Association between pathologic response in metastatic lymph nodes after preoperative chemoradiotherapy and risk of distant metastases in rectal cancer: An analysis of outcomes in a randomized trial

Journal Article · Thu Feb 01 04:00:00 EST 2007 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2006.08.065· OSTI ID:20944675

Bujko, Krzysztof ^[1]; Michalski, Wojciech M.S. ^[2]; Kepka, Lucyna ^[1]; Nowacki, Marek P ^[3]; Nasierowska-Guttmejer, Anna ^[4]; Tokar, Piotr ^[5]; Dymecki, Dariusz ^[6]; Pawlak, Mariusz ^[7]; Lesniak, Tadeusz ^[8]; Richter, Piotr ^[9]; Wojnar, Andrzej ^[10]; Chmielik, Ewa ^[11]

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1. Department of Radiotherapy, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw (Poland)
2. Department of Biostatistics, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw (Poland)
3. Department of Colorectal Cancer, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw (Poland)
4. Department of Pathology, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw (Poland)
5. Department of Radiotherapy, Oncological Center, Opole (Poland)
6. Department of Surgery, Medical Academy, Gdansk (Poland)
7. Department of Surgery, Oncological Center, Lodz (Poland)
8. Department of Surgery, Oncological Center, Bielsko Biala (Poland)
9. Department of Surgery, Medical Academy, Krakow (Poland)
10. Department of Pathology, Silesian Oncological Center, Wroclaw (Poland)
11. Department of Pathology, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice (Poland)

Purpose: To compare 5 x 5 Gy preoperative radiotherapy with immediate surgery vs. preoperative chemoradiotherapy (50.4 Gy, 5-fluorouracil, leucovorin) with delayed surgery in a randomized trial for cT3-T4 low-lying rectal cancer. Despite the downstaging effect of chemoradiotherapy, similar long-term outcomes were observed in both groups. Methods: The Cox model was used to evaluate the prognostic value of ypTN ('yp' denotes that pathologic classification was performed after initial multimodality therapy) categories and the surgical margin status in 291 patients. Results: Disease-free survival (DFS) (hazard ratio [HR] 1.05, 95% confidence interval [CI], 0.73-1.51), distant metastases (HR, 1.17; 95% CI, 0.77-1.78), and local control (HR, 1.45; 95% CI, 0.74-2.84) were similar in both arms. The ypN status was the only independent prognostic factor for DFS (p < 0.001). An interaction (p = 0.016) between N stage and the assigned treatment was demonstrated. For ypN-negative patients, DFS was similar in both arms (HR, 0.83, 95% CI, 0.47-1.48); however, for ypN-positive patients, DFS was worse in the chemoradiotherapy arm (HR, 1.73; 95% CI, 1.07-2.77). The 4-year (median follow-up) DFS rate in N-positive patients was 51% in the 5 x 5-Gy arm vs. 25% in the chemoradiotherapy arm. The corresponding 4-year rates for the incidence of local recurrence and distant metastases were 14% vs. 27% (HR, 1.95; 95% CI, 0.78-4.86) and 38% vs. 68% (HR, 2.05; 95% CI, 1.21-3.48). Conclusion: N-positive disease after chemoradiotherapy indicates radiochemoresistance. N-positive disease after 5 x 5 Gy RT includes both radiosensitive and radioresistant tumors, because the interval between radiotherapy and surgery was too short for radiosensitive cancer to undergo necrosis. Thus, the greater risk of distant metastases recorded in the chemoradiotherapy arm suggests that radiochemoresistance of nodal metastases from rectal cancer is associated with a high potential for developing distant metastases.

• OSTI ID: 20944675
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 2 Vol. 67; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CARCINOMAS
CITROVORUM FACTOR
CLASSIFICATION
COMBINED THERAPY
HEALTH HAZARDS
LYMPH NODES
METASTASES
NECROSIS
PATIENTS
RADIOTHERAPY
RECTUM
SURGERY
URACILS