Tore Amundsen

Phase III Study by the Norwegian Lung Cancer Study Group: Pemetrexed Plus Carboplatin Compared With Gemcitabine Plus Carboplatin As First-Line Chemotherapy in Advanced Non–Small-Cell Lung Cancer

PURPOSE To compare pemetrexed/carboplatin with a standard regimen as first-line therapy in advanced non-small-cell lung cancer NSCLC. PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were randomly assigned to receive pemetrexed 500 mg/m(2) plus carboplatin area under the curve (AUC) = 5 (Calverts formula) on day 1 or gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles. The primary end point was health-related quality of life (HRQoL) defined as global quality of life, nausea/vomiting, dyspnea, and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the lung cancer-specific module LC13 during the first 20 weeks. Secondary end points were overall survival and toxicity. Results Four hundred thirty-six eligible patients were enrolled from April 2005 to July 2006. Patients who completed the baseline questionnaire were analyzed for HRQoL (n = 427), and those who received > or = one cycle of chemotherapy were analyzed for toxicity (n = 423). Compliance of HRQoL questionnaires was 87%. There were no significant differences for the primary HRQoL end points or in overall survival between the two treatment arms (pemetrexed/carboplatin, 7.3 months; gemcitabine/carboplatin, 7.0 months; P = .63). The patients who received gemcitabine/carboplatin had more grade 3 to 4 hematologic toxicity than patients who received pemetrexed/carboplatin, including leukopenia (46% v 23%, respectively; P < .001), neutropenia (51% v 40%, respectively; P = .024), and thrombocytopenia (56% v 24%, respectively; P < .001). More patients on the gemcitabine/carboplatin arm received transfusions of RBCs and platelets, whereas the frequencies of neutropenic infections and thrombocytopenic bleedings were similar on both arms. CONCLUSION Pemetrexed/carboplatin provides similar HRQoL and survival when compared with gemcitabine/carboplatin with less hematologic toxicity and less need for supportive care.

Perfusion abnormalities in pulmonary embolism studied with perfusion MRI and ventilation-perfusion scintigraphy: an intra-modality and inter-modality agreement study

To compare perfusion magnetic resonance imaging (MRI) and ventilation‐perfusion scintigraphy (V‐P scan) in the study of perfusion abnormalities in pulmonary embolism (PE) and to compare the PE results to the findings previously reported for pneumonia and chronic obstructive pulmonary disease (COPD), in terms of perfusion abnormalities.

Influence of comorbidity on survival, toxicity and health-related quality of life in patients with advanced non-small-cell lung cancer receiving platinum-doublet chemotherapy.

AIM OF THE STUDY To investigate whether patients with severe comorbidity receiving platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) have a shorter overall survival, experience more toxicity or more deterioration of health-related quality of life (HRQoL) than other patients during treatment. PATIENTS AND METHODS Patients enrolled onto a phase III trial comparing pemetrexed/carboplatin with gemcitabine/carboplatin as first-line therapy of stage IIIB/IV NSCLC were analysed. Eligible patients had performance status 0-2 and adequate kidney/liver/bone-marrow function. Comorbidity was assessed from hospital medical records using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Toxicity was graded using the CTCAE v3.0 and the patients reported HRQoL on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30/LC13. RESULTS Data from 402 of the 436 of the patients enrolled onto the phase III trial were analysed. The patients with severe comorbidity had similar survival as other patients (6.9 versus 8.1months; p=.34), similar frequency of neutropenia (48% versus 42%; p=.16), but experienced more neutropenic fevers (12% versus 5%; p=.012) and deaths from neutropenic infections (3% versus 0%; p=.027). They had more thrombocytopenia (46% versus 36%; p=.03), but not more thrombocytopenic bleedings (3% versus 4%; p=.65). In general, the patients with severe comorbidity reported poorer HRQoL, but not significantly more deterioration of HRQoL. CONCLUSIONS The results from our study suggest that patients with advanced NSCLC who have severe co-existing disorders benefit from and tolerate platinum-doublet chemotherapy as well as other patients. They do, however, appear to have a higher risk of acquiring infections when neutropenic.

Plasma Homocysteine Levels in Patients With Deep Venous Thrombosis

Increased risk of arterial and venous thromboembolic disease is well documented in the homocystinuric patient. There is growing evidence that hyperhomocysteinemia is an independent risk factor for premature arteriosclerotic disease, including cerebral, peripheral, and coronary vascular diseases. So far no association has been established between hyperhomocysteinemia and venous thromboembolism. We studied 35 patients, young adults (age less than 56 years) with venographically and/or ultrasonographically verified deep venous thrombosis (DVT). Patients with coexisting diseases were excluded. Plasmahomocysteine levels before and after intake of methionine were measured 3 months or more after the time of diagnosis and compared with 39 control subjects. We found no significant difference in plasmahomocysteine levels between the young adults with deep venous thrombosis and control subjects. This indicates that hyperhomocysteinemia is not a frequent cause of DVT.

Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer

Abstract Background. Sarcopenia is a defining feature of cancer cachexia associated with physical decline, poor quality of life and poor prognosis. Thus, maintaining muscle mass is an important aim of cachexia treatment. Many patients at risk for developing cachexia or with cachexia experience side effects of chemotherapy that might aggravate the development of cachexia. However, achieving tumor control might reverse the catabolic processes causing cachexia. There is limited knowledge about muscle mass changes during chemotherapy or whether changes in muscle mass are associated with response to chemotherapy. Patients and methods. In this pilot study, patients with advanced non-small cell lung cancer (NSCLC) receiving three courses of palliative chemotherapy were analyzed. Muscle mass was measured as skeletal muscle cross sectional area (SMCA) at the level of the third lumbar vertebrae using CT images taken before and after chemotherapy. Results. In total 35 patients, 48% women, mean age 67 years (range 56–86), participated; 83% had stage IV disease and 71% were sarcopenic at baseline. Mean reduction in SMCA from pre- to post-chemotherapy was 4.6 cm2 (CI 95% −7.3–−1.9; p < 0.002), corresponding to a 1.4 kg loss of whole body muscle mass. Sixteen patients remained stable or gained SMCA. Of these, 14 (56%) responded to chemotherapy, while two progressed (p = 0.071). Maintaining or gaining SMCA resulted in longer median overall survival (loss: 5.8 months, stable/gain: 10.7 months; p = 0.073). Stage of disease (p = 0.003), treatment regimen (p = 0.023), response to chemotherapy (p = 0.007) and SMCA change (p = 0.040), but not sarcopenia at baseline, were significant prognostic factors in the multivariate survival analyses. Conclusion. Almost half of the patients had stable or increased muscle mass during chemotherapy without receiving any cachexia treatment. Nearly all of these patients responded to the chemotherapy. Increase in muscle mass, but not sarcopenia at baseline, was a significant prognostic factor.

Prolonged Survival in Patients with Lung Cancer with Diabetes Mellitus

Introduction: Patients with lung cancer have a high frequency of comorbidity. Data on the impact of diabetes mellitus, the most frequent endocrine disorder, on the prognosis of lung cancer are conflicting. The aim was to investigate the impact of diabetes mellitus on survival in lung cancer. Method: We analyzed data from a cohort, the Nord-Trøndelag Health Study (HUNT study) linked to the Norwegian Cancer Registry and controlled the results using two lung cancer studies, the Pemetrexed Gemcitabine study and the Norwegian Lung Cancer Biobank. Survival in lung cancer with and without diabetes mellitus was compared using the Kaplan-Meier method and Cox regression model for each study and the studies combined. Results: One thousand six hundred seventy-seven cases of lung cancer were included, 1031 from HUNT study, 436 from the Pemetrexed Gemcitabine study, and 210 from the Norwegian Lung Cancer Biobank registry, and among these 77 patients had diabetes mellitus. In the combined analysis, patients with lung cancer with diabetes mellitus had increased survival compared with those without (p = 0.005). The 1-, 2-, and 3-year survival in patients with lung cancer with and without diabetes mellitus were 43% versus 28%, 19% versus 11%, and 3% versus 1%, respectively. Adjusting for age, gender, histology, and stage of disease in the Cox regression model, the hazard ratio for survival in patients with lung cancer with diabetes mellitus was 0.55 (95% CI, 0.41–0.75) as compared with without. Conclusion: Patients with lung cancer with diabetes mellitus have an increased survival compared with those without diabetes mellitus.

Perfusion magnetic resonance imaging of the lung: characterization of pneumonia and chronic obstructive pulmonary disease. A feasibility study

Perfusion magnetic resonance (MR) imaging is a promising new method for detection of perfusion defects in the diagnosis of pulmonary embolism. In the present study we evaluated the first‐pass characteristics of perfusion MR imaging in patients with pneumonia or chronic obstructive pulmonary disease (COPD), frequent differential diagnoses to pulmonary embolism. Dynamic contrast‐enhanced MR images of 12 patients with acute pneumonia and 13 patients with exacerbation of COPD were acquired in both the coronal and transaxial planes (an inversion recovery prepared gradient‐echo sequence using 0.05 mmol/kg gadodiamide/injection). The MR images and the signal intensity (SI) versus time curves were characterized for each disease entity and compared with normal lung and the findings in pulmonary embolism from our previous study. The perfusion MR images of pneumonia showed distinct regions of increased contrast enhancement; in COPD with signs of emphysema (11 of the 13 COPD patients), the images showed a coarse pattern of reduced contrast enhancement. The SI versus time curves of pneumonia, COPD with signs of emphysema, and normal lung were statistically different, the respective pooled SI values (±95% CI) being as follows: mean baseline SI, 20.7 (1.1), 7.4 (0.4), and 8.5 (0.3); mean peak SI, no peak, 12.9 (1.5), and 27 (4.6); and mean max change of SI in percent, 110 (27), 79 (22), and 205 (52). Perfusion MR imaging of pneumonia and COPD with signs of emphysema showed first‐pass that were characteristics promising for diagnostic use. Both the MR images and the SI versus time curves were different from the perfusion characteristics in normal lung and pulmonary embolism shown previously. J. Magn. Reson. Imaging 2000;12:224–231.

Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group.

Background:Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare a non-platinum with a platinum combination.Methods:Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0–2. Patients received up to three cycles of vinorelbine 60 mg m−2 p.o.+gemcitabine 1000 mg m−2 i.v. day 1 and 8 (VG) or vinorelbine 60 mg m−2 p.o. day 1 and 8+carboplatin area under the curve=5 (Calverts formula) i.v. day 1 (VC). Patients ⩾75 years received 75% of the dose. Endpoints were overall survival, health-related quality of life (HRQoL), toxicity, and the use of radiotherapy.Results:We randomised 444 patients from September 2007 to April 2009. The median age was 65 years, 58% were men and 25% had PS 2. Median survival was VG: 6.3 months; VC: 7.0 months, P=0.802. Vinorelbine plus carboplatin patients had more grade III/IV nausea/vomiting (VG: 4%, VC: 12%, P=0.008) and grade IV neutropenia (VG: 7%, VC: 19%, P<0.001). Infections, HRQoL and the use of radiotherapy did not differ significantly between the treatment groups.Conclusion:The two regimens yielded similar overall survival. The VG combination had only a slightly better toxicity profile.

Navigated bronchoscopy: a technical review.

Background:Navigated bronchoscopy uses virtual 3-dimensional lung model visualizations created from preoperative computed tomography images often in synchronization with the video bronchoscope to guide a tool to peripheral lesions. Navigated bronchoscopy has developed fast since the introduction of virtual bronchoscopy with integrated electromagnetic sensors in the late 1990s. The purposes of the review are to give an overview and update of the technological components of navigated bronchoscopy, an assessment of its clinical usefulness, and a brief assessment of the commercial platforms for navigated bronchoscopy. Methods:We performed a literature search with relevant keywords to navigation and bronchoscopy and iterated on the reference lists of relevant papers, with emphasis on the last 5 years. Results:The paper presents an overview of the components necessary for performing navigated bronchoscopy, assessment of the diagnostic accuracy of different approaches, and an analysis of the commercial systems. We were able to identify 4 commercial platforms and 9 research and development groups with considerable activity in the field. Finally, on the basis of our findings and our own experience, we provide a discussion on navigated bronchoscopy with focus on the next steps of development. Conclusions:The literature review showed that the peripheral diagnostic accuracy has improved using navigated bronchoscopy compared with traditional bronchoscopy. We believe that there is room for improvement in the diagnostic success rate by further refinement of methods, approaches, and tools used in navigated bronchoscopy.

Can dogs smell lung cancer? First study using exhaled breath and urine screening in unselected patients with suspected lung cancer.

Abstract Background. On the basis of our own experience and literature search, we hypothesised that a canine olfactory test may be useful for detecting lung cancer in an unselected population of patients suspected to have lung cancer. Material and methods. We conducted a prospective study of 93 patients consecutively admitted to hospital with suspected lung cancer. Exhaled breath and urine were sampled before the patients underwent bronchoscopy. The canine olfactory test was performed in a double-blinded manner. Sensitivity and specificity were outcome measures. Results. With 99% sensitivity, the olfactory test demonstrated that dogs have the ability to distinguish cancer patients from healthy individuals. With an intensified training procedure, the exhaled breath and urine tests showed sensitivity rates of 56–76% and specificity rates of 8.3–33.3%, respectively, in our heterogeneous study population. Conclusion. Although the olfactory test appears to be a promising tool for the detection of cancer, the main challenge is to determine whether the test can sufficiently discriminate between patients at risk, patients with benign disease, and patients with malignant disease. We need to gain a deeper understanding of this test and further refine it before applying it as a screening tool for lung cancer in clinical settings.