Andrew Kneebone

Post-prostatectomy radiation therapy: Consensus guidelines of the Australian and New Zealand Radiation Oncology Genito-Urinary Group

BACKGROUND AND PURPOSE Three randomised trials have demonstrated the benefit of adjuvant post-prostatectomy radiotherapy (PPRT) for high risk patients. Data also documents the effectiveness of salvage radiotherapy following a biochemical relapse post-prostatectomy. The Radiation Oncology Genito-Urinary Group recognised the need to develop consensus guidelines on to whom, when and how to deliver PPRT. MATERIALS AND METHODS Draft guidelines were developed and refined at a consensus conference in June 2006 attended by 63 delegates where urological, radiotherapy and diagnostic imaging experts spoke on aspects of PPRT. Unresolved issues were further developed by working parties and redistributed until consensus was reached. RESULTS Central to the recommendations is that patients with positive surgical margins, seminal vesicle invasion and/or extracapsular extension have a high risk of residual local disease and should be informed of the options of either immediate adjuvant radiotherapy or active surveillance with early salvage in the event of biochemical recurrence. Salvage radiotherapy should be instituted at the earliest confirmation of biochemical recurrence. Detailed contouring guidelines have been developed, defining the regions at risk of residual microscopic disease which should be included in the clinical target volume. The recommended doses are 60-64Gy for adjuvant, and 60-66Gy for salvage radiotherapy. The role of hormone therapy in conjunction with PPRT is yet to be defined. CONCLUSIONS These consensus guidelines have been developed to give clinical and technical guidance to radiation oncologists and urologists in the management of high risk post-prostatectomy patients.

Improved survival in young women with colorectal cancer.

BACKGROUND:Studies have reported the effect of gender in the context of assessing predictors of survival from colorectal cancer (CRC); however, few have specifically addressed the impact of gender on the clinical and pathological outcomes of CRC. Appreciation of gender disparities may assist in the implementation of measures to address these differences, and improve the overall outcomes of patients with CRC.METHODS:The South Western Sydney Colorectal Tumour Group registry, which encompasses a population in excess of 800,000, prospectively collects data on new patients with CRC. Data from 1997 to 2004 were collected, including demography, site, grade, histopathology, stage, treatment, and survival.RESULTS:In total, 2,050 consecutive patients (44% women) with CRC were analyzed. Compared to men, women were older (median 69 yr, range 27–95 yr vs 67, range 22–92 yr, P= 0.001), had more emergency surgery for CRC-related complications (18.8% vs 15.1%, P= 0.03), had more proximal cancers (42.2% vs 31.5%, P < 0.001), had more poorly differentiated cancers (16.9% vs 12.9%, P= 0.01), and had fewer radiotherapy treatments for Dukes B and C rectal cancers (36.4% vs 48.1%, P= 0.02). Young women (aged 50 yr and below) had significantly better overall survival compared to young men; in this group, female gender predicted improved overall survival independent of age, emergency surgery, site, grade, and stage (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25–0.86, P= 0.01). Similarly, young women had significantly better cancer-specific survival (HR 0.46, 95% CI 0.25–0.85, P= 0.01). However, older women (aged over 50 yr) had worse survival independent of age, emergency surgery, site, grade, and stage (HR 1.38, 95% CI 1.14–1.68, P= 0.001). There were no gender differences in screening, histopathology, stage, or utilization of chemotherapy.CONCLUSIONS:This study demonstrated an opposing effect of gender on overall and cancer-specific survival at either side of the age of 50 yr. The protective effect of estrogen on CRC may be an important factor. Women had a greater proportion of emergency surgery, which was related to the predominance of proximal cancers in this gender. Women also had more proximal cancers, thereby limiting flexible sigmoidoscopy as a screening test.

The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial.

PURPOSE Acute rectal complications occur in the majority of patients receiving external-beam radiotherapy for carcinoma of the prostate. Sucralfate has been proposed to reduce radiation-induced mucosal injury by forming a protective barrier on ulcer bases, binding local growth factors, and stimulating angiogenesis. However, there is conflicting clinical evidence as to whether sucralfate, taken prophylactically during radiotherapy, can ameliorate the symptoms of acute radiation proctitis. METHODS AND MATERIALS A double-blind randomized trial was conducted at four Radiation Oncology Departments in Sydney, Australia, between February 1995 and June 1997. A total of 338 patients with clinically localized prostate cancer receiving small volume radiotherapy, of whom 335 were evaluable, were randomized to receive either 3 g of oral sucralfate suspension or placebo twice a day during radiotherapy. Patients kept a daily record of their bowel symptoms and were graded according to the RTOG/EORTC acute toxicity criteria. RESULTS One hundred sixty-four patients received sucralfate and 171 received placebo. Both groups were well balanced with regard to patient, tumor, treatment factors, and baseline symptoms, except that the placebo group had a significantly more liquid baseline stool consistency score (p = 0.004). Patients kept a daily diary of symptoms during radiotherapy. After adjusting for baseline values, there was no significant difference between the two groups with regard to stool frequency (p = 0.41), consistency (p = 0.20), flatus (p = 0.25), mucus (p = 0.54), and pain (p = 0.73). However, there was more bleeding in the sucralfate group, with 64% of patients noticing rectal bleeding, compared with 47% in the placebo group (p = 0.001). There was no significant difference between the two groups with respect to RTOG/EORTC acute toxicity (p = 0.88; sucralfate 13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively). CONCLUSION This study suggests that oral sucralfate taken prophylactically during radiotherapy does not ameliorate the symptoms of acute radiation proctitis and may increase acute bleeding. The cause of the increased bleeding in the sucralfate group is unclear. As the pathogenesis of acute and late reactions are different, late follow-up, which includes sigmoidoscopic evaluation, is currently being performed on this cohort of patients.

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.

Australian & New Zealand Faculty of Radiation Oncology Genito-Urinary Group: 2010 consensus guidelines for definitive external beam radiotherapy for prostate carcinoma

External beam radiotherapy for prostate cancer has undergone substantial technological and clinical advances in the recent years. The Australian & New Zealand Faculty of Radiation Oncology Genito‐Urinary Group undertook a process to develop consensus clinical practice guidelines for external beam radiotherapy for prostate carcinoma delivered with curative intent, aiming to provide guidance for clinicians on the appropriate integration of clinical evidence and newer technologies. Draft guidelines were presented and discussed at a consensus workshop in May 2009 attended by radiation oncologists, radiation therapists and medical physicists. Amended guidelines were distributed to radiation oncologists in Australia, New Zealand and Singapore for comment, and modifications were incorporated where appropriate. Evidence based recommendations for risk stratification, the role of image‐guided and intensity‐modulated radiation therapy, prescribed dose, simulation and treatment planning, the role and duration of neo‐adjuvant/adjuvant androgen deprivation therapy and outcome reporting are presented. Central to the guidelines is the recommendation that image‐guided radiation therapy should be used when definitive external beam radiotherapy for prostate cancer is prescribed. The consensus guidelines provide a co‐operatively developed, evidence‐based framework for contemporary treatment of prostate cancer with external beam radiotherapy.

A randomized trial evaluating rigid immobilization for pelvic irradiation

BACKGROUND Accuracy and reproducibility of the patients position is fundamental to the successful delivery of radiation therapy. In recent years, a number of pelvic immobilization techniques have been developed. Few have been evaluated in randomized trials, and many of these studies have produced contradictory and inconclusive results. PURPOSE To assess whether the use of rigid immobilization devices improve the accuracy and reproducibility of prostate irradiation to a clinically useful degree. METHODS AND MATERIALS A total of 100 patients receiving radical irradiation for either prostate or bladder cancer were randomized to be treated with or without the use of rigid immobilization (RI) devices. Of these, 96 patients were suitable for analysis. The control group consisted of the patients being simulated and treated in the prone position with no immobilization devices. Patients randomized to the immobilized arm were simulated and treated prone using a customized Uvex cast of the pelvis as well as ankle- and shoulder-stabilizing devices. Weekly orthogonal port films (PFs) were obtained for each patient. Using previously specified bone landmarks, we measured variations in the isocenter position on each PF compared with the simulation film. The assessors were unaware of the treatment assignment. Patient comfort, skin toxicity, and treatment times were recorded. RESULTS The average simulation-to-treatment deviation of the isocenter position was 8.5 mm in the control group and 6.2 mm in the immobilization group (p < 0.001). In the control arm, 30.9% of port films had isocenter deviations >10 mm compared with 10.6% in the immobilized arm (p = 0.001). For the control group, average deviations in the anteroposterior, right-left, and superior-inferior directions were 5.2 mm, 3.2 mm, and 4.3 mm, respectively, compared with 2.9 mm, 2.1 mm, and 3.9 mm for the immobilized group (p = <0.001, p < 0.001, p = 0.55). The RTOG skin reaction was greater with in patients with a cast (28% having Grade 2 toxicity vs. 10% in the control arm), although this was not statistically significant (p = 0.68). Patients in both groups found the treatment position comfortable: 90% in the immobilized group and 87% in the control group scored the treatment position either reasonably or very comfortable. Treatment times were very similar between the two groups: the average treatment time was 15.5 min in the control group vs. 16.1 min in the immobilized group (p = 0.82). CONCLUSIONS The use of rigid immobilization improves the accuracy of treatment delivery for the prone position, especially in the anteroposterior direction. Of clinical importance, the number of major deviations >10 mm (that is, that would result in a geographic miss) was reduced from 31% to 11%.

Clinical and Pathologic Outcomes of Colorectal Cancer in a Multi-Ethnic Population

BACKGROUND & AIMS The influence of birthplace on the clinical and pathologic outcomes of colorectal cancer (CRC) in Australia is unknown. Addressing inequalities in health care provision in immigrant groups may improve the overall quality of CRC care. METHODS The South Western Sydney Colorectal Tumour Group registry prospectively collects data on new patients with CRC from a population of 800,000. Survival data were cross-linked with the New South Wales population death registry. RESULTS From 1997 to 2004 there were 1496 patients (55% males) who were recruited and grouped according to country of birth: Australia, 64%; Southern Europe, 19%; Asia, 12%; and the Middle East, 5%. Significant heterogeneity in CRC characteristics was found, especially in Asians. Compared with Australians, Asians were diagnosed at a younger age (median age, 64 vs 70 y; P < .001, 25.6% were younger than 50 years vs 9.5%; P < .001), had fewer poorly differentiated cancers (8.9% vs 17.7%; P = .004), and fewer metastatic cancers (12.1% vs 21.0%; P = .001). Being Asian-born was associated with improved overall survival independent of age, emergency surgery, grade, and stage (hazard ratio, 0.66; 95% confidence interval, 0.47-0.93; P = 0.02). CRC screening was especially low among Asian- and Middle Eastern-born patients. Complications and treatment were not affected by birthplace, indicating no differences in the provision or acceptance of care based on birthplace. CONCLUSIONS Despite an equitable distribution of resources, we found significant heterogeneity in presentations and outcomes according to birthplace, with improved survival in Asian-born patients. The lower rates of screen-detected CRC in Asian- and Middle Eastern-born patients and their younger ages at diagnosis indicate that targeted screening strategies may need to be implemented.

Promising results of a cooperative group phase II trial of preoperative chemoradiation for locally advanced rectal cancer (TROG 9801)

PURPOSEThis article reports the overall survival, failure-free survival, local failure, and late radiation toxicity of a phase II trial of preoperative radiotherapy with continuous infusion 5-fluorouracil for rectal cancer after a minimum 3.5 years of follow-up.METHODSEligible patients were those with newly diagnosed localized adenocarcinoma of the rectum, within 12 cm of the anal verge, staged T3–T4 and deemed suitable for curative resection. Radiotherapy (50.4 Gy in 28 fractions in five weeks and three days) was given with continuous infusion 5-fluorouracil throughout the course of radiotherapy.RESULTSA total of 82 patients were accrued in 13 months. The median follow-up time was 4.1 (range, 2.3–4.5) years. There were 55 males (67 percent) and the median age was 59 (range, 27–87) years. Patients were staged pretreatment as T3 (89 percent) and resectable T4 (11 percent). Endorectal ultrasound was performed in 70 percent and magnetic resonance imaging in another 5 percent. The four-year overall and failure-free survival rates were 82 percent (95 percent CI: 72–89) and 69 percent (95 percent CI: 58–78), respectively. The cumulative incidence of local failure at four years was 3.9 percent (95 percent CI: 1.3–11). Risk of failures, local and distant, has not reached a plateau phase.CONCLUSIONThis regimen can be delivered safely and without leading to a significant increase in late toxicity. It provides excellent local control and favorable overall survival. There is a need for longer follow-up than has commonly been used for the proper evaluation of failures after an effective regimen of preoperative chemoradiation.

Surgical management of colorectal cancer in south-western Sydney 1997−2001: a prospective series of 1293 unselected cases from six public hospitals

Background:  The aim of the present study is to provide local data for the management of colorectal cancers in the south‐western Sydney health area from 1997 to 2001.

Direct tumor invasion in colon cancer: correlation with tumor spread and survival.

PurposeThis study examined the correlation between depth of local invasion in colon cancer and tumor spread and patient survival.MethodsA cohort of 796 patients with a complete set of TNM staging information following an elective resection for colon cancer was selected. The rates of lymph node and distant metastasis, tumor differentiation, and extramural venous invasion for different tumor (T) categories were compared. The effects of initial tumor (T) category on overall patient survival were studied.ResultsThe depth of local tumor invasion correlated strongly with nodal involvement (P = 0.0001), rates of extramural venous invasion (P = 0.0002), poor differentiation (P = 0.0001), and distant metastasis (P = 0.0001). Fifty-seven percent of the patients remained lymph node-negative and distant metastasis-negative irrespective of their depth of tumor invasion had no impact on overall survival (P = 0.49). For patients with lymph node or distant metastasis (43 percent), depth of tumor invasion had significant impact on overall survival (P = 0.001). Thirteen percent of T3N1, 33 percent of T3N2, 40 percent of T4N1, and 68.percent of T4N2 cases had distant metastasis at presentation.ConclusionTwo types of colon cancer were observed: locally active and tendency to metastasize. For the latter, overall mortality and the risk of metastasis increased with depth of tumor invasion.