[Treatment of cervix cancer in Denmark]. / Behandlingen af cancer cervicis uteri i Danmark.

The current status of cervical cancer treatment in Denmark is discussed. Diagnostic aspects and problems of classification are presented briefly supplemented with a comment on new prognostic parameters based on a semiquantitative score system and flow cytometry. Surgery is the treatment of election for the early stages whereas radiotherapy is the treatment of choice in advanced stages. Chemotherapy should only be employed in the framework of clinical trials. It is concluded that centralised treatment should be maintained.

Primary radiotherapy of T1 squamous cell carcinoma of the larynx: analysis of 478 patients treated from 1963 to 1985.

Radiotherapy was administered to 478 consecutively treated patients with laryngeal T1 squamous cell carcinoma between 1963-1985. One hundred and seventeen had a supraglottic, 358 a glottic, and 3 a subglottic tumor. Supraglottis: 71% males; 49% T1a; 14 patients with nodes. Glottis: 90% males; 82% T1a; 1 patient with node. The 10-year value for local control in the supraglottic group was 55% and in the glottic group 81%. No difference was observed between T1a and T1b. Regional nodes and distant metastases were seldom seen in the glottic, but frequently observed in the supraglottic group. The treatment results appeared to be most favorable in women. The 10-year corrected survival for supraglottic and glottic tumors demonstrated a highly significant difference, 67% compared to 94%. There was a significantly increasing incidence of events with lower tumor differentiation. Split-course and conventional radiotherapy gave equal treatment results, but late complications were significantly more common with the former. A major problem was new primary cancers, which within 20 years occurred in 34% of patients surviving a supraglottic tumor and in 23% of the glottic patients. The predominant new site was the lung (23% and 13%, respectively). Thus, in the glottic group more patients died from the new cancer than from the glottic carcinoma.

Misonidazole combined with split-course radiotherapy in the treatment of invasive carcinoma of larynx and pharynx: report from the DAHANCA 2 study.

Between October 1979 and May 1985, 626 patients with pharynx and larynx carcinoma were randomized to two different split-course radiation regimens and given either misonidazole (MISO; 11 g/m2) or placebo during the initial 4 weeks of treatment. Patients in the different treatment groups were evenly distributed among stages. The small number of females (136) gave an uneven distribution, thus making analysis difficult. The results show that females had a statistically better loco-regional control (45 vs. 33%; 5-year actuarial value). Overall, the MISO treated group did not have a significantly better control rate than the placebo groups (37 vs. 34%). However, a difference was found in patients with pharynx carcinomas (38 vs. 27%; p less than 0.05). The pre-irradiation hemoglobin (Hb) concentration was found to be a prognostic parameter. In females, loco-regional control for IIb values below or above 8 mmol/l were 37 and 47%, respectively. In males, the same values were below or above 9 mmol/l 26 and 38%. Hb influence on local control was only seen in supraglottic and pharynx tumors. This effect was independent of tumor size, which also was of prognostic value. In addition Hb concentration and MISO had an apparent additive effect. Thus in the male pharynx group, placebo patients with low Hb had a 14% disease rate compared to 40% in MISO treated patients with Hb above 9 mmol/l. MISO induced significant peripheral neuropathy in 26% of the treated patients, whereas other drug related side effects were minimal and tolerable.

Comparison of conventional and split-course radiotherapy as primary treatment in carcinoma of the larynx.

Based on our experience with conventional, daily irradiation, a split-course radiation schedule was introduced in 1978. The schedule, which was based on Cohen's models for squamous cell carcinoma and vascular damage respectively, predicted an improved tumour control and a reduced rate of late complications, e.g. late oedema, if the conventional, daily treatment was replaced by a split-course schedule. The schedule has later been abandoned, but the experience gained from split-course treatment at various dose levels has been analysed and the results compared with those obtained by conventional radiation. The data allowed construction of dose-response curves and estimation of iso-effect doses. Split-course treatment was associated with a significantly reduced therapeutic ratio because, disappointingly, it did not improve tumour control, and the severity of late complications grew. No late complications were avoided by introducing a 3-week pause in the radiation therapy regimen, nor was the tumour response improved despite a 12-Gy increase in total dose. This indicates a significant repopulation corresponding to more than 0.5 Gy/day, equivalent to an up to 100-fold increase of the number of clonogenic tumour cells during the pause--an increase that occurred despite the decrease, clinically, of the tumours during this period.

A new system for patient fixation in radiotherapy.

A new system for patient fixation in radiation treatment is described. The system consists of an airtight plastic bag with a contents of polysterol microspheres. A valve allows evacuation which results in a rigid close fitting cast. The system was compared with conventional foam cast fixation in 29 patients who were treated for carcinoma of the breast. The patients received radiation treatment over 22 fractions, and portal X-ray pictures were obtained at every second treatment. The portal films were compared with the stimulator radiographs and the variation in the position of the centre cross were measured in cranio-caudal and transversal direction as well as the rotation of the centre cross. The results showed that the daily reproducibility of the patient set-up was considerably improved by the new system, the centre cross deviation of the position of the actual radiation field to the centre cross of the intended field being less than 1 mm in 50% of the cases. The system is time-saving and cheap compared to conventional fixation systems.

Primary radiotherapy of larynx and pharynx carcinoma--an analysis of some factors influencing local control and survival.

An analysis of 950 patients with carcinoma of the larynx and pharynx was performed to identify factors of importance for local control and survival other than the TNM-classification. All patients were treated with primary radiotherapy, with doses ranging between 60-68 Gy in 6-7 weeks. The achievement of local-regional control by primary radiotherapy was highly correlated with disease-free survival (98% actuarial 5 year probability), which was significantly better than in patients who failed in the primary treatment but were salvaged by radical surgery. Furthermore, occurrence of distant metastases were almost all associated with failure to control the primary tumor. Sex was found to be a dominant prognostic factor, and in all sites and stages, women had a significantly better prognosis both with regard to local control and survival. The degree of histopathological differentiation was not significantly correlated with local control but with the incidence of distant metastases, which was significantly higher in patients with poorly differentiated tumors. In both males and females the pre-treatment hemoglobin concentration was correlated with the probability of primary tumor control and survival but only in patients with pharyngeal and to a lesser degree supraglottic tumors. In these groups, patients with hemoglobin levels above 13 g% (females) and 14.5 g% (males) had a significantly better prognosis than comparable patients with lower hemoglobin values. Such correlation could not be detected in patients with glottic tumors. The influence of tumor size was analyzed in a larger group of 1,060 patients with laryngeal carcinoma. In this group a notable correlation between tumor size and prognosis was observed within the various T-categories, indicating the tumor size as a significantly important parameter related to both probability of local control and survival. The study reveals that head and neck cancer is a heterogeneous disease and it is demonstrated that attention should be given to the various prognostic parameters since important therapeutic achievement is otherwise lost.

Malignant tumours of the paranasal sinuses and nasal cavity. A series of 180 patients.

In a series of 180 malignant tumours in the paranasal sinuses and nasal cavity the largest groups comprised 90 epidermoid carcinomas, 25 adenocarcinomas, and 19 adenocystic carcinomas. The epidermoid carcinomas were classified according to various proposed methods. The planned treatment schedule for carcinoma was 57 to 60 Gy in 30 fractions over 42 days, followed 8 to 12 weeks later by radical surgery. In the group of 80 patients with epidermoid carcinomas treated with radical intention, the 5-year corrected survival was 42 per cent. The prognosis has been analysed against a number of parameters, and it is found that sex, tumour size, and histologic score are important but neither totally independent nor evenly distributed parameters.

Squamous cell carcinoma of the nasal vestibule. Treatment results.

Sixty-six patients with squamous cell carcinoma of the nasal vestibule were treated, the majority with radiation therapy, and the results of the treatment are analysed. Twenty-two patients (35%) had local recurrence. A classification proposed by Wang was found useful, showing that a high proportion of small tumours (T1 + T2) was cured (81% and 52%) and that possible local recurrence in these patients could be treated successfully with surgery (12 of 22); locally advanced tumours (T3) had a bad prognosis (local recurrence 88%, death 56%). As an alternative, tumour size can be used as a prognostic parameter. The 5-year crude survival was 61.4 +/- 6.8%. Women seem to have a lower local recurrence rate than men.

Carcinoma of the larynx. Series of 410 patients treated primarily with 60Co irradiation.

From 1965 to 1983 410 patients were treated for laryngeal carcinoma at the radium centre and the ENT department in Odense. No change in pattern of disease could be traced during the period of 18 years. The treatment was predominantly 60Co irradiation with salvage surgery. 1977 to 1979 bleomycin, methotrexate and vincristine were given before irradiation. In 1979 split course radiation therapy was introduced in the treatment of stage II, III and IV cases and the patients were randomized, half of them receiving the radiosensitizer misonidazole, half of them placebo. Between 75 and 80 per cent of the patients were cured. Whereas chemotherapy did not change the survival some improvements may be traced in the period after 1979.

Laryngeal carcinoma. IV. Analysis of treatment results using the Cohen model.

Long term results, obtained in the treatment of 308 patients with laryngeal carcinoma are analysed with respect to local recurrence and complications. In this analysis the Cell Population Kinetic model, proposed by COHEN (1971) is used. The model for squamous cell carcinoma is found to be useful and in close agreement with observations of local recurrence, although a slight modification may be justified from the present data. No special model exists for late edema, but the model for late effects in the vascular stroma seems to be useful in this respect. Based on the model, a working hypothesis has been proposed, by which it is possible to predict the frequency of local recurrence and late edema. An optimum treatment schedule is calculated and converted to a split-course technique.

Laryngeal carcinoma. III. Treatment results in relation to microscopic score.

Long term treatment results for 254 patients with laryngeal carcinoma, primarily treated by irradiation, have been analysed according to a microscopic score, indicating the degree of malignancy. Deaths from carcinoma are significantly correlated to the microscopic score. It is strongly indicated that such correlations also exist for local recurrence/residual tumour and regional lymph node metastases. Therefore it is concluded that the microscopic grading system is a valuable prognostic factor supporting, and additional to, the T.N. classification. Larger series are needed in order to obtain correlations in subgroups, and accordingly primary therapeutic consequences can only be suggested, in doubtful cases.

Laryngeal carcinoma. II. Analysis of treatment results using the Ellis model.

An analysis of 308 patients with carcinoma of the larynx was performed with respect to local recurrence and complications in relation to treatment level. The patients received primary irradiation with some difference in absorbed dose but with an equal fractionation schedule. Analysed in subgroups, correlations between local recurrence and treatment level were either demonstrated or strongly indicated. This is confirmed in a comparison with approximately 1 500 cases collected from the literature. Correlations between complications and treatment level were not found, but nevertheless indicated with respect to late edemas, which again are supported by comparison with approximately 800 cases collected from the literature. The risk of pharyngo-cutaneous fistula after total laryngectomy seems to be rather independent of irradiation level, although slightly dependent on field size. An optimum level of treatment has been estimated and brought into use since January 1978.

Laryngeal carcinoma. I. Treatment results.

A series of 359 patients with carcinoma of the larynx was found to be very close to being representative of the northern part of Jutland, Denmark (north of Kongeåen). No unequivocal change in the disease as regards sex, age, histology, symptoms and signs, and stage of disease could be observed during the period 1963 to 1972. A not statistically significant improvement in the corrected mortality appeared. The level of complications after irradiation and secondary surgery was found to be low. A statistically significant, better prognosis was found for females than for males in the glottic group.

Epidermoid carcinoma of the larynx. VI. Histologic grading in the clinical evaluation.

A multifactorial microscopic grading of malignancy was performed on a clinically well examined series of 129 patients with laryngeal carcinoma. The microscopic score was statistically significantly correlated to the frequency or regional lymph-node metastases and to the death rate. It afforded important supplementary information for the T-classification and for the prognosis. Microscopic grading is an essential supplement to the clinical evaluation of risk groups.

Carcinoma of the larynx. V. Relationship between biologic effect and failure of irradiation.

Among 147 patients with laryngeal carcinoma, treated with 60Co irradiation and followed for 5 to 10 years, there were 5 cases of recurrence due to incorrectly placed fields. The glottic cases consisted of one group below and one above a Partial Tolerance of 1 650 ret. In the latter group the recurrence rate was significantly lower than in the former. Higher ret levels did not lower the residual tumour or recurrence rate in the glottic group but seemed to lower the rate in the supraglottic group.