Stereotactic Radiosurgery: From a Prescribed Physical Radiation Dose Toward Biologically Effective Dose

Radiosurgery or stereotactic radiosurgery was invented by Swedish neurosurgeon Lars Leksell in 1951. defined as “delivery of a single, high dose irradiation to small and critically located intracranial volume through the intact skull.” His initial efforts were focused on developing noninvasive method create lesions within brain, using radiation rather than conventional blade. In 1968, first Gamma Knife (GK) unit (Elekta AB) appeared Stockholm, multiple cobalt 60 sources (currently 192 sources). Refinement device steadily ensued, starting with Perfexion model (2005), GK became completely automatized. Clinical applications currently include benign malignant brain tumors, vascular malformations, functional indications (such facial pain [trigeminal neuralgia], tremor, psychiatric disorders). Treatment have progressively expanded both cranial spine radiosurgery. However, addresses, physical construction, only disorders. Arteriovenous malformations (AVMs) are abnormal connections between arteries veins that bypass capillary system. This engenders an elevated pressure (named hyperdebit) inside AVM venous drainage, increased risk rupture attendant hemorrhage. The hyperdebit can also provoke “blood steal phenomenon” may be clinically manifested epilepsy other neurologic deficits.1Raboud M. Tuleasca C. Maeder P. et al.Gamma knife for arteriovenous malformations: general principles preliminary results Swiss cohort.Swiss Med Wkly. 2018; 148: w14602PubMed Google Scholar Management includes observation, microsurgical resection (direct approach), endovascular treatment (embolization agents), radiosurgery, used alone combination. took place early 1970s Karolinska, Sweden. exact effects single-dose single-session/fraction) delivery tissue not yet elucidated. Such depend delivered dose, treated target volume), underlying indication which is used. selection requires consideration existing dose-response data, including desired end point (obliteration malformation, tumor control, relief trigeminal neuralgia) well injury surrounding structures. prescribed doses 11 15 Gy some tumors (vestibular schwannoma meningioma), 20 24 AVM, 90 neuralgia, 130 thalamotomy tremor. AVMs, such leads radiobiologic effect, inducing progressive obliteration while provoking gradual endothelial hyperplasia vasculature, further engendering narrowing subsequent vessel occlusion.2Szeifert G.T. Timperley W.R. Forster D.M.C. Kemeny A.A. Histopathological changes cerebral following radiosurgery.Prog Neurol Surg. 2007; 20: 212-219Crossref PubMed Scopus (32) Radiobiology (also termed biology) involves study ionizing living things, especially health radiation. Controlled classically medical imaging techniques (radiotherapy, radiosurgery). (physical) developed during several decades clinical experience. principles, governing radiotherapy multifraction (multisession) treatments, do necessarily apply single-fraction, high-dose, (the former rapid falloff outside targeted volume). been typically referred 4 R’s: repair, repopulation, reoxygenation, reassortment. One essential aspects has guided community rates strongly correlated.3Flickinger J.C. Pollock B.E. Kondziolka D. Lunsford L.D. A analysis malformation after radiosurgery.Int J Radiat Oncol Biol Phys. 1996; 36: 873-879Abstract Full Text PDF (253) major breakthrough occurred when Flickinger4Pollock Flickinger proposed radiosurgery-based grading system malformations.J Neurosurg. 2002; 96: 79-85Crossref (240) AVMs based relevant factors volume, patient’s age years, anatomic location; this enabled prediction practice, (before radiosurgery) remain closely correlated. Indeed, failure obliterate reflect either insufficient (sometimes diminished limit complications large-volume deep-seated AVMs) incomplete targeting (not covering complete AVM) due various reasons, previously pointed out al.5Pollock Maitz A. Factors associated successful radiosurgery.Neurosurgery. 1998; 42 (discussion 1244-1247): 1239-1244Crossref (281) 1989, term biologically effective (BED) coined design cell survival radiobiology.6Fowler J.F. 21 years dose.Br Radiol. 2010; 83: 554-568Crossref (321) It aimed at quantitatively indicating biologic effect any (multiple sessions irradiation) considering new factor, time, accounting DNA repair 2012, Hopewell al7Hopewell J.W. Millar W.T. Lindquist Radiobiological principles: their application therapy.Prog 2012; 25: 39-54Crossref (17) questioned common belief (single-session/fraction) single-fraction exposure. al advocated total reflected additional cumulative variable number individual smaller from isocenters/sources (192 GK) employed cover volume. plan elaborated one isocenter (monoisocentric plan) isocenters (multi-isocentric plan). therapy, space central rays beams pass. GK, classical monoisocentric plans performed (trigeminal tremor (thalamotomy) but confined (AVMs; particularly metastasis). neuralgia plans, decay (>5.26 years), time vary factor “fresh” “old” because radioactive decay, less radioactivity up 5 later old sources. fact, it takes more deliver same Calculating parameter BED recently undertaken al8Tuleasca Paddick I. al.Establishment therapeutic ratio neuralgia: critical importance versus dose.World 2020; 134: e204-e213Crossref (20) large cohort patients neuralgia. Conventionally, regarded salient allows efficacy (disappearance pain) predicts toxicity (hypesthesia appearance). More recently, suggested better predictor compared dose. Moreover, narrow variations 70 97.9 Gy, ranges much widely, namely, 1550 2600 Gy2.47. With span, example, hypesthesia would increase 5% approximately 1800 Gy2.47 42% Gy2.47.8Tuleasca multi-isocentric calculation straightforward, Canney.9Millar Canney P.A. Derivation equations describing fractionated protracted irradiation, processes. Part equations.Int Biol. 1993; 64: 275-291Crossref (40) Several approaches proposed, simplified models, application. We studied radiosurgery.10Tuleasca Peciu-Florianu Leroy H.A. Vermandel Faouzi Reyns N. Biologically unruptured upfront radiosurgery: series 149 consecutive cases.J 2020 Jul 24; ([Online ahead print]): 1-11Crossref (8) For uniformly most cases, varied 106.7 246.8 found higher values predicted accurately.10Tuleasca current issue Mayo Clinic Proceedings, Nesvick collaborators11Nesvick C.L. Graffeo C.S. Brown P.D. al.The role biological predicting malformations.Mayo Clin Proc. 2021; 1157-1164Abstract (0) extend prior studies group. analyzed 352 (physical 18 Gy). authors concluded cutoff 133 needed achieve rates. Taken conjunction our study,10Tuleasca provide insights into understanding radiobiology AVMs. As collaborators underscore, becomes metric predict likelihood mainly derived animal studies. such, clinicians expertise should involved we extrapolate concepts single-session identical. Thus, models carefully interpreted. sum, key objective advancing ascertaining its minimizing inadvertent damaging nontargeted tissues. represents important addition substantial corpus contributions his colleagues significantly advanced field. Dr gratefully acknowledges receipt grant “Jeune Chercheur en Recherche Clinique” University Lausanne, Faculty Biology Medicine. Role Biological Effective Dose Predicting Obliteration After Stereotactic Cerebral MalformationsMayo ProceedingsVol. 96Issue 5PreviewTo determine whether predictive (SRS) (AVMs). Full-Text