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직장암에 수술 전 항암화학방사선 동시 병용요법 후 종양의 병리학적 반응에 영향을 주는 임상적 예측 인자

Clinical Factors Predicting the Pathologic Tumor Response after Preoperative Concurrent Chemoradiotherapy for Rectal Cancer

  • 이지혜 (이화여자대학교 의학전문대학원 방사선종양학교실) ;
  • 이경자 (이화여자대학교 의학전문대학원 방사선종양학교실)
  • Lee, Ji-Hae (Department of Radiation Oncology, School of Medicine, Ewha Womans University) ;
  • Lee, Kyung-Ja (Department of Radiation Oncology, School of Medicine, Ewha Womans University)
  • 발행 : 2008.12.31

초록

목 적: 직장암에 수술 전 항암화학요법과 방사선치료를 동시에 병용시행한 후 완치절제술 후 병리학적 완전관해율과 종양 병기 하향률에 영향을 주는 예측인자를 후향적으로 분석하여 환자에 따른 맞춤치료의 가능성을 알기 위하여 본 연구를 시도하였다. 대상 및 방법: 2000년 5월부터 2008년 3월까지 국소적으로 진행된 직장암으로 진단받고 원격전이가 없는 환자 39명을 대상으로 수술 전 항암화학요법과 골반강에 방사선치료 50.4 Gy ($45{\sim}59.4\;Gy$)를 시행한 후 완치적 수술후 절제된 조직을 병리학적으로 관찰하여 완전관해율과 종양 및 림프절의 병기하향률을 측정하였다. 항암화학요법은 39명 중 38명은 방사선치료 1주와 5주에 각각 1주간 5-fluorouracil과 leucovorin을 연속적으로 정맥 주입하였으며 1명은 방사선치료기간 중 하루에 2회 capecitabine를 복용하였다. 결 과: 병리학적 완전관해를 보인 환자는 39명 중 12명(31%), 종양-병기하향을 보인 환자는 24명(63%)이었으며 임상적으로 림프절이 양성인 환자 28명 중 12명은(43%) 병리학적으로 하향되었으며 2명은 임상적으로 림프절이 음성이었으나 병리학적으로 양성을 보였다. 단변량분석에 의하면 종양의 둘레범위가 직장의 50% 미만(p=0.031), 종양의 길이가 5 cm 미만(p=0.004), 치료 후 CEA 수치가 3.0 mg/mL 이하(p=0.015)인 환자에서 병리학적 완전관해율이 높았다. 또한 선암(p=0.045), 방사선량이 50 Gy 이상(p=0.021)인 환자에서 병기-하향률이 높았고, 방사선 치료 기간이 42일 이하인(p=0.018)환자에서 림프절-병기하향률이 높았다. 다변량분석에 의하면 종양의 둘레범위가 50% 미만(HR 0.150; p=0.028), 종양의 길이가 5 cm 미만인(HR 0.084; p=0.005) 환자에서 통계학적으로 유의하게 병리학적 완전관해율이 높았으며, 방사선량이 50 Gy 이상 높은 경우(HR 0.115; p=0.025) 종양-병기하향률이 높았고 방사선치료 기간이 42일 이하인(HR 0.028; p=0.010) 경우 림프절-병기하향률이 높았다. 병리학적 완전관해에 영향을 주는 예측인자는 종양의 둘레범위와 종양의 길이이었으며, 종양-병리하향에 영향을 주는 예측인자는 방사선량, 림프절-병기하향에 영향을 주는 예측인자는 방사선치료 기간이었다. 이러한 예측인자를 파악함으로써 환자의 치료결과를 예측할 수 있으며 위험인자가 있는 환자에 좀 더 적극적인 치료계획을 설정하는 데 도움이 될 것으로 생각한다.

Purpose: The objective of this retrospective study was to identify predictive factors for the complete pathologic response and tumor downstaging after preoperative concurrent chemoradiotherapy for locally advanced rectal cancer. Materials and Methods: Between the years 2000 and 2008, 39 patients with newly diagnosed rectal cancer without prior evidence of distant metastasis received preoperative concurrent chemoradiotherapy followed by surgery. The median radiation dose was 50.4 Gy (range, $45{\sim}59.4\;Gy$)). Thirty-eight patients received concurrent infusional 5-fluorouracil and leucovorin, while one patient received oral capecitabine twice daily during radiotherapy. Results: A complete pathologic response (CR) was demonstrated in 12 of 39 patients (31%), while T-downstaging was observed in 24 of 39 patients (63%). N-downstaging was observed in 18 of 28 patients (64%), with a positive node in the CT scan or ultrasound. Two patients with clinical negative nodes were observed in surgical specimens. The results from a univariate analysis indicated that the tumor circumferential extent was less than 50% (p=0.031). Moreover, the length of the tumor was less than 5 cm (p=0.004), while the post-treatment carcinoembryonic antigen (CEA) levels were less than or equal to 3.0 ng/mL (p=0.015) and were significantly associated with high pathologic CR rates. The univariate analysis also indicated that the adenocarcinoma (p=0.045) and radiation dose greater than or equal to 50 Gy (p=0.021) were significantly associated with high T-downstaging, while a radiotherapy duration of less than or equal to 42 days (p=0.018) was significantly associated with N-downstaging. The results from the multivariate analysis indicated that the lesser circumferential extent of the tumor (hazard ratio [HR] 0.150; p=0.028) and shorter tumor length (HR, 0.084; p=0.005) independently predicted a higher pathologic CR. The multivariate analysis also indicated that a higher radiation dose was significantly associated with higher T-downstaging (HR, 0.115; p=0.025), while the shorter duration of radiotherapy was significantly associated with higher N-downstaging (HR, 0.028; p=0.010). Conclusion: The circumferential extent of the tumor and its length was a predictor for the pathologic CR, while radiation dose and duration of radiotherapy were predictors for tumor downstaging. Hence, these factors may be used to predict outcomes for patients and to develop further treatment guidelines for high-risk patients.

키워드

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