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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.

Purpose : The association between early radiological lung reactions consequent upon radiotherapy and patients' symptoms is not well established. This prospective study examined the association between symptoms experienced by the patient, clinical findings observed by the physician and reactions visible in chest X-ray as interpreted by a radiologist, as well as the association between skin or breast symptoms and lung symptoms induced by radiotherapy after different methods of surgery. Methods : Altogether 207 consecutive breast cancer patients entered the trial between 1st October 1997 and 31st December 1998. Chest X-rays were taken at entry and 3, 6 and 12 months after radiotherapy. The frequency and intensity of symptoms as well as clinical and chest X-ray findings were assessed over time. Results : Skin and breast symptoms were common after radiotherapy but seldom severe (9%). Lung reactions were seen in chest X-ray in 47% of patients in re-evaluation by a radiologist at 3 months. The frequency of lung or skin symptoms did not correlate with chest X-ray findings, but there was a significant correlation between skin and lung symptoms. Radiotherapy after conservative surgery for node-positive breast cancer caused lung reactions seen in chest X-ray more often than after mastectomy when using other techniques. The reactions were most common at the 6 month evaluation ( P =0.01). Concomitant adjuvant chemo- or endocrine therapy did not significantly increase the incidence of lung reactions. Conclusions : Skin, breast and lung symptoms were frequent after radiotherapy, but there was no real association between lung or skin symptoms and chest X-ray findings. The only correlation noted was between skin or breast symptoms and lung symptoms experienced by patients. Radiotherapy after conservative surgery was more frequently linked to chest X-ray findings than radiotherapy after mastectomy. We conclude that routine chest X-ray after radiotherapy gives no more clinically relevant information than the symptoms of the patient and we do not recommend routine chest X-rays for that reason.

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.

The combination of carboplatin and etoposide was evaluated in 61 previously untreated patients with extensive small cell lung cancer. Treatment was given at four-week intervals with 450 mg/m2 of carboplatin intravenously (i.v.) on day 1 and etoposide 100 mg/m2 i.v. on days 1-3. The response was complete in 5 (9%) and partial in 28 (50%) of the 56 evaluable patients (overall response rate 59%). The median time to progression after response as well as the median survival time in all evaluable patients was 4.6 months. WHO grade 3 and 4 leukopenia and thrombocytopenia occurred in 8% and 11% of the courses respectively. Two treatment-related deaths were registered. The combination of carboplatin and etoposide used in the present study produced acceptable response rate and toxicity, but duration of response and median survival were shorter than expected from earlier studies.

The relation between tumor characteristics, irradiation technique, local tumor control and survival was retrospectively studied in 323 patients with non-small cell lung cancer who started radical radiotherapy in 1974-1981. At that time three non-randomized different fractionation schedules were used: 16 x 3.25 Gy, total dose 52 Gy, 3 fractions/week (schedule 1), 11 x 4 Gy, total dose 44 Gy, 2 fractions/week (schedule 2) and 25 x 2 Gy, total dose 50 Gy, 5 fractions/week (schedule 3). The highest survival rates were observed in the patient group treated according to schedule 2. The 2-year survival rate was 30% compared with 18% and 6% in the patients treated according to schedule 1 and 3 respectively. However, this can at least partly be explained by patient selection. A correlation between size of the tumor, target volume and survival was observed: the larger the tumor, the poorer the survival. Pleural effusion showed to be an unfavorable prognostic factor. The prognosis of inoperable lung cancer on the whole remained poor: the 1-year survival rate was 43% and 2-year survival rate 16%. Only 3% of the patients lived at least five years.

The aim of this study was to evaluate radiation-induced pulmonary abnormalities of breast cancer patients. Altogether 202 consecutive patients receiving postoperative radiotherapy entered the study. Plain chest radiographs taken at entry and 3, 6 and 12 months after radiotherapy were evaluated according to modified Arriagada classification. In addition, pulmonary symptoms were recorded. Supplementary high-resolution computed tomography (HRCT) was employed in a subgroup of patients (n?=?15). Plain radiographs were interpreted by a radiologist, and uncertain findings were re-evaluated by a radiologist together with a radiation oncologist. Grade 2 pneumonitis was the most common abnormality. The proportion of patients yielding a grade 2 finding was 22.5%, 28.1%, and 16.0% at three, six, and twelve months, respectively. There were 2 normal findings in HRCTscans, and 8 in plain radiographs of the same patients. Radiological lung abnormalities are common after radiotherapy, but they are usually reversible, and their significance for the patient's well-being is minor. No correlation between symptoms and lung or pleural reactions was seen.

The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically acceptable results in certain cases selectively (relative seriality model with Seppenwoolde et al and Gagliardi et al parameter sets). The use of published parameters should be considered as safe only after their examination using local clinical data. The variation of inter-patient radiosensitivity seems to play a significant role in the prediction of such low incidence rate complications. Scoring grades were combined to give stronger evidence of radiation pneumonitis since their differences could not be strictly associated with dose. This obviously reveals a weakness of the scoring related to this endpoint, and implies that the probability of radiation pneumonitis induction may be too low to be statistically analysed with high accuracy, at least with the latest advances of dose delivery in breast radiotherapy.

The inter-physician and inter-patient variability in planning target volume delineation for the radiotherapy of breast cancer after conservative surgery is presented. Eleven experienced radiation oncologists determined the planning target volume (PTV) for four breast cancer patients. Delineation was based on CT slices taken at intervals of 15 mm. The variability in target volume delineation was determined by measuring the volumes in units of cc and the position of the drawn PTVs. Statistical analysis was based on X/R-charts and on Pareto chart and analysis. The maximum range in PTV for one patient was from 670 to 1,200 cc. The observations of three physicians were in excess of the warning limit altogether 18 times. The methods used in this study clearly reveal inter-physician variability in PTV delineation and widest variations found are not acceptable. Training targeted to some physicians and more detailed and unambiguous protocols for PTV delineation are needed.

Although DNA aneuploidy and high proliferative activity (S-phase fraction, SPF) of tumour cells, measured by flow cytometry, have proved to be indicators of poor prognosis in most solid tumours, there have been conflicting results in lung cancer studies. During a four-year period we studied the prognostic significance of DNA ploidy and SPF in 99 surgically treated lung cancer patients. Flow cytometric analysis was done from archival, formalin-fixed, paraffin-embedded tumour specimens. DNA index and SPF were determined, using MultiCycle software with sliced nuclear correction to compensate for debris. There were 61 DNA diploid and 38 DNA aneuploid tumours. The median SPF was 10.2%. Neither ploidy nor SPF was associated with previously known prognostic factors. Survival was poorer in patients with aneuploid tumours than in the other patients, but the difference was not statistically significant. DNA ploidy and SPF thus do not seem to be useful prognostic indicators in surgically treated lung cancer.

DNA flow cytometric analysis was done from 100 paraffin-embedded non-small cell (NSCLC) and 29 small cell lung carcinomas (SCLC). Most of the patients had locally advanced disease and all were considered inoperable and treated by radiotherapy. DNA aneuploidy was detected in 62 (62%) of the NSCLCs and in 20 (69%) of the SCLCs. Radiotherapy induced a slightly more extensive and prolonged tumour regression in DNA-aneuploid NSCLC with high S-phase fraction (SPF) than in those with low SPF and no evidence of aneuploidy. However, neither in NSCLC nor in SCLC were significant survival differences detected between DNA-diploid and DNA-aneuploid cases or between those with low ( 12%) S-phase fraction (SPF). Neither did the degree of differentiation have prognostic significance in this material.

Oneology, the study of neoplastic diseases, is generally referred to as the cancer problem (Rubin, 1983). It is the study of a large variety of tumors of malignant nature with lethal potential. In spite of its lethal character, it is nowadays far from synonymous with “an incurable disease”. Much progress has been achieved to cope with all aspects of the cancer problem.