An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab.

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase.

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).

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.

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.

Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) intercalated TKI with chemotherapy for -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 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.

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.

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.

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.

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.

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.

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.

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).

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 %.

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.

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.

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.

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.

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.

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.

Randomized clinical trial on the effects of adenosine 5'-triphosphate infusions on quality of life, functional status, and fatigue in preterminal cancer patients.

Context: One potential agent to improve symptoms and quality of life (QoL) in advanced cancer patients is adenosine 5'-triphosphate (ATP). Several reports suggest that ATP may positively affect QoL and survival in patients with advanced non-small-cell lung cancer.

Objectives: To investigate the effects of ATP infusions on QoL parameters in patients with preterminal cancer of mixed tumor types.

Correlates of osteoporosis in chronic obstructive pulmonary disease: An underestimated systemic component.

Rationale: Chronic obstructive pulmonary disease (COPD) patients are at increased risk of osteoporosis. Osteoporosis is under diagnosed and under treated in these patients and the underlying mechanisms remain unclear. To date, screening recommendations for osteoporosis in COPD patients are not available.

Diagnostic assessments of spirometry and medical history data by respiratory specialists supporting primary care: are they reliable?

Aim: To determine the intra- and inter-observer reliability of respiratory specialists' diagnostic assessments of spirometry and written medical history data obtained from primary care.

Method: Five respiratory specialists assessed spirometry data and the history of 156 patients randomly selected from referrals to an asthma/COPD-service. The inter-observer reliability was evaluated.

Intravenous ATP infusions can be safely administered in the home setting: a study in pre-terminal cancer patients.

The aim of the study was to investigate the safety of adenosine 5'-triphosphate (ATP) administration at home in pre-terminal cancer patients. Included were patients with cancer for whom medical treatment options were restricted to supportive care, who had a life expectancy of less than 6 months, a World Health Organization performance status 1 or 2, and suffered from at least one of the following complaints: fatigue, anorexia or weight loss >5% over the previous 6 months. Side effects were registered systematically on a standard form according to the National Cancer Institute (NCI) Common Toxicity Criteria.