A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)†.

BACKGROUND: Nitroglycerin (NTG) increases tumor blood flow and oxygenation by inhibiting hypoxia-inducible-factor (HIF)-1. A randomized phase II study has shown improved outcome when NTG patches were added to vinorelbine/cisplatin in patients with advanced nonsmall-cell lung cancer (NSCLC). In addition, there is evidence that the combination of bevacizumab and HIF-1 inhibitors increases antitumor activity. PATIENTS AND METHODS: In this randomized phase II trial, chemo-naive patients with stage IV nonsquamous NSCLC were randomized to four cycles of carboplatin (area under the curve 6)-paclitaxel (200 mg/m(2))-bevacizumab 15 mg/kg on day 1 every 3 weeks with or without NTG patches 15 mg (day -2 to +2) followed by bevacizumab with or without NTG until progression. Response was assessed every two cycles. Primary end point was progression-free survival (PFS). The study was powered (80%) to detect a decrease in the hazard of tumor progression of 33% at α = 0.05 with a two-sided log-rank test when 222 patients were enrolled and followed until 195 events were observed. RESULTS: Between 1 January 2011 and 1 January 2013, a total of 223 patients were randomized; 112 control arm and 111 experimental arm; response rate was 54% in control arm and 38% in experimental arm. Median [95% confidence interval (CI)] PFS in control arm was 6.8 months (5.6-7.3) and 5.1 months (4.2-5.8) in experimental arm, hazard ratio (HR) 1.27 (95% CI 0.96-1.67). Overall survival (OS) was 11.6 months (8.8-13.6) in control arm and 9.4 months (7.8-11.3) in experimental arm, HR 1.02 (95% CI 0.71-1.46). In the experimental arm, no additional toxicity was observed except headache (6% versus 52% in patients treated with NTG). CONCLUSION: Adding NTG to first-line carboplatin-paclitaxel-bevacizumab did not improve PFS and OS in patients with stage IV nonsquamous NSCLC.

Development and Portability of a Text Mining Algorithm for Capturing Disease Progression in Electronic Health Records of Patients With Stage IV Non-Small Cell Lung Cancer.

PURPOSE: The objective was to develop and evaluate the portability of a text mining algorithm for prospectively capturing disease progression in electronic health record (EHR) data of patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunochemotherapy. METHODS: This study used EHR data from patients with mNSCLC receiving immunochemotherapy (between October 1, 2018, and December 31, 2022) in four Dutch hospitals. A text mining algorithm for capturing disease progression was developed in hospitals 1 and 2 and then transferred to hospitals 3 and 4 to evaluate portability. Performance metrics were calculated by comparing its outcomes with manual chart review. In addition, data were simulated to come available over time to assess performance in real-time applications. Median progression-free survival (PFS) was calculated using the Kaplan-Meier method to compare text mining with manual chart review. RESULTS: During development and portability, the text mining algorithm performed well in capturing disease progression, with all performance scores >90%. When real-time performance was simulated, the performance scores in all four hospitals exceeded 90% from week 15 after the start of follow-up. Although the exact progression dates varied in 46 patients of 157 patients with progressive disease, the number of patients labeled with progression too early (n = 24) and too late (n = 22) was well balanced with discrepancies ranging from -116 to 384 days. Nevertheless, the PFS curves constructed with text mining and manual chart review were highly similar for each hospital. CONCLUSION: In this study, an accurate text mining algorithm for capturing disease progression in the EHR data of patients with mNSCLC was developed. The algorithm was portable across different hospitals, and the performance over time was good, making this an interesting approach for prospective follow-up of multicenter cohorts.

The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer.

INTRODUCTION: Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations. MATERIALS AND METHODS: This was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kg/m2 (normal weight and reference), 25.0-29.9 kg/m2 (overweight) or ≥30.0 kg/m2 (obese). For survival analyses adjusted hazard ratios [aHR] were calculated using multivariate Cox regression analysis. Secondary outcomes were analyzed using multivariate logistic regression providing adjusted odd ratios [aOR]. RESULTS: Overweight patients (n=174) had a significantly better OS (aHR=0.72, 95%-CI:0.59-0.89) and PFS (aHR=0.74, 95%-CI:0.61-0.90) compared to normal weight patients (n=268). OS nor PFS were different in obese (n=51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR=3.47, 95%-CI:1.75-6.90). CONCLUSION: This study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kg/m2, and to verify calculated dosing of carboplatin for appropriateness.

Current status of research on osteoporosis in COPD: a systematic review.

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of osteoporosis. However, the prevalence, correlates and effectiveness of treatment of osteoporosis in COPD patients remain unclear. We performed a systematic review of the literature to answer three questions. 1) What is the prevalence of osteoporosis in COPD? 2) What are identified correlates of osteoporosis in COPD? 3) What are the effects of treatment of osteoporosis in COPD? A computerised literature search in MEDLINE/PubMed and the Cochrane database was carried out. In addition, reference lists were searched by hand and authors were contacted if necessary. The prevalence of osteoporosis and osteopenia varied 9-69% and 27-67%, respectively. Prevalence of osteoporosis was generally higher than in healthy subjects and some other chronic lung diseases. Correlates of osteoporosis in COPD are mainly measures of body composition, disease severity and the use of corticosteroids, although causality has not been proven. Effects of treatment of osteoporosis have not been investigated in samples consisting of COPD patients only. Longitudinal follow-up to assess determinants of osteoporosis in COPD and randomised placebo-controlled trials on the effects of treatment of osteoporosis in patients with COPD only are warranted.

[Acute abdominal pain and fever in a young woman as the first symptoms of lymphangioleiomyomatosis]. / Acute buikpijn en koorts bij een jonge vrouw als eerste verschijnselen van lymfangioleiomyomatose.

A previously healthy 28-year-old woman presented to the emergency clinic with acute severe abdominal pain and high fever. A diagnostic laparoscopy was performed, during which a large retroperitoneal tumour was found. A CT-scan of the abdomen and thorax confirmed the presence of a retroperitoneal mass but also revealed multiple renal angiomyolipomas and extensive cystic lesions in all lung fields. Based on these findings, the diagnosis lymphangioleiomyomatosis (LAM) was suspected, and later confirmed by histological examination of a biopsy specimen. The acute abdomen and fever appeared to have been caused by a Streptococcus agalactiae infection of the retroperitoneal lymphangiomyoma, which was treated with intravenous antibiotics. LAM is a very rare disease affecting mostly women of childbearing age and presenting almost exclusively with pulmonary symptoms. This is the first description of LAM presenting with an acute surgical abdomen and fever due to infection of a lymphangiomyoma.

Negligible influence of comorbidity on prognosis of patients with small cell lung cancer: a population-based study in the Netherlands.

Management of small cell lung cancer (SCLC) among elderly is complex because of decreased organ functions and interactions with comorbidity. Since elderly patients are often excluded from clinical trials, little is known about the way they are treated and outcome. We evaluated the prognostic effects of rising age and comorbidity in unselected Dutch SCLC patients (Eindhoven Cancer Registry). Elderly patients received chemotherapy less often and the dose was also reduced more often. Cardiovascular diseases, hypertension or diabetes lowered the proportion receiving combined chemotherapy and radiotherapy among patients with limited disease. About 80% of the patients receiving chemotherapy suffered from a side effect, which was not related to age. After adjustment for age, gender, stage and treatment modality, comorbidity had a negligible prognostic effect. Chemotherapy (in combination with radiotherapy) seemed to improve survival, however, toxicity and quality of life in these patients should be evaluated thoroughly in future randomized studies.

Segmental spinal anaesthesia for cholecystectomy in a patient with severe lung disease.

Occasionally patients awaiting heart or lung transplant because of terminal disease require other types of surgery, but present significant challenges to the anaesthetist because of impaired organ function. Regional anaesthesia may have much to offer such patients and we here report one who underwent successfully a laparoscopic cholecystectomy under segmental subarachnoid (spinal) anaesthesia performed at the low thoracic level. The anatomical and physiological consequences of such a technique are discussed.