Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study.

BACKGROUND: This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications. PATIENTS AND METHODS: Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 × 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin). RESULTS: Patients (N = 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P = 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P = 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR = 1.08, 95% CI 0.70-1.23, P = 0.60, 35% versus 32% and HR = 1.10, 95% CI 0.68-1.23, P = 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P = 0.66), grade 3+ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. CONCLUSION: The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.

The PTPN13 Y2081D (T>G) (rs989902) polymorphism is associated with an increased risk of sporadic colorectal cancer.

AIM: Colorectal cancer (CRC) is one of the most common cancers worldwide and, although the majority of cases are sporadic, its development and progression depends on a range of factors: environmental, genetic and epigenetic. A variety of genetic pathways have been described as being crucial in CRC, including protein tyrosine phosphatases (PTPs). PTPN13 (also called FAP-1) is a non-receptor PTP and interacts with a number of important components of growth and apoptosis pathways. It is also involved in the inhibition of Fas-induced apoptosis. METHOD: The single nucleotide polymorphism genotype at Y2081D (T>G) (rs989902) of PTPN13 exon 39 was determined in DNA extracted from blood samples from 174 sporadic CRC patients and 176 healthy individuals. Also, a meta-analysis was performed based on three articles accessed via the PubMed and ResearchGate databases. RESULTS: The risk of CRC was 2.087 times greater for patients with the GG genotype than for those with the TT genotype (P = 0.0475). In the meta-analysis, a significantly increased risk of cancer associated with the G allele was observed in the squamous cell carcinoma of the head and neck subgroup (TT vs GG+GT, OR 1.23, 95% CI [1.02, 1.47], P = 0.0258), and a significantly decreased risk in the breast cancer subgroup (TT vs GG+GT, OR 0.63, 95% CI [0.41, 0.96], P = 0.0334) and in the CRC subgroup (GT+TT vs GG, OR 0.51, 95% CI [0.41, 0.95], P = 0.0333). CONCLUSION: PTPN13 rs989902 is significantly associated with the risk of CRC in the Polish population. Given that this report provides the first evidence of an association of PTPN13 rs989902 with the risk of CRC in a Caucasian population, further large scale studies are necessary to confirm this finding.

Patient's Education Before Mastectomy Influences the Rate of Reconstructive Surgery.

Breast reconstruction (BR) should be offered and discussed to each woman with breast cancer who planned for mastectomy, except the cases with severe comorbidities. However, the majority of these patients do not undergo reconstructive surgery. A 20-question survey was administered to a group of 50 women (age 29-83 years, median 53) treated with mastectomy. 22.4 % underwent reconstruction of the breast, 24.5 % declared an interest in BR in the future, 53.1 % were not interested in reconstructive surgery. 51.2 % obtained information concerning BR before surgery, 58.1 % after and 44.2 % both before and after mastectomy. 59.2 % were informed about reimbursement. Information given before surgery had a statistically significant impact on performing reconstruction or a declared interest in BR (X 2 = 4.950, df = 1, p < 0.05), as well as information about reimbursement (X 2 = 8.875, df = 1, p < 0.05). Age <55 years was another significant factor (X 2 = 13.522, df = 1, p < 0.05, C Pearson = 0.525). Level of education did not impact upon the choice (p > 0.05). The main reasons for the refusal were fear of complications (47.4 %), priority to recovery over aesthetic (36.8 %), age, defined by the patient as "advanced" (31.6 %), high level of acceptance of the body after amputation (31.6 %), fear of cancer recurrence (26.3 %) and fear of the pain and discomfort (15.8 %). Each patient who planned for mastectomy should obtain sufficient information regarding breast reconstruction. Exact information is of special benefit to women discouraged by imagined disadvantages of surgery. Patients' education impacts the quality of life-not only before surgery but also lifelong after finishing the treatment.

Whole-body electromyostimulation to fight sarcopenic obesity in community-dwelling older women at risk. Resultsof the randomized controlled FORMOsA-sarcopenic obesity study.

The effect of whole body-electromyostimulation in community-dwelling women ≥70 with sarcopenic obesity was heterogeneous, with high effects on muscle mass, moderate effects on functional parameters, and minor effects on fat mass. Further, we failed to determine a supportive effect of additional protein-enriched dietary supplementation in this albeit predominately well-nourished group. INTRODUCTION: The aim of the study was to determine the effect of whole-body electromyostimulation (WB-EMS) on sarcopenic obesity (SO) in community-dwelling women more than 70 years with sarcopenic obesity. METHODS: Seventy-five community-dwelling women ≥70 years with SO were randomly allocated to either a WB-EMS-application with (WB-EMS &P; 24.9 ± 1.9 kg/m2) or without (WB-EMS; 25.2 ± 1.8 kg/m2) dietary supplementation (150 kcal/day, 56 % protein) or a non-training control group (CG; 24.7 ± 1.4 kg/m2). WB-EMS consisted of one weekly session of 20 min (85 Hz, 350 µs, 4 s of strain-4 s of rest) performed with moderate to high intensity. Primary study endpoint was the Sarcopenia Z-Score constituted by skeletal muscle mass index (SMI, as assessed by dual energy X-ray absorptiometry), grip strength, and gait speed, and secondary study endpoint was body fat (%). RESULTS: Sarcopenia Z-score comparably increases in the WB-EMS and the WB-EMS&P-group (p ≤ .046). Both groups differ significantly (p ≤ .001) from the CG which deteriorated significantly (p = .006). Although body fat changes were most pronounced in the WB-EMS (-0.9 ± 2.1; p = .125) and WB-EMS&P (-1.4 ± 2.5; p = .028), reductions did not statistically differ (p = .746) from the CG (-0.8 ± 2.7; p = .179). Looking behind the covariates, the most prominent changes were determined for SMI, with a significant increase in both EMS-groups (2.0-2.5 %; p ≤ .003) and a decrease in the CG (-1.2 ± 3.1 %; p = .050) with significant between-group differences (p = .001). CONCLUSION: WB-EMS is a safe and attractive method for increasing muscle mass and functional capacity in this cohort of women 70+ with SO; however, the effect on body fat is minor. Protein-enriched supplements did not increase effects of WB-EMS alone.

Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.

BACKGROUND: Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. PATIENTS AND METHODS: Patients with fixed cT3 or cT4 cancer were randomized either to 5 × 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. RESULTS: Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54. CONCLUSIONS: No differences were observed in local efficacy between 5 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 × 5 Gy schedule with consolidation chemotherapy. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.

Upper Extremity Lymphedema After Axillary Lymph Node Dissection: Prospective Lymphoscintigraphic Evaluation.

This prospective study was designed to evaluate changes in upper extremity lymphatic drainage after ALND in comparison to the preoperative status using lymphoscintigraphy. The study enrolled 44 women (mean age: 57.95; range: 35-80) with a new diagnosis of unilateral invasive breast carcinoma who had been scheduled to undergo ALND. This was a substudy of the physiotherapeutic project, in which subjects after ALND were randomized into 4 groups treated with: 1) rehabilitation exercises; 2) manual lymphatic drainage; 3) pneumatic compression pump; and 4) education only. Clinical evaluation which included arm measurements and lymphoscintigraphy was performed in every subject before surgery and 3 times after surgery (1-6 weeks, 1 and 2 years after ALND). Follow-up was completed in 44 subjects at 1 year and in 32 subjects at 2 years. Lymphedema diagnosis was made in 4 subjects 1 year after ALND (9%) and in 8 subjects 2 years after ALND (25%). Among them, respectively, only 50% and 62% noticed and reported lymphedema. Quantitative analysis of lymphoscintigrams and photoplethysmography results did not reveal upper extremities lymphatic transport and/or venous function impairment after the ALND procedure. Qualitative analysis of lymphoscintigrams revealed most commonly disappearance of previously functional lymph nodes and appearance of dermal backflow in subjects who developed lymphedema. Conversely, appearance of functional lymph nodes in different locations after ALND may indicate protection from development of upper extremity lymphedema.

Exercise and fractures in postmenopausal women. Final results of the controlled Erlangen Fitness and Osteoporosis Prevention Study (EFOPS).

UNLABELLED: The EFOPS trial clearly established the positive effect of long-term exercise on clinical low-trauma fractures in postmenopausal women at risk. Bearing in mind that the complex anti-fracture exercise protocols also affect a large variety of diseases of increased age, we strongly encourage older adults to perform multipurpose exercise programs. INTRODUCTION: Physical exercise may be an efficient option for autonomous fracture prevention during increasing age. The aim of the study was to evaluate the effect of exercise on clinical overall fracture incidence and bone mineral density (BMD) in elderly subjects at risk. METHODS: In 1998 initially, 137 early-postmenopausal, osteopenic women living in Erlangen-Nuremberg, Germany, were included in the EFOPS trial. Subjects of the exercise group (EG; n = 86) conducted two supervised group and two home exercise sessions/week while the control group (CG; n = 51) was requested to maintain their physical activity. Primary study endpoints were clinical overall low-trauma fractures determined by questionnaires, structured interviews, and BMD at the lumbar spine and femoral neck assessed by dual-energy X-ray absorptiometry. RESULTS: In 2014, 105 subjects (EG: n = 59 vs. CG: n = 46) representing 1680 participant-years were included in the 16-year follow-up analysis. Risk ratio in the EG for overall low-trauma fractures was 0.51 (95% confidence interval (95% CI) 0.23 to 0.97, p = .046), rate ratio was 0.42 (95% CI 0.20 to 0.86, p = .018). Based on comparable baseline values, lumbar spine (MV -1.5%, 95% CI -0.1 to -2.8 vs. -5.8%, -3.3 to -7.2%) and femoral neck (-6.5%, -5.2 to -7.7 vs. -9.6%, -8.2 to 11.1%) BMD decreased in both groups; however, the reduction was more pronounced in the CG (p ≤ .001). CONCLUSION: This study clearly evidenced the high anti-fracture efficiency of multipurpose exercise programs. Considering furthermore the favorable effect of exercise on most other risk factors of increasing age, we strongly encourage older adults to perform multipurpose exercise programs.

Peak-bone-mass development in young adults: effects of study program related levels of occupational and leisure time physical activity and exercise. A prospective 5-year study.

SUMMARY: Young adulthood is characterized by profound life-style changes. This study suggests that reduction of sport or exercise, induced by alteration of the occupational situation, negatively impacts generation/maintenance of peak bone mass. In order to compensate occupational-related reductions of physical activity, workplace exercise programs will be helpful. INTRODUCTION: Only few studies have determined the effect of physical activity or physical exercise on bone mineral density (BMD) in the period of late skeletal maturation, i.e. around peak bone mass. The aim of this article was to determine the long-term effect of different levels of physical activity and exercise directly and indirectly derived by occupation during young adulthood. METHODS: Sixty-one male and female dental students (DES) and 53 male and female sport students (SPS) 21±2 years old were accompanied over the course (4.8±0.5 years) of their study program. BMD at the lumbar spine (LS), hip, and whole body (WB) were determined using dual-energy X-ray absorptiometry. RESULTS: Parameters of physical activity increased non-significantly in both groups with no relevant differences between the groups. Indices of exercise, however, increased significantly in the SPS group while a significant decrease was assessed for the DES group. Independent of gender, BMD of the SPS increased significantly (p≤0.007) at all skeletal sites (LS, 2.4±3.9%; hip, 1.6±3.5%; WB, 1.8±2.8%) while BMD of the DES remained unchanged at LS (-0.6±4.4%, p=0.432) and WB (0.5±1.9%, p=0.092) but decreased significantly at the hip (-1.9±4.3%, p=0.010). BMD-changes at LS, hip, and WB differ significantly between SPS and DES (p≤0.017). Results remained unchanged after adjusting for baseline BMD-values that differed (p=0.030 to p=0.082) in favor of the SPS group. CONCLUSION: Changes of exercise levels directly or indirectly caused by occupational factors during young adulthood significantly affected generation and/or maintenance of peak bone mass. Compensatory exercise is thus highly relevant for bone health of young adults.

Effect of block-periodized exercise training on bone and coronary heart disease risk factors in early post-menopausal women: a randomized controlled study.

The purpose of this 12 month randomized exercise intervention was to determine the effect of a block-periodized multipurpose exercise program on bone mineral density (BMD) and parameters of the metabolic syndrome (MetS) in early post-menopausal women. Eighty-five subjects (52.3 ± 2.4 years) living in the area of Erlangen (Germany) were randomly assigned into an exercise (EG, n=43) or a wellness-control group (CG: n=42). The EG performed a periodized multipurpose exercise program with 4-6-week blocks of high-intensity bone-specific exercise intermitted by 10-12 weeks of exercise dedicated to increase endurance and reduce cardiac and metabolic risk factors. The CG performed a low-volume/low-intensity "wellness" program to increase well-being. After 12 months, significant exercise effects were observed for the lumbar spine (LS) BMD as assessed by quantitative computed tomography [total BMD (EG: -0.3 ± 2.1% vs CG: -2.1 ± 2.2%, P=0.015); trabecular BMD (EG: -0.7 ± 3.4% vs CG: -4.7 ± 4.9%, P=0.001) and dual-energy x-ray absorptiometry (DXA) (EG: -0.1 ± 2.2% vs CG: -2.0 ± 2.0%, P=0.002)]. However, no significant effects were observed for total hip BMD as assessed by DXA (P=0.152). Although all MetS parameters were favorably affected among the EG, only the effect for waist circumference was significant. In summary, short periods of bone-specific intervention embedded in longer periods of exercises dedicated to improve cardiovascular and metabolic risk factors positively affected BMD at the LS.

Exercise and fractures in postmenopausal women: 12-year results of the Erlangen Fitness and Osteoporosis Prevention Study (EFOPS).

UNLABELLED: This trial is the first exercise study that focuses on fracture incidence as a primary study endpoint. Although we marginally failed to determine significant effects on "overall" fracture risk (p = .074) or rate ratio (p = .095), our findings further increased the evidence that exercise relevantly prevents fractures in the elderly. INTRODUCTION: The purpose of this study is to determine the effect of strictly supervised long-term exercise training on "overall" fracture incidence and bone mineral density (BMD) in postmenopausal osteopenic women. METHODS: Eighty-five early postmenopausal (1-8 years), osteopenic women living in the area of Erlangen-Nuremberg, Germany without any medication or diseases affecting bone metabolism were assessed after 12 years of supervised exercise (EG) or unvarying lifestyle (control, CG). Exercisers were encouraged to perform two group sessions/week and two home training sessions/week. Calcium and vitamin D supplementation was provided for both groups. "Overall" fractures were determined by questionnaires and structured interviews. The BMD was assessed at lumbar spine and proximal femur by dual-energy X-ray absorptiometry. RESULTS: "Overall" fracture risk ratio in the EG was 0.32 (95% confidence interval (CI), 0.08 to 1.05; p = .074), and the rate ratio for "overall" fractures was 0.38 (95% CI, 0.11 to 1.15; p = .095). BMD changes at lumbar spine (EG, -0.8%; 95% CI, 0.8% to -2.7% vs. CG, -4.0%; 95% CI, -2.4% to -5.7%; p = .011) and femoral neck (EG, -3.7%; 95% CI, -2.4% to -5.0% vs. CG, -6.7%; 95% CI, -5.3% to -8.2%; p = .003) significantly differed between both groups. CONCLUSION: Although we marginally failed to determine significant effects on overall fracture risk or rate ratio, our study increased the body of evidence for the fracture prevention efficiency of exercise programs, with special regard on bone strength (as assessed by bone mineral density measurement). Future studies should focus on subjects more prone to fractures to generate enough statistical power to clearly determine this issue.

Axillary lymph nodes and arm lymphatic drainage pathways are spared during routine complete axillary clearance in majority of women undergoing breast cancer surgery.

Alterations in axillary lymph nodes (ALNs) after complete axillary lymph node dissection (ALND) in comparison to the preoperative status were evaluated using lymphoscintigraphy performed preoperatively and 1-6 weeks after surgery in 30 women with a new diagnosis of unilateral, invasive breast carcinoma. Analysis of lymphoscintigrams revealed that ALNs after surgery were present in 26 of 30 examined women. In comparison to preoperative status, they were visualized in the same location (12 women), in the same and additionally in different locations (9 women), or only in different locations (4 women). No lymph nodes were visualized in one woman and lymphocoele were in 4 women. Thus, after ALND, a variable number of axillary lymph nodes remain and were visualized on lymphoscintigraphy in the majority of women. The classical ALND, therefore, does not allow complete dissection and removal of axillary nodes with total disruption of axillary lymphatic pathways, accounting in part for the variable incidence and severity of lymphedema after the procedure.

Abdominosacral resection is not related to the risk of neurological complications in patients with low-rectal cancer.

OBJECTIVE: Some authors claim that the risk of sacrectomy-related neurological complications is a serious limitation of abdominosacral resection (ASR). We determined the incidence of neurological complications in patients with a low-rectal cancer who were treated by ASR. METHOD: The clinical records of 54 consecutive patients with low-rectal cancer who were operated on by ASR were analysed. The occurrence of neurological complications in these patients was compared with that of 140 consecutive patients with cancer of the mid- and upper rectum who underwent anterior resection (AR) during the same period. Neurological complications were defined as bowel, bladder or sexual dysfunction, gait abnormalities and local parasthesiae persisting for more than 6 months following surgery. RESULTS: There were no persisting neurological complications after either AR or ASR. At the end of hospitalization, the 16 of 140 and 12 of 54 of those treated with AR and ASR had neurological complications, which fell to five of 140 and three of 53 at 3 months, respectively; at 6 months, no one treated had any complications. CONCLUSION: Neurological complications after AR and ASR were similar but recovery was complete at 6 months following surgery.

Fas expression in primary breast cancer is related to neoplastic infiltration of perilymphatic fat.

PURPOSE: Various studies have revealed that both Fas and its ligand play an important role in cancer biology. The aim of our study was to determine if there is a relationship between the expression of Fas or Fas-ligand in breast cancer and the presence of malignant cells in perilymphatic fat. MATERIAL/METHODS: Tumor samples from 147 consecutive breast cancer patients, aged 35-81 (median, 59), were subjected to analysis. The expressions of Fas and Fas-ligand were determined immunohistochemically. RESULTS: The expression of Fas, but not Fas-ligand, was significantly less frequent in breast cancer patients in whom malignant cells infiltrated through the perilymphatic fat (p=0.042). The infiltration of paranodal fatty tissue occurred more often in cases of ductal carcinomas (p=0.008), larger primary tumors (pT>or=2, p=0.030) and regional lymph node involvement (pN>or=1, p=0.021). Univariate analysis revealed that perilymphatic fat infiltration shortened overall survivals in breast cancer patients (p=0.05), similarly to postmenopausal status (p=0.034), age >60 years (p=0.05) and regional lymph node involvement (p=0.05). None of the aforementioned factors, however, was revealed as an independent predictor of survival in multivariate analysis. CONCLUSIONS: The study showed that lack of Fas in primary breast cancer is associated with perilymphatic fat infiltration. Consequently, both the absence of Fas in the primary tumor and the occurrence of neoplatic cells in paranodal fatty tissue should be considered in the prognosis, complementing existing conventional factors.

Metastases to the internal mammary lymph nodes as the only spread of ductal breast cancer: case description.

The present paper describes a case of a breast cancer patient in whom lymphoscintigraphy identified metastases in the internal mammary nodes whilst the axillary lymphatic center was tumor-negative. Because of the lymph node involvement, cancer was restaged from original I to IIIc. Consequently, the patient was qualified for chemotherapy with docetaxel and doxorubicin. The case described is another contribution for the routine application of sentinel lymph node biopsy (SLNB) in breast cancer patients.

Therapeutic results in low-rectal cancer patients treated with abdominosacral resection are similar to those obtained by means of anterior resection in mid- and upper-rectal cancer cases.

AIMS: To present the experiences of the Regional Comprehensive Cancer Center in Wroclaw with abdominosacral resection (ASR) carried out in low-rectal cancer patients. METHODS: Rectal cancer patients (n=294) were operated on by the same surgical team using the standardized TME technique between May 5, 1998 and February 23, 2001. Depending on the distance from the anal verge, the primary tumor was removed by means of standard abdominal resection (AR-mid- and upper-rectal cancers) or abdominosacral resection (ASR-low-rectal cancers). The patients who underwent the different operative procedures were comparable in terms of distributions of age, gender, tumor infiltration depth and regional lymph node involvement with no significant statistical difference between the groups. RESULTS: Ninety-seven cases were excluded from the analysis of survival based on exclusion criteria defined. Consequently, 197 cases were left for further analysis, including 154 patients operated on by AR and 43 who underwent ASR. AR and ASR patients did not differ significantly in terms of postoperative morbidity (11% and 14%, respectively), observed (57.1% vs. 60.4%) and relative 5-year survivals (74.3% vs. 73.2%) and the cumulative 5-year local recurrence rate (5.8% vs. 4.7%). CONCLUSION: The combined use of the modern TME technique and the "historical" abdominosacral excision of the rectum seems to give new, potentially attractive perspectives for successful surgical treatment of low-rectal cancers.

Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy does not alter anal sphincter preservation or postoperative complications compared with short-course radiotherapy alone in patients with clinical stage T3 or T4 resectable rectal cancer. The aim of this study was to compare survival, local control and late toxicity in the two treatment groups. METHODS: The study randomized 312 patients to receive either preoperative irradiation (25 Gy in five fractions of 5 Gy) and surgery within 7 days or chemoradiation (50.4 Gy in 28 fractions of 1.8 Gy, bolus 5-fluorouracil and leucovorin) and surgery 4-6 weeks later. The median follow-up of living patients was 48 (range 31-69) months. RESULTS: Early radiation toxicity was higher in the chemoradiation group (18.2 versus 3.2 per cent; P < 0.001). The actuarial 4-year overall survival was 67.2 per cent in the short-course group and 66.2 per cent in the chemoradiation group (P = 0.960). Disease-free survival was 58.4 versus 55.6 per cent (P = 0.820), crude incidence of local recurrence was 9.0 versus 14.2 per cent (P = 0.170) and severe late toxicity was 10.1 versus 7.1 per cent (P = 0.360) respectively. CONCLUSION: Neoadjuvant chemoradiation did not increase survival, local control or late toxicity compared with short-course radiotherapy alone.