Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke
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The production of free radicals is inevitably associated with metabolism and other enzymatic processes. Under physiological conditions, however, free radicals are effectively eliminated by numerous an...Chemotherapy and radiation are an integral part of cancer treatment; more than half of all cancer patients will undergo one or both therapies. With significant advances in radiation and chemotherapy, the number of long-term cancer survivors has dramatically increased over the years. However, there is a growing concern about radiation and chemotherapy-induced secondary malignancies.
Secondary malignancy means cancer that develops entirely separately from primary cancer due to chemotherapy and or radiation. It may take months or years to develop but is directly caused by the carcinogenic factors of chemotherapy and radiation. It is estimated that roughly 10% of cancer survivors will develop secondary cancer related to their primary cancer treatment.
It is well known that chemotherapy and radiation treatment are highly toxic and may cause severe side effects while on treatment. However, treatment is also linked to a higher risk of developing other disorders later in life, for example, high blood pressure, heart disease, osteoporosis, renal failure, and secondary cancers. Many of the secondary cancers are skin cancers, such as basal cell or squamous cell carcinoma, which can be treated easily. Others, however, are more serious and can be fatal, such as acute leukemia. Let’s talk about these more serious cancers, but first, we need to discuss what leukemia means.
There are 4 main types of leukemia: Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Acute Lymphocytic Leukemia, and Chronic Lymphocytic Leukemia. Myeloid means that cancer starts in immature red blood cells, white blood cells, or platelets. Lymphocytic means that it starts in immature lymphocytes (a type of white blood cell) in the bone marrow. Acute means that cancer develops quickly. Chronic means that it develops more slowly and a person may not experience early symptoms. These early symptoms may be vague and may mimic other medical conditions. Chronic leukemia is usually diagnosed after routine blood testing.
The most common chemotherapy-induced cancer is Acute Myeloid Leukemia (AML). Typically, there is a long latency period, meaning cancer will typically start to develop 5-10 years after the initial chemotherapy or radiation treatment. Linda S. Sutton, MD, says that “developing secondary cancer from cancer treatment is a relatively rare occurrence.” However, chemotherapy patients are 5 times more likely to develop AML than the normal population. There are several risk factors that contribute to the potential of developing AML, as well as certain chemotherapy agents.
Some people have conditions other than cancer, and radiation is used for treatment. For example, rheumatologic or dermatologic conditions and infectious diseases are sometimes treated with radiation therapy. This therapy will cause an increased risk of developing cancer in the future due to the mutagenesis of normal tissue.
It is suggested that certain agents in radiation and chemotherapy are associated with increased risk too, for example, alkylating agents (nitrogen mustard, cyclophosphamide, procarbazine), topoisomerase inhibitors, vinca alkaloids (vincristine, vinblastine), and anthracycline agents (like doxorubicin). These agents are shown to be more carcinogenic, although not all to the same degree, and more study is needed in this field to really determine the leukemogenic potency of individual drugs.
Proton therapy is radiation therapy that uses protons (positively charged atomic particles) to treat cancer. Protons cause less damage to healthy cells than other forms of radiation therapy, such as X-rays. The benefits of proton therapy for cancer are that it can be used to treat tumors near or in critical areas of the body, such as the brain, spine, and chest.
Proton therapy allows doctors to more selectively deliver high-dose radiation and has been shown to deliver higher cure rates than traditional radiation treatment even in some of the most challenging situations. Radiation is more local than chemotherapy however, the x-rays continue to deposit radiation as they exit the body, therefore, damaging nearby tissues. Proton therapy targets cancer cells with a “pencil beam” providing more precision and less “exit dose”, so not only does it reduce overall toxicity but also minimizes side effects which help to maintain quality of life during treatment.
Proton therapy has been shown to reduce the possibility of developing radiation and chemotherapy induced secondary malignancies. by 66%. It is already indicated for pediatric patients that can’t tolerate radiation or chemotherapy, and in patients with eye or brain tumors, or tumors in the spinal cord or brain stem where radiation poses an unacceptable risk.
The National Cancer Institute (NCI) is currently studying proton therapy to see if it is a better option for treating some types of cancer. The NCI is also studying ways to make proton therapy more available and affordable for patients.
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