Biomedical subjects

M Molls

Publications and source records attributed to M Molls.

At least 19 recordsLinked to original sources

PubMed2007

Squamous cell carcinoma and Zenker diverticulum.

Squamous cell carcinoma in a Zenker diverticulum is a very rare condition. We report a case of a patient with a Zenker carcinoma, who was primarily functionally inoperable and therefore received neoadjuvant radiochemotherapy before cardiac bypass surgery. After a complicated course with cardiogenic shock and myocardial infarction, a re-evaluation of functional risk analysis and the tumor situation revealed operability. Subsequently, partial hypopharyngectomy and partial cervical esophageal resection with lymphadenectomy was performed. Reconstruction of the gastrointestinal continuity was made by interposition of a free small bowel graft and microvascular anastomosis. The postoperative course showed a small anastomotic leakage of the hypopharyngeal-small bowel anastomosis, which was successfully treated conservatively.

Aged↗

PubMed2006

Intercellular adhesion molecule-1: a consistent inflammatory marker of the cutaneous radiation reaction both in vitro and in vivo.

BACKGROUND: Radiation damage to skin is a key diagnostic and prognostic parameter for patients accidentally exposed to radiation. Moreover, skin is a target organ for crucial side-effects of routine radiotherapy. The pathophysiology of the cutaneous radiation reaction is in many respects still unknown. The acute inflammatory radiation reaction of skin has been shown to involve alterations in cell-cell and cell-matrix interactions, which are mediated by cellular adhesion molecules. OBJECTIVES: To evaluate the effect of ionizing radiation on intercellular adhesion molecule-1 (ICAM-1) expression in human skin cells. METHODS: Dermal monolayer cells, a three-dimensional skin model and skin biopsies were investigated for ICAM-1 expression after ionizing radiation using flow cytometry, quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. ICAM-1 expression in monolayer cells pretreated with protein kinase inhibitors and dexamethasone prior to irradiation was analysed by flow cytometry. RESULTS: Using different sources of skin cells, we demonstrated a consistent upregulation of both ICAM-1 mRNA and protein expression by ionizing radiation. Blocking experiments revealed that tumour necrosis factor-alpha, another ICAM-1 inducer, does not account for the effect of radiation. Radiation-induced upregulation of ICAM-1 expression was significantly attenuated by inhibitors to protein kinase C, mitogen-activated protein (MAP) ERK kinase, p38 MAP kinase and phosphatidylinositol 3-kinase. The anti-inflammatory agent dexamethasone suppressed the effect of radiation on ICAM-1 expression, suggesting its usefulness to treat the cutaneous radiation reaction. CONCLUSIONS: Our data suggest that ICAM-1 is a consistent inflammatory parameter of the cutaneous radiation reaction both in vitro and in vivo that might provide new therapeutic options for diagnosis and treatment of effects of radiation.

Aged↗

PubMed2004

Responders benefit from neoadjuvant radiochemotherapy in esophageal squamous cell carcinoma: results of a prospective phase-II trial.

BACKGROUND: We present the results of a prospective phase-II-study of neoadjuvant combined radiochemotherapy followed by surgical resection in patients with histological proven locally advanced squamous cell carcinoma of the esophagus located at or above the level of the tracheal bifurcation. METHODOLOGY: Between February 1995 and March 2000 a total of 76 patients with esophageal squamous cell carcinoma (uT3/4N0/+-categories) received simultaneous combined neoadjuvant radiochemotherapy consisting of a continuous intravenous infusion of 5-fluorouracil (300 mg/m2/day) 7 day per week concurrently with conventional fractioned external beam radiation therapy (2 Gy/day), five fractions per week up to a total dose of 30 Gy. RESULTS: Radiochemotherapy related acute severe toxicity rate (CTC-grade-III) occurred in 34 patients, two patients died. Sixty-four patients underwent surgery with a complete resection in 48 patients. Three patients died during a 90-day post-operative course. The histopathological workup revealed no viable residual tumour cells in eight patients (ypCR) and according to the modified criteria of Mandard in 26 patients a histopathological response. Twenty-two of these patients underwent a R0-resection. The median follow-up time was 5.4 years with an overall median survival time of 20.6 months. The median survival in the 26 responders was 32.3 months versus 19.5 months in 38 non-responders (p=0.03). CONCLUSIONS: Patients with locally advanced squamous cell carcinoma of the esophagus, who respond to preoperative neoadjuvant combined radiochemotherapy, seem to have more benefit from subsequent resection than non-responding patients.

Adult↗

PubMed2003

[Indications for neoadjuvant therapy in rectal carcinoma].

Pre- and postoperative adjuvant treatments for locally advanced, operable (R0 resection) rectum carcinoma have led to improved results. In principle, according to the interdisciplinary consensus of the German Cancer Society, the recommended treatment for rectum carcinoma (T3/4; N0; M0; any T stage; N+; M0) is still postoperative adjuvant radiochemotherapy. In the meantime, however, based on the good results obtained from various clinical trials preoperative adjuvant treatment is favored internationally. Not only does this treatment scheme show a comparably better compliance of the patients but it also seems to be better tolerated. One treatment option for resectable T3 tumors immediately followed by surgery is the sole hypofractionated preoperative 3-4 field external beam radiotherapy. An additional benefit can be expected from protracted preoperative radiochemotherapy (single dose 2 Gy, total dose >40 Gy, chemotherapy based on 5-FU) followed by operation several weeks later. For T4 tumors with expected R1 or R2 resection, preoperative treatment is urgently recommended. A further aim in compliance with the surgical approach (R0 resection!) and multimodal treatment may be for individual cases the preservation of continence.

Antineoplastic Agents↗

PubMed2003

Influence of differing radiotherapy strategies on treatment results in diffuse large-cell lymphoma: a review.

In the absence of evidence from randomised trials, radiation treatment of diffuse large-cell lymphoma of B-cell type represents an area of controversy with considerable differences in patterns of practice. The present literature survey aims at clarification of the role of radiotherapy in combined modality settings by identification of dose-response relationships, predictive factors for local control, and potential pitfalls in the interpretation of retrospective studies. Radiotherapy might increase local control in initially involved areas and is usually delivered to these sites (involved-field treatment). Combined modality treatment is currently recommended for patients in stage I or II if they are not treated in the context of prospective studies. Whether involved-field consolidation radiotherapy after systemic treatment in patients with bulky, stage III-IV lymphomas should be routinely recommended is presently unclear. Definition of bulky disease is arbitrary and varied between 6 and 10cm, reflecting a considerable difference in the number of clonogenic tumour cells. Several retrospective and one prospective randomised study suggest improved disease-free and overall survival by radiotherapy in advanced stages. The 5-year local control by radiotherapy was 93-98%. Currently, we recommend the following minimum doses for involved-field radiotherapy derived from this literature survey. Lymphomas with initial size <3.5 cm (possibly <6 cm) can be treated with 30 or 30.6Gy when a complete remission (CR) has been achieved by chemotherapy. The next group might be sufficiently controlled by 36Gy, but it remains unclear whether the cut-off should be 6cm or higher. Forty Gy appears to control tumours in the range of 7-10cm. Most likely, 45Gy does not have to be exceeded for larger lesions. Data on those with less than CR are contradictory. Judging the amount of viable tumour in these patients is problematic, but crucial to determine the intensity of further treatment. The value of positron emission tomography is still under investigation. Because the difference between doses of 30 and 40Gy might actually make a difference for the long-term toxicity of radiotherapy in some of the normal tissues and organs at risk (salivary glands, orbital structures, lung, heart, etc.), it appears prudent to resolve the open questions in prospective trials with careful documentation of side effects.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Report of a male patient with brain metastases from breast cancer.

As in female patients, the clinical course in male patients with breast cancer is determined mainly by tumor stage. The literature contains very limited data on either the occurrence or the treatment of CNS metastases. This paper presents the case report of a 69-year-old man with multiple brain metastases 7 years after a diagnosis of lymph-node positive breast cancer, which had earlier already spread to the bones and liver. Whole-brain irradiation with a total dose of 30Gy resulted in palliation of symptoms. Nevertheless, survival was very short (7 weeks from diagnosis). Patients with metastatic breast cancer are at risk for the development of brain metastases. When performance status is poor the survival of patients with brain metastases is very limited. Treatment recommendations are the same as those for female patients with brain metastases from breast cancer.

Aged↗

PubMed2002

[Quality management and experiences with the "cancer center"].

BACKGROUND: The goal of quality management in oncology is to achieve the best possible therapeutic outcome. Improved diagnostic methods, more sophisticated therapies in various fields of specialisation and the increased implementation of multimodal therapies have led to considerable advances in the treatment of certain tumors in recent years. However, these advances depend on an interdisciplinary approach necessitating an increased division of labour. These in turn, because of the more complex organizational requirements within hospitals, make greater demands on quality management. METHODS: In October 1999 first steps were taken in the Klinikum rechts der Isar der TU München to organisationally integrate the various institutions involved in the treatment of patients with gastro-intestinal tumors. All the oncologic competence available was bundled in a Cancer Center thus creating the structural prerequisites for interdisciplinary quality management. A daily multidisciplinary Tumor Board, a computer-supported interdisciplinary information and communications system, an interdisciplinary Disease Management Team, an outpatients department and a study centre were all called into life. RESULTS: By the time the outpatients department went into service in November 2001 all the other structural innovations underlying interdisciplinary quality management had already been implemented. Since October 1999 2438 patients had been presented to the Tumor Board, 74% of them with primarily curative intent. CONCLUSIONS: The disease-oriented structure of the Cancer Center has proved worthwhile. The impact of the structure on the quality of processes and results, however, has yet to be evaluated.

Ambulatory Care↗

PubMed2002

Computer analysis of mFISH chromosome aberration data uncovers an excess of very complicated metaphases.

PURPOSE: To analyse spectra of chromosome aberrations induced in vitro by low LET radiation, in order to characterize radiation damage mechanisms quantitatively. METHODS: Multiplex fluorescence in situ hybridization (mFISH) allows the simultaneous identification of each homologous chromosome pair by its own colour. mFISH data, specifying number distributions for colour junctions in metaphases of human peripheral blood lymphocytes 72 hours after exposure in vitro to a 3 Gy gamma-ray dose, were combined with similar, previously published results. Monte Carlo computer implementations of radiobiological models for chromosome aberration production guided quantitative analyses, which took into account distribution of cells among different metaphases and lethal effects or preferential elimination of some aberrations at cell division. RESULTS AND CONCLUSIONS: Standard models of DNA damage induction/repair/misrepair explain the main trends of the data as regards the fraction of metaphases having a particular number of colours involved in colour junctions. However, all standard models systematically under-predict the observed fraction of metaphases where a large number of different chromosomes participate in aberrations. An early appearance of chromosomal instability could explain most of the discrepancies.

Chromosome Aberrations↗

PubMed2001

Fatigue, serum cytokine levels, and blood cell counts during radiotherapy of patients with breast cancer.

PURPOSE: To assess the level of fatigue during the course of adjuvant radiotherapy (RT) of breast cancer patients and its relation to anxiety, depression, serum cytokines, and blood count levels. METHODS AND MATERIALS: Forty-one patients who received adjuvant RT after breast-conserving surgery were prospectively studied. All patients underwent RT without concomitant chemotherapy. Patients rated their fatigue with two standardized self-assessment instruments, the Fatigue Assessment Questionnaire and a visual analog scale on fatigue intensity, before RT, during weeks 1-5 of RT, and 2 months after RT completion. In addition, the anxiety and depression levels were assessed with the Hospital Anxiety and Depression Scale. A differential blood cell count and the serum levels of the cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were determined in parallel to the fatigue assessments. RESULTS: Fatigue intensity as assessed with the visual analog scale increased (p <0.001) until treatment week 4 and remained elevated until week 5. Two months after RT, the values had fallen to the pretreatment levels. Fatigue measured with the Fatigue Assessment Questionnaire did not increase significantly during treatment, but the subscores on physical (p = 0.035) and cognitive (p = 0.015) fatigue were elevated during treatment weeks 4 and 5. Affective fatigue did not change significantly. Anxiety, as rated with the Hospital Anxiety and Depression Scale, declined during RT (p = 0.002), but the Hospital Anxiety and Depression Scale depression score did not change significantly. IL-1beta, IL-6, and tumor necrosis factor-alpha levels did not change during therapy and did not correlate with fatigue. Peripheral blood cell levels declined significantly during therapy and were still low 2 months after treatment. Until treatment week 5, lymphocytes were reduced to almost 50% of their initial values. Hemoglobin levels did not correlate with fatigue. CONCLUSIONS: We observed an increase in fatigue during adjuvant RT of patients with breast cancer. Fatigue returned to pretreatment levels 2 months after treatment. No evidence was found that anxiety, depression, serum levels of IL-1beta, IL-6, tumor necrosis factor-alpha, or declining hemoglobin levels were responsible for the treatment-induced fatigue.

Adult↗

PubMed2001

[Radiotherapy of prostate carcinoma].

As well as radical prostatectomy external body radiotherapy (EBRT) offers the chance of cure in non-metastasized prostate cancer. With total doses of 70 Gy or more, conventional fractionated RT can achieve 2-years biological no-evidence of disease (bNED) of more than 90% and about 50% in tumor stages with low and medium risk of metastases respectively. In early stages (T 1-2 Nx) recurrence free survival is after ten years 43-76%, in T1b-T2 pNO stages it is about 90% and comparable to those after radical prostatectomy. In T3-tumors recurrence free survival is from 32-42%. In randomized studies an advantage of conformal to conventional planned EBRT could be impressively demonstrated. Severe sequelae of the intestinal and urogenital tract could be seen in less than 5%, of treated patients. The value of combined hormonal and radiation therapy is not yet cleared. In early stages results by pure EBRT are convincing so that hormonal therapy might be superfluous. In locally advanced stages a preceding hormonal therapy might decrease the tumor volume by reducing the tumor cell load and, therefore, reduce the conformally irradiated volume. The irradiation of the pelvic or abdominal lymphatic drainage did not improve overall survival in published studies so far though improving the locoregional tumor control rates. Due to the large irradiated volume and simple radiation techniques sequelae were impressively increased. A participation in running national or international studies to clarify the value of postoperative EBRT, RT of pelvic lymph nodes, dose escalation and combined hormonal and radiation therapy will be reasonable.

Dose Fractionation, Radiation↗

PubMed2001

Tumor hypoxia, p53, and prognosis in cervical cancers.

BACKGROUND: The p53 protein is involved in the regulation of initiation of apoptosis. In vitro, p53-deficient cells do not respond to hypoxia with apoptosis as do p53-normal cells, and this may lead to a relative growth advantage of cells without a functioning p53 under hypoxia. On the basis of this hypothesis, a selection of cells with a functionally inactive p53 may occur in hypoxic tumors. The development of uterine cervical carcinomas is closely associated with infections of human papilloma viruses, which may cause a degradation of the tumor suppressor gene p53, resulting in a restriction of apoptosis. Thus, cervical cancers have often a functionally inactive p53. The purpose of our clinical study was therefore to investigate the association between p53, hypoxia, and prognosis in cervical cancers in which the oxygenation status can be determined by clinical methods. MATERIAL AND METHODS: Seventy patients with locally advanced squamous cell cervical cancer Stages IIB (n = 14), IIIB (n = 49), and IVA (n = 7) were investigated in the period from 1996 through 1999. All were treated with definitive radiotherapy with curative intent by a combination of external radiotherapy plus high-dose-rate afterloading. Before therapy, tumor oxygenation was measured with a needle probe polarographically using the Eppendorf histograph. Hypoxic tumors were defined as those with pO(2) measurements below 5 mm Hg (HF5). Pretreatment biopsies were taken and analyzed immunohistologically for p53 protein expression with the DO-7 antibody. The DNA index was measured by flow cytometry. The statistical data analysis was done with SPSS 9.0 for Windows. RESULTS: The 3-year overall survival was 55% for the whole group of patients. Clinical prognostic factors in a multivariate analysis were pretreatment hemoglobin level (3-year survival 62% for patients with a pretreatment hemoglobin > or =11 g/dl vs. 27% for hemoglobin <11 g/dl, p = 0.006) and FIGO stage (Stage IIB: 65%; Stage IIIB: 60%; Stage IVA: 29%, p = 0.01). Sixty of the 70 tumors showed positive immunohistologic staining for p53 protein (transformed p53 = tp53), and 10/70 were negative (wild-type p53 = wtp53); p53 expression had no significant impact on survival (50% for tp53 vs. 79% for wtp53, p = 0.11). FIGO stage and anemia had no impact on p53 expression. Forty-nine of 70 tumors were hypoxic (HF5+), and 21 showed no hypoxia (HF5-). Hypoxic carcinomas were more frequently positive for p53 as compared to nonhypoxic tumors (27% vs. 13%, p = 0.011) and showed a trend toward a lower survival (48% vs. 70%, p = 0.07). In a further multivariate analysis, the impact of a combination of p53 expression and hypoxia on survival was examined. After adjusting for FIGO stage and pretreatment anemia, patients with wtp53 tumors had the best prognosis (3-year survival 79%) followed by tp53-HF5(-) patients (57%), and the most unfavorable prognosis was observed for tp53-HF5(+) patients (47%). The DNA index was higher in tp53 carcinomas compared to wtp53 tumors, 1.97 +/- 0.4 vs. 1.67 +/- 0.1, p = 0.05. The highest DNA index was found in hypoxic tumors with transformed p53 (2.2 +/- 3.1). CONCLUSIONS: Advanced stage and pretreatment hemoglobin level are independent prognostic factors in cervical carcinomas. The immunohistologic detection of (a functionally inactive) p53 and the presence of hypoxia had no prognostic impact, if analyzed as single parameters. However, the combination of both parameters was able to discriminate different prognostic subgroups. Moreover, hypoxic cancers were more often immunohistologically positive for tp53 protein and had a higher DNA index with the highest DNA index in tumors with both hypoxia and tp53 protein expression. These findings in summary support the theory that the tumor's microenvironment may influence the biologic behavior via hypoxia.

Adult↗

PubMed2001

[Local tumor control and cosmetic outcome following breast-conserving surgery and radiation up to a total dose of 56 Gy without boost in breast cancer].

PURPOSE: To evaluate overall survival, local tumor control and cosmetic outcome after breast-conserving surgery followed by radiotherapy without boost irradiation. PATIENTS AND METHODS: In a retrospective study 270 breast cancer patients were treated with breast conserving surgery combined with a homogenous radiation of the tumor bearing breast up to a total dose of 56 Gy without local boost irradiation. Mean follow-up was 48 months. Local tumor control, side effects, cosmetic results and contentment with treatment were assessed using physical examinations and interviews based on a standardized questionnaire. RESULTS: Cause-specific survival at 5 years after treatment was 88.3%, actuarial disease-free survival at 5 years was 76.1%. Within 23 to 78 months after treatment 12 patients suffered from ipsilateral breast recurrence. The actuarial freedom from local recurrence (single tumor manifestation) was 96.8% at 5 years after treatment, 89% at 10 years. The occurrence of local failures was not significantly correlated to tumor size, margins, grading, nodal status, age or lymphangiosis. 15.6% of the patients developed distant metastases. In all patients treatment was performed without interruption. Side effects were predominantly of mild degree, no severe side effects were detected. 73% of physicians and 81% of patients scored their cosmetic outcome as excellent or good. 93% of patients would again decide in favor of this procedure. Whereas use of adjuvant chemotherapy as well as subcutaneous reconstruction of breast tissue did not significantly affect breast cosmesis, analysis demonstrated impaired cosmetic results related to a larger breast size. CONCLUSION: The data of this study show that tumor control achieved by breast conserving surgery in combination with a radiation technique up to a total dose of 56 Gy which omits boost irradiation is within the range of literature data. Side effects of the therapy were tolerable. The treatment displayed a good compatibility with tolerable side effects and good cosmetic results.

Actuarial Analysis↗

PubMed2001

Predictive value of the tumor oxygenation by means of pO2 histography in patients with advanced head and neck cancer.

PURPOSE: The purpose of this analysis was to evaluate the potential of the tumor oxygenation by means of Eppendorf pO2 histography as a predictive test to select patients for treatment alternatives. PATIENTS AND METHODS: Pretreatment tumor pO2 histographies of locoregional lymph node metastases were assessed in 194 patients with squamous cell carcinoma of the head and neck. Included in the analysis were 134 patients who received a primary radio- or radiochemotherapy with a radiation dose of > or = 60 Gy, and who had no distant metastasis at beginning of the therapy. RESULTS: The Cox regression analysis revealed the fraction of pO2 values < or = 2.5 mm Hg (p = 0.004), age (p = 0.04) and radiotherapy/radiochemotherapy (p = 0.03) as significant independent prognostic factors for the survival. The positive and negative predictive values were calculated using different cut-off values of the fraction of pO2 values < or = 2.5 mm Hg and the survival status at 1 or 2 years after beginning of the therapy as endpoint. The highest positive and negative predictive values of all cut-off values were 0.50 and 0.41 at 1 year, and 0.81 and 0.26 at 2 years. CONCLUSIONS: Our data confirm the influence of the tumor oxygenation on the prognosis of patients with squamous cell carcinoma of the head and neck after radiotherapy. However, the calculated positive and negative predictive values suggest that the pO2 histography alone is not sufficient to be used as a predictive test to successfully select patients for treatment alternatives.

Adult↗

PubMed2001

Tumor hypoxia and systemic levels of vascular endothelial growth factor (VEGF) in head and neck cancers.

BACKGROUND: Hypoxia is the most important stimulus for the up-regulation of vascular endothelial growth factor (VEGF), one of the key cytokines for angiogenesis. We have investigated the possible relationship between tumor hypoxia and systemic levels of VEGF. PATIENTS AND METHODS: 56 patients with head and neck cancers underwent measurement of tumor volume (pretreatment CT scans), tumor oxygenation (pO2 histography) and serum levels of VEGF. The hemoglobin level ranged from 9.1 to 16 g/dl. The absolute amount of hypoxic tumor (hypoxic tumor volume) was determined as the product of the absolute tumor volume and the relative frequency of hypoxic (< 5 mm Hg) measurements in the pO2 histography. RESULTS: The serum VEGF levels in the 56 head and neck cancer patients ranged from 102 to 1699 pg/ml (median 405 pg/ml, mean 527 +/- 396 pg/ml). Elevated serum-VEGF levels (> 700 pg/ml) were found in 14/56 patients (25%). Serum-levels of VEGF were significantly and independently correlated with hypoxic tumor volume (R2 = 0.63, p < 0.001), but also with total tumor volume, hemoglobin levels, platelet counts and tumor hypoxia. There was no correlation with T and N category, histological grading, and age. CONCLUSIONS: The strong and independent impact of the hypoxic tumor volume on systemic VEGF levels suggests that the absolute amount of hypoxia within a tumor represents the most important stimulus for up-regulation of angiogenesis. Anemia acts as a co-factor via worsening of tumor tissue oxygenation.

Adult↗

PubMed2001

[Stereotactic radiation therapy with a modified linear accelerator in patients with brain metastases].

UNLABELLED: The aim of the study was to analyze the results of stereotactic radiotherapy using a linear accelerator in patients with brain metastases. We quantified the following clinical parameters: tumor response and tumor control after therapy, survival, and side effects. Results of the treatment were compared with those from traditional treatment strategies such as surgery and whole brain irradiation. Sixty patients with brain metastases (80 lesions, 36 men and 24 women, mean age 57 years) were treated with stereotactic radiotherapy. The mean follow-up time was 13 months. CONCLUSION: Stereotactic radiotherapy is an important option in the treatment strategy for patients with brain metastases. In comparison to whole brain irradiation, stereotactic radiotherapy achieved a higher local tumor control with a lower rate of side effects. In comparison to surgery, stereotactic radiotherapy has the advantages of shorter treatment time and lower treatment-related morbidity and mortality.

Adult↗

PubMed2001

A new class of drugs for BNCT? Borylated derivatives of ferrocenium compounds in animal experiments.

A new class of drugs, borylated derivatives of ferrocenium compounds, which show a comparatively facile synthesis is investigated on their boron neutron capture accumulation. Investigations focused on the fast and effective testing of 12 ferrocene derivatives with tetracoordinated boron atoms, which should accumulate in rodent tumors. The macroscopic studies on time-dependent boron distributions and boron concentrations in mice were carried out by inductively coupled plasma-atomic emission spectrometry, inductively coupled plasma-mass spectrometry, and quantitative neutron capture radiography. The determination of boron concentrations after injection of 2b showed high boron contents in spleen, liver, kidneys, less in lung and muscle, and poor in integral blood, blood plasma, tumor, and brain. It is interesting to note that 2b penetrates the blood-brain barrier which may be advantageous in the treatment of astrocytomas and glioblastomas.

Animals↗

PubMed2001

[Association between elevated serum VEGF and polarographically measured tumor hypoxia in head and neck carcinomas].

PURPOSE: Clinical investigation of a potential relationship between VEGF concentration in serum (sVEGF) and polarographically measured tumor oxygenation in patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: In 56 patients with SCCHN we estimated the classical tumor parameters, the sVEGF concentration (immunoassay) and the tumor oxygenation (Eppendorf pO2 histograph). The platelet count and the tumor volume were evaluated simultaneously. RESULTS: In a unifactorial analysis the total volume (132 cm3 vs. 38 cm3), the hypoxic subvolume (HSV = total volume multiplied with the relative frequency of values < or = 5 mm Hg/63 cm3 vs. 10 cm3) and the platelet count (380 10(9)/l vs. 271 10(9)/l) were significantly higher in the patient group with a sVEGF level > 707 pg/ml compared to the group with a sVEGF below this threshold. The multifactorial analysis confirmed significant effects for the hypoxic subvolume and the platelet count. Regarding hypoxic subvolume and sVEGF as continuous parameters a significantly positive correlation was found. This correlation remained somewhat weaker but significant after inclusion of the platelet count as covariate. CONCLUSION: On base of our data a clinical association between elevated sVEGF and polarographically measured tumor hypoxia could be confirmed. This was possible considering not only the relative grade of hypoxia but also the absolute amount of hypoxic regions. The VEGF released from platelets during blood clotting influences the sVEGF level essentially, however, the hypoxia effect was not completely deleted. Due to the platelet effect an estimation of sVEGF is not able to substitute polarographical measurement of tumor pO2. Therefore in an ongoing study we investigate whether VEGF values estimated in plasma are better correlated with the polarographically measured tumor pO2 than serum VEGF levels.

Adult↗

PubMed2001

Correlation between postoperative 3-[(123)I]iodo-L-alpha-methyltyrosine uptake and survival in patients with gliomas.

UNLABELLED: The aim of this study was to evaluate the prognostic value of SPECT imaging using the amino acid analog 3-[(123)I]iodo-L-alpha-methyltyrosine (IMT) in patients with gliomas. METHODS: One hundred fourteen consecutive patients with newly diagnosed gliomas were examined by IMT SPECT (low-grade glioma, n = 12; anaplastic astrocytoma or oligodendroglioma, n = 46; glioblastoma, n = 56). Seventy-one of these patients had undergone tumor resection 4-6 wk before SPECT imaging (group A). Forty-three patients with unresectable tumors were examined after stereotactic biopsy (group B). IMT uptake at the site of the tumor was assessed visually and quantified relative to a contralateral reference region (IMT uptake ratio). After IMT SPECT, all patients were treated with conformal radiotherapy. The median follow-up time was 27 mo. RESULTS: In group A, focal IMT uptake at the resection site was visible in 52 of 71 patients (73%). Median survival was only 13 mo in these patients, whereas median survival was reached in patients without focal IMT uptake (P = 0.02). Furthermore, the intensity of IMT uptake significantly correlated with survival: patients with an IMT uptake ratio > 1.7 were at a 4.6 times higher risk of death than were patients with a lower IMT uptake (P < 0.001). The IMT uptake ratio remained a significant prognostic factor when age and grading were included in a multivariate model. In contrast, IMT uptake did not correlate with survival in group B (P = 0.95). CONCLUSION: In patients with unresectable high-grade gliomas, IMT uptake appears not to correlate with the biologic aggressiveness of tumor cells. Nevertheless, the clear association between focal IMT uptake after tumor resection and poor survival suggests that IMT is a specific marker for residual tumor tissue. Therefore, IMT SPECT is expected to become a valuable tool for the planning and monitoring of local therapeutic modalities.

Adult↗