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Improved treatment outcome and lower skin toxicity with intensity-modulated radiotherapy vs. 3D conventional radiotherapy in anal cancer

Verbessertes Behandlungsergebnis und geringere Hauttoxizität mit der intensitätsmodulierten Strahlentherapie im Vergleich zur dreidimensionalen konventionellen Strahlentherapie beim Analkarzinom

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Abstract

Purpose

Radiochemotherapy is the standard treatment for anal carcinoma (ACa). Intensity-modulated radiotherapy (IMRT) has been introduced, allowing focused irradiation of the tumor area. Whether physical benefits of IMRT translate to clinical benefits has not been sufficiently demonstrated.

Methods

We retrospectively reviewed data from 82 patients with newly diagnosed ACa. Patients treated with IMRT were compared with previous patients treated with conventional three-dimensional computational radiotherapy (3D-CRT). The influence of IMRT on complete remission and acute and chronic side effects was analyzed in univariate and multivariate analyses.

Results

39/40 patients treated with IMRT were in complete remission after 1 year compared to 31/39 patients treated with 3D-CRT (p = 0.014). Multivariate analysis confirmed tumor T stage as well as lack of IMRT treatment as risk factors for persistent tumor at 6 months. No significant benefits of IMRT were apparent at later timepoints (median follow up 52 months, IQR: 31.5–71.8 months). Patients treated with IMRT had a significantly lower degree of skin toxicity (median 2 vs. 3 in a scale ranging from 0 to 3, p = 0.00092). Rates of hematological toxicity/proctitis were not reduced and rates of acute diarrhea increased (p = 0.034). Median length of hospitalization tended to be shorter in patients treated with IMRT (n. s.).

Conclusion

We present a real-world experience of shifting radiation technique from conventional 3D-CRT to IMRT. IMRT patients had better tumor control at 1 year and lower degrees of skin toxicity. Our data indicate that IMRT can enable therapies with lower side effects with equal or better oncological results for patients with ACa.

Zusammenfassung

Hintergrund

Die definitive Radiochemotherapie stellt den Goldstandard für die Therapie des Analkarzinoms (ACa) dar. Die in den letzten Jahren eingeführte intensitätsmodulierte Strahlentherapie (IMRT) erlaubt eine fokussierte Bestrahlung des Tumorgebiets unter Schonung der umliegenden Strukturen. Ob diese Vorteile auch einen klinischen Benefit bringen, wurde bis jetzt nur ungenügend untersucht.

Methodik

Es erfolgte eine retrospektive Analyse von 82 Patienten mit der Neudiagnose eines ACa, mit einem Vergleich zwischen Patienten, die mit IMRT versus mit der traditionell durchgeführten 3D-konformalen Radiotherapie (3D-CRT) behandelt wurden. Es wurde der Einfluss der IMRT auf das Erreichen einer klinischen Remission sowie auf Rezidivrate und Nebenwirkungen untersucht.

Ergebnisse

Die Remissionsrate 1 Jahr nach Ende der Bestrahlung der Patienten lag in der IMRT-Gruppe bei 97,5 % (39/40) vs. 79,5 % (31/39) in der 3D-CRT-Gruppe (p = 0,014). Die multivariate Analyse bestätigte das T‑Stadium als auch die 3D-CRT-Therapie als Risikofaktor für Tumorpersistenz nach 6 Monaten. Weitere Effekte der IMRT-Therapie bei späteren Zeitpunkten wurden nicht beobachtet (medianer Follow-up 52 Monate; IQR 31,5–71,8 Monate). Patienten unter IMRT hatten signifikant weniger schwere Hauttoxizität (median 2 vs. 3 in einer Skala von 0–3; p = 0,00092). Hämatologische Toxizität/Proktitis waren vergleichbar, akute Diarrhoe trat bei IMRT-Patienten häufiger auf (p = 0,034). Die mediane Hospitalisierungsdauer war bei IMRT-Patienten tendenziell verkürzt (ohne statistische Signifikanz).

Schlussfolgerung

Wir präsentieren „Real-world“-Daten des Übergangs der RT von der 3D-CRT- zur IMRT-Technik. Die IMRT-Patienten hatten eine höhere Remissionsrate nach 6 Monaten und eine niedrigere Rate für Hauttoxizitäten. Die IMRT-Therapie führt beim ACa zu insgesamt weniger Nebenwirkungen bei mindestens gleichwertigem oder sogar besserem onkologischem Outcome.

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Abbreviations

3D-CRT:

Three-dimensional computational radiotherapy

5‑FU:

5‑Fluorouracil

ACa:

Anal carcinoma

CI:

Confidence interval

CR:

Complete response

CT:

Computed tomography

CTCAE:

National Cancer Institute Common Terminology Criteria for Adverse Events

HIV:

Human immunodeficiency virus

HPV:

Human papillomavirus

IMRT:

Intensity-modulated radiotherapy

MMC:

Mitomycin

MRI:

Magnetic resonance imaging

OR:

Odds ratio

RTOG:

Radiation Therapy Oncology Group

SIB:

Simultaneous integrated boost

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Acknowledgements

The authors would like to thank Brian Lang, Department of Biosystems Science and Engineering, ETH Basel, for help with the statistics.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland

    Matthias Sauter, Simon Bütikofer, Henriette Heinrich, Gerhard Rogler, Stephan R. Vavricka & Benjamin Misselwitz

  2. University Center for Gastrointestinal and Liver Diseases, Clarunis, Basel, Switzerland

    Matthias Sauter & Stephan R. Vavricka

  3. Division of Gastroenterology, Triemli Hospital, Zurich, Switzerland

    Matthias Sauter & Henriette Heinrich

  4. Division of Radio-Oncology, Triemli Hospital, Zurich, Switzerland

    Norbert Lombriser, Georg Keilholz & Helmut Kranzbühler

  5. Department of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland

    Benjamin Misselwitz

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  1. Matthias Sauter
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Contributions

MSa, BM, SV, NL: study design. MSa, SB, GK, BM: data acquisition. MSa, SB, NL, SV, HH, BM, MSa, FB: data analysis. MSa, SB, GK, NL, BM: drafting of manuscript. All authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Matthias Sauter.

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Conflict of interest

M. Sauter, N. Lombriser, S. Bütikofer, G. Keilholz, H. Kranzbühler, H. Heinrich, G. Rogler, S.R. Vavricka, and B. Misselwitz declare that they have no competing interests.

Caption Electronic Supplementary Material

66_2019_1534_MOESM1_ESM.pdf

Supplementary Figure S1: Rates of complete response at 6 months and at end of study. Statistical analysis: Fisher’s exact test. IMRT: intensity modulated radiotherapy, 3D-CRT: three-dimensional computational radiotherapy

66_2019_1534_MOESM2_ESM.pdf

Supplementary Figure S2: Acute side effects of treatment and length of hospitalization. Statistical analysis: Fisher’s exact test, Mann-Whitney‑U test. IMRT: intensity modulated radiotherapy, 3D-CRT: three-dimensional computational radiotherapy

66_2019_1534_MOESM3_ESM.pdf

Supplementary Figure S3: Chronic side effects of treatment. Statistical analysis: Fisher’s exact test. IMRT: intensity modulated radiotherapy, 3D-CRT: three-dimensional computational radiotherapy

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Sauter, M., Lombriser, N., Bütikofer, S. et al. Improved treatment outcome and lower skin toxicity with intensity-modulated radiotherapy vs. 3D conventional radiotherapy in anal cancer. Strahlenther Onkol 196, 356–367 (2020). https://doi.org/10.1007/s00066-019-01534-6

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