• Tuberculosis and Respiratory Diseases
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• v.76 no.1
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• pp.1-7
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• 2014

Maintenance therapy has emerged as a novel therapeutic paradigm for advanced non-small-cell lung cancer (NSCLC). Maintenance therapy that aims to sustain a clinically favorable state after first-line chemotherapy has two strategies. Switch maintenance therapy entails switching to a new and non-cross-resistant agent in an alternating or sequential manner, on completion of first-line chemotherapy. Continuous maintenance therapy keeps ongoing administration of a component of the current regimen after four to six cycles of chemotherapy, if there is a stable disease, or better response. Both maintenance therapies can be continued, until disease progression. The potential evidence regarding maintenance therapy includes providing the opportunity to receive additional treatment, through sustaining tumor shrinkage, and delayed emergence of tumor-related symptom. Thus far, debates over the parameters used to predict the effectiveness of maintenance therapy, financial burden, and uncertainty of improving the quality of life exist. Despite many debates, maintenance therapy, which is currently recommended, has been disclosed to be beneficial.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.352-358
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• 2005

Microsatellites are short tandem repeated nucleotide sequences that are present throughout the human genome. Variations in the repeat number or a loss of heterozygosity around the microsatellites have been termed a microsatellite alteration (MA). A MA reflects the genetic instability caused by an impairment in the DNA mismatch repair system and is suggested to be a novel tumorigenic mechanism. A number of studies have reported that MA in the DNA extracted from the plasma occurs at varying frequencies among patients with a non-small cell lung carcinoma (NSCLC). The genomic DNA from 9 subjects with a non-small cell lung cancer (squamous cell cancer 6, adenocarcinoma 2, non-small cell lung cancer1) and 9 age matched non-cancer control subjects (AMC: tuberculosis 3, other inflammatory lung disease 6) and 12 normal control subjects (NC) were extracted from the peripheral blood leukocytes and plasma. Three microsatellite loci were amplified with the primers targeting the Gene Bank sequence D21S1245, D3S1300, and D3S1234. MA in the form of an allelic loss or a band shift was examined with 6% polyacrylamide gel electrophoresis and silver staining. None (0/12) of the NC subjects less than 40 years of age showed a MA in any of the three markers, while 88.9%(8/9) of the AMC above 40 showed a MA in at least one of the three markers (p<0.05). Sixty percent(6/10) of the control subjects with a smoking history showed a MA in one of the three markers, while 9.1%(1/11) of the control subjects without smoking history showed a MA (p<0.05). However, not only did 66.7%(6/9) of lung cancer patients show a MA in at least one of the three markers but so did 88.9%(8/21) of the AMC patients (p>0.05). In conclusion, a MA in the D21S1245, D3S1300, and D3S1234 loci using DNA extracted from the plasma was detected in 66.7% of lung cancer while no MA was found in the young non-smoking control subjects. However, many of the non-cancer control subjects (aged smokers) also showed a MA, which compromised the specificity of the MA analysis as a screening test. Therefore, a further study with a larger sample size will be needed.

• Journal of Chest Surgery
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• v.53 no.3
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• pp.93-103
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• 2020

Background: Risk assessment for pulmonary resection in patients with early-stage non-small-cell lung cancer (NSCLC) is important for minimizing postoperative morbidity. Depletion of skeletal muscle mass is closely associated with impaired nutritional status and limited physical ability. We evaluated the relationship between skeletal muscle depletion and early postoperative complications in patients with early-stage NSCLC. Methods: Patients who underwent curative lung resection between 2016 and 2018 and who were diagnosed with pathological stage I/II NSCLC were included, and their records were retrospectively analyzed. The psoas volume index (PVI, ㎤/㎥) was calculated based on computed tomography images from routine preoperative positron emission tomography-computed tomography. Early postoperative complications, defined as those occurring within 90 days of surgery, were compared between the lowest sex-specific quartile for PVI and the remaining quartiles. Results: A strong correlation was found between the volume and the cross-sectional area of the psoas muscle (R²=0.816). The overall rate of complications was 57.6% among patients with a low PVI and 32.8% among those with a normal-to-high PVI. The most common complication was prolonged air leak (low PVI, 16.9%; normal-to-high PVI, 9.6%), followed by pneumonia (low PVI, 13.6%; normal-to-high PVI, 7.9%) and recurrent pleural effusion (low PVI, 11.9%; normal-to-high PVI, 6.8%). The predictors of overall complications were low PVI (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07-4.09; p=0.03), low hemoglobin level (OR, 0.686; 95% CI, 0.54-0.87; p=0.002), and smoking history (OR, 3.93; 95% CI, 2.03-7.58; p<0.001). Conclusion: Low PVI was associated with a higher rate of early postoperative complications in patients with early-stage NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4013-4018
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• 2015

Objective: To explore the clinical application of recombinant human endostatin (Endostar) in the treatment of patients with non-small cell lung cancer (NSCLC) in Chinese mainland. Materials and Methods: A total of 75 patients diagnosed as NSCLC were randomly divided into control group (37 cases) and treatment group (38 cases). Control group was treated with postoperative complementary chemotherapy containing two-agent platinum protocol on postoperative d21, 3 weeks as a cycle, for totally 4~6 cycles. On this basis, treatment group was added with Endostar $7.5mg/m^2$ on postoperative d8~9, 3~4 h/time, qd, 14 weeks as a cycle, for totally 4 cycles. The interval between every two cycles was 7 d. The 5-year progression-free survival (PFS), 5-year survival time and complications in both groups were observed. Results: Compared with control group, the average PFS increased evidently in treatment group by 9.8 months (41.6 months vs. 31.8 months), and there was significant difference (P<0.05). And the median PFS was 42.5 months in treatment group, obviously longer than that in control group (33.7 months) by 8.8 months (P<0.05). Additionally, the 5-year overall survival rate (OS), average survival time and median survival time (MST) were 47.4%, 50.1 months and 59.3 months in treatment group, significantly higher than the 29.7%, 42.1 months and 43.5 months in control group (P<0.05). Only 1 patient showed poor healing of surgical wound in treatment group, but no surgery-associated complication was found in control group. Moreover, the postoperative complementary therapy-connected complication rates were 63.2% (24/38) and 59.5% (22/37) in treatment group and control group respectively, but there was no significant difference (P>0.05). Conclusions: The application of Endostar combined with sensitive platinum-contained chemotherapeutic agents in the postoperative complementary chemotherapy can be widely used in clinic because it can significantly prolong the long-term survival time of patients with NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5119-5124
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• 2012

Purpose: The aim of this retrospective study was to determine response rates, progression-free survival (PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastatic non-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-line chemotherapy. Methods: We retrospectively evaluated the file records of patients treated with gemcitabine plus paclitaxel in advanced or metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was as follows: gemcitabine $1500mg/m^2$ and paclitaxel 150 mg/m2 administered every two weeks. Results: Forty-eight patients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; median age, 56 years old (range 38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease (SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the median PFS was 2.7 months (95% CI 1.8-3.6). Grade 3 and 4 hematologic toxicities, including neutropenia (n=4, 8.4%), and anemia (n=3, 6.3%) were encountered, but no grade 3 or 4 thrombocytopenia. One patient developed febrile neutropenia. There were no interruption for reasons of toxicity and no exitus related to therapy. Conclusion: The combination of two-weekly gemcitabine plus paclitaxel was an effective and well-tolerated second-line chemotherapy regimen for advanced or metastatic NSCLC patients previously treated with platinum-containing chemotherapy. Although the most common and dose limiting toxicities were neutropenia and neuropathy, this regimen was tolerated well by the patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10967-10970
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• 2015

Objective: To analyze the efficacy and survival associated factors of gefitinib combined with cisplatin and gemcitabine for advanced non-small cell lung cancer. Materials and Methods: A total of 57 patients with advanced non-small cell lung cancer (NSCLC), who received platinum-based chemotherapy regimens for more than 1 cycle, were treated with gefitinib combined with cisplatin and gemcitabine until disease progression. Efficacy, survival time and adverse reactions were observed. The Kaplan-Meier method was adopted for analysis of survival and Cox regression for associated influencing factors. Results: The patients were followed up until October 31, 2013, and the median follow-up time was 19 months. Of 57 patients, there were 4 (7.0%) with complete remission (CR), 8 (14.0%) with partial remission, 31 (54.4%) with stable disease, and 14 (24.6%) with disease progression. The remission rate was 21.1% and the disease control rate was 75.4%. The median progression-free survival (PFS) time and the median overall survival time were 10 months and 15.2 months. The one-year, two-year and three-year survival rates were 47.4%, 23.3% and 10.0%. Gender and pathological types were the independent risk factors influencing PFS time (P=0.028, P=0.009). Tumor pathological type and early efficacy were independent factors for the prognosis (P=0.018, P=0.000). Adverse reactions were mostly rashes of I~II degree and diarrhea and slightly increasing level of aminopherase. The skin adverse event incidence of III degree or above was 1.8% (1/57) and brain metastasis was foudn in 31.6% (18/57). Conclusions: Gefitinib combined with cisplatin andgemcitabine, is effective for patients with IIIb~IV NSCLC who received multiple cycles of chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5971-5976
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• 2015

Background: Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC. Materials and Methods: This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis. Results: The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was $3.2{\pm}1.7g/dL$ (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC. Conclusions: This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.

• Journal of Chest Surgery
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• v.32 no.10
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• pp.910-915
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• 1999

Background: Positron emission tomography(PEFT) using fluorine-18 deoxyglucose(FDG), showing increased FDG uptake and retention in malignant cells, has been proven to be useful in differentiating malignant from benign tissues. We indertook the prospective study to compare the accuracy of the whole-body FDG PET with that of the conventional chest computed tomography(CT) for nodal staging of non-small-cell lung cancers(NSCLC). Material and Method: FDG PET and contrast enhanced CT were performed in 36 patients with potentially resectable NSCLC. Each Imaging study was evaluated independently, and nodal stations were localized according to the AJCC regional lymph nodes mapping system. Extensive lymph node dissection(1101 nodes) of ipsi- and contralateral mediastinal nodal stations was performed at thoracotomy and/or mediastinoscopy. Image findings were compared with the histopathologic staging results and were analyzed with the McNema test(p) and Kappa value(k). Result: The sensitivity, specificity, positive predictive value, and negative predictive value of CT for ipsilateral mediastinal nodal staging were 38%, 68%, 25%, 79%, and 61%, and those of PET were 88%, 71%, 47%, 95%, and 75%(p>0.05, K=0.29). When analyzed by individual nodal group(superior, aortopulmonary window, and inferior), the sensitivity, specificity, positive predictive value, and negative predictive value of CT were 27%, 82%, 22%, 85%, and 73%, and those of PET were 60%, 87%, 92%, and 82%(p<0.05, k=0.27). Conclusion: FDG PET in addition to CT appears to be superior to CT alone for mediastinal staging of non-small cell lung cancers.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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• pp.9-15
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• 2022

Anti-cancer and therapeutic effects using therapeutic radioisotopes have been demonstrated by various studies, and it is well-known that therapeutic radioisotopes are useful in cancer treatment. Recently, one of the therapeutic radioisotopes, scandium is emerging as a radioisotope applicable to PET imaging (⁴³Sc, ⁴⁴Sc) and therapy (⁴⁷Sc) in cancer theranostic approach. However, ⁴⁷Sc has little known radiobiological and therapeutic efficacy compared to other therapeutic radioisotopes. Here, we investigated the quality and therapeutic efficacy of ⁴⁷Sc radioisotope produced by our production/isolation technology at the research reactor 'HANARO' in KAERI (Korea Atomic Energy Research Institute). We showed that the therapeutic efficacy of ⁴⁷Sc, produced by our production/isolation technology, effectively suppressed epidermal growth factor receptor (EGFR)-targeted non-small cell lung cancer (NSCLC) cells. Consequently, these results suggest that the high quality of the produced ⁴⁷Sc by our production/isolation technology enables the development of therapeutic strategies for cancer treatment and radiopharmaceuticals using ⁴⁷Sc.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.2.1-2.22
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• 2022

Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.