Adoption of total neoadjuvant therapy for locally advanced rectal cancer Journal Article


Authors: Cercek, A.; Roxburgh, C. S. D.; Strombom, P.; Smith, J. J.; Temple, L. K. F.; Nash, G. M.; Guillem, J. G.; Paty, P. B.; Yaeger, R.; Stadler, Z. K.; Seier, K.; Gonen, M.; Segal, N. H.; Reidy, D. L.; Varghese, A.; Shia, J.; Vakiani, E.; Wu, A. J.; Crane, C. H.; Gollub, M. J.; Garcia-Aguilar, J.; Saltz, L. B.; Weiser, M. R.
Article Title: Adoption of total neoadjuvant therapy for locally advanced rectal cancer
Abstract: IMPORTANCE: Treatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases. OBJECTIVE To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified. EXPOSURES Of the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil-and oxaliplatin-based chemotherapy followed by chemoRT). MAIN OUTCOMES AND MEASURES Treatment and outcome data for the 2 cohortswere compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK. RESULTS Of the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemo RT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemo RT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36%in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort. CONCLUSIONS AND RELEVANCE Our findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation. © 2018 American Medical Association. All rights reserved.
Journal Title: JAMA Oncology
Volume: 4
Issue: 6
ISSN: 2374-2437
Publisher: American Medical Association  
Date Published: 2018-06-14
Start Page: e180071
Language: English
DOI: 10.1001/jamaoncol.2018.0071
PROVIDER: scopus
PMCID: PMC5885165
PUBMED: 29566109
DOI/URL:
Notes: Article -- Export Date: 1 August 2018 -- Source: Scopus
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MSK Authors
  1. Leonard B Saltz
    615 Saltz
  2. Philip B Paty
    379 Paty
  3. Marc J Gollub
    113 Gollub
  4. Neil Howard Segal
    115 Segal
  5. Mithat Gonen
    726 Gonen
  6. Jose Guillem
    379 Guillem
  7. Zsofia Kinga Stadler
    159 Stadler
  8. Diane Lauren Reidy
    164 Reidy
  9. Jinru Shia
    475 Shia
  10. Martin R Weiser
    351 Weiser
  11. Rona Denit Yaeger
    82 Yaeger
  12. Abraham Jing-Ching Wu
    209 Wu
  13. Garrett Nash
    141 Nash
  14. Larissa Temple
    185 Temple
  15. Efsevia Vakiani
    170 Vakiani
  16. Jesse Joshua Smith
    55 Smith
  17. Christopher   Crane
    43 Crane
  18. Kenneth Seier
    24 Seier