[Guideline on 'non-small cell lung carcinoma; staging and treatment'],[Guideline on 'non-small cell lung carcinoma; staging and treatment']

Contains fulltext : 47959tjan-heijnen.pdf (publisher's version ) (Closed access)A national, evidence-based guideline on the staging and treatment of patients with non-small cell lung carcinoma (NSCLC) has been compiled by the various disciplines involved. The initial diagnostic measures in patients with suspected lung cancer include history taking, physical examination and chest x-ray. Additional examinations include CT scan of the chest and upper abdomen, bronchoscopy, and 18F-fluorodeoxyglucose-positron-emission-tomography(FDG-PET)-scintigraphy, if curative therapy is planned. Cervical mediastinoscopy or endoscopic echography with fine needle aspiration can be performed for mediastinal tissue staging. The preferred treatment in stage I, II or limited III is radical resection. Postoperative radiotherapy is recommended in cases of incomplete resection and can be considered in patients in whom mediastinal lymph-node metastases are unexpectedly encountered. Chemoradiotherapy is recommended in locally advanced NSCLC. In patients with NSCLC stage I-III and poor performance status, palliative radiotherapy may be the only feasible treatment. Some patients with NSCLC stage III and stage IV can be offered palliative chemotherapy and supportive care. In cases of doubt about operability, resectability, significant pulmonary or cardiac comorbidity or combined treatment, a specialist centre should be consulted. Diagnostics should be completed within 3-5 weeks. Ensuing surgery or radiotherapy should be carried out within 2 weeks. Follow-up of patients with NSCLC includes history taking, physical examination and an optional chest x-ray. In the first year after treatment patient visits are planned quarterly, in the second year half-yearly and then yearly for at least five years

Using data assimilation to investigate the causes of Southern Hemisphere high latitude cooling from 10 to 8 ka BP

From 10 to 8 ka BP (thousand years before present), paleoclimate records show an atmospheric and oceanic cooling in the high latitudes of the Southern Hemisphere. During this interval, temperatures estimated from proxy data decrease by 0.8 °C over Antarctica and 1.2 °C over the Southern Ocean. In order to study the causes of this cooling, simulations covering the early Holocene have been performed with the climate model of intermediate complexity LOVECLIM constrained to follow the signal recorded in climate proxies using a data assimilation method based on a particle filtering approach. The selected proxies represent oceanic and atmospheric surface temperature in the Southern Hemisphere derived from terrestrial, marine and glaciological records. Two mechanisms previously suggested to explain the 10–8 ka BP cooling pattern are investigated using the data assimilation approach in our model. The first hypothesis is a change in atmospheric circulation, and the second one is a cooling of the sea surface temperature in the Southern Ocean, driven in our experimental setup by the impact of an increased West Antarctic melting rate on ocean circulation. For the atmosphere hypothesis, the climate state obtained by data assimilation produces a modification of the meridional atmospheric circulation leading to a 0.5 °C Antarctic cooling from 10 to 8 ka BP compared to the simulation without data assimilation, without congruent cooling of the atmospheric and sea surface temperature in the Southern Ocean. For the ocean hypothesis, the increased West Antarctic freshwater flux constrainted by data assimilation (+100 mSv from 10 to 8 ka BP) leads to an oceanic cooling of 0.7 °C and a strengthening of Southern Hemisphere westerlies (+6%). Thus, according to our experiments, the observed cooling in Antarctic and the Southern Ocean proxy records can only be reconciled with the reconstructions by the combination of a modified atmospheric circulation and an enhanced freshwater flux

Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: Results from 2 phase I studies

Background: The objectives were to determine the maximum tolerated dose (MTD) of pemetrexed and cisplatin with concurrent radiotherapy. Secondary objectives include incidence and nature of acute and late toxicities, tumor response and overall survival. Patients and methods: Treatment naive patients received 1 cycle of cisplatin 80 mg/m(2) in study I (stage III NSCLC), 75 mg/m(2) in study II (LD-SCLC) and pemetrexed 500 mg/m(2) before the phase I part. In study I, patients were treated in cohorts with escalating cisplatin doses (60-80 mg/m(2)), pemetrexed doses (400-500 mg/m(2)) and concurrent escalating radiotherapy doses (66 Gy in 33-27 fractions). In study II, patients were treated with cisplatin 75 mg/m(2) and escalating pemetrexed doses (400-500 mg/m(2)) with concurrent escalating radiotherapy doses (50-62 Gy). Results: The trials closed prematurely: study I because of poor accrual, study II because of sponsor decision. Thirteen patients were treated: 4 with NSCLC, 9 with LD-SCLC. No dose-limiting toxicity was observed. There was no grade 4 toxicity, grade 3 hematological toxicity was mild. One patient developed grade 3 acute esophagitis, but was able to complete radiotherapy without delay. Two patients experienced grade 2 late pulmonary toxicity, 1 complete response, 6 partial responses and 1 progressive disease were observed. Conclusions: Although the studies stopped too early to assess MTD, we have demonstrated that the combination of cisplatin and pemetrexed with concurrent radiotherapy up to 66 Gy (33 x 2 Gy) is well tolerated and this new combination shows activity in NSCLC. Pemetrexed is the first 3rd generation cytotoxic found to be tolerable at full dose with concurrent radiotherapy. (C) 2009 Elsevier Ireland Ltd. All rights reserved