Dependable Advice by SRS Financials

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Stereotactic radiosurgery SRS Financials is an established non-invasive ablative therapy for brain metastases. Early medical trials with SRS proved that tumor Command charges are top-quality to entire Mind radiotherapy (WBRT) by itself. Because of this, WBRT as well as SRS was widely adopted for individuals by using a minimal range of brain metastases (“limited quantity” customarily signifies one-four). Subsequent trials focused on answering no matter whether WBRT upfront was essential in any respect. According to latest randomized controlled trials (RCTs) and meta-analyses evaluating SRS alone to SRS in addition WBRT, adjuvant WBRT leads to superior intracranial Handle; nevertheless, within the expense of neurocognitive working and Standard of living. These adverse results of WBRT can also negatively influence on survival in more youthful clients. Depending on the outcome of these scientific tests, therapy has shifted to SRS on your own in sufferers by using a minimal range of metastases. Moreover, RCTs are assessing the purpose of SRS by yourself in clients with >four Mind metastases. New developments in SRS involve fractionated SRS for large tumors and the integration of SRS with targeted systemic therapies that cross the blood Mind barrier and/or stimulate an immune response. We existing In this particular evaluation the current superior amount evidence and rationale supporting SRS since the normal of take care of clients with minimal brain 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 position of neurosurgery had been proven during the nineties as a method to attain local Command and lengthen survival, it absolutely was reserved to the minority of sufferers presenting with one metastasis and no other ailment over and above the brain [four-seven]. Continue to missing was a focal ablative non-invasive treatment that would be utilized efficiently to some Significantly broader population of patients with brain metastases. This set the phase for the event of stereotactic radiosurgery (SRS). SRS is actually a focused ablative radiation remedy sent with sub-millimeter precision for the tumor localized in three-Proportions in one-5 fractions.

The main focus of this critique is to summarize The existing large level evidence to make clear the role of SRS as ideal management for patients presenting with constrained Mind metastases. In addition, we provide an overview of your emerging apps of SRS because it continues to evolve into a cure alternate to WBRT, Along with the intent to maximize neurcognitive purpose and quality of life (QOL).

PATHOPHYSIOLOGY OF Mind METASTASES

Circulating tumor cells (CTCs) can disseminate from a Main tumor mass to kind distant colonies by implantation at an ectopic web site, like the brain [eight-ten]. To do so demands CTCs to arrest throughout the circulation, extravasate from your bloodstream or lymphatics to the Mind, and survive and proliferate [11-thirteen]. The entire process of metastatic colonization consists of a direct conversation of CTCs with endothelial cells and astrocytes within the brain microenvironment. By way of example, CTCs that have arrested inside the capillary mattress immediate community endothelial cells to remodel the adjacent ecosystem to market tumour mobile progress and invasion [14-sixteen]. Further, metastatic tumour cells recruit systemic stromal cells, like fibroblasts, to aid with early colonization , and co-choose regional stromal cells, for example reactive astrocytes and microglia, to promote tissue invasion [fifteen, 18, 19]. Astrocytes within the tumour microenvironment could also Enjoy a role in protecting tumour cells from chemotherapy-induced cytotoxicity, via a nonetheless being described system requiring mobile-cell Get in touch with [twenty, 21]. Tumour cells, via launch of migration inhibitory element, interleukin-eight, and plasminogen activator inhibitor 1, induce astrocyte activation and modify the inflammatory milieu to reinforce tumor-cell proliferation in vitro [22-24]. These molecular procedures symbolize novel and understudied possible therapeutic targets for the procedure of intracranial metastatic ailment.

SRS was at first a really useful resource intensive therapy presented only at specialised centers and indicated only for metastatic clients with a great daily life expectancy. The obstacle lay in prognosticating people proficiently and Due to this fact the Radiation Therapy Oncology Team (RTOG) recursive partitioning analysis (RPA) [28, 29] was created. Based on the affected individual's Karnofsky Functionality Position (KPS), age, status of the key tumor and presence of extracranial illness, sufferers were being grouped into course one, two or 3 with corresponding median survivals of 7.one, four.2 and 2.three months, respectively. Although a major development at enough time, the RPA is currently thought of extremely simplistic as present oncologic final decision creating is a lot more intricate incorporating molecular, histological, medical and radiographic condition features. You will discover now far more advanced classification applications, like the diagnosis-unique graded prognostic evaluation (DS-GPA). This technique provides histology-precise estimates of survival and may different, for example, the most favorable breast most cancers people by having an expected survival of twenty five months (outstanding KPS and luminal B variety breast most cancers) from your minimum favorable clients with an envisioned survival of 3 months (inadequate KPS and basal-like breast most cancers) . Irrespective of improvements in prognostication of clients with brain metastases, doctors are still mostly struggling to precisely forecast lengthy-phrase survivors. A analyze asking skilled medical professionals to estimate survival of a a hundred and fifty clients with specifics of most cancers type, range of brain metastases, neurological presentation, further-cranial disorder position, KPS, RPA course, prior complete-brain radiotherapy, and synchronous or metachronous presentation, confirmed that a lot more than forty five% of predictions have been off by over 6 months and eighteen% were off by more than 12 months . Further more innovations in prognostic exams like the “liquid biopsy” (a non-invasive blood exam that may detect tumor DNA or RNA fragments or CTCs) are necessary As well as in enhancement . These combine Sophisticated individual and tumor distinct genomic information into the equation, as a way to accomplish personalised survival predictions.

Operation continues to become a crucial treatment method choice for sufferers with constrained Mind metastases. It can be indicated when metastases are significant (>three-four cm), or each time a pathologic analysis is needed. Furthermore, operation is favored within the presence of significant edema necessitating prolonged high dose dexamethasone, or to potentially reverse neurological deficits. If not, the current proof implies the efficacy of SRS is sufficient to achieve strong community control that may be comparable to surgery. Whilst there won't be any RCTs immediately comparing The 2, a number of trials have been claimed comparing SRS to SRS with WBRT (Desk 1), and is An important emphasis of this assessment.

HR: hazard ratio, WHO: globe overall health organization, KPS: Karnofsky efficiency status, WBRT: complete brain radiotherapy, SRS: stereotactic radiosurgery, yr: year, mos: months, NS: not sizeable, NR: not recorded, NA: not applicable, HVLT-R: Hopkins Verbal Studying Examination revised.

Individuals in the observation group experienced either medical procedures alone or SRS by yourself. Purposeful result wasn't analyzed separately by operation or SRS by itself.

The very first RCTs analyzing SRS mimicked the look of the First surgical scientific studies for Mind metastases, and evaluated the addition of SRS to WBRT [33, 34]. These studies confirmed that SRS enhanced nearby Command, as well as a survival gain in chosen individuals with a single Mind metastasis was revealed. These trials have been successful in shifting the paradigm from WBRT alone to WBRT in addition SRS for clients presenting with restricted brain metastases and a fantastic overall performance standing.

The following series of medical trials have been meant to remedy if WBRT was whatsoever required, and when compared SRS by yourself to SRS with adjuvant WBRT. Three RCTs have already been documented in patients presenting with as many as four metastases [35-37] plus a forth in abstract form . Aoyama et al. reported the very first RCT, randomizing 132 individuals to SRS on your own (65 patients) or WBRT furthermore SRS (sixty seven clients). The key endpoint was Mind tumor recurrence. Even though the one-yr nearby Manage amount was significant with SRS by itself at seventy three%, added local Regulate with adjuvant WBRT at 89%, was observed. Furthermore, adjuvant WBRT lessened the rate of distant intra-cranial relapse at one calendar year from sixty four% to 42%. However, these gains in intra-cranial Regulate did not translate into a bonus with respect to cognition, according to Mini-Psychological Standing Test (MMSE), nor survival. In addition, patients experienced better costs of necrosis and leukoencephalopathy from the WBRT arm. The trial was As a result prosperous in offering the primary level one proof to explain the relative affect of SRS alone as opposed to SRS with WBRT.

Instead of the normal endpoint of survival or intra-cranial Manage, Chang et al. took another solution and evaluated neurocognition as the principal endpoint. Importantly, the validated Hopkins Verbal Studying Take a look at-Revised (HVLT-R) assessment Resource, was used to measure neurocognitive operating as opposed to the MMSE which is not a delicate test for neurocognition . Fifty-8 patients had been randomized to SRS by yourself (n = thirty) or WBRT plus SRS (n = 28). Early stopping procedures had been invoked in the interim Investigation, and the examine concluded that SRS by itself was favored with regard towards the chance of neurocognitive drop at 4 months write-up-treatment. This advantage was recognized Regardless of the one calendar year nearby Management and distant Mind Handle fees favoring adjuvant WBRT with absolute gains of 33% and 27%, respectively. The intracranial Management results were In step with the effects from the Aoyama review, but what wasn't envisioned was the survival gain observed within the SRS alone arm. The median survival was fifteen months inside the SRS on your own arm and 6 months inside the SRS with WBRT arm (p = 0.003). This survival final result induced the demo to undergo considerable scrutiny with several arguing that the survival benefit for SRS alone was a results of imbalances in between the two arms, as more patients handled with SRS furthermore WBRT had increased further-cranial (far more liver and adrenal metastases) and intracranial sickness (larger sized quantity of Mind metastases) .

The ecu Corporation for Investigate and Treatment method of Cancer (EORTC) also took a different strategy with their Main endpoint focusing on purposeful independence . They utilized, nonetheless, the greater clinically familiar Environment Wellbeing Firm (WHO) efficiency status (PS) scale, and calculated the time to WHO PS deterioration to more than two. This RCT concluded the addition of WBRT didn't improve the median duration of purposeful independence (SRS by yourself: 10.0 months vs SRS plus WBRT: nine.5 months). The secondary final result of QOL, measured While using the validated EORTC-QLQC30 Software, was observed to generally be even worse in patients who been given WBRT in many QOL domains . Importantly, these outcomes ended up observed Inspite of adjuvant WBRT lowering the two-yr community failure charge (31% to 19%), distant Mind failure (forty eight% to 33%), and the necessity for salvage therapies (51% vs. sixteen%). No considerable differences in survival have been noticed albeit the trial was not run to address survival.

These 4 trials have set up the function of SRS by yourself given that the regular of treatment in sufferers with a constrained range of brain metastases, but they've got not been meant to Examine the impression of WBRT on General survival.

The inclusion requirements over the RCTs analyzing SRS alone to SRS moreover WBRT have been equivalent (Desk one), nevertheless, the principal endpoints were being completely distinct, and no demo was made to Consider In general survival. To better clarify the outcomes of nearby Management, distant Mind Command and survival, a meta-Evaluation (MAL) was executed by Tsao, Xu and Sahgal in 2012 . They reported hazard ratios for nearby Handle and distant brain Management favoring adjuvant WBRT at 2.61 and 2.15, respectively, but ended up unable to combine the survival final results on account of limits in just how the info ended up claimed. Sahgal et al. then executed somebody individual knowledge (IPD) MAL of precisely the same RCTs aimed toward assessing treatment method effects on survival, and perform sub-group analyses . With regard to In general survival, a procedure outcome was noticed favoring SRS by itself in clients ≤fifty a long time. In older people, no survival drawback was noticed with SRS on your own. With respect to distant brain Command, a treatment method result was also observed with threat reductions in the event of recent brain metastases in more mature sufferers handled with WBRT, but no profit from the youthful patients (≤fifty a long time) addressed with WBRT. As envisioned, regional Manage was improved with added WBRT in all age groups. The concordance between a survival detriment and not enough benefit in distant Mind Handle In spite of procedure with WBRT, while in the young clients, led the authors to hypothesize that exposure towards the identified harms of WBRT (talked about intimately beneath) may negatively impact client survival. This speculation is provocative, and continues to be to become validated.

Quite possibly the most convincing trial design to confirm the adverse results of WBRT is usually to randomize individuals without any visualized brain metastases to observation or WBRT. This is accomplished in research assessing prophylactic cranial irradiation (PCI) in each smaller mobile lung most cancers (SCLC) [forty four, forty five] and non-little mobile lung cancer (NSCLC) [forty six, forty seven]. PCI, not dissimilar on the addition of WBRT to SRS, has been proven to cut back the potential risk of intra-cranial relapse. However, this obtain arrives with the price of a damaging effect on QOL. As an example, major improves in exhaustion, appetite loss, nausea and vomiting and leg weak spot were being noticed in patients with considerable phase SCLC at six and twelve months post PCI . Moreover, in locally Superior NSCLC people, a higher drop in HVLT-R measures of speedy and delayed remember were noticed even nearly one year post-PCI . With respect to longer-time period adverse consequences of WBRT, a devastating consequence is usually the event of leukoencephalopathy. In fact, radiation-induced dementia costs are already described to generally be as superior as 11% in long-time period Mind metastases survivors (>twelve months) right after WBRT , and claimed being larger in clients treated with WBRT and SRS versus SRS alone [35, fifty].

Abnormal N-methyl-D-aspartate (NMDA) receptor stimulation, just like the pathophysiology inherent to Parkinson's dementia , has become postulated as one particular mechanism conveying the adverse neurocognitive results of WBRT. As a technique to mitigate the danger, RTOG 0614 evaluated memantine, a neuroprotective agent that blocks pathologic stimulation of NMDA, in a sizable randomized placebo managed demo involving 554 clients. At 24 weeks, 64% of clients without having memantine and fifty four% with memantine had cognitive functionality failure based upon assessment While using the HVLT-R. Although the primary endpoint did not arrive at significance a result of the high attrition amount, there was a powerful craze (p = 0.059) supporting memantine procedure. Assessment of secondary endpoints showed that memantine appreciably prolonged time to cognitive decrease and yielded remarkable outcomes for executive function, processing velocity and delayed recognition at 24 weeks. In the end, these details present nearly all of individuals go through cognitive dysfunction with WBRT, Which pharmacologic methods to mitigate the danger by focusing on identical pathways associated with Parkinson's dementia can be deserving of more investigation.

Even further Perception into WBRTs’ system of injury has originate from a current Stage two demo assessing hippocampal avoidance WBRT (HA-WBRT). Subtle modern radiation technological innovation was placed on Restrict dose publicity into the hippocampus to not more than eighty% of the prescribed 30Gy in ten fractions . This non-randomized stage 2 trial measured neurocognitive purpose using the HVLT-R, and in contrast outcomes to historic controls dealt with with conventional WBRT from a RTOG trial databases. HA-WBRT resulted in a seven% drop during the necessarily mean relative HVLT-R delayed remember, which was noticeably lower compared to the 30% decline received from historic controls. Though this examine is encouraging with regards to restricting toxicity from WBRT, a randomized trial is required to fully have an understanding of the therapeutic benefit Within this technologically complicated form of WBRT.

In 2012, the American Society for Therapeutic Radiation Oncology posted an proof-primarily based guideline having a number of tips about the management of Mind metastases . Considering that that time, the proof from medical trials has created it distinct that the preferred up-entrance radiation cure choice for patients with confined Mind metastases is SRS on your own. In reality, the American Society for Radiation Oncology (ASTRO) has not long ago created a definitive recommendation inside their Pick Wisely marketing campaign and suggest not to routinely incorporate adjuvant WBRT to SRS for confined brain metastases . Moreover, the not long ago revised National Detailed Cancer Community (NCCN) suggestions now support SRS alone even over and above Those people individuals with “limited” metastases, and don't specify an higher limit for the volume of metastases . The latter is forward wondering; metastasis counting is probably going irrelevant and what issues is if not the suitability of the individual for SRS [fifty seven-59]. For that reason, the onus is now not on people who treat with SRS on your own to justify the omission of WBRT; relatively it is on individuals who treat with WBRT within a SRS suited affected individual.

WHAT ABOUT THE Affected person WITH Additional EXTENSIVE BRAIN METASTASES?

Preceding technological limitations in SRS engineering limited the appliance of SRS to people with only a few brain metastases. Developments in mounted body and frameless SRS systems now allow for treatment of diverse metastases in a single session [60, 61].

The initial key possible review assessing SRS by itself for various Mind metastases was claimed in 2014 . Approximately 1200 individuals with 1-ten SRS suitable metastases were being treated with SRS alone working with Gamma Knife technologies (Elekta AB, Stockholm, Sweden). The Evaluation was broken down in accordance with the 455 people with 1 metastases, 531 sufferers with two to four metastases and 208 with 5 to 10 metastases. Survival, distant brain relapse, and local Manage costs were not significantly various in individuals with five to 10 metastases vs . two to 4 metastases. These outcomes are of significant importance since they problem the dogma that clients with a lot more than 4 metastases will not likely get pleasure from SRS alone as a result of shortened survival and will inevitably are unsuccessful somewhere else in the Mind. Hence, this demo delivers proof to support SRS by yourself in very good KPS patients with nearly 10 metastases, presented the individual tumor volume is not more than ten mL and < 3 cm in longest diameter, and the overall cumulative quantity of all tumors within the Mind is ≤15 mL. Several randomized trials are now evaluating WBRT by itself vs . SRS alone in similar clients, and in advancement is usually a demo assessing SRS on your own vs . WBRT additionally SRS boost in sufferers with 10 to twenty metastases.

Qualified THERAPIES IN COMBINATION WITH Mind RADIATION

As compared with traditional chemotherapy, many qualified agents have larger penetration in the blood-brain barrier and generate response in the brain. Spectacular advancements in disease Handle are increasingly being noticed even for histologies like melanoma that were Earlier thought of not just radioresistant but chemoresistant. Table 2 [63-75] summarizes picked scientific trials analyzing the efficacy of targeted therapies by itself or together with radiation therapy in the treatment method of Mind metastases. Although, with targeted therapies on your own some amazing response premiums are noticed, development-free-survival (PFS) charges are frequently small (< eight months). These effects are usually not too dissimilar from what continues to be attained with WBRT on your own [33, 53]. The exception is in EGFR mutant non-little cell lung cancers dealt with which has a tyrosine kinase inhibitor. From the analyze by Wu et al. such as, the median PFS was >fifteen months in EGFR mutant tumours dealt with with erlotinib.

Desk 2. Summary of selected trials of qualified therapy alone or together with Mind radiation for that treatment method of brain metastases.

PFS: progression no cost survival, nPFS: neurologic development cost-free survival, OS: Total survival, NSCLC: non-tiny cell lung cancer, EGFR: epidermal advancement component receptor, WBRT: complete brain radiotherapy, SRS: stereotactic radiosurgery, mos: months, wks: weeks, NS: not sizeable, NR: not recorded, NA: not applicable

Number of trials have mixed qualified therapies with radiation, and these are typically also summarized in Desk two. While, randomized evidence remains lacking, There's recommendation from retrospective knowledge that The mixture might produce enhanced outcomes. In the retrospective Investigation of a future cohort of sufferers dealt with with SRS for melanoma brain metastases, the team that obtained ipilimumab experienced a substantially longer median survival (21.three vs four.9 months) . However, warning ought to be exercised as concurrent targeted therapy and radiation cure might not be as innocuous as Beforehand believed. The RCT analyzing SRS with WBRT on your own, as opposed to in combination with erlotinib or temozlomide, documented significantly increased Quality 3 to 5 toxicity premiums in the combination arm; far more importantly, survival was even worse although it did not get to statistical importance . A major limitation of the study was that the specific therapy wasn't biomarker-driven and could in part account for your lousy survival noticed. Caution also has to be taken as There may be proof that brain metastases and primary tumors may possibly harbor distinctive genetic alterations. In a single analyze of 86 matched brain metastases and primary tumors, clinically useful alterations in fifty three% of Mind metastases weren't detected in the primary tumor .

The emerging evidence implies that targeted therapies will Perform a big job in the therapy of brain metastases. We postulate that While focused brokers is probably not powerful in managing gross sickness in the Mind, they may be effective in managing micro-metastatic illness from the brain. Consequently, a logical approach may very well be to combine targeted therapies with SRS by itself, conquering the limitation of SRS in addressing micrometastatic illness during the Mind and leading to less distant brain failures. Another several years will yield enjoyable info as there are a number of trials in development utilizing this approach.

Improvements IN SRS - INDICATIONS AND APPLICATIONS

As tumors get much larger, SRS dosing is counter-intuitively lowered with regard to tumor Handle, to maintain basic safety to the normal Mind tissue; or else, the potential risk of radiation necrosis gets prohibitive . Consequently, tumors larger than 4 cm have commonly been excluded from single portion SRS. Should the tumors are non-operable, then these sufferers happen to be dealt with with WBRT Regardless of its lousy neighborhood Regulate. The advent of non-invasive head immobilization products, on-board image-direction systems and Superior radiation supply software has bring about the exercise of hypofractionated frameless stereotactic radiotherapy (SRT) [sixty, 78]. Basically by fractionating, the protection profile with respect to the normal brain tissue toxicity is enhanced, and the full tumor dose can be escalated this kind of that doses like 24Gy in 3 fractions and thirty-40Gy in five fractions are actually commonplace. A person interesting retrospective sequence documented better fees of control and reduce charges of toxicities with hypofractionated SRT (36Gy in 6 fractions) as compared with solitary portion SRS . On the other hand, this observe is still in its infancy and we are in need of a RCT to find out if one fraction SRS should be reserved just for compact metastases (e.g. one-two centimeters), as the information advise even worse regional Handle for more substantial tumors [eighty, 81]. Figure one can be an illustration of the efficacy of hypofractionated SRT in a considerable tumor. This client might have normally been excluded from solitary fraction SRS and dealt with with WBRT upfront (plus or minus a SRS boost), or operated on.

A. MRI of three.6cm appropriate cerebellar metastases from lung cancer. B. Highly conformal treatment method prepare Using the 100% (environmentally friendly line) and eighty% (blue line) isodose traces wrapping tightly round the gross tumour (crimson colorwash), and preparing target quantity (orange colorwash). The brainstem (blue colorwash) is spared from higher dose. (B) MRI two months article completion of radiation (30Gy in 5 fractions). C. Entire resolution with the tumour at 1 year.

In article-operative sufferers, the apply of routinely managing with WBRT can be turning out to be outdated. There may be escalating use of SRS on the publish-operative surgical cavity as a method to spare individuals within the adverse results of WBRT and to further improve neighborhood control [82-ninety three]. On the Sunnybrook Odette Cancer Center, Now we have adopted hypofractionated SRT as our normal of treatment, delivering 30-35Gy in five fractions towards the write-up-operative tumor bed . Fractionation has the benefit of reducing the adverse effects to the normal tissues, provided that the targets are generally huge and irregularly formed. Our initial benefits have revealed 1 12 months nearby Regulate rates of ∼80% in patients which have either recurred and re-operated upon immediately after earlier WBRT, or in clients with no prior heritage of WBRT and operated on. There is certainly an ongoing analyze evaluating write-up-surgical cavity solitary portion SRS alone as opposed to WBRT and could be a practice-defining examine .

In the last numerous many years, medical trials have educated us about the appropriate administration of individuals with brain metastases. To begin with, SRS was considered an adjunct to WBRT in chosen clients presenting which has a restricted amount of Mind metastases. However, the part of WBRT has given that been questioned as We have now figured out of its opportunity to adversely affect QOL and neurocognition. Consequently, SRS alone has emerged as the current conventional of treatment with Stage 1 evidence to assistance its apply. Present study is centered on the analysis of broader purposes of SRS to quite a few scientific situations that were traditionally regarded absolute indications for WBRT. As an example, SRS by itself is at this time being evaluated from the therapy of five or maybe more brain metastases, As well as in write-up-operative clients. A completely new era of trials can also be emerging investigating the impact of qualified therapies concurrent with SRS.

Clinical trials in patients with Mind metastases are An important problem as summarized by the modern stories from your Reaction Assessment in Neuro-Oncology (RANO) brain metastases team [95, 96]. They advocate for trial structure and response evaluation that trials be tumor or biomarker particular, that assessment be based on contrast-Increased MRI, that baseline and recurring neurocognitive and QOL screening be carried out with validated and sensitive instruments, that stratification be based on further-cranial illness standing, Which proper timing be considered with regard to endpoint tests. Ultimately, the oncology Group has recognized that the development of brain metastases is not the terminal oncologic celebration with the earlier.

CONFLICTS OF Desire, Fiscal DISCLOSURES

Dr. Arjun Sahgal has been given honorarium from past educational seminars for Medtronic Kyphoplasty division and Elekta AB, Dr. Sahgal has also gained study grants from Elekta AB, normally there isn't any conflicts of interest to disclose.

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