Reliable Direction by SRS Financials

Stereotactic radiosurgery SRS Financials is a longtime non-invasive ablative therapy for brain metastases. Early clinical trials with SRS proved that tumor Management fees are excellent to full Mind radiotherapy (WBRT) alone. Therefore, WBRT plus SRS was extensively adopted for sufferers that has a limited number of brain metastases (“restricted range” customarily means one-4). Subsequent trials focused on answering no matter whether WBRT upfront was important in the slightest degree. Determined by current randomized controlled trials (RCTs) and meta-analyses evaluating SRS by yourself to SRS moreover WBRT, adjuvant WBRT leads to greater intracranial Manage; on the other hand, for the cost of neurocognitive operating and Standard of living. These adverse outcomes of WBRT could also negatively impact on survival in more youthful clients. Dependant on the outcomes of those research, therapy has shifted to SRS on your own in people that has a restricted quantity of metastases. Furthermore, RCTs are assessing the part of SRS on your own in sufferers with >4 brain metastases. New developments in SRS consist of fractionated SRS for large tumors and the integration of SRS with targeted systemic therapies that cross the blood Mind barrier and/or encourage an immune reaction. We current On this overview The present high amount proof and rationale supporting SRS since the common of take care of patients with confined Mind metastases, and rising programs of SRS.

Brain metastases are a significant cause of morbidity and mortality in patients with metastatic cancer, with an incidence of up to 65% during the course of illness [1, 2]. The most common primary sites are lung, melanoma, renal, breast and colorectal cancer . Options for patients with brain metastases had been limited to whole brain radiotherapy (WBRT) or supportive care alone, and systemic chemotherapy was often discontinued. The development of brain metastases was viewed as an oncologic terminal event.

As systemic therapies have become more efficacious in patients with metastatic disease, improved survival rates are now being observed. In addition, the patterns of disease progression are shifting such that the incidence of brain metastases is increasing while extra-cranial disease remains controlled. This phenomena is likely a consequence of the central nervous system (CNS) being a sanctuary site from drug penetration. As a result, the management of brain metastases has become a major focus of research, with the intent to improve intra-cerebral control and decrease neurologic deaths.

Although the role of neurosurgery were set up during the nineties as a method to accomplish neighborhood control and extend survival, it was reserved for the minority of patients presenting with an individual metastasis and no other illness outside of the Mind [four-seven]. Still missing was a focal ablative non-invasive treatment that would be applied successfully to some A great deal broader population of clients with Mind metastases. This set the phase for the event of stereotactic radiosurgery (SRS). SRS is often a focused ablative radiation treatment method shipped with sub-millimeter precision towards the tumor localized in a few-Proportions in one-5 fractions.

The main focus of the critique is always to summarize the current large amount evidence to make clear the job of SRS as optimum management for individuals presenting with confined Mind metastases. In addition, we offer an outline of the emerging applications of SRS as it proceeds to evolve into a treatment method alternate to WBRT, Using the intent to maximize neurcognitive purpose and Standard of living (QOL).

PATHOPHYSIOLOGY OF Mind METASTASES

Circulating tumor cells (CTCs) can disseminate from a primary tumor mass to form distant colonies as a result of implantation at an ectopic internet site, such as the brain [eight-ten]. To do so demands CTCs to arrest within the circulation, extravasate from your bloodstream or lymphatics into your brain, and endure and proliferate [eleven-thirteen]. The whole process of metastatic colonization requires a direct interaction of CTCs with endothelial cells and astrocytes within the brain microenvironment. For instance, CTCs which have arrested throughout the capillary mattress direct neighborhood endothelial cells to remodel the adjacent surroundings to promote tumour cell advancement and invasion [14-sixteen]. Even further, metastatic tumour cells recruit systemic stromal cells, which include fibroblasts, to aid with early colonization , and co-opt nearby stromal cells, including reactive astrocytes and microglia, to promote tissue invasion [fifteen, 18, 19]. Astrocytes within the tumour microenvironment may Engage in a role in defending tumour cells from chemotherapy-induced cytotoxicity, through a nonetheless being defined system necessitating mobile-cell contact [twenty, 21]. Tumour cells, via launch of migration inhibitory aspect, interleukin-eight, and plasminogen activator inhibitor 1, induce astrocyte activation and modify the inflammatory milieu to reinforce tumor-mobile proliferation in vitro [22-24]. These molecular procedures depict novel and understudied feasible therapeutic targets for that therapy of intracranial metastatic disorder.

SRS was at first an exceedingly source intense therapy offered only at specialized facilities and indicated just for metastatic individuals with a fantastic everyday living expectancy. The problem lay in prognosticating people successfully and Due to this fact the Radiation Therapy Oncology Group (RTOG) recursive partitioning Evaluation (RPA) [28, 29] was designed. Based upon the affected person's Karnofsky Effectiveness Position (KPS), age, position of the primary tumor and presence of extracranial disease, individuals were grouped into class 1, 2 or three with corresponding median survivals of 7.1, four.two and 2.three months, respectively. While An important growth at the time, the RPA is now thought of overly simplistic as current oncologic selection building is a great deal more elaborate incorporating molecular, histological, scientific and radiographic disorder features. There are actually now extra subtle classification instruments, like the diagnosis-unique graded prognostic evaluation (DS-GPA). This system delivers histology-unique estimates of survival and might independent, for instance, essentially the most favorable breast most cancers clients with the envisioned survival of twenty five months (superb KPS and luminal B style breast most cancers) through the least favorable clients with the predicted survival of 3 months (poor KPS and basal-like breast cancer) . In spite of developments in prognostication of clients with brain metastases, doctors remain mainly not able to properly forecast extended-time period survivors. A research inquiring skilled physicians to estimate survival of a a hundred and fifty individuals with information regarding most cancers sort, range of brain metastases, neurological presentation, added-cranial sickness status, KPS, RPA class, prior total-Mind radiotherapy, and synchronous or metachronous presentation, confirmed that a lot more than 45% of predictions ended up off by more than 6 months and 18% have been off by much more than 12 months . Additional improvements in prognostic assessments including the “liquid biopsy” (a non-invasive blood exam that can detect tumor DNA or RNA fragments or CTCs) are necessary and in growth . These Blend Superior client and tumor precise genomic information and facts to the equation, in order to achieve personalised survival predictions.

Surgery carries on for being a crucial treatment method choice for sufferers with constrained brain metastases. It is actually indicated when metastases are significant (>3-4 cm), or when a pathologic analysis is necessary. Also, operation is most popular from the presence of substantial edema requiring extended high dose dexamethasone, or to possibly reverse neurological deficits. If not, The present proof implies which the efficacy of SRS is enough to attain strong community Handle which is akin to surgical procedure. Although there are no RCTs straight evaluating the two, several trials happen to be described comparing SRS to SRS with WBRT (Table 1), and is a major aim of the overview.

HR: hazard ratio, WHO: globe health and fitness Group, KPS: Karnofsky functionality status, WBRT: total Mind radiotherapy, SRS: stereotactic radiosurgery, yr: 12 months, mos: months, NS: not important, NR: not recorded, NA: not relevant, HVLT-R: Hopkins Verbal Finding out Test revised.

Individuals during the observation group experienced either surgical treatment alone or SRS on your own. Purposeful final result wasn't analyzed independently by surgical procedure or SRS by yourself.

The first RCTs evaluating SRS mimicked the design of your initial surgical studies for brain metastases, and evaluated the addition of SRS to WBRT [33, 34]. These studies verified that SRS improved regional Management, along with a survival gain in picked people with an individual Mind metastasis was demonstrated. These trials had been effective in shifting the paradigm from WBRT alone to WBRT furthermore SRS for patients presenting with confined Mind metastases and a very good general performance status.

Another series of medical trials were meant to solution if WBRT was in the slightest degree essential, and when compared SRS by itself to SRS with adjuvant WBRT. A few RCTs have been reported in patients presenting with as much as 4 metastases [35-37] plus a forth in abstract form . Aoyama et al. reported the initial RCT, randomizing 132 individuals to SRS by itself (sixty five individuals) or WBRT furthermore SRS (67 patients). The primary endpoint was Mind tumor recurrence. Even though the one-calendar year area Command price was large with SRS by itself at seventy three%, further community Regulate with adjuvant WBRT at 89%, was observed. In addition, adjuvant WBRT minimized the rate of distant intra-cranial relapse at 1 12 months from 64% to forty two%. However, these gains in intra-cranial Command did not translate into an advantage with regard to cognition, depending on Mini-Mental Position Test (MMSE), nor survival. In addition, patients experienced better premiums of necrosis and leukoencephalopathy during the WBRT arm. The demo was Hence successful in furnishing the 1st degree 1 proof to explain the relative effect of SRS on your own as opposed to SRS with WBRT.

Rather than the normal endpoint of survival or intra-cranial Handle, Chang et al. took a distinct strategy and evaluated neurocognition as the first endpoint. Importantly, the validated Hopkins Verbal Mastering Check-Revised (HVLT-R) assessment Resource, was used to evaluate neurocognitive performing as opposed to the MMSE which isn't a sensitive examination for neurocognition . Fifty-eight people were being randomized to SRS by yourself (n = thirty) or WBRT in addition SRS (n = 28). Early halting regulations were being invoked for the interim Examination, as well as the review concluded that SRS alone was favored with respect towards the likelihood of neurocognitive decrease at four months submit-cure. This gain was recognized despite the 1 year nearby Manage and distant brain Management rates favoring adjuvant WBRT with absolute gains of 33% and 27%, respectively. The intracranial Regulate outcomes ended up In step with the effects in the Aoyama analyze, but what was not predicted was the survival advantage noticed during the SRS by yourself arm. The median survival was fifteen months while in the SRS alone arm and six months from the SRS with WBRT arm (p = 0.003). This survival result triggered the demo to bear significant scrutiny with quite a few arguing the survival gain for SRS alone was a results of imbalances in between The 2 arms, as additional sufferers handled with SRS additionally WBRT experienced better excess-cranial (extra liver and adrenal metastases) and intracranial condition (more substantial volume of brain metastases) .

The European Firm for Investigation and Remedy of Cancer (EORTC) also took a unique strategy with their Key endpoint specializing in functional independence . They utilized, nevertheless, the greater clinically acquainted Entire world Wellbeing Corporation (WHO) general performance status (PS) scale, and measured enough time to WHO PS deterioration to greater than two. This RCT concluded that the addition of WBRT didn't Enhance the median duration of practical independence (SRS by itself: 10.0 months vs SRS plus WBRT: nine.5 months). The secondary consequence of QOL, measured With all the validated EORTC-QLQC30 tool, was observed to become even worse in patients who been given WBRT in a number of QOL domains . Importantly, these results were being noticed Even with adjuvant WBRT minimizing the 2-12 months local failure level (31% to 19%), distant Mind failure (48% to 33%), and the need for salvage therapies (fifty one% vs. sixteen%). No considerable dissimilarities in survival were being noticed albeit the demo wasn't powered to address survival.

These 4 trials have established the job of SRS by yourself as being the conventional of treatment in individuals with a constrained quantity of Mind metastases, but they have got not been designed to Consider the effects of WBRT on All round survival.

The inclusion criteria throughout the RCTs analyzing SRS alone to SRS additionally WBRT ended up similar (Table 1), on the other hand, the principal endpoints ended up fully diverse, and no demo was designed to Assess General survival. To higher make clear the outcomes of regional Command, distant brain Manage and survival, a meta-Investigation (MAL) was carried out by Tsao, Xu and Sahgal in 2012 . They noted hazard ratios for neighborhood Manage and distant brain control favoring adjuvant WBRT at 2.sixty one and 2.15, respectively, but had been not able to mix the survival benefits as a consequence of constraints in the way in which the info have been reported. Sahgal et al. then done somebody individual information (IPD) MAL of exactly the same RCTs directed at assessing procedure effects on survival, and conduct sub-group analyses . With regard to Total survival, a therapy influence was observed favoring SRS by yourself in patients ≤50 decades. In older people, no survival drawback was noticed with SRS by yourself. With regard to distant brain Regulate, a therapy influence was also noticed with possibility reductions in the development of new Mind metastases in older clients dealt with with WBRT, but no benefit in the more youthful patients (≤50 yrs) treated with WBRT. As anticipated, local Handle was enhanced with additional WBRT in all age teams. The concordance in between a survival detriment and deficiency of advantage in distant Mind Command Regardless of cure with WBRT, while in the younger individuals, led the authors to hypothesize that publicity towards the acknowledged harms of WBRT (mentioned in detail underneath) may negatively effect individual survival. This speculation is provocative, and stays to get validated.

By far the most convincing trial structure to confirm the adverse results of WBRT should be to randomize individuals without having visualized brain metastases to observation or WBRT. This is performed in research assessing prophylactic cranial irradiation (PCI) in both modest mobile lung most cancers (SCLC) [44, 45] and non-little cell lung most cancers (NSCLC) [forty six, 47]. PCI, not dissimilar for the addition of WBRT to SRS, has actually been shown to cut back the chance of intra-cranial relapse. On the other hand, this gain comes with the expenditure of the negative effect on QOL. One example is, sizeable increases in fatigue, urge for food reduction, nausea and vomiting and leg weak point ended up noticed in clients with substantial stage SCLC at 6 and 12 weeks post PCI . Moreover, in domestically advanced NSCLC sufferers, a better decline in HVLT-R steps of fast and delayed recall have been noticed even around one 12 months put up-PCI . With respect to more time-time period adverse effects of WBRT, a devastating consequence is often the development of leukoencephalopathy. In fact, radiation-induced dementia costs are noted to be as superior as eleven% in very long-expression brain metastases survivors (>12 months) right after WBRT , and documented for being higher in clients treated with WBRT and SRS rather than SRS on your own [35, 50].

Extreme N-methyl-D-aspartate (NMDA) receptor stimulation, much like the pathophysiology inherent to Parkinson's dementia , continues to be postulated as one particular system explaining the adverse neurocognitive results of WBRT. As being a technique to mitigate the risk, RTOG 0614 evaluated memantine, a neuroprotective agent that blocks pathologic stimulation of NMDA, in a significant randomized placebo managed demo involving 554 sufferers. At 24 weeks, sixty four% of individuals without the need of memantine and 54% with memantine experienced cognitive function failure dependant on assessment Using the HVLT-R. Even though the Main endpoint didn't achieve importance as a result of high attrition fee, there was a strong craze (p = 0.059) supporting memantine treatment method. Evaluation of secondary endpoints confirmed that memantine considerably extended the time to cognitive decrease and yielded superior benefits for govt perform, processing velocity and delayed recognition at 24 weeks. Ultimately, these facts display nearly all clients suffer cognitive dysfunction with WBRT, and that pharmacologic approaches to mitigate the risk by targeting very similar pathways involved in Parkinson's dementia might be worthy of even further investigation.

Further insight into WBRTs’ mechanism of damage has come from a current Stage 2 trial analyzing hippocampal avoidance WBRT (HA-WBRT). Refined contemporary radiation technological innovation was placed on Restrict dose publicity on the hippocampus to not more than eighty% from the prescribed 30Gy in 10 fractions . This non-randomized phase two trial measured neurocognitive functionality utilizing the HVLT-R, and in contrast outcomes to historic controls handled with common WBRT from the RTOG demo databases. HA-WBRT resulted within a 7% drop in the indicate relative HVLT-R delayed remember, which was considerably decreased than the thirty% drop received from historic controls. While this review is encouraging concerning restricting toxicity from WBRT, a randomized demo is required to fully comprehend the therapeutic price With this technologically complex sort of WBRT.

In 2012, the American Modern society for Therapeutic Radiation Oncology published an proof-primarily based guideline using a series of recommendations over the management of brain metastases . Because that time, the evidence from clinical trials has manufactured it obvious that the preferred up-entrance radiation cure selection for people with minimal Mind metastases is SRS on your own. In truth, the American Modern society for Radiation Oncology (ASTRO) has recently designed a definitive advice within their Opt for Properly marketing campaign and recommend not to routinely insert adjuvant WBRT to SRS for constrained brain metastases . What's more, the just lately revised National Thorough Most cancers Network (NCCN) recommendations now aid SRS on your own even beyond People patients with “confined” metastases, and do not specify an upper Restrict for the quantity of metastases . The latter is ahead contemplating; metastasis counting is likely irrelevant and what matters is normally the suitability of the affected individual for SRS [fifty seven-59]. Hence, the onus is no more on those that address with SRS alone to justify the omission of WBRT; relatively it truly is on individuals who handle with WBRT within a SRS suitable individual.

How about THE Affected person WITH MORE Intensive BRAIN METASTASES?

Prior technological restrictions in SRS technologies restricted the appliance of SRS to clients with just a few Mind metastases. Developments in mounted frame and frameless SRS systems now permit remedy of various metastases in a single session [60, sixty one].

The very first important potential analyze evaluating SRS by yourself for numerous Mind metastases was reported in 2014 . Roughly 1200 individuals with 1-10 SRS qualified metastases had been handled with SRS by itself working with Gamma Knife technologies (Elekta AB, Stockholm, Sweden). The Evaluation was broken down in accordance with the 455 patients with one metastases, 531 people with two to 4 metastases and 208 with 5 to ten metastases. Survival, distant Mind relapse, and native Management fees were not significantly distinct in patients with 5 to ten metastases vs . 2 to 4 metastases. These outcomes are of key significance as they obstacle the dogma that clients with a lot more than four metastases will likely not take advantage of SRS by yourself resulting from shortened survival and may inevitably fall short somewhere else from the Mind. Hence, this demo delivers proof to guidance SRS by yourself in excellent KPS patients with as many as 10 metastases, delivered the person tumor quantity is not more than ten mL and < 3 cm in longest diameter, and the full cumulative volume of all tumors in the Mind is ≤fifteen mL. Many randomized trials are presently analyzing WBRT alone vs . SRS alone in comparable people, and in progress is really a demo analyzing SRS alone as opposed to WBRT in addition SRS boost in individuals with ten to twenty metastases.

Focused THERAPIES Together WITH Mind RADIATION

As compared with traditional chemotherapy, numerous qualified agents have larger penetration in the blood-brain barrier and yield reaction within the brain. Spectacular advancements in disease Command are now being observed even for histologies for instance melanoma which were Earlier regarded as not merely radioresistant but chemoresistant. Desk two [sixty three-seventy five] summarizes picked clinical trials assessing the efficacy of focused therapies by yourself or together with radiation therapy within the treatment method of Mind metastases. Even though, with focused therapies by yourself some impressive response prices are observed, development-free-survival (PFS) costs usually are brief (< 8 months). These outcomes will not be far too dissimilar from what has long been obtained with WBRT alone [33, fifty three]. The exception is in EGFR mutant non-modest cell lung cancers taken care of by using a tyrosine kinase inhibitor. While in the examine by Wu et al. by way of example, the median PFS was >15 months in EGFR mutant tumours handled with erlotinib.

Desk two. Summary of selected trials of specific therapy on your own or in combination with Mind radiation for that treatment method of brain metastases.

PFS: development no cost survival, nPFS: neurologic development no cost survival, OS: Over-all survival, NSCLC: non-modest cell lung cancer, EGFR: epidermal advancement component receptor, WBRT: complete brain radiotherapy, SRS: stereotactic radiosurgery, mos: months, wks: months, NS: not sizeable, NR: not recorded, NA: not relevant

Number of trials have mixed targeted therapies with radiation, and these are also summarized in Desk 2. While, randomized evidence remains to be lacking, You can find recommendation from retrospective data that The mix may possibly bring about enhanced outcomes. Inside the retrospective analysis of the prospective cohort of clients handled with SRS for melanoma Mind metastases, the group that acquired ipilimumab had a significantly extended median survival (21.3 vs 4.9 months) . However, warning must be exercised as concurrent specific therapy and radiation remedy is probably not as innocuous as Beforehand believed. The RCT analyzing SRS with WBRT on your own, as opposed to together with erlotinib or temozlomide, noted appreciably better Quality three to 5 toxicity prices in The mix arm; far more importantly, survival was worse although it didn't achieve statistical importance . An important limitation of this examine was which the targeted therapy was not biomarker-driven and will partly account with the bad survival noticed. Caution also must be taken as There may be evidence that Mind metastases and primary tumors may perhaps harbor unique genetic alterations. In one analyze of 86 matched Mind metastases and primary tumors, clinically enlightening alterations in fifty three% of Mind metastases were not detected in the principal tumor .

The rising evidence suggests that qualified therapies will play a substantial purpose during the treatment method of Mind metastases. We postulate that Despite the fact that targeted agents is probably not successful in controlling gross condition while in the brain, They could be successful in controlling micro-metastatic ailment in the brain. As a result, a rational strategy could possibly be to combine focused therapies with SRS alone, overcoming the limitation of SRS in addressing micrometastatic sickness in the Mind and leading to less distant brain failures. Another number of years will generate thrilling facts as There are a selection of trials in progress employing this approach.

Improvements IN SRS - INDICATIONS AND Apps

As tumors get more substantial, SRS dosing is counter-intuitively reduced with respect to tumor control, to maintain basic safety to the conventional brain tissue; normally, the chance of radiation necrosis turns into prohibitive . Consequently, tumors bigger than four cm have normally been excluded from single portion SRS. If your tumors are non-operable, then these individuals are actually taken care of with WBRT Inspite of its poor area control. The appearance of non-invasive head immobilization units, on-board graphic-guidance devices and Highly developed radiation supply software program has bring on the apply of hypofractionated frameless stereotactic radiotherapy (SRT) [60, seventy eight]. In essence by fractionating, the safety profile with regard to the conventional Mind tissue toxicity is enhanced, and the total tumor dose might be escalated this kind of that doses like 24Gy in three fractions and thirty-40Gy in 5 fractions are actually commonplace. 1 appealing retrospective series described greater rates of Regulate and reduce rates of toxicities with hypofractionated SRT (36Gy in six fractions) as compared with single fraction SRS . On the other hand, this observe remains to be in its infancy and we're wanting a RCT to ascertain if one portion SRS ought to be reserved just for little metastases (e.g. 1-two centimeters), as the data counsel worse regional Management for greater tumors [80, eighty one]. Figure one is really an example of the efficacy of hypofractionated SRT in a significant tumor. This client would have otherwise been excluded from solitary fraction SRS and taken care of with WBRT upfront (in addition or minus a SRS boost), or operated on.

A. MRI of 3.6cm suitable cerebellar metastases from lung most cancers. B. Really conformal remedy approach Together with the a hundred% (environmentally friendly line) and eighty% (blue line) isodose strains wrapping tightly within the gross tumour (crimson colorwash), and arranging focus on quantity (orange colorwash). The brainstem (blue colorwash) is spared from significant dose. (B) MRI two months post completion of radiation (30Gy in five fractions). C. Comprehensive resolution with the tumour at one year.

In publish-operative individuals, the practice of routinely treating with WBRT is also becoming outdated. You can find expanding utilization of SRS into the article-operative surgical cavity as a method to spare sufferers through the adverse results of WBRT and to boost community Command [eighty two-ninety three]. With the Sunnybrook Odette Cancer Centre, We've adopted hypofractionated SRT as our typical of care, delivering 30-35Gy in five fractions for the publish-operative tumor mattress . Fractionation has the advantage of reducing the adverse outcomes to the traditional tissues, on condition that the targets tend to be significant and irregularly formed. Our Preliminary results have demonstrated 1 12 months nearby Regulate fees of ∼80% in people who definitely have either recurred and re-operated upon after past WBRT, or in individuals without having prior historical past of WBRT and operated on. There exists an ongoing study assessing post-surgical cavity one fraction SRS by yourself versus WBRT and may be a apply-defining analyze .

Over the past many many years, clinical trials have knowledgeable us about the appropriate administration of clients with Mind metastases. Originally, SRS was thought of an adjunct to WBRT in selected sufferers presenting which has a restricted range of brain metastases. Even so, the job of WBRT has considering that been questioned as Now we have acquired of its probable to adversely affect QOL and neurocognition. Consequently, SRS by yourself has emerged as The existing standard of care with Degree 1 evidence to aid its observe. Current analysis is focused on the evaluation of broader programs of SRS to several medical situations that were historically deemed absolute indications for WBRT. One example is, SRS by yourself is now remaining evaluated while in the treatment of five or more brain metastases, As well as in article-operative individuals. A different era of trials can be emerging investigating the impression of targeted therapies concurrent with SRS.

Clinical trials in sufferers with Mind metastases are a major challenge as summarized from the recent reports through the Response Evaluation in Neuro-Oncology (RANO) Mind metastases team [95, 96]. They advise for demo structure and reaction assessment that trials be tumor or biomarker particular, that assessment be dependant on distinction-Improved MRI, that baseline and repeated neurocognitive and QOL tests be carried out with validated and sensitive devices, that stratification be determined by excess-cranial disease position, Which appropriate timing be thought of with regards to endpoint tests. Eventually, the oncology Neighborhood has regarded that the development of brain metastases is not the terminal oncologic event with the past.

CONFLICTS OF Desire, Economic DISCLOSURES

Dr. Arjun Sahgal has received honorarium from past educational seminars for Medtronic Kyphoplasty division and Elekta AB, Dr. Sahgal has also obtained research grants from Elekta AB, usually there aren't any conflicts of desire to reveal.