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An Analysis of Prognostic Factors Affecting the Outcome of Radiation Therapy for Nasopharyngeal Carcinoma (비인강암의 방사선치료 곁과 및 생존율에 관한 예후인자 분석)

  • Jung, Young-Yeon;Kim, Ok-Bae;Kim, Jin-Hee
    • Radiation Oncology Journal
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    • v.23 no.2
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    • pp.71-77
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    • 2005
  • Purpose: This retrospective study was conduced to analyze the treatment results and to evaluate the prognostic factors affecting the survival of nasopharyngeal carcinoma patients. Materials and Methods: From 1987 to 2002, we analyzed 43 patients who had nasopharyngeal carcinomas that were histologically confirmed and who had also completed the planned radiation therapy course at Keimyung University Dongsan Medical Center According to the 6th edition of American Joint Committee on Cancer staging system, 12 patients ($27.9\%$) were at Stage 11, 13 ($30.2\%$) were at Stage III and 18 ($41.9\%$) were at Stage IV Histopathologically, there were 15 ($34.9\%$) squamous cell carcinomas, 8 ($18.5\%$) nonkeratinizing carcinomas, 17 ($39.5\%$) undifferentiated carcinomas, and 3 ($7.0\%$) lymphoepitheliomas. Among the total 43 patients, 31 patients ($72.1\%$) were treated with only radiation therapy. Neoadjuvant chemotherapy was peformed on 7 patients ($16.3\%$) and concurrent chemoradiotherapy was performed on S patients ($11.6\%$). Cisplatin and 5-Fluorouracil were administered to 11 patients for 4 cycles, and Cisplatin and Taxotere were administered to 1 patient for 6 cycles. The range of the total radiation dose delivered to the primary tumor was from 61.2 to 84 Gy (median 70.4 Gy), The follow-up period ranged from 2 to 197 months with median follow-up of 84 months. Results: The local control rate at 6 months after radiation therapy was $90.7\%$. The five year overall survival and disease free survival rates were $50.7\%$ and $48.9\%$, respectively. On the multivariate analysis, the age, T-stage ($T_{1-3}\;vs\;T_4$), N-stage and AJCC stage were the statistically significant prognostic factors affecting survival (p<0.05). The patterns of failure were as follows: local failure only in 3 patients ($7.0\%$), local and systemic failure in 1 patient ($2.3\%$), and distant metastasis only in 11 patients ($25.6\%$). Conclusion: The prognostic factors affecting the outcome of nasopharyngeal carcinoma were age, T-stage (7$T_{1-3}\;vs\;T_4$), N-stage and stage. Because systemic metastasis was the main failure pattern noted for nasopharyngeal carcinoma, systemic chemotherapy is needed to decrease the rate of distant metastasis for nasopharyngeal carcinoma. In audition, research for more effective chemotherapeutical regimens and schedules is also needed.

Effects of Fractionated Stereotactic Radiotherapy for Primary Hepatocellular Carcinoma (원발성 간암의 분할 정위방사선치료 효과)

  • Choi Byeong Ock;Kang Ki Mun;Jang Hong Seok;Lee Snag-wook;Kang Young Nam;Chai Gyu Young;Choi Ihl Bhong
    • Radiation Oncology Journal
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    • v.23 no.2
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    • pp.92-97
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    • 2005
  • Purpose : Reports on the outcome of curative radiotherapy for the primary hepatocellular carcinoma (HCC) are rarely encountered in the literature. in this study, we report our experience of a clinical trial where fractionated stereotactic radiotherapy (SRT) was used in treating a primary HCC. Materials and Methods : A retrospective analysis was peformed on 20 patients who had been histologically diagnosed as HCC and treated by fractionated SRT. The long diameter of tumor measured by CT was $2\~6.5$ cm (average: 3.8 cm). A single dose of radiation used in fractionated SRT was S or 10 Gy: each dose was prescribed based on the planning target volume and normalized to $85\~99\%$ isocenter dose. Patients were treated $3\~5$ times per week for 2 weeks, with each receiving a total dose of 50 Gy (the median dose: 50 Gy). The follow up period was $\~55$ months (the median follow up period: 23 months). Results : The response rate was $50\%$ (12 patients), with 4 patients showing complete response ($20%$), 8 patients showing partial response ($40\%$), and 8 patients showing stable disease ($40\%$). The 1-year and 2-year survival rates were $70.0\%$ and $43.1\%$, respectively, and the median survival time was 20 months. The 1-year and 2-year disease free survival rates were $65\%$ and $32.5\%$, respectively, and the median disease-free survival rate was 19 months. Some acute complications of the treatment were noted as follows: dyspepsia in 12 patients ($60\%$), nausea/emesis in 8 patients ($40\%$), and transient liver function impairment in 6 patients ($30\%$). However, there was no treatment related death. Conclusion : The study indicates that fractionated SRT is a relatively safe and effective method for treating primary HCC. Thus, fractionated SRT may be suggested as a local treatment for HCC of small lesion and containing a single lesion, when the patients are inoperable or operation is refused by the patients. We thought that fractionated SRT is a challenging treatment modality for the HCC.

Reirradiation in Rcurrent Cervical Cancer Following Definite Radiation Therapy (근치적 방사선치료 후 재발한 자궁경부암의 재 방사선치료)

  • Kim, Jin-Hee;Choi, Tae-Jin;Kim, Ok-Bae
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.230-236
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    • 2001
  • Purpose : To evaluate treatment results in terms of local control, complications and survival after reirraidiation in recurrent cervical cancer following definite radiation therapy. Material and methods : From November 1987 through March 1998, eighteen patients with recurrent cervical cancer following definite radiation therapy were subsequently treated with reirradiation at Keimyung University Dongsan Medical Center. In regard to the initial FIGO stage, one patient was stage la, five were stage IIa, three were IIb, two were IIb and two were IVa. The age range was 37 to 79 years old with median age of 57. The time interval from initial definite radiation therapy to recurrence ranged from 6 to 122 months with a median of 58 months. The recurrent sites were the uterine cervix in seven patients, vagina in ten and pelvic lymph node in one. Reirradiation was peformed with external radiation and intracavitary radiation in twelve patients, external radiation and implantation in four and external radiation alone in two. The range of external radiation dose was $2,100\~5,400\;cGy$ and the range of the total radiation dose was $3,780\~8,550\;cGy$. The follow-up periods ranged from 8 to 20 months with median of 25 following reirradiation. Results : Fourteen of eighteen patients $(78\%)$ had local control just after reirradiation. The two year disease free survival (2YDFS) rate was $53.6\%$. There were statistically significant differences in the 2YDFS according to both recurrent site (2YDFS $28.5\%$ in uterine cervix, $71.4\%$ in vagina, (p=0.03)) and the total dose (2YDFS $71.8\%$ in >6,000 cGy , $25\%$ in $\leq6,000$ cGy, p=0.007). Seven of ten patients who were followed for more than 20 months remain alive and disease free (7/18, $39\%$). Patients treated with external radiation and intracavitary radiation had a higher rate of 2YDFS. Seven patients including 4 patients with no local control experienced local failure in the uterus or vagina and two patients died with distant metastasis. Complications included rectal bleeding in 3 patients, bowel obstruction treated with surgery in two, hematuria in one, radiation cystitis in two, soft tissue swelling in two and vaginal necrosis spontaneously healed in one. There was no statistical difference in complications according to the total dose or the time to recurrence from initial radiation. Conclusion : In patients with recurrence following definite radiation therapy in the uterine cervical cancer, reirradiation may be effective but requires an effort to reduce radiation induced severe complications.

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The Role of Fas in Radiation Induced Apoptosis in vivo (방사선에 의한 Apoptosis에서 Fas의 역할)

  • Kim, Sung-Hee;Seong, Jin-Sil;Seong, Je-Kyung
    • Radiation Oncology Journal
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    • v.20 no.3
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    • pp.246-252
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    • 2002
  • Purpose : It has been recognized that interaction of the Fas : Fas ligand plays an important role in radiation-induced apoptosis. The purpose of this study was to investigate the role of Fas mutation in radiation-induced apoptosis in vivo. Materials and Method : Mice with mutations in Fas, $MRL/Mpj-Fas^{Ipr}$, and its normal control, MRL/Mpj, were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed and their spleens were collected at different time intervals. Tissue samples were stained with hematoxylin-eosin and the numbers of apoptotic cells were scored. Regulating molecules of apoptosis including p53, Bcl-2, Bax, $Bcl-X_L,\;and\;Bcl-X_S$ were also analyzed by Western blotting. Results : At 25 Gy irradiation, the level of apoptosis reached the peak value at 8 hr after radiation and recovered to the normal value at 24 hr after radiation in MRL/Mpj mice. In contrast, the peak apoptosis level appeared at 4 hr after radiation in $MRL/Mpj-Fas^{Ipr}$. At 8 hr after radiation, the levels of apoptosis in MRL/Mpj mice and $MRL/Mpj-Fas^{Ipr}$ mice were $52.3{\pm}7.8\%\;and\;8.0{\pm}8.6\%$, respectively (p<0.05). The expression of apoptosis regulating molecules, p53, $Bcl-X_L\;and\;Bcl-X_S$, increased in MRL/Mpj mice in response to radiation; p53 with a peak level of 3-fold at 8 h, $Bcl-X_L$ with a peak level of 3.3-fold at 12 h, and $Bcl-X_S$ with a peak level of 3-fold at 12 h after 25 Gy radiation. Bcl-2 and Bax did not show significant change in MRL/Mpj mice. However in $MRL/Mpj-Fas^{Ipr}$ mice, the expression levels of p53, Bcl-2, Bax, $BCl-X_L\;and\;BCl-X_S$ showed no significant change. Conclusion : The level of radiation-induced apoptosis was lower in Fas mutated mice, Ipr, than in control mice. This seemed to be related to the lack of radiation-induced p53 activation in the Ipr mice. This result suggests that Fas plays an important role in radiation-induced apoptosis in vivo.

Radiation Dose of Lens and Thyroid in Linac-based Radiosurgery in Humanoid Phantom (선형가속기형 방사선수술시 인형 팬텀에서 수정체 및 갑상선 선량)

  • Kim, Dae-Yong;Kim, Il-Han
    • Radiation Oncology Journal
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    • v.16 no.4
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    • pp.517-529
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    • 1998
  • Purpose : Although many studies have investigated the dosimetric aspects of stereotactic radiosurgery in terms of target volume, the absorbed doses at extracranial sites: especially the lens or thyroid - which are sensitive to radiation for deterministic or stochastic effect -have infrequently been reported. The aim of this study is to evaluate what effects the parameters of radiosurgery have on the absorbed doses of the lens and thyroid in patients treated by stereotactic radiosurgery, using a systematic plan in a humanoid phantom. Materials and Methods : Six isocenters were selected and radiosurgery was planned using the stereotactic radiosurgery system which the Department of Therapeutic Radiology at Seoul National University College of Medicine developed. The experimental radiosurgery plan consisted of 6 arc planes per one isocenter, 100 degrees for each arc range and an accessory collimator diameter size of 2 cm. After 250 cGy of irradiation from each arc, the doses absorbed at the lens and thyroid were measured by thermoluminescence dosimetry. Results : The lens dose was 0.23$\pm$0.08$\%$ of the maximum dose for each isocenter when the exit beam did not pass through the lens and was 0.76$\pm$0.12$\%$ of the maximum dose for each isocenter when the exit beam passed through the lens. The thyroid dose was 0.18$\pm$0.05$\%$ of the maximum dose for each isocenter when the exit beam did not pass through the thyroid and was 0.41$\pm$0.04$\%$ of the maximum dose for each isocenter when the exit beam Passed through the thyroid. The passing of the exit beam is the most significant factor of organ dose and the absorbed dose by an arc crossing organ decides 80$\%$ of the total dose. The absorbed doses of the lens and thyroid were larger as the isocenter sites and arc planes were closer to each organ. There were no differences in the doses at the surface and 5 mm depth from the surface in the eyelid and thyroid areas. Conclusion : As the isocenter and arc plane were placed closer to the lens and thyroid, the doses increased. Whether the exit beams passed through the lens or thyroid greatly influenced the lens and thyroid dose. The surface dose of the lens and thyroid consistently represent the tissue dose. Even when the exit beam passes through the lens and thyroid, the doses are less than 1$\%$ of the maximum dose and therefore, are too low to evoke late complications, but nevertheless, we should try to minimize the thyroid dose in children, whenever possible.

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Efficacy of Small Bowel Displacement System in Post-Operative Pelvic Radiation Therapy of Rectal Cancer (소장 용적 측정을 통한 직장암의 수술 후 방사선치료 시 사용하는 소장 전위 장치(Small Bowel Displacement System : SBDS) 의 효용성 검토)

  • Ahn Yong Chan;Lim Do Hoon;Kim Moon Kyung;Wu Hong Gyun;Kim Dae Yong;Huh Seung Jae
    • Radiation Oncology Journal
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    • v.16 no.1
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    • pp.63-69
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    • 1998
  • Purpose : This study is to evaluate the efficacy of small bowel displacement system(SBDS) in post-operative pelvic radiation therapy(RT) of rectal cancer patients by measurement of small bowel volume included in the radiation fields receiving therapeutic dose. Materials and Method : Ten consecutive new rectal cancer patients referred to the department of Radiation Oncology of Samsung Medical Center in May of 1997 were included in this study. All patients were asked to drink $Castrographin^(R)$ before simulation and were laid prone for conventional simulation and CT scans with and without SBDS. The volume of opacified small bowel on CT scans, which was to be included in the radiation fields receiving therapeutic dose, was measured using Picture archiving and communication system (PACS). Results : The average small bowel volumes with and without SBDS were 176.0ml(5.2-415.6ml) and 185.1ml(54.5-434.2ml), respectively The changes of small bowel volume with SBDS compared to those without SBDS were more than $10\%$ decrease in three, less than 10% decrease in two, less than $10\%$ increase in three, and more than $10\%$ increase in two patients. Conclusion : No significant advantage of using SBDS in post-operative pelvic RT for rectal cancer patients has been shown by small bowel volume measurement using CT scan considering additional effort and time needed for simulation and treatment setup.

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Feasibility of Reflecting Improvement of Tumor Hypoxia by Mild Hyperthermia in Experimental Mouse Tumors with $^18F-Fluoromisonidazole$ (저온온열치료에 의한 종양 내 저산소상태 개선효과를 $^18F$-Fluoromisonidazole의 섭취 변화를 이용한 평가)

  • Lee Sang-wook;Ryu Jin Sook;Oh Seung Joon;Im Ki Chun;Chen Gi Jeong;Lee So Ryung;Song Do Young;Im Soo Jeong;Moon Eun Sook;Kim Jong Hoon;Ahn Seung Do;Shin Seong Soo;Lee Kyeong Ryong
    • Radiation Oncology Journal
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    • v.22 no.4
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    • pp.288-297
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    • 2004
  • Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

Comparative Study of Cyclioxygenase-2 Expression and HER-2/neu Amplification in Korean and Caucasian Women with Early-Onset Breast Carcinoma (한국인과 백인 젊은 여성 유방암 환자에서 Cyclooxygenase-2 발현과 HER-2/neu 증폭의 비교 연구)

  • Choi, Doo-Ho;Kim, Eun-Seog;Kim, Yong-Ho;Jin, So-Young;Lee, Dong-Wha;Haffty, Bruce G.
    • Radiation Oncology Journal
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    • v.22 no.4
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    • pp.307-315
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    • 2004
  • Purpose: The purpose of this work was to study the differences of cyclooxygenase (COX-2) expression between Korean and Caucasian patients with early-onset breast carcinoma by immunohistochemistry. The test were analyzed to find a correlation between COX-2 and other biomarkers including HER-2/neu amplification, because we previously reported that a significant difference had been found in the expression of HER-2/neu between the two races. Furthermore, we investigated prognostic significance of COX-2 in korean patients. Materials and Methods: Sixty Korean women who were diagnosed breast carcinoma at 45 years old or younger and 60 Caucasian women with breast carcinoma were selected for this study. The median age of both groups was 37 years and tumor sizes were distributed evenly between the two group. Paraffin embedded blocks of primary tumor were processed for immunohistochemical staining of COX-2. The COX-2 expression was evaluated according to the percentage of positive cells and the intensity of staining. And the results were compared with the data of the previous studies to find correlation between COX-2 and other parameters and survival data. Results: Proportion of the COX-2 expression in total patients was $27.6\%$. The percentage of tumors that stained positive for COX-2 in korean and Caucasian women with early-onset breast carcinoma were $37.9\%$ and $20.8\%$, respectively. The difference was statistically not significant(p=0.090). Expression of COX-2 was not associated with several clinicopathologic parameters including HER-2/neu overexpression, but negative estrogen receptor status was correlated with significance (p=0.046). The 5 year disease free survival rate for patients with COX-2 expression was $67.9\%$, compared to $81.9\%$ of the COX-2 negative patients and the result was statistically not significant. Conclusions : A significant difference was not found in the expression of COX-2 between the two groups of patients with early-onset breast carcinoma. And correlation between COX-2 and other parameters was not observed except estrogen receptor negativity. Large scaled further research including radiotherapy factors will be needed to identify COX-2 as a prognostic role in patients with early-onset breast carcinoma.

Development of Respiration Gating RT Technique using Moving Phantom and Ultrasound Sensor: a feasibility study (동 팬텀과 초음파 센서를 이용한 호흡운동 조절 방사선치료 기술 개발)

  • Lee Suk;Lee Sang Hoon;Shin Dongho;Yang Dae Sik;Choi Myung Sun;Kim Chul Yong
    • Radiation Oncology Journal
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    • v.22 no.4
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    • pp.316-324
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    • 2004
  • Purpose : In radiotherapy of tumors in liver, enough planning target volume (PTV) margins are necessary to compensate breathing-related movement of tumor volumes. To overcome the problems, this study aims to obtain patients' body movements by using a moving phantom and an ultrasonic sensor, and to develop respiration sating techniques that can adjust patients' beds by using reversed values of the data obtained. Materials and Methods : The phantom made to measure patients' body movements is composed of a microprocessor (BS II, 20 MHz, 8K Byte), a sensor (Ultra-Sonic, range $3\~3$ m), host computer (RS232C) and stepping motor (torque 2.3 Kg) etc., and the program to control and operate it was developed. The program allows the phantom to move within the maximum range of 2 cm, its movements and corrections to take place In order, and x, y and z to move successively. After the moving phantom was adjusted by entering random movement data (three dimensional data form with distance of 2 cm), and the phantom movements were acquired using the ultra sonic sensor, the two data were compared and analyzed. And then, after the movements by respiration were acquired by using guinea pigs, the real-time respiration gating techniques were drawn by operating the phantom with the reversed values of the data. Results : The result of analyzing the acquisition-correction delay time the three types of data values and about each value separately shows that the data values coincided with one another within $1\%$ and that the acquisition-correction delay time was obtained real-time $(2.34{\times}10^{-4}sec)$. Conclusion : This study successfully confirms the clinic application possibility of respiration gating techniques by using a moving phantom and an ultrasonic sensor. With ongoing development of additional analysis system, which can be used in real-time set-up reproducibility analysis, it may be beneficially used in radiotherapy of moving tumors.

Hypofractionated Radiotherapy for Small-sized Hepatocellular Carcinoma as Salvage Therapy: Sustained Local Control and Safety (작은 크기의 재발성 간세포암에 대한 구제치료로 소분할 방사선치료: 국소 제어율과 안전성)

  • Bae, Sun-Hyun;Park, Hee-Chul;Lim, Do-Hoon;Lee, Jung-Ae;Choi, Moon-Seok;Lee, Joon-Hyoek;Koh, Kwang-Cheol;Paik, Seung-Woon;Yoo, Byung-Chul
    • Radiation Oncology Journal
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    • v.28 no.2
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    • pp.85-90
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    • 2010
  • 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.