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  • Over the past two decades, neurosurgery has been transformed by technological advancements, interdisciplinary collaboration, and a deeper understanding of the brain
  • Breakthroughs like functional magnetic resonance imaging and minimally invasive surgery have enhanced diagnostics and treatments, steering the field away from its conventional practices 
  • By 2040, such changes will continue and accelerate as neurosurgery embraces augmented reality interfaces, robotics, and artificial intelligence, facilitating personalised interventions based on individual genetic profiles
  • The future of neurosurgery will not only showcase technological excellence but also a heightened commitment to ethical principles prioritising patient welfare and societal wellbeing
 
Neurosurgery 2040
 
Over the past two decades, neurosurgery has undergone a transformation, marked by increased precision, less invasive procedures, and swifter recovery, all driven by technological advances, interdisciplinary collaboration, and an enhanced comprehension of the brain. Progress ranges from neuroimaging technologies to refined surgical techniques. This Commentary briefly describes the milestones and ethical considerations of neurosurgery up to ~2040.
 
Since 2000, the convergence of technologies such as functional magnetic resonance imaging (fMRI) and minimally invasive surgery has improved diagnostic approaches and treatment methodologies. Departing from conventional norms, the advent of personalised medicine and the rise of neurostimulation hold the promise of advancing our comprehension and treatment of neurological disorders.
 
Looking forward to ~2040, we foresee these trends intensifying, with operating rooms (OR) equipped with state-of-the-art technologies like augmented reality interfaces, robotics, and artificial intelligence (AI), synergising with human expertise. Envisage progress in targeted medicine to also continue and further disrupt neurosurgical treatments by customising interventions according to individuals' distinctive genetic profiles and incorporating developments in gene therapies. As these technologies augment cognitive capabilities, addressing ethical concerns to increase in importance will become more relevant. Prioritising moral considerations will be essential to ensure responsible and compassionate utilisation of these tools.
 
Furthermore, the upcoming collaboration spanning various fields is positioned to speed up, playing a crucial role in driving neurosurgery to unprecedented levels. This cooperative endeavour is expected to break down traditional barriers and enhance our understanding of the complexities of the brain. Looking forward to 2040, an intensified sense of purpose among healthcare providers is predicted, highlighted by heightened global awareness and strategic initiatives aimed at reducing healthcare disparities by broadening access to neurosurgical expertise worldwide. Underscoring the increasing significance of robust ethical guidelines and ongoing dialogues, we highlight the importance of steering the path of neurosurgery beyond technical innovations. Contemplate a growing focus on ethical principles that prioritise patient welfare and societal wellbeing, indicating that the future of neurosurgery will be characterised by a blend of technological expertise and a more pronounced commitment to human values and purpose.
  
In this Commentary

This Commentary has two parts. Its overall aim is to nudge neurosurgeons and providers to reflect on their current modus operandi and strategically prepare for the future. Part 1, Neurosurgery since 2000, briefly describes technological developments and interdisciplinary collaboration, which have improved diagnostics, treatments, and our understanding of the complexities of the brain. Part 2, Neurosurgery 2040, anticipates integrated operating rooms where augmented reality, robotics, and AI merge with human expertise. This forward-looking approach stresses interdisciplinary collaboration and a purpose-driven mindset to enhance access to efficacious therapies.
 
Part 1
Neurosurgery since 2000
 
Over the past two decades, neurosurgery has evolved at a pace unparalleled in its history. From advancements that have improved diagnosis to the refinement of surgical techniques, the field, since the turn of the millennium, has been a testament to the determined pursuit of knowledge and the inventive spirit within the medical community. We briefly describe aspects of this transformative journey, shedding light on a few key milestones, ethical considerations, and the promising trajectory that lies ahead.
 
Technologies such as fMRI, diffusion tensor imaging (DTI), and positron emission tomography (PET) have become essential tools to improve diagnostics. Concurrently, minimally invasive surgical approaches, guided by real-time imaging, have not only reduced invasiveness but have also improved patient outcomes. The collaboration between advanced neuroimaging and refined surgical methods marks a shift in neurological care, by facilitating more precise and effective interventions. Indeed, a hallmark of neurosurgery's evolution since 2000 has been the increased use of precision medicine. Departing from the traditional one-size-fits-all approach, the field has shifted towards tailoring treatments based on individual genetic, molecular, and physiological characteristics. Genetic profiling, biomarker identification, and targeted therapies have emerged as effective tools to enhance diagnostic accuracy and pave the way for the expansion of personalised therapies. This departure from conventional approaches suggests a future where neurosurgical treatments are as unique as the individuals they seek to assist.
 
Empowered by technological progress, surgeons can now probe the brain with newfound precision and safety. Minimally invasive approaches, including endoscopic and stereotactic procedures, have minimised trauma, accelerated recovery times, and expanded the scope of what is surgically achievable. Neuron-navigation systems and robotic-assisted surgeries have further enhanced neurosurgical practice, redefined possibilities, and improved outcomes. The rise of minimally invasive procedures has not only reshaped neurosurgery but has also facilitated patient-friendly approaches over traditional open surgeries. Techniques such as endoscopic and laparoscopic procedures significantly reduce physical tolls on patients, improve recovery times, and minimise complications. Equipped with specialised tools and advanced imaging, neurosurgeons can navigate through the brain's structures with minimal disruption, and not only provide medical advantages but also cosmetic benefits and faster postoperative rehabilitation.
Since 2000, neurostimulation has introduced novel therapeutics for various neurological disorders. Technologies such as deep brain stimulation (DBS) and spinal cord stimulation (SCS) have brought relief to conditions such as Parkinson's disease and chronic pain. The integration of adaptive neurostimulation guided by real-time feedback, represents a shift towards personalised and adaptive treatments, offering hope for an improved quality of life.
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Brain disorders and the changing nature of neurosurgery
The burgeoning field of neurogenetics investigates the interplay between genes and complex neural networks. Personalised therapies, which have evolved from unravelling unique genetic signatures, hold promise for conditions such as Alzheimer's, Parkinson’s, and epilepsy. Neurogenetics not only carries the potential for targeted interventions but also provides insights into the individuality of our minds, suggesting a new era where the enigmas of cognition are elucidated.
 
Interdisciplinary approaches drive breakthroughs in neurosurgery that go beyond traditional boundaries. The fusion of neuroscience with engineering, computer science, and genetics enhances our understanding of the brain, leading to creative solutions. Whether neurosurgeons collaborate with engineers or data scientists, these partnerships redefine possibilities within the field, pointing towards a future where the complexities of the brain are unravelled through a range of capabilities. Translational research in neurological disorders provides additional hope by linking theoretical breakthroughs to tangible results. The combined efforts of researchers, clinicians, and pharmaceutical experts expedite the development of innovative therapies, bringing optimism to those affected by neurosurgical disorders.
 
Neurosurgical progress brings hope, yet finding a balance between technological development and ethical challenges is essential. While innovations hold promise, the ethical considerations associated with interventions related to the brain, including matters such as informed consent and privacy, become increasingly complex. Thus, it is crucial to reconcile the progress in neurosurgery with an awareness of ethical responsibilities, ensuring the utmost respect for the human mind.

 
Part 2
Neurosurgery 2040
 
Neurosurgery 2040 envisions a future shaped by ongoing developments since 2000, described in Part 1. Though predicting specifics is challenging, key trends are gaining momentum and set to rapidly redefine the field over the next two decades. The integration of AI and novel technologies, collaborative efforts across disciplines, a shift towards patient-focused precision care, improved accessibility to neurosurgical interventions, and a heightened focus on ethical considerations collectively signal the nature of forthcoming transformation. While these trends have been evolving since 2000, it is important to note the accelerated pace at which they are expected. This underscores the need for clinicians and providers to proactively prepare for imminent paradigm shifts. This section offers a partial glimpse into potential aspects of neurosurgery in 2040, emphasising the urgency for adaptation and innovation.
 
In January 2024, Neuralink, founded by Elon Musk in 2016, achieved a significant milestone by successfully implanting its inaugural device into a human patient. This marked progress towards realising Musk's visionary goal of helping individuals grappling with paralysis and diverse neurological conditions. Concurrently, Jaguar Gene Therapy secured FDA approval for its gene therapy designed to address genetic manifestations of autism spectrum disorder and Phelan-McDermid syndrome, instilling hope in thousands of individuals who have lacked effective treatment options.
 
While traumatic brain injury (TBI) continues to be a pervasive global health concern, affecting millions annually, (in the US ~2m cases each year), the resultant annual global burden on healthcare, patients, families, and society amounts to ~US$400bn. The current gold standard management of severe TBI involves an invasive procedure, which entails drilling a hole in the skull to insert a catheter for monitoring intracranial pressure (ICP). However, the evolution of neurosurgical techniques suggests that this invasive process will become obsolete by 2040. Emerging innovations are poised to replace it with a non-invasive method for monitoring ICP.
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Healthcare 2040

Such breakthroughs provide a glimpse into the future landscape of neuro-trauma and neuro-disorders expected by 2040, highlighting the rapid pace of progress in the field. It seems plausible to posit that, as neurosurgery undergoes these, and other, changes, clinicians and healthcare providers will witness a paradigm shift, fostering an evolution in patient outcomes and reshaping neurological care.
Expect the continued development and increasing adoption of minimally invasive techniques, neuroimaging, nanotechnology, and targeted therapies. These advancements are poised to replace standard surgical approaches in neurosurgery, leading to a significant improvement in the overall patient experience and making interventions more accessible. The future of neurosurgery envisions the use of microscopic robotics for intricate procedures, steering away from invasive surgeries and embracing non-invasive alternatives. AI techniques are set to play a crucial role, serving as co-pilots by analysing real-time data. Additionally, genetic insights will inform tailored interventions in this collaborative environment, blurring interdisciplinary boundaries and signalling a departure from conventional approaches. The focal point of this shift is personalised care.

Within this evolving ecosystem, genetic profiling empowers neurosurgeons to design custom neural implants and gene therapies. This has the potential to significantly reduce the need for invasive procedures. These changes highlight the urgency for adaptation and innovation in the field, underscoring the importance of staying at the forefront of these technological and medical advancements.
 
By 2040, a confluence of neurogenetics, personalised neurosurgical therapies, and genetic engineering is anticipated to surpass conventional medical norms. Novel technologies will unravel the intricate interplay between genetics and neurological disorders, delivering custom-made solutions, significantly reducing risks, and optimising therapeutic outcomes. In the approaching years leading up to 2040, Western providers are positioned to align themselves with a defined 'purpose' and actively participate in initiatives aimed at enhancing access to high-quality healthcare. While these pursuits complement the traditional focus on maximising returns for investors, they are increasingly becoming an intrinsic part of the worldview and demands of Generation Z. The imperative for traditional providers to adopt a purpose-driven ethos and acknowledge their global responsibilities is important, and encouraged by a growing call for greater inclusivity. Foresee a surge in global awareness regarding healthcare disparities, prompting a commitment to leveraging technology for the advancement of worldwide healthcare accessibility. A socially responsible approach, incorporating ethical business practices and community engagement, is not only a moral imperative but is also foreseen to contribute significantly to the enduring sustainability of the MedTech industry.
 
As we approach 2040, Western neurosurgical providers will be expected to adopt a sharper 'ethical' focus, particularly in response to the escalating utilisation of neural implants and genetic therapies. While many MedTechs currently profess ethical awareness, the impending changes in neurosurgery underscore the necessity for a significant revaluation and augmentation of ethical strategies.
 
As neurosurgery advances with the further introduction of disruptive technologies and heightened cognitive capabilities, ethical considerations are projected to take centre stage. Deliberations on fairness, consent, and the definition of "normal" cognitive function converge with the emergence of neuroenhancement techniques and the integration of brain-computer interfaces. Ethical frameworks will be indispensable to mitigate and prevent biases in AI algorithms, address privacy concerns, and ensure the judicious utilisation of genetic information.
 
Effectively navigating these moral complexities demands not only technical innovation but also a robust moral compass to align enhanced cognition with human values. The evolving interplay between ethical considerations and technical progress underscores the imperative for ongoing dialogues among neuroscientists, ethicists, and policymakers. The overall objective is to shape the future of neurosurgery not solely through technological advancements but by integrating ethical principles that prioritise patient welfare and contribute to societal wellbeing.
  
Takeaways
 
We have described the transformative journey that neurosurgery has undertaken over the past two decades and provided a glimpse into its future. From the integration of breakthrough neuroimaging technologies to the emergence of precision medicine, neurosurgery has evolved, promising enhanced diagnostics and personalised therapies.
 
As we cast our gaze forward to 2040, a future unfolds where operating rooms are integrated with augmented reality interfaces, robotics, and AI, working in tandem with human expertise. Precision medicine takes centre stage, tailoring neurosurgical interventions to individual genetic profiles. However, the progress is not without its ethical challenges. The heightened cognitive abilities brought about by innovative technologies demand an appreciation for morality to ensure responsible and compassionate use. We stress the increasing significance of interdisciplinary collaboration, transcending traditional boundaries to foster a deeper understanding of the brain, and suggest a future where medical technology providers embrace a heightened sense of purpose, addressing global healthcare disparities by expanding access to neurosurgical expertise worldwide. Emphasising the critical role of robust ethical frameworks and ongoing dialogues, the Commentary suggests the future of neurosurgery should not only be defined by technical prowess but must also prioritise ethical principles that safeguard patient welfare and societal wellbeing.
 
Overall, the Commentary is a nudge for neurosurgery clinicians and providers to reflect on their current positions and prepare for a different future as the field is developing fast. Our two-part exploration, spanning the past two decades and projecting into Neurosurgery 2040, encourages a forward-looking approach marked by interdisciplinary collaboration and a purpose-driven mindset. The vision presented suggests that the future of neurosurgery will be characterised by a blend of technological expertise and a commitment to human values, ensuring that the field continues to develop ethically and deliver impactful, accessible, and compassionate care to individuals worldwide.
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  • Oncologists increasingly use targeted agents directed at molecular features of cancer cells
  • There is increased off label use of these new targeted agents without evidence to support the practice
  • A landmark study concludes that off label use of targeted agents show no benefit and should be discouraged
  • Professor Gabra, head of cancer at Imperial College, says more research is needed
 

Despite significant progress in cancer care over the past decade, there remain substantial challenges in the treatment of advanced cancers. This has increased off-label use of newer drugs based on molecular studies of tumours, largely without much evidence to support the practice.

A landmark clinical study, known as SHIVA, led by Christophe le Tourneau, a senior medical oncologist at the Institut Curie in Paris, raised expectations among both doctors and patients, because it is one of the first randomized studies to explore molecularly targeted agents applied outside their indicated use (off-label) among those with advanced cancers for whom standard therapies had failed.
 
Findings, published in Lancet Oncology, September 2015, concluded that, “off-label use of molecularly targeted agents should be discouraged,” since the study detected no improvement in survival rates when compared to treatments selected by clinicians that were not based on such sophisticated DNA profiling. 

What are the implications of the study’s negative findings for personalised medicine?

Christophe le Tourneau

In the videos below Le Tourneau describes the SHIVA trail and some of the challenges it faced.

   

   
    

The context

Cancer is a heterogeneous, complex, and challenging disease to treat. Tumours formerly categorized as a single entity on the basis of microscopic appearance are now known to be diverse in their molecular characteristics. Cancer chemotherapy is on an evolutionary path from non-specific cytotoxic drugs that damage both tumour and normal cells to targeted agents that are directed at unique molecular features of cancer cells, and aims to produce greater effectiveness with less toxicity.
 
Over the past decade our understanding of cancer and the basis of its treatment has been significantly changed by the advent of rapid and cheap DNA sequencing technology. The application of these sophisticated analytic techniques to arrive at a therapy for a particular cancer has been called “personalized oncology.” The idea of personalized cancer care based on molecular characteristics of the tumour promises to expand the boundaries of precision medicine. Numerous case reports and other observations have suggested that therapy targeted at molecular characteristics of a tumour can have significant beneficial effects.
 
These personalized therapeutic strategies have rendered traditional classifications of many cancers redundant, because they have advanced our understanding of the underlying biology and molecular mechanisms of specific cancers. Cancer is no longer considered a single disease entity, and is now being subdivided into molecular subtypes with dedicated targeted and chemotherapeutic strategies. The concept of using information from a patient's tumour to make therapeutic and treatment decisions has changed the landscapes of both cancer care and cancer research.

 

The SHIVA study

The SHIVA study, carried out at eight academic centres in France and conducted in 195 patients with metastatic cancer resistant to standard care, was a proof-of-concept, open-label, randomized controlled study. The patients were randomly assigned to receive either molecularly targeted agents (used off-label) chosen on the basis of the molecular profile of the tumour; or therapy based on the clinician's choice. The median follow-up period was 11.3 months. Findings showed a median progression free survival (PFS) of 2.3 months for patients receiving targeted therapy, versus 2.0 months for patients receiving therapy based on the clinician's choice.

"So far, no evidence from our randomised clinical trial supports the use of molecularly targeted agents outside their indications on the basis of tumour molecular profiling . . . . . Our findings suggest that off-label use of molecularly targeted agents outside their indications should be discouraged, and enrolment into clinical trials encouraged," says Le Tourneau and his colleagues.
 

More research required

Hani Gabra, Professor of Medical Oncology and Head of Cancer, Imperial College London says, "SHIVA is important because it is the first randomized study carried out in this complex area of matching drugs to genomic profiles of tumours. Despite the fact that the results are negative we should continue research in this area because personalised medicine is a relatively new area. One thing to note is that the molecularly targeted agents used in SHIVA were single agents, which could increase resistance and reduce the agent’s efficacy. In clinical practice we tend to use several targeted agents in combination in order to counteract drug resistance. SHIVA tested specific agents and specific targets, which resulted in disappointing findings. This doesn’t necessarily negate the overall strategy, but it does suggest that more research is necessary to test the overall strategy, and this might be more challenging.”
 

Takeaways

SHIVA is one of several on going and proposed studies aimed at defining the role of targeting sequencing of tumours in an endeavour to enhance therapy. The SHIVA study did not uncover any new positive evidence to help in the management of advanced cancers. Le Tourneau and his colleagues suggest further studies in a subset of patients that have tumours with molecular alterations in the chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Oncologists, while disappointed by SHIVA’S results, still hold out hope for their patients and advocate further studies.

 
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