Rectal cancer: preoperative versus postoperative irradiation as a component of adjuvant treatment
Section snippets
Preoperative vs postoperative irradiation
When both surgery and radiation are indicated in an adjuvant setting, differences of opinion exist regarding the preferred sequence of each modality. Potential advantages of preoperative irradiation (± concurrent and maintenance chemotherapy) include the damaging effect on cells that may be spread locally or distantly at the time of resection and downstaging of lesions in an attempt to improve the rate of sphincter preservation. The major advantage of postoperative irradiation (± concurrent and
Results and prognosis
Results will be presented as a function of disease presentation and whether complete surgical resection is feasible for primary lesions. For lesions that appear to be high-risk but resectable with negative margins, results in adjuvant trials of both preoperative and postoperative irradiation will be discussed (single v combined modality).
Trial design and results of pertinent randomized studies will be presented with a focus on 3 independent scientific endpoints identified at the 1990 National
Complications and therapeutic ratio
An optimal therapeutic ratio between local control and complications is achieved only with close interaction between the surgeon and the radiation oncologist and the use of sophisticated radiation techniques.37, 38, 39, 40 In the Massachusetts General Hospital postoperative rectal adjuvant series that used shaped multiple-field irradiation techniques, bladder distention, and so on, the incidence of small bowel obstruction requiring operative intervention was the same in patients receiving
Summary and future directions for adjuvant therapy
The impact of pre- and postoperative irradiation ± chemotherapy on both disease-relapse and survival in major randomized adjuvant rectal cancer trials is summarized in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9.
Single-modality rectal adjuvants
Neither irradiation nor chemotherapy as single adjuvant modalities achieve all suggested criterion of efficacy except for the large Swedish preoperative irradiation trial.21 Adjuvant irradiation reduces the rate of local relapse in both prospective nonrandomized as well as randomized preoperative and postoperative trials, but this has not translated into an improvement in OS in most series because of a lack of impact on distant metastases. The only published trial in which single-modality
Combined modality rectal adjuvants
Only combined modality postoperative adjuvant treatment has consistently shown efficacy in all scientific endpoints as noted in 2 prospectively randomized US trials (GTSG 717524, 25 and Mayo/NCCTG 79-47-5126) and a third trial from Norway27). In both of the US studies, bolus 5-FU was administered during irradiation, and patients received additional chemotherapy either after irradiation plus 5-FU (GTSG) or both before and after (Mayo/NCCTG) the combined modality segment of treatment. In the
Sequencing of systemic chemotherapy and concurrent chemoradiation
A delay in concurrent chemoradiation to allow the delivery of 2 cycles of systemic chemotherapy has been the routine in most phase III rectal adjuvant postoperative chemoradiation trials in the United States, starting with Mayo/NCCTG 794751.26 However, the improvement in 4-year DFS found in the phase III trial from Seoul, Korea, suggests that we may need to reevaluate the sequencing of systemic chemotherapy and chemoradiation in subsequent postoperative adjuvant chemoradiation trials. It would
Results by TN stage and treatment method (rectal cancer-pooled analyses): future implications
In the initial pooled analysis of 2,551 eligible patients who received postoperative adjuvant treatment,35 OS and DFS were dependent on both TN stage Table 3, Table 4 and NT stage Table 5, Table 6. Even among N2 patients, T stage influenced 5-year OS (T1-2, 69%; T3, 48%; T4, 38%; P < .001) (Table 5). Three risk groups of patients were defined: (1) intermediate, T3N0 and T1-2N1; (2) moderately high, T4N0, T1-2N2, and T3N1; and (3) high, T3N2, T4N1, and T4N2. For Group 1, 5-year OS rates were 74%
Clinical investigations and treatment algorithms
Future trials need to continue to define optimal combinations of chemo-radiation (what drugs, route and timing of delivery, sequencing of irradiation and chemotherapy, etc.) and to determine whether some patients can be spared the most aggressive treatment combinations (i.e., limited T3N0 and T1-2 N1 lesions). There is a need to evaluate which drug(s) and what method of administration should be used during irradiation to enhance its effect and which drugs are necessary to alter systemic
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2005, LancetCitation Excerpt :After a median follow-up of 2 years, the local recurrence rate was 2·4% in the radiation group compared with 8·2% in the control group (p<0·001); however, overall survival was not improved. Several important conclusions can be drawn from this trial: radiotherapy reduced the risk of local recurrence in low (inferior margin <10 cm from the anal verge) but not in high rectal cancers and was only beneficial in stage II and III tumours.119 Neoadjuvant short-term radiation did not lead to tumour downstaging and did not reduce the local recurrence rate in patients with positive margins.120,121
Radiotherapy in rectal cancer: Current status
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