PURPOSE Preoperative chemoradiation therapy for rectal cancer seems to improve local control, anal sphincter preservation, resectability, and possibly survival in patients. However, there are several adverse effects, too.
The aim of this study is to analyze the disadvantages of preoperative chemoradiation for rectal cancer. METHODS We retrospectively reviewed 139 patients who were treated by using preoperative chemoradiation for an adenocarcinoma of the rectum between January 1995 and December 2004. All patients had fixed or locally advanced lesions, as determined by digital rectal examination. No distant metastasis was proven before preoperative chemoradiation. All of the patiedts received the full scheduled dose of radiation (range, 5,000~5,400 rad).
Concurrent intravenous chemotherapy with 5-fluorouracil (425 mg/m2/day) and leucovorin (45 mg/day) was administered continuously on days 1~5 and 29~33. The mean interval between chemoradiation and surgery was 4~6 weeks. After preoperative chemoradiation, 117 patients underwent an operation. We reviewed the side effects of preoperative chemoradiation, postoperative complications, and distant metastases detected during the preoperative period after preoperative chemoradiation and during the operation. RESULTS The side effects of preoperative chemoradiation were diarrhea (23%), radiation dermatitis (2.2%), fistula (0.7%), sepsis (0.7%), and rectal bleeding (0.7%). Two patients died from sepsis and rectal bleeding. The postoperative complications were bowel obstruction in 9 cases (7.7%), wound seroma in 8 cases (6.8%), wound infection in 5 cases (4.3%), anastomotic leakage in 5 cases (7.1%), rectovaginal fistula in 2 cases (2.8%), an enterocutaneous fistula in 2 cases (1.7%), and a vesicocutaneous fistula in 1 case (0.8%). Distant metastases were detected in 14 patients (10.1%) after preoperative chemoradiation. CONCLUSIONS Although preoperative chemoradiation can be performed safely, careful management for the side effects of preoperative chemoradiation and for postoperative complications is necessary. We need a more sensitive study method for detecting distant metastasis of rectal cancer, especially during scheduled preoperative chemoradiation.
PURPOSE The conventional surgical treatment for patients with potentially curable low rectal cancer is abdominoperineal resection. Recently there has been increasing interest in the use of preoperative radiation therapy and sphincter-saving procedure as primary therapy for selected low rectal cancers. We report our institutional experience with this approach. METHODS From 1995 to 1997, Twelve patients with resectable distal rectal cancer were offered sphincter-saving procedure, excluding the patients whose pretreatment tumor presentation demonstrated fixation to anal sphincter or puborectalis muscle. The distance from the anal verge to the distal tumor margin at initial diagnosis ranged from 1 to 5 cm. Patients received a median 50.4 Gy and chemotherapy Surgery was carried out 4 to 8 weeks after radiation. RESULTS No patient had toxic reaction that required interruption of chemoradiation. Four patients (33%) had complete pathologic response, but one patient with complete clinical response had residual cancer. Seven patients underwent hand-sewn coloanal anastomosis and five patients transanal excision en bloc. All patients were able to successfully undergo a sphincter-saving procedure. With a mean follow-up of 23 months (range, 6~32), the authors noted no recurrence or complication. Sphincter function was good in 92%. Daily bowel movements was two (range, 1~10). CONCLUSION Preoperative chemoradiation appears promising in terms of better patient compliance, lesser toxicity, and downstaging tumor, making the sphincter-saving procedure feasible in carefully selected cases. Surgical resection remains essential to confirm and to achieve complete clinical remission. The results of preoperative chemoradiation and sphinctersaving procedure are encouraging, but more experience is needed to determine whether this approach ultimately has similar local control and survival rate compared to standard surgery.
PURPOSE Preoperative radiation treatment with concomittant intravenous infusion of 5-fluorouracil has been known to be effective in shrinking and downstaging the tumor. Treatment with Doxifluridine (synthetic 5-deoxynucleoside derivative) medication prolongs drug exposure to tumor tissue, so it can be considered synergistic to concurrent radiotherapy.
Intravenous 5-FU and oral Doxifluridine were compared with respect to tumor response, toxicity, and quality of life of patients. METHODS Twenty eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998 were included. Intravenous 5-FU (450 mg/m2/day) and leucovorin (20 mg/m2) was given for five consecutive days during first and fifth weeks of irradiation therapy (50.4 Gy) (N=14). Oral Doxifluridine (700 mg/m2/day) and leucovorin (20 mg/m2) was given daily during radiation treatment (N=14). Quality of life was scored according to twenty two activity items (good: >77, fair: >58, poor: <57).
Surgical resection was performed four weeks after completion of concurrent chemoradiation treatment. Tumor response was classified as CR (Complete Response), PR (Partial Response: 50% diminution of tumor volume or downstaging), or NR (No Response). RESULTS Tumor response was CR: 3/14 (21.4%), PR: 7/14 (50%) and NR: 4/14 (28.6%) in IV arm versus CR: 2/14 (14.2%), PR: 6/14 (42.9%) and NR: 6/14 (42.9%) in oral arm (p=0.16, 0.23, 0.24, respectively). Quality of life was poor (36.4% vs 33.3%), fair and good (63.6% vs 66.7%, respectively) between IV arm and oral arm. Systemic recurrence during follow up periods was 1/14 (7.1%) in IV arm and 2/14 (14.3%) in oral arm, respectively (p=0.307). One local recurrence was observed in oral arm. Hematologic toxicity was 3/14 (21.4%) in IV arm versus 4/14 (28.5%) in oral arm, respectively.
Gastrointestinal toxicity was 2/14 (14.3%) versus 5/14 (35.7%) and stomatitis was observed in IV arm (1/14, 7.1%) CONCLUSION: Oral doxifluridine based chemotherapy shows a comparable tumor response and oncologic results, but there was no benefits as far as quality of life and toxicity were concerned.
PURPOSE Concurrent chemoradiation treatment (CCRT) for locally advanced rectal cancer is an important modality for curative resection, but its tumor response shows wide spectrum. The aim of study is to investigate any correlation between a related genetic mutations, proliferative index and tumor response after CCRT. METHODS A twenty three patients with rectal cancer, which preoperatively staged as over T3N1 or T4 determined by transrectal ultrasonography and MRI. Enrolled patients were given 5 FU 450 mg/m2 and leucovorin 20 mg/m2 intravenously for 5 days during the first and fifth weeks of radiation therapy (45~54 Gy). 4 weeks after completion of scheduled treatment, surgical resection was performed. Tumor response was classified into CR (complete remission), PR (partial response: 50% of diminution of tumor volume and downstaging), NR (no response). Paraffin-embedded tissues obtained before chemoradiation treatment were studied with immunohistochemical staining of p53, Bcl-2 and Ki-67. The extent of tumor response was correlated with proliferative activity as measured by immunostaining of Ki-67 proliferative antigen and expression of p53 and bcl-2 oncoproteins (less than 10%: negative, 10~25%: , 25~50%: , more than 50%: , Ki-67: to count a labeled cells per 1,000 cells). RESULTS All patients were resectable. CR was obtained in 4 (17.4%), PR in 10 (43.3%) and NR in 9 (39.2%). p53 mutation was noted in 16 (70%). p53 mutation was found in NR: 5 (31.3%), PR: 9 (56.2%), CR: 2 (12.5%), respectively. Bcl-2 expression was noted in 11 (48%). NR as in 4 (36.3%), PR: 3 (28.4%) and CR: 4 (36.3%), respectively. Ki-67 labeling index was NR: 615.4 446.2, PR: 663.2 296.4, CR: 765.5 188.3, respectively (CR PR Vs NR, p=0.029). CONCLUSIONS Immunohistochemical Expression of p53 and bcl-2 does not correlate with tumor response after CCRT, but Ki-67 labeling may be useful parameters for good radiosensitive tumor selected for CCRT.