Adjuvant Isolated Limb Perfusion Research Articles

Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities – Long-term follow-up of a randomised trial

Introduction: Isolated limb perfusion (ILP) is a treatment option most commonly used in the treatment of melanoma in-transit metastases of the extremities. The principle idea is to surgically isolate a region of the body and then deliver a high concentration of a chemotherapeutic agent together with hyperthermia. There have been three randomised trials exploring whether adjuvant ILP to patients with recurrent or high-risk primary melanomas increases survival; one of these trials has now been updated with a 25-year follow-up.Methods: The original study randomised 69 patients (between 1981 and 1989) with their first satellite or in-transit recurrence to either wide excision (WE group, n = 36 patients) or to WE and adjuvant ILP (WE + ILP group, n = 33 patients). Follow-up data 25 years later concerning survival and cause of death was retrieved from the Swedish National Cause of Death Register.Results: In the WE + ILP group there were 20 deaths (61%) due to melanoma compared with 26 deaths (72%) in the WE group (p = 0.31). Median melanoma-specific survival was 95 months for WE + ILP compared to 38 months for the WE group, an almost 5 year benefit without statistical significance (p = 0.24).Discussion: There is no evidence that adjuvant ILP prolongs survival in patients with high-risk or recurrent melanoma; however, the existing randomised trials are largely underpowered to detect such a difference. New studies are exploring systemic immunological effects of ILP, and a combination of regional therapy and immunotherapy may serve as a rationale for new trials using ILP in the future.

Prognostic Scoring in Patients With Melanoma After Adjuvant Isolated Limb Perfusion

The clinical course in melanoma is variable. The aim of the present study was to assess adjuvant isolated limb perfusion (ILP) efficacy using a surrogate comparison of observed survival versus Cochran-predicted survival. All patients in a single university hospital with primary, non-ulcerated limb melanoma who had undergone adjuvant ILP over 10 years (1986-1995) were studied. Clinical and pathological details including follow-up and survival were prospectively recorded in a national database. All patients were risk scored, as described by Cochran et al., to yield individual survival probability at the end of 3, 5 and 10 years and this was compared with observed survival at corresponding intervals. There were 85 patients who had adjuvant ILP for primary non-ulcerated limb melanoma. Of these, 14 deaths were observed (O) within the 10-year follow-up period. The Cochran score predicted (E) 20 deaths within 10 years (O/E ratio 0.7). The O/E ratios for deaths in the 0 to 3, 3 to 5, and 5 to 10 year intervals were 8/7.4, 5/6.0, and 1/6.5, respectively; prediction of late deaths tended to be overestimated. When patients were grouped by predicted 10-year mortality (<20%, 20-40%, >40%) the overestimation was found to occur mainly in the highest risk group: O/E ratios were 6/5.9, 6/8.4, and 2/5.6, respectively (P = 0.10, Hosmer-Lemeshow test). The observed and expected survival in patients receiving adjuvant ILP at the end of 3 and 5 years are comparable. The Cochran scoring system overestimated deaths during the 5 to 10 year interval. It is not clear whether this observation is a consequence of ILP efficacy or inaccuracy of the Cochran score.

Prognostic scoring in patients with melanoma after adjuvant Isolated Limb Perfusion (ILP)

Prognostic scoring in patients with melanoma after adjuvant Isolated Limb Perfusion (ILP)

Thirty-five years of isolated limb perfusion for melanoma: indications and results.

Isolated limb perfusion (ILP) for limb melanoma remains controversial despite its frequent use for over 35 years. To determine whether it has proven benefits, reported results have been reviewed. The value of adjuvant ILP cannot be determined from the multitude of retrospective studies on this subject. Preliminary results of the large European Organization for Research and Treatment of Cancer-World Health Organization-North American Perfusion Group trial suggest that patients with melanomas of 1.5-3.0 mm in thickness who do not undergo elective lymph node dissection may have a locoregional control benefit from ILP. However, as long as a definite survival advantage for ILP has not been demonstrated, such treatment does not seem justified for these patients. The value of prophylactic ILP after resection of recurrent limb melanoma is also scientifically unproven. The potential prevention of further limb recurrence for only a limited period of time, as demonstrated in a rather small Swedish trial, probably does not justify routine use of ILP in these patients; a large international trial will be needed to assess whether ILP provides a survival advantage. For those with locally inoperable limb melanoma, ILP appears to be the treatment of choice since it results in complete disappearance of all macroscopic disease in a substantial proportion of patients, removing the need for amputation and providing palliation of symptoms. However, high limb recurrence rates and short duration of response need improvement. Results of alternative treatments should be compared prospectively with those of ILP in this clinical situation.

Isolated limb perfusion: what is the evidence for its use?

This study was conducted to assess the best available evidence for the use of isolated limb perfusion. Following the principles of Evidence-Based Medicine, we reviewed the best available evidence for isolated limb perfusion (ILP) for melanoma and soft tissue sarcoma (STS) of the limb. Adjuvant ILP with melphalan (M-ILP) to wide local excision cannot be recommended for patients with primary melanoma with a limited regional benefit and no increase in overall survival (level 1b evidence). Prophylactic M-ILP next to the excision of recurrent melanoma has resulted in a nonsignificant decrease in recurrence rate (33% to 50%), with a significantly longer recurrence-free interval (10 to 17 months), but no survival benefit (level 2b evidence). Therapeutic M-ILP, with or without tumor-necrosis factor alpha and interferon gamma (T(I)M-ILP), seems indicated in unresectable melanoma (level 3 to 4 evidence). In unresectable STS of the limbs, limb salvage can be obtained in 57% to 86% of patients with neoadjuvant T(I)M-ILP (level 3 evidence). A comparison of level 3 to 4 studies on ILP and other neoadjuvant treatment modalities for unresectable STS shows that ILP results in the highest limb salvage rate with the lowest complication rate. Based on level 3 to 4 evidence, ILP is indicated in unresectable locoregional (recurrent) melanoma and unresectable STS of the limbs. Level 1 and 2b evidence does show an effect of prophylactic ILP on micrometastatic disease in locoregional (recurrent) melanoma of the limb. ILP seems the most effective limb sparing, neoadjuvant treatment modality when compared with other neoadjuvant treatment options for unresectable STS of the limb (level 3 to 4 evidence), although randomized studies are lacking.

Long-term functional morbidity after mild hyperthermic isolated limb perfusion with melphalan

Aims: To assess long-term functional morbidity in patients entered in the prospective randomized EORTC trial investigating the role of adjuvant isolated limb perfusion (ILP) with melphalan for high-risk primary melanoma. Methods: In 65 patients (ILP 36, wide excision only 29), limb circumference and joint mobility measurements were performed on the treated and the contralateral limb after a mean interval of 48 months after primary treatment. The two treatment groups were comparable regarding age, sex distribution, percentage of skin grafts or regional lymph-node dissections, and interval between primary treatment and physical measurements. Results: None of the patients had severe complaints of the treated limb at the time of analysis. The ankle suffered most from ILP, with a statistical significant restricted extension in approximately 40% of the perfused patients. Abduction of the shoulder was minimally affected in treated upper limbs, probably as a result from the formation of scar tissue after axillary lymph-node dissection. Although no significant differences could be demonstrated in the circumference of upper or lower limbs, atrophy was seen in 24% of perfused lower limbs. Of the five perfused patients who developed oedema, four had also undergone a regional lymph-node dissection. Conclusion: This risk of long-term functional morbidity should be weighed against the possible advantages of ILP in patients with limb melanoma or sarcoma.

A single centre prospective study of adjuvant isolated limb perfusion (ILP)

A single centre prospective study of adjuvant isolated limb perfusion (ILP)

A single-centre prospective study of adjuvant isolated limb perfusion (ILP)

A single-centre prospective study of adjuvant isolated limb perfusion (ILP)

Results of a single centre prospective study of adjuvant isolated limb perfusion (ILP)

Results of a single centre prospective study of adjuvant isolated limb perfusion (ILP)

A single centre prospective study of adjuvant isolated limb perfusion (ILP)

Mckay, A. J.; Scott, R. N.; Lingam, M. K.; Byrne, D. S.; Burnside, G.; MacKie, R. Author Information

Isolated Limb Perfusion for Localized Melanoma of the Extremity

The therapeutic efficacy of isolated limb perfusion in patients with localized melanoma of the extremity remains controversial. We compared patients treated at the University of Texas M.D. Anderson Cancer Center, Houston, with wide local excision and isolated limb perfusion using either melphalan or imidazole carboxamide with a group matched for prognostic factors from the University of Alabama at Birmingham and the University of Sydney (Australia) who were treated with wide local excision alone. No significant difference in disease-free or overall survival rates was found between patients treated with wide local excision with adjuvant isolated limb perfusion or wide local excision alone. However, a subset of patients with thicker lesions (greater than 2.0 mm) treated with wide local excision and isolated limb perfusion using melphalan had a significant improvement in both disease-free and overall survival rates. These data suggest that isolated limb perfusion using melphalan may improve survival rates in selected patients with localized melanoma of the extremity who are at increased risk for local and regional micrometastases, and justifies the continued study of this treatment approach in prospective clinical trials.