Clinical validation of the LKB model and parameter sets for predicting radiation-induced pneumonitis from breast cancer radiotherapy.

The choice of the appropriate model and parameter set in determining the relation between the incidence of radiation pneumonitis and dose distribution in the lung is of great importance, especially in the case of breast radiotherapy where the observed incidence is fairly low. From our previous study based on 150 breast cancer patients, where the fits of dose-volume models to clinical data were estimated (Tsougos et al 2005 Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy Phys. Med. Biol. 50 3535-54), one could get the impression that the relative seriality is significantly better than the LKB NTCP model. However, the estimation of the different NTCP models was based on their goodness-of-fit on clinical data, using various sets of published parameters from other groups, and this fact may provisionally justify the results. Hence, we sought to investigate further the LKB model, by applying different published parameter sets for the very same group of patients, in order to be able to compare the results. It was shown that, depending on the parameter set applied, the LKB model is able to predict the incidence of radiation pneumonitis with acceptable accuracy, especially when implemented on a sub-group of patients (120) receiving [see text]|EUD higher than 8 Gy. In conclusion, the goodness-of-fit of a certain radiobiological model on a given clinical case is closely related to the selection of the proper scoring criteria and parameter set as well as to the compatibility of the clinical case from which the data were derived.

Quality control in health care: an experiment in radiotherapy planning for breast cancer patients after mastectomy.

PURPOSE: The importance of evaluating and improving quality in clinical practice is now generally acknowledged. In this study we estimated different sources of variation in radiotherapy planning for breast cancer patients after mastectomy and sought to test the applicability of a reproducibility and repeatability (R&R) study in a clinical context. METHODS: Eleven radiation oncologists planned radiotherapy three times for three different kinds of breast cancer patients without knowing they were handling the same patient three times. Variation was divided into different components: physicians as operators, patients as parts, and repeated measurements as trials. Variation due to difference across trials (repeatability), that across the physicians (reproducibility), and that across the patients (variability) were estimated, as well as interactions between physicians and patients. Calculation was based on the sum of squares, and analysis was supported by various graphical presentations such as range charts and box plots. RESULTS: Some parts of the planning process were characterized by higher and different kinds of variation than the others. Interphysician variation (i.e., reproducibility) was not high but there were some clearly outlying physicians. The highest variation was in repeatability (= intraphysician variation). The major part of the variation was, however, that from patient to patient: 33% of the total in Parameter 1 and 85% of the total in Parameter 2. CONCLUSIONS: R&R studies are applicable and are needed to evaluate and improve quality in clinical practice. This kind of analysis provides opportunities to establish which kinds of patients require particularly careful attention, which points in the process are most critical for variation, which are the most difficult aspects for each physician and call for more careful description in documents, and which physicians need further training.

Estrogen and progesterone receptors in breast cancer: relationships to tumour histopathology and survival of patients.

Estrogen receptor (ER) and progesterone receptor (PR) concentrations were measured in the tumours of 399 cases of primary breast carcinoma. Histological type and histological grading was also analysed. The correlation between survival and histological grading was observed and found to be of high significance statistically. Longer survival of patients with ER- and/or PR-positive tumours was also observed, but the ER and PR prognostic value did not reach the same magnitude as histological alone. The prognostic accuracy in breast cancer, when histological grading, ER and PR were used together, failed to reach statistically significant values. A lower proportion of ER- and PR-positive tumours were found in histological grade III. The majority of the tumours belonging to specific histological variants of carcinoma were ER- and/or PR-positive. Relationships between ER, PR, menopausal status, and age were also noted. It was apparent that the prognostic value of PR concentrations in the tumour was more relevant than that of ER alone.

Effects of simulated herbivory on tillering and reproduction in an annual ryegrass,Lolium remotum.

This study examined the overall impact of simulated herbivory on tillering and reproductive performance of an annual ryegrass,Lolium remotum. The interaction between herbivore damage and intraspecific competition and the effect of the timing of damage were also studied. The experimental plants were sown at two densities and were randomly assigned to eight different damage treatments consisting of artificial leaf area removal by clipping with scissors or removal of one-third of the ripening seeds. The treatments were executed at two flowering stages. The pattern of tiller development differed significantly among treatments and between densities. At the lower density, earlier treatments delayed tiller development more than the same treatments executed later. At the higher density, all treatments delayed tiller development. The density effect was significant for all reproductive traits measured. The reproductive output of plants grown at the higher density was lower and the negative treatment effects were stronger than at the lower density. The treatment effect was significant for seed dry weight per plant and individual seed weight but not for number of seeds per plant. There were no statistically significant interaction effects between the damage treatments and density, suggesting that the plants responded to the damage similarly, irrespective of the density. The plants did not totally compensate for losses due to damage at either density, even though they slightly increased their resource allocation to sexual reproduction at the higher density.

Flow cytometric analysis of tumor DNA profile related to response to treatment and survival in small-cell lung cancer.

Flow cytometric (FCM) analysis of tumor DNA ploidy and S-phase fraction (SPF) has been widely used to predict prognosis and treatment response in many malignant tumors, but rarely in small-cell lung cancer (SCLC). In the present study, tumor DNA ploidy and SPF were measured from paraffin-embedded tumor biopsy samples of 36 small-cell lung cancer patients treated with combination chemotherapy and radiotherapy. Aneuploidy was detected in 69% of the tumors. There was a statistically non-significant trend towards more aneuploidy among extensive disease (ED) patients as compared to patients with limited disease (LD): 80% versus 65%, respectively (p = 0.69). The mean SPF was 21.3% (+/-7.6) in patients with LD and 29.0% (+/-5.3) in patients with ED, the difference (7.6%) being statistically significant (p = 0.008, 95% CI for the difference 2.2-13.1). No significant differences was detected in the survival of aneuploid and diploid patients or patients with low (< or = 24.9%) and high (> 24.9%) SPF. Similarly, no significant difference was observed between aneuploid and diploid cases in relation to response to treatment or response duration. It is concluded that the difference detected in the SPF with LD and ED of SCLC may indicate the biological aggressiveness of extensive SCLC.

Human plasma antioxidant capacity during radiotherapy for lung cancer: a clinical study.

Even though it is well established that oxygen-free radicals are the main mechanism responsible for the cytotoxicity produced during radiotherapy, the role of the human antioxidant defense system in clinical radiation oncology is still to be clarified. Changes in the human plasma total peroxyl radical trapping capacity (TRAP) and its individual components were followed during clinical radiotherapy for lung cancer. Sixteen patients receiving radical-aimed radiotherapy provided blood samples nine times during the treatment. Our hypothesis was that oxygen-free radical production increased by irradiation should decrease the plasma TRAP as a consequence of oxidative stress. Only a moderate reduction of the plasma TRAP was found during the therapy in the study group taken as a whole, but the development pattern of TRAP and its unidentified components were clearly different in those patients showing complete or partial response to the treatment and those in which the disease progressed unabated. Plasma ascorbate levels showed no significant changes during radiotherapy. A decrease in vitamin E concentrations was seen after 6 Gy (p=0.05). Uric acid concentrations increased towards the end of the radiotherapy in both response groups (p=0.02 at 50 Gy). In this study, 26.6% of the plasma TRAP was due to unidentified antioxidants (UNID).

Experiences with the use of the 131I-hippuran test as an indicator in functional patency of ventriculocardiac shunts in hydrocephalic children.

In this paper a method is presented that provides information on the function of ventriculocardiac shunts in hydrocephalic children. There is good correlation between clinically and operatively demonstrated obstruction of the shunts as well as with clinically found free C.S.F. passage through the shunt. However, the greatest benefit is provided with the aid of the present method in cases with equivocal obstruction of the shunt where in our experience some operations of the shunt could be postponed or completely avoided in some cases. Because of its simplicity, safety, rapidity, and easy repeatability the method is recommended for routine ambulatory and hospital use.

Abdominal ultrasound findings during and after treatment of childhood acute lymphoblastic leukemia.

BACKGROUND: The treatment of acute leukemia in childhood has been increasingly successful. Concurrently, severe leukemia-related gastrointestinal complications have become more common. METHODS: We evaluated the findings of the abdominal ultrasound (US) examinations of 52 children with acute lymphoblastic leukemia (ALL) who had severe clinical symptoms indicating infection or abdominal complication during chemotherapy treatment or after the cessation of such treatment and assessed the impact of these findings on patients' subsequent treatment and survival. RESULTS: Our study presents ten cases of typhlitis with a prevalence of 9%, all of which were rapidly diagnosed by US and had a favourable outcome. We also found focal intra-abdominal parenchymal lesions in six children, five of them due to fungal infection and one due to leukemic infiltration. Several other intra-abdominal pathologies significant for the patients' treatment are also reported. DISCUSSION: We believe that abdominal US is a useful, rapid, safe, and accurate imaging method for children with ALL suspected to suffer from leukemia- or chemotherapy-related gastrointestinal complications. More invasive imaging methods are seldom needed. CONCLUSIONS: According to our results, abdominal US gives the necessary information in most of the cases and provides prompt diagnosis, which may prevent possible fatal complications.

Effects of fractionated radiotherapy on bone blood flow in man.

Effects of fractionated irradiation on bone blood flow during and some months after the radiotherapy were measured with a 133Xe washout method from the greater trochanteric regions of human femurs. The results suggest that at low dose levels (CRE from 250 to 1050 reu) the decrease in bone blood flow is small. However, there seems to be a significant decrease in blood flow (about 50%) several months after the irradiation.