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.

Clinical observation of gemcitabine and concomitant three-dimensional conformal radiotherapy in the treatment of locally advanced non-small cell lung cancer

Objective： To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy （3D-CRT） for locally advanced non-small cell lung cancer （NSCLC）. Methods： From April 2002 to June 2005, 38 patients with inoperable stage Ⅲ NSCLC were treated with gemcitabine and 3D-CRT simultaneously. Chemotherapy consisted of intravenously gemcitabine 350 mg/m^2 on days 1, 8, 15, 22, 29, 36.3D-CRT was delivered up to a total dose of 60-64 Gy with a 2.0 Gy dose fraction per day, 5 days per week. Results： The overall response rates of primary tumor and mediastinum metastatic node were 86.8% （33/38） and 90.6% （29/32） respectively, and 91.7% （22/24） and 78.6% （11/14） for squamous cell carcinoma and adenocarcinoma respectively. The acute side effects of patients were mostly myelosuppression, nausea, vomiting, radiation-induced esophagitis and pneumonitis （RTOG 1/11）, however, all of them were cured. Conclusion： Concurrent application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.

Effect of intensity modulated radiation therapy combined with paclitaxel+ endostar chemotherapy on serum malignant molecule levels in patients with locally advanced non-small cell lung cancer

Objective: To discuss the effect of intensity modulated radiation therapy combined with paclitaxel + endostar chemotherapy on serum malignant molecule levels in patients with locally advanced non-small cell lung cancer. Methods: Patients with locally advanced NSCLC who were treated in the hospital between February 2015 and January 2017 were collected and divided into control group (n=59) and research group (n=59) by random number table. Control group received the routine paclitaxel + endostar chemotherapy after the operation, and research group underwent intensity modulated radiation therapy combined with paclitaxel +endostar chemotherapy after the operation. The differences in serum levels of NSCLC-related tumor markers and angiogenesis indexes were compared between the two groups before and after treatment. Results: Before treatment, the differences in serum levels of NSCLC-related tumor markers and angiogenesis indexes were not statistically significant between the two groups. After treatment, serum TK1, CYFRA21-1, Pro-GRP, CEA, CA125 and SCC-Ag levels of research group were lower than those of control group;serum EGFR, COX-2, VEGF, HIF-1 and MMP-2 levels of research group were lower than those of control group. Conclusion:Postoperative intensity modulated radiation therapy combined with paclitaxel + endostar chemotherapy can effectively reduce the serum malignant molecule levels and optimize the illness in patients with local advanced NSCLC.

Clinical analysis of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer

Objective:The purpose of this study was to assess the curative effect and adverse reaction of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer(NSCLC).Methods:This prospective randomized controlled trial included 115 patients with locally advanced NSCLC were randomly divided into experimental and control groups and were treated from January 2007 to January 2010.The experimental group of 63 cases was treated with two cycles of induction chemotherapy before operation,radical surgery had been performed about three weeks after completion of chemotherapy,followed by received two cycles of chemotherapy.And the control group(52 cases) was treated at first with radical surgery,then treated with four cycles of chemotherapy.Two groups of the cases received routine thoracic radiotherapy with a total dose of 45 Gy.One cycle of gemcitabine combined with cisplatin regimen included gemcitabine 1000 mg/m2 on day 1 and day 8 and cisplatin 25 mg/m2 on day 1,day 2 and day 3 by intravenous infusion,with 21 days as one cycle.The tumor recurrence was evaluated by chest CT and abdominal B-ultrasound.Efficacy and toxicity results were compared by two groups.Results:All patients were followed up for three months to two years.The surgical stage of the experimental group reduced,two-years disease-free survival and postoperative recovery in the experimental group were better than in the control group,the difference was statistical significant.Toxicity and side effect after chemotherapy were mainly bone marrow suppression and gastrointestinal reactions,other complications included thrombocytopenia,leukopenia,anemia,liver and kidney dysfunction were no significant difference in two groups.Conclusion:Preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced lung cancer can reduce the surgical staging and extend the postoperative disease-free survival.

The effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer

Objective： The aim of the research was to study the effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer （NSCLC）. Methods： Twelve cases of stage III NSCLC in Tumor Radiotherapy Center of our hospital （the Affiliated Hospital of Medical College Qingdao University, China） were collected from July 2011 to July 2012; all patients were under 75 years old with clear pathology, measurable lesions and good personal statement. They were randomly divided into combined treatment group （D1 ＋ D2） and control group （D1）. The control group （D1） only received radiotherapy to the chest; combined treatment group （D1 ＋ D2） received low-dose splenic irradiation plus conventional dose irradiation. Flow cytometry was used to detect the peripheral blood T lymphocyte immune indexes of patients before, during and after the treatment, classification by five blood cell analyzer was used to determine white blood cells, neutrophils, hemoglobin and platelet count. The radiation induced toxicity including esophagitis, pneumonia and gastrointestinal reaction was observed, as well as the dose when it happened. Results： There was no significant difference in the ratio between two groups in cells CD4＋, CD8＋ and CD4＋/CD8＋ after radiotherapy （P 〉 0.05）. There was no change in these indicators in combined treatment group after treatment （P 〉 0.05）, but it decreased in control group （P 〈 0.05）. There was no significant difference in the incidences of radiation esophagitis, pneumonia, gastrointestinal reactions and bone marrow suppression between two groups （P 〉 0.05）, but the patients in combined treatment group seemed to tolerate high dose well （P 〈 0.05）. Conclusion： Low-dose splenic irradiation combined with radiotherapy to the chest can alleviate the injury degree of acute radiation induced the toxicity of locally advanced NSCLC patients, through affect the patient＇s immune function.

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.

Impact of Cardiac Dose on Overall Survival in Lung Stereotactic Body Radiotherapy (SBRT) Compared to Conventionally Fractionated Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)

Purpose: To examine possible association between heart irradiation and Overall Survival (OS) in lung SBRT patients and to compare observed associations with cardiac toxicity models previously derived in LA-NSCLC patient studies. Materials and Methods: 197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB-approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient specific covariates associated with OS. Heart dosimetry was represented by VD indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox models with patient specific covariates and single VD index per model was used to find a range of doses which were predictive for OS. A digital subdivision of the heart was further used to determine the spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while the fine subdivision divided heart into 64 segments. Knowledge constrained Fused Lasso operator was used to derive a more complete model which correlated heart dosimetry with OS. Results of statistical analysis were compared to predictions of a model of cardiac toxicity in LA-NSCLC patients. Results: Higher age (p < 0.001), higher stage (p < 0.001) and squamous cell histology (p = 0.001) were associated with reduced OS. Whole heart DVH analysis did not reveal associations between heart irradiation and reduced OS. Coarse subdivision of the heart into four segments revealed that the irradiation of two inferior segments of the heart with low doses was associated with reduced OS, V2Gy in the right-inferior segment (HR = 1.012/1%, p = 0.02), and V1Gy in the left-inferior segment (HR = 1.01/1%, p = 0.04). Maximum dose in the right-inferior segment of the heart was also associated with reduced OS (HR = 1.02/Gy, p = 0.02). Fine subdivision of the heart into 64 segments revealed that approximately 25% of heart volume in the inferior part of the heart (15/64 segments), when irradiated to doses in the 1 Gy - 5 Gy range, were predictive for reduced OS (HR = 1.01/1%, p = 0.01). A previously derived model of cardiac toxicity in LA-NSCLC patients did not predict a reduction of OS due to heart irradiation in lung SBRT patients, because of relatively low doses to the heart in most lung SBRT patients. Conclusions: Doses lower than 5 Gy in the inferior segments of the heart may be associated with reduced overall survival in patients treated for lung lesions with SBRT. Stage and histology of the disease, as well as patients’ age, were also associated with overall survival. Comparisons of cardiac toxicity patterns in LA-NSCLC patients and lung SBRT patients suggest different etiology of cardiac toxicity in the two groups.

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 dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

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

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

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy

BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.