A racial bias test with tertiary cancer centre employees: why anti-racist measures are required for First Nations Australians cancer care equity.

Objective To examine implicit bias in employees at a cancer centre using an Australian race (Aboriginal-white) Implicit Association Test (IAT), in an attempt to understand a potential factor for inequitable outcomes of First Nations Australians cancer patients. Methods All employees at an Australian cancer centre were invited to take part in a web-based, cross-sectional study using an Australian race IAT. The results were analysed using Welch t-tests, linear regression and ANOVA. Results Overall, 538/2871 participants (19%) completed the IAT between January and June 2020. The mean IAT was 0.147 (s.d. 0.43, P < 0.001, 95% CI 0.11-0.18), and 60% had a preference for white over First Nations Australians. There was no significant mean difference in IAT scores between sub-groups of gender, age or clinical/non-clinical employees. 21% of employees (95% CI 17.65-24.53) had moderate to strong preference for white over First Nations Australians, compared to 7.1% with moderate to strong preference for First Nations over white Australians (95% CI 5.01-9.09). Conclusions Inequitable cancer survival for First Nations patients has been well established and cancer is now the leading cause of mortality. This paper documents the presence of racial bias in employees at one cancer centre. We argue that this cannot be understood outside the history of colonialism and its effects on First Nations Australians, healthcare workers and our society. Further research is required to evaluate measures of racism, its effect on health care, and how to eliminate it.

Comparison of CT and positron emission tomography/CT coregistered images in planning radical radiotherapy in patients with non-small-cell lung cancer.

Imaging with F-18 fluorodeoxyglucose positron emission tomography (PET) significantly improves lung cancer staging, especially when PET and CT information are combined. We describe a method for obtaining CT and PET images at separate acquisitions, which allows coregistration and incorporation of PET information into the radiotherapy (RT) planning process for non-small-cell lung cancer. The influence of PET information on RT planning was analysed for 10 consecutive patients. Computed tomography and PET images were acquired with the patient in an immobilization device, in the treatment position. Using specially written software, PET and CT data were coregistered using fiducial markers and imported into our RT planning system (Cadplan version 6). Treatment plans were prepared with and without access to PET/CT coregistered images and then compared. PET influenced the treatment plan in all cases. In three cases, geographic misses (gross tumour outside planning target volume) would have occurred had PET not been used. In a further three cases, better planning target volume marginal coverage was achieved with PET. In four patients, three with atelectasis, there were significant reductions in V20 (percentage of the total lung volume receiving 20 Gy or more). Use of coregistered PET/CT images significantly altered treatment plans in a majority of cases. This method could be used in routine practice at centres without access to a combined PET/CT scanner .

Display of positron emission tomography with Cadplan.

Recent clinical experience at Peter MacCallum Cancer Institute (PMCI) with the use of unregistered Positron Emission Tomography (PET) images for radiotherapy target marking in the lung suggests that co-registered PET images would be invaluable. PMCI has three radiotherapy treatment planning systems but none of them currently is able to display or co-register PET images with Computed Tomography (CT) images. This paper details the approach taken to display co-registered PET images with the CADPLAN treatment planning system. CT Image files are normally transferred to Cadplan by DICOM transfer, but the Cadplan DICOM server will not receive (has no presentation context for) PET images. The fundamental design of the CADPLAN system envisages display of only a single image dataset, which must be a CT scan for planning reasons. The problem of data transfer is crudely solved by File Transfer Protocol (FTP) over the network. Fortunately the multislice format of the PET image files makes individual transfer manageable. A menu based C program running at the same time as Cadplan is invoked to sample the DICOM PET Image and create multiple Cadplan CART image format files that are co-registered with each existing transverse CT slice. With the Cadplan in contour mode, the program allows the co-registered PET images to be swapped in and out of the image section of the CART files promptly, while keeping the contour information. This allows radiotherapy target volumes to be marked using transverse PET emission images, and effectively circumvents the design constraints prohibiting the display of more than one image set. Contours can be over-laid for review on reconstructed sagittal or coronal views of CT or PET images constructed using the standard Cadplan tools. Co-registration is facilitated by identical positioning with the aid of lasers and FDG loaded fiducial markers on the PET scanner and CT couch. A polyurethane cast fixed with EFFILOCK is used to ensure identical patient orientation on the CT and PET couches. Since both imaging modalities are without significant geometric distortion the co-registration is then simply a translation. PET transmission images can be used for co-registration verification. The practical implementation of display of PET images with CADPLAN has enabled us to begin a trial of 10 patients, the results of which will be reported separately.

Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer.

PURPOSE: To determine the maximum-tolerated dose of tirapazamine when combined with cisplatin and radiation in patients with T3/4 and/or N2/3 squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The starting schedule was conventionally fractionated radiotherapy (70 Gy in 7 weeks) with concomitant cisplatin 75 mg/m2 and tirapazamine 290 mg/m2 (before cisplatin) in weeks 1, 4, and 7 and tirapazamine alone 160 mg/m2 three times a week in weeks 2, 3, 5, and 6. Positron emission tomography scans for tumor hypoxia (18F misonidazole) were performed before and during radiotherapy. RESULTS: We treated 16 patients with predominantly oropharyngeal primary tumors, including 10 patients with T4 or N3 disease. Febrile neutropenia occurred toward the end of radiotherapy in three out of six patients treated on the initial dose level. Two of these patients also developed grade 4 acute radiation reactions. Another 10 patients were treated with the same doses, but the week 5 and week 6 tirapazamine doses were omitted. This resulted in less neutropenia and only one dose-limiting toxicity (DLT) (febrile neutropenia), and eight out of 10 patients completed treatment without any dose omissions. In these 10 patients, the acute radiation toxicities were not obviously enhanced compared with chemoradiotherapy regimens using concurrent platinum and fluorouracil. 18F misonidazole scans detected hypoxia in 14 of 15 patients at baseline, with only one patient having detectable hypoxia at the end of treatment. With a median follow-up of 2.7 years, the 3-year failure-free survival rate was 69% (SE, 12%), the 3-year local progression-free rate was 88% (SE, 8%), and the 3-year overall survival rate was 69% (SE, 12%). CONCLUSION: DLT was due unexpectedly to febrile neutropenia, which could be overcome by omitting tirapazamine in weeks 5 and 6. The combination of tirapazamine, cisplatin, and radiotherapy resulted in remarkably good and durable clinical responses in patients with very advanced head and neck cancers. It warrants further investigation.

Radiation with concurrent late chemotherapy intensification ('chemoboost') for locally advanced head and neck cancer.

The aim of this study was to review our experience with a treatment regimen that combined conventionally fractionated radiation therapy (70 Gy over 7 weeks) with chemotherapy (cisplatin and fluorouracil), given concurrently in the last 2 weeks of radiation therapy in patients with previously untreated advanced squamous cell cancer of the head and neck region.Twenty-eight patients, all but two having UICC stage IV disease, were treated at the Peter MacCallum Cancer Institute between November 1995 and April 1998. Planned chemotherapy consisted initially of continuous infusion at 10 mg/m(2) per day of cisplatin and 400 mg/m(2) per day of fluorouracil on days 1-5 of weeks 6 and 7 of a conventionally fractionated course of radiotherapy. After the first 14 patients, the dose of fluorouracil was reduced to 360 mg/m(2) per day because of acute toxicity.36.8 months), with an estimated 50% surviving at 2 years (CI, 29-71%). Sixteen patients (57%) developed confluent mucositis and 11 (39%) developed patchy mucositis. The median duration of mucositis for these 27 patients was 1.5 months. Seventeen patients (61%) required nutritional support for a median duration of 1.4 months. Fourteen patients (50%) had grade three skin reactions, and 12 (43%) had one or more other significant (Grade 3) toxicities, predominantly infective. Grade 3 late toxicity has been observed in three patients to date (three xerostomia, including one with severe depression), and one patient had chronic ulceration of the oral tongue (grade 4). This chemoradiation regimen achieved an excellent complete response rate and good locoregional control at 2 years in patients with a poor initial prognosis. Acute toxicity was significant but manageable. The regimen offers an alternative to surgery and postoperative radiation therapy in locally advanced head and neck cancer.

Adjuvant high-dose rate brachytherapy with or without external beam radiotherapy post-hysterectomy for endometrial cancer.

The purpose of this study was to evaluate patient selection, local control, survival and late toxicity of posthysterectomy adjuvant radiotherapy and compare adjuvant external beam therapy and high-dose rate (HDR) brachytherapy versus HDR brachytherapy alone. A retrospective analysis was performed on a series of 225 patients with endometrial cancer treated with external beam radiotherapy and HDR brachytherapy or HDR brachytherapy alone posthysterectomy from 1985 to June 1993. Of these 225 patients, 82 received external beam radiotherapy and brachytherapy and 143 received brachytherapy alone. The HDR fraction size was 8.5 Gy prescribed to the mucosal surface; two fractions were given after external beam and four fractions if brachytherapy alone was used. The median follow-up was 6.9 years. The patients who received combined external beam and brachytherapy had higher stage and grade tumors. The survival outcome was similar for either group when matched for stage. Overall relapse-free survival at five years was 96% and 81%, respectively for brachytherapy alone and combined adjuvant therapy. Pelvic recurrence was seen in 2.7% of patients. Toxicity was more common with external beam radiotherapy and brachytherapy compared to brachytherapy alone (45.1% vs 23.1%, P = 0.003). However, moderate or severe toxicity was rare but again was more common in the combined radiotherapy group (8.5% vs 2.1%, P = 0.04). There was a non-significant trend to increased toxicity after lymphadenectomy and external beam radiotherapy compared with patients who did not have a staging lymphadenectomy prior to external beam radiotherapy (62% vs 38%, P = 0.16). Adjuvant radiotherapy can be individualized and be based upon the information provided by the pathological specimens, which excluded external beam radiotherapy if a lymphadenectomy was performed and there was no evidence of extra-uterine disease. This study found more toxicity associated with adjuvant radiotherapy compared with other studies, but this may reflect different reporting criteria. There was more toxicity related to external beam radiotherapy and brachytherapy compared to brachytherapy alone. The two HDR brachytherapy protocols used in this series appear effective and safe.

High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer.

PURPOSE: To evaluate the outcome of post-hysterectomy adjuvant vaginal high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: A retrospective analysis was performed on a series of 143 patients with endometrial cancer treated with HDR brachytherapy alone post-hysterectomy from 1985 to June 1993. Of these patients, 141 received 34 Gy in four fractions prescribed to the vaginal mucosa in a 2-week period. The median follow-up was 6.9 years. Patients were analyzed for treatment parameters, survival, local recurrence, distant relapse, and toxicity. RESULTS: Five-year relapse free survival and overall survival was 100% and 88% for Stage 1A, 98% and 94% for Stage IB, 100% and 86% for Stage IC, and 92% and 92% for Stage IIA. The overall vaginal recurrence rate was 1.4%. The overall late-toxicity rate was low, and no RTOG grade 3, 4, or 5 complications were recorded. CONCLUSION: These results are similar to reported international series that have used either low-dose-rate or HDR brachytherapy. The biological effective dose was low for both acute and late responding tissues compared with some of the HDR brachytherapy series, and supports using this lower dose and possibly decreasing late side-effects with no apparent increased risk of vaginal recurrence.

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients.

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.

High-dose-rate brachytherapy in the management of carcinoma of the cervix: an 8-year Australian experience.

High-dose-rate brachytherapy was introduced at this hospital for the treatment of gynaecological malignancy in 1985. A retrospective analysis was performed of 103 patients with cervix cancer treated with this technique from 1985 to June, 1993. The patients were analyzed for treatment parameters, response, survival, relapse and toxicity. Five-year survival was 78% for Stage 1B, 72% for Stage 2A, 42% for Stage 2B and 29% for Stage 3B. The severe late toxicity rate was 4.9%. These results are similar to reported international series that have used either low-dose-rate or high-dose-rate brachytherapy.

Use of the comet assay to investigate possible interactions of nitric oxide and reactive oxygen species in the induction of DNA damage and inhibition of function in an insulin-secreting cell line.

We have previously used the comet assay to demonstrate that the nitric oxide donor 3-morpholinosydnonimine (SIN-1) produces DNA damage in rat islets of Langerhans and in the SV40-transformed insulin-secreting hamster cell line, HIT-T15. Damage is not prevented by the addition of superoxide dismutase (SOD). In the present study, we have compared SIN-1, which generates nitric oxide, superoxide anion and hydrogen peroxide, with two other nitric oxide donors, S-nitrosoglutathione (GSNO) and the tetra-iron-sulphur cluster nitrosyl, Roussin's black salt (RBS). We have used the comet assay as a highly sensitive method to measure DNA-damaging ability, and also measured inhibition of DNA synthesis and inhibition of insulin secretion. We have examined the effect of SOD and catalase on each of these endpoints in HIT-T15 cells following a 30-min exposure to the compounds (24 h for DNA synthesis). All compounds produced a significant dose-dependent increase in strand-breakage formation and all inhibited DNA synthesis and glucose-stimulated insulin secretion. RBS was the most potent. SOD did not reduce the responses observed with any of the compounds. Catalase largely prevented DNA strand breakage, inhibition of DNA synthesis and inhibition of insulin secretion by SIN-1, but had no effect on responses to GSNO or RBS. Addition of SOD together with catalase gave no greater protection against SIN-1 than catalase alone. The nitric oxide and superoxide anion produced by SIN-1 are though to combine to form highly reactive peroxynitrite. In addition, H2O2 may be formed in the presence of SIN-1 and may form hydroxyl radical in the presence of a transition metal, such as Fe2+. It appears that in insulin-secreting cells, the effects of SIN-1 are largely mediated by this latter mechanism. In contrast, GSNO and RBS appear to act by a different mechanism, not overtly involving reactive oxygen species. GSNO and H2O2 show no significant interaction in the induction of DNA strand breaks. Both nitric oxide and H2O2 are effective, directly or indirectly, as DNA strand-breaking agents, inhibitors of DNA synthesis and inhibitors of insulin secretion.

Lymphocyte predominant Hodgkin's disease: a clinicopathologic comparative study of histologic and immunophenotypic subtypes.

PURPOSE: To compare the clinicopathologic features of the histologic and immunophenotypic subgroups of lymphocyte predominant Hodgkin's disease. METHODS AND MATERIALS: A retrospective review of 64 patients with lymphocyte predominant Hodgkin's disease treated at the Peter MacCallum Cancer Institute, Melbourne, was performed. Nodular and diffuse histological subtypes were confirmed by review of hematoxylin and eosin paraffin sections. Immunophenotyping with monoclonal antibodies L26 (B-cell origin) and Leu M1 (Hodgkin's phenotype) were available in 36 patients. RESULTS: The estimated freedom from progression and estimated overall survival at 10 years was 74% standard error (SE 5.8%) and 85% (SE 5.2%), non-Hodgkin's respectively. There were no significant differences in freedom from progression or overall survival when nodular and diffuse histology were compared. Similarly the presence of B-cell markers did not influence prognosis. There was only one case of secondary non-Hodgkin's lymphoma. CONCLUSION: Our results are consistent with major reported series displaying no differences between any of the subgroups of lymphocyte predominant Hodgkin's disease.