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. 2021 Dec 3;13(23):6111.
doi: 10.3390/cancers13236111.

Newborn Screening for the Detection of the TP53 R337H Variant and Surveillance for Early Diagnosis of Pediatric Adrenocortical Tumors: Lessons Learned and Way Forward

Karina C F Tosin  1 , Edith F Legal  2 , Mara A D Pianovski  3 , Humberto C Ibañez  2 , Gislaine Custódio  4 , Denise S Carvalho  1 , Mirna M O Figueiredo  4 , Anselmo Hoffmann Filho  2 , Carmem M C M Fiori  5 , Ana Luiza M Rodrigues  3 , Rosiane G Mello  2   6 , Karin R P Ogradowski  2   6 , Ivy Z S Parise  2 , Tatiana E J Costa  7 , Viviane S Melanda  8 , Flora M Watanabe  9 , Denise B Silva  7 , Heloisa Komechen  2   4 , Henrique A Laureano  2 , Edna K Carboni  9 , Ana P Kuczynski  9 , Gabriela C F Luiz  9 , Leniza Lima  10 , Tiago Tormen  10 , Viviane K Q Gerber  11 , Tania H Anegawa  12 , Sylvio G A Avilla  9 , Renata B Tenório  9 , Elaine L Mendes  9 , Rayssa D Fachin Donin  4 , Josiane Souza  9 , Vanessa N Kozak  3 , Gisele S Oliveira  3 , Deivid C Souza  3 , Israel Gomy  6   9 , Vinicius B Teixeira  2 , Helena H L Borba  13 , Nilton Kiesel Filho  9 , Guilherme A Parise  4 , Raul C Ribeiro  14 , Bonald C Figueiredo  1   2   4   6
Affiliations

Newborn Screening for the Detection of the TP53 R337H Variant and Surveillance for Early Diagnosis of Pediatric Adrenocortical Tumors: Lessons Learned and Way Forward

Karina C F Tosin et al. Cancers (Basel). .

Abstract

The incidence of pediatric adrenocortical tumors (ACT) is high in southern Brazil due to the founder TP53 R337H variant. Neonatal screening/surveillance (NSS) for this variant resulted in early ACT detection and improved outcomes. The medical records of children with ACT who did not participate in newborn screening (non-NSS) were reviewed (2012-2018). We compared known prognostic factors between the NSS and non-NSS cohorts and estimated surveillance and treatment costs. Of the 16 non-NSS children with ACT carrying the R337H variant, the disease stages I, II, III, and IV were observed in five, five, one, and five children, respectively. The tumor weight ranged from 22 to 608 g. The 11 NSS children with ACT all had disease stage I and were alive. The median tumor weight, age of diagnosis, and interval between symptoms and diagnosis were 21 g, 1.9 years, and two weeks, respectively, for the NSS cohort and 210 g, 5.2 years, and 15 weeks, respectively, for the non-NSS cohort. The estimated surveillance/screening cost per year of life saved is US$623/patient. NSS is critical for improving the outcome of pediatric ACT in this region. Hence, we strongly advocate for the inclusion of R337H in the state-mandated universal screening and surveillance.

Keywords: TP53 R337H; adrenocortical tumor; genetic testing; neonatal screening; surveillance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Follow-up flowchart for R337H screening and ACT treatment. * Provided at the study center or at another center closest to the participant home address.
Figure 2
Figure 2
Cost of screening and surveillance. Considering a life expectancy of 60 years, the cost per year of life saved is US$623 per patient.
Figure 3
Figure 3
A neonatal and surveillance proposal for the state of Paraná (and state of Santa Catarina with approximately 50% of the projected numbers for Paraná). First step (neonatal screening) expected to be included in the universal Parana and Santa Catarina’s state panel, and provided free of charge. Subsequent steps (eligibility/enrollment) would require the parents’ consent and acceptance to be trained to detect and report early signs and symptoms of ACT.
See this image and copyright information in PMC

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