Locally Advanced, Unresectable Pancreatic Cancer Treated by Stereotactic Radiation Therapy

Chul-Won Choi(최철원),Mi-Sook Kim(김미숙),Chul-Koo Cho(조철구),Seong-Yul Yoo(류성열),Kwang-Mo Yang(양광모),Hyung-Jun Yoo(유형준),Dong-Han Lee(이동한),Young-Hoon Ji(지영훈),Chul-Ju Han(한철주),Jin Kim(김진),Young-Han Kim(김영한) 대한방사선종양학회 2006 Radiation Oncology Journal Vol.24 No.1

목 적: 국소적으로 진행된, 절제 불가능한 췌장암 치료에 있어 고식적 방사선 치료와 비교하여 CyberKnife (CK)를 이용한 정위 방사선 치료의 생존율 및 급성 독성에 대해 분석하고자 하였다. 대상 및 방법: 2003년 4월부터 2004년 4월까지의, Eastern Cooperative Oncology Group (ECOG) 활동도 3 이하이며 CT 및 PET/CT로 평가하여 원격 전이 없는 국소 진행된 췌장암 환자 19명을 대상으로 하였다. 대상 환자는 점차 방사선량을 증가시키는 방법으로 33 Gy, 36 Gy, 39 Gy를 3분할로 각각 6명, 4명, 9명에서 CK를 이용한 정위 방사선 치료를 시행하였으며, 생존율 및 Radiation Therapeutic Oncology Group (RTOG) acute radiation morbidity criteria에 의한 위장관 독성을 분석하였다. 또한 나이, 성별, ECOG 수행 점수, 항암 치료,우회로 조성술(bypass surgery) 여부, 방사선량, CA19-9, 계획용 표적 체적(planning target volume, PTV), CT상 주위 장기 및 혈관 침범 여부 등을 Log Rank test를 이용하여 예후 인자를 평가하였다.결 과: 본 연구에서 중앙 생존 기간은 11개월, 1년 생존율은 36.8%였다. 추적 조사 기간 중(범위 3∼20개월, 중앙값 10개월) 유의한 위장관 급성 독성은 관찰되지 않았다. 단일 인자 분석에서 계획용 표적 체적만이 유의한 예후 인자로 80 cc 이하인 경우가 80 cc 이상인 경우보다 생존율이 높았으며(p-value<0.05), 나이, 성별, ECOG 수행 점수, 항암 치료, 우회로 조성술, CA19-9 수치, 주위 장기 및 혈관 침범 여부 등에서는 통계적으로 유의한 차이를 보이지 않았다. 다인자 분석에서는 65세 이하인 경우와 PTV 80 cc 이하인 경우에서 생존율이 높았다. 결 론: 고식적 방사선 치료, 고선량 입체조형 방사선 치료(high dose conformal radiation therapy), 수술 중 방사선 치료(intraoperative radiation therapy) 또는 세기 조절 방사선 치료(intensity modulated radiation therapy, IMRT)를 이용한 최근의 결과와 비교하여 CK를 이용한 정위 방사선 치료는 생존율 측면에서 비슷하거나 나은 결과를 보였다. 또한 심각한 부작용은 관찰되지 않았으며 짧은 기간의 치료로 환자에게 편의를 제공할수 있어 결과적으로 삶의 질을 향상시킬 수 있을 것이다. 따라서, 이 새로운 치료 방법은 국소 진행된, 절제불가능한 췌장암 환자에서 심각한 부작용 없는 효과적인 치료가 될 것으로 생각된다. 또한 계획용 표적 체적은 CK 치료의 유용한 예후 인자로 사용될 것이다. Purpose: In order to find out whether stereotactic radiation therapy (RT) using CyberKnife (CK) could improve survival rate and lower acute toxicity compared to conventional RT. Materials and Methods: From April 2003 through April 2004, 19 patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤3 and locally advanced pancreas cancer without distant metastasis, evaluated by CT or PET/CT, were included. We administered stereotactic RT consisting of either 33 Gy, 36 Gy or 39 Gy in 3 fractions to 6, 4 and 9 patients, respectively, in an effort to increase the radiation dose step by step, and analyzed the survival rate and gastrointestinal toxicities by the acute radiation morbidity criteria of Radiation Therapeutic Oncology Group (RTOG). Prognostic factors of age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA19-9, planning target volume (PTV), and adjacent organ and vessel invasion on CT scan were evaluated by Log Rank test. Results: The median survival time was 11 months with 1-year survival rate of 36.8%. During follow-up period (range 3∼20 months, median 10 months), no significant gastrointestinal acute toxicity (RTOG grade 3) was observed. In univariate analysis, age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA19-9 level, and adjacent organ and vessel invasion did not show any significant changes of survival rate, however, patients with PTV (80 cc showed more favorable survival rate than those with PTV>80 cc (p-value<0.05). In multivariate analysis, age younger than 65 years and PTV>80 cc showed better survival rate. Conclusion: In terms of survival, the efficacy of stereotactic radiation therapy using CK was found to be superior or similar to other recent studies achieved with conventional RT with intensive chemotherapy, high dose conformal RT, intraoperative RT (IORT), or intensity modulated RT (IMRT). Furthermore, severe toxicity was not observed. Short treatment time in relation to the short life expectancy gave patients more convenience and, finally, quality of life would be increased. Consequently, this could be regarded as an effective novel treatment modality for locally advanced, unresectable pancreas cancer. PTV would be a helpful prognostic factor for CK.

만성 B형 간염에 대한 Thymosin의 효과

한철주(Chul Ju Han),이효석(Hyo Suk Lee),김정룡(Chung Yong Kim) 대한소화기학회 1996 대한소화기학회지 Vol.28 No.1

N/A Background/Aims: Chronic hepatitis B is a common and progressive disease, but a satisfactory antiviral therapy has not been developed. Thymosin al(TQ1) was reported to be effective for chronic hepatitis B with few side effects. We planned pilot trial to evaluate the efficacy of Tal for patients in Korea, a HBV endemic area. Methods: A small scale prospective randomized controlled trial was performed. Seventeen patients who had been clinica]ly diagnosed as chronic hepatitis B and positive for HBeAg were enrolled and randomly a.;signed to either treated or control group. Nine patients in treated group received Tal 1.6 mg twice a week for 24 weeks, and 8 patients in control group were just followed up. Serum HI3eAg, anti-Hbe, HBV DNA, liver function tests were done rnonthly. The criteria for response was defined as loss of HBeAg, HBV DNA and near normalization of ALT at the completion of therapy(at 6th month). After the end of therapy patients were followed up for 18 months. Results: Initially no difference in age, sex, ALT, HBV DNA level between treated and control group was noticed. Serum HBV DNA concentration was less than 250 pg/ml in 44%(4/9) of treated group. In treated group the response rate was 11%(1/9) at best which was not statistically different from that of control(13%; 1/8). The ALT level of treated group decreased during 18 months follow-up after the completion of therapy, but it was not statistically different from that of control group. Cirrhotic progression was noticed in 44%(4/9) of treated patients. Conclusions: These findings suggest that thymosin does not have a remarkable effect on chronic hepatitis B in a hepatitis B endemic area. (Korean J Gastroenterol 1996;28: 66-73)

간세포암종에서 전신항암화학요법의 최신 지견 (해설논문)

한철주 ( Chul Ju Han ) 대한간학회 2008 Clinical and Molecular Hepatology(대한간학회지) Vol.14 No.1

최신 연구 소개 : HBsAg 정량검사가 만성 B형간염에 대한 항바이러스제 치료종료 후 지속적 치료반응을 예측할 수 있을까?

한철주 ( Chul Ju Han ) 대한소화기학회 2011 대한소화기학회지 Vol.58 No.6

이 연구는 telbivudine을 투여받은 만성 B형간염 환자들에서 치료 중 혈청 HBsAg 농도가 치료 종료 후 지속적인 치료반응(sustained response, SR)을 예측할 수 있는지를 규명하고자 하였다. 17명의 만성 B형간염 환자를 후향적으로 분석하였는데, 환자들은 104주 간 매일 600 mg의 telbivudine을 투여 받았으며, 치료 중 및 치료 종료 후 혈청 hepatitis B Virus (HBV) DNA와 HBsAg을 주기적으로 측정하였다. 측정 시점은 치료 전, 치료 중 24주, 52주, 104주, 치료 종료 후24주, 52주, 76주, 104주였다. 치료 종료 시점에서 HBsAg<2log10 IU/mL이면, 치료 종료 2년 후의 SR을 정확히 예측하였는데, 양성 예측도(positive predictive value, PPV)는 93%, 음성 예측도(negative predictive value, NPV)는 100%였다. 또한 재발 없이 SR을 유지한 환자에서만 치료 종료 후 2년간 혈청 HBsAg 농도가 꾸준히 하락하는 소견을 보였다. 치료중 24주 및 52주째의 혈청 HBsAg 감소율은 동 시점에서의 혈청 HBV DNA 감소율보다 더 우수한 SR의 예측지표였는데, 24주째 HBsAg 감소율이 0.8 log10 IU/mL 이상이면 PPV 75%, NPV 86%였고, 52주째 HBsAg 감소율이 1 log10 IU/mL 이상이면 PPV 75%, NPV 86%였다. 따라서 이 연구를 통해 telbivudine으로 치료를 받은 만성 B형간염 환자에서 치료 종료 시점에서의 혈청 HBsAg 농도가 SR의 강력한 예측지표이며, 치료 중 24주째 및 52주째 혈청 HBsAg 감소율이 혈청 HBV DNA 감소율에 비해 더 나은 SR의 예측지표임을 알 수 있었다. On-treatment serum HBsAg level is predictive of sustained off-treatment virologic response to telbivudine in HBeAg-positive chronic hepatitis B patients. (J Clin Virol 2010;48:22-26)

간세포암종의 새로운 치료: Systemic therapy : 전신항암화학요법

한철주 ( Chul Ju Han ) 대한간학회 2008 Clinical and Molecular Hepatology(대한간학회지) Vol.14 No.2(S)

간외 전이로 처음 발견된 간세포암종 간외 전이가 있는 간세포암종에 대한 systemic doxorubicin-cisplatin (AP) 감량요법 후 완전 관해에 도달한 2예

남승범 ( Seung Bum Nam ),한철주 ( Chul Ju Han ),이호진 ( Ho Jin Lee ),김연주 ( Youn Joo Kim ),양기영 ( Ki Young Yang ),박수철 ( Su Cheol Park ),김진 ( Jin Kim ),김유철 ( Yu Cheol Kim ) 대한간암학회 2010 대한간암학회지 Vol.10 No.-

The effect of systemic chemotherapy in patients with advanced HCC is very limited, not only in regard to poor response to cytotoxic chemotherapeutic agents but also poor tolerance to therapy and related adverse effects. Herein, we report two cases of hepatocellular carcinoma (HCC) with extrahepatic metastasis who achieved complete remission following administration of doxorubicin and cisplatin in reduced dosage. The first case was a 41-year-old male who had HCC with multiple lung and intraabdominal lymph nodes metastasis. After 9 cycles of chemotherapy with 50% reduced dosage, he achieved a complete remission of both primary and metastatic lesions. He showed no evidence of disease for 11 more months during follow-up and still lives without recurrence. The second case was a 61-year-old female who had HCC with inferior vena cava thrombosis and multiple lung metastasis. After one cycle of treatment with 25% reduced dosage, she underwent life-threatening toxicities and poor tolerance to chemotherapy and further treatment was discontinued. However, she achieved a complete remission of both primary and metastatic lesions. Following 26 months of recurrence free period, she suffered from a recurrent tumor near previously treated lesion, which was successfully treated by TACE and radiation therapy. This modified doxorubicin and cisplatin regimen in reduced dosage could be used as means of evading life threatening toxicity and selecting out responders to systemic chemotherapy with reduced risk.

간세포암종에 대한 Cyberknife 치료 후 완전관해가 왔던 환자에서 하반신 마비가 발생한

노금엽 ( Geum Youb Noh ),한철주 ( Chul Ju Han ),김연주 ( Youn Joo Kim ),양기영 ( Ki Young Yang ),박수철 ( Su Cheol Park ),김진 ( Jin Kim ),김유철 ( Yu Cheol Kim ),김미숙 ( Mi Sook Kim ) 대한간암학회 2011 대한간암학회지 Vol.11 No.2

Radiation therapy (RT) is one of the managements for unresectable hepatocellular carcinoma (HCC). Traditionally, RT has played only a limited role in HCC treatment because of its low efficacy and the low tolerance of the liver for this modality. However, as the technology of RT grows rapidly in recent years, indication of RT for HCC has been extended remarkably. Stereotactic body radiation therapy (SBRT) is a technique that allows precise delivery of a large ablative radiation dose to the tumor while sparing normal surrounding tissue in 1 to 5 fractions. As RT becomes useful therapeutic strategy, the important problem is that there could be serious complication after RT. Here we present a case of 54 years old male with advanced stage of HCC, who underwent a serious neurologic complication of paraplegia following Cyberknife (CK) treatment. He had a huge HCC in right lobe of the liver, and initially transarterial chemoembolization (TACE) was performed with an unsatisfactory response. Therefore, CK was performed, and another TACE was done for a new lesion, which was followed by remarkable complete remission of the tumor. However, paraplegia developed in both of his lower extremities a year after CK. Investigation has shown radiation myelitis as the cause of paralysis. Three and a half years have passed since CK treatment, and HCC is still in complete remission state, however, paraplegia is persistent now. Radiation myelitis should be considered as a complication, when CK is applied to treatment of HCC.

C 형 만성 간질환 환자에서 혈청 Alanine Aminotransferase 치와 혈청 C 형 간염 바이러스 개체수와의 관계

유권(Kwon Yoo),한철주(Chul Ju Han),이효석(Hyo Suk Lee),김정룡(Chung Yong Kim) 대한내과학회 1995 대한내과학회지 Vol.49 No.4

N/A Objectives: We studied the correlation between HCV RNA titer and level of log(ALT) in chronic hepatitis C to know the pathogenetic role of HCV, using heminested reverse transcription-polymerase chain reaction and end point dilution method with standard internal control HNA. Methods: Fifty-two patients with chronic hepatitis C were enrolled and their serum HCV RNA were detected by heminested reverse transcription-polymerase chain reaction and serum HCV RNA concentrations were quantitated by end point dilution method using mutated HCV RNA molecule as a standard internal control. Results: 1) Detection limit of HCV RNA titer by our heminested RT-PCR method was 10'copies/ml. 2) HCV RNA was detected in the sera of 31patients with chronic hepatitis C(59.6%) 3) The serum HCV RNA concentration showed wide range of distribution from 10(3) to 10(11)copies/ml. 4) There was no significant correlation bet ween HCV RNA titer and level of log(ALT). Conclusion: This suggests that the direct cytopathic effect of HC:V, if present, is less likely to be the main mechanism of liver injury in chronic hepatitis C.

TACE와 Sorafenib 치료 후 수술을 시행한 간세포암종

노금엽 ( Geum Youb Noh ),한철주 ( Chul Ju Han ),김연주 ( Youn Joo Kim ),양기영 ( Ki Young Yang ),박수철 ( Su Cheol Park ),김진 ( Jin Kim ),김유철 ( Yu Cheol Kim ),최윤희 ( Yoon Hee Choi ),이효락 ( Hyo Rak Lee ) 대한간암학회 2011 대한간암학회지 Vol.11 No.1

Surgical resection for hepatocellular carcinoma (HCC) is one of the managements, showing improved long term survival. Nowadays, it is being accepted as the main curative treatment. However, the biggest problem we used to face is that surgery cannot be applied at the point of presentation in many patients due to advanced stage. Here we present a case of 54 years old female, who had transarterial chemoembolization (TACE) and sorafenib due to advanced stage of HCC, and later underwent curative surgery due to remarkable response. She had a CT scan of abdomen, which showed multiple huge masses. HCC was confirmed by ultrasonography-guided liver biopsy. TACE was performed once. After TACE, the size of masses increased. Therefore, sorafenib was administered and then continued for 9 months. As partial response was obtained at that time, surgical resection was successfully done. In the pathological report of removed tumor, we could confirm total necrosis of tumor. Now, it`s been 6 months and she is followed up without any recurrence.

위암 발견에 있어 철결핍 지표들의 유용성

정진모(Jin Mo Jung),한철주(Chul Ju Han),홍영준(Young Joon Hong),조현호(Hyun Ho Cho),김영호(Young Ho Kim),최대현(Dae Hyun Choi),조상형(Sang Hyung Cho),조광희(Kwang Hee Cho),김진(Jin Kim),정숙향(Sook Hyang Jung),김유철(You Choul Kim) 대한소화기학회 2002 대한소화기학회지 Vol.39 No.3

Background/Aims: Cancers of the gastrointestinal tract might cause chronic occult blood loss leading to iron deficiency. The aim of this study was to determine the usefulness of the tests for iron deficiency in detection of stomach cancer. Methods: Seventy one patients with advanced gastric cancer (AGC), 13 patients with early gastric cancer (EGC), and 104 patients with functional GI disorder (FGID) as a control were consecutively enrolled in this study. The test results for iron-deficiency parameters such as hemoglobin, serum ferritin, serum iron, total iron binding capacity, and transferrin-saturation rates were compared among the groups. Incidence of iron deficiency or anemia was compared among the groups. Results: The levels of hemoglobin, serum ferritin, serum iron, and the rates of transferrin saturation were significantly lower in the AGC group than in the control group. These differences were even marked in male patients. They were not significantly different between the EGC group and the control group. In male patients with AGC, the incidence of anemia or iron deficiency was markedly higher than the control group. Conclusions: In males over 50 years, tests for iron-deficiency parameters such as hemoglobin, serum ferritin, serum iron, and transferrin saturation might be helpful in detection of AGC. Further study is needed to reveal whether these tests are helpful in the early detection of stomach cancer. (Korean J Gastroenterol 2002;39:179-185)