M. A. Nooy

The treatment of advanced ovarian carcinoma (I): Clinical variables associated with prognosis

New therapy regimens including cytoreductive surgery and cisplatin-based combination chemotherapy have improved survival for a small group of patients with advanced ovarian carcinoma. However, for the entire group survival remains poor. In this analysis of 65 patients treated at Leiden University Medical Center, the patient group that benefited the most from this approach was characterized by a younger age, good performance status, less extensive disease, low histologic grade and the absence of peritoneal carcinomatosis and ascites, and residual disease less than or equal to 15 mm (successful cytoreduction) after the first operation. Patients who did not have these favorable characteristics but in whom the first operation resulted in residual disease less than or equal to 15 mm, did survive worse than the other patients with individual tumor nodules less than or equal to 15 mm, but still better than those in whom a successful cytoreduction at the first operation could not be achieved. The diameter of the largest residual disease, the diameter of the largest metastasis before cytoreduction, and the presence of ascites and peritoneal carcinomatosis influenced prognosis. Thus the initial tumor burden as well as the burdened tumor volume left behind are of significance with respect to prognosis. However, in the Cox regression analysis the performance status and ascites proved to be the only independent factors influencing survival. A prospective study is needed to establish the proper value of cytoreductive surgery in advanced ovarian carcinoma.

Monitoring the effect of chemotherapy in Ewing's sarcoma of bone with MR imaging

Magnetic resonance (MR) imaging was performed in 26 patients with Ewings sarcoma of bone preceding and following neoadjuvant chemotherapy, to assess tumour response non-invasively prior to surgery. T1- and T2-weighted spin echo images were obtained. Changes including intra- and extramedullary signal intensities, tumour demarcation, tumour volume and the appearance of residual extramedullary tumour were compared with histopathology of the resected specimens. Reduction of tumour volume was significantly higher in good responders. Other single parameters did not correlate with histologic tumour response. However, when several MR parameters summarized in a classification system were combined, a positive correlation with histopathologic response was found. A limited decrease of tumour volume (<25%) and/or residual soft tissue mass following chemotherapy correlated with a poor response. An inhomogeneous, well-defined cuff of abnormal tissue encircling the bone and/or radiological disappearance of the soft tissue tumour component following chemotherapy correlated with good response. Twenty-three out of 26 patients were correctly classified by MR as good or poor responders. Minimal residual disease (<10% of the entire tumour volume), observed histologically, could not be identified with MR imaging. Tumour volume reduction and residual extramedullary tumour, rather than changes of signal intensity, are major features for evaluating the response to chemotherapy in Ewings sarcoma.

Can conventional radiographs be used to monitor the effect of neoadjuvant chemotherapy in patients with osteogenic sarcoma

Abstract Objective. The objective of this study was to assess the effectiveness of conventional radiography in predicting histopathologic response in patients with osteogenic sarcoma who were treated with preoperative chemotherapy. Design and patients. The radiographs of 22 patients with an osteogenic sarcoma, taken before and after neoadjuvant chemotherapy, were reviewed. Tumour location, size, radiographic appearance, margination, cortical destruction and periosteal reaction were evaluated. The findings were correlated with the histopathologic response of the surgical specimen. Results. None of the findings proved to be of predictive value for the histopathologic response. Increase in tumour diameter and increase in ossification and/or calcification, which were seen in more than half of the patients, did not correlate with response. Conclusion. Conventional radiographs do not contribute to the identification of good or poor responders.

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

Abstract 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.

Classification of histopathologic changes following chemotherapy in Ewing's sarcoma of bone

A uniform classification of response to chemotherapy is essential to allow comparison of local effect and ultimate prognosis between different therapy schedules. We define a histological grading system for assessment of the response to chemotherapy in Ewings sarcoma, based on the amount and architectural pattern of residual histologically viable-appearing tumour, the preferential sites of minimal residual tumour and the amount of tumour necrosis. Twenty-six consecutive patients with a biopsy-proven Ewings sarcoma were treated with chemotherapy prior to surgery. The effect of chemotherapy was evaluated microscopically on the specimens obtained after surgery. Response to chemotherapy was classified as minimal or no effect (<10% tumour necrosis), moderate effect (solid areas of remnant viable tumour), minimal residual disease, and no evidence of disease (100% tumour necrosis or well-vascularized fibrous tissue). The subperiosteal area in particular, and, less frequently, soft tissues and intramedullary compartment were identified as sites of predilection for persistence of microscopic viable tumour foci, frequently depicted as pseudo-rosettes in a characteristic scattered pattern. Although it is not well known whether morphological viability of these residual clusters in Ewings sarcoma indicates biological viability, accurate preoperative local staging, with special attention to preferential sites of residual viable tumour, is essential. The proposed grading system can be used to standardize assessment of chemotherapy in trials, and may serve as a standard for non-invasive monitoring of preoperative chemotherapy with magnetic resonance imaging.

Mitoxantrone as first line cytotoxic therapy in advanced breast cancer: Preliminary results of a phase II study

Mitoxantrone, 14 mg/m2 repeated every 3 weeks was administered to postmenopausal patients with advanced measurable breast cancer previously untreated with cytotoxic agents. Response was achieved in 16 out of 28 (44%) evaluable patients and in four of the patients (with soft tissue disease) the response was complete. The median duration of response was 10+ months with a range from 4-12+ months. At doses which cause significant hematological toxicity other objective and subjective toxicities were remarkably mild.

Magnetic resonance relaxation times of normal tissue in the course of chemotherapy: a study in patients with bone sarcoma

To study the effect of chemotherapy on normal fat, skeletal muscle, and bone marrow, T1 and T2 relaxation times were measured in 15 patients with bone sarcoma before and after each cycle of preoperative chemotherapy. A section plane containing the tumor and if possible the nonaffected extremity was imaged with combined multiecho spin echo and inversion recovery pulse sequences. T1 and T2 relaxation times were calculated in the normal-appearing tissues. Although some variation was found in the values in the individual patient and between patients, no systematic changes of relaxation times of fat, muscle, or bone marrow occurred in the course of treatment. We conclude that the chemotherapy used in bone sarcoma has no effect on relaxation times of normal fat, muscle, and bone marrow, and that therefore these tissues may serve as a reference for the signal intensity of tumor.