J Cancer 2022; 13(4):1336-1345. doi:10.7150/jca.61005 This issue

Research Paper

A Proposal for Future Modifications on Clinical TNM Staging System of Retinoblastoma Based on the American Joint Committee on Cancer Staging Manual, 7th and 8th Editions

Yacoub A. Yousef, MD1✉, Ibrahim Qaddoumi, MD2, Ibrahim Al-Nawaiseh, MD1, Mona Mohammad, MD1, Dalia AlRimawi3, Mario Damiano Toro, MD, PhD4,5✉, Sandrine Zweifel, MD4, Robert Rejdak, MD, PhD5, Rashed Nazzal, MD6, Mustafa Mehyar, MD1, Imad Jaradat, MD7, Iyad Sultan, MD8, Maysa Al-Hussaini, MD9

1. Department of Surgery (Ophthalmology), King Hussein Cancer Centre, Amman, Jordan.
2. Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
3. Department of Biostatistics, King Hussein Cancer Centre, Amman, Jordan.
4. Department of Ophthalmology, University of Zürich, Zürich, Switzerland.
5. Chair and Department of General and Pediatric Ophthalmology, Medical University of Lublin, Lublin, Poland.
6. Shami Eye Center, Amman, Jordan.
7. Department of Radiation Oncology, King Hussein Cancer Centre, Amman, Jordan.
8. Department of Pediatric Oncology, King Hussein Cancer Centre, Amman, Jordan.
9. Department of Pathology and Laboratory Medicine, King Hussein Cancer Centre, Amman, Jordan.

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Citation:
Yousef YA, Qaddoumi I, Al-Nawaiseh I, Mohammad M, AlRimawi D, Toro MD, Zweifel S, Rejdak R, Nazzal R, Mehyar M, Jaradat I, Sultan I, Al-Hussaini M. A Proposal for Future Modifications on Clinical TNM Staging System of Retinoblastoma Based on the American Joint Committee on Cancer Staging Manual, 7th and 8th Editions. J Cancer 2022; 13(4):1336-1345. doi:10.7150/jca.61005. Available from https://www.jcancer.org/v13p1336.htm

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Abstract

Graphic abstract

Importance: The 8th edition of the American Joint Committee on Cancer (AJCC) staging manual incorporated new changes from its 7th edition for classifying retinoblastoma (RB).

Objective: We assessed the comparative prognostic values of the 7th and 8th editions of the AJCC clinical (cTNM) staging manuals for RB and suggested modifications for future edition accordingly.

Design: A retrospective, observational study.

Setting: King Hussein Cancer Centre.

Participants: A cohort of 478 patients and 565 eyes with RB.

Main Outcomes and Measures: Main outcome measures included demographics; tumor features, AJCC cTNM stage, and eye salvage rates. The prognostic performance of the different staging systems was assessed with the concordance index (C-index) and likelihood ratio χ2 tests.

Results: The overall eye salvage rate was 65%. Stage migration occurred for 330 (48%) eyes with the AJCC Staging Manual, 8th edition. Based on the 7th edition AJCC staging, the eye salvage rate was 94% (n=177) for T1 tumors (98% for T1a, 93%for T1b, and 90%for T1c), 69% (n=204) for T2 tumors (73% for T2a and 62%for T2b), and 51% (n=40) for T3 tumors. Based on the 8th edition AJCC staging, the eye salvage rate was 95% (n=139) for T1 tumors (98% for T1a and 93% for T1b), 68% (n=281) for T2 tumors (90%for T2a and 66%for T2b), and 12% (n=1) for T3 tumors. With our proposed cTNM modifications, the eye salvage rate was 94% (n=177) for T1 tumors (98%for T1a, 93%for T1b, and 90% for T1c), 66% (n=243) for T2 tumors (73% for T2a, 62% for T2b, and 55% for T2c), and 12% (n=1) for T3 tumors. As estimated by odds ratios, more advanced cTNM stage (regardless of the cTNM staging system) was significantly associated with an increased chance of treatment failure (P < .0001). The C-index for both the 8th edition and the proposed modifications were approximately equal, and both were higher than that of the 7th edition. However, the proposed modifications had the highest likelihood ratio χ2 value and the best bootstrap 95% confidence interval.

Conclusions and Relevance: Our proposed modifications on the clinical TNM Staging System for RB harbor more detailed subgroup classification criteria that provides better prognostic value for eye globe salvage than the published similar (but not identical) AJCC Staging Manual, 7th and 8th editions, furthermore these modifications may resolve the discrepancies in the previously published different classification systems for RB.

Keywords: Retinoblastoma, Globe salvage, Staging system, Prognosis, American Joint Committee on Cancer