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Biomedical subjects

E Huland

Publications and source records attributed to E Huland.

At least 19 recordsLinked to original sources
PubMed2001

Human prostate cancer regulates generation and maturation of monocyte-derived dendritic cells.

BACKGROUND: The progression of prostate cancer is accompanied by a marked suppression of the immune system, including the apoptotic death of dendritic cells (DC) responsible for the induction of antitumor immunity. In this study, we evaluated whether prostate cancer might inhibit DC generation and maturation in vitro. METHODS: DC were generated from peripheral blood monocytes in the presence of the human prostate cell line LNCaP or nonmalignant cells, and characterized by light microscopy, FACScan analysis, and ability to stimulate T-cell proliferation. RESULTS: Prostate cancer significantly inhibited the conversion of monocytes into DC, which was assessed by the expression of DC markers CD1a and CD83. These cells were weak stimulators of T-cell proliferation, suggesting that DC generated in the prostate cancer microenvironment are functionally inhibited. CONCLUSIONS: Prostate cancer not only kills mature DC, but also inhibits their generation and maturation, resulting in decreased production of antigen-presenting cells and inhibition of their functional activity.

Antigens, CD↗
PubMed2001

Systemic chemotherapy and chemoimmunotherapy for metastatic renal cell cancer.

We review the current literature on systemic therapy for patients with metastatic renal cell carcinoma. Metastatic renal cell carcinoma remains highly resistant to chemotherapy and hormonal agents not justifying its use as a single agent. Interleukin-2 immunotherapy is the most effective treatment for metastatic renal cell carcinoma available today. There is evidence that interleukin-2 improves survival and yields long-lasting remissions in selected patients; the optimal dose and schedule still need to be defined. Response rates in patients treated with subcutaneous interleukin-2 are similar to those achieved with high-dose bolus intravenous applications. Questions remain concerning quality of life and benefit-to-risk ratio with respect to immunotherapy in individual patients. Different routes of administration of interleukin-2 such as local application, promise to improve quality of life and survival times.

Antineoplastic Agents↗
PubMed2001

Relevance of p53 gene alterations for tumor recurrence in patients with superficial transitional cell carcinoma of the bladder.

PURPOSE: The prognostic relevance of p53 protein accumulation in muscle-invasive bladder carcinoma is well documented, but the prognostic relevance of p53 alterations in superficial bladder tumors remains uncertain. Immunohistochemical data are divergent, possibly because of the use of nonstandardized techniques. We therefore investigated the relevance of p53 gene point mutations and loss of heterozygosity (LOH) for tumor recurrence. The results of this molecular analysis were compared with accumulation of the p53 protein as shown by immunohistochemistry. MATERIAL AND METHODS: Representative tumor tissue was selected and microdissected from 40 patients (pTa, 18 patients; pT1, 22 patients; grade I, 7 patients; grade II, 28 patients; grade III, 5 patients). Polymerase chain reaction (PCR) was carried out with exons 5-8. All PCR products were screened for p53 mutations with temperature-gradient gel electrophoresis (TGGE). When mobility shift was observed, direct nucleotide sequencing was performed. Detection of LOH was performed with nonradioactive microsatellite analysis using three markers (TP 53, D17S513 and D17S786) on chromosome 17p. Immunohistochemistry was performed with the DO 7 antibody. Tumor samples with p53 accumulation of 5% or more positive nuclei were classified as positive. Univariate analysis for disease-free survival was performed using Kaplan-Meier analysis and the log-rank test. RESULTS: TGGE and direct sequencing detected mutations in 10 of 40 patients (2 of 18 pTa and 8 of 22 pT1 patients). LOH was detected in 11 patients. Both a mutation and LOH were detected in 3 patients. p53 immunohistochemistry detected at least 5% positive nuclei in 28 of 40 patients (70%). After a median follow-up of 26 months 14 patients suffered disease recurrence. Whereas disease-free survival did not correlate with a mutation (p = 0.77, log-rank test), LOH (p = 0.2) or a mutation in combination with LOH (p = 0.23), a positive p 53 immunoreaction was significantly associated with short disease-free survival (p = 0.009). CONCLUSION: Despite the relatively high percentage of patients with p53 gene alteration in this population no significant correlation between the detection of molecular alteration and disease recurrence could be found. We conclude that, in contrast to immunohistochemical accumulation, gene alterations play only a minor role in tumor recurrence of p53 in patients with superficial transitional cell carcinoma of the bladder, and that immunohistochemical accumulation of the p53 protein has to be explained by mechanisms other than gene mutations.

Carcinoma, Transitional Cell↗
PubMed2000

[Treatment of metastatic renal cell carcinoma. Value of immunotherapy compared with surgery of metastases].

The prognosis for patients in whom metastatic renal cell carcinoma (RCC) is not treated is unfavorable, with a reported 5-year survival of 0-18%. Before the era of immunotherapy and in the absence of effective nonsurgical therapy, resection of metastases was the accepted way to prolong survival, giving a 5-year survival of 7-69%. Retrospective studies have shown that several clinical factors are associated with a relatively good prognosis. Some patients will benefit from resection of metastases, but most patients with metastatic RCC are not candidates for such aggressive surgery. The use of interleukin-2 has demonstrated that immunotherapy can produce durable remissions. Without randomized trials, it is difficult to know whether survival is longer than that in untreated patients, but there is clear evidence that immunotherapy improves survival and yields long-lasting remissions in selected patients. Many questions remain concerning quality of life and the benefit-to-risk ratio of immunotherapy, but it is the most effective treatment for metastatic RCC.

Carcinoma, Renal Cell↗
PubMed2000

Local cytokine therapy of cancer: interleukin-2, interferons and related cytokines.

Local therapy with interleukin-2 (IL-2) and other cytokines may be a very effective way to treat cancer. This was the theme of the First Symposium on Local Cytokine Therapy of Cancer: Interleukin-2, Interferons and Related Cytokines, in Hamburg, 29 April-1 May 1999. The abstracts are published in Anticancer Research 19: 1995-2016 (1999). Here we present a report.

Animals↗
PubMed2000

Human glandular kallikrein 2: a potential serum marker for predicting the organ confined versus non-organ confined growth of prostate cancer.

PURPOSE: We measured serum levels of human glandular kallikrein 2 (hK2) in patients with prostate cancer treated with radical retropubic prostatectomy for clinically localized prostate cancer to determine whether preoperative hK2 levels discriminate stage pT2a/b from pathological stage T3a or greater cancer. This finding would help to predict preoperatively the organ confined versus non-organ confined growth of prostate cancer. MATERIALS AND METHODS: A total of 68 consecutive men underwent radical retropubic prostatectomy for clinically localized prostate cancer. Serum was obtained 1 day preoperatively before prostatic manipulation. hK2, and total and free prostate specific antigen (PSA) were measured using immunofluorometric assays. Mean, median and range of hK2, total and free PSA, and the ratio of free-to-total PSA (percent free PSA) were calculated. Each analyte or combination of analytes was evaluated to determine whether it significantly contributed to enhance the discrimination of organ confined from non-organ confined cancer. We calculated the statistical significance of observed differences using the Mann-Whitney U and Kruskal-Wallis tests. Sensitivity and specificity calculations were performed for hK2, total PSA and the algorithm, (hK2) x (total PSA/free PSA) in addition to receiver operating characteristics curves and the respective areas under the curves. Multivariate logistic regression analysis was done for hK2, and total and free PSA RESULTS: Disease was organ and non-organ (extraprostatic extension) confined in 38 and 30 men, respectively. In organ confined cancer mean hK2 was significantly lower than in non-organ confined cancer (0.09 ng./ml., range less than 0.03 to 0.23 versus 0.30, range 0.04 to 0.94, p <0.0001). In addition, there was significantly higher free and total but not percent free PSA in non-organ than in organ confined cases. There were also statistically significant differences in hK2, free PSA and total PSA at each pathological disease stage (p <0.001, <0.01 and <0.05, respectively). Sensitivity for detecting organ confined disease was 37% at 100% specificity (correct identification of all non-organ confined cancer) using hK2 measurements compared with a sensitivity of 14% for total PSA. At a specificity of 95%, sensitivity was 40% for hK2 versus 23% for total PSA, which was a statistically significant gain in sensitivity (p <0.05). Receiver operating characteristics curves demonstrated that hK2 had the largest area under the curve, followed by the algorithm, (hK2) x (total PSA/free PSA), and total PSA (0.76, 0.75 and 0.72, respectively). However, none of area under the curve differences was statistically significant. CONCLUSIONS: Compared with total and free PSA hK2 testing improved the preoperative evaluation of patients who underwent radical retropubic prostatectomy due to the superior discrimination of organ from non-organ confined cancer.

Adenocarcinoma↗
PubMed2000

Advanced prostate cancer is associated with a decrease in serum luteinizing hormone.

OBJECTIVE: Depletion of serum LH by LHRH agonists is used as a therapeutic treatment in hormone-sensitive prostate cancer (PCa). However, little information on serum LH in different patient groups is available. METHODS: Patients with biopsy-proven PCa, men with BPH (biopsy-proven absence of PCa), two subgroups (serum PSA <4 ng/ml; PCa and BPH), and a PCa cohort before and after radical prostatectomy were analyzed for serum LH, testosterone (T), dihydrotestosterone (DHT), total and free PSA by immunological procedures. RESULTS: PCa patients with cancer volumes >10 cm(3), or with advanced Gleason scores, had significantly lower LH values than men in a cancer-free control group (PSA <4 ng/ml). Eight weeks after radical prostatectomy, LH levels had returned to the level of the control group (p<0.0001). These alterations were not accompanied by corresponding changes of serum androgens. Introduction of a PSA/LH ratio appeared to increase the differences between BPH and PCA groups ranked according to Gleason scores, versus PSA or LH alone. However, the calculation of ROC curves indicated that PSA/LH ratios may not improve the discrimination of malignant and benign forms of the disease, compared to presently used parameters. CONCLUSIONS: A significant reduction of circulating LH is observed in the most advanced forms of PCa. The effect does not come about by T- or DHT-mediated feedback inhibition. Since LH values after prostatectomy returned to practically the same levels as seen in the control group (BPH with <4 ng/ml PSA), it appears that the healthy prostate has no marked influence on serum LH while advanced PCa induces a decrease in serum LH.

Adult↗
PubMed2000

A comparison of systemic versus inhaled recombinant IL-2 administration for the treatment of metastatic renal cell carcinoma.

The aim of the current study was to compare the objective response and survival rates of patients with mRCC treated with IL-2 administered either systemically (SYST, subcutaneously) or via inhalation (INH), using relatively large sample sizes to afford a more meaningful comparison. We used univariate and multivariate analyses to retrospectively evaluate the data from two different databases generated from 277 patients treated with IL-2 during the 1993-1997 period, one developed at the University Hospital Hamburg-Eppendorf, and the other at Chiron-Amsterdam. Patients treated with INH IL-2 tended to have a poorer ECOG performance status than patients receiving SYST IL-2. Of 75 patients receiving INH IL-2, eight (10.7%) achieved an objective response; of 202 patients administered SYST IL-2, 45 (22.2%) achieved an objective response. The median survival time was 13.8 months for patients receiving INH IL-2 and 13.1 months for patients treated with SYST IL-2. One- and two-year survival rates were also comparable for the two treatment modalities (one-year: INH, 55%; SYST, 56%; two-year: INH, 28%; SYST, 26%). There was no significant difference in the likelihood of survival for patients receiving INH IL-2 versus SYST IL-2 (risk ratio = 0.82, P = 0.27). Patients administered INH IL-2 experienced considerably less toxicity and complications than patients administered SYST IL-2. We conclude that INH IL-2 treatment is at least as effective as SYST IL-2 treatment in promoting the survival of patients with mRCC. Given that INH IL-2 treatment of patients with a poorer ECOG performance status elicited a survival rate comparable to that seen with SYST IL-2 treatment of patients with a superior performance status, the potential exists for INH IL-2 treatment to be even more effective for patients having a better performance status. Additionally, INH IL-2 treatment is considerably less toxic and associated with fewer complications than SYST IL-2 treatment, thus providing a therapeutic option for otherwise untreatable patients, offering patients a relatively good quality of life, and requiring fewer co-medications. Nonetheless, selection of an IL-2 treatment modality should be based on several patient-related considerations. Moreover, these two IL-2 treatment modalities need not be mutually exclusive.

Administration, Inhalation↗
PubMed2000

Overview of interleukin-2 inhalation therapy.

PURPOSE: Locoregional administration of interleukin (IL)-2, which acts physiologically as a local hormone, is an effective therapeutic modality. Diverse preclinical and clinical models have described methods of administration that expose tumor tissues to continuously high levels of cytokines. Regional administration of IL-2 that does not raise intravascular IL-2 levels induces local and systemic immunomodulation and produces objective local tumor responses. Most importantly, regional therapy is much less toxic than systemic IL-2 therapy. PATIENTS AND METHODS: We review clinical experiences using inhaled IL-2 therapy for the treatment of pulmonary metastases in roughly 300 patients with a variety of primary tumors. This includes our own 10-year single-institution experience with inhaled IL-2 therapy in the treatment of 188 metastatic renal cell carcinoma patients with progressive pulmonary metastases. Patients in our clinic are treated with 18 to 36 million IU of recombinant IL-2, administered 90% by inhalation and 10% subcutaneously, until disease progression. A variety of doses and schedules of inhaled IL-2 have been investigated alone and in combination with systemic therapies. RESULTS: Inhalation of IL-2 has been reported to prevent progression of pulmonary and mediastinal metastases of metastatic renal cell carcinoma, breast and ovarian carcinoma, and melanoma. Inhaled IL-2 alone is well tolerated; a dose-dependent cough is the major adverse event. A significant dose-dependent increase in lymphocytes and eosinophils has been observed in bronchoalveolar lavage in patients and animals. Dose and schedule can influence outcome. In a phase I trial using inhaled IL-2 alone in patients with a variety of primary malignancies, once-daily inhalation of IL-2 at doses up to 15 million IU/m2 was well tolerated but did not result in prolonged stabilization of pulmonary disease. In a multidose phase I trial, using 5-times-daily inhalation of natural IL-2, pulmonary lesions in three of 14 (21%) metastatic renal cell carcinoma patients responded, and a similar multicenter trial demonstrated a 29% response rate. Among 188 metastatic renal cell carcinoma patients treated with inhaled recombinant IL-2 at the Clinic Eppendorf, progression of pulmonary metastases was prevented in 68% of patients for a median duration of 7 months, and overall survival was significantly improved compared with expected survival (Elson's risk analysis; 17.2 vs 5.3 mo). All patients, including high-risk patients, appeared to benefit. Encouraging results have also been reported in patients with metastatic melanoma and gynecologic tumors when inhaled IL-2 was used as second-line therapy to treat pulmonary metastases. CONCLUSIONS: The efficacy of inhaled IL-2, alone or in combination with systemic immunotherapy, immunochemotherapy, or chemotherapy, has been documented in a variety of malignancies. All reports confirm low toxicity, thus providing important quality-of-life benefits. Moreover, patients not eligible for systemic IL-2 therapy may be treated with inhalation therapy.

Administration, Inhalation↗
PubMed2000

Detection of loss of heterozygosity in the p53 tumor-suppressor gene with PCR in the urine of patients with bladder cancer.

PURPOSE: Detection of loss of heterozygosity (LOH) has been described in various carcinomas on the basis of meticulous molecular techniques. Because of lack of simple and rapid techniques, LOH has not achieved common use in routine tumor diagnosis. A recently found variable number of tandem repeats (VNTR) segment in intron 1 of the p53 gene was described as highly polymorphic and therefore useful in detecting LOH. We used a rapid technique for detection of LOH in the p53 gene of patients with transitional cell carcinoma (TCC) of the bladder. The technique was based on the polymerase chain reaction (PCR) and agarose gel electrophoresis as described for other carcinomas previously. We evaluated whether TCC screening and surveillance could be performed detecting LOH in the urinary sediment. MATERIALS AND METHODS: We investigated 29 patients with TCC of the bladder (pTa 12 patients; pT1 10 patients; pT2 - pT4 seven patients; grade 1 one patient; grade 2 19 patients; grade 3 nine patients). DNA was prepared by standard methods from white blood cells, tumor tissue, normal bladder mucosa, and urinary sediments. The amplification of the VNTR region was performed with PCR. PCR products were run in parallel lanes on 4.5% agarose gels. RESULTS: Of the 29 patients, 23 (79.3%) were found to have two different alleles ("informative cases") for the VNTR region. Of the 23 informative cases LOH was detected in the tumor tissue of 10 patients (43.5%). Referring to the total population 10 of 29 patients (34.4%) revealed LOH. In all patients with LOH in the tumor, LOH was also detected in the urinary sediment. LOH was not detected in the histologically benign bladder mucosa. CONCLUSION: We present a simple and rapid technique based on PCR and agarose gel electrophoresis for the detection of LOH in tumor and urinary sediment of patients with TCC of the bladder. The ability to detect LOH not only in tumor tissue but also in urinary sediment offers an attractive approach for noninvasive diagnosis and surveillance of bladder cancer patients.

Carcinoma, Transitional Cell↗
PubMed1999

[Treatment of pulmonary metastases from kidney cell carcinoma with inhalational interleukin-2. 10-year experience Hamburger Unicenter].

Systemic immunotherapy, notably with interleukin-2 (IL-2) and interferon-alpha (IFNalpha), has yielded a response rate of 10 % to 30 % in metastatic renal cell carcinoma. However, systemic immunotherapy is limited by severe side effects, and long-lasting response is rare. Tumor palliation and quality-of-life are important end points for evaluating the clinical benefits of immunotherapy. Experimental and clinical treatment models have proved that local IL-2 application is less toxic than systemic treatment and is therapeutically effective. Here we report long-term experience with inhalation IL-2 therapy in 188 patients who had progressive pulmonary metastatic renal cell carcinoma. High-dose inhalation of IL-2 was used with low-dose systemic IL-2 or IFNalpha. Maximal toxicity over the total treatment time was mild, and the low incidence of WHO grade 3 toxicity (24 %) allowed social activities and performance of social roles. Comedication for systemic side effects was required only in half of the patients. Inhaled IL-2 prevented progress of pulmonary metastases in 68 % of patients for a median period of 9.8 months. Median survival was 12.4 months compared with the expected 5.3 months and quality-of-life did not differ substantially from pretreatment status. Local treatment can be applied alone or in combination with systemic therapy and can increase therapeutic efficacy.

Administration, Inhalation↗
PubMed1999

Significance and metabolism of complexed and noncomplexed prostate specific antigen forms, and human glandular kallikrein 2 in clinically localized prostate cancer before and after radical prostatectomy.

PURPOSE: We studied plasma concentrations and elimination rates of prostate specific antigen (PSA) complexed to alpha1-antichymotrypsin and alpha2-macroglobulin, free PSA, total PSA (free PSA plus PSA alpha1-antichymotrypsin) and human glandular kallikrein 2 before, during and after radical retropubic prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: Plasma was collected and frozen within 10 minutes after sampling from 18 patients undergoing radical retropubic prostatectomy for prostate cancer. One sample was drawn preoperatively. Subsequent sampling intervals were 5 to 20 minutes perioperatively, 2 to 4 hours during the first 12 postoperative hours and 24 to 48 hours until postoperative day 14. Free PSA, PSA alpha1-antichymotrypsin, total PSA, PSA alpha2-macroglobulin and human glandular kallikrein 2 were measured with time resolved immunofluorometric assays. RESULTS: Preoperatively PSA alpha2-macroglobulin was undetectable (less than 2 ng./ml.) in 17 of 18 patients. Human glandular kallikrein 2, free PSA and total PSA but not PSA alpha1-antichymotrypsin were significantly higher in patients with extraprostatic cancer (pT3a-pT4a, pN1) compared to those with organ confined cancer (pT2a/b). Surgical manipulation of the prostate caused no detectable elevation of human glandular kallikrein 2, PSA alpha1-antichymotrypsin or PSA alpha2-macroglobulin. In contrast, a mean 9.6-fold increase (range 3.4 to 22) in free PSA was noted 5 minutes after prostatectomy. Free PSA was eliminated from plasma in a biphasic exponential pattern with an early plasma half-life of 55 minutes and a late plasma half-life of 18 hours. PSA alpha1-antichymotrypsin decreased slowly, whereas human glandular kallikrein 2 was detectable only 12 hours after prostatectomy. PSA alpha2-macroglobulin remained at insignificant, nondetectable concentrations during the entire perioperative and postoperative period. CONCLUSIONS: Release of free PSA contributes to the elevation of plasma total PSA after prostatectomy. Free PSA is enzymatically inactive as the release does not result in subsequent elevation of PSA alpha1-antichymotrypsin or PSA alpha2-macroglobulin. Biphasic exponential elimination of free PSA may be explained by rapid extracellular redistribution (early half-life) and glomerular filtration in the kidneys (late half-life). Our data suggest rapid metabolism of human glandular kallikrein 2 but do not support suggestions of the significance in vivo of complex formations with alpha2-macroglobulin as a major means to eliminate PSA from plasma in patients with clinically localized prostate cancer.

Aged↗
PubMed1999

Early prostate-specific antigen relapse after radical retropubic prostatectomy: prediction on the basis of preoperative and postoperative tumor characteristics.

OBJECTIVES: This study was undertaken to distinguish between patients who will and will not benefit from a retropubic radical prostatectomy (RRP) for clinically localized prostatic carcinoma (PCa) on the basis of preoperative and postoperative tumor characteristics. METHODS: Data of 318 consecutive patients who underwent RRP for clinically localized PCa were reviewed. Preoperative characteristics used included clinical stage, findings on transrectal ultrasonography, prostate-specific antigen (PSA) values, Gleason grade, number of positive biopsies, number of biopsies containing any Gleason grade 4 and/or 5 cancer, and number of biopsies with predominant (>50% of cancerous tissue) Gleason grade 4 and/or 5 cancer. Postoperative characteristics included pathologic stage, Gleason grade, margin status, cancer volume, and volume of Gleason grade 4 and/or 5 cancer. The impact on biochemical relapse after RRP were calculated by Cox regression and CART (classification and regression tree) analysis to establish low, intermediate, and high risk of recurrence. RESULTS: Of patients who underwent RRP, 66% showed no evidence of relapse after a follow-up of 42 months. All preoperative and postoperative characteristics showed a significant association with biochemical relapse. Cox regression of preoperative characteristics showed the number of positive biopsies with predominant Gleason grade 4 and/or 5 cancer to be the most accurate predictor of failure (p < 0.0001), followed by the number of positive biopsies and PSA. CART analysis distinguished between four risk groups on the basis of the same characteristics as in the Cox regression. The low-risk group consisted of 232 patients (75.1%) and the high-risk group of 17 patients (5.5%); corresponding Kaplan-Meier curves showed a 2-year PSA-free survival rate of 97% for the low-risk group and 20% for the high-risk group. Cox regression of postoperative characteristics recognized the volume of Gleason grade 4 and/or 5 as the characteristic with the strongest association with biochemical failure. CART analysis distinguished between four risk groups, using the volume of high-grade cancer as the most influential characteristic. The corresponding Kaplan-Meier curves showed for the low-risk group (n = 79; 29.6%) a PSA-free survival rate of 96% after 42 months and for the high-risk group (n = 47; 17.6%) a 21% PSA-free survival rate after 42 months. CONCLUSION: For preoperative and postoperative estimation of biochemical recurrence after RRP, a quantitative analysis of high-grade cancer, expressed by the number of preoperative biopsy cores containing high-grade cancer and the volume of cancer, proved to be the best predictor of relapse. CART analysis might be useful in advising patients for their best therapy options. However, defined characteristics of risk groups should be evaluated with new prospective data before they are used routinely.

Adenocarcinoma↗
PubMed1999

Subjective and objective prospective, long-term analysis of quality of life during inhaled interleukin-2 immunotherapy.

PURPOSE: We conducted both a subjective and objective, prospective quality-of-life analysis during high-dose (36 x 10(6) immunizing units/d) inhalational interleukin (IL)-2 treatment (mean treatment time, 13.4 months) of 15 patients with metastatic renal cell carcinoma (mRCC). Additionally, quality of life for 10 patients with mRCC receiving low-dose (9 x 10(6) IU/m(2)/d for 5 days) intravenous IL-2 treatment also was evaluated. PATIENTS AND METHODS: Patients responded to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire QLQ-C30 before and during inhalational IL-2 treatment at 1, 3, 6, 9, and 12 months and before and once during intravenous IL-2 treatment. A clinician assessed patient well-being using the Quality of Well-Being scale to calculate once weekly quality-adjusted life-years (QALYs) during inhalational IL-2 treatment. RESULTS: Patients completed 103 questionnaires and clinicians performed 892 QALY calculations. For patients treated with inhalational IL-2, the mean quality-of-life score deteriorated modestly but significantly 1 month after treatment initiation (15.1%, P =.01) but did not differ significantly from pretreatment scores after 3, 6, 9, and 12 months of treatment. Inhalational IL-2 therapy stabilized patient quality of life for a mean of 13.4 months. The resulting QALY calculation for patients on inhalation IL-2 was 70.1% of 13.4 months, representing 9.4 months of QALY. In comparison, patients who received intravenous IL-2 showed a more marked, statistically significant deterioration in mean quality-of-life score during treatment (27%, P =.006); moreover, three of these 10 patients experienced treatment-related toxicity that prevented questionnaire completion. CONCLUSION: Quality-of-life analysis during immunotherapy provides valuable information regarding cancer treatment outcomes.

Activities of Daily Living↗
PubMed1999

Ultrasensitive detection of prostate specific antigen in the followup of 422 patients after radical prostatectomy.

PURPOSE: We validated our ultrasensitive prostate specific antigen (PSA) assay based on lyophilization and 4-fold concentration of patient sera with the clinical long-term followup and according to histopathological characteristics of 422 patients treated with radical retropubic prostatectomy for prostate cancer. MATERIALS AND METHODS: Each serum sample was divided into 2 aliquots for standard and 4-fold concentrated (ultrasensitive) detection. Samples were analyzed by the same unmodified DPC-Immulite PSA assay. Biochemical relapse was defined as an increase of at least 0.10 ng./ml. in native serum (equivalent to 0.025 ng./ml. in concentrated serum). Mean followup was 449 days (range 29 to 2,057). Kaplan-Meier analysis of standard and ultrasensitive detection results was done, and findings were correlated with pathological stage, Gleason grade, total cancer volume, Gleason grade 4 cancer volume and margin status. Significance of earlier detection in ultrasensitive versus standard detection was calculated with the log rank (Mantel-Cox) test with p <0.05 considered significant. RESULTS: Of 442 patients 88 (20.8%) experienced biochemical recurrence. Of this cohort 28 (31%) demonstrated early failure on the ultrasensitive assay which was later confirmed on the standard assay, 37 (42%) had failure simultaneously on both assays and 23 (26%) had failure on the ultrasensitive but remained disease-free on the standard assay. Average time for ultrasensitive assay detection of recurrence was 288 days (standard 555). Kaplan-Meier analysis revealed significant advantages in earlier detection of recurrence with the ultrasensitive assay, and close correlation with pathological stage, Gleason grade, margin status and Gleason grade 4 cancer volume. Time advantages of ultrasensitive versus standard detection were greater for advanced cancers (pT3a/b or greater, Gleason 3 + 4 or greater) than for small, low grade tumors. All patients who had positive results on the standard assay had a previous (28) or simultaneous (37) positive ultrasensitive result. With standard detection 25% of all relapses were evident within the first year of surgery and with ultrasensitive detection the percentage increased to 85.7%. On both assays 334 patients remained free of biochemical recurrence. CONCLUSIONS: Our ultrasensitive PSA assay is useful for early detection of biochemical relapse after radical retropubic prostatectomy. It not only provides the same accuracy as conventional PSA assays but also offers the advantage of detecting recurrence about 300 days earlier. Thus, long-term results of radical retropubic prostatectomy series can be calculated sooner. The clinical impact of this assay will be obvious once curative treatment options are available if applied at the earliest time of evident tumor recurrence.

Follow-Up Studies↗