To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors.
ASCO convened an Expert Panel and conducted a systematic review of the literature.
Thirty-two ...randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base.
Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non-small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy.Additional information is available at www.asco.org/neurooncology-guidelines.
Patients with glioma frequently suffer from deficits of neurocognitive functioning (NCF), though few studies have assessed NCF in localized glioma patients prior to surgery. One hundred and three ...patients (M age = 52.0; M education = 14.6 years) with histologically confirmed glioma in the right (RTL: n = 30; 57 % glioblastoma) or left temporal lobe (LTL: n = 73; 49 % glioblastoma) completed presurgical neuropsychological assessment. Impairment of NCF was identified in 75 % of all patients. Notably, patients with RTL glioma were most frequently impaired on measures of verbal memory and executive functioning, and at similar rates as the LTL group. Nonetheless, χ
2
tests revealed that impairment rates were significantly higher in the LTL group on attention and object naming tests (p ≤ .05). Independent-samples t-tests revealed that mean performances of patients with LTL glioma were also significantly below RTL patients on measures of attention (p = .01), verbal learning and memory (p = .05), and language (p < .03). A trend was observed in which anterior LTL tumors were associated with reduced verbal learning and medial LTL lesions with delayed recall problems, though patients with lesions involving multiple LTL regions exhibited the greatest difficulty across all verbal memory measures. Significant group differences in NCF performances remained so after controlling for FLAIR volume and tumor histology. These findings indicate that temporal lobe glioma frequently present with impaired NCF, though impairments are often milder in RTL compared to LTL patients. Nonetheless, the relatively frequent verbal memory impairment in the RTL group underscores the bilaterality of verbal memory processes.
Various tumor characteristics have been associated with neurocognitive functioning (NCF), though the role of tumor grade has not been adequately examined.
Seventy-two patients with histologically ...confirmed grade IV glioma (n = 37), grade III glioma (n = 20), and grade II glioma (n = 15) in the left temporal lobe completed preoperative neuropsychological assessment. Rates of impairment and mean test performances were compared by tumor grade with follow-up analysis of the influence of other tumor- and patient-related characteristics on NCF.
NCF impairment was more frequent in patients with grade IV tumor compared with patients with lower-grade tumors in verbal learning, executive functioning, as well as language abilities. Mean performances significantly differed by tumor grade on measures of verbal learning, processing speed, executive functioning, and language, with the grade IV group exhibiting worse performances than patients with lower-grade tumors. Group differences in mean performances remained significant when controlling for T1-weighted and fluid attenuated inversion recovery MRI-based lesion volume. Performances did not differ by seizure status or antiepileptic and steroid use.
Compared with patients with grade II or III left temporal lobe glioma, patients with grade IV tumors exhibit greater difficulty with verbal learning, processing speed, executive functioning, and language. Differences in NCF associated with glioma grade were independent of lesion volume, seizure status, and antiepileptic or steroid use, lending support to the concept of "lesion momentum" as a primary contributor to deficits in NCF of newly diagnosed patients prior to surgery.
Purpose DNX-2401 (Delta-24-RGD; tasadenoturev) is a tumor-selective, replication-competent oncolytic adenovirus. Preclinical studies demonstrated antiglioma efficacy, but the effects and mechanisms ...of action have not been evaluated in patients. Methods A phase I, dose-escalation, biologic-end-point clinical trial of DNX-2401 was conducted in 37 patients with recurrent malignant glioma. Patients received a single intratumoral injection of DNX-2401 into biopsy-confirmed recurrent tumor to evaluate safety and response across eight dose levels (group A). To investigate the mechanism of action, a second group of patients (group B) underwent intratumoral injection through a permanently implanted catheter, followed 14 days later by en bloc resection to acquire post-treatment specimens. Results In group A (n = 25), 20% of patients survived > 3 years from treatment, and three patients had a ≥ 95% reduction in the enhancing tumor (12%), with all three of these dramatic responses resulting in > 3 years of progression-free survival from the time of treatment. Analyses of post-treatment surgical specimens (group B, n = 12) showed that DNX-2401 replicates and spreads within the tumor, documenting direct virus-induced oncolysis in patients. In addition to radiographic signs of inflammation, histopathologic examination of immune markers in post-treatment specimens showed tumor infiltration by CD8
and T-bet
cells, and transmembrane immunoglobulin mucin-3 downregulation after treatment. Analyses of patient-derived cell lines for damage-associated molecular patterns revealed induction of immunogenic cell death in tumor cells after DNX-2401 administration. Conclusion Treatment with DNX-2401 resulted in dramatic responses with long-term survival in recurrent high-grade gliomas that are probably due to direct oncolytic effects of the virus followed by elicitation of an immune-mediated antiglioma response.
Intraoperative MRI for Brain Tumors Rogers, Cara Marie; Jones, Pamela S.; Weinberg, Jeffrey S.
Journal of neuro-oncology,
02/2021, Letnik:
151, Številka:
3
Journal Article
Recenzirano
Introduction
The use of intraoperative imaging has been a critical tool in the neurosurgeon’s armamentarium and is of particular benefit during tumor surgery. This article summarizes the history of ...its development, implementation, clinical experience and future directions.
Methods
We reviewed the literature focusing on the development and clinical experience with intraoperative MRI. Utilizing the authors’ personal experience as well as evidence from the literature, we present an overview of the utility of MRI during neurosurgery.
Results
In the 1990s, the first description of using a low field MRI in the operating room was published describing the additional benefit provided by improved resolution of MRI as compared to ultrasound. Since then, implementation has varied in magnetic field strength and in configuration from floor mounted to ceiling mounted units as well as those that are accessible to the operating room for use during surgery and via an outpatient entrance to use for diagnostic imaging. The experience shows utility of this technique for increasing extent of resection for low and high grade tumors as well as preventing injury to important structures while incorporating techniques such as intraoperative monitoring.
Conclusion
This article reviews the history of intraoperative MRI and presents a review of the literature revealing the successful implementation of this technology and benefits noted for the patient and the surgeon.
After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the ...surgical cavity improved time to local recurrence compared with that for surgical resection alone.
In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants.
Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8–20·4). 12-month freedom from local recurrence was 43% (95% CI 31–59) in the observation group and 72% (60–87) in the SRS group (hazard ratio 0·46 95% CI 0·24–0·88; p=0·015). There were no adverse events or treatment-related deaths in either group.
SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy.
National Institutes of Health.
Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent ...glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope (n = 3), fatigue (n = 1), wound infection (n = 2), and pain at time of device connection (n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery.
MRI-guided laser interstitial thermal therapy (LITT) is the selective ablation of a lesion or a tissue using heat emitted from a laser device. LITT is considered a less invasive technique compared to ...open surgery that provides a nonsurgical solution for patients who cannot tolerate surgery. Although laser ablation has been used to treat brain lesions for decades, recent advances in MRI have improved lesion targeting and enabled real-time accurate monitoring of the thermal ablation process. These advances have led to a plethora of research involving the technique, safety, and potential applications of LITT.LITT is a minimally invasive treatment modality that shows promising results and is associated with decreased morbidity. It has various applications, such as treatment of glioma, brain metastases, radiation necrosis, and epilepsy. It can provide a safer alternative treatment option for patients in whom the lesion is not accessible by surgery, who are not surgical candidates, or in whom other standard treatment options have failed. Our aim is to review the current literature on LITT and provide a descriptive review of the technique, imaging findings, and clinical applications for neurosurgery.
The goal of glioma surgery is maximal safe resection. These intrinsic brain neoplasms, however, lack a clear margin and frequently infiltrate eloquent areas of the brain thus making their surgical ...resection challenging. This review first focuses on discussion of preoperative investigations that aid in anatomical and functional tumor characterization that help define tumor extent and determine the feasibility of complete resection. The second part of this review outlines intraoperative adjuncts that help identify tumor infiltrated tissues during surgery to maximize the extent of resection. In addition, we discuss the principles of intraoperative functional cortical and subcortical mapping and monitoring that enable maximal tumor resection while minimizing the risk of postoperative neurological deficit. Combined use of different modalities before and during surgery is encouraged to meet surgical goals and to ensure best patient outcome.
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