International journal of radiation oncology, biology, physics 2014-03-15
Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer.
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.
Related Questions
Are there any bladder constraints for preoperative short course rectal RT?
While I appreciate thoughts on constraints by Fields et al., PMID 31673654 (14 patients), or even our paper from Myerson et al., PMID 24606849 (76 patients), I think these are superseded by the higher level of evidence from the RAPIDO study (462 patients w/ SCRT).The RAPIDO study (appendix F, page 8...
With the RAPIDO trial demonstrating efficacy of short course XRT as part of TNT for locally advanced rectal cancer, is there a role for short course XRT to be integrated into watch and wait programs?
Great question, and one our group has discussed extensively. Our group currently uses short course radiation nearly exclusively in the treatment of locally advanced rectal cancer. One notable exception (at least so far) is if the patient desires NOM. Our rationale is that there aren’t as many data f...
Would you consider short course RT for rectal cancer in the post-op setting given COVID-19?
I would not use short course in the postoperative setting. Virtually all of the data on short course are preoperative, where most of the irradiated bowel is removed surgically. The patient would get over the acute reaction from short course postoperatively, but I have major concerns about late effec...
How would you approach a low-lying rectal cancer wtih para-aortic lymphadenopathy?
I will assume that the question is one of management for oligometastatic nodal M1 disease--i.e. one or two para aortic lymph nodes and no other extrapelvic disease. In the past I've treated a few cases like this, as well as a few that were M1 by virtue of inguinal or iliac nodal metastases. The comb...
Can short course radiation therapy (5 Gy x 5 fractions) be given for low lying rectal tumors, near the sphincter but not involving it?
The anal sphincter toxicity of short-course radiation therapy versus long-course chemoradiation therapy is an interesting question. We know from a robust experience in anal squamous cell carcinoma that long course radiation does carry a significant risk of sphincter tone issues in the long-term, eve...
What is your typical target/field when treating a patient with 5 Gy x 5 fractions pre-operatively for rectal cancer?
The European experience with short course preoperative radiotherapy uses treatment portals that are somewhat smaller than what many of us utilize in the US. At Washington University we have a long experience (that pre-dates the Swedish trials) with 4Gy X 5fx for readily resectable tumors. The cases ...
In what situations can short course RT (5 Gy x 5fx) be used instead of chemoRT for rectal cancer?
My take? Preop short course RT is grossly underutilized in the US for locally advanced rectal cancer.Progress is slow but we are getting there; the 2019 version of the NCCN guidelines lists SCRT followed by resection as a standard option for patients w/ T3 or N+ disease as long as the CRM is clear b...