Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. @*Materials and Methods@#The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. @*Results@#Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor кB, and G2/M cell cycle arrest. @*Conclusion@#The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT.

Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. @*Materials and Methods@#The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. @*Results@#Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor кB, and G2/M cell cycle arrest. @*Conclusion@#The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT.

Tumor Control and Overall Survival after Stereotactic Body Radiotherapy for Pulmonary Oligometastases from Colorectal Cancer: A Meta-Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In pulmonary oligometastases from colorectal cancer (POM-CRC), the primarily recommended local therapy is metastasectomy. Stereotactic body radiotherapy (SBRT) is another local therapy modality that is considered as an alternative option in patients who cannot undergo surgery. The purpose of this meta-analysis is to demonstrate the effects of SBRT on POM-CRC by integrating the relevant studies. @*Materials and Methods@#The authors explored MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS, and selected studies including patients treated with SBRT for POM-CRC and availability of local control (LC) or overall survival (OS) rate. In this meta-analysis, the effect of SBRT was presented in the form of the LC and OS rates for 1, 2, 3, and 5 years after SBRT as pooled estimates, and the frequency of pulmonary toxicity of grade 3 or higher after SBRT (PTG3-SBRT). @*Results@#Fourteen full texts among the searched 4,984 studies were the objects of this meta-analysis. The overall number of POM-CRC patients was 495 as per the integration of 14 studies. The pooled estimate LC rate at 1, 2, 3, and 5 years after SBRT was 81.0%, 71.5%, 56.0%, and 61.8%, and the OS rate was 86.9%, 70.1%, 57.9%, and 43.0%, respectively. The LC and OS rates gradually declined until 3 years after SBRT in a similar pattern. Among the 14 studies, only two studies reported PTG3-SBRT as 2.2% and 10.8%, respectively. @*Conclusion@#For POM-CRC, SBRT is an ablative therapy with a benefit on LC and OS rates and less adverse effects on the lung.

Analysis of Motion-dependent Clinical Outcome of Tumor Tracking Stereotactic Body Radiotherapy for Prostate Cancer

BACKGROUND: To analyze clinical outcome of CyberKnife (CK) tumor-tracking stereotactic body radiotherapy (SBRT) for prostate cancer (Pca) according to the magnitude of intra-fractional prostate motion. METHODS: Medical records and daily treatment logs for 71 patients who received CK tumor-tracking SBRT were retrospectively analyzed. Statistical relationships between prostate motion and various outcome results, including local recurrence (LR), biochemical failure (BF), and treatment-related toxicity, were investigated in order to evaluate motion-dependent efficacy of tumor-tracking SBRT for Pca. RESULTS: In a total 71 patients, 3 (4.2%) patients with LR, 12 (16.9%) patients with BF, and 22 (31%) patients with grade-II or worse toxicities to rectal or bladder (22 to rectal, 22 to bladder and 8 patients to both) were observed in a median follow-up of 47 months. Magnitudes of intra-fractional tumor motion along superior-inferior, right-left, and anterior-posterior (AP) axes were 0.15 ± 0.31, 0.12 ± 0.19, and 0.73 ± 0.32 mm, respectively. Radial magnitude was estimated to be 1.0 ± 0.35 mm. Intra-fractional movement was not significantly correlated with tumor control. However, it was significant correlated with the incidence of grade-II or worse toxicity to rectum or bladder particularly when tumor motion was in the AP axis. CONCLUSION: Our quantitative results revealed that toxicity related to SBRT treatment was highly sensitive to intra-fractional prostate movements, although local-tumor control was not affected by such movements. Our results demonstrate that precise motion correction is essential in prostate SBRT, even if it seems to be small.

Who Really Benefits from 3D-Based Planning of Brachytherapy for Cervical Cancer?

BACKGROUND: Although intracavitary radiotherapy (ICR) is essential for the radiation therapy of cervical cancer, few institutions in Korea perform 3-dimensional (3D)-based ICR. To identify patients who would benefit from 3D-based ICR, dosimetric parameters for tumor targets and organs at risk (OARs) were compared between 2-dimensional (2D)- and 3D-based ICR. METHODS: Twenty patients with locally advanced cervical cancer who underwent external beam radiation therapy (EBRT) following 3D-based ICR were retrospectively evaluated. New 2D-based plans based on the Manchester system were developed. Tumor size was measured by magnetic resonance imaging. RESULTS: The mean high risk clinical target volume (HR-CTV) D90 value was about 10% lower for 2D- than for 3D-based plans (88.4% vs. 97.7%; P = 0.068). Tumor coverage did not differ between 2D- and 3D-based plans in patients with tumors ≤ 4 cm at the time of brachytherapy, but the mean HR-CTV D90 values in patients with tumors > 4 cm were significantly higher for 3D-based plans than for 2D-based plans (96.0% vs. 78.1%; P = 0.017). Similar results were found for patients with tumors > 5 cm initially. Other dosimetric parameters for OARs were similar between 2D- and 3D-based plans, except that mean sigmoid D2cc was higher for 2D- than for 3D-based plans (67.5% vs. 58.8%; P = 0.043). CONCLUSION: These findings indicate that 3D-based ICR plans improve tumor coverage while satisfying the dose constraints for OARs. 3D-based ICR should be considered in patients with tumors > 4 cm size at the time of brachytherapy or > 5 cm initially.

Carotid sparing intensity modulated radiotherapy on early glottic cancer: preliminary study

PURPOSE: To compare the dose distribution between carotid sparing intensity modulated radiotherapy (IMRT) and opposed lateral field technique (LAFT), and to determine the effects of carotid sparing IMRT in early glottic cancer patients who have risk factors for atherosclerosis. MATERIALS AND METHODS: Ten early glottic cancer patients were treated with carotid sparing IMRT. For each patient, the conventional LAFT plan was developed for comparison. IMRT and LAFT plans were compared in terms of planning target volume (PTV) coverage, conformity index, homogeneity index, and the doses to planning organ at risk volume (PRV) for carotid arteries, spinal cord and pharyngeal constrictor muscle. RESULTS: Recurrence was not observed in any patients during the follow-up period. V95% for PTV showed no significant difference between IMRT and LAFT plans, while V100% was significantly higher in the IMRT plan (95.5% vs. 94.6%, p = 0.005). The homogeneity index (11.6%) and conformity index (1.4) in the IMRT plan were significantly better than those in the LAFT plans (8.5% and 5.1, respectively) (p = 0.005). The median V5Gy (90.0%), V25Gy (13.5%), and V50Gy (0%) for carotid artery PRV in the IMRT plan were significantly lower than those in the LAFT plan (99.1%, 89.0%, and 77.3%, respectively) (p = 0.005). CONCLUSION: Our study suggests that carotid sparing IMRT can significantly decrease the dose to carotid arteries compared to LAFT, and it would be considered for early glottic cancer patient with high risk of atherosclerosis.

Stereotactic Body Radiation Therapy for Low- to Intermediate-risk Prostate Adenocarcinoma

The aim of the present study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for low- to intermediate-risk prostate adenocarcinoma. Thirty-nine patients were retrospectively reviewed. The SBRT was delivered using the CyberKnife with the fiducial tracking method combined with In-tempo imaging. The gross target volume, which included the prostate only, was delineated on the fused CT/MRI scans. The prescription dose was delivered every other day as 5 fractions of 7.5 Gy. Venous blood was obtained before and after SBRT to assess the prostate-specific antigen (PSA) level. Toxicity was evaluated using the CTCAE, v4.03. The median follow-up time was 30.0 months. The median initial PSA level was 7.7 ng/mL. PSA levels decreased in all patients treated with SBRT, and after 5 months, the median PSA was less than 2 ng/mL. The rate of overall 3-yr actuarial biochemical failure free survival was 93.9%. Acute side effects were generally comparable with those of previous studies. The PSA change and toxicity after SBRT for low- to intermediate-risk prostate adenocarcinoma indicates favorable biochemical responses and tolerable levels of toxicity. Additionally short course treatment may produce cost benefit and convenience to patients.

Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer

PURPOSE: We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). MATERIALS AND METHODS: Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. RESULTS: The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. CONCLUSION: We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

Concurrent chemoradiotherapy for elderly patients with stage III non-small cell lung cancer

PURPOSE: Combined chemoradiotherapy is standard management for locally advanced non-small cell lung cancer (LA-NSCLC), but standard treatment for elderly patients with LA-NSCLC has not been confirmed yet. We evaluated the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for elderly patients with LA-NSCLC. MATERIALS AND METHODS: Among patients older than 65 years with LA-NSCLC, 36 patients, who underwent CCRT were retrospectively analyzed. Chemotherapy was administered 3-5 times with 4 weeks interval during radiotherapy. Thoracic radiotherapy was delivered to the primary mass and regional lymph nodes. Total dose of 54-59.4 Gy (median, 59.4 Gy) in daily 1.8 Gy fractions and 5 fractions per week. RESULTS: Regarding the response to treatment, complete response, partial response, and no response were shown in 16.7%, 66.7%, and 13.9%, respectively. The 1- and 2-year overall survival (OS) rates were 58.2% and 31.2%, respectively, and the median survival was 15 months. The 1- and 2-year progression-free survivals (PFS) were 41.2% and 19.5%, respectively, and the median PFS was 10 months. Regarding to the toxicity developed after CCRT, pneumonitis and esophagitis with grade 3 or higher were observed in 13.9% (5 patients) and 11.1% (4 patients), respectively. Treatment-related death was not observed. CONCLUSION: The treatment-related toxicity as esophagitis and pneumonitis were noticeably lower when was compared with the previously reported results, and the survival rate was higher than radiotherapy alone. The results indicate that CCRT is an effective in terms of survival and treatment related toxicity for elderly patients over 65 years old with LA-NSCLC.

Quantitative Analysis of Myosin Heavy Chain Expression Change in Laryngeal Muscle after Irradiation in Rats

PURPOSE: Radiotherapy for head and neck cancer does not impair the voice quality as much as laser treatment or surgery, but it can induce muscle wasting and fibrosis and symptoms of dry mouth. We investigated the effect of irradiation on the myosin heavy chain (MyHC) expression in laryngeal muscles. MATERIALS AND METHODS: Rats were irradiated with one dose of 10, 15, 20, 25, 30, or 35 Gy and other rats were irradiated with 20 Gy. The thyroarytenoid (TA), posterior cricoarytenoid (PCA), and cricothyroid (CT) muscles were subjected to reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Two weeks after irradiation with 10, 15, or 20 Gy, all the MyHC type expressions had decreased in a dose-dependent manner in the TA, PCA, and CT muscles, and especially the expression of MyHC IIa decreased much more than the expressions of the other MyHC isoforms in all muscles. In the 20 Gy-irradiated rats, almost all the MyHC isoform expressions declined over 12 weeks in the TA, PCA, and CT muscles, except for the MyHC I expression in the PCA and CT muscle. The MyHC IIa expression was markedly decreased in all the muscles. CONCLUSION: The laryngeal muscles responded differently to radiation, but they showed a time-dependent and long-lasting decrease in the expressions of all the MyHC isoforms in the TA, PCA, and CT muscles. In particular, the expression of the MyHC IIa isoform in all the muscles may be more sensitive to irradiation than the expressions of the other MyHC isoforms.

Comparison of Three- and Four-dimensional Robotic Radiotherapy Treatment Plans for Lung Cancers / 대한방사선종양학회지

PURPOSE: To compare the dose distributions between three-dimensional (3D) and four-dimensional (4D) radiation treatment plans calculated by Ray-tracing or the Monte Carlo algorithm, and to highlight the difference of dose calculation between two algorithms for lung heterogeneity correction in lung cancers. MATERIALS AND METHODS: Prospectively gated 4D CTs in seven patients were obtained with a Brilliance CT64-Channel scanner along with a respiratory bellows gating device. After 4D treatment planning with the Ray Tracing algorithm in Multiplan 3.5.1, a CyberKnife stereotactic radiotherapy planning system, 3D Ray Tracing, 3D and 4D Monte Carlo dose calculations were performed under the same beam conditions (same number, directions, monitor units of beams). The 3D plan was performed in a primary CT image setting corresponding to middle phase expiration (50%). Relative dose coverage, D95 of gross tumor volume and planning target volume, maximum doses of tumor, and the spinal cord were compared for each plan, taking into consideration the tumor location. RESULTS: According to the Monte Carlo calculations, mean tumor volume coverage of the 4D plans was 4.4% higher than the 3D plans when tumors were located in the lower lobes of the lung, but were 4.6% lower when tumors were located in the upper lobes of the lung. Similarly, the D95 of 4D plans was 4.8% higher than 3D plans when tumors were located in the lower lobes of lung, but was 1.7% lower when tumors were located in the upper lobes of lung. This tendency was also observed at the maximum dose of the spinal cord. Lastly, a 30% reduction in the PTV volume coverage was observed for the Monte Carlo calculation compared with the Ray-tracing calculation. CONCLUSION: 3D and 4D robotic radiotherapy treatment plans for lung cancers were compared according to a dosimetric viewpoint for a tumor and the spinal cord. The difference of tumor dose distributions between 3D and 4D treatment plans was only significant when large tumor movement and deformation was suspected. Therefore, 4D treatment planning is only necessary for large tumor motion and deformation. However, a Monte Carlo calculation is always necessary, independent of tumor motion in the lung.

Concurrent Chemoradiotherapy in Elderly Patients with Locally Advanced Esophageal Carcinoma / 대한방사선종양학회지

PURPOSE: The effect of concurrent chemoradiotherapy was analyzed in elderly patients when used in the treatment of locally advanced esophageal cancer. MATERIALS AND METHODS: The retrospective analysis included 28 elderly patients aged 65 or older, with histopathologically confirmed squamous cell carcinoma of the esophagus, underwent concurrent chemoradiotherapy from January 2001 to July 2007. The squamous cell carcinoma disease stages included 8 patients (28.8%) in stage IIa, 10 patients (35.7%) in stage IIb, and 10 patients (35.7%) in stage III. Fractionated radiotherapy was performed with a 6 MV or 10 MV X-ray for 45~63 Gy (median: 59.4 Gy). Chemotherapy was applied concurrently with the initiation of radiotherapy. A 75 mg/m2 dose of Cisplatin was intravenously administered on day 1. Further, 5-FU 1,000 mg/m2 was continuously administered intravenously from days 1 to 4. This regimen was performed twice at 3-week intervals during radiotherapy. Two cycles of consolidation chemotherapy was performed after radiotherapy. RESULTS: The follow-up period was 3~72 months (median: 19 months). The treatment responses after concurrent chemoradiotherapy included a complete response in 11 patients (39.3%), a partial response in 14 patients (50.0%), and no response in 3 patients (10.7%). The overall response rate was 89.3% (25 patients). The overall 1-, 2- and 3-year survival rates were 55.9%, 34.6% and 24.2%, respectively. The median survival time was 15 months. Two-year survival rates of patients with a complete response, partial response, and no response were 46.2%, 33.0%, and 0%, respectively. The stage and tumor response after concurrent chemoradiotherapy were statistically significant prognostic factors related with survival. No treatment-related deaths occurred in this study. CONCLUSION: Concurrent chemoradiotherapy is a relatively effective treatment without serious complications in elderly patients with locally-advanced esophageal cancer.

Preliminary Report of the 1998~1999 Patterns of Care Study of Radiation Therapy for Esophageal Cancer in Korea / 대한방사선종양학회지

PURPOSE: For the first time, a nationwide survey in the Republic of Korea was conducted to determine the basic parameters for the treatment of esophageal cancer and to offer a solid cooperative system for the Korean Pattern of Care Study database. MATERIALS AND METHODS: During 1998~1999, biopsy-confirmed 246 esophageal cancer patients that received radiotherapy were enrolled from 23 different institutions in South Korea. Random sampling was based on power allocation method. Patient parameters and specific information regarding tumor characteristics and treatment methods were collected and registered through the web based PCS system. The data was analyzed by the use of the Chi-squared test. RESULTS: The median age of the collected patients was 62 years. The male to female ratio was about 91 to 9 with an absolute male predominance. The performance status ranged from ECOG 0 to 1 in 82.5% of the patients. Diagnostic procedures included an esophagogram (228 patients, 92.7%), endoscopy (226 patients, 91.9%), and a chest CT scan (238 patients, 96.7%). Squamous cell carcinoma was diagnosed in 96.3% of the patients; mid-thoracic esophageal cancer was most prevalent (110 patients, 44.7%) and 135 patients presented with clinical stage III disease. Fifty seven patients received radiotherapy alone and 37 patients received surgery with adjuvant postoperative radiotherapy. Half of the patients (123 patients) received chemotherapy together with RT and 70 patients (56.9%) received it as concurrent chemoradiotherapy. The most frequently used chemotherapeutic agent was a combination of cisplatin and 5-FU. Most patients received radiotherapy either with 6 MV (116 patients, 47.2%) or with 10 MV photons (87 patients, 35.4%). Radiotherapy was delivered through a conventional AP-PA field for 206 patients (83.7%) without using a CT plan and the median delivered dose was 3,600 cGy. The median total dose of postoperative radiotherapy was 5,040 cGy while for the non-operative patients the median total dose was 5,970 cGy. Thirty-four patients received intraluminal brachytherapy with high dose rate Iridium-192. Brachytherapy was delivered with a median dose of 300 cGy in each fraction and was typically delivered 3~4 times. The most frequently encountered complication during the radiotherapy treatment was esophagitis in 155 patients (63.0%). CONCLUSION: For the evaluation and treatment of esophageal cancer patients at radiation facilities in Korea, this study will provide guidelines and benchmark data for the solid cooperative systems of the Korean PCS. Although some differences were noted between institutions, there was no major difference in the treatment modalities and RT techniques.

The Effect of Recombinant Human Epidermal Growth Factor on Cisplatin and Radiotherapy Induced Oral Mucositis in Mice / 대한방사선종양학회지

PURPOSE: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. MATERIALS AND METHODS: Twenty-four ICR mice were divided into three groups? the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days 1~5. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. RESULTS: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. CONCLUSION: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.

Paclitaxel and Cisplatin with Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Stage IIIB Non-small Cell Lung Cancer / 대한방사선종양학회지

PURPOSE: Combined modality therapy including chemotherapy, surgery and radiotherapy is considered the standard of care for the treatment of stage III non-small cell lung cancer (NSCLC). This study was conducted to evaluate the efficacy of paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC. MATERIALS AND METHODS: Between July 2000 and October 2005, thirty-nine patients with stage IIIB NSCLC were treated with two cycles of induction chemotherapy followed by concurrent chemoradiotherapy. The induction chemotherapy included the administration of paclitaxel (175 mg/m2) by intravenous infusion on day 1 and treatment with cisplatin (75 mg/m2) by intravenous infusion on day 1 every 3 weeks. Concurrent chemoradiotherapy included the use of paclitaxel (60 mg/m2) plus cisplatin (25 mg/m2) given intravenously for 6 weeks on day 43, 50, 57, 71, 78 and 85. Thoracic radiotherapy was delivered with 1.8 Gy daily fractions to a total dose of 54~59.4 Gy in 6~7 weeks (median: 59.4 Gy). RESULTS: The follow up period was 6~63 months (median: 21 months). After the induction of chemotherapy, 41.0% (16 patients) showed a partial response and 59.0% (23 patients) had stable disease. After concurrent chemoradiotherapy, 10.3% (4 patients) had a complete response, 41.0% (16 patients) had a partial response, and the overall response rate was 51.3% (20 patients). The 1-, 2-, 3-year overall survival rates were 66.7%, 40.6%, and 27.4% respectively, with a median survival time of 20 months. The 1-, 2-, 3-year progression free survival rates were 43.6%, 24.6%, and 24.6%, respectively, with median progression free survival time of 10.7 months. Induction chemotherapy was well tolerated. Among 39 patients who completed the entire treatment including chemoradiotherapy, 46.3% (18 patients) had esophagitis greater than grade 3 and 28.2% (11 patients) had radiation pneumonitis greater than grade 3. CONCLUSION: Paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC seems to be an effective treatment. Occurrence of esophagitis and pneumonitis represents a significant morbidity and suggests a modification of the treatment regimen, either with the chemotherapy schedule or with radiotherapy treatment planning.

Effects of Recombinant Human Epidermal Growth Factor on the Proliferation and Radiation Survival of Human Fibroblast Cell Lines in Vitro / 대한방사선종양학회지

PURPOSE: To explore the effect of recombinant human EGF on the proliferation and survival of human fibroblast cell lines following irradiation. MATERIALS AND METHODS: Fibroblast was originated human skin and primary cultured. The trypan blue stain assay and MTT assay were used to study the proliferative effects of EGF on human fibroblast cell lines in vitro. An incubation of fibroblasts with rhEGF for 24 hours immediately after irradiation was counted everyday. Cell cycle distributions were analyzed by FACS analysis. RESULTS: Number of fibroblast was significantly more increased rhEGF (1.0 nM, 10 nM, 100 nM, 1,000 nM) treated cell than control after 8 Gy irradiation. Most effective dose of rhEGF was at 160 nM. These survival differences were maintained at 1 week later. Proportion of S phase was significantly increased on rhEGF treated cells. CONCLUSION: rhEGF cause increased fibroblast proliferation following irradiation. We expect that rhEGF was effective for radiation induced wound healing.

Early Therapeutic Effects of Cyberknife Radiosurgery on Trigeminal Neuralgia / 대한방사선종양학회지

PURPOSE: We evaluated whether Cyberknife radiosurgery is an effective and safe method of therapy for medically intractable trigeminal neuralgia (TN). MATERIALS AND METHODS: We retrospectively analyzed the outcome of 26 patients, who failed to surgery or were not suitable candidates for invasive intervention and were treated by Cyberknife radiosurgery between March 2004 and May 2005. Radiosurgery doses of 60~64 Gy were delivered to the 80% isodose line prescribed to an 6 mm length of the nerve, sparing the most proximal 3 mm away from the trigeminal nerve root entry zone (median dose: 64 Gy). RESULTS: Follow-up period was 3~15 months (median follow-up period: 9 months) Preliminary results from a cohort of 26 patients undergoing Cyberknife radiosurgery for TN showed that pain relief was achieved in 50% (13/26) of patients within the first 24 hrs after treatment. At last follow-up, 96.2% (25/26) of patients reported early pain relief within 7 days. Treatment failure developed in 2 of 26. Poor response occurred in one patient and relapse was observed in the other patient. 3 patients had hypoesthesia (11.5%), which was the only complication observed with any of our patients. CONCLUSION: With these results, authors assumed that Cyberknife radiosurgery for TN could be one of safe and effective therapeutic methods.

Thymidine phosphrylase (TP) in cancer-infiltrating inflammatory cells in stomach cancer: the significance of TP in prognosis and tumor angiogenesis / 대한내과학회지

BACKGROUND: Thymidine phosphorylase (TP) is an enzyme catalyzing the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate. TP plays a role in angiogenesis. Evidences suggest that infiltrating inflammatory cells adjacent cancer cells may affect tumor cell behavior. To evaluate each of these significances of TP expression in cancer cell and cancer-infiltrating inflammatory cells, we investigated TP expression patterns in cancer cells and infiltrating inflammatory cells adjacent cancer cells separately and the relationship between TP expression and angiogenesis or survival. METHODS: Immunohistochemistry assays were performed with anti-TP monoclonal antibody (Roche Japan) and anti-factor VIII polyclonal antibody (Dako) on 92 paraffin-embedded tissue samples from stomach cancer patients. A single pathologist scored the slides for percent positivity of tumor cells, intensity, localization and distribution of expression. TP reactivity in tumor cells (cancer) and infiltrating mononuclear cells adjacent cancer cells (matrix) was separately accessed. According to the pattern of TP expression, subjects were divided into 4 groups for further analysis: cancer(C;+)/matrix(M;+), cancer(+)/matrix(-), cancer(-)/matrix(+) and cancer(-)/matrix(-). With these 4 subsets of TP expression patterns, we evaluated cancer cell differentiation, intratumoral microvessel density, extent of tumor invasion, LN stage, and patient survival to find any differences among the subsets. RESULTS: Of 92 stomach cancer tissue, C/M(+/+), C/M(+/-), C/M(-/+), and C/M(-/-) were observed in 33patients, 19, 30, and 10, respectively. Microvessel density scores were higher in cancer(+)/matrix(-) group compared in cancer(-)/matrix(-) group (p=0.02). Of 4 TP expression subsets, other clinical factors such as histology, extent of tumor invasion, and LN metastasis were not associated with TP expression. CONCLUSION: This study suggested the TP in cancer-infiltrating inflammatory cell as well as cancer cells themselves may play an important role in angiogenesis as co-active factors in stomach cancer.

Effects of Fractionated Stereotactic Radiotherapy for Primary Hepatocellular Carcinoma / 대한방사선종양학회지

PURPOSE: Reports on the outcome of curative radiotherapy for the primary hepatocellular carcinoma (HCC) are rarely encountered in the literature. In this study, we report our experience of a clinical trial where fractionated stereotactic radiotherapy (SRT) was used in treating a primary HCC. MATERIALS AND METHODS: A retrospective analysis was performed on 20 patients who had been histologically diagnosed as HCC and treated by fractionated SRT. The long diameter of tumor measured by CT was 2~6.5 cm (average: 3.8 cm). A single dose of radiation used in fractionated SRT was 5 or 10 Gy; each dose was prescribed based on the planning target volume and normalized to 85~99% isocenter dose. Patients were treated 3~5 times per week for 2 weeks, with each receiving a total dose of 50 Gy (the median dose: 50 Gy). The follow up period was 3~55 months (the median follow up period: 23 months). RESULTS: The response rate was 60% (12 patients), with 4 patients showing complete response (20%), 8 patients showing partial response (40%), and 8 patients showing stable disease (40%). The 1-year and 2-year survival rates were 70.0% and 43.1%, respectively, and the median survival time was 20 months. The 1-year and 2-year disease free survival rates were 65% and 32.5%, respectively, and the median disease-free survival rate was 19 months. Some acute complications of the treatment were noted as follows: dyspepsia in 12 patients (60%), nausea/emesis in 8 patients (40%), and transient liver function impairment in 6 patients (30%). However, there was no treatment related death. CONCLUSION: The study indicates that fractionated SRT is a relatively safe and effective method for treating primary HCC. Thus, fractionated SRT may be suggested as a local treatment for HCC of small lesion and containing a single lesion, when the patients are inoperable or operation is refused by the patients. We thought that fractionated SRT is a challenging treatment modality for the HCC.

Induction Chemotherapy Followed by Radiotherapy for Stage IV Hypopharyngeal Cancer / 대한방사선종양학회지

PURPOSE: Hypopharyngeal cancer is diagnosed at the advanced stage in most cases, which the prognosis known to be poor. Thus, the efficacy of induction chemotherapy followed by radiotherapy, with regards to the response and survival rate for stage IV hypopharyngeal cancer patients, was examined. MATERIALS AND METHODS: From July 1998 to February 2000, 18 cases were diagnosedas AJCC stage IV hypopharyngeal cancer without distant metastasis. These patients were treated with induction chemotherapy followed by radiotherapy, and the results retrospectively analyzed. The regimen of the induction chemotherapy was the 5-FU and cisplatincombination, at 3-week intervals for, 2 cycles. The total radiation dose for the primary lesion and metastatic lymph nodes was 68.4~72.0 Gy (median: 70.2 Gy). RESULTS: The median follow up period was 28 months, ranging from 7 to 99 months. The 3-year overall survival and disease-free survival rate were 41.7 and 31.1%, respectively. In 6 cases (33.3%), conservation of the larynx for over 3 years was possible. After the induction chemotherapy there were 16 partial responses (88.8%), 1 complete response and 1 with no response (5.6% each), therefore, 17 of the 18 cases (94.6%) showed responses. After the completion of the induction chemotherapy and radiotherapy, a complete response was noted in 13 cases (72.2%), a partial response in 5 (27.8%), with an overall response rate of 100%. In the analysis of the prognostic factors influencing the survival rate, the 3-year and disease-free survival rates for the complete and partial response groups were 43.1, and 20.0%, and 39.6, and 20.0%, respectively (p=0.0003, p=0.002). Only the final response after treatment completion was statistically significant. CONCLUSION: For stage IV hypopharyngeal cancer, induction chemotherapy followed by radiotherapy was an effective treatment, with no severe side effects.