Abstract
Purpose
Combined radiochemotherapy (RCT) for gastric cancer with three-dimensional conformal radiotherapy (3D-CRT) results in ablative doses to the upper left kidney, while image-guided intensity-modulated radiotherapy (IG-IMRT) allows kidney sparing despite improved target coverage. Renal function in long-term gastric cancer survivors was evaluated with 3T functional magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and 23Na imaging.
Patients and methods
Five healthy volunteers and 13 patients after radiotherapy were included: 11×IG-IMRT; 1×3D-CRT; 1× “positive control” with stereotactic body radiotherapy (SBRT) of a metastasis between the spleen/left kidney. Radiation doses were documented for the upper/middle/lower kidney subvolumes. Late toxicity was evaluated based on CTC criteria, questionnaire, and creatinine values. Morphological sequences, DWI images, and 23Na images were acquired using a 1H/23Na-tuned body-coil before/after intravenous water load (WL). Statistics for [23Na] (concentration) and apparent diffusion coefficient (ADC) values were calculated for upper/middle/lower renal subvolumes. Corticomedullary [23Na] gradients and [23Na] differences after WL were determined.
Results
No major morphological alteration was detected in any patient. Minor scars were observed in the cranial subvolume of the left kidney of the 3D-CRT and the whole kidney of the control SBRT patient. All participants presented a corticomedullary [23Na] gradient. After WL, a significant physiological [23Na] gradient decrease (p < 0.001) was observed in all HV and IG-IMRT patients. In the cranial left kidney of the 3D-CRT patient and the positive control SBRT patient, the decrease was nonsignificant (p = 0.01, p = 0.02). ADC values were altered nonsignificantly in all renal subvolumes (all participants). Renal subvolumes with doses ≥ 35 Gy showed a reduced change of the [23Na] gradient after WL (p = 0.043). No participants showed clinical renal impairment.
Conclusions
Functional parameters of renal 23Na MRI after gastric IG-IMRT are identical to those of healthy volunteers, in contrast to renal subvolumes after ablative doses in the control and 3D-CRT patient. While kidney doses to the cortex below 20–25 Gy in fractional doses of ~ 1 Gy in IG-IMRT (combined with intensified chemotherapy) do not seem to cause significant MRI morphological or functional alterations, doses of > 35 Gy in 1.5–2 Gy fractions clearly result in impairment.
Zusammenfassung
Zielsetzung
Die Radiochemotherapie (RCT) des Magenkarzinoms mit 3-dimensionaler konformaler Strahlentherapie (3D-CRT) belastet den linken Nierenoberpol mit ablativen Strahlendosen. Die bildgeführte, intensitätsmodulierte Strahlentherapie (IG-IMRT) ermöglicht die Aussparung des Nierenparenchyms bei verbesserter Zielvolumenabdeckung. Die Nierenfunktion wurde mit 3 T-funktioneller MRT (diffusionsgewichtete Bildgebung; DWI) und 23Na-Bildgebung in einer Kohorte von Patienten mit langem Follow-up ausgewertet.
Patienten/Methoden
Es wurden 5 gesunde Probanden (HV) und 12 Patienten mit Magenkarzinom (11-mal IG-IMRT; 1-mal 3D-CRT) sowie ein Patient als „positive-Kontrolle“ (nach Behandlung einerMetastase zwischen Milz und linker Niere mit SBRT [„stereotactic-body-radiotherapy“]) untersucht. Die Bestrahlungsdosen wurden für die oberen, mittleren und unteren Nierenetagen getrennt dokumentiert. Spättoxizität wurde basierend auf den allgemeinen Toxizitätskriterien (CTC, Common Toxicity Criteria), mittels Fragebogen und anhand der Kreatininwerte bestimmt. Morphologische Sequenzen, DWI- und 23Na-Bilder wurden mit einer 1H/23Na-Spule vor und nach intravenöser Flüssigkeitszufuhr („water load“, WL) akquiriert. Die statistische Auswertung erfolgte für [23Na]-Konzentration und ADC („apparent diffusion coefficient“)-Werte getrennt nach Subvolumina (obere, mittlere und untere Nierenetagen). Kortikomedulläre [23Na]-Gradienten und [23Na]-Unterschiede nach WL wurden bestimmt.
Ergebnisse
Grobmorphologische Veränderungen wurden nicht detektiert. Kleine narbige Veränderungen wurden im linken Nierenoberpol (3D-CRT) und in der ganzen Niere des SBRT-Kontollpatienten beobachtet. Alle Untersuchten zeigten physiologische kortikomedulläre [23Na]-Gradienten. Nach WL wurde in allen HV und IG-IMRT-Patienten ein signifikanter physiologischer Abfall des [23Na]-Gradienten beobachtet (p < 0,001). Im linken Nierenoberpol des 3D-CRT-Patienten und dem „positivKontroll-SBRT“-Patienten war dieser Abfall nicht signifikant (p = 0,01; p = 0,02). Die ADC-Werte änderten sich in allen Subvolumina nicht signifikant. Subvolumina, die mit Dosen ≥ 35 Gy bestrahlt wurden, zeigten einen eingeschränkten Abfall des [23Na]-Gradienten nach WL (p = 0,043). Kein Patient wies eine klinische Symptomatik auf.
Schlussfolgerung
Funktionelle Parameter der 23Na-MRT der Niere nach adjuvanter IG-IMRT sind identisch zu gesunden Probanden, im Gegensatz zu Nierensubvolumina, die mit ablativen Dosen belastet wurden. Während kortikale Dosen unter 20–25 Gy in Fraktionsdosen von ~ 1 Gy nach IG-IMRT (kombiniert mit intensivierter Chemotherapie) keine MR-morphologischen oder funktionellen Veränderungen verursachen, resultieren Dosen von > 35 Gy in Fraktionsdosen von 1,5–2 Gy in manifesten Beeinträchtigungen.
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Acknowledgments
Parts of these studies were supported by research grants from Elekta AB, Stockholm, Sweden, and Siemens Healthcare, Erlangen, Germany.
J. Boda-Heggemann is supported by the Ministerium für Bildung und Forschung, Baden-Württemberg and the ESF (European Social Funds).
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S. Haneder, J.M. Budjan, S.O. Schoenberg, S. Konstandin, L.R. Schad, R.D. Hofheinz, V. Gramlich, F. Wenz, F. Lohr and J. Boda-Heggemann state that there are no conflicts of interest.
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Haneder, S., Budjan, J., Schoenberg, S. et al. Dose-dependent changes in renal 1H-/23Na MRI after adjuvant radiochemotherapy for gastric cancer. Strahlenther Onkol 191, 356–364 (2015). https://doi.org/10.1007/s00066-014-0787-x
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DOI: https://doi.org/10.1007/s00066-014-0787-x
Keywords
- Gastric cancer
- Functional 23Na-MRI
- Diffusion-weighted imaging
- Image-guided IMRT
- Kidney radiation tolerance