Survival after induction chemotherapy and surgical resection for high-grade soft tissue sarcoma. Is radiation necessary?

BACKGROUND: Induction chemotherapy can produce dramatic necrosis in sarcomas-raising the question of whether or not radiation is necessary. This study reviews the clinical outcome of a subset of patients with high-grade extremity soft tissue sarcomas (STS) who were treated with induction chemotherapy and surgical resection but without radiation. METHODS: Nonmetastatic, large, high-grade STS of the pelvis and extremities were treated with intra-arterial cisplatin, adriamycin, and, after 1995, ifosfamide. After induction, oncologic resection and histologic evaluation were performed. Good responders with good surgical margins were not treated with radiation. RESULTS: Thirty-three patients, with a median follow-up of 5 years, were included. Limb salvage rate was 94%. Median tumor necrosis was 95%. Four patients developed metastatic disease with three subsequent deaths. Two local recurrences occurred; both patients were salvaged with reresection and adjuvant external beam radiotherapy, although one died of metastatic disease 10 years later. Relapse-free and overall survival is 80% and 88% at 5 and 10 years by Kaplan-Meier analysis. CONCLUSIONS: Intensive induction chemotherapy can be extremely effective for high-grade STS, permitting limb-sparing surgery in lieu of amputation. Radiation may not be necessary if a good response to induction chemotherapy and negative wide margins are achieved. All patients with large, deep, high-grade STS of the extremities should be considered candidates for induction chemotherapy.

Adult acute leukemia. Aggressive treatment improves survival.

Although improvements in the management of adults with acute leukemia have lagged behind those seen in the treatment of children, there are clear reasons for optimism. Combination chemotherapy for acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) in adults results in complete remissions in 50-85% of patients. An increasing number of these patients remain in continuous remission for over two years with a significant proportion (15-25%) disease-free after five years. Those who remain in remission for more than five years have a low incidence of relapse and many may be cured. Nevertheless, there are still many problems to be solved. Improved, less toxic induction regimens are needed. The roles of maintenance, late intensification, and central nervous system prophylaxis remain unresolved. The results of bone marrow transplantation for adults with AML in remission are encouraging enough to make this an attractive form of therapy for any patient younger than age 40 with a histocompatible sibling. New forms of treatment, such as immunotherapy and monoclonal antibodies, remain investigational.

The neutrophil response to polyvinyl sponge implantation.

Neutrophil release and migration in mice were studied over a 24-hr period after the sc implantation of a single polyvinyl sponge. The release of neutrophils from the marrow was evaluated by directly counting the residual neutrophils in the femoral marrow of animals with sponges. Sponge and tissue neutrophil content was determined by extraction and assay of myeloperoxidase (MPO), a marker enzyme for neutrophils. A maximum depletion of 48% of the mature neutrophils in the marrow was observed 5 hr after sponge implantation, in keeping with significant release of neutrophils for migration to the sponge. The released cells were not found in the circulating granulocyte pool, since neutropenia was noted. The accumulation of neutrophils in the sponge increased throughout the 24-hr period, whereas in the tissue adjacent to the sponge maximum accumulation of neutrophils occurred within 7 hr. In fact, neutrophils migrated to at least three sites--the sponge, the skin overlying the sponge, and the skin in which an incision had been made to insert the sponge. The sponge content of neutrophils represented 0.3-33% of the neutrophils migrating to the combined lesion (sponge and skin sites). Therefore, if the neutrophil response to foreign body implantation is to be measured in its entirety, it is necessary to quantify not only the neutrophils within the foreign body but also those in the tissues surrounding it. These studies describe an animal model for neutrophil release and migration to tissues following a standard stimulus. It is proposed that this model may be useful in exploring the factors which influence the release and migration of neutrophils in vivo.

Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker.

We examined the hypothesis that myeloperoxidase (MPO), a plentiful constituent of neutrophils, might serve as a marker for tissue neutrophil content. To completely extract MPO from either neutrophils or skin, hexadecyltrimethylammonium bromide (HTAB) was used to solubilize the enzyme. With this detergent treatment, 97.8 +/- 0.2% of total recoverable MPO was extracted from neutrophils with a single HTAB treatment; 93.1 +/- 1.0% was solubilized with a single treatment of skin. Neutrophil MPO was directly related to neutrophil number; with the dianisidine-H2O2 assay as few as 10(4) neutrophils could be detected. The background level of MPO within uninflamed tissue was 0.385 +/- 0.018 units per gram of tissue, equivalent to only 7.64 +/- 0.36 X 10(5) neutrophils. In experimental staphylococcal infection, skin specimens contained 34.8 +/- 3.8 units MPO per gram, equivalent to 8.55 +/- 0.93 X 10(7) neutrophils. These studies demonstrate that MPO can be used as a marker for skin neutrophil content: it is recoverable from skin in soluble form, and is directly related to neutrophil number. Further, normal skin possesses a low background of MPO compared to that of inflamed skin.

Granulocyte transfusion in septic canine neonates.

Newborn dogs were inoculated intratracheally with 0.5-1.0 X 10(8) Staphylococcus aureus/g body weight. Neutropenia (490 +/- 280 neutrophils/mm 3 versus 8,390 +/- 490 control, mean +/- S.E., P less than 0.001), and depletion of the marrow neutrophil storage pool (3 +/- 1% versus 27 +/- 2% storage neutrophils, P less than 0.001) occurred 5-6 h following the inoculation. All animals died at 6-10 h. Additional inoculated pups were selected at random to receive transfusions of either granulocytes, plasma or red blood cells. Granulocyte transfusions (3 X 10(9) neutrophils/kg) improved survival (P less than 0.005), but plasma and red blood cells did not.