The treatment of mesenchymal astrocytoma and glioblastoma multiforme requires the cooperation of several medical professionals working together as a comprehensive multidisciplinary treatment team. It is essential to receive treatment in order to control tumor growth and maintain as good a quality of life as possible. Standard treatment options include surgery, radiotherapy and chemotherapy, as well as medications used to control various adverse effects. Hongmin Bai, Department of Neurosurgery, Guangzhou General Hospital, Guangzhou Military Region The following can give you an idea of what to expect at each stage of treatment for glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), and which physicians you should primarily contact at each stage. If you have GBM, you will usually receive both radiation therapy and the first stage of chemotherapy. If you have AA, you will usually start chemotherapy after you have finished radiation. Your specific treatment may be different, so please consult with your physician for your personal “treatment plan”. The treatment process for newly diagnosed glioblastoma multiforme patients 1) Detection of glioblastoma multiforme – CT/MR scan 2) Surgery + biopsy – definitive diagnosis (contact neurosurgeon) 3) Recovery/rehabilitation – hospital and home 4, Radiation therapy: every weekday, in hospital for 6 weeks (30 days) Chemotherapy: e.g., temozolomide (contact your healthcare professional) 5, Surviving with a tumor (GBM)-symptomatic treatment (contact your healthcare professional) Chemotherapy: e.g., temozolomide (contact your healthcare professional) Course of treatment for patients with mesenchymal astrocytomas 1, Detection of mesenchymal Astrocytoma – CT/MRI scan performed 2. Surgery + biopsy – definitive diagnosis (contact neurosurgeon) 3. Response/recovery – hospital and home ( Contact your healthcare professional) 4. Radiation and/or chemotherapy At this stage, your physician will decide if and when you need radiation and chemotherapy (contact your healthcare professional) 5. Survival with tumor (AA) – Symptomatic treatment (contact your healthcare professional) Medications used to control adverse effects, such as glucocorticoids, anticonvulsants, antibiotics (contact your healthcare professional) What if the tumor comes back (or progresses)? If the tumor recurs or progresses after surgery, radiation, and chemotherapy, your physician may consider other treatments, including surgery and/or chemotherapy in this case. Diagnosis After a physical and neurological examination, most patients undergo a computed tomography scan (also known as a CT or CAT scan) and magnetic resonance imaging (MRI).A CT scan is a special type of x-ray that uses a computer to obtain a three-dimensional image of a particular part of the body.MRI imaging provides a clear picture of the soft tissues of the body through the use of powerful magnetic forces. Both types of scans can be used to determine the location and size of a tumor, which is critical for surgery. In addition, it is difficult to make a definitive diagnosis based on imaging alone, so a biopsy-a small sample of tissue may be needed to determine the type of brain tumor. Key Points Other Imaging Scans Magnetic Resonance Spectroscopy (MRS) Often used as part of an MRI exam, MRS is used to determine the levels of different chemicals in tissues to differentiate between normal and tumor tissues. Diffusion Tension Imaging (DTI) and Blood Oxygenation Dependent Brain Functional Imaging (BOLD-fMRI): to understand the location of functional areas of the brain; Perfusion Imaging (PWI): to understand the blood supply within the tumor and to determine the presence of high-grade transformation. Positron emission computed tomography (PET) provides images of brain activity (rather than brain structure) by measuring the rate at which the tumor metabolizes glucose. Surgery The first step in the treatment of high-grade gliomas is to remove as much of the tumor tissue as possible while trying to minimize damage to normal brain tissue. AA or GBM surgery is usually not able to remove all of the tumor because some tiny tumor cells can hide in normal tissue. And some locations of the tumor, even if they can be detected, may be intentionally left in place by the physician in order to preserve normal brain function. The goal of surgery is to remove as much of the tumor as possible in order to reduce the pressure on the brain tissue and relieve some of the symptoms you are currently experiencing, such as headaches, muscle weakness, and numbness. It is generally accepted that the smaller the amount of tumor remaining, the more likely that radiation and chemotherapy will be effective. After routine surgery for a brain tumor, a hospital recovery period of 7-10 days or more is usually required. Your surgeon will likely ask you to come in for a follow-up at 4 weeks after surgery. Since it is not possible to remove all of the tumor cells with surgery, it is vital to have other treatments such as radiation and chemotherapy. New Surgical Techniques: If you are still in good condition, you can opt for wake-up surgery, which is a craniotomy under general anesthesia with an intraoperative wake-up call to locate your main functional areas (such as motor and speech areas) and maximize the removal of the tumor while preserving the vital functional areas. Intraoperative wake-up surgery is an internationally used surgical procedure to minimize post-operative dysfunction, to maximize the removal of the lesion, to avoid removal of a small portion of the tumor due to the surgeon’s excessive concern about post-operative dysfunction, and to avoid permanent neurological dysfunction due to intra-operative damage to the functional areas, consult your neurosurgeon for more details. Radiation Therapy Radiation therapy involves the use of radiation to destroy and kill cancer cells so that they cannot proliferate, while minimizing damage to surrounding healthy tissue. Although radiation can affect all cells, normal cells can tolerate the effects of radiation better or recover more easily than cancer cells. During radiation therapy, most patients with high-grade gliomas will need to be in the hospital every weekday (Monday through Friday) for 6 weeks (30 treatments over 42 days). You will need to make your daily treatment appointments and choose a regular time slot to receive your radiotherapy. There is usually a ‘localization’ process before radiotherapy begins, where your CT and M RI scans are used to pinpoint the target area in the brain. During the “positioning” process, a lightweight custom molded mask is placed over your head and neck to hold the head and neck in place to ensure that the same areas of the brain are precisely targeted each time. The large machine used makes a noise similar to that of a vacuum cleaner as it moves into position. You will be able to breathe normally during the radiation treatment, but you will need to remain still while the machine is working. Radiation therapy does not cause any pain and you will not see or feel any rays. If radiation therapy is successful, necrosis (dead tissue) will occur in the area of the tumor. It is not possible to tell immediately after radiation therapy whether it is effective or not, because it takes days or weeks for cancer cells to begin to die after treatment and continues to die until weeks to months after the radiation therapy is over. As a result of the treatment response, your first MRI scan after radiation therapy may look worse than it did before. However, your first scan after radiation therapy will be considered your “new baseline” and will be compared to your subsequent scans. It is difficult to determine the effectiveness of treatment based on the results of the scan at first. Often CT and MRI scans 4-6 weeks after radiotherapy and your functional status at that time can give an indication of the effect of radiotherapy on the affected area. The effects of treatment are often more clearly understood as time goes on. Every patient’s response to radiation therapy is different, but most patients tolerate radiation therapy with few adverse effects other than hair loss, nausea, and fatigue. Side effects of radiation therapy usually begin to appear around week 2 or 3 and can last up to 2/3 of the entire treatment at worst. Thankfully, most of the adverse effects can subside gradually and there are medications and other methods that can be taken to alleviate the discomfort. However, for some patients hair loss in the treated area may be permanent. Long-term damage from radiation therapy is very rare, but there may be some damage to the areas of the brain that receive the highest dose of irradiation. Varying degrees of brain swelling (edema) may also sometimes occur, and it is often difficult for your physician to determine whether this is caused by the radiation therapy or the tumor itself. Your physician may prescribe glucocorticoid medications to control the brain edema. Management of Common Adverse Effects of Radiation Therapy Fatigue – Your body uses a lot of energy to cope with the effects of radiation therapy on normal cells. During and after radiation therapy, many people are unable to do as many tens as they used to and can feel fatigued. Helpful tips for dealing with symptoms of fatigue: 1. To conserve energy, do fewer things and take more breaks when necessary (e.g., find time to take a nap during the day). 2, Do only the most essential things and dispatch these in order of importance to ensure that the most important things get done first. 3, Try to get more sleep at night. 4. Clear others to help with shopping, cooking, or other household chores. Ensure that you are taking in plenty of 15 and water, and that your food contains enough calories and nutrients, which can help to relieve fatigue. Nausea/Vomiting – You may feel nauseous for a few hours after treatment. Useful tips for dealing with nausea: 1. Eat a light diet a few hours before radiotherapy. 2. Foods or drinks containing speak can make you feel better, such as gingerbread or ginger tea. Guidelines for postoperative rehabilitation after transoral pharyngeal surgery for patients with skull base depression 1. Soft foods are usually the mainstay of the diet for a month after surgery. For example, lean meat noodles, minced meat with thin rice, tofu, steamed egg, green vegetable porridge and so on. Wang Jianhua, Department of Orthopedic Surgery, Guangzhou General Hospital, Guangzhou Military Command, Guangzhou, China 2. After 1 month of surgery, you can eat as usual. However, avoid spicy, stimulating food. 3, pay attention to oral cleaning, every time after eating to develop the habit of gargling. Especially gargle the throat. 4, the base of the skull depression through surgery to fall into the occipital foramen magnum of the cervical vertebrae pulled down to reset, early mainly by titanium plate fixation, after surgery, generally have to wear a neck collar to protect. Within 3 months after the surgery, we should pay attention to minimize the movement of head down and head turning, because the bones are not yet fused at this time. Too much unfavorable movement will affect the healing. 5, after surgery should be regularly reviewed, generally 3 months after surgery to do the first review, to observe the bone fusion. For young and pediatric patients, due to the rapid growth and fusion of bone, the neck circumference can be removed after 3 months depending on the situation. For elderly and slow-healing patients, the wearing time of neck braces should be prolonged according to the situation. 6. 6 months after surgery is the second time point for review. You should keep in touch with the surgeon. At this time, you can return to the hospital to do a thin-layer CT scan with coronal and sagittal reconstruction to observe the fusion of the implant. 7, one year after the operation (12 months) should be re-examined, at this time, the majority of patients with good bone fusion, return to normal work and life. 8.Children should be followed up annually until adulthood. Adult patients can be rechecked every other year after 1 year. Receive guidance from your doctor. Hair loss – After 2-3 weeks of radiation therapy, almost everyone will experience hair loss in the area of radiation collection. It may take up to a year for the hair to grow back, but thereafter the hair may become thinner or undergo some hair texture changes, and some patients may develop permanent baldness. Useful tips for dealing with hair loss: 1. Once your hair starts to fall out, you may choose to shave your head in order to avoid bald patches. 2.If you plan to buy a wig, it is best to do so early in your treatment so that it is easier to pick the right hair color and style for you. 3. You can also try wearing a hat or wrapping your head in a bandana. In any case, it is most important that you feel comfortable and confident. 4. If you prefer to go bareheaded, please take care to protect yourself from the sun and cold. Skin Symptoms – The skin in and around the treatment area may be dry, itchy or red. Useful tips for dealing with skin symptoms: 1. Avoid exposing damaged skin to sunlight. 2.Do not use creams, cosmetics or soaps on damaged skin; check with your physician about which supplies are safe. 3.Use lukewarm (not hot) water when showering. Chemotherapy Chemotherapy is the application of anticancer drugs (cytotoxic drugs) to destroy or kill tumor cells. Typically, the treatment plan will vary depending on whether you have glioblastoma multiforme (GBM) or mesenchymal astrocytoma (AA). Principles of Chemotherapy for Brain Tumors In general, chemotherapeutic agents used for brain tumors, like those used for other systemic tumors, primarily inhibit DNA synthesis and replication. The key to the success of chemotherapy lies in the fact that tumor cells are subjected to chemotherapeutic agents that are sensitive to them and in sufficient concentrations for a sufficient period of time. The anatomical structure most important for chemotherapy of brain tumors is the blood-brain barrier (bIood_b rain-ba rrier, BBB). It consists of tight junctions in the endothelium of brain capillaries that control the diffusion of substances passing through the capillaries based on factors such as lipid solubility, molecular weight, and protein binding. Since extracranial metastases of primary brain tumors are rare, chemotherapy for brain tumors is required to achieve as high a concentration of the drug as possible at the tumor site in the central nervous system (CNS) and as low a concentration as possible in the rest of the body, thus increasing the efficacy of the treatment and decreasing the incidence of toxic side effects. The decision to administer chemotherapy depends on your individual situation. Factors to consider should include age, pathologic diagnosis, previous treatment, toxicities, and general health. Chemotherapy for malignant glioma For newly diagnosed GBM, TMZ synchronous radiotherapy combined with adjuvant chemotherapy can be used: In the synchronous radiotherapy phase, TMZ 75mg/m 2 is given orally for 42 days. 4 weeks after the end of radiotherapy, TMZ adjuvant chemotherapy, 150mg/m 2, for 5 consecutive days, 28 days as a course of treatment, if well tolerated, then incremented to 200mg/m 2 in subsequent chemotherapy sessions, recommended adjuvant chemotherapy for 6 courses. Nimustine hydrochloride (ACNU, or other alkylating agents carzapine, simustine) is recommended for patients with GBM who are not eligible for TMZ. Regimens of nitrosoureas chemotherapeutic agents: (1) PCV regimen (lomustine + methylbenzyl callus + vincristine): 8 weeks as a course of treatment, not more than 6 courses. Oral lomustine (CCNU) 110 mg/m 2 on day 1; daily oral methylbenzylhydrazine (PCB) 60 mg/m 2 on days 8-21; and intravenous vincristine (VCR) 1.4 mg/m 2 (maximal dose 2ms) on day 8 and day 29. (2) ACNU combination regimen: every 6 weeks as a course of treatment, a total of 4-5 courses of treatment. 90 mg/m 2 of ACNU intravenously, day 1; Teniposide, 60 mg/m 2 intravenously daily, days 1-3. For patients with recurrence, it should be considered according to the site of recurrence, tumor size, intracranial pressure, and the patient’s basic condition. Reoperation is recommended for localized recurrence: for patients who are not suitable for reoperation, radiation therapy and/or chemotherapy may be recommended; for those who are not suitable for re-radiation therapy if they have previously received radiotherapy, chemotherapy is recommended; for those who have failed chemotherapy, a change in the chemotherapy regimen and/or investigational treatments including molecularly-targeted therapies are recommended. Glioma chemotherapy drug profile 1, nitrosoureas, including lomustine (CCNU). Carmustine (BCNU), nimustine (ACNU). These drugs mainly alkylate tumor cell DNA at multiple sites, leading to DNA cross-linking and single or double strand breaks, and ultimately inhibit DNA repair and inhibit RNA synthesis. The main adverse effect of this class of drugs is myelosuppression, which is delayed and cumulative toxicity, and irreversible pulmonary fibrosis. 2, Temozolomide (TMZ), TMZ is a new alkylating agent. After oral absorption, the drug automatically breaks down and forms active alkylated substances, which methylate the DNA of tumor cells and ultimately impede the initiation of DNA replication and lead to cell apoptosis. The drug crosses the blood-brain barrier well, and the concentration of the drug in the cerebrospinal fluid is almost 30% of the plasma concentration.TMZ can be used as a stand-alone chemotherapy or concurrently with radiotherapy (simultaneous radiotherapy and chemotherapy). The main adverse effects are nausea, constipation, fatigue and moderate myelosuppression, which is non-accumulative and can be recovered within 1-2 weeks. 3, Procarbazide (PCBZ), is – a kind of oral alkylating agent, mostly used in combination chemotherapy, the main adverse effects are myelosuppression, nausea, fatigue and skin rash. 4, vincristine and oncotoxin drugs, vincristine class of representative drugs for vincristine (VCR) and vincristine (VLB), commonly used in combination chemotherapy, with a certain degree of peripheral neurotoxicity. Oncotoxin class representative drugs for etoposide, due to the ability of the drug through the blood-brain barrier is weaker, so more as part of the combination chemotherapy, the main adverse reactions for the digestive tract and blood toxicity. 5, molecular targeting drugs a bevacizumab. Targeted therapy represented by bevacizumab is currently under research. The incidence of gastrointestinal perforation caused by bevacizumab is 1-2%. The key to the success of chemotherapy for brain tumors is that the tumor cells receive chemotherapeutic agents that are sensitive to them and in sufficient concentrations for a sufficient period of time What is a common adverse reaction to chemotherapy when? Most chemotherapy drugs are used to kill fast-growing cells, but they often fail to distinguish between normal cells and tumor cells. As a result, these drugs can affect normal cells in addition to tumor cells, causing adverse reactions.