Stereotactic radiosurgery with immune checkpoint inhibitors for brain metastases: a meta-analysis study

Badrigilan, Samireh; Meola, Antonio; Chang, Steven D.; Rezaeian, Shahab; Nemati, Hossein; Almasi, Tinoosh; Rostampour, Nima

doi:10.1080/02688697.2021.2022098

Cited by 8 publications

(5 citation statements)

References 73 publications

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“…However, a faster onset of radionecrosis (1–2 months vs 9–18 months) was reported in one study 9. Importantly, differences in overall survival and follow-up time among patients treated with immunotherapy may obscure results as radionecrosis typically develops after 1-year post-treatment 8 29 31 32. While available data overall suggests a low-risk of radionecrosis with combination therapy, there are ongoing prospective trials (NCT02696993 and NCT02858869) for NSCLC patients that may offer more clarity as to its safety profile.…”

Section: Discussionmentioning

confidence: 96%

“…Meta-analyses evaluating combination SRS and immunotherapy with either melanoma, NSCLC and renal cell carcinoma histologies have failed to identify that immunotherapy is associated with a significantly higher risk of radionecrosis than SRS alone 27 29 30. However, a faster onset of radionecrosis (1–2 months vs 9–18 months) was reported in one study 9.…”

Section: Discussionmentioning

confidence: 99%

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Whole brain radiation therapy resulting in radionecrosis: a possible link with radiosensitising chemoimmunotherapy

Ngu,

Werner,

D' Amico

et al. 2023

BMJ Case Rep

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Radionecrosis describes a rare but serious complication of radiation therapy. In clinical practice, stereotactic radiosurgery (SRS) is increasingly used in combination with systemic therapy, including chemotherapy, immune checkpoint inhibitor and targeted therapy, either concurrently or sequentially. There is a paucity of literature regarding radionecrosis in patients receiving whole brain radiation therapy (WBRT) alone (without additional SRS) in combination with immunotherapy or targeted therapies. It is observed that certain combinations increase the overall radiosensitivity of the tumorous lesions. We present a rare case of symptomatic radionecrosis almost 1 year after WBRT in a patient with non-squamous non-small cell lung cancer on third-line chemoimmunotherapy. We discuss available research regarding factors that may lead to radionecrosis in these patients, including molecular and genetic profiles, specific drug therapy combinations and their timing or increased overall survival.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Whole brain radiation therapy resulting in radionecrosis: a possible link with radiosensitising chemoimmunotherapy

Ngu,

Werner,

D' Amico

et al. 2023

BMJ Case Rep

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“…While TKI represents the current elective treatment choice for driver mutations [28,29], these mutations usually correlate with a higher incidence of brain metastases, reaching up to 20-30% of some patient populations, particularly those with ALK translocation [30]. Several studies have investigated the efficacy and timing of local intracranial treatments in this setting, but no consensus has yet been reached [31,32]. Although TKIs are active in the central nervous system, providing patients up to 10 months PFS without irradiation [33,34], it is speculated that this approach could allow for local treatment deferral.…”

Section: Discussionmentioning

confidence: 99%

Upfront Advanced Radiotherapy and New Drugs for NSCLC Patients with Synchronous Brain Metastases: Is the Juice Worth the Squeeze? A Real-World Analysis from Lombardy, Italy

Corrao

Franchi

Zaffaroni

et al. 2023

Cancers

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Aim: Healthcare administrative databases represent a valuable source for real-life data analysis. The primary aim of this study is to compare effectiveness and cost profile in non-small-cell lung cancer (NSCLC) patients harboring synchronous brain metastases (BMs) who received non-chemo first-line systemic therapy with or without advanced radiotherapy (aRT). Methods: Diagnostic ICD-9-CM codes were used for identifying all patients with a new diagnosis of lung cancer between 2012 and 2019. Among these, patients who had started a first-line systemic treatment with either TKIs or pembrolizumab, alone or in combination with intensity-modulated or stereotactic RT, were selected. Clinical outcomes investigated included overall survival (OS), progression-free survival (PFS), and time-to-treatment failure (TTF). The cost outcome was defined as the average per capita cumulative healthcare direct costs of the treatment, including all inpatient and outpatient costs. Results: The final cohort included 177 patients, of whom 58 were treated with systemic treatment plus aRT (STRT) and 119 with systemic treatment alone. The addition of aRT to systemic treatment was associated with a significantly better OS (p = 0.020) and PFS (p = 0.041) than systemic therapy alone. The ICER (incremental cost-effectiveness ratio) value indicated an average cost of €3792 for each month of survival after STRT treatment and confirmed clinical effectiveness but higher healthcare costs. Conclusions: This real-world study suggests that upfront aRT for NCLSC patients with synchronous BMs represents a valid treatment strategy, boosting the efficacy of novel and emerging drug classes with sustainable costs for the health service. Translational relevance: The present real-world study reports that the use of upfront advanced radiotherapyaRT and new-generation systemic agents, such as TKIs and pembrolizumab, may have higher oncological control and an improved cost-effectiveness profile than the use of new-generation systemic agents alone in NCLSC patients with synchronous brain metastases. Acquired evidence can also be used to inform policymakers that adding advanced radiotherapy results is a sustainable cost for the health service. Since approximately 50% of patients do not meet RCT inclusion criteria, a significant proportion of them is receiving treatment that is not evidence-informed; therefore, these results warrant further studies to identify the best radiotherapy timing and possible dose escalation approaches to improving treatment efficacy in patient subgroups not typically represented in randomized controlled trials.

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“…In recent years, the association of SRS and immunotherapy for the treatment of BMs was tested in several retrospective series. Three meta-analyses showed better LC and OS when the two treatment modalities are concurrently administered (1 y LC: 73.2–89.2%; 1 y OS: 64.6–68%) versus a sequential approach (1 y LC: 67.8–69.5%; 1 y OS: 42.7–58%) [ 149 , 150 , 151 ]. In addition to the increased LC, the synergy between RT and ICIs also seemed to improve distant intracranial control, reducing the risk of developing new brain lesions [ 152 ].…”

Section: Srs and Systemic Therapy (St)mentioning

confidence: 99%

Modern Stereotactic Radiotherapy for Brain Metastases from Lung Cancer: Current Trends and Future Perspectives Based on Integrated Translational Approaches

Levis,

Gastino,

De Giorgi

et al. 2023

Cancers

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Brain metastases (BMs) represent the most frequent metastatic event in the course of lung cancer patients, occurring in approximately 50% of patients with non-small-cell lung cancer (NSCLC) and in up to 70% in patients with small-cell lung cancer (SCLC). Thus far, many advances have been made in the diagnostic and therapeutic procedures, allowing improvements in the prognosis of these patients. The modern approach relies on the integration of several factors, such as accurate histological and molecular profiling, comprehensive assessment of clinical parameters and precise definition of the extent of intracranial and extracranial disease involvement. The combination of these factors is pivotal to guide the multidisciplinary discussion and to offer the most appropriate treatment to these patients based on a personalized approach. Focal radiotherapy (RT), in all its modalities (radiosurgery (SRS), fractionated stereotactic radiotherapy (SRT), adjuvant stereotactic radiotherapy (aSRT)), is the cornerstone of BM management, either alone or in combination with surgery and systemic therapies. We review the modern therapeutic strategies available to treat lung cancer patients with brain involvement. This includes an accurate review of the different technical solutions which can be exploited to provide a “state-of-art” focal RT and also a detailed description of the systemic agents available as effective alternatives to SRS/SRT when a targetable molecular driver is present. In addition to the validated treatment options, we also discuss the future perspective for focal RT, based on emerging clinical reports (e.g., SRS for patients with many BMs from NSCLC or SRS for BMs from SCLC), together with a presentation of innovative and promising findings in translational research and the combination of novel targeted agents with SRS/SRT.

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Stereotactic radiosurgery with immune checkpoint inhibitors for brain metastases: a meta-analysis study

Cited by 8 publications

References 73 publications

Whole brain radiation therapy resulting in radionecrosis: a possible link with radiosensitising chemoimmunotherapy

Whole brain radiation therapy resulting in radionecrosis: a possible link with radiosensitising chemoimmunotherapy

Upfront Advanced Radiotherapy and New Drugs for NSCLC Patients with Synchronous Brain Metastases: Is the Juice Worth the Squeeze? A Real-World Analysis from Lombardy, Italy

Modern Stereotactic Radiotherapy for Brain Metastases from Lung Cancer: Current Trends and Future Perspectives Based on Integrated Translational Approaches

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