Biomedical subjects

Michael Bamberg

Publications and source records attributed to Michael Bamberg.

At least 19 recordsLinked to original sources

PubMed2007

Proctitis after external-beam radiotherapy for prostate cancer classified by Vienna Rectoscopy Score and correlated with EORTC/RTOG score for late rectal toxicity: results of a prospective multicenter study of 166 patients.

PURPOSE: To evaluate the Vienna Rectoscopy Score (VRS) as a feasible and effective tool for detecting and classifying pathologic changes in the rectal mucosa after radiotherapy (RT) for prostate cancer, and, also, to correlate its findings with the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) score for late rectal toxicity. METHODS AND MATERIALS: A total of 486 patients with localized prostate cancer underwent external-beam RT up to 70 or 74 Gy within an Austrian-German prospective multicenter trial. In 166 patients, voluntary rectal sigmoidoscopy was performed before and at 12 and/or 24 months after RT. Pathologic findings such as telangiectasia, congested mucosa, and ulcers were graded (Grades 0-3) and summarized according to the VRS. Late rectal side effects (EORTC/RTOG) were documented and correlated with the corresponding VRS. RESULTS: Before RT, 99% had a VRS score of 0. The median follow-up was 40 months. Overall, a late rectal side effects grade or score 1-3 was detected in 43% by EORTC/RTOG compared with 68% by VRS (p < 0.05). Grades 0, 1, 2, and 3 late rectal side effects were found using EORTC/RTOG in 57%, 11%, 28%, and 3%, respectively; the corresponding percentages were 32%, 22%, 32%, and 14% for a VRS of 0, 1, 2, and 3, respectively. A significant coherence between the VRS and EORTC/RTOG was found (p < 0.01). CONCLUSIONS: The VRS is a feasible and effective tool for describing and classifying pathologic findings in the rectal mucosa after RT within a multicenter trial. The VRS and EORTC/RTOG showed a high coherence. However the VRS was significantly more sensitive.

Aged↗

PubMed2006

External beam radiotherapy as postoperative treatment of diffuse pigmented villonodular synovitis.

PURPOSE: Diffuse pigmented villonodular synovitis is a rare proliferative disorder of synovial membranes with invasive and expansive growth patterns. Radical synovectomy is regarded as the treatment of choice. However, because of the high recurrence rates, additive treatment might be useful. Radiotherapy (RT) has been evaluated with positive results, but the optimal treatment schedules are vague. We have reviewed our experience with postoperative RT in cases of suspected or proven residual disease. METHODS AND MATERIALS: Between December 1996 and January 2006, 7 diffuse pigmented villonodular synovitis patients underwent RT at our institution. The most common location was the knee joint (5 patients). All patients underwent radical surgery and were treated subsequently with 6-MV photon RT. The total doses applied were 30-50 Gy, depending on the resection status and estimated risk of relapse. For analysis, we retrospectively reviewed all patients in April 2006. RESULTS: The mean follow-up time was 29 months (range, 3-112 months). RT had no acute adverse effects. At the assessment, no evidence was found of recurrent or persisting disease in any patient. Of the 7 patients, 6 reported asymptomatic limb function and excellent quality of life; 1 patient had persistent restriction of joint movement after repeated surgery. No radiotherapeutic late effects were seen. CONCLUSION: The results of our series have confirmed the efficacy and safety of postoperative RT for diffuse pigmented villonodular synovitis. Hence, this treatment should be considered for patients with suspected or proven residual disease.

Adolescent↗

PubMed2006

Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03.

PURPOSE: To evaluate toxicity and efficacy of the combination of lomustine, temozolomide (TMZ) and involved-field radiotherapy in patients with newly diagnosed glioblastoma (GBM). PATIENTS AND METHODS: Thirty-one adult patients (median Karnofsky performance score 90; median age, 51 years) accrued in two centers received involved-field radiotherapy (60 Gy in 2-Gy fractions) and chemotherapy with lomustine 100 mg/m2 (day 1) and TMZ 100 mg/m2/d (days 2 to 6) with individual dose adjustments according to hematologic toxicity. RESULTS: A median of five courses (range, one to six courses) were delivered. WHO grade 4 hematotoxicity was observed in five patients (16%) and one of these patients died as a result of septicemia. Nonhematologic toxicity included one patient with WHO grade 4 drug-induced hepatitis (leading to discontinuation of lomustine and TMZ) and one patient with WHO grade 2 lung fibrosis (leading to discontinuation of lomustine). The progression-free survival (PFS) rate at 6 months was 61.3%. The median PFS was 9 months (95% CI, 5.3 to 11.7 months), the median overall survival time (MST) was 22.6 months (95% CI, 12.5 to not assessable), the 2-year survival rate was 44.7%. O6-methylguanine-DNA methyltransferase (MGMT) gene-promoter methylation in the tumor tissue was associated with longer PFS (P = .014, log-rank test) and MST (P = .037). CONCLUSION: The combination of lomustine, TMZ, and radiotherapy had acceptable toxicity and yielded promising survival data in patients with newly diagnosed GBM. MGMT gene-promoter methylation was a strong predictor of survival.

Administration, Oral↗

PubMed2006

Hyperfractionated, accelerated chemoradiation with concurrent mitomycin-C and cisplatin in locally advanced head and neck cancer, a phase I/II study.

BACKGROUND: To determine the outcome, acute and late toxicity in locally advanced head and neck cancer stage IVA with mitomycin-C (MMC), cisplatin (DDP) chemotherapy and hyperfractionated accelerated radiation therapy (C-HART). PATIENTS AND METHODS: Thirty-five patients, with squamous cell cancer of the oral cavity (20%), oropharynx (37%), hypopharynx (26%) and larynx (17%), received 30 Gy (2 Gy every day) followed by 1.4 Gy bid to a total of 70.6 Gy concurrently with MMC 10mg/m(2) (day 1 plus 36) and DDP 6 mg/m(2) given Mondays through Fridays during weeks 1-3. Median follow up was 19 months. RESULTS: C-HART was given as planned in 12 of 35 patients, with radiotherapy completed per protocol in 91%. Overall, patients received 70% of the intended dose of MMC and 91% of DDP. Mucositis CTC III/IV occurred in 27%, leucopenia CTC III/IV in 47%, and three early deaths were observed. Osteoradionecrosis occurred in 14% with cT4-tumours. At 3 years the locoregional control and survival rates were 60% and 46%, respectively. CONCLUSION: C-HART resulted in promising overall response with acceptable toxicity. Mucositis is a frequent, severe toxicity in patients treated with C-HART for head and neck cancer. While it appears that mucositis and hematological toxicity may lead to hospitalization and omitting of the second dose of mitomycin C, its impact on radiotherapy interruptions is marginal.

Adult↗

PubMed2006

Role of radiotherapy in supratentorial primitive neuroectodermal tumor in young children: results of the German HIT-SKK87 and HIT-SKK92 trials.

PURPOSE: To assess the outcome of young children with supratentorial primitive neuroectodermal tumor (stPNET) treated by intensive postoperative chemotherapy alone compared with treatment with chemotherapy and delayed radiotherapy (RT). PATIENTS AND METHODS: From 1987 to 1992, children younger than 3 years of age with stPNET were enrolled in the HIT-SKK87 trial in Germany and Austria. After surgery, low-risk patients received maintenance chemotherapy before RT. In high-risk patients, intensive induction chemotherapy was followed by maintenance chemotherapy until delayed RT was initiated. In the following trial, HIT-SKK92 methotrexate-based chemotherapy was applied. In children with complete remission after three cycles, therapy was finished without irradiation. Otherwise, radiotherapy or salvage chemotherapy was administered. RESULTS: Twenty-nine children were eligible (age, 3.0 to 37.0 months). All children received chemotherapy. In 15 children, no RT was administered. Four children had tumor progression during chemotherapy and underwent irradiation. In 10 patients, RT was given after chemotherapy. Overall survival (OS) and progression-free survival (PFS) rates after 3 years were 17.2% and 14.9%, respectively. Twenty-four children relapsed (13 at the tumor site only, three at distant site, and eight at both local and distant sites). Positive impact on survival was observed in children with complete resection but without statistical significance. Administration of RT was the only significant predictive factor for OS and PFS. Only one child not having RT survived. CONCLUSION: Outcome of infants and babies with stPNET is unsatisfactory. Omission of RT jeopardizes survival, even if intensive chemotherapy is applied. We suggest to limit any delay of RT to a maximum of 6 months even in young children.

Child, Preschool↗

PubMed2006

Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway.

BACKGROUND: The anticancer drug Ukrain (NSC-631570) which has been specified by the manufacturer as semisynthetic derivative of the Chelidonium majus L. alkaloid chelidonine and the alkylans thiotepa was reported to exert selective cytotoxic effects on human tumour cell lines in vitro. Few clinical trials suggest beneficial effects in the treatment of human cancer. Aim of the present study was to elucidate the importance of apoptosis induction for the antineoplastic activity of Ukrain, to define the molecular mechanism of its cytotoxic effects and to identify its active constituents by mass spectrometry. METHODS: Apoptosis induction was analysed in a Jurkat T-lymphoma cell model by fluorescence microscopy (chromatin condensation and nuclear fragmentation), flow cytometry (cellular shrinkage, depolarisation of the mitochondrial membrane potential, caspase-activation) and Western blot analysis (caspase-activation). Composition of Ukrain was analysed by mass spectrometry and LC-MS coupling. RESULTS: Ukrain turned out to be a potent inducer of apoptosis. Mechanistic analyses revealed that Ukrain induced depolarisation of the mitochondrial membrane potential and activation of caspases. Lack of caspase-8, expression of cFLIP-L and resistance to death receptor ligand-induced apoptosis failed to inhibit Ukrain-induced apoptosis while lack of FADD caused a delay but not abrogation of Ukrain-induced apoptosis pointing to a death receptor independent signalling pathway. In contrast, the broad spectrum caspase-inhibitor zVAD-fmk blocked Ukrain-induced cell death. Moreover, over-expression of Bcl-2 or Bcl-xL and expression of dominant negative caspase-9 partially reduced Ukrain-induced apoptosis pointing to Bcl-2 controlled mitochondrial signalling events. However, mass spectrometric analysis of Ukrain failed to detect the suggested trimeric chelidonine thiophosphortriamide or putative dimeric or monomeric chelidonine thiophosphortriamide intermediates from chemical synthesis. Instead, the Chelidonium majus L. alkaloids chelidonine, sanguinarine, chelerythrine, protopine and allocryptopine were identified as major components of Ukrain. Apart from sanguinarine and chelerythrine, chelidonine turned out to be a potent inducer of apoptosis triggering cell death at concentrations of 0.001 mM, while protopine and allocryptopine were less effective. Similar to Ukrain, apoptosis signalling of chelidonine involved Bcl-2 controlled mitochondrial alterations and caspase-activation. CONCLUSION: The potent proapoptotic effects of Ukrain are not due to the suggested "Ukrain-molecule" but to the cytotoxic efficacy of Chelidonium majus L. alkaloids including chelidonine.

Alkaloids↗

PubMed2006

First experiences of radiation treatment planning with PET/CT.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) is composed of modern CT and PET technology in one machine enabling examinations of patients in one session in the same position. Its value for modern radiation treatment planning is under investigation. METHODS: In 53 patients with head-and-neck (n = 11), non-small cell lung (n = 16), prostate (n = 14) and other cancers (n = 12), a PET/CT investigation was performed. During the diagnostic examination process an integrated scan under radiation treatment-planning conditions was included. Interpretation and delineation of macroscopic tumor were done in an interdisciplinary approach. Treatment changes occurred after critical interpretation of the PET/CT findings by the responsible radiotherapist. Analysis is descriptive with regard to changes in treatment intention, mode, radiation volumes and doses. RESULTS: Examinations were well tolerated. CT datasets in treatment position could be used for planning. Delineation of macroscopic tumor led to changes of the planning target volume after PET/CT 15 times, total dose was modified twelve times. PET/CT examinations led to changes of the general treatment mode in 19 cases. Using the separate CT and PET datasets, fusion in the planning software was easily performed in all patients due to the use of the same positioning and immobilization devices in PET/CT. CONCLUSION: Despite the low number of patients and an expected bias of selection, the first results are encouraging to perform more extended and detailed trials of this technology in radiotherapy planning. Whether PET/CT is superior to PET alone is part of ongoing investigations.

Adult↗

PubMed2006

Total-body irradiation--role and indications: results from the German Registry for Stem Cell Transplantation (DRST).

BACKGROUND AND PURPOSE: Total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry. MATERIAL AND METHODS: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center. RESULTS: For autologous HSCT approximately 10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, approximately 80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, approximately 35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI. CONCLUSION: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished.

Acute Disease↗

PubMed2006

[Evaluation of flat-rate payment in radiation oncology. German experience with disease-related groups for inpatient funding in radiation oncology].

PURPOSE: In Germany a new casemix-related reimbursement system with "diagnosis related groups" (DRGs) for inpatient treatment was started in 2003. The first German system G-DRG 1.0 was developed on the basis of the Australian AR-DRG version 4.1. German inpatient treatment in radiation oncology was not specifically represented in this system due to the very different health care systems. As the DRG system was planned as a pricing system with severe effects on the funding of radiation oncology departments, an adjustment was urgently needed. For the modification, national data about pattern of care and economic relevance were needed. METHODS: For 3,689 cases treated in radiation oncology departments from eleven hospitals data were collected prospectively concerning diagnosis, length of stay, procedures and high-cost drugs and treatments. The DRGs were analyzed for homogeneity in length of stay and costs. Readmission frequency and interval were analyzed and the relevance of existing reimbursement regulations for this situation was evaluated. RESULTS: It could be shown, that radiation therapy implicated additional expenses for oncologic inpatients. These additional costs were not represented in the G-DRG 1.0 reimbursement system. Chemotherapy was an additional cause for economically inhomogeneous oncologic DRGs. The complex sequence of cases for the same patient could be shown, and that the rules for reimbursement of readmissions have to take these sequential treatments into account. Based on these data, modifications of the reimbursement system were suggested. In the following G-DRG version for the year 2004, 21 DRGs were designed for patients receiving radiation therapy. The regulations concerning the readmission of oncologic patients were modified. The correlation between the number of radiation therapy fractions and the total expense was acknowledged in the following year (G-DRG system 2005) and resulted in 35 DRGs. The version for 2006 showed the solidity of these solutions with almost unchanged definitions of these DRGs. CONCLUSION: This evaluation revealed the deficits in the G-DRG system 1.0 (and the AR-DRG system 4.1) related to the inpatient treatment in radiation oncology departments. Modifications could be proposed for following years. In 2004-2006, the regulatory boards adopted several implications of these data for the improvement of the German casemix-based hospital-financing system.

Diagnosis-Related Groups↗

PubMed2006

3-D Conformal radiotherapy of localized prostate cancer within an Austrian-German multicenter trial: a prospective study of patients' acceptance of the rectal balloon during treatment.

PURPOSE: Patients with localized prostate cancer are treated with 3D radiotherapy using a rectal balloon catheter for internal immobilization of the prostate, thereby reducing the radiation dose to the dorsal rectal wall. The purpose of the study was to investigate clinical feasibility and the influence of acute rectal side effects and pre-existing hemorrhoids on patients' acceptance of the rectal balloon catheter. METHODS AND MATERIALS: 442 patients who underwent primary radiation therapy for localized prostate cancer were included in this prospective Austrian-German multicenter trial. The total radiation dose was either 70 Gy or 74 Gy. Acute rectal side effects were documented using the EORTC/RTOG grading score (European Organisation for Research and Treatment of Cancer/Radiation Therapy 225 Oncology Group) at weeks 2, 4 and 7 of radiation treatment. Within the same time intervals patients were interviewed about their tolerance of the rectal balloon catheter, evaluating five categories of acceptance (1 = no major complaints, 2 = pain at/during application, 3 = signs of blood at the balloon catheter after application but without any pain, 4 = signs of blood at the balloon catheter after application and pain, 5 = balloon application had to be stopped). Voluntary rectoscopy prior to radiotherapy was performed in 310 patients. RESULTS: 429/442 patients (97 %) were treated with the balloon catheter. No major complaints were reported in 79 % of the patients and no acute rectal side effects were seen in 52 % of the patients. Grade 1 side effects were seen in 31 % patients, Grade 2 in 17 % and Grade 3 in 0.5 %. Balloon use had to be stopped in only 4 % of the patients. There was significant correlation between balloon discomfort and rectal side effects (p < 0.01). The presence of hemorrhoids in 36 % patients prior to irradiation had no influence on balloon tolerance. CONCLUSIONS: The rectal balloon can be used in 3D radiotherapy of localized prostate cancer with a high degree of acceptance by the patients. Use of the balloon is safe within daily clinical treatment. Patients reporting acute rectal side effects experienced significantly more balloon discomfort, but the presence of hemorrhoids was not found to influence acceptance of the balloon.

Aged↗

PubMed2006

Advances in the treatment of testicular cancer.

Testicular cancer is the most common solid tumour in young men, and the treatment of testicular germ cell tumours (TGCT) has been called a success story of medical oncology, germ cell cancer being regarded as the "model of a curable neoplasm". Even with metastatic disease, high cure rates can be achieved: the overall 5-year survival for all stages of TGCT is approximately 80%. Today, elaborate systems for prognostic evaluation for gonadal and extragonadal germ cell tumours facilitate the choice of the most appropriate therapy for individual patients. In doing so, the ultimate goal of treatment is tumour-free survival for any patient with TGCT. This goal has already been reached for >99% of the patients with early-stage tumours, as well as for the majority of patients with advanced disease (56% of patients with metastases are considered to have a good prognosis at the time of diagnosis; the 5-year survival rate for this group is 90%). However, patients with 'intermediate' or 'poor' prognosis at the time of diagnosis, as well as patients with relapsed disease after cisplatin-containing therapy, still have an unsatisfactorily low 5-year survival rate after standard therapy with PEB (cisplatin, etoposide, bleomycin) of only 80%, 45-55% and 20-25%, respectively.Therefore, our goals must be (i) to limit acute and chronic toxicity by avoiding overtreatment for patients with localised disease and/or good prognosis with advanced disease; and (ii) to identify patients with poor prognosis and treat them in specialised centres, where not only is optimal interdisciplinary care available but new treatment strategies are being applied. For example, tandem high-dose chemotherapy regimens might be effective in achieving higher cure rates in these patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Role of radiotherapy in anaplastic ependymoma in children under age of 3 years: results of the prospective German brain tumor trials HIT-SKK 87 and 92.

BACKGROUND AND PURPOSE: To evaluate the outcome of very young children with anaplastic ependymoma after delayed or omitted radiotherapy (RT). MATERIALS AND METHODS: Children under age of 3 years with anaplastic ependymoma were enrolled in the HIT-SKK 87 trial from 1987. After surgery, low-risk patients (R0, M0) received maintenance chemotherapy until elective RT at age of three. In high-risk patients (R+, M+) intensive induction chemotherapy was followed by maintenance chemotherapy and subsequently delayed RT. If there was, progression radiotherapy started immediately. In the HIT-SKK 92, trial MTX-based chemotherapy was applied. RT was administered in non-responders only. RESULTS: Thirty-four children with anaplastic ependymoma were eligible (age 1.0-33.0 months). All children received chemotherapy. In 13 children, no RT was administered. Preventive RT after chemotherapy was given in nine, and salvage RT in 12 children. OS and PFS rates after 3-year were 55.9 and 27.3%, respectively. Twenty-five children relapsed. Positive impact on survival was observed in children with higher age, M0-stage, complete resection, and treatment with radiotherapy. Without RT only 3/13, children survived. CONCLUSION: Delaying RT jeopardizes survival even after intensive chemotherapy. Predominant site of failure is the primary tumor site. RT of the neuraxis should be omitted in localized disease.

Age Factors↗

PubMed2005

3-D conformal radiotherapy of localized prostate cancer: a subgroup analysis of rectoscopic findings prior to radiotherapy and acute/late rectal side effects.

BACKGROUND AND PURPOSE: To identify endoscopic pathological findings prior to radiotherapy and a possible correlation with acute or chronic rectal side effects after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. PATIENTS AND METHODS: Between 03/99 and 07/02, a total of 298 patients, who consented in a voluntary rectoscopy prior to radiotherapy were included into the analysis. Patients were treated with a total dose of either 70 or 74 Gy. Pathological rectoscopic findings like hemorrhoids, polyps or diverticula were documented. Acute and late rectal side effects were scored using the EORTC/RTOG score. RESULTS: The most frequent pathological endosopic findings were hemorrhoids (35%), polyps (24%) and diverticula (13%). Rectal toxicity was mostly low to moderate. Grade 0/1 cumulative acute and late rectal side effects were 82 and 84%, grade 2 were 18 and 17%, respectively. We could not identify any correlation between preexisting pathological findings and rectal side effects by statistical analysis. CONCLUSIONS: There is no evidence that prostate cancer patients presenting with endoscopic verified pathological findings in the rectal mucosa at diagnosis are at an increased risk to develop rectal side effects when treated with 3D-CRT of the prostatic region.

Aged↗

PubMed2005

Treatment-outcome for synchronous head-and-neck and oesophageal squamous cell carcinoma.

BACKGROUND AND PURPOSE: Although head & neck and oesophageal carcinomas occur synchronously in up to 12%, almost no data on feasibility and outcome after radiotherapy are available. MATERIALS AND METHODS: From 1989 to 2002, 24 patients were treated at Tuebingen University and Fulda hospital with a radiation based, curative approach. These were analyzed retrospectively. RESULTS: The median overall survival was 37 (1-69) months with a few long-term survivors with a median follow-up of 26 months for patients at risk. 7 local recurrences occurred. No major toxicity was seen. DISCUSSION: Even though the prognosis of synchronous head & neck and oesophageal carcinomas is grim, long-term survival is possible. A radiation-based approach is feasible and can be chosen for a curative treatment approach which we recommend.

Aged↗

PubMed2005

Array-based comparative gene expression analysis of tumor cells with increased apoptosis resistance after hypoxic selection.

Tumor hypoxia is an adverse prognostic factor. In a recent study, we could demonstrate that cyclic hypoxia selects for hypoxia-tolerant tumor cells, which are cross-resistant to other stimuli of mitochondrial death pathways. In contrast, sensitivity of the cells to death-receptor ligands was mainly not affected. The aim of the present study was to further elucidate cellular changes induced by cyclic hypoxia and to identify alterations in gene expression pattern upon hypoxic selection by means of DNA-microarray analysis. Our data reveal that cyclic hypoxia resulted in the selection of cells with resistance to doxorubicine and radiation. Furthermore, hypoxic selection was accompanied by constitutive changes of the gene expression pattern with downregulation of 156 and upregulation of 82 genes. Most of the differentially regulated genes were involved in cellular responses to hypoxia and reoxygenation. While many of the genes that were downregulated upon hypoxic selection represent genes that are usually upregulated by acute hypoxia, the genes that were upregulated represent genes that are involved in stress resistance and anti-apoptotic signalling. Most importantly, hypoxic selection was not associated with changes of single apoptosis relevant genes, but with alterations in gene expression levels of a wide variety of genes indicating a more complex adaptation process.

Apoptosis↗

PubMed2005

Intensity modulated radiotherapy for high risk prostate cancer based on sentinel node SPECT imaging for target volume definition.

BACKGROUND: The RTOG 94-13 trial has provided evidence that patients with high risk prostate cancer benefit from an additional radiotherapy to the pelvic nodes combined with concomitant hormonal ablation. Since lymphatic drainage of the prostate is highly variable, the optimal target volume definition for the pelvic lymph nodes is problematic. To overcome this limitation, we tested the feasibility of an intensity modulated radiation therapy (IMRT) protocol, taking under consideration the individual pelvic sentinel node drainage pattern by SPECT functional imaging. METHODS: Patients with high risk prostate cancer were included. Sentinel nodes (SN) were localised 1.5-3 hours after injection of 250 MBq 99mTc-Nanocoll using a double-headed gamma camera with an integrated X-Ray device. All sentinel node localisations were included into the pelvic clinical target volume (CTV). Dose prescriptions were 50.4 Gy (5 x 1.8 Gy / week) to the pelvis and 70.0 Gy (5 x 2.0 Gy / week) to the prostate including the base of seminal vesicles or whole seminal vesicles. Patients were treated with IMRT. Furthermore a theoretical comparison between IMRT and a three-dimensional conformal technique was performed. RESULTS: Since 08/2003 6 patients were treated with this protocol. All patients had detectable sentinel lymph nodes (total 29). 4 of 6 patients showed sentinel node localisations (total 10), that would not have been treated adequately with CT-based planning ('geographical miss') only. The most common localisation for a probable geographical miss was the perirectal area. The comparison between dose-volume-histograms of IMRT- and conventional CT-planning demonstrated clear superiority of IMRT when all sentinel lymph nodes were included. IMRT allowed a significantly better sparing of normal tissue and reduced volumes of small bowel, large bowel and rectum irradiated with critical doses. No gastrointestinal or genitourinary acute toxicity Grade 3 or 4 (RTOG) occurred. CONCLUSION: IMRT based on sentinel lymph node identification is feasible and reduces the probability of a geographical miss. Furthermore, IMRT allows a pronounced sparing of normal tissue irradiation. Thus, the chosen approach will help to increase the curative potential of radiotherapy in high risk prostate cancer patients.

Aged↗

PubMed2005

The angiogenesis inhibitor NM-3 is active against human NSCLC xenografts alone and in combination with docetaxel.

The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1 H-2-benzopyran-3-yl) propionic acid (NM-3) has completed phase I clinical evaluation as an orally bioavailable angiogenesis inhibitor. NM-3 directly kills both endothelial and tumor cells in vitro at low mM concentrations and is effective in the treatment of diverse human tumor xenografts in mice. The present work has assessed the activity of NM-3 against human non-small-cell lung cancer (NSCLC) cells when used alone and in combination with docetaxel. The results demonstrate that NM-3 decreases clonogenic survival of NSCLC cells at clinically achievable concentrations. The results also demonstrate that NM-3 is effective in the treatment of NSCLC (A549, NCI-H460) tumor xenografts in mice. Moreover, NM-3 potentiated the antitumor activity of docetaxel against NSCLC xenografts without increasing toxicity. Our findings indicate that NM-3 may be effective alone or in combination with docetaxel in the treatment of patients with NSCLC.

Angiogenesis Inhibitors↗

PubMed2005

Reirradiation alternating with docetaxel and cisplatin in inoperable recurrence of head-and-neck cancer: a prospective phase I/II trial.

PURPOSE: Inoperable locoregional recurrences of head-and-neck cancer in a previously irradiated volume represent a therapeutic dilemma. Chemotherapy alone has no curative potential, whereas reirradiation and concurrent chemoradiation can salvage a small fraction of patients. Mucosal toxicity of concurrent chemoradiation requires substantial dose reduction of chemotherapy. Alternating chemoradiation offers the chance to give both full-dose chemotherapy and radiotherapy. The latter may provide a particular advantage for recurrent, potentially radiation resistant tumors. The feasibility and efficacy of a full-dose docetaxel containing alternating chemoradiation schedule was tested. PATIENTS AND METHODS: Twenty-seven patients (Karnofsky performance status score >/=70%) with histologically proven recurrent squamous cell cancer that occurred >/= 6 months in a previously irradiated area (>/= 60 Gy) were considered unresectable and unsuitable for brachytherapy. Alternating chemoradiation consisted of 3 cycles of docetaxel 60 mg/m(2) d1 and cisplatin 15 mg/m(2) d2-5, q d22, and involved field radiotherapy 2.0 Gy every day d8-12, d15-19, d29-33, and d36-40 (40.0 Gy total dose). Dose reduction of docetaxel to 50 mg/m(2) was necessary, because of hematologic toxicity in the first 12 patients. RESULTS: Alternating chemoreirradiation was applied as planned in 12 of 27 patients, with reirradiation completed per protocol in 81%. Overall, patients received 83% of the intended dose of docetaxel and 73% of cisplatin. Third-degree common toxicity criteria mucositis occurred in 15%, leukopenia of >/= third degree by common toxicity criteria in 37%, and 3 early deaths were observed. Median time to follow-up, time to local progression, median survival, and 3-year survival rates were 42 months, 10 months, 10 months, and 18%, respectively. CONCLUSIONS: Alternating chemoreirradiation in recurrences of head-and-neck cancer resulted in 80% overall response with acceptable toxicity. A significant minority of patients had durable tumor control with a chance of long-term survival.

Adult↗