Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic: A population-based observational study.

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1-12 2020: pre-COVID-19, weeks 12-20 2020: 1st peak, weeks 21-41 2020: recovery, weeks 42-53 2020: 2nd peak, weeks 1-20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77-0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72-0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p < .001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.

Prognostic Implication of KRAS G12C Mutation in a Real-World KRAS-Mutated Stage IV NSCLC Cohort Treated With Immunotherapy in The Netherlands.

Introduction: With the approval of G12C inhibitors as the second line of treatment for KRAS G12C-mutated NSCLC, and the expanding research regarding targeting KRAS, it is key to understand the prognostic implication of KRAS G12C in the current first line of treatment. We compared overall survival (OS) of patients with stage IV KRAS G12C-mutated NSCLC to those with a KRAS non-G12C mutation in a first-line setting of (chemo)immunotherapy. Methods: This nationwide population-based study used real-world data from The Netherlands Cancer Registry. We selected patients with stage IV KRAS-mutated lung adenocarcinoma diagnosed in 2019 to 2020 who received first-line (chemo-)immunotherapy. Primary outcome was OS. Results: From 28,120 registered patients with lung cancer, 1185 were selected with a KRAS mutation, of which 494 had a KRAS G12C mutation. Median OS was 15.5 months (95% confidence interval [CI]: 13.6-18.4) for KRAS G12C versus 14.0 months (95% CI:11.2-15.7) for KRAS non-G12C (p = 0.67). In multivariable analysis, KRAS subtype was not associated with OS (hazard ratio = 0.95, 95% CI: 0.82-1.10). For the subgroup with programmed death-ligand 1 at 0% to 49% who received chemoimmunotherapy, median OS was 13.3 months (95% CI: 10.5-15.2) for G12C and 9.8 months (95% CI: 8.6-11.3) for non-G12C (p = 0.48). For the subgroup with programmed death-ligand 1 more than or equal to 50% who received monoimmunotherapy, the median OS was 22.0 months (95% CI: 18.4-27.3) for G12C and 18.9 months (95% CI: 14.9-25.2) for non-G12C (p = 0.36). Conclusions: There was no influence of KRAS subtype (G12C versus non-G12C) on OS in patients with KRAS-mutated stage IV NSCLC treated with first-line (chemo)immunotherapy.

Survival of patients with KRAS G12C mutated stage IV non-small cell lung cancer with and without brain metastases treated with immune checkpoint inhibitors.

INTRODUCTION: Few data is available on whether brain metastases (BM) influence survival in patients with stage IV KRAS G12C mutated (KRAS G12C+ ) non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitor (ICI) +/- chemotherapy ([chemo]-ICI). METHODS: Data was retrospectively collected from the population-based Netherlands Cancer Registry. The cumulative incidence of intracranial progression, overall survival (OS) and progression free survival (PFS) was determined for patients with KRAS G12C+ stage IV NSCLC diagnosed January 1 - June 30, 2019, treated with first-line (chemo)-ICI. OS and PFS were estimated using Kaplan-Meier methods and BM+ and BM- groups were compared using log-rank tests. RESULTS: Of 2489 patients with stage IV NSCLC, 153 patients had KRAS G12C+ and received first-line (chemo)-ICI. Of those patients, 35% (54/153) underwent brain imaging (CT and/or MRI), of which 85% (46/54) MRI. Half of the patients with brain imaging (56%; 30/54) had BM, concerning one-fifth (20%; 30/153) of all patients, of which 67% was symptomatic. Compared to BM-, patients with BM+ were younger and had more organs affected with metastasis. Around one-third (30%) of patients with BM+ had ≥5 BM at diagnosis. Three quarters of patients with BM+ received cranial radiotherapy prior to start of (chemo)-ICI. The 1-year cumulative incidence of intracranial progression was 33% for patients with known baseline BM and 7% for those without (p = 0.0001). Median PFS was 6.6 (95% CI 3.0-15.9) and 6.7 (95% CI 5.1-8.5) months for BM+ and BM- (p = 0.80), respectively. Median OS was 15.7 (95% CI 6.2-27.3) and 17.8 (95% CI 13.4-22.0) months for BM+ and BM- (p = 0.77), respectively. CONCLUSION: Baseline BM are common in patients with metastatic KRAS G12C+ NSCLC. During (chemo)-ICI treatment, intracranial progression was more frequent in patients with known baseline BM, justifying regular imaging during treatment. In our study, presence of known baseline BM did not influence OS or PFS.

[Current and future therapeutic options for COVID-19]. / Recente en toekomstige behandelingen bij covid-19.

The anti-inflammatory agents dexamethasone (corticosteroid), and tocilizumab and sarilumab (IL6-inhibitors) are effective in the treatment of late COVID-19. Other anti-inflammatory agents, like anakinra (IL1-inhibitor), baricitinib and tofacitinib (JAK-inhibitors) and lenzilumab (GM-CSF-inhibitor) have also shown positive results in late COVID-19. For the treatment of early COVID-19, the inhalation corticosteroid budesonide is regarded as an off-label treatment option. Virus-inhibitors, like remdesivir, molnupiravir and nirmatrelvir/ritonavir decrease the risk of hospitalization and the development of severe COVID-19 by patients with early symptoms. Monoclonal antibodies have shown limited or no efficacy against the omicron-variant of SARS-CoV-2. Fluvoxamine, l-arginine, AT-527 and ensovibep are considered as potential promising new therapies for the treatment of early COVID-19.

Use of potentially inappropriate medication in older patients with lung cancer at the end of life.

OBJECTIVES: Medications at the end of life should be used for symptom control. Medications which potential adverse effects outweigh their expected benefits are called 'potentially inappropriate medications' (PIMs). PIMs are related with adverse drug events and reduced quality of life. In this study, we investigated to what extent PIMs are dispensed to older patients with lung cancer in the last month of life. METHODS: We selected patients with lung cancer, aged 65+, diagnosed between 2009 and 2014, and who died before April 1st 2015 from the population-based Netherlands Cancer Registry (NCR). The NCR is linked to the PHARMO Database Network, that includes medications dispensed by community pharmacies in the Netherlands. The eight PIM groups were based on the OncPal Deprescribing Guideline: aspirin, dyslipidaemia medications, antihypertensives, osteoporosis medications, peptic ulcer prophylaxis, oral hypoglycaemics, vitamins and minerals. RESULTS: Data of 7864 patients with lung cancer were analyzed. Median age was 74 year (IQR = 70-79) and 67% was male. 45% of all patients received at least one PIM in their last month of life. Taking into account all dispensed medications, patients receiving PIMs received more different medications compared to those receiving no PIMs, respectively 10 (SD = 5) vs. 3 (SD = 4) different medications (P < 0.001). CONCLUSION: Almost half of the older patients with lung cancer in the Netherlands received PIMs in their last month of life. Since PIM use is associated with reduced quality of life, it is important that health care professionals continue to critically assess which medication can be discontinued at the end of life.

Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial.

BACKGROUND: The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak. METHODS: This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged ≥18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10). FINDINGS: Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0·95 [95% CI 0·76-1·20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0·51 [0·27-0·95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0·52 (95% CI 0·26-1·05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1·07 (0·63-1·80; p=0·81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0·0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events. INTERPRETATION: The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. FUNDING: Amsterdam Medical Center Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ZonMW, and the European Union Innovative Medicines Initiative 2.

Chest computed tomography and alveolar-arterial oxygen gradient as rapid tools to diagnose and triage mildly symptomatic COVID-19 pneumonia patients.

BACKGROUND: In the coronavirus disease 2019 (COVID-19) pandemic, rapid clinical triage is crucial to determine which patients need hospitalisation. We hypothesised that chest computed tomography (CT) and alveolar-arterial oxygen tension ratio (A-a) gradient may be useful to triage these patients, since they reflect the severity of the pneumonia-associated ventilation/perfusion abnormalities. METHODS: A retrospective analysis was performed in 235 consecutive patients suspected for COVID-19. The diagnostic protocol included low-dose chest CT and arterial blood gas analysis. In patients with CT-based COVID-19 pneumonia, the association between "need for hospitalisation" and A-a gradient was investigated by a multivariable logistic regression model. The A-a gradient was tested as a predictor for need for hospitalisation using receiver operating characteristic curve analysis and a logistic regression model. RESULTS: 72 out of 235 patients (mean±sd age 55.5±14.6 years, 40% female) screened by chest CT showed evidence for COVID-19 pneumonia. In these patients, A-a gradient was shown to be a predictor of need for hospitalisation, with an optimal decision level (cut-off) of 36.4 mmHg (95% CI 0.70-0.91, p<0.001). The A-a gradient was shown to be independently associated with need for hospitalisation (OR 1.97 (95% CI 1.23-3.15), p=0.005; A-a gradient per 10 points) from CT severity score (OR 1.13 (95% CI 0.94-1.36), p=0.191), National Early Warning Score (OR 1.19 (95% CI 0.91-1.57), p=0.321) or peripheral oxygen saturation (OR 0.88 (95% CI 0.68-1.14), p=0.345). CONCLUSION: Low-dose chest CT and the A-a gradient may serve as rapid and accurate tools to diagnose COVID-19 pneumonia and to select mildly symptomatic patients in need for hospitalisation.

Synchronous peritoneal metastases from lung cancer: incidence, associated factors, treatment and survival: a Dutch population-based study.

Peritoneal metastases (PM) from lung cancer are rare and it is unknown how they affect the prognosis of patients with lung cancer. This population-based study aimed to assess the incidence, associated factors, treatment and prognosis of PM from lung cancer. Data from the Netherlands Cancer Registry were used. All patients diagnosed with lung cancer between 2008 and 2018 were included. Logistic regression analysis was performed to identify factors associated with the presence of PM. Cox regression analysis was performed to identify factors associated with the overall survival (OS) of patients with PM. Between 2008 and 2018, 129,651 patients were diagnosed with lung cancer, of whom 2533 (2.0%) patients were diagnosed with PM. The European Standardized Rate of PM increased significantly from 0.6 in 2008 to 1.4 in 2018 (p < 0.001). Age between 50 and 74 years, T3-4 tumour stage, N2-3 nodal stage, tumour morphology of a small cell lung cancer or adenocarcinoma, and the presence of systemic metastases were associated with the presence of PM. The median OS of patients with PM was 2.5 months. Older age, male sex, T3-4 tumour stage, N2-3 nodal stage, not receiving systemic treatment, and the presence of systemic metastases were associated with a worse OS. Synchronous PM were diagnosed in 2.0% of patients with lung cancer and resulted in a very poor survival.

Digital versus analogue chest drainage system in patients with primary spontaneous pneumothorax: a randomized controlled trial.

BACKGROUND: Patients with a primary spontaneous pneumothorax (PSP) who are treated with chest tube drainage are traditionally connected to an analogue chest drainage system, containing a water seal and using a visual method of monitoring air leakage. Electronic systems with continuous digital monitoring of air leakage provide better insight into actual air leakage and changes in leakage over time, which may lead to a shorter length of hospital stay. METHODS: We performed a randomized controlled trial comparing the digital with analogue system, with the aim of demonstrating that use of a digital drainage system in PSP leads to a shorter hospital stay. RESULTS: In 102 patients enrolled with PSP we found no differences in total duration of chest tube drainage and hospital stay between the groups. However, in a post-hoc analysis, excluding 19 patients needing surgery due to prolonged air leakage, hospital stay was significantly shorter in the digital group (median 1 days, IQR 1-5 days) compared to the analogue group (median 3 days, IQR 2-5 days) (p 0.014). Treatment failure occurred in 3 patients in both groups; the rate of recurrence within 12 weeks was not significantly different between groups (16% in the digital group versus 8% in the analogue group, p 0.339). CONCLUSION: Length of hospital stay was not shorter in patients with PSP when applying a digital drainage system compared to an analogue drainage system. However, in the large subgroup of uncomplicated PSP, a significant reduction in duration of drainage and hospital stay was demonstrated with digital drainage. These findings suggest that digital drainage may be a practical alternative to manual aspiration in the management of PSP. TRIAL REGISTRATION: Registered 22 September 2013 - Retrospectively registered, Trial NL4022 (NTR4195).

A phase II study of sorafenib in patients with platinum-pretreated, advanced (Stage IIIb or IV) non-small cell lung cancer with a KRAS mutation.

PURPOSE: Sorafenib inhibits the Ras/Raf pathway, which is overactive in cancer patients with a KRAS mutation. We hypothesized that patients with non-small cell lung cancer (NSCLC) with KRAS mutation will benefit from treatment with sorafenib. EXPERIMENTAL DESIGN: In this phase II study, patients with KRAS-mutated, stage IIIb or IV NSCLC that progressed after at least one platinum-containing regimen were treated with sorafenib. Treatment consisted of sorafenib 400 mg twice daily until disease progression or unacceptable toxicity. Pretreatment serum from each patient was obtained to predict outcome using a proteomic assay (VeriStrat). Primary endpoint was disease control rate (DCR) at 6 weeks. RESULTS: Fifty-nine patients were entered between May 2010 and February 2011. Fifty-seven patients started sorafenib. Mean age was 58.5 (SD = ±8.1) years, 16 male/41 female, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0/1/2 24/30/3. At 6 weeks, 5 partial response, 25 stable disease, and 27 progressive disease were observed; DCR was 52.6%. Median duration of treatment was 9 weeks. The median progression-free survival (PFS) was 2.3 months and median overall survival (OS) was 5.3 months. Patients with a prediction of good prognosis according to VeriStrat serum proteomics assay showed a significantly superior PFS [HR, 1.4; 95% confidence interval (CI), 1.0-1.9] but not OS (HR, 1.3; 95% CI, 0.9-1.7). Sorafenib-related grade III/IV toxicity was reported in 10 patients (17.5%); all but one patient experienced grade III skin toxicity (14.0%) or grade III gastrointestinal toxicity (8.8%). CONCLUSION: Treatment with sorafenib has relevant clinical activity in patients with NSCLC harboring KRAS mutations. Further randomized study with this agent is warranted as single-agent or combination therapy.

Restaging of mediastinal nodes with transbronchial needle aspiration after induction chemoradiation for locally advanced non-small cell lung cancer.

INTRODUCTION: Selecting the appropriate treatment strategy for patients with locally advanced non-small cell carcinoma (NSCLC) is of utmost importance to determine patient outcome. Previous studies have shown that nodal down-staging after induction therapy and definitive local irradiation in these patients better predict survival when combined with surgery. However, nodal restaging can be technically difficult. We investigated the role of transbronchial needle aspiration (TBNA) in mediastinal restaging of patients who had completed induction cytotoxic therapy. METHODS: A total of 14 patients with proven stage IIIa-N2 NSCLC who received chemotherapy or chemo-radiotherapy as induction regimen between 2005 and 2006 were studied. Outpatient flexible bronchoscopy with TBNA was performed in all patients under local anesthesia, and 17 TBNA procedures were performed. TBNA results were matched against the histopathology of surgical specimens. RESULTS: Seventeen lymph nodes in 14 patients who had undergone induction therapy were sampled. Positron emission tomography (PET) scan results of 11 patients were also available for comparison. All positive TBNA procedures had positive PET scans. However, for five patients with lymph nodes measuring 9 to 17 mm, the PET scans were falsely positive, as mediastinoscopy and subsequent surgically resected lymph nodes revealed no tumor. TBNA achieved a correct diagnosis in 71% of patients who underwent mediastinal restaging and obviated further need for invasive procedures in 35%. CONCLUSION: For patients presenting with locally advanced NSCLC who are surgical candidates after induction chemo- and/or radiotherapy, TBNA should be considered as the initial procedure of choice for restaging of the mediastinum.

Can mediastinal nodal mobility explain the low yield rates for transbronchial needle aspiration without real-time imaging?

BACKGROUND: The diagnostic yields with transbronchial needle aspiration (TBNA) for mediastinal nodes are highly variable. Nodal positions, as assessed on a breath-hold conventional CT scan, do not account for nodal motion. We studied nodal motion on four-dimensional (4D) CT scans. METHODS: A total of 47 mediastinal nodes were identified on 4D CT scans performed for radiotherapy planning in 25 patients with lung cancer. Nodes were mainly located at stations 4R, 4L, 7, and 2R, and each identified node was contoured in all 10 phases of the 4D CT scan. Nodal motion was correlated with changes in carina position. RESULTS: The mean (+/- SD) nodal diameter was 10.2 +/- 4.0 mm; and the mean nodal volume was 1.8 +/- 2.3 mL. Movement was maximal in the craniocaudal axis (mean length, 4.7 +/- 2.3 mm), and the corresponding mean mediolateral and ventrodorsal movements were 2.8 +/- 1.9 mm and 2.4 +/- 1.8 mm, respectively. The mean three-dimensional displacement of the nodal center was 6.2 +/- 2.9 mm, and it exceeded 10 mm in five nodes. The nodal mass was constantly present in only 25 +/- 14% of the region encompassing all nodal positions. The mean variation in craniocaudal distance between all nodes and the carina position during respiration was 5.3 +/- 2.1 mm (range, 2.2 to 10.5 mm). CONCLUSIONS: Both nodal motion and the varying distance between the carina and nodal position may explain the lower diagnostic yields for TBNA procedures performed without real-time guidance.

Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung.

PURPOSE: To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung carcinoma. EXPERIMENTAL DESIGN: Phase I, dose-escalating study of SLIT Cisplatin given in two sessions daily. Safety data, including laboratory variables, adverse events, pulmonary function tests, and radiographic imaging, were collected and analyzed for all patients to determine toxicity. Pharmacokinetic monitoring was done during the first course. RESULTS: Seventeen patients and one tracheostomy patient on compassionate use received treatment. Aerosolized cisplatin was well tolerated. No dose-limiting toxicity was observed at the maximum delivered dose. Safety data showed no hematologic toxicity, nephrotoxicity, ototoxicity, or neurotoxicity. Most common adverse events were nausea (64.7%), vomiting (47.1%), dyspnea (64.7%), fatigue (64.7%), and hoarseness (47.1%). Pharmacokinetic data showed very low plasma platinum levels only with the longest repeated inhalations. Common Toxicity Criteria grade 2 decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide after one course occurred both in two patients and grade one decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide in six and five patients, respectively. Direct airway deposition via the tracheostomy resulted in clinical deterioration after two cycles best described as bronchitis, completely reversible within days. Overall response: stable disease in 12 patients and progressive disease in 4 patients (one patient received one cycle). CONCLUSIONS: Aerosolized liposomal cisplatin was found to be feasible and safe.

Initial bronchoscopic treatment for patients with intraluminal bronchial carcinoids.

OBJECTIVE: Carcinoid of the lung is considered low-grade malignancy, and less invasive treatment may therefore be considered. We analyzed the long-term outcome of initial bronchoscopic treatment in patients with intraluminal bronchial carcinoids. METHODS: Initial bronchoscopic treatment was applied to improve presurgical condition, to obtain tissue samples for proper histologic classification, and to enable less extensive parenchymal resection. For intraluminal bronchial carcinoid, complete tumor eradication with initial bronchoscopic treatment was attempted. High-resolution computed tomography in addition to bronchoscopy was used to determine intraluminal versus extraluminal tumor growth. Surgery followed in cases of atypical carcinoid, residue, or recurrence. RESULTS: Seventy-two patients, 43 of them female, have been treated (median age 47 years, range 16-80 years). Median follow-up has been 65 months (range 2-180 months). Fifty-seven (79%) had typical carcinoids and 15 (21%) had atypical carcinoids. Initial bronchoscopic treatment resulted in complete tumor eradication in 33 of 72 cases (46%), 30 typical and 3 atypical. Thirty-seven of 72 cases (51%), 11 atypical, required surgery (2 for late detected recurrences). Two patients had metastatic atypical carcinoid, 1 already at referral. Of the 6 deaths, 1 was tumor related. CONCLUSIONS: Initial bronchoscopic treatment is a potentially more tissue-sparing alternative than immediate surgical resection in patients with intraluminal bronchial carcinoids. For successful tumor eradication with initial bronchoscopic treatment in central carcinoids, assessment of intraluminal versus extraluminal growth may be of much more importance than histologic division between typical and atypical carcinoid. Disease-specific mortality is low, and long-term outcome has been excellent. Implementation of initial bronchoscopic treatment had no negative impact on surgical treatment outcome.

Assessing a system to capture stray aerosol during inhalation of nebulized liposomal cisplatin.

The aim of this study was to determine the efficacy of using a high-efficiency particulate air (HEPA) filter air cleaning system, a demistifier, to reduce the potential risk of fugitive aerosol contact in health care personnel working with patients inhaling nebulized liposomal encapsulated SLIT (Sustained-release Lipid Inhalation Targeting) Cisplatin. Filters were used to sample platinum in the air outside the tent and from the tent's exhaust stream. Air collection was performed under three conditions: (1) during patient dosing (14 h of air collection); (2) immediately after the patient has left the demistifier tent (4 h of air collection); and (3) when 7 mL of drug product was nebulized to dryness in the tent without a patient being present. Filters were collected, and placed in an extraction solvent. Subsequently, the solvent was assayed for platinum content by inductively coupled plasma-mass spectrometry (ICP-MS). Platinum levels in the extraction solvent were indistinguishable from the blank controls for all conditions. Measured levels were below workplace exposure limits established for cisplatin by the Occupational Safety and Health Administration (i.e., 2 ng . (L(1)). In addition, the demistifier was able to effectively capture aerosolized SLIT Cisplatin following nebulization of 7 mL of drug product to dryness in the tent. The demistifier tent is effective at containing any nebulized liposomal encapsulated cisplatin during patient treatment. Importantly, because the tent's HEPA filtration system is effective at removing any nebulized liposomal cisplatin, the exhausted air, which is free of platinum, can be returned into the room with no additional ventilation precautions.