Concomitant preoperative radiochemotherapy in operable locally advanced rectal cancer

PURPOSE: The aim of this study was to examine the effectiveness of a combination of preoperative radiotherapy and chemotherapy for operable locally advanced rectal cancer (Stages II and III). METHODS: Chemotherapy and radiotherapy are started jointly on day one of the therapy. 5-Fluorouracil is given in a dosage of 1000 mg/ m²/day as a continuous 24-hour infusion for 4 days. Mitomycin C is given as a bolus intravenous at a dosage of 10 mg/m² the first day. The radiation therapy is given to a total dosage of 37.8 Gy. Surgery is generally performed four to five weeks following completion of the radiation therapy. From March 1990 to April 1993, 34 patients with histologically documented adenocarcinoma of the rectum have been treated. Twenty-one lesions were located in the lower third of the rectum. Twenty-nine neoplasms were judged by initial clinical staging as Stage III. RESULTS: Patients compliance to the treatment have been 97 percent. Toxicity of treatment has been low (15 percent). Tumor sizes decreased 50 percent or more in about 80 percent of patients. Distance of the tumor from the anal canal increased in all but seven cases. Twenty-two anterior resections have been performed. The morbidity rate has been 24 percent. No postoperative mortality has been reported. Histologic examination of surgical specimens after integrated treatment showed in 10 cases a tumor confined to the rectal wall (T2), in 3 patients only a residual tumor limited to submucosa (T1), and in 5 (15 percent) patients no evidence of neoplastic cells (T0). CONCLUSIONS: We conclude that preoperative radiochemotherapy was generally well tolerated; in all cases we had a reduction of tumor sizes, surgery presented no technical difficulties, and there was the effect of stage reduction.     

Pre-operative radiochemotherapy of locally advanced rectal cancer

AIM. To evaluate results of pre-operative radiochemotherapy followed by surgery for 15 patients with locally advanced un-resectable rectal cancer.METHODS: 15 patients with advanced non-resectable rectal cancer were treated with pre-operative irriadiation of 40-46Gy plus concomitant chemotherapy (5-FU+LV and 5‘-DFuR) (RCS group). For comparison, 27 similar patients,treated by preoperative radiotherapy (40-50Gy) plus surgery were served as control (RS group).RESULTS: No radiochemotherapy or radiotherapy was interrupted and then was delayed because of toxicities in both groups. The radical resectability rate was 73.3% in the RCS group and 37.0% (P=0.024) in RS group. Sphincter preservation rates were 26.6% and 3.7% respectively(P=0.028). Sphincter preservation rates of lower rectal cancer were 27.3% and 0.0% respectively (P=0.014). Responserates of RCS and RS groups were 46.7 % and 18.5 %(P=0.053). The tumor downstage rates were 8(53.3%)and 9 (33.3%) in these groups (P=0.206). The 3-year overall survival rates were 66.7% and 55.6% (P=0.485), and the disease free survival rates were 40.1% and 33.2%(P=0.663). The 3-year local recurrent rates were 26.7% and 48.1% (P=0.174). No obvious late effects were found in either groups.CONCLUSION: High resectability is possible following preoperative radiochemotherapy and can have more sphincters preserved. It is important to improve the quality of the patients‘ life even without increasing the survival or local control rates. Preoperative radiotherapy with concomitant full course chemotherapy (5-Fu+LV and 5‘-DFuR) is effective and safe.     

Accuracy of transrectal ultrasound in predicting pathologic stage of rectal cancer before and after preoperative radiation therapy

Transrectal ultrasound (TRUS) and CT scan staging of rectal cancers before, and TRUS staging after, 45 Gy of irradiation were compared with the pathologic stage of the resected specimen in 19 patients. Accuracy of TRUS before and after irradiation, and of CT scan before irradiation, was 32 percent, 63 percent, and 53 percent, respectively. CT scan before and TRUS after irradiation predicted lymph node involvement in 79 percent and 68 percent of cases, respectively. Positive predictive value for lymph node involvement before irradiation was 60 percent for CT scan and 37.5 percent for TRUS; after irradiation, it was 50 percent for TRUS. Negative predictive value was 100 percent for CT scan and TRUS before radiation and 88 percent for TRUS after irradiation. Preoperative radiation therapy makes TRUS and CT scan less effective as staging techniques. The absence of lymph nodes on TRUS and CT scan before and after irradiation is reliable.Read in part at the Tripartitate Meeting, Birmingham, England, June 19 to 22, 1989.     

Prospective comparative study of magnetic resonance imaging versus transrectal ultrasound for preoperative staging and follow-up of rectal cancer

The efficiency of magnetic resonance imaging (MRI) and that of transrectal ultrasound (TRUS) were compared in preoperative staging of 15 patients with rectal cancer and in postoperative follow-up of 12 patients. Thirteen of the 15 patients evaluated for preoperative staging were operated on. Preoperative staging and pathologic finding were identical in 11 patients (84.6 percent) examined by TRUS and in 10 patients (76.9 percent) examined by MRI. Recurrent cancer was detected in 3 of 12 patients in the follow-up group. MRI was able to diagnose correctly 10 of 12 patients (83.2 percent), one patient was misdiagnosed, and in one patient the MRI could not distinguish between fibrous tissue and recurrent cancer. TRUS diagnosed correctly only 5 of 12 patients (41.6 percent). One was falsely diagnosed, and, in 6 patients (50 percent), this examination could not differentiate between fibrous tissue and recurrent tumor. According to our results, both MRI and TRUS have a place in the preoperative staging of patients with rectal cancer. The main differences between the two methods were in the differential diagnoses of fibrous tissue and recurrent cancer. MRI being more specific in detection of recurrence.Read at the XIIIth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Graz, Austria, June 24 to 28, 1990.     

Liver metastases:Contrast-enhanced ultrasound compared with computed tomography and magnetic resonance

The development of ultrasound contrast agents with excellent tolerance and safety profiles has notably improved liver evaluation with ultrasound(US)for several applications,especially for the detection of metastases.In particular,contrast enhanced ultrasonography(CEUS)allows the display of the parenchymal microvasculature,enabling the study and visualization of the enhancement patterns of liver lesions in real time and in a continuous manner in all vascular phases,which is similar to contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging.Clinical studies have reported that the use of a contrast agent enables the visualization of more metastases with significantly improved sensitivity and specificity compared to baseline-US.Furthermore,studies have shown that CEUS yields sensitivities comparable to CT.In this review,we describe the state of the art of CEUS for detecting colorectal liver metastases,the imaging features,the literature reports of metastases in CEUS as well as its technique,its clinical role and its potential applications.Additionally,the updated international consensus panel guidelines are reported in this review with the inherent limitations of this technique and best practice experiences.     

Pathological features of rectal cancer after preoperative radiochemotherapy

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. We examined the surgical specimens of 17 patients after preoperative radiochemotherapy to estimate and grade the histological reactions. A proposal for a grading system for tumor regression (not yet available in the literature) has also been described. All but one of the carcinomas showed different degrees of tumor regression. A total regression was not observed after standardised pathological work up. In only one case a locally curative resection was not possible. We think that preoperative radiochemotherapy is able to reduce tumor mass thus achieving operability in non-curatively operable cases. We recommend standards of pathological work up and regression grading for further studies comparing surgery and radiochemotherapy of rectal carcinoma.

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Résumé. Le traitement standard d'un cancer du rectum est chirurgical, toutefois la radiochimiothérapie pré-opératoire est appelée à jouer un r?le croissant, en particulier dans les formes localement avancées de la maladie. Afin d'estimer le pronostic et l'effet de la radiochimiothérapie, il est important d'évaluer les constatations pathologiques secondaires à la radio-chimiothérapie. Nous avons analysé les prélèvements opératoires de dix-sept patients après radio-chimiothérapie pré-opératoire dans le but d'estimer et de graduer les réactions histologiques. Nous décrivons également une proposition d'un système de graduation de la régression tumorale, ce qui n'existe pas encore dans la littérature. A l'exception d'un cancer, toutes les tumeurs présentaient des degrés divers de régression. Une régression totale n'a pas été observée après une technique standard d'analyses pathologiques. Dans un seul de nos cas, une résection curative locale n'a pas été possible. Nous pensons que la radio-chimiothérapie pré-opératoire est capable de réduire le volume tumoral à un point tel qu'il est possible d'opérer des cas qui, initialement, n'auraient pas pu être traités de manière curative. Nous conseillous une technique standard d'analyses pathologiques et de graduation de la régression tumorale qui devrait être utile à l'étude comparative des résultats chirurgicaux et de la radio-chimiothérapie du cancer du rectum.

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Accepted: 25 November 1996     

Local staging of rectal cancer with transrectal ultrasound and endorectal magnetic resonance imaging

PURPOSE: The aim of the present study was to compare the accuracy of endorectal coil magnetic resonance imaging with transrectal ultrasound in staging rectal carcinoma. METHODS: Twenty-six consecutive patients with rectal carcinoma, histologically proven by endoscopic biopsy, were staged with both endorectal coil magnetic resonance imaging and transrectal ultrasound and then underwent radical surgery. The preoperative staging was compared with histologic findings of the operative specimen according to TNM classification. RESULTS: Endorectal coil magnetic resonance imaging showed better results but was not statistically significantly different from transrectal ultrasound in evaluating T (accuracy, 84.6 vs. 76.9 percent): four overstaged and no understaged cases for the former and five overstaged cases and one understaged case for the latter. Both procedures showed similar results in evaluating N: 81 percent sensitivity and 66 percent specificity for endorectal coil magnetic resonance imaging and 72 percent sensitivity and 80 percent specificity for transrectal ultrasound. CONCLUSIONS: An accurate locoregional staging of rectal cancer is essential for the planning of optimal therapy for rectal cancer. Endorectal coil magnetic resonance imaging and transrectal ultrasound showed similar results; the former is more expensive, whereas the latter is operator dependent. At present the use of endorectal coil magnetic resonance imaging seems to be justified only in selected low rectal cancers where transrectal ultrasound yielded doubtful results. However, a more extensive study is necessary to compare the advantages of these diagnostic techniques.     

Comparative study of transrectal ultrasonography, pelvic computerized tomography, and magnetic resonance imaging in preoperative staging of rectal cancer

PURPOSE: The preoperative assessment of rectal cancer wall invasion and regional lymph node metastasis is essential for the planning of optimal therapy. This study was done to determine the accuracy and clinical usefulness of transrectal ultrasonography, pelvic computed tomography, and magnetic resonance imaging in preoperative staging. METHODS: A total of 89 patients with rectal cancer were examined with transrectal ultrasonography (n=89), pelvic computed tomography (n=69), and magnetic resonance imaging with endorectal coil (n=73). The results obtained by these diagnostic modalities were compared with the histopathologic staging of specimens. RESULTS: In staging depth of invasion, the overall accuracy was 81.1 percent (72/89) by transrectal ultrasonography, 65.2 percent (45/69) by computed tomography, and 81 percent (59/73) by magnetic resonance imaging. Overstaging was 10 percent (9/89) by transrectal ultrasonography, 17.4 percent (12/69) by computed tomography, and 11 percent (8/73) by magnetic resonance imaging; and understaging was 8 of 89 (8.9 percent) by transrectal ultrasonography, 12 of 69 (17.4 percent) by computed tomography, and 6 of 73 (8 percent) by magnetic resonance imaging. In staging lymph node metastasis, the overall accuracy rate was 54 of 85 (63.5 percent) in transrectal ultrasonography, 39 of 69 (56.5 percent) in computed tomography, and 46 of 73 (63 percent) in magnetic resonance imaging. The sensitivity was 24 of 45 (53.3 percent) in transrectal ultrasonography, 14 of 25 (56 percent) in computed tomography, and 33 of 42 (78.5 percent) in magnetic resonance imaging; and specificity was 30 of 40 (75.0 percent) in transrectal ultrasonography, 25 of 44 (56.8 percent) in computed tomography, and 13 of 31 (41.9 percent) in magnetic resonance imaging. The accuracy in detection of positive lateral pelvic lymph nodes under magnetic resonance imaging (n=8) was 12.5 percent. The accuracy in detection of posterior vaginal wall invasion was 100 percent in transrectal ultrasonography (n=7) and 100 percent in magnetic resonance imaging (n=3), but 28.5 percent in computed tomography (n=7). CONCLUSIONS: Both transrectal ultrasonography and magnetic resonance imaging with endorectal coil exhibited similar accuracy and were superior to conventional computed tomography in preoperative assessment of depth of invasion and adjacent organ invasion. Because transrectal ultrasonography is a safer and more cost-effective modality than magnetic resonance imaging, transrectal ultrasonography is an appropriate method for preoperative staging of rectal cancer. Further efforts will be needed to provide a better staging of lymph node involvement.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

The predictive value of metabolic response to preoperative radiochemotherapy in locally advanced rectal cancer measured by PET/CT

Background  To evaluate the value of positron emission tomography using fluorodeoxyglucose and computer tomography scan (FDG-PET/CT) for prediction of histopathological response of preoperative radiochemotherapy (RCTX) in patients with rectal carcinoma. Methods  Thirty patients with uT3 rectal carcinoma were examined by FDG-PET/CT at baseline, 14 days after initiation, and after completion of preoperative RCTX. The FDG decreases seen with PET scanning from baseline to day 14 (early metabolic response) and after completion of therapy (late metabolic response) were compared with histopathological tumor response. One patient denied surgery after RCTX. Results  The mean (±SD) reduction of tumor FDG uptake in histopathologically responding compared to non-responding tumors was −44.3% (±20.1%) versus −29.6% (±13.1%) (p = 0.085) at day 14 and −66.0% (±20.3%) versus −48.3% (±23.4%) (p = 0.040) after completion of RCTX. Best differentiation of histopathological tumor response was achieved by a cut-off value of 35% reduction of initial FDG uptake at day 14 and 57.5% after completion of therapy. Applying the cut-off values as a criterion for metabolic response, histopathological response was predicted with a sensitivity of 74% (14/19) at day 14 and 79% (15/19) after completion of therapy. The positive predictive value for early metabolic response was 82% (14/17) and for late metabolic response was 83% (15/18). Histopathological evidence of accumulated peritumoral inflammation cells was associated with a minor FDG decrease in five histopathologically responding patients, and influenced the results with negative predictive values of 58% (7/12) and 64% (7/11) at the early and late time points, respectively. Conclusions  Metabolic response to a preoperative RCTX using FDG-PET/CT in rectal cancer patients can be correlated with histopathological response, but FDG uptake of peritumoral inflammation cells limited the results and led to false negative results.     

直肠癌术前放疗进展

2004年德国CAO/ARO/AIO-94临床研究奠定了局部晚期直肠癌术前新辅助放化的治疗策略。近年来,全世界对于如何进一步提高放化疗疗效和个体化治疗在放疗同期药物配比、新辅助放化疗前加入诱导化疗、延长新辅助放化疗至手术间隔期、放化疗后器官保留和中国患者适应性等五方面进行了探索,本文将对上述方面进行阐述。     

Intensified neoadjuvant radiochemotherapy for locally advanced rectal cancer: a review

Background The rate of local recurrence of locally advanced rectal cancer (stage III and IV according to the criteria of Union Internationale Contre Le Cancer) is still high, and also the rate of distant metastases. There are a lot of phase I/II trails of intensified neoadjuvant radiochemotherapy with different chemotherapeutic agents and current protocols to radiotherapy. Aim The objective of this review of literature was to evaluate the necessity, the results, and comparability of the different regimes and to evaluate a potential impact on later adjuvant chemotherapy.     

Extensive surgery after high-dose preoperative chemoradiotherapy for locally advanced recurrent rectal cancer

PURPOSE: This was a pilot study of high-dose preoperative concurrent radiation and chemotherapy before extensive surgery in patients with locally advanced recurrent rectal cancer. Here we report on curative resectability, acute toxicities during chemoradiotherapy, surgical complications, local control, and three-year survival rates achieved with this aggressive multimodal regimen. METHODS: Between 1994 and 1997, 35 previously nonirradiated patients with pelvic recurrence of rectal cancer were entered in the study. All patients presented with tumor contiguous or adherent to adjacent pelvic organs and were not deemed amenable to primary curative surgery. A total radiation dose of 50.4 Gy with a small-volume boost of 5.4 to 9 Gy was delivered in conventional fractionation (single dose, 1.8 Gy). 5-Fluorouracil was scheduled as a continuous infusion of 1,000 mg/m²/day on Days 1 to 5 and 29 to 33. Six weeks after completion of chemoradiotherapy, patients were reassessed for resectability, and radical surgery was attempted whenever feasible. RESULTS: After preoperative chemoradiotherapy 28 of 35 patients (80 percent) underwent resection with curative intent. In 16 of 35 patients (57 percent) extended resection of adjacent organs was performed. Resections with negative margins were achieved in 17 patients (61 percent); 9 patients had microscopic, and 2 patients had gross residual disease. There was no postoperative mortality. Fourteen patients (44 percent) experienced postoperative complications. Toxicity from chemoradiotherapy occurred mainly as diarrhea (National Cancer Institute Common Toxicity Criteria Grade 3; 23 percent), dermatitis (Grade 3; 11 percent), and leucopenia (Grade 3; 11 percent). One patient died of tumortoxic multiple organ failure during chemoradiotherapy. With a median follow-up of 27 months, local re-recurrence after curative resection was observed in only three patients (18 percent); six patients developed distant metastases. Three-year actuarial survival rate was significantly improved after complete resection (82 percent) as compared with noncurative surgery (38 percent;P=0.03). CONCLUSION: A combination of high-dose preoperative chemoradiotherapy followed by extended surgery can achieve clear resection margins in more than 60 percent of patients with recurrent rectal tumor not amenable to primary surgery. An encouraging trend evolved for this multimodal treatment to improve long-term local control and survival rate.Presented at the meeting of the German Society for Radiation Oncology, Radiation Biology and Medical Physics (DEGRO), Nürnberg, Germany, November 7 to 10, 1998.     

Transrectal ultrasound and computed tomography in preoperative staging of lower rectal adenocarcinoma

A comparison of transrectal ultrasound (TRUS) and computed tomography (CT) for staging of rectal carcinoma was performed. Thirty-two patients were examined by TRUS and 30 by CT. The results of these preoperative examinations were compared with postoperative histopathological findings. TRUS had an accuracy of 81% and it predicted perirectal tumor growth with a sensitivity of 90% and a specificity of 67%, whereas the corresponding figures for CT were 52%, 67%, and 27%. These findings indicate that TRUS is more efficient than CT in staging local tumor growth in rectal cancer. Neither technique, however, can reliably identify lymph node metastases, since no correlation was found between lymph node size as observed on CT and TRUS and tumor involvement as evaluated histopathologically.     

Long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer

Background and aims The purpose of this study was to assess the long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer. Materials and methods Between April 1990 and June 2005, all patients who underwent surgery for low rectal cancer with a pretreatment diagnosis of T3 or resectable T4 without distant metastasis were enrolled. The total dose of radiation was 45 Gy. Patients with a partial or complete response were defined as radiotherapy responders (RT-R) and the others as radiotherapy non-responders (RT-NR). Patients who did not receive radiotherapy were termed the non-radiotherapy group (NRT). The endpoint of this study was overall survival and local and/or distant metastasis. Results There were 24 patients in RT-R, 26 in RT-NR, and 40 in NRT. Gastrointestinal complications were commonly observed in all groups. RT-R had a significantly higher incidence of genitourinary complications. Five-year overall survival rate was 79.6% in RT-R, 58.9% in RT-NR, and 58.8% in NRT. The difference was significant in favor of RT-R over the others (P = 0.015, 0.024, respectively). Five-year local recurrence-free survival rate was 100% in RT-R, 81.5% in RT-NR, and 74.9% in NRT. RT-R had significantly improved local control compared with the others (P = 0.034, 0.021, respectively). Five-year distant metastasis-free survival was not statistically different among all groups. Conclusions Survival benefit of preoperative radiotherapy was limited to responders. Considering the increased risk of adverse effects, identification of predictors of radiosensitivity is required in order to provide the most suitable treatment for individual patients.     

Endoscopic ultrasound and magnetic resonance imaging for re-staging rectal cancer after radiotherapy

AIM: To compare the sensitivity and specificity of two imaging techniques, endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI), in patients with rectal cancer after neoadjuvant chemoradiation therapy.And we compared EUS and MRI data with histological findings from surgical specimens.METHODS: Thirty-nine consecutive patients (51.3% Male; mean age: 68.2 ± 8.9 years) with histologically confirmed distal rectal cancer were examined for staging.All patients underwent EUS and MRI imaging beforeand after neoadjuvant chemoradiation therapy.RESULTS: After neoadjuvant chemoradiation, EUS and MRI correctly classified 46% (18/39) and 44% (17/39) of patients, respectively, in line with their histological T stage ( P > 0.05). These proportions were higher for both techniques when nodal involvement was considered:69% (27/39) and 62% (24/39). When patients were sorted into T and N subgroups, the diagnostic accuracy of EUS was better than MRI for patients with T0-T2 (44% vs 33%, P > 0.05) and N0 disease (87% vs 52%, P = 0.013). However, MRI was more accurate than EUS in T and N staging for patients with more advanceddisease after radiotherapy, though these differencesdid not reach statistical significance.CONCLUSION: EUS and MRI are accurate imaging techniques for staging rectal cancer. However, after neoadjuvant RT-CT, the role of both methods in the assessmentof residual rectal tumors remains uncertain.     

Endorectal ultrasound and magnetic resonance imaging in rectal cancer staging

The majority of rectal cancers have local disease only at presentation, but despite meticulous surgery, a number of factors will influence outcome. Preoperative identification of adverse prognostic factors provides a rational basis for selecting preoperative therapy. Thin section MRI can influence preoperative therapeutic algorithms by T and N staging, demonstrating operability, and the potential risk of circumferential margin involvement. Endosonography may contribute to this, but has a greater role in determining intramural invasion for early tumors. The assessment of residual tumor after chemoradiotherapy remains difficult; PET scanning has been used in this situation [32], but has not been compared with MRI and is unlikely to show only residual cells with extensive fibrosis.     

A comparison of computed tomography and endorectal ultrasound in staging rectal cancer

Endorectal ultrasound was used prospectively to stage 85 patients with rectal cancer. All patients had surgical exploration and histological analysis. Demonstration of tumour, extension into perirectal fat and lymph node involvement were evaluated. Eighty-one tumours were successfully imaged by endorectal ultrasound. The results suggest that: (1) endorectal ultrasound is more accurate than CT in detecting the site of tumour; (2) endorectal ultrasound is more accurate than CT in detecting perirectal fat infiltration; (3) endorectal ultrasound is slightly more accurate than CT in detecting level II lymph node involvement.     

Influence of anemia on tumor response to preoperative chemoradiotherapy for locally advanced rectal cancer

Purpose  

In rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection, we evaluated the influence of anemia on tumor response to preoperative CRT.