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Childhood cancer, whose World Day is celebrated today, Thursday, has little to do with adult tumors.
In both cases, there are cells that go crazy and begin to multiply uncontrollably, but they are very different diseases: their origin is different and so is their frequency.
“Luckily,” says pediatric oncologist Lucas Moreno (Menorca, 45 years old), childhood cancer affects few patients.
“There is one cancer in children for every 200 in adults.
It is a minority disease or, rather, a group of diseases because there is not just one cancer, there are 40 types,” explains this doctor, head of the Pediatric Oncology and Hematology service at the Vall d'Hebron Hospital in Barcelona.
Moreno admits that, precisely, the low frequency of cases complicates the investigation and progress is made little by little.
The oncologist has just published a study in the Journal
of Clinical Oncology
where they prove that an innovative combination of drugs shows a slight improvement in children with very aggressive neuroblastoma.
When there is no cure, the key is to buy time.
More information
In the trenches against childhood cancer: “Not only the patient gets sick, but the whole family”
Ask.
Why do childhood tumors appear?
In adults, experts say that if we improve our lifestyle, we can prevent 40% of tumors.
Answer.
Children's cancers are totally different and environmental factors do not influence them.
They are developmental alterations: during embryonic development, some cells remain that do not function well and at some point, they begin to grow.
Q.
Is childhood cancer still a great unknown?
A.
The low frequency makes it more difficult to research it, obtain resources and gather the data that is needed.
In the last decade, there has been a very important advance in the knowledge of what happens in tumors.
No causes have been identified that produce it, but what happens for them to grow has been identified.
But there are still not many examples of success of new drugs as has happened in adult oncology.
Q.
Is the cancer creation process the same as in adults?
A.
What ends up happening is crazy cell proliferation.
What triggers it, we still don't know, but what begins to happen, yes: in adult cancers, environmental factors cause mutations to accumulate, cells break down, and when they reach a certain level, it is when they start to grow.
In children's tumors, there are few mutations;
What there is most are chromosomal alterations, things on a larger scale, and also in the epigenome, which is not so much in the DNA sequence, but in how it folds, how they come together...
Q.
Can these alterations be reversed or anticipated?
A.
Not yet because those environmental factors are not known.
There are also no population screening programs because they are tumors that grow very quickly.
One area in which we are growing is the 10% of cancers that are related to some genetic characteristic that makes it easier to develop a tumor: when these genes are identified, the entire family is investigated so that, if cancer appears, it is found more clearly.
“80% of children with cancer are cured, but many have to live with consequences”
Q.
What is usually the prognosis?
A.
The most common cancers in children and adolescents are leukemias, lymphomas and brain tumors.
In cancer in general, survival results are good: more than 80% are cured.
But of that 80%, many have to live with consequences from the treatment they have received that affect their quality of life.
Q.
What kind of consequences?
A.
For example, a patient who has a bone tumor and who has to get a hip prosthesis or a knee prosthesis: living your entire life with a prosthesis creates a series of limitations in your life.
Another example: receiving radiotherapy to the brain when you are young can affect your neurodevelopment, how you learn, your school performance... and, in other parts of the body, it can cause another tumor 10 or 20 years later.
There are patients who undergo cancer treatment and have absolutely no after-effects and return to their normal lives without problems.
But there are others who have that risk throughout their lives.
Q.
You have explained the global forecast, but where are the lights and shadows?
A.
The ones that have the best results are leukemias, lymphomas and some kidney tumors, which have a cure rate of more than 90% and, in these, the most important thing now is to refine the treatment as much as possible to have fewer sequelae.
On the other hand, there are other examples, such as brain tumors, such as high-grade gliomas, and solid tumors, such as some sarcomas and neuroblastomas—especially when there are metastases—in which we do not cure even half of the patients.
And there the challenge is to look for new drugs to improve these results.
Q.
In neuroblastoma you have just had positive results with a study that combines chemotherapy with a monoclonal antibody.
A.
This is a clinical trial for high-risk neuroblastoma, which is the one that has metastases, when they have relapsed.
What we're trying to do is try all the new things that are available, and we're trying a monoclonal antibody that prevents the vessels that bring food to the tumor from growing.
What we publish is that this has improved the response, that the patients' tumors are reduced or that the patients are tumor-free for longer.
Less than 10% of neuroblastoma patients who relapse survive.
It is a very resistant disease.
Lucas Moreno, head of Pediatric Oncology and Hematology at Vall d'Hebron, at the entrance to the mother-child area of the health center. Albert Garcia (Albert Garcia)
Q.
In that study they said that the response rate was 26% with the new therapeutic approach compared to 18% with chemotherapy alone.
How is this data interpreted?
A.
This is such a resistant disease and where so many things have been tried so many times, that any small improvement allows children to live longer without the disease recurring.
If this works a little and we add another combination to it in the next trial and this also improves, we gradually build that improvement.
Q.
Where are the great difficulties in finding treatments that will reverse the disease?
A.
One of them is the biology of the tumors because they are very aggressive tumors and do not respond to anything.
The fact that it occurs in few patients makes it more difficult to test the drugs.
Also, cancer in children is an area where pharmaceutical companies do not have great interest due to its infrequency.
Now, there are incentives and obligations for companies that work in pediatric cancer and there are more and more that do, but there is still not a large volume like in adults.
Q.
In adults, there has been a revolution in the last decade with the introduction of new drugs.
What is the situation of the therapeutic arsenal in children?
A.
This great explosion of precision oncology and immunotherapy in adults has not been reflected in pediatric cancer.
We still don't have that large number of drugs available.
Many have been tried and do not work;
and others have not yet arrived.
Despite all those approved for adults, we can count on one hand the new drugs that are available for children.
Q.
The great revolution in recent years has been CAR-T [a cellular therapy that consists of extracting T lymphocytes from the patient, modifying them in the laboratory with genetic engineering and returning them to the patient so that they can better combat the tumor]?
A.
The great revolution until the previous decade was to combine and make the most of the treatment we already have (chemotherapy, radiotherapy and surgery).
CAR-Ts have come to fill specific gaps in specific diseases where they have indeed changed the paradigm.
Today there is only one CAR-T available for leukemias in a specific situation and there the results have changed.
But there is no CAR-T for solid tumors, for other hematological tumors... They have not yet changed the paradigm of entire pediatric oncology, but in specific situations where they do have a very important role.
“Environmental factors do not influence childhood cancer;
They are developmental disorders.”
Q.
What is cooking that will mark the future of therapies?
A.
Now there is a great movement in which CAR-Ts are being manufactured that have value for pediatric cancer because they go against targets that these tumors do have.
It's still early, but we have a lot of hope because there are going to be many clinical trials in different applications for brain tumors, for neuroblastomas, for leukemias in other situations... And among all that, we do think that there will be a revolution.
Q.
Where is gene therapy?
A.
Gene therapy has not yet reached childhood cancer, but it has reached some hematological diseases that can end in childhood cancer.
When a disease is caused because a gene has stopped working, if there is a way to replace some cells with others in which that gene is fixed, that fixes your disease.
In hematological diseases, it will result in those patients having fewer cancers.
It will avoid collateral damage.
Q.
What are the big unknowns that remain to be resolved in childhood cancer?
A.
A very important one is to know what makes tumors resistant.
Because we do have first-line treatments for almost all tumors, but there are many that learn to become resistant and the cells escape.
And we still don't know how to prevent them from becoming resistant or block those mechanisms to prevent them from becoming metastatic and reappearing.
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