Towards a Brighter Horizon: Future Paradigms in Brain Tumor Therapies-Q&A session with an expert.
(Focus - India)
In 2020, approximately 308,102 individuals across the globe were diagnosed with primary brain or spinal cord tumors and the same year witnessed the loss of nearly 251,329 lives globally due to primary cancerous brain and central nervous system tumors (Cancer.Net Editorial Board). The complex nature of these tumors and their potential to disrupt neurological function make them a formidable adversary. However, the field of medicine has undergone a remarkable evolution, with groundbreaking discoveries, innovative therapies, and enhanced collaborative approaches shaping the future of healthcare, ultimately leading to improved patient well-being.
How the brain tumor diagnosis and treatment evolved over the years? What interesting trends are on the horizon?
To learn more about it, we connected with Dr. Veekshith Shetty, a renowned Neurosurgeon from India who discussed about promising new treatments for brain tumors and mentioned that the future outlook for patients with brain tumors is considered optimistic, with ongoing research and collaboration. He also highlighted the societal impact and the economic burden associated with the condition and suggested key strategies to improve patient outcomes in the future.
Dr. Veekshith Shetty is a Consultant Neurosurgeon currently serving at Manipal Hospital, Bangalore, Karnataka, India.
First medical touchpoint for brain tumor patients can vary, but it often includes primary care physicians, neurologists, or emergency room physicians. To ensure proper diagnosis and that patients are referred to a neurosurgeon, it is essential for healthcare providers to maintain a high index of suspicion for brain tumors, especially when patients present with persistent, worsening, or unusual neurological symptoms.
We understand that the symptoms of brain tumors often mimic symptoms of other more common diseases, like multiple sclerosis, headaches, or migraines, and physicians often diagnose and prescribe treatment for another ailment. What are the common symptoms of brain tumors, and how do they differ from other neurological conditions?
Dr. Veekshith - Common symptoms of brain tumors include persistent headaches, nausea, vomiting, seizures, difficulty with speech, vision or hearing problems, changes in mood or personality, memory problems, and weakness or numbness in parts of the body. These symptoms can indeed resemble those of other neurological conditions, such as multiple sclerosis, headaches, or migraines. The key difference between brain tumor symptoms and those of other neurological conditions often lies in the pattern and progression of symptoms. Brain tumor symptoms may worsen over time, while migraine symptoms are usually episodic and temporary. Multiple sclerosis symptoms can come and go, but they typically develop more gradually than brain tumor symptoms. Additionally, brain tumors may cause seizures, which are less common in multiple sclerosis and migraines.
Which specialties are the first medical touchpoint for brain tumor patients?
Dr. Veekshith - It depends on where the patient turns up. When someone presents with progressive symptoms, neurological symptoms of a headache, or anything else, and if they meet their physician, it's often the physicians who request a scan and get a scan. Sometimes they get referred to a neurologist who then does a scan and picks up these brain tumors. But a person coming with seizures for the first time or if they develop stroke-like symptoms, for example, they lose control of one half of the body, they will end up in an emergency in a casualty setup. And that's where they have a scan, which gets picked up.
So, the first medical touchpoint for brain tumor patients can vary, but it often includes primary care physicians, neurologists, or emergency room physicians. To ensure proper diagnosis and that patients are referred to a neurosurgeon, it is essential for healthcare providers to maintain a high index of suspicion for brain tumors, especially when patients present with persistent, worsening, or unusual neurological symptoms.
What can be done to ensure proper diagnosis and that patients are referred to neuro-oncologist?
Dr. Veekshith - Collaboration and communication between different medical specialties are crucial in facilitating timely and accurate diagnosis. Primary care physicians, neurologists, and other specialists should be aware of the common symptoms of brain tumors and consider brain imaging studies (such as MRI or CT scans) when appropriate. Furthermore, increasing awareness among the public about the signs and symptoms of brain tumors can help encourage patients to seek medical attention earlier, leading to more timely diagnoses and referrals to neurosurgeons.
What are the risk factors for developing brain tumors, and are there any preventative measures that can be taken?
Dr. Veekshith - We are not aware of the risk factors for brain tumors yet. But we normally see that as we get older, the risk of developing brain tumors increases because most of the tumors are seen in patients over 60 years of age. Some types of brain tumors are more common in males, while others are more common in females, and most of the tumors we often see in men. But having said that, if you have certain inherited genetic conditions such as neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome can increase the risk of developing brain tumors. And there's another condition called Von Hippel-Lindau disease (VHL); they develop a tumor at some point in life in the brain. And the other interesting group of patients is, for example, children who receive radiation for leukemias; when you follow them up, you do notice that some of them may develop tumors in a brain tumor. So, exposure to radiation during childhood is a risk factor. So, these are some risk factors, but if someone were to develop a brain tumor without one, I wouldn't be surprised.
GammaTile therapy presents a significant advancement in the treatment of recurrent brain tumors, including brain metastases, high-grade gliomas, and recurrent meningiomas. This therapy addresses several challenges associated with traditional standard-of-care treatment, typically involving surgery followed by conventional radiation therapy.
How can genetic testing be used to make informed treatment decisions?
Dr. Veekshith - Genetics plays a significant role in developing some brain tumors, particularly in individuals with inherited genetic syndromes. Genetic testing can be used to identify individuals at increased risk for these conditions, allowing for early monitoring and intervention if needed. In addition to identifying at-risk individuals, genetic testing of the tumor can provide valuable information to inform treatment decisions. By analyzing the genetic makeup of the tumor, healthcare providers can gain insights into the tumor's behavior, aggressiveness, and potential response to specific therapies. This information can help guide the selection of the most appropriate treatment plan for each patient, potentially improving outcomes and reducing side effects. And more importantly, I think if there is an individual who has inherited such a gene, and as there is a risk of transmitting this disease to their children, they can make informed decisions about having a family.
If we talk about treatments, historically, the standard-of-care treatment for metastatic brain tumors involves surgery and conventional radiation. In July 2018, GammaTile Therapy received FDA 510(k) regulatory clearance to treat all types of recurrent brain tumors. ,  So, how does GammaTile compare to other treatment options for brain tumors regarding safety, efficacy, and patient outcomes?
Dr. Veekshith - GammaTile therapy presents a significant advancement in the treatment of recurrent brain tumors, including brain metastases, high-grade gliomas, and recurrent meningiomas. This therapy addresses several challenges associated with traditional standard-of-care treatment, typically involving surgery followed by conventional radiation therapy.
In the traditional approach, there is often a delay in starting radiation therapy after surgery as the patient needs time to recover. However, we know that even after tumor removal, there is often a microscopic spread of the tumor cells beyond the visible margins, which cannot be completely removed during surgery. Ideally, we would like to start radiotherapy to target these residual cells as soon as possible.
GammaTile Therapy offers a novel solution to this problem. It is a surgically targeted radiation therapy (STaRT) that involves placing small biodegradable collagen tiles embedded with Cesium-131 radiation sources directly in the tumor bed immediately after tumor removal. This allows for the immediate start of radiation therapy, targeting the residual tumor cells. Additionally, GammaTile Therapy provides a more localized treatment, delivering higher radiation doses directly to the tumor site while minimizing exposure to the surrounding healthy brain tissue. This targeted approach could reduce the side effects often associated with traditional radiation therapy.
Furthermore, GammaTile Therapy enhances patient convenience and compliance. It eliminates the need for multiple hospital visits for radiation therapy, which traditionally lasts several weeks. This reduction in hospital visits may also improve the patient's quality of life during treatment.
Teserpaturev, as you rightly mentioned, has conditional and time-limited marketing approval. So it's not for everyone. It's only on a subset of patients they've tried. But having said this, I think oncolytic virus therapy is one of the big frontiers now in the treatment of glioblastoma, as glioblastoma does recur early and only less than 5% of people live up to five years following diagnosis.
So, are there any factors that should be considered doctor when making a treatment decision that involves GammaTile Therapy?
Dr. Veekshith - See, this has so far been approved only for recurrent tumors. It is being studied whether it is a suitable strategy during the first diagnosis. There are many regulatory issues too because it needs a proper setup as it's radiation at the end of the day. Hence, you need a medical physicist and radiation oncologist.
In India, there are numerous other factors that need to be taken into consideration. While we haven't implemented this system in India yet, it is highly likely that it will be introduced soon. The continuous advancements and improvements in results provide a strong indication that within the next few years, this therapy will become available.
How has its use impacted the treatment landscape of brain tumors?
Dr. Veekshith - The introduction of GammaTile Therapy has significantly impacted the treatment landscape of brain tumors. It has broadened the range of available treatment options, providing a new tool that combines the precision of surgery with the power of radiation therapy. This advancement can potentially improve patient outcomes, including survival rates, and can help shape the future direction of brain tumor treatment. However, more research and clinical trials are needed to fully understand its long-term benefits and potential limitations.
Glioblastoma is one of the most difficult tumors to treat with conventional therapy options. In June 2021, Teserpaturev, an oncolytic virus-based immunotherapy, received a conditional and time-limited marketing approval in Japan to treat malignant glioma based on a Japanese phase 2 clinical trial in patients with GBM. ,  What are your thoughts on this?
Dr. Veekshith - Teserpaturev, as you rightly mentioned, has conditional and time-limited marketing approval. So it's not for everyone. It's only on a subset of patients they've tried. But having said this, I think oncolytic virus therapy is one of the big frontiers now in the treatment of glioblastoma, as glioblastoma does recur early and only less than 5% of people live up to five years following diagnosis.
How might the development of Teserpaturev revolutionize the treatment of brain tumors, and what advantages does this treatment offer over traditional treatment options?
Dr. Veekshith - The advent of oncolytic virus therapy, such as Teserpaturev, marks an exciting frontier in treating glioblastoma, one of the most challenging brain tumors. Oncolytic viruses are naturally occurring or genetically engineered to selectively infect and eliminate cancer cells without damaging healthy tissues. Unlike gene therapy, which uses viruses as carriers for transgene delivery, oncolytic virus therapy leverages the virus as an active therapeutic agent.
Teserpaturev, though currently granted conditional and time-limited marketing approval in Japan, represents a pivotal step in oncolytic virus research and offers promising potential for improving patient outcomes. There are numerous reasons why Teserpaturev, and similar therapies, might revolutionize brain tumor treatment:
Targeted Therapy: Oncolytic viruses like Teserpaturev are engineered to selectively target and destroy cancer cells, sparing healthy cells. This targeted approach could reduce side effects and complications associated with traditional treatments like radiation and chemotherapy, which often indiscriminately damage healthy cells.
Immune Response Activation: Oncolytic virus therapy can stimulate the patient's immune system to recognize and attack cancer cells more effectively. This 'immunotherapeutic' effect could lead to a more durable and long-lasting response against brain tumors.
Combination Therapy Potential: Studies have indicated potential synergistic effects when oncolytic viruses are combined with radiation or chemotherapy. This combination could enhance anti-tumor effects and potentially extend patient survival.
Personalized Treatment: As our understanding of the mechanisms and characteristics of oncolytic viruses like Teserpaturev expands, it may become possible to customize these therapies to individual patients' tumor profiles, enhancing their effectiveness further.
Despite the promising potential of Teserpaturev, it is essential to continue rigorous clinical trials to fully understand its safety, efficacy, and long-term impact on patient outcomes. Only through detailed exploration can we ascertain its advantages over traditional treatment options and firmly establish its place in the overall treatment landscape for brain tumors. This ongoing research is crucial in pursuing more effective and patient-centered treatments for glioblastoma.
What are the other promising new treatments being developed for brain tumors?
Dr. Veekshith - The standard of care for most brain tumors is surgery followed by radiation and chemotherapy. Precise strategies based on tumor-intrinsic dominant signaling pathways and tumor-specific antigenic profiles may ultimately improve outcomes for GBM patients. Several promising new treatments are being developed for brain tumors that leverage various approaches to target and destroy cancer cells. Some of these include:
Focused ultrasounds: Most toxins and medicines cannot cross over from blood into the brain because there's a barrier that exists, designed by nature to protect the brain. For example, if you accidentally ingest a toxin, you don't want the toxin to enter the brain, right? So, this barrier also prevents some chemotherapy medicines from entering the brain. By using a focused beam of ultrasounds, researchers are trying to break this barrier. Preclinical studies have shown that low-intensity pulsed ultrasound increased the concentrations of systemically administered drug therapies in the brain parenchyma in animal models and prolonged survival in GBM preclinical models.
Nanotechnology: Nanoparticles are being developed to deliver drugs directly to brain tumors, potentially increasing the effectiveness of chemotherapy while minimizing side effects on healthy tissue.
Tumor-treating fields (TTF): TTF is a noninvasive treatment that uses low-intensity electric fields to disrupt cancer cell division, potentially slowing or stopping tumor growth. It has shown promise in clinical trials for glioblastoma and other brain tumors.
Targeted therapy: These treatments block specific molecular pathways or genetic mutations that drive tumor growth and survival. Examples include small molecule inhibitors and monoclonal antibodies that target proteins like EGFR, VEGF, or PDGF.
Cancer virus therapy: Cancer vaccines target tumor-associated antigens to induce an immune response against tumors.
Immunotherapy: Immunotherapy, which harnesses the body's immune system against cancer, has led to important clinical advances over the past few years. Various immunotherapies are being explored, such as immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapies like CAR-T cell therapy which are genetically engineered immune T-cells. Treatment with immune checkpoint inhibitors demonstrated improved overall survival in some melanoma patients with brain metastases, suggesting immunotherapy as a potential treatment option for CNS tumors. To date, clinical trials have revealed that immune checkpoint inhibitors have limited efficacy in GBM, where < 10% of patients show long-term responses. Although immunotherapy's success in treating GBM has remained elusive, immunotherapy remains one of the most promising future treatment options.
So yes, there are a lot of new treatments, and it is getting more and more exciting. We have challenges finding out an ideal form of therapy, but I think it's just a matter of time. We will notice the change as we better understand brain tumors and these treatments. All we need is just one form of therapy to click, and then the rest will progressively fall into place.
The brain tumor is not just limited to the patient but also to their families and caregivers. So it can cause significant physical, cognitive, and emotional challenges for the patients and the family looking after them. It ultimately leads to reduced quality of life and can cause functional impairments. And this burden, unfortunately, extends to the caregivers and the families because they need to support and assist the affected individual.
What is the future outlook for patients with this condition?
Dr. Veekshith - The future outlook for patients with brain tumors is gradually improving as researchers continue to develop and refine these new treatments. While many challenges remain, such as overcoming the blood-brain barrier and understanding the complex biology of brain tumors, these advancements offer hope for more effective treatments, better patient outcomes, and, ultimately, improved survival rates.
Collaboration between researchers, clinicians, and pharmaceutical companies, along with ongoing clinical trials, will be crucial in identifying and translating the most promising therapies into clinical practice. Additionally, as our understanding of brain tumor biology improves, personalized treatment approaches tailored to individual patients' tumor profiles are expected to play an increasingly important role in future brain tumor management.
What is the impact of brain tumors on society?
Dr. Veekshith - See, the brain tumor is not just limited to the patient but also to their families and caregivers. So it can cause significant physical, cognitive, and emotional challenges for the patients and the family looking after them. It ultimately leads to reduced quality of life and can cause functional impairments. And this burden, unfortunately, extends to the caregivers and the families because they need to support and assist the affected individual.
It also has an economic impact; for example, if the family's breadwinner is affected by a brain tumor, they may get into severe financial hardship. The costs associated with brain tumor treatment, rehabilitation, and long-term care can be substantial, placing financial strain on patients, families, and healthcare systems. Additionally, brain tumors may result in loss of productivity, as patients often face difficulties in maintaining employment or returning to work due to their symptoms and treatment side effects.
Brain tumors, particularly malignant and aggressive ones, require ongoing research to develop new treatments, improve existing ones, and ultimately find a cure. This demands significant investments of time, effort, and financial resources from various stakeholders, including researchers, funding agencies, and pharmaceutical companies.
How can we raise awareness and promote research to improve patient outcomes?
Dr. Veekshith - To raise awareness and promote research to improve patient outcomes, several strategies can be employed:
Public awareness campaigns: Educate the general public about the signs and symptoms of brain tumors to encourage early detection and diagnosis. This can involve leveraging social media, public events, and collaborations with patient advocacy organizations.
Government and private sector support: Advocate for increased funding and resources for brain tumor research from government agencies and private organizations to accelerate the development of new treatments and diagnostic tools.
Collaborative research initiatives: Foster collaboration between researchers, healthcare providers, and pharmaceutical companies to share knowledge, resources, and expertise, ultimately speeding up the pace of innovation and discovery in brain tumor research.
Patient-centered research: Engage patients, families, and advocacy organizations in the research process to ensure that their perspectives and needs are considered when setting research priorities and developing new treatments.
Education and training: Encourage and support the education and training of healthcare professionals, scientists, and researchers specializing in neuro-oncology to ensure a robust workforce dedicated to improving brain tumor patient outcomes.
Doctor, what is your takeaway message to the patients or to their caregivers regarding effective management of this condition?
Dr. Veekshith - It is important to educate the society. Ideally, we want the patients to seek medical attention much earlier in the disease rather than much later. If picked up early, these brain tumors earlier, can be treated with better outcomes. One of the things I actively do is to educate and encourage the general public to go and seek medical attention if they experienced any symptoms, which could be related to a brain tumor. I would say that all hope is not lost. I encourage my patients to understand what the diagnosis is, understand what the implications are, and how we go about treating it. At the end of the day, the doctor, the patient, and the patient's family are all involved. As a doctor, It is more important for me to educate and encourage my patients to ask questions because better understanding makes the treatment process easier to navigate.
With help of patient support groups, one can get in touch with other individuals diagnosed with brain tumors and their families who can share their experience. I believe by engaging such patient support groups, we can improve outcomes. There are a lot of challenges, but at the end of the day, if we all come together as a group and support each other's causes, we'll have much better outcomes.
Thank you so much for your time and your insight. It was a pleasure talking to you.