BACKGROUND: Whole-brain radiotherapy (WBRT) is a standard and effective approach for brain metastases, but it is linked to neurocognitive complications, specifically issues related to the hippocampus. Innovative strategies are being explored to enhance outcomes. However, a consensus is yet to be reached in this field. Our aim is to investigate the efficacy and safety of WBRT combined with simultaneous integrated boost (SIB), memantine, and hippocampal avoidance (HA) techniques in treatment of brain metastases.
METHODS: In this systematic review and meta-analysis, we comprehensively searched PubMed, MEDLINE, Embase, and Cochrane for studies reporting the efficacy and toxicity of WBRT-based combination therapies from inception to September 19, 2023. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic.
RESULTS: Among 2175 articles, 29 studies involving 3460 patients were included. The meta-analysis revealed that compared to WBRT alone, combination therapies significantly mitigated neurocognitive function decline (RD = -0.09, 95% CI [-0.18-0.01]; P = 0.03) and intracranial control failure (RR = 0.86, 95% CI [0.52-1.44]; P = 0.02), without increasing the risk of hippocampal recurrence or high-grade toxicities. Notably, HA-WBRT + SIB/memantine demonstrated improved neurocognitive outcomes and survival benefits.
CONCLUSIONS: WBRT-based combination therapies demonstrate improved efficacy and comparable safety to WBRT alone, with specific emphasis on the effectiveness of HA-WBRT + Memantine and HA-WBRT + SIB in optimizing therapeutic outcomes for brain metastases.

In patients requiring prophylactic cranial irradiation (PCI) or whole-brain radiotherapy (WBRT) for brain metastases (BMs), hippocampal avoidance (HA) has been shown to preserve neurocognitive function and quality of life. Here, we aim to estimate the incidence of hippocampal and perihippocampal BMs and the subsequent risk of local undertreatment in patients undergoing hippocampal sparing radiotherapy.
MEDLINE, Embase, and Scopus were searched with the terms \"Hippocampus\", \"Brain Neoplasms\", and related terms. Trials reporting on the incidence of hippocampal and/or perihippocampal BMs or hippocampal failure rate after PCI or WBRT were included.
Forty records were included, encompassing a total of 5,374 patients with over 32,570 BMs. Most trials employed a 5 mm margin to define the HA zone. In trials reporting on BM incidence, 4.4 % (range 0 - 27 %) and 9.2 % (3 - 41 %) of patients had hippocampal and perihippocampal BMs, respectively. The most common risk factor for hippocampal BMs was the total number of BMs. The reported failure rate within the HA zone after HA-PCI or HA-WBRT was 4.5 % (0 - 13 %), salvageable with radiosurgery in most cases. SCLC histology was not associated with a higher risk of hippocampal failure (OR = 2.49; p = 0.23). In trials comparing with a conventional (non-HA) PCI or WBRT group, HA did not increase the hippocampal failure rate (OR = 1.90; p = 0.17).
The overall incidence of hippocampal and perihippocampal BMs is considerably low, with a subsequent low risk of local undertreatment following HA-PCI or HA-WBRT. In patients without involvement, the hippocampus should be spared to preserve neurocognitive function and quality of life.

UNASSIGNED: The standard of care in patients with solitary brain metastasis involves surgical resection and postoperative whole-brain radiotherapy (WBRT). However, WBRT is associated with adverse effects, mainly neurocognitive deterioration. Stereotactic radiosurgery (SRS) is a more targeted form of radiation therapy that could be as effective as WBRT without the detrimental neurocognitive decline.
UNASSIGNED: We performed the first systematic review and meta-analysis comparing postoperative SRS versus postoperative WBRT in patients with one resected brain metastasis. PubMed, Scopus, and Cochrane library were systematically searched for studies comparing the efficacy of the two radiation modalities in terms of local and distant brain control, leptomeningeal disease control, and overall survival. Additionally, we extracted patients\' neurocognitive function and quality of life after each postoperative radiation form.
UNASSIGNED: Four studies with 248 patients (128: WBRT, 120: SRS) were included in our analysis. There was no difference between SRS and WBRT in the risk of local recurrence (RR = 0.92, CI = 0.51-1.66, p = 0.78, I2 = 0%) and leptomeningeal disease (RR = 1.21, CI = 0.49-2.98, p = 0.67, I2 = 18%), neither in the patients\' overall survival (HR = 1.06, CI = 0.61-1.85, p = 0.83, I2 = 63%). Nevertheless, SRS appeared to increase the risk of distant brain failure (RR = 2.03, CI = 0.94-4.40, p = 0.07, I2 = 61%). Neurocognitive function and quality of life in the SRS group were equal or superior to the WBRT group.
UNASSIGNED: Although SRS may increase the risk of distant brain failure, it appears to be as effective as WBRT in terms of local control, risk of leptomeningeal disease, and overall survival while sparing the patients of the detrimental, WBRT-associated cognitive deterioration.

OBJECTIVE: This review will focus on the late neurological complications from cranial irradiation and relevant mitigation strategies.
BACKGROUND: Radiotherapy (RT) remains an important pillar in the management of brain metastases. Patients being treated in the modern era do experience longer survival, because of superior intra- and extra-cranial disease control. As a result, they can be more prone to developing and manifesting late complications post-brain radiotherapy.
METHODS: A search and narrative review of prospective clinical trials relating to neurological toxicity outcomes was conducted.
CONCLUSIONS: Neurological toxicities can be challenging to diagnose and manage and should be considered during consideration of radiotherapy in brain metastasis, hence more emphasis should be placed on prevention and upfront mitigation of these complications, with novel strategies showing promising results in prospective trials being adopted into clinical practice.

OBJECTIVE: The reviewed literature supports a treatment regimen for primary central nervous system lymphoma (PCNSL) that includes induction chemotherapy, followed by one consolidation therapy. High-dose chemotherapy supported by autologous stem-cell transplantation (ASCT) is the most studied option, but its effects are controversial. The aim of this study was to evaluate the efficacy and safety of ASCT for newly diagnosed PCNSL by means of a meta-analysis.
METHODS: The PubMed, Embase, and Cochrane Library databases were systematically searched for studies published until May 20, 2021. Included studies were prospective studies of patients with newly diagnosed PCNSL treated with ASCT. The pooled rates and 95% confidence intervals (CIs) were determined for all outcomes. Subgroup analysis was conducted to compare the relative risk (RR) with 95% CIs for the complete remission (CR) rate and the hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS).
RESULTS: Thirteen prospective studies including 348 patients were analyzed. The pooled CR rate, overall response rate, and relapse rate were 80% (95% CI, 71-88%, I2 = 67.06%, p = 0.00), 95% (95% CI, 87-100%, I2 = 73.65%, p= 0.00), and 19% (95% CI, 15-24%, I2 = 76.18%, p = 0.00), respectively. The pooled 2- and 5-year PFS and OS rates were 74% (95% CI, 68-80%, I2 = 3.90%), 65% (95% CI, 51-77%, I2 = 74.61%), 80% (95% CI, 72-88%, I2 = 57.54%), and 69% (95% CI, 53-83%, I2 = 83.89%), respectively. Hematological toxicity and infections were more common adverse events above grade 3. The pooled treatment-related mortality was 3% (95% CI, 1-6%, I2 = 28.18%, p = 0.16). In the group analysis of ASCT compared with whole-brain radiotherapy, there were no significant differences in the CR rate (RR, 1.00, 95% CI, 0.88-1.14, p = 0.971), relapse rate (RR, 0.44, 95% CI, 0.06-3.10, p = 0.408), PFS (HR, 1.28, 95% CI, 0.81-2.01, p = 0.29), or OS (HR, 1.62, 95% CI, 0.97-2.69, p = 0.06). Cognitive functions were preserved or improved after ASCT.
CONCLUSIONS: ASCT is a feasible approach for consolidation with good tolerability for newly diagnosed PCNSL patients. High-quality randomized controlled trials are still needed to confirm the effects of ASCT.
BACKGROUND: https://www.crd.york.ac.uk/prospero/, identifier CRD42021268422.

The modern treatment of patients with primary central nervous system lymphoma (PCNSL) consists of two phases: induction, currently represented by a high-dose-methotrexate-based polychemotherapy, and consolidation. The optimal consolidation therapy has not been defined yet, but several strategies, such as whole-brain radiotherapy (WBRT), high-dose chemotherapy supported by autologous stem cell transplantation (HDC/ASCT) or nonmyeloablative chemotherapy, have been addressed in important randomized trials.
This review provides an overview of the current role of consolidation strategies in young and fit patients with newly diagnosed PCNSL. Publications in English language, peer-reviewed, from high-quality international journals, edited from 2003 to 2021 were identified on PubMed.
Consolidation treatment significantly improved outcomes of PCNSL. Radiotherapy had represented for years the only choice in the consolidation therapy, but large randomized trials have demonstrated that HDC/ASCT is equally effective and associated with lower neurotoxicity risk in patients younger than 65-70 years. Encouraging results have been obtained using reduced-dose WBRT, while a recent randomized trial failed to demonstrate that consolidation with nonmyeloablative chemotherapy is more effective than HDC/ASCT in PCNSL patients. A personalized consolidation treatment, driven also by a response prediction model based on radiological and molecular details, may improve the management of PCNSL patients.

AIDS-related primary central nervous system lymphoma (AR-PCNSL) is an AIDS-defining disease that usually occurs when the CD4 count is less than 50 cells/μl. The frequency of the disease has substantially decreased in the era of highly active antiretroviral therapy (HAART). Prognosis is poor with rapid progression leading to death within 2-3 months if left untreated.
A 65 years old male presented to medical attention with gait disturbance, weight loss and slight left-sided hemiparesis. Human immunodeficiency virus infection was diagnosed with an initial CD4 count of 116 cells/µl and a viral load of 260,000 copies/ml. Magnetic resonance imaging of the brain revealed three brain lesions involving the right frontal lobe and the left parietal lobe, which on biopsy led to a diagnosis of AR-PCNSL. HAART was initiated with whole-brain radiotherapy (WBRT), and the patient declined systemic chemotherapy. Due to poor performance status, he was transferred to palliative care. Under HAART, he slowly recovered with normalization of CD4 count and undetectable viral load. Medical imaging showed complete remission (CR) of the brain lesions. At 3-year follow-up, the patient remains in CR, but presented mild neurocognitive dysfunction possibly secondary to WBRT.
Nowadays, treatment paradigm parallels that of primary central nervous system lymphoma in the immunocompetent population based on systemic chemotherapy (primarily high-dose intravenous methotrexate and steroids) in association with HAART. The role of WBRT is questionable because of late neurotoxic effects.

Background & Objectives: Radiotherapy is standard treatment for patients with brain metastases (BMs), although it may lead to radiation-induced cognitive impairment. This review explores the impact of whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) on cognition.
METHODS: The PRISMA guidelines were used to identify articles on PubMed and EmBase reporting on objective assessment of cognition before, and at least once after radiotherapy, in adult patients with nonresected BMs.
RESULTS: Of the 867 records screened, twenty articles (14 unique studies) were included. WBRT lead to decline in cognitive performance, which stabilized or returned to baseline in patients with survival of at least 9-15 months. For SRS, a decline in cognitive performance was sometimes observed shortly after treatment, but the majority of patients returned to or remained at baseline until a year after treatment.
CONCLUSIONS: These findings suggest that after WBRT, patients can experience deterioration over a longer period of time. The cognitive side effects of SRS are transient. Therefore, this review advices to choose SRS as this will result in lowest risks for cognitive adverse side effects, irrespective of predicted survival. In an already cognitively vulnerable patient population with limited survival, this information can be used in communicating risks and aid in making educated decisions.

UNASSIGNED: Whole-brain radiation therapy (WBRT) is an effective therapeutic modality in patients with brain metastases. However, nearly 90% of patients undergoing WBRT suffer from a neurocognitive function (NCF) impairment at diagnosis, and up to two-thirds will experience a further decline within 2-6 months after WBRT. Focal-dose reduction on bilateral hippocampus is thought to improve NCF preservation. The aim was to present a systematic review of clinical results on NCF after hippocampal-sparing (HS) WBRT.
UNASSIGNED: A systematic review of published literature was performed on PubMed and the Cochrane Library. Only prospective clinical trials reporting NCF outcome in patients treated with HS-WBRT have been analyzed.
UNASSIGNED: A total of 165 patients from three studies were included. These studies are characterized by small sample size and different methods in terms of WBRT technique but with similar planning analysis and NCF assessment tests. No significant changes in NCF (i.e., verbal and nonverbal learning memory, executive functions, and psychomotor speed) between baseline and 4-month follow-up after RT and only a mean relative decline in delayed recall at 4 months (7% compared to 30% of historical control) were observed.
UNASSIGNED: Considering preliminary results on NCF preservation, further studies seem justified in patients undergoing brain irradiation for brain metastases or referred for prophylactic cranial irradiation to evaluate long-term effects on NCF and quality of life.

Brain metastases from endometrial adenocarcinoma are quite rare. Here, we report a case of a 64-year-old woman who presented with a history of left limb weakness of 45 days\' duration. Her medical history was significant for the endometrial carcinoma diagnosed 13 years earlier, for which she had undergone a total hysterectomy. The patient received a craniotomy and was finally diagnosed with brain metastasis from endometrial adenocarcinoma. We performed a MEDLINE search of the pertinent literature, searching for information focusing on the diagnosis, mechanism, treatment, and prognosis of this rare tumor type.