Retrospective study of acute toxicity following short-course preoperative radiotherapy

Hartley, A.; Giridharan, S.; Gray, L; Billingham, Lucinda; Ismail, Tariq; Geh, J I

doi:10.1046/j.1365-2168.2002.02136.x

Cited by 30 publications

(21 citation statements)

References 33 publications

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“…Radiotherapy doses, target volumes, as well as duration were, for most of the patients, in conformity with protocol. Radiotherapy-induced toxicity was consistent with previous experiences reported [28,29].…”

Section: Discussionsupporting

confidence: 90%

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Feasibility of adequate resectable rectal cancer treatment in a third-level hospital

et al. 2009

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Section: Discussionsupporting

confidence: 90%

“…Median duration of radiotherapy was 6.00 days (5.56-6.44; CI 95%). Radiotherapy-induced toxicity was vithdrawn similar to that in previous reports [28,29].…”

Section: Resultssupporting

confidence: 78%

Feasibility of adequate resectable rectal cancer treatment in a third-level hospital

et al. 2009

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“…Thus, based upon this subgroup analysis, supported by subgroup analyses of the Stockholm I + II studies (52) and the TME study (48, 53), surgery after 5Gyx5 should be performed within 11 days from the start of RT, or delayed for several weeks in order to minimize surgical morbidity and mortality. Even if similar experience has been reported by others (54, 55), the conclusion is based upon retrospective studies, and should be interpreted cautiously. In an analysis of the Stockholm III trial after 657 randomized patients (585 analyzed) (56) and in a validation set to the Dutch study (48), the increased toxicity after a slight delay was no longer seen.…”

Section: Time Interval After Short-course Radiotherapy To Surgerysupporting

confidence: 50%

“…Actually, it is possible that surgical morbidity after short-course RT is less if surgery is delayed than if performed immediately, but this is confounded by patients who were operated upon after a brief delay of only a few days, revealing increased surgical morbidity (51). There may be a time-period after short-course RT during which surgery should not be performed (48, 52, 54, 55), even if there are indications that knowledge about the increased morbidity seen when surgery is performed between 10 and 20 days after the first 5 Gy fraction can be handled (48, 56). Delaying surgery after long-course CRT also appears safe.…”

Section: Discussionmentioning

confidence: 99%

Optimal Time Intervals between Pre-Operative Radiotherapy or Chemoradiotherapy and Surgery in Rectal Cancer?

Glimelius

2014

Front. Oncol.

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Background: In rectal cancer therapy, radiotherapy or chemoradiotherapy (RT/CRT) is extensively used pre-operatively to (i) decrease local recurrence risks, (ii) allow radical surgery in non-resectable tumors, and (iii) increase the chances of sphincter-saving surgery or (iv) organ-preservation. There is a growing interest among clinicians and scientists to prolong the interval from the RT/CRT to surgery to achieve maximal tumor regression and to diminish complications during surgery.Methods: The pros and cons of delaying surgery depending upon the aim of the pre-operative RT/CRT are critically evaluated.Results: Depending upon the clinical situation, the need for a time interval prior to surgery to allow tumor regression varies. In the first and most common situation (i), no regression is needed and any delay beyond what is needed for the acute radiation reaction in surrounding tissues to wash out can potentially only be deleterious. After short-course RT (5Gyx5) with immediate surgery, the ideal time between the last radiation fraction is 2–5 days, since a slightly longer interval appears to increase surgical complications. A delay beyond 4 weeks appears safe; it results in tumor regression including pathologic complete responses, but is not yet fully evaluated concerning oncologic outcome. Surgical complications do not appear to be influenced by the CRT-surgery interval within reasonable limits (about 4–12 weeks), but this has not been sufficiently explored. Maximum tumor regression may not be seen in rectal adenocarcinomas until after several months; thus, a longer than usual delay may be of benefit in well responding tumors if limited or no surgery is planned, as in (iii) or (iv), otherwise not.Conclusion: A longer time interval after CRT is undoubtedly of benefit in some clinical situations but may be counterproductive in most situations. After short-course RT, long-term results from the clinical trials are not yet available to routinely recommend an interval longer than 2–5 days, unless the tumor is non-resectable at diagnosis.

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“…Although it is probable that the levels of factors analyzed in the biopsies reflect anastomotic area levels, this cannot be certain. There are indications that timing of surgery after radiotheraphy is important to reduce complication rate [25]. A sub group analysis, showed lower levels of MMP-2 in rectal mucosa in irradiated patients operated three days after radiotherapy compared with patients operated four days after treatment.…”

Section: Discussionmentioning

confidence: 96%

Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa and tumour matrix metalloproteinases and plasminogen components

et al. 2009

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BACKGROUND. Preoperative radiotherapy reduces recurrence but increases postoperative morbidity. The aim of this study was to explore the effect of radiotherapy in rectal mucosa and rectal tumour extracellular matrix (ECM) by studying enzymes and growth factors involved in ECM remodeling. MATERIALS AND METHODS. Twenty patients with short-term preoperative radiotherapy and 12 control patients without radiotherapy were studied. Biopsies from rectal mucosa and tumour were collected prior to radiotherapy and at surgery. Tissue MMP-1, -2, -9, TIMP-1, uPA, PAI-1, TGF-beta1 and calprotectin were determined by ELISA. Biopsies from irradiated and non-irradiated peritoneal areas were also analysed. RESULTS. Radiotherapy increased the tissue levels of MMP-2 and PAI-1 in both the rectal mucosa and tumours while calprotectin and uPA showed an increase only in the mucosa after irradiation. The increase of calprotectin was due to an influx of inflammatory cells as revealed by immunohistochemistry. Prior to irradiation, the tumour tissues had increased levels of MMP-1, -2, -9, total TGF-beta1, uPA, PAI-1 and calprotectin compared to mucosa, while TIMP-1 and the active TGF-beta1 fraction showed no statistical difference. CONCLUSIONS. This study indicates a radiation-induced effect on selected ECM remodeling proteases. This reaction may be responsible for early and late morbidity. Interference of this response might reduce these consequences.

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Retrospective study of acute toxicity following short-course preoperative radiotherapy

Abstract: Surgery within 1 week of completing short-course preoperative radiotherapy improved preoperative staging and use of an optimal radiotherapy technique will result in fewer patients at risk of acute toxicity.

Cited by 30 publications

References 33 publications

Feasibility of adequate resectable rectal cancer treatment in a third-level hospital

Feasibility of adequate resectable rectal cancer treatment in a third-level hospital

Optimal Time Intervals between Pre-Operative Radiotherapy or Chemoradiotherapy and Surgery in Rectal Cancer?

Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa and tumour matrix metalloproteinases and plasminogen components

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