scholarly journals Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
David Fisch ◽  
Farastuk Bozorgmehr ◽  
Daniel Kazdal ◽  
Jonas Kuon ◽  
Laura V. Klotz ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Systemic Treatment ◽  
Smoking Status ◽  
Stage Iv ◽  
Patient Characteristics ◽  
Large Cell ◽  
Platinum Drug ◽  
Baseline Serum ◽  
Secondary Stage ◽  
Metastatic Sites

BackgroundLarge-cell neuroendocrine lung carcinoma (LCNEC) is a rare pulmonary neoplasm with poor prognosis and limited therapeutic options.MethodsWe retrospectively analyzed all patients with metastatic LCNEC in the records of a large German academic center since 2010.Results191 patients were identified with a predominance of male (68%) smokers (92%) and a median age of 65 years. The single most important factor associated with outcome was the type of systemic treatment, with a median overall survival (OS) of 26.4 months in case of immune checkpoint inhibitor administration (n=13), 9.0 months for other patients receiving first-line platinum doublets (n=129), and 4.0 months with non-platinum chemotherapies (n=17, p<0.01). Other patient characteristics independently associated with longer OS were a lower baseline serum LDH (hazard ratio [HR] 0.54, p=0.008) and fewer initial metastatic sites (HR 0.52, p=0.006), while the platinum drug type (cisplatin vs. carboplatin) and cytotoxic partner (etoposide vs. paclitaxel), patients’ smoking status and baseline levels of tumor markers (NSE, CYFRA 21-1, CEA) did not matter. 12% (23/191) of patients forewent systemic treatment, mainly due to tumor-related clinical deterioration (n=13), while patient refusal of therapy (n=5) and severe concomitant illness (n=5) were less frequent. The attrition between successive treatment lines was approximately 50% and similar for platinum-based vs. other therapies, but higher in case of a worse initial ECOG status or higher serum LDH (p<0.05). 19% (36/191) of patients had secondary stage IV disease and showed fewer metastatic sites, better ECOG status and longer OS (median 12.6 vs. 8.7 months, p=0.030). Among the 111 deceased patients with palliative systemic treatment and complete follow-up, after exclusion of oligometastatic cases (n=8), administration of local therapies (n=63 or 57%) was associated with a longer OS (HR 0.58, p=0.008), but this association did not persist with multivariable testing.ConclusionsHighly active systemic therapies, especially immunotherapy and platinum doublets, are essential for improved outcome in LCNEC and influence OS stronger than clinical disease parameters, laboratory results and other patient characteristics. The attrition between chemotherapy lines is approximately 50%, similar to other NSCLC. Patients with secondary metastatic disease have a more favorable clinical phenotype and longer survival.

Temporal trends and factors associated with receipt of systemic therapy among patients undergoing cytoreductive nephrectomy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 503-503
Author(s):  
Marc C. Smaldone ◽  
Elizabeth Handorf ◽  
Simon Kim ◽  
Robert Houston Thompson ◽  
Brian Addis Costello ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Systemic Treatment ◽  
Temporal Trends ◽  
Stage Iv ◽  
Patient Characteristics ◽  
The Elderly ◽  
Policy Implications ◽  
Cytoreductive Nephrectomy ◽  
Potential Health ◽  
To Receive

503 Background: We evaluated temporal patterns in the utilization of systemic therapy among patients undergoing cytoreductive nephrectomy (CN) for metastatic Renal Cell Carcinoma (mRCC) from a large national cancer registry and assessed patient characteristics associated with receipt of systemic treatment. Methods: We reviewed the National Cancer Database to identify patients with stage IV RCC who underwent CN between 1998-2010. Systemic therapy was defined as any treatment with immunotherapy and/or chemotherapy (including targeted agents). We evaluated the association between clinicopathologic features and receipt of systemic therapy using multivariable logistic regression with generalized estimating equations, and assessed the interaction of treatment with time, stratified as immunotherapy (1998-2004) versus targeted-therapy (2005-2010) eras. Results: Of 22,409 patients with mRCC undergoing CN, 8,830 (39%) received systemic therapy. Receipt of systemic therapy increased from 32% in 1998 to 49% in 2010 (p<0.001), largely due to increased utilization of chemotherapy (13.9% vs. 46.7%; p<0.001). Following adjustment, increasing patient age (51-60 years: OR 0.82 [CI 0.73-0.92]; 61-70 years: OR 0.67 [CI 0.59-0.76]; ≥71 years: OR 0.36 [CI 0.31-0.43]), as well as coverage with Medicaid (OR 0.61 [CI 0.5-0.74]), Medicare (OR 0.70 [CI 0.62-0.79]), or no insurance (OR 0.75 [CI 0.63-0.91]) were associated with decreased utilization of systemic therapy. Although use of systemic therapy in the elderly (≥71 years) and in patients with Medicare/Medicaid remained lower throughout the study period, each of these cohorts was significantly more likely to receive systemic treatment in the targeted versus immunotherapy era (all p values <0.05). Conclusions: Utilization of systemic therapy among patients undergoing CN has increased over time, coinciding with the introduction of targeted therapies. Nevertheless, still less than half of such patients receive systemic treatment. While the etiology for lack of treatment is likely multifactorial, the potential health policy implications of continued disparities in care warrant further investigation.

scholarly journals Chemotherapy for pulmonary large cell neuroendocrine carcinomas: does the regimen matter?

2017 ◽  
Vol 49 (6) ◽  
pp. 1601838 ◽  
Author(s):  
Jules L. Derks ◽  
Robert Jan van Suylen ◽  
Erik Thunnissen ◽  
Michael A. den Bakker ◽  
Harry J. Groen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Stage Iv ◽  
Large Cell ◽  
Hazard Ratio ◽  
Cell Lung Carcinoma ◽  
Netherlands Cancer Registry ◽  
Panel Review

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC.The Netherlands Cancer Registry and Netherlands Pathology Registry (PALGA) were searched for patients with stage IV chemotherapy-treated LCNEC (2003–2012). For 207 patients, histology slides were available for pathology panel review. First-line platinum-based combined chemotherapy was clustered as “NSCLC-t”, comprising gemcitabine, docetaxel, paclitaxel or vinorelbine; “NSCLC-pt”, with pemetrexed treatment only; and “SCLC-t”, consisting of etoposide chemotherapy.A panel review diagnosis of LCNEC was established in 128 out of 207 patients. NSCLC-t chemotherapy was administered in 46% (n=60), NSCLC-pt in 16% (n=20) and SCLC-t in 38% (n=48) of the patients. The median (95% CI) overall survival for NSCLC-t chemotherapy was 8.5 (7.0–9.9) months, significantly longer than patients treated with NSCLC-pt, with a median survival of 5.9 (5.0–6.9) months (hazard ratio 2.51, 95% CI 1.39–4.52; p=0.002) and patients treated with SCLC-t chemotherapy, with a median survival of 6.7 (5.0–8.5) months (hazard ratio 1.66, 95% CI 1.08–2.56; p=0.020).In patients with LCNEC, NSCLC-t chemotherapy results in longer overall survival compared to NSCLC-pt and SCLC-t chemotherapy.

Elevated levels of thioredoxin (Trx) in serum correlate with poor outcome in docetaxel (doc)/cisplatin (cis)-treated stage IV non-small cell lung cancer (NSCLC) patients (p)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7628-7628
Author(s):  
M. Molina ◽  
C. Camps ◽  
R. de las Peñas ◽  
G. Alonso ◽  
G. Lopez-Vivanco ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Cell Cycle Control ◽  
Methylation Status ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Negative Regulator ◽  
Baseline Serum ◽  
Specific Pcr ◽  
Cancer Cell Death

7628 Background: Chemotherapy causes the production of reactive oxygen species (ROS), which facilitates cancer cell death. Trx protein functions as a ROS scavenger and a negative regulator of apoptosis signal regulating kinase-1 (ASK-1). High levels of Trx are associated with chemoresistance. 14–3-3s proteins are involved in cell cycle control and protein trafficking. Methods: Trx ELISA and 14- 3–3s methylation-specific PCR were performed in baseline serum from 107 stage IV NSCLC p treated with doc/cis. Results: Median age, 60 (range, 32–79); male, 87 (81.3%). PS: 0, 27 (25.2%); 1, 80 (74.8%). Adenocarcinoma, 46 (43.8%); squamous cell carcinoma, 40 (38.1%); 21 p had large cell or unspecified histology. Complete response, 1 p; partial response, 20 p; overall response rate, 20%. Median Trx level, 97.4 (range, 18.8–763.1). Serum was available for 14–3-3s methylation analysis in only 88 p. 14–3-3s was methylated in 43 p (48.9%). A significant correlation was observed between 14–3-3s methylation status and Trx levels ( Table ). 4 p with methylated and 17 with unmethylated 14–3-3s had Trx levels >182.8 (P=0.003). Median Trx levels were 103.5 in responders and 94.3 in non-responders (P=0.96). Time to progression (TTP) was 5.6 months (m) for 27 p with Trx <49.6, 4.4 m for 53 p with Trx 49.6–182.8, and 3.8 m for 27 p with Trx >182.8 (P=0.02). In a Cox multivariate analysis, Trx levels emerged as an independent variable for TTP when 14–3-3s was included in the model. Hazard ratios: 1.3 for PS1 (P=0.84); 1.05 for 14–3-3s unmethylated (P=0.22); 1.4 for Trx 49.6–182.8 and 1.95 for Trx >182.8 (P=0.04). Conclusions: Serum Trx levels can predict TTP in doc/cis-treated p. The additional role of 14–3-3s methylation may be more clearly demonstrated in cis/gemcitabine regimens. No significant financial relationships to disclose. [Table: see text]

Genetic subtypes of large cell neuroendocrine carcinoma (LCNEC) to predict response to chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9061-9061 ◽  
Author(s):  
Jules Derks ◽  
Noémie Leblay ◽  
Robert Jan van Suylen ◽  
Erik Thunnissen ◽  
Michael den Bakker ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Netherlands Cancer Registry ◽  
Response To Chemotherapy

9061 Background: To treat LCNEC with non-small cell lung carcinoma type chemotherapy (NSCLC-ct, i.e. gemcitabine/taxanes or pemetrexed) or small cell lung carcinoma type (SCLC-ct, i.e. platinum-etoposide) is subject of debate. Molecular studies have identified two mutually exclusive subtypes in LCNEC, the co-mutated TP53 and RB1and the STK11/ KEAP1 (predominantly RB1 wildtype(wt)) group. We investigated if overall survival (OS) and progression free survival (PFS) correlates with targeted next-generation sequencing (TNGS) results in LCNEC treated with NSCLC-ct or SCLC-ct. Methods: For this population based retrospective cohort study all diagnoses of stage IV ct treated high grade neuroendocrine carcinomas (NEC, not being SCLC) were retrieved from the Netherlands Cancer Registry and Pathology Registry (PALGA) (2003-2012). Panel-consensus pathology revision of original tumor slides was performed on (N = 230) and TNGS for genes TP53, RB1, STK11 and KEAP1 analyzed with a multi-sample variant caller (Needlestack). Results: LCNEC was consensus diagnosed in 146/230 and 77 passed quality control for TNGS. Mean coverage was 2832x, a mutation(mt) in TP53 was present in 87%, RB1mt in 46%, STK11mt in 13% and KEAP1mt in 18% of sequenced LCNEC. RB1 was co-altered with TP53 in 94% of LCNEC; mutually exclusive to STK11mt (100%) but not KEAP1mt (57%). NSCLC-ct or SCLC-ct was specified in 92% of patients and RB1wt LCNEC treated with NSCLC-ct (n = 22) showed a trend to better OS compared to SCLC-ct (n = 13) (8.5 months (95% confidence interval (CI): [6.3-10.6]) vs. 5.8 [5.5-6.1] months, p = 0.055). Due to reported resistance in NECs we analyzed NSCLC-ct without pemetrexed-ct; OS was significantly longer for NSCLC-ct (n = 15) compared to SCLC-ct (9.6 [7.7-11.6] vs. 5.8 [5.5-6.1] months, p = 0.026). PFS of RB1wt NSCLC-ct treated patients was significantly longer than SCLC-ct (p = 0.044), without pemetrexed (p = 0.018). In patients with RB1mt LCNEC OS/PFS was not significantly different for NSCLC-ct vs. SCLC-ct. Conclusions: In LCNEC with RB1wt, NSCLC-ct correlates with a more favorable outcome compared to SCLC-ct. However, RB1mt LCNEC treated with NSCLC-ct do similarly worse as SCLC-ct. Prospective studies should be initiated.

14–3-3 σ and checkpoint with forkhead and ring finger (CHFR) methylation in serum in erlotinib-treated non-small-cell lung cancer (NSCLC) patients (p) with EGFR mutations

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7600-7600
Author(s):  
N. Reguart ◽  
R. Porta ◽  
M. Provencio ◽  
F. Cardenal ◽  
M. Cuello ◽  
...  
Keyword(s):  
Methylation Status ◽  
Ring Finger ◽  
Stage Iv ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Complete Response ◽  
Egfr Mutations ◽  
Second Line ◽  
Baseline Serum ◽  
Mutant Egfr

7600 Background: 14–3-3 proteins have 130 potential binding partners, including Cbl. 14–3-3 expression can prevent mutant EGFR binding to Cbl, impairing ubiquitination and endocytosis. 14–3-3s is frequently methylated in NSCLC; we hypothesized that in the presence of EGFR mutations, methylated 14–3-3s could permit the formation of the EGFR-Cbl complex. CHFR is a checkpoint that delays entry into metaphase in response to mitotic stress. Methods: 73 stage IV NSCLC p with EGFR exon 19 deletion or exon 21 L858R mutation received first- or second-line erlotinib single therapy. 14–3-3s and CHFR methylation was examined in the baseline serum of these p. Results: Median age, 63 (range, 26–83); females, 48 p (65.8%); Caucasian, 72 p, Asian, 1 p; never-smokers, 45 p, ex-smokers, 21 p, smokers, 7 p; adenocarcinoma, 64 p, large cell carcinoma, 9. PS: 0, 19 p, 1, 42 p, 2–3, 12 p. 14–3-3s was methylated in 39.7% and CHFR in 42.5% of p. No differences in p characteristics were observed according to methylation status. Complete response was observed in 11.1% of p, and partial response in 75.4%. Overall response was 86.5%. There was a trend toward a higher response rate in p with unmethylated CHFR (94.4% vs 76.6%; P=ns). Overall median time to progression (TTP) and survival (MS) have not been reached either in first- or second-line. However, when split according to methylation status, there was a trend toward better TTP and MS in both first- and second-line in p with methylated 14–3-3s. TTP in second-line in p with methylated 14–3-3s has not been reached, while it was 10.8 months (m) for p with unmethylated 14–3-3s (P=ns). TTP in second-line in p with methylated CHFR was 5.2 m but was not reached for p with unmethylated CHFR (P=0.05). Conclusions: Methylated 14–3-3s can permit Cbl binding to mutant EGFR and predict longer-lasting response to erlotinib in p with EGFR mutations. The precise role of CHFR warrants further research. Complete data will be presented. No significant financial relationships to disclose.

Double-blind randomized phase II trial of carboplatin and pemetrexed with or without OGX-427 in patients with previously untreated stage IV non-squamous non-small-cell lung cancer (NSCLC): The Spruce Clinical Trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS8120-TPS8120
Author(s):  
David R. Spigel ◽  
Howard A. Burris ◽  
F Anthony Greco ◽  
John D. Hainsworth
Keyword(s):  
Phase Ii ◽  
Smoking Status ◽  
Stage Iv ◽  
Treatment Resistance ◽  
Progression Free Survival ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Randomized Phase Ii

TPS8120 Background: OGXE427 is an antisense oligonucleotide (ASO) designed to bind to Hsp27 (heat shock protein 27) mRNA, resulting in the inhibition of production of Hsp27 protein. Hsp27 is over-expressed in many cancers including lung, prostate, breast, and bladder. Increased expression has been associated with inhibition of chemotherapy-induced apoptosis, increased tumor cytoprotection, and the development of treatment resistance. OGX-427 is an inhibitor of Hsp27 that effectively targets and down-regulates Hsp27 mRNA and has been shown to increase apoptosis, inhibit tumor growth, and sensitize cells to various chemotherapy regimens in a variety of malignancies. Based on this preclinical data, addition of an Hsp27 inhibitor to standard chemotherapy may improve the efficacy of treatment. In this randomized phase II study, OGX-427 will be added to a standard carboplatin/pemetrexed regimen, with the goal of improving progression-free survival when compared to carboplatin and pemetrexed alone in the first-line treatment of non-squamous NSCLC patients. Methods: A total of 155 patients will be randomized in a 1:1 ratio. Randomization will be stratified by histology (adenocarcinoma vs. large cell carcinoma) and smoking status (smoker vs. non-smoker). Treatment will include a loading dose period with OGX-427 600 mg or placebo. On day one of each 21 day cycle, patients will receive OGX-427 1000 mg or placebo, pemetrexed 500 mg/m2, and carboplatin AUC 6, all administered IV. On days 8 and 15, OGX-427 or placebo will also be administered. Key eligibility criteria include; untreated recurrent or stage IV predominantly non- squamous NSCLC, measureable disease by RECIST v 1.1, ECOG PS 0 or 1, adequate organ function, and no known CNS disease. Serum Hsp27 levels will be assessed at screening, baseline and during treatment. In addition, archival tissues will be collected and assessed for PTEN (protein expression by IHC) and a panel of gene mutations for correlative analyses.

Peripheral T-cell repertoire alterations are common and affect outcome in large cell neuroendocrine lung carcinoma

Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S53-S54
Author(s):  
P Christopoulos ◽  
M Schneider ◽  
F Bozorgmehr ◽  
W Engel-Riedel ◽  
C Kropf-Sanchen ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Carcinoma ◽  
Large Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire

Increased Prevalence, Complications, and Costs of Smokers Undergoing Total Knee Arthroplasty

2020 ◽  
Author(s):  
Sean S. Rajaee ◽  
Eytan M. Debbi ◽  
Guy D. Paiement ◽  
Andrew I. Spitzer
Keyword(s):  
Total Knee Arthroplasty ◽  
Knee Arthroplasty ◽  
Smoking Status ◽  
Hospital Costs ◽  
Patient Characteristics ◽  
The United States ◽  
Bundled Payment ◽  
Vein Thrombosis ◽  
Total Knee ◽  
Payment Models

AbstractGiven a national push toward bundled payment models, the purpose of this study was to examine the prevalence as well as the effect of smoking on early inpatient complications and cost following elective total knee arthroplasty (TKA) in the United States across multiple years. Using the nationwide inpatient sample, all primary elective TKA admissions were identified from 2012 to 2014. Patients were stratified by smoking status through a secondary diagnosis of “tobacco use disorder.” Patient characteristics as well as prevalence, costs, and incidence of complications were compared. There was a significant increase in the rate of smoking in TKA from 17.9% in 2012 to 19.2% in 2014 (p < 0.0001). The highest rate was seen in patients < 45 years of age (27.3%). Hospital resource usage was significantly higher for smokers, with a length of stay of 3.3 versus 2.9 days (p < 0.0001), and hospital costs of $16,752 versus $15,653 (p < 0.0001). A multivariable logistic model adjusting for age, gender, and comorbidities showed that smokers had an increased odds ratio for myocardial infarction (5.72), cardiac arrest (4.59), stroke (4.42), inpatient mortality (4.21), pneumonia (4.01), acute renal failure (2.95), deep vein thrombosis (2.74), urinary tract infection (2.43), transfusion (1.38) and sepsis (0.65) (all p < 0.0001). Smoking is common among patients undergoing elective TKA, and its prevalence continues to rise. Smoking is associated with higher hospital costs as well as higher rates of immediate inpatient complications. These findings are critical for risk stratification, improving of bundled payment models as well as patient education, and optimization prior to surgery to reduce costs and complications.

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