Reliable Guidance by SRS Financials
Stereotactic radiosurgery SRS Financials is a longtime non-invasive ablative therapy for Mind metastases. Early medical trials with SRS proved that tumor Management charges are superior to entire brain radiotherapy (WBRT) by yourself. Because of this, WBRT plus SRS was broadly adopted for clients using a constrained range of Mind metastases (“restricted amount” customarily suggests one-4). Subsequent trials centered on answering irrespective of whether WBRT upfront was necessary in the least. Determined by present randomized controlled trials (RCTs) and meta-analyses evaluating SRS by yourself to SRS furthermore WBRT, adjuvant WBRT ends in far better intracranial Manage; nevertheless, on the price of neurocognitive performing and Standard of living. These adverse results of WBRT may additionally negatively effect on survival in more youthful people. Depending on the final results of these reports, procedure has shifted to SRS alone in clients using a restricted variety of metastases. Moreover, RCTs are evaluating the part of SRS on your own in sufferers with >4 brain metastases. New developments in SRS contain fractionated SRS for giant tumors and The mixing of SRS with qualified systemic therapies that cross the blood Mind barrier and/or promote an immune response. We present Within this assessment The present large level evidence and rationale supporting SRS since the typical of take care of individuals with restricted 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.
Even though the purpose of neurosurgery had been proven in the 1990s as a method to realize nearby Management and extend survival, it had been reserved with the minority of people presenting with only one metastasis and no other illness further than the brain [four-seven]. Nonetheless lacking was a focal ablative non-invasive therapy that could be applied proficiently to your A lot broader inhabitants of people with Mind metastases. This set the phase for the event of stereotactic radiosurgery (SRS). SRS can be a centered ablative radiation therapy sent with sub-millimeter precision to your tumor localized in 3-Proportions in one-five fractions.
The main focus of this assessment is usually to summarize The existing substantial degree proof to clarify the job of SRS as ideal administration for individuals presenting with constrained Mind metastases. Furthermore, we provide an outline with the rising purposes of SRS as it carries on to evolve right into a therapy choice to WBRT, Using the intent To optimize neurcognitive function and quality of life (QOL).
PATHOPHYSIOLOGY OF BRAIN METASTASES
Circulating tumor cells (CTCs) can disseminate from a Most important tumor mass to variety distant colonies by implantation at an ectopic web page, like the brain [8-10]. To do so involves CTCs to arrest throughout the circulation, extravasate within the bloodstream or lymphatics in to the brain, and survive and proliferate [eleven-thirteen]. The process of metastatic colonization involves a immediate interaction of CTCs with endothelial cells and astrocytes from the brain microenvironment. As an example, CTCs which have arrested within the capillary mattress direct neighborhood endothelial cells to remodel the adjacent surroundings to market tumour cell development and invasion [fourteen-sixteen]. Even more, metastatic tumour cells recruit systemic stromal cells, for example fibroblasts, to help with early colonization , and co-decide local stromal cells, which include reactive astrocytes and microglia, to market tissue invasion [fifteen, eighteen, 19]. Astrocytes throughout the tumour microenvironment may additionally Participate in a job in safeguarding tumour cells from chemotherapy-induced cytotoxicity, via a still to get defined mechanism requiring mobile-mobile Speak to [20, 21]. Tumour cells, as a result of release of migration inhibitory variable, interleukin-eight, 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 represent novel and understudied doable therapeutic targets for your therapy of intracranial metastatic condition.
SRS was initially an incredibly resource intensive therapy provided only at specialized facilities and indicated only for metastatic sufferers with a superb lifestyle expectancy. The problem lay in prognosticating sufferers proficiently and Because of this the Radiation Therapy Oncology Team (RTOG) recursive partitioning Examination (RPA) [28, 29] was made. Based upon the client's Karnofsky Functionality Position (KPS), age, position of the key tumor and presence of extracranial illness, clients ended up grouped into class one, two or three with corresponding median survivals of seven.1, four.two and a pair of.three months, respectively. Despite the fact that An important advancement at enough time, the RPA has become thought of overly simplistic as latest oncologic conclusion producing is much more elaborate incorporating molecular, histological, medical and radiographic sickness features. You'll find now additional complex classification equipment, like the diagnosis-distinct graded prognostic evaluation (DS-GPA). This system presents histology-precise estimates of survival and can independent, for example, one of the most favorable breast cancer individuals by having an predicted survival of twenty five months (fantastic KPS and luminal B variety breast cancer) within the least favorable people by having an predicted survival of three months (lousy KPS and basal-like breast cancer) . In spite of developments in prognostication of individuals with brain metastases, doctors remain largely struggling to precisely forecast very long-term survivors. A review inquiring qualified physicians to estimate survival of a a hundred and fifty patients with information regarding cancer style, range of brain metastases, neurological presentation, extra-cranial sickness position, KPS, RPA course, prior whole-Mind radiotherapy, and synchronous or metachronous presentation, showed that in excess of forty five% of predictions ended up off by in excess of six months and 18% were off by a lot more than 12 months . Even more developments in prognostic assessments such as the “liquid biopsy” (a non-invasive blood take a look at that can detect tumor DNA or RNA fragments or CTCs) are desired and in development . These Mix Highly developed affected person and tumor certain genomic details into the equation, so that you can reach customized survival predictions.
Surgical procedures continues for being a crucial treatment method choice for clients with constrained brain metastases. It truly is indicated when metastases are huge (>three-four cm), or whenever a pathologic diagnosis is necessary. Furthermore, surgical treatment is favored in the existence of significant edema necessitating extended high dose dexamethasone, or to likely reverse neurological deficits. Or else, the current evidence implies that the efficacy of SRS is ample to achieve resilient local Regulate that's comparable to surgery. Though there isn't any RCTs instantly comparing the two, many trials are documented comparing SRS to SRS with WBRT (Desk 1), and is also A serious concentrate of this critique.
HR: hazard ratio, WHO: world overall health Corporation, KPS: Karnofsky general performance standing, WBRT: entire brain radiotherapy, SRS: stereotactic radiosurgery, yr: calendar year, mos: months, NS: not sizeable, NR: not recorded, NA: not applicable, HVLT-R: Hopkins Verbal Finding out Test revised.
People in the observation group experienced either surgical procedures on your own or SRS by itself. Functional final result wasn't analyzed individually by medical procedures or SRS by yourself.
The 1st RCTs assessing SRS mimicked the design of the Preliminary surgical scientific studies for brain metastases, and evaluated the addition of SRS to WBRT [33, 34]. These experiments verified that SRS enhanced community Management, in addition to a survival gain in selected patients with a single brain metastasis was demonstrated. These trials were prosperous in shifting the paradigm from WBRT alone to WBRT as well as SRS for individuals presenting with restricted Mind metastases and a fantastic efficiency position.
Another number of clinical trials ended up meant to response if WBRT was at all essential, and compared SRS on your own to SRS with adjuvant WBRT. Three RCTs are noted in patients presenting with as many as four metastases [35-37] in addition to a forth in abstract form . Aoyama et al. described the first RCT, randomizing 132 sufferers to SRS by itself (sixty five clients) or WBRT as well as SRS (sixty seven people). The first endpoint was brain tumor recurrence. Even though the 1-12 months area control fee was substantial with SRS alone at seventy three%, additional neighborhood Management with adjuvant WBRT at 89%, was observed. Furthermore, adjuvant WBRT lessened the speed of distant intra-cranial relapse at 1 calendar year from sixty four% to forty two%. Even so, these gains in intra-cranial Command didn't translate into a benefit with regard to cognition, determined by Mini-Psychological Standing Test (MMSE), nor survival. Moreover, people experienced larger prices of necrosis and leukoencephalopathy during the WBRT arm. The demo was thus successful in giving the initial stage 1 evidence to explain the relative effect of SRS alone vs . SRS with WBRT.
In lieu of the traditional endpoint of survival or intra-cranial Regulate, Chang et al. took a special approach and evaluated neurocognition as the first endpoint. Importantly, the validated Hopkins Verbal Understanding Test-Revised (HVLT-R) assessment Resource, was used to evaluate neurocognitive performing as opposed to the MMSE which is not a sensitive test for neurocognition . Fifty-8 patients were being randomized to SRS on your own (n = thirty) or WBRT in addition SRS (n = 28). Early halting policies have been invoked within the interim Examination, and also the review concluded that SRS on your own was favored with regard for the chance of neurocognitive drop at 4 months article-treatment. This advantage was recognized Regardless of the 1 yr area Handle and distant brain Handle rates favoring adjuvant WBRT with absolute gains of 33% and 27%, respectively. The intracranial Handle results ended up Consistent with the results in the Aoyama study, but what was not anticipated was the survival benefit observed during the SRS by yourself arm. The median survival was fifteen months while in the SRS by itself arm and six months within the SRS with WBRT arm (p = 0.003). This survival result brought about the demo to undergo sizeable scrutiny with several arguing the survival gain for SRS alone was a results of imbalances between The 2 arms, as extra people handled with SRS in addition WBRT experienced larger additional-cranial (a lot more liver and adrenal metastases) and intracranial sickness (more substantial volume of Mind metastases) .
The eu Firm for Investigation and Therapy of Most cancers (EORTC) also took another tactic with their primary endpoint focusing on useful independence . They utilized, nonetheless, the more clinically familiar Globe Wellness Group (WHO) efficiency position (PS) scale, and calculated enough time to WHO PS deterioration to greater than two. This RCT concluded which the addition of WBRT didn't Enhance the median period of practical independence (SRS by itself: ten.0 months vs SRS furthermore WBRT: 9.5 months). The secondary outcome of QOL, calculated Along with the validated EORTC-QLQC30 Software, was noticed to get even worse in individuals who been given WBRT in numerous QOL domains . Importantly, these outcomes had been observed Irrespective of adjuvant WBRT minimizing the two-yr local failure amount (31% to 19%), distant brain failure (48% to 33%), and the necessity for salvage therapies (51% vs. sixteen%). No important variations in survival were observed albeit the demo wasn't driven to address survival.
These 4 trials have recognized the job of SRS on your own since the standard of care in people using a minimal quantity of brain metastases, but they may have not been created to Appraise the influence of WBRT on Over-all survival.
The inclusion criteria across the RCTs assessing SRS alone to SRS in addition WBRT were being identical (Table 1), on the other hand, the primary endpoints were entirely unique, and no trial was built to Assess Total survival. To higher explain the results of community Handle, distant brain Command and survival, a meta-Examination (MAL) was done by Tsao, Xu and Sahgal in 2012 . They reported hazard ratios for community Command and distant Mind Regulate favoring adjuvant WBRT at two.sixty one and a couple of.fifteen, respectively, but were being unable to combine the survival final results on account of restrictions in the best way the data were reported. Sahgal et al. then performed somebody affected individual data (IPD) MAL of the identical RCTs targeted at assessing cure effects on survival, and perform sub-group analyses . With regard to All round survival, a remedy effect was noticed favoring SRS by yourself in individuals ≤50 yrs. In older sufferers, no survival drawback was observed with SRS alone. With regard to distant brain Handle, a remedy impact was also noticed with danger reductions in the event of latest brain metastases in older patients treated with WBRT, but no gain inside the young clients (≤fifty several years) handled with WBRT. As envisioned, regional Manage was enhanced with further WBRT in all age groups. The concordance concerning a survival detriment and insufficient benefit in distant Mind Manage despite cure with WBRT, while in the youthful clients, led the authors to hypothesize that publicity for the identified harms of WBRT (discussed intimately beneath) may perhaps negatively effect patient survival. This speculation is provocative, and stays to get validated.
Quite possibly the most convincing demo layout to verify the adverse outcomes of WBRT is always to randomize sufferers with no visualized Mind metastases to observation or WBRT. This is performed in studies assessing prophylactic cranial irradiation (PCI) in both equally little cell lung cancer (SCLC) [forty four, forty five] and non-small cell lung most cancers (NSCLC) [forty six, forty seven]. PCI, not dissimilar on the addition of WBRT to SRS, has long been shown to scale back the potential risk of intra-cranial relapse. However, this achieve will come with the price of a adverse impact on QOL. Such as, sizeable will increase in tiredness, hunger loss, nausea and vomiting and leg weak spot were noticed in individuals with substantial phase SCLC at 6 and 12 months publish PCI . Also, in regionally State-of-the-art NSCLC patients, a better decrease in HVLT-R steps of instant and delayed recall were being noticed even approximately one calendar year write-up-PCI . With respect to lengthier-expression adverse results of WBRT, a devastating consequence can be the development of leukoencephalopathy. In fact, radiation-induced dementia fees have already been documented to become as high as eleven% in very long-term brain metastases survivors (>12 months) right after WBRT , and claimed to become better in sufferers handled with WBRT and SRS in contrast to SRS by yourself [35, fifty].
Excessive N-methyl-D-aspartate (NMDA) receptor stimulation, similar to the pathophysiology inherent to Parkinson's dementia , is postulated as 1 mechanism conveying the adverse neurocognitive results of WBRT. Like a strategy to mitigate the risk, RTOG 0614 evaluated memantine, a neuroprotective agent that blocks pathologic stimulation of NMDA, in a considerable randomized placebo managed demo involving 554 individuals. At 24 months, 64% of sufferers devoid of memantine and fifty four% with memantine had cognitive function failure determined by assessment Along with the HVLT-R. Although the Principal endpoint didn't attain importance due to the higher attrition rate, there was a solid craze (p = 0.059) supporting memantine treatment method. Analysis of secondary endpoints showed that memantine considerably extended time to cognitive drop and yielded remarkable benefits for government function, processing pace and delayed recognition at 24 months. Ultimately, these facts show virtually all clients undergo cognitive dysfunction with WBRT, and that pharmacologic strategies to mitigate the risk by focusing on very similar pathways associated with Parkinson's dementia can be worthy of additional investigation.
Further more insight into WBRTs’ mechanism of harm has originate from a latest Period 2 demo analyzing hippocampal avoidance WBRT (HA-WBRT). Sophisticated present day radiation technology was applied to limit dose exposure towards the hippocampus to no more than 80% on the prescribed 30Gy in ten fractions . This non-randomized period two demo calculated neurocognitive functionality utilizing the HVLT-R, and compared results to historic controls dealt with with common WBRT from a RTOG trial databases. HA-WBRT resulted in the seven% drop during the mean relative HVLT-R delayed recall, which was considerably reduced as opposed to thirty% decrease obtained from historic controls. Although this study is encouraging in terms of limiting toxicity from WBRT, a randomized demo is needed to totally have an understanding of the therapeutic benefit With this technologically elaborate sort of WBRT.
In 2012, the American Modern society for Therapeutic Radiation Oncology published an proof-based mostly guideline using a series of recommendations over the administration of Mind metastases . Since that point, the evidence from scientific trials has produced it obvious that the preferred up-front radiation procedure choice for individuals with limited Mind metastases is SRS alone. In fact, the American Culture for Radiation Oncology (ASTRO) has recently created a definitive advice inside their Select Sensibly campaign and endorse to not routinely increase adjuvant WBRT to SRS for restricted brain metastases . Also, the lately revised Countrywide Thorough Cancer Community (NCCN) recommendations now aid SRS on your own even beyond All those patients with “limited” metastases, and don't specify an higher limit for the amount of metastases . The latter is ahead pondering; metastasis counting is likely irrelevant and what matters is in any other case the suitability of the affected person for SRS [57-fifty nine]. Therefore, the onus is not on those that address with SRS by itself to justify the omission of WBRT; relatively it is actually on people that treat with WBRT in the SRS acceptable individual.
How about THE PATIENT WITH MORE Intensive BRAIN METASTASES?
Earlier technological limitations in SRS know-how limited the application of SRS to clients with only some Mind metastases. Advancements in mounted frame and frameless SRS technologies now make it possible for remedy of diverse metastases in a single session [60, 61].
The initial major prospective research assessing SRS by yourself for a number of brain metastases was reported in 2014 . Around 1200 sufferers with one-ten SRS eligible metastases have been dealt with with SRS alone using Gamma Knife technology (Elekta AB, Stockholm, Sweden). The analysis was damaged down in accordance with the 455 people with one metastases, 531 clients with two to four metastases and 208 with five to 10 metastases. Survival, distant Mind relapse, and native Management fees weren't drastically unique in clients with five to ten metastases compared to 2 to 4 metastases. These success are of big significance as they obstacle the dogma that clients with in excess of four metastases won't get pleasure from SRS by yourself as a result of shortened survival and will inevitably are unsuccessful somewhere else within the Mind. Thus, this trial provides proof to aid SRS by yourself in great KPS patients with as much as ten metastases, supplied the individual tumor quantity is no more than 10 mL and < 3 cm in longest diameter, and the overall cumulative volume of all tumors from the brain is ≤fifteen mL. Numerous randomized trials are currently assessing WBRT alone as opposed to SRS alone in very similar individuals, As well as in advancement is a trial assessing SRS by yourself versus WBRT as well as SRS Improve in patients with ten to 20 metastases.
Specific THERAPIES IN COMBINATION WITH BRAIN RADIATION
In comparison with standard chemotherapy, a number of specific brokers have larger penetration from the blood-Mind barrier and yield response during the brain. Remarkable advancements in disease Management are increasingly being observed even for histologies like melanoma which were Beforehand regarded don't just radioresistant but chemoresistant. Table 2 [sixty three-75] summarizes picked medical trials evaluating the efficacy of specific therapies by yourself or together with radiation therapy in the therapy of Mind metastases. Despite the fact that, with targeted therapies by itself some amazing reaction prices are noticed, development-no cost-survival (PFS) fees tend to be limited (< eight months). These final results are not far too dissimilar from what continues to be realized with WBRT alone [33, 53]. The exception is in EGFR mutant non-modest mobile lung cancers treated by using a tyrosine kinase inhibitor. In the research by Wu et al. as an example, the median PFS was >15 months in EGFR mutant tumours addressed with erlotinib.
Desk 2. Summary of selected trials of targeted therapy alone or in combination with Mind radiation for the treatment method of brain metastases.
PFS: development free survival, nPFS: neurologic progression free of charge survival, OS: Over-all survival, NSCLC: non-compact mobile lung most cancers, EGFR: epidermal growth aspect receptor, WBRT: complete brain radiotherapy, SRS: stereotactic radiosurgery, mos: months, wks: months, NS: not significant, NR: not recorded, NA: not relevant
Few trials have combined targeted therapies with radiation, and these are generally also summarized in Desk two. While, randomized proof continues to be lacking, There is certainly suggestion from retrospective knowledge that The mixture may possibly cause improved outcomes. In the retrospective analysis of the future cohort of people treated with SRS for melanoma brain metastases, the team that gained ipilimumab had a substantially lengthier median survival (21.three vs 4.nine months) . On the other hand, caution must be exercised as concurrent targeted therapy and radiation cure might not be as innocuous as previously assumed. The RCT assessing SRS with WBRT alone, as opposed to in combination with erlotinib or temozlomide, claimed drastically better Quality 3 to five toxicity fees in The mixture arm; more importantly, survival was even worse even though it did not arrive at statistical significance . An important limitation of this research was which the targeted therapy was not biomarker-pushed and could in part account for that bad survival noticed. Warning also needs to be taken as There may be evidence that brain metastases and primary tumors may harbor distinctive genetic alterations. In a single examine of 86 matched Mind metastases and first tumors, clinically insightful alterations in fifty three% of Mind metastases weren't detected in the primary tumor .
The emerging evidence implies that targeted therapies will Engage in an important function inside the procedure of Mind metastases. We postulate that Even though specific brokers is probably not effective in controlling gross illness from the Mind, They could be effective in handling micro-metastatic condition inside the brain. Therefore, a reasonable technique could possibly be to combine targeted therapies with SRS on your own, overcoming the limitation of SRS in addressing micrometastatic disease within the Mind and bringing about much less distant Mind failures. Another number of years will produce remarkable data as There are a selection of trials in development utilizing this system.
Improvements IN SRS - INDICATIONS AND Programs
As tumors get greater, SRS dosing is counter-intuitively lowered with regard to tumor Management, to maintain safety to the traditional brain tissue; if not, the chance of radiation necrosis gets prohibitive . Subsequently, tumors higher than four cm have usually been excluded from single portion SRS. When the tumors are non-operable, then these patients have already been taken care of with WBRT despite its very poor regional Command. The arrival of non-invasive head immobilization equipment, on-board picture-advice programs and Highly developed radiation delivery program has cause the apply of hypofractionated frameless stereotactic radiotherapy (SRT) [sixty, 78]. Fundamentally by fractionating, the protection profile with regard to the normal Mind tissue toxicity is improved, and the whole tumor dose can be escalated these that doses like 24Gy in 3 fractions and 30-40Gy in five fractions at the moment are not unusual. One particular fascinating retrospective sequence reported better charges of Command and lower fees of toxicities with hypofractionated SRT (36Gy in six fractions) as compared with solitary portion SRS . Nevertheless, this exercise remains in its infancy and we have been looking for a RCT to determine whether one portion SRS should be reserved just for little metastases (e.g. one-2 centimeters), as the information counsel even worse local Regulate for much larger tumors [80, eighty one]. Determine 1 is an example of the efficacy of hypofractionated SRT in a large tumor. This individual would've otherwise been excluded from single fraction SRS and dealt with with WBRT upfront (furthermore or minus a SRS Improve), or operated upon.
A. MRI of three.6cm appropriate cerebellar metastases from lung most cancers. B. Hugely conformal remedy approach with the 100% (green line) and 80% (blue line) isodose lines wrapping tightly around the gross tumour (red colorwash), and organizing goal volume (orange colorwash). The brainstem (blue colorwash) is spared from higher dose. (B) MRI 2 months publish completion of radiation (30Gy in 5 fractions). C. Total resolution of the tumour at one calendar year.
In write-up-operative clients, the practice of routinely treating with WBRT is likewise getting out-of-date. There may be raising utilization of SRS for the publish-operative surgical cavity as a means to spare people within the adverse outcomes of WBRT and to further improve community control [82-93]. For the Sunnybrook Odette Most cancers Centre, We have now adopted hypofractionated SRT as our regular of treatment, delivering thirty-35Gy in 5 fractions on the put up-operative tumor bed . Fractionation has the advantage of reducing the adverse effects to the conventional tissues, given that the targets are typically substantial and irregularly formed. Our First final results have revealed one 12 months neighborhood control premiums of ∼80% in clients who've possibly recurred and re-operated upon immediately after earlier WBRT, or in patients without prior history of WBRT and operated on. There exists an ongoing study assessing post-surgical cavity solitary portion SRS alone compared to WBRT and could be a practice-defining examine .
In the last a number of a long time, scientific trials have informed us about the appropriate administration of people with brain metastases. Originally, SRS was thought of an adjunct to WBRT in selected sufferers presenting that has a minimal number of Mind metastases. However, the job of WBRT has given that been questioned as We've realized of its opportunity to adversely have an effect on QOL and neurocognition. As a result, SRS alone has emerged as The present typical of care with Level 1 evidence to assist its exercise. Present-day research is focused on the evaluation of broader applications of SRS to a number of clinical conditions which were ordinarily viewed as complete indications for WBRT. Such as, SRS by itself is now remaining evaluated during the procedure of five or even more brain metastases, and in put up-operative people. A brand new era of trials is likewise rising investigating the effect of focused therapies concurrent with SRS.
Scientific trials in individuals with Mind metastases are An important problem as summarized via the latest studies within the Reaction Evaluation in Neuro-Oncology (RANO) brain metastases group [95, ninety six]. They recommend for trial style and design and reaction evaluation that trials be tumor or biomarker unique, that evaluation be according to contrast-Increased MRI, that baseline and recurring neurocognitive and QOL screening be done with validated and sensitive devices, that stratification be based on more-cranial ailment status, Which correct timing be deemed regarding endpoint screening. Ultimately, the oncology community has acknowledged that the development of brain metastases is no more the terminal oncologic occasion from the earlier.
CONFLICTS OF Desire, Money DISCLOSURES
Dr. Arjun Sahgal has acquired honorarium from prior instructional seminars for Medtronic Kyphoplasty division and Elekta AB, Dr. Sahgal has also acquired research grants from Elekta AB, usually there aren't any conflicts of desire to disclose.