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David B. Kurland, Monica C. Mureb, Albert H. Liu, Alexandra H. Seidenstein, Eddie Stern, and Erich G. Anderer

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Monica Mureb, Danielle Golub, Carolina Benjamin, Jason Gurewitz, Ben A. Strickland, Gabriel Zada, Eric Chang, Dušan Urgošík, Roman Liščák, Ronald E. Warnick, Herwin Speckter, Skyler Eastman, Anthony M. Kaufmann, Samir Patel, Caleb E. Feliciano, Carlos H. Carbini, David Mathieu, William Leduc, DCS, Sean J. Nagel, Yusuke S. Hori, Yi-Chieh Hung, Akiyoshi Ogino, Andrew Faramand, Hideyuki Kano, L. Dade Lunsford, Jason Sheehan, and Douglas Kondziolka

OBJECTIVE

Trigeminal neuralgia (TN) is a chronic pain condition that is difficult to control with conservative management. Furthermore, disabling medication-related side effects are common. This study examined how stereotactic radiosurgery (SRS) affects pain outcomes and medication dependence based on the latency period between diagnosis and radiosurgery.

METHODS

The authors conducted a retrospective analysis of patients with type I TN at 12 Gamma Knife treatment centers. SRS was the primary surgical intervention in all patients. Patient demographics, disease characteristics, treatment plans, medication histories, and outcomes were reviewed.

RESULTS

Overall, 404 patients were included. The mean patient age at SRS was 70 years, and 60% of the population was female. The most common indication for SRS was pain refractory to medications (81%). The median maximum radiation dose was 80 Gy (range 50–95 Gy), and the mean follow-up duration was 32 months. The mean number of medications between baseline (pre-SRS) and the last follow-up decreased from 1.98 to 0.90 (p < 0.0001), respectively, and this significant reduction was observed across all medication categories. Patients who received SRS within 4 years of their initial diagnosis achieved significantly faster pain relief than those who underwent treatment after 4 years (median 21 vs 30 days, p = 0.041). The 90-day pain relief rate for those who received SRS ≤ 4 years after their diagnosis was 83.8% compared with 73.7% in patients who received SRS > 4 years after their diagnosis. The maximum radiation dose was the strongest predictor of a durable pain response (OR 1.091, p = 0.003). Early intervention (OR 1.785, p = 0.007) and higher maximum radiation dose (OR 1.150, p < 0.0001) were also significant predictors of being pain free (a Barrow Neurological Institute pain intensity score of I–IIIA) at the last follow-up visit. New sensory symptoms of any kind were seen in 98 patients (24.3%) after SRS. Higher maximum radiation dose trended toward predicting new sensory deficits but was nonsignificant (p = 0.075).

CONCLUSIONS

TN patients managed with SRS within 4 years of diagnosis experienced a shorter interval to pain relief with low risk. SRS also yielded significant decreases in adjunct medication utilization. Radiosurgery should be considered earlier in the course of treatment for TN.

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I. Jonathan Pomeraniec, Zhiyuan Xu, Cheng-Chia Lee, Huai-Che Yang, Tomas Chytka, Roman Liscak, Roberto Martinez-Alvarez, Nuria Martinez-Moreno, Luca Attuati, Piero Picozzi, Douglas Kondziolka, Monica Mureb, Kenneth Bernstein, David Mathieu, Michel Maillet, Akiyoshi Ogino, Hao Long, Hideyuki Kano, L. Dade Lunsford, Brad E. Zacharia, Christine Mau, Leonard C. Tuanquin, Christopher Cifarelli, David Arsanious, Joshua Hack, Ronald E. Warnick, Ben A. Strickland, Gabriel Zada, Eric L. Chang, Herwin Speckter, Samir Patel, Dale Ding, Darrah Sheehan, Kimball Sheehan, Svetlana Kvint, Love Y. Buch, Alexander R. Haber, Jacob Shteinhart, Mary Lee Vance, and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors.

METHODS

This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes.

RESULTS

The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17–2.68, p = 0.006).

CONCLUSIONS

SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

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Ching-Jen Chen, Dale Ding, Cheng-Chia Lee, Kathryn N. Kearns, I. Jonathan Pomeraniec, Christopher P. Cifarelli, David E. Arsanious, Roman Liscak, Jaromir Hanuska, Brian J. Williams, Mehran B. Yusuf, Shiao Y. Woo, Natasha Ironside, Rebecca M. Burke, Ronald E. Warnick, Daniel M. Trifiletti, David Mathieu, Monica Mureb, Carolina Benjamin, Douglas Kondziolka, Caleb E. Feliciano, Rafael Rodriguez-Mercado, Kevin M. Cockroft, Scott Simon, Heath B. Mackley, Samer G. Zammar, Neel T. Patel, Varun Padmanaban, Nathan Beatson, Anissa Saylany, John Y. K. Lee, Jason P. Sheehan, and on behalf of the International Radiosurgery Research Foundation

OBJECTIVE

Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus.

METHODS

The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death.

RESULTS

The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively.

CONCLUSIONS

Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.