NEW YORK – "I wish I would not have this hand now," said my son 4 when he waked morning morning.
"Why, my girlfriend?"
"Because it's not good," he said, pulling his fingers almost without a left hand left with a stronger partner.
Already exacerbated with fear and worrying about the waterfall of Natan's symptoms, I was worried to hear him describing how his body betrayed him.
March 2017. Over the previous year, the signs had arisen that something was wrong. First, Natan's voice weakens. He repeated repeatedly ill with lung infections. Every passing week appeared to bring a new warning. He cheated when eating or drinking. His left foot had to drag. He would walk and fall while playing. He shifted his eyes quickly from side to side. When we spoke to a bright boy, it was harder to connect, as if a heavy fog had settled between him and the world.
Now, Natan was days away from intense surgery to eliminate part of the tumor that ultimately found doctors find growth, such as a weed, from a spinal cord. He had attacked his brain bracket and beyond, promptly stimulating the nerves that control breathing, swallowing and moving. After left without checking it could kill him.
But even if successful, the surgery would only be measuring a stop gap, a starting point in a process that would offer our family to the forefront of medical science. Here, the genomic revolution, as is known, has made it possible to understand and address what drives some cancers and other diseases. With tissue taken from the tumor, doctors told us, they would determine whether it was caused by a rare genetic mutation, which could significantly alter the course of its treatment.
A few years earlier, that course would have been incredibly simple: more than one year of chemotherapy that could prevent the tumor from growing. Patients like Natan may need to repeat this penalty treatment several times during childhood and face life of an increasing impairment as the mass prevents them from their ability to breathe or walk alone. Now, we were told, there was a small chance that Natan could beat the tumor back by swallowing a pillow twice a day, with a few side effects, if any.
In the 15 years since scientists complete the first map of someone's genome – the sequence of the DNA molecules of each individual's genetic blueprint – the process has become phased faster and cheaper. With the information that proves such a product on tumor cells, researchers develop drugs to target, one by one, genetic abnormalities that cause diseases, extend and improve lives Thousands of thousands of people whose illness was once a death sentence. And they just started.
"Dengeng years ago, we did not understand the cancer, and we did not understand the drugs," said Dr Richard Schilsky, chief medical officer at the American Clinical Oncology Association. "Now, we are really able to study the patient's cancer, get some information on what is being driven, and in some cases, identify effective, established therapies that can target those drivers. That's a big difference. "
These developments also bring new risks to patients, who are already dealing with destructive diagnosis, that can be encouraged to consider expensive new treatments with little evidence of their effectiveness or their safety. It's a debate in the cancer community: How to scare the hope for a little against the likelihood that most patients will not find a solution in these therapies.
"Most people do not benefit, but some do it, and that's what's driving the field forward," said Schilsky.
In Natan's case, we learned that one of the new targeted therapies that were approved to treat cancers of aggressive adults has been amazing in one small group of children with similar slow growing tumors. If the DNA sequence turned the relevant adoption, the experts told us, Natan would be a candidate for the drug.
I did not deprive the treatment of evidence, and one whose long-term effects were not known. As a US health editor for Reuters News for many years, I had worked on chronicling the pledge and the symptoms of detailed medication of what's called. I knew questioning claims for new drugs that "melted away" temperatures.
The professional was now personally, so I and my husband were just as suspicious as learning how much we could for the options for Natan. We consulted with family and friends in the medical field and tapping referral networks in our Jewish community. We interviewed experts and read what research we could find out. It was totally, especially on top of the emotional and physical doll of caring for a sick child, but we did not have any choice.
The survival of our little boy was at stake.
Natan was a little baby and a healthy child, active and bad playing with an older brother. It was our only complaint that it often woke up at night, but during those years, there was always a reasonable explanation: feeding, ripping, rubbish growth.
Our first real panic was removed in spring 2016. Natan, then 3, woke up one Sunday with a virtual nose, but otherwise it seemed right. I left the gym. Within that hour, a loud fever shook, and when I returned, my husband was holding it over the bathroom sink, sprinkling cold water on his face.
"He went wet, so he did not breathe," he said. "I have called an ambulance."
After a few days in hospital receiving treatment for pneumonia, Natan gave her a re-appointment. The speed of its decline was worried, but it seemed similar to other parents' stories about incredible respiratory diseases but that they can be treated in young children and our own pre-school campaigns with pneumonia and bronchitis.
Soon we began to think about why sleep was still impaired, and why his voice had started to sound softly and broadly.
The first doctor visits did not turn anything unusual. When anyone recommended more detailed tests, such as a sleep study, my husband and I, being vigilant of unnecessary medical interventions, would ask what practical difference the information might do.
Natan mentioned many mornings by school. "I'm sick!" He would say, even if his essential signs seemed normal.
Within months, it became clear that we needed more answers. When Natan returned to the primary school in September, her voice was barely heard to her teachers. He would sometimes seem to cheat when eating or drinking. He gave an ear infection to a sinus infection that led to bronchitis. When he finished a course of antibiotics, he was soon back in his pediatric office or emergency room, finding it hard to breathe.
"There's no reason that a normal neurological child should sound like that," said pulmonologist after listening to a bit of breath.
Thanksgiving, the tests began to get depressed, as did the medicines Natan needed daily. The list of "complaints" grew on its chart longer after each visit: noisy breathing, sleeping breathing, chronic bronchitis, asthma. He had his hospitals again for pneumonia during Christmas. Nothing we were doing was doing better, and that our disorders fed our anxiety.
Natan mentioned many mornings by school. "I'm sick!" He would say, even if his essential signs seemed normal. At work, I was surprised by the feeling that his teacher or guardian would call at any moment to say he had given the best to breathe. When I came up from the class, I noticed his heavy grasp, how he stepped forward as he walked, and how his eyes appeared.
All new experts who introduced Natan's case indicated another symptom, which is now more suggestive of neurological disorder: the rapid, indirect, eye movements of the weakness on the left side of his body. But we still did not have any explanation.
"What is the diagnosis?" Insisting my husband at every medical visit.
At the end of February 2017, we both sat in the hospital's hospital, waiting to hear when Natan had disappeared from anesthesia for an MRI scan. We tried to keep our worst fears checked.
"When this is over, we should take the boys to the beach for a month. This is the best medication," said my husband.
I looked at the clock. The call from the nursing station had not come in, although more time was over and I was antsy.
"Let's go up the stairs," I said. Then my cell phone ringed.
This was the neurologist who ordered the MRI. The scan showed something unusual: a major "infiltrating" accident in the oblongate medulla, the structure at the lower end of the brain brain that controls breathing and other non-specific functions. The thickest part was tightly tightened into the cervix, with packs turned up to mid and midnight, which regulates balance and motor balance.
"What does that mean?" I asked.
"You need to talk to a neuro-oncologist," he says, adding that she was trying to get an appointment to us within a few days. "There's no sign of a brain rising fluid, so you can take your son home."
"Do you tell me that my son has a huge massive tumor, but should he go home now?" I asked.
We refused to let someone who could interpret the scan speak to us.
One hour later, an expert on pediatric brain tumors told us that Natan's harm was a rare, slow and growing type, which appeared in around 100 cases a year in the United States. Natan may have even been born with him, and she was only big enough to disrupt the nerves that ran through her 4-year-old brain piece, which is a thumbnail structure An adult that connects the brain and the strand.
These dying nerves lost their ability to regulate Natan's walking and mimic movements, breathing, swallowing and sleeping rhythms.
"At least you have a diagnosis that explains everything," says the doctor. "It can take some longer families to reach this point."
"I WILL MAKE THIS HUMANTS OUT"
Like many people who face a crisis, we called on all the resources we had for us. We were fortunate to have access to excellent doctors and world-renowned hospitals close to their homes. The health insurance provided through my employer covered almost all of our expenses.
Every week after we received the diagnosis, Natan had a six-hour surgery at Newy-Presbyterian / Weill Cornell Medical Center. Dr Mark Souweidane, director of pediatric neurological surgery at Weill Cornell and Sloan Memorial Cancer Center, drew around 20 percent of the tumor, most of it in the cervical bone. Further venturing into the brainstem, where the tumor was harder to distinguish from healthy tissue, had been too dangerous.
Within days, the tumor type pathology tests confirmed: slowly growing ganglobioma, a mixture of cells that include elements of the central nervous system and supportive tissue.
The good news was that gliomas of such a low grade are not malignant, which means that this is different from aggressive cancer, they do not grow rapidly and generally do not spread to organs others. In many cases, they give the best to grow completely when patients reach their 20s. But the great size and location of the tumor had already harmed and really could Natan swallow and breathe. This means that it is at risk of breathing fluids and small amounts of food to respiratory tract, resulting in fatal pneumonia or disturbance.
It would take another two months to have sequences results carried out separately by Weill Cornell and Sloan Kettering, where we were trying to re-confirm the genetic profile of the tumor.
At that time, we focused on the recovery of Natan of the operation, with weeks spent in hospital and an acute rehabilitation center.
Removing part of the tumor helped to improve some symptoms. The rapid eye movements had almost gone. In daily therapy sessions, Natan was learning to use her left hand again and to walk without failing. But we were noticing or confronting new problems: hearing loss, severe sleeping apnea, long boats of fluids that show a sign of cerebral tumors.
I tried to stick to the idea that the surgery would be somehow enough for a few months, or years before the tumor proceeded further. I even hoped that he would stop growing alone, as a few doctors had suggested, and were afraid of the new unexpectedness that they would face in treatment. Even without great complications after surgery, it was frail, physically and emotionally.
My husband was incredible to wait to see if the tumor was growing further before starting some form of therapy.
"We feel we're sitting around expecting a miracle to happen," he said. "I want this tumor out."
The sequence confirmed that a mutation of the name BRAF V600E, often seen as adults with cancerous skin cancer melanoma, drops Natan tumor.
"I have something for you," said Dr. Matthias Karajannis, Sloan Kettering's pediatric neuro-oncology, told us when we met us to review the results of the tests. "Something" was a drug of the dabrabenib name, sold by Novartis AG under the Tafinlar brand name. It has helped keep a significant percentage of melanoma patients alive after five years when it is used with a second drug, Mekinist, a major improvement on older therapies.
Karajannis recommended that we use a Tannel to handle Natan. Although chemotherapy is the first standard treatment for low-level scientific gluomas that can not be abstracted, early evidence showed that the new therapy could be much more effective.
In some cases, he said, "the tumors have only melted away."
Roche's Herceptin, or trastuzumab, introduced in 1998, was the first "targeted" cancer therapy, interfere with a protein that promotes growth in around 20 per cent of breast cancer patients. The drug has improved general survival rates, especially among women with earlier period cancers.
The next major development came in 2001, with the approval of Gleevec Novartis, or imatinib. Gleevec Gleevec and the deadly blood cancer known as chronic myelogenous leukemia (CML) to long-term illness, which can be controlled. For almost all CML patients, ill-blood cells contain a combination of two genes that are usually separate. Gleevec blocks the activity of the after-drained genes and leaves untreated healthy cells – a huge increase on chemotherapy that may be fatal, which is toxic to infectious and healthy cells.
With the success of Gleevec, the race was about to find other targeted therapies: For every possible new drug, that meant the initial identification of an aberrant gene that fired a type of cancer and then invented it a drug to resist that harassment.
The reality is much more complicated as researchers learn about the multiple influences at work in cancer cells. Many Gleevec-targeted therapies help a small percentage of patients with only one type of cancer, and often for just one or two years before their tumor cells create new mutations to get out of & # 39 ; r drug.
"This feeling we are going to conquer cancer with these methods," said Dr David Hyman, the leading early drug development in Sloan Kettering, leading research into new therapies targeted. Now the medical community has recognized that cancer "is a series of rare diseases," all have unique biological mechanisms.
Yet, these new drug finds can change life for small groups of patients. The U.S. Food and Drug Administration has approved more than 30 prescribed therapy based on the results of genomic tests. Most of these treatments have been introduced to the US market since 2012.
"For many patients, unfortunately, we do not find magic", but it's also an area that is under development, "said Karajannis in an interview. "Just a few years ago, we did not have any treatment options."
A study published in April in the JAMA Oncology magazine estimated that 15 per cent of almost 610,000 advanced cancer patients in the United States could be considered candidates for treatments based on genomic sequence, and that That's about 7 percent likely to show some benefit.
Xalkori Pfizer and Roche Alecensa, for example, target mutations that occur in about five percent of small cell lung cancer patients who are not small. In late November, Loxo Oncology received newcomer U.S. approval. for Vitrakvi, a pill that was shown to collect a wide variety of tumors that were driven by TRK fusion, which had a genetic anomaly in fewer than one percent of all cancer patients.
Thalar side effects were much less than chemo, the experts said. But her long-term safety was in children – and still – unknown.
Sales of such types of treatments have been targeted around the world to $ 28 billion last year, according to a GlobalData Plc research company.
Within the small community of children with low-grade gliomas, the potential came to a targeted approach almost a decade ago, when two different BraF abnormalities were identified in these tumors. The BRAF V600E mutation appears in around 10 percent of the 1,000 US children diagnosed with low grade gliomas each year. The research coincided with the development of the Taffin, which was originally approved in 2013 for melanoma patients with the BRAF mutation.
At a medical conference in Copenhagen in October 2016, just as we started to investigate the symptoms of Natan, Dr Mark Kieran, then director of the pediatric brain tumor program, introduced at the Dana-Farber Cancer Institute and Boston Children's Hospital, data on 32 children and They were treated with Pub.
All children's tutors were positive for the BRAF V600E mutation, and almost a quarter of them found that their tumors dropped or stopped growing on the drug. In two cases, the tumors disappeared, while more than half stimulated 11 patient tumors. The side effects were relatively small – rash, fatigue, fever.
Less than a year later, we read about those results and think: Could that be a sufficient proof to use on our child?
My husband and canvassed as many authoritative sources as possible. We specifically wanted to hear more about treating children's diagnosis exactly the same as Natan: brain brainstem ganglichioma with BRAF V600E mutation. We reached a number of leading pediatric neurrokeologists. Some had treated, or followed, a few dozen patients like Natan. Others had direct clinical experience with handmade, or no.
They told us that chemotherapy and the new drug were viable options, but they were different from what they emphasized. Some seemed more supportive of chemotherapy. They noted the data collected over decades showing that 25 per cent to 40 per cent of low-grade llioma patients found that their tumors were giving the best to grow after chemotherapy, which was usually including one or more weeks of carboplatin and vincristine. Even if the disease returned, the majority of children survived to be an adult, the studies showed.
There were potential side effects of chemotherapy while a patient in treatment was severe, including neuratathy – nerve damage that could cause pain and weakness of weakness – and the risk of bleeding or severe infection. But there was no other cognitive or long-term damage thereafter.
The survival data was successful with many types of low grade gliomas, including tumors that were enhanced by surgical removal. Brainstem gangliogliomas such as Natan are a very small subset. Research and more recent clinical experience suggested chemotherapy was much less effective in children with brainstem tumors, especially those with BRAF V600E mutation, resulting in repetitions and worse survival rates.
"Do not trust this tumor!" Dr Eric Bouffet, head of neuro-oncology at the Hospital for Sick Children (SickKids) in Toronto said and co-author of a Thalar study. Bouffet was familiar with many low-caliber patients in Canada. He and his colleagues continue to study their results and track data from other medical centers around the world.
The BRAF mutation seems to make the tumors more aggressive, Bouffet told us during a telephone consultation. He told us about children, like Natan, whose brain cerebral tumors cause severe sleep apnea, a sudden stop in breathing. One boy died asleep before he had a therapy, said Bouffet.
Tidal side effects were much less bright, the experts said, and children who use the medication did not lose school as chemistry patients. They could enjoy family holidays. But her long-term safety was in children – and still – unknown and will take years to set up.
The medical literature was also scarce. One of the earliest case studies, from 2014, told the incredible 21-year-old story whose ganglobioma branch has returned after multiple rounds of chemotherapy and radiation, leaving it in a wheelchair. He moved dramatically dramatically with Pubs, and began to walk again, but to experience fatal brain hemorrhage within weeks. His doctors were wondering if such a great rapid recovery had contributed to the bleeding.
A second report showed an optimistic outcome for a baby with a huge, low-grade glioma that dramatically stimulated within two months of treatment, saving his life.
When we consulted Kieran for Natan's case, he recommended that we should first consider chemotherapy, given his safety record, and if he did not, try a Thalar. Previous treatment with chemistry had also been required to register children in the Novartis clinical trial.
There was good reason for notice. Even when drugs are being tested on hundreds of patients, security problems can take years to report. Regulators are now more willing to approve targeted therapies, especially those that handle higher cancers, based on tests in smaller patient groups. For someone who has some months to live and no other options, the risk may be worthwhile. But did the extinguishment be appropriate with slow growing tumors?
We wanted to understand why Kieran, who led to a Tidal clinical trial, would not recommend using it from the start. In June, as soon as we believe Natan was on the way, we took Boston. After examining our son and almost two hours of detailed discussion, Kieran gave a new goal to the new therapy.
In a recent interview, he said, when we met that he had just begun to discuss therapies such as Tafar Fawr Novartis as a first line treatment with other families, depending on the circumstances of the patient.
"The conversation we'd have with a family five years earlier would have been quite different," he said. There is now enough data to consider BRAF that is appropriate from the bat to patients such as Natan, provided families acknowledge that the image may change as more data comes to. obvious, he said.
Not all the patients of the luxury have to wait for that information: "You can not always say, let's wait for three years and see how the data goes," says Kieran. Dana-Farber recently left the development of pediatric cancer therapy in Bristol-Myers Squibb.
Through all our research and consultations with specialists, one details stood out: There was an opportunity that a Thain would actually compress Natan's tumor, unlikely as a result of chemo. If he did so, his symptoms could improve, assuming that the nerves had not been damaged or inappropriate. We needed to give him that opportunity.
Two weeks later, pharmacist Sloan Kettering showed me how to turn Tannel into a liquid to swallow Natan safely. In our kitchen, I said the capsule white powder into a tasty lemonade Kool-Aid, and Novartis said that it is the only drink that can abolish this advanced medication. I tried hard not to spoil anything. Our insurance covered most of the cost, but I was still aware of the replacement cost of just one pill, at almost $ 100 worth.
In the first few weeks, we have had a close eye for unusual reactions. One night, Natan was almost passing by obvious reason. Another night, he lightened his temperature to 105 degrees. It turns viruses. For a few days, ducks fell over his body. Again, it is suspected that there is a virus.
And we noticed something else. After a little more than a week, Natan's voice, almost unacceptable for months, was resonating loudly. At first, we suspected it was real. But Natan was so proud he could now hear himself, and speak for his brother, that he would calm and sing spontaneously.
Over the summer, tests confirmed that his hearing had returned. His gait grew steadily and stronger. With a whistle in his eye, Natan would take an extra deep breath to the nurse and watched the monitor as his oxygen levels ticked from 99 percent to 100. He was pulled off respiratory medications and antibiotics that had been a highway for almost a year.
The next MRI showed Natan, in October 2017, the result of many beyond what we had to allow ourselves to hope: almost all of its tumors find out gone "He looks almost like a normal brain," said Karajannis.
My husband and I have asked ourselves if we could noticed the symptoms earlier, and whether treatment in that time would trigger Natan from the worst of his illness. But given the speed of science developed, we believe that the opposite is true in our case: If we had to find the tumor earlier , Natan would have most likely chemotherapy predominantly susceptible and severe effects every week for more than one year, benefit.
Natan's treatment success does not provide any guarantees. No-one can tell how long the medication will work, which should take the drug indefinitely or stop, or whether it is at any risk.
The science is also moving on. Novartis is beginning to test Tafinlar plus Mekinist – the combination used to treat melanoma patients – against chemotherapy in children whose low-grade gliomas show BRAF V600E mutations to see if the combination works better , and longer. The drug addict has also reduced the requirement for patients to have a previous treatment with chemistry to register. A new generation of BRAF therapies from companies, including Array BioPharma and AstraZeneca, are in clinical trials. We hope that if a Tunnel stops working for Natan some time, there will be a new therapy there to replace.
It's been more than a year since Natan started treatment. He started running again, jumping, swimming, and climbing. He is now the first degree, excited to get to school every day and see his friends.
Natan now swallows her capsule with a sip of water, flashing pipes every time. He has traveled on holiday, even abroad, without misleading. On our last trip, he chose a new T-shirt for himself. In the forefront, he says: "Never give her up."
Not by Michele Gershberg
Editing photos: Steve McKinley
Video: Jillian Kitchener, Craig Hettich, Mike Wood
Design: Pete Hausler
Edited by John Blanton