Académie royale de Médecine de Belgique


Résumé de Giorgio Perilongo

(Séance du 14 décembre 2013)


by Giorgio PERILONGO, MD (Department of Pediatrics – University of Padua – Italy, invited.            

Solid tumors in children represent a quite heterogeneous group of neoplasms. Thus, considering the amount of knowledge which has been accumulated during the recent history of modern oncology, an individual “tumor journey” should be described to gain a coherent and comprehensive picture of  what has happened in the field of Pediatrics. The topic of my talk will be “Hepatoblastoma”, which is a tumor I have been most involved with, both clinically and scientifically. Hepatoblastoma (HB) is the most frequent malignant primary liver tumor occurring in children. It is a quite rare neoplasm with a yearly incidence of 6.2 cases per million children. Its origin is related to a disorder in the genetic mechanisms regulating normal hepatic organogenesis.

The “Journey” through the last 50 years started with surgery. Indeed, up to the early 70ies, the only children who could be cured were those with a completely removable tumor. The first report by Howat, in 1971, included 14 cases of resected malignant liver tumors in children with only 3 long term survivors and 30%   perioperative death due to bleeding.  

In 1982, the first report describing the role of a combined surgical and systemic chemotherapy approach was published, with a disappointing 30% 5 yr-overall survival. Nevertheless, that paper marked the official adoption by the pediatric oncology community of the concept of combined treatment of HB with chemotherapy and surgery.

The late eighties and the early nineties were marked by the launch, both in North America and in Europe, of large cooperative multi-center, prospective randomized trials of chemotherapy. Those trials were fostered by the first convincing evidence of the capacity of cisplatin to reduce the tumor volume, making surgical removal more likely and safer, and to sterilize micrometastases. Projected 5 yr-survival rates in the 60% range were achieved. HB was proved to be chemosensitive and the multidisciplinary approach was adopted.

During the nineties and the most recent years, the PRETEXT system, based on a precise, anatomical extension of the tumor at diagnosis was validated, allowing comparison of the results of different trials and prediction of complete surgical resection. Orthotopic liver transplantation, in properly selected patients who are not candidates for partial hepatectomy because of the tumor extension, was validated as first line therapy within a multimodality treatment approach. High risk patients were identified with poor prognosis (presentation with metastases and/or low serum alpha-fetoprotein and/or with the histological subtype of “small cell undifferentiated HB”) in comparison with an almost 90% 5-y survival in children with a ”standard HB” treated with minimal chemotherapy. Large cooperative clinical trial between the North American and the European Childhood HB study groups are being launched with a single huge database. Understanding of the relevant genetic mechanisms underlying HB development, hopefully, would allow the development of biologically driven innovative therapies.