Subscribe to RSS
DOI: 10.1055/s-0030-1262523
© Georg Thieme Verlag KG Stuttgart ˙ New York
Das Optimult-Studienkonzept – Grundlage für selektiven Einsatz neoadjuvanter Radiochemotherapie auf MRT-Basis?
The Optimult Study Concept – Selective Neoadjuvant Chemoradiation Therapy Based on Preoperative MRI?Publication History
Publication Date:
30 August 2010 (online)
![](https://www.thieme-connect.de/media/zblchir/201004/lookinside/thumbnails/10.1055-s-0030-1262523-1.jpg)
Zusammenfassung
Optimale Chirurgie des Rektumkarzinoms im mittleren und unteren Rektumdrittel in Form der totalen mesorektalen Exzision reduziert die Lokalrezidivrate erheblich. Allerdings wurde gezeigt, dass diese Rate beim fortgeschrittenen Rektumkarzinom durch multimodale Therapiekonzepte weiter verbessert wird. In Deutschland ist derzeit die neoadjuvante Radiochemotherapie für diese Tumoren am verbreitetsten. Das klinische Staging mittels Endosonografie, CT und / oder MRT ist allerdings insbesondere hinsichtlich der Lymphknotenkategorie unsicher, woraus eine Übertherapie von einer erheblichen Anzahl von Patienten, basierend auf einem Overstaging, resultiert. Dies bedeutet, dass ein Teil der Patienten Nebenwirkungen und Langzeitfolgen der neoadjuvanten Therapie in Kauf nehmen muss, ohne dass damit ein onkologischer Gewinn verbunden ist. Die Prognose eines Patienten mit lokal fortgeschrittenem Rektumkarzinom hängt jedoch nicht nur von der T- und N-Kategorie ab, sondern auch vom Abstand des Tumors zum zirkumferenziellen Resektionsrand bei der pathologischen Beurteilung. Letzterer ist im Gegensatz zur T- und N-Kategorie prätherapeutisch sehr genau mittels MRT-Untersuchung vorherzusagen. Wenngleich in Fallserien gezeigt werden konnte, dass mit primärer optimaler Chirurgie bei freien zirkumferenziellen Resektionrändern im MRT niedrige Lokalrezidivraten erzielt werden können, wurde dieses Konzept bisher nicht in einer randomisierten Studie untersucht. Wir planen deshalb eine randomisierte zweiarmige Studie mit Patienten, deren Rektumkarzinom 2 mm oder mehr Abstand vom zirkumferenziellen Resektionsrand im MRT aufweist. Diese werden entweder primär operiert (Interventionsarm) oder neoadjuvant radiochemotherapiert mit anschließender Chirurgie (Kontrollarm). Falls sich im Interventionsarm Lokalrezidivraten nicht unterlegen denen im Kontrollarm zeigen ließen, würde diese Studie die Basis für ein individualisiertes Behandlungskonzept, basierend auf präoperativer MRT-Bildgebung, darstellen. Damit wäre eine Reduktion von Radiochemotherapien bei Patienten möglich, die davon keinen onkologischen Gewinn haben.
Abstract
Optimal surgery for rectal cancer, i. e., total mesorectal excision in the middle and lower rectum reduces local recurrence substantially. Multi-modal therapy further improves the rate of local recurrence in advanced rectal cancer. In Germany neoadjuvant chemoradiation therapy is most frequently given for these tumours. However, clinical staging by endosonography, CT scan and / or MRI is unreliable, particulary as regards lymph node category, which entails overtreatment of a relevant number of patients secondary to overstaging. Thus, a subgroup of patients has to tolerate side effects and long-term sequelae of neoadjuvant therapy without having oncological benefit from this pretreatment. It is of note that the prognosis of patients with advanced rectal cancer depends not only on the T and N category but also on the free circumferential margin of the tumour as determined by pathological examination. In contrast to the T and N category, the latter may be predicted before treatment by pelvic MRI. While several case series demonstrated that low local recurrence rates are achieved in patients when preoperative MRI showed free circumferential margins, this concept was never tested in a randomised controlled trial. We, therefore, designed a two-armed randomised study with patients who suffer from rectal cancer and who have 2 mm or more free circumferential margins on their preoperative MRI. These patients are either operated without pretreatment (intervention arm) or receive neoadjuvant chemoradiation therapy with subsequent surgery (control arm). If local recurrence in the intervention arm is not inferior to the control arm, this study may form the basis for an individualised therapeutic concept for rectal cancer based on preoperative MRI. Potentially, chemoradiation therapy may be avoided in the future for patients who will have no oncological benefit from this treatment modality.
Schlüsselwörter
Rektumkarzinom - Lokalrezidiv - Lebensqualität
Key words
rectal carcinoma / cancer - local recurrence of tumour growth - quality of life
Literatur
Der Artikel wurde geändert gemäß folgendem Erratum vom 13.10.2010:
Erratum
M. E. Kreis, T. Junginger, C. Rödel, V. Heinemann, K. Nikolaou, U. Mansmann, K. W. Jauch
Das Optimult-Studienkonzept – Grundlage für selektiven Einsatz neoadjuvanter Radiochemotherapie auf MRT-Basis?
Zentralbl Chir 2010; 135: 302–306
Der Artikel enthält Fehler in der Schreibweise zweier Autoren.
Der Name des einen Autors muss V. Heinemann lauten, nicht V. Heinemanne.
Der Name des anderen Autors muss K. Nikolaou lauten, nicht Konstantin N.
- 1 Enker W E. Designing the optimal surgery for rectal carcinoma. Cancer. 1996; 78 1847-1850
- 2 Junginger T, Hermanek P, Oberholzer K et al. Rektumkarzinom: Behandeln wir zu häufig neoadjuvant? Vorschläge zu einer selektiveren, MRT-basierten Indikation. Zentralbl Chir. 2006; 131 275-284
- 3 Bokey E L, Öjerskog B, Chapuis P H et al. Local recurrence after curative excision of the rectum for cancer without adjuvant therapy: role of total anatomic dissection. Br J Surg. 1999; 86 1164-1170
- 4 Heald R J, Husband E M, Ryall R D. The mesorectum in rectal cancer surgery – the clue to pelvic recurrence?. Br J Surg. 1982; 69 613-616
- 5 Sebag-Montefiore D, Stephens R J, Steele R et al. Preoperative radiotherapy versus slelective posopterative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomized trial. Lancet. 2009; 373 811-820
- 6 Kapiteijn E, Marijnen C A, Nagtegaal I D et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001; 345 638-646
- 7 Sauer R, Becker H, Hohenberger W German Rectal Cancer Study Group et al.,. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004; 351 1731-1740
- 8 Wong R K, Berry S, Spithoff K Gastrointestinal Cancer Disease Site Group (2010) et al.,. Preoperative or postoperative therapy for stage II or III rectal cancer: an update practice guideline. Clin Oncol (R Coll Radiol). 2010; 22 265-271
- 9 Nagtegaal I D, Marijnen C AM, Kranenberg E K et al. Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma. Am J Surg Pathol. 2002; 26 350-357
- 10 Rau B, Hohenberger P, Gellermann J et al. T4 rectal carcinoma. Surgical and multimodal therapy. Chirurg. 2002; 73 147-153
- 11 Bujko K, Nowacki M P, Nasierowska-Guttmejer A et al. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol. 2004; 72 15-24
- 12 Buijko K, Kepka L, Michalski W et al. Does rectal cancer shrinkage induced by preoperative radio(chemo)therapy increase the likelihood of anterior resection? A systematic review of randomised trials. Radiother Oncol. 2006; 80 4-12
- 13 Maurer C A, Z’Graggen K, Renzulli P et al. Total mesorectal excision preserves male genital function compared with conventional rectal cancer surgery. Br J Surg. 2001; 88 1501-1505
- 14 Peeters K C, van de Velde C J, Leer J W et al. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients – a Dutch colorectal cancer group study. J Clin Oncol. 2005; 23 6199-6206
- 15 Pollack J, Holm T, Cedermark B et al. Long-term effect of preoperative radiation therapy on anorectal function. Dis Colon Rectum. 2006; 49 345-352
- 16 Gervaz P, Rotholtz N, Pisano M et al. Quantitative short-term study of anal sphincter function after chemoradiation for rectal cancer. Arch Surg. 2001; 136 192-196
- 17 Ammann K, Kirchmayr W, Klaus A et al. Impact of neoadjuvant chemoradiation on anal sphincter function in patients with carcinoma of the midrectum and low rectum. Arch Surg. 2003; 138 257-261
- 18 Jang N Y, Han T J, Kang S B et al. The short-term effect of neoadjuvant chemoradiation on anorectal function in low and midrectal cancer: analysis using preoperative manometric data. Dis Colon Rectum. 2010; 53 445-449
- 19 Pietrzak L, Bujko K, Nowacki M P et al. Quality of life, anorectal and sexual functions after preoperative radiotherapy for rectal cancer: report of a randomised trial. Radiother Oncol. 2007; 84 217-225
- 20 Pietsch A P, Fietkau R, Klautke G et al. Effect of neoadjuvant chemoradiation on postoperative fecal continence and anal sphincter function in rectal cancer patients. Int J Colorectal Dis. 2007; 22 1311-1317
- 21 Birbeck K F, Macklin C P, Tiffin N J et al. Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery. Ann Surg. 2002; 35 449-457
- 22 Bittner R, Burghardt J, Gross E (Arbeitsgruppe Workflow Rektumkarzinom II) et al.. Qualitätsindikatoren bei Diagnostik und Therapie des Rektumkarzinoms. Zentralbl Chir. 2007; 132 85-94
- 23 Glynne-Jones R, Mawdsley S, Pearce T et al. Alternative clinical end points in rectal cancer – are we getting closer?. Ann Oncol. 2006; 17 1239-1242
- 24 Mawdsley S, Glynne-Jones R, Grainger J et al. Can histopathologic assessment of circumferential margin after preoperative pelvic clearance therapy for T3–T4 rectal cancer predict for 3-year disease-free survival?. Int J Radiat Oncol Biol Phys. 2005; 63 745-750
- 25 Strassburg J, Junginger T, Trinh T et al. Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status. Int J Colorect Dis. 2008; 23 1099-1107
- 26 Eriksen M T, Wibe A, Haffner J Norwegian Rectal Cancer Group et al.,. Prognostic groups in 1 676 patients with T3 rectal cancer treated without preoperative radiotherapy. Dis Colon Rectum. 2007; 50 156-167
- 27 Nagtegaal I D, Marijnen C AM, Kranenberg E K et al. Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma. Am J Surg Pathol. 2002; 26 350-357
- 28 Nagtegaal I D, Quirke P. What is the role of the circumferential margin in the modern treatment of rectal cancer. J Clin Oncol. 2008; 26 303-312
- 29 Nagtegaal I D, Gosens M J, Marijnen C A et al. Combinations of tumor and treatment parameters are more discriminative for prognosis than the present TNM system in rectal cancer. J Clin Oncol. 2007; 25 1647-1650
- 30 Beets-Tan R GH, Beets G L. Rectal cancer: Review with emphasis on MR imaging. Radiol. 2004; 232 335-346
- 31 Brown G, Richards C J, Newcombe R G et al. Rectal carcinoma: thin-section MR imaging for staging in 28 patients. Radiology. 1999; 211 215-222
- 32 MERCURY Study Group . Diagnostic accuracy of preoperative magnetic resonance imaging in predictiong curative resection of rectal cancer: prospective observational study. Br Med J. 2006; 333 779-784
- 33 Hermanek P, Junginger T, Merkel S et al. High-resolution magnetic resonance imaging (MRI) in patients with rectal carcinoma: Effectiveness in selection for neoadjuvant treatment. Recent Res Devel Cancer. 2006; 8 39-56
- 34 Crawshaw A, Hennigan R, Smedley F H et al. Perioperative radiotherapy for rectal cancer: the case for a selective pre-operative approach – the third way. Colorectal Dis. 2003; 5 367-372
- 35 Burton S, Brown G, Daniels I R Royal Marsden Hospital, Colorectal Cancer Network et al. on behalf of the. MRI directed multidisciplinary team preoperative treatment strategy: the way to eliminate positive circumferential margins?. Br J Cancer. 2006; 94 351-357
- 36 Chau I, Brown G, Cunningham D et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol. 2006; 24 668-674
- 37 Engelen S, Lahaye M J, Beets-Tan R G et al. Tailored treatment of primary rectal cancer based on MRI: does it reduce the number of incomplete resections? Abstract. Ann Oncol. 2008; 19 Suppl 1 1-17
- 38 Brown G, Daniels I R. Preoperative staging of rectal cancer: the MERCURY research project. Recent Results Cancer Research. 2005; 165 58-74
- 39 Schmiegel W, Pox C, Reinacher-Schick A et al. S3-Leitlinie „Kolorektales Karzinom“. Z Gastroenterol. 2008; 46 1-73
- 40 Hermanek P, Hohenberger W, Fietkau R et al. Individualized MRI-based neoadjuvant chemoradiation for middle and lower rectal carcinoma. Colorectal Dis. 2009; [Epub ahead of print]
Prof. Martin E. Kreis
Klinikum der Universität München · Chirurgische Klinik und Poliklinik
Marchioninistraße 15
81377 München
Deutschland
Phone: 0 89 / 70 95 65 61
Fax: 0 89 / 70 95 88 94
Email: martin.kreis@med.uni-muenchen.de