Angiogenesis, the formation of new blood vessels, has been suggested to provide important prognostic information in prostate cancer. The aim of this study was to investigate, whether microvessel density (MVD) at diagnosis was correlated with disease-specific survival in a non-curative treated population of prostate cancer patients. MVD was immunohistochemically (factor VIII-related antigen) quantified in archival tumours obtained at diagnosis in 221 prostate cancer patients. The maximal MVD was quantified inside a 0.25 mm2 area of the tumour and the median MVD was 43 (range 16-151). MVD was statistically significantly correlated with clinicopathological characteristics and disease-specific survival. A multivariate analysis demonstrated that MVD was a significant predictor of disease-specific survival in the entire cancer population, as well as in the clinically localized cancer population. These findings suggest that quantitation of angiogenesis reflects the spontaneous clinical outcome of prostate cancer.
Primary treatment with bleomycin, methotrexate and vincristine for two weeks followed by curatively intended 60Co irradiation was administered to 153 patients consecutively referred to the three main treatment centres in Denmark over more than a two-year period. Seventy-one laryngeal and 82 pharyngeal squamous cell carcinomas were evaluated. According to the TNM classification (UICC) 76 patients had stage III and 77 patients stage IV disease. The immediate response (complete + partial) to chemotherapy was 20 per cent. Judging from frequency of local recurrence, metastases as well as survival the treatment results were not obviously improved. A high frequency of complications was observed after this combination of chemotherapy and irradiation, and it was often impossible to fulfil the irradiation to the planned dose in appropriate time.
In a prospective study, the value of the clinical follow-up after treatment for head and neck cancer has been assessed. A total of 407 visits in 377 patients were recorded during a three month period in 1993 at the two major radiotherapy departments in Denmark. The results showed that 61% of follow-up visits included one or more problems either related to treatment morbidity or tumour recurrence. About 50% of all visits included treatment related normal tissue problems, and 30% had problems that required intervention. Although the majority of problems occurred within a few years after treatment, 47% of patients at three to four years observation time still had one or more problems. A total of 34 new tumour recurrences were found in the period, and of these 11 (32%) were asymptomatic. It is concluded that head and neck cancer patients have both tumour and normal tissue problems several years after the end of treatment. Since effective salvage treatment improves local control significantly, early detection of possible recurrence is important. A follow-up period of four to five years is recommended-preferably by qualified experts in the management of both recurrent disease and treatment morbidity.
The hyperthermic research during the last 100 years is reviewed with the aim to describe a research activity which has been performed in parallel to and associated with the development of radiation oncology. Basic and clinical research in several Scandinavian centres has made major international contributions to the establishment of a rationale for and implementation of hyperthermia as a combined modality treatment with chemotherapy or radiation in oncology. At the same time it has been demonstrated that collaboration and integration easily could be performed within the Scandinavian centres. Hyperthermic oncology is therefore a typical example of how research involving both biological, physical/engineering, and clinical skills in a proper environment can create valuable results.
Local tumor control is analyzed in a series of 181 patients treated with definitive megavoltage radiotherapy (RT) for histologically proven squamous cell carcinoma of the oropharynx. Considerable variation in treatment time stemmed from the general use of a split-course technique in 49 patients treated from 1978 to 1985. Incomplete follow-up, in those patients alive and well at the termination of the study or who have died from metastases or intercurrent disease before developing a local recurrence, was allowed for by using a multi-variate mixture model. The tumor control probability (TCP) after radiotherapy showed a significant dependence on the following tumor and treatment characteristics: (a) tumor size: the number of tumor target cells increases approximately as the fourth root of estimated tumor volume; (b) sex: the estimated TCP in males is lower than in females with the same characteristics; (c) histopathological differentiation: well-differentiated tumors have a lower TCP than poorly and intermediately differentiated; (d) hemoglobin concentration: patients in the upper normal range have a significantly higher TCP than others; (e) total dose: there is a significant dose-response relationship; and (f) overall treatment time: TCP decreased with increasing overall time, the dose equivalent of proliferation with 2 Gy per fraction was 0.68 Gy/day with 95% confidence limits [0.05, 1.3] Gy/day. The TCP did not depend significantly on subsite within the oropharynx or nodal disease at presentation. The data were consistent with an alpha/beta ratio of the linear-quadratic model of 10 Gy.
A review of the DAHANCA-group's projects concerning cancer of the head and neck over 20 years is presented. Apart from the first, all projects were randomized trials. Two projects with neoadjuvant chemotherapy have not shown any notable tumour control or better survival. More than 1800 patients suffering from cancer of the head and neck treated in the five oncological centres of the country were included in the three projects concerning radiosensitizers and radiotherapy. The radiation has been accelerated during the years making it more effective. Each of the three projects has improved the local control rate by 11-15% and the survival is enhanced by 11-13% for each project. Cooperation between our five oncological centres has given good results and increased the survival for patients with head and neck cancer. It is now routine to give the radiosensitizer tablets Nimorazol 1 1/2 hours before radiation and to give six fractions weekly to patients with squamous cell cancer in the supraglottic region, pharynx and oral cavity.
All prostate cancer patients (719 patients) within a specified population were studied in order to assess both the overall economic burden of this disease to the health-care economy and its burden to the individual patient. The economic burden was estimated as the total lifetime expense (1995 prices) of all palliative hospital treatment. The expenses associated with prostate cancer therapy averaged US$ 19755 per person. By extrapolation, palliative therapy for this disease currently consumes almost 1% of the entire Danish health-care budget. A total of 62% of the patients died from the disease. During hospitalization these patients on average required three times as much hospital care as other patients and about one-third needed regular treatment with opiates or equivalent drugs. Under the present circumstances we cannot recommend an aggressive strategy towards localized prostate cancer even though the incidence of this disease is increasing at an alarming speed and its economic and human costs are excessive.
Based on the results from the DBCG 82 trial, breast conserving therapy (BCT) has been implemented as standard in Denmark since 1989, and today constitutes more than 70% of the primary treatment. Our aim was to evaluate the implementation of BCT as a routine procedure in patients treated according to the DBCG 89 program and compare recurrence pattern and survival both overall and when separated in age groups, with the results from the randomized DBCG 82?TM trial.
A total of 1847 patients treated between 1989 and 1999 were included in a retrospective population-based cohort study. Data from the DBCG database were completed via search through the Danish Pathology Data Bank and medical records.
Median follow-up time was 17 years. At 20 years the cumulative incidences of local recurrence (LR) and disease-specific mortality (DSM) were 15.3% and 25.8%, respectively. Twenty-year overall survival (OS) and recurrence-free survival were 63.7% and 43.1%, respectively. Subdivided by age groups cumulative incidences at 20 years were LR: 18.9%, 10.5% and 12.4%, and DSM: 28.9%, 18.9% and 28.4% in young (=45 years), middle-aged (46-55 years) and older (=56 years) women, respectively. In an adjusted analysis age maintained a significant and independent effect on both LR and DSM.
The DBCG 82?TM program was successfully implemented. The women treated with BCT in the DBCG 89 program displayed equal failure pattern and improved survival in comparison with women from the DBCG 82?TM protocol. Occurrence of first failure and mortality varied with age; demonstrated by increased risk of LR, DM and DSM in the young patients and increased risk of DM and DSM in the older patients, compared to the middle-aged patients.
In the nineties, several national protocols by the Danish Head and Neck Cancer Study group DAHANCA and other randomized trials, which have included several thousand patients, were performed on squamous cell carcinoma of the head and neck, now the most common malignant disease worldwide. It is a locoregional disease and distant metastases are rarely seen at diagnosis. Radiotherapy and surgery are thus the treatment of choice, with radiotherapy being the treatment modality if organ conservation is required. Since the late eighties there has been a strong focus on the importance of overall treatment time for the outcome of curative radiotherapy for these carcinomas. Based on the results of the Danish protocols it was concluded that the schedule of radiotherapy should be given with the shortest possible overall treatment time. In fact, as a consequence of the loco-regional control rate, the disease-specific and overall survival have shown a significant dependency on the overall treatment time: when this is short, the most beneficial results are achieved. Furthermore, treatment with 6 fractions per week is now the standard radiotherapy in Denmark in most head and neck carcinomas, associated with hypoxic modification using nimorazole. The response to accelerated fractionation is however heterogeneous and until proper predictive factors can be identified and further clarified which are the patients who truly benefit from accelerated fractionation, the radiotherapy schedules should secure a sufficient dose to all patients.