[Cancer treatment in Skane and in Sjaelland. Do differences concerning examination and treatment explain reduced survival among Danish cancer patients?]. / Kraeftbehandling i Skåne og på Sjaelland. Er forskelle i udredning og behandling med til at forklare danske kraeftpatienters dårligere overlevelse?

INTRODUCTION: Danish cancer patients generally have a poorer survival than Swedish cancer patients. The difference is most pronounced for certain tumour types, e.g. common types such as lung, breast, colorectal, and prostate cancer. The reasons are not clear. The present article examines if differences in the diagnostic workup and treatment can explain some of this variation. MATERIAL AND METHODS: Aspects of the diagnostic workup and treatment of the above mentioned four cancer types are examined using data from cancer registry analyses and official reports. These data are seen in the context of counts of trained personnel and equipment in cancer diagnostics and treatment in the two countries. RESULTS: With regard to lung and breast cancer, the data seem to indicate that Danish patients are diagnosed later, and that Denmark lags behind in treatment capacity. With regard to rectal cancer, the data seem to indicate that concentrating operations in fewer hospitals, and improvements in operation technique have been introduced earlier in Sweden than in Denmark. With regard to prostate cancer, however, the data seem to indicate that many more indolent cases that do not need treatment are diagnosed in Sweden than in Denmark. The total capacity for oncologic treatment, both in terms of trained personnel and equipment, seen in relation to the size of the population, is considerably larger in Southern Sweden than in Eastern Denmark. DISCUSSION: The data for some of the common cancer types seem to indicate that problems in the areas of sufficient capacity for diagnostic workup and treatment may explain some of the difference in survival between Danish and Swedish cancer patients.

The prognostic value of body protein in patients with lung cancer.

Lung cancer is a major cause of death in many countries. To improve the results of treatment, more individualized therapy is necessary; for this, it is necessary to identify new prognostic factors. In 21 patients with lung cancer (17 with non-small-cell lung cancer and 4 with small-cell lung cancer) that had received radiation treatment, the amount of body protein was estimated with in vivo neutron activation analysis. Patients in whom body protein decreased had recurrences of the disease earlier and a poorer survival than patients whose body protein increased. A clear relationship was seen between changes in the body's protein content and recurrence-free survival. To better evaluate the prognostic value of body protein content in patients with lung cancer, a larger number of patients and a longer follow-up period are needed.

What margins should be added to the clinical target volume in radiotherapy treatment planning for lung cancer?

BACKGROUND: The planning target volume in radiotherapy treatment planning takes into account both movements of the clinical target volume (CTV) and set-up deviations. MATERIALS AND METHODS: A group of patients who received radiotherapy for lung cancer were studied. In order to measure the CTV movements due to respiration and other internal organ motions, fluoroscopy was performed for 20 patients. To study the accuracy and reproducibility of patient and beam set-up, 553 electronic portal images from 20 patients were evaluated. Discrepancies between planned and actual field positions were measured and the systematic and random errors were identified. The combined effect of these geometrical variations was evaluated. RESULTS: The average CTV movement with quiet respiration was about 2.4 mm in the medio-lateral and dorso-ventral directions. Movement in the cranio-caudal direction was on average 3.9 mm with a range of 0-12 mm. The systematic set-up errors were on average 2.0 mm in the transversal plane and 3.0 mm in the cranio-caudal direction. The random errors can be described by their standard deviations of 3.2 and 2.6 mm. In this study, the combined effect of the two parameters (CTV movement and set-up deviations) varied between 7.5 and 10.3 mm in different anatomical directions. CONCLUSIONS: In our daily clinical routine, we use a margin of 11 mm in the transversal plane and 15 mm cranially and caudally, also taking into account other unquantified variations and uncertainties.

Body protein as a prognostic instrument for cancer patients?

Many cancer patients are affected by loss of appetite, weight loss and fatigue in the course of disease. These symptoms reduce the patients' quality of life, increase morbidity, and lessen tolerance to anti-tumor treatment. In some cases the symptoms are partly caused by various treatment modalities. The aim of this study was to investigate if radiotherapy affects the body weight and body protein of patients, and if changes in body protein have any clinical significance.

Quality assurance in brachytherapy: the role of the ICRU in achieving uniformity in dose and volume specification for reporting.

A quality assurance programme in brachytherapy implies a general consensus on the method of dose and volume specification for reporting. This in turn implies a consensus on certain definitions of terms and concepts. For several decades, the ICRU (International Commission on Radiation Units and Measurements) has been actively involved in an effort to reach a consensus between different brachytherapy centres worldwide, and to improve uniformity in reporting. The ICRU has prepared two reports containing recommendations for reporting brachytherapy treatments. The first, report #38 published in 1985, deals with intracavitary therapy in gynecology. The second deals with interstitial therapy, and is now in press. A summary of these two ICRU reports is presented here. Some definitions of terms and concepts are first recalled and discussed: Total Reference Air Kerma (TRAK), gross tumor volume (GTV), clinical target volume (CTV), treated volume, mean central dose, dose uniformity parameters, etc. Specific recommendations for reporting interstitial and intracavitary brachytherapy are then presented.

The role of radiotherapy in breast conserving treatment.

Radiotherapy in breast conserving procedures is instrumental for reducing the frequency of a breast relapse, and may even improve survival. The treatment can be associated with morbidity, that is not negligible. A high-quality technique is needed in order to achieve an optimal therapeutic ratio.

Progress in radiotherapy.

The 100 years which have elapsed since W.C. Röntgen discovered the x-rays in 1895 have given us a large body of knowledge about the sue of ionizing radiation, and also taught us enough to allow for a statement that there is still much room for improvement. Even if it is always difficult to look into the future, it seems today that such improvements in the first hand may imply sophistications of already existing methods. This will not be without impact. For Europe, it is estimated that improvements in radiotherapy will raise the cure rates in all cancer patients by a substantial figure. It is the purpose of this communication to try to describe such future improvements. Another at least equally important factor would be to make this treatment modality available to all patients who are considered to benefit from it.

Neutron therapy--the historical background.

Neutron therapy was first introduced by Stone et al. in 1938, i.e. more than 10 years earlier than electron beam therapy and only 6 years after the discovery of neutrons. In spite of the impressive accomplishment in generating an adequate therapy beam, time was also found for careful radiobiological studies of neutron beams. However, it was not considered that for a certain early reaction the late effects were much greater with neutrons than with x-rays. The severe late sequelae in proportion to the few good results motivated the closure of this therapy. Neutron therapy was again introduced in Hammersmith hospital at the end of the 1960's. The major reason seems to have been to overcome the oxygen effect. Encouraging results were reported. It was argued that the very favourable statistics on local tumour control were obtained at the expense of more frequent and more severe complications. A clinical trial in Edinburgh seemed to indicate this, but it was not proved in the end as the two trials differed regarding fractionation. Today about 16,000 patients have been treated with neutrons. The neutron beams now used differ significantly, both regarding dose distributions and microdosimetrical properties, from those utilized earlier. The advantage of neutrons is still, however, controversial. There are indications that neutron treatment may be favourable for some tumours. A careful cost-benefit study ought to be performed before the creation of a neutron therapy centre in Sweden as the group of patients suitable for neutrons is limited, and there may be new possibilities for improvement of photon and electron treatment with much smaller resources.

Dose specification with 3-D dose planning (ICRU 'level 3').

The availability of constantly more sophisticated algorithms and methods for dose planning (denoted 'level 3' procedures by the ICRU) makes it possible to use accordingly more complex treatment techniques. Such procedures have the potential of reducing irradiation of organs at risk and other healthy tissue. However, they suffer from a substantially more difficult set-up of the patient and verification of the treatment. This will introduce additional sources of error, systematic as well as random, which will be of importance for dose reporting. The purpose of this paper is to point out some of these problems and to suggest a method for reporting which is the least sensitive to these 'new' sources of error.

The total incidence of loco-regional recurrence in a randomized trial of breast cancer TNM stage II. The South Sweden Breast Cancer Trial.

We studied loco-regional recurrence during follow-up (median observation time 8 years) in 1,153 patients, who underwent modified mastectomy and were randomly assigned to one of the following postoperative treatments; Premenopausal patients: radiotherapy, cyclophosphamide, or both; Post-menopausal patients: radiotherapy, tamoxifen, or both. Recurrence occurred in a total of 419 patients, 123 of whom had loco-regional recurrence with or without distant metastasis. The loco-regional recurrence rate was 7% in the irradiated subgroups and 17% in the non-irradiated subgroups, the corresponding cure rates being 43% and 58%. Complete remission of all local recurrence was obtained after the first treatment in 67% of the cases, and was persistent in 67% of them (44% overall). Complete remission was obtained in all patients with local recurrence who received local treatment only, and was persistent in 65%. Of local recurrences treated with a combination of surgery, radiotherapy and hormone therapy, complete response was obtained in 94% of the patients, and was persistent in 94% of them (88% overall). Complete remission of all regional recurrence was obtained after the first treatment in 58% of the patients and was persistent in 67% of them (39% overall). Postoperative radiotherapy reduced not only the total number of loco-regional recurrences but also the number of uncontrolled loco-regional recurrences. Aggressive local treatment would appear to yield both satisfactory initial control and, when combined with the hormone therapy, a high rate of persistent loco-regional control.

Long-term effects on pulmonary function of mantle radiotherapy in patients with Hodgkin's disease.

Twenty-five patients (21-45 years old) treated for Hodgkin's disease with mantle radiotherapy but no chemotherapy underwent chest radiography and pulmonary testing with spirometry, pulmonary mechanics and exercise test combined with arterial blood gas analysis, lung scintigraphy, assessment of pulmonary artery pressure with Doppler cardiography and vector ECG 10-20 years after treatment. The doses to mediastinum ranged from 35-43 (mean 40) Gy given in 26 fractions with the split-course technique. Radiographic signs of slight to moderate pulmonary fibrosis were seen in 18 patients. Minor restrictive ventilatory defects were found with decreased VC, TLC and lung compliance and increased maximal elastic recoil. Little evidence of airflow obstruction was found. Exercise capacity was decreased in three individuals but the mean value for the study group as a whole was normal. Arterial PO2 at maximum exercise was reduced but no patient had diminished hemoglobin saturation. Lung scintigraphy showed defects in 21 patients, mostly consisting of slight abnormalities at the lung periphery and apices. The perfusion seemed to be more affected than the ventilation, suggesting primary vascular lesions. Twelve patients showed signs of right ventricular hypertrophy in vector ECG and four of these had systolic pulmonary artery pressure greater than or equal to 30 mm Hg. The observed abnormalities were mostly of a minor degree and few clinically significant long-term effects of mantle radiotherapy on pulmonary function were observed.

Long-term effects of adjuvant tamoxifen and/or radiotherapy. The South Sweden Breast Cancer Trial.

In a multicenter trial of adjuvant therapy in stage II breast cancer, 719 postmenopausal patients were randomized to one of three treatment regimens: radiotherapy only or in combination with adjuvant tamoxifen for one year, or adjuvant tamoxifen without radiotherapy. At twelve years of follow-up (median 9 years), no statistically significant differences in survival or recurrence-free survival were observed. However, the rate of loco-regional recurrency was lower among patients treated with both radiotherapy and tamoxifen. The rate of bilateral breast cancer was reduced in tamoxifen-treated patients whereas the rate of new primary malignancies other than breast cancer was somewhat higher in tamoxifen-treated patients. Adjuvant therapy in breast cancer may influence not only breast cancer recurrences and mortality but also later disease patterns and cause-specific mortality.

Late cardiac effects after mantle radiotherapy in patients with Hodgkin's disease.

Twenty-five patients (21-45 years old) treated for Hodgkin's disease with mantle radiotherapy but no chemotherapy underwent cardiac testing with myocardial scintigraphy during exercise, Echo-Doppler cardiography and CT-examination, 10-20 years after treatment. Four of twenty-six (15%) young patients had serious cardiac complications after mantle therapy, and reduced systolic and/or diastolic function; and minor valvular disturbances were often found. One 36-year-old female died of myocardial infarction 4 years after therapy, one 39-year-old male had two non-lethal infarctions after 14 years, one 36-year-old male with no symptoms had severe reversible ischemia and three proximal coronary artery stenoses, and one 32-year-old female with constrictive pericarditis had pericardeictomy 14 years after therapy. In 23/24 patients the pericardial thickness was normal and no pericardial effusion was found. 23/24 patients had normal working capacity, but myocardial scintigraphy was normal in only 9 patients. 11/25 patients had reduced systolic function and in 12/24 patients the diastolic function was reduced. 11/25 patients had abnormal valvular or subvalvular structures. Valvular stenosis was not found but aortic, mitral and tricuspidal regurgitations were found in 1/25, 9/25 and 22/25, respectively. In all but two cases the regurgitations were mild. We conclude that mediastinal irradiation must be considered a risk factor for cardiac disease. It may be advisable to reduce other risk factors in these patients.

Arterial rupture after microwave-induced hyperthermia and radiotherapy. With reference to two patients treated for recurrence in previously operated and irradiated areas.

Two patients who developed frank arterial bleeding after combined microwave-induced hyperthermia and radiotherapy are described. One patient received re-irradiation and hyperthermia for recurrent metastatic neck nodes of a mesopharyngeal carcinoma. Full course radiotherapy had been given 6 years previously and a right-sided radical neck node dissection had been performed 4 months earlier because of recurrent neck node metastases. Six weeks after the combined therapy for a second recurrence, which achieved complete remission, a fatal rupture of the carotid artery occurred. The other patient received re-irradiation and hyperthermia for a chest wall recurrence of a breast carcinoma, treated 5.5 years previously by sector resection and tangential beam radiotherapy, and treated again 2 years earlier with extensive surgery for a local recurrence. A frank arterial bleeding from the treated region was seen after 7 months, but could be arrested with surgery. This important complication in combined hyperthermia and radiotherapy does not seem to have been recognized before. Different explanations are discussed, such as the previous local treatment as well as high temperature and atherosclerosis per se.

Radical radiotherapy in prostatic carcinoma.

During the years 1978-1986 111 fairly elderly patients with prostatic carcinoma in clinical stages B, C, or D, and usually having tumours that were poorly differentiated, received radical radiotherapy to the prostate and bladder and to the adjacent lymph node regions. The side effects were comparable to those reported in the literature. During the follow-up 72% of the patients sooner or later (actuarial analysis) developed local recurrence or distant metastases. The projected survival rate at 8 years was 25%, and should be compared with the 65% expected for an age-matched Swedish male population. After 3 years the two survival curves became rather parallel, indicating a 'cure' rate of the order of 49%. There was a significant difference in survival between patients clinically judged to have only intracapsular carcinoma and those considered to have extracapsular carcinoma. The relatively modest survival figures in the present series reflect the malignant nature of poorly differentiated carcinoma of the prostate.

Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial.

STUDY OBJECTIVE: To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN: Birth year cohorts of city population separately randomised into study and control groups. SETTING: Screening clinic outside main hospital. PATIENTS: Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS: Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT: Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS: All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS: In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS: Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.

Prognostic factors influencing survival in combined radiotherapy and surgery of squamous cell carcinoma of the esophagus with special reference to a histopathologic grading system.

Sixty-six patients with squamous cell carcinoma of the esophagus were treated with combined surgery and radiotherapy, mostly in a sandwich fashion. Fourteen patients received misonidazole during preoperative radiotherapy. Prospective cumulative survival at 1, 2, and 5 years was 60%, 35%, and 17%, respectively. Original biopsy specimens and operation specimens were evaluated according to a histopathologic grading system based on an evaluation of the tumor cell population in terms of cell differentiation, structure, nuclear polymorphism, and the frequency of mitotic figures. The tumor-host relationship was also estimated by the mode of invasion, stage of invasion, vascular invasion, and degree of lymphocytic infiltration. A multivariate regression analysis according to Cox and actuarial survival were used to determine the relative contributions of the clinical and histopathologic parameters to patient outcome. The major results were as follows: (1) patients who were old (70 to 80 years) fared as well as younger patients (P = 0.9198); (2) tumor site did not influence therapeutic outcome (P = 0.1100); (3) there was an insignificant difference in survival between patients with M0 and M1 disease (P = 0.7130); (4) radical surgery gave better survival; (5) misonidazole administered preoperatively was associated with worse survival (P = 0.0147); and (6) the histopathologic malignancy grading score system was very useful for prognostication--the tumor-host score in the operative specimen was the strongest of all analyzed predictive parameters. Since palliation was excellent in all patients treated in the combined fashion, selection criteria should be wide for such a program, not the least since long-term survival is possible also for patients with very advanced tumors.