Childhood cancer Awareness (Action) Month - Day 23

This is Michael.

Today I would like to discuss just ONE of the reasons why research is so necessary for children's cancer. The reason is that there are too many options available to parents when they are told their child has cancer. That probably sounds like a good thing, but it is not. What do I mean by that? I mean to say that because not enough research has been done into the causes and treatment of the 12 major types of cancer seen in children, there are varying opinions by leading institutions as to how to treat it.  

For example, Cannon was diagnosed with stage IV high risk neuroblastoma. When parents are told of this diagnosis, they have a choice of treatment protocol to make:  how to go about treating the cancer and trying to eradicate it forever and giving their child a chance to live. Except…..there is a problem:  the parents have to choose a course of treatment. If they choose to go to Memorial Sloan Kettering or that is the hospital of the initial diagnosis, MSK has a protocol that they believe is best and gives the child the best chance of survival. If they choose Children’s Hospital of Philadelphia, Columbus Children’s Hospital, Arnold Palmer Children’s, or any of the children’s hospitals belonging to a network called the Children’s Oncology Group (COG), those hospitals have a different protocol of treating the cancer. If the child is at St. Jude's, Baylor University/Texas Children’s Hospital, in Germany or in other places in Europe--- that is 4 more different ways that the doctors and those institutions believe is best to treat the child. 

Which to choose? And at a time when the parents are completely devastated by the diagnosis, probably not thinking clearly and are forced to make a decision quickly to get treatment started as fast as possible. THIS, all because not enough is known about children’s cancer and not even the leading pediatric oncologists in the world can agree or know enough to have a consensus as to how to give our kids the best chance to live and not develop side effects, secondary cancers and damage to vital organs. And you know what is the worst part about this? Children with cancer, treated with all of these different protocols, are still dying... 7 per day, and don’t you think that some of the parents of these unnecessarily lost souls doubt the choice they made and wonder if they should have decided on a different protocol that might have had a different effect? Melissa and I have seen it; the parent of the child unnecessarily lost, grieving for their loss and wondering aloud if they should have chosen a different hospital because that hospital offered a different treatment protocol. All because not enough is known about pediatric cancer.

It is wrong. It is unjust. And it is unnecessary. Read below about just some (not all) of the different choices parents are forced to make in the treatment of neuroblastoma once it is diagnosed. 

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Source:  Children's Neuroblastoma Cancer Foundation (CNCF)

Differing protocols among institutions: All treatments for newly diagnosed high risk neuroblastoma share many components, but differences in protocols do exist, due to continued efforts to increase survival rates using various approaches. Currently, each of the national and international cooperative pediatric oncology groups, such as the Children’s Oncology Group (COG), the International Society of Pediatric Oncology (SIOP), and the German Society for Pediatric Oncology and Hematology (GPOH), have clinical trials for newly diagnosed NB cases. In addition, some institutions treating a large number of NB cases, such as Memorial Sloan-Kettering Cancer Center (MSKCC), Baylor/Texas Children’s, and St. Jude’s Children’s Research Hospital, have their own single-institution or multi-institution frontline protocol. The chemotherapy agents (and their administration and dose), number of induction cycles, timing of stem cell collection, timing of surgery, type of radiation therapy, use (or not) of transplant, conditioning regimen for transplant, timing of Accutane, and use (or not) of antibodies – all of these components differ somewhat in the various frontline protocols.

Chemotherapy: COG protocol uses six cycles, the German protocol uses either six or eight cycles (half are randomized to two extra cycles of topotecan), and the European SIOP protocol uses eight 10-day cycles of a rapid chemotherapy administration (termed “Rapid COJEC”). MSKCC’s protocol uses five cycles of induction chemo. Baylor/Texas Children’s pilot protocol also uses five cycles, but includes low-dose etoposide and high-dose cisplatin in the first two cycles to determine if an improved response rate will result from a high-dose/low-dose mix (called “chemo-switching”).

Surgery/Resection of the Tumor: The necessity of full removal (gross total resection) in high-risk cases remains a subject of controversy among some NB specialists. Some oncologists believe that total removal of the primary tumor, though desirable, is not a necessity because chemotherapy and radiation given subsequent to surgery will destroy any remaining disease, and cite complications in difficult surgeries. Others have concluded that complete resection is related to increased survival.

Stem cell transplant:  Stem cell transplant is high-dose chemotherapy or other treatment so severely suppressing the bone marrow that a subsequent “transplant” or “rescue” infusion of stem cells is required. Transplant has been frequently used since the 1980s for consolidation for high-risk NB.  Three randomized studies of patients accrued since the 1980s -- most notably the phase III study CCG-3891 conducted by the Children’s Cancer Group and published in 1999 -- have suggested that survival is improved with transplant.

Subsequently, autologous stem cell transplant has been widely adopted for treatment of high-risk NB. Double and triple autologous tandem transplants have also been tested in pilot studies, as well as allogeneic transplants.

Some institutions offer their own unique regimens for transplant, such as using donor or cord blood for the source of stem cells, or using a new combination of chemotherapy, or using triple tandem transplants, and some institutions use protocols from closed trials. Most conditioning regimens use mega-doses of chemotherapeutic agents—usually drugs not used in the induction phase—while less common regimens use chemo with total body irradiation (TBI) or MIBG radiation therapy. In the current European SIOP trial, children are randomized to one of two different chemo combinations.

A notable exception to the use of transplant for high-risk NB cases is MSKCC, whose frontline protocols have not included stem cell transplant since 2004 and instead use antibody treatment for consolidation. Doctors at MSKCC say they have not observed myeloablative consolidation treatments to have a significant impact on survival rates in their studies over the past 15 years.[22]  After successful response to induction chemotherapy and surgery, patients on MSKCC’s current protocol move on to local radiation, 3F8 antibodies, and Accutane.

Radiation: Children diagnosed with high-risk disease routinely undergo radiation therapy after induction chemotherapy and surgery. In protocols that include stem cell transplant, radiation therapy usually begins after the patient is released from the hospital. 

Even children whose tumors have been completely removed receive radiation to the primary site of disease.  Some institutions also radiate bone sites where NB was present at diagnosis, even if those tumors have completely responded to chemotherapy; other places radiate only the spots still showing before transplant. At least one protocol includes MIBG radiation therapy if remaining disease is detected by MIBG scan before transplant.

Antibodies: Our bodies manufacture antibodies that create an immune response to bacteria, viruses, and other foreign substances to help keep us healthy.  Ordinarily, a child’s immune system will not attack NB because the cancer is a part of the child’s body.  Monoclonal antibody therapy (monoclonal refers to development from one clone) uses mouse antibodies produced in the laboratory from plasma (myeloma) cells. The antibodies used in NB treatment attach to a ganglioside (a fat-sugar complex molecule) on the NB cell called GD2. Because the antibody alerts the child’s own immune system to attack the NB cell the antibody is attached to, the cancer cell is destroyed. Long-term immune response may be initiated by antibody treatments in some cases.

COG currently offers a phase III study (COG-ANBL0032) of the monoclonal antibody ch14.18 (administered with “cytokines” to augment the immune response to the antibody) to patients following completion of frontline treatment protocols that include stem cell transplant. After an early review of 226 children enrolled determined significantly higher survival with antibodies, the study was amended in April 2009 to stop randomization and allow all patients subsequently enrolled to receive the antibody.  The study will continue until final accrual goal of 423 is met, and it is anticipated that ch14.18 will be part of standard treatment for all COG protocols.  The ch prefix indicates the antibody is “chimeric” or part human (75%) and part mouse (25%) in its formulation. In the current European  trial the use of the same antibody ch14.18 is randomized (but without the use of cytokines). 

MSKCC uses a 100% mouse-derived 3F8 antibody treatment for high-risk patients who complete induction therapy with a good response. GM-CSF (granulocyte-macrophage colony-stimulating factor—a “cytokine” that stimulates the immune system) is usually given with 3F8. This antibody has been in use for two decades. MSKCC reports that their studies have shown improved survival among their patients who successfully complete at least four cycles of 3F8 antibody therapy.

Did everyone notice in reading this excerpt that for every single major part of a child’s treatment, none of the different institutions agree? And the differences are dramatic in some circumstances and not even close to being similar in others.  What does this say? It says that NONE OF THEM HAVE THE ANSWER. And that is not acceptable. It is not acceptable that less than 4% of research funding at the government level is dedicated to children’s cancer and that all of the 12 types are left to fight over that insulting amount. Shameful.

Kids are dying everyday, and cancer is the #1 killer of children by disease in developed countries--- what more needs to be said to act and do more???

For ALL the parents who have lived this personal hell, have lost a child unjustly to children's cancer or are battling every day not to, please help raise awareness, act and please donate blood, please donate time, money and effort to fund children's cancer research so that someday, someday... parents won’t have to make a choice of which protocol to treat their newly diagnosed child AND cancer in children will NEVER exist. 

Thank You.

 

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