Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Burden of comorbidities: Osteoporotic vertebral fracture during non-small cell lung cancer - the BONE study.

INTRODUCTION: Immunotherapy and targeted therapy have extended life expectancy in non-small cell lung cancer (NSCLC) patients, shifting it into a chronic condition with comorbidities, including osteoporosis. This study aims to evaluate the prevalence and incidence of osteoporotic vertebral fracture (OPVF) during NSCLC follow-up, identify risk factors of OPVF, and determine the impact on overall survival (OS). METHODS: We performed a longitudinal single-center retrospective cohort study involving patients with histologically proven NSCLC of any stage. Chest-abdomen-pelvis computed tomography (CAP CT) at diagnosis and during follow-up were double-blind reviewed to determine OPVF site, count, type, time to incident OPVF, and trabecular volumetric bone density (TVBD). An institutional expert committee adjudicated discrepancies. Binary logistic regression was used to predict the occurrence of incident OPVF. OS was calculated using the Kaplan-Meier method. RESULTS: We included 289 patients with a median follow-up of 29.7 months. OPVF prevalence was 10.7% at inclusion and 23.2% at the end of follow-up. Cumulative incidence was 12.5%, with an incidence rate of 4 per 100 patient-years. Median time to incident OPVF was 13 months (IQR: 6.7-21.2). Seven of the 36 patients with incident OPVF received denosumab or bisphosphonates. In multivariable analysis, independent risk factors for incident OPVF were BMI < 19 kg/m2 (OR: 5.62, 95%CI 1.84-17.20, p = 0.002), lower TVBD (OR: 0.982 per HU, 95%CI 0.97-0.99, p = 0.001) and corticosteroid use (OR: 4.77, 95%CI: 1.76-12.89, p = 0.001). OPVF was not significantly associated with OS. CONCLUSIONS: Osteoporosis should be screened for in NSCLC patients. Thoracic oncologists must broaden the use of steroid-induced osteoporosis recommendations.

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de langue francaise (GOLF).

BACKGROUND: Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. METHODS: A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. RESULTS: The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. CONCLUSIONS: Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

[Non-infectious respiratory emergencies in patients with cancer]. / Urgences respiratoires (non infectieuses) du patient d'onco-hématologie.

Patients with a solid tumor or hematologic malignancy are often addressed to emergency units for an acute respiratory complication associated with the underlying cancer or secondary to treatments. The current article is part of a thematic series: "Intensive care and emergencies in solid tumours and blood cancer patients" and will develop the following points: (1) malignant proximal airway obstruction and, more specifically, the role of therapeutic bronchoscopy; (2) superior vena cava syndrome by tumor compression and/or secondary to thrombosis (diagnosis, local and systemic treatments); (3) cancer-related pulmonary embolism (incidence, indications for low-molecular weight heparins and direct oral anticoagulants). Other respiratory emergencies will be dealt in the other articles of this series.

Phase II trial of PTK787/ZK 222584 (vatalanib) administered orally once-daily or in two divided daily doses as second-line monotherapy in relapsed or progressing patients with stage IIIB/IV non-small-cell lung cancer (NSCLC).

BACKGROUND: The objective of this multicenter, prospective uncontrolled phase II trial was to determine efficacy, safety and tolerability of vatalanib, an oral angiogenesis inhibitor targeting all known vascular endothelial growth factor receptors, in the second-line treatment of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC-proven tumor progression during or after one platinum-based chemotherapy regimen received a fixed dose of 1250 mg vatalanib either once-daily dosing (QD) or two divided daily dosing (TDD: 500 mg a.m. + 750 mg p.m.) until disease progression or unacceptable toxicity. Primary end point was the disease control rate (DCR) at 12 weeks. RESULTS: Fifty-four and 58 patients were enrolled to the QD and TDD arms. DCR at 12 weeks was 35% in the QD and 37% in the TDD arm. The best overall response included one (2%) patient with confirmed partial response with QD and three (5%) with TDD. Median progression-free survival and overall survival were 2.1/7.3 months in the QD arm and 2.8/9.0 months with TDD arm. This therapy showed a moderate toxicity profile for the majority of patients. CONCLUSIONS: In the chosen patient population, vatalanib QD and TDD dosing demonstrated potential benefits in tumor size reduction, DCR, and survival.

Patients avec cancers thoraciques et COVID-19 : au cœur de la tempête: Patients with chest cancer and COVID-19: at the heart of the storm.

A meta-analysis of the Chinese studies in April 2020, including 3600 patients with cancer and COVID-19, first reported an increase of the COVID-19 risk and the case-fatality in these patients. Then, North-American and European series confirmed the increased COVID-19 risk for patients with cancer, as the increased risk of severe COVID-19 and death, when compared with general population, adjusting for age. Patients with lung cancer have the highest risk of severe respiratory forms, and the highest risk of SARS-CoV2-induced death (25 to 30%), after patients with hematological cancers. Metastatic patients, with poor PS, and those having received a cytotoxic chemotherapy within the weeks preceding SARSCoV2 infection, are those with the highest risk of death. Conversely, being treated with immune checkpoint inhibitors would not favor the cytokine storm, which makes the severity of COVID-19. SARS-CoV2 pandemic, beyond having needed the generalization of drastic social distancing measures in hospitals, also needed organizational changes, to allow healthcare continuity for cancer patients. Adaptation of therapeutic protocols was needed, with increased intervals between cycles, the choice of less toxic protocols, the systematic use of hematological growth factors, and teleconsultations follow-up. Lastly, mRNA-based SARS-CoV2 vaccines are efficient in patients with thoracic cancer, provided the interval of 21/28 days between the two injections is maintained, since protective immunization seems delayed, especially after cytotoxic chemotherapy. Only 13% of patients with very low protective antibodies titers would need a third booster injection, with a clear rise in protective antibodies titers induced by such a third injection.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Definitions, outcomes, and management of hyperprogression in patients with non-small-cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: The advent of immune checkpoint inhibitors (ICI) has been a breakthrough in the care of patients with non-small-cell lung cancers (NSCLC). However, physicians are now facing a previously unidentified clinical situation called hyperprogression (HP), which presents as a fast and unexpected increase in tumor burden. HP's existence and specificity to ICIs remains controversial because a widely acknowledged definition is currently lacking. Meanwhile, management remains elusive. METHODS: Medical records from all consecutive NSCLC patients who were treated with ICI from 2015 to 2018 were retrospectively analyzed. The HP incidence rate was calculated according to five definitions (tumor growth rate [TGR]ratio, ΔTGR, tumor growth kinetic [TGK], RECIST, and time to treatment failure [TTF]), and the agreement between such definitions was determined. The HP impact on overall survival (OS) was then assessed. The association between HP (defined using the TGRratio definition) and clinical and biological variables was also assessed. Clinical HP management and its impact on outcomes were described. RESULTS: We identified 169 consecutive ICI-treated patients, with potential HP accounting for 11.3 %, 5.7 %, 17.0 %, 9.6 %, and 31.7 % patients, according to TGRratio, ΔTGR, TGK, RECIST, and TTF definitions. Agreement between the different HP definitions was highly heterogeneous (range 29 %-77 %) and globally poor. HP was associated with shorter OS, compared to standard RECIST progressive disease, but this difference only reached statistical significance when using the TTF definition. TGRratio-based HP was significantly associated with hepatic metastases. In TGRratio-based HP patients, neither resuming chemotherapy nor corticosteroids use was associated with statistically significant impact on overall survival. CONCLUSION: We found fairly heterogeneous HP rates using different definitions. TTF was the only definition leading to significantly worsened OS. Further studies are needed to provide consensus recommendations for the assessment, definition, and management of HP, whose existence is likely real.

Detection of secondary causes of spontaneous pneumothorax: Comparison between computed tomography and chest X-ray.

PURPOSE: The aim of this study was to compare the effectiveness of chest X-ray to that of thoracic computed tomography (CT) for the detection of the causes of secondary spontaneous pneumothorax (SP). METHODS: A prospective cohort of patients with SP was studied. All chest X-ray and CT examinations of the patients were reviewed retrospectively by an expert radiologist blinded to clinical data. The concordance between the CT examination and chest X-ray was assessed using the Cohen Kappa coefficient (κ), based on a bootstrap resampling method. RESULTS: A total of 105 patients with SP were included. There were 78 men and 27 women, with a mean age of 34.5 years±14.2 (SD) (range: 16-87 years). Of these, 44/105 (41%) patients had primary SP and 61/105 (59%) had secondary SP due to emphysema (47/61; 77%), tuberculosis (3/61, 5%), lymphangioleiomyomatosis (3/61; 5%), lung cancer (2/61, 3%) or other causes (6/61; 10%). Apart from pneumothorax, CT showed abnormal findings in 85/105 (81%) patients and chest X-ray in 29/105 (28%). Clinically relevant abnormalities were detected on 62/105 (59%) CT examinations. The concordance between chest X-ray and CT was fair for detecting emphysema (κ=0.39; 95% CI: 0.2420-0.55), moderate for a mass or nodule (κ=0.60; 95% CI: 0.28-0.90), fair for alveolar opacities (κ=0.39; 95% CI: -0.02-1.00), and slight for interstitial syndrome (κ=0.20; 95% CI: -0.02-0.85). CONCLUSION: Chest X-ray is not sufficient for detecting the cause of secondary SP. As the detection of the cause of secondary SP may alter the therapeutic approach and long-term follow-up in patients with SP, the usefulness of a systematic CT examination should be assessed in a prospective trial.

[Brain and medullar neurosarcoidosis, complicated by stroke with local vasculitis]. / Neurosarcoïdose cérébrale et médullaire compliquée d'un accident vasculaire cérébral avec vasculite locale.

Central nervous system localizations of sarcoidosis remain rare. The brain, mainly the posterior fossa, or the spinal cord, mainly cervical, may be involved. We report the case of a white female presenting a stroke of the head of the caudate nuclei with spontaneous hemorrhage transformation related to and associated with rare encephalic and spinal cord sarcoidosis. The magnetic resonance angiography (MRA) of the intracranial vessels showed images of vasculitis. Treatment of the neurologic localizations was difficult.

[Bevacizumab and invasive procedures: practical recommendations]. / Bevacizumab et actes invasifs: recommandations pratiques.

As first line chemotherapy Bevacizumab, associated with a platinum based regime, improves survival in patients with metastatic, non small cell, non epidermoid bronchial carcinoma. Marketing authorization for this indication was obtained in 2007. This treatment produces specific secondary effects related to its anti-angiogenic action. Physiologically, vascular endothelial growth factor (VEGF) is important in the process of scar formation. Bevacizumab inhibits scar formation and may encourage bleeding. The aim of this article is to analyse the specific risks associated with invasive procedures and to produce practical recommendations. Unfortunately there are few data in the literature. We depend, therefore, principally on studies of neo-adjuvant chemotherapy in metastatic colo-rectal cancer prior to excision of hepatic metastases and on our own experience of excision of pulmonary metastases from solid tumours treated with bevacizumab. We recommend a delay of 2 days between implantation of an intravenous device and the initiation of bevacizumab, a delay of at least 5 weeks between the last injection of bevacizumab and invasive surgery and a delay of 4 weeks between surgery and the initiation of bevacizumab treatment. Obviously, referral to a medico-surgical team experienced in the management of these patients is strongly recommended.

[Perfusion and diffusion-weighted MR imaging in the early staging and the follow-up of patients with lung cancer]. / IRM de perfusion et de diffusion dans le bilan initial et le suivi des patients atteints de cancer bronchique.

Tissue characterization is a major and ultimate goal of imaging, whether morphological (Computed Tomography, Magnetic Resonance Imaging) or metabolic (PET-FDG-[18F]). Functional imaging, using the MRI, began several years ago with the perfusion of lung nodules and very recently with diffusion-weighted imaging applied to the lung cancer. The authors review the interest and the place of diffusion-weighted and perfusion MR imaging in the diagnosis, early staging and follow-up of patients with lung cancer.

[Association between thymic MALT lymphoma and Sjögren's syndrome]. / Association d'un lymphome thymique de type MALT et d'un syndrome de Gougerot-Sjögren.

INTRODUCTION: Thymic mucosa-associated lymphoid tissue (MALT) lymphoma is a rare pathology, often associated with autoimmune diseases. The authors report the case of an Asian woman with Sjögren's syndrome. OBSERVATION: A 48-year-old Chinese woman, without past medical history and a non-smoker, presented an alteration in her overall condition, dyspnoea at exercise, inflammatory polyarthralgia, and a dry eye and mouth syndrome over the last few months. Thoracic tomodensitometry detected an anterior heterogenic cystic mediastinal mass. A mediastinotomy was performed. The diagnosis of the surgical biopsy was thymic MALT lymphoma. The authors also diagnosed Sjögren's syndrome with the presence of four diagnostic criteria. Chemotherapy by rituximab, cyclophosphamide, vincristine, prednisone induced major tumoral regression. The patient declined surgery and will be monitored. CONCLUSION: Thymic MALT lymphoma is a rare pathology. There is a high correlation with autoimmune diseases, like Sjögren's syndrome. Its appearance is that of an anterior mediastinal mass with a cystic component. The treatment is not well codified and is most often based on surgical resection, eventually followed by chemotherapy or radiotherapy. As far as the authors know, this is the second case of thymic MALT lymphoma treated by exclusive chemotherapy.

Diagnostic of mediastinal lymphadenopathy in extrathoracic cancer: A place for EBUS-TBNA in real life practice?

INTRODUCTION: Mediastinal lymphadenopathy in patients with extrathoracic malignancy is common. To obtain tissue proof of metastatic spread, EBUS-TBNA is an alternative to mediastinoscopy or thoracoscopy, but there are limited data about its diagnostic performance. The aim of this study was to determine the diagnostic accuracy of EBUS-TBNA for the evaluation of mediastinal lymphadenopathy in patients with extrathoracic cancers. METHODS: We performed a multicenter retrospective study based on an online questionnaire to collect data from January 2011 to December 2012 in all patients with proven extrathoracic malignancy (current or past) and suspected mediastinal lymph node metastases who underwent EBUS-TBNA for diagnosis. RESULTS: Hundred and eighty-five patients were included. Extrathoracic malignancies observed were urological (43), breast (35), gastrointestinal (33), head and neck (30), melanoma (11), lymphoma (6), and others (27). EBUS-TBNA confirmed malignancy in 93 patients (50.3%): concordant metastases in 67 (36.2%); new lung cancer in 25 (13.5%); and 1 unidentified cancer. The diagnostic accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were respectively 54.6%, 68.4%, 100%, 53.3%, and 100%. CONCLUSION: Mediastinoscopy remain the reference, but EBUS-TBNA may be considered as first line investigation in patients with suspected mediastinal lymph node metastases and extrathoracic malignancy. It prevented a surgical procedure in 50.3% of patients.

[Other thoracic cancers. Bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar carcinoma feature: a clinico-pathological spectrum]. / Carcinome bronchioloalvéolaire (CBA) et adénocarcinome pulmonaire avec composante bronchioloalvéolaire (ADC-CBA): un continuum anatomoclinique.

Bronchioloalveolar carcinoma (BAC) is a primary pulmonary adenocarcinoma (ADC) developed from the terminal respiratory unit. Its restrictive definition adopted by the 1999 WHO pathological classification needs a complete tumor resection to exclude any signs of histological invasion. Although IIIB-IV tumors were excluded from the strict WHO definition of BAC, the first international workshop on BAC in 2004 had focussed on the need to include in the same spectrum of disease pure BAC and ADC with BAC feature (ADC-WBF). BAC and ADC-WBF affect more frequently women, non-smokers and Asian people than other non small cell carcinoma. Their predominant lepidic and aerogenous tumor progression results in a frequent pneumonic, multifocal or diffuse presentation and explains why death is more frequently related to bilateral pulmonary involvement than extra-thoracic metastasis. Natural history is slower and prognosis better than for other ADC. Surgical resection remains the best therapeutic option for localized tumors. High frequency of epidermal growth factor receptor (EGFR) expression on tumor cells and its gene amplification and/or mutation as well as a particular sensitivity of this entity to EGFR tyrosine kinase inhibitors offer new strategy of therapeutical management in patients with non resectable tumor. However, the place of chemotherapy has recently been revisited.

Effect of cannabis and tobacco on emphysema in patients with spontaneous pneumothorax.

PURPOSE: To compare imaging findings on thoracic computed tomography (CT) examination in patients with primary spontaneous pneumothorax (SP), depending on their tobacco and/or cannabis consumption. MATERIALS AND METHODS: A total of 83 patients who had thoracic CT for primary SP were prospectively included. There were 65 men and 18 women with a median age of 33 years (IQR: 27; 44 years). The patients were further categorized into three groups according to their smoking habits. Thirteen patients were non-smokers, 38 were tobacco only smokers and 32 were tobacco and cannabis smokers. CT examinations were retrospectively reviewed for the presence of blebs, centrilobular and paraseptal emphysema and lung nodules in each group for comparison. RESULTS: Emphysema was detected in 43/85 patients (51.8%), including 1/13 patients (7.7%) in the non-smoking group, 19/38 patients (50%) in the tobacco only group and 23/32 patients (71.9%) in the tobacco and cannabis smokers, with no difference between tobacco only and tobacco and cannabis smokers. No differences in type and location of emphysema was found between tobacco only and tobacco and cannabis smokers. Tobacco and cannabis smokers with emphysema were significantly younger than tobacco only smokers with emphysema (35 vs. 46 years, respectively) (P=0.009). CONCLUSION: The prevalence of emphysema visible on CT is not different between tobacco and tobacco/cannabis smokers, however, it occurs at a younger age in tobacco and cannabis smokers. This result suggests that cannabis, when added to tobacco, may lead to emphysema at a younger age.

[Neoadjuvant chemoradiation in non-small cell lung cancer]. / La chimioradiothérapie préopératoire des cancers bronchiques non à petites cellules.

In 2006 preoperative chemoradiation is a major part of the treatment of stage III locally advanced non-small cell lung cancer. Previous studies have clearly demonstrated the feasibility both regarding toxicities and resectability rates of the sequential and concurrent combination of radiation to chemotherapy in a neoadjuvant setting. However, induction chemoradiation has never been randomly compared to exclusive preoperative chemotherapy. Besides, the doses of radiation and the optimal drug combination remain undetermined at the time. Regarding the global therapeutic strategy of stage III non-small cell lung cancer, recently reported phase III trials evaluating the role of surgical resection after induction chemotherapy or chemoradiation, all showed the prognostic importance of the tumoral and mediastinal downstaging to select patients really benefiting from surgery. These developments make of the treatment of locally advanced non-small cell lung cancer a model for multimodal therapeutic strategies combining chemotherapy, radiotherapy and surgery.

[Postoperative chemotherapy in non-small cell lung cancer]. / La chimiothérapie postopératoire des cancers bronchiques non à petites cellules.

Since 2000, seven prospective randomized studies were published or reported comparing surgery and surgery with post-operative chemotherapy for the treatment of non-small cell lung cancer (NSCLC). Four trials (IALT, UFT, JBR10 and ANITA) are positive and have proved the benefit obtained with post-operative chemotherapy for the stages II and IIIA. For the stage IB, this survival increase is also probable, especially for the tumors higher than 4 cm. Several biologic markers are under investigation as predictors of the benefit of the chemotherapy.

[Bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar features: a clinico-pathological spectrum]. / Carcinome bronchio-alvéolaire (CBA) et adénocarcinome pulmonaire avec composante bronchio-alvéolaire (ADC-CBA) : un continuum anatomoclinique.

Bronchioloalveolar carcinoma (BAC) is a pulmonary adenocarcinoma (ADC) developing in the terminal respiratory units. The restrictive definition adopted by the 1999 WHO pathological classification requires a complete resection of the tumour to exclude any evidence of histological invasion. Although IIIB-IV tumours were excluded from the strict WHO definition of BAC, the first international workshop on BAC in 2004 focussed on the need to include in the same disease spectrum both pure BAC and ADC with BAC features (ADC-BAC). BAC and ADC-BAC more frequently affect women, non-smokers and Asians than other non-small cell carcinomas. Their predominantly lepidic airway progression frequently results in a multifocal or diffuse pneumonic presentation and explains why death is more frequently due to bilateral pulmonary involvement than extrathoracic metastases. The natural history is slower and the prognosis better than other ADC. Surgical resection remains the best therapeutic option for localised tumours. The high incidence of epidermal growth factor receptor (EGFR) expression on tumour cells and its gene amplification and/or mutation together with a particular sensitivity of this entity to EGFR tyrosine kinase inhibitors, offer a new strategy of therapeutic management in patients with unresectable tumours. However, the place of chemotherapy has recently been re-evaluated.

[Predicting the response to chemotherapy in patients with non-small cell lung cancer]. / Prédiction de la réponse à la chimiothérapie dans les CBNPC : applications pratiques.

The prognosis of patients with non-small cell lung cancer continues to be poor. Multimodality treatment strategies including chemotherapy are indicated for almost all stages of the disease. To be able to customize chemotherapy based on individual patients' clinical or biological markers is a priority for translational research. Several possible markers need to be validated. In this review, we will discuss the potential of ERCC1 (excision repair cross complementary group 1) to predict sensitivity to cisplatinum, of tubuline-beta, class III for vinca-alkaloids and taxanes, RRM1 (ribonucleotide transferase subunit 1) for gemcitabine and lastly demographic parameters as well biological parameters for erlotinib. Data will be presented separately for patients with metastatic disease and for those where it is localized.