50-Year History of the Evolution of Spinal Metastatic Disease Management

Abstract

Spine metastases are a significant source of morbidity in oncology. Treatment of these spine metastases largely remains palliative, but advances over the past 50 years have improved the effectiveness of interventions for preserving functional status and obtaining local control while minimizing morbidity. While the field began with conventional external beam radiation as the primary treatment modality, a series of paradigm shifts and technological advances in the 2000s led to a change in treatment patterns. These advances allowed for an increased role of surgical decompression of neural elements, a shift in the stereotactic capabilities of radiation oncologists, and an improved understanding of the radiobiology of metastatic disease. The result was improved local control while minimizing treatment morbidity. These advances fit within the larger framework of metastatic spine tumor management known as the Neurologic, Oncologic, Mechanical, and Systemic (NOMS) disease decision framework. This dynamic framework takes into account the neurological function of the patient, the radiobiology of their tumor, their degree of mechanical instability, and their systemic disease control and treatment options to help determine appropriate interventions based on the individual patient. Herein, we describe the 50-year evolution of metastatic spine tumor management and the impact of various advances on the field.

1. Introduction

Spine metastases are a significant source of morbidity in oncology patients and affect approximately 20% of the cancer population.[1,2] Despite improved survival rates seen with the development of newer systemic agents over the past decade, the treatment for metastatic spine disease remains largely palliative with the goal of achieving pain relief, functional neurologic recovery, improving health-related quality of life, long-term tumor control, and an early return to systemic therapy. In the past 50 years we have witnessed revolutionary advances in both spine radiation and surgery that have fundamentally improved the ability to provide effective, durable palliation with a significant reduction in treatment-related morbidity. Early treatment for spine metastases largely was based on low-quality evidence stemming from small, non-randomized studies that were heavily influenced by institutional bias. This resulted in a lack of consensus regarding optimal treatment strategies.

In the 1970s, outcomes from decompressive laminectomies without instrumentation resulted in very poor outcomes due to iatrogenic instability and postoperative neurologic decline.[3] Consequently, for the subsequent two decades, the treatment pendulum swung away from surgery and toward conventional external beam radiation therapy (cEBRT) (i.e., 30 Gy in 10 fractions) as first line treatment despite a recognition that this radiation strategy was ineffective for solid-tumor malignancies. In the early 1990s, newly developed segmental instrumentation systems were applied to spine-tumor reconstruction leading to improved outcomes and a re-evaluation of the role of surgery.[4] In 2005, Patchell et al. published a prospective randomized trial that firmly established the benefit of surgery plus cEBRT over cEBRT alone in the treatment of solid-tumor spine metastases.[5] This ushered in an era of aggressive surgery, including complicated anterior transcavitary approaches and en bloc resections. [4,6–11]

Over the past 15 years, the development of spine stereotactic radiosurgery (sSRS) has fundamentally changed the treatment paradigm.[12–17] The ability of sSRS to deliver ablative radiation doses that are histology independent changed the indications for and types of surgery required.[14,18,19] The pendulum has swung back toward radiation as the principal treatment modality with surgery used in selective cases as an adjuvant to sSRS for recovery of neurologic function, improvement in radiation target volume coverage within spinal cord dose constraints, and spinal reconstruction.[12,20,21] Intralesional gross total or en bloc excisions are no longer required and largely have been supplanted by separation surgery to create a safe sSRS target through epidural decompression.[13,22]

As radiation and surgical techniques evolved, so too did patient treatment algorithms. The NOMS decision framework developed at Memorial Sloan Kettering Cancer Center (MSK) in 2004 is currently the most commonly used system internationally and is updated every 5 years to integrate new evidence-based medicine and advances in technology.[21] The four sentinel decision points in NOMS are Neurologic, Oncologic, Mechanical (stability) and Systemic disease. The Neurologic assessment considers both clinical and radiographic parameters, including the presence of myelopathy, functional radiculopathy and the degree of epidural spinal cord compression (ESCC). The Oncologic consideration reflects the most effective strategy for achieving local tumor control, which is principally based on the expected radiation and systemic treatment responses. Mechanical stability considers whether an interventional procedure or external orthosis is required to treat the sequelae of pathologic fractures. The final consideration is the extent of systemic disease and medical co-morbidities, which are often the most important determinants of whether a patient is a candidate for surgery or radiation therapy. In this paper, the evolution of critical advances leading to current treatment paradigms will be assessed in the context of the NOMS decision framework.

2. Neurologic and Oncologic

2.1. The Intersection of Radiation and Surgery

The neurologic and oncologic considerations are combined to optimize the preservation of neurologic function and local tumor control. The role of radiation therapy and surgery has evolved over the past five decades in large part due to the development of sSRS, which provides histology independent, durable tumor control and has revolutionized the NOMS framework in both the neurologic and oncologic domains.[14,16–18] Prior to the 2000s, cEBRT was the only widely available modality for treating spine metastases.[5] The dose fractionation scheme was selected to minimize toxicity to organs at risk (OARs) such as the spinal cord, kidneys, bowel, and esophagus, but was largely ineffective at controlling that vast majority of spine metastases. In 1978, Gilbert and Posner at MSK first reported a differential radiosensitivity to cEBRT, which was subsequently confirmed by numerous other studies that stratified responses based on tumor histology.[3,12] In a review by Gerszten et al., hematologic and hormone-driven solid tumors (i.e., breast and prostate carcinoma) were considered good responders, demonstrating 80% 2-year local tumor control rates, compared to the remaining solid tumors which demonstrated 30% 2-year local control rates and median durable responses of 3 months.[12] Despite the very poor responses in most spine metastases, the substantial morbidity associated with surgery provided the rationale for the continued use of cEBRT as first line therapy regardless of tumor histology, the degree of spinal cord compression, or neurologic injury.[4,6]

Early surgical approaches relied on laminectomies without supplemental instrumentation. This approach was ineffective for decompressing the spinal cord and created iatrogenic instability often associated with neurologic decompensation, progressive pain, and deformity. In the 1990s through mid-2000s there was a resurgence of interest in utilizing advanced surgical approaches combined with the development of new anterior and posterior segmental instrumentation, specifically pedicle and lateral mass screw-rod fixation.[4,6,7] Materials transitioned from stainless steel to titanium, which improved postoperative MR-imaging and the fidelity of radiation delivery. New anterior reconstruction techniques were introduced, including polymethylmethacrylate (PMMA), titanium and PEEK carbon fiber cages, and anterior plating systems.[25–27]

During this period, the goal of operations for spine metastases was not only spinal cord decompression for neurological function, but also gross total resection of the tumor followed by cEBRT to achieve durable tumor control.[4–6,8] Early in this period of surgical evolution, transarterial embolization for hypervascular tumors (i.e., renal cell carcinoma) was developed, which facilitated safer intralesional, gross total tumor resection.[28–32] Initially, transcavitary retroperitoneal and thoracotomy approaches were adopted from general and thoracic surgery to provide direct access for intralesional vertebral body and paraspinal tumor resection as well as epidural spinal cord decompression.[4,33] However, anterior transcavitary approaches proved to be prohibitively morbid in most metastatic patients who often had significant medical co-morbidities and extensive disease burdens in addition to prior surgeries and radiation treatments. The inherent morbidity of anterior transcavitary approaches led to the development of posterolateral thoracotomy-type approaches such as the lateral extracavitary and costotransversectomy approaches.[34–37] Ultimately, the field shifted to posterior-only approaches such as the single-staged posterolateral transpedicular approach (PTA), which allowed for circumferential decompression of the spinal cord and reconstruction of the vertebral body with PMMA and Steinman pins followed by long-segment posterior instrumentation.[8,20] In 2000, Wang et al. reported 140 patients undergoing PTA for high-grade epidural spinal cord compression (ESCC).[8] Overall, 75% of non-ambulatory patients regained the ability to walk and 90% achieved good to excellent outcome scores (ECOG 0 to 2). Complications occurred in 14.3% of patients with a wound complication rate of 11.4%. The median overall survival in their study population was 7.7 months.

With surgical techniques improving, the role of surgery vs. cEBRT remained unclear until 2005 when Patchell et al. reported a landmark prospective randomized trial comparing cEBRT to surgery followed by cEBRT for patients presenting with high-grade spinal cord compression due to radioresistant solid-tumor malignancies.[5] Exquisitely radiosensitive hematologic malignancies and germ cell tumors were excluded. In every outcome variable, the surgical-arm demonstrated improved outcomes compared to the cEBRT cohort, including maintenance or recovery of ambulation and bowel and bladder function, lower narcotic requirements, and improved survival. Based on the Patchell trial and numerous other studies demonstrating good surgical outcomes, Bilsky et al. reported Cochrane review–based recommendation of the Spine Oncology Study Group (SOSG) that patients with high-grade spinal cord compression resulting from solid tumor malignancies should undergo surgery followed by radiation therapy.[13]

Whereas the Patchell study was critically important in defining the role of surgery, the truly groundbreaking advance over the past 20 years in the treatment of metastatic spine tumors has been sSRS. sSRS is defined as the delivery of high-dose, hypofractionated, photon-beam radiation often defined as 16 to 24 Gy single fraction or 24 to 40 Gy in 2 to 5 fractions.[15,17,38] sSRS is delivered using highly conformal techniques, such as image-guided intensity modulated radiation therapy (IGRT) and volumetric arc therapy (VMAT), which precisely target the tumor within the constraints of normal tissue tolerance.[39] Hypofractionated radiation overcomes the radioresistance seen with cEBRT by substantially increasing the biologic equivalent dose, which leads to increased lethal double-stranded DNA breaks and invokes unique radiobiologic mechanisms such as endothelial apoptosis that is mediated by the acid sphingomyelinase pathway and cytotoxic T-cell immunogenic responses.[19,40,41] The benefits of sSRS compared to cEBRT include shorter treatment times, delivery of an ablative radiation dose resulting in histology-independent, durable tumor control, and the ability to safely re-irradiate those who have failed prior radiation.[14,18,22]

The major constraint on the safe delivery of a cytotoxic-tumoral radiation dose is spinal cord toxicity. The spinal cord dose received is contingent upon the degree of ESCC. In 2010, Bilsky et al. reported the development of a validated ESCC scoring system predicated on MR-based axial T2-weighted images that standardized reporting.[42] The result was a highly reliable and validated system for assessing the feasibility of delivering a cytotoxic sSRS dose to the tumor within spinal cord constraints. In this system, 0 is bone only; 1a, b, and c are different degrees of thecal sac compression without spinal cord compression; 2 is spinal cord compression with CSF visualized; and 3 is spinal cord compression with CSF obliterated. Traditionally ESCC grades 2 and 3 are considered to be high-grade ESCC.

Numerous studies have demonstrated the benefit of using sSRS in achieving durable local control rates greater than 85% as definitive treatment for radioresistant solid tumor metastases presenting with ESCC 0 to 1c.[14,16,17] Yamada et al. demonstrated dose-dependent outcomes in 811 tumors treated in a cohort of 657 patients at MSK.[14] The prescription dose to the planning target volume ranged from 16 to 24 Gy single fraction. Dose was analyzed as a continuous variable and an optimal cut point was used to establish a low dose vs. high dose cohort with a median dose of 16.4 Gy and 22.4 Gy, respectively. The local failure rate in the low- and high-dose cohorts was 5% vs. 0.41% at one year and 20% vs 2.1% at 4 years, respectively. The only significant factor in the incidence of local failure was the dose of sSRS. As opposed to cEBRT, the tumor histology and size of the tumor did not impact tumor control rates for sSRS. These studies led to a change in the recommended treatment of solid tumor spine metastases presenting with ESCC 0 To 1c, particularly those presenting with oligometastatic disease.

Based on the superb outcomes using sSRS, Bilsky et al. in a Cochrane review from the SOSG made a strong recommendation that patients with RCC in the absence of spinal cord compression (i.e., ESCC 0 to 1c) undergo stereotactic radiosurgery rather than en bloc resection.[13] This paper represented a major paradigm shift and helped sSRS to become first-line therapy for radioresistant oligometastatic disease rather than en bloc resections, which were increasingly being applied to oligometastatic spine disease despite a paucity of published data demonstrating improved local-tumor control or survival and most case reports uniformly failing to account for the significant surgical morbidity associated with the technique.[4,6,9,34,44] Klekamp and Samii reported outcomes using aggressive intralesional surgery followed by cEBRT, which demonstrated a cumulative incidence of local recurrence at 1 year of 70% and increasing to 96% at 4 years.[9] A major determinant of recurrence in this study was radioresistant solid tumor histology.

Whereas the indications for surgery have remained unchanged since the publication of the Patchell study, the efficacy of postoperative sSRS has shifted surgical objectives.[18,20,22,27] The improved local control of sSRS allowed for separation surgery, a surgical technique whereby the thecal sac is decompressed and reconstituted to create a 2mm margin between the tumor and the spinal cord for targeting constraints. The technique is similar to that of PTA, but the histology independent responses of sSRS eliminated the need for gross total resection of lesions and only requires targeting of the residual epidural tumor and associated bony or paraspinal involvement.[18,22,27] Laufer et. al. evaluated the strategy of separation surgery followed by sSRS (i.e., hybrid therapy) in 186 patients operated on for high-grade ESCC for predominantly radioresistant tumor histologies, with 50% of those patients having failed prior radiation therapy.[22] The three dose strategies used were high-dose single fraction (24 Gy), high-dose hypofractionated (24 to 30 Gy in 3 fractions) and low-dose hypofractionated (18 to 36 in 5 to 6 fractions). The 1-year cumulative recurrence rate was 16.4%, but patients undergoing high-dose single fraction or high dose hypofractionated radiation had local recurrence rates of 9% and 4%, respectively. Hussain et al. recently reported hybrid therapy for RCC using the same dose strategies with a median dose of 27 Gy in 3 fractions (i.e., high-dose hypofractionated).[18] The 1-yr and 2-yr cumulative incidence of recurrence were 4.6% and 8.2%, respectively. Overall, 90% of patients remained ambulatory with an ECOG of 0 to 2 at one year follow-up.

3. Complications and Limitations

3.1. Radiation Therapy Complications and Limitations

Ablative sSRS doses have been established to achieve optimal tumor control and pain relief, but equally as critical, so have dose constraints for OARs. The major OARs are the spinal cord and cauda equina, but the radiation port often also includes functional nerve roots, the brachial and lumbosacral plexuses, esophagus, bowel, kidneys, and the vertebral body. Using current OAR constraints, toxicity is typically mild and self-limited and includes diarrhea, esophagitis, mucositis, dysphagia, neuritis, and myositis. Organ displacement strategies have been developed to create safer targets for sSRS such as saline infusions into the retroperitoneum to displace the bowel and kidneys and thoracoscopic placement of hydrogel to temporarily displace the esophagus away from the spine.[39,45] Vertebral compression fractures (VCF’s) after sSRS have been reported with an incidence ranging from 6% to 39%.[46,47] Jawad et. al. reported that the higher incidence of VCF’s is observed in those receiving higher dose sSRS;[48] however, Virk et. al. reported that a small minority of these fractures are symptomatic and require treatment such as percutaneous cement augmentation.[47] The improved tumor control demonstrated with higher dose sSRS mitigates the symptomatic fracture risk.

The most significant concern with regard to sSRS toxicity is radiation-induced myelitis. Gibbs et al. reported outcomes from a multi-institutional review of sSRS in which 0.6% (6/1075) developed myelitis.[49] Similarly, MSK reviewed a series of 476 patients undergoing sSRS where the spinal cord dose was limited to a Dmax of 14Gy and reported a 0.42% risk of reversible spinal cord injury.[14] However, this spinal cord constraint prevents effective treatment of tumors with high-grade ESCC even in the absence of myelopathy or cauda equina syndrome. Michael Lovelock et. al. conducted a dose failure analysis in which they found that all post-sSRS tumor progression had received less than 15Gy to even a small percentage of the planning target volume.[50] Accepting a cord Dmax of 14 Gy with a 10%/mm dose falloff, the consequence would be either underdosing at the margin of the spinal cord with a high-risk of epidural tumor progression and progressive ESCC or conversely overdosing the spinal cord with resultant myelitis. Rothrock et. al. recently reported outcomes in 31 tumors presenting with grade 2 ESCC that were treated with hypofractionated radiation doses (i.e., 24 to 50 Gy in 3 to 5 fractions) with 1- and 2-year incidence of loco-regional failure in their study was 10.4% and 22%, respectively.[38] Treatment related radiographic fractures occurred in 12% of patients. This study suggests that the treatment of high-grade metastatic ESCC is possible, but progress in this sphere has been incremental to date. ESCC grade 3 compression and those presenting with myelopathy from solid tumor malignancies continue to require surgical intervention in accordance with the Patchell study.[5]

3.2. Surgical Complications and Limitations

The epidural decompression technique of separation surgery has largely remained the same as that described for PTA surgery, but significant advances in spinal implants have decreased surgical morbidity, improved radiation delivery, and enhanced postoperative MR-imaging for recurrence. Traditionally, for a single spine segment decompression, screw-rod instrumentation was placed a minimum of two levels above and two levels below the index tumor level.[20] Recently PMMA-augmented pedicle screws have been integrated into separation surgery which allows instrumentation to be placed at single segments adjacent to the index level.[27,51] PMMA overcomes the two major hurdles leading to implant failure: osteoporosis and adjacent segment-tumor progression. Papers reviewing failed fixation of long vs. short-PMMA augmented constructs showed virtually identical failure rates requiring revision of 2.8% and 2.2%, respectively.[27] Screw placement for PMMA delivery is improved with intraoperative CT-image guidance and robotic trajectory planning.

The second major advance in spinal implants was the development of PMMA-augmented PEEK carbon fiber screw-rod systems which were introduced in 2020.[52] This is the first instrumentation system created specifically for patients with spine tumors as opposed to current screw-rod systems which were developed for deformity, degenerative, and trauma indications. As opposed to titanium, PEEK-carbon fiber does not create radiographic artifacts on MR-imaging which can obscure the detection of tumor-recurrence. Additionally, PEEK carbon fiber does not create shielding issues that need to be accounted for in photon-beam sSRS treatment.[26] It is also the only implant material that reliably can be used with charged particle proton-beam and carbon-ion radiation, which increasingly are being integrated into treatment algorithms for metastatic spine tumors.[53–56]

From a complication perspective, wound dehiscences and infections are major sources of postoperative morbidity. SSRS reduces wound complications compared to cEBRT. Ghogawala et al. performed a retrospective review of 123 patients in which they demonstrated a 46% risk of wound complications or infection when pre-operative cEBRT was delivered within 6 weeks of open surgical treatment.[57] Keam et al. reviewed a cohort of 165 patients undergoing preoperative radiation using either cEBRT or sSRS.[58] The wound complication rate with cEBRT vs. sSRS was 17% vs. 6% (p=.11), respectively. Although not statistically significant, the ability to spare the operative corridor using IGRT delivery of sSRS will continue to lower this complication rate and permit safe delivery of perioperative sSRS.

The majority of post-surgical infections are soft tissue related as opposed to osteomyelitis. Seyfer and Joseph described trapezius flaps for wound salvage in 1984.[59] Similarly, Vitaz et al. described 37 patients salvaged with local advancement or transposition flaps for wound dehiscence or infection following surgery for spine malignancies or degenerative disease.[60] The mean number of surgeries for wound salvage was 1.3, and 70% of those cases had positive wound cultures. Overall, 92% of patients healed from their index revision surgery and the spinal implants were salvaged in 97% of cases. These flaps are now standard for treating wound infections and dehiscences and increasingly are being used prophylactically during the index surgery.

4. Mechanical Instability

In NOMS, mechanical instability is a separate consideration from the neurologic and oncologic assessments as radiation does not play a role in the treatment of pathologic fractures. Using a modified Delphi approach, the SOSG defined, codified and validated the Spine Instability Neoplastic Score (SINS) to assess tumor-related fractures.[61] The weighted system combines the presence of mechanical pain with 5-radiographic criteria including tumor location, bone quality, vertebral body fracture, posterior element involvement, and degree of deformity. SINS has been critically important in standardizing the assessment and treatment of pathologic fractures.

Minimally invasive percutaneous bone cement augmentation procedures were developed early in the 2000s to stabilize thoracic and lumbar burst and compression fractures. The most commonly used techniques, vertebroplasty and kyphoplasty, are controversial regarding pain relief in the treatment of osteoporotic fractures. Two prospective trials demonstrated no difference between percutaneous bone cement augmentation and best medical management.[62,63] Conversely, in 2011, Berenson et al. reported outcomes from the CAFÉ’ study, a prospective randomized trial comparing kyphoplasty to non-operative therapy for pathologic vertebral compression fractures.[64] Patients undergoing kyphoplasty demonstrated a significant reduction in pain, improvements in quality of life, and functional recovery at one month that was maintained at one year follow-up.

A failure analysis of standalone percutaneous bone cement augmentation demonstrated that patients with vertebral compression fractures who additionally had posterior element disease did not experience significant pain improvement. This problem led to the strategy of kyphoplasty at the index fracture level and the placement of percutaneous cement-augmented pedicle screws to provide an additional posterior tension band. In a review of 44 patients, Moussazadeh et al. reported outcomes demonstrating that all patients presenting with severe pain resolved to minimal or no pain postoperatively.[51] This construct was durable with the exception of one asymptomatic screw pull-out and one adjacent-level vertebral body fracture.

5. Systemic

The final consideration in the management of spine metastases is the assessment of systemic disease and medical co-morbidities that impact the ability for patients to tolerate the proposed treatment and to determine if it is rational in the context of their disease. It must be recognized that many treatment decisions are made urgently or emergently, rendering the need to make these decisions often with limited information and work-up. In metastatic disease, expected survival is often used as a major determinant for the type of treatment offered. Survival has been extended for virtually every metastatic tumor histology due to the development and integration of biologics and checkpoint inhibitors. Rothrock, et. al demonstrated the impact of newer systemic agents in a 20-year review of metastatic spine surgical data at MSK.[65] Their work demonstrated a 20% improvement in survival over that time period. Newer predictive survival models also have been developed and validated in the era of biologic and checkpoint inhibitors with two examples being the SORG nomogram[66] and the New England Metastatic Spine Score.[67] Massad et al. demonstrated that these models were better at predicting 1-year survival compared to traditional scoring systems such as the Tomita, revised Tokuhashi, and revised Bauer scores.[68] Additionally, Massad et al. developed machine learning algorithms to assess frailty, mortality and complications related to metastatic spine tumor surgery.[69] This analysis demonstrated that patients with sarcopenia and lower visceral and subcutaneous adiposity had significantly worse postoperative outcomes and more limited survival.

Although it seems somewhat counterintuitive that local radiation can impact systemic disease control, the integration of sSRS into the treatment of oligometastatic tumors (i.e., 1 to 5 metastases) has now been demonstrated in multiple studies to improve survival.[16,17,70,71] Palma et al. reported outcomes from the SABR-COMET trial, a randomized phase 2 trial assessing overall survival in patients with a controlled primary tumor who were treated with standard of care (SOC) vs. SOC plus stereotactic ablative radiotherapy (SABR) for 1 to 5 metastases.[16] The 5-year overall survival rate was 17.7% in those receiving SOC vs. 42.3% in those receiving additional SABR (p=.006). Zelefsky et al. reported outcomes from a phase 3 randomized trial examining the utility of high-dose single fraction radiation (24 Gy) compared to high-dose hypofractionated radiation (9 Gy x 3 fraction) in the treatment of oligometastatic bone disease.[17] Single fraction radiation demonstrated lower rates of local recurrence compared to the hypofractionated regimen with rates of 2.7% and 5.8% at 2 and 3 year vs. 9.1% and 22%, respectively (p=.0048). A significant difference was also seen in the 2- and 3-year cumulative incidence of distant metastatic progression, which was 5.3% in the single fraction cohort vs. 10.7% and 22.5% in the hypofractionated cohort, respectively (p=.010).

6. Conclusion

Extraordinary strides have been made over the past 50 years in providing effective palliation for this very complicated patient population. Advances in radiation, surgery, and interventional procedures have improved local tumor control while lessening morbidity. The NOMS framework was developed to incorporate new technologies and evidence based medical advances as they become available over time, and as a result, has remained relevant over the past decade of oncologic advancement. As we begin to incorporate genomics into decision making as both predictors of radiation response and overall survival, changes to the NOMS framework are on the horizon. While the past 50 years have seen numerous advances, the potential for explosive and impactful growth within the field of spine oncology is imminent. Research into the ability to maximize the radiobiologic mechanisms of sSRS through combination therapy with radiosensitizers such as VEGF-TKI therapy or through the induction of the abscopal effect with combination checkpoint inhibitors carries with it the alluring promise of improved therapeutic efficacy through less invasive treatments.

Synopsis:

The past 50 years have seen remarkable advances in the ability to deliver stereotactic, ablative doses of radiation to the spine, enabling a paradigm shift away from gross total lesion resection to the less morbid concept of separation surgery. As the treatment options and their associated morbidity have evolved, the Neurologic, Oncologic, Mechanical, and Systemic (NOMS) decision framework has served as a dynamic tool to help guide decision making. Herein we will describe these advances as well as the utility of the NOMS decision framework.