Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System

doi:10.1245/s10434-015-4842-3

Multicenter Study

. 2015 Dec;22 Suppl 3(Suppl 3):S985-91.

doi: 10.1245/s10434-015-4842-3. Epub 2015 Aug 28.

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System

M Amit^{1

2}, T C Yen³, C T Liao³, P Chaturvedi⁴, J P Agarwal⁴, L P Kowalski⁵, Hugo F Kohler⁵, A Ebrahimi^{6

7}, J R Clark⁶, C R Cernea⁸, S J Brandao⁸, M Kreppel⁹, J Zöller⁹, M D Fliss¹⁰, G Bachar¹¹, T Shpitzer¹¹, V A Bolzoni¹², P R Patel¹³, S Jonnalagadda¹⁴, K T Robbins¹⁴, N G Iyer¹⁵, T Skanthakumar¹⁵, J P Shah¹⁶, S G Patel¹⁶, Z Gil^{17

18}

Affiliations

¹ The Laboratory for Applied Cancer Research, Clinical Research Institute at Rambam, Rappaport Institute for Research in Medical Science, Haifa, Israel.
² Department of Otolaryngology, Head and Neck Surgery, Head and Neck Center, Rambam Medical Center, Rappaport School of Medicine, The Technion, Israel Institute of Technology, 66036, Haifa, Israel.
³ Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ Tata Memorial Hospital, Mumbai, India.
⁵ A.C. Camargo Cancer Center, São Paulo, Brazil.
⁶ Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia.
⁷ Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
⁸ Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil.
⁹ Department of Oral and Cranio-Maxillo and Facial Plastic Surgery, University of Cologne, Cologne, Germany.
¹⁰ Department of Pathology, Tel Aviv Medical Center, Tel Aviv, Israel.
¹¹ Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Israel.
¹² Department of ENT, University of Brescia, Owensboro, Italy.
¹³ University of Auckland, Auckland, New Zealand.
¹⁴ Southern Illinois University School of Medicine, Springfield, IL, USA.
¹⁵ Singhealth/Duke-NUS Head and Neck Centre, National Cancer Centre Singapore, Singapore, Singapore.
¹⁶ Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁷ The Laboratory for Applied Cancer Research, Clinical Research Institute at Rambam, Rappaport Institute for Research in Medical Science, Haifa, Israel. moranamit@gmail.com.
¹⁸ Department of Otolaryngology, Head and Neck Surgery, Head and Neck Center, Rambam Medical Center, Rappaport School of Medicine, The Technion, Israel Institute of Technology, 66036, Haifa, Israel. moranamit@gmail.com.

PMID: 26314876
PMCID: PMC4941785
DOI: 10.1245/s10434-015-4842-3

Multicenter Study

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System

M Amit et al. Ann Surg Oncol. 2015 Dec.

. 2015 Dec;22 Suppl 3(Suppl 3):S985-91.

doi: 10.1245/s10434-015-4842-3. Epub 2015 Aug 28.

Authors

Affiliations

¹ The Laboratory for Applied Cancer Research, Clinical Research Institute at Rambam, Rappaport Institute for Research in Medical Science, Haifa, Israel.
² Department of Otolaryngology, Head and Neck Surgery, Head and Neck Center, Rambam Medical Center, Rappaport School of Medicine, The Technion, Israel Institute of Technology, 66036, Haifa, Israel.
³ Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ Tata Memorial Hospital, Mumbai, India.
⁵ A.C. Camargo Cancer Center, São Paulo, Brazil.
⁶ Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia.
⁷ Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
⁸ Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil.
⁹ Department of Oral and Cranio-Maxillo and Facial Plastic Surgery, University of Cologne, Cologne, Germany.
¹⁰ Department of Pathology, Tel Aviv Medical Center, Tel Aviv, Israel.
¹¹ Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Israel.
¹² Department of ENT, University of Brescia, Owensboro, Italy.
¹³ University of Auckland, Auckland, New Zealand.
¹⁴ Southern Illinois University School of Medicine, Springfield, IL, USA.
¹⁵ Singhealth/Duke-NUS Head and Neck Centre, National Cancer Centre Singapore, Singapore, Singapore.
¹⁶ Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁷ The Laboratory for Applied Cancer Research, Clinical Research Institute at Rambam, Rappaport Institute for Research in Medical Science, Haifa, Israel. moranamit@gmail.com.
¹⁸ Department of Otolaryngology, Head and Neck Surgery, Head and Neck Center, Rambam Medical Center, Rappaport School of Medicine, The Technion, Israel Institute of Technology, 66036, Haifa, Israel. moranamit@gmail.com.

PMID: 26314876
PMCID: PMC4941785
DOI: 10.1245/s10434-015-4842-3

Abstract

Background: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1).

Objective: The aim of this study was to evaluate prognostic heterogeneity in the stage III category.

Methods and patients: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011.

Results: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2).

Conclusions: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

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Conflict of interest statement

Conflict of interest: none for any authors

Figures

**Figure 1**
Kaplan-Meier analysis of stage III patients according to TNM groups (T1N1, T2N1, T3N0, and T3N1). (A) 5-year overall survival (OS) and (B) disease-specific survival (DSS). (C) 5-year OS and (D) DSS of patients with T1-2N1/T3N0 (red line) and T3N1 (blue line) disease.

**Figure 2**
Kaplan-Meier analysis of (A) 5-year overall survival (OS) and (B) disease-specific survival (DSS) of patients with T3N1 and different stage IV groups (T1N2, T2N2, T3N2, T4N0, T4N1 and, T4N2) disease. (C) 5-year OS and (D) DSS of patients with stage II (red line) and stage III after removal of T3N1 (blue line) disease.

See this image and copyright information in PMC

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Lee LA, Huang CG, Tsao KC, Liao CT, Kang CJ, Chang KP, Huang SF, Chen IH, Fang TJ, Li HY, Yang SL, Lee LY, Hsueh C, Lin CY, Fan KH, Chang TC, Wang HM, Ng SH, Yen TC. Lee LA, et al. Medicine (Baltimore). 2015 Nov;94(47):e2069. doi: 10.1097/MD.0000000000002069. Medicine (Baltimore). 2015. PMID: 26632712 Free PMC article.

References

1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. - PubMed
1. Edge SB, BD, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC Cancer Staging Manual. 7. New York, NY: Springer; 2010.
1. Groome PA, Schulze K, Boysen M, Hall SF, Mackillop WJ. A comparison of published head and neck stage groupings in carcinomas of the oral cavity. Head & neck. 2001;23:613–624. - PubMed
1. Manikantan K, Sayed SI, Syrigos KN, et al. Challenges for the future modifications of the TNM staging system for head and neck cancer: case for a new computational model? Cancer treatment reviews. 2009;35:639–644. - PubMed
1. Hall SF, Groome PA, Irish J, O’Sullivan B. TNM-based stage groupings in head and neck cancer: application in cancer of the hypopharynx. Head & neck. 2009;31:1–8. - PubMed

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[1] Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. - PubMed

[2] Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. - PubMed

[3] Edge SB, BD, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC Cancer Staging Manual. 7. New York, NY: Springer; 2010.

[4] Edge SB, BD, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC Cancer Staging Manual. 7. New York, NY: Springer; 2010.

[5] Groome PA, Schulze K, Boysen M, Hall SF, Mackillop WJ. A comparison of published head and neck stage groupings in carcinomas of the oral cavity. Head & neck. 2001;23:613–624. - PubMed

[6] Groome PA, Schulze K, Boysen M, Hall SF, Mackillop WJ. A comparison of published head and neck stage groupings in carcinomas of the oral cavity. Head & neck. 2001;23:613–624. - PubMed

[7] Manikantan K, Sayed SI, Syrigos KN, et al. Challenges for the future modifications of the TNM staging system for head and neck cancer: case for a new computational model? Cancer treatment reviews. 2009;35:639–644. - PubMed

[8] Manikantan K, Sayed SI, Syrigos KN, et al. Challenges for the future modifications of the TNM staging system for head and neck cancer: case for a new computational model? Cancer treatment reviews. 2009;35:639–644. - PubMed

[9] Hall SF, Groome PA, Irish J, O’Sullivan B. TNM-based stage groupings in head and neck cancer: application in cancer of the hypopharynx. Head & neck. 2009;31:1–8. - PubMed

[10] Hall SF, Groome PA, Irish J, O’Sullivan B. TNM-based stage groupings in head and neck cancer: application in cancer of the hypopharynx. Head & neck. 2009;31:1–8. - PubMed

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Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System

Affiliations

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System

Authors

Affiliations

Abstract

Conflict of interest statement

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