Biomedical subjects

S D Fossa

Publications and source records attributed to S D Fossa.

At least 19 recordsLinked to original sources

PubMed2005

Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours.

EORTC protocol 30924 is an international randomized trial reporting a 7.3 year update of a 2 weekly regimen of high-dose intensity chemotherapy with M-VAC plus granulocyte colony stimulating factor (HD-M-VAC) compared to classic M-VAC in advanced transitional cell carcinoma (TCC). Two hundred and sixty three untreated patients with bidimensionally measurable TCC were included. In an intention to treat analysis, there were 28 complete responses (CR) (21%) and 55 partial responses (PR) (41%), for an overall response rate (RR) of 64% on the HD-M-VAC arm. On M-VAC, there were 12 CR (9%) and 53 PR (41%), for an overall RR of 50% . The P-value for the difference in CR was 0.009; and for RR, was 0.06. After a median follow-up of 7.3 years, 24.6% are alive on the HD-M-VAC arm vs. 13.2% on the M-VAC arm. Median progression-free survival was better with HD-MVAC (9.5 months) vs. M-VAC (8.1 months). The mortality hazard ratio (HR) was 0.76. The 2-year survival rate for HD-M-VAC was 36.7% vs. 26.2% for M-VAC. At 5 years, the survival rate was 21.8% in the HD-M-VAC vs. 13.5%. Median survival was 15.1 months on HD-MVAC and 14.9 months on M-VAC. There was one death from toxicity in each arm; and more patients died to malignant disease in the M-VAC arm (76%) than in the HD-M-VAC arm (64.9%). With longer follow-up initial results have been confirmed, and shows that HD-M-VAC produces a borderline statistically significant relative reduction in the risk of progression and death compared to M-VAC.

Adult↗

PubMed2005

Adjuvant bleomycin, vincristine and cisplatin (BOP) for high-risk stage I non-seminomatous germ cell tumours: a prospective trial (MRC TE17).

Adjuvant BEP (bleomycin, etoposide, cisplatin) is effective treatment for high-risk clinical stage I (HRCS1) non-seminomatous germ cell tumours (NSGCT), but the known toxicities of etoposide, and the expansion of the HR group to any patient with vascular invasion (50% of patients), led the Medical Research Council to pilot the BOP regimen. Patients received two courses of BOP 14 days apart: cisplatin 50 mg m(-2) days 1 and 2, vincristine 1.4 mg m(-2) (max. 2 mg) days 2 and 8, bleomycin 30,000 IU days 2 and 8. Primary outcome was relapse rate; quality of life, fertility, hearing and lung function were assessed pre- and post-treatment. In all, 100 patients were required. A total of 115 eligible patients were registered, all received two courses of chemotherapy. Median follow-up is 70 months; two relapses have occurred and the 5-year relapse-free rate is 98.3% (95% confidence interval (CI) 95.5%, 99.9%). As assessed by clinicians during treatment, complete (reversible) alopecia was present in 20% of patients; World Health Organization (WHO) grade 1/2 neurotoxicity was present in 41%/5% of patients during treatment and 22%/1% at 6 months. However, 12% of patients reported 'quite a bit' or 'very much' pain/numbness/tingling in hands/feet 2 years after chemotherapy. Mature follow-up confirms high efficacy for two courses of cisplatin-based adjuvant chemotherapy in HRCS1 NSGCT. Substituting vincristine for etoposide decreases alopecia, but gives a low incidence of significant neuropathy. There are no clearcut advantages to 2 x BOP over 2 x BEP, except for patients who wish to maximise the chance of avoiding significant alopecia.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

Europe↗

PubMed2002

Prognostic variables for response and outcome in patients with extragonadal germ-cell tumors.

BACKGROUND: This investigation evaluates prognostic variables in patients with seminomatous and non-seminomatous extragonadal germ-cell tumors (EGCT) in order to identify relevant factors for long-term outcome following cisplatin-based chemotherapy. PATIENTS AND METHODS: Patients from six countries treated at 11 centers in Europe and the USA from 1975 to 1996 were evaluated retrospectively. Uni- and multivariate analyses of prognostic variables for survival and for response to chemotherapy were performed. RESULTS: Data were available for 635 EGCT patients, 104 with seminomatous and 524 with non-seminomatous EGCT (n = 7 not specified). For non-seminomatous EGCT the following independent adverse factors were identified: presence of either liver, lung or central nervous system metastases, primary mediastinal tumor or elevation of pretreatment beta-human gonadotropin; for extragonadal seminoma (only univariate) adverse factors were: presence of liver metastases, two or greater metastatic sites or International Germ Cell Cancer Collaborative Group (IGCCCG) grouping (intermediate versus good). Integration of these variables produced the following prognostic risk groupings: 'excellent prognosis', all seminomatous EGCT (89% 5-year survival rate); 'intermediate low', 'intermediate high' and 'poor', all non-seminomatous EGCT with a 69, 55 and 17% 5-year survival rate, respectively. The decreased survival among the different groups was due to a lower rate of favorable objective remissions and a higher rate of relapses. Classification and regression tree (CART) modeling confirmed histology and location of primary tumor as the major prognosticators. For the subgroup of patients with mediastinal non-seminoma, the 2-year survival rate ranged from 34 to 84%. Multivariate testing for the probability to respond to chemotherapy revealed non-seminomatous histology, primary mediastinal tumor site, and the presence of liver, lung or CNS metastases as independent adverse factors. CONCLUSIONS: In EGCT, prognostic variables for the outcome and for the response to chemotherapy could be identified, which in part differ from gonadal GCT. The proposed model might help to better understand the specific prognosis of EGCT and to tailor risk-adapted treatment strategies. In addition, CART analysis demonstrated the heterogenous prognosis of patients with mediastinal non-seminoma.

Abdominal Neoplasms↗

PubMed2002

Analysing longitudinal continuous quality of life data with dropout.

Quality of Life (QL) is becoming an increasingly popular endpoint in phase III cancer clinical trials. However, there is still no agreement as to what is the optimal approach to analysis. In this paper we review some concepts which should be considered during a QL analysis. We present two modelling approaches that have been substantively developed in other research fields: selection models and pattern-mixture models. These models are compared using data from an EORTC clinical trial in poor-prognosis prostate cancer patients. It is illustrated that, although selection models and pattern mixture are probabilistically equivalent, they may shed completely different light on data from a modeller's point of view.

Clinical Trials, Phase III as Topic↗

PubMed2001

Incidence of metachronous testicular cancer in patients with extragonadal germ cell tumors.

BACKGROUND: The frequency of subsequent testicular cancer (referred to as metachronous testicular cancer) in men who have had previous testicular cancer is relatively high. The rate of metachronous testicular cancer in men with extragonadal germ cell tumors (EGCTs), however, is largely unknown. We conducted a retrospective study of EGCT patients to determine the incidence, cumulative risk, and specific risk factors for metachronous testicular cancers. METHODS: A standardized questionnaire about patient characteristics, the extent of EGCT disease, any second malignancies, and treatments received was completed for 635 patients with EGCTs identified from the medical records of 11 cancer centers in Europe and the United States from 1975 through 1996. Comparisons with age group-specific data from the Saarland, Germany, population-based cancer registry were used to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to analyze survival data and cumulative risk. All statistical tests were two-sided. RESULTS: Sixteen EGCT patients (4.1%) developed metachronous testicular cancers, with a median time between diagnoses of 60 months (range, 14-102 months). The risk of developing metachronous testicular cancers was statistically significantly increased in patients with EGCTs (observed = 16; expected = 0.26; SIR = 62; 95% confidence interval [CI] = 36 to 99) and in subsets of EGCT patients with mediastinal location (SIR = 31; 95% CI = 8 to 59), retroperitoneal location (SIR = 100; 95% CI = 54 to 172), and nonseminomatous histology (SIR = 75; 95% CI = 43 to 123). The cumulative risk of developing a metachronous testicular cancer 10 years after a diagnosis of EGCT was 10.3% (95% CI = 4.9% to 15.6%) and was higher among patients with nonseminomatous EGCTs (14.3%; 95% CI = 6.7% to 21.9%) and retroperitoneal EGCTs (14.2%; 95% CI = 5.6% to 22.8%) than among patients with seminomatous EGCTs (1.4%; 95% CI = 0.0% to 4.2%) and mediastinal EGCTs (6.2%; 95% CI = 0.1% to 12.2%). CONCLUSIONS: Patients with EGCTs, particularly those with retroperitoneal or nonseminomatous tumors, but also those with primary mediastinal EGCTs, are at an increased risk of metachronous testicular cancer.

Adolescent↗

PubMed2001

Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924.

PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high-dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was.009; and for the overall response, it was.06. There was no statistically significant difference in survival (P =.122) or time to progression (P =.114). Progression-free survival was significantly better with HD-MVAC (P=.037; hazard ratio.75; 95% CI.58 to.98). The median progression-free survival time was 9.1 months on the HD-MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free survival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% CI, 5.9% to 17.4%). CONCLUSION: With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.

Adult↗

PubMed2001

Extragonadal seminoma: an international multicenter analysis of prognostic factors and long term treatment outcome.

BACKGROUND: The objectives of this study were to evaluate the long term outcome of patients with extragonadal seminomatous germ cell tumors (GCT) so that prognostic variables for disease recurrence and patient survival could be identified and to access the efficacy of different treatment modalities. METHODS: Six hundred thirty-five patients with extragonadal GCT who were treated consecutively at 11 centers in the United States and Europe during the cisplatin-based chemotherapy era between 1975 and 1996 were evaluated retrospectively. RESULTS: Fifty-two patients with primary retroperitoneal GCT (50%) and 51 patients with primary mediastinal GCT (49%) of pure seminomatous histology were identified (n = 1 patient with a primary cervical lymph node) representing 16.4% of 635 patients with extragonadal GCT who were included in the data base. The median age was 37 years (range, 18-70 years). Treatment consisted of platin-based chemotherapy in 77 patients (74%), radiotherapy in 9 patients (9%), and combined modality in 18 patients (17%). Ninety-two percent of patients (95% confidence interval, 87-97%) achieved a favorable response to primary therapy. After a median follow-up of 61 months (range, 1-211 months), 18 patients (17%) have had recurrent disease: 14% of those who received chemotherapy and 67% of those who received radiation therapy. The 5-year progression free survival rate favored the chemotherapy group, with 87% compared with 33% for irradiated patients (P = 0.006), whereas the overall survival rates were equal (90% vs. 67%; P = 0.13). No differences in overall survival or progression free survival were observed among patients with primary retroperitoneal and mediastinal seminoma. Prognostic factors that were identified to influence survival negatively were liver metastases (P = 0.01) and two or more metastatic sites (P = 0.04). CONCLUSIONS: In patients with extragonadal seminoma, a survival rate of > 90% at 5 years is achieved with adequate cisplatin-based chemotherapy. Compared with patients with nonseminomatous extragonadal GCT, no difference in long term survival exists between patients with primary retroperitoneal or mediastinal seminoma location. Primary radiotherapy seems to be associated with a significantly higher rate of disease recurrence, although most patients will be salvaged by subsequent chemotherapy.

Adolescent↗

PubMed2001

Second-line chemotherapy in patients with relapsed extragonadal nonseminomatous germ cell tumors: results of an international multicenter analysis.

PURPOSE: Relapsed extragonadal germ cell tumors patients (EGGCT) are treated with identical salvage chemotherapy regimens, as are patients with metastatic testicular cancer. This investigation evaluates the results of second-line chemotherapy in nonseminomatous EGGCT and tries to identify prognostic factors for survival. PATIENTS AND METHODS: We conducted a retrospective review of 142 patients treated at eleven European and American centers between 1975 and 1996. All had received cisplatin-containing regimens as induction treatment. RESULTS: Twenty-seven of 142 patients (19%) were long-term disease-free, 11% with primary mediastinal and 30% of patients with primary retroperitoneal disease. Median follow-up since start of salvage treatment was 11 months (range, 1 to 157) for all patients and 45 months (range, 6 to 157) for surviving patients. Forty-eight patients (34%) received high dose chemotherapy with autologous bone marrow transplant at relapse, and 10 of these patients (21%) are continuously disease-free. Primary mediastinal location (P =.003), sensitivity to cisplatin (P =.003), elevated beta-HCG at relapse (P: =.04), and normal LDH at diagnosis (P =.01) were shown to be significant negative prognostic factors for overall survival in univariate; mediastinal location [relative risk ratios (HR) = 1.9; 95% confidence intervals (CI), 1.2 to 3.0] and sensitivity to cisplatin [HR = 2.4; 95% CI, 1.1 to 5.2] were significant negative prognostic factors in multivariate analysis. CONCLUSION: Although current salvage strategies will cure between 20% and 50% of recurrent metastatic testicular cancer, relapsed nonseminomatous EGGCT patients appear to have an inferior survival rate, in particular in case of primary mediastinal location. Mediastinal primary tumor and inadequate response to cisplatin-based induction chemotherapy have been identified as independent negative prognostic factors, both associated with an approximately two-fold higher risk for failure of salvage treatment.

Adolescent↗

PubMed2001

Spermatogenesis after unilateral orchiectomy for testicular cancer in patients following surveillance policy.

PURPOSE: Only limited information is available on the natural course of spermatogenesis in patients with testicular cancer who underwent unilateral orchiectomy and surveillance. We analyze long-term exocrine function of the remaining testicle in patients following surveillance policy. MATERIALS AND METHODS: Sperm counts and serum follicle-stimulating hormone (FSH) levels were available in 60 nonrelapsing cases approximately 3 weeks (baseline), 1 year and 2 years or greater after orchiectomy. Contralateral testicular cancer subsequently developed in 2 men. RESULTS: At baseline 36 patients were normospermic (10 or greater x 106/ml.), 7 were azoospermic and 17 were oligospermic. After 1 year 45 patients were normospermic. Mean sperm concentrations increased significantly from 26 to 39 x 106/ml. during year 1 after orchiectomy. Elevated serum FSH at baseline was associated with incomplete recovery of spermatogenesis, although sperm counts improved in 3 of 7 patients. Furthermore, in the 2 initially oligospermic patients with subsequent contralateral testicle cancer transient normospermia was observed after 1 year. After orchiectomy fatherhood was recorded in 28 men and was assisted by fertilization using fresh semen in 2. CONCLUSIONS: In nonrelapsing testicular cancer cases on surveillance, initially reduced spermatogenesis recovers during year 1 after orchiectomy especially if baseline serum FSH is normal. Transient recovery also occurs in patients in whom contralateral testicular cancer subsequently develops. In high risk patients and in initially oligospermic patients with plans for future fatherhood, the period of improved spermatogenesis may be used for multiple semen cryopreservations enabling subsequent assisted fertilization.

Adult↗

PubMed2000

The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors.

BACKGROUND: Apart from a recognized association between extragonadal mediastinal germ cell tumors (GCT) and the occurrence of hematologic malignancies, the risk of developing second nongerminal solid tumors after the diagnosis or treatment of extragonadal GCT is unknown. METHODS: Six hundred thirty-five consecutive patients with extragonadal GCT treated at 11 centers in the U.S. and Europe during the era of cisplatin-based chemotherapy (1975-1996) were included into a large database. These patients were evaluated for the occurrence of second malignancies. RESULTS: No treatment-related leukemia was observed in 611 patients treated with chemotherapy. In 7 patients, second solid tumors were observed, resulting in a frequency of 1.86% (95% confidence interval [95% CI], 1.79-1.93%) after a median follow-up of 55 months (95% CI, 50-60 months) (annual incidence, 0.30% [95% CI, 0.14-0.59]). Four solid tumors (57%) developed in patients with primary mediastinal and 3 tumors (43%) developed in patients with retroperitoneal GCT. Three patients (43%) had a nonseminomatous and 4 patients (57%) had a seminomatous histology. Six patients had been treated with chemotherapy and one patient with radiotherapy. Six of 7 solid tumors (86%) had developed within 5 years and 7 of 7 solid tumors within 10 years of diagnosis. The median time period to the occurrence of neoplasia was 47 months (range, 9-145 months). Four cutaneous tumors were observed (melanoma, two patients; basal cell carcinoma, one patient; and squamous cell carcinoma, one patient); the other three tumors were angiosarcoma, nonsmall cell lung carcinoma, and colorectal carcinoma. The overall risk for developing a second tumor was not increased compared with an age-matched general population with a standard incidence ratio (SIR) of 1.49 (95% CI, 0.60-3.06). An elevated risk for skin tumors was observed in all extragonadal GCT patients (SIR, 4.00 [95% CI, 1. 09-10.24]), as well as in the subgroup of patients treated with chemotherapy (SIR, 5.33 [95% CI, 1.45-13.65]). CONCLUSIONS: This analysis excludes an increased biologic risk of developing second solid malignancies in patients with extragonadal GCT except for the previously reported association between primary mediastinal nonseminoma and hematologic disorders. The overall risk of developing second malignancies in extragonadal GCT patients appears to be comparable to that in patients with primary testicular carcinoma. The incremental occurrence of skin malignancies in patients treated with chemotherapy should be investigated further.

Adolescent↗

PubMed2000

Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors.

BACKGROUND: The association between primary germ cell tumors of the mediastinum (the space between the lung pleura that contains the heart and other chest viscera) and hematologic malignancies has been described by retrospective analysis of patients treated at individual clinical centers. To better characterize the risk of hematologic disorders in patients with extragonadal germ cell tumors and to describe the clinical and biologic features of the disorders, we studied an unselected population in a large, international, multicenter database. METHODS: Six hundred thirty-five patients treated at 11 centers in the United States and Europe from 1975 through 1996 were evaluated retrospectively. RESULTS: A hematologic disorder was observed in 17 patients with germ cell tumors. All cases developed among the 287 patients with primary mediastinal nonseminomatous germ cell tumors, giving an incidence rate in this group of 2.0% (95% confidence interval [CI] = 1.1%-3.1%) per year over a median follow-up time of 3 years. The risk of developing hematologic disorders was statistically significantly increased in patients with primary mediastinal nonseminomatous germ cell tumors in comparison with the age-matched general population (standardized incidence ratio = 250; 95% CI = 140-405). The median time to onset of hematologic neoplasia was 6 months (range, 0-47 months), and the median survival after diagnosis of the hematologic disorder was 5 months (range, 0-16 months) (two-sided P<.0001, comparing survival from the time of diagnosis of the germ cell tumor of patients with and without hematologic disorders). CONCLUSION: In our study, approximately one in 17 patients with primary mediastinal nonseminomatous germ cell tumors was affected by a hematologic disorder, whereas no cases were seen among 334 patients with other extragonadal germ cell tumors. The hematologic disorder had a statistically significant impact on prognosis, with none of the 17 reported patients surviving for more than 2 years.

Adolescent↗

PubMed2000

A medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party.

The UK Medical Research Council conducted this trial of carboplatin chemotherapy in advanced seminoma to compare single agent carboplatin with a standard combination of etoposide with cisplatin. The use of single agent carboplatin was expected to be associated with reduced toxicity. A total of 130 patients with advanced seminoma were randomly assigned to treatment with either single agent carboplatin (C) at a dose of 400 mg/m(2)to be corrected for glomerular filtration rate outside the range 81-120 ml min(-1)and to be administered on day 1 of a 21 day cycle to a total of 4 cycles or to etoposide + platinum (EP). The trial was designed as an equivalence study aiming to exclude a reduction in the 3-year progression-free survival in patients allocated to carboplatin of between 10 and 15%, requiring initially a target accrual of 250 patients (90% power significance level 5% (one-sided)). The trial closed after 130 patients had been randomized following recommendation by an independent data monitoring committee. At a median follow-up time of 4.5 years, 81% of patients had been followed up for at least 3 years and 19 patients have died. The estimated PFS rate (95% Confidence Intervals (CI)) at 3 years was 71% (60-82%) in patients allocated C and 81% (71-90%) in those allocated EP; the 95% CI for the difference in 3 year PFS was - 6% to +19%. The hazard ratio of 0.64 (95% CI 0.32-1.28) favoured EP but the difference was not statistically significant (log rank chi-squared = 1.59 P = 0.21). The 3-year survival rate was 84% (75-92%) in those allocated C, and 89% (81-96%) in those allocated EP. The hazard ratio for survival was 0.85 with 95% CI, 0.35-2.10, log rank chi-squared = 0.12, P = 0.73. The trial has not demonstrated statistically significant differences in the major survival endpoints comparing single agent carboplatin with a combination of etoposide + cisplatin. This cannot be taken as an indication of equivalence since the limited size of this trial rendered it unable to exclude a 19% lower progression-free survival and survival in those treated with single agent carboplatin which would be important clinically. Standard initial chemotherapy for advanced seminoma should be based on cisplatin combinations and the role of carboplatin awaits the outcome of further studies.

Antineoplastic Agents↗

PubMed1999

Defining an international research agenda for quality of life in men with prostate cancer.

BACKGROUND: While the traditional goal in the management of patients with prostate cancer has been to maximize survival, the recent advent of the medical outcomes movement has underscored the importance of patient-centered issues, such as health-related quality of life (HRQOL). METHODS: In this paper we present a comprehensive approach to the study of HRQOL in men with prostate cancer. We begin by defining HRQOL in general, discussing its measurement, and placing it in the context of prostate cancer. We then describe the primary goals of HRQOL research and present examples of validated instruments. We finish by proposing a quality of life research agenda for the next two decades. RESULTS: Contemporary perspectives on HRQOL are based on the World Health Organization's definition of health as not merely the absence of disease, but as a state of physical, emotional, and social well-being. HRQOL measurement must adhere to the strict methodological principles of survey psychometrics and is best accomplished with any of several validated instruments. Once collected, HRQOL information is useful for prostate cancer patients facing difficult treatment decisions. CONCLUSIONS: A solid foundation for HRQOL research has been built in early- and late-stage prostate cancer. It includes the development of new instruments and the establishment of descriptive data. This groundwork will allow investigators to address more complex research issues, such as interpreting interactions among HRQOL domains, presenting HRQOL data to future patients, optimally timing HRQOL data collection, uncovering innate and alterable factors that influence HRQOL, and exploring the intercultural nuances of HRQOL assessment.

Health↗

PubMed1999

Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party.

BACKGROUND: Because metastatic nonseminomatous germ cell cancer is a rare but treatable cancer, we have explored whether there is an association between the experience of the treating institution with this disease and the long-term clinical outcome of the patients, particularly patients with a poor prognosis. METHODS: We analyzed data on 380 patients treated in one of 49 institutions participating in the European Organization for Research and Treatment of Cancer/ Medical Research Council randomized trial of four cycles of bleomycin-etoposide-cisplatin followed by two cycles of etoposide-cisplatin versus three cycles of bleomycin-vincristine-cisplatin followed by three cycles of etoposide-ifosfamide-cisplatin-bleomycin, both treatment regimens given with or without filgrastim (granulocyte colony-stimulating factor). Institutions were divided into four groups based on the total number of patients entered in the trial. The groups were compared by use of the Cox proportional hazards model stratified for treatment with filgrastim and for patient prognosis as defined by the International Germ Cell Consensus Classification Group. With the use of this classification, only 65 % of the patients had a poor prognosis. RESULTS: Patients treated in the 26 institutions that entered fewer than five patients into the trial had an overall survival that was statistically significantly worse (two-sided P = .010; hazard ratio = 1.85; 95% confidence interval = 1.16-3.03) than that of patients treated in the 23 institutions that entered five patients or more. Overall survival and failure-free survival were similar among institutions that entered at least five patients. The observed effect may be related to differences in adherence to the chemotherapy protocol and in the frequency and extent of surgery for residual masses, although only the differences in dose intensity achieved statistical significance. CONCLUSIONS: Patients treated in institutions that entered fewer than five patients into the trial appeared to have poorer survival than those treated in institutions that entered a larger number of patients with "poor-prognosis" nonseminoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Spermatocytic seminoma as compared to classical seminoma: an immunohistochemical and DNA flow cytometric study.

UNLABELLED: Based on immunohistochemistry (IHC) and DNA ploidy, different paths of carcinogenesis have been suggested for spermatocytic seminoma (SS) and classical seminoma (CS). The present study extends current knowledge on the above parameters. METHOD: Seventeen SSs and twenty-two CSs were assessed by IHC for placental-like alkaline phosphatase (PLAP), c-kit, cytokeratin and adhesion carbohydrate molecyles. All SSs and 11 CSs were also analysed for DNA ploidy. RESULTS: All CSs, but none of the SSs, were positive for PLAP. C-kit positivity was found in 7 of 17 SSs and in all CSs. The other IHC parameters were similarly distributed among the evaluated SSs and CSs. Fourteen SSs were diploid or polyploid, and three were aneuploid. All CSs were aneuploid. CONCLUSION: The new observation of c-kit positivity in about 40% of SSs suggests that at least some of the SSs originate from primordial cells. The predominantly diploid or polyploid DNA pattern indicates that SSs follow a pathogenetic pathway which is most probably different from that of CSs.

Adult↗

PubMed1998

Postchemotherapy residual masses in germ cell tumor patients: content, clinical features, and prognosis. Medical Research Council Testicular Tumour Working Party.

BACKGROUND: In a retrospective study that included a detailed histopathologic review, the clinicopathologic features of patients with germ cell tumors (GCT) and resectable residual masses after chemotherapy were assessed. METHODS: Histologic material from 153 patients was available for review. Recorded details included primary histologic diagnosis, location, size and number of metastases, marker levels before and after chemotherapy, and completeness of surgical excision. A median of seven histologic sections per resection were reviewed by two pathologists independently (and together when disagreement occurred). In each case, details were recorded regarding fibrosis, necrosis, hemorrhage, embryonal carcinoma (undifferentiated teratoma), yolk sac tumor, choriocarcinoma (trophoblastic tumor), differentiated teratoma (mature and immature), dysplasia in somatic tissues, and non- germ cell tumor (GCT) malignancies. The percentage of the sample that each of these components comprised was also estimated. RESULTS: The median postchemotherapy follow-up time was 7 years, and 38 of 153 patients (25%) experienced disease progression. In a multivariate analysis, incomplete resection of all residual masses (in 38 patients) and the presence of malignant elements (in 23 patients) were independent risk factors for progression. In the subset of patients in whom all masses were completely resected, the presence of embryonal carcinoma (undifferentiated teratoma) was the single most significant risk factor for progression. Seven percent of patients had this factor, which was associated with a 2-year progression free survival rate of 12.5%, compared with 88.0% where this component was absent. CONCLUSIONS: Progression free survival can be predicted well by the completeness of excision of residual masses and the presence of malignant germ cell elements. The latter confers a relatively poor prognosis even if all of these elements are completely resected.

Disease-Free Survival↗

PubMed1998

Intratubular germ cell neoplasia of the contralateral testis in testicular cancer: defining a high risk group.

PURPOSE: We define a group of testis cancer patients who are at high risk for carcinoma in situ of the contralateral testis and, therefore, a second germ cell tumor. MATERIALS AND METHODS: The histology was reviewed in 186 testis cancer patients who underwent contralateral testicular biopsy either because of a history of testicular maldescent or an atrophic contralateral testis (defined as a volume of 12 ml. or less). Testicular volume, semen analysis, serum gonadotropin levels, serum testosterone and estradiol levels were assessed in the majority of patients. RESULTS: Univariate analyses identified contralateral testicular atrophy, low sperm density, young age at presentation and low Johnsen score as factors associated with increased risk of a positive biopsy. A history of maldescent in the absence of atrophy was associated with carcinoma in situ prevalence of only 4%. Multivariate analysis identified only testicular atrophy and age at presentation as independent determinants of a positive biopsy. Testis cancer patients with a small contralateral testis had a 20% and those presenting at age 30 years or younger had a 34% prevalence, respectively, of carcinoma in situ on contralateral testis biopsy (95% confidence interval 20 and 46%, respectively). CONCLUSIONS: Testis cancer patients with an atrophic contralateral testis who present before the age of 31 years are at high risk for carcinoma in situ of the contralateral testis and, therefore, a second germ cell tumor. It is estimated that this group comprises 6% of all testis cancer patients. We predict that a policy of performing contralateral testicular biopsy will produce positive results for carcinoma in situ in a third of these patients and will detect contralateral carcinoma in situ in approximately 40% of all testis cancer patients.

Adult↗