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G Bacci

Publications and source records attributed to G Bacci.

At least 37 records · Page 2Linked to original sources
PubMed1994

Treatment recommendations for osteosarcoma and adult soft tissue sarcomas.

During the past 20 years, dramatic improvements have been obtained in the treatment of localised osteosarcoma of the extremities, both in the rates of disease-free survival and in quality of life. Twenty years ago 80 to 90% of the patients died, in spite of mutilating surgery, but now about 75% survive and avoid the necessity of amputation. This is due to the introduction of very effective combined treatments, mostly also using preoperative chemotherapy. One of the major issues is that of intensive preoperative chemotherapy, which improves both limb salvage and survival. A multidisciplinary approach is necessary to obtain good results. When the role of adjuvant or neoadjuvant chemotherapy is not accurately defined for soft tissue sarcomas, particular emphasis is given to the staging of the diseases and to the important role of local treatment in the survival of these patients. A combination of radiation therapy and surgery is strongly recommended.

Antineoplastic Agents↗
PubMed1994

[Nonmetastatic osteosarcoma of the limbs treated with neoadjuvant chemotherapy: correlation of tumor volume evaluated by CT and prognosis].

A relationship between tumor volume and prognosis has been demonstrated in extraosseaous solid tumors, soft tissue tumors and Ewing's sarcoma. Fifty-five osteosarcoma patients, treated according to IOR-OS/NEO 3 protocol, have been studied in an attempt to verify if tumor volume is also a significant prognostic factor for the osteosarcoma of the extremities. Tumor volume was measured by CT-Scan. A trend towards a better prognosis for smaller tumors was observed, but no statistically significant differences were demonstrated according to the tumor size in the population studied. The authors conclude that for patients with osteosarcoma of the extremities, tumor volume can not be considered an adequate prognostic factor on the basis of which to tailor the chemotherapy treatment, as been recently proposed by other authors.

Adolescent↗
PubMed1993

Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin.

BACKGROUND: Neoadjuvant chemotherapy is the most accepted treatment for localized osteosarcoma. This has led to a great improvement in limb-sparing surgery and in disease-free survival. Patients with a good response to preoperative chemotherapy showed a higher disease-free survival rate. Current studies examine the possibility of patients whose limbs could be rescued with a poor necrosis and a reduction of the side effects related to aggressive treatments. METHODS: Between September 1986 and December 1989, 164 patients entered the second neoadjuvant study conducted at the Rizzoli Institute, Bologna, Italy, for non-metastatic osteosarcoma of the extremities. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate intravenously (i.v.) followed by cisplatin intraarterially and doxorubicin i.v. After surgery, patients classified as good responders (> 90% tumor necrosis) received three more cycles of these drugs, whereas poor responders (< 90% tumor necrosis) had more chemotherapy, which included ifosfamide and etoposide in addition to the other three drugs. RESULTS: Limb salvage was performed in 83% of cases. At an average follow-up of 54 months (36-76), 109 patients (66%) were continuously disease-free, 2 died from doxorubicin cardiotoxicity, and 52 experienced metastases and 3 had local recurrence. In two of these three patients, metastases followed local recurrence. The 5-year actuarial continuously disease-free survival rate was 63%, with no differences between good and poor responders. Excluding 20 patients who had major protocol violations, the projected continuous disease-free survival rate was 71%. CONCLUSIONS: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of nonmetastatic osteosarcoma of the extremities, avoiding amputation in most cases. Ifosfamide and etoposide seem to be effective in patients who did not respond to preoperative chemotherapy.

Adolescent↗
PubMed1993

Prognostic significance of serum alkaline phosphatase measurements in patients with osteosarcoma treated with adjuvant or neoadjuvant chemotherapy.

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.

Adult↗
PubMed1993

Serum methotrexate (MTX) concentrations and prognosis in patients with osteosarcoma of the extremities treated with a multidrug neoadjuvant regimen.

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)

Adolescent↗
PubMed1993

Influence of adriamycin dose in the outcome of patients with osteosarcoma treated with multidrug neoadjuvant chemotherapy: results of two sequential studies.

The results of two sequential studies of neoadjuvant chemotherapy for osteosarcoma of the extremities performed at Rizzoli Institute between 1986 and 1991 in 228 patients are presented. In both studies preoperative chemotherapy consisted of two cycles of high dose methotrexate (HDMTX), cisplatinum (CDP) and adriamycin (ADM). Postoperatively the good responder patients were treated with the same drugs used before surgery while in the poor responder patients ifosfamide was added to these three drugs. The preoperative treatment was the same in both studies while after surgery in the second protocol either the cumulative dose of ADM (270 mg/m2 instead of 360 mg/m2) or the single dose per cycle of this drug (60 mg/m2 instead of 90 mg/m2) was reduced. These changes in the last protocol were done to reduce the cardiotoxicity of ADM that was high in the first study (2 deaths and 1 heart transplantation). Since in the last protocol--in comparison with the first protocol--after surgery chemotherapy was restarted earlier and ADM was administered not as a single drug but in combination with the CDP the dose intensity of ADM was unchanged while the dose intensity of MTX, CDP and ifosfamide was higher than in the first study. The preliminary results of the 84 patients treated in the second study show a 2-year disease free survival significantly lower than that achieved in the 144 patients treated in the first study (37/51--73% vs 123/144--85%: P < 0.008). In addition, even if in the last study there were no cases of clinical cardiotoxicity due to ADM, there was a significantly higher percentage of severe myelodepression that led to two deaths for infectious complications. These results suggest that in neoadjuvant treatment of osteosarcoma the total dose of ADM and/or the single dose per cycle of the same drug are an important determinant of outcome and that increasing the dose-intensity of less toxic but less active agents, MTX, CDP and ifosfamide, at the expense of the more active and more toxic agent, ADM, can lead to a poorer outcome without reducing toxicity.

Adolescent↗
PubMed1993

No advantages in the addition of ifosfamide and VP-16 to the standard four-drug regimen in the maintenance phase of neoadjuvant chemotherapy of Ewing's sarcoma of bone: results of two sequential studies.

Between January 1988 and December 1990, 74 patients with localized Ewing's sarcoma of bone were treated with a new protocol that consisted of an initial 6-week period of chemotherapy with vincristine (VCR), adriamycin (ADM) and cyclophosphamide (EDX) followed by local therapy and additional chemotherapy with the same drugs previously indicated plus ifosfamide and VP-16. The rationale for the addition of ifosfamide and VP-16 to the four drugs of the standard chemotherapy of this tumor was that this drug combination was previously very effective in the treatment of metastases from Ewing's sarcoma even in patients who did not respond to cyclophosphamide. As local treatment all patients were offered surgery, when feasible (70 cases). Forty-three patients accepted and 27 refused. These patients, as the 4 patients in whom surgery was not considered feasible, were treated with radiation therapy alone (50-60 Gy). In the remaining patients amputation was performed in 4 cases, rotationplasty in 3 and resection in 36. Where conservative surgery was marginal or intralesional (30 cases), radiotherapy at lower doses (40-45 Gy) was also delivered. At a mean follow-up of 3.5 years (2-7), 43 patients (58%) remained continuously disease-free and 31 relapsed (29 with metastases and 2 with both metastases and local recurrences). These results do not differ from those obtained at our Institution in 98 patients treated between 1983 and 1988 with a neoadjuvant protocol in which only VCR, ADM, EDX and dactinomycin (DAC) were used (3-year continuously disease-free survival (CDFS) respectively of 54% and 55%). Despite the fact that these results came from a nonrandomized study, the Authors conclude that the addition of ifosfamide and VP-16 to the four-drug standard regimen did not improve the outcome of the patients with Ewing's sarcoma of bone which remains a lethal disease in about 50% of the cases. These findings stress the need to find more effective chemotherapeutic regimens for the associated treatment of this tumor.

Adolescent↗
PubMed1993

Prognostic significance of histopathologic response to chemotherapy in nonmetastatic Ewing's sarcoma of the extremities.

PURPOSE: To evaluate more accurately the effectiveness of preoperative chemotherapy in the treatment of patients with Ewing's sarcoma, we studied histopathologically the chemotherapeutic response and correlated it to oncologic outcome. PATIENTS AND METHODS: Between June 1983 and December 1989, 68 patients with nonmetastatic Ewing's sarcoma of the extremities were treated at our institute with preoperative chemotherapy (without radiation therapy) and surgery. The specimens were retrospectively evaluated for areas of viable tumor cells and graded from I to III (macroscopic, microscopic, or no residual disease, respectively) in a blinded fashion. Clinical follow-up data were available on all patients for a mean of 60 months (range, 32 to 111). RESULTS: This histopathologic analysis was strongly correlated with oncologic outcome (P = .004). Patients who demonstrated grade III response (no identifiable viable tumor nodules present) had improved 5-year disease-free survival rates as compared with patients with grade II (microscopic nodes present; P = .023; 90% v 53%) and grade I responses (macroscopic nodules present; P = .0003; 90% v 32%). Patients with grade II necrosis had statistically improved survival rates over those with grade I necrosis (53% v 32%; P = .074). CONCLUSION: This new histopathologic analysis technique for the evaluation of neoadjuvant chemotherapy effectiveness (which does not rely on tumor volume for its assessment) is a valuable prognostic indicator for patients with Ewing's sarcoma treated with surgery. Based on this preliminary report, cases of grade I or II chemotherapeutic tumor response should be considered clinical failures and a different, more aggressive postoperative chemotherapy regimen should be considered.

Adolescent↗
PubMed1993

Complications and surgical indications in 144 cases of nonmetastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy.

From September 1986 to December 1989, 144 patients with osteosarcoma of the extremities were treated with combined surgery and neoadjuvant chemotherapy. The disease-free survival was 79% for good responders (necrosis greater than 90%) and 72% for poor responders (necrosis less than 90%), and the local recurrence rate was low. Improvement in long-term prognosis and the increase of limb-sparing surgery determine a higher rate of immediate and late complications. Most of the complications were observed in limb-salvage procedures; 63% of these procedures presented one or more complications. In nine rotationsplasties, there were four complications, and in 13 amputations no complications were observed. Therefore, 55% of patients were affected by surgical complications. Twenty-eight complications were considered minor (not requiring surgery), whereas 77 complications were major. Functional results, evaluated according to Enneking's new system, were higher than 50% in two thirds of the limb-salvage procedures. Complications in limb-salvage procedures are more influenced by the type of reconstruction than by the surgical procedure used. Probably the most troublesome consequence of surgical complications in osteosarcoma is the deviation or delay in administering postoperative chemotherapy, which jeopardizes survival.

Adolescent↗
PubMed1993

The role of surgical therapy in patients with nonmetastatic Ewing's sarcoma of the limbs.

Of 131 patients with primary Ewing's sarcoma (ES) with extremity locations, treated between April 1972 and May 1987, 13 had amputation; 56 had a local resection with 31 (55%) requiring radiation therapy (RT) as an adjuvant to local therapy. Sixty-two of 131 patients (47%) had RT only. Local recurrences were reported in 5% of patients treated with surgery alone, 1% of the group treated with surgery and radiation therapy, 24% of patients treated with radiation therapy alone (46% for cesium-radiation therapy, and 12% with cobalt-radiation therapy).

Adolescent↗
PubMed1993

[Osteosarcoma of the extremities metastatic at presentation. Results obtained with primary chemotherapy followed by simultaneous resection of the primary and metastatic lesion].

From September 1986 to September 1990 35 patients affected by osteosarcoma of the extremities with synchronous metastasis were treated with two cycles of high-dose methotrexate IV, cisplatin IA and adriamycin IV followed, in 22, by simultaneous resection of the primary and metastatic tumor. Six patients progressed and were not operated on, 7 patients with complete response of pulmonary nodules underwent surgical resection of the primary lesion. A complete histological examination of the resected specimens was always performed to evaluate the percentage of necrosis produced by chemotherapy on both the primary and metastatic tumor. After surgery the patients received 3 more cycles of the same drugs as used preoperatively plus ifosfamide. The histological response of the primary tumour was "good" (90% or more tumour necrosis) in 8 patients (27%) and "poor" (less than 90% of tumour necrosis) in 21 (73%) while in the 75 metastatic nodules the resulting necrosis was good in 18 (24%) and poor in 57 (74%). A good correlation between the histological response in the primary and metastatic tumour was observed. At an average follow-up of 30 months (R 12-60), 13 patients are alive, 10 disease-free, and 3 with uncontrolled disease. This data suggest that prognosis of osteosarcoma of the extremities with synchronous metastases remains poor even with a very aggressive treatment. Our results also seem to confirm the validity of the present strategy in the treatment of non metastatic osteosarcoma: to introduce new drugs postoperatively in patients poor responder can allows a better treatment of microscopic disease and can improve the prognosis for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Osteosarcoma of the extremity metastatic at presentation: results achieved in 26 patients treated with combined therapy (primary chemotherapy followed by simultaneous resection of the primary and metastatic lesions).

From September 1986 to December 1989, 26 selected patients with high-grade osteosarcoma of the extremities metastatic at presentation were treated with primary chemotherapy (high doses of methotrexate, -cisplatinum and adriamycin) followed by surgery. Twenty-one cases underwent resections of the primary and metastatic tumor at the same time; owing to the disappearance of lung metastases after preoperative chemotherapy in 3 cases, only the primary tumor was operated on. Due to progression of the disease in 2 patients, no surgery was performed. Histologic examination of the resected specimen was performed to evaluate the percentage of necrosis produced by chemotherapy on the primary and metastatic tumor. After surgery, the patients received further chemotherapy with the same drugs used preoperatively plus ifosfamide and VP-16. The histologic response of the primary tumor was good (> 90% tumor necrosis) in 25% of the cases; in the resected metastatic nodules, 23% had good responses. A discrepancy between the histologic response of the primary and secondary tumor was observed in only 15% of the cases. These results seem to confirm the validity of the strategy (widely used today in the neoadjuvant treatment of non-metastatic osteosarcoma) of changing the postoperative treatment when the histologic response of the primary tumor is poor. At an average follow-up of 3.5 years, only 6 patients remained disease-free; 19 patients relapsed and 1 patient died for adriamycin cardiotoxicity. Of the 19 relapsed patients, 16 died and 3 are still alive but with uncontrolled disease. These results are much worse than those obtained in 144 cases of non-metastatic osteosarcoma of the extremities treated in the same period with the same preoperative chemotherapy (77% with good response in the primary tumor and 78% with continuous disease-free survival). The data suggest that a very effective neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities gives disappointing results in osteosarcoma of the extremities which is metastatic at presentation.

Adolescent↗
PubMed1992

Effect of intra-arterial versus intravenous cisplatin in addition to systemic adriamycin and high-dose methotrexate on histologic tumor response of osteosarcoma of the extremities.

In neoadjuvant treatment of osteosarcoma of the extremities intra-arterial (IA) instead of intravenous (IV) administration of cisplatinum (CDDP) has been advocated to improve local response and consequently increase the percentage of limb salvages and the cure rate. Since the major local advantages from the IA use of CDDP have been recently questioned, a comparative prospective study was performed at the Rizzoli Institute between July 1990 and September 1991. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate (HDMTX), followed 6 days later by CDDP and adriamycin (ADM), HDMTX and ADM were delivered intravenously while CDDP was delivered according to previous randomization, either intra-arterially or intravenously. Of the 79 patients who entered the study 40 received CDDP IA and 39 CDDP IV. The percentage of clinical and radiological response of the tumor as well as the percentage of limb salvage procedures performed was the same in the two groups. However the rate of good histological response (tumor necrosis greater than 90%) was significantly higher in the group of patients who received IA CDDP than in the patients who received the drug intravenously (77.5% vs 46%: p less than 0.01). No differences in terms of local or systemic side effects were found in the two groups. A longer follow-up is necessary to establish if this improved good response rate achieved with IA CDDP will lead to an improved cure rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Limb sparing versus amputation in osteosarcoma. Correlation between local control, surgical margins and tumor necrosis: Istituto Rizzoli experience.

Three hundred fifty-five patients with osteosarcoma were surgically managed at the Istituto Ortopedico Rizzoli between 1983 and 1988. Three hundred two patients performed two cycles of neoadjuvant chemotherapy according to two different protocols consecutively activated; the remaining 53 patients were immediately operated on without neoadjuvant treatment. Follow-up ranged from 19 to 88 months, with a mean of 51 months. Demolitive surgery was performed in 116 patients (33%), while conservative in 239 patients (67%). A radical margin was achieved only in patients undergoing amputations: no radical surgical margins were achieved by local resection: 174 resected patients (73%) had wide margins, while 34 (14%) had marginal margins; 20 patients had contaminated margins and 11 patients (5%) had intralesional margins. Wide or marginal margins were achieved in 208 (87%) of the patients managed by local resection. Local recurrence was identified in 24 of 355 patients (7%). Incidence of local recurrence is strictly related to surgical margin, but above all, to tumor necrosis induced by neoadjuvant chemotherapy. In fact, neoadjuvant chemotherapy makes limb salvage feasible in the majority of cases without increasing the risk of local recurrence: in the group of patients immediately operated on without neoadjuvant chemotherapy, the incidence of local recurrence is dramatically high even when the surgical margins are adequate.

Adolescent↗
PubMed1992

Primary chemotherapy and delayed surgery for osteosarcoma of the extremities with synchronous metastases.

From September 1986 to September 1989 11 patients affected by osteosarcoma of the extremities with synchronous metastases were treated with two cycles of high-dose methotrexate i.v., cisplatin i.a. and adriamycin i.v. followed by simultaneous resection of the primary and metastatic tumor. A complete histological examination of the resected specimens was always performed to evaluate the percentage of necrosis produced by chemotherapy on both the primary and metastatic tumor. After surgery the patients received 3 more cycles of the same drugs as used preoperatively plus ifosfamide. The histological response of the primary tumor was 'good' (90% or more tumor necrosis) in 4 patients and 'poor' (less than 90% of tumor necrosis) in 7, while in the 34 metastatic nodules the resulting necrosis was good in 8 and poor in 26. A good correlation between the histological response in the primary and metastatic tumor was observed, particularly for poor responders (91% of poor responses also in metastatic nodules). At an average follow-up of 42 months, only 3 patients are alive, 2 disease-free, and one with uncontrolled disease. These data suggest that the prognosis of osteosarcoma of the extremities with synchronous metastases remains poor, even with a very aggressive treatment. Our results also seem to confirm the validity of the present strategy in the treatment of non-metastatic osteosarcoma: introducing new drugs post-operatively in poor responding patients can allow a better treatment of microscopic disease and can improve the prognosis for these patients.

Adolescent↗