The development of practice standards for radiation oncology in Australia: a tripartite approach.

In many areas of health care, practice standards have become an accepted method for professions to assess and improve the quality of care delivery. The aim of this work is to present the development of practice standards for radiation oncology in Australia, highlighting critical points and lessons learned. Following a review of radiotherapy services in Australia, a multidisciplinary group with support from the Australian Government developed practice standards for radiation oncology in Australia. The standards were produced in a multistep process including a nationwide survey of radiotherapy centres and piloting of the standards in a representative subset of all Australian radiotherapy centres. The standards are grouped into three sections: Facility management (covering staffing, data management, equipment and processes); Treatment planning and delivery (providing more detailed guidance on prescription, planning and delivery); Safety and quality management (including radiation safety, incident monitoring and clinical trials participation). Each of the 16 standards contains specific criteria, a commentary and suggestions for the evidence required to demonstrate compliance. The development of the standards was challenging and time consuming, but the collaborative efforts of the professions resulted in standards applicable throughout Australia and possibly further afield.

Patient-reported complications from fiducial marker implantation for prostate image-guided radiotherapy.

OBJECTIVES: To report on complications from transrectal ultrasound-guided insertion of fiducial markers for prostate image-guided radiotherapy. METHODS: 234 patients who underwent transrectal fiducial marker insertion for prostate cancer image-guided radiotherapy were assessed retrospectively by questionnaire with regard to the duration and severity of eight symptoms experienced following the procedure. Pain during the implantation procedure was assessed according to the Wong-Baker faces pain scale. RESULTS: Of 234 patients, 32% had at least one new symptom after the procedure. The commonest new symptom following the procedure was urinary frequency affecting 16% of patients who had not been troubled by frequency beforehand. Haematuria, rectal bleeding, dysuria and haematospermia affected 9-13% of patients, mostly at Grade 1 or 2. Pain, obstruction, and fever and shivers affected 3-4% of patients. Grade 3 rectal bleeding, haematuria, fever and shivers, and urinary frequency affected 0.5-1.5% of patients. Only one patient had a Grade 4 complication (i.e. fever and shivers). Overall, 9% of patients had symptoms lasting more than 2 weeks. The commonest symptoms that lasted more than 2 weeks were frequency, dysuria, obstructive symptoms and rectal bleeding. Mean pain score during the procedure was 1.1 (range 0-5). CONCLUSION: Transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy is well tolerated in the majority of prostate cancer patients. Most symptoms were Grade 1 or 2 in severity. Symptoms in the majority of patients last under 2 weeks. The most serious complication was sepsis in our study.

Prospective development of an individualised predictive model for treatment coverage using offline cone beam computed tomography surrogate measures in post-prostatectomy radiotherapy.

The aim of this study is to prospectively evaluate and model surrogate explanatory variables (SEVs) of target coverage and rectal dose pertaining to soft tissue anatomy visualised on cone beam computed tomography (CBCT) for incorporation into post-prostatectomy treatment coverage verification protocols. Twenty post-prostatectomy patients treated with conformal prostate bed radiotherapy (64-74 Gy) underwent CBCT daily at fractions 1 to 5, and then weekly. Treatment coverage was defined on each CBCT using 'PTV95', percentage of the CBCT PTV covered by original treatment fields, and 'RECTD50', dose delivered to 50% of CBCT rectal volume by original treatment fields. Three candidate SEVs for treatment coverage were defined for each scan: anterior rectal wall movement, change in bladder length and bladder base movement. Both anterior rectal wall movement and increase in bladder length predicted for the decreased PTV95 (P < 0.001 for each). Anterior movement of the anterior rectal wall predicted for increased RECTD50 (P < 0.001). Predictive models for the PTV95 and RECTD50 that accept the significant SEVs as inputs were developed. We developed simple CBCT-acquired soft tissue anatomic surrogate measures that signal changes in target coverage and rectal dose during post-prostatectomy radiotherapy. Conventional bony anatomy patient position verification protocols were inadequate in accounting for soft tissue target and organ variation seen with CBCT.

Implementation of daily image-guided radiation therapy using an in-room CT scanner for prostate cancer isocentre localization.

The Tattersall's Cancer Centre has been performing image-guided radiation therapy (IGRT) using an in-room CT on rails since 2003 to verify accurate patient setup position (relative to bony anatomy) immediately prior to treatment delivery for prostate cancer patients. While the concept of online correction for bony anatomy is well established, the use of an in-room CT scanner also enables the collection and offline analysis of soft tissue volumetric data. Although initially IGRT was implemented under a research protocol, in-room CT verification has continued to be used to measure and correct for patient setup variations for all patients undergoing intensity modulated radiation therapy (IMRT) treatments. The present paper outlines the protocol that was used to implement IGRT using an in-room CT scanner at the Tattersall's Cancer Centre. Online corrections that minimize patient setup uncertainties allow confidence in delivering dose escalation as well as decreasing the margins required around the target volume. With improvements in auto-contouring tools, IGRT will also have the ability to measure and correct for variations in target and critical structure positioning online, rather than the current offline methods utilized.

Radiation for prostate cancer.

The balance between tumour control and normal tissue damage with conventional radiotherapy is critical to outcome and morbidity in the treatment of localised prostate cancer. Recent technological advances have allowed a reduction in the amount of normal tissue included in target treatment volumes. This reduces morbidity and allows dose escalation, theoretically increasing the likelihood of tumour control. The methods used to achieve dose escalation are discussed and the available evidence for their safety and efficacy, relative to conventional treatment, is reviewed. Although there are no randomised studies to provide evidence of increased survival, the available evidence supports the hypothesis that dose escalation produces survival rates equivalent to surgical series and provides a realistic choice for patients.

A randomized trial of hypofractionated schedules of palliative radiotherapy in the management of bladder carcinoma: results of medical research council trial BA09.

PURPOSE: To compare the efficacy and toxicity of two hypofractionated radiotherapy schedules for the improvement of local symptoms from muscle-invasive bladder cancer. METHODS AND MATERIALS: A multicenter randomized trial was conducted comparing the efficacy and toxicity of two radiotherapy schedules (35 Gy in 10 fractions and 21 Gy in 3 fractions) for symptomatic improvement in patients considered unsuitable for curative treatment through disease stage or comorbidity. The primary outcome measures were overall symptomatic improvement of bladder-related symptoms at 3 months and changes in bladder- and bowel-related symptoms from pretreatment to end-of-treatment and 3-month assessments. Overall symptomatic improvement was defined prospectively as the improvement in one bladder-related symptom of at least one grade at 3 months, with no deterioration in any other bladder-related symptom. RESULTS: Five hundred patients were recruited, but data on symptomatic improvement at 3 months was only available on 272 patients. Of these, 68% achieved symptomatic improvement (71% for 35 Gy, 64% for 21 Gy), with no evidence of a difference in efficacy or toxicity between the two arms. There was no evidence of a difference in survival between the two schedules (hazard ratio [HR] = 0.99, 95% CI 0.82-1.21, p = 0. 933). CONCLUSION: This is the largest prospective trial to date in the palliative treatment of bladder cancer, and provides baseline data against which other results may be compared. The use of 21 Gy in 3 fractions appears as effective as 35 Gy in 10 fractions, although modest differences in survival, symptomatic improvement rates, and toxicity can not be reliably excluded.

Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group.

PURPOSE: To compare relapse rates and toxicity associated with para-aortic (PA) strip or PA and ipsilateral iliac lymph node irradiation (dogleg [DL] field) (30 Gy/15 fractions/3 weeks) for stage I testicular seminoma. PATIENTS AND METHODS: Between July 1989 and May 1993, 478 men with testicular seminoma stage I (T1 to T3; no ipsilateral inguinoscrotal operation before orchiectomy) were randomized (PA, 236 patients; DL, 242 patients). RESULTS: Median follow-up time is 4.5 years. Eighteen relapses, nine in each treatment group, have occurred 4 to 35 months after radiotherapy; among these, four were pelvic relapses, all occurring after PA radiotherapy. However, the 95% confidence interval (CI) for the difference in pelvic relapse rates excludes differences of more than 4%. The 3-year relapse-free survival was 96% (95% CI, 94% to 99%) after PA radiotherapy and 96.6% (95% CI, 94% to 99%) after DL (difference, 0.6%; 95% confidence limits, -3.4%, +4.6%). One patient (PA field) has died from seminoma. Survival at 3 years was 99.3% for PA and 100% for DL radiotherapy. Acute toxicity (nausea, vomiting, leukopenia) was less frequent and less pronounced in patients in the PA arm. Within the first 18 months of follow-up, the sperm counts were significantly higher after PA than after DL irradiation. CONCLUSION: In patients with testicular seminoma stage I (T1 to T3) and with undisturbed lymphatic drainage, adjuvant radiotherapy confined to the PA lymph nodes is associated with reduced hematologic, gastrointestinal, and gonadal toxicity, but with a higher risk of pelvic recurrence, compared with DL radiotherapy. The recurrence rate is low with either treatment. PA radiotherapy is recommended as standard treatment in these patients.

Death due to thyroid metastases from renal cell carcinoma.

Renal cell carcinoma is a tumour that is well recognized to metastasize widely and to behave in an unpredictable manner. We report a patient with a renal cell carcinoma that metastasized to the thyroid and resulted in death from associated respiratory compromise. The clinical features of cancers metastasizing to the thyroid are discussed and the apparent over-representation of renal cell carcinoma in symptomatic thyroid metastases is highlighted. The uncertainty about whether metastases arise more frequently in pre-existing abnormal thyroid glands is also reviewed.

Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party.

In a retrospective study, data from 302 patients with metastatic testicular seminoma treated with chemotherapy between 1978 and 1990 in 10 European centres were analysed to evaluate the role, if any, of postchemotherapy treatment with irradiation. The primary endpoint of this study was the progression-free survival rate after chemotherapy with or without additional radiotherapy. This was related to the type of primary chemotherapy, sites and sizes of pre- and postchemotherapy masses, the extent of surgical resection after chemotherapy and the use of radiotherapy. 174 patients had residual disease at the end of chemotherapy. The most important prognostic factors for progression were the presence of any visceral metastases or raised LDH prechemotherapy, and the presence of residual disease at visceral sites after chemotherapy. Approximately half the patients with residual masses underwent postchemotherapy radiotherapy, with selection based predominantly on institutional practice. In patients receiving platinum-based chemotherapy, no significant difference was detected in progression-free survival whether or not radiotherapy was employed. Patients receiving BEP (bleomycin, etoposide and cisplatin) had a progression-free survival rate of 88% (95% CI, 80-96%) uninfluenced by postchemotherapy radiotherapy. In patients with residual masses confined to the abdomen after platinum-based chemotherapy, the absolute benefit to radiotherapy was estimated to be 2.3%. The potential benefit of postchemotherapy radiotherapy is minimal, and so it is concluded that the use of adjuvant radiotherapy to residual masses after platinum-based chemotherapy for metastatic seminoma is unnecessary.

Identification of intermediate-risk prostate cancer patients treated with radiotherapy suitable for neoadjuvant hormone studies.

We undertook a retrospective review of patients presenting with apparently localised prostatic carcinoma to a single practitioner for consideration of radiation therapy to clarify the characteristics of those patients who might benefit from the use of neo-adjuvant androgen deprivation. Of 133 patients referred between January 1989 and June 1994, 85 were considered suitable for radical therapy, of whom 31 were treated with hormone therapy prior to radiotherapy, frequently on the basis of an elevated PSA. Increasing PSA levels (p = 0.0016) and Gleason grade (p = 0.026) were independent variables for relapse. It was possible to define three prognostic groups of patients, on the basis of initial PSA and Gleason grade. Those of intermediate risk (PSA < 10 micrograms/l, Gleason score 8-10; PSA 10-25 micrograms/l, Gleason 5-7 or 8-10; PSA > 25 micrograms/l, Gleason score 2-4) had a superior duration of disease-free survival if given initial hormone therapy. This group of patients is potentially the most likely to benefit from such an approach and should be enrolled in prospective randomised studies of neoadjuvant androgen deprivation.

Reversible changes in radiation response induced by all-trans retinoic acid.

PURPOSE: The aim was to establish a model of reversible radiosensitization in human tumor cell lines by all-trans retinoic acid without influencing cell cycle or differentiation. METHODS AND MATERIALS: Three human carcinoma cell lines (one bladder and two lung lines) were incubated in medium containing delipidized serum with or without varying concentrations of all-trans retinoic acid for a range of time periods, and their acute response to radiation measured by clonogenic assay. Cell phenotype was monitored using growth rates, morphology, and intermediate filament expression. RESULTS: Two of the three cell lines (those in which cell kill was predominantly through reparable damage beta in control cultures) showed an increase in radiosensitivity with retinoic acid, at a concentration with no discernable effect on phenotype (10(-7) M). No significant change in alpha values was observed. The values for beta increased from 0.057 to 0.109 and from 0.039 to 0.075, corresponding to dose modification factors of 1.59 and 1.67. When retinoic acid was removed prior to irradiation, cell survival returned to control levels by 48 h. CONCLUSION: Radiosensitization occurred at retinoic acid concentrations that did not otherwise perturb the cells; the effect may be due to inhibition of DNA repair in cells usually competent at repair. The model provides a method of altering radiosensitivity in selected cell lines without genetic mutation, which may enable investigation of DNA repair mechanisms.

Fundamental bases of combined therapy in lung cancer: cell resistance to chemotherapy and radiotherapy.

This overview briefly examines the mechanisms of drug resistance in lung cancer, including multidrug resistance and its atypical phenotypes, the role of cytoplasmic protectors such as glutathione, and resistance at the level of the DNA through topoisomerases, gene amplification or mutation, and DNA repair. Understanding of radioresistance is less advanced, but resistance may arise through limitation of the amount of DNA damage inflicted or by its subsequent modification by intracellular protectors or DNA repair. The mechanisms of radioresistance are generally distinct from those of chemoresistance providing a rationale for the use of combined modality therapy.

Radical treatment for primary bladder cancer: where are we and where do we go from here? A review.

The management of the primary tumour in muscle-invasive bladder cancer is determined more by geographical location than by firm evidence of the superiority of either surgery or radiotherapy over the other. Recent technological advances in both specialties may change their acceptability and efficacy, but as yet none has been fully evaluated. The effect of chemotherapy on primary tumour control may also influence management choices. There is a need to reexamine the merits of surgery and radiotherapy in the modern era.