삼차신경통에 대한 사이버나이프 방사선수술의 조기 치료 효과

문성권(Seong Kwon Mun),최병옥(Byung Ock Choi),최일봉(Ihl Bohng Choi),강영남(Young Nam Kang),장지선(Ji Sun Jang),강기문(Ki Mun Kang) 대한방사선종양학회 2006 Radiation Oncology Journal Vol.24 No.2

목 적: 삼차신경통 환자에서 사이버나이프 방사선수술이 효과적이며 안전한 치료방법인지 알아보고자 하였다. 대상 및 방법: 2004년 3월부터 2005년 5월까지 수술 후 실패하였거나 수술이 부적합한 삼차신경통 환자 26명을 대상으로 사이버나이프 방사선수술을 시행하여 후향적 분석을 하였다. 치료 표적은 삼차신경근 진입구역으로부터 3 mm 떨어진 지점의 삼차신경 최고 근위부를 제외한 6 mm 길이의 삼차신경 부위를 설정하고, 그 부위에 80% 등선량 곡선에 단일 조사로 총방사선량은 60∼64 Gy를 조사하였다(중앙선량: 64 Gy). 결 과: 추적관찰기간은 3∼15개월이었다(중앙추적관찰기간 : 9개월). 대상환자 26명에서 사이버나이프 방사선 수술 후 24시간 이내에 50% (13/26)에서 통증 완화를 관찰하였으며. 7일 이내에 조기 통증 완화를 보였던 환자는 96.2% (25/26)이었다. 치료 실패는 7.7% (2/26)에서 나타났으며 통증 개선 실패와 통증 재발이 각각 1명에서 관찰되었다. 치료 부작용으로 안면감각 감퇴가 11.5% (3/26)에서 관찰되었다. 결 론: 삼차신경통 환자를 대상으로 사이버나이프 방사선수술을 시행한 예비 결과로 비교적 안전하며, 효과적인 치료임을 확인하였다. Purpose: We evaluated whether Cyberknife radiosurgery is an effective and safe method of therapy for medically intractable trigeminal neuralgia (TN). Materials and Methods: We retrospectively analyzed the outcome of 26 patients, who failed to surgery or were not suitable candidates for invasive intervention and were treated by Cyberknife radiosurgery between March 2004 and May 2005. Radiosurgery doses of 60∼64 Gy were delivered to the 80% isodose line prescribed to an 6 mm length of the nerve, sparing the most proximal 3 mm away from the trigeminal nerve root entry zone (median dose: 64 Gy). Results: Follow-up period was 3∼15 months (median follow-up period: 9 months) Preliminary results from a cohort of 26 patients undergoing Cyberknife radiosurgery for TN showed that pain relief was achieved in 50% (13/26) of patients within the first 24 hrs after treatment. At last follow-up, 96.2% (25/26) of patients reported early pain relief within 7 days. Treatment failure developed in 2 of 26. Poor response occurred in one patient and relapse was observed in the other patient. 3 patients had hypoesthesia (11.5%), which was the only complication observed with any of our patients. Conclusion: With these results, authors assumed that Cyberknife radiosurgery for TN could be one of safe and effective therapeutic methods.

인간 유방암 세포 이식마우스에서 EGFR/HER2 복합 Tyrosine Kinase 억제제인 GW572016에 의한 방사선증진효과

김연실(Yeon Sil Kim),노광원(Kwang Won Roh),채수민(Soo Min Chae),문성권(Seong Kwon Mun),윤세철(Sei Chul Yoon),장홍석(Hong Seok Jang),정수미(Su Mi Chung) 대한방사선종양학회 2007 Radiation Oncology Journal Vol.25 No.4

목 적: EGFR, HER2 과발현 인간 유방암 세포를 이용한 종양이식 마우스에서 EGFR/HER2 복합 Tyrosine Kinase 억 제제인 GW572016이 방사선반응성에 미치는 영향을 알아보고 종양조직의 EGFR/HER2 수용체 억제효과 및 EGFR down stream signal pathway 단백인 ERK 1/2, PI3K/Akt 억제효과를 알아 보고자 하였다. 대상 및 방법: SUM 102와 SUM 149 EGFR 과발현 세포와 SUM 185, SUM 225 HER2 과발현 세포를 우측 옆구리 피하에 접종하여 종양이식마우스를 만들었다. 이식마우스는 2군으로 나누어 한 군은 GW572016에 의한 EGFR/HER2 수용체 억제와 down stream signal 단백의 활성변화를 Immunoprecipitation과 Western blot의 방법을 사용하여 관찰하였고 다른 한군은 GW572016에 의한 방사선감수성 변화를 알아보기 위해 1) 대조군, 2) GW572016 단독군, 3) 방사선단독군, 4) GW572016+방사선병용투여군으로 나누어 종양성장을 비교 관찰하였다. 결 과: GW572016에 의해서 SUM 149, SUM 185 이식종양에서 EGFR 및 HER2 수용체의 활성이 억제되었으며 특히 SUM 185, HER2 과발현 이식종양에서는 ERK 1/2 down stream 단백의 활성도 억제되었다. SUM 225 HER2 과발현 이식종양에서는 이전의 in vitro실험에서와 달리 GW572016에 의해 HER2수용체의 활성변화가 없었으나 ERK 1/2, Akt의 활성은 모두 억제되었다. GW572016에 의해 SUM 149과 SUM 185에서 종양성장억제효과가 관찰되었고 특히 SUM 149에서는 GW572016과 방사선치료병용군에서 종양성장억제효과가 좀더 뚜렷하여 방사선감수성을 증가시키는 것으로 생각되었다. 결 론: GW572016은 EGFR 혹은 HER2 과발현 유방암세포에서 EGFR/HER2 수용체 억제와 down stream signal 단백의 활성을 억제시켰으며 SUM 149에서는 방사선감수성을 증가시키는 것으로 생각된다. 향후 EGFR을 표적으로 하는 억제제치료에서 EGFR 수용체억제뿐 아니라 down stream 단백의 활성억제 여부가 방사선 감수성 및 저항성의 극복과 관련이 있으리라는 근거를 설명할 수 있으며 향후 좀더 깊이 있는 연구가 필요하다. Purpose: We examined the effect of the dual EGFR/HER2 tyrosine kinase inhibitor, GW572016, on EGFR/HER2 receptor phosphorylation, inhibition of downstream signaling and radiosensitization in either an EGFR or HER2 overexpressing human breast cancer xenograft. Materials and Methods: We established SCID mice xenografts from 4 human breast cancer cell line that overexpressed EGFR or HER 2 (SUM 102, SUM 149, SUM 185, SUM 225). Two series of xenografts were established. One series was established for determining inhibition of the EGFR/HER2 receptor and downstreamsignaling activities by GW572016. The other series was established for determining the radiosensitization effect of GW572016. Inhibition of the receptor and downstream signaling proteins were measured by the use of immunoprecipitation and Western blotting. For determining the in vivo radiosensitization effect of GW572016, we compared tumor growth delay curves in the following four treatment arms: a) control; b) GW572016 alone; c) radiotherapy (RT) alone; d) GW572016 and RT. Results: GW572016 inhibited EGFR, HER2 receptor phosphorylation in SUM 149 and SUM 185 xenografts. In addition, the p44/42 MAPK (ERK 1/2) downstream signaling pathway was inactivated by GW572016 in the SUM 185 xenograft. In the SUM 225 xenograft, we could not observe inhibition of HER2 receptor phosphorylation by GW572016; both p44/42 MAPK (Erk1/2) and Akt downstream signal protein phosphorylation were inhibited by GW572016. GW572016 inhibited growth of the tumor xenograft of SUM 149 and SUM 185. The combination of GW572016 and RT enhanced growth inhibition greater than that with GW572016 alone or with RT alone in the SUM 149 xenograft. GW572016 appears to act as an in vivo radiosensitizer. Conclusion: GW572016 inhibited EGFR/HER2 receptor phosphorylation and downstream signaling pathway proteins. GW572016 modestly inhibited the growth of tumor in the SUM 185 xenograft and showed radiosensitization in the SUM 149 xenograft. Our results suggest that a better predictor of radiation response would be inhibition of a crucial signaling pathway than inhibition of a receptor.

국소 진행된 비인강암의 방사선-항암제 병용요법

손석현(Seok Hyun Son),김지윤(Ji Yoon Kim),김연실(Yeon Sil Kim),김성환(Sung Whan Kim),문성권(Seong Kwon Mun),조승호(Seung Ho Cho),박영학(Young Hak Park),홍영선(Young Seon Hong) 대한두경부종양학회 2006 대한두경부 종양학회지 Vol.22 No.2

Objective :This retrospective study was designed to evaluate the anti-tumor efficacy and toxicities of the radia-tion therapy(RT) combined with cisplatin-based chemotherapy in locally advanced nasopharyngeal cancer(NPC). Materials and Methods :Fifty three patients with locally advanced NPCs(AJCC stage II, III, IV) received curative RT and cisplatin-based chemotherapy. Duration of follow-up ranged from 5.5 to 201 months(median 50.8 months). Nineteen patients(35.8%) were treated with induction chemotherapy including cisplatin 100mg/m 2 for 1 day and 5-fluorouracil 1g/m 2 for 5 days followed by RT(Induction CTx-RT). Another 34 patients (64.2%) were treated with concurrent chemoradiation(CCRT) using cisplatin 100 mg/m 2 (D1, 22, 43). Results :Thirty-six(67.9%) and 11(20.8%) patients achieved clinical complete response and partial response, respectively. The pattern of failure was as follows:14 locoregional recurrence(26.4%) and 7 distant metastasis (13.2%). Among them, two patients(3.8%) had both locoregional and distant failure. Median overall survival (OS) and progression-free survival(PFS) were 85.5 months and 87.5 months, respectively. Five-year OS rate was 57.1%. The stage(AJCC), tumor response to chemoradiation and T stage were significant prognostic fac-tors for OS(p=0.0113, p=0.0362 and p=0.0469). The stage(AJCC), tumor response to chemoradiation were also significant prognostic factors for PFS(p=0.0329, p=0.0424). Compared to each treatment group(Induction CTx-RT vs. CCRT), there were no significant differences in OS and PFS(p=0.7000, p=0.8261). Grade 3-4 mucositis, nausea/vomiting and hematological toxicities were noticed in 35.8%, 11.3% and 13.2%, respec-tively. Delayed RT over 2 weeks was inevitable in 26.5%. Seventeen patients(50%) successfully completed planned 3 courses of cisplatin in CCRT group. Conclusions :RT combined with cisplatin-based chemotherapy in locally advanced NPC showed high res-ponse rate, good locoregional control, and survival rate. As expected, frequency of acute toxicities increased, and the patient’s compliance to treatment was need to be improved. Although our data could not show additional survival benefit of CCRT compare to that of induction chemotherapy followed by RT, patients’ accrual and further follow-up are required due to limitation of retrospective study.