Nathan W. Pearlman

Phase II Multicenter Study of Neoadjuvant Biochemotherapy for Patients With Stage III Malignant Melanoma

PURPOSE To determine the relapse-free survival, overall survival, and response rate of patients with stage III melanoma treated with neoadjuvant biochemotherapy in a multicenter setting. PATIENTS AND METHODS Patients with pathologically proven stage III melanoma, either via clinical detection or sentinel lymph node positivity, were eligible for enrollment. Patients received two cycles of preoperative biochemotherapy followed by complete regional lymphadenectomy and two postoperative courses of biochemotherapy. The biochemotherapy regimen consisted of the following: cisplatin 20 mg/m2 on days 1 to 4, dacarbazine 800 mg/m2 on day 1 only, vinblastine 1.6 mg/m2 on days 1 to 4, interleukin-2 total dose of 36 MU/m2 during 4 days, and interferon alfa 5 MU/m2 on days 1 to 5. Growth factor support was administered with each cycle. RESULTS Ninety-two patients were eligible for the study. At a median follow-up of 40.4 months, relapse-free survival and overall survival are 64% and 78%, respectively. There was a lower relapse rate and improved survival for patients with a positive sentinel lymph node compared with patients with clinically detected lymph nodes, although this difference did not reach statistical significance. Of the 50 patients with measurable disease, the overall response rate was 26%. Toxicity of the biochemotherapy was high but generally manageable. CONCLUSION The current study has expanded the preliminary evidence on neoadjuvant biochemotherapy for stage III melanoma.

A case-control study of late recurrence of malignant melanoma

Late recurrence of malignant melanoma is uncommon but appears to be a growing problem. It is unclear whether late recurrence has a better prognosis than early recurrence. Since the answer may influence treatment, we compared recurrence sites and subsequent survival in 35 patients with disease-free intervals of 72 to 240 months (median: 127 months) with 35 case-controls who had relapse at 4 to 56 months (median: 26.7 months). The distribution of recurrence sites in early relapse was 66% in regional nodes or soft tissue and 34% in distant soft tissue or viscera. In late relapse, this distribution was 49% in regional nodes or soft tissue and 51% in distant soft tissue or viscera (no significant differences). Median survival for patients with early and late recurrences in regional nodes or soft tissue was 26 and 44 months, respectively (no significant differences); 5-year survival was 27% and 33%, respectively (no significant differences). Median survival was similar for early or late relapse in distant soft tissue or viscera (8 and 10 months, respectively), as was 5-year survival (0% and 6%, respectively). These results suggest that the metastatic pattern and survival after recurrence are similar for patients with early and late recurring melanoma.

A prospective study of preoperative chemotherapy and split-course irradiation for locally advanced or recurrent oral/pharyngeal squamous carcinoma.

TWO COURSES OF PREOPERATIVE CHEMOTHERAPY (methotrexate, bleomycin, cisplatin) were combined with split-course irradiation (2,000 rad/10 preop., 4,000 rad/20 postop.) and prospectively compared with standard therapy (surgery and/or irradiation alone) for locally advanced or recurrent oral/pharyngeal squamous cancer. The chemoradiotherapy arm (Ch-XRT) had 31 patients; the standard therapy arm 28 randomized (RC) and 20 concomitantly-treated (CC) patients. Treatment-related mortality was 17% for Ch-XRT; 10% for RC + CC. Number of patients NED at completion of treatment was 74% for Ch-XRT; 83% for RC + CC (NS). Median survival, however, was 17 months for Ch-XRT, 9 months for CC, and 12 months for RC. In addition, survival at 40 + months was 45% for Ch-XRT versus 21–22% for RC and CC (p < 0.05). Thus, Ch-XRT seems to have promise in advanced oral/pharyngeal cancer, but needs revision to decrease toxicity.

Cancer of the colon and rectum in high-risk patients.

The experience with colorectal cancer at the Denver Veterans Administration Hospital was retrospectively reviewed to characterize the high-risk population with this disease and to determine what impact, if any, screening high-risk patients might have on overall survival rates. The high-risk patients comprised 12 per cent of the overall population with colorectal cancer and did not differ from the latter in terms of age of onset, distribution of tumors, type of symptoms at diagnosis, or survival with a given stage of disease. They did, however, have more stage A and B lesions and a better overall survival than did the general population with colorectal cancer, as a result of screening. The findings suggest that surveillance of high-risk groups is beneficial. Until ways are found to increase the number of patients eligible for inclusion in this group, however, these benefits are unlikely to lead to improved survival of the general population with colorectal cancer.

Modified radical neck dissection and postoperative radiotherapy in squamous cell head and neck cancer

Between 1978 and 1982, 41 patients with clinically staged N1, N2, or N3b disease underwent unilateral or bilateral modified radical neck dissection. Five patients died free from their original disease with less than 24 months follow-up. Twenty-four patients with histologically positive nodes received postoperative radiotherapy with 2 (8 percent) neck recurrences. Another four patients with histologically positive nodes refused postoperative radiotherapy and had two (50 percent) neck recurrences. Three patients did not respond to radiotherapy at the time of their surgery and had no neck recurrences. The final five patients had histologically negative nodes, did not receive radiotherapy, and had no neck recurrences. These results suggest that modified radical neck dissection can be used in lieu of the classical radical dissection in many patients with clinically positive nodes who have squamous cell head and neck cancer without compromising survival.

A neoadjuvant biochemotherapy approach to stage III melanoma: analysis of surgical outcomes

AIMS Completion lymph node dissection (CLND) and adjuvant therapy are recommended for node-positive melanoma patients. We sought to analyze our institutions experience with neoadjuvant biochemotherapy in stage III patients. METHODS Clinical information was extracted from a retrospective database on stage III melanoma patients. Eligible patients received two cycles of biochemotherapy prior to their CLND. RESULTS There were 153 patients available for analysis. The average tumor depth was 2.5 mm. More than half of all patients presented with sentinel lymph node-positive disease. Surgical complications occurred in 23% of patients. Patients who experienced an adverse event during their neoadjuvant therapy had a worse overall survival when compared with those who did not (p = 0.005). CONCLUSION Our data suggest that aggressive neoadjuvant treatment prior to CLND does not impact surgical complications. Our surgical outcomes are similar to the current literature when adjuvant therapy is used in stage III melanoma. The inability to tolerate neoadjuvant therapy in stage III melanoma is a negative prognostic indicator.

Analysis of melanoma recurrence following a negative sentinel lymph node biopsy

Little attention has been paid to the characteristics and outcomes of patients who experience distant, local or regional recurrence of melanoma following a negative sentinel lymph node biopsy. This article aims to review the published literature on the topic and presents some general summaries regarding this patient population. Patients who experience a disease recurrence following a negative sentinel lymph node biopsy have a worse overall survival compared with patients with a positive sentinel lymph node biopsy. The implications and possible explanations for these findings are discussed in order to both underscore the need for in-depth investigation of local, regional or distant melanoma recurrence among patients following a true negative sentinel lymph node biopsy, as well as increased efforts to minimize the rate of false negative sentinel lymph node biopsies.