Sequential short-course radiation therapy and chemotherapy in the neoadjuvant treatment of rectal adenocarcinoma

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Abstract

Background: There is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy. Methods: We reviewed the records of 26 patients with locally advanced rectal adenocarcinoma. All patients underwent short course radiotherapy (5 Gy X 5 fractions) followed by chemotherapy [either modified infusional and bolus 5-fluorouracail and oxalipatin (mFOLFOX6) or capecitabine and oxaliplatin] prior to consideration for surgery. A full course of chemotherapy was defined as at least 8 weeks of chemotherapy. Results: There were five clinical (c) T2, 16 cT3, and five cT4 rectal tumors, with 88% cN+. Twenty-five patients received a median of 4 cycles (range 3 to 8) of mFOLFOX6 (with one cycle defined as a two-week period); one patient received 3 cycles of capecitabine and oxaliplatin. All patients completed SCRT; 81% completed the full course of neoadjuvant chemotherapy with 19% requiring dose reductions in chemotherapy, most commonly due to neuropathy. Nineteen patients underwent post-treatment endoscopic evaluation, and nine patients were noted to achieve a complete clinical response (CCR). Six of the nine patients who achieved CCR opted for a non-operative approach of watch-and-wait. Twenty patients underwent surgical resection; pathologic complete response was observed in seven (35%) of these twenty. The main radiation-associated toxicity was proctitis with CTCAE Grade 2 proctitis observed in seven patients (27%). Post-operative Clavien-Dindo Grade 3 complications within 30 days of surgery were identified in six patients (30%), with no Grade 4 or 5 adverse events. Median length of hospital stay was 4.5 days (range 2-16 days); three patients were readmitted within a 30 day period. Conclusions: Short course preoperative radiotherapy followed by neoadjuvant chemotherapy was well-tolerated and achieved oncologic outcomes that compare favorably with short-course radiation therapy alone or long-course chemoradiotherapy. This regimen is associated with high rates of clinical and pathologic complete response.

Original languageEnglish (US)
Article number147
JournalRadiation Oncology
Volume14
Issue number1
DOIs
StatePublished - Aug 19 2019

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Neoadjuvant Therapy
Adenocarcinoma
Radiotherapy
Drug Therapy
oxaliplatin
Proctitis
Length of Stay
Consolidation Chemotherapy
Chemoradiotherapy
Rectal Neoplasms
Ambulatory Surgical Procedures

Keywords

  • Rectal cancer
  • Short-course chemoradiotherapy
  • Watch and wait

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

@article{085a81d0d7224690aba773abcc101b25,
title = "Sequential short-course radiation therapy and chemotherapy in the neoadjuvant treatment of rectal adenocarcinoma",
abstract = "Background: There is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy. Methods: We reviewed the records of 26 patients with locally advanced rectal adenocarcinoma. All patients underwent short course radiotherapy (5 Gy X 5 fractions) followed by chemotherapy [either modified infusional and bolus 5-fluorouracail and oxalipatin (mFOLFOX6) or capecitabine and oxaliplatin] prior to consideration for surgery. A full course of chemotherapy was defined as at least 8 weeks of chemotherapy. Results: There were five clinical (c) T2, 16 cT3, and five cT4 rectal tumors, with 88{\%} cN+. Twenty-five patients received a median of 4 cycles (range 3 to 8) of mFOLFOX6 (with one cycle defined as a two-week period); one patient received 3 cycles of capecitabine and oxaliplatin. All patients completed SCRT; 81{\%} completed the full course of neoadjuvant chemotherapy with 19{\%} requiring dose reductions in chemotherapy, most commonly due to neuropathy. Nineteen patients underwent post-treatment endoscopic evaluation, and nine patients were noted to achieve a complete clinical response (CCR). Six of the nine patients who achieved CCR opted for a non-operative approach of watch-and-wait. Twenty patients underwent surgical resection; pathologic complete response was observed in seven (35{\%}) of these twenty. The main radiation-associated toxicity was proctitis with CTCAE Grade 2 proctitis observed in seven patients (27{\%}). Post-operative Clavien-Dindo Grade 3 complications within 30 days of surgery were identified in six patients (30{\%}), with no Grade 4 or 5 adverse events. Median length of hospital stay was 4.5 days (range 2-16 days); three patients were readmitted within a 30 day period. Conclusions: Short course preoperative radiotherapy followed by neoadjuvant chemotherapy was well-tolerated and achieved oncologic outcomes that compare favorably with short-course radiation therapy alone or long-course chemoradiotherapy. This regimen is associated with high rates of clinical and pathologic complete response.",
keywords = "Rectal cancer, Short-course chemoradiotherapy, Watch and wait",
author = "Jia, {Angela Y.} and Amol Narang and Bashar Safar and Atif Zaheer and Adrian Murphy and Nilofer Azad and Gearhart, {Susan L} and Fang, {Sandy H} and Jonathan Efron and Tam Warczynski and Amy Hacker-Prietz and Jeffrey Meyer",
year = "2019",
month = "8",
day = "19",
doi = "10.1186/s13014-019-1358-1",
language = "English (US)",
volume = "14",
journal = "Radiation Oncology",
issn = "1748-717X",
publisher = "BioMed Central",
number = "1",

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TY - JOUR

T1 - Sequential short-course radiation therapy and chemotherapy in the neoadjuvant treatment of rectal adenocarcinoma

AU - Jia, Angela Y.

AU - Narang, Amol

AU - Safar, Bashar

AU - Zaheer, Atif

AU - Murphy, Adrian

AU - Azad, Nilofer

AU - Gearhart, Susan L

AU - Fang, Sandy H

AU - Efron, Jonathan

AU - Warczynski, Tam

AU - Hacker-Prietz, Amy

AU - Meyer, Jeffrey

PY - 2019/8/19

Y1 - 2019/8/19

N2 - Background: There is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy. Methods: We reviewed the records of 26 patients with locally advanced rectal adenocarcinoma. All patients underwent short course radiotherapy (5 Gy X 5 fractions) followed by chemotherapy [either modified infusional and bolus 5-fluorouracail and oxalipatin (mFOLFOX6) or capecitabine and oxaliplatin] prior to consideration for surgery. A full course of chemotherapy was defined as at least 8 weeks of chemotherapy. Results: There were five clinical (c) T2, 16 cT3, and five cT4 rectal tumors, with 88% cN+. Twenty-five patients received a median of 4 cycles (range 3 to 8) of mFOLFOX6 (with one cycle defined as a two-week period); one patient received 3 cycles of capecitabine and oxaliplatin. All patients completed SCRT; 81% completed the full course of neoadjuvant chemotherapy with 19% requiring dose reductions in chemotherapy, most commonly due to neuropathy. Nineteen patients underwent post-treatment endoscopic evaluation, and nine patients were noted to achieve a complete clinical response (CCR). Six of the nine patients who achieved CCR opted for a non-operative approach of watch-and-wait. Twenty patients underwent surgical resection; pathologic complete response was observed in seven (35%) of these twenty. The main radiation-associated toxicity was proctitis with CTCAE Grade 2 proctitis observed in seven patients (27%). Post-operative Clavien-Dindo Grade 3 complications within 30 days of surgery were identified in six patients (30%), with no Grade 4 or 5 adverse events. Median length of hospital stay was 4.5 days (range 2-16 days); three patients were readmitted within a 30 day period. Conclusions: Short course preoperative radiotherapy followed by neoadjuvant chemotherapy was well-tolerated and achieved oncologic outcomes that compare favorably with short-course radiation therapy alone or long-course chemoradiotherapy. This regimen is associated with high rates of clinical and pathologic complete response.

AB - Background: There is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy. Methods: We reviewed the records of 26 patients with locally advanced rectal adenocarcinoma. All patients underwent short course radiotherapy (5 Gy X 5 fractions) followed by chemotherapy [either modified infusional and bolus 5-fluorouracail and oxalipatin (mFOLFOX6) or capecitabine and oxaliplatin] prior to consideration for surgery. A full course of chemotherapy was defined as at least 8 weeks of chemotherapy. Results: There were five clinical (c) T2, 16 cT3, and five cT4 rectal tumors, with 88% cN+. Twenty-five patients received a median of 4 cycles (range 3 to 8) of mFOLFOX6 (with one cycle defined as a two-week period); one patient received 3 cycles of capecitabine and oxaliplatin. All patients completed SCRT; 81% completed the full course of neoadjuvant chemotherapy with 19% requiring dose reductions in chemotherapy, most commonly due to neuropathy. Nineteen patients underwent post-treatment endoscopic evaluation, and nine patients were noted to achieve a complete clinical response (CCR). Six of the nine patients who achieved CCR opted for a non-operative approach of watch-and-wait. Twenty patients underwent surgical resection; pathologic complete response was observed in seven (35%) of these twenty. The main radiation-associated toxicity was proctitis with CTCAE Grade 2 proctitis observed in seven patients (27%). Post-operative Clavien-Dindo Grade 3 complications within 30 days of surgery were identified in six patients (30%), with no Grade 4 or 5 adverse events. Median length of hospital stay was 4.5 days (range 2-16 days); three patients were readmitted within a 30 day period. Conclusions: Short course preoperative radiotherapy followed by neoadjuvant chemotherapy was well-tolerated and achieved oncologic outcomes that compare favorably with short-course radiation therapy alone or long-course chemoradiotherapy. This regimen is associated with high rates of clinical and pathologic complete response.

KW - Rectal cancer

KW - Short-course chemoradiotherapy

KW - Watch and wait

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U2 - 10.1186/s13014-019-1358-1

DO - 10.1186/s13014-019-1358-1

M3 - Article

VL - 14

JO - Radiation Oncology

JF - Radiation Oncology

SN - 1748-717X

IS - 1

M1 - 147

ER -