Faculty Bibliography

Stage I cutaneous malignant melanomas between 0.76 and 1.69 mm thick (Breslow measurement) in BANS (upper part of the back, posterior aspects of the arms, posterior and lateral aspects of the neck, posterior aspect of the scalp) areas have been reported to portend a relatively poor prognosis compared to non-BANS sites. We were unable to confirm the 15% poorer survival for BANS area lesions (84% BANS, 99% non-BANS) originally reported. In this report of 211 patients, malignant melanomas in BANS sites had a 4.6% poorer 5-year cumulative survival rate (88.9% BANS, 93.5% non-BANS; p = 0.35). Although many more patients need to be studied, we believe this small difference in survival is insufficient to influence therapeutic management strategies

A polyvalent melanoma tumor antigen vaccine was prepared from antigens shed by a pool of human melanoma cells cultured in serum-free medium. The vaccine contained multiple melanoma associated antigens (MAAs) and was free of detectable fetal calf serum (FCS) proteins and Dr antigens. Three batches of vaccine prepared several months apart contained the same spectrum of tumor antigens. Thirteen patients with metastatic malignant melanomas were immunized intradermally with escalating doses of the vaccine in a Phase I study. There was no toxicity other than transient urticaria at the injection site. Humoral immunity, assayed by indirect immunoprecipitation, was augmented in five (38%) patients. Cellular immunity, assayed by delayed-type cutaneous hypersensitivity, was induced in four (31%) patients. Skin tests to a control vaccine prepared from pooled allogeneic lymphocytes were negative. Cutaneous metastases regressed completely in one patient who is now disease free after 2 years, and multiple cutaneous metastases have remained stable for 14 months in another patient. These results indicate that active immunization to a partially characterized polyvalent melanoma antigen vaccine is safe and can increase immunity to melanoma in some patients

The clinical course and histopathologic factors of 50 consecutive patients treated for dermatofibrosarcoma protuberans were reviewed. Forty-eight patients were observed until the present time or death. No patient had distant metastases develop, although 16 patients had 18 recurrences of the dermatofibrosarcoma protuberans at the site of initial therapy. There was no correlation between the diameter of the primary lesion and the incidence of recurrence. There was no correlation between the histologic pattern of invasion and recurrence. However, a trend toward decreasing recurrence was noted with increasing minimal margins of resections (41 per cent less than 2 centimeters versus 24 per cent greater than or equal to 2 centimeters). The lowest incidence of recurrence (20 per cent) was noted with minimal margins of resection greater than or equal to 3 centimeters. Five year recurrence free survival rates increased with increasing margins of resection--59 per cent less than 1 centimeter; 66 per cent greater than or equal to 1 centimeter; 70 per cent greater than or equal to 2 centimeters, and 80 per cent greater than or equal to 3 centimeters. No patient had distant metastases and no change in histologic pattern was noted with progressive local recurrence

In order to test the possible cardiac-sparing effect of doxorubicin administered by six-hour intravenous infusion and to prospectively evaluate the role of resting left ventricular ejection fraction in monitoring these patients, 33 women with advanced breast cancer were treated with combination chemotherapy containing 5-fluorouracil, cyclophosphamide, and doxorubicin. Doxorubicin was administered via a femoral catheter as a six-hour infusion. Cardiac function was monitored prior to therapy and at intervals during therapy by history and physical examination and by measurement of resting left ventricular ejection fraction with gated pool radionuclide angiography. Twenty-six responses were observed (complete response, seven [21 percent]; partial response, 19 [57 percent]). Systemic toxicity included alopecia, myelosuppression, and nausea and vomiting. There was a progressive fall in resting left ventricular ejection fraction during treatment from a median baseline value of 0.63. Mean fall from baseline left ventricular ejection fraction at a cumulative doxorubicin dose of 200 to 300 mg/m2 was 0.06 (p less than 0.005); at 301 to 449 mg/m2 it was 0.09 (p less than 0.0005); and at 450 mg/m2 or greater it was 0.15 (p less than 0.0005). Clinical congestive heart failure developed in three patients. Even though the decrease in left ventricular ejection fraction was often within the 'normal range' (left ventricular ejection fraction 0.50 or greater), these changes were progressive and appeared to be part of a continuum of doxorubicin-induced myocardial damage. Steady-state infusion levels of doxorubicin in plasma ranged from 90 to 120 nM. They confirm the hypothesis that lower concentrations can be achieved by continuous infusion rather than by bolus infusion. In this study, however, administration of doxorubicin by six-hour infusion did not appear to have a major cardiac-sparing effect. Studies of anthracycline cardiac toxicity should include determination of baseline left ventricular ejection fraction and serial observations during therapy. Failure to include deteriorations in function above an arbitrary cutoff point or to make observations only at higher cumulative doses may underestimate drug-induced myocardial damage

In summary, we believe that in the following situations elective regional lymph node dissection should not usually be performed: Patients whose primary malignant melanomas are in situ or have a maximal thickness of less than 1.0 mm. The incidence of regional node metastases in the latter group is so low that regional lymph node dissection is not justified. Patients whose primary malignant melanomas are in the midline of the head and neck or the trunk. Bilateral nodal dissections in these two regions of the body in the absence of a clearly demonstrable therapeutic advantage are not justified. Whether radioisotopic localizing studies will add greater definition to this group remains to be seen. Elderly patients or those with serious intercurrent disease. They should not undergo elective nodal dissection unless the primary malignant melanoma is very thick and lies directly over its nodal group. Patients with systemic metastases. For all remaining patients, the therapeutic or at very least prognostic advantages of elective regional lymph node dissections have been outlined. Conversely, an adverse effect on the course of the disease has never been demonstrated. We adhere to a policy that includes these procedures as primary therapy, provided they are performed with minimal morbidity. Should a surgeon elect not to perform such a procedure in the absence of clinically suspicious lymphadenopathy, careful clinical evaluation at 2-month intervals for the first 2 to 3 years following primary excision, with more prolonged intervals thereafter, would appear prudent. Until such time as effective means of eradicating systemic metastatic malignant melanoma exist, surgery remains the treatment of choice for this potentially fatal neoplasm. Efforts to develop effective adjuvant treatment based on the precise means of delineating prognosis that have thus far been developed has eluded investigators. A reasoned surgical approach is still required in our judgment until the identification and treatment of premalignant precursor lesions are universal or effective systemic therapy is available