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Time course of pain response and toxicity after whole-nerve-encompassing LINAC-based stereotactic radiosurgery for trigeminal neuralgia—a prospective observational study

Zeitverlauf von Schmerzansprechen und Toxizität nach LINAC-basierter stereotaktischer Radiochirurgie der gesamten Nervenzirkumferenz bei Trigeminusneuralgie – eine prospektive Beobachtungsstudie

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Abstract

Purpose

To prospectively evaluate the time course of pain response and toxicity after linear accelerator-based whole-nerve-encompassing radiosurgery (LINAC-SRS) using a uniform treatment schedule for dosing and target volume definition in patients with refractory trigeminal neuralgia.

Methods

From December 2012 to December 2016, 21 patients were treated using a standardized protocol. Patients received LINAC-SRS with 70 Gy to the cisternal portion while aiming for the 90% isodose to fully envelope the nerve in one cross-sectional plane. Data on pain, analgesics, and toxicity were gathered prospectively. Four time intervals (1–6, 6–12, 12–18, and 18–24 months) were defined and compared to baseline and each other.

Results

The median follow-up from radiotherapy was 16 months. Freedom from pain was achieved at least once in 90.5, 81.0, and 85.7% of patients for everyday pain, rest pain, and pain peaks, respectively. At 1–6 months, pain was significantly reduced in everyday routine (mean VAS, 2.0/10 vs. 5.8/10; P = 0.004), at rest (1.5/10 vs. 4.0/10; P = 0.002), and for pain peaks (2.9/10 vs. 10/10; P < 0.001), as was the number of analgesics (mean 1.5 vs. 2.9; P < 0.001). No significant increase in pain or analgesics was observed for subsequent time intervals. At last follow-up, reduction in pain compared to baseline for everyday routine (2.1/10 vs. 5.8/10; P = 0.010) and for pain peaks (3.3/10 vs. 10/10; P < 0.001) was significant, whereas it was not for rest pain (1.8/10 vs. 3.9/10; P = 0.073). Most toxicities were related to trigeminal nerve impairment, with 42.9% reporting new-onset hypoesthesia at last follow-up.

Conclusion

This study provides prospective data after whole nerve encompassing LINAC-SRS for trigeminal neuralgia. No significant pain relapse was observed.

Zusammenfassung

Zielsetzung

Prospektive Untersuchung des Zeitverlaufs von Schmerzansprechen und Toxizität nach linearbeschleunigerbasierter stereotaktischer Radiochirurgie (LINAC-SRS) bei therapierefraktärer Trigeminusneuralgie unter Verwendung eines einheitlichen Therapieprotokolls für Dosis- und Zielvolumendefinition mit Behandlung der gesamten Nervenzirkumferenz.

Methoden

Von Dezember 2012 bis Dezember 2016 wurden 21 Patienten entsprechend eines standardisierten Therapieprotokolls behandelt. Die Patienten erhielten eine Einzeit-LINAC-SRS mit 70 Gy auf den zisternalen Nervus trigeminus. Das komplette Umschließen der Nervenzirkumferenz in einer Schnittebene durch die 90%-Isodose war Ziel der Bestrahlungsplanung. Schmerzansprechen, Anzahl der benötigten Analgetika und Toxizität wurden prospektiv erhoben. Vier Zeitintervalle (1–6, 6–12, 12–18 und 18–24 Monate) wurden definiert und mit dem Ausgangsstatus sowie untereinander verglichen.

Ergebnisse

Das mediane Follow-up betrug 16 Monate. Komplette Schmerzfreiheit wurde in 90,5%, 81,0% bzw. 85,7% der Patienten jeweils in den Kategorien Alltagsschmerz, Ruheschmerz und Schmerzspitzen erreicht. Im Zeitintervall von 1–6 Monaten nach Radiotherapie waren die Schmerzen im Alltag signifikant reduziert (Mittelwert Visuelle Analogskala [VAS] 2,0/10 vs. 5,8/10; P = 0,004), ebenso in Ruhe (Mittelwert 1,5/10 vs. 4/10; P = 0,002) und bei Schmerzspitzen (Mittelwert 2,9/10 vs. 10/10; P < 0,001). Außerdem konnte die Zahl der Analgetika signifikant reduziert werden (Mittelwert 1,5 vs. 2,9; P < 0,001). In den weiteren Zeitintervallen wurde kein signifikanter Schmerzrückfall oder steigender Analgetikaverbrauch mehr beobachtet. Beim letzten Follow-up-Termin war eine signifikante Schmerzreduktion für den Alltagsschmerz (2,1/10 vs. 5,8/10; P = 0,010) und für Schmerzspitzen (3,3/10 vs. 10/10; P < 0,001) zu verzeichnen, jedoch nicht für den Ruheschmerz (1,8/10 vs. 3,9/10; P = 0,073). Die meisten Nebenwirkungen waren Einschränkungen in der Funktion des N. trigeminus mit neuaufgetretener Hypästhesie in 42,9% der Patienten beim letzten Follow-up.

Schlussfolgerung

Die vorliegende Studie liefert prospektive Daten nach LINAC-SRS der gesamten Nervenzirkumferenz bei Trigeminusneuralgie. Es wurde kein signifikanter Schmerzrückfall beobachtet.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Radiation Oncology, Friedrich-Alexander-University Erlangen-Nuremberg, Universitaetsstraße 27, 91054, Erlangen, Germany

    Selim Koca,  Luitpold Distel,  Dorota Lubgan,  Thomas Weissmann,  Ulrike Lambrecht, Marga Lang-Welzenbach,  Sabine Semrau,  Rainer Fietkau,  Sebastian Lettmaier &  Florian Putz

  2. Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Ilker Eyüpoglu,  Barbara Bischoff &  Michael Buchfelder

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  1. Selim Koca
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  2. Luitpold Distel
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Corresponding author

Correspondence to Florian Putz.

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Conflict of interest

S. Koca, L. Distel, D. Lubgan, T. Weissmann, U. Lambrecht, M. Lang-Welzenbach, I. Eyüpoglu, B. Bischoff, M. Buchfelder, S. Semrau, R. Fietkau, S. Lettmaier, and F. Putz declare that they have no competing interests.

Ethical standards

All procedures performed were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments. Ethical approval was obtained from the local Ethical Testing Committee. Informed consent was obtained from all patients.

Additional information

The present work was performed in fulfillment of the requirements for obtaining the degree “Dr. med.”

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Koca, S., Distel, L., Lubgan, D. et al. Time course of pain response and toxicity after whole-nerve-encompassing LINAC-based stereotactic radiosurgery for trigeminal neuralgia—a prospective observational study. Strahlenther Onkol 195, 745–755 (2019). https://doi.org/10.1007/s00066-019-01450-9

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