Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study

186

137

Retinoblastoma (RB) is the most common intraocular malignancy in childhood. Approximately 40% of retinoblastomas are hereditary and due to germline mutations in the RB1 gene. Children with hereditary RB are also at risk for developing a midline intracranial tumor, most commonly pineoblastoma. We recommend intensive ocular screening for patients with germline RB1 mutations for retinoblastoma as well as neuroimaging for pineoblastoma surveillance. There is an approximately 20% risk of developing second primary cancers among individuals with hereditary RB, higher among those who received radiotherapy for their primary RB tumors. However, there is not yet a clear consensus on what, if any, screening protocol would be most appropriate and effective. Neuroblastoma (NB), an embryonal tumor of the sympathetic nervous system, accounts for 15% of pediatric cancer deaths. Prior studies suggest that about 2% of patients with NB have an underlying genetic predisposition that may have contributed to the development of NB. Germline mutations in ALK and PHOX2B account for most familial NB cases. However, other cancer predisposition syndromes, such as Li-Fraumeni syndrome, RASopathies, and others, may be associated with an increased risk for NB. No established protocols for NB surveillance currently exist. Here, we describe consensus recommendations on hereditary RB and NB from the AACR Childhood Cancer Predisposition Workshop.

Section: Rasopathiesmentioning

confidence: 99%

Retinoblastoma and Neuroblastoma Predisposition and Surveillance

Kamihara

Bourdeaut

Foulkes

et al. 2017

186

137

“…Because the known spectrum of CMMRD cancers during childhood is increasing, suggestions for the addition of whole-body MRI (WBMRI) are being considered, as for Li-Fraumeni syndrome (25). Several reports demonstrate early detection and survival benefit, especially in brain tumors and gastrointestinal tumors by WBMRI, brain MRI, and endoscopy, respectively (16,26).…”

Section: Surveillance Protocolmentioning

confidence: 99%

“…These include bone and soft-tissue sarcomas, genitourinary cancer, and other cancers occurring more frequently from the latter part of the first decade of life. Second is the encouraging data from the implementation of WBMRI in patients with Li-Fraumeni syndrome (3,25) and the high feasibility of the tool in children who do not require anesthesia, which give strong consideration for its use in CMMRD. The current suggestion is to implement WBMRI once a year at 6 year of age or when anesthesia is not needed.…”

Section: Surveillance Protocolmentioning

confidence: 99%

Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood

Tabori

Hansford

Achatz

et al. 2017

Self Cite

185

202

Replication proofreading is crucial to avoid mutation accumulation in dividing cells. In humans, proofreading and replication repair is maintained by the exonuclease domains of DNA polymerases and the mismatch repair system. Individuals harboring germline mutations in genes involved in this process are at increased risk of early cancers from multiple organs. Biallelic mutations in any of the four mismatch repair genes MSH2, MSH6, MLH1, and PMS2 result in one of the most aggressive childhood cancer predisposition syndromes, termed constitutional mismatch repair deficiency or constitutional mismatch repair deficiency syndrome (CMMRD). Data gathered in the last decade allow us to better define the clinical manifestations, tumor spectrum, and diagnostic algorithms for CMMRD. In this article, we summarize this information and present a comprehensive consensus surveillance protocol for these individuals. Ongoing research will allow for further definition of replication repairdeficient cancer syndromes, assessing the cost-effectiveness of such surveillance protocols and potential therapeutic interventions for these children and families. Clin Cancer Res; 23(11); e32-e37. Ó2017 AACR.See all articles in the online-only CCR Pediatric Oncology Series.

“…Considerable site-to-site variations arise from differing scanner platforms and technological capabilities, the tumors and syndromes under surveillance, and departmental/radiologist preference. The most recent published protocols specific for WBMRI in pediatric oncology utilize a fluid-sensitive sequence in the coronal plane, with additional optional sequences and imaging planes (1,(6)(7)(8)(17)(18)(19), and are summarized in Table 2. As documented in the table, scan times vary significantly between protocols depending on number and type of sequences used.…”

Section: Technical Factors: Sequences and Imaging Planesmentioning

confidence: 99%

“…Although lung nodules are increasingly identified on WBMRIsome studies showing high sensitivities for lesions between 4 and 10 mm-WBMRI screening for pulmonary metastases is not yet advocated, and chest CT remains the reference standard (5,6 As well as a systematic approach and detailed knowledge improving lesion detection, as Anupindi and colleagues highlighted, it is equally important to carry out "risk stratification" to minimize false positive findings (18). WBMRI is only one part of a surveillance program, and findings should be interpreted in conjunction with other clinical and imaging data (17,18). Nonspecific findings with a low likelihood of being related to the syndrome in question can likely be managed conservatively in an otherwise asymptomatic patient rather than initiating a more intensive, and possibly invasive, diagnostic pathway.…”

Section: Wbmri Interpretation and Reportingmentioning

confidence: 99%

Pediatric Cancer Predisposition Imaging: Focus on Whole-Body MRI

Greer

Voss

States

2017

The American Association for Cancer Research convened a meeting of international pediatric oncologists, geneticists, genetic counselors, and radiologists expert in childhood cancer predisposition syndromes (CPS) in October 2016 to propose consensus surveillance guidelines. Imaging plays a central role in surveillance for most, though not all, syndromes discussed. While encompassing the full gamut of modalities, there is increasing emphasis on use of nonionizing radiation imaging options such as magnetic resonance imaging (MRI) in children and adolescents, especially in the pediatric CPS population. In view of rapid evolution and widespread adoption of whole-body MRI (WBMRI), the purpose of our review is to address WBMRI in detail. We discuss its place in the surveillance of a range of pediatric CPS, the technical and logistical aspects of acquiring and interpreting these studies, and the inherent limitations of WBMRI. We also address issues associated with sedation and use of gadolinium-based contrast agents in MRI in children.