[Show abstract][Hide abstract] ABSTRACT: PURPOSE: While the overall prognosis of non-molecularly selected advanced non-small cell lung cancer (NSCLC) patients is poor, a subset of these patients has durable survival. We examined which clinical factors might be predictive for this favourable outcome. PATIENTS AND METHODS: Long-term NSCLC survivors (LTS, i.e. >2 years) were retrieved from all our out- and in-patient contacts in a 6 month period (March-August 2009). LTS records were compared with a group of short-term survivors (STS). Both baseline clinical factors (sex, age, smoking status, weight loss, performance status, co-morbidity, histological subtype, place and number of metastasis) and treatment-related features (number and type of therapeutic lines, response, duration of treatment-free interval) were compared. RESULTS: 31 LTS were retrieved (stage IV patients with potentially radical treatment options, e.g. solitary brain or adrenal metastasis, were excluded), and compared with 34 STS. In the LTS group, median survival was 53 months, with 47% of patients alive at 5 years, in the STS patients this was 9.7 months, with 24% alive at 1-year. Baseline factors had little predictive value, but response to 1st line therapy (P=0.0001), response duration (P=0.009), and the number of systemic lines (P=0.0023) were of importance. CONCLUSION: These data confirm the existence of LTS in patients with advanced NSCLC. There are very little clinical factors at the time of diagnosis that help to distinguish future LTS from STS patients. Factors related to the effect of 1st line treatment are important, and further prospects of patients achieving a 2-year survival are in general quite good.
Lung cancer (Amsterdam, Netherlands) 10/2012; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The greatest news of the past year in this field was the first large-scale early detection trial that could prove a 20% reduction in lung cancer-related mortality by screening high-risk individuals with low-dose computed tomography (LDCT). Several expert groups and medical societies have assessed the data and concluded that LDCT screening for lung cancer is, however, not ready for large-scale population-based implementation. Too many open questions remain, such as definition of the at-risk population, timing and intervals of screening, optimal method of acquisition and interpretation of the images, how to handle (false) positive findings, and especially cost-effectiveness in relation to other lung cancer prevention strategies, mainly smoking cessation. Further analyses and several ongoing European trials are eagerly awaited. Much hope also resides in the use of biomarkers, as their use in, e.g., blood or exhaled air may provide more easy-to-use tests to better stratify high-risk populations for screening studies. While exciting research is ongoing in this domain-e.g. with microRNAs-none of the tests has yet reached sufficient validation for clinical use. Early central lung cancers are more difficult to visualise by CT. For these patients, standard bronchoscopy, complemented by autofluoresence endoscopy, has been studied in different screening and follow-up settings.
[Show abstract][Hide abstract] ABSTRACT: Disease-specific mortality is the final outcome of a lung cancer screening trial, therefore cause of death verification is crucial. The use of death certificates for this purpose is debated because of bias, inaccurate completion and incorrect ante mortem diagnoses. A cause of death evaluation process was designed to ensure a uniform and unbiased determination of the graduation of certainty that lung cancer was the underlying cause of death. An independent clinical expert committee will review the medical files of all deceased participants once diagnosed with lung cancer and will make use of a flow chart and predetermined criteria. A pilot study of fifty cases was conducted to determine the performance of this process and to compare the outcome with the official death certificates. The independent review has shown an agreement of 90% (kappa 0.65), which demonstrates a uniform classification. The sensitivity and specificity of the death certificates for lung cancer specific mortality were 95.2 and 62.5%. This demonstrates a limited distinctive character of the death certification process in lung cancer patients. Our results imply that the final outcome of a lung cancer screening trial cannot reliably be established without predetermined criteria and an independent review of blinded cases.
Lung cancer (Amsterdam, Netherlands) 05/2012; 77(3):522-5. · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Treatment naïve 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).
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.
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.
Lung cancer (Amsterdam, Netherlands) 09/2010; 69(3):302-6. · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ovarian cancer is the second most common gynaecologic malignancy. Ovarian carcinomas typically metastasize to multiple sites via exfoliation, lymphatic spread or direct invasion. We present a rare case of a very late recurrence of ovarian carcinoma into the thoracic wall, heralded by thoracic pain in a patient otherwise disease-free for 23 years. This unusual and late presentation of an ovarian cancer metastasis underscores the need for continued awareness and attention to new symptoms in patients with ovarian cancer who show prolonged disease-free intervals.
[Show abstract][Hide abstract] ABSTRACT: fter the disappointing experience with lung cancer screening studies based on chest x-ray and/or sputum cytology several decades ago, great expectations are now in place on screening with modern low-dose spiral computed tomography (LDSCT) scan. The prevalence data of one of these randomized studies is reported in this issue of our journal.1 The definition of screening—adapted from Stedman's Concise dictionary—consists of an examination of a group of usually asymptomatic individuals to detect those with a high probability of having a given disease, typically by means of an inexpensive, safe, and well-performing diagnostic test.2 To reach the real goal—reduction of lung cancer related mortality—four conditions need to be in place: a sensitive test for detection of small lesions; small lesions need to be associated with truly early stage disease; an effective treatment is available for these lesions; and acceptable morbidity and cost of the screening tool. Screening for lung cancer by LDSCT has been studied extensively in the past decade, and it looks like this might become the long awaited tool. Looks like, because until today, all the available data have been gathered from many—some even very large—cohort studies, but not yet from large randomized controlled trials. These nonran- domized studies show promising results. In the I-ELCAP trial in asymptomatic smokers or past smokers, for instance, 85% of lung cancers were detected in stage I, and the estimated 10-year survival rate of patients whose stage I lung cancer was removed by surgery was 92%.3 This suggests that LDSCT is a sensitive tool that is able to detect small lesions associated with truly early stage, for which an effective therapy is available. This does not prove, however, that the strategy results in a reduction of lung cancer related mortality. This evidence can only come from the eagerly awaited results from two large randomized controlled trials that are currently running, the American National Lung Screening Trial, started in 2002, and the Dutch-Belgian Nederlands-Leuvens Longkanker Screening Onderzoek (NELSON) trial, started in 2003.4,5 The long-term postscreening follow-up on the primary end point of reduction of lung cancer mortality in participants in the National Lung Screening Trial and the NELSON trial is planned to end in 2009 and 2014, respectively. Until then, the "pro and con debate" on CT screening for lung cancer will probably remain a "battle over lung scans."6,7 Some other, smaller RCTs have been setup in Italy, France, and in Denmark, the Danish randomized lung cancer CT screening trial (DLCST), whose first round or prevalence CT results are reported now.1 This DLCST has been designed in accordance with the NELSON trial to allow pooling of both study data together once both screening trials will have been finished. The combined data on lung cancer-specific mortality of around 20,000 included individuals will then give these two CT lung cancer screening trials an 80% power to show a lung cancer mortality reduction of at least 25%.5 Although waiting for the final results of these trials' follow-up period by the year 2014, it is interesting to compare the first round CT screening results of the DLCST to the previously reported results from other series. The lung cancer detection rate of 0.83% (17 cases of lung cancer in 2052 participants) is lower than previously reported in nonran- domized CT screening trials. As pointed out by the authors, this result is not easily explainable at this time, and results of the lung cancer prevalence in their control group
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2009; 4(5):563-4. · 4.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The TNM staging reflects the anatomic extent of lung cancer and estimates the survival expectation. Addition of FDG-PET to conventional staging (CS) improves accuracy, but few data have described the impact of this on long-term survival in relation to treatment.
To study the influence of FDG-PET on long-term outcome.
Long-term outcome data of patients were retrieved out of previously published PET studies of the Leuven Lung Cancer Group. All patients had a potential for radical treatment, and at least 5-year follow-up data. Patients were dichotomized in early (I-IIIA) versus late (IIIB-IV) stages.
A first analysis - comparison of the 2 staging algorithms, CS alone versus CS+PET - confirmed the better staging capabilities of the latter. A second analysis, focusing on discordant findings and interaction of both staging algorithms, demonstrated that patients with early stage on PET did well, while those with late stage on PET did poorly, irrespective of findings on CS. The third analysis focused on the relation between treatment choices at the multidisciplinary board and outcome, which is especially relevant in patients with discordant finding on CS and CS+PET. From all radically treated patients, only those with early stage on CS+PET had a good outcome, but not those with early stage on CS and an unexplained late stage finding on PET.
This long-term follow-up analysis confirms that addition of PET to CS results in better stage designation and prognosis. Additionally, discordant findings between CS and CS+PET should be considered relevant, with need for cytological/histological examination.
[Show abstract][Hide abstract] ABSTRACT: Coccidioidomycosis is an endemic fungal infection of the new world caused by Coccidioides immitis. Because of its low incidence in the European continent, the disease is not well known in Belgium. A 34-year-old male was referred by his general physician with a chronic cough and a nodular infiltrate on chest X-ray. Because a malignant tumour was suspected, a diagnostic work-up was performed and, finally, a broad excision of the pulmonary lesion was carried out. The unsuspected diagnosis of chronic coccidioidomycosis was eventually made based on identification of the filamentous fungus in mycological culture of the lung tissue, and the presence of the typical spherules with endospores upon histopathologic examination. The patient later admitted to have been travelling to Arizona frequently in the past year for professional reasons. Coccidioides spp. should always be considered as a possible aetiologic agent of pulmonary infection in former residents and recent travellers to regions where the fungus is endemic.
[Show abstract][Hide abstract] ABSTRACT: Surgical resection in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC) is usually reserved for patients with mediastinal downstaging after induction chemotherapy (IC). However, clinical restaging is often inaccurate, and there are insufficient data to conclude that all patients with persistent mediastinal disease will not benefit from surgery, or that all patients with mediastinal clearance benefit from surgery. We created a data-based restaging strategy combining morphometric tissue analysis of mediastinal lymph nodes (LNs) and 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) response monitoring in the primary tumor.
Baseline and repeat FDG-PET after IC, as well as complete resection specimens of both mediastinal LNs and primary tumor, were available in 30 patients. Histologic response grading was performed by means of conventional morphometric procedures. Mediastinal response grading combined with the percentage decrease of maximum standardized uptake value (SUV(max)) on the primary tumor was correlated with survival.
Patients with persistent major mediastinal LN involvement have a 5-year overall survival rate of 0%. The 5-year overall survival rate for patients with cleared or persistent minor mediastinal LN involvement was significantly higher in patients with a more than 60% decrease in SUV(max) on the primary tumor as compared with patients with a less than 60% decrease in SUV(max) (62% v 13%; log-rank P = .002).
These data may suggest that (1) persistent mediastinal disease after IC does not always exclude favorable outcome after surgery; (2) serial FDG-PET may select surgical candidates among patients with mediastinal downstaging or persistent minor disease; (3) persistent major mediastinal disease has a poor prognosis and such patients should not be considered for surgery.
Journal of Clinical Oncology 04/2008; 26(7):1128-34. · 18.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the case of an unexpected 18F-fluorodeoxyglucose-avid lesion in the right lower abdomen in a patient with otherwise "very limited" (T1N0) small cell lung cancer (SCLC). Additional imaging and endoscopic studies showed no abnormality. The patient was treated for presumed very limited disease SCLC, with resection, adjuvant chemotherapy, and prophylactic brain irradiation. Follow-up fusion positron emission tomography-computed tomography revealed an unusual SCLC complication.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2008; 3(2):174-6. · 4.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: To evaluate the feasibility and results after multimodality treatment for malignant pleural mesothelioma (MPM) combining induction chemotherapy (Pemetrexed-cisplatinum), followed by extrapleural pneumonectomy (EPP) and radical hemichest radiotherapy (single centre phase II study).
Methods: Thirty consecutive MPM patients were accepted for multimodality treatment between March 2003 and December 2006. Inclusion criteria's were age <65 years, good performance to complete treatment protocol and epithelial type T2N2M0 or less or other types T2N1M0 or less.
Results: We evaluate all patients referred to us for treatment of MPM on a prospective manner (n=64). Thirty patients were included in the study. Twenty-three patients presented with epithelial type, two withdesmoplastic type, one with sarcoma type and four with mixed type. Seven patients were refused for surgery because of progressive disease after induction chemotherapy. Ninteen patients underwent EPP, three patients were irresectable due to chest wall invasion and one for esophageal invasion. Postoperative mortality after EPP was 10.5% (n=2). Surgical complications were re-thoracotomy for bleeding (n=1), atrial fibrillation (n=6), ARDS (n=1) and DVT (n=1). One patient did not finish the radiotherapy course because of tumour recurrence and one patient died shortly after the radiotherapy due to BOOP. Mean survival after diagnosis was 17.8 months in resected patients (n=19) and 21.4 months in patients who completed the full multimodality treatment (n=15).
Conclusions: Multimodality treatment of MPM is feasible and can be performed with acceptable morbidity and mortality. Patients completing the protocol experienced a survival benefit. Careful selection is mandatory to define potential target groups.
Interactive Cardiovascular and Thoracic Surgery 05/2007; 6(Supplement 2):S181-S217. · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidermal growth factor receptor tyrosine kinase inhibitors represent a new treatment option for patients with advanced nonsmall cell lung cancer (NSCLC). This retrospective study examined to what extent previous clinical trial experience matches large-scale Western community implementation of this treatment. In the Belgian expanded access programme, the data from 513 patients with advanced or metastatic NSCLC, not suitable for further chemotherapy and receiving oral gefitinib 250 mg.day(-1) until disease progression, death or unacceptable toxicity, were analysed. The median (range) duration of gefitinib treatment was 2.3 months (0.0-32.7). Its use was predominantly in second- or third-line treatment. The overall response and disease control rates were 8.9 and 41.2%, respectively. In univariate analysis, response was more common in females and never-smokers. In multivariate analysis, female sex was the only significant predictive factor (odds ratio (OR) (95% confidence interval (CI)) 0.329 (0.129-0.839)). Symptom improvement was reported in 108 patients of whom 32 (29.6%) had an objective response, 66 (61.1%) experienced disease stabilisation and 10 (9.3%) progressed. Gefitinib was well tolerated; only 7.8% of the patients reported grade 3 or 4 toxicity. The overall median survival was 4.7 months, with a 1-yr survival rate of 21%. Survival was strongly influenced by a better performance status (PS) (good PS: hazard ratio (HR) (95%CI) 0.110 (0.077-0.157)) and adenocarcinoma with bronchioloalveolar carcinoma features histology (HR (95%CI) 0.483 (0.279-0.834)). In conclusion, the activity of gefitinib was confirmed in the present large Western community implementation study. Response, present in a small subgroup, led to a rewarding survival and could be predicted by sex only. Baseline performance status and adenocarcinoma with bronchioloalveolar carcinoma features histology were significant factors for survival.
European Respiratory Journal 02/2007; 29(1):128-33. · 6.36 Impact Factor