How to Achieve a Higher Pathologic Complete Response in Patients With Locally Advanced Rectal Cancer Who Receive Preoperative Chemoradiation Therapy

The current standard of care for treating patients with locally advanced rectal cancer includes preoperative chemoradiation therapy (PCRT) followed by a total mesorectal excision and postoperative adjuvant chemotherapy. A subset of these patients has achieved a pathologic complete response (pCR) and they have shown improved disease-free and overall survival compared to non-pCR patients. Thus, many efforts have been made to achieve a higher pCR through PCRT. In this review, results from various ongoing and recently completed clinical trials that are being or have been conducted with an aim to improve tumor response by modifying therapy will be discussed.

Prognostic Impact of Immunonutritional Status Changes During Preoperative Chemoradiation in Patients With Rectal Cancer

PURPOSE: Previous studies have demonstrated the prognostic impact of the prognostic nutritional index (PNI), a proposed indicator of immunonutritional statuses of surgical patients, on patients with various gastrointestinal cancers. Although the prognostic impact of the PNI on patients with colorectal cancer has been well established, its value has not been studied in patients treated with preoperative chemoradiation (pCRT). This study aimed to evaluate the prognostic impact of PNI on patients receiving pCRT for locally advanced rectal cancer (LARC). METHODS: Patients with LARC who underwent curative pCRT followed by surgical resection were enrolled. The PNI was measured in all patients before and after pCRT, and the difference in values was calculated as the PNI difference (dPNI). Patients were classified according to dPNI (10). Clinicopathologic parameters and long-term oncologic outcomes were assessed according to dPNI classification. RESULTS: No significant intergroup differences were observed in clinicopathologic parameters such as age, histologic grade, tumor location, tumor-node-metastasis stage, and postoperative complications. Approximately 53% of the patients had a mild dPNI (10). Univariate and multivariate analyses identified the dPNI as an independent prognostic factor for disease-free status (P < 0.01; hazard ratio [HR], 2.792; 95% confidence interval [CI], 1.577–4.942) and for cancer-specific survival (P = 0.012; HR, 2.469; 95%CI, 1.225–4.978). CONCLUSION: The dPNI is predictive of long-term outcomes in pCRT-treated patients with LARC. Further prospective studies should investigate whether immune-nutritional status correction during pCRT would improve oncologic outcomes.

Preoperative chemoradiation therapy for upper gastric cancer：a retrospective study for its efficacy and safety / 中国肿瘤临床

Objective:To investigate the efficacy, safety, and overall survival of advanced upper gastric cancer patients who received preoperative chemoradiation therapy. Methods:A total of 62 patients who received preoperative chemotherapy or chemoradiation therapy in the Department of Gastrointestinal Surgery of Beijing Cancer Hospital&Institute were retrospectively observed to determine the efficacy and safety and to perform survival analysis of preoperative chemoradiation therapy. Results:Results of the postoperative pathology showed that the number of patients with T4 and N3 stages was significantly lower in the preoperative chemoradiation therapy group than in the preoperative chemotherapy group (P<0.05). In addition, the differences between the two groups in terms of safety and toxicity were not significant (P≥0.05). Analysis also showed that the differences between the two groups in terms of survival were not significant (P≥0.05). Conclusion:Patients with advanced upper gastric cancer can gain a potential survival advantage from preoperative chemoradiation therapy. Compared with preoperative chemotherapy, preoperative chemoradiation therapy was performed without increased risk of toxicity and insecurity. Preoperative chemoradiation therapy can also improve the local control ratio, especial y the control ratio of lymphatic metastasis. However, the final results of survival analysis depend on long-term follow-up of patients.

Late Complications after Preoperative Chemoradiation for Rectal Cancers / 고신대학교의과대학학술지

OBJECTIVES: To compare the late complications after operations for rectal cancers with and without preoperative chemoradiation. METHODS: From January 2003 to December 2005, 55 patients underwent operation after preoperative chemoradiation for adenocarcinoma of the rectum. All of them received the full scheduled dose of radiation with concurrent chemotherapy. The interval between preoperative chemoradiation and surgery was 4-6 weeks. 47 patients who had tumors below 8 cm from the anal verge were enrolled into the study group (CRT group). During same period, we selected 153 patients who had adenocarcinoma of the rectum below 8cm from the anal verge, underwent surgery alone without postoperative radiotherapy non-CRT group). We compared the early and the late postoperative complications between the CRT group and the non-CRT group. RESULTS: Of the late complications, the incidence of anastomotic stricture was significantly higher in the CRT group (P = 0.018). The incidence of anal stricture was higher in the CRT group (P = 0.164). In the CRT group, 3 cases (17.6%) had failed to preserve the anal function due to moderate or severe anal stricture. Of the 3 cases, protective ileostomy was persistent in 2 cases, colostomy was performed in one case. Otherwise, the late complications of the CRT group were intestinal obstruction in 2 cases (4.3%), lymph edema in 2 cases (4.3%). CONCLUSION: In CRT group, failure of anal function preservation due to anastomotic stricture or anal stricture was more common and serious than non-CRT group. We emphasize the need for careful management for postoperative anal stricture after preoperative chemoradiation.

Clinical Impact of Tumor Regression Grade after Preoperative Chemoradiation for Locally Advanced Rectal Cancer: Subset Analyses in Lymph Node Negative Patients

BACKGROUND: We investigated the prognostic significance of tumor regression grade (TRG) after preoperative chemoradiation therapy (preop-CRT) for locally advanced rectal cancer especially in the patients without lymph node metastasis. METHODS: One-hundred seventy-eight patients who had cT3/4 tumors were given 5,040 cGy preoperative radiation with 5-fluorouracil/leucovorin chemotherapy. A total mesorectal excision was performed 4-6 weeks after preop-CRT. TRG was defined as follows: grade 1 as no cancer cells remaining; grade 2 as cancer cells outgrown by fibrosis; grade 3 as a minimal presence or absence of regression. The prognostic significance of TRG in comparison with histopathologic staging was analyzed. RESULTS: Seventeen patients (9.6%) showed TRG1. TRG was found to be significantly associated with cancer-specific survival (CSS; P = 0.001) and local recurrence (P = 0.039) in the univariate study, but not in the multivariate analysis. The ypN stage was the strongest prognostic factor in the multivariate analysis. Subgroup analysis revealed TRG to be an independent prognostic factor for the CSS of ypN0 patients (P = 0.031). TRG had a stronger impact on the CSS of ypN (-) patients (P = 0.002) than on that of ypN (+) patients (P = 0.521). In ypT2N0 and ypT3N0, CSS was better for TRG2 than for TRG3 (P = 0.041, P = 0.048), and in ypN (-) and TRG2 tumors, CSS was better for ypT1-2 than for ypT3-4 (P = 0.034). CONCLUSION: TRG was found to be the strongest prognostic factor in patients without lymph node metastasis (ypN0), and different survival was observed according to TRG among patients with a specific histopathologic stage. Thus, TRG may provide an accurate prediction of prognosis and may be used for f tailoring treatment for patients without lymph node metastasis.

Abdominoperineal Resection in the Treatment of Locally-advanced Low Rectal Cancer: Is Preoperative Chemoradiation Advantageous?

PURPOSE: An abdominoperineal resection (APR) has a poor prognosis. However, limited studies about the prognostic factors in APR and the role of preoperative chemoradiotherapy (CRT) have been performed even though in rectal cancer, the application of preoperative CRT provides better local control compared to postoperative CRT. The aim of this study was to identify the prognostic factors and the impact of preoperative CRT in patients who undergo an APR. METHODS: A retrospective analysis was conducted with a total of 133 patients who underwent an APR, cT3, cT4, or cN(+) patients, for rectal cancer between January 1995 and October 2004. Fifty-one patients treated with preoperative CRT (Group 1) were compared with 82 APR patients treated with postoperative CRT (Group 2). Oncologic outcomes were compared between the two groups, and the clinicopathologic factors affecting the treatment outcomes were evaluated. RESULTS: The median follow-up period was 61.2 mo (range 6 to 194 mo). Circumferential margin (CRM) involvement was significantly associated with local recurrence (LR) and with disease-free survival in APR patients (P<0.001, P=0.011). The 5-yr LR rate was significantly lower in Group 1 than in Group 2 (P=0.013) in the univariate analysis, but no difference was noted in multivariate analysis (P=0.315). In Group 1, CRM involvement, tumor size, and lymph node metastasis were significantly lower than they were in Group 2 (P=0.043, P=0.003, P<0.001). CONCLUSION: For achieving adequate oncologic outcomes in APR patients, an adequate CRM should be acquired with an optimal operation. In addition, preoperative CRT would be helpful for high-risk APR patients with a threatening CRM margin, providing the benefit of tumor downstaging.

Disadvantages of Preoperative Chemoradiation in Rectal Cancer

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.

Does preoperative chemoradiation therapy in locally advanced rectal cancer increase rate of sphincter preserving surgery: A prospective clinical trial.

Objective: To evaluate the influence of preoperative chemoradiation in locally advanced rectal cancer on ability to perform sphincter preserving surgery. Methods: Between 1998 and 2005, a prospective clinical trial of preoperative chemoradiation therapy (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with bolus infusion of 5-fluorouracil (200 mg/m2/day) or capecitabine (2000mg/m2/day) was given to 42 rectal cancer patients admitted to the Department of Surgery, Siriraj Hospital, Bangkok, Thailand. The pretreatment stage distribution, as determined by endorectal ultrasonography and computed tomography of the pelvis, included uT3N0 in 90.48% and uT3N1 in 9.52% of cases. Approximately 6 weeks after completion of CTX/XRT, surgery was performed in every patient. The choice of the surgical procedure was based on the surgeon’s discretion. Results: The patient population consisted of 25 males (59.52%) and 17 females (40.48%) who had a median age of 57 years (range 32-79 years). Distal border of the tumors were located at a median of 5 cm (range 2-10 cm) above the anal verge. Thirty cases (71.43%) had distal border of the tumors within 6 cm from the anal verge. The pathological tumor stages were T1N0 in 2 cases (4.76%), T2N0 in 9 cases (21.43%), T2N1 in 4 cases (9.52%), T3N0 in 12 cases (28.57%), T3N1 in 8 cases (19.05%), T3N2 in 2 cases (4.76%) and T4N0 in 1 case (2.38%). The results included 9.52% pathological complete response, 42.86% downstaging and 50% sphincter preservation rate. Of the tumors located < 6 cm from the anal verge, sphincter preservation was accomplished in 30% of the patients. The pretreatment location of distal border of the tumors (< 6 cm vs. > 6 cm from anal verge) was the only factor predictive of sphincter preservation (p < 0.001). No local recurrence was detected during the period of follow up (median 23 months). Conclusion: The administration of preoperative chemoradiation for locally advanced rectal cancer is associated with tolerable toxicity and high rates of tumor downstaging. The preoperative chemoradiation and tumor downstaging do not increase rate of sphincter preservation in locally advanced rectal cancer.

Preoperative Chemoradiation Followed by Total Mesorectal Excision for Locally Advanced Rectal Cancer: Oncologic Outcomes According to Pathologic T and N Stage

PURPOSE: Tumor response of patients with locally advanced rectal cancer after chemoradiation showed 60~70% of tumor volume reduction and T and N downstaging. Curative resection with total mesorectal excision should be followed for good oncologic outcomes. This study was designed to analyze the oncologic outcomes in patients who received preoperative chemoradiation followed by total mesorectal excision for locally advanced rectal cancer according to pathologic T and N stage. METHODS: Total 108 patients with locally advanced rectal cancer treated between 1989 and 2000. All patients were analyzed retrospectively and staged as T3, 4 N (+) by transrectal ultrasonography and pelvic MRI. All patients received a 5, 040 cGy of radiation over 5 weeks and systemic intravenous bolus chemotherapy 5 FU 450 mg/m2 and leucovorin 20 mg/m2 for 5 days was given during first and fifth weeks of radiation treatment, followed four to six weeks later by radical surgery. RESULTS: Among 108 patients there were 74 males and 34 females. Mean age was 54.4 years in male and 52.3 years in female. Mean follow up periods was 41.3 months. Complete follow up was in 96.4% of patients. Curative resection was done in 90 patients (83.3%). The most common type of surgery was low anterior resection in 40 (44.4%) and unresectable patients in 10 (9.3%). Postoperative morbidities were wound infection (n=10, 9.2%), anastomostic leakage (n=2, 1.9%), and anastomotic stricture (n=1, 0.9%). After chemoradiation, tumor stage were as follows: pathologic complete remission was in 7 (6.5%), pT1, T2 N0 (stage I) was in 21 (19.4%), T3N0 (stage II) was in 28 (25.9%) and T3 N (+) (stage III) was in 34 (31.5%). The rate of local recurrence was 10.7% in stage II and 20.6% in stage III. Systemic recurrence was 21.4% in stage II and 47.1% in stage III. 5 year survival rate according to T stage was T0 (100%), T1 (100%), T2 (79.5%), T3 (43.7%), T4 (33.3%) (p=0.0088). According to N stage, N (-)(72.0%) and N (+) (35.7%)(p=0.002). Among T3 patients, 5 year survival rate was N (-)(58.2%) vs. N (+)(32.0%)(P=0.0228). CONCLUSION: Preoperative chemoradiation followed by total mesorectal excision downstaged locally advanced rectal cancer and showed high resectability. Clinical outcomes correlated with pathologic T and N downstaging. Patients who did not show pathologic T and N downstaging showed high local and systemic failure and poor prognosis.

Clinical Results of Postoperative Chemoradiation on Advanced Rectal Cancers: Tumor Response, Toxicities, and Morbidity

PURPOSE: Adjuvant chemotherapy and radiotherapy have been considered effective treatments in advanced rectal cancers. Recently, several studies have reported that preoperative chemoradiation (CRT) may have advantages over postoperative CRT, particularly in reducing local recurrence and preserving the anal sphincter. We studied the short-term efficacy of preoperative CRT for locally advanced rectal cancers. METHODS: Between Jun. 2000 and Aug. 2003, 23 patients were treated with preoperative CRT, followed by surgery (pre-CRT) and 31 patients were treated with chemoradiation postoperatively (post-CRT). We compared these two groups for the incidence and degree of side effects from CRT, postoperative complications, type of surgery, including anal sphincter preservation, and short-term recurrence. RESULTS: The average age and male-to-female ratio of the pre- and the post-CRT groups were 58+/-11, years and 13:10, and 61+/-14 and 14:17, respectively. T downstagings were observed in 17 of 23 (74%) pre-CRT patients. On the RTOG-EORTC scale, the patients who showed hematological, intestinal and dermal side effects in the pre-CRT group and in the post-CRT group were 5, 5, 2 and 5, 2, 4, respectively and the difference was not statistically significant (P=0.41). Anal sphincter preserving surgical procedures were performed 91.3% (21/23) and 83.9% (26/31) of the patients in the pre- and the post-CRT groups, respectively. But this difference was not statistically significant (P=0.4). Postoperative complications in the pre-CRT group were anastomosis site leakages (n=3) and rectovaginal fistula (n=1). In the post-CRT group, complications were two anastomosis site leakages. Four of the 31 post-CRT group patients had recurrences such as locoregional area (n=2), liver (n=1), and lung (n=1) while no patient was observed in pre- CRT group. CONCLUSIONS: Although pre-CRT group showed higher incidence of complications than post-CRT group, these were managed easily and safely. Pre-CRT seems to be an effective modality for treating advanced rectal cancers particularly for preserving anal sphincter. Long-term follow- up data are needed to clarify the effect of pre-CRT.

Analysis of Criteria for Tumor Response after Preoperative Chemoradiation Therapy for Locally Advanced Rectal Cancer: Correlation between Tumor Volume Reduction and Histopathologic Downstaging

PURPOSE: Preoperative chemoradiation treatment (CCRT) for locally advanced rectal cancer has been known to be safe and effective. The aim of study is to find any correlation between tumor volume reduction and histopathologic downstaging in locally advanced rectal cancer by preoperative CCRT. METHODS: A total of 16 patients of rectal cancer were selected. They had been T3,4 N (+) preoperatively staged by using a transrectal ultrasonography and pelvic MRI. Radiation was given, a total of 5,040 cGy over 5 weeks, and systemic chemotherapy was also given 5 FU 450 mg/m2 and leucovorin 20 mg/m2 concurrently intravenously during the first and the fifth week of CCRT. Surgery was done 4~6 weeks after completion of CCRT. A 3D CT image was obtained with AcQsim PQ 5000 3D (Philips, USA). Tumor volume was measured before and after CCRT. RESULTS: The type of operative procedures were abdominoperineal resection 7, low anterior resection 5, coloanal anastomosis 3 and Hartmann operation 1. Volume reduction was ranged from 14.6% to 84.4%. Over a 50% tumor volume reductions were in 9 patients (56.2%). Pathologic complete remission was observed in 2 patients (12.5%), who showed 72% and 58.5% tumor volume reductions. Patients showing pT and/or pN downstaging patients (N=9) had a 55.9% tumor reductions (14.6~84.4%), and patients showing no pT and/or pN downstaging (N=7) had 51.8% volume reduction (24.7~79%). CONCLUSIONS: Preoeperative CCRT has been thought to be able to decrease tumor size and volume and to increase respectability. However, among our 9 patients who showed over 50% tumor volume reductions, 3 patients did not show any T and N downstaging, which is really important for long-term oncologic outcomes.

The Outcome of Preoperative Chemoradiation to Locally Advanced Rectal Cancer

PURPOSE: Tumor downstaging after preoperative chemoradiation has been associated with an intent to improve anal sphincter preservation, resectability, local control, and possibly survival in locally advanced rectal cancer. We performed this study to evaluate the outcome of preoperative chemoradiation for locally advanced rectal cancer. METHODS: We retrospectively reviewed the cases of 82 patients who had been treated by using preoperative chemoradiation combined with surgery for adenocarcinoma of the rectum between January, 1995, and December, 2002. All patients had fixed or locally advanced lesions, which had been detected by using digital rectal examination. No distant metastasis was proven before preoperative chemoradiation. All of the patients received the full scheduled dose of radiation (range, 3,000~5,400 cGy). Concurrent intravenous chemotherapy with 5-fluorouracil (450 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 5.6 weeks (2.7~9.6 weeks). The survival rate was estimated by using the Kaplan-Meier method and the log-rank test. We compared the survival of locally advanced rectal cancers treated by using preoperative chemoradiation with surgery with that of 444 patients with resectable rectal cancers treated by using curative surgery alone during same period. RESULTS: A curative resection could be performed on 64 of the 82 patients (78.2%). A sphincter-preserving surgery was performed on 42 patients (51.2%). A pathologic complete response (pCR) occurred in 6 patients (7.3%). The 5-year survival rates of patients with a pCR was 66.7%. In the comparison of the 5-year survival rates between patients with locally advanced rectal cancer treated by using preoperative chemoradiation with curative surgery and patients with rectal cancer treated by using curative surgery alone, those of stage I, stage II, and stage III cancers were 100% vs. 89.5%, 86.9% vs. 86.3%, and 52.9% vs. 63.3%, respectively (P>0.05). CONCLUSIONS: The survival rates for patients with locally advanced rectal cancers, which are expected to be unresectable or non-curative, treated by using preoperative chemoradiation with surgery were similar to those for patients with resectable rectal cancers treated by using curative surgery alone. We think that preoperative chemoradiation with surgery improves the survival of patients with locally advanced rectal cancer. J Korean Soc Coloproctol 2004;20:277-282

Prospective Randomized Trial Comparing Intravenous 5 Fluorouracil and Oral Doxifluridine as Preoperative Concurrent Chemoradiation for Locally Advanced Rectal Cancer

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.

p53, Bcl-2 and Ki-67 Expression according to Tumor Response after Concurrent Chemoradiation Treatment for Advanced Rectal Cancer

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.

The Treatment Results of Preoperative Concurrent Chemoradiation in Locally Advanced Rectal Cancer / 대한암학회지

PURPOSE: To assess the tumor response, sphincter preservation, acute toxicity and survival with preoperative concurrent chemoradiation in locally advanced rectal cancer. MATERIALS AND METHODS: Fifty-four patients were treated with preoperative chemoradiaton for tumor downstaging and sphincter preservation. Radiation was delivered to whole pelvis to 45 Gy followed by a boost 5.4 Gy to primary tumor site. Chemotherapy consists of concurrent 2 cycles of 5-fluorouracil (500 mg/m2/day) and leucovorin (20 mg/m2/day). Surgery was performed approximately 6 weeks after treatment. RESULTS: Median follow-up period and rate were 48 months and 98%, respectively. The downstaging including primary tumor and lymph node occurred in 64%. Three of 53 patients (6%) had pathologic complete response. The resectability of tumor was 98%. A sphincter preservation was possible in 61%. Three patients developed grade 4 hematologic toxicity. Grade 3 skin erythema and diarrhea were 24% and 18%, respectively. The 5-year survival and local disease-free survival were 62% and 89%, respectively. Local failure and distant metastasis rate were 9% and 35%, respectively. CONCLUSION: Preoperative chemoradiation affords considerable downstaging with acceptable acute toxicity and postoperative morbidity. Also sphincter preservation is feasible by improved downstaging of tumor. This treatment could be improved local control of tumor, and may have a potential for long-term survival.

Selective Approach to Sphincter-Saving Procedure after Chemoradiation in Low Rectal Cancer

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.

The Effects of Preoperative Chemoradiation Therapy in Pectal Cancer

To evaluate the effects of the preoperative chemoradiation therapy(CRT) for rectal cancer. 31 rectal cancer patients received preoperative CRT. A total 3060cGy of radiation was given in 3 weeks, 180cGy for a fraction. 425mg/m2/day of 5-FU and 20mg/m2/day of leucovorin were continuously infused in the first 5 days of the preoperative radiation therapy. A IV injection of Mitomycin C 10mg/m2 was given on the first day. A digital rectal examination, endoscopy with biopsy, barium enema, chest X-ray, hepatobiliary ultrasonography & IV bolus CT were done before and after CRT. Clinically, 19 patients(61.3%) and pathologically, 16 patients(51.6%) showed reduced tumor size. In 7 patients (22.6%), there was no residual tumor in the pathologic specimen. Digital rectal examination was possible in 23 patients. 16(69.5%) of them had a decrease in height of ulcer margin on digital rectal examination. Seven of the fifteen patients showed decreased perirectal fat tissue infiltration. There was no severe toxicity which might delay the curative surgery. In conclusion, preoperative chemoradiation therapy in rectal cancer was very effective in reducing tumor size and perirectal fat tissue infiltration without considerable toxicity.