To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on ...Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.
HER2 mutations have been identified as oncogenic drivers in lung cancers and are found in 1–2% of lung adenocarcinomas. There is, to date, no standard of care for these patients. We thus aim to study ...the therapeutic outcomes of patients harboring HER2 mutations and establish the efficacy of various drug regimens.
This retrospective cohort study in European centers assessed patients with advanced non-small-cell lung cancer (NSCLC), a known HER2 exon-20 insertion, treated with chemotherapy and/or HER2-targeted drugs.
We identified 101 eligible patients from 38 centers: median age 61 years (range: 30–87), 62.4% women, 60.4% never-smokers. All tumors were adenocarcinomas. Concomitant EGFR mutations, ALK translocations, and ROS translocations were observed in 5, 1, and 1 patients, respectively. The median number of treatment lines was 3 (range: 1–11). The median overall survival was 24 months. Overall response rate (ORR) and the median progression-free survival (PFS) with conventional chemotherapy (excluding targeted therapies) were 43.5% and 6 months in first-line (n = 93), and 10% and 4.3 months in second-line (n = 52) therapies. Sixty-five patients received HER2-targeted therapies: trastuzumab = 57, neratinib = 14, afatinib = 9, lapatinib = 5, T-DM1 = 1. ORR was 50.9% and PFS was 4.8 months with trastuzumab or T-DM1.
This series shows the chemosensitivity of HER2-driven NSCLC, and the potential interest of HER2-targeted agents. Our results should help to define the best therapeutic strategy for these patients and to orient future clinical trials.
We present an original severe case of tularemia with cutaneous damage, lymphadenopathy and pericarditis ; pathology of increasing incidence in Europe due to global warming.
A 33-years-old women ...consulted emergency unit for altered general condition, anorexia, hyperthermia at 38,3°C, dyspnea and dry cough evolving for few days. Her only history was Crohn's disease with introduction of an anti-TNF alpha for 3 months. The interrogation found regular forest walks ». Treatment with Amoxicillin/clavulanic acid 1g 3 times daily and curative anticoagulation was started after the initial diagnosis of infectious pneumonia associated with pulmonary embolism. The patient reconsulted 2 weeks later for clinical deterioration associated with skin lesions. The chest CT scan showed increased mediastinal lymphadenopathy and a circumferential pericardial effusion ; quantified at 5mm on transthoracic ultrasound. Tularemia serology was positive in IgG at 400IU/mL. Despite an adapted antibiotic therapy with Ciprofloxacin, the patient presented a new brutal clinical deterioration. A pericardiocentesis was performed and the analysis revealed a predominantly neutrophilic exudate and a strongly positive PCR Francisella tularensis. Gentamicin 5mg/kg was associated allowing a resolution of the symptoms.
Tularemia is one of the pathologies whose atypical presentation with pericarditis (favored by a certain immunodepression) worsens the prognosis. Global warming influences the epidemiology of inoculation diseases, including tularemia, making it more frequent.
•In asymptomatic patients, chemotherapy alone was the most commonly recommended 1st line treatment.•For symptomatic patients, WBRT was the most common 1st line treatment.•Significant variation in ...decision-making exists among European SCLC experts.
Brain metastases (BM) are common in patients with small cell lung cancer (SCLC). In recent years, the role of whole brain radiotherapy (WBRT) for brain metastases in lung cancer is being reevaluated, especially in the context of new systemic treatments available for SCLC. With this analysis, we investigate decision-making in SCLC patients with BM among European experts in medical oncology and radiation oncology.
We analyzed decision-making from 13 medical oncologists (selected by IASLC) and 13 radiation oncologists (selected by ESTRO) specialized in SCLC. Management strategies of individual experts were converted into decision trees and analyzed for consensus.
In asymptomatic patients, chemotherapy alone is the most commonly recommended first line treatment. In asymptomatic patients with limited volume of brain metastases, a higher preference for chemotherapy without WBRT among medical oncologists compared to radiation oncologists was observed.
For symptomatic patients, WBRT followed by chemotherapy was recommended most commonly. For limited extent of BM in symptomatic patients, some experts chose stereotactic radiotherapy as an alternative to WBRT.
Significant variation in clinical decision-making was observed among European SCLC experts for the first line treatment of patients with SCLC and BM.
•Second-line therapy of stage IV SCLC is heterogeneous among European experts.•After 6 months from first-line treatment, 92 % recommend platinum re-challenge.•3–6 months after first-line treatment no ...consensus was found.•In very early recurrence CAV for fit & topotecan for unfit patients was recommended.
Stage IV small cell lung cancer (SCLC) is associated with short survival and progression after first-line systemic therapy frequently occurs within months. Although topotecan is approved for second-line treatment, its efficacy is limited, and treatment heterogeneity exists.
The decision-making patterns for second line treatment of 13 European medical oncologists with expertise in SCLC were analyzed.
The two criteria most relevant to decision-making were the performance status and the interval of recurrence since first-line treatment.
With an interval of less than 3 months since the end of first-line chemotherapy, 62 % of the experts recommended cyclophosphamide, doxorubicin and vincristine (CAV) for fit patients and 54 % recommended topotecan for unfit patients. For an interval of more than 6 months, a clear consensus for a re-challenge with a platinum doublet was achieved (92 %). However, there was no consensus on the second-line therapy with an interval of 3–6 months since the end of first-line therapy.
Real world practice may differ from recommendations in general guidelines and cannot always be directly derived from trial results as other factor such as habits, patient’s preference, convenience or costs have to be factored in.
Endpoints in cancer clinical trials Fiteni, F; Westeel, V; Pivot, X ...
Journal of visceral surgery,
02/2014, Letnik:
151, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary Endpoints are measurable clinical and biological findings that are used for the development and assessment of treatment options. In the treatment of cancer, endpoints can be classified into ...two categories: “patient-centered clinical endpoints” including overall survival (OS) and health-related quality of life (QoL), and “tumor-centered clinical endpoints” such as progression-free survival. Surrogate endpoints are tumor-centered clinical endpoints that can be used as substitutes for patient-centered clinical endpoints, particularly OS. The choice of endpoints in oncology trials is a major problem. The published Consolidated Standards of Reporting Trials (CONSORT) best-practice guidelines encourage the reporting of clearly defined primary and secondary outcome measures. OS is the gold standard of endpoints but as increasing numbers of effective salvage treatments become available for many types of cancer, much larger numbers of patients are included; this requires a longer follow-up period and increases the cost of clinical trials. Thus, tumor-centered clinical endpoints that can be assessed earlier and used as surrogates for overall survival are increasingly studied, but most of them currently lack standardized definitions to enable cross comparison of results among different clinical trials and they have not been validated as surrogate endpoints. In addition, the variability of their definition can strongly impact the trial's conclusions by affecting both statistical power and estimation. In this context, QoL constitutes an available and useful surrogate endpoint for trials to ensure treatment benefit from both the patient and public health points of view. Methodological research should be pursued to develop standard outcome definitions for use in cancer clinical trials and to define a standardized longitudinal analysis of QoL data.
Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or ...expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway.
Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers.
The first patient will be enrolled in January 2021, with results expected in 2028.
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