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

Angela Y. Jia, Amol Narang, Bashar Safar, Atif Zaheer, Adrian Murphy, Nilofer S. Azad, Susan Gearhart, Sandy Fang, Jonathan Efron, Tam Warczynski, Amy Hacker-Prietz, Jeffrey J Meyer

Research output: Contribution to journalArticle

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

Sequential short-course radiation therapy and chemotherapy in the neoadjuvant treatment of rectal adenocarcinoma. / Jia, Angela Y.; Narang, Amol; Safar, Bashar; Zaheer, Atif; Murphy, Adrian; Azad, Nilofer S.; Gearhart, Susan; Fang, Sandy; Efron, Jonathan; Warczynski, Tam; Hacker-Prietz, Amy; Meyer, Jeffrey J.

In: Radiation Oncology, Vol. 14, No. 1, 147, 19.08.2019.

Research output: Contribution to journalArticle

Jia, AY, Narang, A, Safar, B, Zaheer, A, Murphy, A, Azad, NS, Gearhart, S, Fang, S, Efron, J, Warczynski, T, Hacker-Prietz, A & Meyer, JJ 2019, 'Sequential short-course radiation therapy and chemotherapy in the neoadjuvant treatment of rectal adenocarcinoma', Radiation Oncology, vol. 14, no. 1, 147. https://doi.org/10.1186/s13014-019-1358-1
Jia, Angela Y. ; Narang, Amol ; Safar, Bashar ; Zaheer, Atif ; Murphy, Adrian ; Azad, Nilofer S. ; Gearhart, Susan ; Fang, Sandy ; Efron, Jonathan ; Warczynski, Tam ; Hacker-Prietz, Amy ; Meyer, Jeffrey J. / Sequential short-course radiation therapy and chemotherapy in the neoadjuvant treatment of rectal adenocarcinoma. In: Radiation Oncology. 2019 ; Vol. 14, No. 1.
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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.",
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AU - Jia, Angela Y.

AU - Narang, Amol

AU - Safar, Bashar

AU - Zaheer, Atif

AU - Murphy, Adrian

AU - Azad, Nilofer S.

AU - Gearhart, Susan

AU - Fang, Sandy

AU - Efron, Jonathan

AU - Warczynski, Tam

AU - Hacker-Prietz, Amy

AU - Meyer, Jeffrey J

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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.

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