Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer

Robert J. Myerson, Benjamin Tan, Steven Hunt, Jeffrey Olsen, Elisa Birnbaum, James Fleshman, Feng Gao, Lannis Hall, Ira Kodner, Albert Lockhart, Matthew Mutch, Michael Naughton, Joel Picus, Caron Rigden, Bashar Safar, Steven Sorscher, Rama Suresh, Andrea Wang-Gillam, Parag Parikh

Research output: Contribution to journalArticle

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Abstract

Background Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%). Conclusion This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.

Original languageEnglish (US)
Pages (from-to)829-836
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume88
Issue number4
DOIs
StatePublished - Mar 15 2014
Externally publishedYes

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chemotherapy
Rectal Neoplasms
radiation therapy
Radiotherapy
cancer
surgery
Drug Therapy
cycles
Morbidity
grade
oxaliplatin
Fluorouracil
confidence
Therapeutics
Confidence Intervals
Background Radiation
intervals
Leucovorin
background radiation
Cytotoxins

ASJC Scopus subject areas

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

Cite this

Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer. / Myerson, Robert J.; Tan, Benjamin; Hunt, Steven; Olsen, Jeffrey; Birnbaum, Elisa; Fleshman, James; Gao, Feng; Hall, Lannis; Kodner, Ira; Lockhart, Albert; Mutch, Matthew; Naughton, Michael; Picus, Joel; Rigden, Caron; Safar, Bashar; Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea; Parikh, Parag.

In: International Journal of Radiation Oncology Biology Physics, Vol. 88, No. 4, 15.03.2014, p. 829-836.

Research output: Contribution to journalArticle

Myerson, RJ, Tan, B, Hunt, S, Olsen, J, Birnbaum, E, Fleshman, J, Gao, F, Hall, L, Kodner, I, Lockhart, A, Mutch, M, Naughton, M, Picus, J, Rigden, C, Safar, B, Sorscher, S, Suresh, R, Wang-Gillam, A & Parikh, P 2014, 'Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer', International Journal of Radiation Oncology Biology Physics, vol. 88, no. 4, pp. 829-836. https://doi.org/10.1016/j.ijrobp.2013.12.028
Myerson, Robert J. ; Tan, Benjamin ; Hunt, Steven ; Olsen, Jeffrey ; Birnbaum, Elisa ; Fleshman, James ; Gao, Feng ; Hall, Lannis ; Kodner, Ira ; Lockhart, Albert ; Mutch, Matthew ; Naughton, Michael ; Picus, Joel ; Rigden, Caron ; Safar, Bashar ; Sorscher, Steven ; Suresh, Rama ; Wang-Gillam, Andrea ; Parikh, Parag. / Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer. In: International Journal of Radiation Oncology Biology Physics. 2014 ; Vol. 88, No. 4. pp. 829-836.
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abstract = "Background Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78{\%}) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9{\%}) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75{\%}) patients. At surgery, 53 patients (70{\%}) had ypT0-2 residual disease, including 21 (28{\%}) ypT0 and 19 (25{\%}) ypT0N0 (complete response); 24 (32{\%}) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95{\%} (95{\%} confidence interval [CI]: 89{\%}-100{\%}) and 87{\%} (95{\%} CI: 76{\%}-98{\%}). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42{\%}), 15 ypT0N0 (39{\%}), and 33 ypT0-2 (87{\%}). Conclusion This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.",
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T1 - Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer

AU - Myerson, Robert J.

AU - Tan, Benjamin

AU - Hunt, Steven

AU - Olsen, Jeffrey

AU - Birnbaum, Elisa

AU - Fleshman, James

AU - Gao, Feng

AU - Hall, Lannis

AU - Kodner, Ira

AU - Lockhart, Albert

AU - Mutch, Matthew

AU - Naughton, Michael

AU - Picus, Joel

AU - Rigden, Caron

AU - Safar, Bashar

AU - Sorscher, Steven

AU - Suresh, Rama

AU - Wang-Gillam, Andrea

AU - Parikh, Parag

PY - 2014/3/15

Y1 - 2014/3/15

N2 - Background Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%). Conclusion This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.

AB - Background Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%). Conclusion This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.

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