• Radiation Oncology Journal
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• v.19 no.1
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• pp.16-20
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• 2001

Purpose : To evaluate the effectiveness and tolerance of the postoperative radiation therapy for patients with Stage III thymoma and to define the optimal radiotherapeutic regimen Materials and Methods : We retrospectively analyzed the records of 24 patients with Stage III thymoma who were referred for postoperative radiation therapy in our institution from June, 1987 to May, 1999. Surgical therapy consisted of total resection in one patient, subtotal resection in seventeen, and biopsy alone in six patients. Age of the patients was ranged from 20 to 62 years with mean age of 47 years. Male to female ratio was 14 to 10. Radiation therapy was delivered with linear accelerator producing either 6 MeV or 10 MeV photons. The irradiated volume included anterior mediastinum and known residual disease. The supraclavicular fossae were not irradiated. The delivered total dose was ranged from 30 to 56 Gy. One patient received 30 Gy and eighteen patients received minimum of 50 Gy. Follow up period was ranged from 12 months to 8 years with median follow up of 40 months. Results : The overall local control rate for entire group of patients was $67\%$ at 5 years. The cumulative local failure rates at one, three and five year were $18\%,\;28\%\;and\;33\%$, respectively. In patients treated with subtotal resection and biopsy alone, local control rate was $76\%\;and\;33\%$, respectively. The actuarial observed survival rate at 5 years was $57\%$, and actuarial adjusted survival at 5 years was $72\%$. The difference between 5 year survival rates for patients treated with subtotal resection and biopsy alone was not statistically significant $(62\%\;vs\;30\%)$. Conclusion : We might conclude that postoperative radiation therapy was safe and effective treatment for patients with Stage III thymoma. Postoperative radiation therapy is recommended in cases where tumor margin is close or incomplete resection is accomplished.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.104-112
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• 2008

Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7569-7576
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• 2013

Background: The purpose of this article is to present preliminary results of simultaneous boost irradiation radiotherapy for locally advanced nasopharyngeal carcinoma (NPC). Methods: Fifty-eight patients who underwent simultaneous boost irradiation radiotherapy for NPC in Cancer Center of Sun Yat-sen University between September 2004 and December 2009 were eligible. Acute and late toxicities were scored weekly according to the Radiation Therapy Oncology Group (RTOG) acute and late radiation morbidity scoring schemes. An especial focus was on evidence of post-radiation brain injury. Also quality of life was analysed according to the EORTC (European Organisation for Research and Treatment of Cancer) recommendations. Discrete variables were compared by ${\chi}^2$ test. The Kaplan-Meier method was used to calculate the survival rates and generate survival curves. Results: A total of 58 patients with a mean follow-up time of 36 months completed clinical trials.Fifty-seven patients (98.3) achieved complete remission in the primary sites and cervical lymph nodes, with only one patient (1.7%) showing partial remission.The most frequently observed acute toxicities during the concurrent chemoradiotherapy were mucositis and leucopenia. Four patients (6.9%) had RTOG grade 3 mucositis, whereas four patients (6.9%) had grade 3 leucopenia. No patient had grade 4 acute toxicity. Three (5.17%) of the patients exhibited injury to the brain on routine MRI examination, with a median observation of 32 months (range, 25-42months). All of them were RTOG grade 0. The 3-year overall, regional-free and distant metastasis-free survival rates were 85%, 94% and 91%, respectively. Conclusion: Simultaneous boost irradiation radiotherapy is feasible in patients with locally advanced nasopharyngeal carcinoma. The results showed excellent local control and overall survival, with no significant increase the incidence of radiation brain injury or the extent of damage. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.37-45
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• 1991

In order to assess the effects of radiofrequency-induced local hyperthermia on the normal liver, histopathologic findings and biochemical changes after localized hyperthermia in canine liver were studied. Hyperthermia was externally adminsitered using the Thermotron RF-8 (Yamamoto Vinyter Co., Japan; Capacitive type heating machine) with parallel opposed electrodes. Thirteen dogs were used and allocated into one control group (N=3) and two treatment groups according to the treatment temperature. Group I (N=5) was heated with $42.5\pm0.5^{\circ}C$ 30 minutes, and Group II (N=5) was heated with $45\pm0.5^{\circ}C$ for 15-30 minutes. Samples of liver tissue were obtained through a needle biopsy immediately after hyperthermia and T,14, and 28 days after treatment. Blood samples were obtained before treatment and W, 3,5, 7,14 and 28 days after treatment and examined for SGOT, SGPT and alkaline phosphatase. Although SGOT and SGPT were elevated after hyperthermia in both groups (three of five in each group), there was no liver cell necrosis or hyperthermia related mortality in Group 1. A hydropic swelling of hepatocytes was prominent histologic finding. Hyperthermia with $45^{\circ}C$ for 30 minutes was fatal and showed extensive liver cell necrosis. In conclusion, liverdamage dy heat of $42.5\pm0.5^{\circ}C$ for 30 minutes is reversible, and liver damage by heat of $45\pm0.5^{\circ}C$ for 30 minutes can be fatal or irreversible. However, these results cannot be applied directly to human trial. Therefore, in erder to apply hyperthermic treatment on human liver tumor safely, close obsewation of temperature with proper thermometry is mandatory. Hyperthermic treatment should be confined to the tumor area while sparing a normal liver as much as possible.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.25 no.4
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• pp.281-294
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• 1999

Vasospasm causes microvascular surgery to fail as a main factor in the loss of transferred flap dye to the diminution of blood flow in reconstruction surgery. Although there has been extensive research to resolve the vasospasm problem, no one has reached an ideal solution to date. However, cryotherapy, which is often used for destruction of tumor lesions, is being presented as a new way of releasing vasospasm. After making a histomorphometric measurement on vasodialation during the course of 1, 3 and 7 days, 2 and 4 weeks, and 5 months periods and observing the change of blood vessel in a histologic, immunohistochemical, and scanning electronic microscopic approach, the results were as follows : 1. Vascular inner diameters of the experimental 1 and 3 days groups were measured $476.3{\pm}28.20{\mu}m$, $497.15{\pm}48.79{\mu}m$ respectively showing statistically meaningful vasodilation(P<0.05), which continued by the experiment 4 weeks group. However, in the experimental 5 months group, the vascular inner diameter appeared similar to the control groups. Even though the thickness of smooth muscular layers come out to be thinner in all the experimental groups compared to the control group, it was difficult to find any statistical meaningfulness. In addition, the vascular external diameters of every experimental groups were shown to be longer than the control group. 2. In light microscopic view, severe injury was evident on the smooth muscular layer cell from the experimental 1 day group, started recovering partially from the experimental 7 days group, and was mostly restored in the experimental 4 weeks group and layer of adventitial stripping were nearly recoverd 2 weeks group. 3. The PCNA positive cells of smooth muscular layer were observed from the experimental 7 days group and had a tendency to increase by the experimental 2 weeks group. In the experimental 4 weeks and 5 months group, the number of PCNA possitive cells observed was comparable to the control group. 4. ${\alpha}$-SMA level of smooth muscular layer cells, having been significantly lower than the control group in the severly damaged experimental 1 day group. It was seen to be increased in the experimental 7 days group and turned out to show similar ${\alpha}$-SMA level in 4 weeks to the control group. 5. In the view of SEM, the endothelial cells were destructed and falling off, and also present the appearance of flattening in the experiment 1 day group. The endothelial layer cells started partially recovering from the 7 days group after the freezing injury. On 4 weeks and 5 months, the endothelial cells were fully coverd the damaged area, also it's appearance is similar to control group. In conclusion, the vascular freezing after the removal of adventitia caused damages to smooth muscular layer cells, and brought about vasodilation, which continued by the 4th week. The smooth muscular layer cells started partially reviving from the 7rd day after the damage by vascular freezing, and recovered their similar figure to the control group's 4 weeks later. This was considered the result of cells which surround the damaged blood vessel being influxed into the smooth muscular layers. Therefore, this local freezing injury on the blood vessel was thought to be applied clinically to relieve severe vasospasm which cannot be treated by vasodilation drug, a microvascular surgery.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.64-70
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• 2009

Purpose: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable pancreatic cancer. However, the introduction of gemcitabine and the recognition of a benefit in patients with advanced disease stimulated the design of trials that compare chemotherapy alone to concurrent chemoradiation. Therefore, we evaluated role of CCRT for locally advanced unresectable pancreatic cancer. Materials and Methods: We carried out a retrospective analysis of treatment results for patients with locally advanced unresectable pancreatic cancer between January 2000 and January 2008. The radiation was delivered to the primary tumor and regional lymph nodes with a 1~2 cm margin at a total dose of 36.0~59.4 Gy (median: 54 Gy). The chemotherapeutic agent delivered with the radiation was 5-FU (500 mg/$m^2$). The patients who underwent chemotherapy alone received gemcitabine (1,000 mg/$m^2$) alone or gemcitabine with 5-FU. The follow-up period ranged from 2 to 38 months. The survival and prognostic factors were analyzed using Kaplan-Meier method and log-rank test, respectively. Results: Thirty-four patients received concurrent chemoradiotherapy, whereas 21 patients received chemotherapy alone. The median survival time was 12 months for CCRT patients, compared to 11 months for chemotherapy alone patients (p=0.453). The median progression-free survival was 8 months for CCRT patients, compared to 5 months for chemotherapy alone patients (p=0.242). The overall response included 9 partial responses for CCRT and 1 partial response for chemotherapy alone. In total, 26% of patients from the CCRT group experienced grade 3~4 bowel toxicity. In contract, no grade 3~4 bowel toxicity was observed in the chemotherapy alone group. The significant prognostic factors of overall survival were lymph node status, high CA19-9, and tumor location. Conclusion: The response rate and progression-free survival were more favorable in the CCRT group, when compared with the chemotherapy alone group. Therefore, radiation therapy seems to be an effective tool for local tumor control.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.303-308
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• 2002

Purpose : To determine the optimal radiation dose in a localized non-Hodgkin's lymphoma of the head and neck in the treatment setting for combined chemoradiotherapy. Materials an Methods :Fifty-three patients with stage I and II diffuse large ceil non-Hodgkin's lymphoma of the head and neck, who were treated with combined chemoradiotherapy between 1985 and 1998 were retrospectively reviewed. The median age was 49 years, and the male-to-female ratio was approximately 1.6. Twenty-seven patients had stage 1 disease and 26 had stage II. Twenty-three patients had bulky tumors $(\geq5\;cm)$ and 30 had non-bulky tumors (<5 cm). The primary tumors arose mainly from an extranodal organ $(70\%)$, most cases involving Waldeyer's ring $(90\%)$. All patients except one were initially treated with $3\~6$ cycles of chemotherapy, which was followed by radiotherapy. Radiation was delivered either to the primary tumor area alone $(9\%)$ or to the primary tumor area plus the bilateral neck nodes $(91\%)$ with a minimum dose of 30 Gy $(range\;30\~60\;Gy)$. The failure patterns according to the radiation field were analyzed, and the relationship between the dose and the in-field recurrence was evaluated. Results : The 10-year overall survival and the 10-year disease free survival rates were similar at $75\%\;and\;76\%$, respectively. A complete response (CR) after chemotherapy was achieved in 44 patients $(83\%)$. Subsequent radiotherapy showed a CR in all patients. Twelve patients $(23\%)$ had a relapse of the lymphoma after the initial treatment. Two of these patients had a recurrence inside the radiation field. No clear dose response relationship was observed and no significant prognostic factors for the in-field recurrences were identified because of the small number of in-field recurrences. However, for patients with tumors <5 cm in diameter, there were no in-field recurrences after a radiation dose 30 Gy. The 2 in-field recurrences encountered occurred in patients with a tumor $\geq5\;cm$. Conclusion .A dose of 30 Gy is sufficient for local control in patients with a non-bulky (<5 cm), localized, diffuse large cell non-Hodgkin's lymphoma when combined with chemotherapy. An additional boost dose in the primary site is recommended for patients with bulky tumors $(\geq5\;cm)$.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.776-784
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• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.247-257
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• 1989

Thirty patients with nonresectable hepatocellular carcinoma (HCC) due to either locally advanced lesion or association with liver cirrhosis, treated with combined radiotherapy and hyperthermia between April 1988 and July 1988, at Dept. of Radiation Oncology, Yonsei university College of medicine, were analysed. External radiotherapy of a total dose of 3060cGy/3.5 wks was given. Hyperthermia was given twice a week with a total of 6 treatment sessions using 8MHz radiofrequency capacitive type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases hyperthermia was given within 30 minutes after radiotherapy for 30~60min. Temperature was measured by inserting thermocouple into the tumor mass under the ultrasonographic guidance only for those who had not bleeding tendency. As a result, partial response (PR) was achieved in 12 patients (40%), and symptomatic improvement was observed in 22 patients (78.6%) among 28 patients who had suffered from abdominal pain. The most significant factor affecting the tumor response rate was the type of tumor (single massive: 10/14, 71.4%; diffuse infiltrative: 2/10, 20%; multinodular:0/6, 0%; p<0.005). There were not any significant side effects relating to combined treatment. The overall 1 year survival rate was 34%, with 50% in the PR group and 22% in the no response group (NR), respectively. Median survival was 6.5 months and longer for those of PR than of NR (11 mos. vs 5, p<0.05). In conclusion, combined radiotherapy and hyperthermia appeared to be effective in local control and symptomatic palliation of HCC. Further study including a larger number of the patients to confirm its effect in survival and detrimental side effect should be urged.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.5
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• pp.375-395
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• 2006

Purpose: Lingual nerve (LN) damage may be caused by either tumor resection or injury such as wisdom tooth extraction, Although autologous nerve graft is sometimes used to repair the damaged nerve, it has the disadvantage of necessity of another operation for nerve harvesting. Moreover, the results of nerve grafting is not satisfactory. The nerve growth factor (NGF) is well-known to play a critical role in peripheral nerve regeneration and its local delivery to the injured nerve has been continuously tried to enhance nerve regeneration. However, its application has limitations like repeated administration due to short half life of 30 minutes and an in vivo delivery model must allow for direct and local delivery. The aim of this study was to construct a well-functioning $rhNGF-{\beta}$ adenovirus for the ultimate development of improved method to promote peripheral nerve regeneration with enhanced and extended secretion of hNGF from the injured nerve by injecting $rhNGF-{\beta}$ gene directly into crush-injured LN in rat model. Materials and Methods: $hNGF-{\beta}$ gene was prepared from fetal brain cDNA library and cloned into E1/E3 deleted adenoviral vector which contains green fluorescence protein (GFP) gene as a reporter. After large scale production and purification of $rhNGF-{\beta}$ adenovirus, transfection efficiency and its expression at various cells (primary cultured Schwann cells, HEK293 cells, Schwann cell lines, NIH3T3 and CRH cells) were evaluated by fluorescent microscopy, RT-PCR, ELISA, immunocytochemistry. Furthermore, the function of rhNGF-beta, which was secreted from various cells infected with $rhNGF-{\beta}$ adenovirus, was evaluated using neuritogenesis of PC-12 cells. For in vivo evaluation of efficacy of $rhNGF-{\beta}$ adenovirus, the LNs of 8-week old rats were exposed and crush-injured with a small hemostat for 10 seconds. After the injury, $rhNGF-{\beta}$ adenovirus($2{\mu}l,\;1.5{\times}10^{11}pfu$) or saline was administered into the crushed site in the experimental (n=24) and the control group (n=24), respectively. Sham operation of another group of rats (n=9) was performed without administration of either saline or adenovirus. The taste recovery and the change of fungiform papilla were studied at 1, 2, 3 and 4 weeks. Each of the 6 animals was tested with different solutions (0.1M NaCl, 0.1M sucrose, 0.01M QHCl, or 0.01M HCl) by two-bottle test paradigm and the number of papilla was counted using SEM picture of tongue dorsum. LN was explored at the same interval as taste study and evaluated electro-physiologically (peak voltage and nerve conduction velocity) and histomorphometrically (axon count, myelin thickness). Results: The recombinant adenovirus vector carrying $rhNGF-{\beta}$ was constructed and confirmed by restriction endonuclease analysis and DNA sequence analysis. GFP expression was observed in 90% of $rhNGF-{\beta}$ adenovirus infected cells compared with uninfected cells. Total mRNA isolated from $rhNGF-{\beta}$ adenovirus infected cells showed strong RT-PCR band, however uninfected or LacZ recombinant adenovirus infected cells did not. NGF quantification by ELISA showed a maximal release of $18865.4{\pm}310.9pg/ml$ NGF at the 4th day and stably continued till 14 days by $rhNGF-{\beta}$ adenovirus infected Schwann cells. PC-12 cells exposed to media with $rhNGF-{\beta}$ adenovirus infected Schwann cell revealed at the same level of neurite-extension as the commercial NGF did. $rhNGF-{\beta}$ adenovirus injected experimental groups in comparison to the control group exhibited different taste preference ratio. Salty, sweet and sour taste preference ratio were significantly different after 2 weeks from the beginning of the experiment, which were similar to the sham group, but not to the control group.