Reconstruction with fascia lata after extensive chest wall resection: results.

OBJECTIVES: Following extensive chest wall resection, the reconstruction technique should fulfill two opposing functional requirements: adequate rigidity and flexibility of the chest wall during the breathing phases. Reconstruction with fascia lata enables a balance between these two parameters, thus favouring the patients' respiratory dynamics and producing low morbidity and good functional results. METHODS: Sixty patients underwent chest wall reconstruction using fascia lata alone or in combination with titanium plates between 2006 and 2011, due to primary tumours in 28 patients, metastases in 23 and local recurrences in 9. The mean area of resected tissue was 107.7 cm(2), distributed among the anterior, anterolateral, lateral and posterior zones. One-to-eight ribs were resected, and additional sternum resection was performed in 75% of patients. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were evaluated in 33 patients. RESULTS: 46.6% of patients underwent reconstruction with fascia lata alone, 1.6% with fascia lata, DualMesh® and titanium plates and 51.6% with fascia lata and titanium plates. There was no 30-day mortality. All patients were extubated after the operation with no need for reintubation. Five patients had postoperative complications: 2 wound dehiscences, 2 haematomas and 1 seroma. There were no significant differences between preoperative and postoperative FEV1 and FVC measurements in patients with or without lobectomy and wedge resections. CONCLUSIONS: Chest wall reconstruction with fascia lata, alone or in combination with titanium plates, allows the surgeon to perform a dynamic reconstruction without flail chest in extensive exeresis. Risks of infection associated with the use of prosthetic materials are also minimized. In addition, the characteristic flexibility of this tissue makes it a precious tool in paediatric chest wall reconstruction, since fascia lata naturally adapts to the physiological growth of younger bodies, thus reducing the risk of scoliosis and local deformities.

High grade osteosarcoma of the extremities metastatic to the lung: long-term results in 323 patients treated combining surgery and chemotherapy, 1985-2005.

BACKGROUND: Approximately one-third of patients with localized osteosarcoma at presentation relapse as well as about three-fourths of the patients with metastases at diagnosis, about 90% of relapses are lung metastases. The role of lung metastasectomy remains to be determined. PATIENTS: and methods: Three hundred and twenty three patients, 88 with resectable lung metastases at diagnosis and 235 with localized disease at presentation who relapsed with lung metastases were treated. RESULTS: A total of 498 lung surgeries and 607 thoracotomies were performed. The 5 year overall survival was 37%. Final outcome was significantly related to presence or absence of metastasis, time of first relapse and presence of local recurrences. According to stage of the disease, the rate of a 5 year event-free survival (EFS) was 36% for patients with localized disease who later relapsed and 9% for patients with resectable lung metastases at presentation (p<0.0001). However, there were no differences in EFS between patients who underwent two or three thoracotomies and patients who had four or five thoracotomies (7.5 vs 18.7%, p=0.29). CONCLUSIONS: In patients with recurrent resectable pulmonary metastases from high grade osteosarcoma treated with adjuvant or neoadjuvant chemotherapy, thoracotomy should always be considered regardless the number of previous lung relapses and the number of secondary pulmonary lesions.

Local and systemic control of Ewing's bone sarcoma family tumors of the ribs.

BACKGROUND: A retrospective analysis of the results and relapse pattern was evaluated in 34 patients with Ewing's family bone tumors (EFBT) treated at Rizzoli Institute with neoadjuvant chemotherapy between 1983 and 2003. OBJECTIVES: The aim of the study was to evaluate treatment strategy and compare our results with those obtained in other studies. METHODS: Local treatment in these patients was radiotherapy alone in 4 cases, surgery alone in 13 and surgery followed by radiotherapy in 17. RESULTS: Five-year event-free survival (EFS) was 44%, no different from that observed in another 558 patients with EFBT located in other sites treated in the same period with neoadjuvant chemotherapy protocols. Eighteen patients had a systemic relapse, followed by local relapse in two and one patient had a local relapse alone. EFS was significantly correlated to the time interval between onset symptoms and beginning of treatment and, in operated patients to histologic response to preoperative treatment. CONCLUSIONS: We conclude that EFBT of the ribs, when treated with neoadjuvant chemotherapy, have an outcome similar to that of patients with EFBT located in other sites.

"Bubble-like" lung metastases in osteosarcoma patients.

PURPOSE: Cavitation of pulmonary metastases have been reported by several authors either as a spontaneous phenomenon or as a consequence of chemotherapy. We present two cases, with this type of image in follow-up, and 20-45 months after the end of treatment. This was the first sign of pulmonary metastases. RESULTS: Two patients with osteogenic sarcoma developed radiological evidence of pulmonary "bubble-like" cavitation several years following completion of chemotherapy. In one patient the "bubble-like" cavitation transformed into a solid nodule. Both patients had surgical resections of all pulmonary lesions, and histology confirmed presence of viable osteosarcoma metastases. CONCLUSION: The two cases suggest that onset of "bubble-like" cavitation in lung parenchyma of osteosarcoma patients may be the first sign of pulmonary metastases.

High grade osteosarcoma of the extremities with lung metastases at presentation: treatment with neoadjuvant chemotherapy and simultaneous resection of primary and metastatic lesions.

BACKGROUND AND METHODS: Between 1986 and 2001, 162 patients with extremity osteosarcoma and lung metastases at presentation, were treated by neoadjuvant chemotherapy, simultaneous resection of primary and, when feasible, secondary lesions followed by chemotherapy. RESULTS: After neoadjuvant chemotherapy, metastases disappeared in 14 patients, 16 were judged unresectable by both our thoracic surgeons, 132 had primary tumors and lung metastases removed simultaneously. Removal of lung metastases was complete in 123 and incomplete in 9. Histologically lesions were benign in 32 patients. For the 100 patients simultaneously operated with histologically proven lung metastases, 5-year event-free survival (EFS) was 18.9%; 27.4% for the 91 who had a complete resection of pulmonary lesions and entered remission as opposed to none for 9 patients who had incomplete removal of lung nodules. Among these 91, 5-year EFS was significantly higher for patients with monolateral compared to bilateral lesions (27.1% vs. 7.9%, P < 0.02) and when only one to three metastatic nodules were present (40.0% vs. 13.3%, P < 0.0001). CONCLUSIONS: These different results, demonstrate that our treatment had a reasonable survival outcome whereas other groups continue to have dismal prognosis. More efforts should be made to improve survival by identifying new active agents or novel approaches with cellular molecular targets.

Spontaneous regression of lung metastasis from osteosarcoma: a case report.

A case of spontaneous regression of a pulmonary metastasis from high-grade osteosarcoma is reported. The metastasis developed 5 years after chemotherapy and amputation for a distal femur osteosarcoma. The sarcomatous nature of the lesion was histologically confirmed. No treatment was attempted owing to the patient's refusal. The patient was followed up every 3 months and a spontaneous regression of the lesion was documented. Seven years after the diagnosis of lung metastases, no pulmonary nodules or other signs of relapse are present.

Local recurrence and local control of non-metastatic osteosarcoma of the extremities: a 27-year experience in a single institution.

BACKGROUND: Indications and contraindications for limb salvage versus amputation for local treatment of osteosarcoma of the extremity are still controversial. PATIENTS AND METHODS: Patients (1,126) with non-metastatic osteosarcoma of the extremity, treated in a single institution between 1972 and 1999 with different protocols of adjuvant and neoadjuvant chemotherapy were evaluated to establish factors that could influence local recurrence (LR) and outcome. RESULTS: The 5-year event-free survival and overall survival were 55% and 66%. At a follow-up ranging between 5.5 and 32.5 years (mean18.6 years) of the 1,126 evaluated patients, 607 (54%) remained continuously disease-free and 519 relapsed. LR developed in 61 patients (5.4%) after a median time of 2.3 years (0.2-17). For this group of patients the 5-year post-relapse event-free survival and overall survival from the last relapse were, respectively, 11.4% and 16.4%. At the multivariate analyses only surgical margins and histologic response to preoperative treatment resulted to be independent prognostic factors for LR. CONCLUSION: Considering the risk of LR after surgery with inadequate surgical margins and poor prognosis of LR in osteosarcoma, limb salvage procedures should be performed only when adequate margins surgical margins can be achieved. In case of inadequate margins, an immediate amputation should be considered.

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.

Ultrasonography is superior to computed tomography and magnetic resonance imaging in determining superficial resection margins of malignant chest wall tumors.

OBJECTIVE: The purpose of this study was to retrospectively analyze results obtained in 22 patients affected by malignant high-grade chest wall tumors evaluated preoperatively by ultrasonography as well as other imaging techniques. METHODS: Twenty-two patients with chest wall high-grade sarcomas routinely underwent computed tomography, magnetic resonance imaging, total body scintigraphy, and ultrasonography. Ultrasonography was always performed by the same person using an ultrasonography system with a 5- to 13-MHz probe and with color Doppler evaluation of the lesion. Scans were done with the patient positioned as during surgery. Tumor lateral margins were identified, and a line was marked at 4 cm. In 8 patients with local recurrence, the presence of micronodules was also studied. Results of computed tomography, magnetic resonance imaging, and ultrasonography were compared with the surgical specimens. RESULTS: Histologically, all surgical specimens excised according to ultrasonographic margins showed wide margins. Ultrasonography showed micronodules in 6 of 8 patients with local recurrence; histologically, they were all identified as sarcoma nodules. Ultrasonography failed in particular with cervical-mediastinal vessels. CONCLUSIONS: Our results confirm that ultrasonography is feasible and reliable in the study of superficial margins and for detection of micronodules of less than 0.5 cm in diameter.

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).

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.

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.

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.

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.

Bone metastases in osteosarcoma patients treated with neoadjuvant or adjuvant chemotherapy: the Rizzoli experience in 52 patients.

INTRODUCTION: There have been no large-scale studies reporting the outcome of patients with osteosarcoma who first relapse with bone metastases, but there have been several case reports describing a much poorer prognosis for these patients than for those who relapse with lung metastases. METHODS: We compared 52 patients with skeletal metastases as first relapse after neoadjuvant or adjuvant treatment for osteosarcoma of the extremity given at our institution between 1972 and 1999 with 371 contemporary patients treated with the same chemotherapy protocols, who first relapsed with lung metastases. RESULTS: We found that the 52 patients with bone metastases had a higher rate of local recurrences (36% vs. 6%), a lower rate of remission (35% vs. 77%), and lower rates of 5-year event-free survival (11% vs. 27%) and overall survival (13% vs. 31%) (p < 0.01 for all comparisons). INTERPRETATION: The prognosis of patients who relapse with bone metastases--unless they have a single late-appearing metastasis--is worse than the prognosis of patients who first relapse with lung metastases. There was no difference in outcome between patients with single, resectable and late-appearing skeletal metastases and patients relapsing in the lung.

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.

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.

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.

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.

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.