Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis

Stephanie Markovina, Fady Youssef, Amit Roy, Sonya Aggarwal, Shariq Khwaja, Todd DeWees, Benjamin Tan, Steven Hunt, Robert J. Myerson, Daniel T. Chang, Parag J. Parikh, Jeffrey R. Olsen

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Methods and Materials Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log–rank test was used to compare local control, distant metastasis–free survival, disease-free survival, and overall survival. Results Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Conclusions Patients treated with nTNT had higher T-downstaging and superior distant metastasis–free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution.

Original languageEnglish (US)
Pages (from-to)417-426
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume99
Issue number2
DOIs
StatePublished - Oct 1 2017
Externally publishedYes

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Matched-Pair Analysis
Neoadjuvant Therapy
Chemoradiotherapy
metastasis
chemotherapy
Rectal Neoplasms
Disease-Free Survival
radiation therapy
therapy
Radiotherapy
cancer
Neoplasm Metastasis
Drug Therapy
Survival
tumors
Adjuvant Chemoradiotherapy
Kaplan-Meier Estimate
toxicity
Adjuvant Chemotherapy
Standard of Care

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy : Results of a Matched Pair Analysis. / Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J.; Chang, Daniel T.; Parikh, Parag J.; Olsen, Jeffrey R.

In: International Journal of Radiation Oncology Biology Physics, Vol. 99, No. 2, 01.10.2017, p. 417-426.

Research output: Contribution to journalArticle

Markovina, Stephanie ; Youssef, Fady ; Roy, Amit ; Aggarwal, Sonya ; Khwaja, Shariq ; DeWees, Todd ; Tan, Benjamin ; Hunt, Steven ; Myerson, Robert J. ; Chang, Daniel T. ; Parikh, Parag J. ; Olsen, Jeffrey R. / Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy : Results of a Matched Pair Analysis. In: International Journal of Radiation Oncology Biology Physics. 2017 ; Vol. 99, No. 2. pp. 417-426.
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abstract = "Purpose To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Methods and Materials Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log–rank test was used to compare local control, distant metastasis–free survival, disease-free survival, and overall survival. Results Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28{\%} versus 16{\%} (P=.21) and 75{\%} versus 41{\%} (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85{\%} vs 68{\%}, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92{\%} vs 96{\%}, P=.36) and overall survival (96{\%} vs 88{\%}, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Conclusions Patients treated with nTNT had higher T-downstaging and superior distant metastasis–free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution.",
author = "Stephanie Markovina and Fady Youssef and Amit Roy and Sonya Aggarwal and Shariq Khwaja and Todd DeWees and Benjamin Tan and Steven Hunt and Myerson, {Robert J.} and Chang, {Daniel T.} and Parikh, {Parag J.} and Olsen, {Jeffrey R.}",
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T1 - Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy

T2 - Results of a Matched Pair Analysis

AU - Markovina, Stephanie

AU - Youssef, Fady

AU - Roy, Amit

AU - Aggarwal, Sonya

AU - Khwaja, Shariq

AU - DeWees, Todd

AU - Tan, Benjamin

AU - Hunt, Steven

AU - Myerson, Robert J.

AU - Chang, Daniel T.

AU - Parikh, Parag J.

AU - Olsen, Jeffrey R.

PY - 2017/10/1

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N2 - Purpose To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Methods and Materials Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log–rank test was used to compare local control, distant metastasis–free survival, disease-free survival, and overall survival. Results Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Conclusions Patients treated with nTNT had higher T-downstaging and superior distant metastasis–free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution.

AB - Purpose To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Methods and Materials Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log–rank test was used to compare local control, distant metastasis–free survival, disease-free survival, and overall survival. Results Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Conclusions Patients treated with nTNT had higher T-downstaging and superior distant metastasis–free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution.

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