Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma.

BACKGROUND: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. PATIENTS AND METHODS: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. RESULTS: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). CONCLUSIONS: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distress.

Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study.

BACKGROUND: Relapsed or refractory diffuse large B-cell and mantle-cell lymphoma have a poor prognosis. The EPOCH regimen and rituximab monotherapy have demonstrated activity as salvage therapies. Because of their non-overlapping toxicity, we evaluated their combination as salvage therapy in a phase II study. PATIENTS AND METHODS: Patients with relapsed or refractory CD20-positive large B-cell and mantle-cell lymphoma were offered treatment with rituximab 375 mg/m2 intravenously (i.v.) on day 1, doxorubicin 15 mg/m2 as a continuous i.v. infusion on days 2-4, etoposide 65 mg/m2 as a continuous i.v. infusion on days 2-4, vincristine 0.5 mg as a continuous i.v. infusion on days 2-4, cyclophosphamide 750 mg/m2 i.v. on day 5 and prednisone 60 mg/m2 orally on days 1-14. RESULTS: Fifty patients, with a median age of 56 years (range 23-72), entered the study. Twenty-five had primary diffuse large B-cell lymphoma, 18 transformed large B-cell lymphoma and seven mantle-cell lymphoma. The median number of prior chemotherapy regimens was 1.7 (range one to four). The median number of treatment cycles was four (range one to six). Possible treatment-related death occurred in two patients. Objective responses were obtained in 68% of patients (28% complete responses, 40% partial responses). Nineteen patients received consolidating high-dose chemotherapy with autologous stem-cell transplantation. The median follow-up was 33 months. Three patients developed a secondary myelodysplastic syndrome. The median overall survival was 17.9 months; the projected overall survival at 1, 2 and 3 years was 66, 42 and 35%, respectively. The median event-free survival was 11.8 months; the projected event-free survival at 1, 2 and 3 years was 50, 30 and 26%, respectively. CONCLUSION: The rituximab-EPOCH regimen is effective and well tolerated, even in extensively pretreated patients with relapsed or refractory large B-cell lymphoma and mantle-cell lymphoma.

The relative costs of proton and X-ray radiation therapy.

AIM: To study the costs of intensity-modulated proton therapy and intensity-modulated X-ray therapy with the particular goal of understanding their relative differences. To analyse the ratio of the cost per fraction of proton therapy to the cost per fraction of X-ray therapy. MATERIALS AND METHODS: We have used a computer spreadsheet tool in which a large number (typically 130) of input parameters characterizing a particular therapeutic modality can be stored. From these parameters a number of derived variables are computed, and from these derived variables the costs of sub-systems, the entire facility, running costs and cost per fraction and per treatment can be computed. The sensitivity of any given variable (e.g. cost/fraction) to any given parameter (e.g. set-up time) can be explored, together with an estimate of the associated confidence interval. The costs of facility construction and facility operation are considered separately. Key data for the input variables regarding the cost of the therapy equipment (a dominant cost for proton beam therapy) were provided by four commercial vendors. Other costs, such as costs for building construction and shielding or personnel costs, are much more standard and our estimates were primarily based on practical experience. We considered two scenarios: (1) both facilities operating under current conditions; and (2) future facilities where foreseeable improvements in efficiency and a 25% reduction in the cost of the proton equipment were assumed. RESULTS: The construction cost of a current two-gantry proton facility, complete with the equipment, was estimated at 62,500 kEE and of a two-linac X-ray facility at 16,800 kEE. In the case of proton therapy the cost of operation of the facility was found to be dominated, by the business cost (42%--primarily the cost of repaying the presumed loan for facility construction), personnel costs (28%) and the cost of servicing the equipment (21%). For X-ray therapy, the cost of operation was seen to be dominated by the personnel cost (51%) and the business costs (28%). The costs per fraction were estimated to be 1.025 kEE for protons and 0.425 kEE for X-rays--for a ratio of costs of 2.4 +/- 0.35 (85% confidence). In a future facility these costs could be reduced to 0.65 kEE and 0.31 kEE respectively, leading to a ratio of costs of 2.1. A number of further improvements could be imagined which could reduce the ratio of costs by some 20%. If, however, the initial capital investment were 'forgiven,' so that the operating costs need not repay the investment, both the costs and the ratio of costs would be significantly less. We estimate that, under this condition, the future costs of proton and X-ray therapies would be 0.37 kEE and 0.23 kEE, respectively, for a cost-per-fraction ratio of 1.6. This ratio could also be susceptible to a further 20% reduction. CONCLUSIONS: Sophisticated (i.e., intensity-modulated) proton therapy is now, and is likely to continue to be, more expensive than sophisticated (i.e., intensity-modulated) X-ray therapy. The ratio of costs is about 2.4 at present and could readily come down to 2.1, and even, perhaps 1.7 over the next 5 to 10 years. If recovery of the initial investment is not required, the ratio of costs would be much lower, in the range of 1.6 to 1.3. The question of whether the greater cost of proton beam therapy is clinically worthwhile is a cost-effectiveness issue. The goal of this study is to contribute to the former arm of this comparison.

Fusion PET-CT imaging of neurolymphomatosis.

In a patient suffering from peripheral neuropathy due to neurolymphomatosis, fused PET-CT imaging, performed on a novel in-line PET-CT system, showed multiple small nodular lesions extending along the peripheral nerves corresponding to an early relapse of a transformed B-cell non-Hodgkin's lymphoma.

[Descending paralysis caused by wound botulism. A case report]. / Deszendierende Lähmung durch Wundbotulismus. Eine Falldarstellung.

We report on the history and clinical findings of an injecting drug abuser in the Canton of Zurich who presented with multiple deep abscesses in the arms and legs. A diagnosis of wound botulism was made based on his clinical presentation with a rapidly progressing descending paralysis starting at the cranial nerves, a neuromuscular junction disorder on neurophysiologic testing, and normal findings on lumbar puncture. Several cases of wound botulism have occurred in i.v. drug abuse in Switzerland since 1997. We suspect subcutaneous injections of contaminated heroin containing Clostridium spores as sites of entry. Wound botulism caused by Clostridium botulinum is a rare cause of rapidly progressing, generalized, flaccid paralysis and should be considered in patients with a history of i.v. drug abuse presenting with descending paralysis.