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Mario Mercuri

Publications and source records attributed to Mario Mercuri.

At least 19 recordsLinked to original sources
PubMed2006

Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases.

PURPOSE: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. PATIENTS AND METHODS: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. RESULTS: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. CONCLUSION: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.01).

Adolescent↗
PubMed2006

Primary bone osteosarcoma in the pediatric age: state of the art.

The current combination treatment, chemotherapy and surgery, has significantly improved the cure rate and the survival rate of primary bone osteosarcoma. The 5-year survival rate has increased in the last 30 years from 10% to 70%. Even in patients with poor prognosis, such as those with metastases at diagnosis, the 5-year survival rate has reached 20-30% due to chemotherapy and the surgical removal of metastases and primary tumor. However, the most effective drugs are still the same as those employed over the last 20 years as front line neoadjuvant or adjuvant chemotherapy: Doxorubicin, Cisplatin, Methotrexate, Ifosfamide. No standard, second line therapy exists for those who relapse. At relapse, due to the lack of new non-cross-resistant drugs, surgery is still the main option when feasible. Other drugs have been employed in relapsed patients with poor results. This article reviews the state of the art of treatment for bone osteosarcoma in the pediatric age.

Adolescent↗
PubMed2006

Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution.

BACKGROUND: The evaluation variables influencing systemic and local recurrence and final outcome are extremely important in defining risk-adapted treatments for patients with nonmetastatic osteosarcoma of the extremity. METHODS: A homogeneous group of 789 patients treated at a single institution between March 1983 and March 1999 with different protocols of neoadjuvant chemotherapy, with a minimum followup of 5 years, were retrospectively evaluated in relation to gender, age, serum levels of alkaline phosphatase, tumor site and size of the pathologic fracture, type of surgery, protocol of chemotherapy, surgical margins, and histologic response to preoperative treatment. RESULTS: The 5-year event-free survival (EFS) and overall survival rates were 60.1% and 67.5%, respectively. Upon univariate analysis, EFS was significantly related to the age of patients, serum value of alkaline phosphatase, tumor volume, histologic subtype, type of surgery, surgical margins, histologic response to preoperative treatment, and chemotherapy protocol. Local recurrences (4.8%) were significantly correlated with surgical margins. The 5-year post-recurrence EFS survival was 17% and was significantly lower for patients who had a local recurrence and metastases than for those with metastases only. Patients who had a recurrence only in the lung had a post-recurrence survival rate significantly better than others, correlated with the number of metastatic nodules and the length of the disease-free interval. CONCLUSIONS: Upon multivariate analysis, age < or = 14 years, high serum levels of alkaline phosphatase, tumor volume > 200 mL, a two-drug regimen chemotherapy, inadequate surgical margins, and poor histologic response to treatment maintained independent prognostic values on the outcome of nonmetastatic osteosarcoma of the extremities. These factors must be considered when deciding risk-adapted treatments for osteosarcoma patients.

Adolescent↗
PubMed2006

Prognostic factors in non-metastatic Ewing's sarcoma tumor of bone: an analysis of 579 patients treated at a single institution with adjuvant or neoadjuvant chemotherapy between 1972 and 1998.

We aimed to identify pretreatment and treatment factors that may influence the outcome of Ewing's sarcoma family tumors of bone and enable customized therapy for future studies with a retrospective analysis of 579 patients with non-metastatic Ewing's sarcoma treated with combined adjuvant or neoadjuvant chemotherapy at a single institution between 1972 and 1998. We evaluated the prognostic significance of gender, age, site and volume of tumor, serum level of LDH, type of local treatment, type of chemotherapy and histologic response to preoperative treatment. The 5- and 10-year disease-free survival rates were 56.9% and 49.2% respectively. Multivariate analyses showed that all the evaluated factors, with exclusion of the tumor site, were significantly correlated with the 5-year disease-free survival. We concluded that the outcome of non-metastatic ESF of bone tumors is influenced by many clinical and treatment-correlated variables. In order to gain the greatest benefit from treatment, while reducing the morbidity, appropriate therapeutic strategies for different risk groups of patients should be selected. Criteria to stratify patients according to the risk of local or systemic relapse should not be based on a single prognostic factor, but should include all the variables that showed prognostic significance.

Adolescent↗
PubMed2006

Late relapse in osteosarcoma.

The aim of this study was to identify predictive factors of late relapse in nonmetastatic osteosarcoma patients treated at the Rizzoli Institute from 1983 to 1997. Clinical features of patients who had late (>4 y of follow-up) or earlier recurrence were compared. Late relapse was reported in 24 (3.7%) of the 648 patients who entered the studies. A surgical complete remission was achieved in 19 (79%) patients. The 5-year probability of postrelapse survival was 65% for the complete remission patients (48% in the entire group), which was significantly better than that of the patients (5-year postrelapse survival 20%) with an early relapse. Sex, site, and size of the tumor, histologic subtype, alkaline phosphatase and lactate dehydrogenase serum levels, type of surgery, and histologic response did not significantly differ between patients with late or early relapse. No clinical predictive factors of late relapse were identified and a prolonged follow-up is recommended for all patients.

Adolescent↗
PubMed2006

May P-glycoprotein status be used to stratify high-grade osteosarcoma patients? Results from the Italian/Scandinavian Sarcoma Group 1 treatment protocol.

The aim was to evaluate the clinical impact of P-glycoprotein in primary non-metastatic high-grade osteosarcoma patients, treated with neoadjuvant chemotherapy protocols. P-glycoprotein was assessed by immunohistochemistry on paraffin-embedded tissue samples collected at time of diagnosis from 94 osteosarcoma patients, treated with the Italian Sarcoma Group/Scandinavian Sarcoma Group 1 (ISG/SSG 1) protocol. P-glycoprotein-positivity at diagnosis was found in 53/94 ISG/SSG 1 cases (56%) and emerged as the single factor significantly associated with an unfavourable outcome from survival and multivariate analyses. A comparative analysis of the subgroup of 94 patients considered for P-glycoprotein evaluation and the whole series of ISG/SSG 1 patients showed that this marker retained its prognostic value also in the latter group. In osteosarcoma patients treated with doxorubicin-based chemotherapy protocols, P-glycoprotein overexpression at diagnosis is an important adverse prognostic factor for outcome. P-glycoprotein evaluation can therefore constitute the basis for stratifying, at diagnosis, osteosarcoma patients for whom alternative treatments may be considered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Neoadjuvant chemotherapy with high-dose Ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: a joint study by the Italian and Scandinavian Sarcoma Groups.

PURPOSE: To explore the effect of high-dose ifosfamide in first-line treatment for patients < or = 40 years of age with nonmetastatic osteosarcoma of the extremity. PATIENTS AND METHODS: From March 1997 to September 2000, 182 patients were evaluated. Primary treatment consisted of two blocks of high-dose ifosfamide (15 g/m2), methotrexate (12 g/m2), cisplatin (120 mg/m2), and doxorubicin (75 mg/m2). Postoperatively, patients received two cycles of doxorubicin (90 mg/m2), and three cycles each of high-dose ifosfamide, methotrexate, and cisplatin (120 to 150 mg/m2). Granulocyte colony-stimulating factor support was mandatory after the high-dose ifosfamide/cisplatin/doxorubicin combination. RESULTS: No disease progression was recorded during primary chemotherapy, 164 patients (92%) underwent limb-salvage surgery, four patients (2%) underwent rotation plasty, and 11 patients (6%) had limbs amputated. Three (1.6%) patients died as a result of treatment-related toxicity, and one died as a result of pulmonary embolism after pathologic fracture. Grade 4 neutropenia and thrombocytopenia followed 52% and 31% of all courses, respectively, and mild to severe nephrotoxicity was recorded in 19 patients (10%). The median received dose-intensity compared with protocol was 0.82. With a median follow-up of 55 months, the 5-year probability of event-free survival was 64% (95% CI, 57% to 71%) and overall survival was 77% (95% CI, 67% to 81%), whereas seven patients (4%) experienced local recurrence. CONCLUSION: The addition of high-dose ifosfamide to methotrexate, cisplatin, and doxorubicin in the preoperative phase is feasible, but with major renal and hematologic toxicities, and survival rates similar to those obtained with four-drug regimens using standard-dose ifosfamide. Italian Sarcoma Group/Scandinavian Sarcoma Group study I showed that in a multicenter setting, more than 90% of patients with osteosarcoma of the extremity can undergo conservative surgery.

Adolescent↗
PubMed2005

Resection of recurrent pulmonary metastases in patients with osteosarcoma.

BACKGROUND: Surgical resection of lung metastases is widely accepted in osteosarcoma patients. Few data exist on treatment of recurrent pulmonary metastases. The authors of the current study retrospectively analyzed patients with osteosarcoma who received surgery for recurrent lung metastases. METHODS: From 1980 to 2001, 127 metastasectomies were performed on 94 patients. Criteria of eligibility were no metastases beyond the lung, no local recurrence, possibility of achieving complete resection of metastases without causing respiratory insufficiency, acceptable operative risk. Data were statistically elaborated with survival analysis according to Kaplan-Meier method of univariate analysis, life tables and Gehan statistic model, and multivariate analysis using Cox regression test. Results were considered in terms of time from first (DFI1) and second (DFI2) metastasectomy. RESULTS: Of 94 patients operated upon twice, 59 (62.7%) died. Thirty-five (37.3%) are alive; 31 (32.9%) of these are continuously disease-free. The 3- and 5-year event-free actuarial survival curve from first metastasectomy was 45%, and 38%, respectively, whereas from the second metastasectomy, it was 33% and 32%, respectively. According to a Cox regression model, DFI1 has a risk of death of 0.974 times and DFI2 of 0.972 times for every additional month of survival. In multivariate analysis, Cox regression test showed the best predictive model of local recurrence and number of metastases (P = 0.0014). CONCLUSIONS: The authors concluded that patients persistently free of the primary osteosarcoma who developed recurrent resectable metastatic disease of the lung should be considered for reoperation a second, third, or fourth time, as these patients had similar DFI curves after five-years.

Adolescent↗
PubMed2005

Grade of chemotherapy-induced necrosis as a predictor of local and systemic control in 881 patients with non-metastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy in a single institution.

To determine whether necrosis induced by pre-operative chemotherapy correlates with the rate of systemic and local relapse, may change the pattern of relapse and/or may modify the chance of success of post-relapse treatments, we evaluated 881 patients with non-metastatic osteosarcoma of the extremities treated with five different protocols of neoadjuvant chemotherapy and surgery at the same institution between 1983 and 1999. The 5-year disease-free survival (DFS) and overall survival (OS) correlated significantly with the histological response to chemotherapy. Five-year DFS and OS in good and poor responders were 67.9% versus 51.3% (P < 0.0001) and 78.4% versus 63.7% (P < 0.0001), respectively. The prognostic value of the histological response was valid only for osteoblastic and telangiectatic osteosarcoma subtypes. Nonetheless, since they represent more than 70% of all osteosarcomas, we conclude that chemotherapy-induced necrosis has a significant prognostic value, regardless of the type of chemotherapy performed after surgery.

Adolescent↗
PubMed2005

4-Demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548): a promising new candidate for chemotherapeutic treatment of osteosarcoma patients.

The effectiveness of the alkycycline 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548, ladirubicin), a new drug with high antitumour activity against a broad range of neoplasms, was evaluated by using a panel of 32 human osteosarcoma cell lines, including cell lines resistant to doxorubicin, methotrexate, or cisplatin. PNU-159548 resulted to be highly active in all cell lines. No cross-resistance was found with conventional drugs, being PNU-159548 active also in cells resistant to doxorubicin and with a multidrug resistance phenotype (associated with MDR1 gene/P-glycoprotein overexpression), as well as in cells resistant to methotrexate or to cisplatin. Analysis of drug-drug interactions showed that PNU-159548 could be successfully used in combination with all the most important drugs currently used in OS chemotherapy. In fact, the simultaneous administration of PNU-159548 and doxorubicin, methotrexate, or cisplatin produced mostly additive or synergistic effects. Sequential exposure to PNU-159548 followed immediately by doxorubicin, methotrexate, or cisplatin was the most effective sequence of administration, invariably resulting in additive or synergistic effects in both drug-sensitive and drug-resistant osteosarcoma cell lines. In conclusion, the high in vitro effectiveness, the absence of cross-resistance with doxorubicin, methotrexate, or cisplatin and the possibility to be successfully used in combination with these drugs indicate PNU-159548 as a promising candidate to be considered for planning new therapeutic regimens for osteosarcoma patients, who show a decreased response to conventional chemotherapy.

Antibiotics, Antineoplastic↗
PubMed2005

Treatment and outcome of recurrent osteosarcoma: experience at Rizzoli in 235 patients initially treated with neoadjuvant chemotherapy.

The pattern of relapse, treatment and final outcome of 235 patients with osteosarcoma of the extremity who relapsed after neoadjuvant treatments performed between 1986 and 1998 at a single institution is reported. The 235 relapses were treated by surgery, surgery plus second line chemotherapy, and only second line chemotherapy or radiotherapy. The 5-year post-relapse-event-free-survival (PREFS) was 27.6% and the post-relapse-overall-survival (PROS) 28.7%. All 69 patients who are presently alive and free of disease were treated by surgery, alone or combined with chemotherapy. None of patients treated only by chemotherapy or radiotherapy survived. We conclude that it is possible to obtain prolonged survival and cure in about 1/4 of relapsing osteosarcoma patients with aggressive treatments. The complete removal of the recurrence is essential for outcome, while the role of the association of second-line chemotherapy remains to be defined.

Adolescent↗
PubMed2005

Stromal stem cells and platelet-rich plasma improve bone allograft integration.

Early vascular invasion is a key factor in bone allograft incorporation. It may reduce the complications related to slow and incomplete bone integration. Bone-marrow-derived stromal stem cells associated with platelet-rich plasma are potent angiogenic inducers proven to release vascular endothelial growth factor. Our goal was to test whether the combination of stromal stem cells and platelet-rich plasma is able to increase massive allograft integration in a large animal model with sacrifice at 4 months. A critical defect was made in the mid-diaphysis of the metatarsal bone of 10 sheep; the study group received an allograft plus stromal stem cells, platelet-rich plasma, and collagen (six animals) and the control group received only the allograft (four animals). Investigation was done with radiographs, mechanical tests and histomorphometric analysis, including new vascularization. Results showed substantial new bone formation in the allograft of the study group. Bone formation is correlated with better vascular invasion and remodeling of the graft in the study group. These results confirm the key role played by stromal stem cells and platelet-rich plasma in bone repair. Further studies are needed to better define the role stromal stem cells play when implanted alone.

Animals↗
PubMed2005

Long-term survival in high-grade axial osteosarcoma with bone and lung metastases treated with chemotherapy only.

A boy, age 2 years 10 months, with high-grade malignant osteosarcoma of the fifth lumbar vertebra with secondary bilateral pulmonary lesions and bone metastasis at the fifth thoracic vertebra is described. The primary site of disease was inoperable and the patient was treated with chemotherapy only. At present, 83 months from diagnosis and 64 from the end of therapy, he is in very good general condition. Although a surgical approach on the primary and secondary sites is fundamental, this case may be considered an indication of the efficacy of aggressive chemotherapy in treating osteosarcoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Second malignancy in 597 patients with ewing sarcoma of bone treated at a single institution with adjuvant and neoadjuvant chemotherapy between 1972 and 1999.

The relative risk of second tumors in patients with Ewing sarcoma is controversial, and little is known about their treatment and outcome. The purpose of the current study was to define the incidence and features of second tumors among 597 long-term survivors of nonmetastatic Ewing sarcoma treated with adjuvant and neoadjuvant chemotherapy, radiotherapy, and/or surgery. The authors found that the risk of secondary malignancy after adjuvant or neoadjuvant treatment of Ewing sarcoma is higher than that after other childhood or adolescent cancers only after radiotherapy. Based on this, postoperative radiotherapy should be avoided when surgery with adequate margins is feasible.

Adolescent↗
PubMed2004

Primary non-Hodgkin's lymphoma of the bone: treatment and analysis of prognostic factors for Stage I and Stage II.

PURPOSE: Primary non-Hodgkin's lymphomas of the bone (PLB) are very rare diseases accounting for 3%-5% of primary bone tumors. The best treatment for PLB has not been found yet. We report on the experience of the Radiation Oncology Department of Bologna University, Italy, relative to the diagnosis and treatment of this disease. METHODS AND MATERIAL: Seventy-seven patients with newly diagnosed PLB were treated from June 1983 to October 2001. Fifty-six were male (72.7%) and 21 were female (27.3%); the median age was 41.8 years, with a range of 16-84 years. The majority of patients had B-cell high-grade histology. The median follow-up was 149 months. Forty-four patients had a solitary bone lesion (Stage I); and in 33 patients, the tumor was spread to locoregional lymphatic area (Stage II). All patients were treated with radiotherapy (RT) with a median dose of 40 Gy (range, 36-54 Gy), and 67 received an additional anthracycline-based regimen of chemotherapy (combined modality therapy [CMT]). RESULTS: After therapy 73 of 77 patients (94.8%) reached a complete remission. At a median time of 23 months, 14 of 77 patients (18.2%) had a disease relapse. Four of them were treated with RT alone (in these cases tumor lesions were <3 cm and located at sites different from mandible); 10 patients were treated with combined RT and CMT. Actuarial disease-free survival (DFS) and overall survival (OS) at 15 years were, respectively, 76.6% and 88.3%. No local failures were seen. Prognostic factors such as age, sex, stage, and bulky lesions were analyzed. Age (<40 vs. >40 years) was the only significant factor for DFS (85.3% vs. 66.6%, p = 0.03). Bulky lesions apparently did not affect OS (90.9% vs. 72.7%). However, the difference has no statistical significance (p = 0.05). Acute and late toxicity related to the treatment was moderate. CONCLUSIONS: In PLB the CMT seems to produce a better outcome than RT alone; that still remains the best treatment for local disease control. Radiation therapy alone should be reserved for mandibular tumors, which are usually very small and earlier diagnosed.

Adolescent↗
PubMed2004

Osteosarcoma associated with hyperparathyroidism.

The fourth case in the literature is presented of a patient with the rare association of hyperparathyroidism and osteosarcoma. A 56-year-old woman presented with hyperparathyroidism and a lesion in the tibia. Initial diagnosis was brown tumor. Histology, however, revealed osteosarcoma, and the patient was treated accordingly. The experimental induction of osteosarcoma by parathormone in rodent studies makes this finding alarming, considering the increasing use of parathormone in the treatment of osteoporosis. The mechanism by which osteosarcoma is induced in humans cannot be explained based on current knowledge of mechanisms of action of parathyroid hormone.

Bone Neoplasms↗