SummaryBackgroundPreoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer. However, improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed. We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy.MethodsWe undertook a randomised trial in 80 centres in four countries. 1350 patients with operable adenocarcinoma of the rectum were randomly assigned, by a minimisation procedure, to short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent 5-fluorouracil) restricted to patients with involvement of the circumferential resection margin (n=676). The primary outcome measure was local recurrence. Analysis was by intention to treat. This study is registered, number ISRCTN 28785842.FindingsAt the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0·39, 95% CI 0·27–0·58, p<0·0001), and an absolute difference at 3 years of 6·2% (95% CI 5·3–7·1) (4·4% preoperative radiotherapy vs 10·6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0·76, 95% CI 0·62–0·94, p=0·013), and an absolute difference at 3 years of 6·0% (95% CI 5·3–6·8) (77·5% vs 71·5%). Overall survival did not differ between the groups (HR 0·91, 95% CI 0·73–1·13, p=0·40).InterpretationTaken with results from other randomised trials, our findings provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer.FundingMedical Research Council (UK) and the National Cancer Institute of Canada.

In a prospective study of stress injuries of the lower extremities of U.S. Marine recruits, we derived a frequency distribution of stress fractures. The most frequently fractured bone was the tibia (73%), while the single most common site was the posterior calcaneal tuberosity (21%). The natural history of stress fractures by scintigraphy and radiography has been outlined, showing the evolutionary changes on either study as a universal progression independent of injury site or type of stress. An identical spectrum of changes should be present within any group undergoing intense new exercise. The frequency distribution of stress fractures should be a function of differing forms and intensities of exercise, therefore, our figures should not be applied to other groups. We used the presence of a scintigraphic abnormality at a symptomatic site as the criterion for diagnosis of stress fracture. Since the distribution of skeletal radiotracer uptake is directly dependent on local metabolic activity, it is expected that a focal alteration in bone metabolism will result in a scintigram approaching 100% sensitivity for the abnormality (9). In the proper clinical setting, the specificity should approximate this figure; however, a focal, nonstress-related bone abnormality which has not manifested any radiographic change, such as early osteomyelitis, could result in a false-positive examination. Specificity cannot, therefore, be accurately determined without an actual determination of the pathologic changes within the bone, necessarily involving biopsy. In summary, we believe that we have established bone scintigraphy as an early and accurate means for the detection of lower extremity stress fractures, even in the absence of radiographic findings (6). We feel that a focally abnormal scintigram, in the proper clinical setting, establishes the diagnosis of stress fracture, with radiography to be performed at the time of initial work-up only to rule out a non-stress injury (such as complete fracture, fibrous dysplasia, osteomyelitis, primary bone tumor).

Conformal radiotherapy to a dose of 60 Gy in 15 fractions resulted in favorable primary tumor control and overall survival rates in patients with T1-3 N0 M0 NSCLC. Severe toxicities were uncommon with this relatively simple treatment technique.