Feasibility and long-term outcomes of post-chemotherapy-based consolidation radiotherapy in extensive stage small-cell lung cancer

Background:The target definition of consolidation radiotherapy(RT)for extensive stage small-cell lung cancer(ES-SCLC)has not been standardized.This study aimed to demonstrate the feasibility of post-chemotherapy based consolidation RT in ES-SCLC.Methods:All ES-SCLC patients without initial brain metastases who completed≥4 cycles of systemic therapy at Department of Radiation and Medical Oncology,Zhongnan Hospital of Wuhan University from 2012 to 2021 were included in this retrospective study.We correlated the site of first recurrence to the post-chemotherapy-based radiation volume(small-field).Relapse pattern,progression-free survival(PFS)and overall survival(OS)were compared between those received and did not receive consolidation RT.Results:A total of 152 patients were followed up for a median of 31.7 months(interquartile range[IQR],23.9-39.6 months).The median PFS and OS of the cohort were 8.3 months(IQR,6.1-11.2 months)and 16.2 months(IQR,9.9-24.9 months),respectively.Thoracic consolidation RT served not only as an independent prognostic factor for improved PFS in the entire cohort,but also significantly prolonged OS in the subgroup without syn-chronous liver metastases.Small-field consolidation RT markedly reduced in-field recurrences(hazard ratio[HR],0.28[95%CI,0.12-0.38];P<0.001)without increasing out-of-field recurrences(HR,0.40[95%CI,0.13-1.16];P=0.080).No relapse was observed at the margin of the targets.Treatment-related toxicities were moderate,with grade 3 acute radiation pneumonia,radiation esophagitis,and bone marrow suppression rates of 8.3%,3.1%,and 12.5%,respectively.No grade 5 toxicity occurred.Conclusion:Small-field consolidation RT based on post-chemotherapy volume is safe and can significantly im-prove local control in ES-SCLC.

Influence of tumor response on the survival of patients with extensive-stage small-cell lung cancer treated with the etoposide plus cisplatin chemotherapy regimen

Objective In this study, we evaluated the difference of progression-free survival （PFS） and overall survival （OS） between extensive-stage small-cell lung cancer （ES-SCLC） patients who acquired partial response （PR） or complete remission （CR） after two cycles of first-line chemotherapy with the etoposide plus cisplatin （EP） regimen and those who acquired PR or CR after four or six cycles. Methods A total of 106 eligible patients treated with the EP chemotherapy regimen for two to six cycles, at The General Hospital of Shenyang Military Region （China） between November 2004 and Way 2011, were enrolled in this study. RECIST version 1.1 was used for the evaluation of chemotherapy efficiency. We followed up all eligible patients every 4 weeks. All statistical data were analyzed by using SPSS 21.0 statistical package for Windows. Results After a median follow-up of 293 days （range, 62-1531 days）, all patients had died by the cutoff date. Fifty-one patients acquired PR or CR after two cycles of chemotherapy; the median PFS reached 6.0 months （95% CI, 5.1-6.9）, and the median OS was 10.5 months （95% CI, 8.6-12.4）. Twenty-eight patients acquired PR or CR after four or six cycles; the median PFS was 4.8 months （95% CI, 4.4-5.2）, and the median OS was 7.5 months （95% CI, 6.8-8.2）. Both PFS and OS showed a statistical difference between the two groups. Conclusion ES-SCLC patients who acquired PR or CR after two cycles of the EP regimen as first-line therapy had longer PFS and OS than those who acquired PR or CR after four or six cycles.

Incorporation of circulating tumor cells and whole-body metabolic tumor volume of 18F-FDG PET/CT improves prediction of outcome inⅢB stage small-cell lung cancer

Objective: We investigated the correlation between the number of circulating tumor cells(CTCs) and wholebody metabolic tumor volume(WBMTV) measured by 18 F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT).The aim was to evaluate the value of the incorporation of CTC number and WBMTV in the prognostic prediction of stage III small-cell lung cancer(SCLC).Methods: One hundred and twenty-nine patients were enrolled in this study.All patients were treated with four cycles of a platinum-based regimen and concurrent chest irradiation,followed by prophylactic cranial irradiation.Blood samples for CTC analysis were obtained from 112 patients before the initiation of chemotherapy(as a baseline),after cycle 1 and after cycle 4.CTCs were measured using the CELLSEARCH? system.The patients underwent pretreatment FDG PET/CT WBMTV,which included all malignant lesions.The Spearman rank test was used to determine the correlation among CTC counts,WBMTV and disease stage.Overall survival(OS) and progression-free survival(PFS) curves were produced using the Kaplan-Meier method,and survival differences between groups were assessed by the log-rank test.Results: The number of CTCs at baseline did not correlate with WBMTV before the initiation of therapy(P=0.241).The number of CTCs at baseline and the WBMTV before the initiation of therapy were independent relevant factors for PFS and OS.The subgroup analysis(Group A: CTC count >19.5 and a WBMTV >266.5cm~3;Group B: CTC count >19.5 and a WBMTV ≤266.5cm~3; Group C: CTC count ≤19.5 and a WBMTV >266.5cm~3;Group D: CTC count ≤19.5 and a WBMTV ≤266.5cm~3) showed that the differences were statistically significant in the median PFS(Group A vs.D,P<0.001; Group B vs.D,P=0.018; Group C vs.D,P=0.029) and in the median OS(Group A vs.D,P<0.001; Group B vs.D,P=0.012).Conclusions: CTC number and WBMTV are related to progression and death in patients with SCLC.The incorporation of CTC number and WBMTV scans can provide a detailed prognostic prediction for SCLC.

Prognostic value of chemotherapy-induced leukopenia in small-cell lung cancer

Objective: Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and whether it is associated with the survival of SCLC patients. Methods: A retrospective analysis was conducted on data from 445 patients with SCLC who received standard chemotherapy for 4 to 10 cycles. The World Health Organization grading system classifies leukopenia during chemotherapy as follows: absent (grade 0), mild (grades 1 and 2), or severe (grades 3 and 4). The primary endpoint is overall survival (OS). Results: The association between chemotherapy-induced leukopenia and OS was assessed. According to a multivariate Cox model with time-varying covariates, the hazard ratio of death was significantly lower among patients with mild leukopenia than among patients with severe leukopenia at 0.687 (0.506 to 0.943) and 1.414 (1.147 to 1.744), respectively. The median survival was 13 months (95% CI: 11 to 15 months) for patients who did not experience leukopenia, 17 months (95% CI: 14 to 18 months) for those with mild leukopenia, and 14 months (95% CI: 13 to 16 months) for those with severe leukopenia (absent vs. mild vs. severe leukopenia, P=0.047). Conclusion: Leukopenia during chemotherapy is associated with the survival of SCLC patients. Mild leukopenia is strongly associated with longer survival time.

Randomized comparison of lobaplatin plus etoposide and cisplatin plus etoposide chemotherapy in patients with extensive-stage small cell lung cancer

Objective： To compare the efficacy and safety of Lobaplatin plus Etoposide （EL） and Cisplatin plus Etoposide （EP） regimens in chemonaive with extensive-stage small-cell lung cancer （SCLC）. Methods： Between July 2010 and July 2011, a total of 62 patients with extensive-stage small-cell lung cancer who received initial treatment in our hospital and 309 hospital of PLA. 31 patients were randomly assigned to the EL Group： Lobaplatin was given intravenously at a dose of 30 mg/m2 on day 1 and Etoposide 100 mg/m2 on days 1 to 3 of 21-day cycles for a maximum of six cycles. Another 31 patients were assigned to the EP Group： Cisplatin was given intravenously at a dose of 75 mg/m2 on day 1 and Etoposide 100 mg/m2 on days 1 to 3 of 21-day cycles for a maximum of six cycles. We evaluated the efficacy, overall response rate （ORR）, disease control rate （DCR）, the progression-free survival （PFS） and toxicity between the patients of the two groups. Results： All 62 patients were eligible. In the EL group, 2 （6.5%） patients had complete response, 20 （64.5%） patients had partial response, 5 （16.1%） patients had stable disease and 4 （12.9%） patients had progress disease. In the EP group, 2 （6.5%） patients had complete response, 22 （70.9%） patients had partial response, 4 （12.9%） patients had stable disease and 3 （9.7%） patients had progress disease. The ORR of EL and EP group were 70.9% and 77.4%, respectively, showing no significant difference （P = 0.562）. The DCR of both groups were 87% and 90%, respectively, showing no significant difference （P = 0.688）. Median PFS of patients with EL and EP regimens were 5.5 months and 5 months, respectively, showing no significant difference （P = 0.637）. Adverse events were observed in all 62 patients. Grade 1 to 4 anemia was higher in the EP group than in EL group, showing significant difference （P = 0.02）. Grade 3 and 4 thrombocytopenia was seen in 4 patients （12.9%） in EL group and 1 patient （3.2%） in EP group. Although one patient had platelet transfusion owing to Grade 4 thrombocytopenia in EL group, no significant difference （P = 0.637） were shown. The incidence of nausea/vomiting was higher in the EP group than in the EL group （96.7% vs 51.6%, P = 0.00）. Conclusien： The EL regimen is an effective and low-toxicity chemotherapy and no inferior to EP regimen in treatment response, therefore, EL regimen maybe is a good choice for patients with extensive-stage SCLC.

Peripheral blood indices to predict PFS/OS with anlotinib as a subsequent treatment in advanced small-cell lung cancer

Objective:In the phase II ALTER-1202(NCT03059797)trial,anlotinib significantly improved progression-free survival(PFS)and overall survival(OS)in patients with advanced small-cell lung cancer(SCLC)who underwent at least 2 previous chemotherapy cycles,when compared with a placebo group.To identify potential factors for predicting efficacy and prognosis with anlotinib treatment,we analyzed hematological indices at baseline and adverse events(AEs)over the course of anlotinib treatment.Methods:Data were collected from March 2017 to April 2019 from a randomized,double-blind,placebo-controlled,multicenter,phase II trial of anlotinib.Eligible patients were randomly assigned 2:1 to receive anlotinib or placebo until disease progression,intolerable toxicity,or withdrawal of consent.The patients received anlotinib(12 mg)or an analogue capsule(placebo)orally once daily for 14 days every 3 weeks.The hematological indices at baseline and AEs that occurred in the initial 2 treatment cycles were recorded.The Kaplan-Meier test and Cox regression model were used to assess survival differences.Results:A total of 82 patients(81 patients with complete data)were randomly assigned to receive anlotinib,with 38 receiving a placebo as a control.Multivariate analysis indicated that an elevated neutrophil to lymphocyte ratio>7.75 and lactate dehydrogenase>254.65 U/L at baseline were independent risk factors for PFS;basal elevated aspartate aminotransferase>26.75 U/L,neuron specific enolase>18.64 ng/mL,and fibrinogen>4.645 g/L were independent risk factors for OS.During treatment,elevatedγglutamyltransferase and hypophosphatemia were independent predictors for a poor PFS,and elevatedγ-glutamyl transferase and hypercholesterolemia were independent factors for OS.Conclusions:Our study preliminarily defined potential factors that affected the PFS and OS at baseline and during anlotinib treatment in patients with advanced SCLC.Our findings provide a basis for screening the dominant population and for dynamic efficacy monitoring with anlotinib therapy.

Progress in the diagnosis and treatment of extensive-stage small cell lung cancer

Lung cancer, being the most common cancer type, accounts for 13% of all newly diagnosed malignant tumors globally each year. Small cell lung cancer(SCLC) accounts for approximately 15% of newly diagnosed lung cancers each year, but its annual death toll accounts for 25% of that of lung cancer. We summarized relevant clinical studies to elaborate the epidemiology, pathological and clinical characteristics and the treatment status of small cell lung cancer. This paper first described the epidemiology and the pathological and clinical characteristics of SCLC and the systematic treatment of extensive-stage SCLC and then introduced the current targeted therapy and immunotherapy for SCLC to provide clinicians and patients with a more systematic, comprehensive, and beneficial treatment regimen. We expect that these studies can provide clinicians with a clear direction in molecularly targeted therapy or immunotherapy, so that a treatment approach with better antitumor effects and longer-lasting clinical benefits can be provided to the patients.

Histology transformation-mediated pathological atypism in small-cell lung cancer within the presence of chemotherapy:A case report

BACKGROUND The treatment of small-cell lung cancer(SCLC)has progressed little in recent years because of its unique biological activities and complex genomic alterations.Chemotherapy combined with radiotherapy has been widely accepted as the firstline treatment for SCLC.CASE SUMMARY Here,we present a 68-year-old male smoker who was diagnosed with SCLC of the right lung.After several cycles of concurrent chemoradiotherapy,the tumor progressed with broad metastasis to liver and bone.Histopathological examination showed an obvious transformation to adenocarcinoma,probably a partial recurrence mediated by the chemotherapy-based regimen.A mixed tumor as the primary lesion and transformation from SCLC or/and tumor stem cells may have accounted for the pathology conversion.We adjusted the treatment schedule in accord with the change in phenotype.CONCLUSION Although diffuse skeletal and hepatic metastases were seen on a recent computed tomography scan,the patient is alive,with intervals of progression and shrinkage of his cancer.

Changes in tumor-antigen expression profile as human small-cell lung cancers progress

Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein （TAPP）. We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. Methods： SCLC samples （eight surgical resections and three autopsy samples） and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Results： Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of PS3-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Conclusion： Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

¹⁸FDG-PET/CT Is a Useful Tool in Staging Procedure before Chemo-Radiotherapy in Patients with Limited Disease Small-Cell Lung Cancer. Pattern of Failure and Survival Is Analyzed

Background: The purpose of this study was to evaluate the use of 18FDG-PET/CT in staging procedure, the pattern of failure and survival in patients with small-cell lung cancer limited disease (LD-SCLC) undergoing chemo-radiotherapy. Methods: A total of 79 LD-SCLC patients were treated with a combination of chemotherapy and chest radiotherapy. Radiotherapy of the tumour and the pathological lymph nodes was performed either as 45 Gy twice-daily or 46 - 50 Gy once-daily. 18Fluro-2-deoxy-D-glucose (18FDG)-PET/CT was performed in 35 patients as part of the staging procedure. Results: With a median follow-up time of 17 months 6% developed isolated loco-regional failures while 57% developed distant metastases. No isolated regional failures were seen. Median overall survival was 22 months. Patients staged with a 18FDG-PET/CT had a significantly lower incidence of distant failures and a significantly improved overall survival compared with patients only staged with a CT scan (p = 0.03) (median overall survival of 34 versus 17 months, respectively). Conclusion: The pattern of failure showed a high risk of distant metastases but a low incidence of isolated loco-regional failures. Patients staged with an 18FDG-PET/CT had a significantly lower incidence of distant failures and better overall survival, indicating that 18FDG-PET could be beneficial in patients with LD-SCLC before deciding on treatment regimen.

Prognostic factors for the survival of 66 cases with extensive stage-small cell lung cancer

Objective The objective of this retrospective study was to investigate the prognostic factors associated with survival among patients with extensive stage-smal cel lung cancer （ES-SCLC）. Methods Clinical data from 66 patients with ES-SCLC diagnosed via histopathology or cytology between July 2005 and July 2009 at Anyang Tumor Hospital （China） were analyzed. Univariate and multivariate Kaplan-Meier, log-rank, and Cox proportional hazard regression analyses were conducted. Results The 12-, 24-, and 36-month survival rates among patients with ES-SCLC were 40.9%, 13.6%, and 6.1%, respectively. The median survival time （MST） was 10 months. Univariate analyses indicated that weight loss, eficacy of first-line chemotherapy, total number of chemotherapy cycles, treatment meth-od, and serum sodium levels significantly influenced survival among patients with ES-SCLC. Multivariate analyses suggested that the eficacy of first-line chemotherapy, total number of chemotherapy cycles, and serum sodium levels were independent prognostic factors associated with survival. Conclusion The eficacy of first-line chemotherapy, total number of chemotherapy cycles, and serum sodium levels are important prognostic factors for patients with ES-SCLC.

Resection of Lung Cancer with Left Atrium Extension via the Pulmonary Vein: Case Report

A 49-year-old man had an abnormal shadow on chest X-ray. Enhanced chest computed tomography (CT) revealed an 8-cm diameter right lung mass invading the right chest wall, with a tumor thrombus extending from the superior pulmonary vein into the left atrium. Transesophageal echocardiography confirmed that the tumor adjoined the side wall of the atrium. Endobronchial and CT-guided needle biopsy demonstrated a low-grade carcinoma or small cell carcinoma. Operative findings through left atriotomy under cardiopulmonary bypass showed no tumor invasion of the atrium wall, but protrusion through the pulmonary vein. Frozen sections revealed a non-small cell carcinoma. We performed right upper lobectomy with parietal pleura and mediastinal lymph node dissection after detachment of cardiopulmonary bypass. Pathological examination demonstrated a large-cell neuroendocrine carcinoma p-T4N0M0, stage IIIA. The patient recovered without postoperative complications and tolerated two cycles of adjuvant chemotherapy. He was doing well without symptoms of recurrence 42 months after surgery.

Phase I Study to Determine MTD of Docetaxel and Cisplatin with Concurrent Radiation Therapy for Stage Ⅲ Non-Small Cell Lung Cancer

Objective： To evaluate the maximum tolerated dose （MTD） of docetaxel （DCT） and cisplatin （DDP） concurrently with three dimensional （3D） conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer （stage IIIa and IIIb） after 2–4 cycles of induction chemotherapy. Methods： Fourteen patients with histological/cytological proven stage III non–small-cell lung cancer were eligible. 3D or IMRT radiotherapy （60-70Gy in 30-35 fractions, 6-7weeks, 2 Gy/fraction） was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy （CCRT）. The level I dosage was composed of 56 mg/m2 DCT, on day 1 and 28mg/m2 DDP, on day 1 and day 2. The level II was composed of 60 mg/m2 DCT, on day 1 and 30 mg/ m2 DDP, on day 1 and day 2. The level III was composed of 64 mg/m2 DCT, on day 1 and 32 mg/ m2 DDP, on day 1 and day 2. Results： Fourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III （64 mg/m2） and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients. Conclusions： Patients with locally advanced non-small cell lung cancer may tolerate 60mg/m2 docetaxel and 60mg/m2 cisplatin for 2 cycles during concurrent radiotherapy after 2-3 cycles of induction chemotherapy.

Progress in immunotherapy for small cell lung cancer

Small-cell lung cancer(SCLC)is a special type of lung cancer that belongs to highly aggressive neuroendocrine tumors.At present,radiotherapy and chemotherapy remain the mainstay of treatment for SCLC.Progress in targeted therapies for SCLC with driver mutations has been slow,and these therapies are still under investigation in preclinical or early-phase clinical trials,and research on antiangiogenic tyrosine kinase inhibitors(e.g.,anlotinib)has achieved some success.Immunotherapy is becoming an important treatment strategy for SCLC after radiotherapy and chemotherapy.In this article we review the recent advances in immunotherapy for SCLC.

MiR-16-5p plays an inhibitory role in human non-small cell lung cancer through Fermitin family member 2

Increasing evidence indicates that aberrant expressions of some microRNAs are associated with cancer progression.However,the roles and biological mechanisms of miRNA-16-5p in human non-small cell lung cancer(NSCLC)are not to be well studied.Here,we validated that the expression of miR-16-5p was decreased significantly in NSCLC samples and cell lines.The correlation between the clinicopathological features of NSCLC and the miR-16-5p expression showed that the expression of miR-16-5p in non-small cell lung cancer was linked with the advanced TNM stage,positive lymph node metastasis,with short overall survival(OS).Also,a negative correlation between miR-16-5p and Fermitin family member 2(FERMT2)was observed,implying there may be a potential link about their regulation.The hypothesis was further confirmed by in-silico analysis and dual-luciferase reporter assay.Moreover,we demonstrated that the transfections of miR-16-5p mimics could alter some biological characteristics of NSCLC cells remarkably accomplished by the expression variance of FERMT2 in vitro and in vivo assays.Summarily,this study demonstrated that miR-16-5p,as a tumor suppression factor in NSCLC by targeting FERMT2,could serve as one promising biomarker in the prediction for NSCLC patients.

Opportunities and challenges of immune checkpoint inhibitors for extensive-stage small-cell lung cancer

Small-cell lung cancer(SCLC)accounts for 15%–20%of primary lung cancers,and it is characterized by low differentiation,rapid proliferation,and early metastasis.At least two-thirds of SCLC patients present with the extensive stage(ES)at the time of initial clinical diagnosis.Over the last 2 decades,platinum-based combination chemotherapy has remained the standard first-line treatment for SCLC.With the introduction of the immunotherapy era,immunotherapy plus chemotherapy has replaced conventional chemotherapy as the first-line treatment option for ES-SCLC and is recommended by National Comprehensive Cancer Network clinical guidelines.Therefore,in this review,we present the latest research advances in SCLC treatment,predictive biomarkers,and other topics of high interest to provide options for patients with SCLC.

Combination therapy using low‐dose anlotinib and immune checkpoint inhibitors for extensive‐stage small cell lung cancer

Background:This study evaluated the efficacy and safety of low‐dose anlotinib combined with immune checkpoint inhibitors as second‐line or later treatment for extensive‐stage small cell lung cancer(ES‐SCLC).Methods:The study included 42 patients with ES‐SCLC who were treated with low‐dose anlotinib combined with programmed cell death protein 1/programmed cell death‐ligand 1 inhibitors at Henan Cancer Hospital between March 2019 and August 2022.We retrospectively analyzed the efficacy and safety data for these patients.Indicators assessed included progression‐free survival(PFS),overall survival(OS),the overall response rate(ORR),the disease control rate(DCR),and adverse events(AEs).Prognostic factors were identified in univariate and multivariate analyses.Results:Median PFS was 11.0 months(95%CI:7.868–14.132)and median OS was 17.3 months(95%CI:11.517–23.083).The ORR was 28.5%and the DCR was 95.2%.Treatment‐related AEs were noted in 27 patients(64.3%),the most common of which was thyroid dysfunction(26.2%).Grade 3/4 treatmentrelated AEs were observed in two patients(4.8%).Conclusions:A combination of low‐dose anlotinib and immune checkpoint inhibitors as second‐line or later treatment for ES‐SCLC may achieve longer PFS and OS and have manageable AEs.

Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202)

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ≥ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gamma-glutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.

Mutations in the DNA polymerase binding pathway affect the immune microenvironment of patients with small-cell lung cancer and enhance the efficacy of platinum-based chemotherapy

Background:Small-cell lung cancer(SCLC)is characterized by its high malignancy and is associated with a poor prognosis.In the early stages of the disease,platinum-based chemotherapy is the recommended first-line treatment and has demonstrated efficacy.However,SCLC is prone to recurrence and is generally resistant to chemotherapy in its later stages.Methods:Here,we collected samples from SCLC patients who received platinum-based chemotherapy,performed genomic and transcriptomic analyses,and validated our results with publicly available data.Results:SCLC patients with DNA polymerase binding pathway mutations had an improved prognosis after platinum chemotherapy compared with patients without such mutations.Patients in the mutant(MT)group had higher infiltration of T cells,B cells,and M1 macrophages compared with patients without DNA polymerase binding pathway mutations.Conclusions:DNA polymerase binding pathway mutations can be used as prognostic markers for platinum-based chemotherapy in SCLC.

Radiotherapy of brain metastases from small-cell lung cancer: standards and controversies

Small-cell lung cancer (SCLC) has a high propensity to metastasize into the brain. Radiotherapy plays a major role in the treatment of brain metastases (BM) from SCLC. Whole-brain radiotherapy (WBRT) is the standard treatment of BM from SCLC. However, the neurocognitive toxicity and modest efficacy of this approach have led to the increased use of stereotactic radiosurgery. We have no strong evidence for the use of different forms of radiation (WBRT vs. radiosurgery) in SCLC, because BM from this primary tumor were excluded from clinical trials. In this review, the use of radiation in form of WBRT or radiosurgery is discussed in distinct clinical indications: as a primary treatment and at relapse;without prior use of prophylactic cranial irradiation (PCI);and after PCI. Combinations of radiotherapy with chemotherapy are discussed as BM in SCLC occur rarely as a sole event.