Kyung Hwan Shin

Dosimetric comparison of four different external beam partial breast irradiation techniques: Three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, helical tomotherapy, and proton beam therapy

BACKGROUND AND PURPOSE As an alternative to whole breast irradiation in early breast cancer, a variety of accelerated partial breast irradiation (APBI) techniques have been investigated. The purpose of our study is to compare the dosimetry of four different external beam APBI (EB-APBI) plans: three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), helical tomotherapy (TOMO), and proton beam therapy (PBT). METHODS AND MATERIALS Thirty patients were included in the study, and plans for four techniques were developed for each patient. A total dose of 30Gy in 6Gy fractions once daily was prescribed in all treatment plans. RESULTS In the analysis of the non-PTV breast volume that was delivered 50% of the prescribed dose (PD), PBT (mean: 16.5%) was superior to TOMO (mean: 22.8%), IMRT (mean: 33.3%), and 3D-CRT (mean: 40.9%) (p<0.001). The average ipsilateral lung volume percentage receiving 20% of the PD was significantly lower in PBT (0.4%) and IMRT (2.3%) compared with 3D-CRT (6.0%) and TOMO (14.2%) (p<0.001). The average heart volume percentage receiving 20% and 10% of the PD in left-sided breast cancer (N=19) was significantly larger with TOMO (8.0%, 19.4%) compared to 3D-CRT (1.5%, 3.1%), IMRT (1.2%, 4.0%), and PBT (0%, 0%) (p<0.001). CONCLUSIONS All four EB-APBI techniques showed acceptable coverage of the PTV. However, effective non-PTV breast sparing was achieved at the cost of considerable dose exposure to the lung and heart in TOMO.

Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer

BACKGROUND Although trastuzumab therapy improves survival in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, 40% of patients develop brain metastasis (BM) even when extracranial disease is under control. We studied whether trastuzumab therapy beyond or after BM was beneficial to patients with BM. PATIENTS AND METHODS The effect of trastuzumab on survival after BM was analyzed in 78 HER2-positive breast cancer patients. Patients were grouped according to trastuzumab therapy; no treatment and treatment before and after BM were diagnosed. RESULTS Overall survival after the diagnosis of BM as well as time to progression (TTP) of intracranial tumors was prolonged in patients who received trastuzumab after BM was diagnosed. Conversely, BM occurred much later in patients who received trastuzumab before BM. In the multivariate Cox regression model, age at BM <50 years, disease-free interval >or=24 months, TTP of intracranial tumor >or=4.8 months, and trastuzumab treatment after BM were significantly associated with longer survival after the onset of BM. CONCLUSIONS Trastuzumab therapy after the onset of BM in HER2-positive breast cancer patients is associated with a significant survival benefit after BM diagnosis compared with patients who never received or completed trastuzumab before the BM diagnosis.

3D CT-based high-dose-rate brachytherapy for cervical cancer: Clinical impact on late rectal bleeding and local control

BACKGROUND AND PURPOSE To identify the impact of 3D CT-based high-dose-rate intracavitary radiotherapy (ICR) on late rectal bleeding (LRB) and local control (LC) in patients with cervical cancer. MATERIAL AND METHODS The outcomes of 97 consecutive patients treated with 3D CT-based ICR (3D-ICR) were compared with those of 133 consecutive historical patients with conventional 2D brachytherapy planning (2D-ICR). The median follow-up periods were 41 and 56 months for the 3D and 2D groups, respectively. RESULTS The overall rectal bleeding rate was similar between the groups (42% for 3D-ICR vs. 44% for 2D-ICR); however, the incidence of severe LRB was higher in the 2D-ICR group than in the 3D-ICR group (13% vs. 2%, respectively; p=0.02). In multivariate analysis, the factors associated with severe LRB were tumor >4 cm (12% vs. 3%) and 2D-ICR (10% vs. 2%). The LC rates were 97% and 91% for 3D-ICR and 2D-ICR, respectively (p=0.14); the progression-free survival rate was 80% for both groups. A significant difference in the LC rates between the two groups was observed in patients with larger tumor sizes with the tumor diameter of over 4 cm (98% vs. 81% by 3D-ICR vs. 2D-ICR, respectively; p=0.02). CONCLUSIONS The implementation of 3D-ICR in radiotherapy for cervical cancer can reduce the incidence of severe LRB and may improve the LC rate.

Radiation-Induced Cancers From Modern Radiotherapy Techniques: Intensity-Modulated Radiotherapy Versus Proton Therapy

PURPOSE To assess and compare secondary cancer risk resulting from intensity-modulated radiotherapy (IMRT) and proton therapy in patients with prostate and head-and-neck cancer. METHODS AND MATERIALS Intensity-modulated radiotherapy and proton therapy in the scattering mode were planned for 5 prostate cancer patients and 5 head-and-neck cancer patients. The secondary doses during irradiation were measured using ion chamber and CR-39 detectors for IMRT and proton therapy, respectively. Organ-specific radiation-induced cancer risk was estimated by applying organ equivalent dose to dose distributions. RESULTS The average secondary doses of proton therapy for prostate cancer patients, measured 20-60 cm from the isocenter, ranged from 0.4 mSv/Gy to 0.1 mSv/Gy. The average secondary doses of IMRT for prostate patients, however, ranged between 3 mSv/Gy and 1 mSv/Gy, approximately one order of magnitude higher than for proton therapy. Although the average secondary doses of IMRT were higher than those of proton therapy for head-and-neck cancers, these differences were not significant. Organ equivalent dose calculations showed that, for prostate cancer patients, the risk of secondary cancers in out-of-field organs, such as the stomach, lungs, and thyroid, was at least 5 times higher for IMRT than for proton therapy, whereas the difference was lower for head-and-neck cancer patients. CONCLUSIONS Comparisons of organ-specific organ equivalent dose showed that the estimated secondary cancer risk using scattering mode in proton therapy is either significantly lower than the cases in IMRT treatment or, at least, does not exceed the risk induced by conventional IMRT treatment.

Cross-cultural application of the Korean version of the European Organization for Research and Treatment of Cancer (EORTC) Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23)

The aim of this study was to evaluate the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23). A total of 153 patients with breast cancer and 153 normal subjects completed three questionnaires of the Korean version of the EORTC QLQ-BR23. Multitrait scaling analyses demonstrated that all scales met multidimensional conceptualization criteria in terms of convergence and discrimination validity. Cronbach’s alpha coefficients for five multiple-item scales were greater than 0.70 (range, 0.72–0.91). In known-group comparisons, there were marked group differences between patients differing in disease stage. In breast cancer patients, performance on the questionnaires was in the expected direction for almost all functioning and symptom scores. In addition, comparison between the patient and control groups showed that almost all variables discriminated between patients and normal individuals. In conclusion, the Korean version of the EORTC QLQ-BR23 was found to be a reliable and valid measure of quality of life in breast cancer patients, indicating that it should be used in clinical and epidemiological cancer research.

Intensity-modulated radiotherapy with a belly board for rectal cancer

Background and aimIntensity-modulated radiotherapy (IMRT) techniques can reduce the irradiated small bowel volume in rectal cancer patients, but combined use of IMRT and a belly board is yet to be reported on for rectal cancer patients. The aim of this study was to determine whether additional use of a belly board reduced the irradiated small bowel volume observed using IMRT alone in rectal cancer patients.Materials and methodsTwenty patients scheduled to receive preoperative radiotherapy for rectal cancer underwent two series of CT scans, with and without a belly board. IMRT planning was performed using 6-MV photon beams and seven equispaced fields. The bladder, small bowel, and planning target volume (PTV) were analyzed for doses between 10% and 100% of the prescribed dose at 10% intervals. Data were analyzed using Wilcoxon signed rank tests.ResultsThere were no significant differences between patients undergoing IMRT with a belly board and those without a belly board in terms of total small bowel volumes, bladder, and PTV (p=0.571, p=0.841, and p=0.870, respectively). Statistical analysis showed that the irradiated small bowel volume with a belly board was smaller than that without a belly board (p<0.05 at 20–100% dose levels), with the mean relative reduction in the irradiated small bowel volume being 37.8±32.8%.ConclusionIMRT with a belly board is more effective than IMRT alone in reducing the irradiated small bowel volume. These findings suggest that the use of a belly board with IMRT may reduce small bowel complications in preoperative radiotherapy.

Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancer

Tumor hypoxia has a pronounced effect on malignant progression and metastatic spread of human tumors. As carbonic anhydrases (CA) 9 and 12 are induced by the low‐oxygen environment within tumors, we investigated the relationship between the expression of these two CA and the presence of metastatic lymph nodes (LN) in uterine cervical cancer. CA9/CA12 expression was evaluated histochemically in primary cervical cancer tissues of 73 patients who underwent laparoscopic LN staging and two patients with clinical staging before definitive radiotherapy at the National Cancer Center, Korea. We also evaluated CA9 expression in 33 patients with pathologically confirmed metastatic LN. CA9 expression in the primary tumors was significantly associated with LN metastasis (P = 0.03) and poorer disease‐free survival (relative risk, 6.1; 95% confidence interval, 1.3–28.3, P = 0.02, multivariate analysis), whereas CA12 expression did not show such a relationship. In addition, 21 of 24 metastatic LN revealed similar CA9 expression (P = 0.001), suggesting that CA9‐expressing tumor cells had a higher metastatic potential. CA9 was expressed in 45 of 75 (60%) primary tumors, with positive tumor cells observed predominantly in the area away from the blood vessels. In contrast, CA12 expression was observed in only 29 of 74 primary tumors (39%), without a specific pattern. These findings indicate that expression of CA9, but not CA12, in tumors is associated with the presence of LN metastases and poorer prognosis. Selective application of new treatment modalities based on CA9 expression to prevent LN metastases may improve overall treatment outcome in patients with uterine cervical cancer. (Cancer Sci 2007; 98: 329–333)

Phase II trial of proton beam accelerated partial breast irradiation in breast cancer

BACKGROUND AND PURPOSE Here, we report the results of our phase II, prospective study of proton beam accelerated partial breast irradiation (PB-APBI) in patients with breast cancer after breast conserving surgery (BCS). MATERIALS AND METHODS Thirty patients diagnosed with breast cancer were treated with PB-APBI using a single-field proton beam or two fields after BCS. The treatment dose was 30 cobalt gray equivalent (CGE) in six CGE fractions delivered once daily over five consecutive working days. RESULTS All patients completed PB-APBI. The median follow-up time was 59 months (range: 43-70 months). Of the 30 patients, none had ipsilateral breast recurrence or regional or distant metastasis, and all were alive at the last follow-up. Physician-evaluated toxicities were mild to moderate, except in one patient who had severe wet desquamation at 2 months that was not observed beyond 6 months. Qualitative physician cosmetic assessments of good or excellent were noted in 83% and 80% of the patients at the end of PB-APBI and at 2 months, respectively, and decreased to 69% at 3 years. A good or excellent cosmetic outcome was noted in all patients treated with a two-field proton beam at any follow-up time point except for one. For all patients, the mean percentage breast retraction assessment (pBRA) value increased significantly during the follow-up period (p=0.02); however, it did not increase in patients treated with two-field PB-APBI (p=0.3). CONCLUSIONS PB-APBI consisting of 30 CGE in six CGE fractions once daily for five consecutive days can be delivered with excellent disease control and tolerable skin toxicity to properly selected patients with early-stage breast cancer. Multiple-field PB-APBI may achieve a high rate of good-to-excellent cosmetic outcomes. Additional clinical trials with larger patient groups are needed.

The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II-III breast cancer patients with pN0: A multicenter, retrospective study (KROG 12-05)

PURPOSE The purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0. METHODS AND MATERIALS We retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log-rank test and Cox proportional regression analysis. RESULTS Of the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis. CONCLUSIONS PMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.

Simultaneous Integrated Boost Intensity-Modulated Radiotherapy in Patients With High-Grade Gliomas

PURPOSE We analyzed outcomes of simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in patients with high-grade gliomas, compared with a literature review. METHODS AND MATERIALS Forty consecutive patients (WHO grade III, 14 patients; grade IV, 26 patients) treated with SIB-IMRT were analyzed. A dose of 2.0 Gy was delivered to the planning target volume with a SIB of 0.4 Gy to the gross tumor volume with a total dose of 60 Gy to the gross tumor volume and 50 Gy to the planning target volume in 25 fractions during 5 weeks. Twenty patients received temozolomide chemotherapy. RESULTS At a median follow-up of 13.4 months (range, 3.7-55.9 months), median survival was 14.8 months. One- and 2-year survival rates were 78% and 65%, respectively, for patients with grade III tumors and 56% and 31%, respectively, for patients with grade IV tumors. Age (≤50 vs. >50), grade (III vs. IV), subtype (astrocytoma vs. oligodendroglioma or mixed), and a Zubrod performance score (0-1 vs. >2) were predictive of survival. Of 25 (63%) patients who had recurrences, 17 patients had local failure, 9 patients had regional failure, and 1 patient had distant metastasis. Toxicities were acceptable. CONCLUSIONS SIB-IMRT with the dose/fractionation used in this study is feasible and safe, with a survival outcome similar to the historical control. The shortening of treatment time by using SIB-IMRT may be of value, although further investigation is warranted to prove its survival advantage.