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 metastas...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.展开更多
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 ...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.展开更多
Small cell lung cancer (SCLC) is a poorly differentiated, highly malignant neuroendocrine tumor characterized by rapid growth, aggressiveness, and easy recurrence. It is usually found in late clinical stage and the op...Small cell lung cancer (SCLC) is a poorly differentiated, highly malignant neuroendocrine tumor characterized by rapid growth, aggressiveness, and easy recurrence. It is usually found in late clinical stage and the opportunity for surgery is lost. Therefore, surgery is often not used in clinical treatment. Although it is sensitive to chemoradiotherapy, it has a high recurrence rate and lacks effective treatment methods at present. Following chemotherapy and radiotherapy, immunotherapy for small cell lung cancer has become the mainstream research direction. Immunotherapy is profoundly changing the approach to cancer treatment due to its tolerable safety profile, sustained treatment response due to the production of immune memory, and effectiveness in a broad patient population. Immunotherapy for small cell lung cancer is one of the effective treatment methods for small cell lung cancer, and relevant studies are not rare, but there are still shortcomings such as intolerance of side effects and inaccurate evaluation of treatment timing. This article reviews the history of immunotherapy, the mechanism of action of immunodrugs, and the current immunodrugs used in the first-line treatment of extensive small cell lung cancer.展开更多
Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties ...Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.展开更多
Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. ...Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.展开更多
BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metas...BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.展开更多
BACKGROUND Small cell lung cancer(SCLC)exhibits a pronounced tendency for metastasis and relapse,and the acquisition of resistance to chemotherapy and radiotherapy,leading to complexity in treatment outcomes.It is cru...BACKGROUND Small cell lung cancer(SCLC)exhibits a pronounced tendency for metastasis and relapse,and the acquisition of resistance to chemotherapy and radiotherapy,leading to complexity in treatment outcomes.It is crucial to tackle these challenges by advancing targeted therapeutic approaches in ongoing research endeavors.Variant RET fusions have been reported in several solid tumors,but are rarely reported in SCLC.CASE SUMMARY We present the first case of a KIF5B-RET fusion in a 65-year-old male patient with SCLC.To date,the patient has received the 4th line chemotherapy with anlotinib for one year and has shown a sustained favorable partial response.According to the results of next generation sequencing,this SCLC patient harbors the KIF5BRET fusion,suggesting that RET fusion could serve as a promising molecular target for SCLC treatment.Next-generation sequencing(NGS)plays a critical rolein comprehensively assessing the genotype and phenotype of cancer.CONCLUSION NGS can provide SCLC patients with personalized and targeted therapy options,thereby improving their likelihood of survival.展开更多
Small cell lung carcinoma(SCLC)is an aggressive malignancy known for its propensity for early and extensive metastatic spread.Gastric metastasis,where cancer cells disseminate from the lung to the stomach,is a rare bu...Small cell lung carcinoma(SCLC)is an aggressive malignancy known for its propensity for early and extensive metastatic spread.Gastric metastasis,where cancer cells disseminate from the lung to the stomach,is a rare but increasingly recognized complication of SCLC.This review provides a comprehensive overview of gastric metastasis in SCLC,addressing its clinical significance,diagnostic challenges,management strategies,and prognosis.Additionally,it examines the broader metastatic patterns of SCLC and compares them with other malignancies known for gastric metastasis.Gastric metastasis in SCLC,though infrequent,is clinically significant and often indicates advanced disease with a poor prognosis.SCLC typically metastasizes to the liver,brain,bones,and adrenal glands,with the stomach being an unusual site.The incidence of gastric meta-stasis ranges from 1%to 5%in autopsy studies,although this may be underes-timated due to diagnostic difficulties and asymptomatic early lesions.Diagnosing gastric metastasis presents several challenges,including the asymptomatic nature of many cases,limitations of conventional imaging techniques,and difficulties in distinguishing metastatic lesions from primary gastric cancer via endoscopy.Histopathological diagnosis requires careful examination to identify SCLC cells through their characteristic small cell morphology and neuroendocrine markers.Management of gastric metastasis in SCLC typically involves a multidisciplinary approach.Systemic therapy,pri-marily chemotherapy,remains the cornerstone of treatment,with palliative care addressing symptoms and complications.Surgical intervention is usually reserved for specific cases requiring symptomatic relief.The prognosis for patients with gastric metastasis from SCLC is generally poor,reflecting the advanced stage of the disease.Median survival is significantly re-duced compared to patients without gastric metastasis.This review emphasizes the need for enhanced awareness and early detection to improve patient outcomes and highlights the importance of ongoing research into better diagnostic and therapeutic strategies.展开更多
BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limit...BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.展开更多
BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We ...BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man.Transbronchial lung biopsy revealed squamous cell carcinoma.Although enlargement of lymph node 12u was detected,no distant metastases were observed.The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection(ND2a).Based on histopathological findings,the primary lesion was squamous cell carcinoma.A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion.Tumors were detected in two resected lymph nodes(#12u and#11s).Both tumors were pathologically diagnosed as small cell carcinomas.The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging;however,chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.CONCLUSION Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.展开更多
Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung...Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung cancer (ES-SCLC). Systemic treatment consisting of platinum drugs and etoposide chemotherapy is the main treatment method, although the objective effective rate of this combination is 60% - 80%. However, most SCLC patients experience disease progression shortly after initial treatment, with a median overall survival of 10 months. There are few second-line treatment drugs available, and immunotherapy using checkpoint inhibitors has completely changed the treatment of many cancer types. Adding immune checkpoint inhibitors (ICI) to conventional chemotherapy as first-line treatment can improve the survival rate of widespread small cell lung cancer (ES-SCLC), but so far, there are no definitive factors to determine patients who are more likely to benefit from immunotherapy. This review summarizes the results of immunotherapy trials for small cell lung cancer. And a review was conducted on the predictive factors of these trials, with special emphasis on the expression of PD-L1 in small cell lung cancer to determine its clinical value.展开更多
Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effec...Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.展开更多
Extended stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses early as drug-resistant tumor associated with a dismal prognosis. A pair of SCLC cell lines obtaine...Extended stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses early as drug-resistant tumor associated with a dismal prognosis. A pair of SCLC cell lines obtained from a single patient at different time points during treatment allows for the investigation of the changes in gene expression prior to (GLC14) and following cycles of chemotherapy and irradiation (GLC19). GLC19 cells were reported to reveal an increased doubling time and exhibit increased chemoresistance to doxorubicin, etoposide, melphalan and vinblastine. Upregulated transcripts in GLC19, as assessed by microarray analysis, comprised proteins involved in regulation of cellular growth (NGFRAP1/BEX3), adhesion, glutathione metabolism and, in particular, WNT/Notch pathways and the putative cancer stem cell phenotype (CD44, ALDH1A1, and AKR1C1/13). Metallothioneins, tubulins TUBA3/4 and tumor protein p53 inducible protein 11 (TP53IP11) were downregulated in this cell line compared to GLC14. Except increased expression of glutathione transferases no classical markers of chemoresistance were found, pointing to a role of altered growth control/differentiation and reduced accessibility of this SCLC tumor cells growing as multicellular spheroids. In conclusion, treatment of this single SCLC with cyclophosphamide, doxorubicin and etoposide (CDE) followed by radiotherapy ultimately resulted in an enrichment of tumor cells displaying the typical signature of tumor-initiating or cancer stem cells (CIC/CSC).展开更多
Extended-stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses rapidly as drug-resistant tumor. Topotecan (TPT) is the single chemotherapeutic agent approved for ...Extended-stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses rapidly as drug-resistant tumor. Topotecan (TPT) is the single chemotherapeutic agent approved for second-line treatment of SCLC. However, the response to TPT is short-lived and novel treatment modalities need to be developed. Sequential treatment of cytotoxic drugs and inhibitors of cyclin-dependent kinases (CDKs) showed promising preclinical anticancer activity and, in the present work, combinations of TPT with CDK inhibitors olomoucine, roscovitine and CDK4I are shown to exhibit synergistic cytotoxic activity against SCLC cell lines. Highest activity was found against TPT-resistant NCI-H417 and DMS153 cell lines and moderate chemosensitizing effects against a primary SCLC cell line and sensitive GLC19 cells at levels of CDK inhibitors which exerted low toxicity. A combination of 0.6 μM TPT with 0.6 μM roscovitine, exhibiting no significant cytotoxicity as single agents, reduced viability of the TPT-resistant NCI-H417 line (IC50 > 10 μM) by 50%. In the TPT resistant cell lines olomoucine and roscovitine, targeting CDK1,2,5,7, were highly effective, whereas in the more sensitive cell lines CDK4I, inhibiting mainly CDK4/6, showed activity. In NCI-417 cells, preincubation with roscovitine for one day proved synergistic with TPT. Thus, in good accordance with previous findings, CDK inhibitors are able to convert SCLC cancer cells which are cell-cycle arrested by a blockade of topoisomerase I by TPT to apoptotic cells. Since nowadays several CDK inhibitors are at various phases of clinical testing their combination with TPT seems to constitute a promising approach to improve second-line chemotherapy in SCLC.展开更多
Purpose: This work was to study the clinic-epidemiological characteristics of patients with locally advanced NCSLC and to analyze their prognostic factors and also the results of different treatment modalities for loc...Purpose: This work was to study the clinic-epidemiological characteristics of patients with locally advanced NCSLC and to analyze their prognostic factors and also the results of different treatment modalities for local control and their effect on overall survival (OAS). Materials and Methods: This is a retrospective study including 121 patients with primary locally advanced NSCLC diagnosed between 2001 and 2010 at the radiotherapy department , National Cancer Institute, Cairo University, Egypt. Results: The study showed significant correlation between the tumor size 60, moderately differentiated tumors G2 and treatment outcomes;better locoregional control and better survival rates. On the opposite side poorly differentiated tumors G3, tumor size > 7 cm had the worst locoregional control and survival rates. The study also showed significant statistical correlation between treatment modality, locoregional control and survival rates. Patients who were treated by either concommitent chemo-radiotherapy or sequential chemo-radiotherapy had better local control compared to other patients who were treated by radical radiotherapy, and they also had the best survival rates among all the other treatment groups. The average 6 months OAS rates for all studied patients were 60.3% while 12 months survival rates were 38.8%. The median OAS was 7 months. Conclusions: From the present study, we concluded that concomitant chemo-radiotherapy is the treatment of choice for locally advanced non small cell lung cancer;also we concluded that better performance status and higher hemoglobin levels have better treatment outcome in these cases.展开更多
Introduction: Lung cancer is the leading cause of cancer death worldwide with poor survival rates. However, the prognostic factors for survival of patients with lung cancer are not well-established. In this study, we ...Introduction: Lung cancer is the leading cause of cancer death worldwide with poor survival rates. However, the prognostic factors for survival of patients with lung cancer are not well-established. In this study, we examined the impact of routine laboratory biomarkers and traditional factors on survival of patients with non-small cell lung cancer (NSCLC). Method: Secondary data analysis was conducted from a retrospective study of 404 patients with newly diag-nosed lung cancer in 2005-2007 in Taiwan. There were eight routine laboratory biomarkers and eight traditional factors investigated in the analyses. Cox proportional hazards model was used to assess the hazard ratios for the association between risk factors and patient overall survival. The Kaplan-Meier method was used to compare survival curves for each prognostic indicator. Results: High WBC counts (HR = 1.798, 95%CI: 1.225 - 2.639), low Hgb level (HR = 1.437, 95%CI: 1.085 - 1.903), and low serum albumin level (HR = 2.049, 95%CI: 1.376 - 3.052) were significant laboratory prognostic biomarkers for poor NSCLC survival. Additionally we confirmed the traditional prognostic factors for poor overall survival among NSCLC patients, including older age, comorbidity conditions, advanced cancer stage, and non-surgical treatment. Conclusions: This study identified three available laboratory biomarkers, high WBC counts, low Hgb level, and low serum albumin level, to be significant prognostic factors for poorer overall survival in NSCLC patients. Further prognostic evaluation studies are warranted to compare different ethnic groups on the prognostic values of these clinical parameters in NSCLC survival outcomes. These identified prognostic biomarkers should be included in early risk screening of hospitalized lung cancer patient population.展开更多
Background: Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism(SNP) loci with polymorphisms. This study aimed to analyze the all...Background: Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism(SNP) loci with polymorphisms. This study aimed to analyze the allele frequency of SNP loci in MAGE-A3 gene and investigate the relationship between MAGE-A3 gene polymorphisms and clinical factors.Methods: Tumor samples of a cohort of 191 NSCLC patients were collected. EGFR m RNA expression were detected by q RT-PCR. SNPs in whole length of MAGE-A3 gene were detected by direct sequencing. Frequencies of the SNPs were correlated to gene expression, mutation status of EGFR and clinical factors.Results: Sequencing analysis confirmed that allele frequencies of genotypes on SNP loci rs5970360, rs5925210, rs5970361, rs5925211 and rs35123853 were CC(0.681)/CT(0.319), CC(0.660)/CG(0.340), CC(0.681)/CA(0.319), AA(0.984)/AT(0.016) and GG(1.000)/GA(0.000), respectively, which were different from the frequencies and genotypes of MAGE-A3 in SNP database. Chi-square tests showed the EGFR mR NA expression level had significant correlation with the genotypes of SNP loci rs5970360 and rs5925210. But all frequencies of each MAGE-A3 SNPs were not found significantly different between EGFR mutant and wild type patients. MAGE-A3 gene polymorphisms had no significant effects on survival of NSCLC patients.Conclusions: Chinese patients with NSCLC had different SNP patterns of MAGE-A3 in comparison with those in international SNP database. These MAGE-A3 SNP loci might have not prognostic significance. MAGE-A3 SNP loci rs5970360 and rs5925210 might be predictive for EGFR m RNA expression levels and helpful to the selection of patients for epidermal growth factor receptor(EGFR) targeted immunotherapy.展开更多
<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">To examine possible association between heart irradiati...<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Materials and Methods: </span></b><span style="font-family:Verdana;">197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates associated with OS. Heart dosimetry was represented by </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox model</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> with patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates and single </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 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 </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">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.</span><b><span style="font-family:Verdana;"> Results: </span></b><span style="font-family:Verdana;">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, </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span><span><sub><span style="font-family:""><span style="font-family:Verdana;">2</span><i><span style="font-family:Verdana;">Gy</span></i></span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the right-inferior segment (HR = 1.012/1%, p = 0.02), and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><sub><span style="font-family:Verdana;">1</span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><sub><span style="font-family:Verdana;">Gy</span></sub></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 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</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 5</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><span style="font-family:Verdana;"> Doses lower than 5</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">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.</span></span></span>展开更多
Background: The optimal dose of palliative radiotherapy (RT) in symptomatic advanced lung cancer is unclear. Patients and methods: Patients with advanced NSCLC who were indicated for thoracic palliative RT with age up...Background: The optimal dose of palliative radiotherapy (RT) in symptomatic advanced lung cancer is unclear. Patients and methods: Patients with advanced NSCLC who were indicated for thoracic palliative RT with age up to 65 y and Performance Status (PS) 0 - 2 and no significant cardiac or lung co-morbidities were randomized into two fractionation arms: arm A: 30 Gy/10 over 2 weeks and arm B: 27 Gy/6 over 3 weeks (2 fractions per week) using 2 anterior posterior (AP-PA) fields in both arms. Primary end points were symptomatic and radiological tumor response, respiratory functions assessment. Secondary end point was toxicity. Results: From December 2014 to October 2015, 40 patients were randomized, 20 patients in each arm. There was statistically insignificant higher symptomatic improvement in arm B. Four weeks after treatment, 12 out of 40 patients (30%), 6 patients in each arm, had radiological Partial Response (PR) of the primary thoracic lesion without significant difference between the two arms. There was a tendency for improvement in the post treatment mean Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) in each arm without statistical significance. There were no reported skin reactions or esophagitis in both arms up to 4 weeks after treatment. Eleven out of the 40 patients (27.5%), 6 in arm B and 5 in arm A, had radiological signs of radiation pneumonitis without significant difference between both arms. Conclusion: The two RT fractionation schedules showed equal efficacy in terms of symptoms relief, radiological response of the primary thoracic tumor, respiratory functions and toxicity. Thus the 27 Gy/6 fractionation arm appears preferable compared to 30 Gy/10 arm to minimize the patients’ visits and load on the machines.展开更多
Objective: To evaluate the clinical course of patients with small cell lung cancer (SCLC) as second primary malignancy. Methods: Among the 355 patients diagnosed with SCLC at Helen and Harry Gray Cancer Center of ...Objective: To evaluate the clinical course of patients with small cell lung cancer (SCLC) as second primary malignancy. Methods: Among the 355 patients diagnosed with SCLC at Helen and Harry Gray Cancer Center of Hartford Hospital Connecticut USA between 1988 and 1998, the records of 48 patients, which had been diagnosed with other malignancies before their diagnosis of SCLC, were retro- spectively reviewed. Results: Forty-eight patients (13.5%) were diagnosed with other malignancies prior to their SCLC among which 43 had documented smoking history and 93% of them (40/43) were current/former smokers. Of the 28-second primary SCLC patients who were treated with standard method, 11 (39.3%) achieved CR. 12 (42.8%) achieved PR, and the RR was 82.1%. The median survival of the 28 treated with standard method was 11.3 months (5.1-77.7 months), while that of the rest 19 untreated patients (1 of 20 was lost to follow-up) was only 2.0 months (0.5 34.0 months). There was no significant difference in the median survival and RR between 165 treated first primary SCLC (13.5 months and 77.6% respectively) and 28 treated secondary primary SCLC (11.3 months and 82.1% respectively) (P〉0.05). The patients who had prostate cancer were older and subjected to less treatments than those with skin cancer, so their survival was shorter than the latter (3.5 months vs. 15 months, P〈0.05). Conclusion: The response and survival of the treated patients with SCLC as a second malignancy showed no difference as compared to the treated ones with SCLC only. Therefore, an active medical treatment is important to relieve symptom and prolong survival of the second primary SCLC patients.展开更多
基金Yu-Qing Xia Famous Old Chinese Medicine Heritage Workshop of“3+3”Project of Traditional Chinese Medicine Heritage in Beijing,Jing Zhong Yi Ke Zi(2021),No.73National Natural Science Foundation of China,No.81973640+1 种基金Nursery Program of Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine,No.WJYY-YJKT-2022-05China Academy of Traditional Chinese Medicine Wangjing Hospital High-Level Chinese Medicine Hospital Construction Project Chinese Medicine Clinical Evidence-Based Research:The Evidence-Based Research of Electrothermal Acupuncture for Relieving Cancer-Related Fatigue in Patients With Malignant Tumor,No.WYYY-XZKT-2023-20.
文摘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.
文摘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.
文摘Small cell lung cancer (SCLC) is a poorly differentiated, highly malignant neuroendocrine tumor characterized by rapid growth, aggressiveness, and easy recurrence. It is usually found in late clinical stage and the opportunity for surgery is lost. Therefore, surgery is often not used in clinical treatment. Although it is sensitive to chemoradiotherapy, it has a high recurrence rate and lacks effective treatment methods at present. Following chemotherapy and radiotherapy, immunotherapy for small cell lung cancer has become the mainstream research direction. Immunotherapy is profoundly changing the approach to cancer treatment due to its tolerable safety profile, sustained treatment response due to the production of immune memory, and effectiveness in a broad patient population. Immunotherapy for small cell lung cancer is one of the effective treatment methods for small cell lung cancer, and relevant studies are not rare, but there are still shortcomings such as intolerance of side effects and inaccurate evaluation of treatment timing. This article reviews the history of immunotherapy, the mechanism of action of immunodrugs, and the current immunodrugs used in the first-line treatment of extensive small cell lung cancer.
文摘Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.
文摘Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.
文摘BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.
基金Meat Processing Key Laboratory of Sichuan Province,No.22-R-16.
文摘BACKGROUND Small cell lung cancer(SCLC)exhibits a pronounced tendency for metastasis and relapse,and the acquisition of resistance to chemotherapy and radiotherapy,leading to complexity in treatment outcomes.It is crucial to tackle these challenges by advancing targeted therapeutic approaches in ongoing research endeavors.Variant RET fusions have been reported in several solid tumors,but are rarely reported in SCLC.CASE SUMMARY We present the first case of a KIF5B-RET fusion in a 65-year-old male patient with SCLC.To date,the patient has received the 4th line chemotherapy with anlotinib for one year and has shown a sustained favorable partial response.According to the results of next generation sequencing,this SCLC patient harbors the KIF5BRET fusion,suggesting that RET fusion could serve as a promising molecular target for SCLC treatment.Next-generation sequencing(NGS)plays a critical rolein comprehensively assessing the genotype and phenotype of cancer.CONCLUSION NGS can provide SCLC patients with personalized and targeted therapy options,thereby improving their likelihood of survival.
文摘Small cell lung carcinoma(SCLC)is an aggressive malignancy known for its propensity for early and extensive metastatic spread.Gastric metastasis,where cancer cells disseminate from the lung to the stomach,is a rare but increasingly recognized complication of SCLC.This review provides a comprehensive overview of gastric metastasis in SCLC,addressing its clinical significance,diagnostic challenges,management strategies,and prognosis.Additionally,it examines the broader metastatic patterns of SCLC and compares them with other malignancies known for gastric metastasis.Gastric metastasis in SCLC,though infrequent,is clinically significant and often indicates advanced disease with a poor prognosis.SCLC typically metastasizes to the liver,brain,bones,and adrenal glands,with the stomach being an unusual site.The incidence of gastric meta-stasis ranges from 1%to 5%in autopsy studies,although this may be underes-timated due to diagnostic difficulties and asymptomatic early lesions.Diagnosing gastric metastasis presents several challenges,including the asymptomatic nature of many cases,limitations of conventional imaging techniques,and difficulties in distinguishing metastatic lesions from primary gastric cancer via endoscopy.Histopathological diagnosis requires careful examination to identify SCLC cells through their characteristic small cell morphology and neuroendocrine markers.Management of gastric metastasis in SCLC typically involves a multidisciplinary approach.Systemic therapy,pri-marily chemotherapy,remains the cornerstone of treatment,with palliative care addressing symptoms and complications.Surgical intervention is usually reserved for specific cases requiring symptomatic relief.The prognosis for patients with gastric metastasis from SCLC is generally poor,reflecting the advanced stage of the disease.Median survival is significantly re-duced compared to patients without gastric metastasis.This review emphasizes the need for enhanced awareness and early detection to improve patient outcomes and highlights the importance of ongoing research into better diagnostic and therapeutic strategies.
基金Supported by the Foundation of Science and Technology Bureau of Dalian,No. 2021JJ13SN70。
文摘BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.
文摘BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man.Transbronchial lung biopsy revealed squamous cell carcinoma.Although enlargement of lymph node 12u was detected,no distant metastases were observed.The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection(ND2a).Based on histopathological findings,the primary lesion was squamous cell carcinoma.A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion.Tumors were detected in two resected lymph nodes(#12u and#11s).Both tumors were pathologically diagnosed as small cell carcinomas.The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging;however,chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.CONCLUSION Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.
文摘Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung cancer (ES-SCLC). Systemic treatment consisting of platinum drugs and etoposide chemotherapy is the main treatment method, although the objective effective rate of this combination is 60% - 80%. However, most SCLC patients experience disease progression shortly after initial treatment, with a median overall survival of 10 months. There are few second-line treatment drugs available, and immunotherapy using checkpoint inhibitors has completely changed the treatment of many cancer types. Adding immune checkpoint inhibitors (ICI) to conventional chemotherapy as first-line treatment can improve the survival rate of widespread small cell lung cancer (ES-SCLC), but so far, there are no definitive factors to determine patients who are more likely to benefit from immunotherapy. This review summarizes the results of immunotherapy trials for small cell lung cancer. And a review was conducted on the predictive factors of these trials, with special emphasis on the expression of PD-L1 in small cell lung cancer to determine its clinical value.
文摘Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.
文摘Extended stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses early as drug-resistant tumor associated with a dismal prognosis. A pair of SCLC cell lines obtained from a single patient at different time points during treatment allows for the investigation of the changes in gene expression prior to (GLC14) and following cycles of chemotherapy and irradiation (GLC19). GLC19 cells were reported to reveal an increased doubling time and exhibit increased chemoresistance to doxorubicin, etoposide, melphalan and vinblastine. Upregulated transcripts in GLC19, as assessed by microarray analysis, comprised proteins involved in regulation of cellular growth (NGFRAP1/BEX3), adhesion, glutathione metabolism and, in particular, WNT/Notch pathways and the putative cancer stem cell phenotype (CD44, ALDH1A1, and AKR1C1/13). Metallothioneins, tubulins TUBA3/4 and tumor protein p53 inducible protein 11 (TP53IP11) were downregulated in this cell line compared to GLC14. Except increased expression of glutathione transferases no classical markers of chemoresistance were found, pointing to a role of altered growth control/differentiation and reduced accessibility of this SCLC tumor cells growing as multicellular spheroids. In conclusion, treatment of this single SCLC with cyclophosphamide, doxorubicin and etoposide (CDE) followed by radiotherapy ultimately resulted in an enrichment of tumor cells displaying the typical signature of tumor-initiating or cancer stem cells (CIC/CSC).
文摘Extended-stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses rapidly as drug-resistant tumor. Topotecan (TPT) is the single chemotherapeutic agent approved for second-line treatment of SCLC. However, the response to TPT is short-lived and novel treatment modalities need to be developed. Sequential treatment of cytotoxic drugs and inhibitors of cyclin-dependent kinases (CDKs) showed promising preclinical anticancer activity and, in the present work, combinations of TPT with CDK inhibitors olomoucine, roscovitine and CDK4I are shown to exhibit synergistic cytotoxic activity against SCLC cell lines. Highest activity was found against TPT-resistant NCI-H417 and DMS153 cell lines and moderate chemosensitizing effects against a primary SCLC cell line and sensitive GLC19 cells at levels of CDK inhibitors which exerted low toxicity. A combination of 0.6 μM TPT with 0.6 μM roscovitine, exhibiting no significant cytotoxicity as single agents, reduced viability of the TPT-resistant NCI-H417 line (IC50 > 10 μM) by 50%. In the TPT resistant cell lines olomoucine and roscovitine, targeting CDK1,2,5,7, were highly effective, whereas in the more sensitive cell lines CDK4I, inhibiting mainly CDK4/6, showed activity. In NCI-417 cells, preincubation with roscovitine for one day proved synergistic with TPT. Thus, in good accordance with previous findings, CDK inhibitors are able to convert SCLC cancer cells which are cell-cycle arrested by a blockade of topoisomerase I by TPT to apoptotic cells. Since nowadays several CDK inhibitors are at various phases of clinical testing their combination with TPT seems to constitute a promising approach to improve second-line chemotherapy in SCLC.
文摘Purpose: This work was to study the clinic-epidemiological characteristics of patients with locally advanced NCSLC and to analyze their prognostic factors and also the results of different treatment modalities for local control and their effect on overall survival (OAS). Materials and Methods: This is a retrospective study including 121 patients with primary locally advanced NSCLC diagnosed between 2001 and 2010 at the radiotherapy department , National Cancer Institute, Cairo University, Egypt. Results: The study showed significant correlation between the tumor size 60, moderately differentiated tumors G2 and treatment outcomes;better locoregional control and better survival rates. On the opposite side poorly differentiated tumors G3, tumor size > 7 cm had the worst locoregional control and survival rates. The study also showed significant statistical correlation between treatment modality, locoregional control and survival rates. Patients who were treated by either concommitent chemo-radiotherapy or sequential chemo-radiotherapy had better local control compared to other patients who were treated by radical radiotherapy, and they also had the best survival rates among all the other treatment groups. The average 6 months OAS rates for all studied patients were 60.3% while 12 months survival rates were 38.8%. The median OAS was 7 months. Conclusions: From the present study, we concluded that concomitant chemo-radiotherapy is the treatment of choice for locally advanced non small cell lung cancer;also we concluded that better performance status and higher hemoglobin levels have better treatment outcome in these cases.
文摘Introduction: Lung cancer is the leading cause of cancer death worldwide with poor survival rates. However, the prognostic factors for survival of patients with lung cancer are not well-established. In this study, we examined the impact of routine laboratory biomarkers and traditional factors on survival of patients with non-small cell lung cancer (NSCLC). Method: Secondary data analysis was conducted from a retrospective study of 404 patients with newly diag-nosed lung cancer in 2005-2007 in Taiwan. There were eight routine laboratory biomarkers and eight traditional factors investigated in the analyses. Cox proportional hazards model was used to assess the hazard ratios for the association between risk factors and patient overall survival. The Kaplan-Meier method was used to compare survival curves for each prognostic indicator. Results: High WBC counts (HR = 1.798, 95%CI: 1.225 - 2.639), low Hgb level (HR = 1.437, 95%CI: 1.085 - 1.903), and low serum albumin level (HR = 2.049, 95%CI: 1.376 - 3.052) were significant laboratory prognostic biomarkers for poor NSCLC survival. Additionally we confirmed the traditional prognostic factors for poor overall survival among NSCLC patients, including older age, comorbidity conditions, advanced cancer stage, and non-surgical treatment. Conclusions: This study identified three available laboratory biomarkers, high WBC counts, low Hgb level, and low serum albumin level, to be significant prognostic factors for poorer overall survival in NSCLC patients. Further prognostic evaluation studies are warranted to compare different ethnic groups on the prognostic values of these clinical parameters in NSCLC survival outcomes. These identified prognostic biomarkers should be included in early risk screening of hospitalized lung cancer patient population.
基金supported by grants from the Foundation of Guangdong Science and Technology Department(Grant No.2010B031600158,XN Yang)Key Lab System Project of Guangdong Science and Technology Department(Grant No.2012A061400006,YL WU)
文摘Background: Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism(SNP) loci with polymorphisms. This study aimed to analyze the allele frequency of SNP loci in MAGE-A3 gene and investigate the relationship between MAGE-A3 gene polymorphisms and clinical factors.Methods: Tumor samples of a cohort of 191 NSCLC patients were collected. EGFR m RNA expression were detected by q RT-PCR. SNPs in whole length of MAGE-A3 gene were detected by direct sequencing. Frequencies of the SNPs were correlated to gene expression, mutation status of EGFR and clinical factors.Results: Sequencing analysis confirmed that allele frequencies of genotypes on SNP loci rs5970360, rs5925210, rs5970361, rs5925211 and rs35123853 were CC(0.681)/CT(0.319), CC(0.660)/CG(0.340), CC(0.681)/CA(0.319), AA(0.984)/AT(0.016) and GG(1.000)/GA(0.000), respectively, which were different from the frequencies and genotypes of MAGE-A3 in SNP database. Chi-square tests showed the EGFR mR NA expression level had significant correlation with the genotypes of SNP loci rs5970360 and rs5925210. But all frequencies of each MAGE-A3 SNPs were not found significantly different between EGFR mutant and wild type patients. MAGE-A3 gene polymorphisms had no significant effects on survival of NSCLC patients.Conclusions: Chinese patients with NSCLC had different SNP patterns of MAGE-A3 in comparison with those in international SNP database. These MAGE-A3 SNP loci might have not prognostic significance. MAGE-A3 SNP loci rs5970360 and rs5925210 might be predictive for EGFR m RNA expression levels and helpful to the selection of patients for epidermal growth factor receptor(EGFR) targeted immunotherapy.
文摘<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Materials and Methods: </span></b><span style="font-family:Verdana;">197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates associated with OS. Heart dosimetry was represented by </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox model</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> with patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates and single </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 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 </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">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.</span><b><span style="font-family:Verdana;"> Results: </span></b><span style="font-family:Verdana;">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, </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span><span><sub><span style="font-family:""><span style="font-family:Verdana;">2</span><i><span style="font-family:Verdana;">Gy</span></i></span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the right-inferior segment (HR = 1.012/1%, p = 0.02), and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><sub><span style="font-family:Verdana;">1</span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><sub><span style="font-family:Verdana;">Gy</span></sub></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 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</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 5</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><span style="font-family:Verdana;"> Doses lower than 5</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">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.</span></span></span>
文摘Background: The optimal dose of palliative radiotherapy (RT) in symptomatic advanced lung cancer is unclear. Patients and methods: Patients with advanced NSCLC who were indicated for thoracic palliative RT with age up to 65 y and Performance Status (PS) 0 - 2 and no significant cardiac or lung co-morbidities were randomized into two fractionation arms: arm A: 30 Gy/10 over 2 weeks and arm B: 27 Gy/6 over 3 weeks (2 fractions per week) using 2 anterior posterior (AP-PA) fields in both arms. Primary end points were symptomatic and radiological tumor response, respiratory functions assessment. Secondary end point was toxicity. Results: From December 2014 to October 2015, 40 patients were randomized, 20 patients in each arm. There was statistically insignificant higher symptomatic improvement in arm B. Four weeks after treatment, 12 out of 40 patients (30%), 6 patients in each arm, had radiological Partial Response (PR) of the primary thoracic lesion without significant difference between the two arms. There was a tendency for improvement in the post treatment mean Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) in each arm without statistical significance. There were no reported skin reactions or esophagitis in both arms up to 4 weeks after treatment. Eleven out of the 40 patients (27.5%), 6 in arm B and 5 in arm A, had radiological signs of radiation pneumonitis without significant difference between both arms. Conclusion: The two RT fractionation schedules showed equal efficacy in terms of symptoms relief, radiological response of the primary thoracic tumor, respiratory functions and toxicity. Thus the 27 Gy/6 fractionation arm appears preferable compared to 30 Gy/10 arm to minimize the patients’ visits and load on the machines.
文摘Objective: To evaluate the clinical course of patients with small cell lung cancer (SCLC) as second primary malignancy. Methods: Among the 355 patients diagnosed with SCLC at Helen and Harry Gray Cancer Center of Hartford Hospital Connecticut USA between 1988 and 1998, the records of 48 patients, which had been diagnosed with other malignancies before their diagnosis of SCLC, were retro- spectively reviewed. Results: Forty-eight patients (13.5%) were diagnosed with other malignancies prior to their SCLC among which 43 had documented smoking history and 93% of them (40/43) were current/former smokers. Of the 28-second primary SCLC patients who were treated with standard method, 11 (39.3%) achieved CR. 12 (42.8%) achieved PR, and the RR was 82.1%. The median survival of the 28 treated with standard method was 11.3 months (5.1-77.7 months), while that of the rest 19 untreated patients (1 of 20 was lost to follow-up) was only 2.0 months (0.5 34.0 months). There was no significant difference in the median survival and RR between 165 treated first primary SCLC (13.5 months and 77.6% respectively) and 28 treated secondary primary SCLC (11.3 months and 82.1% respectively) (P〉0.05). The patients who had prostate cancer were older and subjected to less treatments than those with skin cancer, so their survival was shorter than the latter (3.5 months vs. 15 months, P〈0.05). Conclusion: The response and survival of the treated patients with SCLC as a second malignancy showed no difference as compared to the treated ones with SCLC only. Therefore, an active medical treatment is important to relieve symptom and prolong survival of the second primary SCLC patients.