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Year of Publication
1.  Role of radiotherapy in local control of non-AIDS associated Kaposi's sarcoma patients in Korea: a single institution experience 
Radiation Oncology Journal  2012;30(4):153-157.
Purpose
There has been no definite consensus on standard treatment, either local or systemic, for the Kaposi's sarcoma (KS). Radiotherapy (RT) can be a good local therapeutic choice especially in non-AIDS associated KS (NAKS) for its indolent behavior.
Materials and Methods
Medical records of 17 KS patients treated with RT at the Seoul National University Hospital from February 1998 to January 2012 were retrospectively reviewed. One human immunodeficiency virus (HIV)+ patient with 3 lesions was excluded. The total number of the lesion was 23 among the 16 patients. The median follow-up period was 27.9 months. Correlation between response and variables was analyzed using the logistic regression model. Median age of the patients was 75 years. All the 23 lesions were located at the extremities. Fourteen (61%) of those had pain or local swelling as the initial presentation. Ten patients had possible causes of immunodeficiency and were regarded as iatrogenic, and other 6 were classic KS. Median dose of RT was 36 Gy.
Results
No KS-related death was observed. Excluding 2 with short-term follow-up only, complete response and partial response were obtained in 2 (9%) and 19 (73%) lesions, respectively. Of those, 3 lesions underwent local progression. Six had out-of-field recurrence after RT. Symptom improvement was achieved in 13 (93%) of 14 patients. Grade 2 skin toxicities were found in 9 lesions but all got improvement after treatment. When divided into responsive and progressive group, free from progression was not related to any of the possible variables.
Conclusion
RT is effective in local control of NAKS resulting great response rate.
doi:10.3857/roj.2012.30.4.153
PMCID: PMC3546282  PMID: 23346533
Kaposi sarcoma; Radiotherapy; Local control
2.  Postoperative radiotherapy for ependymoma 
Radiation Oncology Journal  2012;30(4):158-164.
Purpose
To evaluated the patterns of failure, survival rate, treatment-related toxicity and prognostic factors in postoperative radiotherapy of patients with ependymoma.
Materials and Methods
Thirty patients who underwent surgery and postoperative radiotherapy for ependymoma between the period of June 1994 and June 2008 were reviewed retrospectively. The age of patients ranged from 21 months to 66 years (median, 19 years). Seventeen patients had grade II ependymoma, and 13 had grade III anaplastic ependymoma according to the World Health Organization grading system. The postoperative irradiation was performed with 4 or 6 MV photon beam with median dose of 52.8 Gy (range, 45 to 63 Gy), and radiation field including 2 cm beyond the preoperative tumor volume. Median follow-up period was 51 months (range, 12 to 172 months).
Results
Fourteen out of 30 (46.7%) patients experienced recurrence, and 12 of those died. Among those 14 patients who experienced recurrence, 11 were in-field and 3 were out-of-field recurrence. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 66.7% and 56.1%, respectively. On univariate analysis, tumor grade was a statistically significant prognostic factor for OS and PFS. There were two complications after surgery and postoperative radiotherapy, including short stature and facial palsy on the left side.
Conclusion
We observed good survival rates, and histologic grade was a prognostic factor affecting the OS and PFS. Almost all recurrence occurred in primary tumor site, thus we suggest further evaluation on intensity-modulated radiotherapy or stereotatic radiosurgery for high-risk patients such as who have anaplastic ependymoma.
doi:10.3857/roj.2012.30.4.158
PMCID: PMC3546283  PMID: 23346534
Ependymoma; Anaplastic ependymoma; Radiotherapy; Histologic grade; Stereotatic radiosurgery
3.  Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia 
Radiation Oncology Journal  2012;30(4):165-172.
Purpose
To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused.
Materials and Methods
Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate.
Results
With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT.
Conclusion
In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.
doi:10.3857/roj.2012.30.4.165
PMCID: PMC3546284  PMID: 23346535
Aplastic anemia; Total lymphoid irradiation; Hematopoietic stem cell transplantation
4.  Prognostic value of 18F-fluorodeoxyglucose positron emission tomography, computed tomography and magnetic resonance imaging in oral cavity squamous cell carcinoma with pathologically positive neck lymph node 
Radiation Oncology Journal  2012;30(4):173-181.
Purpose
To evaluate the prognostic value of preoperative neck lymph node (LN) assessment with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), computed tomography (CT), and magnetic resonance imaging (MRI) in oral cavity squamous cell carcinoma (OSCC) patients with pathologically positive LN.
Materials and Methods
In total, 47 OSCC patients with pathologically positive LN were retrospectively reviewed with preoperative 18F-FDG PET and CT/MRI. All patients underwent surgical resection, neck dissection and postoperative adjuvant radiotherapy and/or chemotherapy between March 2002 and October 2010. Histologic correlation was performed for findings of 18F-FDG PET and CT/MRI.
Results
Thirty-six (76.6%) of 47 cases were correctly diagnosed with neck LN metastasis by 18F-FDG PET and 32 (68.1%) of 47 cases were correctly diagnosed by CT/MRI. Follow-up ranged from 20 to 114 months (median, 56 months). Clinically negative nodal status evaluated by 18F-FDG PET or CT/MRI revealed a trend toward better clinical outcomes in terms of overall survival, disease-free survival, local recurrence-free survival, regional nodal recurrence-free survival, and distant metastasis-free survival rates even though the trends were not statistically significant. However, there was no impact of neck node standardized uptake value (SUVmax) on clinical outcomes. Notably, SUVmax showed significant correlation with tumor size in LN (p < 0.01, R2 = 0.62). PET and CT/MRI status of LN also had significant correlation with the size of intranodal tumor deposit (p < 0.05, R2 = 0.37 and p < 0.01, R2 = 0.48, respectively).
Conclusion
18F-FDG PET and CT/MRI at the neck LNs might improve risk stratification in OSCC patients with pathologically positive neck LN in this study, even without significant prognostic value of SUVmax.
doi:10.3857/roj.2012.30.4.173
PMCID: PMC3546285  PMID: 23346536
Oral cavity squamous cell carcinoma; Neck lymph node; Magnetic resonance imaging; X-ray computed tomography; 18F-FDG PET; Prognostic value
5.  Re-irradiation of recurrent esophageal cancer after primary definitive radiotherapy 
Radiation Oncology Journal  2012;30(4):182-188.
Purpose
For recurrent esophageal cancer after primary definitive radiotherapy, no general treatment guidelines are available. We evaluated the toxicities and clinical outcomes of re-irradiation (re-RT) for recurrent esophageal cancer.
Materials and Methods
We analyzed 10 patients with recurrent esophageal cancer treated with re-RT after primary definitive radiotherapy. The median time interval between primary radiotherapy and re-RT was 15.6 months (range, 4.8 to 36.4 months). The total dose of primary radiotherapy was a median of 50.4 Gy (range, 50.4 to 63.0 Gy). The total dose of re-RT was a median of 46.5 Gy (range, 44.0 to 50.4 Gy).
Results
The median follow-up period was 4.9 months (range, 2.6 to 11.4 months). The tumor response at 3 months after the end of re-RT was complete response (n = 2), partial response (n = 1), stable disease (n = 2), and progressive disease (n = 5). Grade 5 tracheoesophageal fistula developed in three patients. The time interval between primary radiotherapy and re-RT was less than 12 months in two of these three patients. Late toxicities included grade 1 dysphagia (n = 1).
Conclusion
Re-RT of recurrent esophageal cancer after primary radiotherapy can cause severe toxicity.
doi:10.3857/roj.2012.30.4.182
PMCID: PMC3546286  PMID: 23346537
Esophageal cancer; Neoplasm recurrence; Re-irradiation; Radiotherapy; Chemotherapy; Toxicity
6.  Changes of the liver volume and the Child-Pugh score after high dose hypofractionated radiotherapy in patients with small hepatocellular carcinoma 
Radiation Oncology Journal  2012;30(4):189-196.
Purpose
To investigate the safety of high dose hypofractionated radiotherapy (RT) in patients with small hepatocellular carcinoma (HCC) in terms of liver volumetric changes and clinical liver function.
Materials and Methods
We retrospectively reviewed 16 patients with small HCC who were treated with high dose hypofractionated RT between 2006 and 2009. The serial changes of the liver volumetric parameter were analyzed from pre-RT and follow-up (FU) computed tomography (CT) scans. We estimated linear time trends of whole liver volume using a linear mixed model. The serial changes of the Child-Pugh (CP) scores were also analyzed in relation to the volumetric changes.
Results
Mean pre-RT volume of entire liver was 1,192.2 mL (range, 502.6 to 1,310.2 mL) and mean clinical target volume was 14.7 mL (range, 1.56 to 70.07 mL). Fourteen (87.5%) patients had 4 FU CT sets and 2 (12.5%) patients had 3 FU CT sets. Mean interval between FU CT acquisition was 2.5 months. After considering age, gender and the irradiated liver volume as a fixed effects, the mixed model analysis confirmed that the change in liver volume is not significant throughout the time course of FU periods. Majority of patients had a CP score change less than 2 except in 1 patient who had CP score change more than 3.
Conclusion
The high dose hypofractionated RT for small HCC is relatively safe and feasible in terms of liver volumetric changes and clinical liver function.
doi:10.3857/roj.2012.30.4.189
PMCID: PMC3546287  PMID: 23346538
Radiotherapy; Hepatocellular carcinoma
7.  Molecular biomarkers in extrahepatic bile duct cancer patients undergoing chemoradiotherapy for gross residual disease after surgery 
Radiation Oncology Journal  2012;30(4):197-204.
Purpose
To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers.
Materials and Methods
Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and β-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated.
Results
At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and β-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes.
Conclusion
There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and β-catenin. Future research is needed on a larger data set or with other molecular biomarkers.
doi:10.3857/roj.2012.30.4.197
PMCID: PMC3546288  PMID: 23346539
Extrahepatic bile duct cancer; Chemoradiotherapy; Immunohistochemistry; Molecular biomarker
8.  The role of postoperative pelvic radiation in stage IV rectal cancer after resection of primary tumor 
Radiation Oncology Journal  2012;30(4):205-212.
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.
doi:10.3857/roj.2012.30.4.205
PMCID: PMC3546289  PMID: 23346540
Rectal neoplasms; Neoplasm metastasis; Radiotherapy; Local neoplasm recurrence
9.  Postoperative chemoradiotherapy in high risk locally advanced gastric cancer 
Radiation Oncology Journal  2012;30(4):213-217.
Purpose
To evaluate treatment outcome of patients with high risk locally advanced gastric cancer after postoperative chemoradiotherapy.
Materials and Methods
Between May 2003 and May 2012, thirteen patients who underwent postoperative chemoradiotherapy for gastric cancer with resection margin involvement or adjacent structure invasion were retrospectively analyzed. Concurrent chemotherapy was administered in 10 patients. Median dose of radiation was 50.4 Gy (range, 45 to 55.8 Gy).
Results
The median follow-up duration for surviving patients was 48 months (range, 5 to 108 months). The 5-year overall survival rate was 42% and the 5-year disease-free survival rate was 28%. Major pattern of failure was peritoneal seeding with 46%. Locoregional recurrence was reported in only one patient. Grade 2 or higher gastrointestinal toxicity occurred in 54% of the patients. However, there was only one patient with higher than grade 3 toxicity.
Conclusion
Despite reported suggested role of adjuvant radiotherapy with combination chemotherapy in gastric cancer, only very small portion of the patients underwent the treatment. Results from this study show that postoperative chemoradiotherapy provided excellent locoregional control with acceptable and manageable treatment related toxicity in patients with high risk locally advanced gastric cancer. Thus, postoperative chemoradiotherapy may improve treatment result in terms of locoregional control in these high risk patients. However, as these findings are based on small series, validation with larger cohort is suggested.
doi:10.3857/roj.2012.30.4.213
PMCID: PMC3546290  PMID: 23346541
Stomach neoplasm; Adjuvant chemoradiotherapy; Neoplasm recurrence; Local
10.  Prognostic implications of tumor volume response and COX-2 expression change during radiotherapy in cervical cancer patients 
Radiation Oncology Journal  2012;30(4):218-225.
Purpose
The relationship between treatment outcomes, alteration of the expression of biological markers, and tumor volume response during radiotherapy (RT) in patients with uterine cervical cancer was analyzed.
Materials and Methods
Twenty patients with cervical squamous cell carcinoma received definitive RT with (n = 17) or without (n = 3) concurrent chemotherapy. Tumor volumes were measured by three serial magnetic resonance imaging scans at pre-, mid-, and post-RT. Two serial punch biopsies were performed at pre- and mid-RT, and immunohistochemical staining for cyclooxygenase (COX)-2 and epidermal growth factor receptor was performed. The median follow-up duration was 60 months.
Results
The median tumor volume response at mid-RT (V2R) was 0.396 (range, 0.136 to 0.983). At mid-RT, an interval increase in the distribution of immunoreactivity for COX-2 was observed in 8 patients, and 6 of them showed poor mid-RT tumor volume response (V2R ≥ 0.4). Four (20%) patients experienced disease progression after 10 to 12 months (median, 11 months). All 4 patients had poor mid-RT tumor volume response (p = 0.0867) and 3 of them had an interval increase in COX-2 expression. Overall survival (OS) and progression-free survival (PFS) decreased in patients with V2R ≥ 0.4 (p = 0.0291 for both). An interval increase in COX-2 expression at mid-RT was also associated with a decreased survival (p = 0.1878 and 0.1845 for OS and PFS, respectively).
Conclusion
Poor tumor volume response and an interval increase in COX-2 expression at mid-RT decreased survival outcomes in patients with uterine cervical cancer.
doi:10.3857/roj.2012.30.4.218
PMCID: PMC3546291  PMID: 23346542
Uterine cervical neoplasms; Radiotherapy; Volume response; Cyclooxygenase-2
12.  Postoperative radiotherapy for endometrial cancer 
Radiation Oncology Journal  2012;30(3):108-116.
Purpose
To investigate the prognostic factors and effectiveness of postoperative radiotherapy alone for endometrial carcinoma.
Materials and Methods
Sixty four patients with stage I-III endometrial cancer (EC) treated with postoperative radiotherapy alone between January 1989 and December 2008 at the Keimyung University Dongsan Medical Center were chosen for the present study. Typically, total hysterectomy, salpingo-oophorectomy and lymphadenectomy were performed on the patient's pelvis. Total dose from 50.4 Gy to 63 Gy was irradiated at pelvis or extended field. Thirteen patients were treated with Co-60 or Ir-192 intracavitary radiotherapy. Follow-up periods were from 7 to 270 months, with a median of 56 months.
Results
Five year overall survival (OS) rate was 58.7%, respectively. Five year disease-free survival (DFS) rate was 59.2%, respectively. In univariate analysis for OS and DFS, stage, menopausal age, type of operation, serosal invasion, and lymph node involvement were found to be statistically significant. Histologic type was marginally significant. In multivariate analysis for OS and DFS, stage, types of operation, histologic type were also found to be statistically significant. Treatment failure occurred in 14 patients. The main pattern of failure was found to be distant metastasis. Time to distant metastasis was from 3 to 86 months (median, 12 months). There were no grade 3 or 4 complications.
Conclusion
Stage, types of operation, and histologic type could be the predictive prognostic factors in patients. We contemplated postoperative radiation as effective and safe treatment method for EC. Additional treatment would be needed to reduce distant metastasis.
doi:10.3857/roj.2012.30.3.108
PMCID: PMC3496844  PMID: 23170289
Endometrial neoplasm; Postoperative procedures; Adjuvant radiotherapy; Prognosis; Menopause
13.  Negative impact of pretreatment anemia on local control after neoadjuvant chemoradiotherapy and surgery for rectal cancer 
Radiation Oncology Journal  2012;30(3):117-123.
Purpose
Although anemia is considered to be a contributor to intra-tumoral hypoxia and tumor resistance to ionizing radiation in cancer patients, the impact of pretreatment anemia on local control after neoadjuvant concurrent chemoradiotherapy (NACRT) and surgery for rectal cancer remains unclear.
Materials and Methods
We reviewed the records of 247 patients with locally advanced rectal cancer who were treated with NACRT followed by curative-intent surgery.
Results
The patients with anemia before NACRT (36.0%, 89/247) achieved less pathologic complete response (pCR) than those without anemia (p = 0.012). The patients with pretreatment anemia had worse 3-year local control than those without pretreatment anemia (86.0% vs. 95.7%, p = 0.005). Multivariate analysis showed that pretreatment anemia (p = 0.035), pathologic tumor and nodal stage (p = 0.020 and 0.032, respectively) were independently significant factors for local control.
Conclusion
Pretreatment anemia had negative impacts on pCR and local control among patients who underwent NACRT and surgery for rectal cancer. Strategies maintaining hemoglobin level within normal range could potentially be used to improve local control in rectal cancer patients.
doi:10.3857/roj.2012.30.3.117
PMCID: PMC3496845  PMID: 23170290
Anemia; Rectal cancer; Neoadjuvant therapy; Concurrent chemoradiotherapy
14.  Treatment outcome in patients with triple negative early stage breast cancers compared with other molecular subtypes 
Radiation Oncology Journal  2012;30(3):124-131.
Purpose
To determine whether triple negative (TN) early stage breast cancers have poorer survival rates compared with other molecular types.
Materials and Methods
Between August 2000 and July 2006, patients diagnosed with stage I, II early stage breast cancers, in whom all three markers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor [HER]-2) were available and treated with modified radical mastectomy or breast conserving surgery followed by radiotherapy, were retrospectively reviewed.
Results
Of 446 patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295 (66.1%) as luminal. TN was more frequently associated with young patients younger than 35 years old (p = 0.002), higher histologic grade (p < 0.0001), and nuclear (p < 0.0001). The median follow-up period was 78 months (range, 4 to 130 months). There were 9 local relapses (2.0%), 15 nodal (3.4%), 40 distant metastases (9.0%), and 33 deaths (7.4%) for all patients. The rates of 5-year OS, DFS, LFS, and DMFS for all patients were 95.5%, 89.9%, 95.4%, and 91.7%, respectively. There were no significant differences in OS, DFS, LFS, and DMFS between triple negative and other subtypes (p > 0.05).
Conclusion
We found that patients with TN early stage breast cancers had no difference in survival rates compared with other molecular subtypes. Prospective study in homogeneous treatment group will need for a prognosis of TN early stage breast cancer.
doi:10.3857/roj.2012.30.3.124
PMCID: PMC3496846  PMID: 23170291
Triple negative breast cancer; Early stage; Overall survival; Disease-free survival; Locoregional relapse-free survival; Distant metastasis-free survival
15.  Nutritional status of patients treated with radiotherapy as determined by subjective global assessment 
Radiation Oncology Journal  2012;30(3):132-139.
Purpose
The purpose of this prospective multi-institutional study was to evaluate the nutritional status of patients undergoing radiotherapy (RT) for treatment of head and neck, lung, or gastrointestinal cancer.
Materials and Methods
A total of 1,000 patients were enrolled in this study at seven different hospitals in Seoul, Korea between October 2009 and May 2010. The nutritional status of patients after receiving 3 weeks of RT was evaluated using subjective global assessment (SGA). The nutritional status of each patient was rated as well nourished (A), moderately malnourished (B), or severely malnourished (C).
Results
The mean age of patients in this study was 59.4 ± 11.9 years, and the male to female ratio was 7:3. According to the SGA results, 60.8%, 34.5%, and 4.7% of patients were classified as A, B, or C, respectively. The following criteria were significantly associated with malnutrition (SGA B or C; p < 0.001): loss of subcutaneous fat or muscle wasting (odds ratio [OR], 11.473); increased metabolic demand/stress (OR, 8.688); ankle, sacral edema, or ascites (OR, 3.234); and weight loss ≥5% (OR, 2.299).
Conclusion
SGA was applied successfully to assess the nutritional status of most patients. The prevalence of malnutrition in a radiation oncology department was 39.2%. The results of this study serve as a basis for implementation of nutrition intervention to patients being treated at radiation oncology departments.
doi:10.3857/roj.2012.30.3.132
PMCID: PMC3496847  PMID: 23170292
Malnutrition; Nutrition assessment; Subjective global assessment; Radiotherapy
16.  Concurrent chemoradiotherapy for elderly patients with stage III non-small cell lung cancer 
Radiation Oncology Journal  2012;30(3):140-145.
Purpose
Combined chemoradiotherapy is standard management for locally advanced non-small cell lung cancer (LA-NSCLC), but standard treatment for elderly patients with LA-NSCLC has not been confirmed yet. We evaluated the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for elderly patients with LA-NSCLC.
Materials and Methods
Among patients older than 65 years with LA-NSCLC, 36 patients, who underwent CCRT were retrospectively analyzed. Chemotherapy was administered 3-5 times with 4 weeks interval during radiotherapy. Thoracic radiotherapy was delivered to the primary mass and regional lymph nodes. Total dose of 54-59.4 Gy (median, 59.4 Gy) in daily 1.8 Gy fractions and 5 fractions per week.
Results
Regarding the response to treatment, complete response, partial response, and no response were shown in 16.7%, 66.7%, and 13.9%, respectively. The 1- and 2-year overall survival (OS) rates were 58.2% and 31.2%, respectively, and the median survival was 15 months. The 1- and 2-year progression-free survivals (PFS) were 41.2% and 19.5%, respectively, and the median PFS was 10 months. Regarding to the toxicity developed after CCRT, pneumonitis and esophagitis with grade 3 or higher were observed in 13.9% (5 patients) and 11.1% (4 patients), respectively. Treatment-related death was not observed.
Conclusion
The treatment-related toxicity as esophagitis and pneumonitis were noticeably lower when was compared with the previously reported results, and the survival rate was higher than radiotherapy alone. The results indicate that CCRT is an effective in terms of survival and treatment related toxicity for elderly patients over 65 years old with LA-NSCLC.
doi:10.3857/roj.2012.30.3.140
PMCID: PMC3496848  PMID: 23170293
Concurrent chemoradiotherapy; Locally advanced; Non-small-cell lung carcinoma; Old age
17.  The impact of beam angle configuration of intensity-modulated radiotherapy in the hepatocellular carcinoma 
Radiation Oncology Journal  2012;30(3):146-151.
Purpose
This treatment planning study was undertaken to evaluate the impact of beam angle configuration of intensity-modulated radiotherapy (IMRT) on the dose of the normal liver in hepatocellular carcinoma (HCC).
Materials and Methods
The computed tomography datasets of 25 patients treated with IMRT for HCC were selected. Two IMRT plans using five beams were made in each patient; beams with equidistance of 72° (Plan I), and beams with a 30° angle of separation entering the body near the tumor (Plan II). Both plans were generated using the same constraints in each patient. Conformity index (CI), homogeneity index (HI), gamma index, mean dose of the normal liver (Dmean_NL), Dmean_NL difference between the two plans, and percentage normal liver volumes receiving at least 10, 20, and 30 Gy (V10, V20, and V30) were evaluated and compared.
Results
Dmean_NL, V10, and V20 were significantly better for Plan II. The Dmean_NL was significantly lower for peripheral (p = 0.001) and central tumors (p = 0.034). Dmean_NL differences between the two plans increased in proportion to gross tumor volume to normal liver volume ratios (p = 0.002). CI, HI, and gamma indices were not significantly different for the two plans.
Conclusion
The IMRT plan based on beams with narrow separations reduced the irradiated dose of the normal liver, which would allow radiation dose escalation for HCC.
doi:10.3857/roj.2012.30.3.146
PMCID: PMC3496849  PMID: 23170294
Hepatocellular carcinoma; Intensity modulated radiation therapy; Radiation therapy
18.  Clinical predictive factors of pathologic tumor response after preoperative chemoradiotherapy in rectal cancer 
Radiation Oncology Journal  2012;30(3):99-107.
Purpose
The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer.
Materials and Methods
The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used (5-fluorouracil and leucovorin, capecitabine, or tegafur/uracil). Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response.
Results
Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR.
Conclusion
Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.
doi:10.3857/roj.2012.30.3.99
PMCID: PMC3496850  PMID: 23170288
Rectal cancer; Preoperative chemoradiotherapy; Predictive factors; Tumor response
19.  Therapeutic results and safety of postoperative radiotherapy for keloid after repeated Cesarean section in immediate postpartum period 
Radiation Oncology Journal  2012;30(2):49-52.
Purpose
To evaluate the effectiveness and safety of postoperative radiotherapy for the treatment of keloid scars administered immediately after Cesarean section.
Materials and Methods
A total of 26 postpartum patients with confirmed keloids resulting from previous Cesarean sections received either 12 or 15 Gy radiotherapy. The radiotherapy was divided into three 6 MeV electron beam fractions administered during the postpartum period immediately following the final Cesarean section. To evaluate ovarian safety, designated doses of radiation were estimated at the calculated depth of the ovaries using a solid plate phantom and an ionization chamber with the same lead cutout as was used for the treatment of Cesarean section operative scars and a tissue equivalent bolus.
Results
In total, the control rate was 77% (20 patients), while six (23%) developed focally elevated keloids (ranging from 0.5 to 2 cm in length) in the middle of the primary abdominal scar. Five patients experienced mild hyperpigmentation. Nonetheless, most patients (96%) were satisfied with the treatment results. The estimated percentage of the applied radiation doses that reached the calculated depth of the ovaries ranged from 0.0033% to 0.0062%.
Conclusion
When administered during the immediate postpartum period, postoperative electron beam radiotherapy for repeated Cesarean section scars is generally safe and produces good cosmetic results with minimal toxicity.
doi:10.3857/roj.2012.30.2.49
PMCID: PMC3429888  PMID: 22984682
Keloid; Radiotherapy; Cesarean section; Ovary
20.  Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases 
Radiation Oncology Journal  2012;30(2):53-61.
Purpose
To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases.
Materials and Methods
Nine patients with multiple (≥4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10-12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions.
Results
The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively.
Conclusion
RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.
doi:10.3857/roj.2012.30.2.53
PMCID: PMC3429889  PMID: 22984683
Multiple brain metastases; Poor prognostic; RapidArc; Volumetric modulated arc therapy
21.  Treatment outcome of conservative surgery plus postoperative radiotherapy for extremity soft tissue sarcoma 
Radiation Oncology Journal  2012;30(2):62-69.
Purpose
To evaluate the treatment outcome and prognostic factor of postoperative radiotherapy for extremity soft tissue sarcoma (STS).
Materials and Methods
Forty three patients with extremity STS were treated with conservative surgery and postoperative radiotherapy from January 1981 to December 2010 at Korea University Medical Center. Median total 60 Gy (range, 50 to 74.4 Gy) of radiation was delivered and 7 patients were treated with chemotherapy.
Results
The median follow-up period was 70 months (range, 5 to 302 months). Twelve patients (27.9%) sustained relapse of their disease. Local recurrence occurred in 3 patients (7.0%) and distant metastases developed in 10 patients (23.3%). The 5-year overall survival (OS) was 69.2% and disease free survival was 67.9%. The 5-year local relapse-free survival was 90.7% and distant relapse-free survival was 73.3%. On univariate analysis, no significant prognostic factors were associated with development of local recurrence. Histologic grade (p = 0.005) and stage (p = 0.02) influenced the development of distant metastases. Histologic grade was unique significant prognostic factor for the OS on univariate and multivariate analysis. Severe acute treatment-related complications, Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4, developed in 6 patients (14.0%) and severe late complications in 2 patients (4.7%).
Conclusion
Conservative surgery with postoperative radiotherapy achieved a satisfactory rate of local control with acceptable complication rate in extremity STS. Most failures were distant metastases that correlate with tumor grade and stage. The majority of local recurrences developed within the field. Selective dose escalation of radiotherapy or development of effective systemic treatment might be considered.
doi:10.3857/roj.2012.30.2.62
PMCID: PMC3429890  PMID: 22984684
Sarcoma; Extremity; Radiotherapy; Postoperative; Treatment outcome
22.  Method of tumor volume evaluation using magnetic resonance imaging for outcome prediction in cervical cancer treated with concurrent chemotherapy and radiotherapy 
Radiation Oncology Journal  2012;30(2):70-77.
Purpose
To evaluate the patterns of tumor shape and to compare tumor volume derived from simple diameter-based ellipsoid measurement with that derived from tracing the entire tumor contour using region of interest (ROI)-based 3D volumetry with respect to the prediction outcome in cervical cancer patients treated with concurrent chemotherapy and radiotherapy.
Materials and Methods
Magnetic resonance imaging was performed in 98 patients with cervical cancer (stage IB-IIIB). The tumor shape was classified into two categories: ellipsoid and non-ellipsoid shape. ROI-based volumetry was derived from each magnetic resonance slice on the work station. For the diameter-based surrogate "ellipsoid volume," the three orthogonal diameters were measured to calculate volume as an ellipsoid.
Results
The more than half of tumor (55.1%) had a non-ellipsoid configuration. The predictions for outcome were consistent between two volume groups, with overall survival of 93.6% and 87.7% for small tumor (<20 mL), 62.9% and 69.1% for intermediate-size tumor (20-39 mL), and 14.5% and 16.7% for large tumors (≥40 mL) using ROI and diameter based measurement, respectively. Disease-free survival was 93.8% and 90.6% for small tumor, 54.3% and 62.7% for intermediate-size tumor, and 13.7% and 10.3% for large tumor using ROI and diameter based method, respectively. Differences in outcome between size groups were statistically significant, and the differences in outcome predicted by the tumor volume by two different methods.
Conclusion
Our data suggested that large numbers of cervical cancers are not ellipsoid. However, simple diameter-based tumor volume measurement appears to be useful in comparison with ROI-based volumetry for predicting outcome in cervical cancer patients.
doi:10.3857/roj.2012.30.2.70
PMCID: PMC3429891  PMID: 22984685
Cervical cancer; Magnetic resonance imaging; Tumor volume; Concurrent chemotherapy and radiotherapy
23.  Effect of troglitazone on radiation sensitivity in cervix cancer cells 
Radiation Oncology Journal  2012;30(2):78-87.
Purpose
Troglitazone (TRO) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist. TRO has antiproliferative activity on many kinds of cancer cells via G1 arrest. TRO also increases Cu2+/Zn2+-superoxide dismutase (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer cells in vitro.
Materials and Methods
Three human cervix cancer cell lines (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase, and catalase activities were measured at 2-10 µM of TRO for 24 hours. Cell cycle was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate. Cell survival by radiation was measured with clonogenic assay.
Results
By 5 µM TRO for 24 hours, the mRNA, protein expression and activity of catalase were increased in all three cell lines. G0-G1 phase cells were increased in HeLa and Me180 by 5 µM TRO for 24 hours, but those were not increased in SiHa. By pretreatment with 5 µM TRO radiation sensitivity was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2 µM TRO which increased catalase but not increased G0-G1 cells, radiosensitization was not observed. ROS produced by radiation was decreased with TRO.
Conclusion
TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation sensitivity through catalase-mediated ROS scavenging according to TRO dose or cell types. The change of radiation sensitivity by combined with TRO is not dependent on the PPARγ expression level.
doi:10.3857/roj.2012.30.2.78
PMCID: PMC3429892  PMID: 22984686
Troglitazone; Cervix cancer; Cell cycle; Catalase; Reactive oxygen species; Radiation sensitivity
24.  Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor α-mediated superoxide dismutase induction in HeLa cells 
Radiation Oncology Journal  2012;30(2):88-95.
Purpose
The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) α and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF).
Materials and Methods
Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay.
Results
In HeLa cells total SOD activity was increased with increasing FF doses up to 30 µM. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPARα and PPARγ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPARα were not increased with FF. However, the mRNA of PPARγ was increased with FF.
Conclusion
FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPARα.
doi:10.3857/roj.2012.30.2.88
PMCID: PMC3429893  PMID: 22984687
Fenofibrate; Radiation sensitivity; Peroxisome proliferator-activated receptor α; Superoxide dismutase
25.  Erratum: Acknowledgments correction 
Radiation Oncology Journal  2012;30(2):96.
doi:10.3857/roj.2012.30.2.96
PMCID: PMC3429894

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