Factors influencing the use of sentinel lymph node biopsy in the Netherlands.

BACKGROUND: In the US, whether a sentinel lymph node biopsy (SLNB) is performed depends on tumor and patient factors, including socioeconomic status (SES) and type of health care insurance. We analyzed which patient and tumor characteristics influenced the use of SLNB in a country where every patient has equal access to healthcare. METHODS: Patients diagnosed with a cutaneous invasive melanoma of ≥1 mm between 2004 and 2011 and living in the northeastern part of the Netherlands were selected from the Netherlands Cancer Registry. Regression analysis was performed to assess the association of patient and tumor characteristics and SLNB use. RESULTS: SLNB was performed in 42 % of the 2,413 included patients. The frequency of performing SLNB increased between 2004 and 2011 from 24 to 55 % (p < 0.001). Patients were less likely to undergo SLNB if they had a melanoma located in the head and neck area (p < 0.001), when they were over 55 years (p = 0.001), and if they had a low SES (p = 0.03). SLNB use was more likely when the diagnosis of melanoma was made in the university hospital (p = 0.045) or when the Breslow thickness was 2.01-4.0 mm (p = 0.03). CONCLUSIONS: The use of SLNB has increased significantly between 2004 and 2011. However, in 2011 it was still performed in only 55 % of the Dutch patients with a melanoma ≥1 mm. In patients with head and neck melanoma, older patients, and patients with low SES, SLNB was less frequently performed. Patients with T3 melanomas and a diagnosis made in the university hospital more often had an SLNB performed.

Primary melanoma location on the scalp is an important risk factor for brain metastasis: a study of 1,687 patients with cutaneous head and neck melanomas.

BACKGROUND: Primary cutaneous head and neck melanomas (HNM) are reported to be associated with a higher incidence of brain metastasis than trunk and limb melanomas (TLM). In this study, the incidence of brain metastases in patients with HNM and risk factors for the development of brain metastases were analyzed. METHODS: From a large, prospectively-collected database, 1,687 HNM patients and 8,793 TLM patients who presented with American Joint Committee on Cancer (AJCC) stage I and II disease were identified. Survival was assessed using the Kaplan-Meier method and multivariate Cox regression analysis. Independent risk factors were determined by binary logistic regression analysis. RESULTS: The incidence of brain metastases 5 years after diagnosis of HNM was 6.7 % compared with 4.7 % for brain metastases from TLM (p = 0.003). Patients with scalp melanomas were most likely to develop brain metastases (12.7 %). Independent risk factors for brain metastasis in patients with HNM were Breslow thickness, ulceration, and scalp location. CONCLUSION: Patients with primary scalp melanomas had a much higher incidence of brain metastasis than patients with melanomas on other head and neck sites, who in turn had a higher incidence than patients with melanomas on sites elsewhere on the body. More intensive monitoring of patients with scalp melanomas, who are at particularly high risk of brain metastasis, might lead to earlier discovery of metastatic disease in the brain, offering the prospect of earlier intervention and better outcomes.

Isolated limb infusion with melphalan and actinomycin D for melanoma: a systematic review.

Isolated limb infusion (ILI) was developed as a simplified and minimally invasive alternative to isolated limb perfusion (ILP) to treat unresectable limb melanoma. A number of centers around the world have reported their results using this procedure. In this study a systematic review of reported ILI experiences was undertaken. A literature search was conducted according to the guidelines for systematic reviews in order to select eligible papers reporting limb toxicity and response rates following ILI using melphalan and actinomycin D to treat limb melanoma. A total of 576 patients from seven publications were included. Regional toxicity following ILI was low: no visible effect of the treatment or slight erythema or edema was observed in 79% of the patients, while considerable erythema and/or edema with blistering was experienced by 19%. In 2% there was a threatened or actual compartment syndrome. No procedure-related amputation was reported. Complete response occurred in 33% of the patients and partial response in 40%, an overall response rate of 73%. Stable disease and progressive disease were achieved in 14% and 13% of the patients, respectively. This first systematic review of ILI procedures using melphalan and actinomycin D indicates that regional toxicity was generally low, with satisfactory response rates. When comparing ILI and ILP, it must be borne in mind that ILI is often performed in significantly older patients and in patients with higher stages of disease, which decreases the likelihood of a favorable response.

Is melphalan dose adjustment according to ideal body weight useful in isolated limb infusion for melanoma?

BACKGROUND: Isolated limb infusion (ILI), introduced in 1992, is a technique used to deliver regional chemotherapy to treat advanced melanoma confined to a limb. Adjusting melphalan dose according to ideal body weight (IBW) has been proposed as a method of decreasing limb toxicity without compromising outcome. The current study analyzed this proposed dose adjustment. METHODS: We reviewed 99 consecutive patients with lower extremity melanomas treated by ILI at our institution between May 1998 and February 2009. Toxicity and outcomes were tested for correlation with differences between administered dose and calculated adjusted dose, both in mg and mg/L, and with differences between actual limb volume and calculated adjusted limb volume. RESULTS: The median actual body weight was 71 kg, whereas the calculated median IBW was 57 kg (p < .001). Median administered melphalan dose was 7.7 mg/L. The median calculated adjusted dose was 6.5 mg/L (range 3.2-9.3 mg/L, p < .001). None of the three aforementioned parameters correlated with either Wieberdink toxicity grade or outcome. BMI did not correlate with toxicity either. Interestingly, a higher total melphalan dose did not only correlate with higher toxicity, but also with a lower response rate. CONCLUSIONS: Adjusting the melphalan dose for IBW does not appear to reduce toxicity following ILI for melanoma. The effect on outcome remains uncertain. More research is needed to optimize melphalan concentrations in individual patients during ILI to limit toxicity without compromising the response.

Does increased experience with isolated limb infusion for advanced limb melanoma influence outcome? A comparison of two treatment periods at a single institution.

BACKGROUND: Isolated limb infusion (ILI) with cytotoxic drugs has been used since 1992 to treat advanced melanoma confined to a limb. Over this time the technique has undergone progressive modification. In this study we evaluated our experience with ILI by analyzing outcome and toxicity from an "early" and a "late" treatment period. METHODS: We compared the results from our institution for 94 patients treated by ILI in the early period (1992-1999) with the results for 91 patients treated in the late period (2000-2007). All patients had advanced limb melanoma and received a combination of melphalan and actinomycin D. RESULTS: The patient characteristics of the early and late groups were similar, but there was greater tumor load in the late group, who had a significantly greater number of lesions (median 4 vs. 5; p = 0.02) and deeper tumor infiltration (p = 0.03). Drug circulation times were longer in the late group: 22 vs. 31 min (p < 0.0001). In the late group, higher initial and final limb temperatures were achieved. Overall response rates were 85% in both groups. The late treatment group showed a trend towards less toxicity (p = 0.06). CONCLUSIONS: Response rates and survival following ILI for advanced melanoma in our late treatment period were similar to those of our early treatment period, despite the significantly greater tumor load of the patients treated in the late period. This could be attributed to increased experience and protocol modifications, which allowed longer drug exposure times and higher limb temperatures to be achieved without increased toxicity.