Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Progress of Immunotherapy Combined with Anti-Angiogenesis Therapy in Lung Cancer

Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditional chemotherapy modalities, many emerging treatments are increasingly significant, such as immunotherapy, anti-angiogenic therapy, and targeted therapy. An increasing number of studies have now shown that anti-angiogenic therapy improves the immune microenvironment by enhancing tumor immunity through normalization of tumor vessels. Immunization combined with anti-angiogenic therapy can exert synergistic effects and improve the prognosis of patients. This article summarizes the extent of benefit, current clinical study data, and future prospects of immunotherapy combined with anti-angiogenic agents in the treatment of advanced NSCLC.

Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Stereotactic body radiation therapy for non-small cell lung cancer:A review

Stereotactic body radiation therapy(SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer(NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility,prescription dose and delivery, and follow up duration varied widely. Threeyears overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.

Review of the current targeted therapies for non-small-cell lung cancer

The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer(NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor(EGFR), and crizotinib which targets anaplastic lymphoma kinase(ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790 Mtargeted agents CO-1686 and AZD9291, and the ALKtargeted agents ceritinib(LDK378), AP26113, alectinib(CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come.

Surgical strategies in the therapy of non-small cell lung cancer

Lung cancer represents the leading cause of cancer mortality worldwide. Despite improvements in preoperative staging, surgical techniques, neoadjuvant/adjuvant options and postoperative care, there are still major difficulties in significantly improving survival, especially in locally advanced non-small cell lung cancer(NSCLC). To date, surgical resection is the primary mode of treatment for stage?Ⅰ?and Ⅱ NSCLC and has become an important component of the multimodality therapy of even more advanced disease with a curative intention. In fact, in NSCLC patients with solitary distant metastases, surgical interventions have been discussed in the last years. Accordingly, this review displays the recent surgical strategies implemented in the therapy of NSCLC patients.

Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment

Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.

Apoptosis block as a barrier to effective therapy in non small cell lung cancer

Lung cancer, is the most common cause of cancer death in men and second only to breast cancer in women. Currently, the first line therapy of choice is platinumbased combination chemotherapy. A therapeutic plateau has been reached with the prognosis for patients with advanced non-small cell lung cancer(NSCLC) remaining poor. New biomarkers of prognosis as well as new therapies focusing on molecular targets are emerging helping to identify patients who are likely to benefit from therapy. Despite this, drug resistance remains the major cause for treatment failure. In this article we review the role of apoptosis in mediating drug resistance in NSCLC. Better understanding of this fundamental biological process may provide a rationale for overcoming the current therapeutic plateau.

Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells

Natural exosomes can express specific proteins and carbohydratemolecules on the surface and hence have demonstrated the great potentials for gene therapy of cancer.However,the use of natural exosomes is restricted by their low transfection efficiency.Here,we report a novel targeting tLyp-1 exosome by gene recombinant engineering for delivery of siRNA to cancer and cancer stem cells.To reach such a purpose,the engineered tLyp-1-lamp2b plasmids were constructed and amplified in Escherichia coli.The tLyp-1-lamp2b plasmids were further used to transfect HEK293T tool cells and the targeting tLyp-1 exosomes were isolated from secretion of the transfected HEK293T cells.Afterwards,the artificially synthesized siRNA was encapsulated into targeting tLyp-1 exosomes by electroporation technology.Finally,the targeting siRNA tLyp-1 exosomes were used to transfect cancer or cancer stem cells.Results showed that the engineered targeting tLyp-1 exosomes had a nanosized structure(approximately 100 nm)and high transfection efficiency into lung cancer and cancer stem cells.The function verifications demonstrated that the targeting siRNA tLyp-1 exosomes were able to knock-down the target gene of cancer cells and to reduce the stemness of cancer stem cells.In conclusion,the targeting tLyp-1 exosomes are successfully engineered,and can be used for gene therapy with a high transfection efficiency.Therefore,the engineered targeting tLyp-1 exosomes offer a promising gene delivery platform for future cancer therapy.

Clinical challenges in neoadjuvant immunotherapy for non-small cell lung cancer

Immune checkpoint inhibitors(ICIs),a type of immunotherapy,have become one of the most important therapeutic options for first-and second-line treatment of advanced non-small cell lung cancer(NSCLC).Recent clinical studies have shown that immunotherapy can offer substantial survival benefits to patients with early-stage or resectable advanced NSCLC.However,considering the importance of timing when using ICIs and their associated adverse events(AEs),the advantages and disadvantages of using these agents need to be weighed carefully when deciding the use of a combined treatment.In addition,the inconsistency between imaging assessment and pathological results poses further challenges to the evaluation of efficacy of neoadjuvant immunotherapy.It is also important to develop new methodologies and discover suitable biomarkers that can be used to evaluate survival outcomes of immunotherapy and identify patients who would benefit the most from this treatment.In this review,we aimed to summarize previous results of ongoing clinical trials on neoadjuvant immunotherapy for lung cancer and discuss the challenges and future perspectives of this therapeutic approach in the treatment of resectable NSCLC.

A Phase Ⅱ Trial of Gefitinib as Maintenance Therapy after First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in China

Objective： To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer （NSCLC） patients who obtained disease control （DC） after first-line chemotherapy in Chinese population. Methods： Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time （OS）, the second end point was disease control rate （DCR） and progression-free survival time （PFS）. DCR included complete response （CR） plus partial response （PR） and plus stable disease （SD）. The impact of epidermal growth factor receptor （EGFR） mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography （DHPLC）. Results： Among 75 enrolled patients, the overall response rate was 37% and the DCR （CR ＋ PR ＋SD） was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type （25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively）. In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS （P=0.029 and 0.017, respectively）, however, rash status was the predictor in terms of PFS （P=0.027）. Conclusion： Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.

Maintaining clarity:Review of maintenance therapy in nonsmall cell lung cancer

The purpose of this article is to review the role of maintenance therapy in the treatment of advanced nonsmall cell lung cancer(NSCLC). A brief overview about induction chemotherapy and its primary function in NSCLC is provided to address the basis of maintenance therapies foundation. The development of how maintenance therapy is utilized in this population is discussed and current guidelines for maintenance therapy are reviewed. Benefits and potential pitfalls of maintenance therapy are addressed, allowing a comprehensive review of the achieved clinical benefit that maintenance therapy may or may not have on NSCLC patient population. A review of current literature was conducted and a table is provided comparing the results of various maintenance therapy clinical trials. The table includes geographical location of each study, the number of patients enrolled, progression free survival and overall survival statistics, post-treatment regimens and if molecular testing was conducted. The role of molecular testing in relation to therapeutic treatment options foradvanced NSCLC patients is discussed. A treatment algorithm clearly depicts first line and second line treatment for management of NSCLC and includes molecular testing, maintenance therapy and the role clinical trials have in treatment of NSCLC. This treatment algorithm has been specifically tailored and developed to assist clinicians in the management of advanced NSCLC.

Better to be alone than in bad company:The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lung cancer(NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.RESULTS All treatment schemes showed an antagonistic effect in all cell lines,independent of the cMET status.Despite their different genetic backgrounds,all cell lines(EBC-1,HCC827,H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7.These results were independent of the treatment schedule.CONCLUSION These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.

MicroRNAs modulation in lung cancer: exploring dual mechanisms and clinical prospects

The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably cancer.Within this context,miRNAs encapsulated in exosomes manifest a diversified impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these processes.This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer.Tumor-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness.Conversely,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective inhibitors.Distinct miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the specific miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.

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.

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.

Studies on Lung Cancer Angiogenesis-Application of Interventional Therapy (A Report of 56 Cases)

OBJECTIVE To investigate the significance of angiogenesis of lung cancer, in order to provide a scientific basis for interventional therapy. METHODS Double-phase enhancementscanning spiral CT and DSA were performed in 56 pathologically confi rmed lung cancer cases, in order to evaluate angiogenesis of the tumors. The patients included 36 males and 20 females, with ages ranging from 33 to 76 years (average of 53). Assessments and indexes for SCT and DSA examinations were as follows: a) Peak value (PV) of the cancerous focus was the difference between the maximum CT value after enhancement and the CT value of a plain scan; b) The abnormally distorted and expanded new vessels of the cancerous focus which could be macroscopically discriminated; c) DSA staining of the focus of cancer was sparse, grid-like and dense. Chemotherapy and embolotherapy via the bronchial artery (interventional therapy) were conducted. Radiotherapy was added for some of the solid tumors with a diameter exceeding 4 cm. RESULTS a) There were 25 cases with a central-type lesion, among which 4 were small cell lung cancers (SCLC) and 21 non-small cell lung cancers (NSCLC). The cases with a peripheral location accounted for 31 of the total, with a maximum diameter of 1.5 to 13.5 cm and a median of 4.2 cm, including 5 small cell lung cancers and 26 NSCLC cases. b) The reinforced PVs of the cancerous foci were as follows: The PV ranged from 45 to 70 Hu in 34 cases, 25 to 45 Hu in 19, and 10 to 25 Hu in 3. Sparse DSA staining occurred in 3 cases, there was uneven grid-like staining in 22 and dense staining in 31; c) The interventional therapy via the bronchial artery was con-ducted twice in 5 cases with the SCLC, and three times in 4 SCLC cases. For 3 of the latter cases, a dose of 5,000 to 7,000 cGy radiation therapy was added during the interventional treatment. Complete remissions (CR) were seen in 88.9% of the cases (8/9) and partial remission (PR) in 11.1% (1/9). Interventional therapy was conducted twice in 8 cases with NSCLC and three times in 30 with NSCLC and four times in 9 cases. Among the total cases, 13 received radiotherapy during interventional therapy, with a radiation dose of 5,000-7,000 cGy; The CR rate was 78.7% (37/47), PR was 14.9% (7/47) and the rate of non-remission was 6.4% (3/47). CONCLUSION Using imaging technology, analysis of angiogenesis of lung cancers was employed to accurately detect and quantify angiogenesis. This analysis was combined for interventional therapy, using embolizing agents and large doses of the anti-tumor drugs and angiogenesis inhibitors. The agents were selectively delivered into the tumor vessels to eliminate the primary tumor, in order to depress distant metastases and thus enhance the curative effect of the therapy.

Partial and Full Arc Volumetric Modulated Arc Therapy in Lung Cancer Stereotactic Body Radiotherapy with Different Definitions of Internal Target Volume Based on 4D CT

Purpose: To investigate the feasibility of partial arc volumetric modulated arc therapy (VMAT) in lung cancer stereotactic body radiotherapy (SBRT), as well the volumetric and dosimetric effects of different internal target volume (ITV) definitions with 4D CT. Methods: Fourteen patients with primary and metastatic lung cancer underwent SBRT were enrolled. Full and partial arc VMAT plans were generated with four different ITVs: ITVall, ITVMIP, ITVAIP and ITV2phases, representing ITVs generated from all 10 respiratory phases, maximum intensity projection (MIP), average intensity projection (AIP), and 2 extreme respiratory phases. Volumetric and dosimetric differences, as well as MU and delivery time were investigated. Results: Partial arc VMAT irradiated more dose at 2 cm away from planning target volume (PTV) (P = 0.002), however, it achieved better protection on mean lung dose , lung V5, spinal cord, heart and esophagus compared with full arc VMAT. The average MU and delivery time of partial arc VMAT were 240 and 1.6 min less than those of full arc VMAT. There were no significant differences on target coverage and organ at risks (OARs) sparing among four ITVs. The average percent volume differences of ITVMIP, ITVAIP and ITV2phases to ITVall were 8.6%, 13.4%, and 25.2%, respectively. Conclusions: Although partial arc VMAT delivered more dose 2 cm out of PTV, it decreases the dose to lung, spinal cord, and esophagus, as well decreased the total MU and delivery time compared with full arc VMAT without sacrificing target coverage. Partial arc VMAT was feasible and more efficient for lung SBRT.

Returning from the afterlife?Sotorasib treatment for advanced KRAS mutant lung cancer:A case report

BACKGROUND Lung cancer is increasing in incidence worldwide,and targeted therapies are developing at a rapid pace.Furthermore,the KRAS specific gene is strongly associated with non-small cell lung cancer(NSCLC).Adult patients with locally advanced or metastatic NSCLC who have tested positive for the KRAS G12C mutation and have progressed after at least one systemic treatment are treated with sotorasib.CASE SUMMARY In this study,we report on an advanced NSCLC with a KRAS G12C mutation.The histological diagnosis indicates stage IVB left lung adenocarcinoma with pelvic and bone metastases,identified as cT4N2bM1c.Using circulating tumor DNA analysis,it was possible to determine the mutation abundance of the KRAS gene exon 2,c.34G>Tp.G12C,which was 32.3%.The patient was advised to take sotorasib as part of their treatment.The imaging data were compared before and after treatment.Furthermore,clinical reassessments and regular serial blood testing were conducted.We found that the patient’s clinical symptoms significantly improved after receiving sotorasib medication,and there were no notable side effects,such as liver toxicity,during the treatment.CONCLUSION Sotorasib has shown promising clinical efficacy in patients with the KRAS G12c mutation and has no apparent toxic side effects.