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Biomedical subjects

G Bacci

Publications and source records attributed to G Bacci.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

[Effects of hydration on plasma concentrations of methotrexate in patients with osteosarcoma treated with high doses of methotrexate].

High dose of methotrexate (HDMTX) with leucovorin rescue requires over-hydratation to avoid nephrotoxicity; nevertheless the relationship between hydratation and plasma MTX levels is unknown. We compared the effects of two different types of hydratation (2 lt/m2 vs 1.5 lt/m2) on plasma MTX levels in two groups of patients with osteosarcoma of the extremities and treated with HDMTX (8 g/m2 IV). Samples were obtained at the end of infusion of MTX and 14 and 38 hours after the start of MTX infusion. At the end of infusion of MTX the medium plasma MTX levels proved significantly higher in the group with low hydratation than in the group with high hydratation (585.5 microns/l vs 427.7 microns/l P less than 0.001). The values obtained at 14 and 38 hours, did not show significant differences. No significant differences were seen between the two groups in term of late elimination of MTX and correlated toxicity. These data show that a low hydratation regime allows higher plasma MTX levels at the end of infusion of HDMTX and does not increase the incidence of late elimination of MTX compared to a high hydratation regime.

Adult↗

Primary lymphoma of bone: long term results in patients treated with vincristine--adriamycin--cyclophosphamide and local radiation.

Primary lymphoma of bone (PLB) is an unusual but well-recognized extranodal presentation of non-Hodgkin's lymphoma. In most series treatment with radiotherapy alone results in a cure rate of approximately 40%. Between January 1972 and December 1982, 26 patients with biopsy proven PLB were treated at the Rizzoli Institute with radiotherapy (4000-5,500 rad) and chemotherapy (vincristine, cyclophosphamide and adriamycin). The minimal clinical staging included complete blood cell counts and serum chemistries, bone radiography, full lung tomography, isotope bone scan, bone marrow biopsy and bipedal lymphoangiograms. At a median follow-up of 13 years (8.5-18.5) there were only three relapses (2 cases of meningeal involvement and 1 recurrence in another bone). No local recurrences nor second tumor in the irradiated field were observed. We conclude that the addition of chemotherapy to radiotherapy results in an excellent cure rate for patients with PLB.

Adolescent↗

Non-metastatic Ewing's sarcoma: results in 98 patients treated with neoadjuvant chemotherapy.

From June 1983 to December 1987, 98 patients with non-metastatic Ewing's sarcoma of bone were treated by a protocol of neoadjuvant chemotherapy consisting of two months of preoperative chemotherapy with vincristine, adriamycin, and cyclophosphamide followed by local treatment and one year of chemotherapy aimed at preventing recurrence using the same drugs plus dactinomycin. Local treatment consisted of surgery in 39 cases (40%), radiation in 34 (34%), and both surgery and radiation in 25 (26%). After an average follow-up of five years, 51 patients (52%) had remained continuously disease-free (CDF), 46 had developed metastasis, of which 20 with local recurrence, and one had developed a radioinduced sarcoma. The site of the tumor (61% of patients with Ewing's sarcoma of the extremities were CDF vs. 35% with tumor of the pelvis) and the kind of local treatment (61% of patients who underwent surgery with or without radiation therapy were CDF vs. 35% of patients treated with radiation therapy alone) were important prognostic factors. These results are similar to those obtained in 59 patients treated from 1979 to 1982 (average follow-up, 10 years) using the same drugs administered according to adjuvant chemotherapy procedure as well as those reported in the only other large study on this subject in the literature (the multi-institution German study CESS-81). The authors conclude that even though neoadjuvant chemotherapy makes surgery possible and easier in Ewing's sarcoma, it does not significantly increase survival when compared to traditional adjuvant treatment.

Adolescent↗

Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities.

Between September 1986 and December 1988, 125 patients with osteosarcoma of the extremities entered the second neoadjuvant study at the authors' institution. Patients received preoperatively two cycles of methotrexate (MTX) intravenously, followed by cisplatinum (CDP) intraarterially, plus adriamycin (ADM) intravenously. After surgery, the patients classified as "good responders" (more than 90% tumor necrosis) received ADM, MTX, and CDP, while the "poor responders" (less than 90% tumor necrosis) had a longer chemotherapy that included ifosfamide and etoposide (VP-16) in addition to MTX, ADM, and CDP. Limb salvage was possible in 85% of patients, 8% had an amputation, and 7% had a rotationplasty. The surgical margins were adequate (radical or wide) in 88% of cases and inadequate (marginal or intralesional) in 12%. At an average follow-up period of 28 months (range, 13 to 41), 109 patients (87%) remained continuously disease free, 15 (12%) relapsed with pulmonary metastases, and one patient (0.8%) had a local recurrence. Compared with the first neoadjuvant study at the authors' institution that used only MTX and CDP preoperatively, the percentage of limb salvages, "good responders," and continuously disease-free survival at two years was significantly higher in the second Rizzoli neoadjuvant study (85%, 74%, and 87% versus 77%, 52%, and 59%). Systemic toxicity because of chemotherapy was superimposable. A retrospective analysis of the real dose intensity for each patient demonstrated a correlation between the intensity of chemotherapy and prognosis.

Adolescent↗

Telangiectatic osteogenic sarcoma of the extremities. Results in 17 patients treated with neoadjuvant chemotherapy.

Seventeen patients with telangiectatic osteogenic sarcoma (TOS) of the extremities were treated with neoadjuvant chemotherapy, according to two different protocols. Preoperatively, the patients received high-dose methotrexate (HD-MTX) and cisplatinum (CPD) (HD-MTX/CPD) and doxorubicin. CPD was delivered intraarterially, the other drugs intravenously. Limb-salvage surgery was performed in 12 instances, and five patients were treated with amputation. Postoperative chemotherapy was tailored according to the grade of chemotherapy-induced necrosis. In 13 cases (86%), the resultant grade of necrosis was greater than 90% (good responders). The mean follow-up interval was 3.5 years with a range of 18 to 78 months. Fourteen patients (82%) remained continuously disease-free, while three patients developed lung metastases. Two of these died because of uncontrolled disease, whereas the third patient is alive and disease-free after metastasectomy. No local recurrences were observed. These results are better than those observed in 215 contemporary cases of conventional osteosarcoma treated with the same protocols. This study confirms that TOS is not a uniformly lethal tumor as suggested by prior reports. By employing neoadjuvant chemotherapy, a high percentage of patients with TOS can be cured, and in most of them, a limb-sparing surgery is possible and safe.

Amputation, Surgical↗

The management of malignant bone tumors in children and adolescents.

A series of 205 pediatric patients affected by osteosarcoma, Ewing's sarcoma, fibrosarcoma, and malignant fibrous histiocytoma of bone were treated from 1978 to 1988. Ninety-eight percent of the patients received chemotherapy and 63% had a surgical resection. Sixty-five percent of all patients were alive at 30 months and were considered disease free. The functional results after surgery were evaluated according to the Musculoskeletal Tumor Society score. In all diaphyseal resections and resections of the upper extremity and pelvis, the results were excellent or good in 60% of the cases. In resections of the proximal femur, distal femur, or proximal tibia and reconstruction with nonexpansible prostheses, the results were excellent or good in 75%. On the other hand, when arthrodeses of the lower extremity were used, only 14% of cases had a good result. This correlates with the resulting lack of articulation and serious limb shortening seen with progression of skeletal growth.

Adolescent↗

Primary chemotherapy and delayed surgery for malignant fibrous histiocytoma of bone in the extremity.

Between March 1983 and September 1988, 22 patients with non-metastatic malignant fibrous histiocytoma MFH of bone of the extremities were treated with two regimens of neo-adjuvant chemotherapy successively activated. Preoperatively, the patients received moderate doses of methotrexate and cisplatinum-Regimen 1- or high dose methotrexate, cisplatinum and adriamycin-Regimen 2. Cisplatinum was delivered intraarteriously, the other drugs intravenously. Limb salvage surgery was performed in 20 patients, and 2 patients were amputated. The surgical margins were adequate (radical or wide) in 18 cases and inadequate (marginal) in 4. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 8 patients. In both regimens postoperative chemotherapy was tailored according to the grade of necrosis determined by preoperative treatment on the primary tumor. At an average follow-up of 40 months (15-70), 15 patients (68%) remained continuously disease-free and 7 relapsed with metastases. No local recurrences were observed. Regimen 2 was slightly more effective than Regimen 1 in terms of good histologic response (5/10 vs 1/12) and continuous disease-free survival (8/10 vs 7/127). The results demonstrate that, as in osteosarcoma, in non-metastatic malignant fibrous histiocytoma of bone in the extremities a high percentage of patients can be cured with neoadjuvant chemotherapy and that in most of them limb sparing surgery is possible and safe.

Adolescent↗

Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities. The Istituto Rizzoli Experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses) and intraarterial cisplatin.

Between March 1983 and June 1986 127 patients with localized osteosarcoma of the extremity were treated with neoadjuvant chemotherapy. Preoperative chemotherapy consisted of two cycles of methotrexate (MTX) (high or moderate doses) followed by 6 days by cisplatin (CDP). Surgery was an amputation or a rotation plasty, or a limb salvage. Necrosis was good in 52% of cases, fair in 36%, and poor in 12%. Postoperative chemotherapy consisted of Adriamycin (doxorubicin [ADM]) and bleomycin (BCD) for poor responders; and ADM, MTX, and CDP for fair responders. Good responders were treated as fair responders or with only MTX and CDP. At a 47-month follow-up, 66 patients remained continuously disease free and 61 patients developed metastases. Six of these patients had also a local recurrence. According to the grade of necrosis, the cumulative disease-free probability at 5 years was 67% for good responders, 42% for fair responders, and for poor responders 10% at 45 months. According to the doses of MTX, survival at 5 years was 58% for patients who received high doses and 42% for patients treated with moderate doses. No differences in the rate of survivors were observed between amputated patients and patients treated with limb salvage. The authors conclude that (1) a limb salvage procedure is possible in about 70% of cases and as safe as demolitive surgery, if adequate surgical margins are achieved; (2) good responders have a better prognosis than fair and poor responders if postoperative chemotherapy is sufficiently prolonged and also includes ADM; (3) a different postoperative chemotherapy for poor responders did not improve their prognosis; and (4) a multidrug regimen using high doses of MTX is probably more effective than moderate doses.

Antineoplastic Combined Chemotherapy Protocols↗

Influence of chemotherapy on perioperative complications in limb salvage surgery for bone tumors.

From 1970 to 1986, 304 patients underwent limb salvage resections for 271 malignant and 33 benign tumors of the extremities. Reconstruction was with a prosthesis or nonbiologic spacer. Nonmechanical complications were analyzed to determine the influence of the site and method of reconstruction and the use of chemotherapy on their incidence and severity. There were 82 shoulder resections, 53 proximal femur resections, and 169 knee resections. No chemotherapy was used in 115 patients; neoadjuvant therapy was used in 128 patients and adjuvant therapy was used in 61. There were 120 complications. The most common complication was infection (36 of 304 patients; 11.8%), which led to amputation in eight patients. Resections about the knee led to more complications than the other sites, particularly if reconstructed with a large cement spacer. Patients who did not receive any chemotherapy had a 25.2% (29 of 115) incidence of complications and those who received adjuvant treatment had a 32.8% (20 of 61) incidence. This compares with a 55.4% (71 of 128) incidence in the neoadjuvant group. After neoadjuvant chemotherapy, reconstruction with an uncemented prosthesis led to the fewest complications.

Antineoplastic Agents↗

Ewing's sarcoma of the pelvis.

Two hundred and thirty-nine patients with Ewing's sarcoma were treated at our institution between 1972 and 1987: 42 of these had lesions in the pelvis, 29 were in the wing of the ilium or involved the sacroiliac joint (type I), 5 were periacetabular (type II), and 8 were in the anterior pelvic arch (type III). Radiotherapy alone was used for the primary lesion in 11 cases, adjuvant chemotherapy in 20 and a neoadjuvant protocol in 22. The overall disease-free survival at a mean follow up of 34 months was 19%. There was no difference in survival related to age or the site in the pelvis, none in disease-free survival with adjuvant and neoadjuvant chemotherapy, or in the incidence of local recurrence and metastases in these two groups. Similarly, there was no difference in disease-free survival between operative treatment, with or without radiotherapy, and radiotherapy alone. There was a slight trend towards better local control of the disease in the former group compared to the latter, although this difference was not statistically significant. Our conclusion is that treatment needs to be planned for each individual patient.

Adolescent↗

The importance of dose-intensity in neoadjuvant chemotherapy of osteosarcoma: a retrospective analysis of high-dose methotrexate, cisplatinum and adriamycin used preoperatively.

The relationship between dose-intensity and outcome was retrospectively analyzed in 125 patients with osteosarcoma of the extremities treated at our institution with neoadjuvant chemotherapy between 1986 and 1988. Before surgery, chemotherapy was performed with high-dose methotrexate (HDMTX) i.v. followed by cisplatinum (CDP) i.a. and adriamycin (ADM) i.v. Postoperative chemotherapy was tailored according to the necrosis induced by preoperative treatment. Patients who were "good responders" had 31-weeks of chemotherapy with the same drugs utilized preoperatively, while "poor responder" patients received a longer treatment (40 weeks) in which ifosfamide and etoposide (VP-16) were added to HDMTX, CDP and ADM. At a median follow-up of 2 years (1-3 years) 100 patients (80%) remained continuously disease-free and 25 patients relapsed: 24 with lung metastases and 1 with local recurrence. According to the real dose-intensity received, calculated as a percentage of the dose intensity projected by the protocol, the continuously disease-free survival was 87% in the 82 patients who received 80% or more of the scheduled dose-intensity and only 65% for the 43 patients who received less than 80% of the projected dose-intensity. This difference is highly significant (P less than 0.01). These results suggest that in neoadjuvant chemotherapy of osteosarcoma the real dose-intensity delivered is a determinant of treatment outcome and therefore every effort should be made to avoid reductions of doses and delays of cycles of chemotherapy in these patients.

Adolescent↗