Developments in radiotherapy

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a review of future developments in radiotherapy and an estimate of the potential benefits of improved radiotherapy in Sweden. The conclusions reached from this review can be summarized as: Successively better knowledge is available on dose-response relationships for tumours and normal tissues at different fractionation schedules and treated volumes. Optimization of dose levels and fractionation schedules should improve the treatment outcome. Improved treatment results may be expected with even more optimized fractionation schedules. The radiosensitivity of the tumour is dependent on the availability of free oxygen in the cells. The oxygen effect has been studied for a long time and new knowledge has emerged, but there is still no consensus on the best way to minimize its negative effect in the treatment of hypoxic tumours. Development in imaging techniques is rapid, improving accuracy in outlining targets and organs at risk. This is a prerequisite for advanced treatment planning. More accurate treatment can be obtained using all the computer techniques that are successively made available for calculating dose distributions, controlling the accelerator and multileaf collimator (MLC) and checking patient set-up. Optimized treatment plans can be achieved using inverse dose planning and intensity modulation radiation therapy (IMRT). Optimization algorithms based on biological data from clinical trials could be a part of future dose planning. New genetic markers might be developed that give a measure of the radiation responsiveness of tumours and normal tissue. This could lead to more individualized treatments. New types of radiation sources may be expected: protons, light ions, and improved beams (and compounds) for boron neutron capture therapy (BNCT). Proton accelerators with scanned-beam systems and energy modulation give good dose distribution. The results reported with carbon ions from Japan and Germany are promising. An interesting development is to verify the dose and position for the irradiated volume with PET on line. Safer margins are obtained and the treatment volume can thus be limited. Very large accelerators are needed to accelerate the carbon ions. Still, it should be possible to keep the costs per patient at the same level as those for other types of advanced radiotherapy, since far fewer treatments per patient are needed. It might also be possible to treat new groups of patients. Increased resources are needed to introduce all the currently available techniques. New types of particle accelerators require large investments and a new structure of radiotherapy in Sweden

Accrual rate-limiting factors in a Swedish randomised ductal carcinoma in situ (DCIS) trial - a demographic study

In the last two decades the introduction of mammographic screening in the Western world has increased the number of diagnosed ductal carcinomas in situ (DCIS) considerably. In situ carcinoma of the breast is considered a heterogeneous disease, the natural history of which is not well known. Thus, appropriate treatment needs to be established. For this reason, a randomised trial studying the effect of breast conserving operation with or without postoperative radiotherapy was instituted in Southern Sweden in 1987. The aim of the present study was to assess patient accrual, identify limiting factors, and evaluate possible ways to influence these factors in order to increase patient accrual. Between 1987 and 1992, 331 patients had been registered with DCIS in the Regional Tumour Registry, 96 of which had been randomised. All 331 were subjected to chart review studying clinical data, mammography reports, cytology and pathology reports to identify inclusion and exclusion criteria according to the design of the trial. It was found that 5% (18/331) had an incorrect diagnosis of DCIS. According to the trial protocol 52% were not eligible (162/313). Fifty-eight per cent (n=88) of the 151 eligible patients had been correctly randomised. The most common reason for exclusion was lesion size. In 21% (66/313) the lesion was 'too large'. Several other limiting factors were identified such as in cytological and pathological definitions and reports, lack of information/awareness in certain physicians, patient reluctance to participate, which in turn may be influenced by the previous factor. With increased information to participating hospitals and considering the above given facts it should be possible to increase accrual from the 28% noted in the present consecutive demographic study to at least one-third of the diagnosed cases of DCIS

Early oral contraceptive use and breast cancer among premenopausal women : Final report from a study in Southern Sweden

In southern Sweden during the 1960s, women began to use oral contraceptives (OCs) extensively at a young age. This case-control study investigates the relationship between the use of OCs and breast cancer development in women in southern Sweden diagnosed in the early 1980s. The risk for breast cancer after OC use among premenopausal women was modeled, after adjustment was made for age, age at menarche, and age at first full-term pregnancy or parity. Both the duration of OC use before 25 years of age and commencement of OC use at a young age were associated with a significant increase in the risk of breast cancer as well as a significant trend. The duration of OC use before the first full-term pregnancy was associated with an increased risk of breast cancer, but it did not show a significant trend. The total duration of OC use was wealdy, but not significantly, associated with breast cancer development. The odds ratio for women starting OC use before 20 years of age was 5.8 [95% confidence interval (CI), 2.6-12.8]; for women using OCs for >5 years before age 25, it was 5.3 (95% CI, 2.1-13.2); and for women using OCs for ≥8 years before first full-term pregnancy, it was 2.0 (95% CI, 0.8-4.7). In multivariate analyses including the different measurements of OC use, only starting age of OC use was significantly associated with breast cancer. The exposure-response relationship between duration of OC use and risk of breast cancer depended on the age at first use of OCs. Given a fixed duration of OC use, the risk increased with younger starting age of OC use. The findings point to the importance of the early reproductive years as risk determinants for breast cancer after OC use

Survival of children with liver tumours in Europe 1978--1989

Hepatic tumours are rare in childhood. Within the frame of the EUROCARE II study, a total of 328 liver tumours in patients aged 0--14 years were reported during the period 1978--1989. The childhood cancer registries in UK and Germany contributed approximately a third of the cases each. Hepatoblastoma accounted for 71% of cases. The 5-year survival was 36% 95% confidence interval (CI) 28--46%, with no significant difference between the genders. Patients aged 10--14 years did worse, especially boys. Survival improved significantly during the study period. Survival in hepatocellular carcinoma was lower, 20% (95% CI 6--52%), and showed no improvement during the study period

Familial breast and ovarian cancer : a Swedish population-based register study

A cohort of offspring of mothers with breast or ovarian cancer diagnosed in 1958-1993 was established using Swedish population-based registers. The children (n = 158,041) were born between 1941 and 1993, and their cancer incidence was followed between 1961 and 1993. A total of 3,257 tumors in 3,102 children were found. Observed numbers of cases were compared with expected numbers based on national calendar year-, age-, and sex-specific incidences. For daughters of women with breast cancer, the standardized morbidity ratios for being diagnosed with breast cancer and ovarian cancer before age 50 years were 1.99 (95% confidence interval (CI): 1.86, 2.14) and 1.28 (95% CI: 1.05, 1.54), respectively. The corresponding figures for daughters of women with ovarian cancer were 1.79 (95% CI: 1.55, 2.07) and 2.38 (95% CI: 1.77, 3.12). The risks were raised if the mother's cancer was diagnosed at a young age, the mother had multiple breast/ovarian diagnoses, or there was a sister with breast/ovarian cancer. Among all offspring, increased risks were found for thyroid cancer, testicular cancer, and malignant melanoma, while lung cancer risk was decreased if the mother had had breast cancer. The authors developed a variance estimator for the standardized morbidity ratio to cope with overdispersion due to dependency within families

Increasing prevalence of adenocarcinoma of the oesophagus and gastro-oesophageal junction: A study of the Swedish population between 1970 and 1997

Objective: To see whether there was an increasing incidence of adenocarcinoma of the oesophagus and gastric cardia in the Swedish population. If there is a rising trend and variations in it can be found, could it be explained as a period or cohort phenomenon:? The data were also compared with the incidence of squamous cell carcinoma and gastric cancer with the gastric cardia excluded. Design: Retrospective study. Setting: Sweden. Subjects: Swedish population. Main Outcome measures: Age standardised incidence for each sex was calculated using the age distribution of the world population as a reference. Age-period-cohort models were fitted to data using Poisson regression to model log incidence rates. Results: For the combined group of adenocarcinoma in the oesophagus and gastric cardia age standardised incidence gradually increased during the study period. The median increase between adjacent five-year intervals was 20% in women and 14% in men. A period effect was evident in men. Conclusion: This study shows that the incidence of adenocarcinoma of the oesophagus and gastroesophageal junction is rising for both men and women in the Swedish population. This is explained as a period effect. As well as previously-described risk factors such as gastro-oesophageal reflux, obesity, and smoking, the increasing incidence can be explained as a shift in classification from squamous cell carcinoma to adenocarcinoma after 1985

Blood transfusion at delivery and risk of subsequent malignant lymphoma in the mother

BACKGROUND AND OBJECTIVES: Blood transfusion has been shown to be a risk factor for non-Hodgkin's lymphoma (NHL).MATERIALS AND METHODS: In a cohort of 77,928 women with bleeding complications at delivery in the period of 1973-1986, subsequent NHL cases were identified and the number was compared with the number expected from national incidence rates. In a case-control study the proportion of transfused NHL cases was compared with the proportion of transfused controls.RESULTS: The observed number of NHL in the cohort was 18 versus 22.0 expected. Information on transfusion was obtained for 15 of the NHL cases and none (0%) was transfused versus 32 out of 136 controls (23%).CONCLUSIONS: Blood transfusion at delivery is not a risk factor for NHL. The immune tolerance induced by pregnancy may reduce the risk of NHL associated with the transfusion of allogeneic blood cells