Prognostic value of tumour regression grade in locally advanced rectal cancer: a systematic review and meta-analysis.

AIM: The current standard of care for locally advanced rectal cancer involves neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision. There is a spectrum of response to neoadjuvant therapy; however, the prognostic value of tumour regression grade (TRG) in predicting disease-free survival (DFS) or overall survival (OS) is inconsistent in the literature. METHOD: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was undertaken using Ovid MEDLINE, Embase and Google Scholar. Inclusion criteria were Stage II and III locally advanced rectal cancer treated with long-course CRT followed by radical surgery. The aim of the meta-analysis was to assess the prognostic implication of each TRG for rectal cancer following neoadjuvant CRT. Long-term prognosis was assessed. The main outcome measures were DFS and OS. A random effects model was performed to pool the hazard ratio (HR) from all included studies. RESULTS: There were 4875 patients from 17 studies, with 775 (15.9%) attaining a pathological complete response (pCR) and 719 (29.9%) with no response. A significant association with OS was identified from a pooled-estimated HR for pCR (HR = 0.47, P = 0.002) and nonresponding tumours (HR = 2.97; P < 0.001). Previously known tumour characteristics, such as ypN, lymphovascular invasion and perineural invasion, were also significantly associated with DFS and OS, with estimated pooled HRs of 2.2, 1.4 and 2.3, respectively. CONCLUSION: In conclusion, the degree of TRG was of prognostic value in predicting long-term outcomes. The current challenge is the development of a high-validity tests to predict pCR.

A phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma.

BACKGROUND: Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can 'normalise' tumour vasculature, thereby improving oxygenation, remains unknown. METHODS: Two cohorts were prospectively enrolled. Cohort A evaluated the implications of hypoxia in STS, using the hypoxic tracer (18)F-azomycin arabinoside (FAZA-PET). In cohort B, sunitinib was added to preoperative RT in a dose-finding phase 1b/2 design. RESULTS: In cohort A, 13 out of 23 tumours were hypoxic (FAZA-PET), correlating with metabolic activity (r(2)=0.85; P<0.001). Two-year progression-free (PFS) and overall (OS) survival were 61% (95% CI: 0.44-0.84) and 87% (95% CI: 0.74-1.00), respectively. Hypoxia was associated with radioresistance (P=0.012), higher local recurrence (Hazard ratio (HR): 10.2; P=0.02), PFS (HR: 8.4; P=0.02), and OS (HR: 41.4; P<0.04). In Cohort B, seven patients received sunitinib at dose level (DL): 0 (50 mg per day for 2 weeks before RT; 25 mg per day during RT) and two patients received DL: -1 (37.5 mg per day for entire period). Dose-limiting toxicities were observed in 4 out of 7 patients at DL 0 and 2 out of 2 patients at DL -1, resulting in premature study closure. Although there was no difference in PFS or OS, patients receiving sunitinib had higher local failure (HR: 8.1; P=0.004). CONCLUSION: In STS, hypoxia is associated with adverse outcomes. The combination of sunitinib with preoperative RT resulted in unacceptable toxicities, and higher local relapse rates.

Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer.

BACKGROUND: Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. METHODS: Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. RESULTS: Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. CONCLUSIONS: Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.

Chemoradiotherapy in the management of primary squamous-cell carcinoma of the rectum.

AIM: To assess the efficacy of chemoradiotherapy in the management of primary squamous-cell carcinoma of the rectum. METHOD: Nine patients with primary squamous-cell carcinoma of the rectum were treated with chemoradiotherapy from 1985 to 2007. All patients were female, with a mean age of 54 years (range 41-72 years). The mean distance of the tumour from the anal verge was 6 cm (range 4-10 cm). Seven patients were treated with curative intent (two postoperative, three preoperative, two chemoradiotherapy alone). Clinical stages for the curative group were T1N0M0 (1), T3N0M0 (3), T3N1M0 (1) and T4N0M0 (2). Chemoradiotherapy consisted of pelvic radiation 45-54 Gy in 1.8 Gy/fraction and concurrent 5-fluorouracil and mitomycin C. The mean follow-up duration for the curative group was 39 months (range 15-120 months). RESULTS: All seven patients treated with curative intent achieved local control. A complete pathological response was seen in all patients after preoperative chemoradiotherapy. Two patients did not have surgery and remained free of disease. One patient with gross residual disease after surgery achieved local control. 18-Fluorodeoxyglucose (FDG) avidity was detected in all patients who had FDG-PET scans. Both primary and metastatic tumours demonstrated FDG-avidity. CONCLUSION: Primary squamous-cell carcinoma of the rectum appears to be very sensitive to chemoradiotherapy. The high complete response rate suggests that chemoradiotherapy alone with salvage surgery for local failure should be further explored. FDG-PET scan may have a role to play in the management of this disease.

Radiation therapy in the treatment of desmoid tumours reduces surgical indications.

BACKGROUND: While several modalities have been proposed for the treatment of desmoid tumour/aggressive fibromatosis, high local recurrence rates have been reported. We present a retrospective study of including patients treated with radiation therapy, some of them in combination with surgical resection. PATIENTS AND METHODS: Thirty-four consecutive patients were included (mean age 40+/-16 years, 9 male). Complete follow-up was available in 31 patients (51+/-36 months). Seventeen patients (50%) were treated with radiation therapy alone, 17 patients with radiation therapy and surgery. Radiation therapy (external beam) was applied in most cases to a total dose of 50.4 Gy in 28 fractions. The lesion was located in the upper extremity in 11 patients, in the lower extremity in 14 cases and on the trunk in 9 cases. RESULTS: Overall recurrence/progression free survival was 88.5% at 5 years and 77.5% at 10 years. Recurrence free survival of the subset of patients undergoing combined treatment with radiation therapy and surgical resection was 83.6% at 5 years and 10 years. In patients who did not receive surgery but only radiation therapy, MRI showed a complete response in 20%, a partial response in 20%, and stable disease in 53% of cases. In this subset, two-third of patient had a metabolic response to radiotherapy (i.e. decrease uptake on the thallium-210 scan after radiotherapy compared to pre-therapy levels). CONCLUSION: Low recurrence rates can be achieved with the use of radiation therapy alone in selected cases. Patients with a metabolic response (decrease) to radiotherapy may be treated with a non-surgical approach. Surgery might be considered in patients with a poor metabolic response to radiotherapy.

The impact of 18-fluorodeoxyglucose positron emission tomography on the staging, management and outcome of anal cancer.

Accurate inguinal and pelvic nodal staging in anal cancer is important for the prognosis and planning of radiation fields. There is evidence for the role of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging and management of cancer, with early reports of an increasing role in outcome prognostication in a number of tumours. We aimed to determine the effect of FDG-PET on the nodal staging, radiotherapy planning and prognostication of patients with primary anal cancer. Sixty-one consecutive patients with anal cancer who were referred to a tertiary centre between August 1997 and November 2005 were staged with conventional imaging (CIm) (including computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound and chest X-ray) and by FDG-PET. The stage determined by CIm and the proposed management plan were prospectively recorded and changes in stage and management as a result of FDG-PET assessed. Patients were treated with a uniform radiotherapy technique and dose. The accuracy of changes and prognostication of FDG-PET were validated by subsequent clinical follow-up. Kaplan-Meier survival analysis was used to estimate survival for the whole cohort and by FDG-PET and CIm stage. The tumour-stage group was changed in 23% (14 out of 61) as a result of FDG-PET (15% up-staged, 8% down-staged). Fourteen percent of T1 patients (3 out of 22), 42% of T2 patients (10 out of 24) and 40% of T3-4 patients (6 out of 15) assessed using CIm, had a change in their nodal or metastatic stage following FDG-PET. Sensitivity for nodal regional disease by FDG-PET and CIm was 89% and 62%, respectively. The staging FDG-PET scan altered management intent in 3% (2 out of 61) and radiotherapy fields in 13% (8 out of 61). The estimated 5-year overall survival (OS) and progression-free survival (PFS) for the cohort were 77.3% (95% confidence interval (CI): 55.3-90.4%) and 72.2% (95% CI: 51.5-86.4%), respectively. The estimated 5-year PFS for FDG-PET and CIm staged N2-3 disease was 70% (95% CI: 42.8-87.9%) and 55.3% (95% CI: 23.3-83.4%), respectively. FDG-PET shows increased sensitivity over CIm for staging nodal disease in anal cancer and changes treatment intent or radiotherapy prescription in a significant proportion of patients.

A phase I trial of Capecitabine+Gemcitabine with radical radiation for locally advanced pancreatic cancer.

Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic cancer (LAPC) has limited efficacy in this disease. The combination of Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent radiosensitisers. The aim of this phase I trial was thus to determine the highest administered dose of the Cap plus Gem combination with radical radiotherapy (RT) for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0-1. During RT, Gem was escalated from 20-50 mg m(-2) day(-1) (twice per week), and Cap 800-2000 mg m(-2) day(-1) (b.i.d, days 1-5 of each week). Radiotherapy 50.4 Gy/28 fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment-related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem; 800/20 mg m(-2) day(-1) (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5 patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1 patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median overall survival was 11.2 months. The addition of Cap and Gem to radical RT was feasible and active and achieved at relatively low doses.

A phase I/II trial of celecoxib with chemotherapy and radiotherapy in the treatment of patients with locally advanced oesophageal cancer.

BACKGROUND: The study's aim was to determine the maximum tolerated dose (MTD) of celecoxib combined with chemoradiotherapy (CRT) for locally advanced oesophageal cancer (OC). METHODS: CRT comprised of 5FU (1000 mg/m(2)/day, days 1-4, weeks 1 & 5), cisplatin (75 mg/m(2), days 1 & 29) and radiotherapy (50 Gy in 25 fractions or 50.4 Gy in 28 fractions). Celecoxib was given daily during CRT at one of five doses (200 mg bd to 600 mg bd). Three to six patients were assigned per dose. RESULTS: Thirteen patients were recruited before trial closure due to external safety concerns regarding celecoxib. Median follow up was 17 months (95% CI 9 - >39). The highest administered dose was 400 mg bd (n=4) with one dose-limiting toxicity at this level: grade 3 rash. Five (38%) and 8(62%) patients had grade 3 non-haematological and haematological toxicities respectively. No grade 4 toxicities occurred. Radiological response rate was 54% (n=7: all CR). Six patients had resection with one pathological CR. Median progression-free and overall survival were 8.8 (95% CI 5.1 - >24.8) and 19.6 months (95% CI 7.3 - >39) respectively. CONCLUSIONS: A MTD was not reached. The regimen was tolerable, indicating that celecoxib can be safely administered with CRT for locally advanced OC.

Preoperative radiotherapy for soft tissue sarcoma: the Peter MacCallum Cancer Centre experience.

AIM: Radiotherapy has been shown to improve local control in combination with limb-sparing or conservative surgery in the management of localised soft tissue sarcoma. Our centre's treatment protocol is to offer preoperative external beam radiotherapy (50.4Gy in 28 fractions) followed by surgery four to six weeks later. The aim of this study is to review the treatment outcome and toxicity of patients treated with this protocol. METHODS: Consecutive patients with localised extremity or truncal soft tissue sarcoma who presented between January 1996 and December 2000 and treated with preoperative radiotherapy followed by limb-sparing surgery were reviewed. Patients with recurrent disease or metastatic disease at diagnosis and patients below the age of 16years were excluded. Local and distant recurrence, overall survival and treatment toxicity were analyzed. RESULTS: Sixty-seven cases were identified (41 males and 26 females). The median age was 52years (range 17 to 82). The majority (79%) had tumours located in the lower limb. The most common histological diagnoses were malignant fibrous histiocytoma and liposarcoma. The median follow-up was 4.1years (range 0.6 to 6.9). There were six local recurrences, two of which were successfully salvaged. Twenty patients developed distant metastases. The estimated 5-year actuarial local recurrence free, distant recurrence free and overall survival were 93%, 68% and 73% respectively. Acute radiotherapy toxicity and wound complications were acceptable and late toxicity was uncommon. CONCLUSION: Preoperative radiotherapy followed by surgery provides effective local control in the management of soft tissue sarcoma.

Natural history of tumour-related sacral obliteration with nerve-root preservation.

Benign aggressive bone tumours can present a dilemma when the definitive treatment options necessitate enormous and permanent functional deficits. Here, we present a case of a massive sacral giant-cell tumour causing dramatic skeletal obliteration, which was successfully treated with radical radiotherapy rather than ablative surgery. The excellent functional outcome highlights the importance of nerve-root preservation in selecting treatment modalities.

Oxaliplatin combined with infusional 5-fluorouracil and concomitant radiotherapy in inoperable and metastatic rectal cancer: a phase I trial.

The aim of this study was to define the recommended dose of oxaliplatin when combined with infusional 5-fluorouracil (5-FU) and concurrent pelvic radiotherapy. Eligible patients had inoperable rectal cancer, or symptomatic primary rectal cancer with metastasis. Oxaliplatin was given on day 1 of weeks 1, 3 and 5 of radiotherapy. Dose level 1 was oxaliplatin 70 mg m(-2) with 5-FU 200 mg m(-2) day(-1) continuous infusion 96 h week(-1). On dose level 2, the oxaliplatin dose was increased to 85 mg m(-2). On dose level 3, the duration of the 5-FU was increased to 168 h per week. Pelvic radiotherapy was 45 Gray (Gy) in 25 fractions over 5 weeks with a boost of 5.4 Gy. Fluorine-18 fluoro deoxyglucose and Fluorine-18 fluoro misonidazole positron emission tomography (FDG-PET and FMISO-PET) were used to assess metabolic tumour response and hypoxia. In all, 16 patients were accrued. Dose-limiting toxicities occurred in one patient at level 2 (grade 3 chest infection), and two patients at level 3 (grade 3 diarrhoea). Dose level 2 was declared the recommended dose level. FDG-PET imaging showed metabolic responses in 11 of the 12 primary tumours assessed. Four of six tumours had detectable hypoxia on FMISO-PET scans. The addition of oxaliplatin to infusional 5-FU chemoradiotherapy was feasible and generally well tolerated. For future trials, oxaliplatin 85 mg m(-2) and 5-FU 200 mg m(-2) day(-1) continuous infusion 96 h week(-1) is the recommended dose when combined with 50.4 Gy of pelvic radiotherapy.

Characterising atherothrombosis in Hong Kong: results of the Hong Kong data from a global atherothrombosis epidemiological survey.

OBJECTIVES: To describe the characteristics of patients in Hong Kong with or at risk of atherothrombosis, to determine the proportion of symptomatic patients with more than one vascular bed affected, and to assess the relationship between ankle brachial index and disease severity. DESIGN: Local participation in an international prevalence study. SETTING: Five centres in Hong Kong. PARTICIPANTS: A total of 210 subjects were recruited (105 women and 105 men). Patients were divided into the symptomatic group (with current or previous atherothrombotic symptoms, n=101) and at-risk group (with no current or previous symptoms, but aged over 55 years with at least two specified risk factors, n=109). MAIN OUTCOME MEASURES: Patient characteristics were described, including the number of arterial beds affected, ankle brachial index, presence of risk factors, and medications taken. RESULTS: Of the symptomatic patients, 30% had more than one arterial bed involved. A total of 55.4% of the symptomatic group and 18.4% of the at-risk group had abnormal ankle brachial index values. Lower ankle brachial indices were associated with a greater number of affected arterial beds. Diabetes mellitus and hypertension were the most prevalent risk factors in the at-risk group. Symptomatic patients were commonly treated with antihypertensive and antiplatelet agents, whereas at-risk patients were mostly treated with antihypertensive and antidiabetic agents. Only 20% of at-risk patients were taking antiplatelet agents. CONCLUSIONS: Ankle brachial index is a useful tool for predicting those at risk of atherothrombosis. This simple measurement can be used as part of the screening process in the general practice. The role of antiplatelet agents in primary prevention of atherothrombotic events in at-risk patients deserves further attention.

A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer.

The purpose of the study was to determine the maximum-tolerated dose (MTD) of oral capecitabine, combined with concurrent, standard preoperative pelvic radiotherapy, when given twice daily, from Monday to Friday throughout the course of radiotherapy, for locally advanced potentially resectable rectal cancer. Maximum-tolerated dose was defined as the total (given in two equally divided doses) oral dose of capecitabine that caused treatment-related grade 3 or 4 toxicity in one-third or more of the patients treated. Radiotherapy involved 50.4 Gy given in 28 fractions in 5 weeks and 3 days. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12 cm of the anal verge suitable for curative resection. Surgery was performed 4-6 weeks from completion of preoperative chemoradiotherapy. In all, 28 patients were enrolled in the study at predefined dose levels: 850 mg m(-2) day(-1) (n=3), 1000 mg m(-2) day(-1) (n=6), 1250 mg m(-2) day(-1) (n=3), 1650 mg m(-2) day(-1) (n=3), 1800 mg m(-2) day(-1) (n=8) and 2000 mg m(-2) day(-1) (n=5). The mean age was 62.3 years (range: 33-80 years). Five patients were female and 23 male. The median distance of tumour from the anal verge was 6 cm (range: 1-11 cm). Endorectal ultrasound was performed in 93% of patients. A total of 26 patients (93%) had T3 disease and two patients had resectable T4 disease. Dose-limiting toxicity (DLT) developed in one patient at dose level 1000 mg m(-2) day(-1) (RTOG grade 3 cystitis). Two of the five patients at dose level 2000 mg m(-2) day(-1) had a total of three DLT (grade 3 perineal skin reaction, grade 3 diarrhoea and grade 3 dehydration). Dose escalation of capecitabine was ceased at 2000 mg m(-2) day(-1) after reaching MTD. None of the eight patients at dose level 1800 mg m(-2) day(-1) developed DLT. All except one patient underwent surgery. A total of 15 patients had the clinical T stage reduced by at least one stage in pathologic specimens. Five patients (19%) achieved a pathologic complete response. We conclude that the MTD of capecitabine was reached at a dose level of 2000 mg m(-2) day(-1), given as 1000 mg m(-2) twice daily, from Monday to Friday throughout the course of preoperative pelvic irradiation of 50.4 Gy. For patients with resectable rectal cancer receiving concurrent, full dose radiotherapy, the recommended dose of capecitabine for further study is 1800 mg m(-2) day(-1) when given in this schedule.

Thallium-201 scintigraphy--a predictor of tumour necrosis in soft tissue sarcoma following preoperative radiotherapy?

AIM: Thallium-201 (Tl-201) scintigraphy in patients with malignant soft tissue tumours was evaluated to determine whether the images correlated with histological response to preoperative radiotherapy. METHODS: We studied 54 patients, median age 32 (range 17-84) years, with non-metastatic, malignant soft tissue tumours diagnosed between 1996 and 2001. Thirty-eight patients had unoperated tumours and 16 patients had previous incomplete excisions. All patients received preoperative radiotherapy followed by surgery. No patient received chemotherapy as part of their initial management. Qualitative analyses of early phase (30 min) and late phase (4 h) Tl-201 scintigraphic images before and after preoperative radiotherapy were compared with the degree of tumour necrosis determined histologically. RESULTS: In the previously unoperated group, all 38 patients had increased TL-201 uptake in the late phase of scanning prior to radiotherapy suggesting metabolically active tissue. In the previously excised group 11 patients had increased Tl-201 uptake in the late phase of scanning prior to radiotherapy. Following radiotherapy, patients with Tl-201 retention on late phase scans had a lower rate of necrosis than patients with minimal retention, p<0.0001. Following radiotherapy, 28 of 29 patients with minimal uptake on the late phase had 80% or more necrosis, while 24 of 25 patients with increased uptake on the late phase had less than 80% necrosis (p<0.0001). Patients with previously excised tumours who had thallium retention following radiotherapy demonstrated evidence of residual disease at surgery. All patients with incompletely excised tumours who had no thallium retention on late phase scanning after radiotherapy demonstrated no evidence of residual disease at surgery. CONCLUSION: Thallium scintigraphy is a readily available investigative tool, which when used in conjunction with other imaging modalities in the assessment of primary and incompletely excised malignant soft tissue tumours, may predict histological tumour response to preoperative radiotherapy.

Wound complications following pre-operative radiotherapy for soft tissue sarcoma.

AIMS: We analysed wound complications in 43 patients with soft tissue sarcoma who were treated with combined pre-operative radiotherapy and surgery. METHODS: All patients received the same protocol of pre-operative radiotherapy at our institution. RESULTS: Thirty-six (84%) patients developed acute skin toxicity following radiotherapy. After wide local excision, 15 patients required primary soft tissue reconstruction with vascularized muscle transfer and four patients underwent free skin flap to enable wound closure as part of their primary surgery. Nineteen patients (44%) developed post-operative wound complications including 10 (23%) patients who required an additional surgical procedure. Four (27%) patients developed flap necrosis in a group of 15 who underwent primary vascularized soft tissue transfer. All required a second vascularized muscular flap. One elderly patient, who had grade 3 acute radiation skin toxicity, had an arterial graft and total hip arthroplasty for a femoral artery aneurysm and an avascular necrosis of the hip, respectively. In our series, age (> or = 40 years) was the only impact factor influencing wound complication after surgery following radiotherapy (P=0.06). CONCLUSIONS: Site of tumour, radiation field size, surgical resection volume, grade of acute radiation toxicity, co-morbidity, and smoking were not demonstrated to have predictive value in wound complication following pre-operative radiotherapy. Although previous papers suggested that vascularized soft tissue transfer could be useful reducing wound morbidity, our results could not confirm this.

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a Phase II trial for the Trans-Tasman Radiation Oncology Group.

PURPOSE: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. METHODS AND MATERIALS: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. RESULTS: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. CONCLUSION: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications.

Optimising treatment for resectable rectal cancer: is preoperative therapy beneficial?

Preoperative radiotherapy is becoming the standard of care for resectable locally advanced adenocarcinoma of the rectum. Its practice is no longer limited to a few specialised cancer centres. Adjuvant preoperative radiotherapy can reduce the risk of local recurrence by 50% compared with surgery alone and it has a moderate effect in improving survival. Treatment-related toxicity is superior to that after postoperative radiotherapy. Early results of preoperative radiotherapy with concurrent chemotherapy are promising, with a low toxicity profile and a high pathological response rate. Advances in technology, endorectal ultrasound and magnetic resonance imaging enable selection of appropriate patients for preoperative radiotherapy.

Primary adenocarcinoma of the anus: a retrospective analysis.

PURPOSE: To report the clinical features and outcome of patients with primary adenocarcinoma of the anus following radiotherapy with or without chemotherapy. METHODS AND MATERIALS: A retrospective analysis was performed on 15 patients referred to Peter MacCallum Cancer Institute between 1981 to 1998 with primary adenocarcinoma of the anus. The median follow-up was 7.5 years. Six patients underwent treatment with curative intent-either chemoradiation or radiotherapy alone. Surgery was mainly limited to either incisional or excisional biopsy. The remaining nine patients were treated with palliative intent because of advanced age, advanced disease, or poor medical status. The biological equivalent doses were calculated for all patients and correlated with time to progression. RESULTS: None of the curative group had relapsed after a median follow-up of 6.6 years. All except one were alive and well. No patient developed any serious long-term toxicity and all patients avoided colostomy. All patients managed with palliative intent died with persistent locoregional disease with a median survival of 0.8 year. CONCLUSION: Primary adenocarcinoma of the anus is a very rare disease that precludes a rigorous analysis. This study demonstrates that radiation and in particular chemoradiation are effective therapies consistent with other recent series and analogous to squamous cell carcinomas of the anus. It also emphasizes the poor prognosis of patients treated with palliative intent.

Radiotherapy in soft tissue sarcoma of the extremities.

The local treatment of soft tissue sarcoma is evolving. Limb-sparing compartmentectomy offers local control but at the expense of function and a high amputation rate. The functional outcome is improved with combined wide excision and radiotherapy, at the same time achieving a similar local control rate. Future directions should include attempts to reduce toxicity and maximise the functional result. As the limb function is ultimately related to the aggressiveness of the local treatment, the optimum surgical margin, radiation volume and dose, require further investigation. The pursuit of local control should not be compromised in the quest for reducing morbidity, as the relationship between local control and survival remains unclear.