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1.  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
2.  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
3.  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
4.  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
5.  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
6.  In vivo verification of regional hyperthermia in the liver 
Radiation Oncology Journal  2014;32(4):256-261.
We performed invasive thermometry to verify the elevation of local temperature in the liver during hyperthermia.
Materials and Methods
Three 40-kg pigs were used for the experiments. Under general anesthesia with ultrasonography guidance, two glass fiber-optic sensors were placed in the liver, and one was placed in the peritoneal cavity in front of the liver. Another sensor was placed on the skin surface to assess superficial cooling. Six sessions of hyperthermia were delivered using the Celsius TCS electro-hyperthermia system. The energy delivered was increased from 240 kJ to 507 kJ during the 60-minute sessions. The inter-session cooling periods were at least 30 minutes. The temperature was recorded every 5 minutes by the four sensors during hyperthermia, and the increased temperatures recorded during the consecutive sessions were analyzed.
As the animals were anesthetized, the baseline temperature at the start of each session decreased by 1.3℃ to 2.8℃ (median, 2.1℃). The mean increases in temperature measured by the intrahepatic sensors were 2.42℃ (95% confidence interval [CI], 1.70-3.13) and 2.67℃ (95% CI, 2.05-3.28) during the fifth and sixth sessions, respectively. The corresponding values for the intraperitoneal sensor were 2.10℃ (95% CI, 0.71-3.49) and 2.87℃ (1.13-4.43), respectively. Conversely, the skin temperature was not increased but rather decreased according to application of the cooling system.
We observed mean 2.67℃ and 2.87℃ increases in temperature at the liver and peritoneal cavity, respectively, during hyperthermia. In vivo real-time thermometry is useful for directly measuring internal temperature during hyperthermia.
PMCID: PMC4283000  PMID: 25568854
Hyperthermia; Thermometry; Radiation therapy; Liver
7.  Radiation recall dermatitis induced by tamoxifen during adjuvant breast cancer treatment 
Radiation Oncology Journal  2014;32(4):262-265.
Tamoxifen and radiotherapy are used in breast cancer treatment worldwide. Radiation recall dermatitis (RRD), induced by tamoxifen, has been rarely reported. Herein, we report a RRD case induced by tamoxifen. A 47-year-old woman had a right quadrantectomy and an axillary lymph node dissection due to breast cancer. The tumor was staged pT2N0; it was hormone receptor positive, and human epidermal growth factor receptor 2 negative. The patient received adjuvant chemotherapy followed by tamoxifen and radiotherapy. After 22 months of tamoxifen, the patient developed a localized heating sensation, tenderness, edema, and redness at the irradiated area of the right breast. The symptoms improved within 1 week without treatment. Three weeks later, however, the patient developed similar symptoms in the same area of the breast. She continued tamoxifen before and during dermatitis, and symptoms resolved within 1 week.
PMCID: PMC4283001  PMID: 25568855
Tamoxifen; Radiation recall dermatitis; Treatment
8.  An 87-year-old patient with repeated oligorecurrences over six years whose disease were treated with radiotherapy alone 
Radiation Oncology Journal  2014;32(4):266-271.
In the clinical state of oligometastases or oligorecurrence, a transitional state between localized and widespread systemic disease, local control of the disease may yield improved systemic control. Radiotherapy may be a good means for controlling oligometastatic tumors, particularly in very old patients for whom surgery may be infeasible. A combination of systemic therapy and local therapy is necessary to prevent systemic progression. Some kinds of cancers found in the elderly are known to be somewhat indolent for systemic progression. So, for very old patients who refuse or cannot tolerate chemotherapy, the use of radical radiotherapy alone to treat oligorecurrences may be very helpful. We successfully treated an 87-year-old patient who had been diagnosed with oligorecurrences three times over six years with radiotherapy alone. The patient is now, about four years after his first radiotherapy for liver metastasis, alive without any evidence of cancer and with fully active performance status.
PMCID: PMC4283002  PMID: 25568856
Oligorecurrence; Oligometastases; Radiotherapy
9.  Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials 
Radiation Oncology Journal  2014;32(3):103-115.
To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.
PMCID: PMC4194292  PMID: 25324981
Radiation normal tissue injury; Protectors; Mitigators
10.  Fate of pulmonary nodules detected by computer-aided diagnosis and physician review on the computed tomography simulation images for hepatocellular carcinoma 
Radiation Oncology Journal  2014;32(3):116-124.
To investigate the frequency and clinical significance of detected incidental lung nodules found on computed tomography (CT) simulation images for hepatocellular carcinoma (HCC) using computer-aided diagnosis (CAD) and a physician review.
Materials and Methods
Sixty-seven treatment-naïve HCC patients treated with transcatheter arterial chemoembolization and radiotherapy (RT) were included for the study. Portal phase of simulation CT images was used for CAD analysis and a physician review for lung nodule detection. For automated nodule detection, a commercially available CAD system was used. To assess the performance of lung nodule detection for lung metastasis, the sensitivity, negative predictive value (NPV), and positive predictive value (PPV) were calculated.
Forty-six patients had incidental nodules detected by CAD with a total of 109 nodules. Only 20 (18.3%) nodules were considered to be significant nodules by a physician review. The number of significant nodules detected by both of CAD or a physician review was 24 in 9 patients. Lung metastases developed in 11 of 46 patients who had any type of nodule. The sensitivities were 58.3% and 100% based on patient number and on the number of nodules, respectively. The NPVs were 91.4% and 100%, respectively. And the PPVs were 77.8% and 91.7%, respectively.
Incidental detection of metastatic nodules was not an uncommon event. From our study, CAD could be applied to CT simulation images allowing for an increase in detection of metastatic nodules.
PMCID: PMC4194293  PMID: 25324982
Computer-assisted diagnosis; Radiotherapy; Hepatocellular carcinoma
11.  Postoperative radiotherapy in salivary ductal carcinoma: a single institution experience 
Radiation Oncology Journal  2014;32(3):125-131.
We reviewed treatment outcomes and prognostic factors for patients with salivary ductal carcinoma (SDC) treated with surgery and postoperative radiotherapy from 2005 to 2012.
Materials and Methods
A total of 16 patients were identified and 15 eligible patients were included in analysis. Median age was 61 years (range, 40 to 71 years) and 12 patients (80%) were men. Twelve patients (80%) had a tumor in the parotid gland, 9 (60%) had T3 or T4 disease, and 9 (60%) had positive nodal disease. All patients underwent surgery and postoperative radiotherapy. Postoperative radiotherapy was delivered using 3-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Locoregional failure-free survival (LRFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Differences in survival based on risk factors were tested using a log-rank test.
Median total radiotherapy dose was 60 Gy (range, 52.5 to 63.6 Gy). Four patients received concurrent weekly chemotherapy with cisplatin. Among 10 patients who underwent surgery with neck dissection, 7 received modified radical neck dissection. With a median follow-up time of 38 months (range, 24 to 105 months), 4-year rates were 86% for LRFFS, 51% for DFFS, 46% for PFS, and 93% for OS. Local failure was observed in 2 patients (13%), and distant failure was observed in 7 (47%). The lung was the most common involved site of distant metastasis.
Surgery and postoperative radiotherapy in SDC patients resulted in good local control, but high distant metastasis remained a major challenge.
PMCID: PMC4194294  PMID: 25324983
Salivary ducts; Radiotherapy; Carcinoma
12.  Clinical outcomes after sentinel lymph node biopsy in clinically node-negative breast cancer patients 
Radiation Oncology Journal  2014;32(3):132-137.
To evaluate non-sentinel lymph node (LN) status after sentinel lymph node biopsy (SNB) in patients with breast cancer and to identify the predictive factors for disease failure.
Materials and Methods
From January 2006 to December 2007, axillary lymph node (ALN) dissection after SNB was performed for patients with primary invasive breast cancer who had no clinical evidence of LN metastasis. A total of 320 patients were treated with breast-conserving surgery and radiotherapy.
The median age of patients was 48 years, and the median follow-up time was 72.8 months. Close resection margin (RM) was observed in 13 patients. The median number of dissected SNB was two, and that of total retrieved ALNs was 11. Sentinel node accuracy was 94.7%, and the overall false negative rate (FNR) was 5.3%. Eleven patients experienced treatment failure. Local recurrence, regional LN recurrence, and distant metastasis were identified in 0.9%, 1.9%, and 2.8% of these patients, respectively. Sentinel LN status were not associated with locoregional recurrence (p > 0.05). Close RM was the only significant factor for disease-free survival (DFS) in univariate and multivariate analysis. The 5-year overall survival, DFS, and locoregional DFS were 100%, 96.8%, and 98.1%, respectively.
In this study, SNB was performed with high accuracy and low FNR and high locoregional control was achieved.
PMCID: PMC4194295  PMID: 25324984
Breast neoplasms; Sentinel lymph node biopsy; Axillary lymph node dissection; Neoplasm recurrence; Local
13.  Outcome of postoperative radiotherapy following radical prostatectomy: a single institutional experience 
Radiation Oncology Journal  2014;32(3):138-146.
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.
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.
The biochemical and toxicity outcome of post-radical prostatectomy radiotherapy in our institution is favorable and comparable to those of other studies.
PMCID: PMC4194296  PMID: 25324985
Prostatic neoplasmsr; Radiation; Prostatectomy; Androgen deprivation therapy
14.  The single institutional outcome of postoperative radiotherapy and concurrent chemoradiotherapy in resected non-small cell lung cancer 
Radiation Oncology Journal  2014;32(3):147-155.
This study was conducted to observe the outcomes of postoperative radiotherapy (PORT) with or without concurrent chemotherapy in resected non-small cell lung cancer (NSCLC) in single institution.
Materials and Methods
From 2002 to 2013, 78 patients diagnosed with NSCLC after curative resection were treated with radiotherapy alone (RT, n = 48) or concurrent chemoradiation (CCRT, n = 30). The indications of adjuvant radiation therapy were N2 node positive (n = 31), close or involved resection margin (n = 28), or gross residual disease due to incomplete resection (n = 19). The median radiation dose was 57.6 Gy (range, 29.9 to 66 Gy).
Median survival time was 33.7 months (range, 4.4 to 140.3 months). The 5-year overall survival (OS) rate was 49.5% (RT 46% vs. CCRT 55.2%; p = 0.731). The 3-year disease-free survival rate was 45.5% (RT 39.4% vs. CCRT 55.3%; p = 0.130). The 3-year local control rate was 68.1% (RT 64.4% vs. CCRT 77.7%; p = 0.165). The 3-year DMFS rate was 56.1% (RT 52.6% vs. CCRT 61.7%; p = 0.314). In multivariate analysis, age ≥66 years and pathologic stage III were significant poor prognostic factors for OS. Treatment failure occurred in 40 patients. Four patients had radiologically confirmed grade 3 radiation pneumonitis.
In NSCLC, adjuvant RT or CCRT after curative surgery is a safe and feasible modality of treatment. OS gain was seen in patients less than 66 years. Postoperative CCRT showed a propensity of achieving better local control and improved disease-free survival compared to RT alone according to our data.
PMCID: PMC4194297  PMID: 25324986
Non-small-cell lung carcinoma; Radiotherapy; Chemoradiotherapy
15.  The safety and efficacy of EGF-based cream for the prevention of radiotherapy-induced skin injury: results from a multicenter observational study 
Radiation Oncology Journal  2014;32(3):156-162.
This study was designed to evaluate the efficacy and safety of topically applied recombinant human epidermal growth factor (rhEGF) for the prevention of radiation-induced dermatitis in cancer patients.
Materials and Methods
From December 2010 to April 2012, a total of 1,172 cancer patients who received radiotherapy (RT) of more than 50 Gy were prospectively enrolled and treated with EGF-based cream. An acute skin reaction classified according to the Radiation Therapy Oncology Group 6-point rating scale was the primary end point and we also assessed the occurrence of edema, dry skin, or pruritus.
The percentage of radiation dermatitis with maximum grade 0 and grade 1 was 19% and 58% at the time of 50 Gy, and it became 29% and 47% after completion of planned RT. This increment was observed only in breast cancer patients (from 18%/62% to 32%/49%). Adverse events related to the EGF-based cream developed in 49 patients (4%) with mild erythema the most common. Skin toxicity grade >2 was observed in 5% of the patients. Edema, dry skin, and pruritus grade ≥3 developed in 9%, 9%, and 1% of the patients, respectively.
Prophylactic use of an EGF-based cream is effective in preventing radiation dermatitis with tolerable toxicity. Further studies comparing EGF cream with other topical agents may be necessary.
PMCID: PMC4194298  PMID: 25324987
Radiation induced dermatitis; Cancer; Radiotherapy; Dermatitis; Epidermal growth factor
16.  Outcomes of stereotactic body radiotherapy for unresectable primary or recurrent cholangiocarcinoma 
Radiation Oncology Journal  2014;32(3):163-169.
To report the results of stereotactic body radiotherapy (SBRT) for unresectable primary or recurrent cholangiocarcinoma.
Materials and Methods
From January 2005 through August 2013, 58 patients with unresectable primary (n = 28) or recurrent (n = 30) cholangiocarcinoma treated by SBRT were retrospectively analyzed. The median prescribed dose was 45 Gy in 3 fractions (range, 15 to 60 Gy in 1-5 fractions). Patients were treated by SBRT only (n = 53) or EBRT + SBRT boost (n = 5). The median tumor volume was 40 mL (range, 5 to 1,287 mL).
The median follow-up duration was 10 months (range, 1 to 97 months). The 1-year, 2-year overall survival rates, and median survival were 45%, 20%, and 10 months, respectively. The median survival for primary group and recurrent group were 5 and 13 months, respectively. Local control rate at 1-year and 2-year were 85% and 72%, respectively. Disease progression-free survival rates at 1-year and 2-year were 26% and 23%, respectively. In univariate analysis, ECOG performance score (0-1 vs. 2-3), treatment volume (<50 vs. ≥50 mL), and pre-SBRT CEA level (<5 vs. ≥5 ng/mL) were significant in overall survival rate. In multivariate analysis, ECOG score (p = 0.037) and tumor volume (p = 0.030) were statistically significant. In the recurrent tumor group, patients with >12 months interval from surgery to recurrence showed statistically significant higher overall survival rate than those with ≤12 months (p = 0.026). Six patients (10%) experienced ≥grade 3 complications.
SBRT can be considered as an effective local modality for unresectable primary or recurrent cholangiocarcinoma.
PMCID: PMC4194299  PMID: 25324988
Radiosurgery; Cholangiocarcinoma
17.  Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma 
Radiation Oncology Journal  2014;32(3):170-178.
We sought to evaluate the clinical outcomes of 3-dimensional conformal radiation therapy (3D-CRT) for portal vein tumor thrombosis (PVTT) alone in patients with advanced hepatocellular carcinoma.
Materials and Methods
We retrospectively analyzed data on 46 patients who received 3D-CRT for PVTT alone between June 2002 and December 2011. Response was evaluated following the Response Evaluation Criteria in Solid Tumors. Prognostic factors and 1-year survival rates were compared between responders and non-responders.
Thirty-seven patients (80.4%) had category B Child-Pugh scores. The Eastern Cooperative Oncology Group performance status score was 2 in 20 patients. Thirty patients (65.2%) had main or bilateral PVTT. The median irradiation dose was 50 Gy (range, 35 to 60 Gy) and the daily median dose was 2 Gy (range, 2.0 to 2.5 Gy). PVTT response was classified as complete response in 3 patients (6.5%), partial response in 12 (26.1%), stable disease in 19 (41.3%), and progressive disease in 12 (26.1%). There were 2 cases of grade 3 toxicities during or 3 months after radiotherapy. Twelve patients in the responder group (15 patients) received at least 50 Gy irradiation, but about 84% of patients in the non-responder group received less than 50 Gy. The 1-year survival rate was 66.8% in responders and 27.4% in non-responders constituting a statistically significant difference (p = 0.008).
Conformal radiotherapy for PVTT alone could be chosen as a palliative treatment modality in patients with unfavorable conditions (liver, patient, or tumor factors). However, more than 50 Gy of radiation may be required.
PMCID: PMC4194300  PMID: 25324989
Radiotherapy; Hepatocellular carcinoma; Portal vein
18.  Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy 
Radiation Oncology Journal  2014;32(3):179-186.
To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting.
Materials and Methods
The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes.
The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%).
In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.
PMCID: PMC4194301  PMID: 25324990
Dose escalation; Prostate cancer; Radiation therapy; Salvage
19.  Treatment outcome of localized prostate cancer by 70 Gy hypofractionated intensity-modulated radiotherapy with a customized rectal balloon 
Radiation Oncology Journal  2014;32(3):187-197.
We aimed to analyze the treatment outcome and long-term toxicity of 70 Gy hypofractionated intensity-modulated radiotherapy (IMRT) for localized prostate cancer using a customized rectal balloon.
Materials and Methods
We reviewed medical records of 86 prostate cancer patients who received curative radiotherapy between January 2004 and December 2011 at our institution. Patients were designated as low (12.8%), intermediate (20.9%), or high risk (66.3%). Thirty patients received a total dose of 70 Gy in 28 fractions over 5 weeks via IMRT (the Hypo-IMRT group); 56 received 70.2 Gy in 39 fractions over 7 weeks via 3-dimensional conformal radiotherapy (the CF-3DRT group, which served as a reference for comparison). A customized rectal balloon was placed in Hypo-IMRT group throughout the entire radiotherapy course. Androgen deprivation therapy was administered to 47 patients (Hypo-IMRT group, 17; CF-3DRT group, 30). Late genitourinary (GU) and gastrointestinal (GI) toxicity were evaluated according to the Radiation Therapy Oncology Group criteria.
The median follow-up period was 74.4 months (range, 18.8 to 125.9 months). The 5-year actuarial biochemical relapse-free survival rates for low-, intermediate-, and high-risk patients were 100%, 100%, and 88.5%, respectively, for the Hypo-IMRT group and 80%, 77.8%, and 63.6%, respectively, for the CF-3DRT group (p < 0.046). No patient presented with acute or late GU toxicity ≥grade 3. Late grade 3 GI toxicity occurred in 2 patients (3.6%) in the CF-3DRT group and 1 patient (3.3%) in the Hypo-IMRT group.
Hypo-IMRT with a customized rectal balloon resulted in excellent biochemical control rates with minimal toxicity in localized prostate cancer patients.
PMCID: PMC4194302  PMID: 25324991
Prostatic neoplasm; Hypofractionation; Rectal Balloon; Radiotherapy; Intensity modulation
20.  Effects of total body irradiation-based conditioning on allogeneic stem cell transplantation for pediatric acute leukemia: a single-institution study 
Radiation Oncology Journal  2014;32(3):198-207.
To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients.
Materials and Methods
From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes.
The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%).
The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.
PMCID: PMC4194303  PMID: 25324992
Total body irradiation; Acute lymphoid leukemia; Acute myeloid leukemia; Child; Stem cell transplantation
21.  Significant fibrosis after radiation therapy in a patient with Marfan syndrome 
Radiation Oncology Journal  2014;32(3):208-212.
Marfan syndrome is one of the collagen vascular diseases that theoretically predisposes patients to excessive radiation-induced fibrosis yet there is minimal published literature regarding this clinical scenario. We present a patient with a history of Marfan syndrome requiring radiation for a diagnosis of a right brachial plexus malignant nerve sheath tumor. It has been suggested that plasma transforming growth factor beta 1 (TGF-β1) can be monitored as a predictor of subsequent fibrosis in this population of high risk patients. We therefore monitored the patient's TGF-β1 level during and after treatment. Despite maintaining stable levels of plasma TGF-β1, our patient still developed extensive fibrosis resulting in impaired range of motion. Our case reports presents a review of the literature of patients with Marfan syndrome requiring radiation therapy and the limitations of serum markers on predicting long-term toxicity.
PMCID: PMC4194304  PMID: 25324993
Marfan syndrome; Radiation therapy; Transforming growth factor beta1; Fibrosis
22.  Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer 
Radiation Oncology Journal  2014;32(2):49-56.
Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer.
Materials and Methods
Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction.
With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively).
Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.
PMCID: PMC4104219  PMID: 25061572
Pancreatic neoplasms; Chemoradiotherapy; CA19-9 antigen
23.  The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University 
Radiation Oncology Journal  2014;32(2):57-62.
To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.
Materials and Methods
Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities.
Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244).
The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.
PMCID: PMC4104220  PMID: 25061573
Cervical cancer; Radiotherapy; Cumulative dose; Rectum; Toxicity; Association
24.  Patterns of failure and prognostic factors in resected extrahepatic bile duct cancer: implication for adjuvant radiotherapy 
Radiation Oncology Journal  2014;32(2):63-69.
To find the applicability of adjuvant radiotherapy for extrahepatic bile duct cancer (EBDC), we analyzed the pattern of failure and evaluate prognostic factors of locoregional failure after curative resection without adjuvant treatment.
Materials and Methods
In 97 patients with resected EBDC, the location of tumor was classified as proximal (n = 26) and distal (n = 71), using the junction of the cystic duct and common hepatic duct as the dividing point. Locoregional failure sites were categorized as follows: the hepatoduodenal ligament and tumor bed, the celiac artery and superior mesenteric artery, and other sites.
The median follow-up time was 29 months for surviving patients. Three-year locoregional progression-free survival, progression-free survival, and overall survival rates were 50%, 42%, and 52%, respectively. Regarding initial failures, 79% and 81% were locoregional failures in proximal and distal EBDC patients, respectively. The most common site was the hepatoduodenal ligament and tumor bed. In the multivariate analysis, perineural invasion was associated with poor locoregional progression-free survival (p = 0.023) and progression-free survival (p = 0.012); and elevated postoperative CA19-9 (≥37 U/mL) did with poor locoregional progression-free survival (p = 0.002), progression-free survival (p < 0.001) and overall survival (p < 0.001).
Both proximal and distal EBDC showed remarkable proportion of locoregional failure. Perineural invasion and elevated postoperative CA19-9 were risk factors of locoregional failure. In these patients with high risk of locoregional failure, adjuvant radiotherapy could be considered to improve locoregional control.
PMCID: PMC4104221  PMID: 25061574
Bile duct neoplasms; Prognosis; Recurrence; Survival analysis
25.  Postoperative radiation therapy following the incomplete resection of a non-small cell lung cancer 
Radiation Oncology Journal  2014;32(2):70-76.
To review the results of postoperative radiation therapy (PORT) for residual non-small cell lung cancer (NSCLC) following surgical resection and evaluate multiple clinicopathologic prognostic factors.
Materials and Methods
A total of 58 patients, who completed scheduled PORT for positive resection margin, among 658 patients treated with PORT from January 2001 to November 2011 were retrospectively analyzed. Radiation therapy was started at 4 to 6 weeks after surgery. Chemotherapy was also administered to 35 patients, either sequentially or concurrently with PORT.
The median age of patients was 63 years (range, 40 to 82 years). The postoperative pathological stage I NSCLC was diagnosed in 10 (17.2%), stage II in 18 (31.0%), and stage III in 30 patients (51.7%). Squamous cell carcinoma was identified in 43, adenocarcinoma in 10, large cell in 1, others in 4 patients. Microscopic residual disease (R1) was diagnosed in 55 patients (94.8%), and the remaining three patients were diagnosed with gross residual disease (R2). The median dose of PORT was 59.4 Gy (range, 50.0 to 64.8 Gy). Chemotherapy was administered to 35 patients (60%), and the median follow-up time was 22.0 months (range, 6.0 to 84.0 months). The 3-year locoregional relapse-free survival and distant metastasis-free survival rates were 82.1% and 52.9%, respectively. The median overall survival was 23.8 months (range, 6.0 to 84.1 months), and the 3-year overall survival rate was 58.2%. Chemotherapy did not influence the failure pattern or survival outcome.
PORT is an effective modality for improving local tumor control in incompletely resected NSCLC patients. Major failure pattern was distant metastasis despite chemotherapy.
PMCID: PMC4104222  PMID: 25061575
Non-small-cell lung carcinoma; R1 resection; Microscopic residual disease; Postoperative radiotherapy

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