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The aim of this study was to analyze tumor control and clinical outcomes of patients with uterine cervical cancer treated by chemoradiotherapy according to pelvic lymph node (PLN) positivity and boost irradiation to PLN and to determine toxicities associated with boost irradiation. We retrospectively reviewed patients with uterine cervical cancer treated with chemoradiotherapy between March 2000 and April 2015. Clinical characteristics, failure pattern, and survival outcomes of patients with or without PLN metastasis and those with or without boost irradiation were analyzed. A total of 80 cases were PLN-negative and 46 were PLN-positive. A total of 11 patients underwent PLN boost irradiation. The 2-year and 5-year overall survival (OS) rates showed significant difference between the PLN-positive and PLN-negative groups (P = .010). The 2-year and 5-year progression-free survival (PFS) rates showed significant difference between the 2 groups (P = .032). The 2-year and 5-year OS rates of the no-boost irradiation group were 82.9% and 58.3%, respectively, whereas all patients in the boost irradiation group were alive at the time of analysis (P = .065). There was no recurrence in the boost irradiation group. The difference in PFS was significant between the boost and the no-boost irradiation groups (P = .023). The 2-year and 5-year pelvic-recurrence free survival (PRFS) did not show significant difference but the tendency of increased risk of pelvic recurrence in no-boost group (boost vs no-boost; 81.9% and 70.2% vs 100% and 100% in 2-year and 5-year PRFS, respectively, P = .156). Boost irradiation to PLN could improve locoregional control especially in large pelvic LN (≥1.5 cm). Our results showed that only 1 acute and late toxicity of higher than grade 3 occurred. PLN metastasis was significant prognostic factor in cervix cancer treated by chemoradiotherapy. In the boost irradiation group, there was no recurrence or death with significantly better PFS. Boost irradiation to PLN is expected to improve locoregional control, but further follow-up and assessment are needed.

Percentage depth dose (PDD) distributions in heterogeneous phantoms with lung and soft bone equivalent media are studied by using the GEANT4 Monte Carlo code. For lung equivalent media, Balsa wood is used, and for soft bone equivalent media, a compound material with epoxy resin, hardener and calcium carbonate is used. Polystyrene slabs put together with these materials are used as a heterogeneous phantom. Dose measurements are performed with Gafchromic EBT2 film by using photon beams from the 6-MV CyberKnife at the Seoul Uridul Hospital. The cone sizes of the photon beams are varied from 5 to 10 to 30 mm. When the Balsa wood is inserted in the phantom, the dose measured with EBT2 film is found to be significantly different from the dose without the EBT2 film in and the dose beyond the Balsa wood region, particularly for small field sizes. On the other hand, when the soft bone equivalent material is inserted in the phantom, the discrepancy between the dose measured with EBT2 film and the dose without EBT2 film can be seen only in the region of the soft bone equivalent material. GEANT4 simulations are done with and without the EBT2 film to compare the simulation results with measurements. The GEANT4 simulations including EBT2 film are found to agree well with the measurements for all the cases within an error of 2.2%. The results of the present study show that GEANT4 gives reasonable results for the PDD calculations in heterogeneous media when using photon beams produced by the 6-MV CyberKnife

OBJECTIVE For several decades, radiotherapy has been widely used to treat metastatic vertebral tumors. This study was designed to assess the feasibility and early clinical outcomes of high-dose radiotherapy to treat such tumors, using helical tomotherapy. METHODS Between June 2009 and December 2011, 51 sites in 36 patients were treated with high-dose radiotherapy using helical tomotherapy for vertebral metastasis. Treatment outcomes and dosimetric analyses of spinal cord were retrospectively evaluated. RESULTS Median follow-up was 11.5 months (range, 6-34.6) for surviving patients. The median total dose and the number of fractions in the primary helical tomotherapy arm were 2700 cGy and 3 fractions, respectively. Actuarial 6-month local control rates were 85.7%, and symptomatic vertebral compression fractures developed in five patients after a median of 4.2 (range, 2.9-5.7) months. Among 13 patients with 19 metastatic sites who showed pre-treatment impairment in neurologic function, five patients (with seven sites) in whom symptoms were mild showed improvement in neuronal function. The median pre-treatment pain visual analog scale score of 7 decreased to a median of 3 after helical tomotherapy (P < 0.001) at a median of 1 month (range, 0.5-3.2) of follow-up. No significant morbidity developed during follow-up except for one grade 3 esophagitis. CONCLUSIONS The use of helical tomotherapy to treat metastatic vertebral tumors appears to be both safe and reliable in terms of local tumor control and early pain relief. Local progression and the risk of compression fracture in patients with pre-existing spinal instability remain the principal factors of limiting improved clinical and functional outcomes. Optimal dose-fractionation schemes and appropriate patient selection are required to achieve better outcomes with high-dose radiotherapy using helical tomotherapy.

Aims We report the results of a retrospective study of stereotactic body radiotherapy (SBRT) using a Cyberknife for prostate cancer. Methods In all 29 patients were treated with hypofractionated SBRT using a Cyberknife at median 36 Gy in five fractions. All the patients were treated with a radical aim. Prostate-specific antigen (PSA) was evaluated at baseline and after radiotherapy. Acute (≤3 months) and late (>3 months) urinary and rectal toxicities were recorded according to the CTCAE version 4.0. Results The median duration of follow up was 41 months. PSA values decreased in a time-dependent way. The median PSA nadir was 0.329 ng/mL, achieved after a median of 23 months’ follow up. Two patients had a PSA failure according to the definition of nadir + 2 ng/mL. Eight patients (28%) had a benign PSA bounce at median 9 months after radiotherapy. CTCAE Grade 2 and 3 late urinary toxicities were reported in 3 and 3%, respectively. One patient had exacerbated urinary symptoms and received an operation. There were no severe late rectal toxicities. Conclusions The preliminary findings of our study suggest SBRT is feasible for prostate cancer treatment. Further studies with more patients and longer follow-up duration are required.

Aim: Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced cervical cancer. This study was undertaken to evaluate the outcomes and the prognostic factors for cervical cancer after CCRT. Material and Methods: The medical records of 174 patients with International Federation of Gynecology and Obstetrics stage IB1–IVA who were treated at three affiliated hospitals of the Catholic University of Korea between January 1999 and December 2008 were reviewed and analyzed. Patients received pelvic radiotherapy with one of three regimens of cisplatin-based chemotherapy concurrently and high-dose rate brachytherapy. The radiation field was extended to include para-aortic lymph nodes, if necessary. Results: The median follow-up period was 29.5 months (range, 5–96 months). Using multivariate analysis, stage (P = 0.014), tumor size (P = 0.043), and clinical response (P = 0.001) had a significant effect on overall survival. Similarly, progression-free survival (PFS) was influenced by stage (P = 0.004), tumor size (P = 0.02), clinical response (P = 0.011), and normalized squamous cell carcinoma antigen level after CCRT (P = 0.007). The 5-year survival rates were 91.7% (standard error, 5.8%) for stages IB1–IIA, 71.5% (standard error, 7.8%) for stage IIB, 44.9% (standard error, 7.8%) for stage III, and 20.9% (standard error, 12.0%) for stage IVA. A total of 151 out of 174 patients (86.8%) completed the planned treatment. Toxicities were manageable with supportive therapy. Conclusions: Cisplatin-based CCRT is well-tolerated. Good clinical response revealed a favorable correlation to survival. A maximal effort to achieve this goal might prolong survival in patients with cervical cancer.

Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1–3) and high total metastatic score group (score 4–7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p < 0.0001). The area under the receiver operating curve of serum CEA for the prediction of brain metastasis was 0.724 (p = 0.0001). The present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.

This study was designed to identify the significance of lymphovascular invasion as a prognosticator for tumor recurrence and survival in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME).Between January 2003 and October 2010, the study included 328 patients with primary rectal cancer who had received preoperative CRT followed by TME. We analyzed the clinicopathologic factors that may be associated with survival, such as age, gender, carcinoembryonic antigen (CEA) value, pathologic T and N stage, tumor response, histologic grade, lymphovascular invasion (LVI), and perineural invasion.Higher pathologic T and N stage, poor tumor response, high-grade histology, and positive LVI were adverse prognostic factors for both disease-free survival (DFS) and overall survival (OS) on the multivariate analysis. Perineural invasion was a significant adverse prognostic factor affecting DFS (P=0.046) but not OS (P=0.08). Increased T and N stage and distant recurrence, but not local recurrence, were significant factors associated with LVI. The LVI-negative group had a higher DFS (71.4 vs. 56.2%, P=0.012) and OS rate (86.7 vs. 63.4%, P=0.020) at 5 years than the LVI-positive group did.Positive LVI had a negative impact on survival in patients with rectal cancer who received preoperative CRT and TME and is significantly associated with an increased chance of distant recurrence. Based on this finding, more tailored adjuvant chemotherapy is warranted for advanced rectal cancer patients with LVI to reduce the distant dissemination of tumor.

Purpose: This study was designed to determine the influencing factors and clinical course of pathologically proven cases of radiation-induced brain injury (RIBI). Materials and Methods: The pathologic records of twelve patients were reviewed; these patients underwent surgery following radiotherapy due to disease progression found by follow-up imaging. However, they were fi nally diagnosed with RIBI. All patients had been treated with 3-dimensional conventional fractionated radiotherapy and/or radiosurgery for primary or metastatic brain tumors with or without chemotherapy. The histological distribution was as follows: two falx meningioma, six glioblastoma multiform (GBM), two anaplastic oligodendroglioma, one low grade oligodendroglioma, and one small cell lung cancer with brain metastasis. Results: Radiation necrosis was noted in eight patients and the remaining four were diagnosed with radiation change. Gender (p = 0.061) and biologically equivalent dose (BED)3 (p = 0.084) were the only marginally infl uencing factors of radiation necrosis. Median time to RIBI was 7.3 months (range, 0.5 to 61 months). Three prolonged survivors with GBM were observed. In the subgroup analysis of high grade gliomas, RIBI that developed

PURPOSE: To evaluate treatment outcomes and prognostic factors in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiation. MATERIALS AND METHODS: From January 2005 to June 2009, 51 patients were treated with concurrent chemoradiation for 3 different aims: locally advanced stage III, locally recurrent disease, and postoperative gross residual NSCLC. Median age was 63 years. Distribution of stages by the 6th edition of American Joint Committee on Cancer (AJCC) was as follows: IIIA (37.3%), IIIB (56.9%). Chemotherapy was administered every week concurrently with radiation using one of the following regimens: paclitaxel (60 mg/m(2)), docetaxel+cisplatin (20 mg/m(2)+20 mg/m(2)), cisplatin (30 mg/m(2)). Total radiation dose was 16-66.4 Gy (median, 59.4 Gy). RESULTS: Median follow-up duration was 40.8 months. The overall response rate was 84.3% with 23 complete responses. The median survival duration for the overall patient group was 17.6 months. The 3-year survival rate was 17.8%. A total of 21 patients had recurrent disease at the following sites: loco-regional sites (23.6%), distant organs (27.5%). In the multivariate analysis of the overall patient group, a clinical tumor response (p=0.002) was the only significant prognostic factor for overall survival (OS). In the multivariate analysis of the definitive chemoradiation arm, the use of consolidation chemotherapy (p=0.022), biologically equivalent dose (BED)(10) (p=0.007), and a clinical tumor response (p=0.030) were the significant prognostic factors for OS.The median survival duration of the locally recurrent group and the postoperative gross residual group were 26.4 and 23.9 months, respectively. CONCLUSION: Our study demonstrated that clinical tumor response was significantly associated with OS in the overall patient group. Further investigations regarding the optimal radiation dose in the definitive chemoradiation and the optimal treatment scheme in locally recurrent NSCLC would be required.

Objective Platinum-based neoadjuvant chemotherapy for locally advanced cervical cancer has some benefits for patients responding to chemotherapy. However, no validated clinical or biologic predictor of response to this chemotherapy has been identified to date. Methods We employ immunohistochemical analysis to determine the expression patterns of the excision repair cross-complementation group1 (ERCC1) protein in pre-treatment cervical biopsy tissue. In total, 43 stage IIB patients had been enrolled in a previous etoposide and cisplatin neoadjuvant phase II clinical trial, allowing comparison of the effects of cisplatin-based neoadjuvant chemotherapy on response in relation to ERCC1 expression. Results Among the 43 patients studied, 34 (79.1%) were positive and 9 (20.9%) were negative for ERCC1. Response to chemotherapy (according to RECIST criteria) was observed in all patients with negative ERCC1 expression. In logistic regression analysis, ERCC1 negativity continued to be an independent predictor for responsiveness to neoadjuvant chemotherapy (p = 0.021). Among the pretreatment factors, low ERCC1 expression was a significant prognostic factor of disease-free survival in multivariate analysis (p = 0.046). Conclusions The ERCC1 expression patterns in pretreatment specimens may thus facilitate the prediction of responses to cisplatin-based NAC. We propose that patients expressing low levels of ERCC1 derive the most benefit from cisplatin-based NAC.

The purpose of this study was to evaluate the accuracy of a glass rod dosimeter (GRD) for relative output factor measurements in the CyberKnife radiosurgery system. The output factors measured with the GRD were compared to those obtained with an ionization chamber, a diode and a Gafchromic film. The GRD was irradiated in a water phantom using an in-house custom designed holder stand. The relative output factors measured with the four dosimeters showed very similar results for collimator diameters larger than 20 mm. The mean value of the output factors of the GRD for the 5 mm collimator was 0.695. The output factor measured with the ionization chamber was approximately 13.7% lower than the corresponding GRD values for the 5 mm collimator. The diode output factors were 3.1% and 1.9% higher than the GRD for the 5 mm and 7.5 mm collimators, respectively. However, the GRD results were in agreement with the measurements obtained with a Gafchromic film for all of the collimator diameters.

In order to provide the optimal design parameters, we have investigated the characteristics of a combination of metal plate and phosphor screen, a typical X-ray sensor in electronic portal imaging system, by using Monte Carlo simulation. Detection efficiency and spatial resolution of the X-ray sensor were estimated based on the bremsstrahlung spectrum of the incident X-ray and for various thicknesses of metal plate and phosphor screen. The detection efficiency was calculated from the total absorbed energy and the spatial resolution was defined from the spatial distribution of the absorbed energy. Simulation results showed a trade-off relationship between the detection efficiency and the spatial resolution. It was also found that the detection efficiency and the spatial resolution were mainly determined by thickness of metal plate and phosphor screen, respectively. The simulation will be useful when determining the optimal thickness of phosphor screen as well as of metal plate for the sensor design of therapeutic X-ray imaging.

Purpose: To determine the impact of stereotactic radiosurgery (SRS) on the clinical course, hormonal status, and follow-up CT/MRI scan of pituitary macroadenomas. Methods and Materials: From July 1988 to March 1996, 24 pituitary macroadenomas had been treated using 6 MV linear accelerator based SRS. They consisted of 11 (45.8%) prolactinomas, 2 (8.3%) growth hormone (GH)-secreting tumors, 1 (4.2%) Cushing’s disease, 8 (33.3%) nonsecreting (nonfunctioning: NF) tumors, and 2 (8.3%) mixed prolactin-growth hormone (PRL-GH)-secreting tumors (M:F = 12:12; aged 21–61 years). Postoperative irradiation was performed in all cases except for the instance of Cushing’s disease. The prescribed dose to tumor center varied from 10 to 27 Gy (mean 21.1 Gy) using a collimator size of 0.5 to 2.5 cm. The follow-up duration ranged from 13 to 89 months (mean 49.2 months). Results from these patients were compared to our results using conventional radiation. Results: Visual acuity and field defect were improved or became normal in 19 (79.2%) cases. Four (16.7%) remained unchanged after the treatment. One (4.1%) progressed 6 years after SRS and subsequently had repeat surgery with conventional boost irradiation. Of the 13 (46.4%) prolactinomas, including two mixed PRL-GH secreting tumors, 11 (84.1%) revealed normal hormonal levels within 1 year after SRS. In contrast, it took 2 years to become normal after conventional radiation therapy. In four GH-secreting tumors including two mixed PRL-GH secreting tumors, SRS and conventional methods showed similar responses. On follow-up imagings of the 21 patients, the mass was completely resolved in 4 (16.7%), including 3 PRLs and one NF, decreased in 11 (45.8%), and unchanged in 5 (16.7%) with central necrosis or cysts. One (4.2%) progressed and was reoperated 6 years after treatment. The complications related to SRS were comparable to those from conventional method. Conclusion: Radiosurgery can be used effectively in patients with pituitary adenoma. In this study, a more rapid hormonal and clinical response was achieved with radiosurgery than with conventional pituitary irradiation treatment.

Purpose Vaginal intraepithelial neoplasia (VAIN), a rare premalignant condition, is difficult to eradicate. We assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with VAIN or carcinoma in situ (CIS) of the vagina after hysterectomy. Materials and Methods We reviewed 34 patients treated for posthysterectomy VAIN or CIS of the vagina by brachytherapy as the sole treatment. All patients underwent a coloposcopic-directed punch biopsy or had abnormal cytology, at least 3 consecutive times. All patients were treated with a vaginal cylinder applicator. The total radiation dose was mainly 40 Gy in 8 fractions during the periods of 4 weeks at a prescription point of the median 0.2 cm (range, 0 to 0.5 cm) depth from the surface of the vaginal mucosa. Results Acute toxicity was minimal. Seven patients had grade 1/2 acute urinary and rectal complications. There were 15 cases of late toxicity, predominantly vaginal mucosal reaction in 12 patients. Of these patients, two patients suffered from grade 3 vaginal stricture and dyspareunia continuously. After a median follow-up time of 48 months (range, 4 to 122 months), there were 2 recurrences and 2 persistent diseases, in which a second-line therapy was needed. The success rate was 88.2%. The average prescription point in failure patients was 1.1 mm from the surface of the vagina compared to an average of 2.6 mm in non-recurrent patients (p=0.097). Conclusion HDR-ICR is an effective treatment method in VAIN patients. In spite of high cure rates, we should consider issues regarding vaginal toxicity and radiation techniques to reduce the occurrence of failure and toxicity.

Intensity Modulated Radiation Therapy (IMRT) is a means of delivering radiation therapy where the intensity of the beam is varied within the treatment field. One of the main problems of IMRT, which becomes even more apparent as the complexity of the IMRT plan increases, is the amazing increase in the number of Monitor Units (MU) required to deliver a fractionated treatment. The difficulty with this increase in MU is its association with increased treatment times and a greater leakage of radiation from the MLCs increasing the total body dose and the risk of secondary cancers in patients. Many approaches have been taken to reduce the complexity. In this study, we used a direct aperture optimization (DAO) IMRT plan Direct aperture optimization IMRT is an IMRT method in which the aperture shapes and aperture weights are optimized simultaneously, and the MLC constraints and the number of segments are directly included in the optimization process. In DAO-IMRT planning, the planner specifies the planning objectives on the basis of the dose volume criteria for the target and critical structures as well as the number of beam segments to be delivered. The optimization only considers aperture shapes that satisfy the conditions set by the MLC. As a result, high-quality DAO-IMRT treatment plans can be generated using fewer segments (apertures) per beam. We investigated the dosimetric and technical differences in using DAO-IMRT. We also compared DAO-IMRT plans with standard beamlet-IMRT plans on phantom in terms of dosimetry, number of segments, and monitor units. In this study, we found that DAO-IMRT can achieve equal or better plans than standard beamlet-IMRT in dose optimization, secondary scattering dose and treatment time. The DAO-IMRT planning is proficient, and the plans can be delivered efficiently because small numbers of segments and monitor units are used.

Purpose To evaluate the effect of pelvic radiotherapy (RT) in patients with stage IV rectal cancer treated with resection of primary tumor with or without metastasectomy. Materials and methods Medical records of 112 patients with stage IV rectal cancer treated with resection of primary tumor between 1990 and 2011 were retrospectively reviewed. Fifty-nine patients received synchronous or staged metastasectomy whereas fifty-three patients did not. Twenty-six patients received pelvic radiotherapy. Results Median overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS) of all patients was 27, 70, and 11 months, respectively. Pathologic T (pT), N (pN) classification and complete metastasectomy were statistically significant factors in OS (p = 0.040, 0.020, and 0.002, respectively). RT did not improve OS or LRFS. There were no significant factors in LRFS. pT and pN classification were also significant prognostic factors in PFS (p = 0.010 and p = 0.033, respectively). In the subgroup analysis, RT improved LRFS in patients with pT4 disease (p = 0.026). The locoregional failure rate of the RT group and the non-RT group were 23.1% and 33.7%, showing no difference in the failure pattern of both groups (p = 0.260). Conclusion Postoperative pelvic RT did not improve LRFS of all metastatic rectal cancer patients; however, it can be recommended to patients with pT4 disease. A complete resection of metastatic masses should be performed if possible.

We report the results of a retrospective study of stereotactic body radiotherapy (SBRT) using a Cyberknife for prostate cancer.In all 29 patients were treated with hypofractionated SBRT using a Cyberknife at median 36 Gy in five fractions. All the patients were treated with a radical aim. Prostate-specific antigen (PSA) was evaluated at baseline and after radiotherapy. Acute (≤3 months) and late (3 months) urinary and rectal toxicities were recorded according to the CTCAE version 4.0.The median duration of follow up was 41 months. PSA values decreased in a time-dependent way. The median PSA nadir was 0.329 ng/mL, achieved after a median of 23 months' follow up. Two patients had a PSA failure according to the definition of nadir + 2 ng/mL. Eight patients (28%) had a benign PSA bounce at median 9 months after radiotherapy. CTCAE Grade 2 and 3 late urinary toxicities were reported in 3 and 3%, respectively. One patient had exacerbated urinary symptoms and received an operation. There were no severe late rectal toxicities.The preliminary findings of our study suggest SBRT is feasible for prostate cancer treatment. Further studies with more patients and longer follow-up duration are required.

Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced cervical cancer. This study was undertaken to evaluate the outcomes and the prognostic factors for cervical cancer after CCRT.The medical records of 174 patients with International Federation of Gynecology and Obstetrics stage IB1-IVA who were treated at three affiliated hospitals of the Catholic University of Korea between January 1999 and December 2008 were reviewed and analyzed. Patients received pelvic radiotherapy with one of three regimens of cisplatin-based chemotherapy concurrently and high-dose rate brachytherapy. The radiation field was extended to include para-aortic lymph nodes, if necessary. The median follow-up period was 29.5 months (range, 5-96 months). Using multivariate analysis, stage (P = 0.014), tumor size (P = 0.043), and clinical response (P = 0.001) had a significant effect on overall survival. Similarly, progression-free survival (PFS) was influenced by stage (P = 0.004), tumor size (P = 0.02), clinical response (P = 0.011), and normalized squamous cell carcinoma antigen level after CCRT (P = 0.007). The 5-year survival rates were 91.7% (standard error, 5.8%) for stages IB1-IIA, 71.5% (standard error, 7.8%) for stage IIB, 44.9% (standard error, 7.8%) for stage III, and 20.9% (standard error, 12.0%) for stage IVA. A total of 151 out of 174 patients (86.8%) completed the planned treatment. Toxicities were manageable with supportive therapy.Cisplatin-based CCRT is well-tolerated. Good clinical response revealed a favorable correlation to survival. A maximal effort to achieve this goal might prolong survival in patients with cervical cancer.

Captopril, an inhibitor of angiotensin I converting enzyme, has been shown to modify radiation damage and prevent radiation injury of normal tissue in rats and pigs. The present study was carried out to determine whether captopril would reduce radiation changes in the proximal small bowel in mice.Mice were subjected to whole body irradiation with 9 Gy or 15 Gy. Captopril was administered in drinking water at a regimen of 62.5 mg/kg/day (captopril group I) and 125 mg/kg/day (captopril group II), continuously from 7 days before irradiation to the end of each designed experiment. The jejunal damage was evaluated microscopically by crypt count per circumference and by histologic damage grading.Crypt number in the sham-irradiated control was 133 +/- 6.8/circumference. In both captopril group I and II, crypt numbers and histologic scores were not significantly different from those in the normal group. The 9 Gy and 15 Gy radiation alone groups showed significantly lower crypt counts and histologic scores compared with the sham-irradiated control group (p0.05). The groups exposed to 9 Gy radiation plus captopril I and II showed significantly higher crypt counts and lower histologic damage scores on the third day, and lower histologic damage scores on the fifth day compared with the 9 Gy radiation alone group (p0.05). The 15 Gy radiation plus captopril I and II groups had significantly higher crypt counts and lower histologic damage scores on the third day than those of the 15 Gy radiation alone group (p0.05). All mice of the 15 Gy radiation group succumbed to intestinal radiation death.Our results suggest that captopril provides protection from acute radiation damage to the jejunal mucosa in mice.

Purpose To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. Methods and Materials Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. Results Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T ( P = .045) and N ( P = .032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS ( P = .025) and overall survival ( P = .031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. Conclusion Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and survival.

PURPOSE: To evaluate the prognostic value of metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) on initial positron emission tomography-computed tomography (PET-CT) and investigate the clinical value of SUVmax for early detection of locoregional recurrent disease after postoperative radiotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: A total of 100 patients with locally advanced HNSCC received primary tumor excision and neck dissection followed by adjuvant radiotherapy with or without chemotherapy. The MTV and SUVmax were measured from primary sites and neck nodes. The prognostic value of MTV and SUVmax were assessed using initial staging PET/CT (study A). Follow-up PET/CT scan available after postoperative concurrent chemoradiotherapy or radiotherapy were evaluated for the SUVmax value and correlated with locoregional recurrence (study B). A receiver operating characteristic (ROC) curve analysis was used to define a threshold value of SUVmax with the highest accuracy for recurrent disease assessment. RESULTS: High MTV (>41 mL) is negative prognostic factor for disease free survival (p = 0.041). Postradiation SUVmax was significantly correlated with locoregional recurrence (hazard ratio, 1.812; 95% confidence interval, 1.361 to 2.413; p < 0.001). A cut-off value of 5.38 from follow-up PET/CT was identified as having maximal accuracy for detecting locoregional recurrence by ROC analysis. CONCLUSION: MTV at staging work-up was significantly associated with disease free survival. The SUVmax value from follow-up PET/CT showed high diagnostic accuracy for the detection of locoregional recurrence in postoperatively irradiated HNSCC.

Purpose We report early preliminary experience with CyberKnife radiosurgery (RS) as salvage treatment for locally recurrent head and neck cancer (HNC). Methods and Materials Between March 2004 and August 2006, 36 patients (44 sites) were treated with CyberKnife RS as reirradiation for locally recurrent HNC. Treatment sites were as follows: nasopharynx (8), maxillary sinus (8), neck lymph nodes (8), skull base (7), nasal cavity (4), retropharyngeal lymph nodes (3), orbit (2), and others (4). Total doses administered were 18–40 Gy (median, 30 Gy) in 3 to 5 fractions to the 65%–85% isodose line for 3–5 consecutive days. Previous external radiation dose ranged from 39.6 to 134.4 Gy (median, 70.2 Gy). Gross tumor volume ranged from 0.2 to 114.9 cm 3 (median, 22.6 cm 3 ). Median follow-up was 17.3 months. Results Thirty-five of 44 sites were evaluated for response. Fifteen (42.9%) sites achieved complete response, 13 sites (37.1%) achieved a partial response, 3 (8.6%) sites maintained stable disease, and 4 sites (11.4%) showed tumor progression. Grade III acute complications were noted in 13 patients. Late complications were observed in three patients (1 bone necrosis, 2 soft tissue necrosis) during follow-up. Conclusion These preliminary results suggest that fractionated stereotactic radiosurgery is an effective treatment modality as a salvage treatment with good short-term local control. The early overall response rate is encouraging. However, more experience and a longer follow-up are necessary to determine the role of fractionated stereotactic radiosurgery as a salvage treatment of locally recurrent HNC and to define long-term complications.

Ionizing radiation has been reported to affect the fibrinolytic activity of exposed tissue. With cultured bovine aortic endothelial cells, radiation suppresses the release of plasminogen activator to the conditioned media, with a concomitant increase in intracellular plasminogen activator. Thus study was undertaken to determine whether radiation-impaired plasminogen activator release can be modified by phorbol ester. We exposed cultured bovine aortic endothelial cells to a sterilizing dose of 10 Gy of gamma-rays and found the treatment led to cell injury, as evidenced by an increased release of prelabeled chromium, and to a reduction of plasminogen activator in the conditioned media with elevated intracellular plasminogen activator in irradiated cells. Phorbol ester enhanced plasminogen activator activity in both sham-irradiated and irradiated endothelial cells. It was interesting to note that the increased plasminogen activator in phorbol ester-stimulated sham-irradiated cells was largely retained inside the cell, while it was released to the conditioned media in irradiated cells. Apparently, altered plasminogen activator activity of radiation-sterilized endothelial cells can be modified by exogenous stimuli.

We analyzed the clinical efficacy and toxicity of concurrent therapy as a first line modality for malignant glioma patients. From 1998 to 2004, 39 patients, 22 with glioblastoma (GM), nine with anaplastic astrocytoma (AA), 7 with anaplastic oligodendroglioma (AO) and 1 with anaplastic oligodendro-astrocytoma (AOA) were enrolled in this study. The median age was 46.2 years (range 8-67). Both external involved field radiotherapy and chemotherapy, composed of CCNU (75-110 mg/m(2)), procarbazine (60 mg/m(2)) and vincristine (1.4 mg/m(2)), were started simultaneously two weeks after surgery. The median progression-free survival time for the GM, AA, and AO patients was 6, 26, and 31 months, respectively. The median survival of the patients with GM and AA was 27 and 41 months. The two-year survival rate of the GM and AA patients was 50.4 and 66.7%, respectively. Grade III/IV hematological toxicity was reduced from 25.6 to 13% after reduction of the dose of CCNU (75 mg/m(2)). Radiation necrosis was confirmed by pathologic examination in four patients (10.3%). The median interval from the completion of radiotherapy to the diagnosis of necrosis was 19 weeks. Modified concurrent chemoradiotherapy may be a feasible option for treating malignant glioma with acceptable toxicity.

We evaluate the correlation of clinical staging on positron emission tomography-computed tomography (PET-CT) and pathologic staging and the prognostic value of PET-CT after induction chemotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC). We analyzed 42 cases of clinical stage IIIA-N2 NSCLC who receive 2 to 4 cycles of preoperative chemotherapy with or without radiation followed by curative resection. The maximum standard uptake value (SUVmax) of the suspected lesion on PET-CT was recorded. PET-CT findings after induction chemotherapy were compared with those of initial PET-CT and pathology after surgery. The accuracy of PET-CT in restaging of the primary tumor after induction chemotherapy was 50.0%. Eighteen (42.8%) of 42 patients were underestimated ycT stage, and 3 (7.1%) of 42 patients was overestimated ycT stage by PET-CT scan. The accuracy of PET-CT in restaging of the nodal disease was 71.4%. Six (14.3%) of 42 patients were underestimated ycN stage, and 6 (14.3%) of 42 patients were overestimated ycN stage as compared with pathologic staging. The 2-year overall survival (OS) and relapse-free survival (RFS) rate were 68.5% and 40.9%, respectively. Complete responders (ycT0N0M0) on PET-CT after induction chemotherapy had a significantly longer RFS time than did incomplete responders (28.3 vs 9.1 months, P = 0.021). Complete response on PET-CT after induction chemotherapy with or without radiation was a good prognosticator for RFS in stage IIIA-N2 NSCLC patients who received surgery. However, response evaluation on PET-CT after induction chemotherapy should be interpreted with caution due to its unacceptable accuracy.

This study was designed to determine the effect of concomitant small field boost irradiation given during preoperative chemoradiotherapy for patients with locally advanced rectal cancer. The study prospectively enrolled 38 patients scheduled for preoperative chemoradiotherapy. Pelvic radiotherapy of 43.2 Gy/24 fractions was delivered and boost radiotherapy of 7.2 Gy/12 fractions was concomitantly administered during the latter half of the pelvic radiotherapy treatment period. Two cycles of a bolus 5-fluorouracil and leucovorin injection in the first and fifth weeks of radiotherapy were administered. The median time to surgery after completion of chemoradiotherapy was six weeks. Tumor responses to chemoradiotherapy were assessed by using magnetic resonance volumetry and postchemoradiotherapy pathology tests to determine tumor downstaging and tumor regression rate. Thirty-six of 38 patients (94.7 percent) underwent the scheduled surgery. The mean tumor volume reduction rate was 70.3 percent, and the clinical response rate was 66.7 percent. The downstaging rates were 41.7 percent for T classification, 85.2 percent for N classification, and 72.2 percent for stage. Tumor regression grades after preoperative chemoradiotherapy were Grade 1 in 5 patients (13.9 percent), Grade 2 in 24 patients (66.7 percent), Grade 3 in 3 patients (8.3 percent), and Grade 4 in 4 patients (11.1 percent). Ten patients (26.3 percent) experienced ≥ Grade 3 acute toxicity. Our data suggest that concomitant boost irradiation does not improve clinical outcomes compared with other published preoperative chemoradiotherapy regimens. In addition, the clinicians choosing to use concomitant small field boost irradiation should be cautious to minimize the risk of unplanned sphincter ablation.

To evaluate the effect of the simulation method on recurrence among the patients who received radiotherapy after breast-conserving surgery (BCS) for early breast carcinoma.Between 1995 and 2000, 70 patients with stage I-II breast carcinoma underwent breast-conserving surgery and adjuvant radiotherapy. Twenty nine patients (41.4%) were simulated with the 2D contour-based method (September 1995 to August 1997) and 41 patients (58.6%) were simulated with the 3D CT-based method (September 1997 to February 2000). To analyze the effect of the simulation method, the patient and treatment characteristics were compared.The characteristics were similar for the patients between the 2D contour-based simulation group and the 3D CT-based simulation group. During a median follow-up period of 75 months, 4 (13.8%) of 29 patients who were treated with 2D simulation and 1 (2.4%) of 41 patients who were treated with 3D simulation group developed treatment failure. The five-year survival rates were 89.2% and 95.1% between the 2D and 3D simulation groups (p=0.196). The five-year disease free survival (DFS) rates were 86.2% and 97.5% between the 2D and 3D simulation groups (p=0.0636). On univariate analysis, age40 (p= 0.0226) and the number of dissected axillary lymph nodeor= 10 (p=0.0435) were independent predictors of improved 5-year DFS.Although our data showed marginal significance for the DFS between the two groups, it is insufficient, due to the small number of patients in our study, to prove whether 3D CT-based simulation might improve the DFS and reduce the risk of recurrence when compared with 2D contour-based simulation. Further study is needed with a larger group of patients.

We evaluated 5-year follow-up of stereotactic body radiation therapy (SBRT) with Cyberknife for prostate cancer patients.Forty-five men with prostate adenocarcinoma who received SBRT using Cyberknife from May 2006 to November 2012 were enrolled in this study. They were prostate cancer patien

We have experienced three cases of extramammary Paget's disease (EMPD) of the vulva that received radiation therapy (RT). Here, we analyze the efficacy of RT and include a literature survey. Three patients with EMPD of the vulva were treated with curative RT between 1993 and 1998. One of the patients had associated underlying adenocarcinoma of the vulva. The total doses of radiation administered were 54~78 Gy/6~8 weeks. Radiation fields encompassed 2 to 3 cm outer margins free from all visible disease including or not including the inguinal area using a 9 MeV electron or a 6 MV photon beam. Follow-up durations after radiotherapy were 0.6~11 years. Complete response was obtained in all three patients. Marginal failure occurred in one patient, and another patient with underlying adenocarcinoma treated by vulvectomy with bilateral inguinal lymph node dissection followed by external RT showed no relapse. Radiation induced side effects were transient acute confluent wet desquamation in the treated area resulting in mild late atrophic skin changes. Although surgery is currently considered the preferred primary treatment for EMPD, it has a high relapse rate due to the multifocal nature of the disease. We conclude that RT is of benefit in some selected cases of EMPD.

Purpose This single institutional study is aimed to observe the outcome of patients who received postoperative radiotherapy after radical prostatectomy. Materials and Methods A total of 59 men with histologically identified prostate adenocarcinoma who had received postoperative radiation after radical prostatectomy from August 2005 to July 2011 in Seoul St. Mary's Hospital of the Catholic University of Korea, was included. They received 45-50 Gy to the pelvis and boost on the prostate bed was given up to total dose of 63-72 Gy (median, 64.8 Gy) in conventional fractionation. The proportion of patients given hormonal therapy and the pattern in which it was given were analyzed. Primary endpoint was biochemical relapse-free survival (bRFS) after radiotherapy completion. Secondary endpoint was overall survival (OS). Biochemical relapse was defined as a prostate-specific antigen level above 0.2 ng/mL. Results After median follow-up of 53 months (range, 0 to 104 months), the 5-year bRFS of all patients was estimated 80.4%. The 5-year OS was estimated 96.6%. Patients who were given androgen deprivation therapy had a 5-year bRFS of 95.1% while the ones who were not given any had that of 40.0% (p < 0.01). However, the statistical significance in survival difference did not persist in multivariate analysis. The 3-year actuarial grade 3 chronic toxicity was 1.7% and no grade 3 acute toxicity was observed. Conclusion The biochemical and toxicity outcome of post-radical prostatectomy radiotherapy in our institution is favorable and comparable to those of other studies.

We investigated the combined effects of p53 gene transfer and irradiation and its still unclear interaction mechanism in human gliomas. Four human glioma cell lines expressing mutant type p53 (U373 and A172) and wild-type p53 (D54MG and EFC-2) were transfected by adenoviral vectors bearing p53 gene at 50 multiplicity of infection. Two days after transfection, cells were irradiated (3, 6, and 9 Gy). The cytotoxicity was evaluated by clonogenic assay. The quantitative analysis of apoptosis and cell cycle analysis were performed using flow cytometry. Irradiation combined with adenoviral p53 transfection significantly increased cytotoxicity, which was additive in cell lines with wild-type p53 and more than additive in cell lines with mutant p53. The combination of two modalities increased the apoptotic population by 14% in A172 cells and 20% in D54 MG cells, which were the sum of apoptosis from each modality. Adenoviral p53 transfection increased the G1 phase fraction and concomitant decrease of radioresistant S phase fraction in A172 and D54MG cells. Our study demonstrated that p53 gene transfer combined with irradiation increased absolute cytotoxicity in human glioma cells used in this experiment. The interaction mechanism for increased cytotoxicity involved, in part, increased apoptosis and change of cell cycle profile.

Purpose To evaluate the treatment outcomes of preoperative versus postoperative concurrent chemoradiotherapy (CRT) on locally advanced rectal cancer. Materials and Methods Medical data of 114 patients with locally advanced rectal cancer treated with CRT preoperatively (54 patients) or postoperatively (60 patients) from June 2003 to April 2011 was analyzed retrospectively. 5-Fluorouracil (5-FU) or a precursor of 5-FU-based concurrent CRT (median, 50.4 Gy) and total mesorectal excision were conducted for all patients. The median follow-up duration was 43 months (range, 16 to 118 months). The primary end point was disease-free survival (DFS). The secondary end points were overall survival (OS), locoregional control, toxicity, and sphincter preservation rate. Results The 5-year DFS rate was 72.1% and 48.6% for the preoperative and postoperative CRT group, respectively (p = 0.05, the univariate analysis; p = 0.10, the multivariate analysis). The 5-year OS rate was not significantly different between the groups (76.2% vs. 69.0%, p = 0.23). The 5-year locoregional control rate was 85.2% and 84.7% for the preoperative and postoperative CRT groups (p = 0.98). The sphincter preservation rate of low-lying tumor showed significant difference between both groups (58.1% vs. 25.0%, p = 0.02). Pathologic tumor and nodal down-classification occurred after the preoperative CRT (53.7% and 77.8%, both p < 0.001). Acute and chronic toxicities were not significantly different between both groups (p = 0.10 and p = 0.62, respectively). Conclusion The results confirm that preoperative CRT can be advantageous for improving down-classification rate and the sphincter preservation rate of low-lying tumor in rectal cancer.

Purpose To evaluate outcome and morbidity in patients with vulvar cancer treated with radiotherapy, concurrent chemoradiotherapy or postoperative radiotherapy. Materials and Methods The records of 24 patients treated with radiotherapy for vulvar cancer between July 1993 and September 2009 were retrospectively reviewed. All patients received once daily 1.8-4 Gy fractions external beam radiotherapy to median 51.2 Gy (range, 19.8 to 81.6 Gy) on pelvis and inguinal nodes. Seven patients were treated with primary concurrent chemoradiotherapy, one patient was treated with primary radiotherapy alone, four patients received palliative radiotherapy, and twelve patients were treated with postoperative radiotherapy. Results Twenty patients were eligible for response evaluation. Response rate was 55% (11/20). The 5-year disease free survival was 42.2% and 5-year overall survival was 46.2%, respectively. Fifty percent (12/24) experienced with acute skin complications of grade III or more during radiotherapy. Late complications were found in 8 patients. 50% (6/12) of patients treated with lymph node dissection experienced severe late complications. One patient died of sepsis from lymphedema. However, only 16.6% (2/12) of patients treated with primary radiotherapy developed late complications. Conclusion Outcome of patients with vulvar cancer treated with radiotherapy showed relatively good local control and low recurrence. Severe late toxicities remained higher in patients treated with both node dissection and radiotherapy.

The work presented in the paper addresses a method for obtaining the optimal dose distribution for LINAC-based stereotactic radiosurgery. As many targets have nonspherical or irregular shapes and three-dimensional dose calculations included in dose optimisation, long computation times are required to determine the optimum isocentre separation and collimator sizes to shape the irregular target using the multiple-isocentre approach, by trial-and-error types of method. The simple approach, using a computer-aided design optimisation technique and a fast approximate dose model, has been developed to find the optimum isocentre positions and collimator sizes quickly and automatically. A spherical dose model has been developed to represent the dose for a standard arc system with a single isocentre. The implementation of computer-aided design algorithms with the spherical dose model and their application to several cases are discussed. It is shown that the spherical dose model gives dose distribution similar to that of the exact dose model, which makes this simple dose model more efficient, with computer-aided design optimisation, in finding optimum isocentre positions and collimator sizes used in stereotactic radiosurgery.

This retrospective study was carried out to evaluate the efficacy and toxicity of radiation therapy (RT) with/without cisplatin-based chemotherapy in nasopharyngeal cancer (NPC).One hundred forty six patients with NPC received curative RT and/or cisplatin-based chemotherapy. Thirty-nine patients were treated with induction chemotherapy (IC), including cisplatin and 5-fluorouracil followed by RT. Another 63 patients were treated with concurrent chemoradiotherapy (CCRT) using cisplatin, and 22 patients were treated with IC followed by CCRT. The remaining 22 patients were treated with RT alone.One hundred four (80.0%) patients achieved complete response (CR), and 23 (17.7%) patients achieved partial response (PR). The patterns of failure were: locoregional recurrences in 21.2% and distant metastases in 17.1%. Five-year overall survival (OS) and progression free survival (PFS) were 50.7% and 45.0%, respectively. Multivariate Cox stepwise regression analysis revealed CR to chemoradiotherapy to be a powerful prognostic factor for OS. CR to chemoradiotherapy and completion of radiation according to the time schedule were favorable prognostic factors for PFS. A comparison of each treatment group (IC --RT vs. CCRT vs. IC --CCRT vs. RT alone) revealed no significant differences in the OS or PFS. However, subgroup analysis showed significant differences in both OS and DFS in favor of the combined chemoradiotherapy group compared with RT alone, for stage IV and T3-4 tumors. Grade 3-4 toxicities were more common in the combined chemoradiotherapy arm, particularly in the CCRT group.This study was limited in that it was a retrospective study, much time was required to collect patients, and there were imbalances in the number of patients in each treatment group. Combined chemoradiotherapy remarkably prolonged the OS and PFS in subgroup patients with stage IV or T3-4 NPC.

Background and Objectives:Brachytherapy is one of the promising therapeutic strategy for the prevention of restenosis. The effects of low dose irradiation (

Purpose: To assess prostate-specific antigen (PSA) kinetics and report on the oncologic outcomes for patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT) using CyberKnife. Methods: We extracted the list and data of 39 patients with clinically localized prostate cancer who had undergone primary SBRT using CyberKnife between January 2008 and December 2012 from the Smart Prostate Cancer database system of Seoul St. Mary's Hospital. Changes in PSA over time, PSA velocity, and PSA nadir were evaluated from the completion of SBRT using CyberKnife. Biochemical recurrence (BCR)-free survival after primary SBRT using CyberKnife was determined using Kaplan–Meier analysis. Results: The rate of PSA decrease was maximal in the first month (median −3.34 ng/mL/mo), which then fell gradually with median values of −1.51, −0.32, −0.28, −0.20, and −0.03 ng/mL/mo for durations of 3, 6, 9, 12, and 24 months after SBRT using CyberKnife, respectively. The median PSA nadir was 0.31 ng/mL after a median 23 months. Kaplan–Meier analysis calculates an actuarial 5-year BCR-free survival after SBRT using CyberKnife as 80.8%. Conclusions: PSA decline occurred rapidly in the first month, and then the rate of PSA decline fell off steadily over time throughout 2 years after treatment. Also, SBRT using CyberKnife leads to long-term favorable BCR-free survival in localized prostate cancer.