COMMENTS
Adjuvant Radiation Therapy and Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma
In Regard to Sabolch et al
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To the Editor: We read with great interest the article by Sabolch et al, “Adjuvant radiation therapy improves local control after surgical resection in patients with localized adrenocortical carcinoma” (1). We congratulate them for their excellent work in studying one of the rarest malignancies; however, there are certain areas of caution related to treating these tumors that need to be considered.
Adrenal cortical carcinoma has a strong association with several cancer-predisposing syndromes, such as Li- Fraumeni, Beckwith-Wiedemann, multiple endocrine neoplasia type 1, Carney complex, and Gardner syndrome (2). Thus, unlike other common malignancies for which definite treatment guidelines can be formulated, a rare malignancy like this that is also associated with many syndromes needs personalized therapy based on the asso- ciated syndromes and underlying genetic defect.
Germline TP53 mutations have also been observed in 50-80% of children and 30-35% of adults with apparent sporadic adrenocortical carcinomas (2), and the presence of adrenocortical carcinoma itself is a stand-alone indication for genetic counseling and testing as per the Chompret criteria (3), regardless of family history. Treatment with radiation therapy in these patients has varying results, ranging from inducing second malignancy to radio- resistance or no effect (4, 5). Aberrant p53 mutations are identified in 40% patients with sporadic adrenocortical carcinomas, and their effect on the outcome of radiation therapy is not known.
The limited success with radiation therapy shown in historical series could be due to the confounding effect of germline mutation p53: in these series patients could be harboring a p53 mutation, which can cause both adrenal cortical carcinoma and radio-resistance.
Hence, local control achieved by treating adrenocortical carcinoma with adjuvant radiation therapy that does not translate into an improvement in recurrence-free survival or overall survival (which could be due to the small patient
numbers, which were insufficient to detect subtle differ- ences, as explained) should be viewed with caution. Inter- pretation of the study results on the basis of mutational status of p53 and other syndrome associations may improve the benefits and help in patient selection.
Kiran Purushothaman, MD Sanudev Sadanandan Vadakke Puthiyottil, DNB, MNAMS Tapesh Bhattacharya, MD Geetha Muttath, MD Department of Radiation Oncology Malabar Cancer Centre Kerala, South India
http://dx.doi.org/10.1016/j.ijrobp.2015.06.018
References
1. Sabolch A, Else T, Griffith KA, et al. Adjuvant radiation therapy improves local control after surgical resection in patients with local- ized adrenocortical carcinoma. Int J Radiat Oncol Biol Phys 2015;92: 252-259.
2. Fonseca AL, Healy J, Kunstman JW, et al. Gene expression and regu- lation in adrenocortical tumorigenesis. Biology (Basel) 2012;2:26-39.
3. Tinat J, Bougeard G, Baert-Desurmont S, et al. 2009 version of the Chompret criteria for Li Fraumeni syndrome. J Clin Oncol 2009;27: e108-e109.
4. Lee JM, Bernstein A. p53 mutations increase resistance to ionizing radiation. Proc Natl Acad Sci U S A 1993;90:5742-5746.
5. Evans DG, Birch JM, Ramsden RT, et al. Malignant transformation and new primary tumours after therapeutic radiation for benign dis- ease: Substantial risks in certain tumour prone syndromes. J Med Genet 2006;43:289-294.
In Reply to Purushothaman et al
CrossMark
To the Editor: We thank the commentators for the insightful observations regarding our research (1, 2). We agree that p53 mutations are prevalent among the population of patients, particularly children, diagnosed with adrenocortical carci- noma. As such, we concur that a consultation with a genetic counselor is routinely warranted for every adreno- cortical carcinoma patient because the results of genetic testing will guide clinical management, including whether