NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022.

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2-4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding molecular profiling of gliomas.

Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.

Impact of the Number of Metastatic Tumors Treated by Stereotactic Radiosurgery on the Dose to Normal Brain: Implications for Brain Protection.

PURPOSE/OBJECTIVES: The purpose of this study was to evaluate the effect of the number of brain lesions for which stereotactic radiosurgery (SRS) was performed on the dose volume relationships in normal brain. MATERIALS AND METHODS: Brain tissue was segmented using the patient's pre-SRS MRI. For each plan, the following data points were recorded: total brain volume, number of lesions treated, volume of brain receiving 8 Gy (V8), V10, V12, and V15. RESULTS: A total of 225 Gamma Knife® treatments were included in this retrospective analysis. The number of lesions treated ranged from 1 to 29. The isodose for prescription ranged from 40 to 95% (mean 55%). The mean prescription dose to tumor edge was 18 Gy. The mean coverage, selectivity, conformity, and gradient index were 97.5%, 0.63, 0.56, and 3.5, respectively. The mean V12 was 9.5 cm3 (ranging from 0.5 to 59.29). There was no correlation between the number of lesions and brain V8, V12, V10, or V15. There was a direct and statistically significant relationship between the brain volume treated (V8, V10, V12, and V15) and total volume of tumors treated (p < 0.001). In our study, the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3. CONCLUSIONS: The number of metastatic brain lesions treated bears no significant relationship to total brain tissue volume treated when using SRS. The fact that the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3 is useful for establishing guidelines. Although standard practice has favored using whole brain radiation therapy in patients with more than 4 lesions, a significant amount of normal brain tissue may be spared by treating these patients with SRS. SRS should be carefully considered in patients with multiple brain lesions, with the emphasis on total brain volume involved rather than the number of lesions to be treated.

Expected motor function change following decompressive surgery for spinal metastatic disease.

Background: Motor function in patients with spinal metastatic disease (SMD) directly impacts a patient's ability to receive systemic therapy and overall survival. Spine surgeons may be in the challenging position to advise a patient on expected motor function outcomes and determine a patient's suitability as a surgical candidate. We present this study to provide this critical information on anticipated motor function change to spine surgeons. Methods: Consecutive patients undergoing spinal surgery for SMD at a National Cancer Institute-designated cancer institute were prospectively enrolled. Patient motor function status before and after surgery was assessed using the standard 0 to 5 five-point muscle strength grading scale. The difference in presurgical and postsurgical motor function (proximal and distal) was used to assess motor function changes following surgery. Results: A total of 171 patients were included. The mean age was 62.7±10.46 years and 40.9% (70) were female. Common primary malignancy types were lung (49), kidney (28), breast (25), and prostate (23). The average proximal and distal motor function difference was 0.38 (standard deviation=1.02, p<.0001) and 0.32 (standard deviation=0.91, p<.0001) respectively showing an improvement following surgery. Patients with proximal presurgical motor function of 2, 3, and 4 had an improved motor function in 73%, 77%, and 73% of the patients. Patients with distal presurgical motor function of 2, 3, and 4 had an improved motor function in 80%, 89%, and 70% of the patients. Conclusions: Most patients undergoing surgery for SMD have a modest improvement in motor function following surgery. The degree of improvement in most instances is less than 1 point on a 0 to 5 motor function scale. This is critical knowledge for a spinal surgeon when evaluating SMD patients with significant preoperative motor function deficits. These results aid spinal surgeons in setting expectations and evaluating the need for rapid spinal decompression.

Lateral Temporal Approach for Image-Guided Stereotactic Biopsy of Pineal Region Tumors.

BACKGROUND: Biopsy of pineal region neoplasms is frequently accomplished by way of endoscopic transventricular access or using an image-guided, computer-assisted stereotactic approach. METHODS: We evaluated a nonorthogonal lateral temporal approach for stereotactic biopsy of pineal region tumors as a variation of previously described stereotactic methods. Magnetic resonance imaging-guided frameless stereotaxy was used to plan and perform biopsies of pineal region tumors using a nonorthogonal trajectory extending from the superior or middle temporal gyri through the temporal stem, anterior to the atrium of the lateral ventricle, and posterior to the corticospinal tract. RESULTS: All patients had an uncomplicated postoperative course and remained at neurologic baseline. No parenchymal or ventricular hemorrhage was present on postoperative scans. A tissue diagnosis was obtained in all patients. CONCLUSIONS: This method appears to be a safe alternative to stereotactic biopsy using other trajectories and provides adequate tissue for definitive diagnosis.

Prospective prediction of clinical drug response in high-grade gliomas using an ex vivo 3D cell culture assay.

BACKGROUND: Clinical outcomes in high-grade glioma (HGG) have remained relatively unchanged over the last 3 decades with only modest increases in overall survival. Despite the validation of biomarkers to classify treatment response, most newly diagnosed (ND) patients receive the same treatment regimen. This study aimed to determine whether a prospective functional assay that provides a direct, live tumor cell-based drug response prediction specific for each patient could accurately predict clinical drug response prior to treatment. METHODS: A modified 3D cell culture assay was validated to establish baseline parameters including drug concentrations, timing, and reproducibility. Live tumor tissue from HGG patients were tested in the assay to establish response parameters. Clinical correlation was determined between prospective ex vivo response and clinical response in ND HGG patients enrolled in 3D-PREDICT (ClinicalTrials.gov Identifier: NCT03561207). Clinical case studies were examined for relapsed HGG patients enrolled on 3D-PREDICT, prospectively assayed for ex vivo drug response, and monitored for follow-up. RESULTS: Absent biomarker stratification, the test accurately predicted clinical response/nonresponse to temozolomide in 17/20 (85%, P = .007) ND patients within 7 days of their surgery, prior to treatment initiation. Test-predicted responders had a median overall survival post-surgery of 11.6 months compared to 5.9 months for test-predicted nonresponders (P = .0376). Case studies provided examples of the clinical utility of the assay predictions and their impact upon treatment decisions resulting in positive clinical outcomes. CONCLUSION: This study both validates the developed assay analytically and clinically and provides case studies of its implementation in clinical practice.

Posterior cerebral artery P1 segment at the stoma during endoscopic third ventriculostomy in adults.

OBJECTIVES: A serious catastrophic complication of endoscopic third ventriculostomy (ETV) is basilar artery (BA) damage. Although the BA has been discussed as the cause of haemorrhage and even pseudoaneurysm, variations of the posterior cerebral artery proximal segment (P1) and its protrusion into the third ventricle floor have not been emphasised. A series of cases are reported in which the P1 segment was located at the stoma during an ETV and was at risk of perforation. Precautionary techniques for complication avoidance are described. METHODS: A retrospective review was performed of all ETVs performed in adults at our institution between 2004 and 2008. Cases were identified in which the P1 segment was noted to herniate into the stoma at the time of third ventricular floor fenestration. RESULTS: Among 65 cases reviewed, six were identified in which the P1 segment significantly herniated into an area of the stoma at the time of third ventricular floor fenestration. In no case was the P1 segment injured by the ETV procedure. Each of the six patients had opaque third ventricle floors. A 'cookie cut' technique was used in which the opaque third ventricle floor was abraded to reveal the underlying translucent membrane, offering an improved view of arteries in the basilar cisterns. In four of six patients, ETV resulted in clinical improvement. CONCLUSIONS: The posterior cerebral artery P1 segment is potentially at risk during ETV in adults as well as in children. Awareness and proper precautions may help reduce injuries to either the P1 or the basilar apex during an ETV.

Preoperative predictors for improvement after surgical untethering in occult tight filum terminale syndrome.

BACKGROUND/AIMS: An occult tight filum terminale syndrome has been described wherein clinical symptoms result from tension on the spinal cord despite nondiagnostic spinal magnetic resonance imaging (MRI). Recent reports have suggested a role for surgical untethering in this patient population; however, controversy remains regarding the surgical treatment of this condition. Owing to the various clinical presentations, the relationship of presenting signs and symptoms to postoperative outcomes might be useful in surgical selection. METHODS: A retrospective review was conducted of 22 pediatric cases of surgical untethering for suspected occult tight filum terminale syndrome. All patients had nondiagnostic MRI findings, defined as a conus medullaris above the L(3) vertebral body and a filum terminale diameter of less than 2 mm. Preoperative symptoms, signs and urodynamic test results were collected and compared with surgical outcomes determined by clinical notes and postoperative urodynamics reports. Abnormal findings on presentation were categorized as dermatologic, urologic, orthopedic and neurologic. RESULTS: Patient age ranged from 7 months to 17 years, and 12 were female. Sixteen (73%) patients experienced subjective and/or objective improvement following surgical untethering. Fourteen patients had abnormal preoperative urodynamic testing, of which 12 underwent postoperative urodynamic testing. Five of these 12 (42%) demonstrated objective improvement postoperatively. Patients presenting with abnormal findings in at least 2 categories were more likely to improve following untethering (88%) than those with abnormalities in only 1 category (20%; p = 0.009). CONCLUSION: Spinal cord untethering is a treatment option for occult tight filum terminale syndrome. Further evaluation of the relationship between preoperative findings and surgical outcomes may facilitate the selection of surgical candidates.

Intracranial stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) is the use of a single high dose of radiation, stereotactically directed to an intracranial region of interest, in order to create a lesion or obliterate a preexisting one. This technology has evolved over the years into the use of multiple radiation sources oriented at a variety of angles, thus permitting the creation of various treatment target shapes. This allows for non-open surgical treatment of intracranial pathologies, which significantly decreases the risk of morbidity. The destruction of pathological tissue following radiosurgery is a stepwise process that involves a number of different stages, beginning with the necrotic stage, followed by the resorption stage, and concluding with the glial scar formation stage. There are currently a number of different delivery methods of SRS, including linear accelerators, Gamma Knife units, and charged particle methods (Bragg-peak and plateau-beam). Various intracranial lesions exhibit different responses to radiosurgery; however, most lesions of appropriate size tend to respond favorably. Radiosurgery is used today in the treatment of brain metastases, meningiomas, vestibular schwannomas, sellar and suprasellar lesions, and arteriovenous malformations. SRS is widely used to treat functional conditions, such as trigeminal neuralgia and intractable tremor. The treatment of intracranial lesions with radiosurgery can result in undesirable effects on the adjacent normal brain, resulting in adverse radiation effects. The distinction between tumor progression and adverse radiation effects can be challenging but is aided by various imaging modalities. Treatment options for this condition include observation, corticosteroids, pentoxifylline and vitamin E, bevacizumab, laser-interstitial thermal therapy, and surgical resection.

Fusarium species intramedullary spinal cord fungus ball: case report.

The Fusarium species are one of the most common opportunistic fungal infections occurring in immunocompromised patients and are associated with high morbidity and mortality. Common sites of infection include blood, skin, nasal passages, lungs, bone, and other visceral organs. There is a paucity of literature on Fusarium infections in the brain, and the true nature and extent of central nervous system involvement is not well described. To the authors' knowledge, there have been no reported cases of Fusarium infection of the spine. The authors report the case of a man with acute myeloblastic leukemia and resultant pancytopenia who presented with fungal sinusitis, upper- and lower-extremity weakness, and cardiopulmonary arrest. Imaging studies revealed a spinal cervical intramedullary ring-enhancing lesion. Because of the progressive nature of his symptoms, neurosurgical intervention involving a C2-3 laminectomy and drainage of the lesion was performed. Intraoperative cultures and histopathology results were positive for Fusarium species and, along with intraoperative findings, were consistent with a fungus ball. The patient was placed on a regimen of intravenous and intrathecal antifungal therapy. Unfortunately, his clinical condition declined postoperatively, and he ultimately died of disseminated infection.

The C7 pedicle as a superior fixation point in spinal stabilization for spinal metastatic disease.

Spinal metastatic disease (SMD) often requires spinal stabilization; however, the cervicothoracic junction can be a challenging area to instrument. An anterior approach may require division of the sternum. A posterior or posterolateral approach may rely on cervical lateral mass screws for superior construct fixation that are more prone to pullout than screws placed in a pedicle. The C7 pedicle is able to support pedicle screw fixation in most instances based on morphological features of the vertebra. When the C7 pedicle is used as a superior fixation point, it aligns with the thoracic pedicles below to create a streamlined posterior construct. In this study, patients undergoing posterior stabilization with C7 pedicle superior fixation were examined. One hundred and thirty-nine consecutive spinal operations at a National Cancer Institute designated cancer center were retrospectively reviewed to identify patients who underwent spinal stabilization for SMD with a C7 pedicle screw placed as the superior fixation point of a posterior construct. Patient age, the primary disease, and clinical and radiographic information were identified. Follow-up duration was noted, and follow-up outcomes were recorded on the basis of the clinical history and the findings on computed tomography (CT) spinal imaging. Three patients were identified who underwent separation surgery for SMD that included posterior spinal stabilization with C7 pedicle screws as the superior fixation point. The average patient age was 70 years and one patient was a woman. The average follow-up time was 20.7 months. There were no occurrences of hardware failure, neurologic deterioration, or protracted pain in the cases analyzed. Overall, there were good surgical outcomes with improvement in pain without neurovascular injury or evidence of hardware failure during follow-up evaluation. These findings add to a small but notable number of studies showing the effectiveness of C7 pedicle screws as a superior fixation point in spinal oncology, specifically in metastatic lesions. In our experience the C7 pedicle has provided a useful superior fixation point solution for the posterior stabilization of high thoracic vertebral body metastases. This surgical option may help spinal surgeons address the stabilization of SMD in the cervicothoracic region.

Instrumented Spinal Stabilization without Fusion for Spinal Metastatic Disease.

OBJECTIVES: Spinal stabilization surgery is an integral part of the treatment of spinal metastatic disease. Bony fusion is the hallmark of spinal stabilization in non-oncology patients. Spinal oncology patients are unlikely to achieve bony fusion because of their overall prognosis and concurrent therapies. Stabilization surgery without fusion may be a reasonable approach for these patients. Literature evaluating the effectiveness of this approach is limited. The object of this study was to investigate the rate of instrumentation failure in patients undergoing posterior spinal instrumented stabilization without fusion for spinal metastatic disease. METHODS: Data from consecutive cases of spinal surgery at our institution during an 81-month period were reviewed. Demographics, clinical notes, and computed tomography findings were recorded and used to evaluate instrumentation failures. Patients who underwent separation surgery that included laminectomy and posterior spinal instrumentation without fusion for spinal metastatic disease and had follow-up computed tomography scans >3 months postoperatively were selected for the study. RESULTS: Twenty-seven patients were included in the study. Mean age was 64.85 ± 6.53 years. Nine patients were women. A mean of 1.61 ± 0.96 laminectomy levels was performed. A mean of 8.26 ± 1.48 screws was inserted. The mean postoperative discharge date was 5.07 ± 1.47 days. Mean follow-up duration was 12.17 ± 11.73 months. None of the patients had a change in instrumentation position, pedicle screw pullout, change in spinal alignment, or progressive deformity. No patient required reoperation or instrumentation revision or replacement. CONCLUSIONS: Our experience suggests that instrumented spinal stabilization without fusion is an acceptable approach for patients with spinal metastatic disease.

Comparison of Operative Time with Conventional Fluoroscopy Versus Spinal Neuronavigation in Instrumented Spinal Tumor Surgery.

OBJECTIVE: Spinal neuronavigation improves accuracy of pedicle screw placement but may increase operative time, and its use in oncologic operations remains relatively unstudied. We compared the use of two-dimensional (2D) fluoroscopy and three-dimensional (3D) spinal neuronavigation relative to operative time in instrumented oncology procedures. METHODS: Consecutive instrumented oncologic spinal operations for multiple myeloma or metastatic disease performed between 2012 and 2014 were retrospectively reviewed. Patients were placed in 2 groups based on the method used for pedicle screw placement: 2D fluoroscopy versus spinal neuronavigation with 3D imaging. These groups were compared by age, number of screws placed, number of laminectomy levels, operative time, estimated blood loss, length of hospital stay after surgery, and rate of reoperation as a result of screw misplacement. RESULTS: Fourteen operations used 2D fluoroscopy and 25 used spinal neuronavigation. In the fluoroscopy and neuronavigation groups, respectively, patient ages were 64.71 ± 7.21 years and 63.24 ± 6.95 years (P = 0.534), number of screws was 8.07 ± 1.98 and 7.84 ± 1.34 (P = 0.667), laminectomy levels were 2.18 ± 1.25 and 1.60 ± 1.02 (P = 0.126), operative time was 200.79 ± 34.99 minutes and 193.48 ± 43.77 minutes (P = 0.596), estimated blood loss was 790.00 ± 769.61 mL and 389.80 ± 551.43 mL (P = 0.068), and length of stay after the operation was 7.64 ± 4.63 days and 6.40 ± 3.23 days (P = 0.331). One patient in the 2D fluoroscopy group and no patients in the spinal neuronavigation group required a reoperation for screw misplacement. CONCLUSIONS: There was no significant difference in length of operative time when neuronavigation was compared with fluoroscopy for instrumented oncologic spinal surgery. There was a trend toward a decrease in estimated blood loss in the neuronavigation cases.

Surgical management of spinal metastatic disease.

Spinal metastatic disease is a common occurrence in oncology. Spinal metastases may result in pain, spinal deformity, and neurologic deterioration. Surgical intervention is a key component in the effective management of spinal metastatic disease. The principles of neural decompression and spinal stabilization are hallmarks of the surgical care for patients with metastatic spinal disease. Several classification systems exist for spinal metastatic disease to aid in assessing preoperative spinal instability and the need for operative intervention. Treatment modalities include separation surgery, stereotactic radiosurgery, conventional radiotherapy, vertebral body augmentation, and laser-interstitial thermal therapy. Various open surgical approaches exist that may be employed to achieve operative goals during separation surgery. The spinal surgeon should be intimately involved in the overall care of patients with spinal metastatic disease to ensure the best clinical outcomes.