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Late complications after radiotherapy for prostate cancer

Spätschäden nach Strahlentherapie bei Prostatakarzinom

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Abstract

Background

The aim of the present study was to analyze in detail the time course of the incidence of radiation-induced late effects. For this purpose, unpublished data of patients treated by radiation therapy in Hamburg in the late 1980s were analyzed. Relatively large volumes were exposed to comparatively high doses, thus leading to a high rate of treatment-related side effects.

Patients and methods

A total of 180 consecutive patients received radiotherapy for prostate cancer. The median age was 66 years (range 41–88 years). The median of the maximum dose was 77.5 Gy (range 56.3–95 Gy) and overall treatment time was 51 days (range 28–128 days). Endpoints analyzed were late complications of grade 3 or higher, overall and disease-free survival, local tumor control, and distant metastases. Data analysis was actuarial and the log-rank test was used to compare the various subgroups.

Results

After 2 years, 80.5 ± 3.2% of the patients were without any complications of grade 3 or higher, and after 5 years a constant level of 70.3 ± 4.0% was approached. When multiple lesions occurred per patient, the later events were disregarded. A total of 66 complications occurred in 42 patients. The percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by an exponential function and a constant fraction. Complications approached a constant level of 70.3% at a rate of 5.3% per month. This means that patients who will develop a complication do so at exponential kinetics and at a relatively high rate, whereas about 70% of the patients will never experience a late effect even over long observation periods. After subdividing the maximum dose into three equal dose groups of 55 patients each (< 73.3 Gy, 73.3–80 Gy, > 80 Gy), the constant fraction decreased from 85.7 to 72.8% and 52.2%, whereas the incidence rate was 4.3%, 7.7%, and 5.6% per month and, thus, almost independent of radiation dose.

Conclusion

For a given group of patients, the rate of the incidence of late complications appears to be independent of radiation dose and (from analyzing data in the literature) independent of the grade of lesions, whereas the fraction of patients without late effects depends on both parameters.

Zusammenfassung

Hintergrund

Ziel der vorliegenden Untersuchung war, den zeitlichen Verlauf der Entwicklung von strahleninduzierten Spätschäden näher zu analysieren. Verwendet wurden bisher unveröffentlichte Daten von Patienten, die Ende der 1980er-Jahre in Hamburg strahlentherapeutisch behandelt worden waren. Damals wurden relativ große Volumina mit relativ hohen Dosen bestrahlt, was zu einer überdurchschnittlich hohen Rate an therapiebedingten Spätnebenwirkungen führte.

Patienten und Methoden

Insgesamt 180 konsekutive Patienten wurden wegen eines Prostatakarzinoms strahlentherapeutisch behandelt. Das Alter der Patienten lag bei 66 Jahren (Spanne: 41–88 Jahre). Der Median der maximalen Gesamtdosis betrug 77,5 Gy (56,3–95 Gy) und der Gesamtbehandlungszeit 51 Tage (28–128 Tage). Die untersuchten Endpunkte waren Spätkomplikationen Grad 3 oder höher, gesamtes und krankheitsfreies Überleben sowie Fernmetastasen. Die Daten der einzelnen Untergruppen wurden aktuarisch mit dem Log-Rank-Test analysiert.

Resultate

Nach 2 Jahren waren 80,5 ± 3,2% der Patienten frei von Spätschäden Grad ≥ 3; nach 5 Jahren wurde ein konstantes Niveau von 70,3 ± 4,0% erreicht. Bei Mehrfachnebenwirkungen pro Patient wurde jeweils nur das erste Ereignis berücksichtigt. Insgesamt traten 66 Komplikationen bei 42 Patienten auf. Der Prozentsatz komplikationsfreier Patienten wird adäquat durch eine Exponentialfunktion und einen konstanten Anteil als Funktion der Zeit nach Beginn der Strahlentherapie beschrieben. Die Spätschäden nähern sich mit einer Rate von 5,3% pro Monat an ein konstantes Niveau von 70,3% an. Das heißt, bei etwa 30% der Patienten, die eine Nebenwirkung erleiden, tritt diese relativ schnell auf, während etwa 70% der Patienten auch nach längeren Beobachtungszeiten keine Spätschäden entwickeln. Nach Unterteilung der Gesamtdosis in drei gleiche Gruppen mit jeweils 55 Patienten (< 73,3 Gy, 73,3–80 Gy, > 80 Gy) nahm der konstante Anteil beschwerdefreier Patienten von 85,7% über 72,8% auf 52,2% ab, während die Inzidenzrate 4,3%, 7,7% bzw. 5,6% pro Monat betrug und damit praktisch unabhängig von der Strahlendosis war.

Schussfolgerung

Innerhalb einer Gruppe bestrahlter Patienten scheint die Inzidenzrate von Spätnebenwirkungen unabhängig von der Strahlendosis und (nach Analyse von Daten aus der Literatur) unabhängig vom Grad des Spätschadens zu sein, während der Anteil der Patienten ohne Schäden von beiden genannten Parametern abhängt.

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Acknowledgment

The authors thank the Erich und Gertrud Roggenbuck Foundation, Hamburg, for funding the present study.

Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

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Correspondence to H. Jung.

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Jung, H., Beck-Bornholdt, HP., Svoboda, V. et al. Late complications after radiotherapy for prostate cancer. Strahlenther Onkol 188, 965–974 (2012). https://doi.org/10.1007/s00066-012-0142-z

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