Postoperative radiotherapy in breast cancer--long-term results from the Oslo study.

The long-term results of a randomized clinical trial evaluating the effect of postoperative radiotherapy as an adjuvant to radical mastectomy are presented. There were 1115 patients including 27 protocol deviants. The follow-up time is 11-20 years. In the first part a conventional roentgen unit was used, and in the second part a 60Co unit, with considerably increased dosage and altered treatment plan. Both types of radiation techniques lowered the incidence of loco-regional recurrences significantly, but had no significant influence on the overall survival. The relapse-free survival was significantly improved by 60Co radiation in Stage II patients, but was unaffected by radiation in the other subgroups. Regarding survival, Stage II patients with medially located tumors seemed to benefit more from 60Co radiation than those with lateral tumors. A significant increase in the number of deaths caused by myocardial infarction was observed in Stage I patients having 60Co radiation, indicating that the radiation dose to the heart is of significance.

Stage I melanoma of the limbs. Immediate versus delayed node dissection.

553 patients with stage I malignant melanoma of the limbs entered a prospective randomized clinical trial carried out by the W.H.O. Collaborating Centres for Evaluation of Methods of Diagnosis and Treatment of Melanoma from September 1967 to January 1974. 286 patients were submitted to wide excision of primary and node dissection at the time as appearance of regional lymph node metastases and 267 to wide excision and immediate node dissection. Survival was identical in the 2 groups. Different subsets of patients were evaluated to assess whether some groups of patients may benefit from immediate node dissection. As regards sex, females and a significantly higher survival rate than males (p < 0.05), but results were not improved by immediate node dissection. Maximum diameter and elevation of primary melanoma were significantly related to survival but also in these cases immediate node dissection did not achieve better results. 63 patients had an excisional biopsy of their melanoma within 4 weeks before final treatment. This procedure did not worsen survival and also in this case immediate node dissection did not improve survival. 273 cases were classified according to histologic type: survival of superficial spreading and nodular melanoma was not different at a statistically significant level after the 2 treatment modalities. 325 cases were considered classifiable according to Clark's levels, out of these 165 were submitted to immediate node dissection. Neither level III nor level IV cases showed higher survival rate after immediate node dissection. Maximum tumor thickness according to Breslow was evaluated in 338 cases: 188 were submitted to wide excision and immediate node dissection. In no clusters of thickness did the enlarged surgical procedure achieve better results. The authors conclude that there is good evidence that in stage I melanoma of the extremities delayed dissection.

Combined surgery and radiation therapy versus surgery alone in primary mammary carcinoma. I. The effect of orthovoltage radiation.

The effect of routine postoperative irradiation in the treatment of carcinoma of the breast has been evaluated. Postoperative irradiation had no effect on the proportion of patients free of disease nor on the survival rate, but the incidence of local recurrence and homolateral supraclavicular lymph node metastasis was reduced. In stage II patients homolateral axillary lymph node metastases were also encountered less frequently in the irradiated group. Distant metastases occurred either in stage II patients with postoperative irradiation as compared with controls.

Squamous-cell carcinoma of the tongue: preoperative interstitial radium and external irradiation. Part II: Survival.

The authors evaluated 300 cases of squamous-cell carcinoma of the anterior two thirds of the tongue treated from 1958 through 1972. Effects of treatment on absolute and relative survival were determined by the log rank method. Selection was non-random, based on the extent of the primary tumor, age, and general condition. Surgery, irradiation, or a combination of preoperative interstitial high-intensity radium needles and resection gave similar results in patients with tumor smaller than 4 cm (T1T2N0). In patients with larger tumor (T3N0) or mobile, unilateral neck metastases (TXN1), irradiation plus surgery produced better survival than irradiation alone. Different radiation techniques are analyzed. Elective external irradiation to the neck is recommended in all cases, even if no enlarged lymph nodes can be palpated.

Surgery in papillary thyroid carcinoma: a review of 730 patients.

Between 1956 and 1978, 1143 patients with thyroid cancer, nearly half of all patients with thyroid carcinomas in Norway in this period, were seen in our hospital. Of 730 papillary cancer patients, 447 were operated with total thyroidectomy (TT), 179 with hemi-thyroidectomy (HT), while 104 patients had minor thyroid resections (RT). Survival and recurrence rates were similar in the TT- and HT-groups. Local recurrences were seen in 15.2% of the patients following total thyroidectomy and in 16.2% following hemi-thyroidectomy; distant metastases were seen in 10.7% and 11.2%, respectively. Beyond the seventh year of follow-up the cumulative survival was similar following total thyroidectomies, hemi-thyroidectomies, and thyroid resections. Unless grossly malignant residues were left behind, the impact of the surgical procedure on prognosis in papillary thyroid cancer seems minor.

Squamous-cell carcinoma of the tongue: preoperative interstitial radium and external irradiation. Part I: Local and regional control.

Results of therapy in 300 patients with squamous-cell carcinoma of the anterior two thirds of the tongue are presented in terms of control of the primary tumor (local) and metastases to the lymph nodes of the neck (regional). Correlation between clinical stage and control was good, with the best results being obtained in stage T1N0 (84% control of tongue, 69% control of neck) and the poorest results in TX N2N3 (9% and 11%, respectively). Different methods of treatment were analyzed separately for various stages of disease and compared with results from other institutions. Possible methods of improving treatment are discussed.

Familial occurrence of papillary thyroid carcinoma.

We report two kindreds from northern Norway with 7 and 4 cases of papillary thyroid carcinoma in otherwise healthy, nonirradiated subjects. While histologic features were comparable the patient's age at the time of diagnosis was lower and lymph node metastases were more frequent in familial than in nonfamilial cases of papillary thyroid carcinoma from the same region. We conclude that genetic factors can predispose the patient for development of papillary thyroid carcinoma. The high local incidence may be due to interaction between susceptibility gene(s) and environmental factors.

Medullary carcinoma of the thyroid in Norway. Clinical course and endocrinological aspects.

A study of the clinical, biochemical and histological findings of 57 patients with medullary thyroid carcinoma (MCT) in Norway, is presented. The diagnosis was established by light and electron microscopy and by measurements of immunoreactive calcitonin (iCT) in serum. The major factor influencing the prognosis was the extension of the disease at presentation. None of the 24 patients with tumour confined to the thyroid gland have died of the disease, and serum iCT was normal in 15 patients. Of 19 patients with regional lymph node metastes only 11 are alive 1 to 14 years after treatment, and of these 9 had increased serum iCt. 14 patients technically inoperable and/or with distant metastases, 12 have died of MCT, 1 are alive with elevated serum iCT. Of 14 patients with raised serum iCT, 8 have no clinical recurrence of the disease from 1 to 15 years after the operation. MCT-associated diseases were found in 8 patients, chronic thyroiditis in 10. Serum iCT was measured in 249 relatives of 42 patients, and abnormal elevations were found in 11 members of 6 families.

Medullary carcinoma of the thyroid. Diagnostic problems.

Light microscopy is usually considered sufficient for the diagnosis of medullary carcinoma of the thyroid (MCT). As stromal amyloid is not always present and the tumor may exhibit great variation in growth pattern, light microscopy alone, however, may lead to misinterpretations. Of 1670 thyroid carcinomas registered durging a 15-year period in Norway, 42 were originally interpreted as MCT. The slides were reviewed and the diagnosis maintained in 33 cases only. Twenty-four additional cases were found by reviewing histopathologic slides from neoplasms originally registered as other types of thyroid tumors. Of 57 cases of MCT, stromal amyloid was demonstrated in 43. Calcitonin measurements and electron microscopy, even on formalin-fixed material, were valuable aids in establishing the correct diagnosis, though none of these methods are unequivocal. Different aspects of the problems concerning the diagnosis of MCT are discussed through the detailed presentation of five patients.

Carcinoma of the tongue in Norway and Wisconsin. I. Incidence and prognosis related to sex and age.

The records of 503 patients with carcinoma of the tongue diagnosed between 1958 and 1972 were reviewed. The preponderance of tongue carcinoma among men was confirmed both in The Norwegian Radium Hospital (NRH) and the University of Wisconsin Hospitals (UW), but it was relatively more frequent among women in NRH and in UW than in southern Europe. More women had on presentation less advanced tumors at NRH than at UW. The incidence of tongue carcinoma in Norway increased steadily with age for both sexes. The sex ratio did not change in Norway such as in England, Canada and the United States. Tumor of the posterior one-third of the tongue was relatively infrequent in women both in NRH and UW, in agreement with reports from other countries. The length of survival was analysed and no significant sex difference was demonstrated. The younger patients had less advanced tumors and a better prognosis.

Carcinoma of the tongue in Norway and Wisconsin. II. Influence of site and clinical stage on local control of the tumor.

The local control rates in patients with squamous cell carcinoma of the tongue, treated between 1958 and 1972, were determined by retrospective analysis of the records of 339 patients at the Norwegian Radium Hospital and of 164 patients at the University of Wisconsin Hospitals. The correlation between the clinical stage and the local control rate was good in Norway, less striking in Wisconsin. As the tumor grew in size it generally became increasingly difficult to control. Irradiation and surgery appeared relatively satisfactory in patients with tumors in early stages, but were often inadequate in the advanced tumors. The differences observed between Norway and Wisconsin were statistically significant only for the tumors of the base of the tongue and T2N0, T3N0 and TxN1 tumors of the anterior two-thirds of the tongue.

Anomalous papillary carcinoma of the thyroid.

Most papillary carcinomas of the thyroid run a surprisingly indolent clinical course, and even widespread lymph node metastases in the neck are not a bad prognostic omen. A small group behaves in a far more aggressive fashion and kills through local invasion of adjacent structures or blood borne metastases. This paper deals with a papillary carcinoma which does not fit into any of these groups. Following hemithyroidectomy for papillary carcinoma in 1970 the patient, a woman aged 70 years, lived comfortably for nine years until she died of what appeared to be an unrelated cause. During these nine years, papillary carcinoma metastases were removed at irregular intervals from unusual locations such as the thoracic wall, both groins, and the thigh. Gross examination, light and electron microscopy, and freeze-etching, all failed to distinguish this tumor from conventional papillary carcinomas. Morphometry showed that the nuclei were significantly larger than those found in other papillary carcinomas, and conventional and flow cytometric DNA analysis proved that the primary tumor and the metastases contained mainly tetraploid cells. One lymph node metastasis had even larger nuclei than the others and also a different, bizarre DNA distribution pattern. This study also showed that the ground glass appearance of the nuclei of papillary thyroid carcinomas does not depend on hypodiploid DNA values. Of about 70 cases of papillary thyroid carcinomas in the world literature studied by conventional or flow cytometric DNA analysis, this case is the only one with tetraploid DNA values. It is therefore tempting to correlate this tetraploidy to its peculiar biologic behavior.

Prognostic factors in liposarcoma.

In a series of 99 liposarcomas, the prognostic impact of the various diagnostic and therapeutic factors was analyzed. The analysis indicated that the tumor size, histologic subtype, and x-ray density are important prognostic factors. The prognosis is also influenced by operability and treatment modalities employed. Treatment strategy should be radical, irrespective of the actual prognostic factors.

Radioimmunoassay of human calcitonin in serum and tissue from healthy individuals and patients with medullary carcinoma of the thyroid gland.

A specific radioimmunological method for measurement of immunoreactive calcitonin (iCT) in human serum and tissue is decribed. Of healthy individuals of both sexes, 85% had measurable iCT in serum (mean, 0.23 ng/ml). Of 29 patients who had received treatment for medullary carcinoma of the thyroid gland (MCT), 19 had increased serum iCT (0.60 ng/ml to 205 ng/ml). Elevated serum iCT was also found preoperatively in 2 MCT patients. Eleven of the patients with abnormal elevations of serum iCT were alive 4 to 13 years after the operation. Concentration of iCT in extracts from MCT varied from 0.5 to 540 ng/ml wet weight. The diagnostic value of this method and its importance for pre- and post-operative evaluation of these patients are improved by the use of selective venous catheterization in basal state and during stimulation of CT secretion.

Inefficacy of immediate node dissection in stage 1 melanoma of the limbs.

From September, 1967, to January, 1974, a clinical trial was carried out by the WHO Melanoma Group to evaluate the efficacy of elective lymph-node dissection in the treatment of malignant melanoma of the extremities with clinically uninvolved regional lymph nodes. Treatment was prospectively randomized: 267 patients to excision of primary melanoma and immediate regional-lymph-node dissection and 286 to excision of primary melanoma and regional-lymph-node dissection at the time of appearance of metastases. The statistical analysis showed no difference in survival between the two groups of patients, regardless of how the data were analyzed (according to sex, site of origin, maximum diameter of primary tumor or Clark's level or Breslow's thickness). Elective lymph-node dissection in malignant malanoma of the limbs does not improve the prognosis and is not recommended when patients can be followed at intervals of three months.