Top

Published in:

Open Access 01-12-2013 | Research article

Prognosis of rectal cancer patients improves with downstaging by intensified neoadjuvant radiochemotherapy - a matched pair analysis

Authors: Leif Schiffmann, Gunther Klautke, Nicole Wedermann, Michael Gock, Friedrich Prall, Rainer Fietkau, Bettina Rau, Ernst Klar

Published in: BMC Cancer | Issue 1/2013

Abstract

Background

Neoadjuvant radiochemotherapy has been proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases in standard protocols of neoadjuvant radiochemotherapy. The present study aimed at addressing the effects of an intensified neoadjuvant radiochemotherapy on long term cancer related and disease free survival.

Methods

A total of 387 patients underwent oncologic resection for rectal cancer in our institution between January 2000 and December 2009. There were 106 patients (27.4%) who received an intensified radiochemotherapy protocol completely and without excluding criteria (study group). A matched pair analysis was performed by comparing the study group with patients undergoing primary surgery and postoperative radiochemotherapy, if necessary and possible (control group). Matching was carried out in descending order for UICC stage, R-status, tumor height, T-, N-, V-, L-, M- and G-category of the TNM-system according to the histopathological staging. Follow-up data included local recurrence rate, cancer related and disease free survival.

Results

In the study group histopathological work-up of the specimen revealed a treatment response in terms of tumor regression in 92.5% (98/106) of these patients. Undergoing intensified neoadjuvant RCT the actuarial cancer related and disease free survival was 67.9% and 70.4%, local recurrence was 5.7% after an observation period of 4.3 ± 2.55 years. In the control group cancer related and disease free survival was 71.7% and 82.7%, local recurrence was 4.7% after an observation period of 3.8 ± 3.05 years revealing no statistical significant difference between the two groups. Moreover, estimated 5-year results of cancer related survival (66.7% vs 67.9% (controls)), the disease free survival (66.7% vs 79.9% (controls)) as well as subgroup analysis of UICC 0-III and UICC IV patients showed no difference between the study and control group as well.

Conclusion

In our study, intensified neoadjuvant radio-chemotherapy shows a high rate of tumor regression. The resulting inferior histopathological tumor stage shows the same long term local control and systemic tumor control as the control group with a primary more favorable tumor stage.

Available only for authorised users

Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R, German Rectal Cancer Study Group: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004, 351: 1731-1740. 10.1056/NEJMoa040694.CrossRefPubMed

Ceelen WP, Van Nieuwenhove Y, Fierens K: Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database Syst Rev. 2009, 10.1002/14651858.CD006041.pub2. Issue 1. Art. No.: CD006041

Fiorica F, Cartei F, Licata A, Enea M, Ursino S, Colosimo C, Cammà C: Can chemotherapy concomitantly delivered with radiotherapy improve survival of patients with resectable rectal cancer? A meta-analysis of literature data. Cancer Treat Rev. 2010, 36: 539-549. 10.1016/j.ctrv.2010.03.002.CrossRefPubMed

Schmiegel W, Pox C, Reinacher-Schick A, Adler G, Fleig W, Fölsch UR, Frühmorgen P, Graeven U, Hohenberger W, Holstege A, Junginger T, Kopp I, Kühlbacher T, Porschen R, Propping P, Riemann JF, Rödel C, Sauer R, Sauerbruch T, Schmitt W, Schmoll HJ, Zeitz M, Selbmann HK: S3-Leitlinie “Kolorektales Karzinom”. Z Gastroenterol. 2008, 46: 1-73.CrossRef

Prall F, Wöhlke M, Klautke G, Schiffmann L, Fietkau R, Barten M: Tumour regression and mesorectal lyph node changes after intensified neoadjuvant chemoradiation for carcinoma of the rectum. APMIS. 2006, 114: 201-210. 10.1111/j.1600-0463.2006.apm_304.x.CrossRefPubMed

Hartley A, Ho KF, McConkey C, Geh JI: Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol. 2005, 78: 934-938. 10.1259/bjr/86650067.CrossRefPubMed

Weiss C, Arnold D, Dellas K, Liersch T, Hipp M, Fietkau R, Sauer R, Hinke A, Rödel C: Preoperative radiotherapy of advanced rectal cancer with capecitabine and oxaliplatin with or without cetuximab: a pooled analysis of three prospective phase I-II trials. Int J Radiat Oncol Biol Phys. 2010, 78: 472-478. 10.1016/j.ijrobp.2009.07.1718.CrossRefPubMed

Rödel C, Bruch HP, Hofheinz R, Lang H, Arnold D: Therapie des Rektumkarzinoms. Onkologie. 2010, 33: 19-23.CrossRefPubMed

Hacker U, Hallek M, Kubicka S: Multimodale Therapie des kolorektalen Karzinoms. Internist. 2010, 51: 1366-1373. 10.1007/s00108-010-2671-9.CrossRefPubMed

10.

Voelter V, Zouhair A, Vuilleumier H, Matter M, Bouzourene H, Leyvraz S, Bauer J, Coucke P, Stupp R: CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II. Br J Cancer. 2006, 95: 710-716. 10.1038/sj.bjc.6603322.CrossRefPubMedPubMedCentral

11.

Rödel C, Sauer R: Integration of novel agents into combined-modality treatment of rectal cancer patients. Strahlenther Onkol. 2007, 183: 227-235. 10.1007/s00066-007-9000-9.CrossRefPubMed

12.

Chitapanarux I, Kamnerdsupaphon P, Lorvidhaya V, Siriwittayakorn P, Tharavichitkul E, Somwangprasert A, Sukthomya V: Preoperative irinotecan/5FU/leucovorin plus concurrent radiotherapy in rectal cancer. Gan To Kagaku Ryoho. 2008, 35: 77-82.PubMed

13.

Rödel C, Knoefel WT, Schlitt HJ, Staib L, Höhler T: Neoadjuvante und operative Therapie des Rektumkarzinoms. Onkologie. 2009, 32: 17-20. 10.1159/000213485.CrossRefPubMed

14.

Klautke G, Küchenmeister U, Foitzik T, Ludwig K, Prall F, Klar E, Fietkau R: Concurrent chemoradiation with capecitabine and weekly irinotecan as randomized treatment for rectal cancer: results from a phase I/II study. Br J Cancer. 2006, 94: 976-981. 10.1038/sj.bjc.6603053.CrossRefPubMedPubMedCentral

15.

Klautke G, Küchenmeister U, Foitzik T, Ludwig K, Semrau S, Prall F, Klar E, Fietkau R: Intensified irinotecan-based neoadjuvant chemoradiotherapy in rectal cancer: four consecutive designed studies to minimize acute toxicity and to optimize efficacy measured by pathologic complete response. Radiother Oncol. 2007, 85: 379-384. 10.1016/j.radonc.2007.10.042.CrossRefPubMed

16.

Gollins SW, Myint S, Susnerwala S, Haylock B, Topham C, Samuel L, Swindell R, Morris J, Mason L, Levine E: Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2). Br J Cancer. 2009, 101: 924-934. 10.1038/sj.bjc.6605258.CrossRefPubMedPubMedCentral

17.

Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T: Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. 2010, 28: 1638-1644. 10.1200/JCO.2009.25.8376.CrossRefPubMed

18.

Dionisi F, Musio D, Raffetto N, Codacci-Pisanelli G, Iannacone E, Caiazzo R, Banelli E: Preoperative intensified radiochemotherapy for rectal cancer: experience of a single institution. Int J Colorectal Dis. 2011, 26: 153-164. 10.1007/s00384-010-1064-9.CrossRefPubMed

19.

Koerberle D, Burkhard R, von Moos R, Winterhalder R, Hess V, Heitzmann F, Ruhstaller T, Terraciano L, Neuweiler J, Bieri G, Rust C, Toepfer M: Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer. BJC. 2008, 98: 1204-1209. 10.1038/sj.bjc.6604297.CrossRef

20.

Heald RJ, Moran BJ, Ryall RD, Sexton R, MacFarlane JK: Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978–1997. Arch Surg. 1998, 133: 894-899. 10.1001/archsurg.133.8.894.CrossRefPubMed

21.

Van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Påhlman L, Glimelius B, van de Velde CJ, Dutch Colorectal Cancer Group: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomized controlled TME trial. Lancet Oncol. 2011, 12: 575-582. 10.1016/S1470-2045(11)70097-3.CrossRefPubMed

22.

Rödel C, Martus P, Papadoupolos T, Füzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C: Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005, 23: 8688-8696. 10.1200/JCO.2005.02.1329.CrossRefPubMed

23.

Lim SB, Yu CS, Hong YS, Kim TW, Park JH, Kim JH, Kim JC: Failure patterns correlate with the tumor response after preoperative chemoradiotherapy for locally advanced rectal cancer. J Surg Oncol. 2012, 10.1002/jso.23198.

24.

Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, German Rectal Cancer Study Group: Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012, 13: 679-687. 10.1016/S1470-2045(12)70187-0.CrossRefPubMed

25.

Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M: Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009, 373: 811-820. 10.1016/S0140-6736(09)60484-0.CrossRefPubMedPubMedCentral

26.

Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, Rutten H, Pahlman L, Glimelius B, Leer JW, van de Velde CJ, Dutch Colorectal Cancer Group: The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007, 246: 693-701. 10.1097/01.sla.0000257358.56863.ce.CrossRefPubMed

27.

Fietkau R, Rödel C, Hohenberger W, Raab R, Hess C, Liersch T, Becker H, Wittekind C, Hutter M, Hager E, Karstens J, Ewald H, Christen N, Jagoditsch M, Martus P, Sauer R, German Rectal Cancer Study Group: Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: results of study CAO/ARO/AIO-94. Int J Radiat Oncol Biol Phys. 2007, 67: 1008-1009. 10.1016/j.ijrobp.2006.10.020.CrossRefPubMed

28.

Zhao L, Bai C, Shao Y, Guan M, Jia N, Xiao Y, Qiu H, Zhang F, Yang T, Zhong G, Chen S: A phase II study of neoadjuvant chemoradiotherapy with oxaliplatin and capecitabine for rectal cancer. Cancer Lett. 2011, 310: 134-139. 10.1016/j.canlet.2011.06.026.CrossRefPubMed

29.

Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H: Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009, 27: 851-856. 10.1200/JCO.2008.17.0506.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/388/prepub

Title: Prognosis of rectal cancer patients improves with downstaging by intensified neoadjuvant radiochemotherapy - a matched pair analysis
Authors: Leif Schiffmann
Gunther Klautke
Nicole Wedermann
Michael Gock
Friedrich Prall
Rainer Fietkau
Bettina Rau
Ernst Klar
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-13-388

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2013

Trends in hepatitis B virus screening at the onset of chemotherapy in a large US cancer center

Derepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNA Hypomethylation

Preclinical evaluation of Sunitinib as a single agent in the prophylactic setting in a mouse model of bone metastases

Increased MiR-221 expression in hepatocellular carcinoma tissues and its role in enhancing cell growth and inhibiting apoptosis in vitro

Higher rate of skin rash in a phase II trial with weekly nanoparticle albumin-bound paclitaxel and cisplatin combination in Chinese breast cancer patients

Time from diagnosis to surgery and prostate cancer survival: a retrospective cohort study

Keynote webinar | Spotlight on antibody–drug conjugates in cancer