작은 크기의 재발성 간세포암에 대한 구제치료로 소분할 방사선치료: 국소 제어율과 안전성

배선현,박희철,임도훈,이정애,최문석,이준혁,고광철,백승운,유병철 대한방사선종양학회 2010 Radiation Oncology Journal Vol.28 No.2

Purpose: To evaluate the rate of tumor response, local control, and treatment-related complications after hypofractionated radiotherapy for recurrent hepatocelluar carcinoma (HCC) less than 5 cm in size. Materials and Methods: Among the HCC patients who were treated by radiotherapy (RT) between 2006 and 2007 after the failure of previous treatment, a total of 12 patients were treated with hypofractionated RT. The criteria for hypofractionated RT was as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to a critical organ, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that irradiated 50% of the prescribed dose. Hypofractionated RT was performed with 50 Gy delivered in 10 fractions, at a rate of 5 fractions per week. The evaluation of tumor response was determined by CT scans performed at 3 months after the cessation of RT, followed by the evaluation of toxicity by Common Terminology Criteria for Adverse Events version 3.0. The median follow-up period after radiotherapy was 18 months. Results: A complete response (CR) was achieved in 5 of 12 lesions (41.7%) at CT performed at 3 months after the cessation, whereas the overall complete response was observed in 7 of 12 cases (58.3%). In-field local control rate was sustained in 83.3% of patients. All patients developed intra-hepatic metastases except for 2 patients. The overall survival rate was 90.0% at 1 year and 67.5% at 2 years, respectively. Three patients developed Grade 1 nausea during RT and 1 patient showed a progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusion: Hypofractionated RT for small-sized HCC as a salvage therapy showed a 58.3% CR rate and 83.3% of local control. Fifty Gy administered in 10 fractions of partial liver irradiation is considered as a tolerable dose that does not cause severe complications. 목 적: 크기가 작은 5 cm 미만의 재발성 간세포암 환자를 대상으로 소분할 방사선치료 후 종양의 반응, 국소제어율 및 소분할 방사선치료와 연관된 부작용을 평가하였다. 대상 및 방법: 2006년부터 2007년까지 국소요법으로 치료한 후 재발한 간세포암 환자 중 구제치료로 소분할 방사선치료를 받은 12명의 환자를 대상으로 후향적 분석을 시행하였다. 소분할 방사선치료의 적용기준은 종양의 크기가 5 cm 미만이고, 중요 정상조직에 인접하지 않으면서, 간세포암에 의한 간문맥 종양 혈전증이 없으며, 처방된 방사선량의 50%가 조사되는 정상 간 용적이 15% 미만인 경우로 제한하였다. 소분할 방사선치료의 1회 조사량은 5 Gy였고, 주 5회 치료하여 2주 동안 총 50 Gy를 조사하였다. 종양의 반응도는 방사선치료 종료 후 3개월에 시행된 간 컴퓨터단층촬영으로 평가하였다. 치료와 연관된 부작용은 Common Terminology Criteria for Adverse Events version 3.0으로 평가하였다. 방사선치료 종료 후 추적관찰기간은 8∼33개월(중앙값 18개월)이었다. 결 과: 방사선치료 후 3개월에 시행한 간 컴퓨터단층촬영에서 완전관해율은 41.7%였고 추적관찰기간에 확인한 전체 완전관해율은 58.3%였다. 방사선치료 부위 내 국소제어율은 83.3%였다. 두 명을 제외한 모든 환자에서 간 내 재발이 발생하였다. 전체 환자의 1년 및 2년 생존율은 각각 90.0%, 67.5%였다. 치료와 연관된 부작용은 3명의 환자가 치료 중 1도의 오심, 식욕부진이 발생하였고 방사선치료 종료 후 복수가 진행한 환자가 1명 있었다. 3도 이상의 중대한 부작용은 없었다. 결 론: 작은 크기의 재발성 간세포암의 구제 치료로서 소분할 방사선치료는 58.3%의 완전관해율과 83.3%의 국소제어율을 보여주었다. 소분할 방사선치료로 5 Gy씩 총 50 Gy를 조사하는 것은 치료와 연관된 심각한 독성 없이 비교적 안전하고 효과적인 방법으로 판단된다.

Feasibility and Efficacy of Stereotactic Ablative Radiotherapy for Barcelona Clinic Liver Cancer-C Stage Hepatocellular Carcinoma

배선현,김미숙,조철구,김금배,박수철,이동한,한철주,김용한 대한의학회 2013 Journal of Korean medical science Vol.28 No.2

The purpose of this study was to assess the feasibility and efficacy of stereotactic ablative radiotherapy (SABR) for liver tumor in patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). We retrospectively reviewed the medical records of 35 patients between 2003 and 2011. Vascular invasion was diagnosed in 32 patients,extrahepatic metastases in 11 and both in 8. Thirty-two patients were categorized under Child-Pugh (CP) class A and 3 patients with CP class B. The median SABR dose was 45 Gy (range, 30-60 Gy) in 3-5 fractions. The median survival time was 14 months. The 1- and 3-yr overall survival (OS) rate was 52% and 21%, respectively. On univariate analysis, CP class A and biologically equivalent dose ≥ 80 Gy10 were significant determinants of better OS. Severe toxicity above grade 3, requiring prompt therapeutic intervention, was observed in 5 patients. In conclusion, SABR for BCLC-C stage HCC showed 1-yr OS rate of 52% but treatment related toxicity was moderate. We suggest that patients with CP class A are the best candidate and at least SABR dose of 80 Gy10 is required for BCLC-C stage.

Low Hepatic Toxicity in Primary and Metastatic Liver Cancers after Stereotactic Ablative Radiotherapy Using 3 Fractions

배선현,김미숙,장원일,조철구,유형준,김검배,한철주,박수철,이동한 대한의학회 2015 Journal of Korean medical science Vol.30 No.8

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity ≥ grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV5Gy-rV35Gy: normal liver volume receiving < X Gy, reverse VXGy). Hepatic toxicity ≥ grade 2 occurred in 10 patients (13%): grade 2 in 9 patients and grade 3 in 1 patient. On univariate analysis, baseline Child-Pugh (CP) score (5 vs. 6-8), normal liver volume, and planning target volume were the significant clinical predictors. All dosimetric parameters were significant: rV20Gy was the most significant predictor. On multivariate analysis, baseline CP score (hazard ratio, 0.026; P = 0.001) was the only significant predictor. In conclusion, SABR using 3 fractions in primary and metastatic liver cancers produces low hepatic toxicity, especially in patients with a baseline CP score of 5. However, further studies are needed to minimize hepatic toxicity in patients with baseline CP scores ≥ 6.

High Dose Involved Field Radiation Therapy as Salvage for Loco-Regional Recurrence of Non-Small Cell Lung Cancer

배선현,안용찬,남희림,박희철,표홍렬,심영목,김진국,Kwhanmien Kim,안진석,안명주,박근칠 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.6

Purpose: To determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals. Materials and Methods: Between 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only. Results: The median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS. Conclusion: The current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery.

A Survey of Stereotactic Body Radiotherapy in Korea

배선현,김미숙,장원일,계철승,김우철,김은석,김진호,김진희,양광모,이규찬,장아람,조선미 대한암학회 2015 Cancer Research and Treatment Vol.47 No.3

Purpose The purpose of this study is to investigate the current status of stereotactic body radiotherapy (SBRT) in Korea. A nationwide survey was conducted by the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology (KROG 13-13). Materials and Methods SBRT was defined as radiotherapy with delivery of a high dose of radiation to an extracranial lesion in ! 4 fractions. A 16-questionnaire survey was sent by e-mail to the chief of radiation oncology at 85 institutions in June 2013. Results All institutions (100%) responded to this survey. Of these, 38 institutions (45%) have used SBRT and 47 institutions (55%) have not used SBRT. Regarding the treatment site, the lung (92%) and liver (76%) were the two most common sites. The most common schedules were 60 Gy/4 fractions for non-small cell lung cancer, 48 Gy/4 fractions for lung metastases, 60 Gy/3 fractions for hepatocellular carcinoma, and 45 Gy/3 fractions or 40 Gy/4 fractions for liver metastases. Four-dimensional computed tomography (CT) was the most common method for planning CT (74%). During planning CT, the most common method of immobilization was the use of an alpha cradle/vacuum-lock (42%). Conclusion Based on this survey, conduct of further prospective studies will be needed in order to determine the appropriate prescribed doses and to standardize the practice of SBRT.

Feasibility and response of helical tomotherapy in patients with metastatic colorectal cancer

배선현,윤진아,문성권,김용호,조광환,신응진,이문성,유창범,고봉민 대한방사선종양학회 2015 Radiation Oncology Journal Vol.33 No.4

Purpose: To investigate the treatment outcome and the toxicity of helical tomotherapy (HT) in patients with metastatic colorectal cancer (mCRC). Materials and Methods: We retrospectively reviewed 18 patients with 31 lesions from mCRC treated with HT between 2009 and 2013. The liver (9 lesions) and lymph nodes (9 lesions) were the most frequent sites. The planning target volume (PTV) ranged from 12 to 1,110 mL (median, 114 mL). The total doses ranged from 30 to 70 Gy in 10–30 fractions. When the α/β value for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the total doses ranged from 39 to 119 Gy10 (median, 55 Gy10). Nineteen lesions were treated with concurrent chemotherapy (CCRT). Results: With a median follow-up time of 16 months, the median overall survival for 18 patients was 33 months. Eight lesions (26%) achieved complete response. The 1- and 3-year local progression free survival (LPFS) rates for 31 lesions were 45% and 34%, respectively. On univariate analysis, significant parameters influencing LPFS rates were chemotherapy response before HT, aim of HT, CCRT, PTV, BED, and adjuvant chemotherapy. On multivariate analysis, PTV ≤113 mL and BED >48 Gy10 were associated with a statistically significant improvement in LFPS. During HT, four patients experienced grade 3 hematologic toxicities, each of whom had also received CCRT. Conclusion: The current study demonstrates the efficacy and tolerability of HT for mCRC. To define optimal RT dose according to tumor size of mCRC, further study should be needed.

Radiation Treatment in Pathologic N0-N1 Patients Treated with Neoadjuvant Chemotherapy Followed by Surgery for Locally Advanced Breast Cancer

배선현,박원,허승재,최두호,남석진,임영혁,안진석 한국유방암학회 2012 Journal of breast cancer Vol.15 No.3

Purpose: This study evaluated the treatment results and the necessity to irradiate the supraclavicular lymph node (SCN) region in pathological N0-N1 (pN0-N1) patients with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery and radiotherapy (RT). Methods: Between 1996 and 2008, 184 patients with initial tumor size >5cm or clinically positive lymph nodes were treated with NAC followed by surgery and RT. Among these patients, we retrospectively reviewed 98 patients with pN0-N1. Mastectomy was performed in 55%. The pathological lymph node stage was N0 in 49% and N1 in 51%. All patients received adjuvant RT to chest wall or breast and 56 patients (57%) also received RT to the SCN region (SCNRT). Results: At 5 years, locoregional recurrence (LRR)-free survival, distant metastasis-free survival, disease-free survival (DFS), and overall survival rates were 93%, 83%, 81%, and 91%, respectively. In pN0 patients, LRR was 7% in SCNRT−group and 5% in SCNRT+ group. In pN1 patients, LRR was 7% in SCNRT- group and 6% in SCNRT+ group. There was no significant difference of LRR, regardless of SCNRT. However, in pN1patients, there were more patients with poor prognostic factors in the SCNRT+ group compared to SCNRT- group. These factors might be associated with worse DFS in the SCNRT+ group, even though RT was administered to the SCN region. Conclusion: Our study showed the similar LRR, regardless of SCNRT in pN0-pN1 breast cancer patients after NAC followed by surgery. Prospective randomized trial is called for to validate the role of SCNRT.

Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma: dosimetric comparison and risk assessment of solid secondary cancer

배선현,김동욱,김미숙,신명희,박희철,임도훈 대한방사선종양학회 2017 Radiation Oncology Journal Vol.35 No.1

Purpose: To determine the optimal radiotherapy technique for gastric mucosa-associated lymphoid tissue lymphoma (MALToma), we compared the dosimetric parameters and the risk of solid secondary cancer from scattered doses among anterior-posterior/ posterior-anterior parallel-opposed fields (AP/PA), anterior, posterior, right, and left lateral fields (4_field), 3-dimensional conformal radiotherapy (3D-CRT) using noncoplanar beams, and intensity-modulated radiotherapy composed of 7 coplanar beams (IMRT_co) and 7 coplanar and noncoplanar beams (IMRT_non). Materials and Methods: We retrospectively generated 5 planning techniques for 5 patients with gastric MALToma. Homogeneity index (HI), conformity index (CI), and mean doses of the kidney and liver were calculated from the dose-volume histograms. Applied the Biological Effects of Ionizing Radiation VII report to scattered doses, the lifetime attributable risk (LAR) was calculated to estimate the risk of solid secondary cancer. Results: The best value of CI was obtained with IMRT, although the HI varied among patients. The mean kidney dose was the highest with AP/PA, followed by 4_field, 3D-CRT, IMRT_co, and IMRT_non. On the other hand, the mean liver dose was the highest with 4_field and the lowest with AP/PA. Compared with 4_field, the LAR for 3D-CRT decreased except the lungs, and the LAR for IMRT_co and IMRT_non increased except the lungs. However, the absolute differences were much lower than <1%. Conclusion: Tailored RT techniques seem to be beneficial because it could achieve adjacent organ sparing with very small and clinically irrelevant increase of secondary solid cancer risk compared to the conventional techniques.

수술 후 보조적 방사선 치료를 포함한 근치적 치료를 받은 유방암 환자들의 뇌전이 발생률과 연관된 인자 분석

배선현,최두호,허승재,임도훈,박원,남희림,양정현,남석진,이정언,임영혁,안진석,박연희 한국유방암학회 2011 Journal of breast cancer Vol.14 No.-

Purpose: To assess the incidence of brain metastasis in patients with breast cancer receiving surgery and adjuvant radiotherapy (RT) and to evaluate subtypes associated with brain metastasis. Methods: We retrospectively reviewed the medical records of 1,000 patients with breast cancer who were treated with surgery and adjuvant RT for a cure between January 2001 and July 2005 at Samsung Medical Center. Seventy-one patients received neoadjuvant chemotherapy before surgery. The pathological stage was I in 430 patients, II in 327, and III in 243. We divided the patients into three subtypes according to immunohistochemistry: triple negative (TN, 245 patients), human epidermal growth factor 2 (HER2) enriched (HE, 166 patients) and positive estrogen receptor or progesterone receptor without HER2 overexpression (EP, 589 patients). The median follow up time was 72 months after surgery. Results: Locoregional failure-free survival rate and distant metastasis-free survival rate at 5 years were 92.8% and 86.1%, respectively. The disease free survival rate and overall survival rate at 5 years were 84.6% and 94.7%, respectively. Thirty-nine patients had brain metastasis, and the brain metastasis-free survival rate at 5 years was 97.2%. A univariate analysis showed that younger age, neoadjuvant chemotherapy, modified radical mastectomy, advanced pathological stage and the TN and HE subtypes were significant risk factors for brain metastasis. A multivariate analysis revealed that age, neoadjuvant chemotherapy, pathological stage and the TN and HE subtypes were statistically significant factors for brain metastasis. Conclusion: The cumulative incidence of brain metastasis was 3.9% after curative treatment. If patients have a clinically suspicious symptoms suggesting brain metastasis, clinicians should be aware that an early brain imaging work up and management are necessary. Because patients with the TN or HE subtypes accompanied by younger age and advanced pathological stage have increased brain metastasis (>10%), annual regular imaging follow-up may be recommended for these high risk patients.

국소 진행성 유방암 환자에서 선행 항암화학요법의 치료결과

배선현,박원,허승재,최두호,남희림,양정현,남석진,이정언,임영혁,안진석,박연희 대한방사선종양학회 2010 Radiation Oncology Journal Vol.28 No.2

Purpose: To evaluate the result of neoadjuvant chemotherapy, surgery, and radiation therapy in locally advanced breast cancer as well as analyze the prognostic factors affecting survival. Materials and Methods: One hundred fifty-nine patients with breast cancer were treated by neoadjuvant chemotherapy between April 1995 and November 2006 at the Samsung Medical Center. Among these patients, we retrospectively reviewed 105 patients treated with neoadjuvant chemotherapy followed by surgery and radiation therapy for a cure with an initial tumor size >5 cm or clinically positive lymph nodes. All patients received anthracycline based chemotherapy except for 2 patients. According to clinical tumor stage, 3 patients (3%) were cT1, 26 (25%) were cT2, 39 (37%) were T3 and 37 (35%) were T4. Initially, 98 patients (93%) showed axillary lymph node metastasis. The follow-up periods ranged from 7∼142 months (median, 41 months) after the beginning of neoadjuvant chemotherapy. Results: Locoregional failure free survival rate and distant metastasis free survival rate at 5 years were 82.1% and 69.9%, respectively. Disease free survival rate and overall survival rate at 5 years were 66.1% and 77.1%, respectively. The results of a univariate analysis indicate that clinical tumor stage, pathologic tumor stage, pathologic nodal stage and pathologic TNM stage were statistically significant factors for disease free survival rate and overall survival rate. Whereas, a multivariate analysis indicated that only hormone therapy was a statistically significant factor for survival. Conclusion: The current study results were comparable to other published studies for neoadjuvant chemotherapy for breast cancer. Hormone therapy was a statistically significant prognostic factor. The patients with early clinical or pathologic stage had a tendency to improve their survival rate. 목 적: 국소 진행성 유방암으로 선행 항암화학요법 후 수술과 방사선치료를 시행한 환자를 대상으로 치료 결과와 예후에 영향을 미치는 인자를 알아보고자 하였다. 대상 및 방법: 1995년 4월부터 2006년 11월까지 삼성서울병원에서 유방암으로 선행 항암화학요법을 받은 환자는 총 159명이었다. 이중에서 진단 당시 종양의 크기가 5.0 cm를 초과하거나 액와림프절 전이가 의심된 유방암 환자로 항암화학요법 후 근치적 수술을 시행하고 방사선치료가 시행된 105명을 대상으로 하였다. 선행 항암화학요법은 2명을 제외한 모든 환자에서 anthracycline을 기반으로 하는 복합항암요법을 사용하였다. 치료 전 임상적 병기는 T1 3명(3%), T2 26명(25%), T3 39명(37%), T4 37명(35%)이었고 액와림프절 전이가 의심되는 사람이 98명(93%)이었다. 선행 항암화학요법을 시작한 날을 기준으로 추적 조사하였고 중앙추적조사기간은 41개월(7∼142개월)이었다. 결 과: 전체 환자의 5년 국소제어율은 82.1%, 원격전이제어율은 69.9%, 무병생존율은 66.1%, 전체생존율은 77.1%이었다. 무병생존율과 전체생존율에 영향을 미치는 인자를 알아보기 위해 단변량분석을 시행하였을 때 임상적 원발병소 병기, 병리학적 원발병소 병기, 병리학적 림프절 병기 그리고 병리학적 TNM 병기가 공통적으로 통계적으로 유의한 인자들이었다. 다변량 분석을 시행하였을 때 호르몬치료 유무만 생존율과 연관된 의미 있는 인자였다. 결 론: 본 연구를 통하여 삼성서울병원에서 국소 진행성 유방암으로 선행 항암화학요법이 시행된 환자의 치료 성적이 지금까지 보고된 다른 선행 항암화학요법 치료 결과와 비교할 때 비슷하거나 나은 결과를 보여주었다. 또한, 호르몬치료를 시행한 경우에만 생존율이 의미 있게 좋았고 임상적 병기나 병리학적 병기가 낮은 경우 생존율이 좋은 경향을 보였다.