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Case Reports
. 2016 Dec;192(12):886-894.
doi: 10.1007/s00066-016-1057-x. Epub 2016 Oct 18.

Simultaneous integrated protection : A new concept for high-precision radiation therapy

Thomas B Brunner  1   2 , Ursula Nestle  3   4 , Sonja Adebahr  3   4 , Eleni Gkika  3   4 , Rolf Wiehle  3   4 , Dimos Baltas  3   4 , Anca-Ligia Grosu  3   4
Affiliations
Case Reports

Simultaneous integrated protection : A new concept for high-precision radiation therapy

Thomas B Brunner et al. Strahlenther Onkol. 2016 Dec.

Abstract
in English, German

Objective: Stereotactic radiotherapy near serial organs at risk (OAR) requires special caution. A novel intensity-modulated radiotherapy (IMRT) prescription concept termed simultaneous integrated protection (SIP) for quantifiable and comparable dose prescription to targets very close to OAR is described.

Materials and methods: An intersection volume of a planning risk volume (PRV) with the total planning target volume (PTV) defined the protection volume (PTVSIP). The remainder of the PTV represented the dominant PTV (PTVdom). Planning was performed using IMRT. Dose was prescribed to PTVdom according to ICRU in 3, 5, 8, or 12 fractions. Constraints to OARs were expressed as absolute and as equieffective doses at 2 Gy (EQD2). Dose to the gross risk volume of an OAR was to respect constraints. Violation of constraints to OAR triggered a planning iteration at increased fractionation. Dose to PTVSIP was required to be as high as possible within the constraints to avoid local relapse.

Results: SIP was applied in 6 patients with OAR being large airways (n = 2) or bowel (n = 4) in 3, 5, 8, and 12 fractions in 1, 3, 1, and 1 patients, respectively. PTVs were 14.5-84.9 ml and PTVSIP 1.8-3.9 ml (2.9-13.4 % of PTV). Safety of the plans was analyzed from the absolute dose-volume histogram (dose to ml). The steepness of dose fall-off could be determined by comparing the dose constraints to the PRVs with those to the OARs (Wilcoxon test p = 0.001). Constraints were respected for the corresponding OARs. All patients had local control at a median 9 month follow-up and toxicity was low.

Conclusion: SIP results in a median dose of ≥100 % to PTV, to achieve high local control and low toxicity. Longer follow-up is required to verify results and a prospective clinical trial is currently testing this new approach in chest and abdomen stereotactic body radiotherapy.

Zielsetzung: Die stereotaktische Radiotherapie nahe serieller Risikoorgane (OAR) erfordert besondere Vorsicht. Wir beschreiben ein neues Konzept für die intensitätsmodulierte Strahlentherapie (IMRT), genannt simultan integrierte Protektion (SIP), das die Dosisverschreibung auf Zielvolumina in unmittelbarer Nähe von OAR quantifiziert.

Material und Methoden: Das Überschneidungsvolumen eines Planungsrisikovolumens (PRV) mit dem gesamten Planungszielvolumen (PTV) definierte das Protektionsvolumen (PTVSIP). Der Rest des PTV repräsentierte das dominierende PTV (PTVdom). Die Planung erfolgte mittels IMRT. Nach ICRU wurde die Dosis auf PTVdom in 3, 5, 8 oder 12 Fraktionen verschrieben. OAR-Grenzdosen wurden als absolute und äquieffektive Dosen zu 2 Gy (EQD2) überprüft. Die Dosis auf das makroskopische Risikovolumen eines OAR musste die Constraints einhalten. Eine Verletzung der OAR-Constraints triggerte eine Planungswiederholung mit höherer Fraktionszahl. Die PTVSIP-Dosis sollte so hoch wie möglich sein, aber innerhalb der Constraints, um Lokalrezidive zu vermeiden.

Ergebnisse: Die SIP-Technik wurde bei 6 Patienten mit den OARs große Atemwege (n = 2) und Darm (n = 4) in 3, 5, 8 und 12 Fraktionen bei jeweils 1, 3, 1 und 1 Patienten angewendet. PTVs maßen 14,5–84,9 ml und PTVSIP 1,8–3,9 ml (2,9–13,4 % des PTV). Die Verträglichkeit der Pläne wurde durch die Analyse der absoluten Dosisvolumenhistogramme (Dosis auf ml) überprüft. Die Steilheit des Dosisabfalls wurde durch den Vergleich der Dosis-Constraints mit der Dosis auf die PRVs gegenüber der Dosis auf die OARs abgelesen (Wilcoxon-Test p = 0,001). Die Constraints für die OARs wurden eingehalten. Alle Patienten zeigten eine Lokalkontrolle bei einem medianen 9‑monatigen Nachbeobachtungszeitraum und niedrige Toxizität.

Schlussfolgerung: SIP ermöglichte eine mediane Dosis von ≥100 % auf das PTV und ergab eine hervorragende Lokalkontrolle bei niedriger Toxizität. Die Verifikation der Ergebnisse erfordert eine längere Nachbeobachtungszeit. Eine prospektive klinische Studie testet derzeit diesen neuen Ansatz für die thorakale und abdominelle Körperstereotaxie.

Electronic supplementary material: The online version of this article (doi: 10.1007/s00066-016-1057-x) contains supplementary material, which is available to authorized users.

Keywords: Efficacy; Intensity-modulated radiotherapy; Organs at risk; Stereotactic body radiation therapy; Toxicity.

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Conflict of interest statement

Compliance with ethical guidelinesConflict of interestT.B. Brunner, U. Nestle, S. Adebahr, E. Gkika, R. Wiehle, D. Baltas, and A.-L. Grosu declare that they have no competing interest.Ethical standardsThis article does not contain any studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
Contouring and planning using the simultaneous integrated protection (SIP) concept. Scheme of a critical organ at risk (OAR; blue, left side) with its planning risk volume (PRV) overlapping with the planning target volume (PTV, pink). The dominant PTV (PTVdom = PTV\PRV; orange) is the prescribed dose in the conventional way, whereas the PTVSIP (=PTV ∩ PRV; purple) is prescribed a lower dose to stay within the dose constraints for the OAR
Fig. 2
Fig. 2
a The planning target volume (PTV, (light pink) intersects with planning risk volume (PRV, green) and organs at risk (OAR), small bowel (orange), in a patient with recurrent pancreatic cancer after resection. b The PRV is subtracted from PTV to define PTVdom (yellow). c The PTVSIP is defined as the intersecting region of PTV with the PRV (PTV ∩ PRV; magenta). d,e An intensity-modulated radiotherapy (IMRT) plan is developed to deliver full dose according to ICRU to PTVdom and a lower dose to PTVSIP respecting the dose constraints for small bowel in 12 fractions (Dmax = 47.4 Gy, D0.5ml = 44.5 Gy, D5ml = 44.4 Gy). Isodose levels as stated on the left side. f Relative dose–volume histogram (DVH). Protection of the 9.2 ml PTVSIP (left solid) compared with PTV (middle solid), ITV (bold dotted) and with PTVdom (right solid); gut (dashes). g Absolute DVH respecting the constraints for gut
Fig. 3
Fig. 3
Dose to planning target volumes (PTV) in 6 patients planned with the simultaneous integrated protection (SIP) concept. For each patient from left to right the relative prescription doses to the dominant non-protection PTV , PTV, and PTVSIP are shown with minimal (min), maximal (max), and mean (filled diamonds) relative doses. OAR organ at risk
Fig. 4
Fig. 4
Examples for a simultaneous integrated protection (SIP) for the optic nerve, the brainstem, and the brachial plexus with dose parameters in Supplementary Table 2. a Axial planning CT of a patient with sinonasal squamous cell carcinoma who was treated with chemoradiotherapy after positive margin resection at the left optic nerve. As she refused left orbital exenteration, PTVdom is treated with 64.8 Gy in 36 fractions. A 0.4 ml SIP volume is employed to respect a 60 Gy constraint to the left optic nerve. b The coronal plane visualizes the yellow 61.5 Gy isodose line around the nerve. c Absolute dose–volume histogram (DVH). d Axial and e sagittal planning CT of a patient with undifferentiated main nasal cavity carcinoma with initially direct contact to the brainstem which was shifted dorsally. Tumor shrinkage after two courses of induction chemotherapy with paclitaxel/cisplatin, then chemoradiotherapy with SIP-IMRT to 54 Gy during phase 1 followed by an adaptive sequential boost (not shown) during phase 2. f Isodoses at the interface between the PTV and the brainstem. g The brainstem constraint of 53 Gy is met as shown in the absolute DVH. h–j Hippocampus protection. h Delineation of the right (sky blue) and left (blue-green) hippocampus with the respective PRVs (yellow) that are generated by a 7 mm isotropic margin to the hippocampi. PTVSIP corresponds to the PRV of the hippocampus minus the hippocampus itself (PTVSIP = PRV[side]\hippocampus[side]). i A total dose of 35 Gy in 14 fractions was prescribed to the PTVdom. Note the 28.0 Gy (green) and the 17.5 Gy (cornflower blue) isodoses at the two SIP volumes. j In the absolute DVH, the hippocampi receive a mean dose of ≤10 Gy. PRV planning risk volume, PTV planning target volume
See this image and copyright information in PMC

References

    1. Adebahr S, et al. Lungtech, an eortc phase ii trial of stereotactic body radiotherapy for centrally located lung tumours: A clinical perspective. Br J Radiol. 2015;88:20150036. doi: 10.1259/bjr.20150036. - DOI - PMC - PubMed
    1. Al-Assar O, et al. Contextual regulation of pancreatic cancer stem cell phenotype and radioresistance by pancreatic stellate cells. Radiother Oncol. 2014;111:243–251. doi: 10.1016/j.radonc.2014.03.014. - DOI - PubMed
    1. Bentzen SM. Preventing or reducing late side effects of radiation therapy: Radiobiology meets molecular pathology. Nat. Rev. Cancer. 2006;6:702–713. doi: 10.1038/nrc1950. - DOI - PubMed
    1. Bhangu A, et al. The role of epithelial mesenchymal transition and resistance to neoadjuvant therapy in locally advanced rectal cancer. Colorectal Dis. 2014;16:O133–143. doi: 10.1111/codi.12482. - DOI - PubMed
    1. Brunner TB, et al. Sbrt in pancreatic cancer: What is the therapeutic window? Radiother Oncol. 2015;114:109–116. doi: 10.1016/j.radonc.2014.10.015. - DOI - PubMed

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