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Second Cancer After Additive Chemotherapy in Patients With Colon Cancer

  • Author Footnotes
    † These authors contributed equally to this work.
    Andreas Teufel
    Correspondence
    Address for correspondence: Andreas Teufel, MD, PhD, Heidelberg University, Division of Hepatology, Division of Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany, Phone: +49 621 383 4983, Fax: +49 621 383 1467
    Footnotes
    † These authors contributed equally to this work.
    Affiliations
    Department of Medicine II, Division of Hepatology, Division of Clinical Bioinformatics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health Baden-Württemberg (CPDBW), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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  • Author Footnotes
    † These authors contributed equally to this work.
    Moying Li
    Footnotes
    † These authors contributed equally to this work.
    Affiliations
    Department of Medicine II, Division of Hepatology, Division of Clinical Bioinformatics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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  • Michael Gerken
    Affiliations
    Regensburg Tumor Center, Institute for Quality Assurance and Health Services Research at the University of Regensburg, Regensburg, Germany
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  • Matthias P. Ebert
    Affiliations
    Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health Baden-Württemberg (CPDBW), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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  • Hans J Schlitt
    Affiliations
    Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
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  • Matthias Evert
    Affiliations
    Department of Pathology, University of Regensburg, Regensburg, Germany
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  • Wolfgang Herr
    Affiliations
    Department of Internal Medicine III, University Medical Center Regensburg, Regensburg, Germany
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  • Monika Klinkhammer-Schalke
    Affiliations
    Regensburg Tumor Center, Institute for Quality Assurance and Health Services Research at the University of Regensburg, Regensburg, Germany
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  • Author Footnotes
    † These authors contributed equally to this work.

      Abstract

      Background

      Additive chemotherapeutic treatment of UICC-stage -III / IV colon cancer with fluorouracil, leucovorin and oxaliplatin is widely accepted as current standard of treatment after R0-resection. However, as patients.. survival is increasing, long-term side effects of chemotherapeutic agents such as second cancer development are becoming increasingly important.

      Patients

      We therefore investigated a total of 2 856 Patients with UICC-stage III / IV colon cancer, 223 of whom (7.8%) had developed a subsequent second cancer.

      Results

      Median follow-up was 73.2 months (range 209.9 months, 95%-CI 69.8-76.9). Most frequent second cancers were prostate cancer (18.4%), colon cancer (16.1%), breast cancers (8.1%), lung cancer (8.1%), rectal cancer (4.9%) and uterine cancer (4.9%). However, in comparison to non-treated patients this did not represent a significantly increased risk for subsequent second cancer in patients after treatment with additive chemotherapy. Of interest, our data suggest a significantly decreased second cancer rate in patients treated with FOLFOX compared to FUFOL for additive treatment.

      Conclusions

      Second cancer development was not increased after additive chemotherapy for colon cancer, which is a novel aspect in the ongoing discussions on reduction of adjuvant treatment to 3 months or treatment of lymph node negative patients.
      Novelty and Impact Statement
      To our knowledge, this is the first population-based study analyzing second cancer development after additive chemotherapy in patients with UICC III-IV colon cancer. The results have an important impact on the surveillance and long-term follow-up of cancer patients.

      Keywords

      Abbreviations:

      CI (confidence interval), CRC (colorectal cancer), CTx (chemotherapy), FOLFOX (folinic acid, fluorouracil and oxaliplatin), 5-FU (5-fluoruracil), HR (hazard ratio), ICD (International Classification of Diseases), Ox (oxaliplatin), UICC (Union Internationale Contre le Cancer)
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