Zusammenfassung
Multimodale Therapiekonzepte wurden in den letzten Jahren in der Behandlung des lokal
fortgeschrittenen Ösophaguskarzinoms (cT3 / 4Nx) etabliert. Dabei kommt vor allem
die neoadjuvante Radiochemotherapie oder die alleinige Chemotherapie zum Einsatz.
Die aktuell vorliegenden Metaanalysen zur neoadjuvanten Therapie des lokal fortgeschrittenen
Ösophaguskarzinoms weisen nur einen Prognosevorteil von 5–10 % bezüglich der 5-Jahres-Überlebensrate
für die Gesamtgruppe der behandelten Patienten auf. Patienten mit einem sehr guten
histopathologischen Ansprechen zeigen jedoch ausgezeichnete Überlebenswahrscheinlichkeiten
trotz eines initial fortgeschrittenen Tumorstadiums. Patienten mit einem schlechten
histopathologischen Ansprechen haben keinen Vorteil oder eher einen Prognosenachteil.
Deshalb wären prädiktive Marker, die eine individualisierte multimodale Therapie beim
lokal fortgeschrittenen Ösophaguskarzinom ermöglichen würden, von großer Bedeutung.
Abstract
Multimodality treatment options have been widely promoted in the therapy for locally
advanced oesophageal cancer (cT3 / 4Nx). Generally neoadjuvant chemotherapy and
combined radiochemotherapy are frequently used in this setting. The recent meta-analyses
evaluating randomised trials of different neoadjuvant therapy protocols prior to surgery
for patients with locally advanced oesophageal cancer showed only a modest improvement
in survivial of 5–10 % survival at 5 years. In contrast, the meta-analyses reveal
that patients with excellent histopathological responses seem to highly benefit from
neoadjuvant regimens. Patients with poor histopathological responses have no benefit
but rather disadvantegeous prognoses. Therefore, predictive markers to allow individualisation
of multimodality treatment in locally advanced esophageal cancer are urgently needed.
Schlüsselwörter
Ösophaguskarzinom - multimodale Therapie - Response-Prädiktion
Key words
oesophageal cancer - multimodality treatment - response prediction
Literatur
- 1
Hölscher A H, Vallböhmer D.
Surgical treatment of esophageal tumors including local ablation.
Zentralbl Chir.
2007;
132
18-36
- 2
Lerut T, Moons J, Coosemans W et al.
Multidisciplinary treatment of advanced cancer of the esophagus and gastroesophageal
junction: a European center's approach.
Surg Oncol Clin N Am.
2008;
17
485-502
- 3
Bhansali M S, Vaidya J S, Bhatt R G et al.
Chemotherapy for carcinoma of the esophagus: a comparison of evidence from meta-analyses
of randomized trials and of historical control studies.
Ann Oncol.
1996;
7
355-359
- 4
Urschel J D, Vasan H, Blewett C J.
A meta-analysis of randomized controlled trials that compared neoadjuvant chemotherapy
and surgery to surgery alone for resectable esophageal cancer.
Am J Surg.
2002;
183
274-279
- 5
Urschel J, Vasan H.
A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation
and surgery to surgery alone for resectable esophageal cancer.
Am J Surg.
2003;
185
538-543
- 6
Kaklamanos I G, Walker G R, Ferry K et al.
Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal
junction: a meta-analysis of randomized clinical trials.
Ann Surg Oncol.
2003;
10
754-761
- 7
Malthaner R, Wong R, Rumble R et al.
Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic review
and meta-analysis.
BMC Med.
2004;
2
35
- 8
Fiorica F, Di Bona D, Schepis F et al.
Preoperative chemoradiotherapy for esophageal cancer: a systematic review and meta-analysis.
Gut.
2004;
53
925-930
- 9
Greer S, Goodney P, Sutton J et al.
Neoadjuvant chemoradiotherapy for esophageal carcinoma: a meta-analysis.
Surgery.
2005;
137
172-177
- 10 Vogt K, Fenlon D, Rhodes S et al. Preoperative chemotherapy for resectable thoracic
esophageal cancer. Cochrane Database of Systematic Reviews 2006 3 CD001556
- 11
Gebski V, Burmeister B, Smithers B M Australian Gastro-Intestinal Trials Group et
al.,.
Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal
carcinoma: a meta-analysis.
Lancet Oncol.
2007;
8
226-234
- 12
Jin H L, Zhu H, Ling T S et al.
Neoadjuvant chemoradiotherapy for resectable esophageal carcinoma: a meta-analysis.
World J Gastroenterol.
2009;
15
5983-5991
- 13
Baldus S E, Mönig S P, Schröder W et al.
Regression of oesophageal carcinomas after neoadjuvant radiochemotherapy: criteria
of the histopathological evaluation.
Pathologe.
2004;
25
421-427
- 14
Schneider P M, Baldus S E, Metzger R et al.
Histomorphologic tumor regression and lymph node metastases determine prognosis following
neoadjuvant radiochemotherapy for esophageal cancer: implications for response classification.
Ann Surg.
2005;
242
684-692
- 15
Vallböhmer D, Hölscher A H, DeMeester S et al.
A multicenter study of survival after neoadjuvant radiotherapy / chemotherapy and
esophagectomy for ypT0N0M0R0 esophageal cancer.
Ann Surg.
2010;
252
744-749
- 16
Fok M, McShane J, Law S YK et al.
Prospective randomised study in the treatment of oesophageal carcinoma.
Asian J Surg.
1994;
17
223-229
- 17
Launois B, Delarue D, Campion J P et al.
Preoperative radiotherapy for carcinoma of the esophagus.
Surg Gynecol Obstet.
1981;
153
690-692
- 18
Gignoux M, Roussel A, Paillot B et al.
The value of preoperative radiotherapy in esophageal cancer: results of a study of
the E.O.R.T.C.
World J Surg.
1987;
11
426-432
- 19
Wang M, Gu X Z, Yin W et al.
Randomized clinical trial on the combination of preoperative irradiation and surgery
in the treatment of esophageal carcinoma: report on 206 patients.
Int J Radiat Oncol Biol Phys.
1989;
16
325-327
- 20
Nygaard K, Hagen S, Hansen H S et al.
Preoperative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized,
multicenter study of preoperative radiotherapy and chemotherapy. The second Scandinavian
trial in esophageal cancer.
World J Surg.
1992;
16
1104-1109
- 21
Arnott S J, Duncan W, Kerr G R et al.
Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized
clinical trial.
Radiother Oncol.
1992;
24
108-113
- 22 Arnott S J, Duncan W, Gignoux M et al. Preoperative radiotherapy for esophageal
carcinoma. Cochrane Database Syst Rev 2005 4 CD001799
- 23 Malthaner R, Fenlon D. Preoperative chemotherapy for resectable thoracic esophageal
cancer. Cochrane Database Syst Rev 2003 4 CD001556
- 24
Medical Research Council Oesophageal Cancer Working Group .
Surgical resection with or without preoperative chemotherapy in oesophageal cancer:
a randomised controlled trial.
Lancet.
2002;
359
1727-1733
- 25
Wijnhoven B P, van Lanschot J J, Tilanus H W et al.
Neoadjuvant chemoradiotherapy for esophageal cancer: a review of meta-analyses.
World J Surg.
2009;
33
2606-2614
- 26
Gaast A V, van Hagen P, Hulshof M et al.
Effect of preoperative concurrent chemoradiotherapy on survival of patients with resectable
esophageal or esophagogastric junction cancer: Results from a multicenter randomized
phase III study.
J Clin Oncol.
2010;
28
15s
(abstract 4004)
- 27
Bollschweiler E, Metzger R, Drebber U et al.
Histological type of esophageal cancer might affect response to neo-adjuvant radiochemotherapy
and subsequent prognosis.
Ann Oncol.
2009;
20
231-238
- 28
Ruhstaller T, Pless M, Dietrich D et al.
Cetuximab in Combination With Chemoradiotherapy Before Surgery in Patients With Resectable,
Locally Advanced Esophageal Carcinoma: A Prospective, Multicenter Phase I B / II
Trial (SAKK 75 / 06).
J Clin Oncol.
2011;
29
626-639
- 29
Gibson M K, Catalano P J, Kleinberg L et al.
E2205: A phase II study to measure response rate and toxicity of neoadjuvant chemoradiotherapy
(CRT) with oxaliplatin (OX) and infusional 5-fluorouracil (5-FU) plus cetuximab (C)
followed by postoperative docetaxel (DT) and C in patients with operable adenocarcinoma
of the esophagus.
J Clin Oncol.
2010;
28
15s
(abstract 4064)
- 30
Lordick F.
Neoadjuvant therapy for squamous cell carcinoma of the esophagus.
Chirurg.
2005;
76
1025-1032
- 31
Semrau R, Vallböhmer D, Hölscher A H et al.
Neoadjuvant therapy of adenocarcinomas of the upper gastrointestinal tract. Status
of radiotherapy.
Chirurg.
2009;
80
1035-1041
- 32
Ruol A, Rizzetto C, Castoro C et al.
Interval between neoadjuvant chemoradiotherapy and surgery for squamous cell cancer
of the thoracic esophagus.
Ann Surg.
2010;
252
788-796
- 33
Bollschweiler E, Besch S, Drebber U et al.
Influence of Neoadjuvant Chemoradiation on the Number and Size of Analyzed Lymph Nodes
in Esophageal Cancer.
Ann Surg Oncol.
2010;
17
3187-3194
- 34
Schneider P M, Metzger R, Schaefer H et al.
Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately
predict histopathologic regression after neoadjuvant chemoradiation for esophageal
cancer.
Ann Surg.
2008;
248
902-908
- 35
Lordick F, Ott K, Krause B J et al.
PET to assess early metabolic response and to guide treatment of adenocarcinoma of
the oesophagogastric junction: the MUNICON phase II trial.
Lancet Oncol.
2007;
8
797-805
- 36
Vallböhmer D, Hölscher A H, Dietlein M et al.
[18F]-Fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic
response and prognosis after completion of neoadjuvant chemoradiation in esophageal
cancer.
Ann Surg.
2009;
250
888-894
- 37
Vallböhmer D, Brabender J, Metzger R et al.
Genetics in the Pathogenesis of Esophageal Cancer: Possible Predictive and Prognostic
Factors.
J Gastrointest Surg.
2010;
23
185-190
Prof. Dr. A. H. Hölscher
Klinik und Poliklinik für Allgemein-, Viszeral- und Tumorchirurgie · Universität zu
Köln
Kerpener Str. 62
50937 Köln
Deutschland
Phone: 02 21 / 4 78 48 01
Fax: 02 21 / 4 78 48 43
Email: Arnulf.Hoelscher@medizin.uni-koeln.de
