Extent of Resection Thresholds in Molecular Subgroups of Newly Diagnosed Isocitrate Dehydrogenase-Wildtype Glioblastoma.

BACKGROUND AND OBJECTIVES: Maximizing the extent of resection (EOR) improves outcomes in glioblastoma (GBM). However, previous GBM studies have not addressed the EOR impact in molecular subgroups beyond IDH1/IDH2 status. In the current article, we evaluate whether EOR confers a benefit in all GBM subtypes or only in particular molecular subgroups. METHODS: A retrospective cohort of newly diagnosed GBM isocitrate dehydrogenase (IDH)-wildtype undergoing resection were prospectively included in a database (n = 138). EOR and residual tumor volume (RTV) were quantified with semiautomated software. Formalin-fixed paraffin-embedded tumor tissues were analyzed by targeted next-generation sequencing. The association between recurrent genomic alterations and EOR/RTV was evaluated using a recursive partitioning analysis to identify thresholds of EOR or RTV that may predict survival. The Kaplan-Meier methods and multivariable Cox proportional hazards regression methods were applied for survival analysis. RESULTS: Patients with EOR ≥88% experienced 44% prolonged overall survival (OS) in multivariable analysis (hazard ratio: 0.56, P = .030). Patients with alterations in the TP53 pathway and EOR <89% showed reduced OS compared to TP53 pathway altered patients with EOR>89% (10.5 vs 18.8 months; HR: 2.78, P = .013); however, EOR/RTV was not associated with OS in patients without alterations in the TP53 pathway. Meanwhile, in all patients with EOR <88%, PTEN-altered had significantly worse OS than PTEN-wildtype (9.5 vs 15.4 months; HR: 4.53, P < .001). CONCLUSION: Our results suggest that a subset of molecularly defined GBM IDH-wildtype may benefit more from aggressive resections. Re-resections to optimize EOR might be beneficial in a subset of molecularly defined GBMs. Molecular alterations should be taken into consideration for surgical treatment decisions in GBM IDH-wildtype.

The detrimental effect of biopsy preceding resection in surgically accessible glioblastoma: results from the national cancer database.

PURPOSE: Aggressive resection in surgically-accessible glioblastoma (GBM) correlates with improved survival over less extensive resections. However, the clinical impact of performing a biopsy before definitive resection have not been previously evaluated. METHODS: We analyzed 17,334 GBM patients from the NCDB from 2010-2014. We categorized them into: "upfront resection" and "biopsy followed by resection". The outcomes of interes included OS, 30-day readmission/mortality, 90-day mortality, and length of hospital stay (LOS). The Kaplan-Meier methods and accelerated failure time (AFT) models were applied for survival analysis. Multivariable binary logistic regression were performed to compare differences among groups. Multiple imputation and propensity score matching (PSM) were conducted for validation. RESULTS: "Upfront resection" had superior OS over "biopsy followed by resection" (median OS:12.4 versus 11.1 months, log-rank p = 0.001). Similarly, multivariable AFT models favored "upfront resection" (time ratio[TR]:0.83, 95%CI: 0.75-0.93, p = 0.001). Patients undergoing "upfront gross-total resection (GTR)" had higher OS over "upfront subtotal resection (STR)", "GTR following STR", and "GTR or STR following initial biopsy" (14.4 vs. 10.3, 13.5, 13.3, and 9.1 months;TR: 1.00 [Ref.], 0.75, 0.82, 0.88, and 0.67). Recent years of diagnosis, higher income, facilities located in Southern regions, and treatment at academic facilities were significantly associated with the higher likelihood of undergoing upfront resection. Multivariable regression showed a decreased 30 and 90-day mortality for patients undergoing "upfront resection", 73% and 44%, respectively (p < 0.001). CONCLUSIONS: Pre-operative biopsies for surgically accessible GBM are associated with worse survival despite subsequent resection compared to patients undergoing upfront resection.

Intraoperative ultrasound for surgical resection of high-grade glioma and glioblastoma: a meta-analysis of 732 patients.

PURPOSE: Here, we conducted a meta-analysis to explore the use of intraoperative ultrasound (iUS)-guided resection in patients diagnosed with high-grade glioma (HGG) or glioblastoma (GBM). Our aim was to determine whether iUS improves clinical outcomes compared to conventional neuronavigation (CNN). METHODS: Databases were searched until April 21, 2023 for randomized controlled trials (RCTs) and observational cohort studies that compared surgical outcomes for patients with HGG or GBM with the use of either iUS in addition to standard approach or CNN. The primary outcome was overall survival (OS). Secondary outcomes include volumetric extent of resection (EOR), gross total resection (GTR), and progression-free survival (PFS). Outcomes were analyzed by determining pooled relative risk ratios (RR), mean difference (MD), and standardized mean difference (SMD) using random-effects model. RESULTS: Of the initial 867 articles, only 7 articles specifically met the inclusion criteria (1 RCT and 6 retrospective cohorts). The analysis included 732 patients. Compared to CNN, the use of iUS was associated with higher OS (SMD = 0.26,95%CI=[0.12,0.39]) and GTR (RR = 2.02; 95% CI=[1.31,3.1]) for both HGG and GBM. There was no significant difference in PFS or EOR. CONCLUSION: The use of iUS in surgical resections for HGG and GBM can improve OS and GTR compared to CNN, but it did not affect PFS. These results suggest that iUS reduces mortality associated with HGG and GBM but not the risk of recurrence. These results can provide valuable cost-effective interventions for neurosurgeons in HGG and GBM surgery.

Imaging predictors of 4q12 amplified and RB1 mutated glioblastoma IDH-wildtype.

INTRODUCTION: Recent studies have identified that glioblastoma IDH-wildtype consists of different molecular subgroups with distinct prognoses. In order to accurately describe and classify gliomas, the Visually AcceSAble Rembrandt Images (VASARI) system was developed. The goal of this study was to evaluate the VASARI characteristics in molecular subgroups of IDH-wildtype glioblastoma. METHODS: A retrospective analysis of glioblastoma IDH- wildtype with comprehensive next-generation sequencing and pre-operative and post-operative MRI was performed. VASARI characteristics and 205 genes were evaluated. Multiple comparison adjustment by the Bejamin-Hochberg false discovery rate (BH-FDR) was performed. A 1:3 propensity score match (PSM) with a Caliper of 0.2 was done. RESULTS: 178 patients with GBM IDH-WT met the inclusion criteria. 4q12 amplified patients (n = 20) were associated with cyst presence (30% vs. 12%, p = 0.042), decreased hemorrhage (35% vs. 62%, p = 0.028), and non-restricting/mixed (35%/60%) rather than restricting diffusion pattern (5%), meanwhile, 4q12 non-amplified patients had mostly restricting (47.4%) rather than a non-restricting/mixed diffusion pattern (28.4%/23.4%). This remained statistically significant after BH-FDR adjustment (p = 0.002). PSM by 4q12 amplification showed that diffusion characteristics continued to be significantly different. Among RB1-mutant patients, 96% had well-defined enhancing margins vs. 70.6% of RB1-WT (p = 0.018), however, this was not significant after BH-FDR or PSM. CONCLUSIONS: Patients with glioblastoma IDH-wildtype harboring 4q12 amplification rarely have restricting DWI patterns compared to their wildtype counterparts, in which this DWI pattern is present in ~ 50% of patients. This suggests that some phenotypic imaging characteristics can be identified among molecular subtypes of IDH-wildtype glioblastoma.

The value of additional electrodes when stereo-electroencephalography is inconclusive.

OBJECTIVE: Stereo-electroencephalography (SEEG) is the preferred method for intracranial localization of the seizure-onset zone (SOZ) in drug-resistant focal epilepsy. Occasionally SEEG evaluation fails to confirm the pre-implantation hypothesis. This leads to a decision tree regarding whether the addition of SEEG electrodes (two-step SEEG - 2sSEEG) or placement of subdural electrodes (SDEs) after SEEG (SEEG2SDE) would help. There is a dearth of literature encompassing this scenario, and here we aimed to characterize outcomes following unplanned two-step intracranial EEG (iEEG). METHODS: All 225 adult SEEG cases over 8 years at our institution were reviewed to extract patient data and outcomes following a two-step evaluation. Three raters independently quantified benefits of additional intracranial electrodes. The relationship between two-step iEEG benefit and clinical outcome was then analyzed. RESULTS: Fourteen patients underwent 2sSEEG and nine underwent SEEG2SDE. In the former cohort, the second SEEG procedure was performed for these reasons-precise localization of the SOZ (36%); defining margins of eloquent cortex (21%); and broadening coverage in the setting of non-localizable seizure onsets (43% of cases). Sixty-four percent of 2sSEEG cases were consistently deemed beneficial (Light's κ = 0.80). 2sSEEG performed for the first two indications was much more beneficial than when onsets were not localizable (100% vs 17%, p = .02). In the SEEG2SDE cohort, SDEs identified the SOZ and enabled delineation of margins relative to eloquent cortex in all cases. SIGNIFICANCE: The two-step iEEG is useful if the initial evaluation is broadly concordant with the original electroclinical hypothesis, where it can clarify onset zones or delineate safe surgical margins; however, it provides minimal benefit when the implantation hypothesis is erroneous, and we recommend that 2sSEEG not be generally utilized in such cases. SDE implantation after SEEG minimizes the need for SDEs and is helpful in delineating surgical boundaries relative to ictal-onset zones and eloquent cortex.

Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (low-grade appearance): a report of the RANO resect group.

BACKGROUND: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement. METHODS: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement. RESULTS: Among 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller postoperative tumor volumes were associated with more favorable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had a more favorable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables. CONCLUSIONS: The absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favorable outcome.

Prognostic evaluation of re-resection for recurrent glioblastoma using the novel RANO classification for extent of resection: A report of the RANO resect group.

BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome. METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to minimize confounding effects when comparing the different RANO classes. RESULTS: We studied 681 patients with first recurrence of Isocitrate Dehydrogenase (IDH) wild-type glioblastomas, including 310 patients who underwent re-resection. Re-resection was associated with prolonged survival even when stratifying for molecular and clinical confounders on multivariate analysis; ≤1 cm3 residual CE tumor was associated with longer survival than non-surgical management. Accordingly, "maximal resection" (class 2) had superior survival compared to "submaximal resection" (class 3). Administration of (radio-)chemotherapy in the absence of postoperative deficits augmented the survival associations of smaller residual CE tumors. Conversely, "supramaximal resection" of non-CE tumor (class 1) was not associated with prolonged survival but was frequently accompanied by postoperative deficits. The prognostic role of residual CE tumor was confirmed in propensity score analyses. CONCLUSIONS: The RANO resect classification serves to stratify patients with re-resection of glioblastoma. Complete resection according to RANO resect classes 1 and 2 is prognostic.

Critical role of the ventral temporal lobe in naming.

OBJECTIVE: Lexical retrieval deficits are characteristic of a variety of different neurological disorders. However, the exact substrates responsible for this are not known. We studied a large cohort of patients undergoing surgery in the dominant temporal lobe for medically intractable epilepsy (n = 95) to localize brain regions that were associated with anomia. METHODS: We performed a multivariate voxel-based lesion-symptom mapping analysis to correlate surgical lesions within the temporal lobe with changes in naming ability. Additionally, we used a surface-based mixed-effects multilevel analysis to estimate group-level broadband gamma activity during naming across a subset of patients with electrocorticographic recordings and integrated these results with lesion-deficit findings. RESULTS: We observed that ventral temporal regions, centered around the middle fusiform gyrus, were significantly associated with a decline in naming. Furthermore, we found that the ventral aspect of temporal lobectomies was linearly correlated to a decline in naming, with a clinically significant decline occurring once the resection extended 6 cm from the anterior tip of the temporal lobe on the ventral surface. On electrocorticography, the majority of these cortical regions were functionally active following visual processing. These loci coincide with the sites of susceptibility artifacts during echoplanar imaging, which may explain why this region has been previously underappreciated as the locus responsible for postoperative naming deficits. SIGNIFICANCE: Taken together, these data highlight the crucial contribution of the ventral temporal cortex in naming and its important role in the pathophysiology of anomia following temporal lobe resections. As such, surgical strategies should attempt to preserve this region to mitigate postoperative language deficits.

Safety and efficacy of bihemispheric sampling via transmidline stereoelectroencephalography.

OBJECTIVE: Stereoelectroencephalography (SEEG) is designed to target distributed cortical networks responsible for electroclinical seizure syndrome and to enable localization of the site of seizure onset in patients with intractable epilepsy. When the preimplantation hypothesis invokes the bilateral mesial frontal lobes, sampling of several deep-seated cortical sites in both hemispheres is required. In this study, the authors have demonstrated the feasibility of sampling bihemispheric areas with intentional implantation of an SEEG electrode crossing the midline (SECM) for sampling the cortex on both sides of the interhemispheric fissure. METHODS: An analysis of 231 consecutive SEEG procedures over 8 years was used to identify instances of bihemispheric sampling by using the transmidline SEEG technique. RESULTS: The authors identified 53 SEEG cases, with a total of 126 electrodes that crossed the interhemispheric fissure; all were in the frontal lobes. Eighty-three electrodes targeted the cingulate gyrus (18 rostral, 43 anterior, and 22 middle), 31 targeted the posterior orbitofrontal region, 8 sampled the medial prefrontal cortex, and 4 targeted nodular heterotopia around the frontal horns. The ictal onset zone was localized to the frontal lobe in 16 cases. SECM isolated interictal and ictal activity in the contralateral hemisphere in 6 cases and independent bihemispheric seizure activity in 2 cases. No hemorrhagic or infectious complications were noted in any of these cases. CONCLUSIONS: Based on this extensive experience of bihemispheric sampling, the authors concluded that this technique is safe and effective. In this series, SECM showed contralateral interictal and/or ictal epileptiform activity in 8 (15%) cases, and 9 (16%) cases (with unilateral implantation) had sufficient data to discard contralateral involvement, contributing to support of the epileptogenic network. SECM may reduce the number of electrodes used to sample bilateral mesial frontal or orbitofrontal cortices, and such an approach may lower the risk of hemorrhage and costs.

Structure activity relationship (SAR) and anticancer activity of pyrrolidine derivatives: Recent developments and future prospects (A review).

Pyrrolidine molecules are a significant class of synthetic and natural plant metabolites, which show the diversity of pharmacological activities. An extensive variety of synthetic pyrrolidine compounds with numerous derivatization like spirooxindole, thiazole, metal complexes, coumarin, etc have revealed significant anticancer activity. Pyrrolidine molecules are found not only as potential anticancer candidates but also retain the lowest side effects. Depending upon the diverse substitution patterns of the derivatives, these molecules have demonstrated an incredible ability to regulate the various targets to give excellent anti-proliferative activities. Taking these into consideration, efforts have been taken by the scientific fraternity to design and develop a potent anticancer scaffold with negligible side effects. In the present review, we cover the latest advancements in the synthesis of pyrrolidine molecules which have promising anticancer activity toward numerous cancer cell lines. Additionally, it also highlights the effectiveness of derivatives via elucidation of Structural-Activity-Relationship (SAR) which is discussed in detail.

Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group.

BACKGROUND: Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (1) explore the prognostic utility of the classification system and (2) define how much removed non-CE tumor translates into a survival benefit. METHODS: The international RANO resect group retrospectively searched previously compiled databases from 7 neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and postoperative MRI were collected. RESULTS: We collected 1,008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC-26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm3) were favorably associated with outcome: patients with "maximal CE resection" (class 2) had superior outcome compared to patients with "submaximal CE resection" (class 3) or "biopsy" (class 4). Extensive resection of non-CE tumor (≤5 cm3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 ("supramaximal CE resection"). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers. CONCLUSIONS: The proposed "RANO categories for extent of resection in glioblastoma" are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such "supramaximal CE resection."

Recent developments in silver nanoparticles utilized for cancer treatment and diagnosis: a patent review.

Nanotheranostics is a young but rapidly expanding science that incorporates elements of therapy and diagnostics in a unique and miniscule area of research. The potential to combine diagnostic and therapeutic abilities inside a complete unit opens up interesting possibilities for innovative biomedical research. Silver-based nanoparticles, for instance, are widely utilized as pharmacological and biomedical imaging molecules, and hence offer a lot of potential for the development of versatile targeted therapy compositions. These nanoparticles have been used for cancer diagnosis and cancer treatments recently. We evaluate major innovations based on silver nanotheranostics technologies in this review paper, with an emphasis on cancer treatment implications. The present review covers papers, from 2010 to 2020.

BRAF/MEK Dual Inhibitors Therapy in Progressive and Anaplastic Pleomorphic Xanthoastrocytoma: Case Series and Literature Review.

Recurrent and anaplastic pleomorphic xanthoastrocytoma (r&aPXA) is a rare primary brain tumor that is challenging to treat. Two-thirds of PXA tumors harbor a BRAF gene mutation. BRAF inhibitors have been shown to improve tumor control. However, resistance to BRAF inhibition develops in most cases. Concurrent therapy with MEK inhibitors may improve tumor control and patient survival. In this study, we identified 5 patients diagnosed with BRAF-mutated PXA who received BRAF and MEK inhibitors over a 10-year interval at our institution. Patient records were evaluated, including treatments, adverse effects (AEs), outcomes, pathology, next-generation sequencing, and MRI. The median age was 22 years (range, 14-66 years), 60% male, and 60% anaplastic PXA. Median overall survival was 72 months (range, 19-112 months); 1 patient died of tumor-related hemorrhage while off therapy, and the other 4 experienced long-term disease control (21, 72, 98, and 112 months, respectively). Dual BRAF/MEK inhibitors were well tolerated, with only grade 1-2 AEs, including rash, neutropenia, fatigue, abdominal discomfort, and diarrhea. No grade 3-5 AEs were detected. A literature review was also performed of patients diagnosed with BRAF-mutated PXA and treated with BRAF and/or MEK inhibitors through August 2021, with a total of 32 cases identified. The median age was 29 years (range, 8-57 years) and the median PFS and OS were 8.5 months (range, 2-35 months) and 35 months (range, 10-80 months), respectively. The most common AEs were grade 1-2 fatigue and skin rash. Results of this case series and literature review indicate that dual-drug therapy with BRAF and MEK inhibitors for r&aPXA with BRAF V600E mutation may delay tumor progression without unexpected AEs.

Optimally targeting the centromedian nucleus of the thalamus for generalized epilepsy: A meta-analysis.

BACKGROUND: Deep brain stimulation (DBS) of the centromedian nucleus (CM) is an effective therapeutic option for select patients with generalized epilepsy. However, several studies suggest that success varies with active contact location within the CM and the exact target remains undefined. OBJECTIVE: To quantify the association between active contact location and outcomes across all published series of CM DBS. METHODS: A literature search using PRISMA criteria was performed to identify all studies that reported active contact locations PLUS outcomes following DBS of the CM for epilepsy. Patient, disease, treatment, and outcome data were extracted for statistical analysis. Active contact locations were analyzed on a common reference frame and weighted by percent seizure reduction at last follow-up. RESULTS: From 184 studies that were screened for review, 3 studies comprising 47 patients met criteria for inclusion and were analyzed. At time of surgery, mean duration of epilepsy was 18 years. Pooled rates of atonic, atypical absence, generalized tonic-clonic, myoclonic, and tonic epilepsies were 38%, 74%, 68%, 14%, and 60%, respectively. Indirect targeting was used in all these studies. After a mean follow-up duration of 2.3 years, 87% of patients were deemed to be responders with mean seizure reduction of 73% (95% CI: [64%-81%]). Optimal location of the active contact was found to be at the dorsal border of the CM. CONCLUSIONS: Success following DBS of the CM for epilepsy varies by active contact location, even within the CM. Our findings suggest that stimulation within the dorsal region of the CM improves outcomes. Additional studies are needed to further refine these findings.

Intraoperative localization and preservation of reading in ventral occipitotemporal cortex.

OBJECTIVE: Resective surgery in language-dominant ventral occipitotemporal cortex (vOTC) carries the risk of causing impairment to reading. Because it is not on the lateral surface, it is not easily accessible for intraoperative mapping, and extensive stimulation mapping can be time-consuming. Here the authors assess the feasibility of using task-based electrocorticography (ECoG) recordings intraoperatively to help guide stimulation mapping of reading in vOTC. METHODS: In 11 patients undergoing extraoperative, intracranial seizure mapping, the authors recorded induced broadband gamma activation (70-150 Hz) during a visual category localizer. In 2 additional patients, whose pathologies necessitated resections in language-dominant vOTC, task-based functional mapping was performed intraoperatively using subdural ECoG alongside direct cortical stimulation. RESULTS: Word-responsive cortex localized using ECoG showed a high sensitivity (72%) to stimulation-induced reading deficits, and the confluence of ECoG and stimulation-positive sites appears to demarcate the visual word form area. Intraoperative task-based ECoG mapping was possible in < 3 minutes, providing a high signal quality, and initial intraoperative data analysis took < 3 minutes, allowing for rapid assessment of broad areas of cortex. Cortical areas critical for reading were mapped and successfully preserved, while also enabling pathological tissue to be completely removed. CONCLUSIONS: Eloquent cortex in ventral visual cortex can be rapidly mapped intraoperatively using ECoG. This method acts to guide high-probability targets for stimulation with limited patient participation and can be used to avoid iatrogenic dyslexia following surgery.

Metastatic Neoplasm Volume Kinetics Following 2-Stage Stereotactic Radiosurgery.

BACKGROUND: Multisession staged stereotactic radiosurgery (SRS) represents an alternative approach for management of large brain metastases (LBMs), with potential advantages over fractionated SRS. This study investigated clinical efficacy and safety of 2-stage stereotactic radiosurgery (2-SSRS) in patients with LBMs. METHODS: Patients with LBMs treated with 2-SSRS between 2014 and 2020 were evaluated. Demographic, clinical, and radiologic data were obtained. Volumetric measurements at first SRS session, second SRS session, and follow-up imaging studies were obtained. Characteristics that might predict response to 2-SSRS were evaluated through Fisher exact or Mann-Whitney U test. RESULTS: The study included 24 patients with 26 LBMs. Median (range) marginal doses for first and second SRS sessions were 15 Gy (14-18 Gy) and 15 Gy (12-16 Gy), respectively. Median (range) tumor volumes at first SRS session, second SRS session, and 3-month follow-up were 8.1 cm3 (1.5-28.5 cm3), 3.3 cm3 (0.8-26.1 cm3), and 2.2 cm3 (0.2-10.1 cm3), respectively. Of 26 lesions, 24 (92%) demonstrated early local control following the first SRS session, with 17 lesions (71%) demonstrating a decrease of ≥30% in T1 postcontrast MRI volume before the second SRS session and 3 lesions (12%) remaining stable. Eventually, 4 lesions showed disease progression after 2-SSRS. The median time to local progression was not reached; the median time to intracranial progression was 9.1 months. CONCLUSIONS: Our study supports the effectiveness and safety of 2-SSRS as a treatment modality for patients with LBMs, especially in poor surgical candidates. The local failure rate and low occurrence of adverse effects are comparable to other staged radiosurgery studies.

Recent developments on 1,8-Naphthalimide moiety as potential target for anticancer agents.

1,8-Naphthalimide moiety is well known to possess various biological activities as it can very well intercalate with DNA. In recent years, much of the attention has been given to the preparation of naphthalimide derivatives by substitution at various positions of the 1,8-naphthalimide ring for their exploration as anticancer agents. These derivatives possess different anticancer properties, which cover a broader range of cancer cell lines. Interestingly, some derivatives include enhanced activity than the reference standards like cisplatin, amonafide, mitonafide, etc., and be selective against the cell lines. The aim is to study the effect of different modulations at various positions of the 1,8-naphthalimide ring with a polyamine, thiourea, benzothiazole, benzimidazole, and formation of metal complexes and bis-naphthalimides that affects the overall cytotoxic properties of the resulting 1,8-naphthalimides. Moreover, the structure-activity relationship of these variations for the resulting derivatives' anticancer properties has also been discussed. Thus, this review will be important for a wide range of researchers to design and development of various 1,8-naphthalimide derivatives with desired drug profiles.