Skip to main content

Advertisement

Log in

Spinal cord constraints in the era of high-precision radiotherapy

Retrospective analysis of 62 spinal/paraspinal lesions with possible infringements of spinal cord constraints within a minimal volume

Dosisbeschränkungen für das Rückenmark im Zeitalter der Hochpräzisionsstrahlentherapie

Retrospektive Auswertung 62 spinaler/paraspinaler Läsionen mit potenzieller Überschreitung kleinstvolumiger Rückenmarksdosen

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Objective

Current constraints aim to minimize the risk of radiation myelitis by the use of restrictive maximal spinal cord doses, commonly 50 Gy. However, several studies suggested that a dose–volume effect could exist. Based on these observations, we evaluated patients receiving potentially excessive doses to the spinal cord within minimal volumes.

Patients and methods

Patients receiving radiotherapy between June 2010 and May 2015 using the NovalisTM (Varian, Palo Alto, CA, USA; Brainlab, Heimstetten, Germany) radiosurgery system were retrospectively analyzed. A total of 56 patients with 62 treated lesions that had been prescribed radiation doses close to the spinal cord potentially higher than the common 50 Gy 2‑Gy equivalent-dose (EQD2) constraint were selected for further analysis. Of these patients, 26 with 31 lesions had no history of previous irradiation, while 30 patients with 31 lesions had been previously irradiated within the treatment field.

Results

According to different dose evaluation approaches (spinal canal, spinal cord contour), 16 and 10 out of 31 primary irradiated lesions infringed constraints. For the 16 lesions violating spinal canal doses, the maximum doses ranged from 50.5 to 61.9 Gy EQD2. Reirradiated lesions had an average and median cumulative dose of 70.5 and 69 Gy, respectively. Dose drop-off was steep in both groups. Median overall survival was 17 months. No radiation myelitis or radiomorphological alterations were observed during follow-up.

Conclusion

This study adds to the increasing body of evidence indicating that excessive spinal cord doses within a minimal volume, especially in a reirradiation setting with topographically distinct high-point doses, may be given to patients after careful evaluation of treatment- and tumor-associated risks.

Zusammenfassung

Zielsetzung

Um das Risiko einer radiogenen Myelitis zu minimieren, sind klinisch gebräuchliche Dosisobergrenzen für das Rückenmark mit 50-Gy-Maximaldosis sehr restriktiv. Einige Veröffentlichungen deuten jedoch darauf hin, dass ein Dosis-Volumen-Effekt besteht. Unter diesem Aspekt wurden Patienten ausgewertet, die kleinstvolumig mit potenziell überhöhten Rückenmarksdosen bestrahlt wurden.

Patienten

Retrospektiv ausgewertet wurden Patienten, die zwischen Juni 2010 und Mai 2015 mit dem NovalisTM-Radiochirurgiesystem (Varian, Paulo Alto, CA, USA; Brainlab, Heimstetten, Deutschland) behandelt wurden. Für weitere Analysen wurden 62 Läsionen bei 56 Patienten mit potenziell überhöhter Rückenmarksdosis (>50 Gy), berechnet als 2‑Gy-Äquivalenzdosis (EQD2), ausgewählt. Von diesen waren 26 Patienten mit 31 Läsionen ohne Vorbestrahlung und 30 Patienten mit 31 Läsionen bereits im gleichen Bereich vorbestrahlt.

Ergebnisse

Unter Verwendung verschiedener Dosisevaluationsverfahren (Spinalkanal, minimal konturierter Rückenmarksbereich) überschritten 16 und 10 der 31 erstmalig bestrahlten Läsionen die Grenze. Bei den 16, die Maximaldosis überschreitenden Läsionen lag die maximale Myelondosis zwischen 50,5 und 61,9 Gy EQD2. Wiederbestrahlte Läsionen hatten eine durchschnittliche/mediane Kumulativdosis von 70,5 und 69 Gy. Der Dosisabfall war in beiden Gruppen sehr steil. Das mediane Gesamtüberleben betrug 17 Monate. Während der Nachsorge wurden keine radiogene Myelitis oder röntgenmorphologische Veränderungen beobachtet.

Schlussfolgerung

Die Studie liefert Hinweise darauf, dass nach sorgsamem Abwägen von Behandlungs- und tumorassoziierten Risiken eine kleinstvolumige Überdosierung des Myelons in Einzelfällen möglich erscheint, insbesondere bei Rebestrahlung mit topographisch unterschiedlich lokalisierten Maximaldosen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Baumann M, Budach V, Appold S (1994) Radiation tolerance of the human spinal cord. Strahlenther Onkol 170(3):131–139

    CAS  PubMed  Google Scholar 

  2. Schultheiss TE (2008) The radiation dose-response of the human spinal cord. Int J Radiat Oncol Biol Phys 71(5):1455–1459

    Article  PubMed  Google Scholar 

  3. Schultheiss TE, Kun LE, Ang KK, Stephens LC (1995) Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys 31(5):1093–1112

    Article  CAS  PubMed  Google Scholar 

  4. Kirkpatrick JP, van der Kogel AJ, Schultheiss TE (2010) Radiation dose-volume effects in the spinal cord. Int J Radiat Oncol Biol Phys 76(3 Suppl):42–49

    Article  Google Scholar 

  5. van der Kogel AJ (1993) Dose-volume effects in the spinal cord. Radiother Oncol 29(2):105–109

    Article  PubMed  Google Scholar 

  6. Medin PM, Boike TP (2011) Spinal cord tolerance in the age of spinal radiosurgery: lessons from preclinical studies. Int J Radiat Oncol Biol Phys 79(5):1302–1309

    Article  PubMed  Google Scholar 

  7. Medin PM, Foster RD, van der Kogel AJ, Sayre JW, McBride WH, Solberg TD (2013) Spinal cord tolerance to single-session uniform irradiation in pigs: implications for a dose-volume effect. Radiother Oncol 106(1):101–105

    Article  PubMed  Google Scholar 

  8. Daly ME, Choi CYH, Gibbs IC, Adler JR, Chang SD, Lieberson RE et al (2011) Tolerance of the spinal cord to stereotactic radiosurgery: insights from hemangioblastomas. Int J Radiat Oncol Biol Phys 80(1):213–220

    Article  PubMed  Google Scholar 

  9. Abbatucci JS, Delozier T, Quint R, Roussel A, Brune D (1978) Radiation myelopathy of the cervical spinal cord: time, dose and volume factors. Int J Radiat Oncol Biol Phys 4(3–4):239–248

    Article  CAS  PubMed  Google Scholar 

  10. Inoue T, Oh R‑J, Shiomi H (2011) New approach for treatment of vertebral metastases using intensity-modulated radiotherapy. Strahlenther Onkol 187(2):108–113

    Article  PubMed  Google Scholar 

  11. Lubgan D, Ziegaus A, Semrau S, Lambrecht U, Lettmaier S, Fietkau R (2015) Effective local control of vertebral metastases by simultaneous integrated boost radiotherapy: preliminary results. Strahlenther Onkol 191(3):264–271

    Article  PubMed  Google Scholar 

  12. Barson AJ (1970) The vertebral level of termination of the spinal cord during normal and abnormal development. J Anat 106(Pt 3):489–497

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Joiner M, van der Kogel A (2009) Basic clinical radiobiology. Hodder Arnold, London

    Google Scholar 

  14. Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHS, 31 March 2003

  15. Kong F‑MS, Ritter T, Quint DJ, Senan S, Gaspar LE, Komaki RU et al (2011) Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Int J Radiat Oncol Biol Phys 81(5):1442–1457

    Article  PubMed  Google Scholar 

  16. Grosu A‑L, Andratschke N, Nieder C, Molls M (2002) Retreatment of the spinal cord with palliative radiotherapy. Int J Radiat Oncol Biol Phys 52(5):1288–1292

    Article  PubMed  Google Scholar 

  17. Kawashiro S, Harada H, Katagiri H, Asakura H, Ogawa H, Onoe T et al (2016) Reirradiation of spinal metastases with intensity-modulated radiation therapy: an analysis of 23 patients. J Radiat Res 57(2):150–156

    Article  PubMed  Google Scholar 

  18. Sahgal A, Ma L, Gibbs I, Gerszten PC, Ryu S, Soltys S et al (2010) Spinal cord tolerance for stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys 77(2):548–553

    Article  PubMed  Google Scholar 

  19. Kirkpatrick JP, Meyer JJ, Marks LB (2008) The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol 18(4):240–243

    Article  PubMed  Google Scholar 

  20. Marucci L, Niemierko A, Liebsch NJ, Aboubaker F, Liu MCC, Munzenrider JE (2004) Spinal cord tolerance to high-dose fractionated 3D conformal proton-photon irradiation as evaluated by equivalent uniform dose and dose volume histogram analysis. Int J Radiat Oncol Biol Phys 59(2):551–555

    Article  PubMed  Google Scholar 

  21. Bijl HP, van Luijk P, Coppes RP, Schippers JM, Konings AWT, van Der Kogel AJ (2005) Regional differences in radiosensitivity across the rat cervical spinal cord. Int J Radiat Oncol Biol Phys 61(2):543–551

    Article  PubMed  Google Scholar 

  22. Hayashi N, Green BA, Gonzalez-Carvajal M, Mora J, Veraa RP (1983) Local blood flow, oxygen tension, and oxygen consumption in the rat spinal cord. Part 1: Oxygen metabolism and neuronal function. J Neurosurg 58(4):516–525

    Article  CAS  PubMed  Google Scholar 

  23. Flickinger JC, Kondziolka D, Lunsford LD (1996) Dose and diameter relationships for facial, trigeminal, and acoustic neuropathies following acoustic neuroma radiosurgery. Radiother Oncol 41(3):215–219

    Article  CAS  PubMed  Google Scholar 

  24. Bijl HP, van Luijk P, Coppes RP, Schippers JM, Konings AWT, van der Kogel AJ (2003) Unexpected changes of rat cervical spinal cord tolerance caused by inhomogeneous dose distributions. Int J Radiat Oncol Biol Phys 57(1):274–281

    Article  PubMed  Google Scholar 

  25. Bijl HP, van Luijk P, Coppes RP, Schippers JM, Konings AWT, van der Kogel AJ (2006) Influence of adjacent low-dose fields on tolerance to high doses of protons in rat cervical spinal cord. Int J Radiat Oncol Biol Phys 64(4):1204–1210

    Article  PubMed  Google Scholar 

  26. Nieder C, Grosu AL, Andratschke NH, Molls M (2006) Update of human spinal cord reirradiation tolerance based on additional data from 38 patients. Int J Radiat Oncol Biol Phys 66(5):1446–1449

    Article  PubMed  Google Scholar 

  27. Nieder C, Grosu AL, Andratschke NH, Molls M (2005) Proposal of human spinal cord reirradiation dose based on collection of data from 40 patients. Int J Radiat Oncol Biol Phys 61(3):851–855

    Article  PubMed  Google Scholar 

  28. Sahgal A, Ma L, Weinberg V, Gibbs IC, Chao S, Chang U‑K et al (2012) Reirradiation human spinal cord tolerance for stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys 82(1):107–116

    Article  PubMed  Google Scholar 

  29. Ang KK, Jiang GL, Feng Y, Stephens LC, Tucker SL, Price RE (2001) Extent and kinetics of recovery of occult spinal cord injury. Int J Radiat Oncol Biol Phys 50(4):1013–1020

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sebastian Zschaeck.

Ethics declarations

Conflict of interest

S. Zschaeck, P. Wust, R. Graf, W. Wlodarczyk, R. Schild, A.H. Thieme, M. Weihrauch, V. Budach, and P. Ghadjar declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Evaluation of the data was approved by the Institutional Ethics Committee.

Additional information

Authors contribution

S. Zschaeck performed the analysis, drafted the manuscript, designed the figures, and calculated the underlying statistics. R. Graf, V. Budach, P. Wust, W. Wlodarczyk, M. Weihrauch, and R. Schild were responsible for treatment and treatment planning. M. Weihrauch provided technical support for the data evaluation. A.H. Thieme, P. Wust, and P. Ghadjar provided ideas and help with the manuscript. P. Wust and P. Ghadjar provided ideas for the analysis, supervised the analysis and data interpretation, and reviewed the manuscript. All authors read and approved the final manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zschaeck, S., Wust, P., Graf, R. et al. Spinal cord constraints in the era of high-precision radiotherapy. Strahlenther Onkol 193, 561–569 (2017). https://doi.org/10.1007/s00066-017-1138-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-017-1138-5

Keywords

Schlüsselwörter

Navigation