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Stylianos Pikis, Adomas Bunevicius, Cheng-Chia Lee, Huai-Che Yang, Brad E. Zacharia, Roman Liščák, Gabriela Simonova, Manjul Tripathi, Narendra Kumar, David Mathieu, Rémi Perron, Selcuk Peker, Yavuz Samanci, Jason Gurewitz, Kenneth Bernstein, Douglas Kondziolka, Ajay Niranjan, L. Dade Lunsford, Nikolaos Mantziaris, and Jason P. Sheehan

OBJECTIVE

As novel therapies improve survival for men with prostate cancer, intracranial metastatic disease has become more common. The purpose of this multicenter study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of intracranial prostate cancer metastases.

METHODS

Demographic data, primary tumor characteristics, SRS treatment parameters, and clinical and imaging follow-up data of patients from nine institutions treated with SRS from July 2005 to June 2020 for cerebral metastases from prostate carcinoma were collected and analyzed.

RESULTS

Forty-six patients were treated in 51 SRS procedures for 120 prostate cancer intracranial metastases. At SRS, the mean patient age was 68.04 ± 9.05 years, the mean time interval from prostate cancer diagnosis to SRS was 4.82 ± 4.89 years, and extracranial dissemination was noted in 34 (73.9%) patients. The median patient Karnofsky Performance Scale (KPS) score at SRS was 80, and neurological symptoms attributed to intracranial involvement were present prior to 39 (76%) SRS procedures. Single-fraction SRS was used in 49 procedures. Stereotactic radiotherapy using 6 Gy in five sessions was utilized in 2 procedures. The median margin dose was 18 (range 6–28) Gy, and the median tumor volume was 2.45 (range 0.04–45) ml. At a median radiological follow-up of 6 (range 0–156) months, local progression was seen with 14 lesions. The median survival following SRS was 15.18 months, and the 1-year overall intracranial progression-free survival was 44%. The KPS score at SRS was noted to be associated with improved overall (p = 0.02) and progression-free survival (p = 0.03). Age ≥ 65 years at SRS was associated with decreased overall survival (p = 0.04). There were no serious grade 3–5 toxicities noted.

CONCLUSIONS

SRS appears to be a safe, well-tolerated, and effective management option for patients with prostate cancer intracranial metastases.

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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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Zachary A. Seymour, Jason W. Chan, Michael W. McDermott, Inga Grills, Hong Ye, Hideyuki Kano, Craig A. Lehocky, Rachel C. Jacobs, L. Dade Lunsford, Tomas Chytka, Roman Liščák, Cheng-Chia Lee, Huai-che Yang, Dale Ding, Jason P. Sheehan, Caleb E. Feliciano, Rafael Rodriguez-Mercado, Veronica L. Chiang, Judith A. Hess, Samuel Sommaruga, Brendan McShane, John Y. K. Lee, Lucas T. Vasas, Anthony M. Kaufmann, and Penny K. Sneed

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.

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Hussam Abou-Al-Shaar, Andrew Faramand, Xiaoran Zhang, Arka N. Mallela, Barton F. Branstetter, Clayton A. Wiley, and L. Dade Lunsford

OBJECTIVE

Cerebral arteriovenous malformations (AVMs) are rare cerebral vascular lesions that are associated with high morbidity and mortality from hemorrhage; however, stereotactic radiosurgery (SRS) is a well-validated treatment modality. Few reports have delineated a subgroup of patients who develop delayed chronic encapsulated expanding hematomas (CEEHs) despite angiographic evidence of AVM obliteration following radiosurgery. In this report, the authors performed a retrospective review of more than 1000 radiosurgically treated intracranial AVM cases to delineate the incidence and management of this rare entity.

METHODS

Between 1988 and 2019, 1010 patients with intracranial AVM underwent Gamma Knife SRS at the University of Pittsburgh Medical Center. In addition to a review of a prospective institutional database, the authors performed a retrospective chart review of the departmental AVM database to specifically identify patients with CEEH. Pertinent clinical and radiological characteristics as well as patient outcomes were recorded and analyzed.

RESULTS

Nine hundred fifty patients with intracranial AVM (94%) had sufficient clinical follow-up for analysis. Of these, 6 patients with CEEH underwent delayed resection (incidence rate of 0.0045 event per person-year). These patients included 4 males and 2 females with a mean age of 45.3 ± 13.8 years at the time of initial SRS. Four patients had smaller AVM volumes (4.9–10 cm3), and 3 of them were treated with a single SRS procedure. Two patients had larger-volume AVMs (55 and 56 cm3), and both underwent multimodal management that included staged SRS and embolization. Time to initial recognition of the CEEH after initial SRS ranged between 66 and 243 months. The time between CEEH recognition and resection ranged from 2 to 9 months. Resection was required because of progressive neurological symptoms that correlated with imaging evidence of gradual hematoma expansion. All 6 patients had angiographically confirmed obliteration of their AVM. Pathology revealed a mixed chronicity hematoma with areas of fibrosed blood vessels and rare areas of neovascularization with immature blood vessels but no evidence of a persistent AVM. All 6 patients reported persistent clinical improvement after hematoma resection.

CONCLUSIONS

CEEH after SRS for AVM is a rare complication with an incidence rate of 0.0045 event per person-year over the authors’ 30-year experience. When clinical symptoms progress and imaging reveals progressive enlargement over time, complete resection of a CEEH results in significant clinical recovery. Knowledge of this rare entity facilitates timely detection and eventual surgical intervention to achieve optimal outcomes.

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Zhishuo Wei, Arka N. Mallela, Andrew Faramand, Ajay Niranjan, and L. Dade Lunsford

BACKGROUND

Invasive sagittal sinus meningiomas are difficult tumors to cure by resection alone. Stereotactic radiosurgery (SRS) can be used as an adjuvant management strategy to improve tumor control after incomplete resection.

OBSERVATIONS

The authors reported the long-term retrospective follow-up of two patients whose recurrent parasagittal meningiomas eventually occluded their superior sagittal sinus. Both patients underwent staged radiosurgery and fractionated radiation therapy to achieve tumor control that extended to 20 years after their initial surgery. After initial subtotal resection of meningiomas that had invaded major cerebral venous sinuses, adjuvant radiosurgery was performed to enhance local tumor control. Over time, adjacent tumor progression required repeat SRS and fractionated radiation therapy to boost long-term tumor response. Staged multimodality intervention led to extended survival in these patients with otherwise unresectable meningiomas.

LESSONS

Multimodality management with radiosurgery and fractionated radiation therapy was associated with long-term survival of two patients with otherwise surgically incurable and invasive meningiomas of the dural venous sinuses.

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Akiyoshi Ogino, L. Dade Lunsford, Hao Long, Stephen Johnson, Andrew Faramand, Ajay Niranjan, John C. Flickinger, and Hideyuki Kano

OBJECTIVE

While extensive long-term outcome studies support the role of stereotactic radiosurgery (SRS) for smaller-volume vestibular schwannomas (VSs), its role in the management for larger-volume tumors remains controversial.

METHODS

Between 1987 and 2017, the authors performed single-session SRS on 170 patients with previously untreated Koos grade IV VSs (volumes ranged from 5 to 20 cm3). The median tumor volume was 7.4 cm3. The median maximum extracanalicular tumor diameter was 27.5 mm. All tumors compressed the middle cerebellar peduncle and distorted the fourth ventricle. Ninety-three patients were male, 77 were female, and the median age was 61 years. Sixty-two patients had serviceable hearing (Gardner-Robertson [GR] grades I and II). The median margin dose was 12.5 Gy.

RESULTS

At a median follow-up of 5.1 years, the progression-free survival rates of VSs treated with a margin dose ≥ 12.0 Gy were 98.4% at 3 years, 95.3% at 5 years, and 90.7% at 10 years. In contrast, the tumor control rate after delivery of a margin dose < 12.0 Gy was 76.9% at 3, 5, and 10 years. The hearing preservation rates in patients with serviceable hearing at the time of SRS were 58.1% at 3 years, 50.3% at 5 years, and 35.9% at 7 years. Younger age (< 60 years, p = 0.036) and initial GR grade I (p = 0.006) were associated with improved serviceable hearing preservation rate. Seven patients (4%) developed facial neuropathy during the follow-up interval. A smaller tumor volume (< 10 cm3, p = 0.002) and a lower margin dose (≤ 13.0 Gy, p < 0.001) were associated with preservation of facial nerve function. The probability of delayed facial neuropathy when the margin dose was ≤ 13.0 Gy was 1.1% at 10 years. Nine patients (5%) required a ventriculoperitoneal shunt because of delayed symptomatic hydrocephalus. Fifteen patients (9%) developed detectable trigeminal neuropathy. Delayed resection was performed in 4% of patients.

CONCLUSIONS

Even for larger-volume VSs, single-session SRS prevented the need for delayed resection in almost 90% at 10 years. For patients with minimal symptoms of tumor mass effect, SRS should be considered an effective alternative to surgery in most patients, especially those with advanced age or medical comorbidities.

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Akiyoshi Ogino, L. Dade Lunsford, Hao Long, Stephen Johnson, Andrew Faramand, Ajay Niranjan, John C. Flickinger, and Hideyuki Kano

OBJECTIVE

While extensive long-term outcome studies support the role of stereotactic radiosurgery (SRS) for smaller-volume vestibular schwannomas (VSs), its role in the management for larger-volume tumors remains controversial.

METHODS

Between 1987 and 2017, the authors performed single-session SRS on 170 patients with previously untreated Koos grade IV VSs (volumes ranged from 5 to 20 cm3). The median tumor volume was 7.4 cm3. The median maximum extracanalicular tumor diameter was 27.5 mm. All tumors compressed the middle cerebellar peduncle and distorted the fourth ventricle. Ninety-three patients were male, 77 were female, and the median age was 61 years. Sixty-two patients had serviceable hearing (Gardner-Robertson [GR] grades I and II). The median margin dose was 12.5 Gy.

RESULTS

At a median follow-up of 5.1 years, the progression-free survival rates of VSs treated with a margin dose ≥ 12.0 Gy were 98.4% at 3 years, 95.3% at 5 years, and 90.7% at 10 years. In contrast, the tumor control rate after delivery of a margin dose < 12.0 Gy was 76.9% at 3, 5, and 10 years. The hearing preservation rates in patients with serviceable hearing at the time of SRS were 58.1% at 3 years, 50.3% at 5 years, and 35.9% at 7 years. Younger age (< 60 years, p = 0.036) and initial GR grade I (p = 0.006) were associated with improved serviceable hearing preservation rate. Seven patients (4%) developed facial neuropathy during the follow-up interval. A smaller tumor volume (< 10 cm3, p = 0.002) and a lower margin dose (≤ 13.0 Gy, p < 0.001) were associated with preservation of facial nerve function. The probability of delayed facial neuropathy when the margin dose was ≤ 13.0 Gy was 1.1% at 10 years. Nine patients (5%) required a ventriculoperitoneal shunt because of delayed symptomatic hydrocephalus. Fifteen patients (9%) developed detectable trigeminal neuropathy. Delayed resection was performed in 4% of patients.

CONCLUSIONS

Even for larger-volume VSs, single-session SRS prevented the need for delayed resection in almost 90% at 10 years. For patients with minimal symptoms of tumor mass effect, SRS should be considered an effective alternative to surgery in most patients, especially those with advanced age or medical comorbidities.

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Akiyoshi Ogino, L. Dade Lunsford, Hao Long, Stephen Johnson, Andrew Faramand, Ajay Niranjan, John C. Flickinger, and Hideyuki Kano

OBJECTIVE

This report evaluates the outcomes of stereotactic radiosurgery (SRS) as the first-line treatment of intracanalicular vestibular schwannomas (VSs).

METHODS

Between 1987 and 2017, the authors identified 209 patients who underwent SRS as the primary intervention for a unilateral intracanalicular VS. The median patient age was 54 years (range 22–85 years); 94 patients were male and 115 were female. Three patients had facial neuropathy at the time of SRS. One hundred fifty-five patients (74%) had serviceable hearing (Gardner-Robertson [GR] grades I and II) at the time of SRS. The median tumor volume was 0.17 cm3 (range 0.015–0.63 cm3). The median margin dose was 12.5 Gy (range 11.0–25.0 Gy). The median maximum dose was 24.0 Gy (range 15.7–50.0 Gy).

RESULTS

The progression-free survival rates of all patients with intracanalicular VS were 97.5% at 3 years, 95.6% at 5 years, and 92.1% at 10 years. The rates of freedom from the need for any additional intervention were 99.4% at 3 years, 98.3% at 5 years, and 98.3% at 10 years. The serviceable hearing preservation rates in GR grade I and II patients at the time of SRS were 76.6% at 3 years, 63.5% at 5 years, and 27.3% at 10 years. In univariate analysis, younger age (< 55 years, p = 0.011), better initial hearing (GR grade I, p < 0.001), and smaller tumor volumes (< 0.14 cm3, p = 0.016) were significantly associated with improved hearing preservation. In multivariate analysis, better hearing (GR grade I, p = 0.001, HR 2.869, 95% CI 1.569–5.248) and smaller tumor volumes (< 0.14 cm3, p = 0.033, HR 2.071, 95% CI 1.059–4.047) at the time of SRS were significantly associated with improved hearing preservation. The hearing preservation rates of patients with GR grade I VS were 88.1% at 3 years, 77.9% at 5 years, and 38.1% at 10 years. The hearing preservation rates of patients with VSs smaller than 0.14 cm3 were 85.5% at 3 years, 77.7% at 5 years, and 42.6% at 10 years. Facial neuropathy developed in 1.4% from 6 to 156 months after SRS.

CONCLUSIONS

SRS provided sustained tumor control in more than 90% of patients with intracanalicular VS at 10 years and freedom from the need for additional intervention in more than 98% at 10 years. Patients with initially better hearing and smaller VSs had enhanced serviceable hearing preservation during an observation interval up to 10 years after SRS.

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L. Dade Lunsford and Dan Leksell

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Anne-Marie Langlois, Christian Iorio-Morin, Andrew Faramand, Ajay Niranjan, L. Dade Lunsford, Nasser Mohammed, Jason P. Sheehan, Roman Liščák, Dušan Urgošík, Douglas Kondziolka, Cheng-chia Lee, Huai-che Yang, Ahmet F. Atik, and David Mathieu

OBJECTIVE

Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations.

METHODS

The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed.

RESULTS

Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression.

CONCLUSIONS

SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.