Classification of airborne 3D point clouds regarding separation of vegetation in complex environments.

Classification of outdoor point clouds is an intensely studied topic, particularly with respect to the separation of vegetation from the terrain and manmade structures. In the presence of many overhanging and vertical structures, the (relative) height is no longer a reliable criterion for such a separation. An alternative would be to apply supervised classification; however, thousands of examples are typically required for appropriate training. In this paper, an unsupervised and rotation-invariant method is presented and evaluated for three datasets with very different characteristics. The method allows us to detect planar patches by filtering and clustering so-called superpoints, whereby the well-known but suitably modified random sampling and consensus (RANSAC) approach plays a key role for plane estimation in outlier-rich data. The performance of our method is compared to that produced by supervised classifiers common for remote sensing settings: random forest as learner and feature sets for point cloud processing, like covariance-based features or point descriptors. It is shown that for point clouds resulting from airborne laser scans, the detection accuracy of the proposed method is over 96% and, as such, higher than that of standard supervised classification approaches. Because of artifacts caused by interpolation during 3D stereo matching, the overall accuracy was lower for photogrammetric point clouds (74-77%). However, using additional salient features, such as the normalized green-red difference index, the results became more accurate and less dependent on the data source.

ReS2tAC-UAV-Borne Real-Time SGM Stereo Optimized for Embedded ARM and CUDA Devices.

With the emergence of low-cost robotic systems, such as unmanned aerial vehicle, the importance of embedded high-performance image processing has increased. For a long time, FPGAs were the only processing hardware that were capable of high-performance computing, while at the same time preserving a low power consumption, essential for embedded systems. However, the recently increasing availability of embedded GPU-based systems, such as the NVIDIA Jetson series, comprised of an ARM CPU and a NVIDIA Tegra GPU, allows for massively parallel embedded computing on graphics hardware. With this in mind, we propose an approach for real-time embedded stereo processing on ARM and CUDA-enabled devices, which is based on the popular and widely used Semi-Global Matching algorithm. In this, we propose an optimization of the algorithm for embedded CUDA GPUs, by using massively parallel computing, as well as using the NEON intrinsics to optimize the algorithm for vectorized SIMD processing on embedded ARM CPUs. We have evaluated our approach with different configurations on two public stereo benchmark datasets to demonstrate that they can reach an error rate as low as 3.3%. Furthermore, our experiments show that the fastest configuration of our approach reaches up to 46 FPS on VGA image resolution. Finally, in a use-case specific qualitative evaluation, we have evaluated the power consumption of our approach and deployed it on the DJI Manifold 2-G attached to a DJI Matrix 210v2 RTK unmanned aerial vehicle (UAV), demonstrating its suitability for real-time stereo processing onboard a UAV.

Evaluation of HoloLens Tracking and Depth Sensing for Indoor Mapping Applications.

The Microsoft HoloLens is a head-worn mobile augmented reality device that is capable of mapping its direct environment in real-time as triangle meshes and localize itself within these three-dimensional meshes simultaneously. The device is equipped with a variety of sensors including four tracking cameras and a time-of-flight (ToF) range camera. Sensor images and their poses estimated by the built-in tracking system can be accessed by the user. This makes the HoloLens potentially interesting as an indoor mapping device. In this paper, we introduce the different sensors of the device and evaluate the complete system in respect of the task of mapping indoor environments. The overall quality of such a system depends mainly on the quality of the depth sensor together with its associated pose derived from the tracking system. For this purpose, we first evaluate the performance of the HoloLens depth sensor and its tracking system separately. Finally, we evaluate the overall system regarding its capability for mapping multi-room environments.

Acculturation and Naturalization: Insights From Representative and Longitudinal Migration Studies in Germany.

In recent years, Western countries have been experiencing a growing wave of immigration. Due to this development, these countries are facing great challenges in successfully integrating large numbers of immigrants and in preserving social cohesion. Research has already developed several assumptions about and models of how acculturation processes occur. The present contribution aims to investigate the relationship between the acculturation (and acculturation profiles) of immigrants and naturalization in their residence countries. Based on representative and longitudinal data, our investigation is a case study on Germany-one of the main receiving countries in recent years. Results show that acculturation in the country of residence is crucial for immigrants' motivation to take up citizenship. Likewise naturalization leads to an increase in identification with the residence country.

Cervical squamous cell lymph node metastases from an unknown primary site: survival and patterns of recurrence after radiotherapy.

INTRODUCTION: The purpose of the present retrospective study was to review outcome and patterns of failure of patients who were treated with radiotherapy for cervical lymph node metastases from an unknown primary site (CUP). PATIENTS AND METHODS: Between 2000 and 2009, 34 patients diagnosed with squamous cell CUP were admitted to radiotherapy in curative intent. In 26 of 34 patients (76%) neck dissection was performed prior to radiotherapy, extracapsular extension (ECE) was seen in 20 of 34 patients (59%). Target volumes included the bilateral neck and panpharyngeal mucosa. Concomitant chemotherapy was applied in 14 of 34 patients (41%). RESULTS: After a median follow-up of 45 months for the entire group, 2 of 34 patients (6%) presented with an isolated regional recurrence, another 2 of 34 patients (6%) developed both local and distant recurrence, and 6 of 34 patients (18%) had distant failure only. Estimated overall survival after 2- and 5 -years was 78% and 63%. All patients with N1 or N2a disease (n=6) were disease free after 5 years. ECE, concomitant chemotherapy and involvement of neck levels 4 and 5 were associated with worse overall survival on univariate analysis. CONCLUSION: Radiotherapy of the panpharynx and bilateral neck leads to excellent local control while distant metastases are the most frequent site of failure and prognostically limiting. Therefore intensified concomitant or sequential systemic therapies should be evaluated in future trials.

Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone.

PURPOSE: To evaluate the influence of regional hyperthermia on rates of complete pathological response (pCR) and sphincter-sparing surgery in the context of an up-to-date radiochemotherapy protocol for locally advanced rectal cancer. METHODS: Between 2007 and 2010, 106 patients with locally advanced cancer of the middle and lower rectum were admitted to neoadjuvant radiochemotherapy either with (n = 61) or without (n = 45) regional hyperthermia. A retrospective comparison was performed between two groups: 45 patients received standard treatment consisting of 5040 cGy in 28 fractions to the pelvis and 5-fluorouracil (RCT group) and 61 patients received the same treatment in combination with regional hyperthermia (HRCT group). Target temperature was 40.5°C for at least 60 min. Total mesorectal excision was performed routinely. RESULTS: pCR was seen in 6.7% of patients in the RCT group and 16.4% in the HRCT group. Patients who received at least four hyperthermia treatments (n = 40) achieved a significantly higher pCR rate (22.5%) than the remaining 66 patients (p = 0.043). Rates of sphincter-sparing surgery were similar in both groups with 64% in the RCT group and 66% in HRCT. When considering only low-lying tumours located within 8 cm of the anal verge prior to treatment, the rate of sphincter-sparing surgery was 57% in the HRCT group compared with 35% in the RCT group (p = 0.077). CONCLUSION: The combination of regional hyperthermia and neoadjuvant radiochemotherapy may lead to an increased pCR rate in locally advanced rectal cancer. Patients with low-lying tumours especially may benefit when additional downsizing allows sphincter-preserving surgery.

Intensity-modulated stereotactic radiotherapy for the treatment of medically inoperable patients with NSCLC stage I.

The standard treatment for stage I non-small cell lung cancer (NSCLC) is lobectomy. However, a considerable number of patients are not eligible for standard lung surgery due to poor pulmonary function or comorbidities. We evaluated the efficacy and tolerability of intensity-modulated stereotactic radiotherapy (IMSRT) with moderate hypofractionation for these patients. Twelve patients were selected for IMSRT. 4D-CT planning was performed by gating CT-scanning positioning. The applied doses ranged between 10x4.5 Gy (80% ID) (N=1), 12x4.5 Gy (95% ID) (N=1) and 10x5.5 Gy (95% ID) (N=10). Long-term follow-up was performed including spirometry and CT for evaluation of local, locoregional and distant control. Even in patients with poor pulmonary function IMRST was safe and well tolerated. No severe acute adverse effects were observed. Estimated local control at 2 years was 90%. Moreover, IMSRT does not induce a significant deterioration of pulmonary function. IMRST is safe and feasible even for patients with very poor pulmonary function. The applied dose provides a high local control rate, although the biological equivalent dose (BED) is lower compared to the average of other SRT regimens. Therefore, IMRST may be an efficient alternative for all NSCLC stage I patients with contraindications to standard lobectomy especially in patients with small tumors in high-risk localisations.

Comparison of different adjuvant radiotherapy approaches in childhood bladder/prostate rhabdomyosarcoma treated with conservative surgery.

BACKGROUND AND PURPOSE: Multimodality treatment approaches provide high local control and satisfying overall survival (OS) for children with localized bladder and/or prostate rhabdomyosarcoma (BP-RMS). However, current strategies including surgery and conventional radiotherapy are compromised by high rates of long-term genitourinary adverse effects. Therefore, a planning study combining organ preserving surgery with three different innovative adjuvant radiotherapy approaches was performed. PATIENTS AND METHODS: A case of a 21-month-old boy with BP-RMS treated with polychemotherapy according to the CWS 2002-P protocol, prostatectomy, partial cystectomy, and adjuvant high dose rate brachytherapy (HDR-BT) was used to perform a planning study comparing HDR-BT with intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) planning. RESULTS: All modalities provide good coverage of the target volume and spare critical normal tissues. Rectum doses could be reduced by 2/3 using IMPT and by 1/3 using BT compared to IMRT. In terms of sparing the pelvis growth plates, BT and IMPT are also superior to IMRT. CONCLUSION: All modalities provide good sparing of normal tissue. BT and IMPT are superior to IMRT with regard to doses on rectum and growth plates. BT is equivalent to IMPT in adequately selected tumors.

Definitive radiotherapy and single-agent radiosensitizing ifosfamide in patients with localized, irresectable soft tissue sarcoma: a retrospective analysis.

BACKGROUND AND PURPOSE: Standard therapy for soft-tissue sarcomas remains complete resection. For primary radiotherapy local control rates of 30-45% have been reported. We analyzed retrospectively 11 cases of radiochemotherapy with single-agent ifosfamide in patients with macroscopic soft-tissue sarcomas. PATIENTS AND METHODS: The patients were treated in irresectable high risk situations. Radiation therapy was performed with median 60 Gy. During the first and fifth week the concomitant chemotherapy with ifosfamide was added. Two patients received trimodal therapy with additional regional hyperthermia. RESULTS: The therapy was completed in 73% of the patients. Average local control time was 91 months, median disease-free-survival/overall-survival was 8/26 months. Five-year rates for local control/disease free survival/overall survival were 70%/34%/34%. The limited prognosis is mainly caused by systemic treatment failure. CONCLUSIONS: The data strongly suggest a better outcome of radiochemotherapy with ifosfamide compared to radiotherapy alone and radiotherapy in combination with other radiosensitizers.

Advanced-stage III/IV follicular lymphoma: treatment strategies for individual patients.

BACKGROUND: In patients with advanced-stage III/IV follicular lymphoma (FL), there are many treatment options available. The current challenge is to choose the optimal strategy for the individual patient. METHODS: The literature was reviewed with respect to treatment strategies in patients with advanced FL by screening the PubMed databank. RESULTS: In advanced-stage III/IV FL, median survival may approach 8-10 years. Treatment strategies include a watch-and-wait strategy, chemoimmunotherapy, monotherapy with rituximab, and - as an experimental approach so far - radioimmunotherapy. The use of autologous hematopoietic stem cell transplantation (HSCT) for patients in first remission or chemosensitive relapse prolongs progression-free survival while the effect on overall survival remains unclear compared to standard chemotherapy. However, long-term results are flawed by high relapse rates and risk of secondary malignancies. In patients with relapsed/chemoresistant disease, allogeneic HSCT constitutes the only curative approach but is associated with high treatment-related mortality. In the palliative setting, low-dose involved-field irradiation constitutes an effective treatment option in order to control local symptoms with potential long-lasting response. CONCLUSION: In case of advanced-disease FL, asymptomatic patients can be managed expectantly. In symptomatic patients, chemoimmunotherapy is regarded as standard therapy. In symptomatic elderly patients with relevant comorbidities, rituximab +/- single-agent chemotherapy, or low-dose involved-field radiotherapy might be appropriate. For younger patients with chemoresistant/relapsed disease, allogeneic HSCT might be considered, since advances in supportive care and better patient selection have resulted in improved outcomes.

Reirradiation with alternating docetaxel-based chemotherapy for recurrent head and neck squamous cell carcinoma: update of a single-center prospective phase II protocol.

PURPOSE: To report follow-up data and results of a dose escalation within a prospective phase II protocol scheduling alternating chemoreirradiation for patients with unresectable locoregional recurrence of head and neck cancer after previous curative-intent radiotherapy. PATIENTS AND METHODS: Chemoreirradiation was initially performed in 27 patients by 40.0 Gy split-course reirradiation (re-RT) alternating with three cycles of docetaxel 50 mg/m(2) day 1 and cisplatin 15 mg/m(2) days 2-5 (first cohort). From 2002 onward, 30 consecutively treated patients received a late-course concomitant boost to 49.6 Gy (second cohort). In July 2008, the survival outcome was analyzed separately for both cohorts and the entire collective (n = 57). RESULTS: The Kaplan-Meier estimates for 1- and 2-year overall survival (OS) were 52% and 24%, respectively (median OS 13.4 months). The median time of locoregional control was 9.6 months, and the actuarial 2-year freedom from distant metastasis rate was 55%. The re-RT dose escalation led to a significant improvement of the median OS (17.4 vs. 9.4 months; p = 0.039). Irrespective of the cohort, severe treatment-related toxicities occurred in about one third of patients. CONCLUSION: The treatment results confirm the efficacy and the safety of escalated re-RT doses in this chemoreirradiation protocol.

Nodal follicular lymphoma: the role of radiotherapy for stages I and II.

PURPOSE: To clarify the role of external-beam radiotherapy (RT) in patients with stage I and II nodal follicular lymphoma (FL). METHODS: The literature was reviewed with respect to different treatment strategies in patients with stage I and II nodal FL by screening the PubMed databank. RESULTS: In patients with stage I and II nodal FL, RT alone with different irradiation techniques (involved-field [IFI]/extended-field [EFI]/total nodal [TNI]/total lymphoid irradiation [TLI]) produces excellent local disease control (approximately 95%) resulting in disease-free survival and overall survival (OS) rates of 37-94% and 40-93% at 5-15 years, respectively. The main cause of failure is out-of-field recurrence. In nonrandomized trials, IFI led to higher relapse rates, but larger irradiation volumes failed to show an impact on OS and were associated with increased toxicity. Additional chemotherapy mostly failed to improve treatment results achieved with RT alone. CONCLUSION: Since there is no evidence so far that the prognosis of stage I and II nodal FL can be improved by the use of EFI/TNI/TLI, IFI is recommended internationally. Adequate irradiation doses range between 25-30 Gy to subclinical disease and 36-40 Gy to involved sites. To further improve the curative potential of RT in early-stage FL, novel combined approaches (e.g., RT + immunotherapy with rituximab) are under investigation.

Monte Carlo vs. pencil beam based optimization of stereotactic lung IMRT.

BACKGROUND: The purpose of the present study is to compare finite size pencil beam (fsPB) and Monte Carlo (MC) based optimization of lung intensity-modulated stereotactic radiotherapy (lung IMSRT). MATERIALS AND METHODS: A fsPB and a MC algorithm as implemented in a biological IMRT planning system were validated by film measurements in a static lung phantom. Then, they were applied for static lung IMSRT planning based on three different geometrical patient models (one phase static CT, density overwrite one phase static CT, average CT) of the same patient. Both 6 and 15 MV beam energies were used. The resulting treatment plans were compared by how well they fulfilled the prescribed optimization constraints both for the dose distributions calculated on the static patient models and for the accumulated dose, recalculated with MC on each of 8 CTs of a 4DCT set. RESULTS: In the phantom measurements, the MC dose engine showed discrepancies < 2%, while the fsPB dose engine showed discrepancies of up to 8% in the presence of lateral electron disequilibrium in the target. In the patient plan optimization, this translates into violations of organ at risk constraints and unpredictable target doses for the fsPB optimized plans. For the 4D MC recalculated dose distribution, MC optimized plans always underestimate the target doses, but the organ at risk doses were comparable. The results depend on the static patient model, and the smallest discrepancy was found for the MC optimized plan on the density overwrite one phase static CT model. CONCLUSIONS: It is feasible to employ the MC dose engine for optimization of lung IMSRT and the plans are superior to fsPB. Use of static patient models introduces a bias in the MC dose distribution compared to the 4D MC recalculated dose, but this bias is predictable and therefore MC based optimization on static patient models is considered safe.

Intensity-modulated radiotherapy optimization in a quasi-periodically deforming patient model.

PURPOSE: To present the implementation of a probability-based, four-dimensional (4D) intensity-modulated radiotherapy (IMRT) planning approach that explicitly optimizes the accumulated dose to moving tissue, estimated using the patient's probability density function (pdf) of respiratory motion. This is termed "optimization in tissue's-eye-view". METHODS AND MATERIALS: The method incorporates 4D Monte Carlo dose calculation in multiple geometries of a respiratory-correlated CT dataset. The instance doses are weighted according to the breathing pdf and accumulated in a common reference geometry, which involves dose warping based on deformable registration. The algorithm produces deliverable multileaf collimator segments and was tested on a sample lung cancer patient dataset with large target excursion. Accumulated doses of the moving target and organs at risk of this plan were compared with those of corresponding margin-based static IMRT plans for free-breathing and gated treatment, as well as target tracking. RESULTS: Target tracking provided best target coverage. Both the presented 4D IMRT approach for free-breathing treatment and gated treatment gave similar results for target coverage and lung dose, with significantly better target coverage than the margin-based static IMRT plan for free-breathing treatment. CONCLUSIONS: The presented 4D planning concept offers an alternative to gating by providing the optimal dose for free-breathing IMRT treatment. Although the focus of this study was 4D lung planning, the approach can be generally applied for IMRT optimization in randomly deforming patient models.

The blockade of endothelin A receptor protects astrocytes against hypoxic injury: common effects of BQ-123 anderythropoietin on the rejuvenation of the astrocyte population.

In the present study the role of endothelin (ET) and its receptors (ETA-R and ETB-R) in cellular mechanisms underlying the resistance of astroglial cells to low oxygen level and development of hypoxia has been investigated. To define the influences of ET and its receptors on survival and on antigenic as well as morphologic differentiation of rat astroglial cells in normoxic (NC) and hypoxic culture (HC) the selective antagonists of ETA-R (BQ-123) and ETB-R (BQ-788) were used. Treatment of HC with BQ-123 caused an increase in cell number and inhibited the hypoxia-induced apoptosis by 37%. BQ-123 decreased the hypoxia-induced cytotoxicity in HC. These effects of BQ-123 were abolished in cultures simultaneously treated with BQ-123 and BQ-788. Administration of BQ-788 alone decreased the number of living cells in NC, but not in HC. The activity of caspase-3/-7 was not changed by exposure of NC and HC to BQ-788. The protection provided by BQ-123 to astroglial cells against cytotoxicity in NC and HC was similar to that of erythropoietin (EPO), a cytokine with established neuroprotective effects. The functional improvement of astroglial cells and slowing down of their differentiation under exposure to BQ-123, or EPO, or BQ-123 + EPO has been evidenced by an increased number of nestin+/glial fibrillary acidic protein-positive (GFAP+) astrocytes accompanied by decrease of nestin-/GFAP+ cells. The simultaneous treatment with BQ-123 and EPO additionally decreased the activities of caspase-3/-7 (64%) and release of LDH into the medium (94%). The benefits in the functional states of astrocytes obtained by combined treatment of HC with BQ-123 and EPO suggest a new therapeutic strategy in treatment of hypoxic brain injury.

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.

Cyclic exposure to hypoxia and reoxygenation selects for tumor cells with defects in mitochondrial apoptotic pathways.

The negative influence of hypoxia on the outcome of malignant tumors may be caused by direct oxygen effects, and potentially, the selection of resistant tumor cells under repetitive hypoxia. To evaluate whether cyclic hypoxia selects for resistant cells and to analyze the underlying mechanisms, the influence of cyclic hypoxia on intracellular death pathways was determined in tumor cells. It could be demonstrated that cyclic hypoxia selects for cells with increased resistance against hypoxia-induced apoptosis. These cells exhibited a cross-resistance against paradigmatic triggers of mitochondrial apoptotic pathways (ionizing radiation/etoposide). In contrast, TRAIL-receptor mediated apoptosis remained unaffected. Thus, cyclic hypoxia selects for cells with defects of the mitochondrial rather than receptor-mediated pathways. Selection of p53-defective cells has been described as a consequence of cyclic hypoxia; therefore, we evaluated the impact of hypoxic selection on activation of p21 and downstream mediators of p53-dependent apoptosis. p53 function and protein levels of key mediators of mitochondrial apoptosis remained unaffected by hypoxic selection. However, radiation-induced conformational changes of Bax were reduced after cyclic hypoxia. In summary, it could be demonstrated that hypoxic stress confers a selection pressure on mitochondrial apoptotic pathways and, consecutively, to an increased resistance toward mitochondrial death triggers.

Molecular ordering of hypoxia-induced apoptosis: critical involvement of the mitochondrial death pathway in a FADD/caspase-8 independent manner.

Dys-regulated growth and improper angiogenesis commonly lead to areas of hypoxia in human tumors. Hypoxia is known to be associated with a worse outcome since a lack of oxygen interferes with the efficacy of chemotherapy or radiotherapy. In parallel, hypoxia-induced apoptosis may also impose a selection pressure favoring growth of more resistant tumor cells. However, the mechanisms of hypoxia-induced apoptosis and the relative contribution of intrinsic and extrinsic apoptotic pathways are not understood. Therefore, Jurkat cell lines with defined defects in the extrinsic or intrinsic signaling cascades were used to evaluate the role of either pathway for induction of apoptosis under hypoxic conditions. Jurkat cells were incubated in hypoxia and the rate of apoptosis induction was determined by Western blotting, fluorescence microscopy and flow cytometry. Hypoxia-induced apoptosis was not affected by lack of caspase-8 or FADD, whereas overexpression of Bcl-2 or expression of dominant-negative caspase-9 mutant rendered the cells resistant to hypoxia-induced apoptosis. These results suggest that hypoxia-induced apoptosis mainly relies on intrinsic, mitochondrial pathways, whereas extrinsic pathways have no significant implications in this process. Thus, in human tumors, hypoxia will mainly lead to the selection of hypoxia-resistant cells with defects in mitochondrial apoptosis signaling pathways.

Influence of hypoxia on TRAIL-induced apoptosis in tumor cells.

PURPOSE: Tumor hypoxia reduces the efficacy of radiotherapy, many types of chemotherapy, and tumor necrosis factor-alpha (TNF-alpha). TRAIL (TNF-alpha-related apoptosis-inducing ligand) is a ligand for death receptors of the TNF superfamily shown to be selectively toxic for tumor cells and thereby a promising antineoplastic tool. The impact of hypoxia on TRAIL-induced apoptosis was examined in this study. METHODS AND MATERIALS: Apoptosis induction and growth rates of various tumor cell lines under hypoxia were evaluated in vitro. Biologically effective induction of hypoxia was verified by determination of hypoxia-inducible factor-1 (HIF-1) activation. The efficacy of TRAIL- and radiation-induced apoptosis under different oxygen conditions was quantified in vitro. The impact of Bcl-2 on TRAIL-induced apoptosis under hypoxia or normoxia was evaluated by comparing cells expressing Bcl-2 with a vector control. RESULTS: Moderate hypoxia caused no growth retardation or apoptosis, but led to activation of HIF-1 as a prerequisite of hypoxic gene induction. Cellular responses to TRAIL differed considerably among the cell lines tested. Hypoxia reduced radiation-induced, but not TRAIL-induced, apoptosis in the tested cell lines. Hypoxia did not induce Bcl-2 expression. Bcl-2 had a minor impact on the efficacy of TRAIL-induced apoptosis. CONCLUSION: Taken together, the data indicate that TRAIL is clearly effective under conditions of proven hypoxia.

Curative approaches to lung cancer in the elderly.

Lung cancer is a common disease in elderly patients, and the increase in the size of the elderly population will lead to an increased proportion of elderly among lung cancer patients in the future. The prognosis of lung cancer is still poor, but curative approaches are feasible for patients with local stage NSCLC and for some patients with limited disease (LD) SCLC. The evidence for these curatively-intended approaches is derived from studies that are usually performed with highly selected patients. Elderly patients are underrepresented, and in daily clinical practice elderly patients are less likely to be treated with full standard approaches. We used the data from studies that focused particularly on the elderly, or provided subgroup information on age, to analyze the feasibility of applying current standard approaches to the elderly. We also discuss alternative approaches. Age alone is a very uncertain prognostic criterion for outcome or tolerability of treatment. It is much more important to obtain a comprehensive geriatric assessment of each individual patient. When adequate patient selection is provided, standard treatment approaches appear to be feasible for elderly (>70 years) patients with good performance status.