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Table of Contents
LETTER TO EDITOR
Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 656-657

Author's reply to Tripathi et al. and Memon et al.


1 Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Center, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
2 Department of Pathology, Tata Memorial Hospital, Tata Memorial Center, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
3 Department of Urology, Tata Memorial Hospital, Tata Memorial Center, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
4 Department of Radiation Oncology, Tata Memorial Hospital, Tata Memorial Center, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
5 Department of Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Center, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India

Date of Submission29-Jul-2020
Date of Decision04-Aug-2020
Date of Acceptance05-Aug-2020
Date of Web Publication19-Sep-2020

Correspondence Address:
Kumar Prabhash
Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Center, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_260_20

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How to cite this article:
Kapoor A, Noronha V, Toshniwal A, Menon S, Joshi A, Patil VM, Menon N, Prakash G, Murthy V, Krishnatry R, Bakshi G, Pal M, Popat P, Sable N, Prabhash K. Author's reply to Tripathi et al. and Memon et al. Cancer Res Stat Treat 2020;3:656-7

How to cite this URL:
Kapoor A, Noronha V, Toshniwal A, Menon S, Joshi A, Patil VM, Menon N, Prakash G, Murthy V, Krishnatry R, Bakshi G, Pal M, Popat P, Sable N, Prabhash K. Author's reply to Tripathi et al. and Memon et al. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Oct 21];3:656-7. Available from: https://www.crstonline.com/text.asp?2020/3/3/656/295506



We would like to thank Tripathi and Agarwal[1] and Memon et al.[2] for their valuable comments on our article and the accompanying editorial published in the last issue of the journal.[3],[4]

We agree with Tripathi and Agarwal that mitotane remains underutilized in resource-constrained settings because of the financial issues.[1] Moreover, as adrenocortical carcinoma shows ethnic variations, there is a greater need to generate genomic sequencing data from the Asian population.[5] These data will not only help to target the mutations in a patient-specific manner but also help in the enrollment of patients in various basket trials. CDK4/6 and checkpoint inhibitors appear promising in this scenario.[6],[7] CDK4 amplification has been reported in around 20% of the patients with adrenocortical carcinoma, and a preclinical study has shown the efficacy of palbociclib, a CDK4/6 inhibitor approved for the treatment of metastatic breast cancer.[6] In a recent Phase II study by Raj et al., pembrolizumab led to an objective response rate of 23% and disease control rate of 52%, with no significant difference in the outcomes with tumor programmed death-ligand 1 expression and microsatellite-high and/or mismatch repair deficient (MSI-H/MMR-D) status.[7] The primary concern pertaining to the use of targeted therapies remains the unavailability of clinical trials in the developing countries, which deprives the patients of potential therapeutic options. There have been initiatives to promote “Global Oncology” from various societies of the developed world, and we hope that with time, the wide gap in cancer care between the developed and developing countries can be narrowed.[8]

As per Memon et al.'s suggestions, we performed a survival analysis for patients for whom the data for secretory versus non-secretory tumors were available. These data were available for a total of 42 patients, of which 22 (52.4%) had secretory tumors. The median overall survival (time from diagnosis to death or censored at last follow-up) was 40 months (95% confidence interval [CI]: 11.2–68.7) for non-secretory versus 94 months (95% CI: 5.5–182.5) for secretory tumors (hazard ratio [HR], 1.6; 95% CI: 0.6–4.2; P = 0.342). Thus, this factor was not statistically significant in our patient cohort, although the significance of this finding is questionable due to the small sample size. Another important point raised by Memon et al. was the survival difference between the patients who received adjuvant mitotane and those who did not. Here, we would like to point out that there are conflicting data for the use of mitotane in the adjuvant setting, wherein a few studies suggest mitotane to be beneficial in terms of the disease-free survival, whereas others do not.[9],[10] The disparity in the results could be explained by the inadequate dosing in a few studies and individual variations in metabolizing mitotane; this mandates measuring the blood levels of mitotane, which is not possible in most resource-constrained settings. We are eagerly awaiting the results of the randomized study, ADUVIO, which is expected to provide a definitive answer to this burning question. As only two patients received adjuvant mitotane in our study, comparison was not done with patients who did not. Moreover, adrenocortical carcinoma being a heterogeneous disease with multiple prognostic factors, a comparison with the historical cohorts might not be beneficial.

In conclusion, collaboration between multiple national centers to produce data from the Indian patients[11] and utilizing various support programs to improve patient care and access to medications are of vital importance. In addition, training the pathologists to report histopathology as per the international standards is another important way forward to identify various prognostic factors and tailor the therapy for each patient.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tripathi A, Agarwal N. Adrenocortical carcinoma: Challenges and opportunities. Cancer Res Stat Treat.2020;3:654-655.  Back to cited text no. 1
    
2.
Memon S, Lila A, Bandgar T. Treatment of adrenocortical carcinoma – Present and future. Cancer Res Stat Treat. 2020;3:655-6.  Back to cited text no. 2
    
3.
Kapoor A, Noronha V, Toshniwal A, Menon S, Joshi A, Patil VM, et al. Exploring the role of systemic therapy in adrenocortical carcinoma-Single center experience. Cancer Res Stat Treat 2020;3:192-200.  Back to cited text no. 3
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Rajappa S. Treating advanced adrenal cortical carcinoma: The long, winding, and endless road. Cancer Res Stat Treat 2020;3:290-2.  Back to cited text no. 4
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Michalkiewicz E, Sandrini R, Figueiredo B, Miranda EC, Caran E, Oliveira-Filho AG, et al. Clinical and outcome characteristics of children with adrenocortical tumors: A report from the International Pediatric Adrenocortical Tumor Registry. J Clin Oncol 2004;22:838-45.  Back to cited text no. 5
    
6.
Fiorentini C, Fragni M, Tiberio GAM, Galli D, Roca E, Salvi V, et al. Palbociclib inhibits proliferation of human adrenocortical tumor cells. Endocr J 2018;59:213-7.  Back to cited text no. 6
    
7.
Raj N, Zheng Y, Kelly V, Katz SS, Chou J, Do RK, et al. PD-1 Blockade in Advanced Adrenocortical Carcinoma. J Clin Oncol 2020;38:71-80.  Back to cited text no. 7
    
8.
Gopal S, Loehrer PJ. Global oncology. JAMA 2019;322:397-8.  Back to cited text no. 8
    
9.
Khan TS, Imam H, Juhlin C, Skogseid B, Gröndal S, Tibblin S, et al. Streptozocin and o, p'DDD in the treatment of adrenocortical cancer patients: Long-term survival in its adjuvant use. Ann Oncol 2000;11:1281-7.  Back to cited text no. 9
    
10.
Icard P, Goudet P, Charpenay C, Andreassian B, Carnaille B, Chapuis Y, et al. Adrenocortical carcinomas: Surgical trends and results of a 253-patient series from the French Association of Endocrine Surgeons study group. World J Surg 2001;25:891-7.  Back to cited text no. 10
    
11.
Noronha V. Making a case for cancer research in India. Cancer Res Stat Treat 2018;1:71-4.  Back to cited text no. 11
  [Full text]  




 

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