Adjuvant therapy for rectal cancer can no longer be ignored.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
M B Barton
Publications and source records attributed to M B Barton.
Osteolymphoma (primary bone lymphoma): an Australian review of 70 cases. Australasian Radiation Oncology Lymphoma Group (AROLG).
BACKGROUND: To examine prognostic factors, treatment outcomes and design future studies for Osteolymphoma (OL)--also known as primary bone lymphoma. METHODS: Between 1979 and 1993, 70 patients with OL were treated in nine Australian centres. The effect of patient-, tumour-, and treatment-related factors on local control, distant disease-free survival and overall survival were assessed by multivariate analysis. RESULTS: Most patients (94%) received radiotherapy (RT) (median dose 40 Gy) and 56% received chemotherapy. Multifocal disease was present in 20% of patients. The five year rates of overall survival and local control were 59% and 82%. Although there was a trend towards better results with the addition of chemotherapy, on multivariate analysis, there were no factors identified which appeared to impact upon overall and disease-free survival. Among the distant recurrences, there was a high proportion in bone (33%). Six patients suffered pathological fractures after treatment. CONCLUSION: High rates of local control were achieved by RT, but the overall survival remains relatively poor, worse than nodal lymphoma. The natural history of the disease suggests that OL may be a distinct entity, different to nodal lymphomas, so the results of clinical trials in nodal lymphoma may not be relevant to OL. Prospective studies could define the outcome of combined modality therapy and set a benchmark for testing further proposals, as well as improving our knowledge of the clinical features of OL.
Adult↗
Delays in referral for palliative radiotherapy.
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Cost-Benefit Analysis↗
Ten-year risk of false positive screening mammograms and clinical breast examinations.
BACKGROUND: The cumulative risk of a false positive result from a breast-cancer screening test is unknown. METHODS: We performed a 10-year retrospective cohort study of breast-cancer screening and diagnostic evaluations among 2400 women who were 40 to 69 years old at study entry. Mammograms or clinical breast examinations that were interpreted as indeterminate, aroused a suspicion of cancer, or prompted recommendations for additional workup in women in whom breast cancer was not diagnosed within the next year were considered to be false positive tests. RESULTS: A total of 9762 screening mammograms and 10,905 screening clinical breast examinations were performed, for a median of 4 mammograms and 5 clinical breast examinations per woman over the 10-year period. Of the women who were screened, 23.8 percent had at least one false positive mammogram, 13.4 percent had at least one false positive breast examination, and 31.7 percent had at least one false positive result for either test. The estimated cumulative risk of a false positive result was 49.1 percent (95 percent confidence interval, 40.3 to 64.1 percent) after 10 mammograms and 22.3 percent (95 percent confidence interval, 19.2 to 27.5 percent) after 10 clinical breast examinations. The false positive tests led to 870 outpatient appointments, 539 diagnostic mammograms, 186 ultrasound examinations, 188 biopsies, and 1 hospitalization. We estimate that among women who do not have breast cancer, 18.6 percent (95 percent confidence interval, 9.8 to 41.2 percent) will undergo a biopsy after 10 mammograms, and 6.2 percent (95 percent confidence interval, 3.7 to 11.2 percent) after 10 clinical breast examinations. For every 100 dollars spent for screening, an additional 33 dollars was spent to evaluate the false positive results. CONCLUSIONS: Over 10 years, one third of women screened had an abnormal test result that required additional evaluation, even though no breast cancer was present. Techniques are needed to decrease false positive results while maintaining high sensitivity. Physicians should educate women about the risk of a false positive result from a screening test for breast cancer.
Adult↗
The doses received by the breast during mantle radiotherapy.
PURPOSE: To accurately measure the dose received by the breast during mantle radiotherapy. METHODS AND MATERIALS: A phantom containing lung-equivalent material was used to measure the doses received by the breast during mantle radiotherapy given by anterior and posterior opposing fields. These were measured using thermoluminescent dosimeters and compared with point dose calculations obtained by computer planning. RESULTS: Most of the breast lies under the lung shields or inferior to the mantle field, but the upper outer quadrant of the breast remains unshielded. In the unshielded areas of the breast, the average dose measured was nearly 13% higher than the dose prescribed at the central axis. In the shielded parts of the breast, the average measured dose was nearly 10% of the dose prescribed at the central axes, decreasing from 18% superiorly to 4% inferiorly. The posterior field contributed 45% to the dose in the breast, even though doses were prescribed at the midplane. The computer calculations systematically varied from measured doses by up to 35%, becoming less accurate towards the inferior edge of the field. CONCLUSIONS: In a conventional course of mantle radiotherapy (for example, 36 Gy in 20 fractions), most of the breast is shielded but will receive a dose of 3-4 Gy, higher than expected largely due to internally scattered radiation passing through the lungs from the posterior field. Computer dose calculations may poorly reflect actual off-axis doses in large fields with complex shielding, containing inhomogeneous tissue.
Breast↗
The role of the gallium scan in primary extranodal lymphoma.
UNLABELLED: The purpose of this study was to examine the factors influencing gallium scan positivity for patients with primary extranodal lymphoma and to examine the role of the gallium scan in staging the disease and assessing response to initial treatment. METHODS: Ninety-two patients with extranodal lymphoma who had a gallium scan were reviewed. The influences of tumor site, size, grade and the presence of clinically detectable disease after biopsy on the rate of gallium scan positivity were analyzed. The role of the gallium scan in staging and selecting treatment was assessed. Nineteen patients had a gallium scan to assess their response to treatment, and its predictive value was reviewed. RESULTS: The overall gallium scan positivity (sensitivity) rate was 70%. This rate was low in patients whose extranodal lymphoma occurred in skin, intestine and testis, or was low grade (0%-25%). When these patients were excluded, the rate rose to 88%. Gallium scan positivity was not related to the presence of clinically detectable disease after biopsy and there was insufficient data about tumor size to determine a relationship. The gallium scan increased the disease stage in six patients (7%) and changed the initial treatment in six patients (7%). The gallium scan became negative in 15 (79%) of those patients who had a gallium scan to assess their response to treatment. All but two of these patients remain alive with a median follow-up of 3.75 yr. CONCLUSION: The gallium scan was rarely positive for patients with skin, intestinal, testicular and low-grade lymphomas, but was otherwise comparable to lymphoma arising in lymph nodes. The result affected staging or treatment in seven patients (8%). After treatment, an initially-positive gallium scan usually became negative, a conversion associated with a favorable outcome.
Citrates↗
Does waiting time affect the outcome of larynx cancer treated by radiotherapy?
AIM: To determine the impact of waiting for radiotherapy on local control in early larynx cancer treated by radiotherapy alone. METHODS: Records of patients with T1 and T2, N0-2 larynx cancer were examined at three radiotherapy centres. Waiting time was defined in three ways, (1) time from biopsy to radiotherapy, (2) time from presentation to radiation department to start of radiotherapy and (3) the minimum of (1) and (2). Time to relapse was the major end point. RESULTS: There were 581 patients with a median follow-up of 6.8 years. Stage distribution was as follows: T1, 370; T2a, 106; T2b, 94; T2 unspecified, 11; N0, 563; N+, 18. Median times from biopsy, presentation and minimum time to treatment were 24, 16 and 15 days, respectively. Ninety percent of minimum waiting times were < or = 31 days. The median dose was 61 Gy in a median of 30 fractions over a median 46 days. Local recurrence occurred in 126 patients. The actuarial recurrence free rate at 5 years was 77% (SE 2%). In a multivariate analysis the significant predictors of relapse were higher T stage, longer treatment duration and increasing field area. Waiting time was not significantly associated with local relapse. CONCLUSION: This study did not show longer waiting time to be a significant predictor of relapse in early larynx cancer. Other end-points which are relevant, such as quality of life, have not been examined. Longer treatment times were significantly associated with relapse.
Adult↗
Health outcomes and radiation therapy: a new era of competition.
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Health Care Costs↗
Preliminary results of combined chemotherapy and radiotherapy for non-AIDS primary central nervous system lymphoma. Trans-Tasman Radiation Oncology Group (TROG).
OBJECTIVES: To assess the results and toxicity of a regimen of combined chemotherapy and radiotherapy for patients with non-AIDS-related primary central nervous system lymphoma. DESIGN: Prospective assessment of patients treated with intravenous methotrexate followed by cranial irradiation between 1 January 1991 and 31 July 1995. PATIENTS AND SETTING: Patients attending nine Australian and New Zealand centres who were eligible and gave informed consent. MAIN OUTCOME MEASURES: Probability of survival at two years, and acute toxicity. RESULTS: Twenty-four patients were treated. Their probability of survival at two years was 70% (95% confidence interval [CI], 45%-95%). The acute toxicity of the regimen was minimal in most cases, but one patient died of treatment-related neutropenia and subsequent sepsis. Two patients showed progression of pre-existing short term memory disturbance, without evidence of recurrent lymphoma. CONCLUSIONS: Combined-modality therapy improves survival in patients with non-AIDS-related primary central nervous system lymphoma, at least in the short term, relative to radiotherapy alone. The combined regimen resulted in only moderate treatment-related morbidity. Longer follow-up is required for a more accurate estimate of late effects and long-term survival prospects.
Antimetabolites, Antineoplastic↗
Primary bone lymphoma (osteolymphoma).
Seventeen patients with primary lymphoma of bone are reviewed. In 15 patients treated with radical radiotherapy, local progression or recurrence occurred in four. The results support the use of radiotherapy alone, using doses of 45-50 Gy. Although small numbers prevent firm conclusions, the inclusion of the whole bone or regional nodes in the irradiated volume did not appear to improve results. Eight patients received systemic chemotherapy with no apparent improvement in rates of relapse. Two patients suffered pathological fractures after radiotherapy in the absence of recurrence at the fracture site; however, osteomyelitis, older age, Paget's disease, high-dose prednisolone and whole-bone radiotherapy may have added to the risk of fracture. Because of the many complex names and selection criteria applied to this condition, literature searching and comparison between studies was difficult. The simple term osteolymphoma is proposed, consistent with other primary bone conditions.
Adult↗
Oropharyngeal cancer in the elderly.
PURPOSE: The poor prognosis of elderly patients in many cancers may be due to less thorough investigation and less aggressive treatment because of the perception that radical treatment will be poorly tolerated and that elderly patients have a limited life expectancy. We wished to assess whether older age is associated with (a) less radical treatment, (b) poorer outcome, or (c) greater toxicity, after adjusting for other possible contributing factors. METHODS AND MATERIALS: A retrospective study of patients with loco-regional oropharyngeal cancer treated between January 1980 and December 1985 was conducted. Patients were treated with radiotherapy, surgery, chemotherapy, or combinations. Cox regression was used to assess age effects while allowing for the influence of other factors. RESULTS: Eighty-eight patients were treated radically and 16 palliatively. Treatment intent (radical or palliative) did not appear to be related to age, before (p = 0.42) or after adjusting for other factors (p = 0.34). In a selected group of 86 radically treated patients ages ranged from 33 to 85 (median 60). There were 35 loco-regional failures and 58 deaths (38 related to oropharyngeal cancer). Older patients were prescribed and received lower doses of radiation. However, older age was not related to the risk of loco-regional recurrence (p = 0.96) or shorter survival (p = 0.67), and was not associated with duration of treatment interruption or severity of toxicity after adjustment for prognostic factors. There was some suggestion of a higher risk of recurrence with increasing age for patients under 70 years but with a risk for patients over 70 at least equal to that of the youngest group. Elderly patients in our study may have been a selected group. CONCLUSION: Older patients with loco-regional oropharyngeal cancer, or at least a subset of them, appear to be able to tolerate radical courses of radiotherapy, and to have similar outcomes as do younger patients.
Adult↗
Split-course accelerated therapy in head and neck cancer: an analysis of toxicity.
PURPOSE: To retrospectively assess a protocol of split-course accelerated radiation therapy (SCAT) for selected head and neck cancers. METHODS AND MATERIALS: SCAT consisted of 1.8 Gy per fraction administered twice daily with a minimum gap between fractions of 6 h. The treatment protocol prescribed an initial 16 fractions followed by a planned 5 to 12 day break, and then a further 20 to 22 fractions for a total dose ranging from 64.8 to 72 Gy delivered in 5 to 6 weeks. RESULTS: Twenty-eight patients received SCAT for histologically confirmed head and neck cancer between January 1987 and August 1991. All patients were followed up until December 1, 1993. The mean potential follow-up time was 4.2 years (range: 2.9-6.2 years). All patients completed the treatment protocol. Thirteen tumors were laryngeal in origin, eight hypopharyngeal, four paranasal sinus, and three oropharyngeal. There were no Stage I, three Stage II, nine Stage III, and 12 Stage IV tumors. Four tumors were not staged (two paranasal sinus cancers and two surgical recurrences). Early and late toxicities were moderate to severe. Confluent mucositis was experienced by 27 of the 28 patients (96%). One patient required a prolonged midtreatment break of 24 days. Nine patients (32%) required narcotic analgesia for pain relief. Eleven patients (39%) required hospitalization for nasogastric feeding or pain control. The median length of hospital stay was 14 days (range 7-98 days). The actuarial rate of severe late toxicity at 3 years was 47% (standard error (SE) = 13%). A complete tumor response was achieved in 86% of patients. The actuarial local control rate at 3 years was 43% (SE = 11%) and the actuarial survival rate at 3 years was 25% (SE = 8%). CONCLUSION: Given the encouraging complete response rate and local control for such advanced tumors, SCAT for locoregionally advanced tumors merits further investigation. However, because of the significant late toxicity observed, the total dose, interfraction interval, and fractionation technique used should be reconsidered.
Actuarial Analysis↗
The meaning of overseas specialist training.
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Australia↗
Radiation therapy: are we getting value for money?
The aim of this study was to examine the long term cost effectiveness of radiotherapy (RT) in the treatment of cancer at the Department of Radiation Oncology, Westmead Hospital, from its inception in 1980 to December 1993. A Kaplan-Meier survival curve was constructed for all patients treated by RT during the study period. The area under this curve represented the average survival. The total number of life years was calculated by multiplying the number of patients by the average survival. Costing for one RT treatment field had previously been derived. The cost included capital costs, building costs and overheads as well as labour, goods and services, and operating costs. The cost per field was multiplied by the total number of fields given each year and the yearly total summed to give the total cost. The total cost was divided by the number of life years to give a cost per life year. An overall percentage survival gain was estimated from departmental results and the literature. Cost per life year gained (LYG) was derived by dividing the cost per life year by the percentage survival gain. Sensitivity analysis was performed with best- and worst-case survival scenarios, and high and low cost per field estimates. A total of 9868 patients were treated by radiotherapy between January 1980 and December 1993. Median follow-up was 4.2 years. Median survival was 2 years. The 5- and 10-year survival rates were 35% and 22%, respectively. The area under the survival curve (the average survival) was 4.75 years. The total number of life years of survival was thus 4.75 x 9868 = 46,873. In 1993, the cost per field was $71.52 (Australian dollars). The total number of fields treated in the study period was 758,097. Hence, the total cost in 1993 dollars was $54,219,097. The survival gain (excluding skin cancer) with RT was 16.1% and the cost/LYG was $7186. Sensitivity analysis of best and worst case scenarios gave costs/LYG of $3920 and $15,632 respectively. Efficient resource allocation can be aided by examining the relative cost-effectiveness of different prevention and treatment strategies. RT is shown to have a lower cost/LYG than other accepted treatments in current practice. Other major treatment modalities should be subjected to the same scrutiny of cost effectiveness as has been applied to RT.
Australia↗
Breast cancer following treatment for Hodgkin's disease: the need for screening in a young population. Australasian Radiation Oncology Lymphoma Group (AROLG)
Several recent publications have highlighted the issue of an increased risk of breast cancer in women treated with radiotherapy, chemotherapy, or combined modality therapy for Hodgkin's disease. The risk is greatest in women 30 years or younger at the time of treatment. In the Australasian Radiation Oncology Lymphoma Group database, 60% of women fell into this age category. This article reviews the available data pertaining to induction of breast cancer by radiotherapy for Hodgkin's disease. Breast examination should now be an integral part of the long term follow up for these women. There is also a case for the use of screening mammography. Any breast mass developing subsequent to treatment for Hodgkin's disease should be regarded with a high index of clinical suspicion and, accordingly, biopsies should be performed in the majority of cases, even when mammography is negative.
Adult↗
Influence of radiotherapy treatment time on control of laryngeal cancer: comparisons between centres in Manchester, UK and Toronto, Canada.
A comparison has been made of the influence of treatment time on tumour control rates for 496 (T2 and T3) larynx cancer cases in Manchester, UK and 1001 (T1-T4) cases in Toronto, Canada. Both series of patients were treated in fairly short overall times, commonly 3 weeks in Manchester and 4-5 weeks in Toronto. All the tumour control data were analysed using the same method to obtain values of fitted dose, fractionation and time parameters. The analysis showed the following. (a) Differences between the total combined (T2 + T3) data sets from the two centres, fitted using direct analysis and the LQ model incorporating a parameter for overall treatment time, were not significant (p = 0.17) and close similarity in control rates was observed using treatment regimens common to both series. (b) The Manchester series over 9-41 days and the Toronto series over 14-84 days are both consistent in showing for (T2 + T3) tumours the presence of a mean time factor of 0.6-0.8 Gy/day required to abrogate the decrease in tumour control concomitant with an increase in overall treatment time from the minimum the maximum employed in each series. (c) When a parameter was included in the model to test for the possible presence of a lag period before the time factor became operative, the lag was not significant for the Toronto data, in contrast to a significant lag for the Manchester data alone (T2 + T3 data).(ABSTRACT TRUNCATED AT 250 WORDS)
Carcinoma, Squamous Cell↗
The effect of treatment time and treatment interruption on tumour control following radical radiotherapy of laryngeal cancer.
A significant effect of overall treatment time on local control was found in a retrospective review of 1012 radically irradiated squamous cell carcinomas of the larynx. The actuarial local relapse free rate (LRFR) at 5 years for the whole group was 59%. The effect of treatment time on local control was modelled to the linear-quadratic equation. Using logistic regression analysis treatment time and dose were significant (p = 0.008 and p = 0.04, respectively). When the analysis was adjusted for the influence of stage and laryngeal subsite treatment time remained a significant prognostic factor (p = 0.02). The derived value of gamma/alpha was 0.7 Gy/day and when adjusted for stage and sub-site 0.8 Gy/day. This equates to a dose increment to maintain iso-effective local control of 0.64 Gy/day and 0.73 Gy/day respectively for daily fractions of 2.5 Gy and an assumed alpha/beta for tumour of 25 Gy. To provide an estimate of the clinical impact of treatment interruptions not compensated for by dose escalation a Cox regression was performed. Significant variables were T stage, N stage, sex, total dose and total length of treatment interruption. Using the proportional hazard model it was calculated that each day of treatment interruption resulted in an increase in the hazard of local relapse by 4.8% (p = 0.006). Based on our data it was calculated that this would result in a decrease in local control of 1.4% for each day of uncompensated treatment interruption.
Canada↗
Improving influenza vaccination performance in an HMO setting: the use of computer-generated reminders and peer comparison feedback.
We evaluated a program for improving influenza immunization performance in a health maintenance organization (HMO). The HMO implemented several interventions successively from 1984-87: a postcard reminder to members at high risk for complications of influenza, a computer-generated reminder to the physician at the time of any primary care visit by high-risk patients, performance feedback to chiefs of service, and, finally, retrospective feedback to each physician comparing his/her performance with that of the other physicians. We examined immunization rates for a group of members older than age 65, a high-risk group under age 65, and a group of diabetic members who had not been subject to the reminders (vs a group who had been covered by the program). Vaccination rates were increased in those diabetic members who received reminders. Nevertheless, among members younger and older than age 65 whose experience was observed over three flu seasons, a significant increase in vaccination rates was not achieved until physician feedback was added to the program. We conclude that each element of the reminder and feedback program has contributed to the overall increase in vaccination rates at the HMO and that effective ongoing influenza immunization programs can be implemented in practice settings with appropriate systems support.
Aged↗