Radiosurgery

Radiation necrosis diagnosis

Radiation necrosis diagnosis

Latest Pubmed Related Articles

Unfortunately, symptomatic radiation necrosis is notoriously hard to diagnose and manage. The features of RN overlap considerably with tumor recurrence and misdiagnosing RN as tumor recurrence may lead to deleterious treatment which may cause detrimental effects on the patient 1)

Differentiating radiation necrosis from tumor progression on standard magnetic resonance imaging (MRI) is often difficult and advanced imaging techniques may be needed to make an accurate diagnosis.

Mayo et al. performed a literature review addressing the radiographic modalities used in the diagnosis of radiation necrosis.

Differentiating radiation necrosis from tumor progression remains a diagnostic challenge and advanced imaging modalities are often required to make a definitive diagnosis. If diagnostic uncertainty remains following conventional imaging, a multi-modality diagnostic approach with perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), single photon emission spectroscopy (SPECT), and radiomics may be used to improve diagnosis.

Several imaging modalities exist to aid in the diagnosis of radiation necrosis. Future studies developing advanced imaging techniques are needed 2).

Mangesius et al. provide the experience of a tertiary tumor center with this important issue in neurooncology and provide an institutional pathway for dealing with this problem 3).

Differential diagnosis

Radiation necrosis differential diagnosis.

1)

Vellayappan B, Tan CL, Yong C, Khor LK, Koh WY, Yeo TT, Detsky J, Lo S, Sahgal A. Diagnosis and Management of Radiation Necrosis in Patients With Brain Metastases. Front Oncol. 2018 Sep 28;8:395. doi: 10.3389/fonc.2018.00395. PMID: 30324090; PMCID: PMC6172328.
2)

Mayo ZS, Halima A, Broughman JR, Smile TD, Tom MC, Murphy ES, Suh JH, Lo SS, Barnett GH, Wu G, Johnson S, Chao ST. Radiation necrosis or tumor progression? A review of the radiographic modalities used in the diagnosis of cerebral radiation necrosis. J Neurooncol. 2023 Jan 12. doi: 10.1007/s11060-022-04225-y. Epub ahead of print. PMID: 36633800.
3)

Mangesius J, Mangesius S, Demetz M, Uprimny C, Di Santo G, Galijasevic M, Minasch D, Gizewski ER, Ganswindt U, Virgolini I, Thomé C, Freyschlag CF, Kerschbaumer J. A Multi-Disciplinary Approach to Diagnosis and Treatment of Radionecrosis in Malignant Gliomas and Cerebral Metastases. Cancers (Basel). 2022 Dec 19;14(24):6264. doi: 10.3390/cancers14246264. PMID: 36551750; PMCID: PMC9777318.

Aggressive vertebral hemangioma

Aggressive vertebral hemangioma

Treatment

Accurate preoperative diagnosis is essential because they are highly vascular with a high tendency for intraoperative bleeding.

Management of aggressive VHs involves pre-op embolization, spinal surgery, and reconstruction. Pain management, physical rehabilitation, and close neurological follow-up are imperative to near-total recovery 1).

Surgery

Surgery is required in cases of rapid or progressive neurological symptoms like compressive myelopathy or radiculopathy.

Vertebral hemangioma resection can be a real challenge for spine surgeons, given the high potential of massive intraoperative bleeding. For this reason, preoperative transarterial embolization of this tumor is supported by the available literature 2).

A navigation-guided drill is highly helpful for real-time monitoring of ongoing tumor resection. It enables safely resection of the tumor, especially in the anterior cortical surface of the vertebral body, and easily resections even hard tumors. This method results in reducing residual tumors and maintaining safe resection 3).

Radiotherapy

Radiotherapy can be used in patients with slowly progressive neurological deficits.

CT guided alcohol injection

While CT-guided direct alcohol injection is effective in the management of symptomatic and aggressive vertebral hemangiomas, spinal angiography and trans-arterial embolization of the blood supply to the vertebral body hemangioma, prior to the direct transpedicular alcohol embolization of the lesion, improves the safety of the procedure 4).

Radiofrequency ablation

Other emerging options in cases of aggressive hemangiomas include radiofrequency ablation with a hemostatic agent (e.g. FLOSEAL, Baxter, USA), and bone autograft placement 5).

Minimally invasive procedures may be successful in smaller lesions 6).

Case reports

The case of a pregnancy who was diagnosed with an aggressive vertebral hemangioma that further led to progressive paraparesis. We had to take the fact that she was pregnant into account in the diagnostic procedure, the choice of examination method, and also the method of therapy. The goal of this case report is threefold: (1) provide an overview of the possible methods of management, specifically imaging, which will aid in diagnosis and based on that, (2) determine the appropriate therapy, and (3) review the risks and benefits of each will be presented when choosing individual approaches 7).

1)

Goraya GS, Singhal S, Paul BS, Paul G. Aggressive Vertebral Hemangioma: The Mystery of Spastic Legs Unveiled by a Purple Shoulder. Cureus. 2022 Jan 24;14(1):e21568. doi: 10.7759/cureus.21568. PMID: 35228927; PMCID: PMC8873442.
2)

Fiore G, Bertani GA, Tariciotti L, Borsa S, Paolucci A, Taramasso L, Locatelli M, Pluderi M. Vertebral Body Infarction after Transarterial Preoperative Embolization of a Vertebral Hemangioma. J Neurol Surg A Cent Eur Neurosurg. 2021 Dec 12. doi: 10.1055/s-0041-1739215. Epub ahead of print. PMID: 34897610.
3)

Nagashima Y, Nishimura Y, Haimoto S, Eguchi K, Awaya T, Ando R, Akahori S, Hara M, Natsume A. Piecemeal resection of aggressive vertebral hemangioma using real-time navigation-guided drilling technique. Nagoya J Med Sci. 2021 Nov;83(4):861-868. doi: 10.18999/nagjms.83.4.861. PMID: 34916728; PMCID: PMC8648519.
4)

Srinivasan G, Moses V, Padmanabhan A, Ahmed M, Keshava SN, Krishnan V, Joseph BV, Raju KP, Rajshekhar V. Utility of spinal angiography and arterial embolization in patients undergoing CT guided alcohol injection of aggressive vertebral hemangiomas. Neuroradiology. 2021 Nov;63(11):1935-1945. doi: 10.1007/s00234-021-02788-7. Epub 2021 Aug 24. PMID: 34427707.
5)

Canbay S, Kayalar AE, Gel G, Sabuncuoğlu H. A novel surgical technique for aggressive vertebral hemangiomas. (2019) Neurocirugia (Asturias, Spain). 30 (5): 233-237. doi:10.1016/j.neucir.2018.08.003
6)

Vasudeva VS, Chi JH, Groff MW. Surgical treatment of aggressive vertebral hemangiomas. Neurosurg Focus. 2016 Aug;41(2):E7. doi: 10.3171/2016.5.FOCUS16169. PMID: 27476849.
7)

Ridzoňová L, Fedičová M, Andráš T, Urdzík P, Gdovinová Z. Lower-limb progressive paraparesis management and diagnosis overview in a pregnant woman with vertebral haemangioma. Womens Health (Lond). 2022 Jan-Dec;18:17455057221099018. doi: 10.1177/17455057221099018. PMID: 35574823.

World Health Organization grade 3 meningioma

World Health Organization grade 3 meningioma

Papillary meningioma

Rhabdoid meningioma

Anaplastic meningioma

Mast cells (MCs) were present in as many as 90 % of all high grade meningiomas mainly found in the perivascular areas of the tumor. A correlation between peritumoral edema and MCs was found.

Accumulation of MCs in meningiomas could contribute to the aggressiveness of tumors and to brain inflammation that may be involved in the pathogenesis of additional disorders 1).

Treatment

From the available data, surgical resection followed by RT and salvage therapy can lead to extended survival 2).

Adjuvant radiotherapy and stereotactic radiosurgery

For a systematic review, studies analyzing the effectiveness of adjuvant radiotherapy and stereotactic radiosurgery in grade 3 (gr. 3) meningioma were reviewed. Thirty studies met the inclusion criteria for qualitative synthesis, and 6 studies were assessed in quantitative analysis. In quantitative analysis, the weighted average of hazard ratios for adjuvant RT in univariate analyses of overall survival (OS) was 0.55 (CI: 0.41; 0.69). The median 5-year OS after adjuvant RT in gr. 3 meningiomas were 56.3%, and the median OS ranged from 24 to 80 months for patients treated with adjuvant RT versus 13 to 41.2 months in patients not treated. For stereotactic radiosurgery, the 3-year progression-free survival was 0% in one study and 57% in another. The 2-year OS ranged from 25 to 75% in 2 studies. The quality of evidence was rated as “very low” in 14 studies analyzed, and considerable allocation bias was detected. Treatment toxicity was reported in 47% of the studies. The severity, according to the CTCAE, ranged from grades I-V and 5.3 to 100% of patients experiencing complications. Adjuvant RT is usually considered the standard of care for WHO grade 3 meningiomas, although supporting evidence was of low quality. Better evidence from registries and prospective trials can improve the evidence base for adjuvant fractionated radiotherapy in malignant meningiomas 3).

1)

Polyzoidis S, Koletsa T, Panagiotidou S, Ashkan K, Theoharides TC. Mast cells in meningiomas and brain inflammation. J Neuroinflammation. 2015 Sep 17;12(1):170. doi: 10.1186/s12974-015-0388-3. PubMed PMID: 26377554.
2)

Rosenberg LA, Prayson RA, Lee J, Reddy C, Chao ST, Barnett GH, Vogelbaum MA, Suh JH. Long-term experience with World Health Organization grade III (malignant) meningiomas at a single institution. Int J Radiat Oncol Biol Phys. 2009 Jun 1;74(2):427-32. doi: 10.1016/j.ijrobp.2008.08.018. PMID: 19427553.
3)

Bergner A, Maier AD, Mirian C, Mathiesen TI. Adjuvant radiotherapy and stereotactic radiosurgery in grade 3 meningiomas – a systematic review and meta-analysis. Neurosurg Rev. 2022 May 11. doi: 10.1007/s10143-022-01773-9. Epub ahead of print. PMID: 35543810.

Low-Grade Glioma Radiotherapy Dose

Low-Grade Glioma Radiotherapy Dose

Adjuvant radiation is often used in patients with low-grade gliomas with high-risk characteristics with a recommended dose of 45-54 Gy. Byrne et al. used the National Cancer Database (NCDB) to see which doses were being used and if any difference was seen in outcome.

They queried the NCDB for patients with WHO Grade 2 primary brain tumors treated with surgery and adjuvant radiotherapy. We divided the cohort into dose groups: 45-50 Gy, 50.4-54 Gy, and > 54 Gy. Multivariable logistic regression was used to identify predictors of low and high-dose radiation. Propensity matching was used to account for indication bias.

Results: We identified 1437 patients meeting inclusion criteria. The median age was 45 years and 62% of patients were > 40 years old. Nearly half of patients (48%) had astrocytoma subtype and 70% had a subtotal resection. The majority of patients (69%) were treated to doses between 50.4 and 54 Gy. Predictors of high dose radiation (> 54 Gy) were increased income, astrocytoma subtype, chemotherapy receipt, and treatment in a later years (2014). The main predictors of survival were age > 40, astrocytoma subtype, and insurance type. Patients treated to a dose of > 54 Gy had a median survival of 73.5 months and was not reached in those treated to a lower dose (p = 0.0041).

This analysis showed that 50.4-54 Gy is the most widely used radiation regimen for the adjuvant treatment of low-grade gliomas. There appeared to be no benefit to higher doses, although unreported factors may impact the interpretation of the results 1).

Postoperative policies of “wait-and-see” and radiotherapy for low-grade glioma are poorly defined. A trial in the mid 1980s established the radiation dose.

A phase III prospective randomized trial of low- versus high-dose radiation therapy for adults with supratentorial low-grade astrocytoma, oligodendroglioma, and oligoastrocytoma found somewhat lower survival and slightly higher incidence of radiation necrosis in the high-dose RT arm. The most important prognostic factors for survival are histologic subtype, tumor size, and age 2).

Two prospective trials found no difference in OS or PFS between different XRT doses (EORTC trial 3): 45 Gy in 5 weeks vs. 59.4 Gy in 6.6 weeks; Intergroup study 4) 50.4 vs. 64.8 Gy).

1)

Byrne E, Abel S, Yu A, Shepard M, Karlovits SM, Wegner RE. Trends in radiation dose for low-grade gliomas across the United States. J Neurooncol. 2022 Feb 23. doi: 10.1007/s11060-022-03962-4. Epub ahead of print. PMID: 35199246.
2)

Shaw E, Arusell R, Scheithauer B, O’Fallon J, O’Neill B, Dinapoli R, Nelson D, Earle J, Jones C, Cascino T, Nichols D, Ivnik R, Hellman R, Curran W, Abrams R. Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol. 2002 May 1;20(9):2267-76. PubMed PMID: 11980997.
3)

Karim ABMF, Maat B, Hatlevoll R, et al. A random- ized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844. Int J Radiation Oncology Biol Phys. 1996; 36:549–556
4)

Shaw E, Arusell R, Scheithauer B, O’Fallon J, O’Neill B, Dinapoli R, Nelson D, Earle J, Jones C, Cascino T, Nichols D, Ivnik R, Hellman R, Curran W, Abrams R. Prospective randomized trial of low- versus high-dose radiation therapy in adults with supra- tentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol. 2002; 20:2267–2276

Vestibular Schwannoma Gamma Knife radiosurgery complications

Vestibular Schwannoma Gamma Knife radiosurgery complications

Patients treated with Stereotactic radiosurgery for vestibular schwannoma can have a similar complication profile to those treated with intracranial surgery. Vestibular Schwannoma Meta-analysis from early experience showed that 44% with serviceable hearing prior to treatment retained their ability after SRS, a statistically equivalent rate to the surgical data. This evidence also suggest that 37.9% of patients have other complications 1).

In the mid-1970s, early facial weakness occurred in 38% and facial numbness in 33%. This has gradually decreased to less than 2% in the 1990s. Preservation of hearing (unchanged or almost unchanged) is currently achieved in 65 to 70%. Tinnitus is rarely changed by the treatment. The risks of intracranial bleeding, infection, and CSF leak are avoided because of the non-invasive nature of the treatment. Hydrocephalus directly induced by the tumor occurred in 9.2% of patients. On the other hand, a treatment%related peritumoral reaction sufficient to block the CSF circulation and require shunt insertion was seen in only 1.4%. Based on experiences worldwide, the incidence of secondary neoplasia seems to be 0.1%. The effectiveness of GKR together with its low complication rate makes it a suitable treatment for anyone, regardless of age and general health 2).

Malignant transformation is possible 3). , and long-term post-SRS surveillance MRI is important 4).

Patients receiving > 13 Gy were significantly more likely to develop trigeminal neuropathy than those receiving < 13 Gy (p < 0.001) 5).

Case reports

Pollack et al. described an acute facial and acoustic neuropathy following gamma knife surgery (GKS) for vestibular schwannoma (VS). This 39-year-old woman presenting with tinnitus underwent GKS for a small right-sided intracanalicular VS, receiving a maximal dose of 26 Gy and a tumor margin dose of 13 Gy to the 50% isodose line. Thirty-six hours following treatment she presented with nausea, vomiting, vertigo, diminished hearing, and a House-Brackmann Grade III facial palsy. She was started on intravenous glucocorticosteroid agents, and over the course of 2 weeks her facial function returned to House-Brackmann Grade I. Unfortunately, her hearing loss persisted. A magnetic resonance (MR) image obtained at the time of initial deterioration demonstrated a significant decrease in tumor enhancement but no change in tumor size or peritumoral edema. Subsequently, the patient experienced severe hemifacial spasms, which persisted for a period of 3 weeks and then progressed to a House-Brackmann Grade V facial palsy. During the next 3 months, the patient was treated with steroids and in time her facial function and hearing returned to baseline levels. Results of MR imaging revealed transient enlargement (3 mm) of the tumor, which subsequently returned to its baseline size. This change corresponded to the tumor volume increase from 270 to 336 mm3. The patient remains radiologically and neurologically stable at 10 months posttreatment. This is the first detailed report of acute facial and vestibulocochlear neurotoxicity following GKS for VS that improved with time. In addition, MR imaging findings were indicative of early neurotoxic changes. A review of possible risk factors and explanations of causative mechanisms is provided 6).

Pseudoprogression

see Vestibular Schwannoma pseudoprogression.

1)

Kaylie DM, Horgan MJ, Delashaw JB, McMenomey SO. A meta-analysis comparing outcomes of microsurgery and gamma knife radiosurgery. Laryngoscope. 2000 Nov;110(11):1850-6. doi: 10.1097/00005537-200011000-00016. PMID: 11081598.
2)

Norén G. Long-term complications following gamma knife radiosurgery of vestibular schwannomas. Stereotact Funct Neurosurg. 1998 Oct;70 Suppl 1:65-73. doi: 10.1159/000056408. PMID: 9782237.
3)

Yanamadala V, Williamson RW, Fusco DJ, Eschbacher J, Weisskopf P, Porter RW. Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. World Neurosurg. 2013 Mar-Apr;79(3-4):593.e1-8. doi: 10.1016/j.wneu.2012.03.016. Epub 2012 Apr 2. PubMed PMID: 22480982.
4)

Kawashima M, Hasegawa H, Shin M, Shinya Y, Katano A, Saito N. Outcomes of stereotactic radiosurgery in young adults with vestibular schwannomas. J Neurooncol. 2021 Jul 9. doi: 10.1007/s11060-021-03803-w. Epub ahead of print. PMID: 34241770.
5)

Sughrue ME, Yang I, Han SJ, Aranda D, Kane AJ, Amoils M, Smith ZA, Parsa AT. Non-audiofacial morbidity after Gamma Knife surgery for vestibular schwannoma. J Neurosurg. 2013 Dec;119 Suppl:E4. Review. PubMed PMID: 25077327.
6)

Pollack AG, Marymont MH, Kalapurakal JA, Kepka A, Sathiaseelan V, Chandler JP. Acute neurological complications following gamma knife surgery for vestibular schwannoma. Case report. J Neurosurg. 2005 Sep;103(3):546-51. doi: 10.3171/jns.2005.103.3.0546. PMID: 16235688.

Gamma Knife radiosurgery for cavernous malformation

Gamma Knife radiosurgery for cavernous malformation

Stereotactic radiosurgery (SRS) is a therapeutic option for repeatedly hemorrhagic cavernous malformations (CMs) located in areas deemed to be high risk for resection. During the latency period of 2 or more years after SRS, recurrent hemorrhage remains a persistent risk until the obliterative process has finished. The pathological response to SRS has been studied in relatively few patients.

Gamma Knife radiosurgery (GKRS) has been used to treat cavernous malformations (CMs) located in basal ganglia and thalamus. However, previous reports are limited by small patient population.

Hu et al. retrospectively reviewed the clinical and radiological data of 53 patients with CMs of basal ganglia and thalamus who underwent GKRS at West China Medical Center between May 2009 and July 2018. All patients suffered at least once bleeding before GKRS. The mean volume of these lesions was 1.77 cm3, and the mean marginal dose was 13.2 Gy. After treatment, patients were followed to determine the change in symptom and hemorrhage event.

The mean follow-up period was 52.1 months (6.2-104.3 months). The calculated annual hemorrhage rate (AHR) was 48.5% prior to GKRS and 3.0% after treatment (p < 0.001). The Kaplan-Meier analysis revealed that 2-, 3-, and 5-year hemorrhage-free survival were 88, 80.9, and 80.9%, respectively. Preexisting symptoms were resolved in 11 patients, improved in 14, and stable in 5. Only 2 patients (3.8%) developed new neurological deficit.

This study suggests that AHR after GKRS was comparable to the recorded AHR of natural history (3.1-4.1%) in previous studies. GKRS is a safe and effective treatment modality for CMs of basal ganglia and thalamus. Considering the relative insufficient understanding of natural history of CMs, future study warrants longer follow-up 1)

Meta-analysis

Wen et al., from the West China Hospital performed a meta-analysis is to evaluate the clinical efficacy of gamma knife radiosurgery for treating cavernous malformation.

PUBMED, OVID EMBASE, and OVID MEDLINE electronic databases are searched. The primary outcome is hemorrhage rate and this meta-analysis is performed with REVMAN 5.3.

9 studies are included in this meta-analysis. The overall RR of hemorrhage rate of pre-GKRS and post-GKRS is 6.08(95% CI: 5.04-7.35). The overall RR is 3.03(95% CI: 2.65-4.11) between the hemorrhage rate of pre-GKRS and the first 2 years of post-radiosurgery, and the overall RR is 12.13 (95% CI: 1.73-85.07) comparing pre-GKRS with 2 years after GKRS. There is no significant difference of the hemorrhage rate between the first 2 years of post-radiosurgery and 2 years after GKRS (RR =2.81, 95% CI: 0.20-13.42). The neurological deficiency is the commonest radiosurgery related complications.

Patients with cerebral CMs, especially who were deep seated and surgically inaccessible, seems to benefit from GKRS due to a reduction of annual hemorrhage rate in the first 2 years, and after that time, despite of a number of cases that suffer from negative side effects of radiation 2).

Case series

Between 1993 and 2018, 261 patients with 331 symptomatic CCMs were treated by GKS. The median age was 39.9 years and females were predominant (54%). The median volume of CCMs was 3.1 mL. The median margin dose was 11.9 Gy treat to a median isodose level of 59%. Median clinical and imaging follow-up times were 69 and 61 months, respectively. After the initial hemorrhage that led to CCM diagnosis, 136 hemorrhages occurred in the period prior to GKS (annual incidence = 23.6%). After GKS, 15 symptomatic hemorrhages occurred within the first 2 years of follow-up (annual incidence = 3.22%), and 37 symptomatic hemorrhages occurred after the first 2 years of follow-up (annual incidence = 3.16%). Symptomatic radiation-induced complication was encountered in 8 patients (3.1%). Mortality related to GKS occurred in 1 patient (0.4%). In conclusion, GKS decreased the risk of hemorrhage in CCM patients presenting with symptomatic hemorrhage. GKS is a viable alternative treatment option for patients with surgically-inaccessible CCMs or significant medical comorbidities 3).

Shin et al. aimed to gain insight into the effect of SRS on CM and to propose possible mechanisms leading to recurrent hemorrhages following SRS.

During a 13-year interval between 2001 and 2013, bleeding recurred in 9 patients with CMs that had been treated using Gamma Knife surgery at the authors’ institution. Microsurgical removal was subsequently performed in 5 of these patients, who had recurrent hemorrhages between 4 months and 7 years after SRS. Specimens from 4 patients were available for analysis and used for this report.

Histopathological analysis demonstrated that vascular sclerosis develops as early as 4 months after SRS. In the samples from 2 to 7 years after SRS, sclerotic vessels were prominent, but there were also vessels with incomplete sclerosis as well as some foci of neovascularization.

Recurrent bleeding after SRS for CM could be related to incomplete sclerosis of the vessels, but neovascularization may also play a role 4).

From 1994 to 2001, 92 patients with 114 CMs were treated by GKS and then followed up for 2-8 years (mean 4.1+/-1.9). We analyzed the MRI features of CMs bleeding, efficacy of GKS, and the complications of treatment. Six pathological specimens after radiosurgery (1 from our group, 5 from other centers) were also assayed.

Among 43 patients who were treated by GKS to control their epilepsy, epileptic paroxysm was alleviated in 36 patients (83.7%), including 12 (27.9%) seizure-free. Rebleeding was confirmed in 9 patients (9.8%) by neuroimage, one of whom died. Transient symptomatic radiation edema occurred in 7 cases (7.6%) within 6-12 months after radiosurgery, and one patient underwent open surgery for cerebral decompression. The main pathological changes of cavernoma were coagulation necrosis and the vessels obliterated gradually after radiosurgery.

It is feasible to treat small and surgically high risk CMs by radiosurgery. The treatment has to be prudent in an acute bleeding and symptomatic progression. Optimal treatment timing and dose planning are prerequisites to reduce radiation-related complications. GKS is safe and effective to control the epilepsy caused by CMs, and also to bring down the rebleeding rate after a latency interval of several years 5).

Gamma knife radiosurgery for brainstem cavernous malformation

Gamma knife radiosurgery for brainstem cavernous malformation.

1)

Hu YJ, Zhang LF, Ding C, Tian Y, Chen J. Gamma Knife Radiosurgery for Cavernous Malformations of Basal Ganglia and Thalamus: A Retrospective Study of 53 Patients. Stereotact Funct Neurosurg. 2021 Jun 9:1-8. doi: 10.1159/000510108. Epub ahead of print. PMID: 34107485.
2)

Wen R, Shi Y, Gao Y, Xu Y, Xiong B, Li D, Gong F, Wang W. The efficacy of gamma knife radiosurgery for cavernous malformation: a meta-analysis and review. World Neurosurg. 2018 Dec 21. pii: S1878-8750(18)32869-9. doi: 10.1016/j.wneu.2018.12.046. [Epub ahead of print] Review. PubMed PMID: 30583131.
3)

Lee CC, Wang WH, Yang HC, Lin CJ, Wu HM, Lin YY, Hu YS, Chen CJ, Chen YW, Chou CC, Liu YT, Chung WY, Shiau CY, Guo WY, Hung-Chi Pan D, Hsu SPC. Gamma Knife radiosurgery for cerebral cavernous malformation. Sci Rep. 2019 Dec 24;9(1):19743. doi: 10.1038/s41598-019-56119-1. PMID: 31874979; PMCID: PMC6930272.
4)

Shin SS, Murdoch G, Hamilton RL, Faraji AH, Kano H, Zwagerman NT, Gardner PA, Lunsford LD, Friedlander RM. Pathological response of cavernous malformations following radiosurgery. J Neurosurg. 2015 Oct;123(4):938-44. doi: 10.3171/2014.10.JNS14499. Epub 2015 Jun 19. PubMed PMID: 26090838.
5)

Liu AL, Wang CC, Dai K. [Gamma knife radiosurgery for cavernous malformations]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2005 Feb;27(1):18-21. Chinese. PMID: 15782486.

Cavernous sinus hemangioma Gamma Knife surgery

Cavernous sinus hemangioma Gamma Knife surgery

A study aimed to evaluate the efficacy of Gamma Knife surgery (GKS) on cavernous sinus hemangioma and to analyze the temporal volume change.

Cho et al. retrospectively reviewed the clinical data of 26 cavernous sinus hemangioma patients who were treated with GKS between 2001 and 2017. Before GKS, 11 patients (42.3%) had cranial neuropathies and 5 patients (19.2%) complained of headache, whereas 10 patients (38.5%) were initially asymptomatic. The mean pre-GKS mass volume was 9.3 mL (range, 0.5-31.6 mL), and the margin dose ranged from 13 to 15 Gy according to the mass volume and the proximity to the optic pathway. All cranial neuropathy patients and half of headache patients showed clinical improvement. All 26 patients achieved mass control; remarkable responses (less than 1/3 of the initial mass volume) were shown in 19 patients (73.1%) and moderate responses (more than 1/3 and less than 2/3) in 7 patients (26.9%). The mean final mass volume after GKS was 1.8 mL (range, 0-12.6 mL). The mean mass volume at 6 months after GKS was 45% (range, 5-80%) compared to the mass volume before GKS and 21% (range, 0-70%) at 12 months. The higher radiation dose tended to induce more rapid and greater volume reduction. No treatment-related complication was observed during the follow-up period. GKS could be an effective and safe therapeutic strategy for CSCH. GKS induced very rapid volume reduction compared to other benign brain tumors 1).

An international multicenter study was conducted to review outcome data in 31 patients with CSH. Eleven patients had initial microsurgery before SRS, and the other 20 patients (64.5%) underwent Gamma Knife SRS as the primary management for their CSH. Median age at the time of radiosurgery was 47 years, and 77.4% of patients had cranial nerve dysfunction before SRS. Patients received a median tumor margin dose of 12.6 Gy (range 12-19 Gy) at a median isodose of 55%. RESULTS Tumor regression was confirmed by imaging in all 31 patients, and all patients had greater than 50% reduction in tumor volume at 6 months post-SRS. No patient had delayed tumor growth, new cranial neuropathy, visual function deterioration, adverse radiation effects, or hypopituitarism after SRS. Twenty-four patients had presented with cranial nerve disorders before SRS, and 6 (25%) of them had gradual improvement. Four (66.7%) of the 6 patients with orbital symptoms had symptomatic relief at the last follow-up. CONCLUSIONS Stereotactic radiosurgery was effective in reducing the volume of CSH and attaining long-term tumor control in all patients at a median of 40 months. The authors’ experience suggests that SRS is a reasonable primary and adjuvant treatment modality for patients in whom a CSH is diagnosed. 2).

Between August 2011 and April 2014, 7 patients with CSHs underwent GKS. GKS was performed as the sole treatment option in 5 patients, whilst partial resection had been performed previously in 1 patient and biopsy had been performed in 1 patient. The mean volume of the tumors at the time of GKS was 12.5±10.2 cm3 (range, 5.3-33.2 cm3), and the median prescription of peripheral dose was 14.0 Gy (range, 10.0-15.0 Gy). The mean follow-up period was 20 months (range, 6-40 months). At the last follow-up, the lesion volume had decreased in all patients, and all cranial neuropathies observed prior to GKS had improved. There were no radiation-induced neuropathies or complications during the follow-up period. GKS appears to be an effective and safe treatment modality for the management of CSHs 3).

A retrospective analysis of 7 patients with CS hemangiomas treated by GKS between 1993 and 2008. Data from 84 CS meningiomas treated during the same period were also analyzed for comparison. The patients underwent follow-up magnetic resonance imaging at 6-month intervals. Data on clinical and imaging changes after radiosurgery were analyzed.

Six months after GKS, magnetic resonance imaging revealed an average of 72% tumor volume reduction (range, 56%-83%). After 1 year, tumor volume decreased 80% (range, 69%-90%) compared with the pre-GKS volume. Three patients had > 5 years of follow-up, which showed the tumor volume further decreased by 90% of the original size. The average tumor volume reduction was 82%. In contrast, tumor volume reduction of the 84 cavernous sinus meningiomas after GKS was only 29% (P < .001 by Mann-Whitney U test). Before treatment, 6 patients had various degrees of ophthalmoplegia. After GKS, 5 improved markedly within 6 months. Two patients who suffered from poor vision improved after radiosurgery.

GKS is an effective and safe treatment modality for CS hemangiomas with long-term treatment effect. Considering the high risks involved in microsurgery, GKS may serve as the primary treatment choice for CS hemangiomas 4).

References

1)

Cho JM, Sung KS, Jung IH, Chang WS, Jung HH, Chang JH. Temporal Volume Change of Cavernous Sinus Cavernous Hemangiomas after Gamma Knife Surgery. Yonsei Med J. 2020 Nov;61(11):976-980. doi: 10.3349/ymj.2020.61.11.976. PMID: 33107242.
2)

Lee CC, Sheehan JP, Kano H, Akpinar B, Martinez-Alvarez R, Martinez-Moreno N, Guo WY, Lunsford LD, Liu KD. Gamma Knife radiosurgery for hemangioma of the cavernous sinus. J Neurosurg. 2017 May;126(5):1498-1505. doi: 10.3171/2016.4.JNS152097. Epub 2016 Jun 24. PMID: 27341049.
3)

Xu Q, Shen J, Feng Y, Zhan R. Gamma Knife radiosurgery for the treatment of cavernous sinus hemangiomas. Oncol Lett. 2016 Feb;11(2):1545-1548. doi: 10.3892/ol.2015.4053. Epub 2015 Dec 23. PMID: 26893777; PMCID: PMC4734249.
4)

Chou CW, Wu HM, Huang CI, Chung WY, Guo WY, Shih YH, Lee LS, Pan DH. Gamma knife surgery for cavernous hemangiomas in the cavernous sinus. Neurosurgery. 2010 Sep;67(3):611-6; discussion 616. doi: 10.1227/01.NEU.0000378026.23116.E6. PMID: 20647963.

Cerebellopontine Angle Synchronous Tumor

Cerebellopontine Angle Synchronous Tumor

Synchronous cerebellopontine angle (CPA) tumors are a rare entity, heterogeneous lesions with a marked predisposition toward poor facial nerve outcomes, potentially attributable to a paracrine mechanism that simultaneously drives multiple tumor growth and increases invasiveness or adhesiveness at the facial nerve-tumor interface. Preceding nomenclature has been confounding and inconsistent; Graffeo et al. recommended classifying all multiple CPA tumors as “synchronous tumors,” with “schwannoma with meningothelial hyperplasia” or “tumor-to-tumor metastases” reserved for rare, specific circumstances 1).

Treatment

Several publications refer to surgery for such tumors and their classification. Yet, there are no publications on upfront radiosurgery for synchronous CPA tumors.

Simultaneous and stepwise radiosurgery for synchronous CPA tumors seems to be safe and effective. There were no side effects or complications. To the best of our knowledge this is the first report on upfront radiosurgery for synchronous CPA tumors 2).

Case reports

Mindermann and Heckl presented two patients with sporadic synchronous benign CPA tumors who underwent upfront radiosurgery. One patient had two separate schwannomas of the CPA and the other had a cerebellopontine angle schwannoma and a cerebellopontine angle meningioma. One patient underwent stepwise radiosurgery treating one tumor after another and the other patient underwent simultaneous radiosurgery for both tumors at the same time.

Simultaneous and stepwise radiosurgery for synchronous CPA tumors seems to be safe and effective. There were no side effects or complications. To the best of our knowledge this is the first report on upfront radiosurgery for synchronous CPA tumors 3).

A 64-year-old woman and a 42-year-old man presented with symptoms referable to the CPA. Magnetic resonance imaging in both patients revealed 2 separate contiguous tumors. Retrosigmoid craniotomy and tumor removal in each case confirmed VS and meningioma. Systematic literature review identified 42 previous English-language publications describing 46 patients with multiple CPA tumors. Based on Frassanito criteria, there were 4 concomitant tumors (8%), 16 contiguous tumors (33%), 3 collision tumors (6%), 13 mixed tumors (27%), and 11 tumor-to-tumor metastases (23%). Extent of resection was gross total in 16 cases and subtotal in 16 cases (50% each). Unfavorable House-Brackmann grade III-VI function was documented in 27% overall and in 33% of patients with VS and meningioma, a marked increase from the observed range in isolated VS 4).

A 57-year-old female patient presented with headache, speech disturbance, left facial numbness and deafness in the left ear. Magnetic resonance imaging demonstrated two different tumors in the left CPA. These tumors were not in continuity. The tumors were totally removed through the left suboccipital approach. Histopathological examination revealed that the large tumor was a vestibular schwannoma and the smaller was a meningioma. Neurofibromatosis was not diagnosed in the patient. No recurrence was observed at the end of 9 years after the operation. The simultaneous occurrence of vestibular schwannoma and meningioma in the CPA appears coincidental. This association must be kept in mind if two different tumors are detected radiologically in the same CPA 5).

References

1) , 4)

Graffeo CS, Perry A, Copeland WR 3rd, Giannini C, Neff BA, Driscoll CL, Link MJ. Synchronous Tumors of the Cerebellopontine Angle. World Neurosurg. 2017 Feb;98:632-643. doi: 10.1016/j.wneu.2016.11.002. Epub 2016 Nov 12. PMID: 27836701.
2) , 3)

Mindermann T, Heckl S. Radiosurgery for Sporadic Benign Synchronous Tumors of the Cerebellopontine Angle. J Neurol Surg A Cent Eur Neurosurg. 2020 Oct 21. doi: 10.1055/s-0040-1714424. Epub ahead of print. PMID: 33086420.
5)

Izci Y, Secer HI, Gönül E, Ongürü O. Simultaneously occurring vestibular schwannoma and meningioma in the cerebellopontine angle: case report and literature review. Clin Neuropathol. 2007 Sep-Oct;26(5):219-23. doi: 10.5414/npp26219. PMID: 17907598.

IntuitivePlan

IntuitivePlan

http://www.intuitivetherapeutics.com/index.php/en/

Levivier et al. developed a new, real-time interactive inverse planning approach, based on a fully convex framework, to be used for Gamma Knife radiosurgery.

The convex framework is based on the precomputation of a dictionary composed of the individual dose distributions of all possible shots, considering all their possible locations, sizes, and shapes inside the target volume. The convex problem is solved to determine the plan, i.e., which shots and with which weights, that will actually be used, considering a sparsity constraint on the shots to fulfill the constraints while minimizing the beam-on time. The system is called IntuitivePlan and allows data to be transferred from generated dose plans into the Gamma Knife treatment planning software for further dosimetry evaluation.

The system has been very efficiently implemented, and an optimal plan is usually obtained in less than 1 to 2 minutes, depending on the complexity of the problem, on a desktop computer or in only a few minutes on a high-end laptop. Dosimetry data from 5 cases, 2 meningiomas and 3 vestibular schwannomas, were generated with IntuitivePlan. Results of evaluation of the dosimetry characteristics are very satisfactory and adequate in terms of conformity, selectivity, gradient, protection of organs at risk, and treatment time.

The possibility of using optimal, interactive real-time inverse planning in conjunction with the Leksell Gamma Knife opens new perspectives in radiosurgery, especially considering the potential use of the full capabilities of the latest generations of the Leksell Gamma Knife. This approach gives new users the possibility of using the system for easier and quicker access to good-quality plans with a shorter technical training period and opens avenues for new planning strategies for expert users. The use of a convex optimization approach allows an optimal plan to be provided in a very short processing time. This way, innovative graphical user interfaces can be developed, allowing the user to interact directly with the planning system to graphically define the desired dose map and to modify on-the-fly the dose map by moving, in a very user-friendly manner, the isodose surfaces of an initial plan. Further independent quantitative prospective evaluation comparing inverse planned and forward planned cases is warranted to validate this novel and promising treatment planning approach 1).

To compare planning indices achieved using manual and inverse planning approaches for Gamma knife radiosurgery for arteriovenous malformation.

For a series of consecutive AVM patients, treatment plans were manually created by expert planners using Leksell GammaPlan (LGP). Patients were re-planned using a new commercially released inverse planning system, IntuitivePlan. Plan quality metrics were calculated for both groups of plans and compared.

Overall, IntuitivePlan created treatment plans of similar quality to expert planners. For some plan quality metrics statistically significant higher scores were achieved for the inversely generated plans (Coverage 96.8% vs 96.3%, P = 0.027; PCI 0.855 vs 0.824, P = 0.042), but others did not show statistically significant differences (Selectivity 0.884 vs 0.856, P = 0.071; GI 2.85 vs 2.76, P = 0.096; Efficiency Index 47.0% vs 48.1%, P = 0.242; Normal Brain V12 (cc) 5.81 vs 5.79, P = 0.497). Automatic inverse planning demonstrated significantly shorter planning times over manual planning (3.79 vs 11.58 min, P < 10-6 ) and greater numbers of isocentres (40.4 vs 10.8, P < 10-6 ), with an associated cost of longer treatment times (57.97 vs 49.52 min, P = 0.009). When planning and treatment time were combined, there was no significant difference in the overall time between the two methods (61.76 vs 61.10, P = 0.433).

IntuitivePlan can offer savings on the labor of treatment planning. In many cases, it achieves higher quality indices than those achieved by an “expert planner” 2).

References

1)

Levivier M, Carrillo RE, Charrier R, Martin A, Thiran JP. A real-time optimal inverse planning for Gamma Knife radiosurgery by convex optimization: description of the system and first dosimetry data. J Neurosurg. 2018;129(Suppl1):111-117. doi:10.3171/2018.7.GKS181572
2)

Paddick I, Grishchuk D, Dimitriadis A. IntuitivePlan inverse planning performance evaluation for Gamma Knife radiosurgery of AVMs [published online ahead of print, 2020 Aug 4]. J Appl Clin Med Phys. 2020;10.1002/acm2.12973. doi:10.1002/acm2.12973