The history of LITT for the treatment of active brain metastasis and radiation necrosis.

This manuscript reviews advancements in Laser Interstitial Thermal Therapy (LITT) for treating brain metastases and radiation necrosis, emphasizing its minimally invasive nature and precision in targeting deep-seated or eloquent area lesions. It analyzes studies from 2011 to 2024 to evaluate LITT's efficacy, safety, and complications while highlighting the need for standardized clinical endpoints. Despite its potential, LITT remains a secondary treatment due to limited high-level evidence, requiring further research and multidisciplinary collaboration. A systematic PubMed search identified 2,004 articles on LITT for brain metastases and radiation necrosis. Filtering for studies from 2011 to 2024 resulted in 60 selected articles: 4 clinical trials, 22 observational studies, 3 case reports, 2 case series, and the rest review articles. Relevant data were extracted, analyzed, and compiled for this review. LITT is primarily used for lesions unsuitable for open craniotomy, such as deep-seated or eloquent-area tumors. Literature supports its increasing neuro-oncological applications, particularly in brain metastases, gliomas, meningiomas, and radiation necrosis. The evolving landscape of brain metastasis treatment underscores the importance of a multidisciplinary approach incorporating standardized reporting, advanced imaging, and molecular diagnostics. Further innovation and collaboration are needed to optimize LITT's role in neuro-oncology and address treatment challenges in the era of personalized medicine.

Laser Interstitial Thermal Therapy in the treatment of brain metastases and radiation necrosis.

Clinical Factors Associated with Radionecrosis Following Stereotactic Radiosurgery in the Era of Modern Systemic Therapy

Impact of Concurrent Targeted Therapy and Immunotherapy on the Incidence of Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastases

The influence of radio-immunotherapy on the tumor microenvironment of breast-to-brain metastasis and the investigation of novel adjuvant therapies

Many publications report laser-interstitial thermal therapy (LITT) as a viable alternative treatment to craniotomy for radiation necrosis (RN) and re-growing tumor occurring after stereotactic radiosurgery (SRS) for brain metastases. No studies to-date have compared the two options. The aim of this study was to retrospectively compare outcomes after LITT versus craniotomy for regrowing lesions in patients previously treated with SRS for brain metastases. Data were collected from a single-institution chart review of patients treated with LITT or craniotomy for previously irradiated brain metastasis. Of 75 patients, 42 had recurrent tumor (56%) and 33 (44%) had RN. Of patients with tumor, 26 underwent craniotomy and 16 LITT. For RN, 15 had craniotomy and 18 LITT. There was no significant difference between LITT and craniotomy in ability to taper off steroids or neurological outcomes. Progression-free survival (PFS) and overall survival (OS) were similar for LITT versus craniotomy, respectively: %PFS-survival at 1-year = 72.2% versus 61.1%, %PFS-survival at 2-years = 60.0% versus 61.1%, p = 0.72; %OS-survival at 1-year = 69.0% versus 69.3%, %OS-survival at 2-years = 56.6% versus 49.5%, p = 0.90. Craniotomy resulted in higher rates of pre-operative deficit improvement than LITT (p < 0.01). On subgroup analysis, the single factor most significantly associated with OS and PFS was pathology of the lesion. About 40% of tumor lesions needed post-operative salvage with radiation after both craniotomy and LITT. LITT was as efficacious as craniotomy in achieving local control of recurrent irradiated brain metastases and facilitating steroid taper, regardless of pathology. Craniotomy appears to be more advantageous for providing symptom relief in those with pre-operative symptoms.

A New Treatment Paradigm: Neoadjuvant Radiosurgery Before Surgical Resection of Brain Metastases With Analysis of Local Tumor Recurrence

ABSTRACTWith advances in stereotactic and neuroimaging techniques, various minimally invasive image-guided techniques have gained widespread acceptance in the field of neuro-oncology. Laser interstitial thermal therapy (LITT) is an image-guided technique that involves generation of high temperatures using a laser fiber, to ablate pathological tissue. Radiation necrosis (RN) and radiosurgery resistant brain metastasis often pose significant challenges to the treating physicians. In the last two decades, various studies have documented the efficacy of LITT in managing radiosurgery resistant metastases, radiation necrosis, surgically inaccessible malignant gliomas and ablation of epileptogenic foci. The aim of this paper is to summarize the current literature on the efficacy of LITT in patients with radiation necrosis and brain metastasis. We have also touched upon the physical properties of currently available LITT systems and the mechanism of action of laser therapy including histopathological changes.

Identification and Management of Progressive Enhancement After Radiation Therapy for Brain Metastases: Results from a Neurosurgical Survey

Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, functional performance status, age, and number of brain metastases. Patients with good prognosis may benefit from more aggressive treatment because of the potential for prolonged survival for some of them. In this review, we will comprehensively discuss the therapeutic options for treating brain metastases, which arise mostly from a lung cancer primary. In particular, we will focus on the patient selection for combined modality treatment of brain metastases, such as surgical resection or stereotactic radiosurgery (SRS) combined with whole brain irradiation; the use of radiosensitizers; and the neurocognitive deficits after whole brain irradiation with or without SRS. The benefit of prophylactic cranial irradiation (PCI) and its potentially associated neuro-toxicity for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are also discussed, along with the combined treatment of intrathoracic primary disease and solitary brain metastasis. The roles of SRS to the surgical bed, fractionated stereotactic radiotherapy, WBRT with an integrated boost to the gross brain metastases, as well as combining WBRT with epidermal growth factor receptor (EGFR) inhibitors, are explored as well.

Many publications report laser-interstitial thermal therapy (LITT) as a viable alternative treatment to craniotomy for radiation necrosis (RN) and re-growing tumor occurring after stereotactic radiosurgery (SRS) for brain metastases. No studies to-date have compared the two options. The aim of this study was to retrospectively compare outcomes after LITT versus craniotomy for regrowing lesions in patients previously treated with SRS for brain metastases. Data were collected from a single-institution chart review of patients treated with LITT or craniotomy for previously irradiated brain metastasis. Of 75 patients, 42 had recurrent tumor (56%) and 33 (44%) had RN. Of patients with tumor, 26 underwent craniotomy and 16 LITT. For RN, 15 had craniotomy and 18 LITT. There was no significant difference between LITT and craniotomy in ability to taper off steroids or neurological outcomes. Progression-free survival (PFS) and overall survival (OS) were similar for LITT versus craniotomy, respectively: %PFS-survival at 1-year = 72.2% versus 61.1%, %PFS-survival at 2-years = 60.0% versus 61.1%, p = 0.72; %OS-survival at 1-year = 69.0% versus 69.3%, %OS-survival at 2-years = 56.6% versus 49.5%, p = 0.90. This finding persisted on sub-analysis of smaller lesions under < 3cm in diameter. Craniotomy resulted in higher rates of pre-operative deficit improvement than LITT (p < 0.01). On sub-group analysis, the single factor most significantly associated with OS and PFS was pathology of the lesion. About 40% of tumor lesions needed post-operative salvage with radiation after both craniotomy and LITT. LITT was as efficacious as craniotomy in achieving local control of recurrent irradiated brain metastases and facilitating steroid taper, regardless of pathology. Craniotomy appears to be more advantageous for providing symptom relief in those with pre-operative symptoms.

Current Dosing Paradigm For Stereotactic Radiosurgery Alone Following Surgical Resection of Brain Metastases Needs To Be Optimized For Improved Local Control

INTRODUCTION: Brain metastasis (BM) affects up to one-third of adults with cancer and carries a historically bleak prognosis. Thanks to advances in stereotactic radiosurgery (SRS), patients can live longer, and fewer succumb to their intracranial disease. However, rates of in-field recurrence after SRS range from 10–25%, either as true tumor re-growth or radiation necrosis (RN). In this setting, repeat SRS is not recommended and craniotomy may not be feasible or desired by the patient. Laser interstitial thermal therapy (LITT) is an emerging option with promising outcomes. In this study, we investigated outcomes and determined the mechanisms of death among patients with BM who underwent LITT for in-field recurrence after SRS. METHODS: Single institution retrospective review of patients with BM who underwent LITT for in-field recurrence after SRS. RESULTS: Between 2010–2018, seventy (70) patients with BM underwent LITT for in-field recurrence after SRS. At the time of review, 51/70 (72.9%) patients died, 16/70 (22.9%) were alive, and the status of 3/70 (4.3%) was undetermined. Among those who died, death was neurologic in 17/51 (33.3%), non-neurologic in 21/51 (41.2%), and undetermined in 13/51 (25.5%). Median survival after LITT for patients who died from neurologic and non-neurologic causes were 8.9 and 14.3 months, respectively. Mechanisms of neurologic death included progressive intracranial metastatic disease in eight patients and progressive RN in two. Mechanisms of non-neurologic death were nearly all related to progression of primary or systemic disease. CONCLUSIONS: For patients with BM who develop in-field recurrence after SRS, LITT is a viable alternative to craniotomy and can attenuate the neurological burden of this devastating disease. Among our patient population, very few died as the result of intracranial progression. Future studies that investigate which factors predispose patients to intracranial progression despite LITT will further improve its efficacy and ultimately improve the lives of cancer patients.

Stereotactic radiosurgery (SRS) is a method of delivering conformal radiation, which allows minimal radiation damage to surrounding healthy tissues. Adjuvant radiation therapy has been shown to improve local control in a variety of intracranial neoplasms, such as brain metastases, gliomas, and benign tumors (i.e., meningioma, vestibular schwannoma, etc.). For brain metastases, adjuvant SRS specifically has demonstrated positive oncologic outcomes as well as preserving cognitive function when compared to conventional whole brain radiation therapy. However, as compared with neoadjuvant SRS, larger post-operative volumes and greater target volume uncertainty may come with an increased risk of local failure and treatment-related complications, such as radiation necrosis. In addition to its role in brain metastases, neoadjuvant SRS for high grade gliomas may enable dose escalation and increase immunogenic effects and serve a purpose in benign tumors for which one cannot achieve a gross total resection (GTR). Finally, although neoadjuvant SRS has historically been delivered with photon therapy, there are high LET radiation modalities such as carbon-ion therapy which may allow radiation damage to tissue and should be further studied if done in the neoadjuvant setting. In this review we discuss the evolving role of neoadjuvant radiosurgery in the treatment for brain metastases, gliomas, and benign etiologies. We also offer perspective on the evolving role of high LET radiation such as carbon-ion therapy. PubMed was systemically reviewed using the search terms "neoadjuvant radiosurgery", "brain metastasis", and "glioma". ' Clinicaltrials.gov ' was also reviewed to include ongoing phase III trials. This comprehensive review describes the evolving role for neoadjuvant SRS in the treatment for brain metastases, gliomas, and benign etiologies. We also discuss the potential role for high LET radiation in this setting such as carbon-ion radiotherapy. Early clinical data is very promising for neoadjuvant SRS in the setting of brain metastases. There are three ongoing phase III trials that will be more definitive in evaluating the potential benefits. While there is less data available for neoadjuvant SRS for gliomas, there remains a potential role, particularly to enable dose escalation and increase immunogenic effects.

287 Management of brain metastases