Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials.

BACKGROUND: The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT. PATIENTS AND METHODS: Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor. RESULTS: A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40 years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms. CONCLUSION: Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.

Immunoscintigraphy of ovarian cancer with indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody.

The safety and diagnostic accuracy of immunoscintigraphy with the indium-111-labeled monoclonal antibody OV-TL 3 F(ab')2(111In-OV-TL 3 F(ab')2) for diagnosis and follow-up of ovarian cancer was prospectively studied in 31 patients. Planar and SPECT scintigraphy were performed up to 4 days after i.v. injection of 140 MBq 111In-OV-TL 3 F(ab')2. Surgical evaluation was possible in 22 out of 31 patients. Imaging results were compared with X-ray computed tomography, ultrasound, and CA 125 serum level using the histologically confirmed surgical findings as a "gold standard." Apart from a transient rash observed in two patients, no other immediate or delayed adverse reactions were observed. Within the surgically evaluated group, ovarian cancer lesions were detected in 16 out of 17 patients (94%). Of 45 distinct tumor deposits found at operation, 67% were detected and localized with immunoscintigraphy while X-ray computed tomography and ultrasound visualized 53% and 23%, respectively.

Manikin and cochlear implant patient test results with a portable adaptive beamforming processor to suppress the effects of noise.

A simple adaptive beamformer (ABF) was implemented in a real-time portable speech processor and tested with four cochlear implant patients. The ABF algorithm used signals from only two microphones--one behind each ear--to attenuate sounds not arriving from the direction directly in front of the patient, and was compared with a strategy in which the two microphone signals were simply added together (two-microphone broadside strategy). Tests with the four patients were conducted in quiet and in noise. Results at a 0 dB signal-to-noise ratio showed large improvements in speech intelligibility for all patients, when compared to the two-microphone broadside strategy. Physical measurement of the directional characteristics of the ABF processor were made with a Kemar manikin. The effects of reverberation were explored by placing the manikin in different acoustic environments and observing the attenuation of the noise alone at various angles. A near-anechoic environment allowed the noise to be attenuated by as much as 21 dB, whereas in a highly reverberant concrete stairwell, the ABF processor was unable to provide any directional gain beyond about 3 dB.

Fusion and lateralization study with two binaural cochlear implant patients.

Psychophysical studies have been completed with two binaural cochlear implant patients. Results from a fusion and lateralization experiment with both patients are described. As found in an earlier study with the first binaural patient in Australia, the second patient also showed good sensitivity to interaural amplitude differences but poor sensitivity to interaural time delays when compared with normal-hearing subjects. The implications of this result are discussed.

Comparing cisplatin-based combination chemotherapy with EMA/CO chemotherapy for the treatment of high risk gestational trophoblastic neoplasia.

BACKGROUND: Cisplatin-based chemotherapy (etoposide 100 mg/m(2) days 1-5, methotrexate 300 mg/m(2) day 1, cyclophosphamide 600 mg/m(2) day 1, actinomycin D 0.6 mg/m(2) day 2 and cisplatin 60 mg/m(2) day 4, EMACP) was compared to EMA/CO (etoposide 100 mg/m(2) days 1-2, methotrexate 300 mg/m(2) day 1 and actinomycin D 0.5 mg i.v. bolus day 1 and 0.5 mg/m(2) day 2, alternating with cyclophosphamide 600 mg/m(2) day 8 and vincristine 1 mg/m(2) day 8) for the treatment of high-risk gestational trophoblastic neoplasia (GTN). PATIENTS AND METHODS: In the Netherlands, 83 patients were treated with EMACP and 103 patients with EMA/CO. Outcome measures were remission rate, median number of courses to achieve normal human chorionic gonadotrophin (hCG) concentrations, toxicity, recurrent disease rate and disease specific survival. RESULTS: Remission rates were similar (EMACP 91.6%, EMA/CO 85.4%). The median number of courses of EMA/CO to reach hCG normalisation for single-agent resistant disease and primary high-risk disease was three and five courses, respectively, compared to 1.5 (p=0.001) and three (p<0.001) courses of EMACP. Patients treated with EMACP more often developed fever, renal toxicity, nausea and diarrhoea compared to patients treated with EMA/CO. Patients treated with EMA/CO more often had anaemia, neuropathy and hepatotoxicity. CONCLUSION: EMACP combination chemotherapy is an effective treatment for high-risk GTN, with a remission rate comparable to EMA/CO. However, the difference in duration of treatment is only slightly shorter with EMACP. Cisplatin-based chemotherapy in the form of EMACP in this study was not proven more effective than EMA/CO.

Evaluation of a portable two-microphone adaptive beamforming speech processor with cochlear implant patients.

A two-microphone noise reduction technique was tested with four cochlear implant patients. The noise reduction technique, known as adaptive beamforming (ABF), used signals from only two microphones--one behind each ear--to attenuate sounds not arriving from the direction directly in front of the patient. The algorithm was implemented in a portable digital signal processor, and was compared with a strategy in which the two microphone signals were simply added together (two-microphone broadside strategy). Tests with the four patients were conducted in a soundproof booth with target speech arriving from in front of the patient and multitalker babble noise arriving at 90 deg to the left. Results at 0-dB signal-to-noise level (S/N) showed large improvements in speech intelligibility for all patients, when compared to the two-microphone broadside strategy. Precautions were taken to avoid cancellation of the target speech, and, accordingly, subjective tests showed no deterioration in performance for the adaptive beamformer in quiet. Physical measurement of the directional characteristics of the ABF was made with the microphones placed behind the ears of a KEMAR manikin and in the same acoustic environment as used with the patients. Results showed directional gain of approximately 10 dB when the angle of incidence for interfering noise was shifted more than 20 to 30 deg from directly in front of or behind the manikin.(ABSTRACT TRUNCATED AT 250 WORDS)

Psychophysical studies with two binaural cochlear implant subjects.

Psychophysical studies have been completed with two binaural cochlear implant patients. In our earlier studies [van Hoesel et al., J. Acoust. Soc. Am. 94, 3187-3189 (1993); R. J. M. van Hoesel and G. M. Clark, Ann. Otol. Rhinol. Laryngol. Suppl. 106 104, 233-235 (1995)], lateralization experiments showed good sensitivity to interaural amplitudes but poor sensitivity to interaural time delays when compared with normal hearing subjects. In the studies presented here, both temporal and binaural intensity interactions were further explored. Interaural time delay (ITD) perception was investigated using direct measurement of the just-noticeable difference (jnd) in ITD. Both rate and place of stimulation were varied. Binaural rate discrimination was measured and compared with monaural rate perception. Binaural intensity interaction was explored for matched and unmatched place conditions by means of loudness summation and central masking studies. Results showed that ITDs for interaural time delays were large when compared to normal hearing, even when place of stimulation on each of the two sides was carefully matched. The jnds in ITD were similar for stimulation rates from 50 to 200 pps, and increased at 300 pps. Rate difference limens experiments showed similar results for diotic and monaural stimuli, but improved jnds for dichotic presentation at stimulation rates below 150-200 pps. Binaural intensity interactions showed loudness summation effects with both patients, for matched as well as unmatched place conditions. Central masking was also observed with both subjects, although it was not found to be place dependent.

Psychophysical and speech perception studies: a case report on a binaural cochlear implant subject.

Further improvements in speech perception for cochlear implant patients in quiet and in noise should be possible with speech processing strategies using binaural implants. For this reason, presented here is a series of initial psychophysical and speech perception studies on the authors' first binaural cochlear implant patient. For an approximate matching of the places of stimulation on the two sides, the patient usually reported a single percept when the two sides were simultaneously stimulated. Lateralization was strongly influenced by amplitude differences between the electrical stimuli on the two sides, but only weakly by interaural time delays. Speech testing, comparing monaural with binaural electrical stimulation, showed a binaural advantage particularly in noise.

Ewing's sarcoma of bone: oncologic and functional results.

This paper describes 29 patients with Ewing's sarcoma of bone treated between 1975 and 1990 at the University of Nijmegen Hospital, Nijmegen, The Netherlands. Osteomyelitis was the primary diagnosis in 24%. Treatment consisted of chemotherapy in combination with surgery and/or radiotherapy. Nine patients received radiotherapy only; five of them died of disease. Five patients underwent an intralesional excision; four of them died of disease. Twelve patients underwent a wide excision; there is no evidence of disease in any of them. Three patients underwent a radical disarticulation; all died of disease. The disease-free survival at 1.5 years was 66%. This figure at 5 years was 55%. After wide excision and reconstruction in tumors of expendable, femoral or radial bones good functional results were obtained in all cases.