Oncological outcome after hyperthermic isolated limb perfusion for primarily unresectable versus locally recurrent soft tissue sarcoma of extremities.

INTRODUCTION: The management of locally advanced extremity soft tissue sarcomas, particularly in terms of a limb salvage strategy, represents a challenge, especially in recurrent tumors. In the context of a patient-tailored multimodal therapy, hyperthermic isolated limb perfusion (ILP) is a promising limb-saving treatment option. We report the outcome of patients with primarily irresectable and locally recurrent soft tissue sarcoma (STS) treated by ILP. PATIENTS AND METHODS: Data about patient demographics, clinical und histopathological characteristics, tumor response, morbidity and oncological outcome of all patients with STS, who underwent an ILP at our institution in a 10-year period, were retrospectively detected and analyzed. RESULTS: The cohort comprised 30 patients. Two patients were treated with ILP for palliative tumor control, 13 patients because of a local recurrent soft tissue sarcoma (rSTS) and 15 patients because of primarily unresectable soft tissue sarcoma (puSTS). 25 of the 28 patients with curative intention received surgery after ILP (11 pts with rSTS and 14 pts with puSTS). Histopathologically we observed complete response in 6 patients (24%) and partial responses in 19 patients (76%) with a significant better remission in patients with puSTS (p = 0,043). Limb salvage rate was 75%. Mean follow-up was 69 months [range 13-142 months]. Seven (7/11; 64%) patients with rSTS and one (1/14; 7%) patient with puSTS developed local recurrence after ILP and surgery, whereas eight (8/13; 62%) rSTS patients and seven (7/15; 47%) puSTS patients developed distant metastasis. During follow-up, eight patients (28.5%) died of disease (5/13; 38%) rSTS and 3/15 (20%) puSTS. ILP in the group of previously irradiated sarcoma patients (n = 13) resulted in a limb salvage rate of 69% and was not associated in an increased risk for adverse events. DISCUSSION: ILP for advanced extremity STS is a treatment option for both puSTS and rSTS resulting in good local control and should be considered in multimodal management. ILP is also a good option for patients after radiation history.

Palliative second-line treatment with weekly high-dose 5-fluorouracil as 24-hour infusion and folinic acid (AIO) plus oxaliplatin after pre-treatment with the AIO-regimen in colorectal cancer (CRC).

BACKGROUND AND AIMS: The aim of this work was to evaluate the efficacy and safety of second-line treatment with weekly high-dose 5-Fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) and folinic acid (FA) (AIO-regimen) plus Oxaliplatin (L-OHP) after pre-treatment with the AIO regimen, focusing in particular on the efficacy of palliative first- and second-line treatment in colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients with non-resectable distant CRC metastases were enrolled in a prospective phase II study for palliative second-line treatment after previous palliative first-line treatment in accordance with the AIO regimen. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m2 L-OHP in the form of a 2-hour intravenous (i.v.) infusion and 500 mg/m2 FA as a 1 to 2-hour i.v. infusion, followed by 2,600 mg/m2 5-FU administered as a 24-h inf. i.v. once weekly. A single treatment cycle comprised 6 weekly infusions followed by 2 weeks of rest. RESULTS: During second-line treatment, a total of 26 patients received 340 chemotherapy applications. As the main symptom of toxicity, diarrhoea (NCI-CTC toxicity grade 3+4) presented in 5 patients (19%; 95% CI: 4-34), followed by nausea (CTC grade 3) in one patient (4%; 95% CI: 0-11). Twenty-three patients were evaluable for treatment response. The remission data can be summarised as follows: Complete remission (CR): n=1 (4%; 95% CI: 0-13); partial remission (PR): n=3 (13%; 95% CI: 0-27); stable disease (SD): n=11 (48%; 95% CI: 27-68) and progressive disease (PD): n=8 (35%; 95% CI: 15-54). The median progression-free survival (PFS) rate (n=26) was 3.3 months (range 0-11.5), the median survival time counted from the start of second-line treatment (n=26) 11.6 months (range 2.1-33.0) and the median survival time counted from the start of first-line treatment (n=26) 19.9 months (range 7.7-49.8). CONCLUSION: Palliative second-line treatment according to the AIO regimen plus L-OHP is feasible in an outpatient setting and well tolerated by the patients. Tumour control (CR + PR + SD) was achieved in 65% of the patients, the median survival time being 11.6 months. The AIO regimen followed by the 'AIO regimen plus L-OHP' therapy sequence led to a promising median survival time of 19.9 months (range 7.7-49.8).

[Regional chemotherapy--perfusion of the extremities]. / Regionale Chemotherapie--Extremitätenperfusion.

Hyperthermic isolated limb perfusion with cytostatic drugs (HILP) is indicated in locoregional recurrences of malignant melanoma of the limbs. As a neoadjuvant treatment it is also used for non-curatively resectable soft tissue sarcoma or their recurrences on the extremities. Up to now, melphalan is still the standard drug in HILP for malignant melanoma. With melphalan, complete response can be achieved in 65-80% for clinically detectable in transit metastases (+/- regional lymph node metastases). The combination of tumor necrosis factor (TNF) alpha with melphalan has considerably improved response rates of HILP in sarcoma. In more than 80% of the patients the otherwise necessary amputation of the limb can be avoided. The combination of TNF with other drugs than melphalan could possibly further improve results of HILP in sarcoma patients. The high rate of local recurrences of malignant melanoma after HILP poses an unsolved problem yet.

Low bone mineral density after total gastrectomy in males: a preliminary report emphasizing the possible significance of urinary net acid excretion, serum gastrin and phosphorus.

The bone mineral density (BMD) and the associated extracellular status of mineral and acid-base metabolism were evaluated in 11 males, 3-18 years after total gastrectomy (GX). In the lumbar spine, but not in the femoral neck, BMD was decreased in seven, normal in three, and falsely high in one individual. Relative to the limits of normalcy, fasting serum levels of gastrin were low, but normal for calcium, phosphorus, parathyroid hormone, calcitonin and vitamin D, while the level of total alkaline phosphatase was elevated; fasting urine pH and calcium were low, while phosphorus and net acid were high. Regression analyses revealed serum gastrin and phosphorus, and urinary net acid as possible predictors of BMD. It was concluded that over the long-term GX evokes low BMD, but not hyperparathyroidism and deranged vitamin D metabolites. Future studies may focus on gastrin, parathyroid hormone-independent hyperphosphaturia and disturbed acid-base metabolism as indicators of a new extra-cellular equilibrium of minerals.

[Locoregional recurrence of melanomas of the extremities after hyperthermic extremity perfusion: is reperfusion of value?]. / Lokoregionäre Rezidive von Extremitätenmelanomen nach hyperthermer Extremitätenperfusion: Sind Re-Perfusionen sinnvoll?

Isolated limb reperfusion in patients with locoregional recurrence after previous isolated limb perfusion achieves local tumor control in a high percentage of cases. One of the main aims of the repeat procedure is limb salvage, which was possible in 96% of our patients. Complication rate of reperfusion is acceptably low.

[Regional hyperthermic perfusion--therapeutic concept and long term results]. / Die regionale hypertherme Perfusion--Therapiekonzept und Langzeitergebnisse.

Isolation perfusion was introduced in 1957 by Creech and Krementz for treatment of malignancies of the limbs. The isolation of the extremity from the body circulation allows a high concentration of cytostatics without systemic side effects. Regionally metastasizing malignant melanomas with satellites, intransit or lymph node metastases are generally accepted indications for isolation perfusion. There is still controversy about elective adjuvant perfusion in stage I melanoma. Prospective randomized studies must clarify this situation. Krementz demonstrated long-term survival rates between 29% and 52%. Our group of patients with satellites and intransit metastases shows a 10-year survival rate of 48%. Considering the historical data of our patients without perfusion and with a 10-year survival of 11%, there is a highly significant statistical difference. In conclusion, isolation perfusion is the therapy of choice in patients with locally metastasized malignant melanoma of the limbs.