Reliable Steerage by SRS Financials

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Stereotactic radiosurgery SRS Financials is a longtime non-invasive ablative therapy for Mind metastases. Early clinical trials with SRS proved that tumor control costs are remarkable to whole brain radiotherapy (WBRT) on your own. Because of this, WBRT as well as SRS was commonly adopted for people using a confined number of Mind metastases (“confined amount” customarily usually means 1-four). Subsequent trials centered on answering regardless of whether WBRT upfront was required whatsoever. Based upon present randomized controlled trials (RCTs) and meta-analyses evaluating SRS alone to SRS furthermore WBRT, adjuvant WBRT leads to greater intracranial Command; nonetheless, on the cost of neurocognitive functioning and quality of life. These adverse effects of WBRT may negatively effect on survival in youthful individuals. Dependant on the effects of such research, treatment has shifted to SRS by yourself in people using a minimal number of metastases. Additionally, RCTs are assessing the position of SRS alone in patients with >four brain metastases. New developments in SRS involve fractionated SRS for large tumors and the integration of SRS with qualified systemic therapies that cross the blood Mind barrier and/or promote an immune response. We existing Within this overview The existing superior degree proof and rationale supporting SRS as being the normal of look after clients with restricted Mind metastases, and rising purposes 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 purpose of neurosurgery were founded from the 1990s as a way to achieve area Management and extend survival, it was reserved for that minority of patients presenting with one metastasis and no other ailment further than the brain [four-seven]. Nonetheless lacking was a focal ablative non-invasive treatment that might be utilized efficiently to a A lot broader population of individuals with brain metastases. This set the stage for the event of stereotactic radiosurgery (SRS). SRS is actually a centered ablative radiation treatment shipped with sub-millimeter precision towards the tumor localized in 3-Proportions in 1-five fractions.

The main target of this overview would be to summarize the current large degree evidence to make clear the part of SRS as best administration for clients presenting with restricted Mind metastases. In addition, we offer an overview of the emerging programs of SRS because it carries on to evolve right into a remedy option to WBRT, Using the intent To optimize neurcognitive perform and Standard of living (QOL).

PATHOPHYSIOLOGY OF BRAIN METASTASES

Circulating tumor cells (CTCs) can disseminate from a Principal tumor mass to form distant colonies by means of implantation at an ectopic website, like the brain [eight-10]. To take action needs CTCs to arrest within the circulation, extravasate from your bloodstream or lymphatics in the brain, and endure and proliferate [eleven-13]. The entire process of metastatic colonization requires a direct interaction of CTCs with endothelial cells and astrocytes within the Mind microenvironment. For example, CTCs that have arrested in the capillary bed immediate neighborhood endothelial cells to remodel the adjacent atmosphere to advertise tumour cell progress and invasion [14-16]. More, metastatic tumour cells recruit systemic stromal cells, like fibroblasts, to aid with early colonization , and co-decide community stromal cells, for instance reactive astrocytes and microglia, to advertise tissue invasion [15, eighteen, 19]. Astrocytes within the tumour microenvironment may additionally Perform a task in guarding tumour cells from chemotherapy-induced cytotoxicity, by way of a still to get defined mechanism requiring cell-cell Get hold of [20, 21]. Tumour cells, by means of launch of migration inhibitory aspect, interleukin-8, and plasminogen activator inhibitor 1, induce astrocyte activation and modify the inflammatory milieu to enhance tumor-cell proliferation in vitro [22-24]. These molecular procedures symbolize novel and understudied attainable therapeutic targets for the treatment method of intracranial metastatic disorder.

SRS was at first a very resource intensive therapy offered only at specialised centers and indicated just for metastatic clients with a superb lifetime expectancy. The obstacle lay in prognosticating sufferers efficiently and Because of this the Radiation Therapy Oncology Team (RTOG) recursive partitioning Assessment (RPA) [28, 29] was created. Dependant on the client's Karnofsky General performance Standing (KPS), age, position of the principal tumor and presence of extracranial disorder, clients ended up grouped into class 1, 2 or 3 with corresponding median survivals of seven.one, four.two and 2.3 months, respectively. Even though A serious development at some time, the RPA has become viewed as extremely simplistic as recent oncologic decision earning is much more complex incorporating molecular, histological, scientific and radiographic illness traits. You will find now extra advanced classification equipment, such as the diagnosis-specific graded prognostic assessment (DS-GPA). This technique delivers histology-distinct estimates of survival and might independent, one example is, one of the most favorable breast cancer patients with the expected survival of twenty five months (excellent KPS and luminal B form breast cancer) from your minimum favorable individuals using an anticipated survival of 3 months (inadequate KPS and basal-like breast cancer) . Even with advancements in prognostication of clients with Mind metastases, physicians remain mainly not able to accurately forecast prolonged-time period survivors. A analyze inquiring qualified physicians to estimate survival of the one hundred fifty sufferers with details about cancer sort, number of brain metastases, neurological presentation, further-cranial condition standing, KPS, RPA course, prior full-brain radiotherapy, and synchronous or metachronous presentation, showed that a lot more than 45% of predictions have been off by more than 6 months and eighteen% ended up off by a lot more than 12 months . Additional advances in prognostic tests including the “liquid biopsy” (a non-invasive blood examination that can detect tumor DNA or RNA fragments or CTCs) are needed and in advancement . These Merge Superior patient and tumor specific genomic information into your equation, so as to achieve personalised survival predictions.

Surgical procedure proceeds for being an important treatment method selection for individuals with limited Mind metastases. It truly is indicated when metastases are big (>3-4 cm), or any time a pathologic prognosis is required. On top of that, surgical treatment is most popular in the existence of considerable edema necessitating extended high dose dexamethasone, or to possibly reverse neurological deficits. Or else, The existing proof suggests which the efficacy of SRS is ample to realize sturdy nearby Command that is definitely similar to surgery. While there won't be any RCTs specifically evaluating the two, many trials are already described evaluating SRS to SRS with WBRT (Desk 1), and is also A significant aim of the evaluate.

HR: hazard ratio, WHO: globe well being Group, KPS: Karnofsky efficiency position, WBRT: entire brain radiotherapy, SRS: stereotactic radiosurgery, yr: calendar year, mos: months, NS: not considerable, NR: not recorded, NA: not applicable, HVLT-R: Hopkins Verbal Finding out Exam revised.

Patients inside the observation group experienced possibly medical procedures on your own or SRS by itself. Functional final result was not analyzed individually by surgical treatment or SRS by itself.

The primary RCTs assessing SRS mimicked the design on the Preliminary surgical scientific tests for brain metastases, and evaluated the addition of SRS to WBRT [33, 34]. These scientific studies confirmed that SRS improved neighborhood Command, in addition to a survival advantage in picked sufferers with one Mind metastasis was revealed. These trials ended up successful in shifting the paradigm from WBRT alone to WBRT in addition SRS for sufferers presenting with constrained brain metastases and an excellent effectiveness standing.

The next number of clinical trials were being intended to solution if WBRT was in the least important, and in contrast SRS on your own to SRS with adjuvant WBRT. Three RCTs are claimed in sufferers presenting with nearly four metastases [35-37] and a forth in abstract sort . Aoyama et al. documented the first RCT, randomizing 132 sufferers to SRS by itself (sixty five patients) or WBRT furthermore SRS (sixty seven people). The first endpoint was Mind tumor recurrence. Even though the 1-12 months regional control charge was significant with SRS on your own at 73%, extra community Regulate with adjuvant WBRT at 89%, was noticed. Moreover, adjuvant WBRT decreased the rate of distant intra-cranial relapse at 1 calendar year from 64% to 42%. On the other hand, these gains in intra-cranial Management did not translate into a benefit with regard to cognition, based upon Mini-Psychological Status Examination (MMSE), nor survival. Also, clients experienced bigger prices of necrosis and leukoencephalopathy during the WBRT arm. The trial was Hence profitable in furnishing the primary degree one proof to explain the relative influence of SRS by yourself versus SRS with WBRT.

As an alternative to the normal endpoint of survival or intra-cranial Handle, Chang et al. took a unique technique and evaluated neurocognition as the first endpoint. Importantly, the validated Hopkins Verbal Learning Test-Revised (HVLT-R) evaluation Resource, was used to evaluate neurocognitive operating rather than the MMSE which is not a sensitive take a look at for neurocognition . Fifty-8 individuals were being randomized to SRS by yourself (n = 30) or WBRT moreover SRS (n = 28). Early halting principles have been invoked on the interim Assessment, plus the analyze concluded that SRS by yourself was favored with respect to your chance of neurocognitive decrease at 4 months write-up-cure. This advantage was realized despite the one year community Management and distant Mind Manage rates favoring adjuvant WBRT with absolute gains of 33% and 27%, respectively. The intracranial control outcomes have been in keeping with the final results with the Aoyama study, but what was not expected was the survival benefit observed during the SRS alone arm. The median survival was 15 months during the SRS by itself arm and six months in the SRS with WBRT arm (p = 0.003). This survival consequence caused the trial to go through sizeable scrutiny with numerous arguing which the survival advantage for SRS by yourself was a results of imbalances amongst the two arms, as a lot more individuals taken care of with SRS furthermore WBRT experienced higher excess-cranial (more liver and adrenal metastases) and intracranial disease (much larger quantity of brain metastases) .

The European Group for Investigate and Therapy of Cancer (EORTC) also took a distinct method with their Most important endpoint focusing on functional independence . They used, on the other hand, the more clinically familiar Planet Health and fitness Corporation (WHO) functionality status (PS) scale, and calculated the time to WHO PS deterioration to much more than two. This RCT concluded that the addition of WBRT didn't Increase the median length of useful independence (SRS alone: ten.0 months vs SRS moreover WBRT: nine.five months). The secondary result of QOL, calculated With all the validated EORTC-QLQC30 tool, was observed to get worse in people who acquired WBRT in a number of QOL domains . Importantly, these success ended up noticed despite adjuvant WBRT reducing the 2-yr regional failure amount (31% to 19%), distant brain failure (48% to 33%), and the necessity for salvage therapies (fifty one% vs. 16%). No substantial variations in survival were being observed albeit the trial was not run to handle survival.

These four trials have set up the position of SRS on your own since the common of care in patients which has a limited amount of brain metastases, but they've not been built to Examine the impact of WBRT on In general survival.

The inclusion criteria through the RCTs assessing SRS alone to SRS additionally WBRT ended up identical (Table 1), even so, the key endpoints had been completely distinctive, and no trial was made to Examine In general survival. To raised clarify the results of community Handle, distant brain Management and survival, a meta-Examination (MAL) was done by Tsao, Xu and Sahgal in 2012 . They reported hazard ratios for regional control and distant brain Command favoring adjuvant WBRT at two.sixty one and a pair of.15, respectively, but have been not able to mix the survival outcomes as a consequence of restrictions in the best way the info were documented. Sahgal et al. then executed someone patient facts (IPD) MAL of a similar RCTs targeted at assessing cure outcomes on survival, and complete sub-team analyses . With regard to Over-all survival, a remedy effect was observed favoring SRS on your own in people ≤50 yrs. In more mature clients, no survival drawback was noticed with SRS on your own. With respect to distant brain Handle, a therapy impact was also observed with hazard reductions in the development of latest Mind metastases in more mature clients handled with WBRT, but no benefit from the young people (≤fifty many years) handled with WBRT. As anticipated, neighborhood Regulate was improved with more WBRT in all age groups. The concordance between a survival detriment and lack of reward in distant brain Command Even with procedure with WBRT, in the young sufferers, led the authors to hypothesize that publicity to the acknowledged harms of WBRT (talked about intimately underneath) may possibly negatively impression client survival. This hypothesis is provocative, and stays to get validated.

Essentially the most convincing demo style and design to confirm the adverse consequences of WBRT is to randomize clients without any visualized brain metastases to observation or WBRT. This continues to be accomplished in research assessing prophylactic cranial irradiation (PCI) in both equally compact cell lung cancer (SCLC) [forty four, 45] and non-modest mobile lung most cancers (NSCLC) [forty six, forty seven]. PCI, not dissimilar towards the addition of WBRT to SRS, continues to be demonstrated to lessen the potential risk of intra-cranial relapse. However, this obtain comes with the price of the negative effect on QOL. For instance, substantial boosts in fatigue, urge for food loss, nausea and vomiting and leg weak point have been observed in people with substantial stage SCLC at six and 12 months post PCI . Moreover, in regionally Innovative NSCLC patients, a higher decrease in HVLT-R measures of quick and delayed remember have been observed even around 1 yr publish-PCI . With respect to more time-expression adverse results of WBRT, a devastating consequence might be the development of leukoencephalopathy. Without a doubt, radiation-induced dementia costs are actually described to get as high as eleven% in extended-time period Mind metastases survivors (>12 months) right after WBRT , and reported being better in patients dealt with with WBRT and SRS instead of SRS by itself [35, 50].

Too much N-methyl-D-aspartate (NMDA) receptor stimulation, much like the pathophysiology inherent to Parkinson's dementia , continues to be postulated as one particular mechanism explaining the adverse neurocognitive outcomes of WBRT. As being a technique to mitigate the chance, RTOG 0614 evaluated memantine, a neuroprotective agent that blocks pathologic stimulation of NMDA, in a considerable randomized placebo controlled trial involving 554 sufferers. At 24 months, sixty four% of clients without having memantine and 54% with memantine had cognitive functionality failure based on assessment With all the HVLT-R. Although the Key endpoint didn't achieve significance as a result of higher attrition charge, there was a solid pattern (p = 0.059) supporting memantine treatment method. Examination of secondary endpoints showed that memantine substantially prolonged enough time to cognitive decline and yielded exceptional results for executive functionality, processing velocity and delayed recognition at 24 months. In the long run, these knowledge exhibit nearly all of people experience cognitive dysfunction with WBRT, and that pharmacologic methods to mitigate the danger by targeting equivalent pathways linked to Parkinson's dementia may be worthy of further investigation.

Even more Perception into WBRTs’ system of harm has originate from a modern Section 2 trial analyzing hippocampal avoidance WBRT (HA-WBRT). Advanced present day radiation technological innovation was placed on limit dose exposure for the hippocampus to no more than 80% on the prescribed 30Gy in 10 fractions . This non-randomized phase two trial calculated neurocognitive function using the HVLT-R, and as opposed results to historic controls dealt with with regular WBRT from the RTOG trial database. HA-WBRT resulted inside of a seven% drop in the mean relative HVLT-R delayed recall, which was considerably reduced compared to 30% drop received from historic controls. Despite the fact that this examine is encouraging with regards to limiting toxicity from WBRT, a randomized trial is required to completely have an understanding of the therapeutic benefit During this technologically sophisticated type of WBRT.

In 2012, the American Society for Therapeutic Radiation Oncology posted an evidence-centered guideline by using a series of suggestions within the administration of brain metastases . Considering the fact that that point, the evidence from clinical trials has manufactured it distinct that the popular up-entrance radiation remedy selection for patients with constrained Mind metastases is SRS alone. In truth, the American Modern society for Radiation Oncology (ASTRO) has recently manufactured a definitive recommendation inside their Opt for Properly marketing campaign and advise to not routinely incorporate adjuvant WBRT to SRS for confined Mind metastases . Additionally, the lately revised Nationwide Extensive Cancer Network (NCCN) recommendations now support SRS on your own even beyond All those people with “constrained” metastases, and do not specify an upper limit for the quantity of metastases . The latter is ahead imagining; metastasis counting is likely irrelevant and what issues is usually the suitability on the patient for SRS [fifty seven-fifty nine]. Hence, the onus is no longer on individuals who address with SRS on your own to justify the omission of WBRT; rather it is actually on those that handle with WBRT in a SRS suitable patient.

How about THE PATIENT WITH A lot more Intensive Mind METASTASES?

Former technical restrictions in SRS engineering restricted the application of SRS to individuals with just a few Mind metastases. Enhancements in fixed frame and frameless SRS systems now allow cure of diverse metastases in only one session [60, sixty one].

The primary major possible analyze assessing SRS alone for many Mind metastases was described in 2014 . Around 1200 clients with 1-ten SRS eligible metastases had been addressed with SRS by yourself working with Gamma Knife engineering (Elekta AB, Stockholm, Sweden). The analysis was damaged down according to the 455 individuals with one metastases, 531 patients with 2 to four metastases and 208 with 5 to 10 metastases. Survival, distant brain relapse, and local Manage costs were not considerably diverse in people with five to ten metastases as opposed to two to four metastases. These effects are of important significance as they obstacle the dogma that clients with in excess of 4 metastases will not likely get pleasure from SRS by yourself resulting from shortened survival and can inevitably fail somewhere else within the Mind. For that reason, this demo supplies evidence to aid SRS by itself in superior KPS patients with nearly 10 metastases, presented the individual tumor quantity is no more than ten mL and < 3 cm in longest diameter, and the overall cumulative quantity of all tumors inside the Mind is ≤15 mL. Various randomized trials are currently assessing WBRT by itself vs . SRS by itself in equivalent people, As well as in enhancement is really a trial evaluating SRS alone as opposed to WBRT plus SRS Strengthen in clients with ten to 20 metastases.

Focused THERAPIES IN COMBINATION WITH Mind RADIATION

When compared with classic chemotherapy, quite a few focused brokers have better penetration throughout the blood-brain barrier and generate response inside the brain. Dramatic enhancements in condition Handle are increasingly being observed even for histologies including melanoma that were Earlier deemed not just radioresistant but chemoresistant. Desk two [63-75] summarizes selected clinical trials evaluating the efficacy of focused therapies on your own or in combination with radiation therapy while in the procedure of brain metastases. Even though, with focused therapies by itself some spectacular reaction fees are observed, progression-absolutely free-survival (PFS) premiums tend to be short (< 8 months). These outcomes will not be also dissimilar from what is accomplished with WBRT on your own [33, fifty three]. The exception is in EGFR mutant non-little cell lung cancers dealt with which has a tyrosine kinase inhibitor. Within the study by Wu et al. as an example, the median PFS was >15 months in EGFR mutant tumours dealt with with erlotinib.

Desk 2. Summary of picked trials of targeted therapy on your own or together with brain radiation for your remedy of Mind metastases.

PFS: development no cost survival, nPFS: neurologic progression totally free survival, OS: All round survival, NSCLC: non-compact cell lung cancer, EGFR: epidermal expansion aspect receptor, WBRT: total brain radiotherapy, SRS: stereotactic radiosurgery, mos: months, wks: months, NS: not major, NR: not recorded, NA: not applicable

Handful of trials have merged qualified therapies with radiation, and they're also summarized in Table two. Whilst, randomized proof continues to be missing, You can find suggestion from retrospective knowledge that the combination may perhaps produce improved results. From the retrospective analysis of the future cohort of patients addressed with SRS for melanoma brain metastases, the group that been given ipilimumab had a significantly more time median survival (21.three vs 4.9 months) . Even so, warning should be exercised as concurrent targeted therapy and radiation therapy will not be as innocuous as Beforehand thought. The RCT evaluating SRS with WBRT on your own, compared to together with erlotinib or temozlomide, claimed drastically bigger Quality three to 5 toxicity fees in the combination arm; much more importantly, survival was worse although it didn't access statistical importance . An important limitation of the study was that the targeted therapy wasn't biomarker-driven and will in part account for the poor survival noticed. Caution also should be taken as There may be evidence that Mind metastases and primary tumors may possibly harbor unique genetic alterations. In one review of 86 matched brain metastases and primary tumors, clinically useful alterations in fifty three% of brain metastases weren't detected in the first tumor .

The emerging proof suggests that qualified therapies will Engage in a major function within the treatment of brain metastases. We postulate that although specific brokers will not be successful in managing gross condition in the brain, They could be successful in managing micro-metastatic sickness inside the brain. As a result, a logical strategy might be to combine qualified therapies with SRS alone, conquering the limitation of SRS in addressing micrometastatic sickness during the brain and resulting in fewer distant brain failures. The next few years will generate thrilling knowledge as There are a selection of trials in progress using this system.

Improvements IN SRS - INDICATIONS AND APPLICATIONS

As tumors get much larger, SRS dosing is counter-intuitively lowered with respect to tumor Management, to keep up safety to the conventional brain tissue; normally, the potential risk of radiation necrosis becomes prohibitive . Therefore, tumors bigger than 4 cm have generally been excluded from one portion SRS. In the event the tumors are non-operable, then these clients have been dealt with with WBRT Inspite of its bad regional Regulate. The appearance of non-invasive head immobilization devices, on-board impression-guidance devices and Sophisticated radiation delivery application has lead to the apply of hypofractionated frameless stereotactic radiotherapy (SRT) [sixty, 78]. Effectively by fractionating, the protection profile with regard to the traditional brain tissue toxicity is improved, and the full tumor dose may be escalated this kind of that doses like 24Gy in three fractions and 30-40Gy in five fractions at the moment are commonplace. A single appealing retrospective series described higher prices of Command and lessen rates of toxicities with hypofractionated SRT (36Gy in 6 fractions) in comparison with solitary portion SRS . Nonetheless, this exercise remains to be in its infancy and we have been needing a RCT to ascertain whether solitary portion SRS ought to be reserved only for modest metastases (e.g. one-2 centimeters), as the info advise worse regional Regulate for larger tumors [80, 81]. Figure one is definitely an example of the efficacy of hypofractionated SRT in a big tumor. This affected person would have normally been excluded from single fraction SRS and dealt with with WBRT upfront (in addition or minus a SRS Strengthen), or operated on.

A. MRI of 3.6cm right cerebellar metastases from lung cancer. B. Hugely conformal therapy program Along with the 100% (inexperienced line) and 80% (blue line) isodose lines wrapping tightly across the gross tumour (purple colorwash), and scheduling concentrate on quantity (orange colorwash). The brainstem (blue colorwash) is spared from substantial dose. (B) MRI two months article completion of radiation (30Gy in 5 fractions). C. Comprehensive resolution on the tumour at 1 year.

In write-up-operative people, the observe of routinely managing with WBRT is usually getting out-of-date. There's rising usage of SRS on the article-operative surgical cavity as a means to spare patients with the adverse results of WBRT and to improve regional Manage [eighty two-93]. With the Sunnybrook Odette Most cancers Center, We have now adopted hypofractionated SRT as our normal of care, providing 30-35Gy in 5 fractions to your submit-operative tumor mattress . Fractionation has the benefit of minimizing the adverse results to the normal tissues, on condition that the targets are usually large and irregularly formed. Our initial outcomes have revealed one year area Management prices of ∼80% in individuals which have either recurred and re-operated upon just after earlier WBRT, or in people without any prior heritage of WBRT and operated on. There exists an ongoing analyze evaluating submit-surgical cavity solitary portion SRS by yourself vs . WBRT and could be a apply-defining review .

In the last quite a few many years, medical trials have knowledgeable us about the right administration of clients with Mind metastases. At first, SRS was deemed an adjunct to WBRT in chosen patients presenting by using a confined range of Mind metastases. However, the function of WBRT has considering the fact that been questioned as Now we have learned of its opportunity to adversely have an effect on QOL and neurocognition. Subsequently, SRS alone has emerged as The present normal of care with Amount 1 evidence to assistance its apply. Current exploration is centered on the evaluation of broader purposes of SRS to many clinical cases that were ordinarily deemed complete indications for WBRT. For instance, SRS on your own is at this time becoming evaluated while in the procedure of 5 or more Mind metastases, As well as in publish-operative clients. A new period of trials can also be emerging investigating the impact of targeted therapies concurrent with SRS.

Clinical trials in individuals with Mind metastases are A serious obstacle as summarized because of the the latest experiences in the Response Evaluation in Neuro-Oncology (RANO) Mind metastases team [ninety five, ninety six]. They recommend for trial design and style and response assessment that trials be tumor or biomarker distinct, that evaluation be dependant on distinction-Increased MRI, that baseline and repeated neurocognitive and QOL testing be executed with validated and delicate instruments, that stratification be determined by excess-cranial disease status, Which appropriate timing be regarded as with regards to endpoint tests. Finally, the oncology Group has identified that the development of brain metastases is no longer the terminal oncologic celebration on the past.

CONFLICTS OF INTEREST, FINANCIAL DISCLOSURES

Dr. Arjun Sahgal has acquired honorarium from prior educational seminars for Medtronic Kyphoplasty division and Elekta AB, Dr. Sahgal has also been given investigation grants from Elekta AB, or else there isn't any conflicts of interest to disclose.

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