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INTERVIEW

Antonio Sérgio Petrilli: A multifaceted physician

Pediatric oncologist Antonio Sérgio Petrilli describes how he built and now runs one of Brazil’s leading centers for research and treatment of childhood cancer

Petrilli seated in a playroom at GRAACC

Léo Ramos Chaves

Pediatrician Antonio Sérgio Petrilli has been on an unrelenting quest to find innovative and less aggressive treatments for cancer in children and teenagers ever since he returned to Brazil from a spell at Memorial Sloan Kettering Cancer Center in New York, in 1978. Therapeutic options in his home country were at the time limited and often highly mutilating—treatments for a type of bone cancer, called osteosarcoma, frequently required amputation of the arms and legs. Back in São Paulo, he introduced the treatment techniques he had learned in the US at the A.C.Camargo Cancer Center, and pursued a master’s and doctorate degree from the Federal University of São Paulo (UNIFESP), later becoming head of pediatric oncology at the university’s Pediatrics Department. In 1991, Petrilli decided to reach out beyond his clinical and academic duties, joining Jacinto Guidolin, a civil engineer, and Lea Della Casa Mingione, a volunteer, to create the Support Group for Children and Youth with Cancer (GRAACC), a nongovernmental organization (NGO) with a mission of providing enhanced care for cancer patients. With a growing body of volunteers, practitioners, and individual and corporate donors, and with support from UNIFESP, GRAACC built a cancer hospital in the city of São Paulo, where students from the university now also receive training. In 2017, GRAACC provided care to 3,724 children and adolescents, including 406 new cases, and conducted 35,000 consultations, 2,000 surgeries, and 19,000 chemotherapy sessions.

Petrilli, who is married and a father of two, earned his medical degree in 1970 from the University of Campinas (UNICAMP) and currently serves as a tenured professor of pediatric oncology at UNIFESP. He has authored or coauthored 132 scientific articles, and last August received an Octavio Frias de Oliveira Award from the São Paulo State Cancer Institute (ICESP), as Personality of the Year in Oncology. “Being recognized by peers, who select the winners, is very fulfilling,” he said. Petrilli, now 71, takes a keen interest in the molecular biology research being conducted at a laboratory headed by biologist Sílvia Toledo—based on a bank of tumor and tissue samples—to develop more effective ways to treat cancers that are resistant to chemotherapy and radiotherapy. Alongside his roles as professor, medical supervisor, and technical director at the institution, he also helps to raise funds—an average of R$60 million per year—to support the GRAACC hospital. Because of his busy schedule, our interview with him on August 16 had to be cut short so he could go to the São Paulo State Court of Justice to receive a donation of R$712,000. The money came from debt repaid by companies, which is often given to charities.

Age 71
Field
Pediatric Oncology
Institution
Federal University Of São Paulo (Unifesp)
Training
Medical Degree From The University Of Campinas (Unicamp, 1970); Master’s (1987) And Phd (1988) From Unifesp
Publications
132 Scientific Articles

How is childhood cancer different from adult cancer?
It differs in many ways. There are 3 cases of child cancer for every 100 cases of adult cancer, which usually affects people over 50. In children, most cancers result from changes in cell division in tissues that have not yet matured, and are not caused by environmental factors. In adults, tumors shed cells, bleed, and produce markers in the blood, making them easier to prevent and diagnose early. In children, the most effective way to tackle cancer is to make an early diagnosis through clinical examination to determine, for example, whether children have headaches, leg pain, or purple spots on the skin.

Is the approach to treatment also different for children?
Yes. It uses more intensive chemotherapy than for adults, as in children tumors spread more quickly. In adults, cells divide on average every 30 days, whereas in children cell turnover occurs in as little as 48 hours. Children with leukemia initially receive chemotherapy one to three times a week for 30 or 40 days. As in adults, the most significant effect on children is a sharp drop in white blood cell counts. This is, in fact, a desirable effect of chemotherapy. Steady white blood cell levels indicate that the chemotherapy dose is too low and the child or teenager may have a greater tolerance to the drug, in which case the dose has to be raised. Children recover from chemotherapy faster than adults do.

What is your approach to dealing with patients’ parents?
In the past, the most heart-wrenching part was dealing with parents knowing that we didn’t have all the resources we needed for treatment. Today, here at GRAACC, we know we will be engaging the enemy with the best arsenal available. Still, it can be tough. With children, we communicate through drawings and with parents we maintain a constant dialog about their children’s treatment. Teenagers need a special approach. They question things more and require better communication skills. We need to win their trust. We learn that we should not pity patients, but respect them. Clinical nurses, psychologists, nutritionists, professors, resident physicians, and oncologists all work together to motivate patients to fight for survival and engage with the treatment. It is important for patients and families to understand the disease and how the treatment works. Patients need to know beforehand that the drug can sometimes make them nauseous and they may not be able to work, study, or otherwise function during treatment. Today, survival rates are as high as 70% when we leverage the full spectrum of treatment resources available.

We try to motivate patients to fight for survival and engage with the treatment

Even so, cancer also takes a high emotional toll on physicians, such as when a child dies in their care…
The way we think about cancer needs to be removed from the idea of ​​terminality, but it is also important to think about death as being a part of the human experience. Often our patients have a long history with the disease and we prepare them and tell them frankly when drugs haven’t worked. The relationship between physicians, patients, and their families is like a film, not a photograph. Patients can tell what you are feeling from the look in your eye, and from the way you breathe.

What led you to work with children with cancer?
As a resident I had the opportunity to work with a pediatrician whom I admire very much, Alois Bianchi. I met him at the State Civil Servants’ Hospital, where I’d been given a post after graduating from medical school and having spent a year of military service in the Air Force. Bianchi worked part time at the Civil Servants’ Hospital and part time at A.C.Camargo. I had never considered working with cancer patients, but in 1974, after having had the opportunity to work with him at A.C.Camargo, I soon started training in pediatric oncology there. In 1978 I met pediatrician Norma Wollner Steinberg, who passed away in 2017. She agreed to give me a position for training at the Memorial Sloan Kettering Cancer Center, in New York. In Brazil we knew very little about childhood cancer at the time, and mortality was high. A.C.Camargo had a large outpatient center with many children, and mothers weren’t allowed in with their children.

What treatment methods did you use?
We first began to treat leukemia with chemotherapy in the early 1970s. Solid tumors were treated with surgery. Intestinal lymphomas, which respond well to chemotherapy—as I would later learn in the US—were also treated surgically with major resections of the intestinal tract. Children died more of infections due to the chemotherapy and surgery, than of cancer proper. Mortality was very high—between 85% and 90%. So using my own savings, and in the company of my wife and children, I decided to learn about how cancer was treated in the US. I spent a year at Memorial and was exposed to the new ideas that were emerging in pediatric oncology. There I met physician Gerald Rosen, a specialist in bone tumors, and began to take an interest in pursuing a scientific career. Before returning to Brazil I spent a period at MD Anderson Cancer Center in Houston, Texas, where I learned about intraarterial chemotherapy for osteosarcoma with Norman Jaffe. They were beginning to do conservative limb surgeries with preoperative chemotherapy to reduce tumor size before surgery. The physicians would place a catheter close to the tumor and inject the medication, necrotizing the tumor. Before this technique was developed, either the entire bone had to be removed or the affected leg had to be amputated, as was done in Brazil. In the US they used sophisticated catheters that had to be discarded after use. I had become friends with the radiologist who did the catheter placement procedure, and I asked him: “Would you mind if I kept these catheters? I intend to start using these procedures back in Brazil.”

Léo Ramos Chaves GRAACC’s tumor sample bank is being used to improve current treatmentsLéo Ramos Chaves

What did you do on your return to Brazil?
We began to use the leukemia and lymphoma protocols that were being used in the US, and we trained our staff and adapted our techniques. For intraarterial chemotherapy for osteosarcoma, we used catheters that were sent from the US and re-sterilized in Brazil to inject cisplatin, a much more affordable drug—the drugs they used in the US were just too expensive. With physicians Jacyr Quadros and Elvira Côrtes, we used an infusion pump to inject the medication into patients’ arteries, causing their tumors to shrink. There were no orthopedists at A.C.Camargo to perform the catheter procedures, so we invited Helio Consentino, from Santa Casa de Misericórdia, and Valter Penna to initiate intraarterial chemotherapy for osteosarcoma. These were my first bone cancer cases. Next to join our team were orthopedists Reynaldo Gracia, from the São Paulo School of Medicine [now UNIFESP], and Olavo Pires de Camargo, from USP [University of São Paulo]. We now had the first Brazilian group for osteosarcoma treatment, including orthopedists, pathologists, oncologists, and radiologists. We no longer recommended amputation for all cases; at least 60% of patients had their limbs spared. With these changes, survival rates improved from between 15% and 20% to 50%. Today we use methotrexate, which has increased survival rates to 65%. Further developments in orthopedic oncology have enabled us to use biological solutions in which we take a patient’s healthy bone tissue and use it to replace bone tissue which has been removed.

Are there other groups in Brazil working in the same field?
In São Paulo there are groups at several hospitals that are very strong and very much at the forefront of cancer treatment. I remember that before survival rates began to increase, prostheses rarely caused complications because patients never outlived their useful life. Now, with patients receiving much more intensive chemotherapy, patients are out-surviving the useful life of their prostheses. Patients live longer and their prostheses now need to be replaced.

What led you to pursue a graduate degree when you already had so much experience?
My dream was to do a master’s and doctorate to qualify as a lecturer. I was working at A.C.Camargo when I started my graduate degree at the São Paulo School of Medicine, in 1984. When I completed my doctorate, in 1989, an opportunity presented itself to work in the pediatric oncology ward at the university hospital. There were only three beds on the ninth floor of the São Paulo Hospital [linked to UNIFESP] and we worked hard to improve conditions in the ward, where children lacked basic necessities like pajamas or even medicines. We had already accomplished a lot at A.C.Camargo, so in 1990, at UNIFESP, I thought to myself: “Why not do the same here?” Hélio Egydio Nogueira, then director at the São Paulo Hospital, was very helpful in the early days. Jacinto Guidolin, the father of a patient of mine, also played a pivotal role; he was a civil engineer and served as chief executive at GRAACC from 1991 to 2001. Lea Della Casa Mingione was a volunteer at A.C.Camargo and I invited her to come work with us. She, Guidolin, and I founded GRAACC in 1991. We were soon joined by two pediatric oncologists, Flavio Luisi and Nasjla Saba, and a nurse, Carla Dias. In 1992, we leased a house to set up our pediatric oncology clinic; we occupied the first floor of the house, with a nephrology clinic on the second. Conditions were less than ideal, but we soon received help from volunteers and patients’ parents.

Personal archive Jacinto Guidolin (left), Petrilli, and Sérgio Amoroso at the GRAACC hospital construction site in 1998Personal archive

How was GRAACC organized in these early years?
We soon realized that first we needed to clearly articulate what we wanted: a place where we could treat patients. We explained to potential donors that there were professors and several practitioners available from the Department of Pediatrics at the São Paulo School of Medicine, but that we lacked the facilities and resources to treat children with cancer. On another trip to the US, in 1988, I visited a number of childhood cancer treatment centers and was especially impressed by St. Jude Children’s Research Hospital in Memphis, Tennessee. They had a dedicated organization for fundraising, just as we do today. Our approach was modeled after what I saw at St. Jude. We created GRAACC as a nongovernmental organization.

What are the advantages of operating as an NGO?
Organizing GRAACC as an NGO was better for fundraising and accountability, as people were reluctant to donate to a university knowing that the money could be reallocated to other, equally needy, departments. We got around a number of barriers and secured a certificate from CNAS—the National Council for Charities—that allowed us to fundraise and issue receipts on behalf of GRAACC. We approached Banco Itaú, Telefônica, Shopping Eldorado, Fundação Safra, and other companies for donations through people we knew through our patients, and one open door led to another, and another. We were soon able to purchase three houses in Vila Mariana [on the south side of São Paulo], before plans were made for the first of our two current buildings. Another influential figure was Sérgio Amoroso, then director of Fundação Orsa and now our chairman of the board. He invited Guidolin and me to a meeting on a Maundy Thursday at 5:00 p.m. We crossed the city through horrible traffic, during the rush hour preceding the holiday. He later told us he did it to see if we would really show up. He paid for three floors of our first building, adjacent to the one we’re in now.

Cancer has become the leading cause of death for those 1 to 19 years of age

Did you attend meetings with potential donors yourself?
Yes. I had to drop whatever I was doing to meet them and explain our plans. Companies and institutions liked to hear about our work from the volunteers who greeted them at the door, but physicians also delivered their pitch, explaining what we needed. Essentially, we wanted adequate facilities to improve the odds for children and youth with cancer. Attending the meetings was also strategic because it meant that I was able to participate in the project from the outset. Organizations relying entirely on volunteers for fundraising often become plain-vanilla hospitals, with little innovation. Meanwhile, in 1993 we received our first support from McHappy Day [a day when part of McDonald’s revenue from sandwich sales goes to child cancer support institutions]. In the first year we raised close to R$100,000. We approached McDonald’s through Benjamin Kopelman [then a professor of pediatrics at UNIFESP], who knew a director who worked there. They came to see us and liked our project. Gregory Ryan [1950–2017], then CEO of McDonald’s Brazil, came to deliver a check in person. We were then in the middle of building a hospital, but a small one, and I said: “Our dream is to have a building to house the hospital.” He turned to me and asked: “But what’s keeping you from dreaming?” The next time he came by, a while later, he looked at the building and said: “I just didn’t know you were dreaming that big.” During that period, Renato Kherlakian, founder of the clothing brand Zoomp, would organize fashion shows and donate the revenue to GRAACC; I was his daughter’s pediatrician. Andre Guper was particularly instrumental in developing the hospital project. We would never have achieved so much without the vision of entrepreneurs who, in addition to donations, helped with strategic planning. That was well beyond my expertise—they helped to keep costs and expenses in check. At the same time, our volunteers became more active and grew in number. Today we have close to 600 volunteers, who work an average of four hours a week. Many of them are highly engaged. And this completes our triad of donors, volunteers, and the university.

What is the nature of your collaboration with UNIFESP?
We renewed the collaboration agreement in 2017. The plot of land on which this building was built is owned by GRAACC and was purchased with funds raised from private donors. So we are financially independent. When the first building was completed in 1998, we created a board of trustees formed by businessmen, intellectuals, and volunteers. GRAACC invited the Department of Pediatrics at UNIFESP—with no detriment to our financial independence—to manage the technical and scientific aspects of the hospital. It was an absolutely academic arrangement involving lecturing, research, and assistance. Our agreement was that the head of the university’s Oncology Department would be our technical director. His job would be to safeguard the UNIFESP brand within GRAACC. The university allowed us to use their brand and GRAACC became UNIFESP’s Pediatric Oncology Department. Professors could work at GRAACC as if working at the university. Students and resident physicians also work here. We have a multidisciplinary residency program in collaboration with the Office of the Associate Dean for Extension. We train seven pediatric oncologists per year. They complete two or three years of pediatrics training and then three more here. To date we have trained about 190 resident physicians; some have continued with us and others have returned to their states. I work as a professor, technical director, and in fundraising.

To what extent do revenues come from the National Healthcare System (SUS)?
In 2017, 85% of patients received care through the SUS, generating R$15 million in revenue. Private health plans, accounting for 15% of patients, generated R$16 million. We’re going to build two additional inpatient floors here to increase the share of privately insured patients to between 25% and 30%, which should help to improve operating revenues. Our annual expense is R$94 million. We almost always start the year with a deficit of R$64 million, but this is balanced by our approach of raising funds from private donors. Funding from donors comes to around R$81 million, but each real we raise costs us R$0.25, because we have 100 people working on fundraising, headed by Tammy Allensdorf. GRAACC has an active donor base of about 319,000 individuals and companies, with a monthly average of 98,000 donors and with donations ranging from R$5 to R$1,000. We also raise funds through campaigns and events, such as McHappy Day, and government donations, such as the donation I’ll be receiving from the Court of Justice this afternoon.

Léo Ramos Chaves

What is the state of childhood cancer treatment in Brazil today?
With mortality from diarrhea, meningitis, measles and other infectious diseases declining in recent decades, cancer has become the leading cause of death for those 1 to 19 years of age. The same is true in the US and other more developed countries. The incidence of childhood cancer is 16 cases per 100,000 children younger than 19. There are about 12,000 new cases each year; most patients are treated at public centers and 25% to 30% have health insurance. At GRAACC, about 6,000 children aged 0 to 10 survived cancer from 1991 to 2015, with a five-year survival rate of 74% and a ten-year survival rate of 71%. That’s right up there with developed countries.

What is the overall state of cancer treatment?
There are many excellent cancer-care centers in São Paulo, including Itaci, HC USP, Centro Boldrini, in Campinas, and Hospital de Amor, in Barretos, and others in Rio de Janeiro, Porto Alegre, Recife, Brasília, and Curitiba. But many children are still not receiving adequate care. The national survival rate is officially around 50%, but we’re not sure whether that figure is accurate. The Ministry of Health estimates survival largely on the basis of death certificates. We are unable to compile accurate figures because the cause of death is often reported as undetermined. This has been changing, however. In recent years, the number of deaths reported as “cause unknown” has decreased, and the number of cases reported as childhood cancer has increased. I recently went to Belém, Pará, northern Brazil, and visited the Octávio Lobo Children’s Cancer Hospital, which was developed by former residents at GRAACC. It is a public-private partnership operating under an agreement with the state government. They are now in their third year of operation. They initially expected to see 70 new cases a year, but are already treating 170. Children are coming from all over the North of Brazil. They come from remote jungle locations where children would previously die of convulsions and other causes because they couldn’t get a CT scan to diagnose a brain tumor. It may take a while for the survival curve to improve as people are still entering the system at an advanced stage, but eventually it will.

Léo Ramos Chaves

What are GRAACC’s next steps?
One of our priorities for the coming years is to expand our research in genetics. Biologist Sílvia Toledo, who runs our molecular research lab, is leading a project that is investigating the most common genetic mutations in 500 patients with central nervous system tumors, leukemia and retinoblastomas. We’ve already received a sequencer and will be working with the team at Children’s Hospital Los Angeles and the University of Southern California; they’ll be investigating the most frequent mutations there and we’ll be doing the same here. The project budget is R$2.5 million, with funding from private donors. We’ll be using our tumor bank, which has about 10,000 samples of blood and tissue fragments. This material will be highly valuable in precision medicine, which we’ll be doing more of going forward, but is currently used more with adults than with children. Most cancers in children are genetically simpler than those in adults and can be treated with chemotherapy, radiation therapy, and surgery. But greater insight is needed for some types of cancer, such as brain and bone tumors, in which survival rates are lower. We want to better understand the onset and progression of cancer in each patient and tailor the treatment to the genetic changes we detect.

Do you have anyone in mind to replace you at GRAACC?
I have already told the board that I’ll be stepping down on December 23, 2021, shortly more than three years from now, when I turn 75. I’ll be leaving the university and am currently—and gladly— preparing to pass on the torch. It is never a good thing to outstay your usefulness. No organization or institution can retain its quality under a leader who stays past a well-timed retirement. People who are reluctant to step down often undermine what they have achieved. I am preparing four people and the board will decide who will stay. Until then I will retain my duties, my position in leadership, and my habits as an early riser. There’s still plenty to do. But I’ve already begun to phase myself out. I now spend four days a week at my practice, I do Pilates, and go for strolls in the park. After I leave—if I’m still up to the task—I plan on spending more time at my practice and helping other people create projects like GRAACC.

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