Itzal was five years old when he was diagnosed with bladder rhabdomyosarcoma, a very aggressive tumor that required very powerful chemotherapy and mutilating surgery. The little girl started the treatment and endured, for a month, the aftermath of those pills that forced her to take: she vomited, her hair fell and her defenses were so low she could barely approach her little sister, because of the risk that I passed on some pathogen. One month he was with this chemotherapy until at the Vall d'Hebron hospital in Barcelona, a reference center in Spain for sarcomas, they sequenced the genome of their tumor and they discovered that, in reality, that mass in the bladder was an inflammatory myofibroblastic cancer, a tumor that is locally aggressive but does not metastasize. The analysis revealed that in his genetic instruction book there was a failure that made the tumor sensitive to a treatment that was much less aggressive than the chemo he had received. In a few months, the girl responded to that drug and the intervention to remove the tumor was minimally invasive and without sequelae. The genetic analysis of his tumor gave a twist to his prognosis and found something to spare extended in adult oncology: precision personalized medicine saves lives.
The Itzal is one of the 45 cases that have gone through the Comik project (Órmica Ómica en Niños) of Vall d'Hebron, an initiative deployed in the oncology and pediatric surgery service to bring personalized medicine for childhood cancer with a worse prognosis The idea is to find, through the genomic sequencing of solid tumors, the genetic signature of the neoplasms, their entire book of instructions to detect possible anomalies in their genes and look for treatments directed specifically for each tumor. "For each type of tumor, until now we explored the anomalies known for this tumor. Now we want to take a step further and apart from what is well known, see what else we can find, open new perspectives ", synthesizes Raquel Hladun, pediatric oncologist Vall d'Hebron.
Childhood cancer It is considered a rare disease due to the low incidence (one in every 7,000 under 15 years old, about 1,400 new cases a year in Spain). About 80% of cases are cured, but there are between 20% and 30% that have very poor prognosis and limited therapeutic alternatives. The project is aimed at that particular group, children like Itzal, who have a tumor with a poor prognosis. "You go to a very aggressive and mutilating surgery if you do not know that there is a targeted treatment for your tumor. We went from a girl who was receiving a multidrug therapy, with all the consequences that it has, and a possible total or partial bladder resection, a minimally invasive treatment and that does not leave great sequels, "explains Gabriela Guillén, pediatric hospital surgeon , in allusion to the case of Itzal.
The project starts from the traditional tumor biopsy. A part of the tumor tissue is subjected to a molecular analysis to know all its genetic history and detect any anomalies or therapeutic targets in its instruction book. If in the study the specialists find some alteration, it goes to look for possible treatment alternatives directed to the particularities of that tumor in particular. "Although we speak of a patient with neuroblastoma, each neuroblastoma may have some peculiarities that make it different from another patient with that tumor. We want to explore it thoroughly, to know its molecular biology to explore what makes it unique and exclusive to the patient, "adds Hladun.
Childhood cancer It affects one in every 7,000 children under 15 years of age. 80% of cases are cured.
Since the project was launched in 2016 -funded with the center's own funds and not a few difficulties, experts admit-, some 45 children have already passed through the project. 35% have benefited from personalized treatments thanks to the information that revealed the genomic analysis of their tumors. "We had a girl of about six years with a metastatic neuroblastoma. These patients, to date, have a very low survival. We did a very long and aggressive chemo and there was no response. Then we went to a second line of treatment, to which he responded partially. Then, an autologous marrow transplant that requires a very high intensity chemo. He also underwent a quite difficult surgery. But the tumor was refractory to all treatments. We did the sequencing program and found a molecular alteration that made it sensitive to a targeted treatment with which it has been more than two years. The disease has been stable for two years and she is asymptomatic, "says Hladun.
But in addition to the care wing of the Comik project, the pediatric oncologists and surgeons of Vall d'Hebron have developed a strictly scientific branch. From the same biopsy of the tumor, a sample is extracted (if there is enough tissue because what prevails, above all, is to sequence the cancerous mass) to implant in mice. But it is not a subcutaneous implant, but it is carried to the same organ where the tumor has developed in the child. "It is implanted in immunosuppressed mice and, once it has grown in the implanted organ, that tumor expands to other mice and that model is established. And there we could, based on the alterations found in the sequencing, apply some drugs that could be useful and try them on the animal, "says Guillén.
These preclinical models have more validity than if the implantation is subcutaneous or if this is done in cell cultures. "The behavior of tumors depends on the environment they are in. Therefore, it is not the same as the tumor evolves under the skin that it does in the organ of origin." The evolution of these mirror tumors is more similar to evolution what happens in the patient, "says Guillén.
Vall d'Hebron specialists advocate maintaining and expanding this project in time and space, although they defend that, given the few cases of childhood tumors that exist, it is necessary that assistance be centralized to favor specialization. For now, they have already started working with the French hospital Gustave Roussi.