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.

Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report

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.

Palliative Treatment of Locally Advanced Non Metastatic Lung Cancer

Introduction: To determine the proportion and the reasons which lead to palliative treatment in patients initially a candidate for concomitant chemoradiotherapy (CCRT). Methods: 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. Results: 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 - 81] with 86% male. 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%), 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. Conclusion: 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, there is the need to improve the early diagnosis and early management of patients with lung cancer to avoid delayed care.

Effects of Yiqi Gu Ben Decoction combined with DC chemotherapy on serum tumor markers, inflammatory factors and immune function in patients with locally advanced non-small cell lung cancer

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.

Effects of combined treatment of bronchial arterial chemoembolization and radioactive particle implantation on tumor markers and T lymphocyte subsets in locally advanced non-small cell lung cancer

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.

Intraoperative permanent implantation of radioactive I-125 seed for local advanced non small lung cancer

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.

Management of locally advanced non-small cell lung cancer: State of the art and future directions

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.

Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment:A phase 2 clinical trial(BG01-1801)

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.

Aerosolized immunotherapeutic nanoparticle inhalation potentiates PD-L1 blockade for locally advanced lung cancer

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.

Feasibility of cetuximab and chemoradiotherapy combination in Chinese patients with unresectable stage Ⅲ non-small cell lung cancer:a preliminary report

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.

GNRI和CONUT评分对老年局部晚期NSCLC病人放疗后发生≥2级放射性肺炎的预测价值

目的分析老年营养风险指数(GNRI)和营养控制状况(CONUT)评分对老年局部晚期非小细胞肺癌(NSCLC)病人放疗后发生≥2级放射性肺炎(RP)的预测价值。方法选取2019年1月至2022年1月在我院接受放疗的Ⅲ期且年龄≥65岁的老年NSCLC病人81例,放疗后随访3个月,根据病人RP发生情况,将病人分为≥2级RP组(A组,25例)和<2级RP组(B组,56例)。收集病人临床资料和放疗剂量学参数,并计算病人放疗结束时的GNRI和CONUT评分。采用多因素Logistic回归分析老年局部晚期NSCLC病人放疗后发生≥2级RP的影响因素,应用ROC曲线分析GNRI和CONUT评分对≥2级RP的预测价值。结果A组双肺V20(双肺接收>20 Gy剂量照射的肺体积百分比)高于B组(P<0.05);放疗结束时A组GNRI低于B组,CONUT评分高于B组(P<0.05)。多因素Logistic回归分析显示,放疗结束时低GNRI(OR=0.821,95%CI:0.717~0.941)和高CONUT评分(OR=3.653,95%CI:1.944~6.886)是老年局部晚期NSCLC病人放疗后发生≥2级RP的独立危险因素(P<0.01)。ROC曲线分析结果提示,GNRI和CONUT评分预测老年局部晚期NSCLC病人放疗后发生≥2级RP的截断值分别为94.22和4.5分,AUC分别为0.785和0.894;两者联合预测的AUC为0.925,敏感度为0.840,特异度为0.929。结论放疗结束时低GNRI和高CONUT评分是老年局部晚期NSCLC病人放疗后发生≥2级RP的独立危险因素,且两者单独或联合评估对其均具有一定预测价值。

Significance of Multimodality Therapy in Patients with a Superior Sulcus Tumor of the Lung: A Review Article

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.

局部晚期非小细胞肺癌新辅助免疫治疗后单孔胸腔镜手术的应用价值探究

目的探究局部晚期非小细胞肺癌患者接受新辅助免疫治疗后应用单孔胸腔镜手术的价值。方法选取2021年1月—2022年9月启东市人民医院收治的102例局部晚期非小细胞肺癌患者作为研究对象,通过随机数字表法分为对照组(新辅助免疫治疗+传统三孔胸腔镜手术)、治疗组(新辅助免疫治疗+单孔胸腔镜手术),各51例。观察围术期相关指标及疗效。结果相较于对照组,治疗组手术时长更短、术中出血量更少、引流管拔除时间更早、住院时间更短、切口总长度更短、术中总引流量更少,差异有统计学意义(t=3.195、3.493、7.248、5.240、24.622、2.734,P<0.05)。治疗组临床治疗客观有效率(86.27%)明显高于对照组(66.67%),差异有统计学意义(χ^(2)=5.449,P=0.020)。结论局部晚期非小细胞肺癌患者新辅助免疫治疗后单孔胸腔镜手术的应用价值显著,可缩短手术时间、引流管拔除时间、住院时间,减少术中出血量、术中总引流量,切口总长度更短,临床疗效随之提高。

尼妥珠单抗联合同期放化疗治疗表皮生长因子受体阳性局部晚期非小细胞肺癌患者的疗效和安全性分析

目的 探讨尼妥珠单抗联合同期放化疗治疗表皮生长因子受体(EGFR)阳性局部晚期非小细胞肺癌(NSCLC)患者的疗效和安全性。方法 根据治疗方法的不同将84例EGFR阳性局部晚期NSCLC患者分为对照组(n=41,同期放化疗治疗)和联合组(n=43,尼妥珠单抗联合同期放化疗治疗)。比较两组患者的临床疗效、不良反应发生情况及生存情况。结果 联合组患者的总有效率为72.09%,高于对照组患者的46.34%,差异有统计学意义(P﹤0.05)。两组患者胃肠道反应、皮肤溃疡不愈合、皮下组织缺血、肝肾功能损伤、骨髓抑制发生率比较,差异均无统计学意义(P﹥0.05)。联合组患者的2年生存率为83.72%,高于对照组患者的58.54%,差异有统计学意义(P﹤0.05)。结论 尼妥珠单抗联合同期放化疗治疗EGFR阳性局部晚期NSCLC患者的疗效确切,可提高患者的生存率,且安全性较佳,值得临床进一步推广应用。

免疫治疗时代ⅢA/B期非小细胞肺癌的治疗:放疗视角

近年来,免疫治疗的研究进展使非小细胞肺癌(non-small-cell lung cancer,NSCLC)的治疗格局日新月异。因此,如何在免疫治疗的辅助下进一步优化放疗以提高局部控制是临床医师需要关注的问题。本文总结不可手术的局部晚期NSCLC(locally advanced NSCLC,LA-NSCLC)放疗的研究现状,探讨优化放疗与免疫治疗的相关研究进展,并阐述通过放疗技术、靶区勾画、淋巴结照射、亚临床病灶照射、射线选择、剂量分割和放疗搭档等的进一步优化以提升LA-NSCLC治疗疗效。总体而言,在免疫治疗时代,放疗将凸显其优势作用,有待更多大型的临床研究作进一步探索。

卡瑞利珠单抗联合放化疗对局部晚期非小细胞肺癌患者生存预后的影响

目的 探讨卡瑞利珠单抗(Cam)联合放化疗对局部晚期非小细胞肺癌(NSCLC)患者血清程序性细胞死亡受体1(PD-1)、胸苷激酶1(TK1)、基质金属蛋白酶9(MMP-9)和生存预后的影响。方法 选取2018年6月—2020年6月徐州医科大学附属宿迁医院收治局部晚期NSCLC患者60例,并按照随机数表法分为研究组和对照组,每组各30例。研究组采取Cam联合放化疗治疗,对照组采取放化疗治疗,比较两组患者近期疗效情况和治疗前、治疗3个月时T细胞亚群(CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+))和血清PD-1、TK1、MMP-9水平,Kaplan-Meier法分析患者1年生存情况,记录不良反应。结果 治疗3个月时,研究组患者的疾病控制率(86.67%)、客观缓解率(53.33%)均高于对照组(63.33%、26.67%)(P<0.05);两组患者CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)较治疗前均呈升高趋势,且研究组高于对照组(P<0.05);血清PD-1、TK1、MMP-9水平较治疗前均呈降低趋势,且研究组低于对照组(P<0.05);两组患者1年疾病无进展生存期比较差异有统计学意义(Log-rankχ^(2)=4.040,P=0.040);两组患者治疗过程中不良反应比较,差异均无统计学意义(P>0.05)。结论 Cam联合放化疗提高局部晚期NSCLC近期疗效和免疫功能,降低血清PD-1、TK1、MMP-9水平,改善患者预后,安全性好。

局部晚期肺癌放疗中还原型谷胱甘肽对放射性肺炎的影响

目的探究肺部局部晚期放疗中应用还原型谷胱甘肽对放射性肺炎的影响。方法采取随机数表法将南通大学附属如皋医院2017年1月—2020年12月收治的80例晚期肺癌患者分为两组,一组采取单纯调强适形或三维适形放疗,另一组在上述基础上采取还原型谷胱甘肽治疗,前者为对照组,后者为研究组。观察两组不良反应发生率、放射性肺炎发生时间及发生率及相关炎症介质水平变化情况。结果研究组不良反应发生率为15.00%,低于对照组40.00%,差异有统计学意义(χ^(2)=6.270,P<0.05)。研究组放射性肺炎发生率为10.00%,低于对照组30.00%,差异有统计学意义(χ^(2)=5.000,P<0.05)。研究组放射性肺炎发生时间为(76.37±9.56)d,晚于对照组,差异有统计学意义(t=14.781,P<0.001)。治疗后,研究组白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)水平为(61.22±10.14)、(52.48±9.49)、(3996.75±246.73)pg/mL,低于对照组,差异有统计学意义(t=5.221、8.522、11.137,P<0.05);研究组血管紧张素转化酶(ACE)水平为(774.36±135.29)pg/mL,高于对照组,差异有统计学意义(t=6.832,P<0.001)。结论对接受放疗的晚期局部肺癌患者应用还原型谷胱甘肽可改善毒副作用,减轻炎症反应,降低放射性肺炎发生率,延迟放射性肺炎发生时间,值得大力推广和引用。

DCE-MRI联合DWI在局部晚期肺癌合并肺不张患者放疗中的应用

目的:探讨动态对比增强磁共振成像(DCE-MRI)联合弥散加权成像(DWI)在局部晚期肺癌合并肺不张患者放疗中的应用价值。方法:本研究为前瞻性研究,纳入萍乡赣西肿瘤医院2020年6月—2022年6月收治的70例局部晚期肺癌合并肺不张患者,采用随机数字表法分为研究组(n=35)和对照组(n=35)。对照组基于DWI图像勾画放疗靶区,研究组基于DCE-MRI联合DWI图像勾画放疗靶区,所有患者均施行三维适形调强放疗。比较两组患者大体肿瘤体积(GTV)、近期疗效、肺复张情况、放射性并发症发生率。结果:放疗前,研究组GTV小于对照组(P<0.05)。两组客观缓解率(ORR)、疾病控制率(DCR)比较,差异均无统计学意义(P>0.05)。研究组肺复张率高于对照组,放射性食管炎发生率低于对照组(P<0.05)。结论:DCE-MRI联合DWI指导三维适形调强放疗能够提高放疗靶区勾画的精准度,提高局部晚期肺癌合并肺不张患者放疗后的肺复张率,减少放射性食管炎发生。

免疫治疗联合放射性^(125)I粒子植入治疗晚期肺癌患者的临床疗效

目的探讨免疫治疗联合放射性^(125)I粒子植入治疗晚期肺癌患者的临床疗效。方法采用区组随机法将50例局部晚期肺癌患者分为对照组和研究组,每组25例,对照组患者给予放射性^(125)I粒子植入治疗,研究组患者给予放射性^(125)I粒子植入联合卡瑞利珠单抗治疗。比较两组患者的主要观察终点(肿瘤直径、随访1年的无进展生存期)、次要终点[不良事件、客观缓解率(ORR)、疾病控制率(DCR)]。结果研究组患者的ORR、DCR为80.00%、96.00%,与对照组患者的88.00%、100%比较,差异均无统计学意义(P﹥0.05)。接受^(125)I粒子植入治疗的25例对照组患者,均未发生不良事件。接受^(125)I粒子植入联合免疫治疗的25例研究组患者中,任意级别免疫相关不良事件(irAE)的发生率为88.00%,其中1~2级irAE发生率为84.00%,3~5级irAE发生率为4.00%,所有级别最常见irAE为乏力,发生率为44.00%。截至随访结束,对照组患者的中位无进展生存期为3.00个月(95%CI:2.543~3.457),明显短于研究组患者的8.00个月(95%CI:5.552~10.448),差异有统计学意义(P﹤0.01)。治疗后,研究组患者的肿瘤直径小于本组治疗前和对照组,差异均有统计学意义(P﹤0.05)。结论卡瑞利珠单抗联合放射性^(125)I粒子植入治疗,可以延长晚期肺癌患者的中位无进展生存期,减小肿瘤直径。

局部晚期肺癌三维适型放射治疗和调强放射治疗的剂量学比较

目的比较对局部晚期肺癌患者分别采用三维适型放疗(3D-conformal radiotherapy,3D-CRT)与调强放疗(intensity modulated radiation therapy,IMRT)的临床疗效,分析其对剂量学参数、免疫功能所产生的影响。方法选取2020年1月—2020年12月金乡县人民医院肿瘤科诊治的22例局部晚期肺癌患者作为研究对象,按照随机数表法分为A组和B组,各35例,A组给予IMRT,B组给予3D-CRT,对比两组临床疗效、剂量学参数及免疫因子水平、不良反应发生情况。结果两组治疗总有效率、治疗后CD3^(+)CD8^(+)、CD3^(+)CD4^(+)T细胞水平及平均剂量对比,差异无统计学意义(P>0.05)。A组剂量学中的适形指数(conformity index,CI)、异质性指数(heterogeneity index,HI)较B组高,差异有统计学意义(P<0.05)。A组治疗期间不良反应发生率较B组低,差异有统计学意义(P<0.05)。结论针对局部晚期肺癌患者,采用IMRT、3D-CRT皆可获得良好效果,而IMRT能够优化肿瘤靶区剂量,提高靶区适形度,且不良反应更少。