Endoscopic Extended Transsphenoidal Surgery Aiming for Radical Resection of Skull Base Tumors Involving Cavernous Sinus: Assessment of Resectability and Risks of Complications.

BACKGROUND AND OBJECTIVES: Surgical resection of tumors invading the cavernous sinus (CS) still shows therapeutic challenges. For "nonadenomatous" skull base tumors invading in CS, there were only a few reports showing the outcomes of radical resection. Therefore, the outcomes of endoscopic transsphenoidal surgery (ETS) aiming for radical resection thus remain largely unknown regarding resectability and functional results of the cranial nerves. METHODS: We performed ETS aiming for radical resection in 35 skull base tumors involving CS (17 chondrosarcomas, 12 chordomas, 3 meningiomas, and 3 trigeminal schwannomas; median follow-up 36.5 months ranging from 12 to 91 months). Gross total resection (GTR) is attempted in all the cases for real-time findings from electrophysiological monitoring of the cranial nerves. When the tumor was strongly adherent to the cranial nerves or internal carotid artery, maximum volume reduction of the tumor was attempted. RESULTS: GTR was achieved in 28 patients (80.0%), subtotal resection in 3 (8.6%), and partial resection in 4 (11.4%). One patient experienced internal carotid artery injury during surgery. After ETS, 15 patients showed symptom improvement (51.7% in all 29 patients with preoperative cranial nerve symptoms, CNS). Four (11.4%) transiently developed abducens nerve palsy, and one required repair surgery for cerebrospinal leakage. In univariate analyses, extension to the lateral compartment of CS ( P = .04) was significantly associated with reduced achievement of GTR. Previous transcranial surgery was associated with reduced possibility of improvement and worsening in CNS. Eleven patients underwent stereotactic radiosurgery, at a median of 12 months after ETS. 32 patients (91.4%) did not show recurrence at the final follow-up. CONCLUSION: ETS can achieve sufficient surgical resection in most of the patients, with acceptable neurological complications. For patients with CNS, ETS may offer the opportunity for improving CNS. We should also always prioritize avoidance of critical situations by preventing internal carotid artery injury.

Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors.

PURPOSE: We investigated the relationship between RBE-weighted dose (DRBE) calculated with constant (cRBE) and variable RBE (vRBE), dose-averaged linear energy transfer (LETd) and the risk of radiographic changes in skull base patients treated with protons. METHODS: Clinical treatment plans of 45 patients were recalculated with Monte Carlo tool FRED. Radiographic changes (i.e. edema and/or necrosis) were identified by MRI. Dosimetric parameters for cRBE and vRBE were computed. Biological margin extension and voxel-based analysis were employed looking for association of DRBE(vRBE) and LETd with brain edema and/or necrosis. RESULTS: When using vRBE, Dmax in the brain was above the highest dose limits for 38% of patients, while such limit was never exceeded assuming cRBE. Similar values of Dmax were observed in necrotic regions, brain and temporal lobes. Most of the brain necrosis was in proximity to the PTV. The voxel-based analysis did not show evidence of an association with high LETd values. CONCLUSIONS: When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd.

Cone-Beam Computed Tomography Fusion Technique for Vascular Assessment of Skull Base Meningiomas.

OBJECTIVE: Cone-beam computed tomography (CBCT) images for skull base tumors provide detailed vascular information and localization in regard to surrounding bony structures. We report use of the CBCT fusion technique for skull base meningiomas. METHODS: Six patients with petroclival or petrotentorial meningiomas supplied by multiple arterial systems were preoperatively evaluated using CBCT fusion imaging. Fusion images were reconstructed from three-dimensional rotational angiography with contrast agent injections from the internal carotid artery (ICA) and external carotid artery in 4 cases, vertebral artery and external carotid artery in 1 case, and ICA and vertebral artery in 1 case. RESULTS: The feeding pedicles and tumor stains from 2 arterial systems were differentiated by separate colors. The courses and territories of the ICA dural feeders or ICA/vertebral artery pial feeders were easily distinguished from the external carotid artery dural feeders. Anastomoses between thin feeders from different arterial systems could be detected. Mixed stain (stain with both colors) was observed in some tumor compartments, suggesting dual supply from 2 arterial systems and the presence of peritumoral anastomoses. All patients underwent preoperative embolization without complications. CONCLUSIONS: CBCT fusion images clearly visualized the feeders from each arterial system, the vascular compartments within the tumor, and possible peritumoral anastomoses. This technique provides a substantial contribution to both preoperative embolization and surgical resection of skull base meningiomas.

Clinical utility of apparent diffusion coefficient and diffusion-weighted magnetic resonance imaging for resectability assessment of head and neck tumors with skull base invasion.

BACKGROUND: The usefulness of apparent diffusion coefficient (ADC) and diffusion-weighted magnetic resonance imaging (DWI) in the detection of malignant tumors has been reported. The purpose of this study is to clarify the role of ADC and DWI for diagnosis of skull base tumors. METHODS: A total of 27 patients with head and neck tumors with skull base invasions undergoing skull base surgery were enrolled in this study. Pathological findings of dural invasion and bone invasion were compared with the diagnostic imaging. RESULTS: Advanced magnetic resonance imaging techniques revealed that ADC values in regions of pathological bone and dural invasions were significantly lower than in regions of no invasion. The area under the curve of ADC in bone invasions and dural invasions were 0.957 and 0.894, respectively. CONCLUSIONS: Our findings indicate that ADC and DWI are useful tools for the diagnosis of head and neck tumors with skull base invasion.

The Role of Morphologic and Functional Imaging in Pretreatment Assessment.

Anterior skull base (ASB) tumors can be classified into three groups according to their site of origin: (1) sinonasal neoplasms involving or extending through the anterior cranial base; (2) neoplasms which arise from the bony framework of the base itself; (3) neoplasms originating from adjacent intracranial structures. With few exceptions, most of these tumors have a non-specific appearance on CT and MRI, which limits the role of imaging in terms of characterization. However, treatment planning (transnasal endoscopic surgery in particular) mostly depends upon the tumor map, exploiting the potential of modern cross-sectional imaging. As a result, the radiologist who has to evaluate a neoplasm involving the ASB needs to be fully aware of all the technical solutions available and the specific strengths/weaknesses of the different imaging techniques. Knowledge of radiological anatomy (and its variants) is also essential, which includes the ability to translate the CT appearance of structures into the equivalent MR signal (and vice versa). These main prerequisites have to be combined with up-to-date knowledge of treatment options and surgical procedures in order to be able to create a reporting checklist covering all the aspects that are essential for clinical decision making.

Assessment of Factors Associated With Internal Carotid Injury in Expanded Endoscopic Endonasal Skull Base Surgery.

Importance: Injury to the internal carotid artery (ICA) during endoscopic endonasal skull base surgery does not typically occur as an isolated circumstance but often is the result of multiple factors. Objective: To assess the factors associated with ICA injury in an effort to reduce its occurrence. Design, Setting, and Participants: This quality improvement study used a multicenter root cause analysis of ICA injuries sustained during endoscopic endonasal skull base surgery performed at 11 tertiary care centers across 4 continents (North America, South America, Europe, and Asia) from January 1, 1993, to December 31, 2018. A fishbone model was built to facilitate the root cause analysis. Patients who underwent an expanded endoscopic endonasal approach that carried a substantial potential risk of an ICA injury were included in the analysis. A questionnaire was completed by surgeons at the centers to assess relevant human, patient, process, technique, instrument, and environmental factors associated with the injury. Main Outcomes and Measures: Root cause analysis of demographic, human, patient, process, technique, instrument, and environmental factors as well as mortality and morbidity data. Results: Twenty-eight cases of ICA injury occurred during 7160 expanded endoscopic endonasal approach procedures (incidence of 0.4%). The mean age of the patients was 49 years, with a female to male predominance ratio of 1.8:1 (18 women to 10 men). Anatomical (23 [82%]), pathological (15 [54%]), and surgical resection (26 [93%]) factors were most frequently reported. The surgeon's mental or physical well-being was reported as inadequate in 4 cases (14%). Suboptimal imaging was reported in 6 cases (21%). The surgeon's experience level was not associated with ICA injury. The ICA injury was associated with use of powered or sharp instruments in 20 cases (71%), and use of new instruments or technology in 7 cases (25%). Two patients (7%) died in the operating room, and 3 (11%) were alive with neurological deficits. Overall, patient-related factors were the most frequently reported risk factors (in 27 of 28 cases [96%]). Factors associated with ICA injury catalyzed a list of preventive recommendations. Conclusions and Relevance: This study found that human factors were associated with intraoperative ICA injuries; however, they were usually accompanied by other deficiencies. These findings suggest that identifying risk factors is crucial for preventing such injuries. Preoperative planning and minimizing the potential for ICA injury also appear to be essential.

Proton therapy for brain tumours in the area of evidence-based medicine.

ADVANCES IN KNOWLEDGE: This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors.

Intraoperative assessment of skull base tumors using stimulated Raman scattering microscopy.

Intraoperative consultations, used to guide tumor resection, can present histopathological findings that are challenging to interpret due to artefacts from tissue cryosectioning and conventional staining. Stimulated Raman histology (SRH), a label-free imaging technique for unprocessed biospecimens, has demonstrated promise in a limited subset of tumors. Here, we target unexplored skull base tumors using a fast simultaneous two-channel stimulated Raman scattering (SRS) imaging technique and a new pseudo-hematoxylin and eosin (H&E) recoloring methodology. To quantitatively evaluate the efficacy of our approach, we use modularized assessment of diagnostic accuracy beyond cancer/non-cancer determination and neuropathologist confidence for SRH images contrasted to H&E-stained frozen and formalin-fixed paraffin-embedded (FFPE) tissue sections. Our results reveal that SRH is effective for establishing a diagnosis using fresh tissue in most cases with 87% accuracy relative to H&E-stained FFPE sections. Further analysis of discrepant case interpretation suggests that pseudo-H&E recoloring underutilizes the rich chemical information offered by SRS imaging, and an improved diagnosis can be achieved if full SRS information is used. In summary, our findings show that pseudo-H&E recolored SRS images in combination with lipid and protein chemical information can maximize the use of SRS during intraoperative pathologic consultation with implications for tissue preservation and augmented diagnostic utility.

Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy Transfer.

PURPOSE: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. METHODS AND MATERIALS: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. RESULTS: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. CONCLUSION: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.

Prediction of pediatric meningioma recurrence by preoperative MRI assessment.

Preoperative identification of high-recurrent pediatric meningiomas with MRI features would help clinicians to make optimal treatment strategies; however, the relationships between radiological features and recurrence of meningiomas in pediatric population have not been clearly demonstrated yet. The aim of this study is to identify preoperative MRI features which are significant risk factors for recurrence of pediatric meningiomas. From January 2005 to December 2012, we retrospectively reviewed 52 pediatric meningiomas in terms of preoperative MRI features and their clinical data and followed them up from 22 to 128 months (mean 63 months) after the initial surgery. The relationships between these radiological findings and relapse-free survival (RFS) time were assessed initially with univariate Cox analysis and then corrected by multivariate Cox analysis. According to univariate analysis, irregular shape, narrow-based attachment, and skull base location were significantly correlated with shorter time to recurrences of meningiomas in pediatric patients. When corrected by multivariate analysis, irregular shape (P = 0.05; OR 3.442, 95 % CI 1.001-11.831) and narrow-based attachment (P = 0.004; OR 7.164, 95 % CI 1.894-27.09) were strong independent predictive factors for worse RFS of pediatric meningiomas. In pediatric population, narrow-based attachment and irregular shape were significantly correlated with recurrences of meningiomas. Our results could help clinicians to make optimal therapeutic strategies for pediatric patients with intracranial meningiomas before surgery.

Assessment of tumor volumes in skull base glomus tumors using Gluc-Lys[(18)F]-TOCA positron emission tomography.

PURPOSE: To assess a threshold for Gluc-Lys[(18)F]-TOCA positron emission tomography (PET) in target volume delineation of glomus tumors in the skull base and to compare with MRI-based target volume delineation. METHODS AND MATERIALS: The threshold for volume segmentation in the PET images was determined by a phantom study. Nine patients with a total of 11 glomus tumors underwent PET either with Gluc-Lys[(18)F]-TOCA or with (68)Ga-DOTATOC (in 1 case). All patients were additionally scanned by MRI. Positron emission tomography and MR images were transferred to a treatment-planning system; MR images were analyzed for lesion volume by two observers, and PET images were analyzed by a semiautomated thresholding algorithm. RESULTS: Our phantom study revealed that 32% of the maximum standardized uptake value is an appropriate threshold for tumor segmentation in PET-based target volume delineation of gross tumors. Target volume delineation by MRI was characterized by high interobserver variability. In contrast, interobserver variability was minimal if fused PET/MRI images were used. The gross tumor volumes (GTVs) determined by PET (GTV-PET) showed a statistically significant correlation with the GTVs determined by MRI (GTV-MRI) in primary tumors; in recurrent tumors higher differences were found. The mean GTV-MRI was significantly higher than mean GTV-PET. The increase added by MRI to the common volume was due to scar tissue with strong signal enhancement on MRI. CONCLUSIONS: In patients with glomus tumors, Gluc-Lys[(18)F]-TOCA PET helps to reduce interobserver variability if an appropriate threshold for tumor segmentation has been determined for institutional conditions. Especially in patients with recurrent tumors after surgery, Gluc-Lys[(18)F]-TOCA PET improves the accuracy of GTV delineation.

Subcranial approach to tumors of the anterior cranial base: analysis of current and traditional surgical techniques.

Tumors of the anterior cranial base have previously required a craniofacial resection to allow adequate tumor extirpation. An analysis of current and traditional techniques demonstrates a significant reduction in operative time, complication rate, and intensive care unit and total hospital length of stay with the use of the subcranial approach as compared with the traditional frontal craniotomy and lateral rhinotomy approach. The subcranial approach is both cost and time efficient and provides comparable morbidity and mortality rates.