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.

A case-control study of the androgen receptor gene CAG repeat polymorphism in Australian prostate carcinoma subjects.

BACKGROUND: The development of prostate carcinoma is androgen-dependent. The coding sequence of the androgen receptor (AR) gene contains a CAG repeat polymorphism that has been shown to influence AR activity in vitro. Studies of this polymorphism as a prostate carcinoma risk factor have been conflicting. METHODS: A matched case-control design was used in a clinic-based multicenter study of Australian prostate carcinoma subjects. Cancer subjects were matched by age and locality with controls, all of whom had a serum prostate specific antigen (PSA) level of less than 4 mg/L. Conditional logistic regression was used to determine the relative risk of prostate carcinoma dependent on AR gene CAG number. The association of disease characteristics at diagnosis with the polymorphism also was assessed. RESULTS: Five hundred forty-five cases of prostate carcinoma and 456 matched case-control pairs were recruited. Association studies of disease characteristics at diagnosis showed age at diagnosis to be associated with AR CAG number by univariate (P = 0.004) and multivariate (adjusting for PSA, stage, and grade) linear regression (P = 0.018). No association was observed between the polymorphism and disease stage (TNM-based categories; P = 0.277), histologic grade (P = 0.41), or PSA level at diagnosis (P = 0.48). In the pairwise case-control analysis, the odds ratio of prostate carcinoma for a change of 5 CAG repeats gave an odds ratio of 0.9821 (95% confidence interval, 0.84-1.15). CONCLUSIONS: In this Australian study population, the AR CAG repeat polymorphism was not a risk factor for prostate carcinoma, but a shorter repeat sequence was associated with earlier age at diagnosis.

Prostate cancer in Victoria in 1993: patterns of reported management.

OBJECTIVE: To describe the management of newly diagnosed prostate cancer in 1993 during the early prostate specific antigen (PSA) era. DESIGN: Survey of medical practitioners involved in the management of a total sample of incident prostate cancer cases selected from a population-based cancer registry. The survey was conducted in 1996, and the sample was followed up until 1998, to obtain five-year survival data on all patients. SETTING: The State of Victoria, including both public and private health sectors. PATIENTS: All men who were newly diagnosed with prostate cancer in the six months January-June 1993. MAIN OUTCOME MEASURES: Reported management by method of diagnosis; staging investigations; and treatment by observation, hormonal therapy, radical radiotherapy or radical prostatectomy. RESULTS: 1048 of 1117 (94%) cases diagnosed were surveyed. Most of the men (858 [82%]) were older than 65 years: 117 (11%) cancers were detected by screening asymptomatic men, and a further 269 (26%) were found by testing of men with symptoms ("case-found"). The 259 (25%) men treated with definitive local therapies (prostatectomy and curative radiotherapy) were younger (< 75 years), and their disease was clinically more localised (clinical stage, T1-2) and they were often found by screening or case-finding. Men given hormonal therapy (407; 39%) or managed without treatment (373; 36%) tended to be older and more likely to have been diagnosed by transurethral resection of the prostate (TURP). The overall relative survival at five years was 86% and was decreased in men with cancers of higher histological grade or more advanced clinical stage, or who had higher PSA levels. CONCLUSIONS: Although a third of patients were detected by screening or case-finding early in the PSA era, definitive local therapies were used infrequently (25% of the total sample). Most received appropriate treatment.

A quality assurance audit: phase III trial of maximal androgen deprivation in prostate cancer (TROG 96.01).

In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998-1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme.

Prostate cancer and PSA screening.

BACKGROUND: Each year over 12,000 men are diagnosed with prostate cancer in Australia and there is an increasing need to keep up with a reasonable knowledge of the disease for day to day patient management. OBJECTIVE: To summarise the main issues in prostate cancer screening including the methods of diagnosis, treatment and follow up of patients with prostate cancer in all stages of the disease. DISCUSSION: This review is intended as a practical guide to enable general practitioners to play an effective role alongside the other specialists involved in the multidisciplinary management of patients with this common and controversial disease.

Comparison between the clonogenic, MTT, and SRB assays for determining radiosensitivity in a panel of human bladder cancer cell lines and a ureteral cell line.

Using a series of human bladder cancer cell lines and an immortalised normal ureteral cell line, radiosensitivities measured by three different methods after a single dose of X-radiation are compared. Clear differences between cell survival curves obtained using the clonogenic, microtetrazoline (MTT) and sulforhodamine B (SRB) assays are shown. The most sensitive of the assays investigated was the clonogenic assay. The MTT and SRB assays were found to be relatively insensitive especially at lower radiation levels, suggesting that these assays may not be suitable for predicting therapeutic dose schedules in vivo, but will be important for investigating radio-sensitivity in cell lines with very low plating efficiencies. Each assay discriminated between a range of sensitivities in the cell lines examined, and with some minor differences, the ordering of sensitivities using the three assays was similar. Possible explanations for the differences between results obtained with the three assays are discussed.

Heterogeneity of in vitro radiosensitivity in human bladder cancer cells.

Human bladder cancer is often heterogeneous containing biologically different populations. Radiotherapy plus chemotherapy is the most common treatment for invasive disease. However few studies have investigated the role of heterogeneity in determining radiosensitivity. The radiation sensitivities of a parent human bladder cancer cell line (UCRU-BL-17CL) and nine cloned cell lines derived from it were determined. These cloned cell lines were previously shown to exhibit different biological characteristics when grown in nude mice. Radiation sensitivity was determined using both MTT and clonogenic assays. The radiobiological parameters, alpha,beta, and surviving fractions at 2 Gy and 8 Gy from the linear-quadratic model, were used to assess radiation sensitivity in the statistical analyses. The nine clones differed in radiosensitivity by both assays. By MTT, but not by the clonogenic assay, their radiation sensitivities were relatively consistent within each of the three biological groups (non-tumorigenic, tumorigenic, invasive); invasive clones were more sensitive than those of the non-tumorigenic and the tumorigenic groups for all the three-test criteria. The heterogeneity exhibited by this cell line may explain some of the variations in the clinical responses seen in the radiation treatment of invasive bladder cancer.

Symptom duration and delay in referral for palliative radiotherapy in cancer patients: a pilot study.

OBJECTIVE: To estimate the frequency of delay in referral for palliative radiotherapy (PRT), and to identify factors associated with delay. DESIGN: Prospective survey over three months in 1997. SETTING: Radiotherapy department of a cancer centre in Melbourne, Victoria. PARTICIPANTS: 158 consecutive patients prescribed PRT in the lung, breast, urology and haematology units. MAIN OUTCOME MEASURES: Duration of symptoms; incidence of "unreasonable" delay in referral; and incidence of negative clinical outcome associated with referral delay. RESULTS: The median duration of symptoms before prescription of radiotherapy was four weeks. Thirty-eight patients (24%) were considered to have had an unreasonable delay in referral, with median symptom duration of 15 weeks, and median delay in referral of 12 weeks. Causes of delay were classified as "diagnostic uncertainty" (29%), "other treatment given" (18%), "patient related" (18%), "language difficulty" (3%), and "unexplained" (32%). Twenty-seven of these 38 patients (71%) had negative outcomes, including persistent pain, neurological deterioration and persistent respiratory symptoms. CONCLUSIONS: These data suggest that delay in referral for PRT is not uncommon, has a variety of causes and can result in negative clinical outcomes. There appears to be a need for greater awareness of patients' symptoms and of the role of PRT among clinicians caring for patients with cancer.

Relationship between radiation response and p53 status in human bladder cancer cells.

Mutations in the p53 tumour suppressor gene are found at high frequency in bladder cancer. There is strong evidence that p53 plays an important role in controlling the cell cycle after DNA damage by ionizing radiation. However, the effect of loss of p53 function on radiosensitivity is not yet clear. Radiotherapy combined with chemotherapy is the most common treatment for patients with invasive bladder cancer. Recently three bladder cancer cell lines have been established and this paper investigates the p53 status and clonogenic survival of these cell lines following irradiation. It was found that one line expresses wt p53 (UCRU-BL-13) and two lines contain a codon 72 polymorphism (UCRU-BL-17 and UCRU-BL-28). UCRU-BL-17 cells also contain a point mutation affecting codon 280. The level of p53 expression in the cell lines is clearly different, with UCRU-BL-17 expressing a higher level of p53 compared with UCRU-BL-13; UCRU-BL-28 expressed intermediate levels. The clonogenic survival of these cell lines has been determined. It was found that the line expressing a p53 mutation was more sensitive than those with wild type p53, providing support for a model in which loss of p53 function is associated with increased radiosensitivity, possibly due to reduced p53-dependent DNA repair.

The efficacy of treatment for malignant epidural spinal cord compression.

The aims of this study were to document the efficacy of treatment and to identify factors that were predictive of the outcome in malignant epidural spinal; cord compression. The medical records of patients treated at the Prince Henry and Prince of Wales Hospitals in the period 1980-1989 with a diagnosis of malignant epidural spinal cord compression were reviewed. A total of 94 patients were eligible for the study and were treated by radiotherapy alone (37), surgery alone (19) and surgery followed by radiotherapy (38). Efficacy was determined by measuring complete resolution of symptoms and signs at 1 month after presentation, and also by using an overall functional improvement score (FIS). Complete resolution of individual pre-treatment symptoms that were measured 1 month after treatment occurred as follows: pain (30/88), sensory disturbance (12/61), weakness (8/17), bladder dysfunction (10/42), and bowel dysfunction (10/36). Complete resolution of motor deficit occurred in 7/82 and of sensory deficit in 9/73. The ability to walk was regained in 19/51 previously non-ambulatory patients, and bladder function improved sufficiently to remove an indwelling catheter in 9/32 previously catheterized patients. As judged by FIS, 67 patients improved, 15 patients remained stable and 12 patients deteriorated. Of the treatments given, a combination of surgery followed by radiotherapy was associated with the greatest functional improvement (P = 0.001). The coexistence of 'liver failure' was the only patient-related factor identified which was associated with outcome (P = 0.041). The treatment of malignant spinal cord compression appears to be worthwhile; however, the outcome of treatment is not easy to predict from pretreatment factors. A 'functional improvement score' may be useful in assessing treatment efficacy.

The development of a treatment protocol for patients with chronic radiation-induced rectal bleeding.

UNLABELLED: BACKGROUNDS AND METHODS: This study reviews the clinical features and reports the preliminary results of treatment of 34 consecutive patients with clinically significant bleeding from chronic, radiation-induced proctitis, using a combination of endoscopic YAG Laser and the application of topical formalin dressings to the rectal mucosa. RESULTS: Bleeding ceased in 25 patients (74%); bleeding continued but occurred only slightly and occasionally in five patients (15%); and three patients required operation to control the bleeding (9%). One patient relapsed after treatment and died while receiving a further transfusion. CONCLUSIONS: This experience has been used to develop a management protocol for patients with this serious complication.

Autologous bone marrow transplantation for advanced neuroblastoma using teniposide, doxorubicin, melphalan, cisplatin, and total-body irradiation.

BACKGROUND: Disseminated neuroblastoma after infancy has a dismal prognosis; long-term survival with conventional therapy occurs in approximately 10% of cases. PATIENTS AND METHODS: Between 1985 and 1992, we followed a strategy aimed to achieve remission with an induction combination of intensive chemotherapy, primary resection, and tumor-bed radiotherapy (TBRT). Patients who achieved remission proceeded to myeloablative chemoradiotherapy and unpurged autologous bone marrow transplant (ABMT). Twenty-eight patients older than 1 year presented with stage IV disease during the study period; six died of progressive disease and three died of complications of therapy. Nineteen patients achieved remission, two of whom did not receive ABMT. Seventeen patients proceeded to ABMT. Conditioning was with teniposide 130 mg/m2, doxorubicin 30 mg/m2, melphalan 120 mg/m2, cisplatin 80 mg/m2, and total-body irradiation 12 Gy in six fractions (modified VAMP-TBI). RESULTS: Principal nonhematologic toxicities were mucositis and diarrhea. There were no ABMT-related deaths. Two patients relapsed at 8 and 26 months post-ABMT, respectively. Fifteen patients remain in complete remission (CR) at 24 to 102 months (median, 71) from ABMT and 30 to 114 months (median, 78) from diagnosis. Survival rates of all 28 patients are 61% and 50% at 2 and 5 years, respectively, and the disease-free survival (DFS) of the ABMT group is 94% and 87% at 2 and 5 years, respectively. CONCLUSION: Modified VAMP-TBI appears to be an effective conditioning regimen, with 15 of 17 patients remaining disease-free, with no toxic deaths. This result compares favorably with that of other groups. Larger numbers of patients need to be treated to confirm the efficacy of this therapy.

Testicular doses in definitive radiation therapy for localized prostate cancer.

PURPOSE: To measure the dose received by the unshielded testes during a conventional course of 18 MV photon radiotherapy for localized prostate cancer and to identify the factors influencing it. METHODS AND MATERIALS: For each of four patients, a wax block containing thermoluminescent chips was attached to the posterior aspect of the scrotum in close proximity to the testes on each day of treatment during a full course of radical radiotherapy, and dose measurements were obtained. The distances between the thermoluminescent chips and the beam edge were verified by measurement from port films. The accuracy of the in vivo measurements and the factors influencing the testis dose were studied using a phantom arrangement. Six factors were considered: (a) the relative contributions from primary and scattered radiation, (b) the amount of buildup required for the thermoluminescent chips that monitored testis dose, (c) the position of the testes within the scrotum, (d) field size, (e) distance from the field lower border, and (f) the effect of port films. RESULTS: Median daily doses to the testes in four patients ranged from 5 to 7 cGy. Daily doses for the four patients ranged from 4 to 14 cGy. The total dose to the testes over the full course of therapy ranged from 1.8 to 2.4 Gy. The daily dose depended primarily on the distance from the field lower border. This was increased by approximately 2.5 cGy when a 6 MV port film was taken. The relative contributions from primary and scattered radiation were found to be similar. Dose measurements at the posterior aspect of the scrotum overestimated the testis dose by approximately 15%. CONCLUSION: The most important factors influencing the dose received by the testis are the distance from the testes to the field lower border and the occasion of a port film. A knowledge of the number of port films and the average distance from the field lower border to the testes allows a reasonable prediction of testes dose without daily measurement.

Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder.

PURPOSE: To assess prognostic factors for bladder relapse and distant failure following definitive radiotherapy for invasive transitional cell carcinoma (TCC) of the bladder. METHODS AND MATERIALS: Retrospective review of patients treated in the period 1977 to 1990 by definitive radiotherapy. The factors studied included age, sex, T stage, histological grade, tumor multiplicity, ureteric obstruction, total radiation dose, and use of neoadjuvant chemotherapy. The endpoints studied were bladder relapse and distant failure. RESULTS: There were 342 patients with a mean follow-up time of 7.9 years. Bladder relapse was observed in 159 patients. The overall actuarial bladder relapse rate at 5 years was 55% (SE = 3%). Prognostic factors for a higher bladder relapse rate were: tumor multiplicity (p < 0.001), presence of ureteric obstruction (p = 0.001), and higher T stage (p = 0.044). Distant failure occurred in 39 patients. The overall actuarial distant failure rate at 5 years was 28% (SE = 3%). Prognostic factors for a higher distant failure rate were: ureteric obstruction (p = 0.003) and higher T stage (p = 0.030). CONCLUSION: In our study, patients with invasive bladder TCC fell into distinct prognostic groups determined by the three independent factors, ureteric obstruction, tumor multiplicity, and T stage. These factors provided estimated risks of bladder relapse by 5 years which ranged from 34% to 91%. Knowledge of these prognostic factors can help in the selection of patients more suited for bladder preservation by definitive radiotherapy.

The prognostic significance of tumor-associated markers p53, HER-2/neu, c-myc, v-H-ras, PCNA and EGFr of local and distant recurrence in localized human prostatic adenocarcinoma.

The intracellular expression of the gene products of tumor-associated markers p53, proliferative cell nuclear antigen (PCNA), HER-2/neu, c-myc, H-ras, and epidermal growth factor receptor (EGFr) in 86 cases of localized prostatic adenocarcinoma was investigated immunohistochemically in formalin-fixed paraffin-embedded tissue sections after pretreatment with a novel antigen retrieval buffer. A scoring system was devised to assess strength, pattern, and combined strength/pattern of immunostainings in the nucleus and cytoplasm for each immunomarker. The results were evaluated to determine whether overexpression of the gene products in the nucleus and cytoplasm was predictive of local and/or distant tumor recurrence and whether their expression was associated with known clinical prognostic factors. There was no significant relation between p53, PCNA, HER-2/neu, c-myc, and H-ras protein expression with risk of recurrence. EGFr expression showed a trend of increasing risk of tumor recurrence with higher composite score. Analysis of the association with other known prognostic factors in prostatic adenocarcinoma showed that PCNA was significantly correlated with tumor stage while H-ras and HER-2/neu were marginally correlated with prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) pretreatment serum levels, respectively. Together our findings suggest that overexpression of these intracellular oncoproteins in the tumor cells may not play an important role in determining whether prostatic tumors are likely to recur in localized prostatic adenocarcinoma.

Allogeneic and autologous bone marrow transplantation for acute non-lymphoblastic leukaemia.

Bone marrow transplantation (BMT) has had an increasing role in the treatment of acute nonlymphoblastic leukaemia (ANLL). A review of patients transplanted between May 1975 and August 1991 was undertaken in order to evaluate problems and outcome, and examine the role of both autologous and allogeneic BMT at various stages in the treatment of ANLL. Forty-seven patients received either an allogeneic (n = 24) if a suitable donor was identified or autologous (n = 23) BMT if there was no allogeneic donor. Conditioning therapy consisted of total body irradiation (TBI) and cyclophosphamide (n = 14) or busulfan and cyclophosphamide (n = 33) with or without melphalan. Graft-versus-host disease prevention was with methotrexate (n = 9), methotrexate and cyclosporin (n = 10) or T cell depletion (n = 5). Minimum follow-up for surviving patients was 24 months (median 65 months). For patients transplanted in first remission there was a 0% and 9 +/- 6% transplant-related mortality, a 37 +/- 11% and 33 +/- 12% relapse risk and a 63 +/- 11% and 63 +/- 12% event-free survival for autologous and allogeneic BMT, respectively. In second remission, there was a 14% mortality, 50 +/- 20% relapse risk and 43 +/- 19% event-free survival for allogeneic BMT. No patient transplanted in relapse survived. In patients who survived greater than 24 months, late side effects were noted in all 8 (100%) patients given TBI and in 2 of 19 (10.5%) given busulfan.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of external beam radiotherapy in 448 patients with clinically localized adenocarcinoma of the prostate.

The results of external beam radiotherapy for clinically localized adenocarcinoma of the prostate in 448 patients treated in the period 1980-90 were reviewed. The average follow up was 4.9 years. The patients were aged 44-87 years (median 69 years) and all had histopathological evidence of adenocarcinoma by needle biopsy or transurethral resection of prostate. The histopathological grading was: 127 G1; 154 G2; 127 G4; 28 Gx. Clinical staging according to TNM (American Urological Association) was: 29 T0 (A2); 4 T1 (B1); 173 T2 (B2); 176 T3 (C1); 63 T4 (C2); 3 Tx. Routine surgical pelvic lymph node staging was not performed but patients had radiological (computerized tomography scan or lymphogram) nodal staging: 350 N0; 22 N1; 12 N2; 64 Nx. High energy linear accelerator external beam radiotherapy was given by multiple fields to total doses of 50-70 Gy (median 60 Gy). The majority of patients (307, 69%) was treated by a uniform policy under the care of one radiation oncologist (HM). The rates of local and distant failure at 5 years were 10% (s.e. = 2%) and 42% (s.e. = 3%), respectively. The late complication rate at 5 years was 25% (s.e. = 2%), comprising mild 16%, moderate 7% and severe 1.3%. The 5 year overall survival rate was 64% (s.e. = 2%) and the cancer-specific survival rate was 74% (s.e. = 3%). Both histological grade and clinical stage were strongly predictive of overall survival and distant failure. Only histological grade was predictive of local failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Ewing's sarcoma: long-term follow-up in 49 patients treated from 1967 to 1989.

PURPOSE: Review of long-term results of therapy for Ewing's sarcoma in terms of survival, local tumor control, distant failure and complications rates. METHODS AND MATERIALS: Retrospective review of the records of patients with Ewing's sarcoma of bone and soft tissues treated at The Prince of Wales Children's and Prince of Wales Hospitals, Sydney, between 1967 and 1989 and followed-up to July 1991. RESULTS: There were 49 patients with median age 16 years (range 3-33 years) and average potential follow-up time 12.3 years (range 2-24 years). Forty patients presented with localized disease (three with regional lymph node involvement) and nine with distant metastases. Local therapy for the primary was by amputation in three patients, by resection and postoperative radiotherapy in five, and by definitive radiotherapy in 41 (median dose 50 Gy). Forty-four patients received adjuvant multi-agent chemotherapy. The overall actuarial survival rate was 33% (SE = 7%) at 5 years and 30% (SE = 7%) at 10, 15, and 20 years. The factors predictive of shorter survival were distant metastases at diagnosis (p = 0.036) and older age (p = 0.025). The actuarial local control rate for all 49 patients was 75% (SE = 8%) at 5, 10, 15, and 20 years. The only factor predictive of local failure was an inadequate target volume irradiated (p = 0.003). In 40 patients who presented with localized disease only, the actuarial rate of freedom from distant failure at 5 years was 44% (SE = 8%) and at 10, 15, and 20 years was 40% (SE = 8%). Seven patients experienced severe or fatal complications (defined as requiring investigation and treatment in hospital), namely stress fracture in two, fatal osteogenic sarcoma in one, fatal cardiotoxicity in one and severe hemorrhagic cystitis in three. The rate for severe or fatal complications at 5 years was 19% (SE = 8%), at 10 years was 29% (SE = 12%) and at 15 and 20 years was 53% (SE = 21%). CONCLUSION: Survival to 5 years appears to confer probable cure and one third of our patients have achieved this. Long-term follow-up also reveals that an increasing number of patients experience treatment-related complications, the majority of which, however, can be corrected.

Clinical thermoluminescence dosimetry: how do expectations and results compare?

Thermoluminescence dosimetry (TLD) for radiotherapy treatment verification is performed in the Prince of Wales Hospital in Sydney for a wide range of applications: (A) to determine the dose in difficult treatment geometries, (B) to record the dose to critical organs, and (C) to monitor special treatments such as total body irradiation (TBI). TLD measurements were performed with the aim to investigate cases where dose prediction is difficult and not as part of a routine verification procedure. We reviewed 1058 reports of TLD performed during the treatment of 502 patients between 1986 and 1991 to evaluate how the TLD results compare with the dose determined by the treatment plan. Reasons for possible discrepancies should be identified. In 19% of all investigated cases a discrepancy of more than 10% was found between expected and measured doses. The discrepancies could be divided into three groups: (1) errors made in the TLD determination or evaluation, such as placement errors of the TLD chips (21% of all discrepancies); (2) mistakes made during the patient set-up, such as insufficient shielding or inadequate patient immobilisation (30%); (3) inadequate treatment planning and dose calculation procedure, such as wrong inverse square law corrections or errors due to limitations of the two-dimensional treatment planning system used (41% of all). In 8% of all discrepancies the reason remained unclear. A number of changes to treatment plans and modalities (e.g. changed scrotal shield, modified bolus) were introduced due to TLD results. The increasing number of TLD requests per year attests to the value of TLD as a treatment verification method in clinical practice.

Postoperative chemotherapy without radiation in young children with malignant non-astrocytic brain tumours. A report from the Australia and New Zealand Childhood Cancer Study Group (ANZCCSG).

Young children with malignant brain tumours have particularly poor survival and manifest severe sequelae of radiation therapy. A multi-institutional pilot study of post-operative primary chemotherapy for children under 3 years with primitive neuroectodermal tumours (PNET) or ependymoma was initiated in 1987. The chemotherapy protocol comprised carboplatin, vincristine and the "eight drugs in 1 day" regimen. Radiation was recommended only if tumour progression or recurrence was documented. A total of 14 patients between 5 and 36 months of age were enrolled. Seven had supratentorial tumours (PNET, pinealoblastoma, intracranial retinoblastoma) with multiple predictors of adverse outcome. Four of these responded to initial chemotherapy but subsequently progressed and all had died by 16 months from diagnosis. The seven patients with infratentorial tumours (three medulloblastomas, four ependymomas) had more favourable predictors of outcome: no meningeal dissemination and gross macroscopic resection in six of the seven cases. One patient progressed rapidly and died within 5 months. The other six are alive at 37-57 months from diagnosis. Four are in continuous complete remission at 57, 51, 41 and 37 months, respectively from the time of their tumour resection. One is described as having stable disease with a persistent radiographic lesion at 41 months from diagnosis. One has relapsed on two occasions and is the only surviving patient to have been irradiated. Intelligence scores for the six long-term survivors have thus for remained within the normal range. It is suggested that some infants with standard-risk ependymoma and, possibly, medulloblastoma may be cured without radiation therapy.