Advertisement

Strahlentherapie und Onkologie

, Volume 186, Issue 1, pp 30–35 | Cite as

High-Grade Acute Organ Toxicity During Preoperative Radiochemotherapy as Positive Predictor for Complete Histopathologic Tumor Regression in Multimodal Treatment of Locally Advanced Rectal Cancer*

  • Hendrik Andreas Wolff
  • Jochen Gaedcke
  • Klaus Jung
  • Robert Michael Hermann
  • Hilka Rothe
  • Markus Schirmer
  • Torsten Liersch
  • Markus Karl Alfred Herrmann
  • Steffen Hennies
  • Margret Rave-Fränk
  • Clemens Friedrich Hess
  • Hans ChristiansenEmail author
Original Article

Purpose:

To test for a possible correlation between high-grade acute organ toxicity during preoperative radiochemotherapy and complete tumor regression after total mesorectal excision in multimodal treatment of locally advanced rectal cancer.

Patients and Methods:

From 2001 to 2008, 120 patients were treated. Preoperative treatment consisted of normofractionated radiotherapy at a total dose of 50.4 Gy, and either two cycles of 5-fluorouracil (5-FU) or two cycles of 5-FU and oxaliplatin. Toxicity during treatment was monitored weekly, and any toxicity CTC (Common Toxicity Criteria) ≥ grade 2 of enteritis, proctitis or cystitis was assessed as high-grade organ toxicity for later analysis. Complete histopathologic tumor regression (TRG4) was defined as the absence of any viable tumor cells.

Results:

A significant coherency between high-grade acute organ toxicity and complete histopathologic tumor regression was found, which was independent of other factors like the preoperative chemotherapy schedule. The probability of patients with acute organ toxicity ≥ grade 2 to achieve TRG4 after neoadjuvant treatment was more than three times higher than for patients without toxicity (odds ratio: 3.29, 95% confidence interval: [1.01, 10.96]).

Conclusion:

Acute organ toxicity during preoperative radiochemotherapy in rectal cancer could be an early predictor of treatment response in terms of complete tumor regression. Its possible impact on local control and survival is under further prospective evaluation by the authors’ working group.

Key Words:

Rectal cancer Side effects Tumor regression Preoperative radiochemotherapy 

Höhergradige akute Organtoxizität während präoperativer Radiochemotherapie als positiver Prädiktor für komplette histopathologische Regression in der multimodalen Behandlung von lokal fortgeschrittenen Rektumkarzinomen

Ziel:

Überprüfung einer möglichen Korrelation zwischen höhergradiger akuter Organtoxizität während präoperativer Radiochemotherapie und kompletter Tumorregression nach totaler mesorektaler Exzision in der multimodalen Behandlung von lokal fortgeschrittenen Rektumkarzinomen.

Patienten und Methodik:

Im Zeitraum von 2001 bis 2008 wurden 120 Patienten behandelt. Die präoperative Behandlung bestand aus einer normofraktionierten Radiotherapie mit einer Gesamtdosis von 50,4 Gy und entweder zwei Zyklen 5-Fluorouracil (5-FU) oder zwei Zyklen 5-FU und Oxaliplatin. Die Toxizität während der Behandlung wurde wöchentlich untersucht. Jede Toxizität ≥ Grad 2 nach CTC (Common Toxicity Criteria) in Form von Enteritis, Proktitis oder Zystitis wurde dabei als höhergradige Organtoxizität gewertet und für spätere Analysen verwendet. Bei vollständigem histopathologischen Tumoransprechen (TRG4) konnten im Operationspräparat nach neoadjuvanter Therapie keine vitalen Tumorzellen mehr identifiziert werden.

Ergebnisse:

Es fand sich eine signifikante Korrelation zwischen höhergradiger akuter Organtoxizität und kompletter Tumorregression, und zwar in multivariater Analyse unabhängig von anderen Faktoren wie z.B. dem präoperativen Chemotherapieregime. Die Wahrscheinlichkeit für die Patienten mit höhergradigen Nebenwirkungen, eine histopathologische Komplettremission zu entwickeln, war mehr als dreimal höher als für Patienten ohne Toxizität (Odds-Ratio: 3,29, 95%-Konfidenzintervall: [1,01, 10,96]).

Schlussfolgerung:

Höhergradige akute Organtoxizität während präoperativer Radiochemotherapie bei Patienten mit multimodaler Therapie lokal fortgeschrittener Rektumkarzinome könnte einen frühen Prädiktor für das Ansprechen auf die Therapie in Bezug auf die histopathologische Remission darstellen. Ob dieser Parameter auch für die lokale Kontrolle sowie das Gesamtüberleben prädiktiv sein kann, wird in weiteren prospektiven Untersuchungen durch die Arbeitsgruppe der Autoren untersucht.

Schlüsselwörter:

Rektumkarzinom Nebenwirkungen Tumorregression Präoperative Radiochemotherapie 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Beddy D, Hyland JM, Winter DC, et al. A simplified tumor regression grade correlates with survival in locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy. Ann Surg Oncol 2008;15:3471–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Bonner JA, Harari P, Giralt J, et al. The relationship of cetuximab-induced rash and survival in patients with head and neck cancer treated with radiotherapy and cetuximab. Int J Radiat Oncol Biol Phys 2005;63:S73.CrossRefGoogle Scholar
  3. 3.
    Borgmann K, Hoeller U, Nowack S, et al. Individual radiosensitivity measured with lymphocytes may predict the risk of acute reaction after radiotherapy. Int J Radiat Oncol Biol Phys 2008;71:256–64.CrossRefPubMedGoogle Scholar
  4. 4.
    Chavaudra J. Last ICRU recommendations for the prescription, recording and reporting of external bean therapy. Cancer Radiother 1998;2:607–14.CrossRefPubMedGoogle Scholar
  5. 5.
    Christiansen H, Hermann RM, Hille A, et al. Concomitant radiochemotherapy in primary inoperable advanced head and neck cancer with 5-fluorouracil and mitomycin-C. Head Neck 2004;26:845–53.CrossRefPubMedGoogle Scholar
  6. 6.
    Crane CH, Janjan NA, Mason K, et al. Preoperative chemoradiation for locally advanced rectal cancer: emerging treatment strategies. Oncology (Williston Park) 2002;16:39–44.Google Scholar
  7. 7.
    Cuzick J, Sestak I, Cella D, et al. Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol 2008;9:1143–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Dahl O, Horn A, Mella O. Do acute side-effects during radiotherapy predict tumour response in rectal carcinoma? Acta Oncol 1994;33:409–13.CrossRefPubMedGoogle Scholar
  9. 9.
    Daly T, Poulsen MG, Denham JW, et al. The effect of anaemia on efficacy and normal tissue toxicity following radiotherapy for locally advanced squamous cell carcinoma of the head and neck. Radiother Oncol 2003;68:113–22.CrossRefPubMedGoogle Scholar
  10. 10.
    Dellas K, Bache M, Pigorsch SU, et al. Prognostic impact of HIF-1α expression in patients with definitive radiotherapy for cervical cancer. Strahlenther Onkol 2008;184:169–74.CrossRefPubMedGoogle Scholar
  11. 11.
    Deutsche Gesellschaft der epidemiologischen Krebsregister. Broschure „Krebs in Deutschland“, 5. Aufl. Berlin: Robert-Koch-Institut, 2006.Google Scholar
  12. 12.
    Dietz A, Rudat V, Conradt C, et al. Prognostic value of hemoglobin level for primary radiochemotherapy of head-neck carcinomas. HNO 2000;48:655–64.CrossRefPubMedGoogle Scholar
  13. 13.
    Eich HT, Loschcke M, Scheer M, et al. Neoadjuvant radiochemotherapy and radical resection for advanced squamous cell carcinoma of the oral cavity. Outcome of 134 patients. Strahlenther Onkol 2008;184:23–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Fein DA, Lee WR, Hanlon AL, et al. Pretreatment hemoglobin level influences local control and survival of T1–T2 squamous cell carcinomas of the glottic larynx. J Clin Oncol 1995;13:2077–83.CrossRefPubMedGoogle Scholar
  15. 15.
    Gavioli M, Bagni A, Piccagli I, et al. Usefulness of endorectal ultrasound after preoperative radiotherapy in rectal cancer: comparison between sonographic and histopathologic changes. Dis Colon Rectum 2000;43:1075–83.CrossRefPubMedGoogle Scholar
  16. 16.
    Glynne-Jones R, Wallace M, Livingstone JI, et al. Complete clinical response after preoperative chemoradiation in rectal cancer: is a “wait and see” policy justified? Dis Colon Rectum 2008;51:10–9, discussion 9–20.CrossRefPubMedGoogle Scholar
  17. 17.
    Grant DG, Hussain A, Hurman D. Pre-treatment anaemia alters outcome in early squamous cell carcinoma of the larynx treated by radical radiotherapy. J Laryngol Otol 1999;113:829–33.PubMedGoogle Scholar
  18. 18.
    Haydaroglu A, Yurut V, Arican A, et al. The impact of the haemoglobin level on the response to radiotherapy. J BUON 2002;7:31–4.PubMedGoogle Scholar
  19. 19.
    Herrmann T, Petersen S, Hellmich G, et al. Delayed toxicity of brief preoperative irradiation and risk-adjusted postoperative radiotherapy of operative rectal carcinoma. Results of a randomized prospective study. Strahlenther Onkol 1999;175:430–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Nagtegaal ID, Gosens MJ, Marijnen CA, 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;25:1647–50.CrossRefPubMedGoogle Scholar
  21. 21.
    Pradier O, Lederer K, Hille A, et al. Concurrent low-dose cisplatin and thoracic radiotherapy in patients with inoperable stage III non-small cell lung cancer: a phase II trial with special reference to the hemoglobin level as prognostic parameter. J Cancer Res Clin Oncol 2005;131:261–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Rades D, Stoehr M, Meyners T, et al. Evaluation of prognostic factors and two radiation techniques in patients treated with surgery followed by radio(chemo)therapy or definitive radio(chemo)therapy for locally advanced head-and-neck cancer. Strahlenther Onkol 2008;184:198–205.CrossRefPubMedGoogle Scholar
  23. 23.
    Rödel C, Martus P, Papadoupolos T, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 2005;23:8688–96.CrossRefPubMedGoogle Scholar
  24. 24.
    Rödel C, Sauer R. Integration of novel agents into combined-modality treatment for rectal cancer patients. Strahlenther Onkol 2007;183:227–35.CrossRefPubMedGoogle Scholar
  25. 25.
    Saif MW, Hashmi S, Zelterman D, et al. Capecitabine vs continuous infusion 5-FU in neoadjuvant treatment of rectal cancer. A retrospective review. Int J Colorectal Dis 2008;23:139–45.CrossRefPubMedGoogle Scholar
  26. 26.
    Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731–40.CrossRefPubMedGoogle Scholar
  27. 27.
    Sobin LH, Wittekind C. TNM classification of malignant tumours, 6th edn. New York-Toronto: Wiley-Liss, 2002.Google Scholar
  28. 28.
    Strasser H, Grabenbauer GG, Sprung CN, et al. DNA double-strand break induction and repair in irradiated lymphoblastoid, fibroblast cell lines and white blood cells from ATM, NBS and radiosensitive patients. Strahlenther Onkol 2007;183:447–53.CrossRefPubMedGoogle Scholar
  29. 29.
    Trotti A, Byhardt R, Stetz J, et al. Common toxicity criteria: version 2.0. An improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys 2000;47:13–47.CrossRefPubMedGoogle Scholar
  30. 30.
    Vliegen RF, Beets-Tan RG, Vanhauten B, et al. Can an FDG-PET/CT predict tumor clearance of the mesorectal fascia after preoperative chemoradiation of locally advanced rectal cancer? Strahlenther Onkol 2008;184:457–64.CrossRefPubMedGoogle Scholar
  31. 31.
    Vorwerk H, Liersch T, Rothe H, et al. Gold markers for tumor localization and target volume delineation in radiotherapy for rectal cancer. Strahlenther Onkol 2010;185:127–33.CrossRefGoogle Scholar

Copyright information

© Urban & Vogel, Muenchen 2010

Authors and Affiliations

  • Hendrik Andreas Wolff
    • 1
  • Jochen Gaedcke
    • 2
  • Klaus Jung
    • 3
  • Robert Michael Hermann
    • 1
    • 4
  • Hilka Rothe
    • 5
  • Markus Schirmer
    • 6
  • Torsten Liersch
    • 2
  • Markus Karl Alfred Herrmann
    • 1
  • Steffen Hennies
    • 1
  • Margret Rave-Fränk
    • 1
  • Clemens Friedrich Hess
    • 1
  • Hans Christiansen
    • 1
    • 7
    Email author
  1. 1.Department of Radiotherapy and RadiooncologyUniversity Medicine GöttingenGöttingenGermany
  2. 2.Department of SurgeryUniversity Medicine GöttingenGöttingenGermany
  3. 3.Department of Medical StatisticsUniversity Medicine GöttingenGöttingenGermany
  4. 4.Department of Radiotherapy and RadiooncologyÄrztehaus am DiakoBremenGermany
  5. 5.Department of PathologyUniversity Medicine GöttingenGöttingenGermany
  6. 6.Department of Clinical PharmacologyUniversity Medicine GöttingenGöttingenGermany
  7. 7.Universitätsmedizin GöttingenKlinik und Poliklinik für Strahlentherapie und RadioonkologieGöttingenGermany

Personalised recommendations