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Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer

Symptomatische strahleninduzierte Herzerkrankung bei Langzeitüberlebenden nach Ösophaguskarzinom

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Abstract

Purpose

To evaluate clinical and dosimetric factors retrospectively affecting the risk of symptomatic cardiac disease (SCD) in esophageal cancer patients treated with radiotherapy.

Patients and methods

A total of 343 patients with newly diagnosed esophageal cancer were managed with concurrent chemoradiotherapy or radiotherapy alone. Of these, 58 patients were followed at our hospital for at least 4 years. Median clinical follow-up was 79 months. Cardiac toxicity was determined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. The maximum and mean doses to the heart and percentage of the volume were calculated from the dose–volume histograms.

Results

SCD manifested in 11 patients. The heart diseases included three pericardial effusions, one pericardial effusion with valvular disease and paroxysmal atrial tachycardia, three atrial fibrillations, one sinus tachycardia, one coronary artery disease, one chest pain with strongly suspected coronary artery disease, and one congestive heart failure. The actual incidence of SCD was 13.8 % at 5 years. Univariate and multivariate analyses of continuous variables revealed that the risk of developing an SCD depended on the volume of the heart receiving a dose greater than 45 Gy (V45), 50 Gy (V50), and 55 Gy (V55). No other clinical factors were found to influence the risk of SCD. For V45, V50, and V55, the lowest significant cutoff values were 15, 10, and 5 %, respectively.

Conclusion

High-dose and large-volume irradiation of the heart increased the risk of SCD in long-term survivors. Using modern radiotherapy techniques, it is important to minimize the heart dose–volume parameters without reducing the tumor dose.

Zusammenfassung

Ziel

Beurteilung von klinischen und dosimetrischen Faktoren, die mit Risiken eines retrospektiven Auftretens von symptomatischen Herzerkrankungen (SCD) bei Patienten zusammenhängen, die aufgrund eines Ösophaguskarzinoms strahlentherapeutisch behandelt wurden.

Patienten und Methoden

Insgesamt 343 Patienten mit neu diagnostiziertem Ösophaguskarzinom wurden mit kombinierter Chemo- und Strahlentherapie oder nur strahlentherapeutisch behandelt. In dieser Gruppe wurden 58 Patienten über mindestens 4 Jahre beobachtet. Die mediane klinische Beobachtungsdauer betrug 79 Monate. Die kardiale Toxizität wurde mit CTCAE v.4.0 ermittelt. Anhand der Dosis-Volumen-Histogramme wurden maximale und mittlere Strahlendosis im Herzen und der Prozentsatz des Volumens berechnet.

Ergebnisse

Bei 11 Patienten trat eine SCD auf: 3 perikardiale Effusionen, 1 perikardiale Effusion mit Klappenfehler und paroxysmaler atrialer Tachykardie, 3 atriale Fibrillationen, 1 Sinustachykardie, 1 Koronararterienerkrankung, 1 Brustschmerz mit starkem Verdacht auf Koronararterienerkrankung, 1 kongestive Herzinsuffizienz. Die tatsächliche SCD-Inzidenz betrug nach 5 Jahren 13,8%. Uni- und multivariate Analysen mit den stetigen Variablen ergaben, dass das Risiko für eine SCD vom Volumen des Herzens abhängt, das Dosen von mehr als 45 Gy (V45), V50 und V55 erhielt. Keine anderen klinischen Faktoren zeigten Auswirkungen auf das Risiko für symptomatische Herzerkrankungen. Bei V45, V50 und V55 betrug der niedrigste signifikante Toleranzwert jeweils 15, 10 und 5%.

Schlussfolgerung

Hochdosierte, großvolumige Bestrahlungen des Herzens wirkten sich auf das SCD-Risiko bei Langzeitüberlebenden aus. Dosis-Volumen-Parameter für das Herz müssen mit modernen Strahlentherapiemethoden verringert werden, ohne die Tumordosis zu reduzieren.

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Authors and Affiliations

  1. 4–57 Urahune-cho, Minami-ku, Yokohama, Kanagawa-prefecture, Japan

    Ichiro Ogino M.D. & Shigenobu Watanabe

  2. Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan

    Noriaki Iwahashi, Masami Kosuge & Kazuo Kimura

  3. Department of Biostatistics, Yokohama City University Medical Center, Yokohama, Japan

    Kentaro Sakamaki

  4. Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan

    Chikara Kunisaki

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  1. Ichiro Ogino M.D.
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  2. Shigenobu Watanabe
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  3. Noriaki Iwahashi
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  4. Masami Kosuge
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  7. Kazuo Kimura
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Correspondence to Ichiro Ogino M.D..

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I. Ogino, S. Watanabe, N. Iwahashi, M Kosuge, K. Sakamaki, C. Kunisaki, and K. Kimura state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Ogino, I., Watanabe, S., Iwahashi, N. et al. Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer. Strahlenther Onkol 192, 359–367 (2016). https://doi.org/10.1007/s00066-016-0956-1

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