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Hans von der Maase

Publications and source records attributed to Hans von der Maase.

At least 19 recordsLinked to original sources
PubMed2006

Impact of immune parameters on long-term survival in metastatic renal cell carcinoma.

PURPOSE: The purpose of this study was to evaluate the impact of immunologic prognostic factors in combination with established clinical prognostic factors in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: A total of 120 consecutive patients with mRCC received interleukin-2 (IL-2) -based immunotherapy. Baseline tumor biopsies were available from 85 of these patients. Potential prognostic factors were analyzed by univariate and multivariate analyses. RESULTS: Multivariate analysis (N = 120) identified high lactate dehydrogenase, lymph node metastases, low hemoglobin, low Karnofsky performance status, and bone metastases as independent poor prognostic clinical factors. The impact of these clinical factors has been demonstrated by others. Multivariate analysis (n = 85) also identified a high blood neutrophil count (> 6.0 x 10(9)/L; hazard ratio, 2.0; P = .015), the presence of intratumoral neutrophils (> 0 cells/mm2 tumor tissue; hazard ratio, 2.3; P = .001), and low intratumoral CD57+ natural killer cell count (< 50 cells/mm2 tumor tissue; hazard ratio, 2.1; P = .01) as independent poor prognostic immunologic factors. These three independent immunologic parameters had significant discriminatory power as supplemental risk factors in prognostic models based on the clinical risk factors, identifying subgroups within the favorable clinical group with estimated 5-year survival rates of 60%, 25%, and 0%, respectively. These findings were apparent in both our own prognostic model and in an extended Memorial Sloan-Kettering Cancer Center (New York, NY) prognostic model. CONCLUSION: This study points on five clinical and three supplemental immunologic independent prognostic factors of survival in patients with mRCC receiving IL-2.

Adult↗
PubMed2006

Screening for Y microdeletions in men with testicular cancer and undescended testis.

PURPOSE: To investigate a possible association between testicular cancer or undescended testis and Y microdeletions. METHODS: It was designed as a retrospective clinical study. A total of 225 men with testicular cancer or undescended testis were included to study. Fertile men (n = 200) were investigated as a control. Genomic DNA, which was extracted from blood samples were investigated with a fluorescent multiplex PCR protocol for screening for Y microdeletions. RESULTS: A single STS missing was found in eight men; one from the control group (sY153), seven from the patients group. The positive cases showed a single STS missing of marker sY153 and sY139 in testicular cancer (6/185) and undescended testis (1/40) patients, respectively. CONCLUSIONS: Since no contiguous, real Y microdeletions were found in the study population, it seems that Y microdeletions are not a likely common etiological cause of poor spermatogenesis in testicular cancer and undescended testis. However, it remains to be determined whether men having a single STS missing have a risk of developing testis cancer or having undescended testis.

Adult↗
PubMed2006

Elevated serum level of YKL-40 is an independent prognostic factor for poor survival in patients with metastatic melanoma.

BACKGROUND: YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. Cancer cells, macrophages, and neutrophils secrete YKL-40. Its function in cancer is unknown. High serum YKL-40 levels have been associated with a poor prognosis in patients with several solid tumors. The prognostic impact of serum YKL-40 in metastatic melanoma was evaluated. METHODS: YKL-40 was measured in serial serum samples from 110 patients with metastatic melanoma obtained immediately before and during treatment and from 245 healthy subjects. RESULTS: Patients had higher serum YKL-40 values than healthy subjects (P < 0.001). Pretreatment serum YKL-40 was elevated in 45% of the patients and correlated to site of metastases (P = 0.03) and poor performance status (P = 0.002). Multivariate Cox analysis showed that serum YKL-40 (hazard ratio [HR] = 1.9; 95% confidence interval [CI], 1.2-2.8; P = 0.004) and serum lactate dehydrogenase (LDH) (HR = 1.9; 95% CI, 1.2-2.9; P = 0.004) were independent prognostic factors for survival. A combination variable of elevated serum YKL-40 and LDH quadrupled the risk of early death (HR = 4.4; 95% CI, 2.5-7.7; P < 0.001) compared with patients with normal levels. The combination of YKL-40 and LDH had a stronger prognostic impact than the American Joint Committee on Cancer (AJCC) Stage IV classification. Furthermore, serum samples were available from 12 patients during followup. In 9 of 11 patients a significant increase in serum YKL-40 was observed together with disease progression. In one patient with a lasting complete response, serum YKL-40 remained normal. CONCLUSIONS: An elevated serum YKL-40 was an independent prognostic factor for poor survival in patients with metastatic melanoma. When combining serum YKL-40 and LDH, patients could be separated into three prognostic groups based on the number of elevated biomarkers. The findings should be validated in an independent study.

Adipokines↗
PubMed2006

Adoptive transfer of allogeneic cytotoxic T lymphocytes equipped with a HLA-A2 restricted MART-1 T-cell receptor: a phase I trial in metastatic melanoma.

PURPOSE: We did a phase I dose-escalation trial to evaluate the feasibility and safety of intratumoral injections of C Cure 709, an allogeneic, continuous CTL cell line that, restricted by HLA-A2, recognizes MART-1-positive tumor cells through transduction with a T-cell receptor encoding gene. EXPERIMENTAL DESIGN: Cells were administered intratumorally in four dose levels ranging from 10(8) to 10(9) cells/d on days 1, 4, 7, 10, 14, and 28 of each treatment cycle to patients with metastatic melanoma. Main inclusion criteria were HLA-A2 tissue type, MART-1-positive tumor cells, and metastases suitable for ultrasound-guided injections. Patients were assessed for toxicity and response. Three to six patients were treated per dose level. Patients without progressive disease were offered up to three treatment cycles. RESULTS: Fifteen patients received a total of 24 treatment cycles with a total of 266 injections of C Cure 709. Toxicity was minor to moderate and most common injection site reactions were fever, fatigue, nausea/vomiting, and arthralgia/myalgia. Side effects disappeared in general within 24 hours. Toxicity was not dose dependent. One patient obtained a partial response, encompassing both metastases used and not used for intratumoral injections. Remaining patients did not achieve an overall response. In addition, we observed local regression of metastases used for injection in two patients and of metastases not used for injection in one patient. CONCLUSION: Intratumoral injections of C Cure 709 are feasible, safe, and capable of inducing tumor regression. Further investigation in a phase II setting is warranted.

Adult↗
PubMed2006

Serum YKL-40 predicts relapse-free and overall survival in patients with American Joint Committee on Cancer stage I and II melanoma.

PURPOSE: To evaluate the novel tumor biomarker YKL-40 in serial serum samples from patients with American Joint Committee on Cancer (AJCC) stage I and II melanoma from the time of diagnosis and during routine follow-up. Macrophages, neutrophils, and cancer cells secrete YKL-40, and a high serum level has been associated with poor prognosis in patients with several cancer types. PATIENTS AND METHODS: Serum samples from 234 patients with stage I (n = 162) and II (n = 72) melanoma were analyzed for YKL-40 by enzyme-linked immunosorbent assay. Serial samples were obtained before definitive primary surgery and during follow-up. RESULTS: After a median follow-up period of 66 months (range, 1 to 97 months), 41 relapses (18%) and 39 deaths (17%) were observed. Serum YKL-40 treated as an updated continuous covariate were analyzed together with the covariates sex, age, primary tumor site, ulceration, thickness, Clark level and histologic subtype in a Cox proportional hazard model. Serum YKL-40 was an independent prognostic factor of relapse-free survival (hazard ratio [HR], 1.6; 95% CI, 1.1 to 2.5; P = .03) and overall survival (HR, 1.8; 95% CI, 1.2 to 2.6; P = .002) together with thickness and ulceration. The serum level of YKL-40 (dichotomized as normal or elevated) at the time of diagnosis was also an independent prognostic factor for overall survival (HR, 3.6, 95% CI, 1.7 to 7.7; P = .001). CONCLUSION: Serum YKL-40 may be an early biomarker of relapse and survival in patients with AJCC stage I and II melanoma. Serum YKL-40 may also be useful for patient stratification and follow-up in clinical trials. Our results need confirmation in an independent study.

Adipokines↗
PubMed2006

Circulating tyrosinase and MART-1 mRNA does not independently predict relapse or survival in patients with AJCC stage I-II melanoma.

The detection of melanoma cells in peripheral blood has been proposed to select patients with a high risk of relapse. In this study, tyrosinase and melanoma antigen recognized by T cells 1 (MART-1) mRNA expression was evaluated in serial samples obtained before definitive surgery and during follow-up in patients with American Joint Committee on Cancer stage I-II melanoma. Serial samples (n=2,262) were collected from 236 patients from 1997 to 2002. Analyses of the RNA samples were performed with a calibrated reverse transcriptase-PCR assay. Gender, age, primary tumor site, ulceration, thickness, Clark level, and histological subtype were analyzed together with tyrosinase and MART-1 mRNA treated as updated covariates in a Cox proportional-hazard model. After a median follow-up time of 66 months, 42 out of 236 patients (18%) had relapsed. The following variables were significantly associated with relapse-free survival in the univariate analyses: tyrosinase, MART-1, gender, ulceration, thickness, Clark level, and histological subtype. Entering these covariates into a multivariate Cox analysis resulted in thickness as the single independent prognostic factor (P<0.0001), whereas MART-1 (P=0.07) approached significance at the 5% significance level. The serial measurements of tyrosinase and MART-1 mRNA in peripheral blood of stage I-II melanoma patients cannot be demonstrated to have independent prognostic impact on relapse-free survival.

Adult↗
PubMed2006

Tumour-associated macrophages are related to progression in patients with metastatic melanoma following interleukin-2 based immunotherapy.

The aim of the present study was to analyze whether leukocyte subsets in peripheral blood and tumour biopsies obtained before treatment were able to predict response or survival in patients with metastatic melanoma following Interleukin-2 (IL-2) based immunotherapy. Flow cytometry was performed on peripheral blood for CD4(+) T cells, CD8(+) T cells and CD56(+) natural killer (NK) cells. Immunohistochemical analyses were used to identify CD4(+) T cells, CD8(+) T cells, CD57(+) NK cells and CD64(+) (macrophages) cells in tumour biopsies. High numbers of tumour-associated CD64(+) macrophages in tumour biopsies were statistically significantly associated with poor response to treatment. Our data suggest that tumour-associated macrophages may correlate negatively with response, which may be of biological importance for IL-2 based immunotherapy of malignant melanoma.

Adult↗
PubMed2006

Radical radiotherapy for urinary bladder cancer: treatment outcomes.

The exact value of radiotherapy in the treatment of muscle-invasive bladder cancer is difficult to establish, as most studies exploring this issue are retrospective with different procedures for selecting patients for treatment, as well as varying treatment strategies. An estimate of the 5-year overall survival rate following radiotherapy is approximately 35% in consecutive-selected patients and approximately 25% in negative-selected patients.

Dose Fractionation, Radiation↗
PubMed2005

A phase II trial of low-dose total body irradiation and subcutaneous interleukin-2 in metastatic melanoma.

BACKGROUND AND PURPOSE: Our own experimental data suggests a therapeutic synergism between low-dose total body irradiation (LTBI) and interleukin-2 (IL-2). PATIENTS AND METHODS: Forty-five patients received a maximum of 2 cycles of high dose subcutaneous (s.c.) IL-2 and LTBI. One treatment cycle included 5 weeks treatment followed by 2 weeks break and composed of a single radiation fraction 0.1 Gy on days 1, 8, 22 and 30 and IL-2: 18 MU x 2 daily s.c. on days 2 to 5 and days 16-19 as well as 9 MU x 2 daily s.c. on days 9-12 and 31-34. In 17 patients, flow cytometric analyses of the various subpopulations of immune cells were done on blood samples before the first LTBI fraction and 24h after LTBI as well as after the first week of treatment. RESULTS: Two patients (4.4%) had a partial response (PR) and 13 patients (29%) had stable disease (SD). The duration of the partial remission and stable disease did not exceed 3 months. The median overall survival was 5.8 months (95% CI, 4-8 months). Thirty-four of the 58 treatment cycles (74%) were given in 100% of the intended dose without modification or delay. The dose was modified in 15 cycles (26%) because of progression (6), liver toxicity (3), CNS toxicity (2), thrombocytopenia (1), lung morbidity (1) and itching (1). There were no treatment-related deaths. Flowcytometry data showed a significant increase in the percentage of cells carrying the beta chain of IL-2 receptor (CD122+), a significant increase in the percentage of NK cells (CD56+ cells) as well as a significant reduction in the percentage of B cells (CD20+) and monocytes (CD14+). CONCLUSIONS: This LTBI and IL-2 regimen was well tolerated, however it cannot be recommended because of its low clinical efficacy. No indication of increased efficacy or altered toxicity was seen using LTBI.

Adult↗
PubMed2005

Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer.

PURPOSE: To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). PATIENTS AND METHODS: Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival. RESULTS: A total of 405 patients were randomly assigned: 203 to the GC arm and 202 to the MVAC arm. At the time of analysis, 347 patients had died (GC arm, 176 patients; MVAC arm, 171 patients). Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P = .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P = .53). The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC, with an HR of 1.09. The 5-year progression-free survival rates were 9.8% and 11.3%, respectively (P = .63). Significant prognostic factors favoring overall survival included performance score (> 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (<or= three), and the absence of visceral metastases. By adjusting for these prognostic factors, the HR was 0.99 for overall survival and 1.01 for progression-free survival. The 5-year overall survival rates for patients with and without visceral metastases were 6.8% and 20.9%, respectively. CONCLUSION: Long-term overall and progression-free survival after treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.

Antimetabolites, Antineoplastic↗
PubMed2005

A phase II trial of R115777, an oral farnesyl transferase inhibitor, in patients with advanced urothelial tract transitional cell carcinoma.

BACKGROUND: R115777 is a potent farnesyl transferase inhibitor and has significant antitumor effects in vitro and in vivo. METHODS: The objective of the current study was to determine the objective response proportion in patients with metastatic transitional cell carcinoma (TCC) of the urothelial tract who received treatment with R115777 at a dose of 300 mg orally given twice daily for 21 days followed by 7 days of rest for every 4-week cycle. Thirty-four patients with TCC were enrolled in this Phase II study. Patients were allowed to have received a maximum of one prior systemic chemotherapy regimen, not including chemoradiation or neoadjuvant chemotherapy. All patients were required to have an Eastern Cooperative Oncology Group performance status of 0-2 and adequate bone marrow, hepatic, and kidney function. RESULTS: Twice daily administration of oral R115777 was tolerated well. R115777 was absorbed rapidly after oral administration. Grade 3-4 neutropenia (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in 5 patients (15%). Grade 3-4 nonhematologic toxicity was rare, consisting of rash and diarrhea in 1 patient each. Two patients (6%) without prior chemotherapy demonstrated partial responses. Thirteen patients (38%) achieved disease stabilization according to World Health Organization criteria that lasted a median of 4 months. No complete responses were observed. CONCLUSIONS: The objective response rate of R115777 was not sufficient to warrant future investigation in TCC as a single agent. Preliminary evidence of the activity of R115777 in 2 chemotherapy-naive patients may warrant further investigation in combination with first-line chemotherapy.

Administration, Oral↗
PubMed2005

High-density single nucleotide polymorphism array defines novel stage and location-dependent allelic imbalances in human bladder tumors.

Bladder cancer is a common disease characterized by multiple recurrences and an invasive disease course in more than 10% of patients. It is of monoclonal or oligoclonal origin and genomic instability has been shown at certain loci. We used a 10,000 single nucleotide polymorphism (SNP) array with an average of 2,700 heterozygous SNPs to detect allelic imbalances (AI) in 37 microdissected bladder tumors from 17 patients. Eight tumors represented upstaging from Ta to T1, eight from T1 to T2+, and one from Ta to T2+. The AI was strongly stage-dependent as four chromosomal arms showed AI in > 50% of Ta samples, eight in T1, and twenty-two in T2+ samples. The tumors showed stage-dependent clonality as 61.3% of AIs were reconfirmed in later T1 tumors and 84.4% in muscle-invasive tumors. Novel unstable chromosomal areas were identified at chromosomes 6q, 10p, 16q, 20p, 20q, and 22q. The tumors separated into two distinct groups, highly stable tumors (all Ta tumors) and unstable tumors (2/3 muscle-invasive). All 11 unstable tumors had lost chromosome 17p areas and 90% chromosome 8 areas affecting Netrin-1/UNC5D/MAP2K4 genes as well as others. AI was present at the TP53 locus in 10 out of 11 unstable tumors, whereas 6 had homozygous TP53 mutations. Tumor distribution pattern reflected AI as seven out of eight patients with additional upper urinary tract tumors had genomic stable bladder tumors (P < 0.05). These data show the power of high-resolution SNP arrays for defining clinically relevant AIs.

Allelic Imbalance↗
PubMed2005

Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma.

BACKGROUND AND PURPOSE: The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial. PATIENTS AND METHODS: Twenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15 Gyx3 within 5-10 days. RESULTS: Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach. CONCLUSIONS: SRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma.

Adenocarcinoma↗
PubMed2005

Tyrosinase messenger RNA in peripheral blood is related to poor survival in patients with metastatic melanoma following interleukin-2-based immunotherapy.

This study was conducted to examine the prognostic impact of four biomarkers [tyrosinase and MART-1 messenger RNA (mRNA), S100beta protein and lactate dehydrogenase (LDH)] in patients with metastatic melanoma, together with established clinical factors. Tyrosinase and MART-1 mRNA were measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). S100beta was measured using a commercially available immunoassay, and LDH was analysed conventionally. All markers were measured in blood samples before interleukin-2-based immunotherapy in 85 patients with metastatic melanoma. LDH, S100beta, tyrosinase, number of metastatic sites, location of metastatic sites and performance status were all significant factors for survival in univariate analyses. In multivariate analysis, tyrosinase [hazard ratio (HR)=1.6; 95% confidence interval (CI), 1.1-2.6; P=0.04] and LDH (HR=2.0; 95% CI, 1.1-3.5; P=0.02) were both independent prognostic factors for survival. A combination variable of tyrosinase and LDH remained independently associated with survival (P=0.04) after adjusting for the American Joint Committee on Cancer (AJCC) stage IV classification in a multivariate analysis involving both models. It can be concluded that tyrosinase mRNA and elevated LDH are independent prognostic factors for poor survival in this group of 85 patients. Additional studies are needed before the prognostic value of tyrosinase mRNA in metastatic melanoma can be firmly established. Further evaluation of the combined measurement of tyrosinase mRNA and LDH is warranted.

Adult↗