancer(NSCLC).This prospective study aimed to investigate the efficacy and safety of anlotinib plus S-1 for third-or later-line treatment in patients with advanced NSCLC.Methods Patients with histologically or cytologically confirmed NSCLC,and documented disease progression following second-line chemotherapy,and/or epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)treatment were enrolled in this study.The patients were treated anlotinib(8 mg daily d 1–14)and S-1(60 mg/m^2 d 1–14)and the treatment was repeated every 3 weeks.Treatment was continued until disease progression or unacceptable toxicity occurred.The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and adverse events(AEs)were reviewed and evaluated.Results Forty-one patients were enrolled in the study between June 2018 and December 2018.The total ORR and DCR were 26.8%and 80.5%,respectively.The median PFS was 5.2 months[95%confidence interval(CI),3.9 to 6.6 months].In the univariate analysis,there was a significant difference in the median PFS between patients with brain metastases and those without brain metastases(4.8 months vs 5.9 months,respectively;P=0.039).The Eastern Cooperative Oncology Group(ECOG)performance status(P=0.002),lines of therapy(P=0.015),and therapeutic evaluation(P=0.014)were independent factors that influenced PFS.The most common AEs were hypertension,proteinuria,myelosuppression,gastrointestinal reactions,fatigue,and mucositis.Conclusion Anlotinib plus S-1 is an effective and safe regimen for advanced NSCLC as third-or later-line therapy.

Erlotinib usage after prior treatment with gefitinib in advanced non-small cell lung cancer: A clinical perspective and review of published literature

Erlotinib and gefitinib are among the most widely researched, used and available molecularly targeted therapies for treatment of advanced non-small cell lung cancer(NSCLC). They are both tyrosine kinase inhibitors(TKIs) of the epidermal growth factor receptor(EGFR). In the past decade, there have been reports on clinical benefit from use of erlotinib after gefitinib failure in NSCLC patients. A review of published literature on this focussed topic is provided herein. Pooled analysis of published literature shows that majority of patients were female(60.6%), non-smokers(64.5%), had adenocarcinoma histology(88.3%) and were of East Asian ethnicity(92.3%). Presence of sensitizing EGFR mutation was detected in 48.4% of subjects. Disease control rates with prior gefitinib therapy and with subsequent erlotinib treatment were 79.4% and 45.4% respectively. Based upon our review, the most important predictive factor for clinical benefit from erlotinib identified was previous response to gefitinib. The exact explanations for the potential benefit from erlotinib use in this patient population is still not known and further studies are required to determine the role of molecular mechanismsespecially those related to resistance to initial EGFR TKI therapy.

Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer

Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with chemotherapy.There are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the literature.In this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization.Methods:In the first step,we conducted a clinical-pathological characterization of the patients.Afterwards,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-PCR)for the rest of the samples.Results:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of 0-1.We obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,Ca-channels,and Tolllike receptor(TLRs)families.Finally,RT-PCR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(ANCOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

Epidermal growth factor receptor mutation analysis in cytological specimens and responsiveness to gefitinib in advanced non-small cell lung cancer patients

Background： Epidermal growth factor receptor（EGFR） mutation is the key predictor of EGFR tyrosine kinase inhibitors（TKIs） efficacy in non-small cell lung cancer（NSCLC）. We conducted this study to verify the feasibility of EGFR mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying EGFR mutations.Methods： A total of 210 cytological specimens were collected for EGFR mutation detection by both direct sequencing and amplification refractory mutation system（ARMS）. We analyzed EGFR mutation status by both methods and evaluated the responsiveness to gefitinib treatment in patients harboring EGFR mutations by overall response rate（ORR）, disease control rate（DCR） and progression free survival（PFS）.Results： Of all patients, EGFR mutation rate was 28.6%（60/210） by direct sequencing and 45.2%（95/210） by ARMS（P〈0.001） respectively. Among the EGFR wild type patients tested by direct sequencing, 26.7% of them were positive by ARMS. For the 72 EGFR mutation positive patients treated with gefitinib, the ORR, DCR and median PFS were 69.4%, 90.2% and 9.3 months respectively. The patients whose EGFR mutation status was negative by direct sequencing but positive by ARMS had lower ORR（48.0% vs. 80.9%, P=0.004） and shorter median PFS（7.4 vs. 10.5 months, P=0.009） as compared with that of EGFR mutation positive patients by both detection methods. Conclusions： Our study verified the feasibility of EGFR analysis in cytological specimens in advanced NSCLC. ARMS is more sensitive than direct sequencing in EGFR mutation detection. EGFR Mutation status tested on cytological samples is applicable for predicting the response to gefitinib. Abundance of EGFR mutations might have an influence on TKIs efficacy.

A Phase Ⅱ Trial of Gefitinib as Maintenance Therapy after First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in China

Objective： To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer （NSCLC） patients who obtained disease control （DC） after first-line chemotherapy in Chinese population. Methods： Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time （OS）, the second end point was disease control rate （DCR） and progression-free survival time （PFS）. DCR included complete response （CR） plus partial response （PR） and plus stable disease （SD）. The impact of epidermal growth factor receptor （EGFR） mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography （DHPLC）. Results： Among 75 enrolled patients, the overall response rate was 37% and the DCR （CR ＋ PR ＋SD） was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type （25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively）. In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS （P=0.029 and 0.017, respectively）, however, rash status was the predictor in terms of PFS （P=0.027）. Conclusion： Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.

Clinical benefit of COX-2 inhibitors in the adjuvant chemotherapy of advanced non-small cell lung cancer: A systematic review and metaanalysis

BACKGROUND Lung cancer is a major cause of death among patients,and non-small cell lung cancer(NSCLC)accounts for more than 80%of all lung cancers in many countries.AIM To evaluate the clinical benefit(CB)of COX-2 inhibitors in patients with advanced NSCLC using systematic review.METHODS We searched the six electronic databases up until December 9,2019 for studies that examined the efficacy and safety of the addition of COX-2 inhibitors to chemotherapy for NSCLC.Overall survival(OS),progression free survival(PFS),1-year survival rate(SR),overall response rate(ORR),CB,complete response(CR),partial response(PR),stable disease(SD),and toxicities were measured with more than one outcome as their endpoints.Fixed and random effects models were used to calculate risk estimates in a meta-analysis.Potential publication bias was calculated using Egger’s linear regression test.Data analysis was performed using R software.RESULTS The COX-2 inhibitors combined with chemotherapy were not found to be more effective than chemotherapy alone in OS,progression free survival,1-year SR,CB,CR,and SD.However,there was a difference in overall response rate for patients with advanced NSCLC.In a subgroup analysis,significantly increased ORR results were found for celecoxib,rofecoxib,first-line treatment,and PR.For adverse events,the increase in COX-2 inhibitor was positively correlated with the increase in grade 3 and 4 toxicity of leukopenia,thrombocytopenia,and cardiovascular events.CONCLUSION COX-2 inhibitor combined with chemotherapy increased the total effective rate of advanced NSCLC with the possible increased risk of blood toxicity and cardiovascular events and had no effect on survival index.

Coexisting opportunities and challenges:In which scenarios can minimal/measurable residual disease play a role in advanced non-small cell lung cancer?

Curative therapy was not previously available for patients with advanced non-small cell lung cancer(NSCLC);thus,the concept of minimal/measurable(or molecular)residual disease(MRD)was not applicable to these patients.However,advances in targeted and immunotherapy have revolutionized the treatment landscape for patients with advanced NSCLC,with emerging evidence of long-term survival and even the hope of complete remission(CR)by imaging examination.The latest research shows that patients with oligometastatic lung cancer can benefit from local treatment.After removing the lesions,the choice of follow-up therapy and monitoring of the lesions could remain uncertain.MRD plays a role in identifying early-stage NSCLC patients with high risks of recurrence and determining adjuvant therapy after radical treatment.In recent years,evidence has been accumulating regarding the use of circulating cell-free tumor DNA(ctDNA)to assess MRD in solid tumors.This study discussed the possible applications of ctDNA-based MRD monitoring in advanced NSCLC and described the current challenges and unresolved problems in the application of MRD in advanced NSCLC.

Advances in the Treatment of Advanced Non-Small Cell Lung Cancer

In recent years, the incidence of lung adenocarcinoma has been increasing, and now it has become the largest type of non-small cell lung cancer (NSCLC). Currently, treatment of advanced NSCLC consists of several modalities: systemic chemotherapy, local radiation therapy, and targeted therapy (including most recently immunotherapy). In the past decade, the discovery of new molecular subtypes, the search for tumor driver gene mutations, the development of targeted molecular targeted drugs, or targeted therapy to suppress tumor angiogenesis and regulate tumor immune response have been the main directions of NSCLC research and clinical diagnosis and treatment. At present, platinum-based chemotherapy is widely used in NSCLC patients clinically. Platinum-based chemotherapy drugs can effectively prolong the survival time of patients and improve their quality of life, but the incidence of adverse reactions is still high. Therefore, it is necessary to find a drug that can improve the efficacy of patients and reduce the adverse reactions of platinum chemotherapy drugs to NSCLC patients.

Prognostic Clinico-Pathological Features of 99 Cases Advanced Non-Small Cell Lung Cancer—Egyptian National Cancer Institute

Background: Worldwide, lung cancer is the most commonly diagnosed cancer and causes more deaths than any other cancer. In Egypt;it accounts for 7% of male cancer & 3% in females. It is considered to be 3rd most common cancer in Egyptian males & 6th most common of both sexes. Materials and Methods: A total of 99 advanced non-small cell lung cancer patients who underwent first line platinum containing chemotherapy in our institute were included in this study. All clinical and pathological data were collected from patient’s files retrospectively between 2012-2014. Results: All 99 cases were diagnosed at late stage IIIB-IV (59 cases were IIIB).The median age was 54 years (range: 30 - 70) with 53% of cases are ≥ 54 years. 71% were males with male: female ratio of 2.4:1. All male patients were chronic smokers. The most frequent symptom was coughing (68%). Most of the patients had primary lung cancer in the right lung (77%). The most common histological subtype was squamous cell carcinoma (35.4%) with 54 cases present with PS-I, the remain was PS-II. All cases received platinum containing chemotherapy. The majority of cases experienced a progressive disease 60.6%. The median progression free survival (PFS) was 6 months & median overall survival (OS) was 18 months. We found that PS, disease stage, pathological subtypes and response to treatment statistically affect both median OS & PFS. Age affects only OS. Conclusions: Our analysis suggests that some of clinico-pathological factors & response to first line platinum containing regimens affect both OS & PFS of advanced NSCLC. This may be beneficial as prognostic markers and further studies were needed to aid in identification and treatment of these patients.

Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced non-small cell lung cancer： a meta-analysis

目的：系统评价参芪扶正注射液联合吉西他滨加顺铂（GP）化疗方案治疗晚期非小细胞肺癌（Non-smallcelllungcancer,NSCLC）的临床疗效.方法：计算机检索Cochrane Library,Pubmed,Embase,中国期刊全文数据库,中国生物医学文献数据库,中国科技期刊全文数据库和万方数据库等,检索时间限定为建库至2017年1月30日,检索关于参芪扶正注射液联合GP化疗方案治疗晚期非小细胞肺癌的随机对照实验（randomized controlled trial,RCT）,参照Cochrane系统评价的要求,对所有评价参芪扶正注射液联合吉西他滨加顺铂（GP）化疗方案治疗晚期非小细胞肺癌（NSCLC）的随机对照试验进行方法学质量评价、数据提取和数据分析.结果：最终纳入8个研究,共701例患者.参芪扶正注射液联合GP化疗方案能显著提高晚期非小细胞肺癌患者的功能状态（OR=3.44,95%CI[2.26,5.25],P〈0.0001）和临床疗效（OR=1.54,95%CI[1.11,2.13],Z=2.60P=0.009）,能预防GP化疗方案引起的白细胞下降（OR=0.31,95%CI[0.20,0.47],P〈0.0001）、血小板下降（OR=0.58,95%CI[0.37,0.91],P=0.02）、血红蛋白的下降（OR=0.31,95%CI[0.16,0.59],P=0.0004）及胃肠道反应的发（OR=0.38,95%CI[0.24,0.60],P=0.0001）.结论：参芪扶正注射液联合GP化疗方案治疗晚期非小细胞肺癌临床疗效显著,但纳入文献质量低,结论有待高质量的研究加以证明.

Efficacy of gefitinib as a first-line single agent treatment in patients with advanced non-small cell lung cancer

Objective： To assess the efficacy and toxicity of gefitinib as a single agent treatment in Chinese patients with advanced non-small cell lung cancer （NSCLC）. Methods： Forty-five patients with advanced NSCLC were treated with gefitinib at 250 mg daily until the disease progressed or the patient could not tolerate the toxicity. Results： None of the patients achieved a complete response （CR）, while 15 patients achieved a partial remission （PR） and 17 experienced a stable disease （SD）. Thirteen patients continued to have a progressive disease （PD）. The response rate and the disease control rate were 33.3% and 71.1%, respectively. The symptom remission rate was 72.5%, and the median remission time was 8 days. The median survival time was 15.3 months. The median progression-free survival time was 6.0 months. The most common toxicities included rash （53.3%） and diarrhea （33.3%）. Dehydration and pruritus of the skin developed in 26.7% and 22.2% of the patients, respectively. Hepatic toxicity occurred in 6.7% of patients and oral ulceration occurred in 4.4% of patients. Conclusion： Single agent treatment with gefitinib is effective against advanced NSCLC, and is well tolerated in Chinese patients.