COMMENTS
Adjuvant Radiation Therapy and Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma
In Regard to Sabolch et al
CrossMark
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
to pursue radiation therapy. In fact, even in those patients with a family history that is not concerning for malignancy, up to one-third will be found to harbor a p53 mutation (3). Additionally, this rate is much higher in children: there is a 50-80% prevalence of p53 germline mutations in pediatric patients (3, 4). Given the well-known and deleterious inter- action of p53 mutation status with radiation therapy (5-8), we do not recommend adjuvant radiation therapy for patients with such mutations.
Aaron Sabolch, MD Shruti Jolly, MD Department of Radiation Oncology University of Michigan Hospital and Health Systems Ann Arbor, Michigan
http://dx.doi.org/10.1016/j.ijrobp.2015.06.017
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. Purushothaman K, Puthiyottil SSV, Bhattacharya T, Muttath G. In Regard to Salboch. Int J Radiat Oncol Biol Phys 2015;93:465.
3. Fonseca AL, Healy J, Kunstman JW, et al. Gene expression and regu- lation in adrenocortical tumorigenesis. Biology (Basel) 2012;2:26-39.
4. Wasserman JD, Novokmet A, Eichler-Jonsson C, et al. Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: A Children’s Oncology Group study. J Clin Oncol 2015; 33:602-609.
5. Heymann S, Delaloge S, Rahal A, et al. Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li- Fraumeni syndrome. Radiat Oncol 2010;5:104.
6. Bristow RG, Benchimol S, Hill RP. The p53 gene as a modifier of intrinsic radiosensitivity: Implications for radiotherapy. Radiother Oncol 1996;40:197-223.
7. Gudkov AV, Komarova EA. The role of p53 in determining sensitivity to radiotherapy. Nat Rev Cancer 2003;3:117-129.
8. Salmon A, Amikam D, Sodha N, et al. Rapid development of post- radiotherapy sarcoma and breast cancer in a patient with a novel germline “de-novo” TP53 mutation. Clin Oncol (R Coll Radiol) 2007; 19:490-493.
Volumetric Modulated Arc Therapy Planning For Primary Prostate Cancer With Selective Intraprostatic Boost Determined By (18) f-Choline PET-CT
In Regard to Kuang et al
CrossMark
To the Editor: We read with great interest the recent article by Kuang et al (1). In a retrospective study of 30 patients, the authors reported that a planned boost with volume modulated arc therapy (VMAT) for an intraprostatic dominant lesion (IDL) gave a higher calculated tumor control probability (median 95.8% vs 85.2%) than a planned VMAT for the whole prostate. We also reported radiation therapy for prostate cancer guided by positron emission tomography/computed tomog- raphy (PET/CT) scans (2). As a complement, we would like to expand on issues discussed in the article.
The authors described “PET-defined IDL.” The IDL is also denoted “index lesion” or “dominant intraprostatic lesion” (DIL). Pathologists define DIL according to histopathology after radical prostatectomy by stage, tumor volume, and Gleason score (3). According to a histopathology-based definition of DIL, the authors reported that 12 patients (40%) had false-positive PET/CT findings, and 1 patient (3%) had false-negative PET/CT findings. Thus a challenge for a boost for DIL guided by functional imaging is management of false-positive and false-negative prostate segments. The study by the authors included 9 patients (30%) at low risk according to the National Comprehensive Cancer Network; but the National Comprehensive Cancer Network stated it is suffi- cient to give low-risk patients external beam radiation therapy with a standard fractionation for the whole prostate with a moderate dose of 76-79 Gy. Hence for low-risk patients, the planned boost dose of 105 Gy may imply overtreatment.
The authors preferred PET/CT for multiparametric magnetic resonance imaging (mpMRI). However, radio- labeled choline PET/CT has a limited advantage relative to that of mpMRI with T2-weighted imaging, diffusion- weighted imaging, and dynamic contrast-enhanced imag- ing (4). The authors planned monotherapy with VMAT, with or without a boost for DIL. In contrast, Ellis et al (5)
Patients with prostate cancer
SIB HDR BT 10 Gy (PTVDIL) VMAT 76 Gy (PTVProstate)
Patients preferences
cT1-3 NX T0
PS 0 - 1
mpMRI+ DIL
VMAT 95 Gy (PTVProstate)