• Journal of Chest Surgery
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• v.52 no.3
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• pp.131-140
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• 2019

Background: The purposes of this study were to evaluate the appropriateness of the stage migration of stage IIA non-small cell lung cancer (NSCLC) in the seventh edition of the tumor, node, and metastasis classification for lung cancer to stage IIB lung cancer in the eighth edition, and to identify prognostic factors in patients with eighth-edition stage IIB disease. Methods: Patients with eighth-edition stage IIB disease were subclassified into those with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease, and their recurrence-free survival and disease-specific survival rates were compared. Risk factors for recurrence after curative resection were identified in all included patients. Results: Of 122 patients with eighth-edition stage IIB NSCLC, 101 (82.8%) had seventh-edition stage IIA disease and 21 (17.2%) had seventh-edition stage IIB disease. Nonsignificant differences were observed in the 5-year recurrence-free survival rate and the 5-year disease-specific survival rate between the patients with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease. Visceral pleural invasion was a significant risk factor for recurrence in patients with eighth-edition stage IIB NSCLC. Conclusion: The stage migration from seventh-edition stage IIA NSCLC to eighth-edition stage IIB NSCLC was appropriate in terms of oncological outcomes. Visceral pleural invasion was the only prognostic factor in patients with eighth-edition stage IIB NSCLC.

• Journal of Chest Surgery
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• v.55 no.1
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• pp.20-29
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• 2022

Background: Patients with high-risk (HR) operable non-small cell lung cancer (NSCLC) may have unique prognostic factors. This study aimed to evaluate surgical outcomes in HR patients and to investigate prognostic factors in HR patients versus standard-risk (SR) patients. Methods: In total, 471 consecutive patients who underwent curative lung resection for NSCLC between January 2012 and December 2017 were identified and reviewed retrospectively. Patients were classified into HR (n=77) and SR (n=394) groups according to the American College of Surgeons Oncology Group criteria (Z4099 trial). Postoperative complications were defined as those of grade 2 or higher by the Clavien-Dindo classification. Results: The HR group comprised more men and older patients, had poorer lung function, and had more comorbidities than the SR group. The patients in the HR group also experienced more postoperative complications (p≤0.001). More HR patients died without disease recurrence. The postoperative complication rate was the only significant prognostic factor in multivariable Cox regression analysis for HR patients but not SR patients. HR patients without postoperative complications had a survival rate similar to that of SR patients. Conclusion: The overall postoperative survival of HR patients with NSCLC was more strongly affected by postoperative complications than by any other prognostic factor. Care should be taken to minimize postoperative complications, especially in HR patients.

• Journal of Chest Surgery
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• v.55 no.3
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• pp.214-224
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• 2022

Background: Studies of the prognostic role of circulating tumor cells (CTCs) in early-stage non-small cell lung cancer (NSCLC) are still limited. This study investigated the prognostic power of CTCs from the pulmonary vein (PV), peripheral blood (PB), and bone marrow (BM) for postoperative recurrence in patients who underwent curative resection for NSCLC. Methods: Forty patients who underwent curative resection for NSCLC were enrolled. Before resection, 10-mL samples were obtained of PB from the radial artery, blood from the PV of the lobe containing the tumor, and BM aspirates from the rib. A microfabricated filter was used for CTC enrichment, and immunofluorescence staining was used to identify CTCs. Results: The pathologic stage was stage I in 8 patients (20%), II in 15 (38%), III in 14 (35%), and IV in 3 (8%). The median number of PB-, PV-, and BM-CTCs was 4, 4, and 5, respectively. A time-dependent receiver operating characteristic curve analysis showed that PB-CTCs had excellent predictive value for recurrence-free survival (RFS), with the highest area under the curve at each time point (first, second, and third quartiles of RFS). In a multivariate Cox proportional hazard regression model, PB-CTCs were an independent risk factor for recurrence (hazard ratio, 10.580; 95% confidence interval, 1.637-68.388; p<0.013). Conclusion: The presence of ≥4 PB-CTCs was an independent poor prognostic factor for RFS, and PV-CTCs and PB-CTCs had a positive linear correlation in patients with recurrence.

• Clinical Pain
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• v.19 no.2
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• pp.120-123
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• 2020

Rapidly destructive arthrosis is a rare syndrome characterized by narrowing of the joint space and rapid joint destruction within 6~12 months. A 62-year-old woman with anaplastic lymphoma kinase rearranged non-small-cell lung cancer presented with both knee pain and varus deformity. She was treated with crizotinib 500 mg/day for more than 2 years, with partial tumor response. Initial plain radiography showed Kellgren and Lawrence (K-L) grade 1. After 10 months, varus deformity was worsened and plain radiography aggravated to K-L grade 4 despite conservative treatment including activity modification. Diffuse synovitis with massive joint effusion and destruction of anterior cruciate ligament, medial meniscus, medial collateral ligament, and lateral collateral ligament were shown in magnetic resonance imaging. The patient was diagnosed with rapidly destructive arthrosis of knee and underwent a both total knee arthroplasty.

• The Journal of Internal Korean Medicine
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• v.43 no.5
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• pp.838-853
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• 2022

Objectives: The purpose of this study is to report the case of a patient with recurrent L858R mutation non-small-cell lung cancer with brain metastases treated with erlotinib and traditional Korean medicine after gefitinib failure. Methods: The patient was treated with erlotinib beginning in November 2021, and gamma knife surgery was performed on November 8, 2021. The dose of erlotinib was 150 mg/day every four weeks. At the same time, the patient was treated with traditional Korean medicine. Tumor size and cerebral edema were measured using computed tomography and magnetic resonance imaging, respectively. Adverse events were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: After treatment with erlotinib and traditional Korean medicine for six months, the extent of the growing nodule in the right upper lobe decreased during the first three months and remained stable for the following three months. Peritumoral edema showed an increase three months after gamma knife surgery, but partial improvement of cerebral edema was confirmed with additional traditional Korean medicine six months after gamma knife surgery. The symptoms of discomfort and physical activity gradually improved. Conclusions: This case study suggests that the combination of EGFR-TKI and traditional Korean medicine may contribute to a reduction in tumor size and cerebral edema while improving quality of life.

• Journal of Radiation Protection and Research
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• v.48 no.3
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• pp.117-123
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• 2023

Background: We investigated the impact of 0.35 T magnetic field on dose calculation for non-small cell lung cancer (NSCLC) stereotactic ablative radiotherapy (SABR) in the ViewRay system (ViewRay Inc.), which features a simultaneous use of magnetic resonance imaging (MRI) to guide radiotherapy for an improved targeting of tumors. Materials and Methods: Here, we present a comprehensive analysis of the effects induced by the 0.35 T magnetic field on various characteristics of SABR plans including the plan qualities and dose calculation for the planning target volume, organs at risk, and outer/inner shells. Therefore, two SABR plans were set up, one with a 0.35 T magnetic field applied during radiotherapy and another in the absence of the field. The dosimetric parameters were calculated in both cases, and the plan quality indices were evaluated using a Monte Carlo algorithm based on a treatment planning system. Results and Discussion: Our findings showed no significant impact on dose calculation under the 0.35 T magnetic field for all analyzed parameters. Nonetheless, a significant enhancement in the dose was calculated on the skin surrounding the tumor when the 0.35 T magnetic field was applied during the radiotherapy. This was attributed to the electron return effect, which results from the deviation of the electrons ejected from tissues upon radiation due to Lorentz forces. These returned electrons re-enter the tissues, causing a local dose increase in the calculated dose. Conclusion: The present study highlights the impact of the 0.35 T magnetic field used for MRI in the ViewRay system for NSCLC SABR treatment, especially on the skin surrounding the tumors.

• IMMUNE NETWORK
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• v.23 no.4
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• pp.34.1-34.15
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• 2023

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3249-3253
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• 2016

Background: Pemetrexed monotherapy has come to be recognized as one of the standard second-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC). However, there have been no reports of studies that have evaluated the efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon 19 deletion or an L858R point mutation. Materials and Methods: The records of non-squamous NSCLC patients harboring an EGFR mutation who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2010 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. Results: The overall response rate and progression-free survival time (PFS) of the 53 patients with non-squamous NSCLC were 15.1% and 2.3 months, respectively. There were significant differences between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs. 3.3 months) of the exon 19 deletion group and the L858R point mutation group, and a multivariate analysis identified type of EGFR mutation as well as performance status (PS) as independent predictors of PFS. Conclusions: The clinical data obtained in this study provided a valuable rationale for considering type of EGFR mutation as well as non-squamous histology as predictors of the efficacy of pemetrexed monotherapy.

• Herbal Formula Science
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• v.21 no.1
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• pp.51-70
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• 2013

Objectives : The object of this study was to observe anticancer and related immunomodulatory effects of Insamyangyoung-tang extracts (ISYYTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of ISYYTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, which are intact control, tumor bearing control, 5-fluorouracil (FU) 30 mg/kg, ISYYTe 50 mg/kg, ISYYTe 100 mg/kg, ISYYTe 200 mg/kg, each of 8 mice per group were used in the present study. Changes on the body weight, tumor volume and weight, lymphatic organ (spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes NK cell activity and peritoneal macrophage activities, splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. Results : As results of ISYYTe 50, 100 and 200 mg/kg treatment, decreases in the tumor volumes and weights were detected. At histopathological observations, decreases of tumor cell volumes in tumor masses were dose-dependently decreased mediated by increases of apoptosis among tumor cells by treatment of all three different dosages of ISYYTe. As results of tumor cell inoculation, marked decreases of spleen and popliteal lymph node weights, serum IFN-${\gamma}$, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents and splenocytes were observed with histopathological atrophic changes of spleen and popliteal lymph nodes. Conclusions : Over 50 mg/kg of ISYYTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory effects. Although relatively lower anticancer effects were observed in ISYYTe 200 mg/kg treated mice as compared with 5-FU 30 mg/kg treated mice, there are no meaningful favorable immunomodulatory effects were observed after 5-FU treatment in the present study.

• Journal of Chest Surgery
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• v.29 no.11
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• pp.1241-1247
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• 1996

From January 1989 to March 1996, we have operated on 102 cases of non-small cell lung cancer at the department of Thoracic and Cardiovascular Surgery, Yonsei University Wonju College of Medicine. They were clinically evaluated. The results are as follows; 1. The peak incidence of age of primary lung cancer was 5th decade(34.3%) and 6th decade(38.2%). Male to female ratio was 2.5:1. 2. Most of symptoms were respiratory, which were cough(61.8%), sputum(43.l%), chest discomfort and pain(30.4%), dyspnea(27.5%), and hemoptysis(9.8%). Asymptomatic cases were 1.9% of study group. 3. Methods of diagnostic confirmation were bronchoscopic biopsy(59.8%), sputum cytology(17.6%), percutaneous needle aspiration(11.8%) and open biopsy(10.8%). 4. Histopathologic classifications were squamous cell carcinoma(55.9%), adenocarcinoma(30.5%), adenosquamous cell carcinoma(6.9%), large cell carcinoma(4.9%), bronchioalveolar cell carcinoma(0.9%), and mixed cell carcinoma(0.9%). 5. Methods of operation were pneumonectony(47.1%), lobectomy(38.2%), bilobectomy(5.9%), wedge resection(1.9%), exploration(6.9%), and overall resectability was 93.1%. 6. Postoperative staging classifications were Stage I (13.7%), Stage II(31.4%), Stage IIIa(38.3%), Stage IIIb(14.7%), and Stage IV(1.9%). 7. The postoperative complications developed in 9.8%, and operative mortality was 1.9 %. 8. One year survival rate was 81.7%, 3 year 49.7% and 5 year 21.8%. According to stage, 5 year survival rate was 39% in stage I, 24.3% in stage II, 23.9% in stage IIIa.