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Alessandra Longhi

Publications and source records attributed to Alessandra Longhi.

32 records · Page 2Linked to original sources
PubMed2004

Simultaneous osteosarcoma lung metastasis and second primary lung cancer.

Second malignant neoplasms (SMNs) after treatment of children and adolescent cancers have been extensively studied. Lung cancer as an SMN is rare in all type of primary cancer in children and in osteosarcoma as well. The authors reviewed all cases of osteosarcomas treated at their institution from 1975 to 2000 and found 22 cases of SMN, only 1 involving lung cancer. The authors describe this latter case, a 17-year-old girl with a localized osteosarcoma of the tibia who developed simultaneously lung metastases of osteosarcoma and a primitive lung adenocarcinoma only 18 months from the diagnosis. Lung cancer is unusual in youths as a primary malignancy or as a second primary malignancy. The occurrence of a primitive lung cancer together with lung metastases from osteosarcoma is even more unusual, and examination of all new lung nodules is highly recommended.

Adenocarcinoma↗
PubMed2004

Role of surgery in local treatment of Ewing's sarcoma of the extremities in patients undergoing adjuvant and neoadjuvant chemotherapy.

Although more and more patients with Ewing's sarcoma of bone (ESB) are being treated by surgery, the relative role of surgery and radiotherapy in the local treatment of this tumor has yet to be determined. Because the outcome of ESB may differ according to the anatomical site of the tumor, results reported in the literature, which generally refer to series with tumors located in all sites, may be selection biased. Therefore, we have retrospectively evaluated patients with ESB exclusively in the extremity and locally treated by surgery or radiotherapy. Two hundred and sixty-eight patients treated at Rizzoli 1979-1996 for non-metastatic ES of the extremities were assessed. Chemotherapy was administered according to four sequentially activated protocols. One hundred and thirty-six patients were treated by surgery, 70 by surgery and radiotherapy, and 60 patients by radiotherapy. Two patients underwent only chemotherapy. The follow-up range was 5-23 years (mean 13 years). One hundred and fifty-two patients remained continuously free of disease, 108 relapsed, 2 died of chemotherapy toxicity and 6 developed a second malignancy. The 5-year event-free survival (EFS) and overall survival (OS) were respectively 62 and 69%. Although patients of all groups were matched for possible risk factors, the rates of 5-year EFS and local control were significantly lower in patients treated with radiotherapy compared to patients treated by surgery or surgery and radiotherapy (48% vs 66%, p=0.002; 80% vs 94%, p=0.0001). Furthermore, in group 3 there were 6 secondary malignancies. Our results indicate that surgery should always be considered in the local treatment of ES of the extremities. Postoperative radiation therapy must be added in case of inadequate surgical margins.

Adolescent↗
PubMed2003

Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor.

BACKGROUND: In primary central high-grade osteosarcoma, a number of distinct subtypes have been identified, but little is known about the response to chemotherapy. METHODS: The authors investigated whether the subtypes correlated with histologic response to chemotherapy in 1058 patients with osteosarcoma of the extremities who were treated with neoadjuvant chemotherapy over the last 20 years. The tumors were classified as osteoblastic (70%), chondroblastic (13%), fibroblastic (9%), and telangiectatic (6%). At diagnosis, 911 patients had localized disease and 147 had resectable lung metastases. RESULTS: The response to preoperative chemotherapy was good (90% or more tumor necrosis) in 59% of patients and poor (< 90% tumor necrosis) in 41% of patients. The rate of good responses was significantly higher (P = 0.0001) in the fibroblastic (83%) and telangiectatic (80%) tumors and significantly lower in chondroblastic tumors (43%). Prognosis was significantly correlated with the histologic subtypes. The 5-year overall survival rate was significantly higher (P = 0.0001) in fibroblastic (83%) and telangiectatic (75%) tumors than in osteoblastic (62%) and chondroblastic (60%) tumors. In all subtypes, except for the chondroblastic subtype, the 5-year overall survival rate was significantly higher (P = 0.0001) in good responders P = 0.0001 (68%) than in poor responders (52%). CONCLUSIONS: The authors concluded that the histologic subtype of primary central high-grade osteosarcoma of the extremity was strictly correlated with histologic response to chemotherapy and probably, as a consequence, also with prognosis. Further studies are needed to establish whether these results justify a specific therapeutic approach based on the histologic subtype of the tumor.

Adolescent↗
PubMed2003

Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: local and systemic control by amputation or limb salvage after preoperative chemotherapy.

To determine whether a pathologic fracture in osteosarcoma of long bones has prognostic importance, and limb salvage can be safely performed in such cases, we reviewed the surgical treatment and oncologic results in 46 patients with nonmetastatic osteosarcoma of the extremity and pathologic fracture at presentation who had been treated in our Institution with neoadjuvant chemotherapy, between 1983 and 1999. Neoadjuvant chemotherapy was given according to 6 consecutive protocols. Surgery consisted of limb salvage (34 patients), amputation (11 patients) and rotationplasty (1 patient). The average follow-up was 11 (3-20) years. 28 patients remained continuously disease-free, 17 patients relapsed and 1 died of chemotherapy-related toxicity. Despite the high rate of limb salvage, only 2 local failures occurred, 1 after amputation and 1 after limb salvage. The 5-year disease-free survival and overall survival rates were 59% and 65%, respectively, with no differences between amputated and resected patients. These results are similar to those obtained in 689 contemporary patients having an osteosarcoma without a pathologic fracture treated in our Institution, and using the same protocols for chemotherapy. We conclude that with neoadjuvant chemotherapy, osteosarcoma patients presenting with a pathologic fracture can be surgically treated like those with no fracture, and that limb salvage procedures do not increase the risk of local recurrence or death of these patients.

Adolescent↗
PubMed2003

Multimodal therapy for the treatment of nonmetastatic Ewing sarcoma of pelvis.

The purpose of this study was to evaluate the outcome of patients with Ewing sarcoma (ES) of the pelvis, attempting to identify prognostic factors to select patients for more aggressive treatment. Seventy-seven patients with nonmetastatic ES of the pelvis were treated at Rizzoli Institute between 1979 and 1996. Four different protocols of chemotherapy were used successively. Two protocols consisted of VACAc, and two of VACAc plus ifosfamide and etoposide. Local treatment consisted of surgery in 5 patients, radiotherapy in 60, and surgery followed by radiotherapy in 12. Mean follow-up was 11 years (range 5-25 years). Thirty-three patients remained continuously free of disease; 43 relapsed (24 due to metastases and 19 to local recurrence and metastases); 1 died of treatment-related complications. The 5- and 10-year event-free survival rates were 45% and 44%, respectively, and the 5- and 10-year overall survival rates were 48 and 44. These results are significantly worse than the ones achieved in 329 contemporary patients with extrapelvic lesions treated with the same protocols of chemotherapy (5- and 10-year event-free survival = 46% vs. 64% and 44% vs. 69%). Thus, despite associated chemotherapy, the outcome of ES localized in the pelvis remains poor, and new innovative methods for the treatment of this tumor are needed.

Adolescent↗
PubMed2003

Fertility in male patients treated with neoadjuvant chemotherapy for osteosarcoma.

PURPOSE: To evaluate fertility in male patients with osteosarcoma after chemotherapy including high doses of alkylating agents. PATIENTS AND METHODS: Postchemotherapy fertility was evaluated in 96 male patients who received chemotherapy at the authors' institution from 1976 to 1996 for localized bone osteosarcoma of the extremities. Four drugs were administrated (doxorubicin, cisplatin, methotrexate, ifosfamide) at different doses according to six different protocols. Eleven patients were prepubertal and 85 were postpubertal at the time of chemotherapy. The median age of these patients at the time of chemotherapy was 17 years (range 10-42), the median age at the time of the interview was 27 years (range 19-53), and the median follow-up from the end of chemotherapy was 9 years (range 4-17). RESULTS: Of the 96 patients, 26 underwent sperm analysis and 20 showed oligo- or azoospermia. Patients who received high-dose ifosfamide showed a higher incidence of azoospermia. Six patients were normospermic and received no ifosfamide or lower doses of ifosfamide. Eight patients fathered a total of 12 children. No birth defects or congenital anomalies were observed in their offspring. CONCLUSIONS: The rate of sterility was related to ifosfamide dosage. It appears that pubertal maturation is not affected by chemotherapy. No congenital malformations were seen in the children of the few patients who fathered children.

Abnormalities, Drug-Induced↗
PubMed2003

Neoadjuvant chemotherapy for osteosarcoma of the extremity: intensification of preoperative treatment does not increase the rate of good histologic response to the primary tumor or improve the final outcome.

PURPOSE: The aim of this study was to compare the results in terms of histologic response to primary chemotherapy of two sequential studies in osteosarcoma patients preoperatively treated with methotrexate, doxorubicin, cisplatin, and ifosfamide, given at different doses. PATIENTS AND METHODS: Between January 1993 and March 1995, 171 patients with osteosarcoma of the extremity were treated according to a protocol of neoadjuvant chemotherapy with preoperative methotrexate, cisplatin, doxorubicin, and ifosfamide. From April 1995 to December 1999, 196 osteosarcoma patients were preoperatively treated with the same drugs at higher doses. Postoperatively, patients received the same treatment in both studies used, but poor responders (tumor necrosis <95%) had more cycles of treatment than good responders. RESULTS: Comparing the two chemotherapy regimens, there were no significant differences in terms of good histologic response to chemotherapy (69% vs. 62%), 5-year event-free survival (60% vs. 65%), 5-year overall survival (74% vs. 80%), and rate of local recurrence (6% vs. 4%). The 5-year event-free survival was significantly related to the serum level of alkaline phosphatase before treatment (77% for patients with normal values vs. 46% for patients with high values) and the degree of histologic response to preoperative chemotherapy (69% for good responders vs. 54% for poor responders). CONCLUSIONS: Increasing the doses of preoperative chemotherapy does not improve the rate of good histologic response and survival in osteosarcoma of the extremity. The degree of necrosis induced by preoperative treatment probably reflects an innate sensitivity to chemotherapy, which is not altered by increasing drug doses.

Adolescent↗
PubMed2002

High-grade osteosarcoma of the extremity: differences between localized and metastatic tumors at presentation.

BACKGROUND: In osteosarcoma, as in other tumors, the presence of metastases at presentation is generally considered a consequence of late diagnosis. To verify this, the authors investigated whether there was a relationship between the stage of the disease at presentation and several clinical and pathologic characteristics, including the interval between the onset of first symptoms or signs and the final diagnosis. PATIENTS AND METHODS: One thousand seventy-one patients with high-grade osteosarcoma of the extremity were observed between 1980 and 1999. Of these, 891 had a localized tumor and 180 had metastases at the time of diagnosis. RESULTS: Compared with patients with localized disease, patients with detectable metastases at the time of diagnosis had higher serum levels of alkaline phosphatase, larger primary lesions, and tumors often located in the femur and humerus. In terms of time to diagnosis, the interval between the onset of first symptoms and the final diagnosis was significantly shorter in patients with metastases than in patients with localized tumor. This surprising finding probably reflects a more rapid growth of the tumor. CONCLUSIONS: These results suggest a different biologic phenotype and aggressiveness of the tumor in a subgroup of patients and that the stage of the disease at presentation depends more on the properties of these tumors than on late diagnosis.

Adolescent↗
PubMedDate not supplied

Radiation-induced osteosarcoma arising 20 years after the treatment of Ewing's sarcoma.

We report the case of a 17 years old female with a Ewing's sarcoma of the left femur treated with limb sparing surgery followed by local radiotherapy of 45 Gy and adjuvant chemotherapy with vincristine, doxorubicine, cyclophosphamide, actinomycin D. The patient received neoadjuvant chemotherapy for osteosarcoma and a left femur resection with endoprosthesis replacement. The patient is alive and free of disease 4 years after the treatment of this second malignant neoplasm (SMN). This case shows that radioinduced SMN can occurr with relatively low doses of RT (<50 Gy) and that it may occur very late.

Adolescent↗
PubMedDate not supplied

Prognostic significance of serum lactate dehydrogenase in osteosarcoma of the extremity: experience at Rizzoli on 1421 patients treated over the last 30 years.

AIMS: The study evaluated the correlation between pretreatment serum lactate dehydrogenase (LDH) levels with the stage of disease and its clinical prognostic value. METHODS: Pretreatment serum LDH of 1421 patients with osteosarcoma of the extremity were assessed to investigate whether the enzyme correlates with the stage of the tumor. In 860 assessable patients with localized disease, treated according to 10 different protocols of adjuvant (four) and neoadjuvant chemotherapy (six), we also evaluated the correlation between the serum levels of LDH and outcome. RESULTS: According to the stage of disease, the rate of high serum level of LDH was significantly higher in 199 patients with metastatic disease at presentation than in 1222 patients with localized disease (36.6% vs 18.8%; P < 0.0001). In these patients, the 5-year disease-free survival was 39.5% for patients with high LDH levels and 60% for those with normal values. The 5-year disease-free survival correlated with serum level of LDH at univariate and multivariate analysis, although it lost its significance when histologic response to chemotherapy was also considered in the multivarite analysis. CONCLUSIONS: Serum LDH has a prognostic value and it should be considered in evaluating the results of therapeutic trials of chemotherapy, as well as defining a category of patients at high-risk of relapse to be treated with a more aggressive regimen.

Adolescent↗
PubMedDate not supplied

Prognostic significance of serum alkaline phosphatase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: recent experience at Rizzoli Institute.

In 560 patients with high-grade osteosarcoma of the extremity treated with 5 different protocols of neoadjuvant chemotherapy at a single institution between 1983 and 1995, the pre-treatment serum alkaline phosphatase (SAP) was examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease. SAP was normal in 302 (54%) patients and high in 258 (46%). High levels of SAP was observed significantly and independently more frequently in male patients over 14-years-old, and in tumours larger than 150 ml and of osteoblastic subtypes. The 5-year event-free survival (EFS) and overall survival (OS) for all patients were respectively 60 and 68%. With multivariate analysis only two factors were independently correlated with the 5-year EFS: SAP levels (p=0.002) and the grade of chemotherapy-induced necrosis (p=0.0001). The authors conclude that in planning randomized clinical trials of neoadjuvant treatment for osteosarcoma, patients should be stratified according to SAP levels, and that when tailoring the aggressiveness of postoperative chemotherapy to the risk of relapse, in addition to the histologic response to preoperative treatment, the SAP levels should also be considered.

Adolescent↗
PubMedDate not supplied

Effect of oral contraceptive on ovarian function in young females undergoing neoadjuvant chemotherapy treatment for osteosarcoma.

We compared the residual ovarian function and the fertility of two groups of female patients treated at different times at the authors' institution by neoadjuvant chemotherapy for localized osteosarcoma of the extremities. From 1997 to 2000, one group of 31 females received neoadjuvant treatment according to the IOR 6 protocol, which included high-dose ifosfamide, high-dose methotrexate, adryamycin, and cis-platinum. In this group of patients an oral contraceptive (OC) was given in an attempt to prevent post-chemotherapy ovarian failure. Another group of 90 patients was treated between 1974 to 1995 with the same antiblastic drugs according to similar protocols (IOR 1-IOR 5). These patients did not receive OC or other treatment to protect ovarian function. There were no significant differences between the two groups of patients. Early chemotherapy-induced menopause occurred in 3 out of 19 postpubertal patients who received the OC and in 3 out of 71 postpubertal patients in the control group. In the OC group there were 2 cases of thrombophlebitis. No delay in menarche was seen in prepubertal patients. From statistical evaluation we underline that age and alkylant doses are the most important predictive factors for early menopause and that oral contraceptives during chemotherapy do not protect ovarian function in patients receiving high-dose alkylant based chemotherapy.

Adolescent↗
PubMedDate not supplied

Delayed methotrexate clearance in osteosarcoma patients treated with multiagent regimens of neoadjuvant chemotherapy.

We retrospectively studied 790 patients with osteosarcoma treated by neoadjuvant chemotherapy at a single institution between 1983 and 2000 according to different protocols, all including a high dose of methotrexate (HDMTX), to determine the incidence of delayed clearance of HDMTX, and identify patients at high risk for this kind of toxicity. Chemotherapy was administered according to 7 different protocols, successively activated, in which HDMTX was associated with other drugs (cisplatin, adriamycin, ifosfamide) in different combinations. The doses of MTX ranged between 7.5 to 12 g/m(2) and patients received from 1 to 10 cycles with MTX for a total number of 4219 cycles. The incidence of delayed clearance of MTX (plasma values of the drug at 24 h >5 microM/l) was 8.6% per patient and 1.6% per cycle of treatment. In 51 cases the delayed clearance of MTX was "mild" (plasma values of MTX at 24 h between 5 and 19 microM/l) and in 18 cases "severe" (plasma values of MTX at the 24 h >20 microM/l). The delayed clearance of MTX was significantly correlated with the age of patients (16% for patients over 20 vs. 6% for younger patients: p=0.0001) and was significantly more frequent during the first cycles of chemotherapy (7% during the first 3 cycles of treatment vs. 2% during subsequent cycles). There was also a significant correlation (p=0.0001) between the plasma values of MTX at the end of the infusion and at 18 h and the delayed clearance of the drug. In addition to support treatment by increased hydration and sodium bicarbonate, all patients who experienced the delayed clearance of MTX were treated solely with a high dose of leucovorin (HDLV), which was started at the first 18 h. Significant neutropenia and/or thrombocythopenia, increase of serum creatinine, mucositis of varying degrees and vomiting occurred in most cases of severe delayed clearance of MTX, but all patients completely recovered. We conclude that in spite of adequate hydration and urine alkalinization and the use of pharmacokinetically guided leucoverin rescue, delayed clearance of MTX may still occur and that its incidence is higher in older patients and during the first cycles of treatment. However, if "rescue" treatment is started early, the consequent morbility is tolerable and these patients can be rescued using only HDLV, without the need for extracorporeal removal.

Adolescent↗