Enhanced Tumorocidal Effect of Chemotherapy With Preoperative Radiotherapy for Rectal Cancer: Preliminary Results—EORTC 22921

Bosset, Jean-François; Calais, G.; Mineur, Laurent; Maingon, P.; Radošević-Jelić, Ljiljana; Daban, A.; Bardet, É.; Beny, Alexander; Briffaux, A.; Collette, Laurence

doi:10.1200/jco.2005.02.113

Cited by 542 publications

(325 citation statements)

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“…The results of the EORTC study suggested a different radioresponsiveness of the tumor in the bowel wall compared to that of mesorectal lymph nodes, as evidenced by nodal involvement in up to 12% of ypT0 patients. 32 At present, it is unclear whether increased tumor control results in an enhanced probability of sphincter preservation. Although in 2 studies (EORTC 22921; Boulis-Wassif et al) a trend toward increased sphincter preservation was observed in the CRT group, the combined results failed to demonstrate an increase in sphincter preserving surgery following CRT (OR 0.92-1.31, p 5 0.29).…”

Section: Discussionmentioning

confidence: 99%

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis

Ceelen

Fierens

Nieuwenhove

et al. 2009

Intl Journal of Cancer

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Combining chemotherapy with preoperative radiotherapy (RT) has a sound radiobiological rationale. We performed a systematic review and meta-analysis of trials comparing preoperative RT with preoperative chemoradiation (CRT) in rectal cancer patients. The Cochrane Central Register of Controlled Trials, Web of Science, Embase and Medline (Pubmed) were searched from 1975 until June 2007. Dichotomous parameters were summarized using the odds ratio while time to event data were analyzed using the pooled hazard ratio for death. From the primary search result of 324 trials, 4 relevant randomized trials were identified. The addition of chemotherapy significantly increased grade III and IV acute toxicity (p 5 0.002) while no differences were observed in postoperative morbidity or mortality. Preoperative CRT significantly increased the rate of pathological complete response (p < 0.001) although this did not translate into a higher sphincter preservation rate (p 5 0.29). The local recurrence rate was significantly lower in the CRT group (p < 0.001). No statistically significant differences were observed in disease free survival (p 5 0.89) or overall survival (p 5 0.79). Compared to preoperative RT alone, preoperative CRT improves local control in rectal cancer but is associated with a more pronounced treatment related toxicity. The addition of chemotherapy does not benefit sphincter preservation rate or long-term survival. Future trials should address improvements in the rate of distant metastasis and overall survival by incorporating more active chemotherapy. ' UICCKey words: rectal cancer; radiotherapy; surgery The incidence of fatal cases of colorectal cancer in Europe exceeds 200,000 per year. 1 Because of the specific anatomy and biology of rectal cancer, surgery alone historically has been associated with local recurrence in up to 1 in 4 patients. 2 Locally recurrent disease is usually incurable, causes important morbidity and suffering and gives rise to systemic metastases. In the last few decades, improvements in surgical technique have dramatically lowered the incidence of locally recurrent disease. Careful pathological studies have clearly demonstrated that the major cause of local recurrence is the persistence of tumor foci within the mesorectum. 3,4 Intact removal of the entire mesorectum (total mesorectal excision or TME) in cancers of the mid or lower third of the rectum was pioneered by Heald and has resulted in local recurrence rates lower than 5-10%. [5][6][7] Parallel to improvements in surgical technique, adjuvant therapy regimens have been tested in clinical trials in an effort to reduce local recurrence rates. Neoadjuvant radiotherapy (RT) has been shown to significantly decrease local recurrence rate and improve survival provided a biologically equivalent dose (BED) of at least 30 gray (Gy) is administered. 8 The advantages of preoperative over postoperative RT include enhanced effectiveness in well-oxygenated tissue, downstaging of advanced tumors and better treatment compliance. 9 The theoretical ...

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Section: Discussionmentioning

confidence: 99%

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis

Ceelen

Fierens

Nieuwenhove

et al. 2009

Intl Journal of Cancer

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“…The EORTC 22921 (Bosset et al, 2005) and FFCD 9203 (Gerard et al, 2006) trials compared intravenous 5-fluorouracil (5FU) and leucovorin (LV) given during the first and fifth weeks of radiotherapy with radiotherapy alone (dose of RT was 45 Gy in 25 fractions in both arms of the studies). Both trials demonstrated a reduction in the rates of local recurrence at 5 years from 17% with radiotherapy alone to 8 -9% with preoperative CRT, but neither trial showed any difference in overall survival.…”

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confidence: 99%

Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer

et al. 2007

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There is increasing evidence supporting the use of preoperative chemoradiotherapy in patients with locally advanced rectal cancer in an attempt to facilitate complete surgical resection with clear margins. We describe our experience of using a 5-day per week regime of preoperative capecitabine chemoradiotherapy. Between November 2004 and September 2006, 70 patients with MRI-defined locally advanced rectal cancer were selected for treatment. Capecitabine was given at a dose of 900 mg m À2 for 5 days per week combined with 45 Gy of radiotherapy in 25 doses. This regime was well tolerated with 89% of our patients receiving the full dose of chemotherapy and 96% receiving the full dose of radiotherapy. Ninety-three per cent proceeded to macroscopically complete surgical resection. The pathological complete response rate was 9.2% with a node-negative rate of 66%. A negative circumferential margin was achieved by 79% of the patients who underwent resection. Compared to studies using a 7-day per week capecitabine schedule, our results show increased compliance and less dose reductions with comparable pathological outcome. There is clear evidence from two systematic reviews that adjuvant radiotherapy reduces the risk of local recurrence in patients with resectable rectal cancer (Camma et al, 2000; Colorectal Cancer Collaborative, 2001). The greatest benefit is seen when preoperative radiotherapy is used with a biologically equivalent dose of 430 Gy. Further clinical trials were required to assess the benefit of adding concurrent chemotherapy to preoperative radiotherapy.The recent publication of two phase III trials confirms that preoperative concurrent chemoradiation (CRT) is superior to long-course radiotherapy alone in patients with T3/4 or nodepositive resectable rectal cancer. The EORTC 22921 (Bosset et al, 2005) and FFCD 9203 (Gerard et al, 2006) trials compared intravenous 5-fluorouracil (5FU) and leucovorin (LV) given during the first and fifth weeks of radiotherapy with radiotherapy alone (dose of RT was 45 Gy in 25 fractions in both arms of the studies). Both trials demonstrated a reduction in the rates of local recurrence at 5 years from 17% with radiotherapy alone to 8 -9% with preoperative CRT, but neither trial showed any difference in overall survival. A further recent phase III trial has demonstrated that preoperative 5FU CRT is superior to post-operative CRT with a significant reduction in local recurrence from 12 to 6% as well as a significant reduction in both acute and long-term toxicity (Sauer et al, 2004). This evidence will clearly result in an increasing use of fluoropyrimidine-based CRT.Intravenous 5FU-based chemoradiation presents many logistical challenges. Continuous infusion of 5FU requires the insertion of a central venous line with its attendant risks of thrombosis and infection as well as the inconvenience of a portable infusion pump. The use of the bolus 5FU/LV regimen used in the EORTC and FFCD trials requires 10 daily visits to the chemotherapy day unit, with associated waiting time, t...

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“…The European Organisation for Research and Treatment of Cancer (EO-RTC) trial investigated the effect of adding chemotherapy to pre-operative radiotherapy and the role of adjuvant chemotherapy in stages II and IV rectal cancer. As part of the analysis, they found that in addition to there being an increased proportion of mucinous tumours found following neo-adjuvant treatment, this was further enhanced in the group with chemo-and radiotherapy than just pre-operative radiotherapy alone [36]. This phenomenon is not fully understood; however, one explanation offered by the College of American Pathologists is that mucinous change is a feature of response to pre-operative treatment [33].…”

Section: Radiological Diagnosis and Measuring Responsementioning

confidence: 90%

Mucinous carcinoma of the rectum: a distinct clinicopathological entity

Chand

Swift

et al. 2013

Tech Coloproctol

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Purpose The definition of mucinous tumours relies on quantification of the amount of mucus produced by neoplastic cells within the rectum. This has changed over the years to include varying degrees of mucin production. The inconsistency of diagnosis has led to conflicting reports in the literature regarding clinical outcomes and treatment response. A universally accepted definition and improved imaging and surgical techniques in the last decade are now challenging the traditional view of these tumours. The aim of this review was to present the current evidence on the clinicopathological characteristics of mucinous tumours of the rectum. Methods A systematic review was conducted using Preferred Reporting for Systematic Reviews and Meta-Analyses guidelines. A literature search was performed using the Ovid SP to search both EMBASE and MEDLINE databases, Google Scholar and PubMed to find all studies relating to mucinous carcinoma of the rectum. The search dates were between 1 January 1965 and 1 March 2013. Results Mucinous tumours comprise 5-20 % of all rectal cancers and commonly present at a more advanced stage and in younger patients. They are readily identified on MRI, and the diagnosis is confirmed on histological analysis, demonstrating more than 50 % of extracellular mucin within the tumour complex. They carry an overall worse prognosis compared to adenocarcinoma of the same stage. The response to oncological treatment remains controversial. Conclusion Mucinous tumours of the rectum are less well understood than non-mucinous adenocarcinoma. This is due to the inconsistent histopathological definitions of the past making comparison of clinical outcome data difficult. They remain challenging to treat and are associated with a poor prognosis. A universally accepted definition and the role of imaging techniques such as MRI to accurately detect mucinous tumours are likely to lead to a better understanding of these cancers.

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Enhanced Tumorocidal Effect of Chemotherapy With Preoperative Radiotherapy for Rectal Cancer: Preliminary Results—EORTC 22921

Abstract: In patients with rectal cancer, preliminary results of EORTC Trial 22921 indicate that the addition of CT to preop RT induces down-sizing, downstaging, and significant changes in histologic characteristics. Longer follow-up is needed to assess the impact on local control and survival.

Cited by 542 publications

References 33 publications

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis

Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer

Mucinous carcinoma of the rectum: a distinct clinicopathological entity

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