Neurologic Complications in Cancer Patients—Part 2
Dr. Jorg Dietrich is Neuro-Oncologist and Director of the Cancer Neurotoxicity Clinic at Massachusetts General Hospital Cancer Center and Assistant Professor at Harvard Medical School in Boston. In an interview with Dr. Tony Nimeh of PracticeUpdate Oncology, Dr. Dietrich talks about diagnosing treatment-related neurotoxicities and how to distinguish them from cancer-related sequelae (Part 1). He goes on to discuss neurocognitive decline associated with chemotherapy and managing cancer-related seizure and stroke (Part 2).
Neurocognitive decline associated with chemotherapy
Dr. Nimeh: What are the latest findings in the area of neurocognitive decline associated with chemotherapy?
Dr. Dietrich: The latest findings suggest that this problem is more common than previously believed. This is a direct consequence of the fact that people are looking at this issue in greater detail and making more thorough assessments, and there is a much higher awareness that neurocognitive complaints may occur as a consequence of treatment. I think that the oncology community is increasingly embracing the fact that neurological and neurocognitive assessment is part of the workup strategy and that referral to specialists in order to optimize treatment is an important component of patient management.
This field has been largely driven by neuropsychologists over the past 10 to 15 years, and, as I mentioned, these symptoms are more common than previously thought. Further, different patterns of cognitive impairment may occur, either acutely, with some likelihood of improvement and returning back to baselines, or more long-term complications experienced by patients who have difficulties with memory, for instance, and concentration and attention even years after treatment. Now, a whole set of novel applications in terms of advanced imaging have been developed and numerous imaging studies have been published in the past 5 to 8 years, which suggest that both structural and functional changes occur in the central nervous system as a consequence of treatment. This is especially relevant in patients who have not primarily been treated for a brain tumor; they have been treated for tumors outside the nervous system, and yet the central nervous system may take a hit based on the treatment.
To recognize these patterns and to provide supportive strategies and management in terms of symptom improvement is critically relevant. This approach is usually embraced by the patients themselves, and they feel like their symptoms are acknowledged rather than like they are being labeled with having just a depressed state secondary to cancer or difficulties with sleeping.
The component of the field that has really been advancing rapidly in the past decade is based on data that have been derived from preclinical studies to suggest that numerous classes of agents have the potential to disturb neurological function—and the good news is that recovery may be possible. As long as we are able to at least be more sensitive about these issues, I think it will be a matter of time until more powerful ways of minimizing toxicities and more powerful ways of defining strategies to repair the central nervous system can be identified.
Treatment of cancer-associated seizures
Dr. Nimeh: Would you please discuss the difficulties in dealing with cancer-associated seizures? What is known about the use of antiepileptics and other treatment options?
Dr. Dietrich: This is a very common scenario for neuro-oncologists. Seizures in patients with cancers of the central nervous system are very common. The current guidelines suggest that prophylactic treatment with antiepileptic medications is not warranted or needed. Even so, many patients who undergo surgery will be prophylactically covered with an antiepileptic medication in the perioperative period, meaning until about 1 to 2 weeks after surgery. That said, we usually do not start therapy with antiepileptics unless patients have indeed demonstrated and have a history of frank seizures. In these cases, anti-seizure medications are indicated, and I usually follow the traditional guidelines for the management of any other patient with anti-seizure medications.
In the field of neuro-oncology, it is important to consider that some classic antiepileptic drugs, such as phenytoin and phenobarbital, may interact with the action of certain chemotherapeutic agents. In general, the potency of the chemotherapeutic agent may be inhibited with certain antiepileptic drugs because they interfere with liver metabolism and essentially cause degradation of the medication. So, you have to be careful in terms of what drugs to choose and whether certain drugs are preferred in a particular patient’s management. You have to consider potential cross-reactivity and interactions between chemotherapeutic drugs and antiepileptics.
Managing cancer-related stroke
Dr. Nimeh: What progress has been made in understanding the characteristics of cancer-related stroke, as well as treatment and prevention?
Dr. Dietrich: This is another very important topic, and I think it especially affects children who are long-term survivors of cancer therapy, including those who have been treated with prophylactic cranial–spinal radiation or whole brain radiation, because the risk substantially increases for long-term complications of micro-vessel and large-vessel disease. An increased risk has been widely acknowledged in patients who received treatment for tumors of the central nervous system, or even prophylactic treatment to the brain in the setting of leukemias.
In general, the management of strokes or cardiovascular complications follows standard guidelines for any other patient who has these in the absence of an underlying cancer or cancer therapy. What makes things a little bit more complex in cancer patients in general is that many patients have a higher tendency to develop clotting disorders (ie, deep venous thrombosis or pulmonary embolism), and, while this can be a major issue on its own, in the setting of a persistent foramen ovale, crossed embolism can cause cerebral vascular accidents as well. I think it is important to be on high alert for the risk of clotting disorders in both the venous and arterial systems and also to closely follow patients long term. It is particularly important in long-term cancer survivors who have received radiation therapy to the central nervous system, because they will be at risk for ischemic and hemorrhagic strokes.
Managing treatment-related neuropathy
Dr. Nimeh: Where we are in terms of managing treatment-related neuropathy?
Dr. Dietrich: The simple answer is to hold treatment; for instance, platinum compounds that have a very high tendency to cause neuropathies. These neuropathies are a dose-limiting toxicity for these drugs. There is recovery potential with holding drugs. More novel targeted agents may be associated with a very high incidence of neuropathies as well. I think optimal management includes a thorough assessment and awareness of the potential onset of neuropathies, as well as assessment of the extent to which symptoms and signs have progressed over time along with treatment, and then make sure that other causative or potentially treatable factors are ruled out. This again goes into the general neurological management of neuropathies to make sure there are no toxic insults from, for instance, alcohol use. There is an optimal management of diabetes, and it can be ruled-out that any vitamin deficiencies might be contributing to the symptoms of neuropathy.
Dr. Nimeh: Will you please provide us with some closing thoughts regarding the field?
Dr. Dietrich: I think, just to summarize the field, the management of neurological complications is an increasingly important topic in oncology, and it is part of a multidisciplinary team approach to managing patients. Many drugs are known to be neurotoxic; radiation is if applied to the central nervous system. It is important to have a clear, frank discussion about potential complications with patients prior to starting treatment and also to, hopefully, provide supportive management. We will then learn about more preventive strategies and treatment strategies, which will be a big step forward.
The field has developed rapidly in the past decade, and I am very hopeful that we will be in a better place in years to come in terms of offering our patients better treatments and minimizing toxicities, allowing them to have a better life if their cancer can be survived and if long-term side effects can be better managed.
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