Felix Kovner

Long-term follow-up in managing anaplastic astrocytoma by multimodality approach with surgery followed by postoperative radiotherapy and PCV-chemotherapy: phase II trial.

Overall survival and progression-free survival after 5 and 10 years of 31 patients with malignant glioma treated by a combination of surgery, postoperative radiotherapy, and chemotherapy with a PCV regimen (procarbazine, CCNU [lomustine] and vincristine) is described. Parameters were evaluated by age at diagnosis, gender, ethnic origin, pre- and postsurgery Karnofsky Performance Status (KPS) score, limit and amount of surgical resection, histopathologic type, number of chemotherapy courses, time between surgery and radiotherapy, response to combined therapy, and dosage and type of radiotherapy. Progression-free survival was 29% at 24 months and 22% at 60 and 120 months. Overall survival was 47%, 36%, and 36% after 24, 60, and 120 months, respectively. Favorable prognostic factors for survival in univariate analysis were pre- and postoperative KPS (≥70;p = 0.015;p = 0.0025, respectively), age of patients (<40;p = 0.01), number of chemotherapy cycles (≥6;p = 0.02), and radiation dose (≥60 Gy;p = 0.0015). The only significant prognostic factors for overall survival in a stepwise multivariate analysis were irradiation dose (p = 0.0001), number of chemotherapy cycles (p = 0.001), and preoperative KPS (p = 0.05); for progression-free survival it was number of chemotherapy cycles (p = 0.004). Survival was not affected by excision size, radiation method, histopathologic type of tumor, gender, ethnic origin, or time lapsed between surgery and irradiation.

Neoadjuvant treatment with paclitaxel and epirubicin in invasive breast cancer : A phase II study

AbstractBackground and objectives: The modern management of locally advanced breast cancer includes a multimodal approach consisting of neoadjuvant chemotherapy (usually given as initial treatment), surgery, radiotherapy and adjuvant hormone therapy. This therapeutic approach converts many patients with initially unresectable disease to reasonable surgical candidates, with acceptable rates of loco-regional disease control. Induction of a pathological complete response (pCR) with modern chemotherapy agents or combined with immunotherapy, when applicable, should be one of the primary goals of neoadjuvant therapy in order to achieve better disease-free and overall survival in this subset of patients. Neoadjuvant chemotherapy is now standard for patients with locally advanced breast cancer, and this method of treatment has been extended to patients with earlier disease without affecting the treatment outcome. The objectives of this study were: (1) to conduct a phase II study to assess the efficacy and availability of epirubicin and paclitaxel in the neoadjuvant setting in women with locally advanced or high tumour-to-breast ratio breast cancer (no patient in either of these subgroups was a candidate for breast-conserving surgery prior to chemotherapy); (2) to evaluate the incidence of clinically relevant toxicity and, in particular, cardiac toxicity after treatment with an epirubicin + paclitaxel regimen in this group of patients. Methods: In this open-label, phase II, single-centre trial carried out in a university-affiliated tertiary-care municipal hospital, the rate of objective response, evaluated by clinical and pathological examinations, was the primary endpoint of the study. Other endpoints were the rates of breast-conserving surgery, local recurrence, disease-free survival and overall survival. Sixty patients were enrolled from September 1998 to September 2003 with a median follow-up of 56 months (range 16–96). All 60 women met the criteria for inclusion and agreed to participate in the study. They were diagnosed as having locally advanced or high tumour-to-breast ratio breast cancer that did not initially permit breast-conserving surgery. Epirubicin 75 mg/m2 and paclitaxel 175 or 200 mg/m2 were administered for five courses. Rates of adverse events were also analysed. Results: Eight patients experienced a pCR, five had a pathological partial response with an almost complete pathological response, and 39 were able to undergo breast-conserving surgery. Adverse effects were mostly of grade 1 or 2 severity. The most common adverse reactions were fatigue and neutropenic fever. One patient developed local recurrence during the median 56-month follow-up. Among examined biological markers, only estrogen receptor negativity was a strong predictor of a pCR. The rates of disease-free and overall survival following the neoadjuvant combination were similar for those who had tumours positive for the estrogen receptor and those who were negative for this. Conclusion: Treatment with a combination of epirubicin and paclitaxel enabled lumpectomy in a substantial proportion of women who were previously deemed to not be suitable candidates for breast-conserving surgery. Clinical responses were not influenced by the initial tumour volume, and the only statistically significant predictor of pCR was the estrogen receptor status of the tumour.

The correlation between palliation of bone pain by intravenous strontium-89 and external beam radiation to linked field in patients with osteoblastic bone metastases.

We studied the correlation between the efficacy of local external beam radiotherapy and the efficacy of strontium-89 in the palliation of osteoblastic metastatic bone pain in 43 patients with cancer. All 43 had been treated with hormonal or chemotherapy according to the primary malignancies and analgetic pharmacotherapy as needed, 36 received local external beam radiotherapy as a palliative before strontium-89 injection, and all 43 were ultimately treated with strontium-89 as salvage therapy. Responses to the first strontium treatment, and to the first radiation treatment if given, were taken from patient files. Pain was evaluated by Karnofsky performance status, analgesic dosage, and duration of response to treatment translated into numeric scores on a pain duration scale and an integrated response scale. The efficacy of limited field external radiation in metastatic bone pain palliation was 80.6% versus 58.1% for strontium-89. Patients treated with both external radiation and strontium had a positive correlation of 0.4 with a probability of P = 0.0158 between the responses to the 2 treatments, indicating that response to external radiotherapy could be viewed as an indicator of strontium-89 efficacy in metastatic osteoblastic bone pain palliation in the same patient. No significant correlation was found between strontium efficacy and gender, location of metastases to weight-bearing bones, duration of hormonal therapy or chemotherapy, or type of primary neoplasm.

Primary Liposarcoma of the Mediastinum

Patient. A 62-year-old man presented with effort dyspnea, non-productive cough and weakness of 4 month duration. He had no findings on physical examination. Discussion. Chest X-ray revealed a large mass in the left anterior mediastinum. Computerized tomography of the chest showed a well-delineated homogeneous mediastinal mass with fat-equivalent density and a small pleural effusion. Fiberoptic bronchoscopy revealed narrowing of the left main bronchus, secondary to external compression. The bronchial mucosa was normal and brush cytology was negative. A CT-guided fine needle aspiration (FNA) of the mass yielded fragments of cells embedded in myxoid background material and closely packed atypical lipoblasts, compatible with liposarcoma. The patient underwent a left lateral thoracotomy and margibnal resection of the mass. The histopathological examination confirmed the diagnosis of mixed-type liposarcoma, consisted of myxoid and pleomorphic liposarcoma. Postoperative two-field radiation therapy was delivered to the mediastinum for a total midplane dose of 40 Gy. After a disease-free interval of 8 months the disease recurred in the mediastinum and pleura. Palliative chemotherapy achieved a short duration partial response but the patient succumbed to local recurrence 2 years after the diagnosis.

Metastatic disease of the cavernous sinus: contribution of computed tomography and magnetic resonance imaging to diagnosis.

The clinical presentation of metastatic disease to the cavernous sinus includes ophthalmoplegia, pain and sensory deficit along the optic or maxillary branches of the trigeminal nerve. The role of a CT scan and magnetic resonance imaging in the diagnosis is discussed. It was found that magnetic resonance imaging is superior to CT scan in demonstrating the cavernous sinus and pontine borders, especially in lymphomatous involvement of these structures.

Progesterone receptor status and tumor size as possible indicators of axillary lymph node involvement in T1 carcinoma of the breast.

Disagreement persists on the necessity of axillary lymph node dissection for small T1 stage unilateral breast cancers. In this study of 120 women with T1 primary tumors who underwent extensive dissection, better definition of pathological factors that can predict axillary node metastases might have spared 88 (73.3%) who were node negative. We assessed age, tumor size, histology, grade and hormone receptor status as possible indicators of lymph node involvement. As expected, tumor size was a strong predictor of the likelihood of node involvement (p = 0.026 in univariate and p = 0.0024 in multivariate analyses). Progesterone receptor status also correlated significantly (p = 0.0008 in univariate and p = 0.017 in multivariate analyses) with axillary positivity. Tumor grade was found to be significant (p 0.018) only in univariate analysis. These findings contribute to the ongoing search for confident selection of subgroups of patients who will undergo lumpectomy but can safely be spared axillary node dissection.Disagreement persists on the necessity of axillary lymph node dissection for small T1 stage unilateral breast cancers. In this study of 120 women with T1 primary tumors who underwent extensive dissection, better definition of pathological factors that can predict axillary node metastases might have spared 88 (73.3%) who were node negative. We assessed age, tumor size, histology, grade and hormone receptor status as possible indicators of lymph node involvement. As expected, tumor size was a strong predictor of the likelihood of node involvement (p = 0.026 in univariate and p = 0.0024 in multivariate analyses). Progesterone receptor status also correlated significantly (p = 0.0008 in univariate and p = 0.017 in multivariate analyses) with axillary positivity. Tumor grade was found to be significant (p = 0.018) only in univariate analysis. These findings contribute to the ongoing search for confident selection of subgroups of patients who will undergo lumpectomy but can safely be spared axillary node dissection.