A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma.

In a randomized trial of adjuvant chemotherapy, immunotherapy, or immunochemotherapy, 761 evaluable patients with pathological Stage II cutaneous melanoma anywhere on the body or with pathological Stage I melanoma of the trunk (Clark's level 3 to 5) were studied by the World Health Organization International Melanoma Group. Wide local excision and excisional regional lymphadenectomy alone were performed in 185 patients and the results were compared with those of surgery plus chemotherapy with dacarbazine (in 192 patients), surgery plus immunotherapy with bacille Calmette-Guérin vaccine (in 203), and surgery plus chemotherapy combined with immunotherapy (in 181). The rates of disease-free survival and overall survival at 36 months were 30.4 +/- 8.3 per cent (mean +/- S.E.) and 41.6 +/- 10.0 per cent, respectively, after surgical treatment alone; 37.2 +/- 7.9 per cent and 46.5 +/- 8.3 per cent after surgery plus chemotherapy; 34.8 +/- 7.9 per cent and 48.7 +/- 8.7 per cent after surgery plus immunotherapy; and 33.6 +/- 7.9 per cent and 50.0 +/- 8.8 per cent after surgery plus a combination of chemotherapy and immunotherapy. None of the differences between groups was significant, and thus no effect of adjuvant therapy could be demonstrated in this study.

Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities.

Results of a prospective randomized clinical trial conducted by the WHO Collaborating Centers for the Evaluation of Methods of Diagnosis and Treatment of Melanoma are reported. Five-hundred-fifty-three Stage I patients whose limbs were affected entered the study; 267 were submitted to wide excision and immediate node dissection and 286 had wide excision and node dissection at the time clinically positive nodes were detected. Survival curves of the two treatment groups could be superimposed. No subsets of patients benefitted from immediate node dissection. The authors conclude that delayed node dissection is as effective as the immediate dissection in Stage I melanoma of the extremities if the patient can be checked every three months. If the quarterly follow-up is not guaranteed, immediate node dissection is advisable, at least for melanomas thicker than 2 mm.

A case of Burkitt's lymphoma in Bulgaria.

A case of Burkitt's lymphoma is reported in a 5-year-old girl with involvement of the jaw and loosening of the teeth. Bilateral ovarian involvement occurred and subsequently dissemination to the CNS retrobulbar spaces causing exophthalmus, the thyroid, the myocardium, and other sites. The therapeutic plan included irradiation of the mandible and systemic chemotherapy. Due to the rapid deterioration of the patient's condition, irradiation was suspended at 1,200 rads. Chemotherapy was not administered since the bone marrow was completely replaced by lymphomatous tissue.

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.

Spontaneous rosette formation in patients with oral cancer.

The percentage of "total" E-rosettes was studied in the peripheral blood of 38 untreated patients with squamous cell carcinoma of the oral cavity, performing the test at 4 degrees C and at 20 degrees C. At 4 degrees C the quantity of the E-rosettes was higher than at 20 degrees C. The mean value of E-rosettes was strongly reduced only in 17 of these patients with metastases in the regional lymph nodes when compared with a group of 40 normal individuals as well as with the group of remaining 21 patients with localized cancer (P less than 0.001), whatever the temperature of testing. The mean percentage of 20 degrees C E-rosettes was significantly higher in patients with localized disease than in the 22 normal donors (50.2 +/- 3.0% vs 41.8 +/- 2.0%, P less than 0.01) but in favour of 4 degrees C E-rosettes the difference was not significant (57.3 +/- 2.8% vs 54.2 +/- 2.9%). Thus there was a clear correlation between changes of the T cell level and the clinical stage of the disease.

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.

Autoimmunization with irradiated tumour cells in human malignant melanoma.

Thirteen patients have been immunized with their own irradiated melanoma cells on one or more occasions. Following these autografts tumour-specific cytotoxic antibodies were produced, the longest response lasting 14 days. This procedure had no apparent effect on the course of the disease in these patients.

Tumour-specific antibodies in human malignant melanoma and their relationship to the extent of the disease.

Biopsy specimens and sera were obtained from 103 melanoma patients. Autoantibodies were demonstrated by (1) complement-dependent cytotoxicity of autologous melanoma cells in short-term culture; (2) complement-dependent inhibition of ribonucleic acid synthesis; (3) immunofluorescent staining of the cytoplasm of killed melanoma cells and of the surface membrane of viable melanoma cells. Over one-third of the sera studied had antibodies to autologous melanoma cells. Although for technical reasons all three tests could not be performed with the cells from every melanoma, whenever multiple testing was possible there was complete concordance. The autoantibodies were virtually confined to patients in whom the disease was not widely disseminated, and over 80% of such patients had positive sera. In a limited number of patients who have been followed autoantibodies disappeared as the disease progressed to become widely disseminated. Two patients with generalized disease developed autoantibodies following inoculation by their own irradiated tumour cells.TWO TYPES OF AUTOANTIBODIES WERE RECOGNIZED: one, active against antigen(s) in the cell surface membrane, was specific for each tumour-that is, only the autologous serum reacted-and was concerned in the cytotoxic activity; the other reacted with cytoplasmic antigens which appeared to be present in most or all melanoma cells.