Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

Polyethylene glycol improves current methods for circulating extracellular vesicle-derived DNA isolation.

BACKGROUND: Extracellular vesicles (EVs) are small membrane-bound vesicles which play an important role in cell-to-cell communication. Their molecular cargo analysis is presented as a new source for biomarker detection, and it might provide an alternative to traditional solid biopsies. However, the most effective approach for EV isolation is not yet well established. RESULTS: Here, we study the efficiency of the most common EV isolation methods-ultracentrifugation, Polyethlyene glycol and two commercial kits, Exoquick® and PureExo®. We isolated circulating EVs from the bloodstream of healthy donors, characterized the size and yield of EVs and analyzed their protein profiles and concentration. Moreover, we have used for the first time Digital-PCR to identify and detect specific gDNA sequences, which has several implications for diagnostic and monitoring many types of diseases. CONCLUSIONS: Our findings present Polyethylene glycol precipitation as the most feasible and less cost-consuming EV isolation technique.

Integral nutritional approach to the care of cancer patients: results from a Delphi panel.

INTRODUCTION: Malnutrition is a common complication in cancer patients and can negatively affect the outcome of treatments. This study aimed to reach a consensus on nutritional needs and optimize nutritional care in the management of cancer patients at a national level. METHODS: A qualitative, multicenter, two-round Delphi study involving 52 specialists with experience in nutritional support in cancer patients was conducted. RESULTS: Regarding the presence of malnutrition, 57.7% of the participants stated that < 30% of the patients had malnutrition at the time of diagnosis, 40.4% considered that 31-50% had malnutrition during cancer treatment, and 26.9% that > 50% at the end of the treatment. Forty percent of participants believed that the main objective of nutritional treatment was to improve quality of life and 34.6% to improve tolerability and adherence to chemotherapy. The quality nutritional care provided at their centers was rated as medium-low by 67.3%. Enteral and parenteral nutrition was administered to less than 10% and less than 5% of patients in 40.4 and 76.9% of cases, respectively. In relation to nutritional screening at the time of diagnosis, 62.9% of participants considered than screening to assess the risk of malnutrition was performed in < 30% of patients. CONCLUSIONS: There is an important variability in the management of cancer patient nutrition, which is associated with the absence of a national consensus on nutritional support in this field. Given the incidence of nutritional disorders in cancer patients, a specialist in clinical nutrition (regardless of his/her specialty) should be integrated into the strategic cancer plan.

A phase II study of feasibility and toxicity of bevacizumab in combination with temozolomide in patients with recurrent glioblastoma.

PURPOSE: The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ. PATIENTS AND METHODS: Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m(2) days 1-7 and 15-21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks. RESULTS: Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44%) had gross total resection. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9% (95% CI 9.3-40.0%). The median PFS and overall survival (OS) were 4.2 months (95% CI 3.6-5.4 months) and 7.3 months (95% CI 5.8-8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19%; 95% CI 7.2-36.4) were long-term survivors, with a median PFS and OS (50% events) of 9.5 months (95% CI 7.9-23.6) and 15.4 (95% CI 8.9-NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed. CONCLUSIONS: This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy.

[Causes and factors associated with reconciliation errors in medical and surgical services]. / Causas y factores asociados a los errores de conciliación en servicios médicos y quirúrgicos.

OBJECTIVE: The objective of this study was to determine the main causes of errors of medication reconciliation at hospital admission in medical and surgical department and establish factors associated with medication reconciliation errors. MATERIAL AND METHOD: Cross-sectional study. We included all patients admitted to two services and two surgical for a month. To determine the presence of error reconciliation, the pharmacist compared the medication history interview by the order physician. The factors associated with errors were identified by multivariate logistic regression analysis. RESULTS: 221 patients were included, of which 58.4% had at least one error reconciliation. We detected 629 discrepancies, 339 (53.9%) reconciliation errors. The incidence of errors in medical services was 24.3% and in the surgical services 43.0% (p <0.001) in both groups being most prevalent error of omission (46.2% and 50.8%). Regarding factors associated, the equation determines that patients older than 65 years, polymedicated and taking oral antidiabetic are more likely to have an error with a sensibility of 75.2% and a specificity of 68.5%. CONCLUSION: There is a high rate of error reconciliation in medical and surgical patients, which confirms the need to implement a strategy to reduce these errors. Given the difficulty of applying the process to all patients, the strategy must be directed to patients who are at increased risk of error.

Objetivo: Determinar las principales causas de errores de conciliacion de la medicacion al ingreso hospitalario tanto en los servicios medicos, como en los quirurgicos y que factores se asocian a dichos errores de conciliacion. Material y método: Estudio observacional transversal. Se incluyeron todos los pacientes que ingresaron en dos servicios medicos y dos quirurgicos durante un mes. Para determinar la presencia de error de conciliacion se cotejo la historia realizada por el farmaceutico con la del medico prescriptor. Los factores asociados a los errores se identificaron mediante un analisis de regresion logistica multivariante. Resultados: Se incluyeron 221 pacientes, de los cuales el 58.4% presentaron al menos un error de conciliacion. Se detectaron un total de 629 discrepancias, 339 (53.9%) errores de conciliacion. La incidencia de errores en los servicios medicos fue del 24.3% y en los quirurgicos del 43.0% (p.

Lung adenocarcinoma in the era of targeted therapies: histological classification, sample prioritization, and predictive biomarkers.

The arrival of targeted therapies has presented both a conceptual and a practical challenge in the treatment of patients with advanced non-small cell lung carcinomas (NSCLCs). The relationship of these treatments with specific histologies and predictive biomarkers has made the handling of biopsies the key factor for success. In this study, we highlight the balance between precise histological diagnosis and the practice of conducting multiple predictive assays simultaneously. This can only be achieved where there is a commitment to multidisciplinary working by the tumor board to ensure that a sensible protocol is applied. This proposal for prioritizing samples includes both recent technological advances and the some of the latest discoveries in the molecular classification of NSCLCs.

IGFBP-3 methylation-derived deficiency mediates the resistance to cisplatin through the activation of the IGFIR/Akt pathway in non-small cell lung cancer.

Although many cancers initially respond to cisplatin (CDDP)-based chemotherapy, resistance frequently develops. Insulin-like growth factor-binding protein-3 (IGFBP-3) silencing by promoter methylation is involved in the CDDP-acquired resistance process in non-small cell lung cancer (NSCLC) patients. Our purpose is to design a translational-based profile to predict resistance in NSCLC by studying the role of IGFBP-3 in the phosphatidyl inositol 3-kinase (PI3K) signaling pathway. We have first examined the relationship between IGFBP-3 expression regulated by promoter methylation and activation of the epidermal growth factor receptor (EGFR), insulin-like growth factor-I receptor (IGFIR) and PI3K/AKT pathways in 10 human cancer cell lines and 25 NSCLC patients with known IGFBP-3 methylation status and response to CDDP. Then, to provide a helpful tool that enables clinicians to identify patients with a potential response to CDDP, we have calculated the association between our diagnostic test and the true outcome of analyzed samples in terms of cisplatin IC50; the inhibitory concentration that kills 50% of the cell population. Our results suggest that loss of IGFBP-3 expression by promoter methylation in tumor cells treated with CDDP may activate the PI3K/AKT pathway through the specific derepression of IGFIR signaling, inducing resistance to CDDP. This study also provides a predictive test for clinical practice with an accuracy and precision of 0.84 and 0.9, respectively, (P=0.0062). We present a biomarker test that could provide clinicians with a robust tool with which to decide on the use of CDDP, improving patient clinical outcomes.

Targeting Chk2 improves gastric cancer chemotherapy by impairing DNA damage repair.

Our results demonstrate that the addition of cisplatin after paclitaxel-induced mitotic arrest was more effective than individual treatment on gastric adenocarcinoma cells (MKN45). However, the treatment did not induce benefits in cells derived from lymph node metastasis (ST2957). Time-lapse microscopy revealed that cell death was caused by mitotic catastrophe and apoptosis induction, as the use of the caspase inhibitor z-VAD-fmk decreased cell death. We propose that the molecular mechanism mediating this cell fate is a slippage suffered by these cells, given that our Western blot (WB) analysis revealed premature cyclin B degradation. This resulted in the cell exiting from mitosis without undergoing DNA damage repair, as demonstrated by the strong phosphorylation of H2AX. A comet assay indicated that DNA repair was impaired, and Western blotting showed that the Chk2 protein was degraded after sequential treatment (paclitaxel-cisplatin). Based on these results, the modulation of cell death during mitosis may be an effective strategy for gastric cancer therapy.

Analysis of the concordance in the EGFR pathway status between primary tumors and related metastases of colorectal cancer patients:implications for cancer therapy.

Patients with metastatic Colorectal Cancer (mCRC), in which primary tumors are KRAS mutated, have no response to anti-EGFR therapy. However, less than half of mCRC patients with KRAS wild-type primary tumors respond to anti-EGFR therapy. Other downstream effectors of the EGFR pathway are being analyzed to fine-tune KRAS predictive value. However, as the primary tumor is the tissue of analysis that determines the use of anti-EGFR therapy in advanced disease, a high concordance in the status of these effectors between primary tumors and related metastases is required. We analyzed the concordances of downstream EGFR effectors in tumoral pairs of primaries and related metastases in a series of KRAS wild-type patients. One hundred seventeen tumoral pairs from patients with CRC were tested for KRAS mutational status. The level of concordance in the presence of KRAS mutations was 91% between the primary tumor and related metastases. The 70 pairs with KRAS wild-type primary tumors were further analyzed for BRAF and PIK3CA mutational status and for EGFR, PTEN and pAKT expression, and the number of concordant pairs was 70 (100%), 66 (94%), 43 (61%), 46 (66%) and 36 (54%), respectively. Our findings suggest that the mutational status of KRAS, BRAF and PIK3CA in the primary tumor is an adequate surrogate marker of the status in the metastatic disease. On the other hand, the immunohistochemical analysis of EGFR, PTEN and pAKT showed a much higher degree of discordance between primaries and related metastases.

Treatment for ALK-mutated non-small-cell lung cancer: a new miracle in the research race.

The discovery of anaplastic lymphoma kinase (ALK) rearrangements in a subset of patients with nonsmall- cell lung cancer (NSCLC) and its potential blockage by specific inhibitors such as crizotinib has been one of the latest advances in the treatment of this disease. In this article, we will review the most important clinical aspects of ALK alterations in NSCLC patients and the pending questions to answer: the most effective means of diagnosing ALK-rearranged NSCLC, and efficacy, toxicity profile and potential mechanisms of resistance to crizotinib.

DUSP1/MKP1 promotes angiogenesis, invasion and metastasis in non-small-cell lung cancer.

DUSP1/MKP1 is a dual-specific phosphatase that regulates MAPKs activity, with an increasingly recognized role in tumor biology. To understand more about the involvement of DUSP1 in lung cancer, we performed gene expression analyses of parental and DUSP1-interfered H460 non-small-cell lung cancer (NSCLC) cells. Downregulation of DUSP1 induced changes in the expression levels of genes involved in specific biological pathways, including angiogenesis, MAP kinase phosphatase activity, cell-cell signaling, growth factor and tyrosine-kinase receptor activity. Changes in the expression of some of these genes were due to modulation of c-Jun-N-terminal kinase and/or p38 activity by DUSP1. Complementary functional assays were performed to focus on the implication of DUSP1 in angiogenesis and metastasis. In H460 cells, interference of DUSP1 resulted in a diminished capacity to invade through Matrigel, to grow tumors in nude mice and also to induce metastasis through tail-vein injection. Furthermore, the angiogenic potential of H460 cells was also impaired, correlating with a decrease in VEGFC production and indicating that DUSP1 could be required to induce angiogenesis. Finally, we studied whether a similar relationship occurred in patients. In human NSCLC specimens, DUSP1 was mainly expressed in those tumor cells close to CD31 vascular structures and a statistically significant correlation was found between VEGFC and DUSP1 expression. Overall, these results provide evidence for a role of DUSP1 in angiogenesis, invasion and metastasis in NSCLC.

Phase II study of a fixed dose-rate infusion of gemcitabine associated with erlotinib in advanced pancreatic cancer.

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination regimen consisting of gemcitabine-FDR infusion plus erlotinib, in ACP patients. METHODS: Forty-two patients with histologically confirmed, locally advanced or metastatic pancreatic cancer were included in this phase II trial. Main objectives were to assess the efficacy and safety of this regimen. Therapeutic regimen consisted of gemcitabine 1,200 mg/m(2) in 120-min infusion on days 1, 8 and 15, plus erlotinib 100 mg orally once daily. Cycles were repeated every 28 days. RESULTS: A total of 160 courses of gemcitabine-FDR erlotinib were administered (median 3.8 courses per patient). The most common grade 3-4 AEs were neutropenia (21%), thrombocytopenia (10%), skin rash (10%) and asthenia (10%). Complete response was achieved in one patient (2%) and 11 (26%) achieved a partial response. Stable disease and progression disease were observed in 11 patients (26%) and 19 (45%), respectively. Median time to progression was 5 months (95%CI: 3.9-5.8 months) and median overall survival was 8 months (95% CI: 5.1-10.8). One-year survival rate was 35%. CONCLUSIONS: A regimen consisting of gemcitabine-FDR infusion plus erlotinib is active and well tolerated in APC patients. However, the results do not justify the conduct of a Phase III trial.

Checkpoint kinase 1 modulates sensitivity to cisplatin after spindle checkpoint activation in SW620 cells.

Aneuploidy is a common feature of tumours that arise by errors in chromosome segregation during mitosis. The aim of this study was to evaluate possible signaling pathways involved in sensitization to chemotherapy in cells with chromosomal instability. We designed a screen using the fission yeast Squizossaccharomyces pombe, to isolate strains showing a phenotype of chromosome mis-segregation and higher sensitivity to the antitumoral drug Bleomycin. We examined differences in gene expression using a comparative analysis of genome-wide expression of the wild type strain and one of the mutants. The results revealed a set of genes involved in cell cycle control, including Mad3/BubR1 and Chk1. We then studied the levels of these two proteins in colorectal cancer human cell lines with different genomic content. Among these, SW620 cells showed higher BubR1 and Chk1 mRNA levels than control cells under normal conditions. Since Chk1 is required for both S and G2/M checkpoints, and the microtubule-destabilizing agent, nocodazole induces mitotic arrest, we attempted to investigate the potential anticancer effects of nocodazole in combination with cisplatin. These studies showed that SW620 cells undergo synergistic cell death after spindle checkpoint activation followed by cisplatin treatment, suggesting a role of Chk1 in this checkpoint, very likely dependent on BubR1 protein. Importantly, Chk1-depleted SW620 cells lost this synergistic effect. In summary, we propose that Chk1 could be a biomarker predictive of the efficacy of chemotherapy across different types of tumors with aneuploidy. These findings may be potentially very useful for the stratification of patients for treatment.

IGFBP-3 hypermethylation-derived deficiency mediates cisplatin resistance in non-small-cell lung cancer.

Cisplatin-based chemotherapy is the paradigm of non-small-cell lung cancer (NSCLC) treatment; however, it also induces de novo DNA-hypermethylation, a process that may be involved in the development of drug-resistant phenotypes by inactivating genes required for drug-cytotoxicity. By using an expression microarray analysis, we aimed to identify those genes reactivated in a set of two cisplatin (CDDP) resistant and sensitive NSCLC cell lines after epigenetic treatment. Gene expression, promoter methylation and CDDP-chemoresponse were further analyzed in three matched sets of sensitive/resistant cell lines, 23 human cancer cell lines and 36 NSCLC specimens. Results revealed specific silencing by promoter hypermethylation of IGFBP-3 in CDDP resistant cells, whereas IGFBP-3 siRNA interference, induced resistance to CDDP in sensitive cells (P<0.001). In addition, we found a strong correlation between methylation status and CDDP response in tumor specimens (P<0.001). Thus, stage I patients, whose tumors harbor an unmethylated promoter, had a trend towards increased disease-free survival (DFS). We report that a loss of IGFBP-3 expression, mediated by promoter-hypermethylation, results in a reduction of tumor cell sensitivity to cisplatin in NSCLC. Basal methylation status of IGFBP-3 before treatment may be a clinical biomarker and a predictor of the chemotherapy outcome, helping to identify patients who are most likely to benefit from CDDP therapy alone or in combination with epigenetic treatment.

A critical role for choline kinase-alpha in the aggressiveness of bladder carcinomas.

Bladder cancer is one of the most common causes of death in industrialized countries. New tumor markers and therapeutic approaches are still needed to improve the management of bladder cancer patients. Choline kinase-alpha (ChoKalpha) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhibitors of ChoKalpha show antitumoral activity and are expected to be introduced soon in clinical trials. This study aims to assess whether ChoKalpha plays a role in the aggressiveness of bladder tumors and constitutes a new approach for bladder cancer treatment. We show here that ChoKalpha is constitutively altered in human bladder tumor cells. Furthermore, in vivo murine models, including an orthotopic model to mimic as much as possible the physiological conditions, revealed that increased levels of ChoKalpha potentiate both tumor formation (P< or =0.0001) and aggressiveness of the disease on different end points (P=0.011). Accordingly, increased levels of ChoKalpha significantly reduce survival of mice with bladder cancer (P=0.05). Finally, treatment with a ChoKalpha-specific inhibitor resulted in a significant inhibition of tumor growth (P=0.02) and in a relevant increase in survival (P=0.03).

Prognostic value of carcinoembryonic antigen level in rectal cancer treated with neoadjuvant chemoradiotherapy.

BACKGROUND: The purpose of this study was to identify clinical and pathological parameters to improve prediction of disease-free survival (DFS) and overall survival (OS) in patients treated with neoadjuvant chemoradiotherapy for rectal cancer. METHODS: Between July 1995 and May 2007, 148 patients with primary rectal adenocarcinoma received neoadjuvant chemoradiotherapy followed by mesorectal excision. Preoperative treatment included various protocols, UFT and leucovorin (28%) and oxaliplatin-based chemotherapy (72%). Clinical and pathological variables were evaluated in relation to patient outcomes. RESULTS: Thirteen percent of patients achieved a complete pathologic response. No response or minimal response as defined by Dworak (Tumor Regression Grade 0/1) was observed in 30 patients (20%). At a median follow-up of 37 months, the 3-year DFS and OS were 64% and 83%, respectively. Pre-treatment serum carcinoembryonic antigen (CEA) level

Study of the prevalence of tumour-related asthenia in Spanish cancer patients.

INTRODUCTION: Asthenia is the most prevalent symptom in oncological patients but it is underestimated by the majority of healthcare professionals. The aim of the present study is to estimate the prevalence of tumour-related asthenia in the Spanish population, while defining the associated factors. METHODS: An epidemiological, multicentre, cross-sectional study was conducted in oncology services from Spain, including 712 cancer patients (58.4+/-13.5 years). RESULTS: 42.5% patients showed asthenia. This prevalence appeared to be tumour-related (p<0.05) and increased among patients with a more advanced stage of disease or with a worsening of performance status (p<0.001). The prevalence of asthenia increased in the presence of the following factors: chemotherapy (in the past: 52.1% vs. 31.0%; at the time of the study: 46.1% vs. 38.2%), symptomatic treatment (in the past: 60.4% vs. 39.8%; at the time of the study: 61.3% vs. 38.6%), present interferon treatment (100%), anaemia (59.7% vs. 31.3%), dehydration/waterelectrolyte imbalance (58.3% vs. 41.6%), respiratory failure (61.4% vs. 39.7%), liver disease (59.5% vs. 41.3%), malnutrition (76.1% vs. 38.7%), pain (57.7% vs. 27.0%), anxiety (56.1% vs. 38.6%), depression (57.9% vs. 40.0%) and sleep disturbances (51.1% vs. 39.4%). A multivariate logistic regression showed that a model including performance status, patient circumstance, chemotherapy, anaemia, pain and anxiety correctly diagnosed asthenia in 70.9% of cases. CONCLUSIONS: The physiopathology of tumour-related asthenia remains relatively unknown, despite its high prevalence and considerable quality of life impact. Determining factors related to asthenia in clinical practice can favour the use of concrete treatments and improve the conditions of cancer patients.

EGFR and colon cancer: a clinical view.

Signalling pathways that emerge from EGFR activation are critical in colon cancer (CC) biology. Its targeting with specific drugs has opened a new window in the treatment of this disease. In this regard, monoclonal antibodies (mAb) have evidenced a high degree of efficiency opposed to the uselessness of tyrosine-kinase inhibitors. Cetuximab is the mAb that has evidenced most activity in CC. After its initial approval as an irinotecan-resistance reversal agent, cetuximab has demonstrated its efficiency from the first line to heavily pretreated patients. In the first line, its addition may increase response rate to chemotherapy, improving liver metastases resection rate. Another promising approach has been suggested from combination schedules with bevacizumab. Panitumumab has been recently approved for CC. Although there is limited clinical experience, the latest data have confirmed its activity in heavily pretreated patients resulting in a clinical benefit vs. best support care. In spite of the clinical benefits, adverse events and the high sanitary cost derived from these drugs force the selection of patients with the highest probability of benefit. At the moment, when EGFR expression evidenced by immunohistochemistry has no value, skin toxicity and, fundamentally, K-Ras mutations may hint at critical information for confirmatory prospective studies.

Molecular markers in colorectal cancer: genetic bases for a customised treatment.

Colorectal cancer (CRC) is the second leading cause of cancer death in Western countries. CRC treatment is based on the employment of three chemotherapeutic drugs, including 5-fluorouracil, oxaliplatin and irinotecan, and the use of recently incorporated targeted agents directed to vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). The approval of these biologicals and of others to come holds great promise for the improvement of patient outcome. The molecular bases for this lethal disease have been extensively investigated, laying the foundations for a rational and customised treatment approach, expanding the therapeutic index of current drugs and easing the incorporation of new molecules. Individual markers have been mainly investigated based on drug targets and metabolism. Also, the increasing availability of highthroughput technologies has prompted the opportunity for blind studies capable of screening new markers and of identifying the specific oncogenic pathways responsible for drug resistance in a given patient. An updated review of the field is presented in this article.

New screening method for lung cancer by detecting volatile organic compounds in breath.

Lung cancer is a frequent cause of cancer-related deaths in the world. There is no valid screening process and this limits its detection to the late stages, with consequently high mortality rates. Volatile organic compounds (VOC) are chemical compounds (mainly the products of cell catabolism) found as gases in the human breath. Different methods have been developed to analyse VOCs and to compare them in healthy subjects and lung cancer patients. In this review, we summarise the different techniques used to analyse VOC. Many reports have been published with promising results similar to those achieved with accepted screening methods such as mammography. These methods show good perspectives on lung cancer screening.