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Strahlentherapie und Onkologie

, Volume 195, Issue 7, pp 607–614 | Cite as

Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus

  • Oliver J. OttEmail author
  • Manfred Schmidt
  • Sabine Semrau
  • Vratislav Strnad
  • Klaus E. Matzel
  • Ignaz Schneider
  • Dimitrios Raptis
  • Wolfgang Uter
  • Robert Grützmann
  • Rainer Fietkau
Original Article

Abstract

Purpose

To compare results after chemoradiotherapy with and without deep regional hyperthermia in patients with anal cancer.

Methods

Between 2000 and 2015, a total of 112 consecutive patients with UICC stage I–IV anal cancer received chemoradiotherapy with 5‑fluororuracil and mitomycin C (CRT). In case of insufficient tumor response 4–6 weeks after chemoradiotherapy, patients received an interstitial pulsed-dose-rate brachytherapy boost. Additionally, 50/112 patients received hyperthermia treatments (HCRT).

Results

Median follow-up was 41 (2–165) months. After 5 years follow-up, overall (95.8 vs. 74.5%, P = 0.045), disease-free (89.1 vs. 70.4%, P = 0.027), local recurrence-free (97.7 vs. 78.7%, P = 0.006), and colostomy-free survival rates (87.7 vs. 69.0%, P = 0.016) were better for the HCRT group. Disease-specific, regional failure-free, and distant metastasis-free survival rates showed no significant differences. The adjusted hazard ratios for death were 0.25 (95% CI, 0.07 to 0.92; P = 0.036) and for local recurrence 0.14 (95% CI, 0.02 to 1.09; P = 0.06), respectively. Grades 3–4 early toxicities were comparable with the exception of hematotoxicity, which was higher in the HCRT group (66 vs. 43%, P = 0.032). Incidences of late side effects were similar with the exception of a higher telangiectasia rate in the HCRT group (38.0 vs. 16.1%, P = 0.009).

Conclusion

Additional regional hyperthermia improved overall survival, local control, and colostomy rates. Its potential beneficial role has to be confirmed in a prospective randomized setting. Therefore, the HyCAN trial has already been established by our group and is currently recruiting patients (Clinicaltrials.gov identifier: NCT02369939).

Keywords

Anal cancer Chemoradiation Multimodality treatment Deep regional hyperthermia Radiotherapy 

Radiochemotherapie mit und ohne regionale Tiefenhyperthermie bei Plattenepithelkarzinomen des Anus

Zusammenfassung

Hintergrund

Vergleich der Ergebnisse nach Radiochemotherapie mit und ohne regionale Tiefenhyperthermie bei Patienten mit Analkarzinom.

Material und Methode

Zwischen 2000 und 2015 erhielten 112 konsekutive Patienten mit Analkarzinom im UICC-Stadium I–IV eine Radiochemotherapie (CRT) mit 5‑Fluororuracil und Mitomycin C. Bei ungenügender Tumorrückbildung 4–6 Wochen nach Radiochemotherapie wurde ein interstitieller „Pulsed-dose-rate“-Brachytherapie-Boost angeboten. Zusätzlich erhielten 50/112 Patienten eine additive Tiefenhyperthermie (HCRT).

Ergebnisse

Die mediane Nachbeobachtungszeit betrug 41 Monate (Spanne 2–165 Monate). Nach 5 Jahren waren im Vergleich der Patientengruppen mit und ohne Hyperthermie (HCRT vs. CRT) Gesamtüberleben (95,8 vs. 74,5 %; P = 0,045), krankheitsfreies (89,1 vs. 70,4 %; P = 0,027), lokalrezidivfreies (97,7 vs. 78,7 %; P = 0,006) und kolostomiefreies Überleben (87,7 vs. 69,0 %; P = 0,016) in der HCRT-Gruppe signifikant besser. Die krankheitsspezifischen, fernmetastasenfreien, regionären Kontrollraten zeigten keine Unterschiede. Die adjustierten Hazard Ratios waren für Tod 0,25 (95 %-Konfidenzintervall [KI] 0,07–0,92; P = 0,036) und für Lokalrezidiv 0,14 (95 %-KI 0,02–1,09; P = 0,06). Die Akuttoxizität (Grad 3–4) war vergleichbar bis auf die Hämatotoxizität, die in der HCRT-Gruppe höher war (66 vs. 43 %; P = 0,032). Bis auf eine höhere Teleangiektasierate in der HCRT-Gruppe (38,0 vs. 16,1 %; P = 0,009) war die Spättoxizität vergleichbar.

Schlussfolgerung

Die zusätzliche regionale Tiefenhyperthermie hat in der vorliegenden Analyse das Gesamt-, das lokalrezidivfreie sowie das kolostomiefreie Überleben positiv beeinflusst. Dieser mögliche Benefit muss in einer prospektiven randomisierten Studie überprüft werden. Daher wurde von unserer Arbeitsgruppe die HyCAN-Studie initiiert, die bereits Patienten rekrutiert (Clinicaltrials.gov ID: NCT02369939).

Schlüsselwörter

Analkarzinom Radiochemotherapie Multimodale Therapie Regionale Tiefenhyperthermie Strahlentherapie 

Notes

Conflict of interest

O.J. Ott, M. Schmidt, S. Semrau, V. Strnad, K.E. Matzel, I. Schneider, D. Raptis, W. Uter, R. Grützmann, and R. Fietkau declare that they have no competing interests. None of the authors has had relationship with an entity that has a financial interest in the subject matter discussed in this manuscript.

Supplementary material

66_2018_1396_MOESM1_ESM.docx (162 kb)
The supplementary material provides additional Kaplan Meier curves for disease-free survival (DFS), colostomy-free survival (CFS), disease-specific survival (DSS), and distant metastasis-free survival (DMFS).

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Oliver J. Ott
    • 1
    Email author
  • Manfred Schmidt
    • 1
  • Sabine Semrau
    • 1
  • Vratislav Strnad
    • 1
  • Klaus E. Matzel
    • 2
  • Ignaz Schneider
    • 2
  • Dimitrios Raptis
    • 2
  • Wolfgang Uter
    • 3
  • Robert Grützmann
    • 2
  • Rainer Fietkau
    • 1
  1. 1.Department of Radiation OncologyUniversitätsklinikum ErlangenErlangenGermany
  2. 2.Department of SurgeryUniversitätsklinikum ErlangenErlangenGermany
  3. 3.Department of Medical Informatics, Biometry and EpidemiologyUniversity Erlangen-NurembergErlangenGermany

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