Geffen Kleinstern1, Abdul Rishi2, Sara J Achenbach1, Kari G Rabe1, Neil E Kay3, Tait D Shanafelt4, Wei Ding3, Joe F Leis5, Aaron D Norman1, Timothy G Call3, James R Cerhan1, Sameer A Parikh3, Christian L Baum6, Susan L Slager7. 1. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. 2. Department of Internal Medicine, Mercy Hospital, Saint Louis, Missouri. 3. Division of Hematology, Mayo Clinic, Rochester, Minnesota. 4. Division of Hematology, Department of Medicine, Stanford University, Stanford, California. 5. Department of Hematology and Oncology, Mayo Clinic, Phoenix, Arizona. 6. Department of Dermatology, Mayo Clinic, Rochester, Minnesota. 7. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. Electronic address: slager@mayo.edu.
Abstract
BACKGROUND: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls. OBJECTIVE: To evaluate the association of factors associated with SCC risk. METHODS: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC). LIMITATIONS: The sample size decreases when combining all risk factors in a single model. CONCLUSION: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.
BACKGROUND: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls. OBJECTIVE: To evaluate the association of factors associated with SCC risk. METHODS: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC). LIMITATIONS: The sample size decreases when combining all risk factors in a single model. CONCLUSION: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.
Authors: Jerry D Brewer; Tait D Shanafelt; Farzaneh Khezri; Ivette M Sosa Seda; Adeel S Zubair; Christian L Baum; Christopher J Arpey; James R Cerhan; Timothy G Call; Randall K Roenigk; Carin Y Smith; Amy L Weaver; Clark C Otley Journal: J Am Acad Dermatol Date: 2014-12-02 Impact factor: 11.527
Authors: Lindsay M Morton; Rochelle E Curtis; Martha S Linet; Elizabeth C Bluhm; Margaret A Tucker; Neil Caporaso; Lynn A G Ries; Joseph F Fraumeni Journal: J Clin Oncol Date: 2010-10-12 Impact factor: 44.544
Authors: Geffen Kleinstern; Nicola J Camp; Lynn R Goldin; Celine M Vachon; Claire M Vajdic; Silvia de Sanjose; J Brice Weinberg; Yolanda Benavente; Delphine Casabonne; Mark Liebow; Alexandra Nieters; Henrik Hjalgrim; Mads Melbye; Bengt Glimelius; Hans-Olov Adami; Paolo Boffetta; Paul Brennan; Marc Maynadie; James McKay; Pier Luigi Cocco; Tait D Shanafelt; Timothy G Call; Aaron D Norman; Curtis Hanson; Dennis Robinson; Kari G Chaffee; Angela R Brooks-Wilson; Alain Monnereau; Jacqueline Clavel; Martha Glenn; Karen Curtin; Lucia Conde; Paige M Bracci; Lindsay M Morton; Wendy Cozen; Richard K Severson; Stephen J Chanock; John J Spinelli; James B Johnston; Nathaniel Rothman; Christine F Skibola; Jose F Leis; Neil E Kay; Karin E Smedby; Sonja I Berndt; James R Cerhan; Neil Caporaso; Susan L Slager Journal: Blood Date: 2018-04-19 Impact factor: 25.476