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Journal of Radiation Oncology

, Volume 7, Issue 3, pp 213–222 | Cite as

Factors predictive of neoadjuvant versus adjuvant chemoradiotherapy in locally advanced rectal cancer and the impact on overall survival

  • Alex Coffman
  • Dustin Boothe
  • Jonathan Frandsen
  • Molly Gross
  • Thomas Bartley Pickron
  • Courtney L. Scaife
  • Shane Lloyd
Original Research

Abstract

Objectives

We investigated the effect of neoadjuvant versus adjuvant chemoradiotherapy on overall survival as well as the impact of demographic and clinical factors for the selection of each approach utilizing the National Cancer Data Base.

Methods

Adult patients with stage II and stage III adenocarcinoma of the rectum diagnosed from 2004 to 2013 were included. Chi-square analysis was used to compare demographic variables and clinical stage between the patients receiving neoadjuvant and adjuvant chemoradiotherapy. Univariate and multivariate logistic regression modeling was used to identify factors predictive of each treatment strategy. Kaplan-Meier and log-rank analysis and Cox proportional hazard modeling along with propensity score matching using variables known at the time of treatment sequence decision was performed to determine the effect on survival. A separate survival analysis was conducted including margin status to illustrate its effect on survival relative to adjuvant or neoadjuvant chemoradiation therapy.

Results

A total of 20,114 patients were identified: 17,612 (87.6%) received neoadjuvant chemoradiotherapy. Factors associated with receipt of neoadjuvant chemoradiotherapy on multivariate analysis include the following: income greater than $46,000 (p < 0.01), treatment at an academic institution (p < 0.01), living greater than 50 miles from the treatment facility (p < 0.01), and year of diagnosis (p < 0.01). Compared to adjuvant chemoradiotherapy, neoadjuvant chemoradiotherapy was associated with a decreased risk of death on multivariate analysis (p = 0.05). When taking margin status into account, margin positivity in neoadjuvant chemoradiotherapy (NCRT) patients was shown to be a poor prognostic factor. Margin-negative NCRT patients had improved survival compared to margin negative adjuvant chemoradiotherapy (ACRT) patients.

Conclusions

The use of neoadjuvant chemoradiotherapy for locally advanced rectal cancer is possibly associated with an overall survival benefit compared to ACRT subject to the limitations of this analysis. Margin status affects survival greatly.

Keywords

Rectal neoplasms Neoadjuvant therapy Survival Chemoradiation 

Notes

Acknowledgements

The authors would like to acknowledge Michelle Denney for help in preparing this manuscript for publication.

Compliance with ethical standards

Funding

No funding was received for this study.

Conflict of interest

Shane Lloyd declares personal fees from Sirtex. All the other authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

13566_2018_350_MOESM1_ESM.docx (17 kb)
ESM 1 (DOCX 17 kb)

References

  1. 1.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30CrossRefGoogle Scholar
  2. 2.
    National Comprehensive Cancer Network (2016) Rectal Cancer (Version 2) https://www.nccn.org/store/login/login.aspx?. ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed 12/01/2016
  3. 3.
    Gastrointestinal Tumor Study Group (1985) Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 312(23):1465–1472Google Scholar
  4. 4.
    Douglass HO Jr, Moertel CG, Mayer RJ, Thomas PR, Lindblad AS, Mittleman A, Stablein DM, Bruckner HW; Gastrointestinal Tumor Study Group (1986) Survival after postoperative combination treatment of rectal cancer. N Engl J Med 315(20):1294–1295CrossRefGoogle Scholar
  5. 5.
    Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, Twito DI, Morton RF, Veeder MH, Witzig TE, Cha S, Vidyarthi SC (1991) Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324(11):709–715CrossRefGoogle Scholar
  6. 6.
    Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R, German Rectal Cancer Study Group (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351(17):1731–1740CrossRefGoogle Scholar
  7. 7.
    Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ, Wolmark N (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27(31):5124–5130CrossRefGoogle Scholar
  8. 8.
    Maldonado G, Greenland S (1993) Simulation study of confounder-selection strategies. Am J Epidemiol 138(11):923–936CrossRefGoogle Scholar
  9. 9.
    Budtz-Jørgensen E, Keiding N, Grandjean P, Weihe P (2007) Confounder selection in environmental epidemiology: assessment of health effects of prenatal mercury exposure. Ann Epidemiol 17(1):27–35CrossRefGoogle Scholar
  10. 10.
    National Cancer Data Base. American College of Surgeons. [Online]. Available: https://www.facs.org/quality-programs/cancer/ncdb. Accessed 31 Mar 2016
  11. 11.
    Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rödel C (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol Off J Am Soc Clin Oncol 30(16):1926–1933CrossRefGoogle Scholar
  12. 12.
    Hav M, Libbrecht L, Geboes K, Ferdinande L, Boterberg T, Ceelen W, Pattyn P, Cuvelier C (2015) Prognostic value of tumor shrinkage versus fragmentation following radiochemotherapy and surgery for rectal cancer. Virchows Arch Int J Pathol 466(5):517–523CrossRefGoogle Scholar
  13. 13.
    Al-Sukhni E, Attwood K, Mattson DM, Gabriel E, Nurkin SJ (2016) Predictors of pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Ann Surg Oncol 23(4):1177–1186CrossRefGoogle Scholar
  14. 14.
    Cook MB, McGlynn KA, Devesa SS, Freedman ND, Anderson WF (2011) Sex disparities in cancer mortality and survival. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 20(8):1629–1637CrossRefGoogle Scholar
  15. 15.
    Nitzkorski JR, Willis AI, Nick D, Zhu F, Farma JM, Sigurdson ER (2013) Association of race and socioeconomic status and outcomes of patients with rectal cancer. Ann Surg Oncol 20(4):1142–1147CrossRefGoogle Scholar
  16. 16.
    Sineshaw HM, Jemal A, Thomas CR, Mitin T (2016) Changes in treatment patterns for patients with locally advanced rectal cancer in the United States over the past decade: an analysis from the National Cancer Data Base. Cancer 122(13):1996–2003CrossRefGoogle Scholar
  17. 17.
    Monson JRT et al (2014) Failure of evidence-based cancer care in the United States: the association between rectal cancer treatment, cancer center volume, and geography. Ann Surg 260(4):625–631; discussion 631-632CrossRefGoogle Scholar
  18. 18.
    Ward MM, Ullrich F, Matthews K, Rushton G, Tracy R, Goldstein MA, Bajorin DF, Kosty MP, Bruinooge SS, Hanley A, Jacobson GM, Lynch CF (2014) Where do patients with cancer in Iowa receive radiation therapy? J Oncol Pract Am Soc Clin Oncol 10(1):20–25CrossRefGoogle Scholar
  19. 19.
    Glimelius B, Isacsson U, Jung B, Påhlman L (1997) Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose-response effect favoring preoperative treatment. Int J Radiat Oncol Biol Phys 37(2):281–287CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Alex Coffman
    • 1
  • Dustin Boothe
    • 2
  • Jonathan Frandsen
    • 2
  • Molly Gross
    • 3
  • Thomas Bartley Pickron
    • 4
  • Courtney L. Scaife
    • 4
  • Shane Lloyd
    • 2
  1. 1.Department of Radiation OncologyLoma Linda University Medical CenterLoma LindaUSA
  2. 2.Department of Radiation Oncology, Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  3. 3.The Iowa ClinicDes MoinesUSA
  4. 4.Department of Surgery, Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA

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