Objectives
To meta-analyze complication rate in computed tomography (CT)-guided transthoracic lung biopsy and associated risk factors.
Methods
Four databases were searched from 1/2000 to 8/2015 for ...studies reporting complications in CT-guided lung biopsy. Overall and major complication rates were pooled and compared between core biopsy and fine needle aspiration (FNA) using the random-effects model. Risk factors for complications in core biopsy and FNA were identified in meta-regression analysis.
Results
For core biopsy, 32 articles (8,133 procedures) were included and for FNA, 17 (4,620 procedures). Pooled overall complication rates for core biopsy and FNA were 38.8 % (95 % CI: 34.3–43.5 %) and 24.0 % (95 % CI: 18.2–30.8 %), respectively. Major complication rates were 5.7 % (95 % CI: 4.4–7.4 %) and 4.4 % (95 % CI: 2.7–7.0 %), respectively. Overall complication rate was higher for core biopsy compared to FNA (
p
< 0.001). For FNA, larger needle diameter was a risk factor for overall complications, and increased traversed lung parenchyma and smaller lesion size were risk factors for major complications. For core biopsy, no significant risk factors were identified.
Conclusions
In CT-guided lung biopsy, minor complications were common and occurred more often in core biopsy than FNA. Major complication rate was low. For FNA, smaller nodule diameter, larger needle diameter and increased traversed lung parenchyma were risk factors for complications.
Key Points
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Minor complications are common in CT-guided lung biopsy
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Major complication rate is low in CT-guided lung biopsy
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CT-guided lung biopsy complications occur more often in core biopsy than FNA
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Major complication rate is similar in core biopsy and FNA
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Risk factors for FNA are larger needle diameter, smaller lesion size
This study aims to assess how clinical outcomes of immunotherapy in real-world (effectiveness) correspond to outcomes in clinical trials (efficacy) and to look into factors that might explain an ...efficacy-effectiveness (EE) gap. All patients diagnosed with stage IV non-small cell lung cancer (NSCLC) in 2015-2018 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. Progression-free survival (PFS) and overall survival (OS) from first-line (1L) pembrolizumab and second-line (2L) nivolumab were compared with clinical trial data by calculating hazard ratios (HRs). From 1950 diagnosed patients, 1005 (52%) started with any 1L treatment, of which 83 received pembrolizumab. Nivolumab was started as 2L treatment in 141 patients. For both settings, PFS times were comparable between real-world and trials (HR 1.08 (95% CI 0.75-1.55), and HR 0.91 (95% CI 0.74-1.14), respectively). OS was significantly shorter in real-world for 1L pembrolizumab (HR 1.55; 95% CI 1.07-2.25). Receiving subsequent lines of treatment was less frequent in real-world compared to trials. There is no EE gap for PFS from immunotherapy in patients with stage IV NSCLC. However, there is a gap in OS for 1L pembrolizumab. Fewer patients proceeding to a subsequent line of treatment in real-world could partly explain this.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The randomized, phase III AVAPERL trial evaluated the safety and efficacy of bevacizumab maintenance with or without pemetrexed in nonsquamous nonsmall-cell lung cancer (nsNSCLC). Progression-free ...survival (PFS) was significantly prolonged with bevacizumab–pemetrexed, but overall survival (OS) data were immature. In this article, we report an independent, updated analysis of survival outcomes in AVAPERL.
Patients with advanced nsNSCLC received first-line bevacizumab (7.5 mg/kg), cisplatin (75 mg/m2), and pemetrexed (500 mg/m2) every 3 weeks (q3w) for four cycles. Nonprogressing patients were randomized to maintenance bevacizumab (7.5 mg/kg) or bevacizumab–pemetrexed (500 mg/m2) q3w until progression or consent withdrawal. The primary end point of the trial was PFS; in this independent OS analysis, participating study centers were contacted to collect survival data on patients still alive at the time of the first analysis.
A total of 376 patients received induction treatment. Disease control was confirmed in 71.9% of patients; 253 patients were randomized to maintenance treatment with bevacizumab (n = 125) or bevacizumab–pemetrexed (n = 128). At a median follow-up of 14.8 months, patients allocated to bevacizumab–pemetrexed had significantly improved PFS versus those on bevacizumab when measured from randomization 7.4 versus 3.7 months, hazard ratio (HR), 0.57, 95% confidence interval (CI) 0.44–0.75); P < 0.0001. OS events occurred in 58% of all patients. OS was numerically longer with bevacizumab–pemetrexed versus bevacizumab when measured from randomization 17.1 versus 13.2 months, HR 0.87 (0.63–1.21); P = 0.29. Second-line therapy was administered in 77% and 70% of patients in the bevacizumab and bevacizumab–pemetrexed arms, respectively. No new adverse events were reported during this updated analysis.
In an unselected population of nsNSCLC patients achieving disease control on platinum-based induction therapy, maintenance with bevacizumab–pemetrexed was associated with a nonsignificant increase in OS over bevacizumab alone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Initial response of small-cell lung cancer (SCLC) to chemotherapy is high, and recurrences occur frequently, leading to early death. This study investigated the prognostic value of circulating tumor ...cells (CTCs) in patients with SCLC and whether changes in CTCs can predict response to chemotherapy.
In this multicenter prospective study, blood samples for CTC analysis were obtained from 59 patients with SCLC before, after one cycle, and at the end of chemotherapy. CTCs were measured using CellSearch® systems.
At baseline, lower numbers of CTCs were observed for 21 patients with limited SCLC (median = 6, range 0–220) compared with 38 patients with extensive stage (median = 63, range 0–14 040). Lack of measurable CTCs (27% of patients) was associated with prolonged survival (HR 3.4; P ≤ 0.001). CTCs decreased after one cycle of chemotherapy; this decrease was not associated with tumor response after four cycles of chemotherapy. CTC count after the first cycle of chemotherapy was the strongest predictor for overall survival (HR 5.7; 95% CI 1.7–18.9; P = 0.004).
Absolute CTCs after one cycle of chemotherapy in patients with SCLC is the strongest predictor for response on chemotherapy and survival. Patients with low initial CTC numbers lived longer than those with higher CTCs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Participants who were at an increased risk for lung cancer were enrolled in a trial to determine whether CT screening reduces mortality from lung cancer. In this study, volume measurements and volume ...doubling times were used to evaluate the noncalcified lung nodules that were detected by CT scanning at baseline and at years 1, 2, and 4 of the trial. With the use of these volumetric methods, the authors found that the chances of finding lung cancer by CT scanning 1 and 2 years after a negative baseline test were 1 in 1000 and 3 in 1000, respectively.
With the use of volumetric methods, the authors found that the chances of finding lung cancer by CT scanning 1 and 2 years after a negative baseline test were 1 in 1000 and 3 in 1000, respectively.
The use of multidetector computed tomography (CT) has increased the chance of finding noncalcified pulmonary nodules,
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,
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and as a result, clinicians often face the problem of deciding on the best course of action with respect to such nodules when they are found in asymptomatic subjects who have an increased risk for lung cancer.
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This difficulty is especially evident in CT-based screening programs for lung cancer. The current practice is to refer participants in these programs for additional diagnostic evaluation if they have a noncalcified nodule that is larger than 5 mm in diameter.
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In designing the Dutch–Belgian randomized . . .
Summary Background Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with ...high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic activity, and we hypothesised that its use in the maintenance setting could improve outcomes. Methods In this open-label, multicentre, randomised phase 3 study, eligible patients had proven malignant pleural or peritoneal mesothelioma and had received a minimum of four cycles of first-line treatment containing at least pemetrexed, with or without cisplatin or carboplatin, and had not progressed on this treatment. Patients were randomly assigned (in a 1:1 ratio, stratified by previous first-line chemotherapy, histological subtype, and recruiting hospital) to receive thalidomide 200 mg per day (including a 2 week run in of 100 mg per day) plus active supportive care or active supportive care alone until disease progression. Patients were required to be registered and to start treatment with thalidomide within 10 weeks after the end of the first-line chemotherapy. Thalidomide was given for a maximum of 1 year or until unacceptable toxicity. The primary endpoint was time to progression. The primary analyses were by intention to treat. The study is registered, ISRCTN13632914. Findings Between May 11, 2004, and Dec 23, 2009, we randomly assigned 222 patients, 111 in each group (one patient on active supportive care later withdrew consent and was excluded from analyses). At the time of this final analysis, median follow-up was 33·1 months (IQR 22·3–66·8), and physician-reported disease progression had occurred in 104 patients in the thalidomide group and 107 in the active supportive care group; 92 patients in the thalidomide group and 93 in the active supportive care group had died. Median time to progression in the thalidomide group was 3·6 months (95% CI 3·2–4·1) compared with 3·5 months (2·3–4·8) in the active supportive care group (hazard ratio 0·95, 95% CI 0·73–1·20, p=0·72). 43 (39%) grade 3 or 4 adverse events were reported in the thalidomide group and 31 (28%) in the active supportive care group; neurosensory events were reported by two (2%) patients on thalidomide and none on active supportive care, cardiac events by two (2%) patients on thalidomide and three (3%) on active supportive care, and thromboembolic events by three (3%) patients on thalidomide and none on active supportive care. Interpretation No benefit was noted in time to progression with the addition of thalidomide maintenance to first-line chemotherapy. Different treatment strategies are needed to improve outcomes in patients with malignant mesothelioma. Funding Dutch Cancer Society (KWF), Eli Lilly, NSW Dust Disease Compensation Board, University of Sydney, and Cancer Australia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Bariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice ...improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects.
Subjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (
H
-glucose and
H
-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.
We observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.
Allogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.
NTR4327.
Abstract Targeted treatment of advanced non-small cell lung cancer patients with afatinib in EGFR mutation or crizotinib in ALK break positive patients results in profound tumor responses but ...inevitably induces resistance. In this review we present currently known resistance mechanisms for afatinib and crizotinib two recently approved drugs. Resistance mechanisms identified for afatinib include c-MET amplification and the V843I EGFR mutation. Expression of FGFR1, increased IL6R/JAK/STAT signaling, enhanced interference with aerobic glycolysis and autophagy are associated with resistance to afatinib. Most common resistance mechanisms for ALK break positive cases are gatekeeper mutations in the ALK gene. Also activation of the EGFR pathway, KRAS mutations, the autophagy pathway and epithelial mesenchymal transition (EMT), have been associated with resistance. Many of the proposed resistance mechanisms need to be functionally studied to proof a causative relationship with resistance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Understanding cancer heterogeneity, its temporal evolution over time, and the outcomes of guided treatment depend on accurate data collection in a context of routine clinical care. We have developed ...a hospital-based data-biobank for oncology, entitled OncoLifeS (Oncological Life Study: Living well as a cancer survivor), that links routine clinical data with preserved biological specimens and quality of life assessments. The aim of this study is to describe the organization and development of a data-biobank for cancer research.
We have enrolled 3704 patients aged ≥ 18 years diagnosed with cancer, of which 45 with hereditary breast-ovarian cancer (70% participation rate) as of October 24th, 2019. The average age is 63.6 ± 14.2 years and 1892 (51.1%) are female. The following data are collected: clinical and treatment details, comorbidities, lifestyle, radiological and pathological findings, and long-term outcomes. We also collect and store various biomaterials of patients as well as information from quality of life assessments.
Embedding a data-biobank in clinical care can ensure the collection of high-quality data. Moreover, the inclusion of longitudinal quality of life data allows us to incorporate patients' perspectives and inclusion of imaging data provides an opportunity for analyzing raw imaging data using artificial intelligence (AI) methods, thus adding new dimensions to the collected data.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We report updated data from a phase 2 randomized study evaluating brigatinib in crizotinib-refractory anaplastic lymphoma kinase–positive NSCLC.
Patients were randomized 1:1 to take either oral ...brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (arm B), stratified by central nervous system (CNS) metastases and best response to crizotinib. The primary end point was investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included independent review committee (IRC)-assessed progression-free survival (PFS), intracranial PFS (iPFS), and overall survival (OS). Exploratory analyses included CNS versus ex-CNS target lesion response and correlation of depth of response with PFS and OS.
Among 222 randomized patients (112 and 110 in arms A and B, respectively), 59 (27%) remained on brigatinib at analysis (median follow-up: 19.6 versus 24.3 months). At baseline, 71% and 67% had brain lesions among A and B arms, respectively. Investigator-assessed confirmed objective response rate was 46% versus 56%. Median IRC-assessed PFS was 9.2 months (95% confidence interval: 7.4–12.8) versus 16.7 months (11.6–21.4). Median OS was 29.5 months (18.2–not reached) versus 34.1 months (27.7–not reached). IRC-confirmed intracranial objective response rate in patients with measurable baseline brain lesions was 50% (13 of 26) versus 67% (12 of 18); median duration of intracranial response was 9.4 versus 16.6 months. IRC-assessed iPFS was 12.8 versus 18.4 months. Across arms, median IRC-assessed PFS was 1.9, 5.5, 11.1, 16.7, and 15.6 months for patients with no, 1%–25%, 26%–50%, 51%–75%, and 76%–100% target lesion shrinkage, respectively. No new safety findings were observed with longer follow-up.
Brigatinib (180 mg once daily with lead-in) continues to demonstrate robust PFS, long iPFS and duration of intracranial response, and high intracranial objective response rate in crizotinib-refractory patients. Depth of response may be an important end point to capture in future targeted therapy trials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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