High fibrinogen levels are associated with poor survival in patients with liposarcoma.

The aim of this study was to evaluate whether (preoperative) plasma levels of fibrinogen, an essential clotting and acute phase protein, are associated with the prognosis of patients with a liposarcoma, a subtype of sarcoma derived from adipose tissue. We performed a retrospective cohort study of 158 patients with liposarcoma treated at the Department of Orthopaedics of the Medical University of Vienna in Austria from May 1994 to October 2021. Kaplan-Meier curves as well as uni- and multivariable Cox proportional hazard models were performed to evaluate the association between fibrinogen levels and overall survival. Elevated fibrinogen was associated with adverse overall survival in cause specific hazards analysis of mortality (hazard ratio [HR] per 10 mg/dL increase: 1.04; 95% CI 1.02-1.06; p < 0.001). This association prevailed in multivariable analysis after adjustment for AJCC tumor stage (HR 1.03; 95% CI 1.01-1.05; p = 0.013). Increasing levels of fibrinogen, a routinely available and inexpensive parameter, predicts the risk of mortality in patients with liposarcoma.

Pulmonary metastasectomy for soft tissue sarcoma--report from a dual institution experience at the Medical University of Vienna.

BACKGROUND: Pulmonary metastasectomy when possible has become therapeutic standard in soft tissue sarcoma patients. However, published reports frequently describe mixed series of patients with bone or soft tissue sarcoma. We report the outcome of 46 soft tissue sarcoma (STS) patients who underwent pulmonary metastasectomy (PM). METHODS: This current analysis includes retrospective survival data from 46 consecutive STS patients with pulmonary metastases who underwent PM at the Medical University of Vienna between January 2003 and December 2013. RESULTS: In total 72 pulmonary metastasectomies were performed. 322 metastatic nodules were resected with a median number of four nodules per intervention and the R0 resection rate was 97.2%. The postoperative complication rate as documented was low. Median follow-up (mFU) was 31.8 months (range 3.7-127.4). Median overall survival as calculated from first detection of metastatic disease was 47.1 months (95% confidence interval (CI)=36.2-58.1 months) and 45.3 months (95% CI=33.3-57.4 months) when calculated from first PM until death or last follow-up (n=46). Five-year overall survival calculated from primary diagnosis was 62% and 32% when estimated from first PM. Previous disease free interval (DFI) as calculated from date of surgery of the primary tumour until the date of diagnosis of lung metastasis was 12.2 months (range 0-140.1 months). Median relapse-free survival (mRFS) after first PM to the date of recurrence of lung metastasis, death or last follow-up was 13.4 months (95% CI=3-23.8 months). CONCLUSION: Median overall survival in this selected patient cohort is 45.3 months. Despite the lack of prospective randomised controlled trials, PM is a reasonable treatment strategy in selected patients.

Pretreatment for bilateral nephroblastomatosis is an independent risk factor for progressive disease in patients with stage V nephroblastoma.

BACKGROUND: Treatment of stage V nephroblastoma is less established and more complex than in unilateral nephroblastoma. METHODS: Retrospective analysis of 121 consecutive patients with stage V nephroblastoma registered from January 1989 to May 2005. Registration, prospective data collection and treatment were carried out within the framework of 3 consecutive SIOP/GPOH-nephroblastoma-trials. RESULTS: 19 patients had metastasis and 29 syndromes at diagnosis. 13 patients had been pretreated for bilateral nephroblastomatosis. 1 patient was not treated and 17 patients had upfront surgery. Preoperative treatment duration ranged from 1-12 weeks (n=103). 1-3 preoperative treatment-cycles resulted in average tumor-volume-reduction of 45%. 1 patient underwent bilateral nephrectomy. 52% of the patients had 2 functioning kidneys after the end of treatment. 20 patients had died after mean follow-up of 8.6 years. 5y-Progression-Free (PFS) and Overall-Survival (OS) were excellent for patients having a localized disease without pretreatment for nephroblastomatosis (5yPFS/OS: 80±4%/93±3%). Metastasis at diagnosis (51±12%/56±12%; p=0.003) and pretreatment for nephroblastomatosis (37±14%/67±13%; p<0.001) were associated with significantly poorer outcome. Cox-regression analysis revealed an independent influence of pretreatment for nephroblastomatosis, metastasis and syndromes on PFS. The latter 2 as well as anaplasia and age (<2 years or >3 years) had an independent influence on OS. CONCLUSIONS: Pretreatment for nephroblastomatosis, metastasis and syndromes are independent risk factors. 1-3 preoperative treatment-cycles are sufficient to achieve save nephron-sparing-surgery in most patients.

Clinical signs of neurofibromatosis impact on the outcome of malignant peripheral nerve sheath tumors.

OBJECTIVE: Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of sarcoma, with a poor outcome. MPNST are regarded as being sporadic or associated with neurofibromatosis type 1 (NF1). Few comparative overall-survival (OS) data in these 2 subsets of MPNST patients exist. The aim of this retrospective study was to assess OS in sporadic and NF1-associated MPNST patients. METHODS: Fourteen consecutive patients with initial localized as well as initial metastatic MPNST were diagnosed and treated in our department. Patients with sporadic MPNST were assigned to group A and those with NF1-associated MPNST to group B. RESULTS: Eight versus 6 patients were allocated to groups A and B. Primary tumors were located on the extremities in all but 1 patient. Two patients in group A and 4 patients in group B experienced a relapse. Four patients died in each of the 2 groups. Median follow-up was 66.2 and 57.2 months in group A and group B, respectively. Median OS in group A was 46.9 months versus 12.7 months in group B. CONCLUSIONS: In this small, single-center study, sporadic-MPNST patients had a longer median OS than those with NF1-associated MPNST.

[The use of frozen sections in the handling of soft tissue tumors]. / Der intraoperative Schnellschnitt im Umgang mit Weichteiltumoren.

Due to the multiplicity of localizations and entities, handling of soft tissue tumors is a very challenging subject requiring intensive interdisciplinary collaboration. With respect to the use of intraoperative frozen sections, the following facts are of special relevance: 1) the usual criteria for malignancy, such as infiltrative growth and high mitotic rate are only restrictedly applicable to soft tissue tumors. 2) Correct diagnosis of the tumor entity often requires not only the use of immunohistochemistry but also the identification of genetic alterations by the polymerase chain reaction and/or fluorescence in situ hybridization. In many centres, 14G core biopsies taken from different tumor areas represent the preferred method for a diagnostic biopsy. Apart from cryocollection additional frozen section investigations are used especially in case of open biopsies for quality control of the submitted material or in cases of excision biopsies to ascertain a highly probable radiological diagnosis. The use of intraoperative frozen sections to clarify the resection margins is generally undisputed but should definitely be restricted to centres specialized and experienced in the handling of soft tissue tumors.

Unique mutational profile associated with a loss of TDG expression in the rectal cancer of a patient with a constitutional PMS2 deficiency.

Cells with DNA repair defects have increased genomic instability and are more likely to acquire secondary mutations that bring about cellular transformation. We describe the frequency and spectrum of somatic mutations involving several tumor suppressor genes in the rectal carcinoma of a 13-year-old girl harboring biallelic, germline mutations in the DNA mismatch repair gene PMS2. Apart from microsatellite instability, the tumor DNA contained a number of C:G→T:A or G:C→A:T transitions in CpG dinucleotides, which often result through spontaneous deamination of cytosine or 5-methylcytosine. Four DNA glycosylases, UNG2, SMUG1, MBD4 and TDG, are involved in the repair of these deamination events. We identified a heterozygous missense mutation in TDG, which was associated with TDG protein loss in the tumor. The CpGs mutated in this patient's tumor are generally methylated in normal colonic mucosa. Thus, it is highly likely that loss of TDG contributed to the supermutator phenotype and that most of the point mutations were caused by deamination of 5-methylcytosine to thymine, which remained uncorrected owing to the TDG deficiency. This case provides the first in vivo evidence of the key role of TDG in protecting the human genome against the deleterious effects of 5-methylcytosine deamination.

Sarcoma of the ewing family in pregnancy: a case report of intrauterine fetal death after induction of chemotherapy.

Ewing's sarcoma is an ultra-orphan disease (2/1,000,000/year) which requires a multimodal therapy approach in high-volume centers. Treatment consists of pre-operative therapy followed by surgery and post-operative combination of chemo-radiotherapy. Experience with diagnosis and therapy of Ewing's sarcoma in pregnancy is very limited. We herein report the case of an atypical Ewing's sarcoma detected in the second trimester of gestation. Neoadjuvant chemotherapy was initiated and resulted in substantial tumor shrinkage and intrauterine fetal death. The rare nature of this condition underlines once more the need for a multidisciplinary team to improve the quality of care for this highly special patient collective.

Automated Marsh-like classification of celiac disease in children using local texture operators.

Automated classification of duodenal texture patches with histological ground truth in case of pediatric celiac disease is proposed. The classical focus of classification in this context is a two-class problem: mucosa affected by celiac disease and unaffected duodenal tissue. We extend this focus and apply classification according to a modified Marsh scheme into four classes. In addition to other techniques used previously for classification of endoscopic imagery, we apply local binary pattern (LBP) operators and propose two new operator types, one of which adapts to the different properties of wavelet transform subbands. The achieved results are promising in that operators based on LBP turn out to achieve better results compared to many other texture classification techniques as used in earlier work. Specifically, the proposed wavelet-based LBP scheme achieved the best overall accuracy of all feature extraction techniques considered in the two-class case and was among the best in the four-class scheme. Results also show that a classification into four classes is feasible in principle however when compared to the two-class case we note that there is still room for improvement due to various reasons discussed.

Abnormalities of the upper extremities on fetal magnetic resonance imaging.

OBJECTIVE: In view of the increasing use of fetal magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography, we sought to demonstrate the visualization of upper extremity abnormalities and associated defects on MRI, with regard to fetal outcomes and compared with ultrasound imaging. METHODS: This retrospective study included 29 fetuses with upper extremity abnormalities visualized with fetal MRI following suspicious ultrasound findings and confirmed by postnatal assessment or autopsy. On a 1.5-Tesla unit, dedicated sequences were applied to image the extremities. Central nervous system (CNS) and extra-CNS anomalies were assessed to define extremity abnormalities as isolated or as complex, with associated defects. Fetal outcome was identified from medical records. MRI and ultrasound findings, when available, were compared. RESULTS: Isolated upper extremity abnormalities were found in three (10.3%) fetuses. In 26 (89.7%) fetuses complex abnormalities, including postural extremity disorders (21/26) and structural extremity abnormalities (15/26), were demonstrated. Associated defects involved: face (15/26); musculoskeletal system (14/26); thorax and cardio/pulmonary system (12/26); lower extremities (12/26); brain and skull (10/26); and abdomen (8/26). Of the 29 cases, 18 (62.1%) pregnancies were delivered and 11 (37.9%) were terminated. MRI and US findings were compared in 27/29 cases: the diagnosis was concordant in 14 (51.9%) of these cases, and additional findings were made on MRI in 13/27 (48.1%) cases. CONCLUSIONS: Visualization of upper extremity abnormalities on fetal MRI enables differentiation between isolated defects and complex ones, which may be related to poor fetal prognosis. MRI generally confirms the ultrasound diagnosis, and may provide additional findings in certain cases.

Tumor-induced hypophosphatemic rickets in an adolescent boy--clinical presentation, diagnosis, and histological findings in growth plate and muscle tissue.

CONTEXT: The mechanism behind disabling muscle weakness in tumor-induced hypophosphatemic rickets is obscure. Histological investigation of growth plate tissue of patients with tumor-induced osteomalacia has so far not been reported. PATIENT: A mesenchymal tumor was detected in the left distal fibula by (68)Ga-DOTATOC in a 17-yr-old boy with adolescent onset of severe hypophosphatemic rickets. Disabling muscle weakness improved within days after surgery, and normal mobility was restored within months. METHODS AND RESULTS: The resected tissue included part of the growth plate allowing immunohistochemical investigation. Positive staining of FGF23 was found in the tumor cells and in hypertrophic chondrocytes, osteoblasts, and osteoclasts of the adjacent growth plate. This distribution matched that found in growth plate tissue of a healthy control. We found positive staining for the somatostatin receptor not only in the tumor but also within the growth plate and adjacent bony tissue in the patient and the healthy control. Muscle tissue provided evidence for a partial defect in respiratory chain complexes I-IV. Biochemical markers were nearly or completely restored to normal 12 months after surgery. CONCLUSIONS: Hypertrophic growth plate chondrocytes are a target or source of FGF23 in tumor-induced osteomalacia. Low serum phosphate, FGF23, or other factors produced by the tumor may interfere with mitochondrial function.

Case Report of Suspected Rhabdomyolysis during Treatment with Trabectedin in a Patient with Metastatic Leiomyosarcoma.

Trabectedin has been reported to occasionally induce rhabdomyolysis. In the present case, continuation of trabectedin was maintained despite suspected rhabdomyolysis related to trabectedin. Creatinine kinase levels dropped to normal levels. We suggest that continuation of trabectedin despite suspected rhabdomyolysis was safe in this specific patient.

Two sporadic spinal neurofibromatosis patients with malignant peripheral nerve sheath tumour.

We analyzed two unrelated male patients in whom neurofibromatosis type 1 (NF1) was not suspected until they presented with malignant peripheral nerve sheath tumours (MPNSTs) in their thirties and forties, respectively. Patient A presented with progressive peroneus paresis due to a rapidly growing MPNST in the thigh. MRI examination revealed multiple symmetrical spinal neurofibromas in this patient as well as in patient B who presented at the age of 42 with paraparesis and an MPNST at spinal level L4. Dermal features in both patients were strikingly mild, therefore both patients were considered belonging to the NF1-subform of spinal neurofibromatosis (SNF). The novel NF1 mutations identified, i.e. splice mutation, c.7675+1G > A, in patient A and two alterations, p.Cys1016Arg and p.2711delVal, located in trans in patient B support the notion that the phenotype of SNF may be related to mutations with possible residual functionality. The MPNSTs of both patients showed LOH affecting chromosome 17 including the NF1 locus. Furthermore, a truncating TP53 mutation was identified in the tumour of patient A. Both alterations are frequent findings in NF1-associated MPNSTs. To our knowledge these are the first MPNST patients with the clinical phenotype of SNF. The clinical course observed in these two patients suggests that nodular plexiform neurofibromas and spinal-nerve-root neurofibromas which may be asymptomatic for a long time and, hence, unrecognized in SNF patients bear the risk for malignant transformation.

HER-2/neu gene amplification in ovarian tumours: a comprehensive immunohistochemical and FISH analysis on tissue microarrays.

AIMS: Data on HER-2/neu overexpression, its correlation to prognosis and the success of treatment with Herceptin((R)) in ovarian carcinomas are scarce and contradictory. Therefore we assessed HER-2/neu expression and amplification in a large series of ovarian tumours by using tissue microarrays (TMAs). METHODS AND RESULTS: Two TMAs containing 173 invasive carcinomas, 36 borderline tumours, 20 granulosa cell tumours, 14 carcinosarcomas, 11 benign cystadenoms and eight other pelvic tumours were constructed to assess HER-2/neu gene amplification by fluorescence in-situ hybridization (FISH) and immunohistochemistry. Immunohistochemistry was successful in 94.3%; 81.8% were HercepTest negative, 11.3% were scored as 1+, 4.1% as 2+ and 2.8% as 3+, including 3.1% of invasive carcinomas, 2.8% of borderline tumours and 7.7% of carcinosarcomas; 83.6% could be analysed successfully by FISH revealing no aberration in 75.8%, low amplification in 2.7% and high amplification in 3.7% of the cases. In 17.8% monosomy, trisomy, polysomy or deletion could be detected. All cases with high-level amplification had 2+ or 3+ scores on immunohistochemistry. CONCLUSIONS: TMA is a feasible tool to study a large number of ovarian cases. Correlation between immunohistochemistry and FISH was excellent. HER-2/neu overexpression or gene amplification does not correlate with histological tumour type, stage, grade or prognosis.

Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells.

High CD99 expression levels and rearrangements of the EWS gene with ETS transcription factor genes characterize the Ewing's sarcoma family of tumors (ESFT). CD99 is a cell surface glycoprotein whose engagement has been implicated in cell proliferation as well as upregulation and transport of several transmembrane proteins in hematopoietic cells. In ESFT, antibody ligation of CD99 induces fast homotypic cell aggregation and cell death although its functional role in these processes remains largely unknown. Here, using an RNAi approach, we studied for the first time the consequences of modulated CD99 expression in six different ESFT cell lines, representing the most frequent variant forms of EWS gene rearrangement. CD99 suppression resulted in growth inhibition and reduced migration of ESFT cells. Among genes whose expression changes in response to CD99 modulation, the potassium-channel modulatory factor KCMF1 was consistently upregulated. In a series of 22 primary ESFT, KCMF1 expression levels inversely correlated with CD99 abundancy. Cells forced to express ectopic KCMF1 showed a similar reduction in migratory ability as CD99 silenced ESFT cells. Our results suggest that in ESFT, high CD99 expression levels contribute to the malignant properties of ESFT by promoting growth and migration of tumor cells and identify KCMF1 as a potential metastasis suppressor gene downregulated by high constitutive CD99 expression in ESFT.

Quality assessment of genetic markers used for therapy stratification.

PURPOSE: Therapy stratification based on genetic markers is becoming increasingly important, which makes commitment to the highest possible reliability of the involved markers mandatory. In neuroblastic tumors, amplification of the MYCN gene is an unequivocal marker that indicates aggressive tumor behavior and is consequently used for therapy stratification. To guarantee reliable and standardized quality of genetic features, a quality-assessment study was initiated by the European Neuroblastoma Quality Assessment (ENQUA; connected to International Society of Pediatric Oncology) Group. MATERIALS AND METHODS: One hundred thirty-seven coded specimens from 17 tumors were analyzed in 11 European national/regional reference laboratories using molecular techniques, in situ hybridization, and flow and image cytometry. Tumor samples with divergent results were re-evaluated. RESULTS: Three hundred fifty-two investigations were performed, which resulted in 23 divergent findings, 17 of which were judged as errors after re-evaluation. MYCN analyses determined by Southern blot and in situ hybridization led to 3.7% and 4% of errors, respectively. Tumor cell content was not indicated in 32% of the samples, and 11% of seemingly correct MYCN results were based on the investigation of normal cells (eg, Schwann cells). Thirty-eight investigations were considered nonassessable. CONCLUSION: This study demonstrated the importance of revealing the difficulties and limitations for each technique and problems in interpreting results, which are crucial for therapeutic decisions. Moreover, it led to the formulation of guidelines that are applicable to all kinds of tumors and that contain the standardization of techniques, including the exact determination of the tumor cell content. Finally, the group has developed a common terminology for molecular-genetic results.

Loss of CD38 correlates with simultaneous up-regulation of human leukocyte antigen-DR in benign prostatic glands, but not in fetal or androgen-ablated glands, and is strongly related to gland atrophy.

OBJECTIVE: To determine whether CD38 loss in benign and malignant prostatic disease is related to human leukocyte antigen (HLA)-DR up-regulation, by assessing the histopathology of the prostate and the effect of androgen deprivation. MATERIALS AND METHODS: Serial sections of frozen fetal (eight), infant (six), normal adult (10), benign hyperplastic (BPH, 24), and primary (10) and hormone-treated (11) carcinomatous human prostatic tissues were analysed by immunohistology for anti-CD38 and HLA-DR antigens. RESULTS: In BPH samples there was a significant correlation between CD38 loss (mean 21% of acini) and HLA-DR up-regulation (mean 20%; P < 0.001). Moreover, 76% of all CD38-negative acini in BPH had HLA-DR up-regulation in the same prostate epithelial cells, predominantly in atrophic and cystic glands, and in cells with retained secretions (74%). In contrast to the uniform expression in normal adult prostate, CD38 was negative or partly expressed in fetal acini (mean 19%) and almost completely negative in acini of the early infant period (mean 0.7%). In contrast to BPH, cancer cells did not selectively up-regulate HLA-DR when CD38 was lost. In patients with cancer treated by androgen deprivation, cancer cells were CD38-negative. CONCLUSIONS: The absence of CD38 and presence of HLA-DR expression in prostatic epithelium is consistent in BPH and tissue surrounding tumour, and strongly related to gland atrophy. This is particularly interesting as HLA-DR triggering can induce apoptosis of cells, whereas CD38 prevents it. A permissive role for androgens to maintain full CD38 expression in epithelial cells is suggested.

Helicobacter pylori in children and adolescents: increase of primary clarithromycin resistance, 1997-2000.

BACKGROUND: The authors evaluate the prevalence of Helicobacter pylori resistance in 117 children and demonstrate the changes over a 4-year period. METHODS: In 117 children and adolescents, H. pylori-positive gastritis was revealed by diagnostic upper endoscopy. Biopsies from the antrum and body of the stomach were tested by histology, urease test, and culture. H. pylori was isolated using standard culture techniques, and susceptibility to amoxicillin, clarithromycin, and metronidazole was tested using the E-test (AB-Biodisk, Sweden). RESULTS: Endoscopy revealed gastric ulcers in 2 of 117 subjects, duodenal ulcers in 6 of 117, and erosive gastritis or duodenitis in 23 of 117. Almost all patients showed antral nodularity. Histology always showed chronic gastritis with different degrees of activity. During the 4-year study period, the authors noticed an increase of primary clarithromycin-resistant H. pylori strains, from 14.3% to 27.6% (mean, 20.3%). Metronidazole resistance varied between 5% and 25%. No resistance to amoxicillin was found. CONCLUSION: Eradication of H. pylori should take place only after testing of susceptibility. The general use of clarithromycin in children should be restricted to better-defined indications. Resistance to clarithromycin of H. pylori may also become a future problem for the treatment of adults.

Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors.

The cytogenetic abnormalities of granulosa cell tumors (GCT) of the ovary are only partially known. Up to now, mainly numerical chromosomal aberrations have been described. Therefore we performed a comprehensive study on paraffin-embedded material of 20 GCT (17 adult, 3 juvenile; patient age between 16 and 78 y) combining comparative genomic hybridization (CGH); fluorescence in situ hybridization (FISH) using DNA-specific probes for chromosome 12, 17, 22, and X; DNA cytometry; and immunohistochemistry (inhibin, p53, Ki67). By DNA cytometry, 16 of 20 tumors (80%) were diploid. However, 6 of 16 diploid tumors (37%) showed aberrations by FISH. FISH revealed monosomy 22 in 8/18 cases (40%); trisomy 12 in 5/20 (25%); monosomy X in 2/20 (10%); and loss of chromosome 17 in one case (5%). The main findings by CGH were gains of chromosomes 12 (6 cases, 33%) and 14 (6 cases, 33%) and losses of chromosomes 22 (7 cases, 35%) and X (1 case, 5%), mostly comprising whole chromosomes or chromosome arms. Inhibin and p53 were expressed in 100% and 95% of the tumors, respectively. The Ki67 index ranged from 0% to 61%. Neither immunohistochemistry, nor DNA cytometry and molecular genetic analysis, provided statistically significant prognostic information. In summary, our study reveals a distinctive pattern of cytogenetic alterations in GCT. Our observations confirm earlier reports that trisomy 12 and 14 are frequent aberrations; however, monosomy 22 seemingly is even more prevalent.

Docetaxel as rescue medication in anthracycline- and ifosfamide-resistant locally advanced or metastatic soft tissue sarcoma: results of a phase II trial.

BACKGROUND: Metastatic soft tissue sarcoma not amenable to curative surgery has a dismal prognosis. Aggressive treatment with anthracyclines and ifosfamide represents the current therapeutic mainstay in these patients, most of whom succumb to relapses. Thus, the efficacy of subsequent therapeutic approaches has to be weighed against toxicity caused by palliative treatment. PATIENTS AND METHODS: Patients with locally advanced or metastatic soft tissue sarcoma refractory to treatment with anthracyclines and ifosfamide were enrolled into the present phase II study. Patients were assigned to receive docetaxel at 100 mg/m2 every three weeks. In case of severe toxicity, patients were switched to a weekly schedule of docetaxel (40 mg/m2). RESULTS: A total of 106 cycles (80% at the scheduled 100 mg/m2 dose level) were administered in 27 patients. Partial response was observed in 4 (15%) patients and 4 (15%) patients experienced disease stabilization. Median progression free survival and overall survival were 2.4 (range: 0.9-23.9) and 7.7 (range: 1.0-44.3) months, respectively. Upon renewed progression, three patients initially responsive to treatment with docetaxel were successfully reinduced by treatment with docetaxel. The safety profile of docetaxel was tolerable and the administration mostly manageable on an outpatient basis. CONCLUSIONS: Our results suggest that docetaxel represents an efficacious and tolerable treatment in a minority of patients refractory to standard treatment. There is a need for better identification of patients most likely to benefit from salvage treatment with docetaxel.