Because there is no survival benefit of amputation for extremity soft tissue sarcomas (STSs), limb-sparing surgery has become the gold standard. Tumor size reduction by induction therapy to render ...nonresectable tumors resectable or facilitate function-preserving surgery can be achieved by tumor necrosis factor α (TNF) -based and melphalan-based isolated limb perfusion (TM-ILP). This study reports the long-term results of 231 TM-ILPs for locally advanced extremity STS.
We analyzed 231 TM-ILPs in 208 consecutive patients (1991 to 2005), who were all candidates for functional or anatomic amputation for locally advanced extremity STS. All patients had a potential follow-up of up to 5 years. TM-ILP was performed under mild hyperthermic conditions with 1 to 4 mg of TNF and 10 to 13 mg/L of limb-volume melphalan. Almost all patients (85%) had intermediate- or high-grade tumors.
The overall response rate (ORR) was 71% (complete response, 18%; partial response, 53%). Multifocal sarcomas had a significantly better ORR of 83% (P = .008). The local recurrence rate was 30% (n = 70); local recurrence rates were highest for multifocal tumors (54%; P = .001) and after previous radiotherapy (54%; P < .001). Five-year overall survival rate was 42%. Survival was poorest in patients with large tumors (P = .01) and with leiomyosarcomas (P < .001). Limb salvage rate was 81%.
We demonstrated that TM-ILP results in a limb salvage rate of 81% in patients with locally advanced extremity STS who would otherwise have undergone amputation. Whenever an amputation is deemed necessary to obtain local control of an extremity STS, TM-ILP should be considered.
Background The purpose of this study was to investigate the long-term outcome and technical feasibility of sternal resection. Methods We performed a 25-year retrospective study of 68 patients who ...underwent a sternectomy for sarcoma, recurrent breast cancer (BC) or radiation-induced necrosis between 1981 and 2006 in two tertiary referral centres (Erasmus Medical Center/Daniel den Hoed Cancer Center and Netherlands Cancer Center/Antoni van Leeuwenhoek Hospital, Netherlands). Patients were treated with curative intent and followed until May 2009. Medical records were reviewed for patient characteristics, indications for surgery, surgical technique, postoperative complications, and survival. Results Sternal resection was performed in 43 sarcoma patients, 17 recurrent BC and 8 patients with radiation-induced necrosis with additional rib resection in the majority of patients and with clavicle resection in 13% of patients. Additional scapula, lung, breast or axilla resection, or both, was performed in 10%. Two patients died postoperatively (3%). Mild complications occurred in 24%, and severe complications (namely, pulmonary complications and reinterventions) in 16% of patients. Radical resection was achieved in 80% and 53% of sarcoma and recurrent BC patients, respectively. Five-year overall survival was 64% and 40% in sarcoma and recurrent BC patients, respectively, with 5-year disease-free survivals of 52% and 15%, respectively. Conclusions Sarcomas, recurrent BC, and radiation-induced necrosis can be successfully managed by sternal resection and reconstruction with curative intent. Low mortality and acceptable morbidity rates justify this operation in a palliative setting as well. Disease-free survival is poor among recurrent BC patients.
Background
Wide resection with tumor-free margins is necessary in soft-tissue sarcomas to minimize local recurrence and to contribute to long-term survival. Information about treatment outcome and ...prognostic factors of adult sarcoma requiring chest wall resection (CWR) is limited.
Methods
Sixty consecutive patients were retrospectively studied for overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Twenty-one prognostic factors regarding survival were analyzed by univariate analysis using the Kaplan-Meier method and the log-rank test.
Results
With a median survival of 2.5 years, the OS was 46% (33%) at 5 (10) years. The LRFS was 64% at 5 and 10 years, and the DFS was 30% and 25% at 5 and 10 years. At the end of the study period, 26 patients (43%) were alive, of which 20 patients (33%) had no evidence of disease and 40 patients (67%) had no chest wall recurrence. In the group of 9 patients with a radiation-induced soft-tissue sarcoma, the median survival was 8 months. Favorable outcome in univariate analysis in OS and LRFS applied for the low-grade sarcoma, bone invasion, and sternal resection. For OS only, age below 60 years and no radiotherapy were significant factors contributing to an improved survival. CWR was considered radical (R0) at the pathological examination in 43 patients. There were 52 patients with an uneventful recovery. There was one postoperative death.
Conclusions
CWR for soft-tissue sarcoma is a safe surgical procedure with low morbidity and a mortality rate of less than 1%. With proper patient selection acceptable survival can be reached in a large group of patients. Care must be given to patients with radiation-induced soft-tissue sarcoma who have a significantly worse prognosis.
Background
Approximately 5–8% of melanoma patients will develop in-transit metastases (IT-mets). Tumor necrosis factor-α (TNF) and melphalan-based isolated limb perfusion (TM-ILP) is an attractive ...treatment modality in melanoma patients with multiple IT-mets. This study reports on a 20 years experience and outlines the evolution and major changes since the introduction of TNF in ILP.
Methods
A total of 167 TM-ILPs were performed in 148 patients, between 1991 and 2009. TM-ILPs were performed at high doses of TNF (3–4 mg) from 1991 to 2004 (
n
= 99) and at low doses of TNF (1–2 mg) from 2004 to 2009 (
n
= 68) under mild hyperthermic conditions (38°C–39.5°C.). Melphalan doses were unchanged at 10–13 mg/l (leg and arm, respectively). Characteristics for the 167 ILPs were: 81 stage IIIB, 65 stage IIIC, and 21 stage IV disease.
Results
The overall response rate was 89% (
n
= 148). (Complete response CR = 61%; partial response PR = 28%). CR rates correlated with stage (
P
= .001) and with high-dose vs. low-dose TNF (70% vs. 49%;
P
< .006). High-dose TNF prolonged local control (median 16 months vs. 11 months;
P
= .076). Survival was not influenced by TNF dose. CR after ILP and number of lesions also correlated with local progression-free interval. Overall survival did correlate with stage of disease (
P
< .001), size of the lesions (
P
= .001), and a CR (
P
< .001).
Conclusions
This 2-decade single-center experience demonstrates that TM-ILP is a safe and effective treatment modality for melanoma patients with multiple IT-mets. Higher dose of TNF was associated with significantly higher CR rates and prolonged local control without an effect on overall survival.
Purpose
The aim of this study was to evaluate the incidence and outcome of melanoma of unknown primary site (MUP) after therapeutic lymph node dissection (TLND) of palpable nodal melanoma metastases. ...Disease-free (DFS) and overall survival (OS) time of MUP patients were analyzed and compared to patients undergoing a TLND for known primary melanomas (MKP).
Methods
This single institution retrospective study analyzed 342 consecutive patients who were treated with 415 TLNDs for palpable nodal disease from 1982 to 2009. Univariate and multivariate analyses included: MUP versus MKP, gender, Breslow thickness, ulceration of primary tumor, site of primary tumor, site of dissection, extracapsular extension, number of collected nodes, number of positive nodes and the node positive ratio.
Results
A total of 47 MUP were identified in 342 patients (13.7%). In univariate analysis, a trend was seen toward better survival for MUP patients compared to MKP patients having 5-year OS rates of 40% and 27%, respectively (
P
= 0.06). Multivariate analysis for OS showed two highly significant factors associated with worse prognosis: extracapsular extension and N3 status (both
P
< 0.001). Two factors were associated with a significant better prognosis: MUP (
P
= 0.03) and a neck dissection (
P
= 0.04).
Conclusions
Patients with MUP showed a statistically significant better OS compared to patients with melanoma metastases from known primary tumors. Presence of extracapsular extension and an increased number of positive nodes are statistically significantly negative prognostic factors for OS. The absence of a primary melanoma in stage III melanoma patients does not preclude surgery.
The aim of this study is to describe the experience with 100 TNF-based ILP for locally advanced melanoma and to determine prognostic factors for response, time to local progression, and survival.
One ...hundred TNF-based ILPs were performed between 1991 and 2003 in 87 patients for whom local control by surgery of in-transit melanoma metastases was impossible. In total, 62 iliac, 33 femoral, and 5 axillary ILPs were performed in mild hyperthermic conditions with 2 to 4 mg of TNF and 10 to 13 mg of melphalan per liter of limb volume.
Overall response was 95%, with 69% complete response, 26% partial response, and 5% no change. Complete response rate differed significantly for patients with IIIA disease versus IIIAB and IV. Local and systemic toxicity was mild to moderate in almost all cases, with no treatment-related death and one treatment-related amputation. Five-year overall survival was 32%; local progression occurred in 55% after a median of 16 months. In complete response patients, 5-year survival was 42% with local progression in 52% at a median of 22 months. Response rate and survival were significantly influenced by stage of disease; (local progression free) survival was influenced by response rate.
TNF-based ILP results in excellent response rates in this patient population with unfavorable characteristics. Response on ILP predicts outcome in patients and reflects aggressiveness of the tumor.
PURPOSE OF REVIEWThe treatment of in-transit metastasis of melanoma remains challenging and is essentially dictated by the biological behavior of melanoma. When lesions are large or numerous, ...isolated limb perfusion (ILP) is an attractive treatment modality. In this review an overview of literature on treatment options of melanoma in-transit metastases will be discussed.
RECENT FINDINGSMost recent studies report on tumor necrosis factor (TNF) and melphalan based ILP (TM-ILP) series or mixed series of TM-ILP and melphalan only based ILP (M-ILP). After TM-ILP complete response rates of 70% (range 44–90%) have been reported, while for M-ILP this is lower with complete response rates of 54% (range 40–76%). The only randomized trial comparing TM-ILP and M-ILP revealed no clear benefit of TNF at 3 months, but improved outcome at 6 months and in patients with bulky disease. Reports on isolated limb infusion (ILI) with melphalan and actinimycin D indicate lower response rates, but similar local control rates as M-ILP at lower cost.
SUMMARYILP is an attractive treatment option in melanoma patients with multiple in-transit metastases. In our opinion TM-ILP is superior to M-ILP as it achieves higher response rates, especially in patients with bulky disease. When lesions are small and in the distal two-thirds of the leg only, ILI is a valuable alternative.
Background
Full-thickness chest wall resection (CWR) is the preferred treatment for breast cancer (BC) patients with extensive isolated locoregional recurrence. It remains a challenge to select ...patients that will benefit most from this treatment. The aim of this study was to define prognostic factors in patients who undergo CWR with curative intent.
Methods
BC patients who underwent a CWR with curative intent for recurrence of disease between 1986 and 2006 were included in this retrospective study. Twenty-two factors were studied in a univariate analyses, and multivariate stepwise Cox regression analyses was performed.
Results
Seventy-seven patients were included in this study. The 5-year overall survival was 25%. There was one postoperative death. Univariate analyses showed that three prognostic factors were significantly correlated with OS and disease-free survival: (1) interval between primary treatment and CWR (
P
= .02 and .004, respectively), (2) chemotherapy for recurrence (
P
= .05 and .05, respectively), and (3) resection specimen smaller than 150 cm
2
(
P
= .03 and .009, respectively). An interval lasting >10 years between primary treatment and CWR remained statistically significantly correlated with better overall survival and disease-free survival after multivariate analyses.
Conclusions
CWR is a safe treatment in patients who have isolated extensive BC recurrence. The best survival outcome was seen in patients after a disease-free interval of ≥10 years. Existing data show that adjuvant radiotherapy and adjuvant hormone therapy for estrogen-positive tumors improves overall survival. Neoadjuvant chemotherapy may be considered in individual patients.
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