Kimberly Levinson1, Anna L Beavis2, Christopher Purdy3, Anne F Rositch4, Akila Viswanathan5, Aaron H Wolfson6, Michael G Kelly7, Krishnansu S Tewari8, Leah McNally9, Saketh R Guntupalli10, Omar Ragab11, Yi-Chun Lee12, David S Miller13, Warner K Huh14, Kelly J Wilkinson15, Nicola M Spirtos16, Linda Van Le17, Yovanni Casablanca18, Laura L Holman19, Steven E Waggoner20, Amanda N Fader21. 1. Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. Electronic address: klevins1@jhmi.edu. 2. Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. Electronic address: abeavis2@jhmi.edu. 3. NRG Oncology, Clinical Trial Development Division, Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States of America. Electronic address: purdyc@nrgoncology.org. 4. Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States of America. Electronic address: arositch@jhu.edu. 5. Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. Electronic address: anv@jhu.edu. 6. Sylvester Comprehensive Cancer Center, Miami, FL, United States of America. Electronic address: awolfson@med.miami.edu. 7. Wake Forest Baptist Medical Center, Winston-Salem, NC, United States of America. Electronic address: mgkelly@wakehealth.edu. 8. University of California Irvine, Orange, CA, United States of America. Electronic address: ktewari@uci.edu. 9. Duke Cancer Institute, Durham, NC, United States of America. Electronic address: leah.mcnally018@duke.edu. 10. University of Colorado Anschutz, Aurora, CO, United States of America. Electronic address: Saketh.Guntupalli@ucdenver.edu. 11. Keck School of Medicine of USC, Los Angeles, CA, United States of America. Electronic address: Omar.Ragab@med.usc.edu. 12. SUNY Health Science Center at Brooklyn, Brooklyn, NY, United States of America. Electronic address: Yi-Chun.Lee@downstatemedical.edu. 13. University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9032, United States of America. Electronic address: David.Miller@UTSouthwestern.edu. 14. University of Alabama at Birmingham, Birmingham, AL, United States of America. Electronic address: Whuh@uabmc.edu. 15. University of Mississippi Medical Center, Jackson, MS, United States of America. Electronic address: kjeanes@umc.edu. 16. Women's Cancer Center, Las Vegas, NV, United States of America. Electronic address: nspirtos@wccenter.com. 17. University of North Carolina School of Medicine, Chapel Hill, NC, United States of America. Electronic address: lvl@med.unc.edu. 18. Walter Reed National Medical Center, Bethesda, MD, United States of America. Electronic address: Yovanni.Casablanca.mil@mail.mil. 19. University of Oklahoma Health Sciences Center, Stephenson Cancer Center, 800 Northeast Tenth St., Oklahoma City, OK, United States of America. Electronic address: Laura-Holman@ouhsc.edu. 20. Case Western Reserve University, Cleveland, OH, United States of America. Electronic address: steven.waggoner@uhhospitals.org. 21. Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. Electronic address: afader1@jhmi.edu.
Abstract
PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.
PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.
Authors: Marvin Rotman; Alexander Sedlis; Marion R Piedmonte; Brian Bundy; Samuel S Lentz; Laila I Muderspach; Richard J Zaino Journal: Int J Radiat Oncol Biol Phys Date: 2006-01-19 Impact factor: 7.038
Authors: Gary L Eddy; Brian N Bundy; William T Creasman; Nick M Spirtos; Robert S Mannel; Edward Hannigan; Dennis O'Connor Journal: Gynecol Oncol Date: 2007-05-09 Impact factor: 5.482
Authors: David H Moore; Chunqiao Tian; Bradley J Monk; Harry J Long; George A Omura; Jeffrey D Bloss Journal: Gynecol Oncol Date: 2009-10-22 Impact factor: 5.482
Authors: Marc Arbyn; Elisabete Weiderpass; Laia Bruni; Silvia de Sanjosé; Mona Saraiya; Jacques Ferlay; Freddie Bray Journal: Lancet Glob Health Date: 2019-12-04 Impact factor: 26.763