Neurosurg Rev DOI 10.1007/s10143-015-0631-5
LETTER TO THE EDITOR
Intraoperative assistive technologies—the way ahead Aliasgar V. Moiyadi 1
Received: 23 December 2014 / Accepted: 28 January 2015 # Springer-Verlag Berlin Heidelberg 2015
Dear Editor, We read with interest the review by Barbosa et al. titled BIntraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies^ [1]. We were intrigued by their use of the terminology Bassistive^ to qualify the intraoperative adjunct. They rightly highlight the scarcity of quality evidence pertaining to this issue. Unlike new drugs which undergo rigorous preclinical and clinical trials before entering routine practice, surgical adjuncts are usually adopted rather more quickly. The exception to this is the ALA story, in which case aminolevulinic acid being a Bdrug^ administered to the patient, it needed to undergo similar phased clinical trials. The acceptance of surgical adjuncts is often fuelled by individual preferences and curiosity. It is often greatly influenced by local economical and logistical considerations, which often override scientific evidence. Further, and more disconcerting, is the fact that data is generated after the technology is embraced, and this data more often than not (at least what is available in the public domain) is almost always positive in favor of the technology. Negative studies are rarely if ever published. In such a situation, critical and systematic review of data emanating from all studies is crucial. In this context, the authors should be congratulated for their effort.
* Aliasgar V. Moiyadi [email protected] 1
Division of Neurosurgery, Department of Surgical Oncology, PS 245, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) and Tata Memorial Hospital (TMH), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India
Having said that, this is not the first such review. There has been an exponential growth of intraoperative assistive technologies, as also the reviews. While the authors’ effort is appreciated, it does not seem to have added any Bclinical practicechanging value.^ The authors themselves refer to the systematic review of IOMR by Kubben et al. in 2012 which was quite exhaustive [4]. Subsequently, a Cochrane review of BImage guided surgery for the resection of brain tumors^ has also been published [2]. This was published in early 2014, and considering its relevance and importance, this paper should have found mention in their discussion, an omission which is surprising. In fact, their paper seems to be a repetition of the Cochrane review with almost exactly the same conclusions. Whereas corroborative original studies are always welcome, even if they just reconfirm previous study results, we do not see any point in having repetitive reviews for the same topic, and that too within the same time frame, with no additional data. It is an effort wasted. Further, no new data is presented (except the study by Wu et al., itself a conference proceeding which is hardly any robust evidence as of now, at least till the study is completed). Further, it is appropriate to point out that almost at the same time another prospective controlled trial for IOMR was published by Kubben et al. [3]. This is actually a negative IOMR study. For an unbiased review, it is essential to look at both sides of the coin. The study by Kubben et al. describes a multicentric randomized trial of intraoperative MR versus conventional navigation. The study was terminated prematurely for futility after an interim analysis revealed no difference in the extent of resection between the two arms. Admittedly, they used a low field MR (0.15 T Polestar) in their interventional arm, and hence, it could be argued that this cannot be extrapolated to high field systems. However, they should be commended for reporting a negative study, which is rarely done. For every positive study, there may be
Neurosurg Rev
unreported negative studies and this must be always borne in mind when critically reviewing evidence. Apart from this obvious shortcoming, Kubben et al. also raise serious concerns about the clinical relevance and hence utility of the study by Senft et al. which is the basis of Barbosa et al. proposing IOMR to be a useful adjunct. The difference in residual tumor volumes in the two arms, in the study by Senft et al., was (though statistically significant) probably not clinically relevant. That is to say that marginal increase in extent of resection, though statistically significant may not translate into survival benefit. Though it remains the best available evidence supporting IOMR, it is worthwhile remembering these limitations. Readers should not be led into believing that there is irrefutable proof of its benefit. Further, as rightly pointed out by Barbosa et al., cost-effectiveness studies are crucial especially when the other objective benefits are limited. In this context, it may be appropriate to note that intraoperative ultrasound has emerged as a potentially useful cost-effective alternative to IOMR [6, 5]. Further well-designed, prospective studies evaluating IOUS as well as comparing IOMR and IOUS are warranted. Having said that, in view of the heterogeneity in patient populations and variability in defining objective outcomes, it is likely that the external validity of most of these Bcontrolled^ trials will be limited, precluding generalized applicability across the population. Therefore, large, well-conducted prospective observational studies would also be extremely helpful in critically evaluating such adjuncts. We believe that IOMR and for that matter any of the adjuncts are certainly a boon. All the benefits (such as surgeon comfort, confidence) in fact cannot be measured objectively. However, when available, all the objective evidence needs to be given due cognizance. We do hope that this correspondence puts in perspective these facts and hope that more studies will address and resolve them in the future. Conflict of interest No conflicts of interests to disclose.
References 1.
2.
3.
Barbosa BJ, Mariano ED, Batista CM, Marie SK, Teixeira MJ, Pereira CU, Tatagiba MS, Lepski GA (2014) Intraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies. Neurosurg Rev. doi:10. 1007/s10143-014-0592-0 Barone DG, Lawrie TA, Hart MG (2014) Image guided surgery for the resection of brain tumours. Cochrane Database Syst Rev 1, CD009685. doi:10.1002/14651858.CD009685.pub2 Kubben PL, Scholtes F, Schijns OE, Ter Laak-Poort MP, Teernstra OP, Kessels AG, van Overbeeke JJ, Martin DH, van Santbrink H (2014) Intraoperative magnetic resonance imaging versus standard neuronavigation for the neurosurgical treatment of glioblastoma: a randomized controlled trial. Surg Neurol Int 5:70. doi:10.4103/21527806.132572
4.
5.
6.
Kubben PLMKJ, Schijns OEMG, ter Laak-Poort MP, van Overbeeke JJ, van Santbrink H (2011) Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. Lancet Oncol 12:1062–1070 Saether CA, Torsteinsen M, Torp SH, Sundstrom S, Unsgard G, Solheim O (2012) Did survival improve after the implementation of intraoperative neuronavigation and 3D ultrasound in glioblastoma surgery? A retrospective analysis of 192 primary operations. J Neurol Surg A 73:73–78 Solheim O, Selbekk T, Jakola AS, Unsgard G (2010) Ultrasoundguided operations in unselected high-grade gliomas—overall results, impact of image quality and patient selection. Acta Neurochir 152: 1873–1886
Comments Guilherme Lepski, Tübingen, Germany We would like to thank Dr. Moyiadi for the constructive criticism regarding our study entitled BIntraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies.^ Although we live in a special moment in history, characterized by great scientific and technological development, as well as the frequent emergence of new technologies, this is also a time of global economic and financial crisis. This global scenario is becoming increasingly problematic and challenging for health care providers. As observed by Dr. Moyiadi, the insertion of new drugs into the therapeutic armamentarium ideally undergoes a rigorous process of validation to assess therapeutic efficacy and biosafety. Unfortunately, this is not always true for all forms of medical technology, especially when it comes to surgical technology. This environment is Bgreedy^ for technological innovations, and new technologies are often incorporated before their effectiveness is proven. In our view, the justification for incorporating new technologies should always be backed by efficacy studies applying rigorous quality standards. We believe this is becoming a trend, and the intention behind the publication of our review study is to draw the scientific community’s attention to this need. However, we disagree with Dr. Moyiadi regarding the Bclinical practice-changing value^ he mentions in his critique of our review. We believe the publication encourages neurosurgeons to use new technologies rationally and to critically evaluate their actual benefits. Moreover, the information we provide can also be used as a reference for health care providers who invest in the established technologies. The fact that other authors defend the same point of view (Kubben et al. 2012 and Barone et al. 2014), although with different nuances, only underscores the value of the publication, in addition to reinforcing this trend in favor of providing savings for health care systems worldwide. In addition, the review conducted using the Cochrane database (Barone et al. 2014) was published online while our article was being prepared for submission to Neurosurgical Review. Although the primary outcome of that article was the same as ours (extent of resection), the databases searched and the periods involved were completely different, which only reinforces the complementary nature of that publication and highlights the current lack of prospective studies in this field. In line with this vision, our group is currently conducting a clinical study to evaluate the efficacy of assistive technologies within neurosurgical oncology. We are pleased to contribute to this discussion and hope that this review motivates other authors to generate robust data in the scope of high-quality prospective trials addressing this important issue.
LETTER TO THE EDITOR
Intraoperative assistive technologies—the way ahead Aliasgar V. Moiyadi 1
Received: 23 December 2014 / Accepted: 28 January 2015 # Springer-Verlag Berlin Heidelberg 2015
Dear Editor, We read with interest the review by Barbosa et al. titled BIntraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies^ [1]. We were intrigued by their use of the terminology Bassistive^ to qualify the intraoperative adjunct. They rightly highlight the scarcity of quality evidence pertaining to this issue. Unlike new drugs which undergo rigorous preclinical and clinical trials before entering routine practice, surgical adjuncts are usually adopted rather more quickly. The exception to this is the ALA story, in which case aminolevulinic acid being a Bdrug^ administered to the patient, it needed to undergo similar phased clinical trials. The acceptance of surgical adjuncts is often fuelled by individual preferences and curiosity. It is often greatly influenced by local economical and logistical considerations, which often override scientific evidence. Further, and more disconcerting, is the fact that data is generated after the technology is embraced, and this data more often than not (at least what is available in the public domain) is almost always positive in favor of the technology. Negative studies are rarely if ever published. In such a situation, critical and systematic review of data emanating from all studies is crucial. In this context, the authors should be congratulated for their effort.
* Aliasgar V. Moiyadi [email protected] 1
Division of Neurosurgery, Department of Surgical Oncology, PS 245, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) and Tata Memorial Hospital (TMH), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India
Having said that, this is not the first such review. There has been an exponential growth of intraoperative assistive technologies, as also the reviews. While the authors’ effort is appreciated, it does not seem to have added any Bclinical practicechanging value.^ The authors themselves refer to the systematic review of IOMR by Kubben et al. in 2012 which was quite exhaustive [4]. Subsequently, a Cochrane review of BImage guided surgery for the resection of brain tumors^ has also been published [2]. This was published in early 2014, and considering its relevance and importance, this paper should have found mention in their discussion, an omission which is surprising. In fact, their paper seems to be a repetition of the Cochrane review with almost exactly the same conclusions. Whereas corroborative original studies are always welcome, even if they just reconfirm previous study results, we do not see any point in having repetitive reviews for the same topic, and that too within the same time frame, with no additional data. It is an effort wasted. Further, no new data is presented (except the study by Wu et al., itself a conference proceeding which is hardly any robust evidence as of now, at least till the study is completed). Further, it is appropriate to point out that almost at the same time another prospective controlled trial for IOMR was published by Kubben et al. [3]. This is actually a negative IOMR study. For an unbiased review, it is essential to look at both sides of the coin. The study by Kubben et al. describes a multicentric randomized trial of intraoperative MR versus conventional navigation. The study was terminated prematurely for futility after an interim analysis revealed no difference in the extent of resection between the two arms. Admittedly, they used a low field MR (0.15 T Polestar) in their interventional arm, and hence, it could be argued that this cannot be extrapolated to high field systems. However, they should be commended for reporting a negative study, which is rarely done. For every positive study, there may be
Neurosurg Rev
unreported negative studies and this must be always borne in mind when critically reviewing evidence. Apart from this obvious shortcoming, Kubben et al. also raise serious concerns about the clinical relevance and hence utility of the study by Senft et al. which is the basis of Barbosa et al. proposing IOMR to be a useful adjunct. The difference in residual tumor volumes in the two arms, in the study by Senft et al., was (though statistically significant) probably not clinically relevant. That is to say that marginal increase in extent of resection, though statistically significant may not translate into survival benefit. Though it remains the best available evidence supporting IOMR, it is worthwhile remembering these limitations. Readers should not be led into believing that there is irrefutable proof of its benefit. Further, as rightly pointed out by Barbosa et al., cost-effectiveness studies are crucial especially when the other objective benefits are limited. In this context, it may be appropriate to note that intraoperative ultrasound has emerged as a potentially useful cost-effective alternative to IOMR [6, 5]. Further well-designed, prospective studies evaluating IOUS as well as comparing IOMR and IOUS are warranted. Having said that, in view of the heterogeneity in patient populations and variability in defining objective outcomes, it is likely that the external validity of most of these Bcontrolled^ trials will be limited, precluding generalized applicability across the population. Therefore, large, well-conducted prospective observational studies would also be extremely helpful in critically evaluating such adjuncts. We believe that IOMR and for that matter any of the adjuncts are certainly a boon. All the benefits (such as surgeon comfort, confidence) in fact cannot be measured objectively. However, when available, all the objective evidence needs to be given due cognizance. We do hope that this correspondence puts in perspective these facts and hope that more studies will address and resolve them in the future. Conflict of interest No conflicts of interests to disclose.
References 1.
2.
3.
Barbosa BJ, Mariano ED, Batista CM, Marie SK, Teixeira MJ, Pereira CU, Tatagiba MS, Lepski GA (2014) Intraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies. Neurosurg Rev. doi:10. 1007/s10143-014-0592-0 Barone DG, Lawrie TA, Hart MG (2014) Image guided surgery for the resection of brain tumours. Cochrane Database Syst Rev 1, CD009685. doi:10.1002/14651858.CD009685.pub2 Kubben PL, Scholtes F, Schijns OE, Ter Laak-Poort MP, Teernstra OP, Kessels AG, van Overbeeke JJ, Martin DH, van Santbrink H (2014) Intraoperative magnetic resonance imaging versus standard neuronavigation for the neurosurgical treatment of glioblastoma: a randomized controlled trial. Surg Neurol Int 5:70. doi:10.4103/21527806.132572
4.
5.
6.
Kubben PLMKJ, Schijns OEMG, ter Laak-Poort MP, van Overbeeke JJ, van Santbrink H (2011) Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. Lancet Oncol 12:1062–1070 Saether CA, Torsteinsen M, Torp SH, Sundstrom S, Unsgard G, Solheim O (2012) Did survival improve after the implementation of intraoperative neuronavigation and 3D ultrasound in glioblastoma surgery? A retrospective analysis of 192 primary operations. J Neurol Surg A 73:73–78 Solheim O, Selbekk T, Jakola AS, Unsgard G (2010) Ultrasoundguided operations in unselected high-grade gliomas—overall results, impact of image quality and patient selection. Acta Neurochir 152: 1873–1886
Comments Guilherme Lepski, Tübingen, Germany We would like to thank Dr. Moyiadi for the constructive criticism regarding our study entitled BIntraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies.^ Although we live in a special moment in history, characterized by great scientific and technological development, as well as the frequent emergence of new technologies, this is also a time of global economic and financial crisis. This global scenario is becoming increasingly problematic and challenging for health care providers. As observed by Dr. Moyiadi, the insertion of new drugs into the therapeutic armamentarium ideally undergoes a rigorous process of validation to assess therapeutic efficacy and biosafety. Unfortunately, this is not always true for all forms of medical technology, especially when it comes to surgical technology. This environment is Bgreedy^ for technological innovations, and new technologies are often incorporated before their effectiveness is proven. In our view, the justification for incorporating new technologies should always be backed by efficacy studies applying rigorous quality standards. We believe this is becoming a trend, and the intention behind the publication of our review study is to draw the scientific community’s attention to this need. However, we disagree with Dr. Moyiadi regarding the Bclinical practice-changing value^ he mentions in his critique of our review. We believe the publication encourages neurosurgeons to use new technologies rationally and to critically evaluate their actual benefits. Moreover, the information we provide can also be used as a reference for health care providers who invest in the established technologies. The fact that other authors defend the same point of view (Kubben et al. 2012 and Barone et al. 2014), although with different nuances, only underscores the value of the publication, in addition to reinforcing this trend in favor of providing savings for health care systems worldwide. In addition, the review conducted using the Cochrane database (Barone et al. 2014) was published online while our article was being prepared for submission to Neurosurgical Review. Although the primary outcome of that article was the same as ours (extent of resection), the databases searched and the periods involved were completely different, which only reinforces the complementary nature of that publication and highlights the current lack of prospective studies in this field. In line with this vision, our group is currently conducting a clinical study to evaluate the efficacy of assistive technologies within neurosurgical oncology. We are pleased to contribute to this discussion and hope that this review motivates other authors to generate robust data in the scope of high-quality prospective trials addressing this important issue.
