Fractionated stereotactic radiotherapy in the treatment of pituitary adenomas.

PURPOSE: The purpose of this work was to evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent pituitary adenomas. PATIENTS AND METHODS: We report on 37 consecutive patients with pituitary adenomas treated with FSRT at our department. All patients had previously undergone surgery. Twenty-nine patients had nonfunctioning, 8 had hormone-producing adenoma. The mean total dose delivered by a linear accelerator was 49.4 Gy (range 45-52.2 Gy), 5 × 1.8 Gy weekly. The mean PTV was 22.8 ccm (range 2.0-78.3 ccm). Evaluation included serial imaging tests, endocrinologic and ophthalmologic examination. RESULTS: Tumor control was 91.9 % for a median follow-up time of 57 months (range 2-111 months). Before FSRT partial hypopituitarism was present in 41 % of patients, while 35 % had anterior panhypopituitarism. After FSRT pituitary function remained normal in 22 %, 43 % had partial pituitary dysfunction, and 35 % had anterior panhypopituitarism. Visual acuity was stable in 76 % of patients, improved in 19 %, and deteriorated in 5 %. Visual fields remained stable in 35 patients (95 %), improved in one and worsened in 1 patient (2.7 %). CONCLUSION: FSRT is an effective and safe treatment for recurrent or residual pituitary adenoma. Good local tumor control and preservation of adjacent structures can be reached, even for large tumors.

Positron-emission tomography CT to identify local recurrence in stage I lung cancer patients 1 year after stereotactic body radiation therapy.

PURPOSE: To evaluate the diagnostic value of positron-emission tomography/computed tomography (PET/CT) in stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT), who have suspicious or unclear local recurrence findings in CT 1 year after treatment. PATIENTS AND METHODS: A group of 29 patients with unclear or suspicious CT findings 1 year after SBRT were examined with PET/CT. The ability of standard uptake values (SUVmax, SUVmean and posttherapeutic reduction in SUV) to detect local failure and identify patients at a high risk of disease-specific death was evaluated using logrank statistics. Histology and clinical follow-up were the gold standards for local recurrence. RESULTS: SUVmean greater than 3.44 (p = 0.001); SUVmax greater than 5.48 (p = 0.009) or a relative reduction in SUVmean or SUVmax of less than 43 (p = 0.030) or 52 % (p = 0.025), respectively, was indicative of local recurrence. These parameters also correlated with an increased risk of disease-specific death: SUVmean greater than 2.81 (p = 0.023); SUVmax greater than 3.45 (p = 0.007) or a relative reduction in SUVmean or SUVmax of less than 32 (p = 0.015) or 52 % (p = 0.013), respectively, was indicative of an increased risk of disease-specific death. CONCLUSION: PET/CT performed 1 year after SBRT can reliably identify local recurrence and therefore help to clarify unclear CT findings. As posttherapeutic glucose metabolism also correlates with disease-specific survival, PET/CT may help to stratify lung cancer patients for additional treatment 1 year after SBRT.

Respiratory gated [18F]FDG PET/CT for target volume delineation in stereotactic radiation treatment of liver metastases.

PURPOSE: The use of 4D-[(18)F]fluorodeoxyglucose (FDG) PET/CT in combination with respiratory gated magnet resonance imaging (MRI) in target volume definition for stereotactic radiation of liver metastases was investigated. METHODS AND MATERIALS: A total of 18 patients received respiration gated FDG-PET/CT and MRI. Data were fused using a rigid co-registration algorithm. The quality of the co-registration was rated on a scale from 1 (excellent) to 5 (poor) for co-registration of MRI with gated PET and ungated PET. Gross tumor volume (GTV) was delineated in CT (GTV (CT)), MRI (GTV(MRI)), and PET (GTV(PET)). MRI- and PET-based GTVs were defined by three observers each. Interobserver variability was calculated for all patients as well as for subgroups with and without previous treatment of liver metastases. All GTVs were compared for all patients and separately for patients with previous local therapy. In addition, a semiautomatic segmentation algorithm was applied on the PET images. RESULTS: Co-registration between MR and PET images was rated with 3.3 in average when non-gated PET was used and improved significantly (p < 0.01) to 2.1 using gated PET. The average GTV(CT) was 51.5 ml, GTV(MRI) 51.8 ml, and the average GTV(PET) 48.1 ml. Volumes delineated in MRI were 9.9% larger compared to those delineated in CT. Volumes delineated in PET were 13.8% larger than in MRI. The differences between the GTVs were more pronounced in patients with previous treatment. The GTVs defined in MRI showed an interobserver variability of 47.9% (84.1% with previous treatment and 26.2% without previous treatment). The PET-defined GTVs showed an interobserver variability of 21% regardless of previous treatment. Semiautomatic segmentation did not provide satisfying results. CONCLUSION: FDG-PET can distinguish vital tumor tissue and scar tissue, and therefore alters the GTV especially in patients with previous local treatment. In addition, it reduces the interobserver variability significantly compared to MRI. However, respiratory gated PET is necessary for good co-registration of PET and MRI.

Dose-escalated simultaneous integrated-boost treatment of prostate cancer patients via helical tomotherapy.

PURPOSE: The goal of this work was to assess the feasibility of moderately hypofractionated simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) with helical tomotherapy in patients with localized prostate cancer regarding acute side effects and dose-volume histogram data (DVH data). METHODS: Acute side effects and DVH data were evaluated of the first 40 intermediate risk prostate cancer patients treated with a definitive daily image-guided SIB-IMRT protocol via helical tomotherapy in our department. The planning target volume including the prostate and the base of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. The boost volume containing the prostate and 3 mm safety margins (5 mm craniocaudal) was treated as SIB to a total dose of 76 Gy (2.17 Gy per fraction). Planning constraints for the anterior rectal wall were set in order not to exceed the dose of 76 Gy prescribed to the boost volume. Acute toxicity was evaluated prospectively using a modified CTCAE (Common Terminology Criteria for Adverse Events) score. RESULTS: SIB-IMRT allowed good rectal sparing, although the full boost dose was permitted to the anterior rectal wall. Median rectum dose was 38 Gy in all patients and the median volumes receiving at least 65 Gy (V65), 70 Gy (V70), and 75 Gy (V75) were 13.5%, 9%, and 3%, respectively. No grade 4 toxicity was observed. Acute grade 3 toxicity was observed in 20% of patients involving nocturia only. Grade 2 acute intestinal and urological side effects occurred in 25% and 57.5%, respectively. No correlation was found between acute toxicity and the DVH data. CONCLUSION: This institutional SIB-IMRT protocol using daily image guidance as a precondition for smaller safety margins allows dose escalation to the prostate without increasing acute toxicity.

Non-invasive diagnosis and monitoring of actinic cheilitis with reflectance confocal microscopy.

BACKGROUND: Actinic cheilitis (AC) represents the equivalent of actinic keratosis on the lip. Various treatment modalities are available and the efficacy of diclofenac in hyaluronic acid has recently been described. Reflectance confocal microscopy (RCM) is a non-invasive imaging technique which has recently been applied for the diagnosis of actinic keratoses. Herein, we describe the applicability of RCM for the diagnosis of AC and for monitoring of treatment response of AC to diclofenac in hyaluronic acid. METHODS: Ten Caucasian patients with clinical suspicion for AC were included in this study. To obtain a non-invasive diagnosis, RCM was performed at baseline, followed by biopsy and respective confocal-histopathological correlation. Six patients with a histological diagnosis of AC were treated with diclofenac in hyaluronic acid, whereby monitoring was performed by RCM. RESULTS: Reflectance confocal microscopy was able to correctly identify 6/7 cases of AC and 3/3 cases of benign lesions. The most important RCM criteria for diagnosis of AC were cellular atypia at the stratum spinosum and granulosum with atypical honeycomb pattern. One patient with AC was misclassified as inflammatory cheilitis by RCM as it showed marked inflammatory response and lacked clear signs of cellular atypia on RCM imaging. Following topical treatment with diclofenac gel, 5/6 patients (83%) showed a good treatment response with regression of dysplasia on consecutive RCM examination. CONCLUSIONS: Reflectance confocal microscopy is a promising tool for the non-invasive diagnosis and monitoring of actinic cheilitis. However, marked inflammation represents a potential diagnostic pitfall. In this regard, biopsy should be performed in doubtful cases.

[Confocal laser scanning microscopy]. / Konfokale Laserscan-Mikroskopie.

The diagnosis of skin diseases relies strongly on clinical inspection and the use of invasive diagnostic procedures. Routine histology requires the removal of tissue for microscopic evaluation, which is associated with pain, and risk of infection as well as scar formation. In the past 15 years a number of non-invasive diagnostic devices have been evaluated for use in clinical and investigative dermatology. A number of studies have assessed the applicability of confocal laser scanning microscopy (LSM) as an optical diagnostic device in dermatology. By correlating LSM images with established features of routine histology, it was possible to define diagnostic LSM parameters for a number of selected skin diseases. Present data supports the use of LSM as an adjunct diagnostic device for selected skin conditions in clinical as well as investigative dermatology. Since LSM examinations may repeatedly be performed, LSM is particularly suited for evaluation of dynamic, neoplastic and regenerative skin processes as well as the definition of disease extent and response to therapy.

Imaging of tumor physiology: impacts on clinical radiation oncology.

As the metabolic microenvironment markedly influences the therapeutic response of malignant tumors, imaging of the microenvironment is one of the goals researcher have been aiming at for years. Several methods such as positron emission tomography, functional magnetic resonance imaging (MRI) or contrast enhanced MRI/CT are now available. For radiation oncology, tumor oxygenation and perfusion are the most important (patho-) physiological parameters that might be included in radiotherapy regimens and treatment planning. In order to overcome resistance of tumor cells resulting from hypoxia, positron emission tomography (PET) using nitroimidazole tracers is the most advanced technique at this time. Since reproducibility of the PET signal/tracer distribution, thresholding and exact quantification are not thoroughly understood and further investigation is needed before including it into radiotherapy regimens. To image tumor perfusion, dynamic contrast enhanced computed tomography (DCE-CT) or dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) are the most suitable techniques. Co-investigation of tumor oxygenation and perfusion should be performed in order to investigate their interaction and consequences for radiooncology.

Reflectance confocal microscopy for noninvasive monitoring of therapy and detection of subclinical actinic keratoses.

BACKGROUND: Actinic keratoses (AK) represent cutaneous carcinoma in situ and have previously been evaluated by reflectance confocal microscopy (RCM). Treatment of AK with imiquimod (IMIQ) 5% cream has been shown to 'highlight' subclinical lesions. OBJECTIVE: The aim of this study was to test the applicability of RCM for noninvasive monitoring of actinic field cancerization and detection of subclinical AK. SUBJECTS AND METHODS: AK and surrounding skin sites with no apparent AK of 11 volunteers were selected for imaging and subsequently classified as 'clinical' and 'subclinical' AK. IMIQ was used 3 times weekly for 4 weeks. RESULTS: RCM was able to detect morphologic features of AK in both clinical and subclinical AK; features were more pronounced in clinical lesions. The immunomodulatory response induced by IMIQ was visualized by RCM. CONCLUSION: Our findings indicate that RCM allows noninvasive monitoring of treatment response in vivo and permits early detection of subclinical AK, thus substantiating the incentive for therapy.

Clinical applicability of a 1 450 nm diode laser as adjunctive treatment for refractory acne.

Acne is a multifactorial disease of the pilosebaceous units of the face and trunk, most commonly affecting young adolescents. Acne still represents the most common concern in dermatologic consultations and despite aggressive multi-treatment regimens, many patients demonstrate a poor response. A number of recent studies have evaluated the role of laser and light therapy in the treatment of acne vulgaris, with variable clinical outcomes. Among them, a 1450 nm diode laser has been shown to improve refractory acne in a clinical setting. The content of this manuscript draws upon current literature and will critically review the role of mid-infrared lasers as adjunctive therapy for acne.

Comparison of UV-induced skin changes in sun-exposed vs. sun-protected skin- preliminary evaluation by reflectance confocal microscopy.

BACKGROUND: UV radiation (UVR) represents the main risk factor for skin cancer. Sunscreens are commonly used to prevent acute and chronic effects of UVR. The efficacy of sunscreens is currently determined by measurement of minimal erythema dose. Reflectance confocal microscopy represents a non-invasive imaging technique that allows the in- vivo characterization of the skin at near histological resolution. OBJECTIVE: The aim of this study was to compare standardized clinical and histological features of UV-exposure with morphological changes detected by RCM. RESULTS: RCM allowed the detection of morphological changes induced by UV including spongiosis, sunburn cells, micro-vesicles and blood vessel dilatation. The appearance of sunburn cells and micro-vesicles was depending on the dose of UV-B and on the individual susceptibility of the study participants. CONCLUSION: RCM seems to be beneficial for the non-invasive evaluation of dynamic changes following acute UV exposure. Similar to histopathology RCM allows the characterization of sunburn cells and micro-vesicle formation as a sign for acute photo damage. RCM may therefore be used for classification of sunburn reaction and to test the efficacy of sunscreens on a cellular level.

Prediction of very short survival in patients with brain metastases from breast cancer.

AIMS: Current prognostic models are not accurate enough to identify brain metastases patients with very short survival, i.e. <2 months, who are unlikely to derive major benefit from whole brain radiotherapy. Our aim was to develop a more reliable model. MATERIALS AND METHODS: This was a retrospective analysis of a German database, which was used to develop a score, and an additional database from Norway, which was used for validation purposes. RESULTS: The groups included 67 and 32 patients, respectively. An analysis of prognostic factors resulted in a risk score based on performance status, extra-cranial metastases, the interval from breast cancer to brain metastases and a need for corticosteroid treatment, which classified 63 of 67 test patients correctly. However, the validation failed and unfortunately the risk score that performed best in the Norwegian patients (31 of 32 correctly predicted) was not applicable to the German patients. CONCLUSIONS: The prediction of short survival is associated with several caveats and seems to result in an unacceptable risk of withholding radiotherapy in patients who actually survive for longer than 2 months.

Noninvasive diagnostic tools for nonmelanoma skin cancer.

Minimally invasive diagnostic tools have received increased attention for diagnosis, screening and management of nonmelanoma skin cancer (NMSC). Several modalities are commercially available, including high frequency ultrasound, optical coherence tomography and confocal microscopy. While systematic clinical analyses are often lacking, recent reports have shown promising results for reflectance confocal microscopy (RCM) for diagnosis of actinic keratoses and basal cell carcinoma.

Ten-year data on 138 patients with endometrial carcinoma and postoperative vaginal brachytherapy alone: no need for external-beam radiotherapy in low and intermediate risk patients.

OBJECTIVE: To evaluate long-term outcome, risk factors, and causes of death in stage I-IIIA endometrial carcinoma (EC) patients treated only with adjuvant vaginal brachytherapy (VB) and to clarify for which subgroups of patients it is safe to omit external-beam radiotherapy (EBRT). METHODS: Out of 224 EC patients receiving postoperative radiotherapy between 1990 and 2002, 138 had VB alone in curative intent (FIGO [2002]: 85%I, 12%II, 3%IIIA; 18 low risk [IA G1-2, IB G1], 103 intermediate risk [IB G2-3, IC G1-2, IIA-B G1-2], 17 high risk [IC G3, IIIA]). After surgery+/-lymphadenectomy, HDR-brachytherapy prescription (in 95.7% of patients) was 3x10 Gy to the surface or 3x5 Gy at 5 mm tissue depths. RESULTS: Median follow-up was 107 months (range 3-185). Three intermediate and 7 high risk-patients relapsed. The 10-year vaginal control was 99.2%, locoregional control was 95.2% (low/intermediate/high risk: 100%/98.9%/68.8%), and disease-free survival (DFS) was 91.7% (100%/96.8%/55.2%). Risk factors for poor DFS were lymphovascular space invasion, > or = 50% myometrial invasion (univariate, p<0.05), pathological FIGO-stage, and grade 3 (uni-/multivariate, p<0.05). Leading causes of deaths (n=41) were cardiovascular disease (29%) and other malignancies (24%) ahead of EC (19.5%). The 10-year overall survival was 68.5% and the disease-specific survival was 92.4%. Thirty-five secondary tumors in 31 patients led to a higher actuarial death rate (10-year 9.9%, 15-year 17.7%) than EC (7.6%). CONCLUSIONS: Restricting adjuvant therapy to VB alone seems to be safe in low and intermediate risk EC and can be recommended. As death rarely relates to early-stage EC, value of adjuvant therapy is probably better reflected by DFS rather than by overall survival.

Dietary lutein/zeaxanthin partially reduces photoaging and photocarcinogenesis in chronically UVB-irradiated Skh-1 hairless mice.

Lutein and zeaxanthin are xanthophyll carotenoids with potent antioxidant properties protecting the skin from acute photodamage. This study extended the investigation to chronic photodamage and photocarcinogenesis. Mice received either a lutein/zeaxanthin-supplemented diet or a standard nonsupplemented diet. Dorsal skin of female Skh-1 hairless mice was exposed to UVB radiation with a cumulative dose of 16,000 mJ/cm(2) for photoaging and 30,200 mJ/cm(2) for photocarcinogenesis. Clinical evaluations were performed weekly, and the animals were sacrificed 24 h after the last UVB exposure. For photoaging experiments, skin fold thickness, suprapapillary plate thickness, mast cell counts and dermal desmosine content were evaluated. For photocarcinogenesis, samples of tumors larger than 2 mm were analyzed for histological characterization, hyperproliferation index, tumor multiplicity, total tumor volume and tumor-free survival time. Results of the photoaging experiment revealed that skin fold thickness and number of infiltrating mast cells following UVB irradiation were significantly less in lutein/zeaxanthin-treated mice when compared to irradiated animals fed the standard diet. The results of the photocarcinogenesis experiment were increased tumor-free survival time, reduced tumor multiplicity and total tumor volume in lutein/zeaxanthin-treated mice in comparison with control irradiated animals fed the standard diet. These data demonstrate that dietary lutein/zeaxanthin supplementation protects the skin against UVB-induced photoaging and photocarcinogenesis.

Actinic keratoses: non-invasive diagnosis for field cancerisation.

BACKGROUND: Actinic keratoses (AKs) are among the most common cutaneous malignancies and have previously been classified as in situ squamous cell carcinoma (SCC) with reported progression rates of up to 20% over 10 years. Since current scientific evidence suggests the presence of multilocular preneoplastic changes in the areas surrounding the affected skin sites, the detection of subclinical AKs remain an ongoing and challenging effort in the clinical and diagnostic management of these lesions. In vivo reflectance confocal microscopy (RCM) has been used for evaluation of the morphological features of non-melanoma skin cancer (NMSC) and RCM evaluation parameters for the diagnosis of AKs have been reported. OBJECTIVES: The objective of this study was to evaluate the RCM-morphology of clinically diagnosed AKs in our study population and to correlate the findings with routine histopathology. PATIENTS/METHODS: Forty four Caucasians (SPT I-III) with a minimum of one actinic keratosis (AK) lesion were included in this study. Evaluation consisted of clinical examination, RCM and routine histology. Reflectance confocal microscopy evaluation parameters included parakeratosis, architectural disarray and keratinocyte pleomorphism. RESULTS: A total of 44 AKs were included in the final analysis. Following blinded evaluation by two independent investigators, 97.7% of all skin samples were identified as AK using RCM. 2.3% were incorrectly identified as normal skin by RCM, while routine histology showed features consistent with AK. CONCLUSIONS: Reflectance confocal microscopy may be a feasible alternative in the diagnosis of AK and may aid in the differentiation against normal skin, as well as in the detection of subclinical disease.

Differentiation between actinic keratoses and disseminated superficial actinic porokeratoses with reflectance confocal microscopy.

BACKGROUND: Clinical differentiation between actinic keratosis (AK) and disseminated superficial actinic porokeratosis (DSAP) may pose a significant challenge, and histological evaluation is often also required for diagnosis. Distinct morphological features can be distinguished upon histopathological examination, but the use of non-invasive tools, such as reflectance confocal microscopy (RCM), may be an eligible alternative for confirmation of diagnosis. OBJECTIVES: The aim of this study was to determine the relevant RCM criteria for the identification of disseminated superficial actinic porokeratoses (DSAPs) and to define distinguishing criteria for DSAPs compared with actinic keratosis (AKs). PATIENTS/METHODS: A total of 20 patients with a clinical diagnosis of AK or DSAP were included in this study. All lesions were evaluated by clinical examination, and RCM and one clinically identified lesion was biopsied for histological confirmation. RESULTS: Cellular and nuclear atypia, inflammation, spongiosis, parakeratosis and changes in epidermal architecture were present in both lesion types (i.e. AKs and DSAPs). However, these features were more pronounced in AKs. Whereas AKs exhibited more disseminated parakeratotic changes, parakeratosis was found focally present on the border of DSAP lesions. Most characteristically, a distinct border corresponding to cornoid lamella in RCM can be identified in DSAPs. CONCLUSIONS: Distinguishing features of DSAPs, such as cornoid lamella, sharp demarcation of the lesion and focal keratinocyte atypia are easily identifiable using RCM, and correlate well with histopathology. Whilst RCM has previously been used in the evaluation of AKs, it has not yet been used to investigate DSAPs. The findings in this study suggest the feasibility of non-invasive tools, such as RCM for the differentiation of AKs and DSAPs. However, further studies are warranted to assess the sensitivity and specificity of RCM in the diagnosis of DSAP.

Identification of thyroxine-binding globulin-San Diego in a family from Houston and its characterization by in vitro expression using Xenopus oocytes.

T4-binding globulin (TBG) is a liver glycoprotein that transports iodothyronines in serum. Several TBG variants with reduced T4 binding affinity have been described, all of which are also characterized by reduced serum TBG concentrations and reduced heat stability. Their loss of binding thus appears to be due to a general defect of the molecule. We now report the occurrence of a variant TBG, detected in a family from Houston, TX, with half the normal T4 binding affinity and heat stability but normal serum concentration and isoelectric focussing pattern. The propositus was identified by reduced total T4 and T3 serum levels. All family members were euthyroid, and inheritance followed an X-linked pattern. Sequence analysis of the TBG gene of the propositus and his heterozygous mother revealed two amino acid substitutions: serine 23 with threonine (S23T), and the known polymorphism leucine 283 with phenylalanine (L283F). These substitutions are identical to those of TBG-San Diego (TBG-SD), a variant with similar properties except for a reduced serum concentration. Expression of recombinant TBG-SD/H with the S23T substitution in Xenopus oocytes reproduced the binding defect and heat lability. The amount of TBG-SD/H synthesized and secreted by the oocytes was not different from that of normal TBG. The difference in serum TBG concentrations in affected members of the San Diego and Houston families thus does not appear to be due to an error in the measurement of TBG, but may be related to differences in the rates of degradation.

Three-dimensional in vitro cocultivation of lung carcinoma cells with human bronchial organ culture as a model for bronchial carcinoma.

We describe the development of a three-dimensional in vitro organ culture model for bronchial carcinoma using bronchial mucosa organ cultures and three different human non-small cell lung cancer cell lines. During precultivation, bronchial fragments obtained as biopsies during routine bronchoscopy had regenerated a complete epithelial covering with a well-preserved organotypic architecture around a nucleus consisting of connective tissue. To create cocultures, different types of confrontation between tumor cells and organ cultures were applied. Histologic light microscopy and scanning electron microscopy were used in analysis. When tumor cells were confronted with completely epithelialized organ cultures, they showed a low incidence of attachment. When organ cultures were wounded before confrontation, tumor cells always attached to the wounded side and showed a progressive invasion into the stromal tissue. Measurements of the penetration depth of tumor cells into the organ cultures after different incubation times permitted the quantitative evaluation of invasion. Histologic studies revealed well-differentiated normal epithelium in spite of long culture periods. Histologic features of the tumors were those of an invasive undifferentiated carcinoma and showed marked similarities to the situation in vivo. The coculture model permits internal controls because it contains both normal human epithelium and human tumor cells in the same organotypic culture. Therefore it offers opportunities for various in vitro investigations on therapeutic and diagnostic modalities of lung cancer, as indicated in this paper by an example of photodynamic procedures with 5-aminolevulinic acid.

[Increased incidence of bronchial carcinomas. What is new in therapy and diagnosis?]. / Immer mehr Bronchialkarzinome. Was gibt es Neues bei Therapie und Diagnostik?

The increasing incidence and continuing poor prognosis of lung cancer make new therapeutic concepts necessary. For stage I and stage II disease, surgery remains the treatment of choice. In the case of inoperable patients, radiotherapy, used alone, may be a curative alternative. To improve the prognosis of stages II and III of non-small-cell lung cancer, multi-modal treatments such as neoadjuvant chemotherapy, combined chemo-/radiotherapy and post-operative irradiation are still being researched. Although present results indicate higher survival rates, these approaches have not yet become standard. The palliative options for stages III and IV have also clearly been expanded in recent years, so that late-stage lung cancer may yet respond to treatment. Such options are, in particular, invasive bronchoscopic procedures, such as treatment with the Nd-YAG laser, cryotherapy, dilatation and the implantation of stents, or intraluminal irradiation. The major and decisive measure, however, is still prevention which, for 85% of all lung cancer consists in the rejection of nicotine abuse. In the meantime, sensitive methods of early diagnosis have also become available. However, they are invasive and thus not suitable for large-scale screening, but are reserved for high-risk patients. Non-invasive methods are currently under development.