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Alessandra Longhi

Publications and source records attributed to Alessandra Longhi.

At least 19 recordsLinked to original sources
PubMed2007

Adjuvant and neoadjuvant chemotherapy for Ewing sarcoma family tumors in patients aged between 40 and 60: report of 35 cases and comparison of results with 586 younger patients treated with the same protocols in the same years.

BACKGROUND: The clinical and pathologic features of 46 patients 40 to 60 years old with Ewing sarcoma family tumor (ESFT) diagnosed at the authors' institute between 1972 and 2000 were reviewed. METHODS: Ten patients with metastatic tumors at presentation went elsewhere for treatment; 35 of 36 remaining cases with localized disease were treated at the authors' institution according to different chemotherapy protocols activated in successive years. In patients with nonmetastatic tumors local treatment was surgery in 9 patients, radiotherapy in 16, and surgery followed by radiotherapy in 10. RESULTS: At follow-up times ranging from 6 and 34 years (mean, 17.8 years), 15 patients (42.9%) remained continuously disease-free, 19 experienced recurrence, and 1 died of chemotherapy-related toxicity. The 5- and 10-year event-free survivals were 42.9% and 35.2%, respectively, and the 5- and 10-year overall survivals were 46.1% and 42.8%, respectively. Comparing this group of patients with 586 cases of younger patients seen in the same period at Rizzoli, the only difference between the 2 groups was a significantly higher rate of tumors located in the soft tissues with a larger volume in the older group. The results achieved were comparable in the 2 groups, although the older group had a lower chemotherapy dose-intensity and a higher rate of WHO grade 4 hematologic toxicity. CONCLUSIONS: For patients with localized disease treated with adjuvant and neoadjuvant chemotherapy the results were essentially comparable in the 2 groups. It is concluded that patients 40 years or older with ESFT should be treated in the same way as younger patients and included in treatment trials for these tumors.

Adult↗
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

Influence of local recurrence on survival in patients with extremity osteosarcoma treated with neoadjuvant chemotherapy: the experience of a single institution with 44 patients.

BACKGROUND: Risk factors for local recurrence (LR) after osteosarcoma, such as surgical margins and histologic response to preoperative treatment, have been well documented, whereas the outcome for patients who locally recur has not been well established yet. METHODS: Retrospective analysis of the management and outcome of 44 patients who developed LR after treatment of osteosarcoma of the extremities with neoadjuvant chemotherapy was performed in a single institution between 1983 and 1999. RESULTS: In 24 patients (54.5%), LR was the first sign of recurrence; in 8 patients (18.2%) LR followed systemic recurrence and in 12 patients (27.3%), the 2 events, local and systemic recurrence, were concurrent. Of the 44 patients, 26 with local recurrences were free of disease, but only 5 were long-term event-free survivors, and 39 patients developed further recurrences: 37 died of the tumor and 2 were alive with uncontrolled disease at the time of last follow-up. The 5-year disease-free survival rate after the last recurrence was 15.9%; it was 25.9% for patients who achieved remission and 0% for the others. The only prognostic factor identified for post-LR disease-free survival was the presence of systemic recurrence at the time of diagnosis of LR or before (5-year postrecurrence event-free survival rate of 29.1% for patients without metastases at the time of local recurrence vs. 0% for those with metastases; P = .02). CONCLUSIONS: These results confirm that patients with osteosarcoma of the extremities who develop LR are at a very significantly high risk of developing metastatic disease and dying of the tumor.

Adolescent↗
PubMed2006

The role of surgical margins in treatment of Ewing's sarcoma family tumors: experience of a single institution with 512 patients treated with adjuvant and neoadjuvant chemotherapy.

PURPOSE: To evaluate the importance of surgical margins for local and systemic control of Ewing's sarcoma family tumors (ESFT). METHODS AND MATERIALS: Between 1979 and 1999, 512 patients with ESFTs entered 4 different adjuvant and neoadjuvant studies performed at a single institution. Of these patients, 335 were treated with surgery alone (196) or surgery followed by radiotherapy at doses of 44.8 Gy (139). We compared their outcome with that of the 177 patients who were locally treated by radiotherapy at 60 Gy. RESULTS: Local control (88.8% vs. 80.2%, p < 0.009) and 5-year disease-free survival (63.8% vs. 47.6%, p < 0.0007) were significantly better in patients treated with surgery and, among them, in those with adequate surgical margins (96.6% vs. 71,7%, p < 0.0008, and 69.6% vs. 46.3%, p < 0.0002). Nonetheless, better results were observed only in extremity tumors. CONCLUSIONS: Surgery is better than radiotherapy in cases of extremity ESFT with achievable adequate surgical margins, and in cases of inadequate surgical margins, adjuvant reduced-dose radiotherapy is ineffective. Therefore, when inadequate margins are expected, patients are better treated with full-dose radiotherapy from the start.

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

No correlation between methotrexate serum level and histologic response in the pre-operative treatment of extremity osteosarcoma.

Our objectives were to evaluate the behavior of different doses of pre-operative methotrexate (MTX) pharmacokinetics, and assess correlations between the osteosarcoma histologic response and MTX serum peak concentrations. In total, 336 patients with osteosarcoma of the extremities were treated with three neoadjuvant protocols of chemotherapy including high-dose MTX (different doses for each protocol), cisplatin and doxorubicin (same doses in all protocols). The doses of MTX were 8 g/m2 in 124 patients, 10 g/m2 in 110 patients and 12 g/m2 in 102 patients. The mean value of peak serum MTX was 801 micromol/l (range 298-1831) with significant intra- and inter-patient variability. For patients treated with 8, 10 and 12 g/m2 it was 587, 735 and 1114 micromol/l, respectively (P < 0.0001). The histologic response to pre-operative chemotherapy was 90% or above tumor necrosis in 62.8% of patients and less than 90% in 37.2%. The grade of histologic response significantly correlated with the histologic subtype of the tumor, whereas no significant association was found between the mean peak of serum MTX and the histologic response. Thus, increasing the dose of MTX increases the MTX serum peaks, but does not correlate with the histologic response of the tumor.

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

Second malignant neoplasm in patients with osteosarcoma of the extremities treated with adjuvant and neoadjuvant chemotherapy.

We evaluated the rate of second malignancies in 1205 patients with osteosarcoma of the extremity treated at our Institution with different protocols of adjuvant and neoadjuvant chemotherapy. Twenty-six patients (2.15%) developed a second malignant neoplasm at a median of 7.6 years (1 to 25 y) after primary osteosarcoma treatment. Of these, 2 developed a third cancer which were not considered in the series. Second neoplasms were leukemia (10), breast (7), lung (2), kidney (2), central nervous system cancer (2), soft tissue (1), parotid (1), and colon (1). The rate of second neoplasms was significantly higher in female patients, and the latent period shorter in hematologic tumors compared with solid tumors. Ten of these 26 patients are disease free at a median of 7.7 years (range 1 to 15 y) after the last treatment. The rate of second malignancies observed in the osteosarcoma group was significantly higher than that observed in the control group of 1160 patients with benign tumors treated in the same period at our Institute (2.2% vs. 0.8%, P<0.009). Our study showed that the risk of second neoplasm within 15 years increased and then leveled off and that although secondary solid tumors could be explained as unrelated cases, leukemias seem to be over represented.

Adolescent↗
PubMed2005

Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy.

Around 1148 patients with non-metastatic osteosarcoma of the extremity were treated in a single institution between 1972 and 1999 with 4 different protocol of adjuvant and 7 different protocols of neoadjuvant chemotherapy. The rate of limb salvage increased from 20% to 71%. The 5-year event-free survival (EFS) and overall survival (OS) were 57% and 66%, respectively. The 10-year EFS and OS were 52% and 57%, respectively, and the results significantly correlated with serum alkaline phosphatase levels; the type of chemotherapy (adjuvant vs neoadjuvant); and with histologic response to pre-operative treatment. Aggressive chemotherapy and surgery could cure about the 60% of patients with osteosarcoma of the extremity. However, since local or systemic relapses, myocardiopathies and a second malignancy are possible even 5 or more years since the beginning of treatment, a long-term follow-up is recommended.

Adolescent↗
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

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

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

Primary high-grade osteosarcoma: comparison between preadolescent and older patients.

The medical records of patients with high-grade osteosarcoma observed at the authors' institution between 1972 and 1999 were reviewed to study whether osteosarcoma in preadolescent patients has a different biology and a worse prognosis than in older patients. To assess epidemiologic differences, the first analysis evaluated 1,603 patients regardless of tumor stage and site and treatment received. In the second analysis, only 1,136 patients (317 preadolescent and 819 older patients) with nonmetastatic extremity osteosarcoma, treated with the same protocols of chemotherapy, were evaluated to assess differences in prognosis and in the pattern of relapse. Most preadolescents were female (56% vs. 44%, P < 0.0001), and most tumors were located in the extremity (95% vs. 5%, P < 0.001). The 5-year event-free survival (60% [95% CI 53-67%] vs. 58% [95% CI 46-63%]), the overall survival (67% vs. 65%), the rate of amputation (24% vs. 25%), time (21 vs. 22 months) and type of first relapse (systemic 98% vs. 95%, local 2.3% vs. 4.7%) the site of first metastases (pulmonary, 87% vs. 89%), and good histologic response to preoperative treatment (65% vs. 63%) were essentially the same. The authors concluded that there is no need to employ different therapies for the two groups.

Adolescent↗
PubMed2005

Height as a risk factor for osteosarcoma.

Previous investigations have suggested that osteosarcoma may be associated with a taller stature, but the relationship between height and osteosarcoma remains controversial. Height at diagnosis was evaluated in a continuous series of 962 osteosarcoma subjects treated between 1981 and 2001. Patients diagnosed during growth (group 1) were separated from those diagnosed in adulthood (group 2). Height (H) and final height (FH) were expressed as standard deviation scores (SDS), calculated by national reference data. Group 1 subjects were above the 50th centile and their mean H-SDS values (0.31 +/- 1.1) were significantly higher than the mean FH-SDS values (P < 0.0001) of the group 2 subjects, both in males and females. In contrast, the mean FH-SDS (0.01 +/- 1.1) of group 2 did not differ from that of the reference population. The highest incidence of osteosarcoma was at 12.5 years in females, 14.5 years in males. These data confirm previous observations of an association between osteosarcoma development and height, at least in growing individuals. The higher incidence during the pubertal spurt, in the anatomic sites of greater growth and in taller individuals, suggests that growth factors play an important role in the pathogenesis of this bone cancer.

Adolescent↗
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↗