Open communication between patients and relatives about illness & death in advanced cancer-results of the eQuiPe Study.

OBJECTIVE: To assess the degree of openness of communication about illness and death between patients with advanced cancer and their relatives during the last three months of the patient's life, and its association with relatives' characteristics and bereavement distress. METHODS: We used data from bereaved relatives of patients with advanced cancer from the prospective, longitudinal, multicenter, observational eQuipe study. Univariate and multivariable linear regression analyses were used to assess the association between the degree of openness of communication (measured using the validated Caregivers' Communication with patients about Illness and Death scale), the a priori defined characteristics of the relatives, and the degree of bereavement distress (measured using the Impact of Event Scale). RESULTS: A total of 160 bereaved relatives were included in the analysis. The average degree of open communication about illness and death between patients with advanced cancer and their relatives was 3.86 on a scale of 1 to 5 (SE=0.08). A higher degree of open communication was associated with a lower degree of bereavement distress (p=0.003). No associations were found between the degree of open communication and the relatives' age (p=0.745), gender (p=0.196), level of education (p>0.773), (religious) worldview (p=0.435), type of relationship with the patient (p>0.548), or level of emotional functioning before the patient's death (p=0.075). CONCLUSIONS: Open communication about illness and death between patients and relatives seems to be important, as it is associated with a lower degree of bereavement distress. Healthcare professionals can play an important role in encouraging the dialogue. However, it is important to keep in mind that some people not feel comfortable talking about illness and death.

Strengths and challenges in current lung cancer care: Timeliness and diagnostic procedures in six Dutch hospitals.

OBJECTIVES: Timely diagnosis of lung cancer (LC) is crucial to achieve optimal patient care and outcome. Moreover, the number of procedures required to obtain a definitive diagnosis can have a large influence on the life expectancy of a patient. Here, adherence with existing Dutch guidelines for timeliness and type and number of invasive and imaging procedures was assessed. MATERIALS AND METHODS: 1096 patients with suspected LC were enrolled in this multicenter prospective study (NL9146). The overall survival, time from referral to the first appointment with the pulmonologist, time to diagnosis and treatment, and the number of imaging and invasive procedures were evaluated. Patients were divided into different diagnostic groupsearly- and advanced stage non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), large cell neuroendocrine carcinoma of the lung (LCNEC), patients without LC and patients without a definitive diagnosis. RESULTS: The majority of patients (66 %) received a definitive diagnosis within 5 weeks, although the time to diagnosis of early-stage LC patients and patients without LC was significantly longer comparted to advanced stage LC. An increase in invasive procedures was seen for early-stage LC compared to advanced stage LC and for 13 % of the advanced stage non-squamous NSCLC patients up to three additional invasive procedures were performed solely to obtain sufficient material for NGS. For patients without a definitive diagnosis, 50 % did undergo at least one invasive procedure, while 11 % did not wish to undergo any invasive procedures. CONCLUSION: These insights could aid in improved LC diagnostics and efficient implementation of new techniques like liquid biopsy and artificial intelligence. This may lead to more timely LC care, a decreased number of invasive procedures, less variability between the diagnostic trajectory of different patients and aid in obtaining a definitive diagnosis for all patients.

The Effects of Artificial Intelligence Assistance on the Radiologists' Assessment of Lung Nodules on CT Scans: A Systematic Review.

To reduce the number of missed or misdiagnosed lung nodules on CT scans by radiologists, many Artificial Intelligence (AI) algorithms have been developed. Some algorithms are currently being implemented in clinical practice, but the question is whether radiologists and patients really benefit from the use of these novel tools. This study aimed to review how AI assistance for lung nodule assessment on CT scans affects the performances of radiologists. We searched for studies that evaluated radiologists' performances in the detection or malignancy prediction of lung nodules with and without AI assistance. Concerning detection, radiologists achieved with AI assistance a higher sensitivity and AUC, while the specificity was slightly lower. Concerning malignancy prediction, radiologists achieved with AI assistance generally a higher sensitivity, specificity and AUC. The radiologists' workflows of using the AI assistance were often only described in limited detail in the papers. As recent studies showed improved performances of radiologists with AI assistance, AI assistance for lung nodule assessment holds great promise. To achieve added value of AI tools for lung nodule assessment in clinical practice, more research is required on the clinical validation of AI tools, impact on follow-up recommendations and ways of using AI tools.

Liquid biopsy-based decision support algorithms for diagnosis and subtyping of lung cancer.

OBJECTIVES: Pathologic subtyping of tissue biopsies is the gold standard for the diagnosis of lung cancer (LC), which could be complicated in cases of e.g. inconclusive tissue biopsies or unreachable tumors. The diagnosis of LC could be supported in a minimally invasive manner using protein tumor markers (TMs) and circulating tumor DNA (ctDNA) measured in liquid biopsies (LBx). This study evaluates the performance of LBx-based decision-support algorithms for the diagnosis of LC and subtyping into small- and non-small-cell lung cancer (SCLC and NSCLC) aiming to directly impact clinical practice. MATERIALS AND METHODS: In this multicenter prospective study (NL9146), eight protein TMs (CA125, CA15.3, CEA, CYFRA 21-1, HE4, NSE, proGRP and SCCA) and ctDNA mutations in EGFR, KRAS and BRAF were analyzed in blood of 1096 patients suspected of LC. The performance of individual and combined TMs to identify LC, NSCLC or SCLC was established by evaluating logistic regression models at pre-specified positive predictive values (PPV) of ≥95% or ≥98%. The most informative protein TMs included in the multi-parametric models were selected by recursive feature elimination. RESULTS: Single TMs could identify LC, NSCLC and SCLC patients with 46%, 25% and 40% sensitivity, respectively, at pre-specified PPVs. Multi-parametric models combining TMs and ctDNA significantly improved sensitivities to 65%, 67% and 50%, respectively. CONCLUSION: In patients suspected of LC, the LBx-based decision-support algorithms allowed identification of about two-thirds of all LC and NSCLC patients and half of SCLC patients. These models therefore show clinical value and may support LC diagnostics, especially in patients for whom pathologic subtyping is impossible or incomplete.

Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR-mutated nonsmall cell lung cancer.

Introduction: Previous studies have shown interference between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy in the cell cycle, thus reducing efficacy. In this randomised controlled trial we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR-mutated nonsmall cell lung cancer (NSCLC). Materials and methods: Treatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0-3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2-16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival, objective response rate (ORR) and toxicity. Results: Between April 2014 and September 2016, 22 patients were randomised equally into both arms; the study was stopped due to slow accrual. Median follow-up was 64 months. Median PFS was 13.7 months (95% CI 5.2-18.8) for CPE and 10.3 months (95% CI 7.1-15.5; hazard ratio (HR) 0.62, 95% CI 0.25-1.57) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.24, 95% CI 0.07-0.83; p=0.02). ORR was 64% for CPE versus 55% for erlotinib monotherapy. Median overall survival was 31.7 months (95% CI 21.8-61.9 months) for CPE compared to 17.2 months (95% CI 11.5-45.5 months) for erlotinib monotherapy (HR 0.58, 95% CI 0.22-1.41 months). Patients treated with CPE had higher rates of treatment-related fatigue, anorexia, weight loss and renal toxicity. Conclusion: Intercalating erlotinib with cisplatin-pemetrexed provides a longer PFS compared to erlotinib alone in EGFR-mutated NSCLC at the expense of more toxicity.

Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer.

Neuron-specific enolase (NSE) is a well-known biomarker for the diagnosis, prognosis and treatment monitoring of small-cell lung cancer (SCLC). Nevertheless, its clinical applicability is limited since serum NSE levels are influenced by hemolysis, leading to falsely elevated results. Therefore, this study aimed to develop a hemolysis correction equation and evaluate its role in SCLC diagnostics. Two serum pools were spiked with increasing amounts of hemolysate obtained from multiple individuals. A hemolysis correction equation was obtained by analyzing the relationship between the measured NSE concentration and the degree of hemolysis. The equation was validated using intentionally hemolyzed serum samples, which showed that the correction was accurate for samples with an H-index up to 30 µmol/L. Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results. Therefore, a hemolysis correction equation should be used to correct falsely elevated NSE concentrations. Results of samples with an H-index above 30 µmol/L should not be reported to clinicians. Application of the equation illustrates the importance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.

Utilization of Molecular Testing and Survival Outcomes of Treatment with First- or Second-line Tyrosine Kinase Inhibitors in Advanced Non-small Cell Lung Cancer in a Dutch Population.

BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) mutation testing is standard-of-care for advanced non-small cell lung cancer (NSCLC). Outcomes of second-/third-line compared to first-line tyrosine kinase inhibitors (TKIs) have shown conflicting results. We investigated utilization of molecular diagnostics and the outcomes of treatment with first-/second-line TKIs in patients with advanced NSCLC. MATERIALS AND METHODS: Retrospective analysis was carried out of 2,206 patients with stage IIIb/IV NSCLC treated between 2008 and 2014 in four hospitals in the Netherlands. RESULTS: The rate of performing molecular diagnostics increased from 20.8% to 74.4% in the study period. The median overall survival of EGFR mutation-positive patients treated with TKIs was superior compared to EGFR mutation-negative patients treated with chemotherapy (720 vs. 274 days, p<0.0001). No difference in overall survival was found between EGFR mutation-positive patients treated only with TKIs compared to those treated with chemotherapy prior to TKIs, or upon progression under TKIs. CONCLUSION: The rate of EGFR testing has improved, increasing the number of patients eligible for targeted therapy. Chemotherapy, prior or subsequent to TKIs, for the treatment of EGFR mutation-positive patients, did not result in significantly better overall survival compared to that achieved with TKIs alone.

Patient reported outcomes following stereotactic ablative radiotherapy or surgery for stage IA non-small-cell lung cancer: Results from the ROSEL multicenter randomized trial.

We report quality of life and indirect costs from patient reported outcomes from the ROSEL randomized control trial comparing stereotactic ablative radiotherapy (SABR, also known as stereotactic body radiotherapy or SBRT) versus surgical resection for medically operable stage IA non-small cell lung cancer. ROSEL closed prematurely after accruing and randomizing 22 patients. This exploratory analysis found the global health related quality of life and indirect costs to be significantly favorable and cheaper, with SABR.

Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer.

OBJECTIVES: As suggested by in-vitro data, we hypothesize that subtypes of KRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens. METHODS: Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinum-based chemotherapy, were retrieved from hospital databases. PRIMARY OBJECTIVE: to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation. RESULTS: 464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of KRAS mutation were G12C (46%), G12V (20%) and G12D (10%). Platinum was combined with pemetrexed (n=334), taxanes (n=68) or gemcitabine (n=62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; p<0.01). Patients treated with bevacizumab in addition to taxanes (n=38) had the highest ORR (62%). The PFS was significantly improved in patients treated with taxanes compared to pemetrexed (HR=0.72, p=0.02), but not OS (HR=0.87, p=0.41). In patients with G12V, significantly improved ORR (p<0.01) was observed for taxanes, but not PFS or OS. Patients with G12C or G12D mutation had comparable ORR, PFS and OS in all treatment groups. CONCLUSION: KRAS mutated NSCLC patients treated with taxane-based chemotherapy had best ORR. Response to chemotherapy regimens was different in types of KRAS mutation. Especially patients with G12V had better response to taxane treatment.

Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.

BACKGROUND: The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. METHODS: Eligible patients in the STARS and ROSEL studies were those with clinical T1-2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). FINDINGS: 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0-47·3) for the SABR group and 35·4 months (18·9-40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85-100) in the SABR group compared with 79% (64-97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017-1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74-100) in the SABR group and 80% (65-97) in the surgery group (HR 0·69 [95% CI 0·21-2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3-4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). INTERPRETATION: SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. FUNDING: Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.

Spontaneous pneumothorax as indicator for Birt-Hogg-Dubé syndrome in paediatric patients.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominantly inherited disorder caused by germline mutations in the folliculin (FLCN) gene. Clinical manifestations of BHD include skin fibrofolliculomas, renal cell cancer, lung cysts and (recurrent) spontaneous pneumothorax (SP). All clinical manifestations usually present in adults > 20 years of age. CASE PRESENTATIONS: Two non-related patients with (recurrent) pneumothorax starting at age 14 accompanied by multiple basal lung cysts on thoracic CT underwent FLCN germline mutation analysis. A pathogenic FLCN mutation was found in both patients confirming suspected BHD. The family history was negative for spontaneous pneumothorax in both families. CONCLUSION: Although childhood occurrence of SP in BHD is rare, these two cases illustrate that BHD should be considered as cause of SP in children.

Interobserver variability for the WHO classification of pulmonary carcinoids.

Pulmonary carcinoids are neuroendocrine tumors histopathologically subclassified into typical (TC; no necrosis, <2 mitoses per 2 mm) and atypical (AC; necrosis or 2 to 10 mitoses per 2 mm). The reproducibility of lung carcinoid classification, however, has not been extensively studied and may be hampered by the presence of pyknotic apoptosis mimicking mitotic figures. Furthermore, prediction of prognosis based on histopathology varies, especially for ACs. We examined the presence of interobserver variation between 5 experienced pulmonary pathologists who reviewed 123 originally diagnosed pulmonary carcinoid cases. The tumors were subsequently redistributed over 3 groups: unanimously classified cases, consensus cases (4/5 pathologists rendered identical diagnosis), and disagreement cases (divergent diagnosis by ≥2 assessors). κ-values were calculated, and results were correlated with clinical follow-up and molecular data. When focusing on the 114/123 cases unanimously classified as pulmonary carcinoids, the interobserver agreement was only fair (κ=0.32). Of these 114 cases, 55% were unanimously classified, 25% reached consensus classification, and for 19% there was no consensus. ACs were significantly more often in the latter category (P=0.00038). The designation of TCs and ACs by ≥3 assessors was not associated with prognosis (P=0.11). However, when disagreement cases were allocated on the basis of Ki-67 proliferative index (<5%; ≥5%) or nuclear orthopedia homeobox immunostaining (+; -), correlation with prognosis improved significantly (P=0.00040 and 0.0024, respectively). In conclusion, there is a considerable interobserver variation in the histopathologic classification of lung carcinoids, in particular concerning ACs. Additional immunomarkers such as Ki-67 or orthopedia homeobox may improve classification and prediction of prognosis.

Patient selection for whole brain radiotherapy (WBRT) in a large lung cancer cohort: Impact of a new Dutch guideline on brain metastases.

BACKGROUND: Median survival after diagnosis of brain metastases is, depending on the Recursive Partitioning Analysis (RPA) classes, 7.1 (class I) to 2.3 months (class III). In 2011 the Dutch guideline on brain metastases was revised, advising to withhold whole brain radiotherapy (WBRT) in RPA class III. In this large retrospective study, we evaluated the guideline's use in daily practice. MATERIAL AND METHODS: Data of 428 lung cancer patients undergoing WBRT for brain metastases (2004-2012) referred from three Dutch hospitals were retrospectively analyzed. Details on Karnofsky performance score (KPS), age, control of primary tumor, extracranial metastases, histology, and survival after diagnosis of brain metastases were collected. RPA class was determined using the first four items. RESULTS: In total 327 patients had non-small cell lung cancer (NSCLC) and 101 small cell lung cancer (SCLC). For NSCLC, 6.1%, 71.9%, and 16.2% were classified as RPA I, II, and III, respectively, and 5.8% could not be classified. For SCLC this was 8.9%, 66.3%, 14.9%, and 9.9%, respectively. Before the revised guideline was implemented, 11.3-21.3% of WBRT patients were annually classified as RPA III. In the year thereafter, this was 13.0% (p = 0.646). Median survival (95% CI) for NSCLC RPA class I, II, and III was 11.4 (9.9-12.9), 4.0 (3.4-4.7), and 1.7 (1.3-2.0) months, respectively. For SCLC this was 7.9 (4.1-11.7), 4.7 (3.3-6.1), and 1.7 (1.5-1.8) months. CONCLUSIONS: Although it is advised to withhold WBRT in RPA class III patients, in daily practice 11.3-21.3% of WBRT-treated patients were classified as RPA III. The new guideline did not result in a decrease. Reasons for referral of RPA III patients despite a low KPS were not found. Despite WBRT, survival of RPA III patients remains poor and this poor outcome should be stressed in practice guidelines. Therefore, better awareness amongst physicians would prevent some patients from being treated unnecessarily.

Cardiac herniation after operative management of lung cancer: a rare and dangerous complication.

Cardiac herniation after pneumonectomy is recognized as a rare complication. This case report describes two cases. The mortality rate of this complication remains high as reported in the literature; in early-recognized cases 50 % and in late or unrecognized cases 100 %. In the following two cases a pneumonectomy was performed as a treatment for lung cancer. Within 48 h after the initial operative treatment, the clinical situation of the patients got worse and radiographic examinations showed a strongly deviated heart. After suspicion of the diagnosis, the patients were immediately transferred to the operation theatre for emergency thoracotomy. Per-operative the diagnosis was confirmed and the heart was returned into its original position while the defect in the pericardial sac was closed with a bovine pericardial patch. Both patients survived these procedures and did not suffer from any further complication.

Risk factors for osteoporosis in Caucasian patients with moderate chronic obstructive pulmonary disease: a case control study.

The prevalence of osteoporosis is high in chronic obstructive pulmonary disease (COPD) patients. The gold standard for the diagnosis of osteoporosis is bone mineral density (BMD) measurements as assessed by dual energy absorptiometry (DXA) scanning as well as vertebral fractures as assessed by instant vertebral assessment (IVA). The aim of this study was to compare COPD GOLD II patients (that is, patients with moderate COPD, stage II, according to the GOLD classification) with osteoporosis (cases) to COPD GOLD II patients without osteoporosis (controls) to identify risk factors for osteoporosis. The diagnosis of osteoporosis was based on BMD and vertebral fractures. Cases (n=49) were matched for gender, age and forced expiratory volume in the first second to controls (n=49). We assessed pulmonary function, body composition, vitamin D, emphysema score (by high-resolution computer tomography), medical history and medication use in all patients. Variables that were significantly different between the cases and controls were included in a logistic regression analysis. COPD patients with osteoporosis had a significantly lower body mass index (BMI) and higher residual volume as the percentage of total lung capacity (RV%TLC) compared to COPD patients without osteoporosis. Decreasing BMI and increasing RV%TLC increased the odds ratio for osteoporosis. Overweight and obese BMI values were protective for osteoporosis. Screening for osteoporosis should be performed even in moderate COPD patients, especially in those with a low BMI and/or a high RV%TLC.

Progression of osteoporosis in patients with COPD: a 3-year follow up study.

Currently, our knowledge on the progression of osteoporosis and its determinants is limited in patients with chronic obstructive pulmonary disease (COPD). Bone mineral density generally remains stable in patients with COPD over a period of 3 years. Nevertheless, the progression of vertebral fractures was not assessed, while an increase of vertebral fractures over time may be reasonable. Aims of the current study were to determine the percentage of newly diagnosed osteoporotic patients after a follow up of 3 years and to identify baseline risk factors for the progression of osteoporosis in COPD. Clinically stable COPD outpatients were included. Lung function parameters, body composition measures, six minute walk distance, DXA-scan and X-spine were assessed at baseline and repeated after 3 years. Prevalence of osteoporosis in COPD patients increased from 47% to 61% in 3 years mostly due to an increase of vertebral fractures. Lower baseline T-score at the trochanter independently increased the risk for the development of osteoporosis. Additionally, baseline vitamin D deficiency increased this risk 7.5-fold. In conclusion, the prevalence of osteoporosis increased over a 3-year period in patients with COPD. Baseline risk factors for the development of osteoporosis are osteopenia at the trochanter and vitamin D deficiency.

Randomized, placebo-controlled phase III study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study.

PURPOSE: Cyclooxygenase-2 (COX-2) protein expression in patients with non-small-cell lung cancer (NSCLC) may be not only a prognostic marker but also predictive for COX-2 inhibition. We hypothesized that COX-2 expression is associated with shorter survival and that celecoxib, being a potent COX-2 inhibitor, increases tumor response and survival. PATIENTS AND METHODS: A phase III study was performed in patients with stage IIIb/IV NSCLC who had pathologic confirmation, no prior chemotherapy, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Treatment consisted of docetaxel and carboplatin every 3 weeks for five cycles. Patients were randomly assigned to receive celecoxib 400 mg or placebo twice daily. COX-2 expression on tumor cells was detected by immunohistochemistry. Primary end point was overall survival (OS). RESULTS: From July 2003 to December 2007, 561 patients were randomly assigned. Toxicity was mild, and no increase in cardiovascular events was observed. Tumor response was 38% in the celecoxib arm and 30% in the placebo arm (P = .08). Median progression-free survival was 4.5 months (95% CI, 4.0 to 4.8) for the celecoxib arm and 4.0 months (95% CI, 3.6 to 4.9) for the placebo arm (hazard ratio [HR], 0.8; 95% CI, 0.6 to 1.1; P = .25). Median OS was 8.2 months (95% CI, 7.5 to 8.8) for both treatment arms (HR, 0.9; 95% CI, 0.6 to 1.2; P = .32). COX-2 expression did not independently predict survival. Benefit from celecoxib, restricted to patients with low COX-2 expression, was not significant when adjusted for prognostic factors. CONCLUSION: In advanced NSCLC, celecoxib does not improve survival. In this study, COX-2 expression was not a prognostic biomarker and had no predictive value when celecoxib was added to chemotherapy.

Osteoporosis in COPD outpatients based on bone mineral density and vertebral fractures.

One of the extrapulmonary effects of chronic obstructive pulmonary disease (COPD) is osteoporosis. Osteoporosis is characterized by a low bone mineral density (BMD) and microarchitectural deterioration. Most studies in COPD patients use dual-energy X-ray absorptiometry (DXA) only to determine osteoporosis; therefore, microarchitectural changes without a low BMD are missed. The aim of this study was to determine the prevalence and correlates of osteoporosis in COPD patients based on DXA, spinal X-rays, and combinations thereof. DXA and spinal X-rays were obtained and pulmonary function tests, body composition, 6-minute walking distance, medical history, and medication use were assessed in 255 clinically stable COPD outpatients of a large teaching hospital in the Netherlands. Half of all patients had radiologic evidence of osteoporosis. Combining the results of DXA with spinal X-rays augmented the proportion of COPD patients with osteoporosis compared with both methods separately. The prevalence of osteoporosis was not significantly different after stratification for Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) stage. Most patients with osteoporosis did not receive pharmacologic treatment. Age, body mass index (BMI), and parathyroid hormone (PTH) level were significant independent correlates for osteoporosis. Chest physicians should be aware of the high prevalence of osteoporosis in patients with COPD, even in the presence of a low GOLD score, as well as especially in elder COPD patients with a low BMI and/or an increased PTH level.

Weekly chemoradiation (docetaxel/cisplatin) followed by surgery in stage III NSCLC; a multicentre phase II study.

BACKGROUND: This prospective study analyzed the feasibility and efficacy of weekly concurrent chemoradiation (docetaxel/cisplatin) followed by surgery. The primary endpoint was radiological response. PATIENTS AND METHODS: Six chemotherapy (docetaxel/cisplatin) cycles were administered on days 1, 8, 15, 22, 29 and 36 with concurrent thoracic radiotherapy in fractions of 1.8 Gy, to a total dose of 45 Gy. Patients underwent surgery depending on results of invasive mediastinal re-staging. RESULTS: Forty-two out of 45 NSCLC stage III patients were evaluable. Nineteen patients showed partial/complete response (46%), 14 stable disease (34%) and eight (20%) progressive disease. Toxicity was mild. The 30-day postoperative mortality was 4.2%. Twenty-four patients (59%) proceeded to surgery and 20 (49%) underwent a complete resection (R0). CONCLUSION: Weekly concurrent chemoradiation (docetaxel/cisplatin) in stage III NSCLC results in a radiological response rate of 46% and mediastinal downstaging in 56%. Complete resection in downstaged patients was achieved in 49% of all patients.

Whole-Body versus Local DXA-Scan for the Diagnosis of Osteoporosis in COPD Patients.

Background. Osteoporosis is an extrapulmonary effect of chronic obstructive pulmonary disease (COPD). Diagnosis of osteoporosis is based on BMD measured by DXA-scan. The best location for BMD measurement in COPD has not been determined. Aim of this study was to assess whole-body BMD and BMD of the hip and lumbar spine (local DXA) in COPD patients and compare the prevalence of osteoporosis at these locations. Methods. Whole body as well as local DXA-scan were made in 168 COPD patients entering pulmonary rehabilitation. Patient-relevant characteristics were assessed. Prevalence of osteoporosis was determined. Characteristics of patients without osteoporosis were compared to patients with osteoporosis on local DXA. Results. A higher prevalence of osteoporosis was found using local DXA compared to whole-body DXA (39% versus 21%). One quarter of patients without osteoporosis on whole body-DXA did have osteoporosis on local DXA. Significant differences in patient characteristics between patients without osteoporosis based on both DXA measurements and patients with osteoporosis based on local DXA only were found. Conclusions. DXA of the hip and lumbar spine should be made to assess bone mineral density in COPD patients. The lowest T-score of these locations should be used to diagnose osteoporosis.