• Radiation Oncology Journal
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• v.22 no.1
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• pp.55-63
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• 2004

Purpose : To evaluate the reflection of tumor motion according to the planning CT scan time. Material and Methods : A model of N-shape, which moved aiong the longitudinal axis during the ventilation caused by a mechanical ventilator, was produced. The model was scanned by planning CT, while setting the relative CT scan time (T: CT scan time/ventilatory period) to 0.33, 0.50, 0.67, 0.75, 1.00, 1.337, and 1.537. In addition, three patients with non-small cell lung cancer who received stereotactic radiosurgery In the Department of Radiation Oncology, Asan Medical Center from 03/19/2002 to 05/21/2002 were scanned. Slow (10 Premier, Picker, scan time 2.0 seconds per slice) and fast CT scans (Lightspeed, GE Medical Systems, with a scan time of 0.8 second per slice) were peformed for each patient. The magnitude of reflected movement of the N-shaped model was evaluated by measuring the transverse length, which reflected the movement of the declined bar of the model at each slice. For patients' scans, all CT data sets were registered using a stereotactic body frame scale with the gross tumor volumes delineated in one CT image set. The volume and three-dimensional diameter of the gross tumor volume were measured and analyzed between the slow and fast CT scans. Results : The reflection degree of longitudinal movement of the model increased in proportion to the relative CT scan times below 1.00 7, but remained constant above 1.00 T Assuming the mean value of scanned transverse lengths with CT scan time 1.00 T to be $100\%$, CT scans with scan times of 0.33, 0.50, 0.57, and 0.75 T missed the tumor motion by 30, 27, 20, and $7.0\%$ respectively, Slow (scan time 2.0 sec) and Fast (scan time 0.8 sec) CT scans of three patients with longitudinal movement of 3, 5, and 10 mm measured by fluoroscopy revealed the increases in the diameter along the longitudinal axis Increased by 6.3, 17, and $23\%$ in the slow CT scans. Conculsion : As the relative CT scan time increased, the reflection of the respiratory tumor movement on planning CT also Increased, but remained constant with relative CT scan times above 1.00 T When setting the planning CT scan time above one respiration period (>1.00 T), only the set-up margin is needed to delineate the planning target volume. Therefore, therapeutic ratio can be increased by reducing the radiation dose delivered to normal lung tissue.

• Journal of Yeungnam Medical Science
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• v.28 no.1
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• pp.31-44
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• 2011

Background: The optimal timing of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKI) in NSCLC patients has not yet been determined. Methods: We separated 228 patients with advanced /metastatic NSCLC treated with gefitinib into an early gefitinib group (patients who received gefitinib as first- or second-line treatment) and a delayed gefitinib group (patients who received gefitinib as third or fourth-line treatment) and attempted to determine whether the timing of gefitinib treatment affected clinical outcomes. Results: Median overall survival (OS), progression free survival (PFS), and median OS from first-line treatment of advanced/metastatic disease (OSt) for 111 patients in the early gefitinib group were 6.2 months, 3.3 months, and 11.6 months. However, median OS, PFS, and OSt for 84 patients in the delayed gefitinib group were 7.8 months, 2.3 months, and 22.7 months. No differences in OS and PFS were observed between the 2 groups. However, OSt was significantly longer in the delayed gefitnib group. Timing of gefitinib therapy was one of the independent predictors of OSt. Hb ${\geq}$ 10 g/dl, and having never smoked, and ECOG performance status ${\leq}1$ were independent predictors of better PFS. Conclusion：Deferral of gefitinib therapy in patientswith advanced ormetastatic NSCLC may be preferable if they are able to tolerate chemotherapy.

• Tuberculosis and Respiratory Diseases
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• v.69 no.2
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• pp.115-118
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• 2010

Paclitaxel has been widely used for treating many solid tumors. Although colonic toxicity is an unusual complication of paclitaxel-based chemotherapy, the reported toxicities include pseudomembranous colitis, neutropenic enterocolitis and on rare occasions ischemic colitis. $Genexol-PM^{(R)}$, which is a recently developed cremophor-free, polymeric micelle-formulated paclitaxel, has shown a more potent antitumor effect because it can increase the usual dose of paclitaxel due to that $Genexol-PM^{(R)}$ does not include the toxic cremophor compound. We report here on a case of a 57-year-old man with advanced non-small cell lung cancer and who developed ischemic colitis after chemotherapy with $Genexol-PM^{(R)}$ and cisplatin. He complained of hematochezia with abdominal pain on the left lower quadrant. Colonoscopy revealed diffuse mucosal hemorrhage and edema from the sigmoid colon to the splenic flexure. After bowel rest, he recovered from his symptoms and the follow-up colonoscopic findings showed that the mucosa was healing. Since then, he was treated with pemetrexed monotherapy instead of a paclitaxel compound and platinum.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.34-43
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• 2005

Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.382-392
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• 2003

Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.299-306
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• 1996

Purpose : Respiratory symptoms related with malignant airway disease have been the main causes of lowered qualify of life and also sometimes may be life-threatening if not properly managed. The authors report the short-term experiences of endobronchial brachytherapy for symptomatic malignant airway obstruction using high dose rate after-loading brachytherapy unit. Materials and Methdos : Twenty-five Patients with symptomatic malignant airway obstruction were treated with endobronchial brachytherapy between the period of December 1994 and March 1996 at Department of Radiation Oncology of Samsung Medical Center Twenty-one ($84\%$) were patients with non-small cell lung cancer, three with tracheal malignancies, and one with recurrence of esophageal cancer. Twenty Patients were given elective external beam radiation therapy, while six were given endobronchial laser evaporation therapy on emergency bases in addition to endobronchial brachytherapy. Three procedures for each patient were planned and total of 70 procedures were completed. Results : Improvement rates of major respiratory symptoms after endobronchial brachytherapy procedures were $88\%$(22/25). $96\%$(22/23), $100\%$ (15/15), and $100\%$(9/9) for cough, dyspnea, hemoptysis and obstructive pneumonia, respectively. ECOG performance scores were improved in $56\%$ of total patients group, while there was no case with worsened ECOG score. Fifteen patients died and the median interval from the start of treatment to death was 4 months (range: $1\~17$ months), while that of ten survivors was 9 months (range $5\~19$ months). There were five patients with controlled intrathoracic disease, who have survived over one rear. All deaths were associated with uncontrolled local and/or distant disease. Four Patients died of massive fatal hemoptysis, three of who received emergency endobronchial laser evaporation therapy before the start of endobronchial brachytherapy. Conclusion : Endobronchial brachytherapy has been confirmed as an excellent palliative treatment modality improving respiratory symptoms as well as patients' general performance status. Based on the current observations, use of endobronchial brachytherapy in curative setting as a boost technique may be warranted.

• Journal of Chest Surgery
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• v.40 no.9
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• pp.593-599
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• 2007

Background: The correlation between levels of brain natriuretic peptide (BNP) and the effect of pulmonary resection on the right ventricle of the heart is not yet widely known. This study aims to assess the relationship between the change in hemodynamic values of the right ventricle and increased BNP levels as a compensatory mechanism for right heart failure following pulmonary resection and to evaluate the role of the BNP level as an index of right heart failure after pulmonary resection. Material and Method: In 12 non small cell lung cancer patients that had received a lobectomy or pnemonectomy, the level of NT-proBNP was measured using the immunochemical method (Elecsys $1010^{(R)}$, Roche, Germany) which was compared with hemodynamic variables determined through the use of a Swan-Garz catheter prior to and following the surgery. Echocardiography was performed prior to and following the surgery, to measure changes in right ventricular and left ventricular pressures. For statistical analysis, the Wilcoxon rank sum test and linear regression analysis were conducted using SPSSWIN (version, 11.5). Result: The level of postoperative NT-proBNP (pg/mL) significantly increased for 6 hours, then for 1 day, 2 days, 3 days and 7 days after the surgery (p=0.003, 0.002, 0.002, 0.006, 0.004). Of the hemodynamic variables measured using the Swan-Ganz catheter, the mean pulmonary artery pressure after the surgery when compared with the pressure prior to surgery significantly increased at 0 hours, 6 hours, then 1 day, 2 days, and 3 days after the surgery (p=0.002, 0,002, 0.006, 0.007, 0.008). The right ventricular pressure significantly increased at 0 hours, 6 hours, then 1 day, and 3 days after the surgery (p=0.000, 0.009, 0.044, 0.032). The pulmonary vascular resistance index [pulmonary vascular resistance index=(mean pulmonary artery pressure-mean pulmonary capillary wedge pressure)/cardiac output index] significantly increased at 6 hours, then 2 days after the surgery (p=0.008, 0.028). When a regression analysis was conducted for changes in the mean pulmonary artery pressure and NT-proBNP levels after the surgery, significance was evident after 6 hours (r=0.602, p=0.038) and there was no significance thereafter. Echocardiography displayed no significant changes after the surgery. Conclusion: There was a significant correlation between changes in the mean pulmonary artery pressure and the NT-proBNP level 6 hours after a pulmonary resection. Therefore, it can be concluded that changes in NT-proBNP level after a pulmonary resection can serve as an index that reflects early hemodynamic changes in the right ventricle after a pulmonary resection.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.168-184
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• 2001

Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.