Background. It is known that many patients with osteosarcoma have high serum alkaline phosphatase (SAP) levels. The prognostic significance of this finding, however, is still controversial. Methods. The pretreatment SAP levels of 656 patients with osteosarcoma of the extremities (107 metastatic and 549 localized at presentation) were examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease. Results. The percentage of patients with increased SAP levels was significantly higher in the metastatic group than in the group of patients with localized disease (91.5% versus 61.3%; P > 0.001). In the latter group, treated with adjuvant and neoadjuvant chemotherapy, the relapse rate was significantly higher in patients with elevated pretreatment SAP levels than in those with normal levels (55.1% versus 26.4%; P > 0.001). Among patients with elevated SAP levels, the percentage of relapses was higher in patients with high levels of the enzyme in comparison with patients with moderately elevated values (66.4% versus 47%; P > 0.05). After treatment, SAP levels almost always return to normal values, and a correlation between postoperative levels of the enzyme and prognosis could not be made. Conclusions. These data demonstrate that in osteosarcoma of the extremities, pretreatment SAP levels have a prognostic value and they should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.
In 163 patients with osteosarcoma of the extremities treated with adjuvant chemotherapy, serum alkaline phosphatase (SAP) levels were evaluated before treatment and successively closely monitored in an attempt to determine whether serum levels of this enzyme had clinical value in predicting the course of the disease. Of 121 patients with elevated preoperative SAP levels, 78 (64%) recurred. Of 42 patients with normal preoperative SAP levels, only 8 (19%) recurred (P less than 0.00001). Of the 140 patients locally treated with amputation, SAP returned to normal values in 77 patients; 46 of these (59%) relapsed. Of the 21 patients whose SAP remained elevated after amputation, all but 2 relapsed (90%). Among 119 patients with normal postoperative values of SAP, at the time of relapse SAP resulted elevated in 22 of 41 patients (53%). These data confirm that in osteosarcoma, preoperative SAP levels have a definite value in establishing the prognosis and that posttreatment follow-up examination should include SAP determination, since persistent elevated or increasing values herald the appearance of a recurrence.
The relationship between the serum concentration of methotrexate and the prognosis has been studied in 108 patients with osteosarcoma of the extremities treated from September 1986 to December 1989 at the Chemotherapy Department of Rizzoli Hospital. The protocol of neoadjuvant chemotherapy included high doses of methotrexate (HDMTX) adriamycin, cisplatinum, ifosfamide and VP-16. After a median follow-up of 40.4 months (range 24-62), 84 (77.7%) of the patients studied remained continuously disease-free (CDF) and 24 relapsed. Significantly higher mean serum MTX concentrations were observed in the patients who remained CDF (669.5 mumol/l) than in the patients who relapsed (571.9 mumol/l) (p < .004). The breaking point of prognostic significance for the serum MTX levels seems to be 700 mumol/l. In fact, according to the mean MTX concentrations, the patients with less than 700 mumol/l showed a significantly lower disease-free survival than the patients with higher mean MTX concentrations (68.12% vs 94.87% p < .0013). The distribution of prognostic variables between the two groups was the same in terms of site and histological type of tumor and alkaline phosphatase serum levels at diagnosis. In the group which had more than 700 mumol/l MTX, a higher percentage of good histological response after primary chemotherapy was observed. This is probably independent from the MTX because no significant preoperative MTX serum levels between good and partially responding patients were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
The pretreatment serum lactic acid dehydrogenase (LDH) level of 246 patients with Ewing's sarcoma of bone (47 metastatic and 199 localized at presentation) was examined to evaluate the use of LDH as a tumor marker. The percentage of patients with increased serum LDH levels was significantly higher in the metastatic group than in the group of patients with localized disease (83% vs 41%; p less than 0.01). In the latter group the relapse rate after treatment with combined therapy was significantly higher in patients with an elevated serum LDH at admission than in those with normal serum levels (68.2% vs 39.3%; p less than 0.01). After local treatment, in 73 out of 82 patients with an elevated serum LDH at admission the enzyme level normalized whereas in 9 it fell but never reached a normal value. The rate of relapse in these two groups was respectively 64% and 100%. The value of serum LDH at the time of recurrence, determined in 62 patients, was elevated in 50 (80.7%). These data demonstrate that in Ewing's sarcoma of bone pretreatment serum LDH levels have a definitive value in establishing the prognosis and could also be used in evaluating the response to therapy. A persistent elevated value of serum LDH, or an increasing value after a transient normalization, is usually followed by relapse.
Six hundred and fifty-six patients with osteosarcoma of the extremities (107 metastatic and 549 with localized disease) were followed from 2.5 to 20 years (average: 10 years) to evaluate whether their pretreatment serum lactate dehydrogenase (LDH) enzyme levels had a clinical value in predicting the course of the disease. The percentage of patients who had an elevated serum LDH at the time of diagnosis was significantly higher in those patients with metastatic disease than those who had localized disease (64% versus 33%, p < 0.0001). For those who presented with localized disease and had an increased serum LDH level, far more ultimately developed a relapse of disease (60% versus 38%, p < 0.0001) than those patients with a normal pre-treatment value. The prognostic significance of the serum LDH was more pronounced for the 247 patients treated with adjuvant chemotherapy (relapse rate of 72% versus 48%; p < 0.0002) than the 271 patients treated with neoadjuvant chemotherapy (relapse rate: 46% versus 28%, p < 0.005). Following treatment, serum LDH levels almost uniformly returned to normal and no correlation between postoperative levels and relapse of disease could be identified. We have demonstrated that in patients with osteosarcoma of the extremities, pretreatment serum LDH levels have a definite prognostic value which should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.
To evaluate the different capabilities of hemo-perfusion (HP) and hemodialysis (HD) treatment in resolving the side effects during high-dose methotrexate (MTX) therapy, an experimental comparative study was done. Under general anesthesia, 12 female Large-White pigs, 35 +/- 5 kg body weight, underwent a bilateral renal vessel ligature to create an acute renal failure and avoid the physiologic elimination of MTX. An MTX i.v. infusion was performed using a dose of 12.5 g/m2 and for a specific time according to its pharmacokinetics. The animals were divided into 2 groups of 6 animals each and connected to the extracorporeal circuit; the first group was submitted to a 1-h HP with an anion exchange resin (Dow 1X-2, Dow Chemical) and the second group to 1-h HD with capillary polysulfone fibers (F6, Fresenius). Blood samples were taken at established intervals for hematological and biochemical evaluations. The results demonstrate a higher capability of HP treatment (P < 0.001) related to HD in MTX removal.
The administration of high doses of Methotrexate (HDMTX) seems to be very effective in neoplastic treatment. Furthermore high doses of the drug could overcome the Methotrexate (MTX) resistance that it is possible to observe in some kind of cancers. To avoid several serious problems in the therapeutical application of HDMTX such as nephrotoxicity, hepatotoxicity and the difficulty to assess the right therapeutic range of the specific antagonist Leucovorin, a Haemoperfusion (HP) treatment could be very usefulL. In this study 3 anion exchange resins with different active group (trimethylammonium, dimethylethanolammonium and dimethylammina) and a spherical petroleum based charcoal were tested both in vitro and ex vivo to evaluate their capability to remove MTX. These results show a good strength and biocompatibility of the 4 sorbents and demonstrate the active group trimethylammonium resin as the most effective one.
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