Opportunities and advances in the use of Proton Radiotherapy for Management of Central Nervous System and Base of Skull Tumors.
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ABSTRACT:
SUBMITTER: Savla B
PROVIDER: S-EPMC10704922 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Opportunities and advances in the use of Proton Radiotherapy for Management of Central Nervous System and Base of Skull Tumors.
Savla Bansi B Alexander Gregory G Pollock Ariel E AE Cohen Justin J Mishra Mark M
Advances in oncology 20220401 1
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Project description:The surgical management of Skull Base Meningiomas (SBMs) has radically changed over the last two decades. Extensive surgery for patients with SBMs represents the mainstream treatment; however, it is often challenging due to narrow surgical corridors and proximity to critical neurovascular structures. Novel surgical technologies, including three-dimensional (3D) preoperative imaging, neuromonitoring, and surgical instruments, have gradually facilitated the surgical resectability of SBMs, reducing postoperative morbidity. Total removal is not always feasible considering a risky tumor location and invasion of surrounding structures and brain parenchyma. In recent years, the use of primary or adjuvant stereotactic radiosurgery (SRS) has progressively increased due to its safety and efficacy in the control of grade I and II meningiomas, especially for small to moderate size lesions. Patients with WHO grade SBMs receiving subtotal surgery can be monitored over time with surveillance imaging. Postoperative management remains highly controversial for grade II meningiomas, and depends on the presence of residual disease, with optional upfront adjuvant radiation therapy or close surveillance imaging in cases with total resection. Adjuvant radiation is strongly recommended in patients with grade III tumors. Although the currently available chemotherapy or targeted therapies available have a low efficacy, the molecular profiling of SBMs has shown genetic alterations that could be potentially targeted with novel tailored treatments. This multidisciplinary review provides an update on the advances in surgical technology, postoperative management and molecular profile of SBMs.
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Project description:The purpose of this study was to investigate whether a new O-ring design radiotherapy delivery system has advantages in radiotherapy planning for skull-base tumors. Twenty-five patients with skull-base tumors were included in this study. Two plans were made using conventional (Plan A) or new (Plan B) techniques. Plan A consisted of four dynamic conformal arcs (DCAs): two were horizontal, and the other two were from cranial directions. Plan B was created by converting horizontal arcs to those from caudal directions making use of the O-ring design radiotherapy system. The micromultileaf collimators were fitted to cover at least 99% of the planning target volume with prescribed doses, 90% of the dose at the isocenter. The two plans were compared in terms of target homogeneity, conformity, and irradiated volume of normal tissues, using a two-sided paired t-test. For evaluation regarding target coverage, the homogeneity indices defined by the International Commission on Radiation Units and Measurements 83 were 0.099 ± 0.010 (mean ± standard deviation) and 0.092 ± 0.010, the conformity indices defined by the Radiation Therapy Oncology Group were 1.720 ± 0.249 and 1.675 ± 0.239, and the Paddick's conformity indices were 0.585 ± 0.078 and 0.602 ± 0.080, in Plans A and B, respectively. For evaluation of irradiated normal tissue, the Paddick's gradient indices were 3.118 ± 0.283 and 2.938 ± 0.263 in Plans A and B, respectively. All of these differences were statistically significant (p-values < 0.05). The mean doses of optic nerves, eyes, brainstem, and hippocampi were also significantly lower in Plan B. The DCA technique from caudal directions using the new O-ring design radiotherapy system can improve target homogeneity and conformity compared with conventional DCA techniques, and can also decrease the volume of surrounding normal tissues that receives moderate doses.
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Project description:Skull base tumors form a highly heterogeneous group. As there are several structures in this anatomical site, a large number of different primary malignancies might develop, as well as a variety of secondary (metastatic) tumors. In this article, the most common malignancies are presented, along with a short histopathologic description. For some entities, an immunohistochemical profile is also given that should be helpful in proper diagnosis. As many pathologic diagnoses nowadays also include genetic studies, the most common genetic abnormalities in skull base tumors are presented.
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Project description:Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma primarily involving the brain, spinal cord, or leptomeninges. PCNSL is associated with a relatively poor prognosis compared to other extranodal diffuse large B-cell lymphomas. However, methotrexate-based induction chemotherapy followed by consolidative chemotherapy or high-dose therapy and autologous stem cell transplantation has improved the survival outcome, together with reduced neurotoxicity. Recent studies found that aberrant activation of the B-cell receptor-signaling pathway and activation of the NF-κB are frequent genetic alterations and could be good targets for the treatment of PCNSL. Herein, we have reviewed the current status and recent advances in the biology and management of PCNSL.
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Project description:BackgroundEpendymoma is treated with maximal surgical resection and localized radiotherapy. Minimizing unnecessary exposure to radiation is of paramount importance for young children. Proton radiotherapy (PRT) spares healthy tissues outside the target region, but reports of clinical outcomes are scarce. We report outcomes for 70 patients treated with PRT for intracranial ependymoma.MethodsSeventy patients with localized ependymoma treated with involved-field PRT at the Massachusetts General Hospital between October 2000 and February 2011 were included.ResultsMedian age at diagnosis was 38 months (range, 3 mo-20 y). Nineteen (27%) patients had supratentorial ependymoma and 51(73%) had infratentorial ependymoma. Forty-six (66%) had gross total resection (GTR), and 24 (34%) had subtotal resection (STR). At a median follow-up of 46 months, 3-year local control, progression-free survival, and overall survival were 83%, 76%, and 95%, respectively. STR was significantly associated with worse progression-free survival (54% vs 88%, P = .001) and overall survival (90% vs 97% for GTR, P = .001). In a subset of patients (n = 14), mean intelligence was 108.5 at baseline and 111.3 after mean 2.05 years of follow-up. In a larger group of patients (n = 28), overall adaptive skills were 100.1 at baseline and 100.8 after 2.21 years of follow-up. Few patients developed evidence of growth hormone deficiency, hypothyroidism, or hearing loss.ConclusionOutcomes for children treated with PRT compare favorably with the literature. STR correlated with inferior outcome. The young age at diagnosis and the proximity of critical structures in patients with ependymoma make PRT an ideal radiation modality.
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Project description:Central nervous system (CNS) metastases are common in breast cancer (BC) patients and are particularly relevant as new treatments for BC are prolonging survival. Here, we review advances in the treatment of CNS metastases from BC, including radiotherapy, systemic therapies, and the evolving role of immunotherapy. The use of radiotherapy and chemotherapy is the cornerstone of treatment for CNS metastases. However, new targeted therapies have recently been developed, including anti-HER2 agents and antibody-drug conjugates that have presented promising results for the treatment of these patients.
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Project description:PurposeTo predict the organ at risk (OAR) dose levels achievable with proton beam therapy (PBT), solely based on the geometric arrangement of the target volume in relation to the OARs. A comparison with an alternative therapy yields a prediction of the patient-specific benefits offered by PBT. This could enable physicians at hospitals without proton capabilities to make a better-informed referral decision or aid patient selection in model-based clinical trials.Methods and materialsSkull-base tumors were chosen to test the method, owing to their geometric complexity and multitude of nearby OARs. By exploiting the correlations between the dose and distance-to-target in existing PBT plans, the models were independently trained for 6 types of OARs: brainstem, cochlea, optic chiasm, optic nerve, parotid gland, and spinal cord. Once trained, the models could estimate the feasible dose-volume histogram and generalized equivalent uniform dose (gEUD) for OAR structures of new patients. The models were trained using 20 patients and validated using an additional 21 patients. Validation was achieved by comparing the predicted gEUD to that of the actual PBT plan.ResultsThe predicted and planned gEUD were in good agreement. Considering all OARs, the prediction error was +1.4 ± 5.1 Gy (mean ± standard deviation), and Pearson's correlation coefficient was 93%. By comparing with an intensity modulated photon treatment plan, the model could classify whether an OAR structure would experience a gain, with a sensitivity of 93% (95% confidence interval: 87%-97%) and specificity of 63% (95% confidence interval: 38%-84%).ConclusionsWe trained and validated models that could quickly and accurately predict the patient-specific benefits of PBT for skull-base tumors. Similar models could be developed for other tumor sites. Such models will be useful when an estimation of the feasible benefits of PBT is desired but the experience and/or resources required for treatment planning are unavailable.
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Project description:Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a "wait-and-see" approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.
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Project description:BackgroundCentral skull base osteomyelitis (CSBO) is an incompletely defined, life-threatening infection of the bones of the cranial vault. We describe the clinical features and outcomes of CSBO in Queensland, Australia, over an 11-year period.MethodsMedical record coding enquiries identified cases of CSBO across 6 tertiary hospitals in Queensland, Australia, from January 2010 to December 2020. Epidemiological, demographic, diagnostic, management, and outcome data were collected from each identified case.ResultsTwenty-two cases of CSBO were identified within the study period; the median age was 73 years with a male predominance (73%). High rates of comorbid disease were detected, with a median Charlson Comorbidity Index score of 5. Diabetes mellitus was the most frequently observed condition. Six cases had bone sampling for microbiological diagnosis while the remainder had superficial sampling of contiguous structures. The most common pathogen isolated was Pseudomonas aeruginosa followed by Staphylococcus aureus, with only 1 case of fungal infection. This series demonstrated a mortality rate of 31.8%, with 45.5% of cases left with long-term sequelae including persistent pain and cranial nerve deficits.ConclusionsFour key observations emerged in this series: (1) advanced age and diabetes mellitus are common risk factors for CSBO, (2) limited surgical intervention occurred, (3) microbiological diagnoses relied primarily on superficial sampling, and (4) significant mortality and morbidity was observed. Prospective studies are needed to better understand the optimal approach to the diagnosis and management of CSBO and to improve clinical outcomes.
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Project description:Supratentorial non-skull base meningiomas are the most common primary central nervous system tumor subtype. An understanding of their pathophysiology, imaging characteristics, and clinical management options will prove of substantial value to the multi-disciplinary team which may be involved in their care. Extensive review of the broad literature on the topic is conducted. Narrowing the scope to meningiomas located in the supratentorial non-skull base anatomic location highlights nuances specific to this tumor subtype. Advances in our understanding of the natural history of the disease and how findings from both molecular pathology and neuroimaging have impacted our understanding are discussed. Clinical management and the rationale underlying specific approaches including observation, surgery, radiation, and investigational systemic therapies is covered in detail. Future directions for probable advances in the near and intermediate term are reviewed.
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