Tumour shrinkage and down staging after preoperative radiation of rectal adenocarcinomas (original) (raw)
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Japanese Journal of Clinical Oncology, 2004
Objective: In order to determine the reliable predictors of response to radiotherapy for rectal cancer, we assessed apoptosis, p53 and p21 in biopsy specimens collected before treatment, and investigated the relationships to the histological effect of irradiation and the degree of tumor shrinkage. Methods: Ninety-three patients with advanced rectal adenocarcinoma were treated with preoperative irradiation of 20 Gy in 10 fractions in combination with intraoperative electron beam irradiation of 15 Gy. We evaluated tumor grade, pathological tumor regression, biological markers associated with apoptosis and proliferation [apoptotic index (AI), p53, p21 and Ki67], and the degree of tumor shrinkage. Results: Considering positivity of p21 and of apoptosis and negativity of p53 as favorable factors in tumor shrinkage, we compared the degree of shrinkage among the patients using the number of favorable factors as the score. The degree of shrinkage was 41.5 -8.5% in patients with three favorable factors, 31.4 -9.7% in patients with two favorable factors and 26.5 -11.2% in patients with one favorable factor. However, there was no significant difference in the proportion of marked regression according to the number of favorable factors. Conclusions: Histological examination of apoptosis, p21 and p53 in biopsy specimens and scoring were considered to be useful predictive methods for assessing the efficacy of radiotherapy for rectal cancer.
Evaluation of Tumor Response after Short-Course Radiotherapy and Delayed Surgery for Rectal Cancer
PloS one, 2016
Neoadjuvant therapy is able to reduce local recurrence in rectal cancer. Immediate surgery after short course radiotherapy allows only for minimal downstaging. We investigated the effect of delayed surgery after short-course radiotherapy at different time intervals before surgery, in patients affected by rectal cancer. From January 2003 to December 2013 sixty-seven patients with the following characteristics have been selected: clinical (c) stage T3N0 ≤ 12 cm from the anal verge and with circumferential resection margin > 5 mm (by magnetic resonance imaging); cT2, any N, < 5 cm from anal verge; and patients facing tumors with enlarged nodes and/or CRM+ve who resulted unfit for chemo-radiation, were also included. Patients underwent preoperative short-course radiotherapy with different interval to surgery were divided in three groups: A (within 6 weeks), B (between 6 and 8 weeks) and C (after more than 8 weeks). Hystopatolgical response to radiotherapy was measured by Mandard&#...
Tumour location and the effects of preoperative radiotherapy in the treatment of rectal cancer
British Journal of Surgery, 2001
Background: Preoperative radiotherapy improves local control and survival in rectal cancer, but may also increase postoperative morbidity and mortality rates. Establishing selection criteria for preoperative radiotherapy is crucial. The tumour level above the anus may be one such criterion. The effect of preoperative radiotherapy in relation to the distance between the tumour and the anus was therefore assessed.
International Journal of Radiation Oncology*Biology*Physics, 2001
Background: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival. Purpose: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy. Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen. Materials: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990. Results: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p ؍ 0.03), with a trend toward improved disease-free survival (p ؍ 0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates. Conclusion: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer.
World Journal of Surgery, 1999
Preoperative radiation therapy (PRT) prior to potential curative resection for rectal adenocarcinoma is not widely accepted. This report evaluates the prognostic factors affecting local recurrence and 5-year survival. This is a retrospective study of 214 patients with primary rectal adenocarcinoma treated from January 1986 to December 1994. A PRT dosage of 45 Gy in 20 fractions was administered to patients with clinically tethered or fixed tumors, and 4 to 8 weeks later surgery was performed (group I). Patients with clinically mobile tumors were treated by surgery alone (group II). There were 130 men and 84 women. The median age was 58 years (range 19 -85 years). There were 111 patients in group I: 7 patients had no microscopic residual tumor, 80 had Dukes' A and B, and 24 had Dukes' C. There were 103 patients in group II: 70 patients were classified as Dukes' A and B and 33 as Dukes' C. The mean follow-up of the entire cohort was 62 months (range 2-132 months). Local recurrence was seen in 17% of patients in group I and 35% in group II (p ؍ 0.002). Distant recurrence in patients with metastatic lymph nodes was seen in 79% of group I and in 34% of group II (p ؍ 0.001). The favorable prognostic factors for local control were the administration of PRT and well differentiated cancer. The favorable prognostic factors for survival were age < 50 years and the absence of lymph node metastasis. The administration of PRT diminishes the risk of local recurrence. The presence of metastatic lymph nodes in the postirradiated specimen is an ominous prognostic factor for survival. Therefore such patients should be considered for adjuvant chemotherapy. Correspondence to: P. Luna-Pérez, M.D., Puerto México 53-101, Col. Roma, México D.F., Mexico CP 06760
Role of Radiation in Intermediate-Risk Rectal Cancer
Annals of Surgical Oncology, 2012
The treatment of rectal cancer has greatly evolved during the last several decades as a result of the understanding of the pathways of cancer spread, natural history of the disease, stages prognosis and prognostic markers. The tendency is clearly to move toward a more personalized approach to these patients based on preoperative staging and response to therapy. Although in the past we have been adding more treatment modalities to surgery to the point that every stage II/III cancer was treated with neoadjuvant chemo and radiotherapy followed by radical surgery by total mesorectal excision with or without sphincter preservation and more chemotherapy to follow, more recently this algorithm has been under discussion and scrutiny. Two of the major topics of controversy are: the use of local excision or even a watch-and-wait approach after a clinical complete response and the need for radiotherapy in the intermediate risk group. In this manuscript we will present the historical perspective that has brought the treatment of rectal cancer to the current standard of care and present the evidence supporting further investigation in the intermediate risk group.
Preoperative radiotherapy for rectal adenocarcinoma: Which are strong prognostic factors?
International Journal of Radiation Oncology Biology Physics, 2005
Purpose: This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors. Methods and Materials: Between 1985 and 1996, 297 patients were treated with preoperative radiotherapy (39 Gy in 13 fractions) and surgery for Stage T2-T4N0-N1M0 rectal adenocarcinoma. Pretreatment staging included a clinical examination and endorectal ultrasonography (EUS) since 1988. Clinical staging was performed by
International Journal of Radiation Oncology*Biology*Physics, 1997
Purpose: To determine predictive factors and prognostic value of tumor downstaging and tumor sterilization after preoperative RT for rectal cancer. Methods and Materials: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma (70 T2, 65 T3, 29 T4, and 3 local recurrences) underwent preoperative RT. Median dose was 44 Gy (5-73 Gy). Surgery was performed in a mean time of 5 weeks after RT. Pathologic specimens have been reviewed by the same pathologist in order to specify the modified Astler Colier chrssification (MAC), and to quantify the residua1 tumor cell density (RTCD). Results: According to the MAC, there was 9 stage 0 (5%), 10 stage A (6%), 103 stage Bl-B3 (62%), and 45 stage Cl-C3 (27%) tumors. Seventeen percent and 56% of the patients who received a dose 244 Gy had respectively a O-A and a B tumor, compared to 4 and 69% in those who received a dose <44 Gy @ = 0.04). Tumor diierentiation and a longer interval before surgery were significantly associated with a more frequent downstaging, and preoperative staging correlated well to the postoperative pathological findings. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells (Group 1); 62 (37%) showed an intermediate RTCD (Group 2); and 43 (26%) a high RTCD (Group 3). No predictive factor of RTCD was statistically significant. In univariate analysis, postoperative staging was a significant prognostic factor, with corresponding 5-year overall survival rates in O-A, B, and C stages of 92,67, and 26% @ < 0.01). RTCD was not a prognostic factor. However, overall and disease-free survival rates for patients with complete pathologic response of 83% at 2 and 5 years suggested a better outcome in this subgroup of patients. Conclusion: The favorable inlluence of higher doses of preoperative RT on pathologic stage has been observed.
Reports of Practical Oncology & Radiotherapy, 2011
The aim of this investigation is to determine the degree of tumor regression by histopathological evaluation of surgical specimen after neoadjuvant chemo-radiotherapy for patients with stage IIIB rectal cancer. Background: The standard therapy for rectal carcinoma is surgical, however, preoperative radiochemotherapy will play an increasing role especially in locally advanced disease. To estimate the prognosis and the effect of radiochemotherapy the postradiochemotherapeutical pathological features are important to assess. Materials and methods: Ten patients with cT3-4, cN1 stage rectal cancer received preoperative chemo-radiotherapy. A total tumor dose of 50 Gy was applied to all patients, with a daily fraction of 2 Gy, 5 times a week, with concomitant Capecitabine 1650 mg/m 2. A pathomorphologic assessment of the therapeutic response of the residual tumor volumes and estimation of tumor control were performed using Dworak's system of tumor regression grading (TRD) from no regression (0) to a complete tumor control (4). Results: Dworak's TRD for the examined patients is as follows: in 20% of the patients no tumor regression was observed-Grade 0, in 30%-Grade 1, in 20%-Grade 2 and in 30% a complete tumor regression was achieved-Grade 4. Four of the patients (40%) presented with borderline resectable tumors before the neoadjuvant chemo-radiotherapy. Nine of the patients (90%) underwent radical surgery. In one case (10%) a radical surgery was not possible. One patient (10%) developed severe radiation enteritis in both the early and late postoperative period, with her tumor regression evaluated as Grade 4. Conclusion: Accurate evaluation of local tumor control using Dworak's tumor regression grading scale after preoperative chemo-radiotherapy gives the basis for a larger investigation and search for a correlation with the prognosis of the disease and individual choice of adjuvant treatment.
Preoperative Irradiation for Rectal Cancer
Annals of Surgery, 1989
112 patients with adenocarcinoma of the rectum were treated using preoperative irradiation followed by excisional surgery on the colorectal surgery service of Jewish Hospital at Washington University Medical Center in St. Louis. There were 68 men and 44 women in this study, with ages ranging from 19 to 94 years of age. In all cases, the rectal cancers were believed to be transmurally invasive based on initial clinical examination. Included in this group were 13 patients with poorly differentiated tumors and 51 patients with tumors fixed to surrounding tissues. Between 1975 and 1980, we used 2000 cGy preoperative irradiation followed by imm te excisional surgery to treat 22 patients. Excisional surgery for cure was divided between abdomino-perineal resection of the rectosigmoid in eleven patients, low anterior resection of the rectosigmoid in eight patients, and a low Hartmann's procedure in three patients. Five-year survival for 20 patients with potentially curable lesions (Dukes' A, B, and C), was 85%, and there was no local recurrence. Between 1980 and 1986, 90 patients were treated with 4500 cGy preoperative irradiation over a 5week period followed by a 6-week waiting period, before excisional surgery. There were 72 patients with Dukes' A, B, and C lesions. Fifty patients underwent abdomino-perineal resection of the rectosigmoid, 33 patients underwent low anterior resection of the rectum, and seven patients underwent a low Hartmann's procedure. Five-year survival was 86%. Local recurrence was 1.8%. Tumor fixation and histologic dedifferentiation were the only factors that influenced survival. Five-year survival of patients with fixed poorly differentiated tumors was 27% as compared to 87% in patients with nonfixed well-differentiated tumors (p < 0.0001). Tumor fixation was not a significant factor in itself. Preoperative external beam irradiation improves survival, local control, and resectability in patients with rectal cancer. This effect may be due to the treatment of the "tangential" margins and local lymph node metastases. Preoperative staging can be accomplished by determining fixation and differentiation of the tumor when preoperative irradiation is used. A DJUVANT RADIATION THERAPY for rectal cancer is still controversial. However, surgical treatment alone continues to result in a high risk of local