Pediatric oncology is justifiably proud of its long tradition of
multi-institutional collaboration in clinical research. Perhaps no other
field of medicine has more effectively shown what can be achieved by
pooling talent and resources to study challenging diseases.
Historically, most collaborative projects were limited to a single
country or continent. However, more progress comes from even broader
international cooperation. With rare cancers, this may be the only way
to gather sufficient patient numbers to address key questions. Sharing
national experiences can also lead to a deeper understanding of the
advantages and risks associated with different therapeutic approaches.
The first steps to increased global cooperation, however, is agreeing on
a common language to describe patient cohorts and consensus standards to
guide diagnosis, evaluation, and treatment. Applying these lofting goals
to pediatric soft tissue sarcomas, the INternational Soft Tissue SaRcoma
ConsorTium (INSTRuCT) was born.
From its initial formative meeting in May 2017, INSTRuCT has patterned
its structure and purpose on the successful model of the International
Neuroblastoma Risk Group (INRG).1,2 The membership of
INSTRuCT is composed of three large cooperative clinical trials
organizations: Children’s Oncology Group (COG), Cooperative
Weichteilsarkom Studiengruppe (CWS), and European paediatric Soft tissue
sarcoma Study Group (EpSSG). The first goal for INSTRuCT is to develop
an international risk stratification system for rhabdomyosarcoma (RMS)
to replace competing systems used in Europe and North America. A common
RMS risk stratification system would facilitate the comparison of
clinical trial results across cooperative groups. Before generating a
RMS risk stratification system, INSTRuCT agreed upon a standard RMS data
dictionary, leveraging the University of Chicago’s Pediatric Cancer Data
Commons expertise in data standardization.3 The
compilation of COG, CWS, and EpSSG data (and data from their legacy
groups) from finished studies into a single INSTRuCT dataset is nearly
complete, and will include more than 7000 patients enrolled on previous
RMS clinical trials. Once the RMS risk stratification project is
finished, INSTRuCT will mine its dataset for answers to questions that
can only be addressed with large, well-annotated clinical data. Future
work will also include expanding the RMS data dictionary and adding a
non-RMS soft tissue sarcoma dataset, also drawn from COG, CWS, and EpSSG
clinical trials.
As the multi-disciplinary members of INSTRuCT were defining their RMS
data dictionary, they realized they had the opportunity to develop
international consensus statements on the diagnosis, evaluation, and
management of pediatric soft tissue sarcomas. Clinical trial protocols
include guidelines for pathologic diagnosis, imaging staging evaluation,
and local control approaches with surgery and radiation therapy varied
by primary anatomic site. INSTRuCT provided the forum for international
discussion and consensus building, with the goal of publishing these
expert opinions for broad dissemination and use by pediatric
oncologists, surgeons, radiation oncologists, radiologists, and
pathologists worldwide. In this issue of Pediatric Blood &
Cancer, Morris et al. publish the one of first in a series of consensus
statements from INSTRuCT, focusing on the surgical management in the
diagnosis and local control of RMS arising in the
extremity.4 Morris et al. outline recommended biopsy
approaches, the rational for routine use of regional lymph node
evaluation including the role of fluorodeoxyglucose positron emission
tomography, and the decision-making behind up-front versus delayed
primary excision. The recommendations are guided by the principles of
maximizing oncologic outcome while maintaining extremity function. Given
the rarity of extremity RMS and the absence of randomized trials
comparing different management strategies, Morris et al. draw upon a
combination of clinical data and expert opinion in their consensus
guidelines, carefully documenting the level of evidence that supports
each of their recommendations. Nonetheless, these guidelines represent
the current state of the art for surgical management of extremity RMS
and the basis for future clinical trial recommendations. A similar
consensus statement on RMS of the female genital tract has also been
published in Pediatric Blood & Cancer, by Lautz et
al.5 With these two consensus statements, the INSTRuCTPediatric Blood & Cancer special series is off to an excellent
start, with manuscripts on the surgical management for other primary
sites and the pathologic evaluation of RMS to follow soon. As INSTRuCT
co-chairs, we are pleased to introduce INSTRuCT to the global pediatric
oncology community and look forward to many more contributions to come.