Already when she was four days old, a lump was discovered on Romi Fogel's foot. When it found out to be cancerous, her mother was horrified at the thought that her daughter would have to get chemotherapy at such an early age. Fortunately, Schneider Children's Medical Center of Israel was at the same time participating in an international clinical trial of an innovative, targeted, biological drug, which is taken as an oral syrup. The tumor shrank quickly, the residual was excised, and from the trauma only a tiny scar remains.

Four days after Romi was born, her mother noticed during a diaper change a small bump that protruded from the baby's left foot. "From the first moment I did not like it, to say the least," says the mother, Anna Fogel, "I immediately felt it is was not good, but I certainly did not take it to the extreme and it did not occur to me that it was a cancerous lump in the foot of a four-day-old baby."

When Romi was a week old, Anna went with her to the pediatrician, who was not under the impression that this was a dangerous finding and advised the mother to just wait, hoping that the lump would disappear on its own. "I'm a nurse, and in this meeting with the pediatrician I wear two hats, the professional and the maternal, which is a powerful multiplier of anxiety. So I asked her to refer my daughter for an ultrasound," she says.

THE SIZE HAS DOUBLED

While waiting for medical imaging to discover the nature of the tumor, the COVID-19 pandemic arrived and with it the first lockdown. The appointment was canceled. "I'm at home, on maternity leave, with three children and a baby who is developing nicely and breastfeeding, but the lump in the foot has already doubled in size," says Anna, "I realized that - lockdown or no lockdown - I have to do something, and fast. So I sent a photo of the foot to the doctor. From the foot, the lesion protruded and had already reached two centimeters." The doctor referred them to the emergency room, where Romi was examined and released to her home with the reassuring diagnosis that it was probably a hemangioma - a benign vascular tumor derived from blood vessels, and a recommendation to consult a dermatologist.

The dermatologist was also under the impression that it was a hemangioma and provided the mother with a prescription for a medicine that is specially prepared per patient. "It took two weeks for us to get the medicine," says Anna, "and then, for two weeks, I gave it to her twice a day - but the lump continued to develop and grow." The doctor realized that the drug was not appropriate for the baby and ordered to stop giving it to her and do a biopsy to diagnose the mass. "It was at this point that I felt under great pressure," Anna describes, "my husband is in furlough at home with three small children without a job, and I, after giving birth, begin a long and frightening journey alone with my baby."

Romi and her mother went back to Schneider Children's Medical Center of Israel where they met Dr. Helen Toledano, a pediatric oncologist, director of the Brain Tumors Unit and a clinical researcher, who presumed that it was cancer and told the worried mother that if it was the type of tumor she suspected, then Romi would be the first baby to participate in Israel in an International clinical study of a new drug that targets exactly this kind of cancer.

An MRI scan clearly showed a solid tumor in the foot. The baby was sent to the National Center for Orthopedic Oncology in Ichilov - a center for tumors of soft tissue and bone. She underwent the biopsy under general anesthesia when she was six weeks old in total. "Because of the strict regulations of the COVID-19, no family member was allowed to join me," the mother said, "and so I found myself alone, in front of the operating room door where my baby was under general anesthesia. I was close to falling apart but told myself I had no choice because there was no one to lift me up, and I just functioned."

"THE TUMOR IS BLEEDING"

After 2 days of hospitalization, Romi was released to her home bleeding from the biopsy incision, and at the same time the tumor continued to grow. The tumor was found to be an infantile fibrosarcoma – a malignant soft tissue sarcoma of infants. The tumor underwent molecular testing to find out if it was suitable for the study and for receiving the experimental drug, with the main requirement being that a specific defective gene NTRK had to mutated in the tumor. "This is an expensive and rare test; and it took two weeks for the desired results to arrive - while the tumor is growing wild, the girl is bleeding from the incision, her hemoglobin values are falling, she is pale, weak and less vital," says Anna. "Her condition needs treatment, and the options were chemotherapy or the new biological medicine. The possibility that the baby will receive chemotherapy at the age of two months so scared me that I did not know what to do with myself."

Dr. Toledano says that “Romi was diagnosed with infantile fibrosarcoma, which probably developed at birth. Standard treatment is chemotherapy to reduce the size of the tumor, and then attempted surgical excision with clear margins. But fortunately, weeks prior to Romi’s diagnosis, Israel received permission to participate in an international trial of a new biological drug that targets the mutation in the tumor itself and destroys it, and is specifically tailored to this molecular alteration. This is a clinical trial that was conducted simultaneously in various countries in Europe and America."

For the parents, this was exciting news. "When I was informed that the specific molecular alteration had been detected in Romi’s tumor that allows Romi to enrol in the trial and receive the new treatment, given as an oral syrup as opposed to chemotherapy in the vein, I was so happy," says the mother.

At the age of two months Romi began to receive the treatment: a couple of milliliters of syrup twice a day. "Because of the time difference between us and the United States, this drug only arrived to us at seven in the evening," says Dr. Toledano. "I didn't go home that day and just waited to put it in Romi's mouth, in my hands; when it happened, the excitement overwhelmed us all. Until the participation of Schneider Children's Medical Center of Israel in the study, children with this disease had to fly to receive this treatment in Germany. Now, every child who is diagnosed will receive treatment here at home, in Israel."

Two days after receiving the first dose of the drug, the tumor began to shrink. After four months only a small remnant remained and it was resected by surgery that left a tiny scar on the bottom of the foot. The pathology showed no tumor remained and the treatment was stopped. Romi is now nearly 6 months after treatment and has fully recovered and is already standing and taking her first steps!