2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

tive randomized trials. However, small, well-designed, and
meaningful clinical trials can yield important information
about the biology, clinical presentation, and treatment options
of rare diseases. Additionally, limited trials taht explore
novel therapies such as ipilimumab and vemurafenib
for pediatric melanoma should be encouraged. Unfortunately,
perhaps as a result of the current infrastructure
constraints, even single-arm cooperative group studies for
rare cancers have had suboptimal enrollment rates. 3,21
Specialized Clinics
Highly specialized clinics for rare diseases is not a new
concept; however, rare cancer clinics that address specific
tumors such as the one developed at the NIH for pediatric
gastrointestinal tumors (GIST; www.pediatricgist.cancer.
gov) are unique and provide a novel model for multidisciplinary
care of pediatric patients with rare cancers. In this
clinic, physicians and other health care professionals from
various disciplines including oncology, surgery, genetics,
and nutrition gather twice a year to study patients with
pediatric and wild-type GIST. Since its inception in 2008,
more than 90 patients have been seen, 38% of whom are
pediatric patients and 41% are young adults. Tissue has
been obtained from 61 patients and fresh frozen tumor in
Author’s Disclosure of Potential Conflicts of Interest
Author
Employment or
Leadership
Positions
Consultant or
Advisory Role
Alberto S. Pappo Ziopharm
Oncology
1. Howlader N, Krapcho M, Neyman N, et al (eds). SEER Cancer Statistics
Review, 1975-2008: Updated November 10, 2011. SEER web site. http://
seer.cancer.gov/csr/1975_2008/index.html. Accessed February 26, 2012.
2. Ferrari A, Bisogno G, De Salvo GL, et al. The challenge of very rare
tumours in childhood: The Italian TREP project. Eur J Cancer. 2007;43(4):
654-659.
3. Pappo AS, Krailo M, Chen Z, et al. Infrequent tumor initiative of the
Children’s Oncology Group: Initial lessons learned and their impact on future
plans. J Clin Oncol. 2010;28(33):5011-5016.
4. Bien E, Godzinski J, Dall’igna P, et al. Pancreatoblastoma: A report from
the European cooperative study group for paediatric rare tumours (EXPeRT).
Eur J Cancer. 2011; 47(15):2347-2352.
5. Brecht IB, Graf N, Schweinitz D, et al. Networking for children and
adolescents with very rare tumors: Foundation of the GPOH Pediatric Rare
Tumor Group. Klin Padiatr. 2009;221(3):181-185.
6. Pastore G, De Salvo GL, Bisogno G, et al. Evaluating access to pediatric
cancer care centers of children and adolescents with rare tumors in Italy: The
TREP project. Pediatr Blood Cancer. 2009;53(2):152-155.
7. Casanova M, Bisogno G, Gandola L, et al. A prospective protocol for
nasopharyngeal carcinoma in children and adolescents: The Italian Rare
Tumors in Pediatric Age (TREP) project. Cancer. Epub 2011 Sep 14.
8. Michalkiewicz E, Sandrini R, Figueiredo B, et al. Clinical and outcome
characteristics of children with adrenocortical tumors: A report from the
International Pediatric Adrenocortical Tumor Registry. J Clin Oncol. 2004;
22(5):838-845.
9. DiGiammarino EL, Lee AS, Cadwell C, et al. A novel mechanism of
tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer.
Nat Struct Biol. 2002;9(1):12-16.
10. Wasserman JD, Zambetti GP, Malkin D. Towards an understanding of
the role of p53 in adrenocortical carcinogenesis. Mol Cell Endocrinol. 2012;
351(1):101-110.
588
five. The clinic has facilitated the study of rare diseases and
has contributed to the understanding of the unique biology
of these tumors. For example, pediatric GIST most commonly
affect females, have epithelioid or mixed morphology,
arise in the stomach, have an indolent clinical course, and
rarely have activating mutations of KIT or PDGFR. In
addition the almost universal lack of SDHB expression in
tumor samples from these patients suggests that defects in
cellular respiration may play a pivotal role in the pathogenesis
of the disease in younger patients. 22
In summary, the study of rare pediatric cancers is challenging.
Multiple mechanisms should be explored in order to
advance our understanding of these diseases. The use of
international registries can help identify the numbers of
patients at risk for a specific rare cancer and can aid in the
collection of biologic specimens in this population. Welldesigned,
single-arm, collaborative clinical trials that incorporate
banking and biologic endpoints can greatly advance
our understanding of these diseases and establish standards
of care for these patient. Preclinical models can more rapidly
aid in the identification of novel druggable targets. Finally,
specialized clinics offer the opportunity to study large numbers
of patients by interested individuals facilitating the
study and specimen collection of pediatric rare cancers.
Stock
Ownership Honoraria
REFERENCES
Research
Funding
Expert
Testimony
ALBERTO S. PAPPO
Other
Remuneration
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21. Casanova M, Bisogno G, Gandola L, et al. A prospective protocol for
nasopharyngeal carcinoma in children and adolescents: The Italian Rare
Tumors in Pediatric Age (TREP) project. Cancer. Epub 2011 Sep 14.
22. Janeway KA, Kim SY, Lodish M, et al. Defects in succinate dehydrogenase
in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations.
Proc Natl Acad Sci USA.2011;108:314-318.