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1.  Treatment outcome of ductal carcinoma in situ patients treated with postoperative radiation therapy 
Radiation Oncology Journal  2014;32(1):1-6.
To evaluate the outcome of ductal carcinoma in situ (DCIS) patients who underwent surgery followed by radiation therapy (RT).
Materials and Methods
We retrospectively reviewed 106 DCIS patients who underwent surgery followed by postoperative RT between 1994 and 2006. Ninety-four patients underwent breast-conserving surgery, and mastectomy was performed in 12 patients due to extensive DCIS. Postoperative RT was delivered to whole breast with 50.4 Gy/28 fx. Tumor bed boost was offered to 7 patients (6.6%). Patients with hormonal receptor-positive tumors were treated with hormonal therapy.
The median follow-up duration was 83.4 months (range, 33.4 to 191.5 months) and the median age was 47.8 years. Ten patients (9.4%) had resection margin <1 mm and high-grade and estrogen receptor-negative tumors were observed in 39 (36.8%) and 20 (18.9%) patients, respectively. The 7-year ipsilateral breast tumor recurrence (IBTR)-free survival rate was 95.3%. Resection margin (<1 or ≥1 mm) was the significant prognostic factor for IBTR in univariate and multivariate analyses (p < 0.001 and p = 0.016, respectively).
Postoperative RT for DCIS can achieve favorable treatment outcome. Resection margin was the important prognostic factor for IBTR in the DCIS patients who underwent postoperative RT.
PMCID: PMC3977126  PMID: 24724045
DCIS; Postoperative RT; IBTR
2.  Transcatheter arterial chemoembolization and radiation therapy for treatment-naïve patients with locally advanced hepatocellular carcinoma 
Radiation Oncology Journal  2014;32(1):14-22.
To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-naïve patients with locally advanced hepatocellular carcinoma (HCC).
Materials and Methods
Eligibility criteria were as follows: newly diagnosed with HCC, the Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59 patients were retrospectively enrolled. All patients were treated with TACE followed by RT. The time interval between TACE and RT was 2 weeks as per protocol. A median RT dose was 47.25 Gy10 as the biologically effective dose using the α/β = 10 (range, 39 to 65.25 Gy10).
At 1 month, complete response was obtained in 3 patients (5%), partial response in 27 patients (46%), stable disease in 13 patients (22%), and progressive disease in 16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%, respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4 months). The median time to progression was 4 months (range, 1 to 35 months). Grade 3 or greater liver enzyme elevation occurred in only two patients (3%) after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%).
The combination treatment of TACE followed by RT with two-week interval was safe and it showed favorable outcomes in treatment-naïve patients with locally advanced HCC. A prospective randomized trial is needed to validate these results.
PMCID: PMC3977127  PMID: 24724047
Hepatocellular carcinoma; Transcatheter arterial chemoembolization; Radiotherapy
3.  A predictive model to guide management of the overlap region between target volume and organs at risk in prostate cancer volumetric modulated arc therapy 
Radiation Oncology Journal  2014;32(1):23-30.
The goal of this study is to determine whether the magnitude of overlap between planning target volume (PTV) and rectum (Rectumoverlap) or PTV and bladder (Bladderoverlap) in prostate cancer volumetric-modulated arc therapy (VMAT) is predictive of the dose-volume relationships achieved after optimization, and to identify predictive equations and cutoff values using these overlap volumes beyond which the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) dose-volume constraints are unlikely to be met.
Materials and Methods
Fifty-seven patients with prostate cancer underwent VMAT planning using identical optimization conditions and normalization. The PTV (for the 50.4 Gy primary plan and 30.6 Gy boost plan) included 5 to 10 mm margins around the prostate and seminal vesicles. Pearson correlations, linear regression analyses, and receiver operating characteristic (ROC) curves were used to correlate the percentage overlap with dose-volume parameters.
The percentage Rectumoverlap and Bladderoverlap correlated with sparing of that organ but minimally impacted other dose-volume parameters, predicted the primary plan rectum V45 and bladder V50 with R2 = 0.78 and R2 = 0.83, respectively, and predicted the boost plan rectum V30 and bladder V30 with R2 = 0.53 and R2 = 0.81, respectively. The optimal cutoff value of boost Rectumoverlap to predict rectum V75 >15% was 3.5% (sensitivity 100%, specificity 94%, p < 0.01), and the optimal cutoff value of boost Bladderoverlap to predict bladder V80 >10% was 5.0% (sensitivity 83%, specificity 100%, p < 0.01).
The degree of overlap between PTV and bladder or rectum can be used to accurately guide physicians on the use of interventions to limit the extent of the overlap region prior to optimization.
PMCID: PMC3977128  PMID: 24724048
Prostate cancers; Organs at risk; Radiation injuries; Computer assisted radiotherapy planning; Intensity-modulated radiotherapy
4.  PET/CT planning during chemoradiotherapy for esophageal cancer 
Radiation Oncology Journal  2014;32(1):31-42.
To evaluate the usefulness of positron emission tomography/computed tomography (PET/CT) for field modification during radiotherapy in esophageal cancer.
Materials and Methods
We conducted a retrospective study on 33 patients that underwent chemoradiotherapy (CRT). Pathologic findings were squamous cell carcinoma in 32 patients and adenocarcinoma in 1 patient. All patients underwent PET/CT scans before and during CRT (after receiving 40 Gy and before a 20 Gy boost dose). Response evaluation was determined by PET/CT using metabolic tumor volume (MTV), total glycolytic activity (TGA), MTV ratio (rMTV) and TGA ratio (rTGA), or determined by CT. rMTV and rTGA were reduction ratio of MTV and TGA between before and during CRT, respectively.
Significant decreases in MTV (MTV2.5: mean 70.09%, p < 0.001) and TGA (TGA2.5: mean 79.08%, p<0.001) were found between before and during CRT. Median rMTV2.5 was 0.299 (range, 0 to 0.98) and median rTGA2.5 was 0.209 (range, 0 to 0.92). During CRT, PET/CT detected newly developed distant metastasis in 1 patient, and this resulted in a treatment strategy change. At a median 4 months (range, 0 to 12 months) after completion of CRT, 8 patients (24.2%) achieved clinically complete response, 11 (33.3%) partial response, 5 (15.2%) stable disease, and 9 (27.3%) disease progression. SUVmax (p = 0.029), rMTV50% (p = 0.016), rMTV75% (p = 0.023) on intra-treatment PET were found to correlate with complete clinical response.
PET/CT during CRT can provide additional information useful for radiotherapy planning and offer the potential for tumor response evaluation during CRT. rMTV50% during CRT was found to be a useful predictor of clinical response.
PMCID: PMC3977129  PMID: 24724049
Esophageal cancer; PET/CT; CCRT; Radiotherapy planning
5.  CT-based quantitative evaluation of radiation-induced lung fibrosis: a study of interobserver and intraobserver variations 
Radiation Oncology Journal  2014;32(1):43-47.
The degree of radiation-induced lung fibrosis (RILF) can be measured quantitatively by fibrosis volume (VF) on chest computed tomography (CT) scan. The purpose of this study was to investigate the interobserver and intraobserver variability in CT-based measurement of VF.
Materials and Methods
We selected 10 non-small cell lung cancer patients developed with RILF after postoperative radiation therapy (PORT) and delineated VF on the follow-up chest CT scanned at more than 6 months after radiotherapy. Three radiation oncologists independently delineated VF to investigate the interobserver variability. Three times of delineation of VF was performed by two radiation oncologists for the analysis of intraobserver variability. We analysed the concordance index (CI) and inter/intraclass correlation coefficient (ICC).
The median CI was 0.61 (range, 0.44 to 0.68) for interobserver variability and the median CIs for intraobserver variability were 0.69 (range, 0.65 to 0.79) and 0.61(range, 0.55 to 0.65) by two observers. The ICC for interobserver variability was 0.974 (p < 0.001) and ICCs for intraobserver variability were 0.996 (p < 0.001) and 0.991 (p < 0.001), respectively.
CT-based measurement of VF with patients who received PORT was a highly consistent and reproducible quantitative method between and within observers.
PMCID: PMC3977130  PMID: 24724050
Radiation-induced lung fibrosis; Fibrosis volume; Quantitative CT; Interobserver variation; Intraobserver variation
6.  Postoperative radiotherapy dose correlates with locoregional control in patients with extra-hepatic bile duct cancer 
Radiation Oncology Journal  2014;32(1):7-13.
To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival.
Materials and Methods
Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%).
The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (≥50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively).
In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.
PMCID: PMC3977131  PMID: 24724046
Bile duct neoplasms; Adjuvant radiotherapy; Radiotherapy dosage
7.  Stereotactic body radiotherapy for solitary spine metastasis 
Radiation Oncology Journal  2013;31(4):260-266.
A clear consensus has not been established regarding the best treatment for solitary bone metastasis. Here, we reviewed the medical records of patients with a controlled primary malignancy who had only solitary spine metastasis without metastasis to the extraspinal bone or viscera and underwent treatment between April 2007 and December 2012 with stereotactic body radiosurgery using CyberKnife, with a total dose of 24 Gy in three to four fractions. During that time, there were only four cases. This was effective in each case, and all the four patients had no local failure and remained alive at a median follow-up of 68 months (range, 64 to 80 months). Although our experience is limited, this study suggests that stereotactic body radiotherapy could be a feasible, safe, effective, and noninvasive alternative treatment for solitary spine metastasis in patients who are medically inoperable or unsuitable for surgery.
PMCID: PMC3912242  PMID: 24501716
Stereotactic body radiotherapy; Solitary spine metastasis; Radiation therapy; Local control
8.  Patterns of care and treatment outcomes for primary thyroid lymphoma: a single institution study 
Radiation Oncology Journal  2013;31(4):177-184.
The aim of this study was to analyze the patterns of care and treatment outcomes in patients with primary thyroid lymphoma (PTL) in a single institution.
Materials and Methods
Medical records of 29 patients with PTL treated between April 1994 and February 2012 were retrospectively reviewed. Diagnosis was confirmed by biopsy (n = 17) or thyroidectomy (n = 12). Treatment modality and outcome were analyzed according to lymphoma grade.
The median follow-up was 43.2 months (range, 3.8 to 220.8 months). The median age at diagnosis was 57 years (range, 21 to 83 years) and 24 (82.8%) patients were female. Twenty-five (86.2%) patients had PTL with stage IEA and IIEA. There were 8 (27.6%) patients with mucosa-associated lymphoid tissue (MALT) lymphoma and the remaining patients had high-grade lymphoma. Patients were treated with surgery (n = 2), chemotherapy (n = 7), radiotherapy (n = 3) alone, or a combination of these methods (n = 17). Treatment modalities evolved over time and a combination of modalities was preferred, especially for the treatment of high-grade lymphoma in recent years. There was no death or relapse among MALT lymphoma patients. Among high-grade lymphoma patients, 5-year overall survival (OS) and 5-year progression-free survival (PFS) were 75.6% and 73.9%, respectively. Complete remission after initial treatment was the only significant prognostic factor for OS (p = 0.037) and PFS (p = 0.003).
Patients with PTL showed a favorable outcome, especially with MALT lymphoma. Radiotherapy alone for MALT lymphoma and chemotherapy followed by radiotherapy for high-grade lymphoma can be effective treatment options for PTL.
PMCID: PMC3912230  PMID: 24501704
Thyroid neoplasms; Non-Hodgkin lymphoma; Physician's practice pattern; Treatment outcome
9.  Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer 
Radiation Oncology Journal  2013;31(4):185-190.
We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC).
Materials and Methods
Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks.
The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively.
We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.
PMCID: PMC3912231  PMID: 24501705
Small cell lung carcinoma; Radiotherapy; Chemotherapy
10.  Long-term results of forward intensity-modulated radiation therapy for patients with early-stage breast cancer 
Radiation Oncology Journal  2013;31(4):191-198.
To observe long-term clinical outcomes for patients with early-stage breast cancer treated with forward intensity-modulated radiation therapy (IMRT), including local control and clinical toxicities.
Materials and Methods
We retrospectively analyzed a total of 214 patients with stage I-II breast cancer who were treated with breast conserving surgery followed by adjuvant breast radiation therapy between 2001 and 2008. All patients were treated using forward IMRT. The whole breast was irradiated to a dose of 50 to 50.4 Gy followed by an 8 to 12 Gy electron boost to the surgical bed.
The median age was 46 years (range, 21 to 82 years) and the medial follow-up time was 7.3 years (range, 2.4 to 11.7 years). Stage T1 was 139 (65%) and T2 was 75 (35%), respectively. Ipsilateral breast recurrence was observed in 3 patients. The 5- and 10-year local control rates were 99.1% and 97.8%, respectively. The cosmetic outcome was evaluated according to the Harvard scale and 89.4% of patients were scored as excellent or good.
The whole breast radiation therapy as an adjuvant treatment using a forward IMRT technique showed excellent long-term local control as well as favorable outcomes of toxicity and cosmesis.
PMCID: PMC3912232  PMID: 24501706
Breast neoplasms; Forward intensity modulated radiation therapy; Local control
11.  Whole pelvic intensity-modulated radiotherapy for high-risk prostate cancer: a preliminary report 
Radiation Oncology Journal  2013;31(4):199-205.
To assess the clinical efficacy and toxicity of whole pelvic intensity-modulated radiotherapy (WP-IMRT) for high-risk prostate cancer.
Materials and Methods
Patients with high-risk prostate cancer treated between 2008 and 2013 were reviewed. The study included patients who had undergone WP-IMRT with image guidance using electronic portal imaging devices and/or cone-beam computed tomography. The endorectal balloon was used in 93% of patients. Patients received either 46 Gy to the whole pelvis plus a boost of up to 76 Gy to the prostate in 2 Gy daily fractions, or 44 Gy to the whole pelvis plus a boost of up to 72.6 Gy to the prostate in 2.2 Gy fractions.
The study cohort included 70 patients, of whom 55 (78%) had a Gleason score of 8 to 10 and 50 (71%) had a prostate-specific antigen level > 20 ng/mL. The androgen deprivation therapy was combined in 62 patients. The biochemical failure-free survival rate was 86.7% at 2 years. Acute any grade gastrointestinal (GI) and genitourinary (GU) toxicity rates were 47% and 73%, respectively. The actuarial rate of late grade 2 or worse toxicity at 2 years was 12.9% for GI, and 5.7% for GU with no late grade 4 toxicity.
WP-IMRT was well tolerated with no severe acute or late toxicities, resulting in at least similar biochemical control to that of the historic control group with a small field. The long-term efficacy and toxicity will be assessed in the future, and a prospective randomized trial is needed to verify these findings.
PMCID: PMC3912233  PMID: 24501707
Prostate neoplasms; Intensity-modulated radiotherapy; Complications
12.  Re-irradiation of unresectable recurrent head and neck cancer: using Helical Tomotherapy as image-guided intensity-modulated radiotherapy 
Radiation Oncology Journal  2013;31(4):206-215.
Re-irradiation (re-RT) is considered a treatment option for inoperable locoregionally recurrent head and neck cancer (HNC) after prior radiotherapy. We evaluated the efficacy and safety of re-RT using Helical Tomotherapy as image-guided intensity-modulated radiotherapy in recurrent HNC.
Materials and Methods
Patients diagnosed with recurrent HNC and received re-RT were retrospectively reviewed. Primary endpoint was overall survival (OS) and secondary endpoints were locoregional control and toxicities.
The median follow-up period of total 9 patients was 18.7 months (range, 4.1 to 76 months) and that of 3 alive patients was 49 months (range, 47 to 76 months). Median dose of first radiotherapy and re-RT was 64.8 and 47.5 Gy10. Median cumulative dose of the two courses of radiotherapy was 116.3 Gy10 (range, 91.8 to 128.9 Gy10) while the median interval between the two courses of radiation was 25 months (range, 4 to 137 months). The response rate after re-RT of the evaluated 8 patients was 75% (complete response, 4; partial response, 2). Median locoregional relapse-free survival after re-RT was 11.9 months (range, 3.4 to 75.1 months) and 5 patients eventually presented with treatment failure (in-field failure, 2; in- and out-field failure, 2; out-field failure, 1). Median OS of the 8 patients was 20.3 months (range, 4.1 to 75.1 months). One- and two-year OS rates were 62.5% and 50%, respectively. Grade 3 leucopenia developed in one patient as acute toxicity, and grade 2 osteonecrosis and trismus as chronic toxicity in another patient.
Re-RT using Helical Tomotherapy for previously irradiated patients with unresectable locoregionally recurrent HNC may be a feasible treatment option with long-term survival and acceptable toxicities.
PMCID: PMC3912234  PMID: 24501708
Recurrent head and neck cancer; Re-RT; Helical Tomotherapy; IG-IMRT; Intensity-modulated radiotherapy; Image-guided radiation therapy
13.  Short-course palliative radiotherapy for uterine cervical cancer 
Radiation Oncology Journal  2013;31(4):216-221.
The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer.
Materials and Methods
Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions.
The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity.
Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.
PMCID: PMC3912235  PMID: 24501709
Cervix uteri; Carcinoma; Palliation; Hypofractionation; Radiotherapy
14.  Prognostic factors for survivals from first relapse in breast cancer patients: analysis of deceased patients 
Radiation Oncology Journal  2013;31(4):222-227.
This study was performed to evaluate prognostic factors for survival from first relapse (SFFR) in stage I-III breast cancer patients.
Materials and Methods
From June 1994 to June 2008, 3,835 patients were treated with surgery plus postoperative radiotherapy and adjuvant chemotherapy for stage I-III breast cancer at Samsung Medical Center. Among them, a total of 224 patients died by June 2009, and 175 deaths were of breast cancer. Retrospective review was performed on medical records of 165 patients who met the inclusion criteria of this study. Univariate and multivariate analysis were done on survivals according to variables, such as age, stage, hormone status of tumor, disease-free interval (DFI), sites of first failure, number of organs involved by recurrent disease (NOR), application of salvage treatments, and existence of brain or liver metastasis (visceral metastasis).
Patients' median overall survival time was 38 months (range, 8 to 123 months). Median SFFR was 17 months (range, 5 to 87 months). Ninety percent of deaths occurred within 40 months after first recurrence. The patients with SFFR ≤1 year had tendency of triple-negativity, shorter DFI (≤2 years), larger NOR (>3), visceral metastasis for first relapse than the patients with SFFR >1 year. In multivariate analysis, longer DFI (>2 vs. ≤2 years), absence of visceral metastasis, and application of salvage treatments were statistically significant prognosticators for longer SFFR.
The DFI, application of salvage treatments, and visceral metastasis were significant prognostic factors for SFFR in breast cancer patients.
PMCID: PMC3912236  PMID: 24501710
Survival; Recurrence; Prognosis; Breast neoplasms
15.  Tumor bed volumetric changes during breast irradiation for the patients with breast cancer 
Radiation Oncology Journal  2013;31(4):228-233.
The aim of this study was to evaluate changes in breast tumor bed volume during whole breast irradiation (WBI).
Materials and Methods
From September 2011 to November 2012, thirty patients who underwent breast-conserving surgery (BCS) followed by WBI using computed tomography (CT) simulation were enrolled. Simulation CT scans were performed before WBI (CT1) and five weeks after the breast irradiation (CT2). The tumor bed was contoured based on surgical clips, seroma, and postoperative change. We retrospectively analyzed the factors associated with tumor bed volumetric change.
The median tumor bed volume on CT1 and CT2 was 29.72 and 28.6 mL, respectively. The tumor bed volume increased in 9 of 30 patients (30%) and decreased in 21 of 30 patients (70%). The median percent change in tumor bed volume between initial and boost CT was -5%. Seroma status (p = 0.010) was a significant factor in tumor bed volume reduction of 5% or greater. However, patient age, body mass index, palpability, T stage, axillary lymph node dissection, and tumor location were not significant factors for tumor bed volumetric change.
In this study, volumetric change of tumor bed cavity was frequent. Patients with seroma after BCS had a significant volume reduction of 5% or greater in tumor bed during breast irradiation. Thus, resimulation using CT is indicated for exquisite boost treatment in breast cancer patients with seroma after surgery.
PMCID: PMC3912237  PMID: 24501711
Breast neoplasms; Radiation; Lumpectomy cavity
16.  Esophageal tolerance to high-dose stereotactic radiosurgery 
Radiation Oncology Journal  2013;31(4):234-238.
Esophageal tolerance is needed to guide the safe administration of stereotactic radiosurgery (SRS). We evaluated comprehensive dose-volume parameters of acute esophageal toxicity in patients with spinal metastasis treated with SRS.
Materials and Methods
From May 2008 to May 2011, 30 cases in 27 patients with spinal metastasis received single fraction SRS to targets neighboring esophagus. Endpoints evaluated include length (mm), volume (mL), maximal dose (Gy), and series of dose-volume thresholds from the dose-volume histogram (volume of the organ treated beyond a threshold dose).
The median time from the start of irradiation to development of esophageal toxicity was 2 weeks (range, 1 to 12 weeks). Six events of grade 1 esophageal toxicity occurred. No grade 2 or higher events were observed. V15 of external surface of esophagus was found to predict acute esophageal toxicity revealed by multivariate analysis (odds radio = 1.272, p = 0.047).
In patients with spinal metastasis who received SRS for palliation of symptoms, the threshold dose-volume parameter associated with acute esophageal toxicity was found to be V15 of external surface of esophagus. Restrict V15 to external surface of esophagus as low as possible might be safe and feasible in radiosurgery.
PMCID: PMC3912238  PMID: 24501712
Esophagus; Radiation tolerance; Stereotactic radiosurgery
17.  The deep inspiration breath hold technique using Abches reduces cardiac dose in patients undergoing left-sided breast irradiation 
Radiation Oncology Journal  2013;31(4):239-246.
We explored whether the deep inspiration breath hold (DIBH) technique using Abches during left-sided breast irradiation was effective for minimizing the amount of radiation to the heart and lung compared to free breathing (FB).
Materials and Methods
Between February and July 2012, a total of 25 patients with left-sided breast cancer underwent two computed tomography scans each with the DIBH using Abches and using FB after breast-conserving surgery. The scans were retrospectively replanned using standardized criteria for the purpose of this study. The DIBH plans for each patient were compared with FB plans using dosimetric parameters.
All patients were successfully treated with the DIBH technique using Abches. Significant differences were found between the DIBH and FB plans for mean heart dose (2.52 vs. 4.53 Gy), heart V30 (16.48 vs. 45.13 cm3), V20 (21.35 vs. 54.55 cm3), mean left anterior descending coronary artery (LAD) dose (16.01 vs. 26.26 Gy, all p < 0.001), and maximal dose to 0.2 cm3 of the LAD (41.65 vs. 47.27 Gy, p = 0.017). The mean left lung dose (7.53 vs. 8.03 Gy, p = 0.073) and lung V20 (14.63% vs. 15.72%, p = 0.060) of DIBH using Abches were not different significantly compared with FB.
We report that the use of a DIBH technique using Abches in breathing adapted radiotherapy for left-sided breast cancer is easily feasible in daily practice and significantly reduces the radiation doses to the heart and LAD, therefore potentially reducing cardiac risk.
PMCID: PMC3912239  PMID: 24501713
Abches; Deep inspiration breath hold; Cardiac toxicity
18.  Efficient approach for determining four-dimensional computed tomography-based internal target volume in stereotactic radiotherapy of lung cancer 
Radiation Oncology Journal  2013;31(4):247-251.
This study aimed to investigate efficient approaches for determining internal target volume (ITV) from four-dimensional computed tomography (4D CT) images used in stereotactic body radiotherapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC).
Materials and Methods
4D CT images were analyzed for 15 patients who received SBRT for stage I NSCLC. Three different ITVs were determined as follows: combining clinical target volume (CTV) from all 10 respiratory phases (ITV10Phases); combining CTV from four respiratory phases, including two extreme phases (0% and 50%) plus two intermediate phases (20% and 70%) (ITV4Phases); and combining CTV from two extreme phases (ITV2Phases). The matching index (MI) of ITV4Phases and ITV2Phases was defined as the ratio of ITV4Phases and ITV2Phases, respectively, to the ITV10Phases. The tumor motion index (TMI) was defined as the ratio of ITV10Phases to CTVmean, which was the mean of 10 CTVs delineated on 10 respiratory phases.
The ITVs were significantly different in the order of ITV10Phases, ITV4Phases, and ITV2Phases (all p < 0.05). The MI of ITV4Phases was significantly higher than that of ITV2Phases (p < 0.001). The MI of ITV4Phases was inversely related to TMI (r = -0.569, p = 0.034). In a subgroup with low TMI (n = 7), ITV4Phases was not statistically different from ITV10Phases (p = 0.192) and its MI was significantly higher than that of ITV2Phases (p = 0.016).
The ITV4Phases may be an efficient approach alternative to optimal ITV10Phases in SBRT for early-stage NSCLC with less tumor motion.
PMCID: PMC3912240  PMID: 24501714
Four-dimensional computed tomography; Internal target volume; Lung cancer; Stereotactic body radiotherapy
19.  Dosimetric evaluation of Tomotherapy and four-box field conformal radiotherapy in locally advanced rectal cancer 
Radiation Oncology Journal  2013;31(4):252-259.
To report the results of dosimetric comparison between intensity-modulated radiotherapy (IMRT) using Tomotherapy and four-box field conformal radiotherapy (CRT) for pelvic irradiation of locally advanced rectal cancer.
Materials and Methods
Twelve patients with locally advanced rectal cancer who received a short course preoperative chemoradiotherapy (25 Gy in 5 fractions) on the pelvis using Tomotherapy, between July 2010 and December 2010, were selected. Using their simulation computed tomography scans, Tomotherapy and four-box field CRT plans with the same dose schedule were evaluated, and dosimetric parameters of the two plans were compared. For the comparison of target coverage, we analyzed the mean dose, Vn Gy, Dmin, Dmax, radical dose homogeneity index (rDHI), and radiation conformity index (RCI). For the comparison of organs at risk (OAR), we analyzed the mean dose.
Tomotherapy showed a significantly higher mean target dose than four-box field CRT (p = 0.001). But, V26.25 Gy and V27.5 Gywere not significantly different between the two modalities. Tomotherapy showed higher Dmax and lower Dmin. The Tomotherapy plan had a lower rDHI than four-box field CRT (p = 0.000). Tomotherapy showed better RCI than four-box field CRT (p = 0.007). For OAR, the mean irradiated dose was significantly lower in Tomotherapy than four-box field CRT.
In locally advanced rectal cancer, Tomotherapy delivers a higher conformal radiation dose to the target and reduces the irradiated dose to OAR than four-box field CRT.
PMCID: PMC3912241  PMID: 24501715
Rectal neoplasms; Helical tomotherapy; Conformal radiotherapy; Radiation dosimetry; Preoperative procedure
20.  A patient who has survived for a long period with repeated radiotherapies for multifocal extrahepatic metastases from hepatocellular carcinoma 
Radiation Oncology Journal  2013;31(4):267-272.
Although significant advances in the treatment of intrahepatic lesions, it is reported that the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. We report a patient with lung, liver, brain, bone and subcutaneous metastasis from HCC who has survived more than 7 years maintaining relatively good performance status as a result of repeated therapies. A 55-year-old male patient with HCC underwent right lobectomy of the liver and cholecystectomy in September 2006. He received wedge resection for lung metastasis twice (July 2009, January 2011) and Gamma Knife stereotactic radiosurgery for brain metastasis (April 2011). Over the last 3 years, he has developed metastasis in subcutaneous tissues, muscle, and bone with pain. He has undergone 7 courses of radiotherapies for subcutaneous tissues, muscle, and bone metastasis and been prescribed sorafenib and he is still capable of all self-care.
PMCID: PMC3912243  PMID: 24501717
Hepatocellular carcinoma; Neoplasm metastasis; Radiotherapy
22.  Fluorodeoxyglucose positron-emission tomography ratio in non-small cell lung cancer patients treated with definitive radiotherapy 
Radiation Oncology Journal  2013;31(3):111-117.
To determine whether the maximum standardized uptake value (SUV) of [18F] fluorodeoxyglucose uptake by positron emission tomography (FDG PET) ratio of lymph node to primary tumor (mSUVR) could be a prognostic factor for node positive non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy (RT).
Materials and Methods
A total of 68 NSCLC T1-4, N1-3, M0 patients underwent FDG PET before RT. Optimal cutoff values of mSUVR were chosen based on overall survival (OS). Independent prognosticators were identified by Cox regression analysis.
The most significant cutoff value for mSUVR was 0.9 with respect to OS. Two-year OS was 17% for patients with mSUVR > 0.9 and 49% for those with mSUVR ≤ 0.9 (p = 0.01). In a multivariate analysis, including age, performance status, stage, use of chemotherapy, and mSUVR, only performance status (p = 0.05) and mSUVR > 0.9 (p = 0.05) were significant predictors of OS. Two-year OS for patients with both good performance (Eastern Cooperative Oncology Group [ECOG] ≤ 1) and mSUVR ≤ 0.9 was significantly better than that for patients with either poor performance (ECOG > 1) or mSUVR > 0.9, 23% (71% vs. 23%, p = 0.04).
Our results suggested that the mSUVR was a strong prognostic factor among patients with lymph node positive NSCLC following RT. Addition of mSUVR to performance status identifies a subgroup at highest risk for death after RT.
PMCID: PMC3797269  PMID: 24137555
Non-small-cell lung carcinoma; Radiotherapy; Positron-emission tomography; Prognosis
23.  Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in patients with advanced maxillary sinus cancer 
Radiation Oncology Journal  2013;31(3):118-124.
The optimal treatment of advanced maxillary sinus cancer has been challenging for several decades. Intra-arterial chemotherapy (IAC) for head and neck cancer has been controversial. We have analyzed the long-term outcome of neoadjuvant IAC followed by radiation therapy (RT) and surgery.
Materials and Methods
Twenty-seven patients with advanced maxillary sinus cancer were treated between 1989 and 2002. Five-fluorouracil (5-FU, 500 mg/m2) was infused intra-arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery was performed 3 to 4 weeks after completion of IAC and RT.
At a median follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall survival in all patients were 63%. The 5-year rates of overall survival of stage T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients with disease recurrence had a local recurrence alone. The 5-year actuarial local control rates in patients with stage T3/T4, and in all patients were 20.0%, 32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to moderate late complications. The tumor extent (i.e., the involvement of either orbit and/or base of skull) appeared to be related with local recurrence.
Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective to improve local tumor control in the patients with advanced maxillary sinus cancer. However, local failure was still the major cause of death. Further investigations are required to determine the optimal treatment schedule, radiotherapy techniques and chemotherapy regimens.
PMCID: PMC3797270  PMID: 24137556
Maxillary sinus neoplasms; Intra-arterial infusion; Radiation therapy; Surgery
24.  Role of radiotherapy for pancreatobiliary neuroendocrine tumors 
Radiation Oncology Journal  2013;31(3):125-130.
We investigated the role of radiotherapy (RT) for pancreatobiliary neuroendocrine tumors (PB-NETs).
Materials and Methods
We identified 9 patients with PB-NETs who received RT between January 2005 and March 2012. Of these 9 patients, 4 were diagnosed with NETs in the pancreas and 5 were diagnosed with NETs in the gallbladder. All patients received RT to the primary tumor or resection bed with a median total irradiation dose of 50.4 Gy, with or without chemotherapy.
The tumor response rate and tumor control rate in the RT field were 60% and 100 %, respectively. All 4 patients who underwent surgery had no evidence of disease in the RT field. Of the 5 patients who received RT to the primary gross tumor, 1 had complete response, 2 had partial response, and 2 had stable disease in the RT field. The median time to progression was 11 months. Of the 9 patients, four patients had no progression, and 5 patients had progression of disease (locoregional, 2; distant, 2; locoregional/distant, 1). Of the 4 patients without progression, 3 were treated with RT in adjuvant or neoadjuvant setting, and one received RT to primary tumor. One patient experienced radiation-induced duodenitis at 3 months after concurrent chemoradiation without treatment-related mortality.
RT can yield local control for advanced PB-NETs. RT should be considered an essential part of multimodality treatment in management of advanced PB-NETs.
PMCID: PMC3797271  PMID: 24137557
Neuroendocrine tumors; Radiotherapy; Treatment outcome
25.  Invasion of the great vessels or atrium predicts worse prognosis in thymic carcinoma 
Radiation Oncology Journal  2013;31(3):131-137.
We evaluated treatment outcomes of thymic carcinomas to determine prognostic factors for survival.
Materials and Methods
Between May 1988 and May 2009, 41 patients had pathologic diagnosis of thymic carcinoma in Seoul National University Hospital, Seoul, Korea. Of these, 40 patients were followed up to 188 months after treatment. The mean age of all patients was 58.3 years and male to female ratio was 23 to 17.
Among 30 patients who underwent surgical resection, 26 achieved R0 resection and postoperative radiotherapy (PORT) was performed in 22 patients (73%). Various chemotherapeutic regimens were given with local treatment modalities, surgery and/or radiotherapy, in 12 patients. The 5-year locoregional control (LRC), distant metastasis-free survival, progression-free survival (PFS), and overall survival were 79.4%, 53.0%, 42.6%, and 63.6%, respectively. Patients with Masaoka stage I or II showed excellent prognosis of 5-year PFS around 90%. In advanced stages, invasion of the great vessels or atrium by thymic carcinomas was negative prognostic factor for PFS in univariate analysis. Lymph node involvement was statistically significant factor for LRC and PFS. Local or regional recurrence was infrequent after surgical resection followed by PORT, while distant metastasis was the major component of treatment failure.
Complete resection followed by PORT provided remarkable local control without severe acute toxicities in patients with stage II and favorable stage III thymic carcinoma. Invasion of the great vessels or atrium was statistically significant prognostic factor for PFS.
PMCID: PMC3797272  PMID: 24137558
Thymic carcinoma; Prognostic factor; Great vessel invasion; Survival

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