Time‐varying association of second primary malignancy and long‐term survival outcomes in patients with head and neck cancer

A high risk of developing second primary malignancy (SPM) has been reported among head and neck cancer patients. Here, we aimed to statistically quantify the impact of SPM development on the survival of head and neck cancer patients. Our study was conducted using the Surveillance, Epidemiology and End Results database to collect the data of 48 316 patients who received curative surgical resection for initial primary head and neck squamous cell carcinoma (IP‐HNSCC) in 1975 to 2019. SPM diagnosis was treated as a time‐varying covariate and multivariable Cox regression analysis was conducted to estimate the association between SPM development and survival, overall or by the subsite of IP‐HNSCC. Of the included patients, 11 238 patients (23.3%) developed SPM during the follow‐up period. A significant reduction in survival was observed among patients with SPM (hazard ratio [HR] for overall survival, 3.30; 95% confidence interval [CI]: 3.20‐3.41). The impact of SPM development on reduced survival was more significant in patients with localized IP‐HNSCC vs regional IP‐HNSCC (HROS, 3.41; 95% CI: 3.24‐3.6 vs HROS, 3.18; 95% CI: 3.05‐3.31; P for interaction <.001). The survival impact of SPM development was more evident in younger patients than in older patients. SPM in lung and bronchus was associated with the most pronounced reduction in survival, overall and across all subsites of HNSCC. Our results indicated that SPM development led to a significant reduction in survival. A greater survival benefit may be achieved through intensive surveillance for SPM in lung and bronchus targeting younger patients and those with localized HNSCC.

[1]  G. Yoo,et al.  African American race as a risk factor associated with a second primary lung cancer after initial primary head and neck cancer , 2022, Head & neck.

[2]  Yuh-Seog Jung,et al.  Long-term Survivorship and Non-cancer Competing Mortality in Head and Neck Cancer: A Nationwide Population-Based Study in South Korea , 2022, Cancer research and treatment.

[3]  D. Kallogjeri,et al.  Development of second primary malignancies after transoral surgery in human papilloma virus‐positive oropharyngeal squamous cell carcinoma , 2022, Head & neck.

[4]  A. Berrington de González,et al.  Association Between Radioactive Iodine Treatment for Pediatric and Young Adulthood Differentiated Thyroid Cancer and Risk of Second Primary Malignancies , 2022, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Shuhong Wu,et al.  Second Primary Malignancy in Patients with Hypopharyngeal Carcinoma: A SEER-Based Study , 2021, International journal of general medicine.

[6]  J. Cramer,et al.  Incidence of Second Primary Lung Cancer After Low-Dose Computed Tomography vs Chest Radiography Screening in Survivors of Head and Neck Cancer: A Secondary Analysis of a Randomized Clinical Trial. , 2021, JAMA otolaryngology-- head & neck surgery.

[7]  Nitin A. Pagedar,et al.  Characterizing head and neck cancer survivors' discontinuation of survivorship care , 2021, Cancer.

[8]  M. Cabana,et al.  Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement. , 2021, JAMA.

[9]  Melissa Jay,et al.  Displaying survival of patient groups defined by covariate paths: Extensions of the Kaplan‐Meier estimator , 2021, Statistics in medicine.

[10]  Kaibo Guo,et al.  Analysis of chemotherapy effect on the second primary malignancy for head and neck cancer patients by a nomogram based on SEER database , 2020, Cancer medicine.

[11]  F. Bertolini,et al.  Second Primary Tumors in head and neck cancer patients: the importance of a "tailored" surveillance. , 2020, Oral diseases.

[12]  Liang Zhou,et al.  Survival prediction and treatment strategies for patients with advanced laryngeal carcinoma: a population-based study , 2020, International Journal of Clinical Oncology.

[13]  H. Sugiyama,et al.  Radiation-Related Risk of Cancers of the Upper Digestive Tract among Japanese Atomic Bomb Survivors. , 2019, Radiation research.

[14]  A. Rademaker,et al.  Practical Guide to Surgical Data Sets: Surveillance, Epidemiology, and End Results (SEER) Database , 2018, JAMA surgery.

[15]  Deepinder P. Singh,et al.  Second Primary Non–Small Cell Lung Cancer after Head and Neck Cancer: A Population-Based Study of Clinical and Pathologic Characteristics and Survival Outcomes in 3597 Patients , 2017 .

[16]  A. Shiotani,et al.  Clinical features and treatment outcomes of Japanese head and neck cancer patients with a second primary cancer , 2017, Asia-Pacific journal of clinical oncology.

[17]  Dale L Preston,et al.  Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958–2009 , 2017, Radiation Research.

[18]  C. V. Barro,et al.  Second primary tumours in head and neck cancer. , 2016 .

[19]  J. H. González-Botas,et al.  Segundos tumores primarios en cáncer de cabeza y cuello , 2016 .

[20]  Q. Trinh,et al.  A Surveillance, Epidemiology and End Results (SEER) database malfunction: perceptions, pitfalls and verities , 2016, BJU international.

[21]  Marta S. Patrucco,et al.  Prognostic impact of second primary tumors in head and neck cancer , 2016, European Archives of Oto-Rhino-Laryngology.

[22]  L. Wilson,et al.  Limitations and biases of the Surveillance, Epidemiology, and End Results database. , 2012, Current problems in cancer.

[23]  R. Hayes,et al.  Second primary cancers after an index head and neck cancer: subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  H. Brenner,et al.  Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. , 2010, The oncologist.

[25]  E. Weiderpass,et al.  Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries , 2008, International journal of cancer.

[26]  E. Taioli,et al.  Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: Review and meta‐analysis , 2007, International journal of cancer.

[27]  J. Shah,et al.  Second primary malignancy of the aerodigestive tract in patients treated for cancer of the oral cavity and larynx , 2005, Head & neck.

[28]  M. Miura,et al.  Site specific dependency of second primary cancer in early stage head and neck squamous cell carcinoma , 2002, Cancer.

[29]  W. Blot,et al.  Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. , 1994, Journal of the National Cancer Institute.

[30]  S. Taylor.  Head and neck cancer. , 1991, Cancer chemotherapy and biological response modifiers.

[31]  S. Warren.  Multiple primary malignant tumors. A survey of the literature and a statistical study , 1932 .