Story of a Survivor from a Glioblastoma with MGMT not methylated
I think it is important to end the year with an article that gives some more hope to patients and their families. Since it is the last article that I will write for this year, I take the chance to tell you that after only 5 months from the beginning of this adventure over 3000 visits to this website have been recorded, 2/3 of which coming from Italy which is is an important result considering that every year in Italy from 1500 to 2000 people discover to have a glioblastoma.
Over these 5 months we have written about thirty articles, developed a chatbot and translated in Italian the guide of the Musella foundation on new diagnoses of brain cancer. For 2020 the goal is to continue managing glioblastoma.it at this rate, publishing at least one new article a week, translating the new edition of the guide when it comes out, strengthening the chatbot making it become something that comes close to an advisor. The idea of an Italian version of the virtual trial project also depends on how many physical and mental energies Emanuele will continue to give us.
The following story is a story of a survivor from a glioblastoma with MGMT methylation status not methylated, a feature in common with the glioblastoma of Emanuele. This type of glioblastoma does not respond well to Temozolomide so it is considered particularly difficult to fight. This story is another story that I have found during the translation of the Musella Foundation Guide. Other stories like this can be found at the link: www.virtualtrials.com/survive.cfm.
… the story of my brain tumor began in late 2006 when I suffered from a series of debilitating crises. Such symptoms would usually involve emergency treatment, but my case was complicated by the fact that I had suffered from epilepsy since childhood. It had been kept under control with drugs and in 2006 I hadn’t had a crisis since years. However, my doctors have attributed these new attacks to my old epilepsy. The drugs were increased but the seizures progressively worsened. One day in early 2007, I woke up with the right half of my face paralyzed, with generalized rigidity on the right side of my body. My wife took me to the emergency room. I underwent a CT scan, which showed a large lesion in my left frontal lobe along the area of motor control.
In February 2007, I underwent surgery and my tumor was completely removed. Before the operation, the surgeon had requested my permission to be as aggressive as possible (permission granted) but he advised me that I had to be prepared for any consequences, including the possibility of paralysis of a part of the body. In fact, my particular postoperative problems were similar to preoperative ones: facial paralysis, weakness of the right side and minor aphasia. These problems were constantly improving in the weeks, months and subsequent years.
I was sent home waiting the pathological result, which arrived in a few days. The diagnosis was glioblastoma, a conclusion confirmed by two other laboratories, which independently analyzed tumor tissue on paraffin slides. I received the usual prognosis for this disease: almost certain recurrence within 1 year, with little chance of surviving more than 3 years. Molecular tests reported that my tumor’s MGMT status was unmethylated, which meant that my tumor was less likely to respond to chemotherapy with alkylating agents such as temozolomide (Temodal).
I looked for therapeutic options. At that time I was living what is now the standard therapy for the treatment of glioblastoma was not yet widely applied.
However, I found and read the famous article by Stupp entitled “Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma”, which also had benefits with the concomitant administration of temozolomide during a 6-week radiotherapy period followed by adjuvant therapy with temozolomide. I found two oncologists who were willing to offer me this therapy and I started immediately.
Even before radiation therapy, I had started reading everything I could find about brain tumors, looking for ways to improve my chances of survival. The PubMed website (www.pubmed.com), the index of medical articles from the National Library of Medicine published worldwide, was an invaluable resource. At one point I came across the Musella foundation website, virtualtrials.com, which provided me with many important information about my illness. I found Ben Williams’ story on that website particularly interesting and the logic behind his compelling therapeutic approach. I read Ben’s book and its periodic updates, which led to an exchange of emails, followed by several telephone conversations. Throughout my ordeal Ben has been a valuable source of knowledge and support, as it has been for many other patients.
I was in the fortunate condition of having had a total resection of my brain tumor. However, I was aware that the chances of recurrence within 1 year were extremely high and that a recurrent tumor is more difficult to control than a newly diagnosed tumor due to its acquired resistance to first-line therapies. My goal, therefore, has become to postpone the recurrence for as long as possible and to do it with all the means at my disposal. The approach I followed was along the lines of that used by Ben Williams: blocking different tumor growth mechanisms by means of a “cocktail” of agents that have shown evidence of efficacy against glioblastoma or other types of cancer.
During the 6 weeks of radiotheray, I had a lot of time to start planning the next phase of treatment. My oncologist proposed 8 28-day cycles of temozolomide according to the standard drug delivery schedule on days 1 to 5 of each cycle followed by 23 free days. I had read that this program provided limited benefit to people like me whose tumor MGMT status was not methylated. But there have been some positive responses from experiments that included a low-dose (metronome) daily schedule, in which the unmethylated state had less influence on the outcomes of temozolomide therapy.
Based on this research I put pressure on my medical team to try out the metronome program that was being considered. In 2007 bevacizumab (Avastin) was becoming popular as an experimental treatment for recurrent glioblastoma. Bevacizumab is an anti-angiogenesis drug that inhibits the growth of new blood vessels to feed the tumor. Based on the positive results of various initial studies, I wanted to add bevacizumab to the proposed metronome therapy for temozolomide. This highly anti-angiogenic approach seemed attractive to me because it had the potential to prevent recurrence by delaying the growth of blood vessels in the tumor area. I have discussed the idea with some prominent neuro-oncologists around the world and have received encouragement from many of them. The doctors at a particular cancer center were particularly enthusiastic and generously offered to write support letters for my plan. With the help of a researcher, I drafted a proposal for my bevacizumab / metronomic temozolomide treatment plan, which I presented to my oncologists. They were interested to see if such a treatment plan could work in a case like mine. Provided that I signed a consent form, they were willing to send the proposal to the hospital’s internal review committee, which approved it as an individual experiment.
Things were going well, but I wanted to pursue a more aggressive strategy and I added chloroquine to therapy after reading articles that showed that it improved the results of chemotherapy. At the same time, I decided to take verapamil, which could potentially inhibit the extrusion of chemotherapy agents by cancer cells and help prevent drug resistance. Another addition was aspirin (200 mg / day), mainly as a prophylaxis against bevacizumab blood clots, but which also has potential anti-cancer effects. Celecoxib was also included in the early stages as there had been promising results in small clinical trials in the treatment of brain tumors and other cancers. Before continuing I had compiled a list of over 60 agents that could potentially contribute to the therapy, which were divided into three categories: (a) they had shown efficacy against some forms of cancer, both in the clinical and preclinical settings; (b) had shown themselves capable of acting synergistically with chemotherapy or other substances already present in my therapy; or (c) had shown positive effects in boosting the immune system. The list was eventually reduced to 27 substances, many of which were natural supplements, for example, green tea extract, fermented papaya extract, omega-3 fish oil, resveratrol, melatonin, mushroom extracts, selenium and so on.
With a few exceptions, my MRI scans have been clean since the summer of 2007. There have been a couple of concerns during the first 2 years, with images showing small degrees of activity in and around the tumor cavity. But these anomalies, which could indicate recurrence, were probably due to radiation damage. In any case, they disappeared over time. I now have annual MRI scans and no changes have been detected for many years. If I had to go back, I would alter many of the details in my treatment plan based on the findings made in the years following my diagnosis.
However, I would not change my therapeutic approach, that is to fight the tumor aggressively using multiple agents at the same time, thus inhibiting as many growth paths as possible. More than 9 years have passed since my diagnosis without signs of recurrence. After passing the 10-year survival point, I will switch from MRI scans once a year to scans every two years. I still believe that my approach has been the most effective way to cure a glioblastoma. For other brain tumor patients, I therefore recommend the following:
- Become as expert as possible about this disease and participate in the formulation of your treatment plan to the best of your ability;
- Make your voice heard;
- Never be afraid to ask questions or offer suggestions, based on what you have learned from other sources (including other patients);
- Finally, if you think your input is being ignored, find another doctor who listens to you. …
If you also have a story to tell, do not hesitate to contact me. We have to collect many stories and raise public awareness on the importance of doing research against this rare and fast growing disease. To do this we also need your stories in addition to the media coverage of the death of famous people affected by the same pathology such as Senator McCain or the television journalist Nadia Toffa.
Almost no new therapy has been found to improve the survival of glioblastoma patients for the past 20 years and the field is littered with drugs that have failed despite promising early data. The last drug to improve life expectancy for few months was Temodal (temozolomide) approved by the FDA in 2005. The only other therapy to improve survival is the Optune device available in USA since 2011. Avastin (bevacizumab) approved by the FDA in 2017 slows down the progression but does not seem to significantly improve survival. For glioblastoma multiforme, which is considered the most difficult tumor to treat together with pancreatic cancer in the USA, the standard for first-line treatment is surgical resection of the tumor followed by temozolomide and radiation therapy, while Avastin is used after relapse, often in combination with experimental therapy administered in a clinical trial. But researchers continue to try with new molecular targets and therapeutic approaches, which is why it is so important to raise public awareness and continue to sustain their efforts.
I don’t know if 2020 will be the year in which glioblastoma multiforme, glioblastoma, GBM or the Terminator, as it is often called, will be defeated but I hope that it is at least the year in which, with the help of all, some important progress will be done. Happy 2020 to all of you!
Hi I would like to talk to you since I have the sabe type of tumor. I have been research but am all alone with my kids so very hard to do. Please help me if you can, Thank you I provided my email if you wish to contact me. Thank you in advance for any help you can provide.
The original source of this article can be found at this link. At the bottom of the page there is a form that you can use to get in touch with the survivor.
Hello, I would love to get in touch with you as my 2 year old nephew has just been diagnosed with grade 4 glioma.
Would like more information as my wife has same glioblastoma with total resection.
Dear Kent, the original source of this article can be found at this link. At the bottom of the page there is a form that you can use to get in touch with the survivor.
Hi, I would love to get in touch. I have been diagnosed with GBM and starting radiation + chemo soon. Any input would help.
Dear Rujuta, the original source of this article can be found at this link. At the bottom of the page there is a form that you can use to get in touch with the survivor.
Please send prayers and hope for my 28 year old son diagnosed 1/21. Completed Radiation and 1 year of Chemo. Tumor fingers are now in Cerebellum. The side effects of the tumor has impacted his walking, moving, speech and cognitive abilites. Just restarted Chemo (Temodar) again along with Avastin, waiting to start the new drug (Tibsovo). He’s so weak and can’t keep anything down. Will he make it?