Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer

Pettersson, David; Cedermark, Björn; Holm, Torbjörn; Radu, Calin; Påhlman, Lars; Glimelius, Bengt; Martling, Anna

doi:10.1002/bjs.6914

Cited by 231 publications

(147 citation statements)

References 35 publications

(39 reference statements)

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“…[135][136][137][138][139][140] In locally advanced rectal cancer, both neoadjuvant CRT and short-course radiotherapy (SCRT) induce significant tumour regression, tumour downstaging and sterilization of perirectal lymph nodes, with better local control compared to surgery alone or postoperative CRT. [141][142][143][144] A complete response on pathology (pCR) is observed in up to 30% of patients, [145] with significantly better oncologic outcomes in patients with pCR than non-responders in terms of local control, distant metastases rate and both 5-year overall and disease-free survival [145].…”

Section: Expc: 909%]mentioning

confidence: 99%

Early rectal cancer: the European Association for Endoscopic Surgery (EAES) clinical consensus conference

et al. 2015

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Section: Expc: 909%]mentioning

confidence: 99%

Early rectal cancer: the European Association for Endoscopic Surgery (EAES) clinical consensus conference

et al. 2015

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“…In addition to, the interim results of Stockholm 3 trial also showed that pCR rates significantly increased from < 1% to 13% in patients receving 5-day short course radiotherapy in immediate surgery and 4-8 weeks delays group, respectively. 10 Although, the authors stated that the time from chemoradiation to surgery can contribute to pCR rates remains speculative than the administration of mFOLFOX6, we can not give up this idea after the equalization time interval from completion of chemoradiation to surgery between treatment groups. In conclusion, the unequal distribution clinical nodal stage and time interval from the end of chemoradiation treatment between treatment groups have had a bias effect on pCR outcome regarding the adding mFOLFOX6 regimen.…”

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confidence: 90%

Adding Chemotherapy After Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer; Promising or not?

Şendur¹

2017

UHOD

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To the editor, Neoadjuvant or adjuvant treatment of stage II or III usually includes locoregional teratment due to the high risk of locoregional recurrence. According to prospective, randomized phase III German Rectal Study Group (CAO/ARA/AIO-94) trial, preoperative chemooradiotherapy significantly improved local control with reduced toxicity compared to postoperative chemoradiotherapy in clinical stage T3 or T4 or node-positive rectal cancer patients.1 In a study of T3 or T4 rectal cancer patients pre-operative concurrent chemoradiotherapy with 5-Fluorouracil and leucovorin combination significantly increased pathological complete response (pCR) rate and significantly decreased local recurrence rate compared to radiotherapy alone despite no overall survival benefit.2 In a systematic review of 5 randomized trials, it was reported that preoperative chemoradiotherapy significantly increased pCR rate and improved local control in resectable stage II and III rectal cancer, but did not improve disease free or overall survival compared to preoperative radiotherapy alone. To increase response rate and overall survival several large randomized phase III trials investigated the efficacy of adding oxaliplatin to concurrent chemoradiotherapy regimen. In NSABP-R04, STAR 01 and ACCORD12/405-prodige 2 trials, addition of oxaliplatin did not improve pCR rate, also increased grade 3-4 toxicity. On the other hands, recently published in a phase III German CAO/ARO/AIO-04 trial, pCR and the primary endpoint 3-year disease free survival (DFS) significantly improved with adding oxaliplatin to preoperative concurrent chemoradiotherapy and postsurgical infusional fluorouracil.

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“…Small bowel toxicity with an increased risk for bowel obstruction is probably the most frequent side effect (5,36,37). The incidence of severe radio toxicity with leukopenia, abdominal pain and diarrhea is around 5% (38,39). The late effects of RT may add to the complications of pelvic surgery.…”

Section: The Biological Phasementioning

confidence: 99%

“…The risk for secondary cancer is increased after irradiation (36) Several studies have demonstrated that LRT and SRT with delay have comparable down staging effect and reduction in the rate of local recurrence (38)(39)(40). There is a clear doseresponse between the RT-dose and the tumour down staging when the same fractionations are compared (35,41).…”

Section: The Biological Phasementioning

confidence: 99%

Response to neoadjuvant treatment in rectal cancer surgery

Loftås

2016

Linköping University Medical Dissertations

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Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT. Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer. Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer. Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour. Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, spe...

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Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer

Abstract: NCT00904813 (http://www.clinicaltrials.gov).

Cited by 231 publications

References 35 publications

Early rectal cancer: the European Association for Endoscopic Surgery (EAES) clinical consensus conference

Early rectal cancer: the European Association for Endoscopic Surgery (EAES) clinical consensus conference

Adding Chemotherapy After Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer; Promising or not?

Response to neoadjuvant treatment in rectal cancer surgery

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