• Journal of Chest Surgery
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• v.52 no.4
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• pp.221-226
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• 2019

Background: Accurate mediastinal lymph node staging is vital for the optimal therapy and prognostication of patients with lung cancer. This study aimed to determine the preoperative risk factors for pN2 disease, as well as its incidence and long-term outcomes, in patients with clinical N0-1 non-small cell lung cancer. Methods: We retrospectively analyzed patients who were treated surgically for primary non-small cell lung cancer from November 2005 to December 2014. Patients staged as clinical N0-1 via chest computed tomography (CT) and positron emission tomography (PET)-CT were divided into two groups (pN0-1 and pN2) and compared. Results: In a univariate analysis, the significant preoperative risk factors for pN2 included a large tumor size (p=0.083), high maximum standard uptake value on PET (p<0.001), and central location of the tumor (p<0.001). In a multivariate analysis, central location of the tumor (p<0.001) remained a significant preoperative risk factor for pN2 status. The 5-year overall survival rates were 75% and 22.9% in the pN0-1 and pN2 groups, respectively, and 50% and 78.2% in the patients with centrally located and peripherally located tumors, respectively. In a Cox proportional hazard model, central location of the tumor increased the risk of death by 3.4-fold (p<0.001). Conclusion: More invasive procedures should be considered when preoperative risk factors are identified in order to improve the efficacy of diagnostic and therapeutic plans and, consequently, the patient's prognosis.

• The Journal of Internal Korean Medicine
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• v.41 no.6
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• pp.1255-1264
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• 2020

Objective: The purpose of this study was to report the effect of Korean medicine on a patient with non-small cell lung cancer with pleural metastasis who had been treated with afatinib. Method: A 61-year old female patient with non-small cell lung cancer with pleural metastasis was treated with acupuncture and herbal medicines, including Yijung-tang, Haengso-tang, Samchulkunbi-tang, Paeamju-bang (Feiai zhu fang), to control various symptoms caused by afatinib. The degree of pain was assessed by a numeric rating scale (NRS) and the quality of life was determined with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) and the EORTC 13-item lung cancer-specific module (EORTC LC-13). Results: After receiving acupuncture and herbal medicines, the patient showed improvement in her back and chest pain, according to the NRS score. Similarly, the Korean medicinal treatments significantly relieved her nausea, vomiting, diarrhea, hemoptysis, and alopecia. However, the EORTC QLQ-C30 assessment suggested that Korean medicinal treatments did not significantly improve the global health status of this patient. Conclusion: Korean medicine could be useful in relieving some of the symptoms occurring after conventional afatinib treatments.

• Radiation Oncology Journal
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• v.32 no.2
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• pp.70-76
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• 2014

Purpose: To review the results of postoperative radiation therapy (PORT) for residual non-small cell lung cancer (NSCLC) following surgical resection and evaluate multiple clinicopathologic prognostic factors. Materials and Methods: A total of 58 patients, who completed scheduled PORT for positive resection margin, among 658 patients treated with PORT from January 2001 to November 2011 were retrospectively analyzed. Radiation therapy was started at 4 to 6 weeks after surgery. Chemotherapy was also administered to 35 patients, either sequentially or concurrently with PORT. Results: The median age of patients was 63 years (range, 40 to 82 years). The postoperative pathological stage I NSCLC was diagnosed in 10 (17.2%), stage II in 18 (31.0%), and stage III in 30 patients (51.7%). Squamous cell carcinoma was identified in 43, adenocarcinoma in 10, large cell in 1, others in 4 patients. Microscopic residual disease (R1) was diagnosed in 55 patients (94.8%), and the remaining three patients were diagnosed with gross residual disease (R2). The median dose of PORT was 59.4 Gy (range, 50.0 to 64.8 Gy). Chemotherapy was administered to 35 patients (60%), and the median follow-up time was 22.0 months (range, 6.0 to 84.0 months). The 3-year locoregional relapse-free survival and distant metastasis-free survival rates were 82.1% and 52.9%, respectively. The median overall survival was 23.8 months (range, 6.0 to 84.1 months), and the 3-year overall survival rate was 58.2%. Chemotherapy did not influence the failure pattern or survival outcome. Conclusion: PORT is an effective modality for improving local tumor control in incompletely resected NSCLC patients. Major failure pattern was distant metastasis despite chemotherapy.

• Journal of Chest Surgery
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• v.56 no.2
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• pp.67-74
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• 2023

Perioperative treatment with conventional cytotoxic chemotherapy for resectable non-small cell lung cancer (NSCLC) has proven clinical benefits in terms of achieving a higher overall survival (OS) rate. With its success in the palliative treatment of NSCLC, immune checkpoint blockade (ICB) has now become an essential component of treatment, even as neoadjuvant or adjuvant therapy in patients with operable NSCLC. Both pre- and post-surgery ICB applications have proven clinical efficacy in preventing disease recurrence. In addition, neoadjuvant ICB combined with cytotoxic chemotherapy has shown a significantly higher rate of pathologic regression of viable tumors compared with cytotoxic chemotherapy alone. To confirm this, an early signal of OS benefit has been shown in a selected population, with programmed death ligand 1 expression ≥50%. Furthermore, applying ICB both pre- and post-surgery enhances its clinical benefits, as is currently under evaluation in ongoing phase III trials. Simultaneously, as the number of available perioperative treatment options increases, the variables to be considered for making treatment decisions become more complex. Thus, the role of a multidisciplinary team-based treatment approach has not been fully emphasized. This review presents up-to-date pivotal data that lead to practical changes in managing resectable NSCLC. From the medical oncologist's perspective, it is time to dance with surgeons to decide on the sequence of systemic treatment, particularly the ICB-based approach, accompanying surgery for operable NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.975-983
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• 1998

Purpose: Frequent deletion of 3p in numerous cancer including lung cancer suggests the presence of tumor suppressor gene. 3p has been analysed by RFLP and PCR-LOH of microsatellite locus. In this study, we observed the deletion of 3p in Korean NSCLC by PCR-LOH of 4 microsatellite loci and investigated the clinical significance. Method: 62 surgically resected NSCLC DNA and normal lung DNA have been analysed by PCR-LOH at three dinucleotide[D3S1228 (3p14.1-14.3), D3S1067 (3p14.3-21.1), D3S1029 (3p21.1-21.3)] and one tetranucleotide[D3S1537 (3p 22-24.2)] repeat microsatellite loci. Results: Among 59 informative cases, 3p deletion by PCR-LOH at four microsatellite loci was found in 31 patients(52.5%). 3p deletion were found in 55% of squamous cell lung cancer and 47% of adenocarcinoma patients. No significant difference has been found in clinical parameters such as staging, smoking and survival according to the status of 3p deletion. Conclusion: Deletions in 3p have played an important role in Korean NSCLC though no clinical significance was detected.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.139-143
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• 2014

Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs $41.0{\pm}3.50%$, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, $4.33{\pm}0.33$ vs $0.33{\pm}0.33$, P=0.01; in SPC-A1, $2.67{\pm}0.33$ vs $0.00{\pm}0.00$, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (> $200{\times}10^9/L$, 3 months versus ${\leq}200{\times}10^9/L$, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.659-668
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• 1993

Background: p53 is currently considered as a tumor suppressive gene product, and its alterations are suggested to be involved in several human malignancies, including non-small cell lung cancers. p53 expression rates are variable in many reports and among cell types. Also, whether the phase of p53 expression is early or late during carcinogenesis is not certain. Thus, We have investigated to evaluate p53 expression rates of the various cell types and tissues and identify expression phase (early or late). Method: We obtained 71 tissue from 50 non-small cell lung cancer patients and performed the simple immunohistochemical staining using nonspecific monoclonal antibody(NCL-p53DO7). Results: 1) In non-small cell lung cancer patients. the expression rate of lungs(46.5%) is higher than that(25.0%) of lymph nodes. But, there is no significant difference between two groups. 2) Among the various cell types, p53 expression rates in squamous cell carcinoma and adenocarcinoma are 58.3% and 50.0% respectively without significant difference. 3) p53 expression rates in various stages are 33.3%, 60.0%, 40.0%, 60.0% and 66.7% in stage I, II, IIIa, IIIb and IV, respectively with no significant difference. 4) p53 expression rates in the various T parameters are 33.3%, 50.0%, 16.7% and 100% in T1, T2, T3 and T4, respectively and p53 expression rates in the various N parameters are 27.3%, 22.2% and 25.0% in N1, N2 and N3, respectively. There are no significant differences in the expression rates among varous T & N parameters. 5) p53 expression rates of lymph nodes in patients who have positive stains in lungs are 12.5% and 50.0% in N1 and N2. 6) p53 expression rates of all lymph nodes in patients who have negative stains in lungs are 0.0%. Conclusion: The above results show that p53 expression rate in non-small cell lung cancers is not correlated with cell type and progression of stage and it is thought to need further investigations about at what phase p53 expression influences the development and progression of lung cancers.

• Radiation Oncology Journal
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• v.2 no.2
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• pp.203-211
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• 1984

From 1979 to 1982, 80 patients with unresectable non-small-cell lung cancer without metastasis were treated with high-dose radiotherapy to the primary and to regional lymph nodes with or without supraclavicular lymphatics in the Department of Therapeutic Radiology, Seoul National University Hospital. Of these, 56 patients$(70\%)$ were completely evaluable, and 59 patients$(74\%)$ had squamous cell carcinoma, 13a large cell undifferentiated carcinoma and 831 adenocarcinoma. 21 patients$(26\%)$ had Stage II and 59 patients$(74\%)$ had Stage III. The complete and partial response rate in the high-dose$(\approx\;6,000\;rad)$ radiotherapy was $70\%\;with\;19\%$ complete response. 69 patients$(86\%)$ failed in the treatment, by the failure pattern, $64\%$ had local failure alone, $35\%$ had local failure and distant metastasis and $1\%$ had distant metastasis alone. The failure rate in the thorax were $76\%$ in squamous cell carcinoma, $40\%$in adenocarcinoma and $20\%$ in large cell undifferentiated carcinoma Preliminary result shows that actuarial survival at 1, 2 and 3 years were $56\%,\;26\%\;and\;20\%$ in overall patients and $64\%,\;37\%\;and\;21\%\;in\;Stage\;II\;and\;54\%1,\;21\%\;and\;18\%$ in Stage III, respectively. Overall median survival was 14 months; 17 months in Stage II and 13 months in Stage m. 8 patients$(10\%)$ have lived a minimum of 2 years with no evidence of disease. There was no fatal complication confirmed to be induced by radiotherapy, so definitive high-dose radiotherapy was tolerated well without major problems and resulted in good local control and survival.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.381-392
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• 2004

Arsenic trioxide($As_2O_3$) was introduced into the treatment of refractory or relapsed acute promyelocytic Ieukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis. Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L. Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5171-5174
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• 2013

Background: This study aimed to explore potential associations between single nucleotide polymorphisms (SNPs) of the x-ray repair cross-complementing group 1 (XRCC1) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) and non-small cell lung cancer (NSCLC) susceptibility in non-smoker Chinese patients. Methods: A total of 200 NSCLC patients and 200 healthy controls with matched age and gender were recruited for genotyping of XRCC1 SNPs (rs2256507 and rs1001581) and CLPTM1L SNPs (rs401681 and rs4975616). Association of these SNPs with NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. Results: The frequencies of genotype and allele in these four loci (rs2256507, rs1001581, rs401681, and rs4975616) were not significantly different between the cases and controls, or between either of the histological subgroups (adenocarcinoma and squamous cell carcinoma) and controls. Conclusions: Although these SNPs are associated with NSCLC risk in patients with a tobacco-smoking habit, this study demonstrated that XRCC1 and CLPTM1L gene SPNs are not linked with NSCLC risk in non-smoking patients, indicating that molecular mechanisms of NSCLC betwee tobacco smokers and non-smokers may be different. Future studies are needed to uncover the underlying molecular mechanisms for NSCLC in non-smokers.