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1.  Prognostic analysis of uterine cervical cancer treated with postoperative radiotherapy: importance of positive or close parametrial resection margin 
Radiation Oncology Journal  2015;33(2):109-116.
To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) in cervical cancer patients who underwent radical hysterectomy followed by postoperative radiotherapy (PORT) in a single institute.
Materials and Methods
Clinicopathologic data of 135 patients with clinical stage IA2 to IIA2 cervical cancer treated with PORT from 2001 to 2012 were reviewed, retrospectively. Postoperative parametrial resection margin (PRM) and vaginal resection margin (VRM) were investigated separately. The median treatment dosage of external beam radiotherapy (EBRT) to the whole pelvis was 50.4 Gy in 1.8 Gy/fraction. High-dose-rate vaginal brachytherapy after EBRT was given to patients with positive or close VRMs. Concurrent platinum-based chemoradiotherapy (CCRT) was administered to 73 patients with positive resection margin, lymph node (LN) metastasis, or direct extension of parametrium. Kaplan-Meier method and log-rank test were used for analyzing LRR, DM, and OS; Cox regression was applied to analyze prognostic factors.
The 5-year disease-free survival was 79% and 5-year OS was 91%. In univariate analysis, positive or close PRM, LN metastasis, direct extension of parametrium, lymphovascular invasion, histology of adenocarcinoma, and chemotherapy were related with more DM and poor OS. In multivariate analysis, PRM and LN metastasis remained independent prognostic factors for OS.
PORT after radical hysterectomy in uterine cervical cancer showed excellent OS in this study. Positive or close PRM after radical hysterectomy in uterine cervical cancer correlates with poor prognosis even with CCRT. Therefore, additional treatments to improve local control such as radiation boosting need to be considered.
PMCID: PMC4493422  PMID: 26157680
Parametrial resection margin; Uterine cervical neoplasms; Postoperative adjuvant radiotherapy
2.  Early treatment volume reduction rate as a prognostic factor in patients treated with chemoradiotherapy for limited stage small cell lung cancer 
Radiation Oncology Journal  2015;33(2):117-125.
To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC).
Materials and Methods
We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%).
With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group.
ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT.
PMCID: PMC4493423  PMID: 26157681
Small cell lung carcinoma; Radiotherapy; Tumor burden
3.  Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer 
Radiation Oncology Journal  2015;33(2):126-133.
To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer.
Materials and Methods
We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method.
The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS.
Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic significance in early uterine cervical cancer patients. More effective systemic treatments might be needed to reduce distant metastasis in these patients.
PMCID: PMC4493424  PMID: 26157682
Adjuvant radiotherapy; Uterine cervical cancer; Hysterectomy; Adjuvant chemotherapy
4.  Morphologic change of rectosigmoid colon using belly board and distended bladder protocol 
Radiation Oncology Journal  2015;33(2):134-141.
This study investigates morphologic change of the rectosigmoid colon using a belly board in prone position and distended bladder in patients with rectal cancer. We evaluate the possibility of excluding the proximal margin of anastomosis from the radiation field by straightening the rectosigmoid colon.
Materials and Methods
Nineteen patients who received preoperative radiotherapy between 2006 and 2009 underwent simulation in a prone position (group A). These patients were compared to 19 patients treated using a belly board in prone position and a distended bladder protocol (group B). Rectosigmoid colon in the pelvic cavity was delineated on planning computed tomography (CT) images. A total dose of 45 Gy was planned for the whole pelvic field with superior margin of the sacral promontory. The volume and redundancy of rectosigmoid colon was assessed.
Patients in group B had straighter rectosigmoid colons than those in group A (no redundancy; group A vs. group B, 10% vs. 42%; p = 0.03). The volume of rectosigmoid colon in the radiation field was significantly larger in group A (56.7 vs. 49.1 mL; p = 0.009). In dose volume histogram analysis, the mean irradiated volume was lower in patients in group B (V45 27.2 vs. 18.2 mL; p = 0.004). In Pearson correlation coefficient analysis, the in-field volume of rectosigmoid colon was significantly correlated with the bladder volume (R = 0.86, p = 0.003).
Use of a belly board and distended bladder protocol could contribute to exclusion of the proximal margin of anastomosis from the radiation field.
PMCID: PMC4493425  PMID: 26157683
Rectal cancers; Belly board; Bladder volume; Anastomotic strength; Anastomotic leakage; Preoperative radiotherapy
5.  Development of new on-line statistical program for the Korean Society for Radiation Oncology 
Radiation Oncology Journal  2015;33(2):142-148.
To develop new on-line statistical program for the Korean Society for Radiation Oncology (KOSRO) to collect and extract medical data in radiation oncology more efficiently.
Materials and Methods
The statistical program is a web-based program. The directory was placed in a sub-folder of the homepage of KOSRO and its web address is The operating systems server is Linux and the webserver is the Apache HTTP server. For database (DB) server, MySQL is adopted and dedicated scripting language is the PHP. Each ID and password are controlled independently and all screen pages for data input or analysis are made to be friendly to users. Scroll-down menu is actively used for the convenience of user and the consistence of data analysis.
Year of data is one of top categories and main topics include human resource, equipment, clinical statistics, specialized treatment and research achievement. Each topic or category has several subcategorized topics. Real-time on-line report of analysis is produced immediately after entering each data and the administrator is able to monitor status of data input of each hospital. Backup of data as spread sheets can be accessed by the administrator and be used for academic works by any members of the KOSRO.
The new on-line statistical program was developed to collect data from nationwide departments of radiation oncology. Intuitive screen and consistent input structure are expected to promote entering data of member hospitals and annual statistics should be a cornerstone of advance in radiation oncology.
PMCID: PMC4493426  PMID: 26157684
Statistics; On-line; Program; Database; Radiation oncology; KOSRO
6.  Exome sequencing in a breast cancer family without BRCA mutation 
Radiation Oncology Journal  2015;33(2):149-154.
We performed exome sequencing in a breast cancer family without BRCA mutations.
Materials and Methods
A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members.
We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined.
Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.
PMCID: PMC4493427  PMID: 26157685
Breast neoplasms; Exome; BRCA
7.  The using of megavoltage computed tomography in image-guided brachytherapy for cervical cancer: a case report 
Radiation Oncology Journal  2015;33(2):155-159.
We present a case of cervical cancer treated by concurrent chemoradiation. In radiation therapy part, the combination of the whole pelvic helical tomotherapy plus image-guided brachytherapy with megavoltage computed tomography of helical tomotherapy was performed. We propose this therapeutic approach could be considered in a curative setting in some problematic situation as our institution.
PMCID: PMC4493428  PMID: 26157686
Cervical cancer; Megavoltage computed tomography; Image-guided brachytherapy
8.  Stereotactic radiotherapy for early stage non-small cell lung cancer 
Radiation Oncology Journal  2015;33(2):57-65.
Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice.
PMCID: PMC4493429  PMID: 26157674
Stereotactic body radiotherapy; Stereotactic radiosurgery; Non-small cell lung cancer
9.  The protective effects of trace elements against side effects induced by ionizing radiation 
Radiation Oncology Journal  2015;33(2):66-74.
Trace elements play crucial role in the maintenance of genome stability in the cells. Many endogenous defense enzymes are containing trace elements such as superoxide dismutase and metalloproteins. These enzymes are contributing in the detoxification of reactive oxidative species (ROS) induced by ionizing radiation in the cells. Zinc, copper, manganese, and selenium are main trace elements that have protective roles against radiation-induced DNA damages. Trace elements in the free salt forms have protective effect against cell toxicity induced by oxidative stress, metal-complex are more active in the attenuation of ROS particularly through superoxide dismutase mimetic activity. Manganese-complexes in protection of normal cell against radiation without any protective effect on cancer cells are more interesting compounds in this topic. The aim of this paper to review the role of trace elements in protection cells against genotoxicity and side effects induced by ionizing radiation.
PMCID: PMC4493430  PMID: 26157675
Trace elements; DNA damage; Side effects; Radiation-protective agent; Radiation
10.  Multi-institutional analysis of T3 subtypes and adjuvant radiotherapy effects in resected T3N0 non-small cell lung cancer patients 
Radiation Oncology Journal  2015;33(2):75-82.
We evaluated the prognostic significance of T3 subtypes and the role of adjuvant radiotherapy in patients with resected the American Joint Committee on Cancer stage IIB T3N0M0 non-small cell lung cancer (NSCLC).
Materials and Methods
T3N0 NSCLC patients who underwent resection from January 1990 to October 2009 (n = 102) were enrolled and categorized into 6 subgroups according to the extent of invasion: parietal pleura chest wall invasion, mediastinal pleural invasion, diaphragm invasion, separated tumor nodules in the same lobe, endobronchial tumor <2 cm distal to the carina, and tumor-associated collapse.
The median overall survival (OS) and disease-free survival (DFS) were 55.3 months and 51.2 months, respectively. In postoperative T3N0M0 patients, the tumor size was a significant prognostic factor for survival (OS, p = 0.035 and DFS, p = 0.035, respectively). Patients with endobronchial tumors within 2 cm of the carina also showed better OS and DFS than those in the other T3 subtypes (p = 0.018 and p = 0.016, respectively). However, adjuvant radiotherapy did not cause any improvement in survival (OS, p = 0.518 and DFS, p = 0.463, respectively). Only patients with mediastinal pleural invasion (n = 25) demonstrated improved OS and DFS after adjuvant radiotherapy (n = 18) (p = 0.012 and p = 0.040, respectively).
The T3N0 NSCLC subtype that showed the most favorable prognosis is the one with endobronchial tumors within 2 cm of the carina. Adjuvant radiotherapy is not effective in improving survival outcome in resected T3N0 NSCLC.
PMCID: PMC4493431  PMID: 26157676
Non-small cell lung cancer; Adjuvant radiotherapy; Prognostic factor
11.  Can we omit prophylactic inguinal nodal irradiation in anal cancer patients? 
Radiation Oncology Journal  2015;33(2):83-88.
To evaluate the appropriateness of prophylactic inguinal nodal irradiation (PINI), we analyzed patterns of failure in anal cancer patients who were inguinal node-negative at presentation and did not receive PINI.
Materials and Methods
We retrospectively reviewed the records of 33 anal cancer patients treated by definitive concurrent chemoradiation therapy (CCRT) between 1994 and 2013. Radiotherapy consisted of a total dose of 44-45 Gy (22-25 fractions in 5 weeks) on the whole pelvis, anus, and perineum. Except inguinal lymphadenopathy was present at initial diagnosis, the entire inguinal chain was not included in the radiation field. In other words, there was no PINI.
The median follow-up duration was 50 months (range, 4 to 218 months). Median survival and progression-free survival (PFS) were 57 months (range, 10 to 218 months) and 50 months (range, 4 to 218 months), respectively. Among the survival, the median follow-up duration was 51 months (range, 12 to 218 months). The 5-year overall survival and PFS rates were 93.4% and 88.8%, respectively. Although none of the patients received inguinal node irradiation for prophylactic purposes, there was no inguinal recurrence.
Treatment of anal cancer by omitting PINI might be considered in selected patients with clinically uninvolved inguinal nodes.
PMCID: PMC4493432  PMID: 26157677
Anus neoplasms; Prophylactic; Radiotherapy; Inguinal; Lymph nodes
12.  Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer 
Radiation Oncology Journal  2015;33(2):89-97.
To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS).
Materials and Methods
From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21.
The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression.
The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication.
PMCID: PMC4493433  PMID: 26157678
Lung; NSCLC; Radiosurgery; Cyberknife; Fiducialless; Marker
13.  Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy 
Radiation Oncology Journal  2015;33(2):98-108.
The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated.
Materials and Methods
Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy.
With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients.
CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited.
PMCID: PMC4493434  PMID: 26157679
Nasopharyngeal carcinoma; Intensity-modulated radiotherapy; Concurrent chemoradiotherapy; Induction chemotherapy
14.  Contemporary treatment with radiosurgery for spine metastasis and spinal cord compression in 2015 
Radiation Oncology Journal  2015;33(1):1-11.
With the progress of image-guided localization, body immobilization system, and computerized delivery of intensity-modulated radiation delivery, it became possible to perform spine radiosurgery. The next question is how to translate the high technology treatment to the clinical application. Clinical trials have been performed to demonstrate the feasibility of spine radiosurgery and efficacy of the treatment in the setting of spine metastasis, leading to the randomized trials by a cooperative group. Radiosurgery has also demonstrated its efficacy to decompress the spinal cord compression in selected group of patients. The experience indicates that spine radiosurgery has a potential to change the clinical practice in the management of spine metastasis and spinal cord compression.
PMCID: PMC4394063  PMID: 25874172
Radiosurgery; Spine metastasis; Stereotactic body radiation therapy (SBRT); Spinal cord compression
15.  Treatment outcomes of neoadjuvant concurrent chemoradiotherapy followed by esophagectomy for patients with esophageal cancer 
Radiation Oncology Journal  2015;33(1):12-20.
To evaluate treatment outcomes and determine prognostic factors in patients with esophageal cancer treated with esophagectomy after neoadjuvant chemoradiotherapy (NCRT).
Materials and Methods
We retrospectively evaluated 39 patients with esophageal cancer who underwent concurrent chemoradiotherapy followed by esophagectomy between 2002 and 2012. Initial clinical stages of patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and stage III in 33 patients (84.6%).
The median age of all the patients was 62 years, and the median follow-up period was 17 months. The 3-year overall survival (OS) rate was 33.6% in all the patients. The 3-year locoregional recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with covariates of age, the Eastern Cooperative Oncology Group performance status, hypertension, diabetes mellitus, tumor length, clinical response, clinical stage, pathological response, pathological stage, lymphovascular invasion, surgical type, and radiotherapy to surgery interval, only pathological stage was an independent significant prognostic factor affecting both OS and LRFS. The complications in postoperative day 90 were pneumonia in 9 patients, anastomotic site leakage in 3 patients, and anastomotic site stricture in 2 patients. Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among these 4 patients was respiratory failure in 3 patients and myocardial infarction in one patient.
Only pathological stage was an independent prognostic factor for both OS and LRFS in patients with esophageal cancer treated with esophagectomy after NCRT. We could confirm the significant role of NCRT in downstaging the initial tumor bulk and thus resulting in better survival of patients who gained earlier pathological stage after NCRT.
PMCID: PMC4394064  PMID: 25874173
Esophageal cancer; Chemoradiotherapy; Esophagectomy; Neoadjuvant therapy
16.  Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer 
Radiation Oncology Journal  2015;33(1):21-28.
We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation.
Materials and Methods
From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (≥7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups.
The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS.
Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.
PMCID: PMC4394065  PMID: 25874174
Prostate cancer; Radiation therapy; Radical prostatectomy; Outcomes; Dose escalation; Comparative effectiveness
17.  Outcome analysis in patients with uterine sarcoma 
Radiation Oncology Journal  2015;33(1):29-35.
To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery.
Materials and Methods
We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months).
The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure.
The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.
PMCID: PMC4394066  PMID: 25874175
Uterus; Sarcoma; Neoplasms by histology type; Pelvic failure; Adjuvant radiotherapy
18.  Post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma 
Radiation Oncology Journal  2015;33(1):36-41.
To evaluate the incidence and risk factors of post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma (HCC).
Materials and Methods
Medical records of 81 patients who have been diagnosed of brain metastases from HCC and underwent surgery, radiosurgery and/or whole brain radiotherapy (WBRT) between January 2000 and December 2013 were retrospectively reviewed.
Intracranial hemorrhage was present in 64 patients (79%) at the time of diagnosis. Median value of alpha-fetoprotein (AFP) level was 1,700 ng/mL. The Eastern Cooperative Oncology Group (ECOG) performance status for 20 patients was greater than 2. Fifty-seven patients underwent WBRT and the others were treated with surgery and/or radiosurgery without WBRT. During follow-up, 12 events of intracranial hemorrhage after treatment were identified. Three-month post-treatment hemorrhage rate was 16.1%. Multivariate analyses revealed that ECOG performance status, AFP, and WBRT were associated with post-treatment hemorrhage (p = 0.013, 0.013, and 0.003, respectively). Kaplan-Meier analysis showed that 3-month post-treatment hemorrhage rate of new lesion was higher in patients treated without WBRT, although statistical significance was not reached. (18.6% vs. 4.6%; p = 0.104). Ten of 12 patients with post-treatment hemorrhage died with neurologic cause.
WBRT should be considered to prevent post-treatment hemorrhage in the treatment of brain metastases from HCC.
PMCID: PMC4394067  PMID: 25874176
Hepatocellular carcinoma; Brain metastases; Intracranial hemorrhages
19.  New methods for optical distance indicator and gantry angle quality control tests in medical linear accelerators: image processing by using a 3D phantom 
Radiation Oncology Journal  2015;33(1):42-49.
In order to keep the acceptable level of the radiation oncology linear accelerators, it is necessary to apply a reliable quality assurance (QA) program.
Materials and Methods
The QA protocols, published by authoritative organizations, such as the American Association of Physicists in Medicine (AAPM), determine the quality control (QC) tests which should be performed on the medical linear accelerators and the threshold levels for each test. The purpose of this study is to increase the accuracy and precision of the selected QC tests in order to increase the quality of treatment and also increase the speed of the tests to convince the crowded centers to start a reliable QA program. A new method has been developed for two of the QC tests; optical distance indicator (ODI) QC test as a daily test and gantry angle QC test as a monthly test. This method uses an image processing approach utilizing the snapshots taken by the CCD camera to measure the source to surface distance (SSD) and gantry angle.
The new method of ODI QC test has an accuracy of 99.95% with a standard deviation of 0.061 cm and the new method for gantry angle QC has a precision of 0.43°. The automated proposed method which is used for both ODI and gantry angle QC tests, contains highly accurate and precise results which are objective and the human-caused errors have no effect on the results.
The results show that they are in the acceptable range for both of the QC tests, according to AAPM task group 142.
PMCID: PMC4394068  PMID: 25874177
Gantry angle; Linear accelerator; Optical distance indicator (ODI); Quality control; Source to surface distance (SSD)
20.  Virtual lymph node analysis to evaluate axillary lymph node coverage provided by tangential breast irradiation 
Radiation Oncology Journal  2015;33(1):50-56.
To investigate the coverage of axillary lymph node with tangential breast irradiation fields by using virtual lymph node (LN) analysis.
Materials and Methods
Forty-eight women who were treated with whole breast irradiation after breast-conserving surgery were analyzed. The axillary and breast volumes were delineated according to the Radiation Therapy Oncology Group (RTOG) contouring atlas. To generate virtual LN contours, preoperative fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans with identifiable LN were fused with the CT scans, and the virtual LN contour were delineated on the CT.
The median level I and II axillary volume coverage percentages at the VD95% line were 33.5% (range, 5.3% to 90.4%) and 0.6% (range, 0.0% to 14.6%), respectively. Thirty-one LNs in 18 patients were delineated (26 in level I and 5 in level II). In the level I axilla, 84.6% of virtual LNs were encompassed by the 95% isodose line. In the level II axilla, by contrast, none of the virtual LNs were encompassed by the 95% isodose volumes. There was a substantial discrepancy between the RTOG contouring atlas-based axillary volume analysis and the virtual LN analysis, especially for the level I axillary coverage. The axillary volume coverage was associated with the body mass index (BMI) and breast volume.
The tangential breast irradiation did not deliver adequate therapeutic doses to the axillary region, particularly those in the level II axilla. Patients with small breast volumes or lower BMI showed reduced axillary coverage from the tangential breast fields. For axillary LN irradiation, individualized anatomy-based radiation fields for patients would be necessary.
PMCID: PMC4394069  PMID: 25874178
Breast neoplasm; Axilla; Lymph nodes; Radiotherapy
21.  Insufficiency fracture after radiation therapy 
Radiation Oncology Journal  2014;32(4):213-220.
Insufficiency fracture occurs when normal or physiological stress applied to weakened bone with demineralization and decreased elastic resistance. Recently, many studies reported the development of IF after radiation therapy (RT) in gynecological cancer, prostate cancer, anal cancer and rectal cancer. The RT-induced insufficiency fracture is a common complication during the follow-up using modern imaging studies. The clinical suspicion and knowledge the characteristic imaging patterns of insufficiency fracture is essential to differentiate it from metastatic bone lesions, because it sometimes cause severe pain, and it may be confused with bone metastasis.
PMCID: PMC4282995  PMID: 25568849
Radiation therapy; Adverse effects; Fracture; Stress
22.  Vertebral compression fractures after spine irradiation using conventional fractionation in patients with metastatic colorectal cancer 
Radiation Oncology Journal  2014;32(4):221-230.
To evaluate the risk of vertebral compression fracture (VCF) after conventional radiotherapy (RT) for colorectal cancer (CRC) with spine metastasis and to identify risk factors for VCF in metastatic and non-metastatic irradiated spines.
Materials and Methods
We retrospectively reviewed 68 spinal segments in 16 patients who received conventional RT between 2009 and 2012. Fracture was defined as a newly developed VCF or progression of an existing fracture. The target volume included all metastatic spinal segments and one additional non-metastatic vertebra adjacent to the tumor-involved spines.
The median follow-up was 7.8 months. Among all 68 spinal segments, there were six fracture events (8.8%) including three new VCFs and three fracture progressions. Observed VCF rates in vertebral segments with prior irradiation or pre-existing compression fracture were 30.0% and 75.0% respectively, compared with 5.2% and 4.7% for segments without prior irradiation or pre-existing compression fracture, respectively (both p < 0.05). The 1-year fracture-free probability was 87.8% (95% CI, 78.2-97.4). On multivariate analysis, prior irradiation (HR, 7.30; 95% CI, 1.31-40.86) and pre-existing compression fracture (HR, 18.45; 95% CI, 3.42-99.52) were independent risk factors for VCF.
The incidence of VCF following conventional RT to the spine is not particularly high, regardless of metastatic tumor involvement. Spines that received irradiation and/or have pre-existing compression fracture before RT have an increased risk of VCF and require close observation.
PMCID: PMC4282996  PMID: 25568850
Spinal neoplasm; Compression fractures; Spinal fractures; Radiotherapy; Colorectal cancer; Risk factors
23.  Prediction of response by FDG PET early during concurrent chemoradiotherapy for locally advanced non-small cell lung cancer 
Radiation Oncology Journal  2014;32(4):231-237.
To evaluate the predictive value of the early response of 18F-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC).
Materials and Methods
FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT.
One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of SUVmax (%ΔSUVmax) were larger in responder group than in non-responder group (55.7% ± 15.6% vs. 23.1% ± 19.0%, p = 0.01). The percent changes of SUVmean (%ΔSUVmean) were also larger in responder group than in non-responder group (54.4% ± 15.9% vs. 22.3% ± 23.0%, p = 0.01). The percent changes of MTV (%ΔMTV) or TLG (%ΔTLG) had no correlation with the tumor response after treatment. All the 7 patients (100%) with %ΔSUVmax ≥ 50% had PR, but only 2 out of 6 patients (33%) with %ΔSUVmax < 50% had PR after CCRT (p = 0.009). Likewise, all the 6 patients (100%) with %ΔSUVmean ≥ 50% had PR, but only 3 out of 7 patients (43%) with %ΔSUVmean < 50% had PR after CCRT (p = 0.026).
The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.
PMCID: PMC4282997  PMID: 25568851
Lung neoplasms; Chemoradiotherapy; Positron-emission tomography; RECIST
24.  Clinical outcome of high-dose-rate interstitial brachytherapy in patients with oral cavity cancer 
Radiation Oncology Journal  2014;32(4):238-246.
To evaluate the clinical outcome of high-dose-rate (HDR) interstitial brachytherapy (IBT) in patients with oral cavity cancer.
Materials and Methods
Sixteen patients with oral cavity cancer treated with HDR remote-control afterloading brachytherapy using 192Ir between 2001 and 2013 were analyzed retrospectively. Brachytherapy was administered in 11 patients as the primary treatment and in five patients as salvage treatment for recurrence after the initial surgery. In 12 patients, external beam radiotherapy (50-55 Gy/25 fractions) was combined with IBT of 21 Gy/7 fractions. In addition, IBT was administered as the sole treatment in three patients with a total dose of 50 Gy/10 fractions and as postoperative adjuvant treatment in one patient with a total of 35 Gy/7 fractions.
The 5-year overall survival of the entire group was 70%. The actuarial local control rate after 3 years was 84%. All five recurrent cases after initial surgery were successfully salvaged using IBT ± external beam radiotherapy. Two patients developed local recurrence at 3 and 5 months, respectively, after IBT. The acute complications were acceptable (≤grade 2). Three patients developed major late complications, such as radio-osteonecrosis, in which one patient was treated by conservative therapy and two required surgical intervention.
HDR IBT for oral cavity cancer was effective and acceptable in diverse clinical settings, such as in the cases of primary or salvage treatment.
PMCID: PMC4282998  PMID: 25568852
Oral cancer; High dose rate; Radiotherapy; Brachytherapy
25.  Is neoadjuvant androgen deprivation therapy beneficial in prostate cancer treated with definitive radiotherapy? 
Radiation Oncology Journal  2014;32(4):247-255.
To determine whether neoadjuvant androgen deprivation therapy (NADT) improves clinical outcomes in patients with prostate cancer treated with definitive radiotherapy.
Materials and Methods
We retrospectively reviewed medical records of 201 patients with prostate cancer treated with radiotherapy between January 1991 and December 2008. Of these, 156 patients with more than 3 years of follow-up were the subjects of this study. The median duration of follow-up was 91.2 months. NADT was given in 103 patients (66%) with median duration of 3.3 months (range, 1.0 to 7.7 months). Radiation dose was escalated gradually from 64 Gy to 81 Gy using intensity-modulated radiotherapy technique.
Biochemical relapse-free survival (BCRFS) and overall survival (OS) of all patients were 72.6% and 90.7% at 5 years, respectively. BCRFS and OS of NADT group were 79.5% and 89.8% at 5 years and those of radiotherapy alone group were 58.8% and 92.3% at 5 years, respectively. Risk group (p = 0.010) and radiation dose ≥70 Gy (p = 0.017) affected BCRFS independently. NADT was a significant prognostic factor in univariate analysis, but not in multivariate analysis (p = 0.073). Radiation dose ≥70 Gy was only an independent factor for OS (p = 0.007; hazard ratio, 0.261; 95% confidence interval, 0.071-0.963).
NADT prior to definitive radiotherapy did not result in significant benefit in terms of BCRFS and OS. NADT should not be performed routinely in the era of dose-escalated radiotherapy.
PMCID: PMC4282999  PMID: 25568853
Prostate cancer; Radiotherapy; Neoadjuvant androgen deprivation; Radiation dose

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