BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally a...BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.展开更多
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 ...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.展开更多
Background:Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer(NSCLC),but acquired resistance presents challenges.The aim of this open-label,multi...Background:Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer(NSCLC),but acquired resistance presents challenges.The aim of this open-label,multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone,a novel genetically engineered epothilone analog and microtubule-stabilizing agent,as a third-or later-line treatment for locally advanced ormetastatic NSCLC.Methods:Patients who had failed standard second-line treatment(including platinum-containing chemotherapy or targeted therapy)received utidelone(40 mg/m?via intravenous injection daily,day 1-5)every 21 days.The primary endpoint was the objective response rate(ORR).Secondary endpoints were the duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.Results:From March 12,2019 to January 18,2021,26 pretreated patients with locally advanced or metastatic NSCLC(100%of patients had received prior platinum and 65.4%patients had received prior taxane treatment)were enrolled(80.8%of patients had adenocarcinoma).At baseline,nine(34.6%)patients had received secondline treatment,10(38.5%)patients had received third-line treatment,and seven(26.9%)patients had received fourth-or later-line treatment.By the data cut-off date of August 10,2021,the median follow-up was 7.49 months(range,1.4-26.7 months).The ORR was 15.4%(95%confidence interval[CI],4.4%-34.9%)in the intention-totreat(ITT)cohort(N=26)and 19.0%(95%CI,5.4%-41.9%)in the per-protocol(PP)cohort(N=21).The disease control rate was 69.2%(95%CI,48.2%-85.7%)and 81.0%(95%CI,58.1%-94.6%)in the ITT and PP cohorts,respectively.The median DoR was 4.1 months(95%CI,3.1-5.1 months)in the ITT cohort.The median PFS was 4.37 months(95%CI,2.50-5.29 months)in the ITT cohort and 4.37 months(95%CI,2.50-9.76 months)in the PP cohort.The median OS was not reached,and the 12-month OS rate was 69%(95%CI,45.1%-84.1%).Grade 3/4 treatment-emergent adverse events occurred in 38.5%of patients,and the most common was peripheral neuropathy(23.1%,all Grade 3),which was manageable with dose modifications.Conclusions:In this clinical trial,utidelone showed promising efficacy and had a manageable safety profile.Furtherclinical studies arewarranted to confirm its role in NSCLC treatment.Trial registration:No.NCT03693547;https://classic.clinicaltrials.gov.展开更多
Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advance...Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.展开更多
Background: The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer (NSCLC). Materials an...Background: The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer (NSCLC). Materials and methods: From October 2009 to January 2013, 48 elderly patients (≥65 years) with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- (A) abraxane (130 mg/m2, days 1, 8); (B) abraxane + nedaplatin (20 mg/m2 days 1-3, q3w). The parameters of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and side effects were evaluated between two arms. Results: Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR (16.7% vs. 26.1%, P=0.665) or DCR (55.3% vs. 56.5%, P=0.871). The median PFS in arm A was 3.3 months [25-75% confidence interval (CI): 3.1-7.2] and 5.5 months (25-75% CI: 3.2-7.0) in arm AP with no statistical significance (P=0.640). The median OS in arm A was 12.6 months (25-75% CI: 5.7-26.2) and 15.1 months (25-75% CI: 6.4-35.3) in arm AP with no statistical significance (P=0.770). The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance (P=0.020). Conclusions: Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.展开更多
Surgery is the first choice of treatment for patients with non-small-cell lung cancer(NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies i...Surgery is the first choice of treatment for patients with non-small-cell lung cancer(NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies include radiotherapy and chemotherapy, as well as complementary and alternative therapies, usually with disappointing results. Bronchial artery infusion(BAI) is a manageable and effective method for treating advanced NSCLC. Outcome is good by BAI due to its repeatability and low toxicity. Icotinib hydrochloride is a newly developed and highly specific epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor and has been safely and efficiently used to treat advanced NSCLC. We herein report a 73-year-old patient with chronic cough, who was diagnosed with advanced NSCLC with the EGFR mutation of L858 R substitution in exon 21, and treated with the combination of oral icotinib and BAI chemotherapy as the first-line therapy, which resulted in a satisfactory clinical outcome. Complete remission of advanced NSCLC can be achieved using the combination of oral icotinib and BAI chemotherapy.展开更多
<strong>Introduction</strong><span style="font-family:Verdana;"><strong>: </strong></span><span style="font-family:Verdana;">To determine the proportion an...<strong>Introduction</strong><span style="font-family:Verdana;"><strong>: </strong></span><span style="font-family:Verdana;">To determine the proportion and the reasons which lead to palliative treatment in patients initially a candidate for concomitant chemoradiotherapy (CCRT).</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Methods</span></b><b><span style="font-family:Verdana;">: </span></b><span style="font-family:Verdana;">A retrospective study including patients followed for locally advanced lung cancer newly diagnosed from April 1, 2016, to 12/31/2017 in the radiotherapy department of the National Oncology Institute who received palliative treatment.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Results</span></b><b><span style="font-family:Verdana;">: </span></b><span style="font-family:Verdana;">We collected 52 patients out of a total of 225 stage III patients (23%) followed by lung cancer candidates for CCRT who had undergone palliative treatment. The mean age in our series was 61.23 years [22</span><span style="font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-family:""> </span><span style="font-family:Verdana;">81] with 86% male</span><span style="font-family:Verdana;">.</span><span style="font-family:Verdana;"> The majority of patients (71%) had Performance Status (PS) ≤ 2. Histological confirmation was obtained by pathological examination in all our patients. It was an adenocarcinoma (ADK) in 54% of cases;squamous cell carcinoma in 46% of cases. The reasons for palliative treatment were mainly due to dosimetric constraints: large tumor volume 22/52 (42%);the tumor location close to the bone marrow in 15 of 52 (29%) patients;and general Performance Status impairment (29%) in 15 of 52 patients. Palliative treatment consisted of palliative chemotherapy in 37 of 52 patients (71%)</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">among whom 19 (51%) were stable after 2 months of chemotherapy, in palliative dose chest radiotherapy on the pulmonary parenchyma and/or mediastinum in 10 of 52 (19%) patients, and supportive care in 5 (10 %) patients. We observed 40/52 (77%) cases of stationary course, 04/52 (8%) cases of progress to metastases, and 08/52 (15%) deaths before radiotherapy.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Conclusion</span></b><b><span style="font-family:Verdana;">: </span></b><span style="font-family:Verdana;">A large proportion of patients followed for locally advanced non-metastatic lung cancer are not eligible for curative treatment. The reasons for the palliative treatment of patients followed for lung cancer candidates for CCRT are variable but for a large proportion of patients due to the deterioration of their state of health during their diagnostic journey. Hence</span><span style="font-family:Verdana;">,</span><span style="font-family:""> </span><span style="font-family:Verdana;">there is </span><span style="font-family:""><span style="font-family:Verdana;">the need to improve the early diag</span><span style="font-family:Verdana;">nosis and early management of patients with lung cancer to avoid delayed care.</span></span>展开更多
The objective of this study was to study the therapeutic effect of Kanglaite injection combined with chemotherapy in the treatment of late-stage nonsmall-cell lung cancer(NSCLC)and also to observe the effect of the co...The objective of this study was to study the therapeutic effect of Kanglaite injection combined with chemotherapy in the treatment of late-stage nonsmall-cell lung cancer(NSCLC)and also to observe the effect of the combination treatment on immune function.92 patients with advanced stage of NSCLC who admitted to First Hospital of Zibo city hospital from May 2017 to October 2018 were randomly divided into experimentagroup and control group,with 46 cases,respectively.The control group was treated with chemotherapy only while the experimental group was treated with Kanglaite injection combined with chemotherapy which was the basic treatment for patients,and the total treatment effective rate,adverse reaction rate,and immune index of the treatments on two groups were compared.The total treatment effective rate of the experimental group was 80.43%,which was significantly higher than that of the control group,which was 63.04%.The incidence of adverse reactions in the experimental group was 36.96%,which was lower than that of the control group(78.26%).The immune indexes of the experimental group(CD3+,CD4+,IgG,and IgA)were better than that of the control group,respectively.The differences between the two groups were statistically significant(P<0.05).During the chemotherapy of late-stage or advanced NSCLC,the addition use of Kanglaite injection has a significant effect on improving tumor control and reducing the side effects of chemotherapy,and helps to improve the immune function of patients;thus,it is worth promoting.展开更多
Objective: To investigate the effects of Yiqi Gu decoction combined with DC chemotherapy on serum tumor markers, inflammatory factors and immune function in patients with locally advanced non-small cell lung cancer. M...Objective: To investigate the effects of Yiqi Gu decoction combined with DC chemotherapy on serum tumor markers, inflammatory factors and immune function in patients with locally advanced non-small cell lung cancer. Methods: A total of 95 patients with locally advanced non-small cell lung cancer were selected as the research objects, according to the random data table they were divided into control group (n=48) and observation group (n=47), patients in the control group were given DC chemotherapy, On the basis of this treatment, the patients in the observation group were given Yiqi Gu decoction treatment, Comparison of the levels of serum tumor markers [antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)], inflammatory factor [C reactive protein (CRP) and tumor necrosis factor-α (TNF-α)] and immune function (CD3+, CD4+, CD8+, CD4+/CD8+)Results: Before treatment, there were no significant difference in the levels of CEA, CA19-9, CRP, TNF-α, CD3+, CD4+, CD8+, CD4+/CD8+ between the two groups;After treatment, the CEA, CA19-9, CRP, TNF-α, CD8+ levels of two groups were significantly lower than those in the same group before treatment, and the decreased range in observation group was significantly higher than the control group, moreover the levels after treatment were obviously lower than control group;After treatment, the levels of CD3+, CD4+, CD4+/CD8+ in the observation group were (64.72±5.25)% , (39.51±5.14)% and (1.35±0.27), which were significantly higher than the same group before treatment, and significantly higher than the control group [(58.57±5.09)%, (31.34±5.06)%, (1.14±0.33)], differences were statistically significant. Conclusion: DC chemotherapy combined with Yiqi Guben Decoction in the treatment of locally advanced non-small cell lung cancer, can effectively reduce the serum tumor marker levels, decrease inflammatory stress, improve immune function, has an important clinical value.展开更多
Objective: To investigate the effects of bronchial arterial chemoembolization combined with radioactive particle implantation on the level of serum tumor markers and T lymphocyte subsets in patients with locally advan...Objective: To investigate the effects of bronchial arterial chemoembolization combined with radioactive particle implantation on the level of serum tumor markers and T lymphocyte subsets in patients with locally advanced non-small cell lung cancer. Methods: A total of 91 cases of locally advanced non-small cell lung cancer patients according to the random data table were divided into the control group (n=45) and observation group (n=46) according to the random data table. Patients in the control group was treated with bronchial arterial chemoembolization, on the basis of the control group, patients in the observation group were treated with radioactive particle implantation, the serum tumor markers and T lymphocyte subsets of the two groups were compared before and after treatment. Results: The levels of CEA, NSE, CA125, CD4+, CD8+, CD4+/CD8+ and NK in the two groups before the treatment were not statistically significant. Compared with the group before treatment, levels of CEA, NSE, CA125and CD8+ of the two groups after treatment were significantly decreased, and after treatment the level of CEA, NSE, CA125and CD8+ in the observation group was significantly lower than those of the control group;The levels of CD4+, CD4+/CD8+ and NK in the two groups after treatment were significantly higher than those in the group before treatment, and the observation group levels were significantly higher than those of the control group. Conclusion: Bronchial artery embolization combined with radioactive particle implantation for locally advanced non-small cell lung cancer, can effectively reduce the serum tumor markers level, improve the level of T cell subsets of patients, has important clinical value.展开更多
Objective: To study the clinical efficacy and methods of permanent implantation of radioactive I-125 seed in surgery for local advanced non small lung cancer (LANSCLC). Methods: From Apr. 2004 to Apr. 2006, the I-125 ...Objective: To study the clinical efficacy and methods of permanent implantation of radioactive I-125 seed in surgery for local advanced non small lung cancer (LANSCLC). Methods: From Apr. 2004 to Apr. 2006, the I-125 seeds were implanted into 30 patients with LANSCLC in surgery. The numbers of seeds were 10–40. The chemotherapy was performed in 10 to 14 days after operation. Results: There was no operative death, and the distribution of seeds and complications were reviewed by CT and X-ray after treatment. The distribution of seeds was satisfactory in all patients. The complete response rate (CR) was 56.6% and the part response (PR) was 26.6%. The overall response rate was 83.3% after 4–24 months of surgery. There was no one occurred radiation pneumonia. Prospective efficacy await further follow-up. Conclusion: Permanent implantation of I-125 seed in surgery for LANSCLC, is a safe and effective method with mild complications.展开更多
Lung cancer is the second most common and the deadliest type of cancer worldwide.Clinically,non-small cell lung cancer(NSCLC)is the most com-mon pathological type of lung cancer;approximately one-third of affected pat...Lung cancer is the second most common and the deadliest type of cancer worldwide.Clinically,non-small cell lung cancer(NSCLC)is the most com-mon pathological type of lung cancer;approximately one-third of affected patients have locally advanced NSCLC(LA-NSCLC,stage III NSCLC)at diag-nosis.Because of its heterogeneity,LA-NSCLC often requires multidisciplinary assessment.Moreover,the prognosis of affected patients is much below satisfac-tion,and the efficacy of traditional therapeutic strategies has reached a plateau.With the emergence of targeted therapies and immunotherapies,as well as the continuous development of novel radiotherapies,we have entered an era of novel treatment paradigm for LA-NSCLC.Here,we reviewed the landscape of relevant therapeutic modalities,including adjuvant,neoadjuvant,and periop-erative targeted and immune strategies in patients with resectable LA-NSCLC with/without oncogenic alterations;as well as novel combinations of chemora-diation and immunotherapy/targeted therapy in unresectable LA-NSCLC.We addressed the unresolved challenges that remain in the field,and examined future directions to optimize clinical management and increase the cure rate of LA-NSCLC.展开更多
Objective: To observe the efficacy and safety of cetuximab combined with chemotherapy in advanced non-small-cell lung cancer (NSCLC), and to investigate the association of status of K-RAS gene mutation and epiderma...Objective: To observe the efficacy and safety of cetuximab combined with chemotherapy in advanced non-small-cell lung cancer (NSCLC), and to investigate the association of status of K-RAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome. Methods: Between Jan. 2006 and Sep. 2009, nineteen patients with advanced NSCLC received cetuximab (〉4 weeks) combined with chemotherapy in Department of Thoracic Oncology at Beijing Cancer Hospital. Response, survival and toxicity were retrospectively assessed, epidermal growth factor receptor (EGFR) protein expression was evaluated by ELISA Kit. The status of K-RAS gene mutation was tested by PCR-RFLP and EGFR gene amplification was measured by EGFR fluorescence in situ hybridization (FISH). Results: Partial response(PR) was observed in 26.3%(5/19) of the patients and stable disease(SD) in 52.6%(10/19). Median progression free survival(PFS) was 6 months (95% CI: 3.6-8.4). Median overall survival (MST) and 1-year survival rate(SR) were 10.6 months (95% CI: 6.6-14.6) and 47.6%, respectively. Mild or moderate skin rash was the most common toxicity related with cetuximab. K-RAS gene mutation, EGFR protein level and amplification have little correlation with prognosis. Conclusion: Cetuximab combined with chemotherapy was tolerable and the skin rash related with cetuximab was mild to moderate. Cetuximab may prolong survival of the patients who failed to previous chemotherapy.展开更多
Despite therapeutic advancements,the prognosis of locally advanced non-small cell lung cancer(LANSCLC),which has invaded multiple lobes or the other lung and intrapulmonary lymph nodes,remains poor.The emergence of im...Despite therapeutic advancements,the prognosis of locally advanced non-small cell lung cancer(LANSCLC),which has invaded multiple lobes or the other lung and intrapulmonary lymph nodes,remains poor.The emergence of immunotherapy with immune checkpoint blockade(ICB)is transforming cancer treatment.However,only a fraction of lung cancer patients benefit from ICB.Significant clinical evidence suggests that the proinflammatory tumor microenvironment(TME)and programmed death-ligand 1(PD-L1)expression correlate positively with response to the PD-1/PD-L1 blockade.We report here a liposomal nanoparticle loaded with cyclic dinucleotide and aerosolized(AeroNP-CDN)for inhalation delivery to deep-seated lung tumors and target CDN to activate stimulators of interferon(IFN)genes in macrophages and dendritic cells(DCs).Using a mouse model that recapitulates the clinical LANSCLC,we show that AeroNP-CDN efficiently mitigates the immunosuppressive TME by reprogramming tumor-associated macrophage from the M2 to M1 phenotype,activating DCs for effective tumor antigen presentation and increasing tumor-infiltrating CD8+T cells for adaptive anticancer immunity.Intriguingly,activation of interferons by AeroNP-CDN also led to increased PD-L1 expression in lung tumors,which,however,set a stage for response to anti-PD-L1 treatment.Indeed,anti-PD-L1 antibody-mediated blockade of IFNs-induced immune inhibitory PD-1/PD-L1 signaling further prolonged the survival of the LANSCLC-bearing mice.Importantly,AeroNP-CDN alone or combination immunotherapy was safe without local or systemic immunotoxicity.In conclusion,this study demonstrates a potential nano-immunotherapy strategy for LANSCLC,and mechanistic insights into the evolution of adaptive immune resistance provide a rational combination immunotherapy to overcome it.展开更多
Bevacizumab,an anti-VEGF monoclonal antibody,has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC(ns-NSCLC).However,the safety and efficacy of bevacizumab for elderly patients ...Bevacizumab,an anti-VEGF monoclonal antibody,has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC(ns-NSCLC).However,the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation.Thus,59 patients were included in the present retrospective study,22 patients in the bevacizumab plus pemetrexed and platinum(B+PP)group,and 37 patients in the pemetrexed and platinum(PP)group.For the entire cohort of patients,the median OS was 33.3 months,and the 1-year and 2-year overall survival rates were 88.5%and 67.8%,respectively.The median OS and 1-year and 2-year OS rates were 20.5 months,70.3%and 0%,respectively,in the B+PP group and 33.4 months,97.0%and 89.4%,respectively,in the PP group(P<0.001).The incidence of grade≥3 adverse events was higher in the B+PP group than in the PP group(27.3%vs.10.8%,respectively;P=0.204).Univariate and multivariate analyses suggested that the receipt of≥5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS,whereas the addition of bevacizumab was an unfavorable prognostic factor.With increased toxicities,the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.展开更多
Objective: In recent years, the combination of cetuximab and chemoradiotherapy (CRT) has been used to treat stage III non-small cell lung cancer (NSCLC); however, limited data are available for Chinese patients. ...Objective: In recent years, the combination of cetuximab and chemoradiotherapy (CRT) has been used to treat stage III non-small cell lung cancer (NSCLC); however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT (CCRT) in Chinese patients with stage III NSCLC. Methods: Eligibility criteria were Zubrod performance status (PS) 0-1, forced expiratory volume in 1 second (FEV1) 〉_1.2 L and adequate organ function. Enrolled patients received weekly cetuximab (initial dose of 400 mg/m2 on day 1 of week 1 and a maintenance dose of 250 mg/m2 on week 2 to the end of CCRT) with cisplatin/vinorelbine (NP) chemotherapy (every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy (TRT) (60-66 Gy/2 Gy). The primary endpoints were toxicity and feasibility. All patients received positron emission tomography- computerized tomography (PET-CT) scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node- metastasis (TNM) stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. Results: Seventeen patients were enrolled and 16 completed the full regime. The overall response rate (ORR) was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval (CI): 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% (95% CI, 60.6-96.9%) and 58.8% (95% CI, 60.6-77.8%), respectively. Three patients remain progression-free to date, and the median progression-free survival (PFS) was 13.5 months (95% CI, 6.8-20.2 months). No treatment-related death occurred; however, 76% of the patients experienced grade 3+ adverse events (AEs), including nansea/vomiting, intestinal obstruction, and esophagitis (〈6%), while other AEs were mostly of hematological nature (71%). The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL (P=0.027), SUV-T (P=0.025), and PS (P=0.006) as potential survival predictors, with a hazard ratio (HR) of 3.4, 3.7, and 9.9, respectively. Conclusions: The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by 18F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.展开更多
Despite the aggressive pursuit of diagnostic and treatment modalities for lung cancer, the treatment outcomes are still not satisfactory, and even patients with surgically resectable non-small cell lung cancer (NSCLC)...Despite the aggressive pursuit of diagnostic and treatment modalities for lung cancer, the treatment outcomes are still not satisfactory, and even patients with surgically resectable non-small cell lung cancer (NSCLC) are often at considerable risk of suffering recurrence and/or death from lung cancer. Regarding the treatment of patients with locally advanced, resectable NSCLC, several retrospective and prospective studies have shown the significance of multimodality treatments with preoperative chemoradiotherapy and surgical treatment. However, no definitive treatment strategies for locally advanced NSCLC patients have yet been established. One of the reasons for the lack of established treatment strategies for patients with locally advanced NSCLC is considered to be the heterogeneity of the population, i.e., cT4N0, cT3-4N1 and cT1a-3N2 tumors are included in stage IIIA disease, and superior sulcus tumors (SSTs) are also included in this classification. With regard to SST, two representative prospective phase II trials indicated the efficacy of surgical treatment following concurrent radiation and chemotherapy. In a study conducted by the Southwest Oncology Group, 110 patients with superior sulcus NSCLC were treated with two cycles of cisplatin and etoposide concurrently with 45 gray (Gy) of radiation, followed by surgical treatment and two additional cycles of chemotherapy postoperatively. The response rate (RR) to the preoperative chemoradiotherapy was 86%, and 83 patients (76%) were able to undergo complete resection. A pathological complete response (CR) was observed in 61 patients (56%), and the five-year survival of all patients and those undergoing complete resection was 44% and 54%, respectively. A phase II study conducted by the Japan Clinical Oncology Group examined the safety and efficacy of preoperative concurrent chemoradiotherapy using mitomycin, vinblastin and cisplatin followed by surgical treatment. Seventy-six patients with SST were enrolled in this study, and all received chemotherapy using two cycles of MVP concurrently with 45 Gy of radiation, followed by surgery. Neoadjuvant chemoradiotherapy resulted in a 61% RR, and pathological complete resection was successfully achieved in 51 patients (68%). A pathological CR was observed in 12 patients (16%), and the disease-free and overall survival rates at five years were 45% and 56%, respectively. Both studies showed the efficacy and tolerability of the multimodality treatment for SST, thus suggesting that multimodality treatment with preoperative chemoradiotherapy followed by surgery may therefore be an effective treatment for resectable SST. We herein review the results of retrospective and prospective studies while assessing the treatment outcomes of NSCLC patients with SST.展开更多
Objective:Several studies have found that epigallocatechin-3-gallate(EGCG)can alleviate acute radiation-induced esophagitis,inhibit pulmonary inflammation and fibrosis,and reduce the severity of cardiovascular disease...Objective:Several studies have found that epigallocatechin-3-gallate(EGCG)can alleviate acute radiation-induced esophagitis,inhibit pulmonary inflammation and fibrosis,and reduce the severity of cardiovascular disease.Therefore,this study was aimed at exploring the influence of EGCG on late radiation toxicity in the heart,esophagus,and lungs among patients with locally advanced lung cancer.Methods:The patients were divided into an EGCG group and a control group,the groups received EGCG and symptomatic treatment,respectively.The Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme was used to determine the late toxicity scores.Tumor responses were evaluated by chest computed tomography(CT),based on the Response Evaluation Criteria in Solid Tumors version 1.1.Results:We retrospectively analyzed 74 patients treated at our hospital from September 2012 to September 2016(37 patients received EGCG and 37 received supportive treatment).The late toxicity scores of the EGCG group decreased compared to those of the control group.An obvious clinical significance was observed for the oral EGCG solution in the treatment and prevention of late cardiac,esophageal,and pulmonary toxicity.However,no significant difference was found(P>0.05).The tumor response rates were similar in the two groups.Moreover,there was no difference in progression-free survival(PFS)between the groups(P>0.05).Conclusion:Oral EGCG solution might alleviate radiation-induced late cardiac,esophageal,and pulmonary toxicity but has no significant effect on the tumor response rate and PFS following radiotherapy.展开更多
文摘BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.
基金funded by the National Natural Science Foundation of China(Grant Nos.81972796,82272845,81972863,and 82030082)the Key Research and Development Program of Shandong(Major Science&Technology Innovation Project Grant No.2021SFGC0501)+1 种基金the CSCO-Haosen Foundation(Grant No.Y-HS202102-0089)the CSCO-Xinda Foundation(Grant No.Y-XD202001-0008)。
文摘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.
文摘Background:Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer(NSCLC),but acquired resistance presents challenges.The aim of this open-label,multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone,a novel genetically engineered epothilone analog and microtubule-stabilizing agent,as a third-or later-line treatment for locally advanced ormetastatic NSCLC.Methods:Patients who had failed standard second-line treatment(including platinum-containing chemotherapy or targeted therapy)received utidelone(40 mg/m?via intravenous injection daily,day 1-5)every 21 days.The primary endpoint was the objective response rate(ORR).Secondary endpoints were the duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.Results:From March 12,2019 to January 18,2021,26 pretreated patients with locally advanced or metastatic NSCLC(100%of patients had received prior platinum and 65.4%patients had received prior taxane treatment)were enrolled(80.8%of patients had adenocarcinoma).At baseline,nine(34.6%)patients had received secondline treatment,10(38.5%)patients had received third-line treatment,and seven(26.9%)patients had received fourth-or later-line treatment.By the data cut-off date of August 10,2021,the median follow-up was 7.49 months(range,1.4-26.7 months).The ORR was 15.4%(95%confidence interval[CI],4.4%-34.9%)in the intention-totreat(ITT)cohort(N=26)and 19.0%(95%CI,5.4%-41.9%)in the per-protocol(PP)cohort(N=21).The disease control rate was 69.2%(95%CI,48.2%-85.7%)and 81.0%(95%CI,58.1%-94.6%)in the ITT and PP cohorts,respectively.The median DoR was 4.1 months(95%CI,3.1-5.1 months)in the ITT cohort.The median PFS was 4.37 months(95%CI,2.50-5.29 months)in the ITT cohort and 4.37 months(95%CI,2.50-9.76 months)in the PP cohort.The median OS was not reached,and the 12-month OS rate was 69%(95%CI,45.1%-84.1%).Grade 3/4 treatment-emergent adverse events occurred in 38.5%of patients,and the most common was peripheral neuropathy(23.1%,all Grade 3),which was manageable with dose modifications.Conclusions:In this clinical trial,utidelone showed promising efficacy and had a manageable safety profile.Furtherclinical studies arewarranted to confirm its role in NSCLC treatment.Trial registration:No.NCT03693547;https://classic.clinicaltrials.gov.
文摘Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.
文摘Background: The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer (NSCLC). Materials and methods: From October 2009 to January 2013, 48 elderly patients (≥65 years) with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- (A) abraxane (130 mg/m2, days 1, 8); (B) abraxane + nedaplatin (20 mg/m2 days 1-3, q3w). The parameters of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and side effects were evaluated between two arms. Results: Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR (16.7% vs. 26.1%, P=0.665) or DCR (55.3% vs. 56.5%, P=0.871). The median PFS in arm A was 3.3 months [25-75% confidence interval (CI): 3.1-7.2] and 5.5 months (25-75% CI: 3.2-7.0) in arm AP with no statistical significance (P=0.640). The median OS in arm A was 12.6 months (25-75% CI: 5.7-26.2) and 15.1 months (25-75% CI: 6.4-35.3) in arm AP with no statistical significance (P=0.770). The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance (P=0.020). Conclusions: Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.
文摘Surgery is the first choice of treatment for patients with non-small-cell lung cancer(NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies include radiotherapy and chemotherapy, as well as complementary and alternative therapies, usually with disappointing results. Bronchial artery infusion(BAI) is a manageable and effective method for treating advanced NSCLC. Outcome is good by BAI due to its repeatability and low toxicity. Icotinib hydrochloride is a newly developed and highly specific epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor and has been safely and efficiently used to treat advanced NSCLC. We herein report a 73-year-old patient with chronic cough, who was diagnosed with advanced NSCLC with the EGFR mutation of L858 R substitution in exon 21, and treated with the combination of oral icotinib and BAI chemotherapy as the first-line therapy, which resulted in a satisfactory clinical outcome. Complete remission of advanced NSCLC can be achieved using the combination of oral icotinib and BAI chemotherapy.
文摘<strong>Introduction</strong><span style="font-family:Verdana;"><strong>: </strong></span><span style="font-family:Verdana;">To determine the proportion and the reasons which lead to palliative treatment in patients initially a candidate for concomitant chemoradiotherapy (CCRT).</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Methods</span></b><b><span style="font-family:Verdana;">: </span></b><span style="font-family:Verdana;">A retrospective study including patients followed for locally advanced lung cancer newly diagnosed from April 1, 2016, to 12/31/2017 in the radiotherapy department of the National Oncology Institute who received palliative treatment.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Results</span></b><b><span style="font-family:Verdana;">: </span></b><span style="font-family:Verdana;">We collected 52 patients out of a total of 225 stage III patients (23%) followed by lung cancer candidates for CCRT who had undergone palliative treatment. The mean age in our series was 61.23 years [22</span><span style="font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-family:""> </span><span style="font-family:Verdana;">81] with 86% male</span><span style="font-family:Verdana;">.</span><span style="font-family:Verdana;"> The majority of patients (71%) had Performance Status (PS) ≤ 2. Histological confirmation was obtained by pathological examination in all our patients. It was an adenocarcinoma (ADK) in 54% of cases;squamous cell carcinoma in 46% of cases. The reasons for palliative treatment were mainly due to dosimetric constraints: large tumor volume 22/52 (42%);the tumor location close to the bone marrow in 15 of 52 (29%) patients;and general Performance Status impairment (29%) in 15 of 52 patients. Palliative treatment consisted of palliative chemotherapy in 37 of 52 patients (71%)</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">among whom 19 (51%) were stable after 2 months of chemotherapy, in palliative dose chest radiotherapy on the pulmonary parenchyma and/or mediastinum in 10 of 52 (19%) patients, and supportive care in 5 (10 %) patients. We observed 40/52 (77%) cases of stationary course, 04/52 (8%) cases of progress to metastases, and 08/52 (15%) deaths before radiotherapy.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Conclusion</span></b><b><span style="font-family:Verdana;">: </span></b><span style="font-family:Verdana;">A large proportion of patients followed for locally advanced non-metastatic lung cancer are not eligible for curative treatment. The reasons for the palliative treatment of patients followed for lung cancer candidates for CCRT are variable but for a large proportion of patients due to the deterioration of their state of health during their diagnostic journey. Hence</span><span style="font-family:Verdana;">,</span><span style="font-family:""> </span><span style="font-family:Verdana;">there is </span><span style="font-family:""><span style="font-family:Verdana;">the need to improve the early diag</span><span style="font-family:Verdana;">nosis and early management of patients with lung cancer to avoid delayed care.</span></span>
文摘The objective of this study was to study the therapeutic effect of Kanglaite injection combined with chemotherapy in the treatment of late-stage nonsmall-cell lung cancer(NSCLC)and also to observe the effect of the combination treatment on immune function.92 patients with advanced stage of NSCLC who admitted to First Hospital of Zibo city hospital from May 2017 to October 2018 were randomly divided into experimentagroup and control group,with 46 cases,respectively.The control group was treated with chemotherapy only while the experimental group was treated with Kanglaite injection combined with chemotherapy which was the basic treatment for patients,and the total treatment effective rate,adverse reaction rate,and immune index of the treatments on two groups were compared.The total treatment effective rate of the experimental group was 80.43%,which was significantly higher than that of the control group,which was 63.04%.The incidence of adverse reactions in the experimental group was 36.96%,which was lower than that of the control group(78.26%).The immune indexes of the experimental group(CD3+,CD4+,IgG,and IgA)were better than that of the control group,respectively.The differences between the two groups were statistically significant(P<0.05).During the chemotherapy of late-stage or advanced NSCLC,the addition use of Kanglaite injection has a significant effect on improving tumor control and reducing the side effects of chemotherapy,and helps to improve the immune function of patients;thus,it is worth promoting.
文摘Objective: To investigate the effects of Yiqi Gu decoction combined with DC chemotherapy on serum tumor markers, inflammatory factors and immune function in patients with locally advanced non-small cell lung cancer. Methods: A total of 95 patients with locally advanced non-small cell lung cancer were selected as the research objects, according to the random data table they were divided into control group (n=48) and observation group (n=47), patients in the control group were given DC chemotherapy, On the basis of this treatment, the patients in the observation group were given Yiqi Gu decoction treatment, Comparison of the levels of serum tumor markers [antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)], inflammatory factor [C reactive protein (CRP) and tumor necrosis factor-α (TNF-α)] and immune function (CD3+, CD4+, CD8+, CD4+/CD8+)Results: Before treatment, there were no significant difference in the levels of CEA, CA19-9, CRP, TNF-α, CD3+, CD4+, CD8+, CD4+/CD8+ between the two groups;After treatment, the CEA, CA19-9, CRP, TNF-α, CD8+ levels of two groups were significantly lower than those in the same group before treatment, and the decreased range in observation group was significantly higher than the control group, moreover the levels after treatment were obviously lower than control group;After treatment, the levels of CD3+, CD4+, CD4+/CD8+ in the observation group were (64.72±5.25)% , (39.51±5.14)% and (1.35±0.27), which were significantly higher than the same group before treatment, and significantly higher than the control group [(58.57±5.09)%, (31.34±5.06)%, (1.14±0.33)], differences were statistically significant. Conclusion: DC chemotherapy combined with Yiqi Guben Decoction in the treatment of locally advanced non-small cell lung cancer, can effectively reduce the serum tumor marker levels, decrease inflammatory stress, improve immune function, has an important clinical value.
基金the National Natural Science Foundation of China(81541061).
文摘Objective: To investigate the effects of bronchial arterial chemoembolization combined with radioactive particle implantation on the level of serum tumor markers and T lymphocyte subsets in patients with locally advanced non-small cell lung cancer. Methods: A total of 91 cases of locally advanced non-small cell lung cancer patients according to the random data table were divided into the control group (n=45) and observation group (n=46) according to the random data table. Patients in the control group was treated with bronchial arterial chemoembolization, on the basis of the control group, patients in the observation group were treated with radioactive particle implantation, the serum tumor markers and T lymphocyte subsets of the two groups were compared before and after treatment. Results: The levels of CEA, NSE, CA125, CD4+, CD8+, CD4+/CD8+ and NK in the two groups before the treatment were not statistically significant. Compared with the group before treatment, levels of CEA, NSE, CA125and CD8+ of the two groups after treatment were significantly decreased, and after treatment the level of CEA, NSE, CA125and CD8+ in the observation group was significantly lower than those of the control group;The levels of CD4+, CD4+/CD8+ and NK in the two groups after treatment were significantly higher than those in the group before treatment, and the observation group levels were significantly higher than those of the control group. Conclusion: Bronchial artery embolization combined with radioactive particle implantation for locally advanced non-small cell lung cancer, can effectively reduce the serum tumor markers level, improve the level of T cell subsets of patients, has important clinical value.
文摘Objective: To study the clinical efficacy and methods of permanent implantation of radioactive I-125 seed in surgery for local advanced non small lung cancer (LANSCLC). Methods: From Apr. 2004 to Apr. 2006, the I-125 seeds were implanted into 30 patients with LANSCLC in surgery. The numbers of seeds were 10–40. The chemotherapy was performed in 10 to 14 days after operation. Results: There was no operative death, and the distribution of seeds and complications were reviewed by CT and X-ray after treatment. The distribution of seeds was satisfactory in all patients. The complete response rate (CR) was 56.6% and the part response (PR) was 26.6%. The overall response rate was 83.3% after 4–24 months of surgery. There was no one occurred radiation pneumonia. Prospective efficacy await further follow-up. Conclusion: Permanent implantation of I-125 seed in surgery for LANSCLC, is a safe and effective method with mild complications.
基金The study was supported by Natural Science Foundation of Zhejiang Province(LTGY23H010004)National Natu-ral Science Foundation of China(82370028)Development Project of Zhejiang Province’s“Jianbing”and“Lingyan”(2023C03067).
文摘Lung cancer is the second most common and the deadliest type of cancer worldwide.Clinically,non-small cell lung cancer(NSCLC)is the most com-mon pathological type of lung cancer;approximately one-third of affected patients have locally advanced NSCLC(LA-NSCLC,stage III NSCLC)at diag-nosis.Because of its heterogeneity,LA-NSCLC often requires multidisciplinary assessment.Moreover,the prognosis of affected patients is much below satisfac-tion,and the efficacy of traditional therapeutic strategies has reached a plateau.With the emergence of targeted therapies and immunotherapies,as well as the continuous development of novel radiotherapies,we have entered an era of novel treatment paradigm for LA-NSCLC.Here,we reviewed the landscape of relevant therapeutic modalities,including adjuvant,neoadjuvant,and periop-erative targeted and immune strategies in patients with resectable LA-NSCLC with/without oncogenic alterations;as well as novel combinations of chemora-diation and immunotherapy/targeted therapy in unresectable LA-NSCLC.We addressed the unresolved challenges that remain in the field,and examined future directions to optimize clinical management and increase the cure rate of LA-NSCLC.
文摘Objective: To observe the efficacy and safety of cetuximab combined with chemotherapy in advanced non-small-cell lung cancer (NSCLC), and to investigate the association of status of K-RAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome. Methods: Between Jan. 2006 and Sep. 2009, nineteen patients with advanced NSCLC received cetuximab (〉4 weeks) combined with chemotherapy in Department of Thoracic Oncology at Beijing Cancer Hospital. Response, survival and toxicity were retrospectively assessed, epidermal growth factor receptor (EGFR) protein expression was evaluated by ELISA Kit. The status of K-RAS gene mutation was tested by PCR-RFLP and EGFR gene amplification was measured by EGFR fluorescence in situ hybridization (FISH). Results: Partial response(PR) was observed in 26.3%(5/19) of the patients and stable disease(SD) in 52.6%(10/19). Median progression free survival(PFS) was 6 months (95% CI: 3.6-8.4). Median overall survival (MST) and 1-year survival rate(SR) were 10.6 months (95% CI: 6.6-14.6) and 47.6%, respectively. Mild or moderate skin rash was the most common toxicity related with cetuximab. K-RAS gene mutation, EGFR protein level and amplification have little correlation with prognosis. Conclusion: Cetuximab combined with chemotherapy was tolerable and the skin rash related with cetuximab was mild to moderate. Cetuximab may prolong survival of the patients who failed to previous chemotherapy.
基金supported in part by NIH/NCI 1R01CA264102-01(D.Z.)Wake Forest Comprehensive Cancer Center P30 CA01219740.A.A.H.is supported by funding from the Department of Veteran’s Affairs(No.2I01BX002559-07)from the National Institutes of Health(No.1R01CA244212-01A1).
文摘Despite therapeutic advancements,the prognosis of locally advanced non-small cell lung cancer(LANSCLC),which has invaded multiple lobes or the other lung and intrapulmonary lymph nodes,remains poor.The emergence of immunotherapy with immune checkpoint blockade(ICB)is transforming cancer treatment.However,only a fraction of lung cancer patients benefit from ICB.Significant clinical evidence suggests that the proinflammatory tumor microenvironment(TME)and programmed death-ligand 1(PD-L1)expression correlate positively with response to the PD-1/PD-L1 blockade.We report here a liposomal nanoparticle loaded with cyclic dinucleotide and aerosolized(AeroNP-CDN)for inhalation delivery to deep-seated lung tumors and target CDN to activate stimulators of interferon(IFN)genes in macrophages and dendritic cells(DCs).Using a mouse model that recapitulates the clinical LANSCLC,we show that AeroNP-CDN efficiently mitigates the immunosuppressive TME by reprogramming tumor-associated macrophage from the M2 to M1 phenotype,activating DCs for effective tumor antigen presentation and increasing tumor-infiltrating CD8+T cells for adaptive anticancer immunity.Intriguingly,activation of interferons by AeroNP-CDN also led to increased PD-L1 expression in lung tumors,which,however,set a stage for response to anti-PD-L1 treatment.Indeed,anti-PD-L1 antibody-mediated blockade of IFNs-induced immune inhibitory PD-1/PD-L1 signaling further prolonged the survival of the LANSCLC-bearing mice.Importantly,AeroNP-CDN alone or combination immunotherapy was safe without local or systemic immunotoxicity.In conclusion,this study demonstrates a potential nano-immunotherapy strategy for LANSCLC,and mechanistic insights into the evolution of adaptive immune resistance provide a rational combination immunotherapy to overcome it.
基金supported by the National Key R&D Program of China(No.2018YFC1313201)the Innovation Project of Shandong Academy of Medical Sciences(No.2019-04)the Academic Promotion Program of Shandong First Medical University(No.2019ZL002).
文摘Bevacizumab,an anti-VEGF monoclonal antibody,has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC(ns-NSCLC).However,the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation.Thus,59 patients were included in the present retrospective study,22 patients in the bevacizumab plus pemetrexed and platinum(B+PP)group,and 37 patients in the pemetrexed and platinum(PP)group.For the entire cohort of patients,the median OS was 33.3 months,and the 1-year and 2-year overall survival rates were 88.5%and 67.8%,respectively.The median OS and 1-year and 2-year OS rates were 20.5 months,70.3%and 0%,respectively,in the B+PP group and 33.4 months,97.0%and 89.4%,respectively,in the PP group(P<0.001).The incidence of grade≥3 adverse events was higher in the B+PP group than in the PP group(27.3%vs.10.8%,respectively;P=0.204).Univariate and multivariate analyses suggested that the receipt of≥5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS,whereas the addition of bevacizumab was an unfavorable prognostic factor.With increased toxicities,the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.
文摘Objective: In recent years, the combination of cetuximab and chemoradiotherapy (CRT) has been used to treat stage III non-small cell lung cancer (NSCLC); however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT (CCRT) in Chinese patients with stage III NSCLC. Methods: Eligibility criteria were Zubrod performance status (PS) 0-1, forced expiratory volume in 1 second (FEV1) 〉_1.2 L and adequate organ function. Enrolled patients received weekly cetuximab (initial dose of 400 mg/m2 on day 1 of week 1 and a maintenance dose of 250 mg/m2 on week 2 to the end of CCRT) with cisplatin/vinorelbine (NP) chemotherapy (every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy (TRT) (60-66 Gy/2 Gy). The primary endpoints were toxicity and feasibility. All patients received positron emission tomography- computerized tomography (PET-CT) scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node- metastasis (TNM) stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. Results: Seventeen patients were enrolled and 16 completed the full regime. The overall response rate (ORR) was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval (CI): 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% (95% CI, 60.6-96.9%) and 58.8% (95% CI, 60.6-77.8%), respectively. Three patients remain progression-free to date, and the median progression-free survival (PFS) was 13.5 months (95% CI, 6.8-20.2 months). No treatment-related death occurred; however, 76% of the patients experienced grade 3+ adverse events (AEs), including nansea/vomiting, intestinal obstruction, and esophagitis (〈6%), while other AEs were mostly of hematological nature (71%). The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL (P=0.027), SUV-T (P=0.025), and PS (P=0.006) as potential survival predictors, with a hazard ratio (HR) of 3.4, 3.7, and 9.9, respectively. Conclusions: The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by 18F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.
文摘Despite the aggressive pursuit of diagnostic and treatment modalities for lung cancer, the treatment outcomes are still not satisfactory, and even patients with surgically resectable non-small cell lung cancer (NSCLC) are often at considerable risk of suffering recurrence and/or death from lung cancer. Regarding the treatment of patients with locally advanced, resectable NSCLC, several retrospective and prospective studies have shown the significance of multimodality treatments with preoperative chemoradiotherapy and surgical treatment. However, no definitive treatment strategies for locally advanced NSCLC patients have yet been established. One of the reasons for the lack of established treatment strategies for patients with locally advanced NSCLC is considered to be the heterogeneity of the population, i.e., cT4N0, cT3-4N1 and cT1a-3N2 tumors are included in stage IIIA disease, and superior sulcus tumors (SSTs) are also included in this classification. With regard to SST, two representative prospective phase II trials indicated the efficacy of surgical treatment following concurrent radiation and chemotherapy. In a study conducted by the Southwest Oncology Group, 110 patients with superior sulcus NSCLC were treated with two cycles of cisplatin and etoposide concurrently with 45 gray (Gy) of radiation, followed by surgical treatment and two additional cycles of chemotherapy postoperatively. The response rate (RR) to the preoperative chemoradiotherapy was 86%, and 83 patients (76%) were able to undergo complete resection. A pathological complete response (CR) was observed in 61 patients (56%), and the five-year survival of all patients and those undergoing complete resection was 44% and 54%, respectively. A phase II study conducted by the Japan Clinical Oncology Group examined the safety and efficacy of preoperative concurrent chemoradiotherapy using mitomycin, vinblastin and cisplatin followed by surgical treatment. Seventy-six patients with SST were enrolled in this study, and all received chemotherapy using two cycles of MVP concurrently with 45 Gy of radiation, followed by surgery. Neoadjuvant chemoradiotherapy resulted in a 61% RR, and pathological complete resection was successfully achieved in 51 patients (68%). A pathological CR was observed in 12 patients (16%), and the disease-free and overall survival rates at five years were 45% and 56%, respectively. Both studies showed the efficacy and tolerability of the multimodality treatment for SST, thus suggesting that multimodality treatment with preoperative chemoradiotherapy followed by surgery may therefore be an effective treatment for resectable SST. We herein review the results of retrospective and prospective studies while assessing the treatment outcomes of NSCLC patients with SST.
基金The authors declare that they have no competing interests.We thank the patients and their families who participated in this studyThis work was supported by the National Natural Science Foundation of China(Grant No.81502667)the Shandong Provincial Natural Science Foundation(ZR2016HM35).
文摘Objective:Several studies have found that epigallocatechin-3-gallate(EGCG)can alleviate acute radiation-induced esophagitis,inhibit pulmonary inflammation and fibrosis,and reduce the severity of cardiovascular disease.Therefore,this study was aimed at exploring the influence of EGCG on late radiation toxicity in the heart,esophagus,and lungs among patients with locally advanced lung cancer.Methods:The patients were divided into an EGCG group and a control group,the groups received EGCG and symptomatic treatment,respectively.The Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme was used to determine the late toxicity scores.Tumor responses were evaluated by chest computed tomography(CT),based on the Response Evaluation Criteria in Solid Tumors version 1.1.Results:We retrospectively analyzed 74 patients treated at our hospital from September 2012 to September 2016(37 patients received EGCG and 37 received supportive treatment).The late toxicity scores of the EGCG group decreased compared to those of the control group.An obvious clinical significance was observed for the oral EGCG solution in the treatment and prevention of late cardiac,esophageal,and pulmonary toxicity.However,no significant difference was found(P>0.05).The tumor response rates were similar in the two groups.Moreover,there was no difference in progression-free survival(PFS)between the groups(P>0.05).Conclusion:Oral EGCG solution might alleviate radiation-induced late cardiac,esophageal,and pulmonary toxicity but has no significant effect on the tumor response rate and PFS following radiotherapy.