Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.

OBJECTIVE: The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs). METHODS: This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic. RESULTS: Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE. CONCLUSIONS: Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.

Dose response and architecture in volume staged radiosurgery for large arteriovenous malformations: A multi-institutional study.

BACKGROUND: Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult. METHODS: This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival. RESULTS: With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy. CONCLUSION: VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.

Tip Design for Safety of Steerable Needles for Robot-Controlled Brain Insertion.

BACKGROUND: Current practice in neurosurgical needle insertion is limited by the straight trajectories inherent with rigid probes. One technique allowing curvilinear trajectories involves flexible bevel-tipped needles, which bend during insertion due to their asymmetry. In the brain, safety will require avoidance of the sharp tips often used in laboratory studies, in favor of a more rounded profile. Steering performance, on the other hand, requires maximal asymmetry. Design of safe bevel-tipped brain needles thus involves management of this tradeoff by adjusting needle gauge, bevel angle, and fillet (or tip) radius to arrive at a design that is suitably asymmetrical while producing strain, strain rate, and stress below the levels that would damage brain tissue. METHODS: Designs with a variety of values of needle radius, bevel angle, and fillet radius were evaluated in finite-element simulations of simultaneous insertion and rotation. Brain tissue was modeled as a hyperelastic, linear viscoelastic material. Based on the literature available, safety thresholds of 0.19 strain, 10 s-1 strain rate, and 120 kPa stress were used. Safe values of needle radius, bevel angle, and fillet radius were selected, along with an appropriate velocity envelope for safe operation. The resulting needle was fabricated and compared with a Sedan side-cutting brain biopsy needle in a study in the porcine model in vivo (N=3). RESULTS: The prototype needle selected was 1.66 mm in diameter, with bevel angle of 10° and fillet radius of 0.25 mm. Upon examination of postoperative CT and histological images, no differences in tissue trauma or hemorrhage were noted between the prototype needle and the Sedan needle. CONCLUSIONS: The study indicates a general design technique for safe bevel-tipped brain needles based on comparison with relevant damage thresholds for strain, strain rate, and stress. The full potential of the technique awaits the determination of more exact safety thresholds.