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.

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

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

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.

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.

Neoadjuvant vs adjuvant pelvic radiotherapy for locally advanced rectal cancer: Which is superior?

The treatment of locally advanced rectal cancer including timing and dosage of radiotherapy, degree of sphincter preservation with neoadjuvant radiotherapy, and short and long term effects of radiotherapy are controversial topics. The MEDLINE, Cochrane Library databases, and meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomized controlled trials and meta-analyses comparing neoadjuvant and adjuvant radiotherapy with surgery to surgery alone for rectal cancer. Neoadjuvant radiotherapy shows superior results in terms of local control compared to adjuvant radiotherapy. Neither adjuvant or neoadjuvant radiotherapy impacts overall survival. Short course versus long course neoadjuvant radiotherapy remains controversial. There is insufficient data to conclude that neoadjuvant therapy improves rates of sphincter preserving surgery. Radiation significantly impacts anorectal and sexual function and includes both acute and long term toxicity. Data demonstrate that neoadjuvant radiation causes less toxicity compared to adjuvant radiotherapy, and specifically short course neoadjuvant radiation results in less toxicity than long course neoadjuvant radiation. Neoadjuvant radiotherapy is the preferred modality for administering radiation in locally advanced rectal cancer. There are significant side effects from radiation, including anorectal and sexual dysfunction, which may be less with short course neoadjuvant radiation.

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.

Survival prognostic analysis of laparoscopic D2 radical resection for locally advanced gastric cancer: A multicenter cohort study

BACKGROUND With the development of minimally invasive surgical techniques,the use of laparoscopic D2 radical surgery for the treatment of locally advanced gastric cancer(GC)has gradually increased.However,the effect of this procedure on survival and prognosis remains controversial.This study evaluated the survival and prognosis of patients receiving laparoscopic D2 radical resection for the treatment of locally advanced GC to provide more reliable clinical evidence,guide clinical decision-making,optimize treatment strategies,and improve the survival rate and quality of life of patients.METHODS A retrospective cohort study was performed.Clinicopathological data from 652 patients with locally advanced GC in our hospitals from December 2013 to December 2023 were collected.There were 442 males and 210 females.The mean age was 57±12 years.All patients underwent a laparoscopic D2 radical operation for distal GC.The patients were followed up in the outpatient department and by telephone to determine their tumor recurrence,metastasis,and survival.The follow-up period ended in December 2023.Normally distributed data are expressed as the mean±SD,and normally distributed data are expressed as M(Q1,Q3)or M(range).Statistical data are expressed as absolute numbers or percentages;theχ^(2) test was used for comparisons between groups,and the Mann-Whitney U nonparametric test was used for comparisons of rank data.The life table method was used to calculate the survival rate,the Kaplan-Meier method was used to construct survival curves,the log rank test was used for survival analysis,and the Cox risk regression model was used for univariate and multifactor analysis.RESULTS The median overall survival(OS)time for the 652 patients was 81 months,with a 10-year OS rate of 46.1%.Patients with TNM stages II and III had 10-year OS rates of 59.6%and 37.5%,respectively,which were significantly different(P<0.05).Univariate analysis indicated that factors such as age,maximum tumor diameter,tumor diffe-rentiation grade(low to undifferentiated),pathological TNM stage,pathological T stage,pathological N stage(N2,N3),and postoperative chemotherapy significantly influenced the 10-year OS rate for patients with locally advanced GC following laparoscopic D2 radical resection for distal stomach cancer[hazard ratio(HR):1.45,1.64,1.45,1.64,1.37,2.05,1.30,1.68,3.08,and 0.56 with confidence intervals(CIs)of 1.15-1.84,1.32-2.03,1.05-1.77,1.62-2.59,1.05-1.61,1.17-2.42,2.15-4.41,and 0.44-0.70,respectively;P<0.05].Multifactor analysis revealed that a tumor diameter greater than 4 cm,low tumor differentiation,and pathological TNM stage III were independent risk factors for the 10-year OS rate in these patients(HR:1.48,1.44,1.81 with a 95%CI:1.19-1.84).Additionally,postoperative chemotherapy emerged as an independent protective factor for the 10-year OS rate(HR:0.57,95%CI:0.45-0.73;P<0.05).CONCLUSION A maximum tumor diameter exceeding 4 cm,low tumor differentiation,and pathological TNM stage III were identified as independent risk factors for the 10-year OS rate in patients with locally advanced GC following laparoscopic D2 radical resection for distal GC.Conversely,postoperative chemotherapy was found to be an independent protective factor for the 10-year OS rate in these patients.

Pemertrexed combined with cisplatin in the treatment of advanced non-small cell lung cancer:a case report and literature review

The aim of our study was to explore the value of second-line treatment for advanced non-small cell lung cancer (NSCLC). One patient with metastatic adenocarcinoma of NSCLC was given second-line treatment of pemertrexed/cisplatin. Follow-up was made to observe progression free survival (PFS) and survival time. She was given 4 cycles first-line treatment of recombinant human endostatin plus gemcitabine/cisplatin previously; the efficacy was CR and PFS was 10.2 months. After the 5th cycle treatment of pemetrexed/cisplatin, the efficacy of the primary tumor was CR, and bone metastases was stable. PFS was 6.6 months, and the patient has been survival for 22 months. Quality of life (QOL) of the patient was improved. When advanced NSCLC is recurrence or metastasis, starting second-line treatment of pemetrexed/cisplatin timely can prolong survival time and improve QOL.

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 1-125 seed in surgery for LANSCLC, is a safe and effective method with mild complications.

基于MRI影像组学构建PD-1/PD-L1抑制剂治疗dMMR/MSI-H直肠癌疗效的预测模型

目的:探讨MRI影像组学模型在程序性细胞死亡蛋白-1(PD-1)/程序性细胞死亡-配体1(PD-L1)抑制剂联合全程新辅助治疗(TNT)局部进展期直肠癌(LARC)的疗效预测价值。方法:收集河南中医药大学第一附属医院PD-1/PD-L1抑制剂联合TNT治疗的80例错配修复基因缺陷(dMMR)/微卫星高度不稳定(MSI-H)基因型中低位LARC患者的临床和影像资料。将入组患者按7∶3比例分为训练集和测试集,提取影像组学特征,从中筛选并构建影像组学模型。描绘影像组学模型的Rad-score与病理金标准之间的受试者工作特征(ROC)曲线,计算曲线下面积(AUC),并评价模型的诊断效能。采用决策曲线分析(DCA)计算风险阈值的范围,并评估临床获益情况。收集湖南省人民医院25例dMMR/MSI-H基因型LARC患者的影像资料作为外部验证集。结果:训练集、测试集及外部验证集三者之间的临床特征无统计学差异(P>0.05)。经过降维处理、t检验及一致性检验以及LASSO交叉验证后,筛选出一阶偏度特征和体积2个特征构建影像组学模型。训练集、测试集和外部验证集的影像组学预测模型ROC曲线的AUC、灵敏度、特异度、阳性预测值和阴性预测值分别为0.920、97.1%、85.7%、91.9%、94.7%;0.885、80.0%、88.9%、92.3%、72.7%;0.875、87.5%、88.9%、93.3%、80.0%。DCA曲线显示,当风险阈值范围为0%~82%时,采用影像组学模型预测LARC患者为病理完全缓解(pCR)的获益大于将所有患者都视为pCR或者无病理完全缓解(npCR)。结论:基于MRI影像组学构建的dMMR/MSI-H型局部进展期直肠癌PD-1/PD-L1抑制剂联合全程新辅助放化疗疗效预测模型,有较大潜力为不同基因分型的直肠癌患者制定个体化治疗策略提供量化依据。

新辅助抗PD-1免疫治疗联合放化疗治疗局部晚期非小细胞肺癌的临床疗效

目的研究新辅助抗PD-1免疫疗法与化疗结合放疗序贯治疗方案治疗局部晚期非小细胞肺癌的临床疗效与安全性。方法回顾性选取2021年3月至2022年3月江苏省肿瘤医院治疗的非小细胞肺癌患者80例。依据治疗方案不同分为研究组和对照组,每组各40例。研究组接受含新辅助抗PD-1疗法的综合放化疗,对照组仅接受标准放化疗。比较两组患者的实体瘤治疗客观缓解率、细胞免疫功能、血清肿瘤因子[癌胚抗原(CEA)、糖类抗原(CA)125、CA199]以及不良反应。结果研究组患者治疗后的客观缓解率为7.00%,明显高于对照组(52.50%),差异有统计学意义(P<0.05)。治疗后,研究组患者的CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)均较治疗前升高,对照组患者的CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)均较治疗前降低,且研究组患者的CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)分别为(64.33±5.16)%、(43.71±4.53)%、(32.54±3.91)%、1.34±0.26,均明显高于对照组[(55.25±5.63)%、(31.87±3.16)%、(28.24±3.89)%、1.13±0.31],差异均有统计学意义(P<0.05)。治疗后,两组患者的血清CEA、CA125、CA199水平均较治疗前降低,且研究组患者的血清CEA、CA125、CA199水平分别为(12.25±4.15)ng/mL、(31.55±5.78)U/mL、(56.62±8.52)U/mL,均明显低于对照组[(18.97±4.36)ng/mL、(38.17±5.81)U/mL、(65.20±8.79)U/mL],差异均有统计学意义(P<0.05)。两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论新辅助抗PD-1免疫治疗联合放化疗相比单纯放化疗对局部晚期非小细胞肺癌有更加明显的优势,能够提高放化疗过程中的机体免疫功能,减少血清肿瘤相关因子,同时没有增加明显的不良反应,可以作为非小细胞肺癌提升疗效的方案在临床中推广应用。

无化疗放射治疗联合免疫检查点抑制剂治疗局部晚期非小细胞肺癌的研究进展

对不可切除的局部晚期非小细胞肺癌(LA-NSCLC)患者,同步放化疗后维持免疫检查点抑制剂治疗仍是标准的治疗方案。部分LA-NSCLC患者因各种原因不适合化疗,表现在治疗方案选择中对无化疗方案的需求。近期研究表明,放射治疗联合免疫检查点抑制剂的治疗策略有良好协同效应和潜在治疗价值。本文主要对无化疗放射治疗联合免疫检查点抑制剂治疗不可切除的LA-NSCLC进行系统总结,有助于更好地了解该治疗模式的机制、优势和局限性,为临床实践提供更有针对性的指导。

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.

LAURA研究建立EGFR突变局部晚期NSCLC的新标准治疗

近年来由于胸部计算机体层摄影(computed tomography,CT)筛查的推广,初诊时局部晚期患者的比例明显增加,占非小细胞肺癌(non-small cell lung cancer,NSCLC)的30%[1]。对于不可切除局部晚期NSCLC,传统的标准治疗为根治性放化疗,其5年无进展生存(progression-free survival,PFS)仅为18.3%,5年总生存(overall survival,OS)为32.1%[2]。PACIFIC[3]与GEMSTONE-301[4]研究结果显示同期/序贯放化疗联合巩固免疫治疗对比单纯放化疗显著提高了患者生存,5年PFS可达33.1%,OS达42.9%[2],成为新的标准治疗。

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.