Carboplatin and paclitaxol (Taxol) as an induction regimen for patients with biopsy-proven stage IIIA N2 non-small cell lung cancer. an EORTC phase II study (EORTC 08958).

The aim of this study was to document the activity and toxicity of paclitaxel (Taxol)/carboplatin when used as induction chemotherapy in patients with stage IIIA N2 non-small cell lung cancer (NSCLC) prior to definitive local treatment within a large, ongoing comparative study (EORTC 08941). 52 eligible, consenting, chemotherapy-naïve patients with NSCLC, median age of 60 years, stage IIIA N2 disease and the ability to tolerate a pneumonectomy received paclitaxel 200 mg/m2 as a 3-h infusion followed by carboplatin at an area under the concentration curve (AUC) of 6 every 3 weeks for three courses. Most patients received three courses. No grade 3/4 anaemia or thrombocytopenia was documented. Over all of the cycles, 6% (3 patients) experienced grade 3 leucopenia while 63% (32/51 patients) experienced grade 3-4 neutropenia. There was 1 patient (2%) with febrile neutropenia, no early or toxic deaths and no hypersensitivity reactions. Severe non-haematological toxicity was uncommon, with the exception of grade 3 alopecia in 39%, lethargy in 8% and myalgia in 6%. Of the eligible patients (n=52), there was one complete response (CR) and 32 partial responses (PR), resulting in a response rate of 64% (95% Confidence Interval (CI) 49%-76%). Of the 15 eligible patients randomised to surgery after induction chemotherapy, 3 patients did not receive surgery and 2 patients (n=12) had no tumour in the mediastinal nodes (17%). Resections were considered complete in 2 of the 12. Median survival for all eligible patients (n=52) was 20.5 months (95% CI 16.1-31.2), with an estimated 1-year survival rate of 68.5% (95% CI 55.2-81.7). In patients with N2 stage IIIA NSCLC, paclitaxel/carboplatin is an active and very well-tolerated induction regimen.

The activity of raltitrexed (Tomudex) in malignant pleural mesothelioma: an EORTC phase II study (08992).

We investigated the activity and toxicity of raltitrexed (Tomudex) as a single agent treatment in patients with Malignant Pleural Mesothelioma (MPM) in a multicentre phase II European Organization for Research and Treatment of Cancer (EORTC) study. This study enrolled chemonaíve patients with histologically-confirmed measurable MPM. Raltitrexed was administered at the dose of 3 mg/m(2) intravenous (i.v.) bolus on an outpatient basis every 3 weeks. A maximum of eight cycles was planned in cases with an absence of progression or unacceptable toxicity. 24 patients received a total of 104 courses. 5 patients (20.8%, 95% confidence interval (CI) 7.1-42.2%) had a partial response (PR), which was confirmed by an independent radiology committee. Toxicity was mild, with diarrhoea, nausea, vomiting, fatigue and neutropenia as the major side-effects, but not exceeding grade 3 toxicity. We conclude that raltitrexed has activity as a single agent in the treatment of MPM, and that further studies with this drug in MPM are warranted.

Intermediate grade osteosarcoma and chondrosarcoma arising in an osteochondroma. A case report of a patient with hereditary multiple exostoses.

A 40 year old man with hereditary multiple exostoses (HME), affecting predominantly his left proximal tibia, distal femur, and proximal femur, underwent resection of an osteochondroma near the trochanter major of his left proximal femur because of malignant transformation of the cartilaginous cap towards secondary peripheral chondrosarcoma. The patient had a history of a papillary thyroid carcinoma four years previously. At examination of the resected specimen, a third malignant tumour, an intermediate grade osteosarcoma (grade II/IV), was found in the osseous stalk of the osteochondroma. Although no mutations were found in the EXT1 and EXT2 genes, the genes involved in HME, or in exons 5-8 of the p53 gene, the development of three malignancies before the age of 40 suggests that this patient is genetically prone to malignant transformation.

Cartilaginous tumors: fast contrast-enhanced MR imaging.

PURPOSE: To differentiate between benign and malignant cartilaginous tumors with fast contrast material-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: In 37 patients, fast contrast-enhanced MR images were obtained in eight enchondromas, 11 osteochondromas, and 18 chondrosarcomas. Start of enhancement-early, within 10 seconds after arterial enhancement; delayed, between 10 seconds and 2 minutes; late, after 5 minutes on spin-echo images-and progression of enhancement were represented with three types of time-signal intensity curves. Findings were correlated with the surgical specimen in 27 cases, curettage material in three cases, and biopsy combined with long-term follow-up findings in seven cases. RESULTS: Start of enhancement and the combination of start and progression of enhancement correlated significantly (P <.001) with benign and malignant tumors. Early enhancement was seen in chondrosarcoma, not seen in enchondroma, and seen in osteochondroma only when growth plates were unfused. The sensitivity was 89%, specificity 84%, positive predictive value 84%, and negative predictive value 89%. Differentiation of malignancy from benignity on the basis of early and exponential enhancement was possible with a sensitivity of 61%, specificity 95%, positive predictive value 92%, and negative predictive value 72%. CONCLUSION: Preliminary results show that in the adult population fast contrast-enhanced MR imaging may assist in differentiation between benign and malignant cartilaginous tumors.

Bone tumors.

We present an overview of the imaging modalities in bone tumors. The imaging strategies of preoperative work-up, monitoring the effect of chemotherapy and the detection of recurrences by long-term follow-up are discussed.

[Malignant cartilage tumors]. / Maligne Knorpeltumoren.

Malignant cartilaginous tumors (chondrosarcomas) are, with a relative frequency of 20%, the second most common malignant tumors of bone after osteosarcoma. The diagnosis of chondrosarcoma can usually be made confidently based on combination of clinical information, radiographs, Gd-enhanced MR imaging, and histologic examination of a biopsy sample. The combination of these parameters is important because accuracy of histologic diagnosis is adversely affected by unrepresentative sampling of these usually large tumors. The prognosis of patients with chondrosarcoma becomes poorer with more axial location, higher histologic grade, larger tumor size and inadequate resection. By careful analysis of radiographs and Gd-enhanced MR imaging the radiologist has the ability to improve the management of patients with chondrosarcoma.

Chondroblastic osteosarcoma: characterisation by gadolinium-enhanced MR imaging correlated with histopathology.

OBJECTIVE: To identify specific features of chondroblastic osteosarcoma on gadopentetate dimeglumine (Gd)-enhanced magnetic resonance (MR) imaging. DESIGN AND PATIENTS: Nine patients with chondroblastic osteosarcoma and a control group of 20 patients with conventional central osteosarcoma were included in this study. The histopathological findings of the surgical specimens were compared with enhancement patterns on static Gd-enhanced MR images. RESULTS: In chondroblastic osteosarcoma septonodular and peripheral rim enhancement represented tumour with a pure chondroid matrix. Non-enhancing and heterogeneous enhancing areas represented tumour with both chondroid and osteoid matrix. In the tumours in the control group enhancement was predominantly heterogeneous but in one it was homogeneous. All these areas corresponded to necrotic or viable osteoid tumour tissue or fibrovascular tissue in areas of necrosis. CONCLUSION: Gd-enhanced MR imaging can assist in obtaining diagnostic biopsy material of chondroblastic osteosarcoma by identifying both osteoid- and chondroid-forming areas.

Usefulness of radiography in differentiating enchondroma from central grade 1 chondrosarcoma.

OBJECTIVE: The purpose of this study was to evaluate clinical symptoms and radiographic features that allow radiologists to differentiate between enchondroma and central grade 1 chondrosarcoma. Such differentiation is important because of differences in management. MATERIALS AND METHODS: Clinical symptoms and location and size of 35 enchondromas and 43 central grade 1 chondrosarcomas were analyzed. Radiographic features were assessed independently by three observers. The chi-square test and linear discriminant analysis were used to identify features with discriminating strength. Kappa values were calculated to validate the consistency of observations among observers. A consensus diagnosis made by histology and long-term follow-up was used as the standard. RESULTS: No statistically significant correlation was found between clinical symptoms and the benign or malignant nature of the neoplasms. Grade 1 chondrosarcomas were more likely to be found in the axial skeleton and in flat bones. Also, chondrosarcomas were significantly larger than enchondromas (p < .001). Ill-defined margins and lobulated contours were the only morphologic features seen on radiographs that allowed significant discrimination (p = .004 and .009, respectively). An optimal combination of four radiographic features still left 72 of the 78 lesions with a 10-90% probability of malignancy, indicative of poor discriminating power. Kappa values generally showed poor to fair agreement. CONCLUSION: Location in the axial skeleton and size greater than 5 cm are the most reliable predictors of central grade 1 chondrosarcoma. Morphologic features seen on radiographs and clinical symptoms do not improve the ability to differentiate between enchondromas and central grade 1 chondrosarcomas.

Tumoral calcinosis.

A patient with tumoral calcinosis involving the buttock and ischial bone is presented. Bone marrow involvement and a pattern of septal enhancement on MR imaging after intravenous administration of Gd-DTPA were very suggestive of a diagnosis of a chondro(sarco) matous musculoskeletal tumor. The absence of an underlying metabolic disorder, the appreciation of fluid-calcium levels within the lesion and knowledge of the macroscopic and microscopic appearance of this disorder have led to the correct diagnosis in this case.

Cartilaginous tumors: correlation of gadolinium-enhanced MR imaging and histopathologic findings.

Gadolinium-enhanced magnetic resonance (MR) images were correlated with histopathologic findings in patients with cartilaginous tumors. Short repetition time/echo time spin-echo MR images obtained before and after intravenous administration of gadopentetate dimeglumine in 34 patients were evaluated. Twenty-four of 27 low-grade chondrosarcomas showed septal enhancement. The enhancing curvilinear speta consisted of fibrovascular tissue. The nonehancing areas consisted of paucicellular hyaline cartilage, cystic mucoid tissue, and necrosis. This enhancement pattern and corresponding histopathologic findings were not seen in three benign osteochondromas or four high-grade chondrosarcomas. Inhomogeneous or homogeneous enhancement correlating with highly cellular areas at histopathologic analysis was seen in all high-grade chondrosarcomas. The three osteochondromas showed peripheral enhancement that correlated with fibrovascular tissue covering the non-enhancing cartilage cap. The authors conclude that septal enhancement on MR images after intravenous administration of gadopentetate dimeglumine improves tissue characterization of cartilaginous tumors and may assist in identifying low-grade chondrosarcoma.