What is Neuroblastoma?

For people who don't know exactly what neuroblastoma is.

First Genomic-based Pediatric Trials Launched in Neuroblastoma

Last November, Dell announced it was donating an initial $4 million including cloud-computing technology to speed up development of personalized medicine trials for children with neuroblastoma and other pediatric cancers. According to the American Cancer Society, about 650 children under the age of 15 are diagnosed with neuroblastoma each year. It is the second most common tumor in children and the most common cancer in babies less than 1 year old. Although 5-year survival rates for children with low- and intermediate-risk neuroblastoma is higher than 95%, only between 40% and 50% of children with high-risk neuroblastoma survive long-term. The disease is responsible for one in seven pediatric cancer deaths.

To increase survival rates, researchers need the ability to analyze a patient's genomic profile quickly and then determine highly targeted, effective therapies for that patient's tumor type, saidGiselle Sholler, MD, Chair of the Neuroblastoma and Medulloblastoma Translational Research Consortium (NMTRC); Co-director of the Van Andel Research Institute (VARI) Pediatric Cancer Translational Research Program; and Director of the Haworth Family Pediatric Oncology Innovative Therapeutics Clinic at the Helen DeVos Children's Hospital in Grand Rapids, Michigan.

Pilot Study

To accomplish that goal, last spring, Dr. Sholler launched the first genomic-based personalized medicine pediatric cancer trial in neuroblastoma. "The program developed over the past 5 years while we were profiling all of our neuroblastoma patients by isolating the neruoblastoma cells from their bone marrow and noticing that they had very different tumor profiles," says Dr. Sholler.

Dr. Sholler worked withCraig Webb, PhD, Co-director of VARI's Pediatric Cancer Translational Research Program, who developed the computer algorithms to analyze the RNA expression of the tumors of each of the five patients in a pilot study, completed in 2010, and then found drugs that targeted each tumor type. All of the children had relapsed from front-line therapy and had no other therapeutic options.

"The Institutional Review Board wanted us to be able to get the data back in real time because neuroblastoma tumors grow so quickly. Our goal was to be able to do a biopsy of each patient's tumor, analyze the data from the gene-expression profile, generate a report, and then bring together members of our molecular tumor board, which includes researchers, oncologists, pharmacists, bioinformaticians, pathologists, and radiologists. The board would discuss each patient's clinical care so far, the status of the patient, and, based on the report, the list of drugs that target the patient's tumor, so that we could create an individual treatment plan. All of this would be done in less than 2 weeks," said Dr. Sholler.

Larger Trial

A larger 14-patient trial opened last summer at five centers by the NMTRC in collaboration with Intervention Insights-there are 11 clinical trial sites nationwide and 7 more are expected to open this year-and three neuroblastoma patients have enrolled so far. Implementation of Dell's cloud supercomputer, which is 1,200% faster than the current technology in use at the Translational Genomics Research Institute (TGen), where the data is stored, will allow Dr. Sholler to not only sequence each patient's RNA expression profile, but his DNA expression profile as well, in less time.

"Sequencing itself takes about 2 weeks, but the analysis that takes time too. Right now, 2 months is the quickest we can get good data to make clinical decisions. The supercomputer will shorten that time to about 2 weeks for RNA sequencing and 1 month for DNA sequencing. We will make clinical decisions based on the RNA sequencing and expression and go through a cycle or two of therapy and then have our second molecular tumor board meeting, when we will have the DNA information as well and we can reassess treatment options," said Dr. Sholler.

Future of Personalized Medicine

"We choose to fund the personalized medicine trials of the NMTRC because neuroblastoma is such a deadly cancer and we wanted to take the cancer and use it as the first model for how we will do this kind of pediatric research going forward," saidJames M. Coffin, PhD, Vice President and General Manager of Dell Healthcare and Life Sciences. "This model of personalized medicine is transferable to every kind of cancer, and we expect to build one of the largest supercomputing platforms in the genomic field."

Analysis of the genomic profiling will be done using software developed by VARI's Pediatric Cancer Translational Research Program and TGen, which Dr. Sholler can then use to create a treatment plan for each patient, using FDA-approved drugs with known pediatric dosing for the specific tumor type. For this study, the FDA has approved the use of a combination of up to four drugs from any drug classification.

"Our goal is to offer these children a good quality of life, and we are not leaning toward the use of high-dose chemotherapies. Instead, we're looking at lower-dose targeted therapies in combination with maybe one or two chemotherapies," said Dr. Sholler.

Although Dr. Sholler's trials are the first attempt in personalized medicine for children with relapsed disease, if successful, genomic-based medicine for pediatric patients with cancer may eventually be used in the front-line setting, where the greatest chance for cure may be possible.

Improving Cure Rates

"Once a child with neuroblastoma has relapsed, there is no curative therapy. We have been able with lower-dose therapies to extend the lives of these children over the past 5 years. If we can understand what's driving the tumors, stop them from growing, and ultimately kill them, that's a cure," Dr. Sholler said.

"I'm hoping that as we validate this type of methodology and bring this to upfront therapy, that's when we're going to see the cure rates change. Right now we treat all the kids with the same high-dose therapy, but only 50% are responding. We're not serving the other 50% very well," she concluded. ■



Source:http://www.ascopost.com/articles/january-15-2012/first-genomic-based-pediatric-trials-launched-in-neuroblastoma/#.TzKO8iIrj-A.facebook

Noah is HAMA positive, please pray!

Noah is HAMA positive, which means he built up resistance to the treatment, please pray!

Novel Cancer Drug Reduces Neuroblastoma Growth By 75 Percent

ScienceDaily (Apr. 23, 2009) — Researchers from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have found a new drug that restricts the growth of neuroblastoma, a childhood brain cancer. The pre-clinical study was presented in the plenary session at the 22nd annual meeting of the American Society of Pediatric Hematology/Oncology.

Alejandro Levy, M.D., fellow at the Children's Cancer Hospital at M. D. Anderson, presented research showing for the first time that the M. D. Anderson-developed drug, 3-BrOP, reduces tumor growth by more than 75 percent as a single agent. The study, conducted with human neuroblastoma cells transplanted into mice, showed how 3-BrOP, a glycolysis inhibitor, starved the cancer cells to death by shutting down their main energy source, glucose.

"We found that neuroblastoma cells, unlike healthy cells, are highly dependent on glycolysis for energy instead of more efficient means of energy production," said Levy. "Glycolysis is a process that breaks down sugar for energy, so by blocking that process with 3-BrOP, we are able to keep the tumors from producing energy, and this disrupts their ability to grow."

According to the American Cancer Society, approximately 650 children, mainly under the age of five, are diagnosed with neuroblastoma in the United States each year. Close to two-thirds of these children are diagnosed after the cancer has metastasized to other parts of the body. For these patients with high-risk neuroblastoma, long-term survival is less than 40 percent because the tumors are often resistant to traditional chemotherapy.

Pre-clinically, 3-BrOP has already been proven effective against other cancers including glioblastoma, colon cancer, lymphoma and acute leukemia. A Phase I clinical trial is planned to open this year for adult patients.

"As we explore alternative options to standard chemotherapy agents, we are finding drugs, like 3-BrOP, that have the potential to destroy cancer cells while leaving healthy cells unharmed," said Patrick Zweidler-McKay, M.D., Ph.D., assistant professor at the Children's Cancer Hospital and senior investigator of the study. "These drugs can often enhance the efficacy of other treatments, potentially leading to more successful combinations and better outcomes for our young patients."

Other investigators on the study were Lauren Akers, D.O., Maurizio Ghisoli, M.D., Timothy Graham, Lizhi Zeng, M.D., Riitta Nolo, M.D., Peter Zage, M.D., Ph.D., Wendy Fang, M.D., Sankaranarayanan Kannan, Ph.D., Anna Franklin, M.D., Peng Huang, M.D., Ph.D., and Patrick Zweidler-McKay, M.D., Ph.D.

Source:http://www.sciencedaily.com/releases/2009/04/090423180239.htm

Neuroblastoma Awareness: Therapy Reduces Dangerous Side-effects of Cancer Treatment in Children

Children given a hormone growth factor alongside chemotherapy for the aggressive cancer neuroblastoma are less likely to suffer a potentially deadly side-effect, according to a major international study published today in the Journal of Clinical Oncology*.

The hormone, called granulocyte colony-stimulating factor (GCSF), was already known to boost production of white blood cells. But this Cancer Research UK-funded study is the first large randomised trial to show it can reduce the complications associated with low white blood cell count in children treated for advanced forms of neuroblastoma.

Around 100 children are diagnosed with neuroblastoma** every year in the UK, usually under the age of five. Overall six out of ten children are successfully treated, but for children with advanced forms of the cancer it is very difficult to treat successfully.

Children diagnosed with advanced forms of neuroblastoma are given particularly intense treatment that combines surgery, radiotherapy and chemotherapy.

But this treatment often carries the side-effect of ‘neutropenia’ - a low white blood cell count. As white blood cells are key components of the immune system, patients who develop neutropenia during treatment are more susceptible to other diseases and complications.

Professor Andy Pearson, lead author of the paper and Cancer Research UK's professor of paediatric oncology at The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust in Sutton, said: “Patients given GCSF immediately after chemotherapy treatment had fewer problems associated with neutropenia, such as fever, infections, days spent in hospital or on antibiotics and gastrointestinal issues.

“Our team previously identified the high dose chemotherapy regimen that is already saving the lives of many children with high risk neurobastoma, and in this study we report finding a new therapy to reduce side-effects for these patients.

“On the strength of these new trial results, all children receiving intense chemotherapy to treat high-risk neuroblastoma will now be given GCSF.”

The work builds on promising results from an earlier study, also funded by Cancer Research UK and led by Professor Pearson at the ICR , which found that giving doses of five chemotherapy drugs – cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide – more frequently offered the best hope of a cure.

This therapy is now being taken forward as the treatment for children in Europe through the International Society of Paediatric Oncology, Europe Neuroblastoma Group (SIOPEN)***.

Kate Law, Cancer Research UK's director of clinical trials, said: "The results of this promising trial mean that children across Europe diagnosed with neuroblastoma will receive a more effective treatment for this disease.

“Cancer Research UK is the largest single funder of children’s cancer research in the country and is at the heart of an international research effort leading to rapid improvements in children surviving cancer with the fewest possible side effects.”


Notes:


*Ladenstein et al., Journal of Clinical Oncology (2010), Randomised trial of prophylactic granulocyte colony stimulating factor during rapid COJEC induction in paediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study.

** Neuroblastoma is a form of childhood cancer which starts in the child's developing nerves and often appears as a tumour in the abdomen, adrenal glands or the nerve tissue at the back of the abdomen. About one hundred children are diagnosed in the UK each year, mostly before the age of five, and the high-risk form of the disease is one of the main causes of cancer-related deaths in children.

*** The SIOPEN Group led by Dr Ruth Ladenstein at St Anna Children’s Hospital in Vienna, Austria and Professor Pearson at the ICR carried out a Cancer Research UK-funded trial in 16 European countries that assessed the clinical benefit of prophylactic GCSF use. The scientists monitored side-effects of rapid, intense chemotherapy in 119 patients who were routinely given GCSF with 120 patients who were only given GCSF if a severe infection developed.

Source: http://insciences.org/article.php?article_id=9316

Neuroblastoma Awareness: Kids with cancer get innovative treatments at new clinic funded by gift to DeVos Children's Hospital

GRAND RAPIDS -- For 8-year-old Ryan Regan, the checkup at the cancer clinic at DeVos Children's Hospital was fun and games.

He laughed when the doctor tickled his belly, showed off a photo of himself in a Superman costume and wandered down the hall to play with friends.

His mother, Cathy Regan, was amazed at how far he had come since he began treatment for neuroblastoma at a pediatric cancer clinic at Helen DeVos Children's Hospital.

"It's a little miracle," said Regan, who lives in Macomb Township in Southeast Michigan.

A grant announced today (Thursday) will provide funding that will allow the clinic to treat more children like Ryan.

The donation of an undisclosed amount of money from Dick and Ethie Haworth establishes the Haworth Family Pediatric Oncology Innovative Therapeutics Clinic, which uses a personalized medicine approach to treating neuroblastoma and other childhood cancers. The director of the clinic, Dr. Giselle Sholler, is also a researcher at Van Andel Institute.

Through the clinic and the institute, the genetic makeup of tumors is analyzed in an effort to determine the best medications to block the cancer. Doctors and researchers in an 11-hospital research consortium are involved in analyzing the test results and choosing the treatment.

Regan said she brought Ryan to the DeVos Children's clinic after doctors at Memorial Sloan-Kettering Cancer Center in New York said they had no more treatment options for him.

Based on the analysis of Ryan's tumor, which formed in his belly and has spread to his liver, Sholler began treating him with three chemotherapy drugs in mid-September. At that point, Ryan weighed only 36 pounds.

"He couldn't walk," his mother said. "He was vomiting. You couldn't pick him up, his liver was so distended. He was on pain meds around the clock."

Ryan's condition improved after the first treatment. In six weeks, he has gained eight pounds -- and lots of energy. One of the goals of the clinic is to use medications with few side effects, so the children can have good quality of life, Sholler said.

That benefit is much appreciated by Regan. Her son has battled cancer for nearly half his life. At 21 months, he was diagnosed with neuroblastoma, a tumor of the peripheral nervous system that typically strikes children 6 and under. The cancer went into remission six months later, but resurfaced when Ryan was 5.

At times, he was treated with high doses of chemotherapy that required three weeks in the hospital for recovery., Regan said.

"We have to drive here, but it's worth it," she said. "His quality of life is awesome."

The clinic is attracting patients from throughout the country and Canada, said Dr. James Fahner, head of pediatric oncology at the hospital. Six children have been treated so far and, eventually, Fahner expects a half-dozen children a week at the clinic.

The clinic's initial focus is on children whose disease has nor responded to therapy, whose cancer has recurred and those whose cancer is so high-risk at diagnosis that standard treatments are not likely to work.

The Haworths said in a statement they made the donation because they believe in the work of the children's cancer program.

"We want to be an encouragement to Dr. Sholler in advancing the science and we look forward to learning about the results of this new initiative," Dick Haworth said.

Source: http://www.mlive.com/news/grand-rapids/index.ssf/2011/11/kids_with_cancer_get_innovativ.html

Neuroblastoma Awareness: Hero: Baby Aerabella

Hi, My name is Danica. My daughter, Aerabella was diagnosed on Sept 22nd
2011 at 9 months old with stage 2A Neuroblastoma. She has a large tumor in
her chest that was found due to an odd cough. Her family doctor insisted a
chest x-ray be done at the Akron Children's Hosptial. We thought she may
have eaten something and had it lodged. Imagine our shock when we were shown
an x-ray with a mass approx 5cm*3cm*2cm in her chest. She was admitted to
the oncology floor later that night. We spent 13 long days and nights at the
hospital while numerous tests and procedures were completed. Bella had her
port placed Sept 23rd and started Chemo that night. She has three more
cycles of Chemo to go. Then hopefully surgery to remove the remaining tumor.
We were very lucky to have caught this early and her prognosis is very good.
She has been doing quite well, the chemo seems to have given her more energy
and made her hyper. She is at the stage where she loves getting
into everything and exploring new things.She has her own facebook page and
has added neuroblastoma awareness in hopes to make her friends all aware of
this horrible cancer. Her address is facebook.com/babyaerabella