Analysis of nerve growth factor (NGF) blood levels in patients with advanced non-small cell lung cancer patients (NSCLC): Its correlation with clinical outcome

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17025-17025
Author(s):  
A. Blasco ◽  
R. Sirera ◽  
C. Camps ◽  
V. Giner ◽  
L. Llobat ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Advanced Nsclc ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Response To Therapy ◽  
Blood Levels ◽  
Dependent Manner ◽  
Lung Cancer Patients ◽  
Response Site

17025 Background: Platinum compounds and taxanes have severe side effects in a dose and time-dependent manner, especially neurotoxicity. NGF plays an important role in growth and differentiation of neuronal components. Our goal was to study NGF levels in plasma and correlate it with patient’s clinico-pathologic characteristics. Methods: The study was performed with 451 patients with advanced NSCLC, stages IIIB-IV and treated with cisplatin and docetaxel. Peripheral blood was collected before therapy. NGF were assessed by commercial ELISA (detection limit, 5 pg/ml). Plasma from 32 age and gender-matched controls was used. Results: 91% of males, mean age 61 y [35–82]. 86 patients in ECOG PS 0–1 and 14 PS2. 71% in stage IV and 29% in IIIB. The histological subtypes were 38% squamous cell, 37% adenocarcinoma, 5% anaplasic large cell and 20% undifferentiated. 77.5% of the metastasis was out of the lung. Patients received a median of 6 cycles of chemotherapy [1–7]. 4% presented complete response (CR), 38% partial response (PR), 25% stable disease (SD) and 30% progressive disease (PD). Patient’s median plasma levels of NGF did not differ significantly from controls: 44 pg/ml [6–176] vs 31 pg/ml [14–144] respectively. There were not differences according to histology, site of metastasis and ECOG; however we could observe significant differences with stage: 25 pg/ml [10–70] in stage IIIB vs 47 pg/ml [6–176] in stage IV (p = 0.008). We could not observe any differences in response to therapy: CR+PR patients presented median NGF of 35 pg/ml [6–92] vs 39 pg/ml [10–165] in the SD+PD group. Splitting the cohort according to NGF median we found two significantly different groups in terms of Overall Survival (OS): patients with NGF <44 pg/ml had a median OS of 10.9 months (m) [7.9–13.9] vs 7.3 m [3–11.5] for patients with NGF >44 pg/ml (p = 0.03). In the multivariate analysis, NGF levels was not predictor for time to progression (TTP) and OS. Conclusions: NGF plasma levels did not differ in patients and controls. In our cohort with advanced NSCLC we have not found any relationship between NGF levels with histology, response, site of metastasis and TTP. By contrast NGF levels are higher in those patients in stage IV and in those presenting poorer OS. No significant financial relationships to disclose.

The quantification of the catalytic subunit of telomerase in plasma is a prognostic factor in advanced non-small cell lung cancer (NSCLC) patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7052-7052
Author(s):  
R. Sirera ◽  
C. Camps ◽  
L. Llobat ◽  
A. Berrocal ◽  
R. M. Bremnes ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Response To Therapy ◽  
Catalytic Subunit ◽  
Stage Iiib ◽  
Circulating Dna ◽  
Nsclc Patients

7052 Background: Qualitative and quantitative analysis of circulating DNA in blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the free amount in plasma of the catalytic subunit of telomerase (hTERT) and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the serum using commercial adsorption columns. The amount of free hTERT in plasma was quantified by using RT-PCR. Results: Median age was 61 years [35–82] and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Median hTERT value was 4856 ng/ml; for patients in IIIB was 4847 ng/ml [263–964826] and 4886 ng/ml [67–4373520] in stage IV (p = 0.75). There was not association between hTERT values and response to therapy, 20588 ng/ml [122–317251] in the CR+PR group vs 50204 ng/ml [67–4373520] in the SD+PD group (p = 0.09). hTERT values were not related with the localization of the metastasis. Dividing the cohort in two sets according to hTERT median we found two significantly different groups in terms of Overall Survival (OS) and Time To Progression (TTP). Patients with hTERT <4856 ng/ml had a median TTP of 5.3 months (m) [4.4–6.1] while for hTERT >4856 ng/ml was 4.1 m [3.5–4.6], (p = 0.0009). OS when hTERT <4856 ng/ml was 10.1m [4.9–11.3] and for hTERT >4856 ng/ml was 8.4 m [7.2–9.5], (p = 0.01). In the multivariate analysis, hTERT was an independent predictive variable for TTP (HR 1.39, CI 95% 1.1–1.7, p = 0.002) and OS (HR 1.27, CI 95% 1.1–1.6, p = 0.04). Conclusions: In advanced NSCLC patients, the quantification of free circulating hTERT in plasma is an affordable and valuable prognostic marker. High plasma hTERT levels are a poor prognostic indicator for TTP and OS. No significant financial relationships to disclose.

Prognostic value of blood levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in advanced non-small cell lung cancer (NSCLC) patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7196-7196
Author(s):  
V. Alberola ◽  
C. Camps ◽  
R. Sirera ◽  
L. Llobat ◽  
A. Blasco ◽  
...  
Keyword(s):  
Growth Factor ◽  
Plasma Levels ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Prognostic Significance ◽  
Stage Iv ◽  
Angiogenic Factors ◽  
Response To Therapy ◽  
Stage Iiib ◽  
Blood Levels

7196 Background: VEGF and bFGF are among the most important angiogenic factors. We have explored these angiogenesis mediators in plasma and its prognostic significance in advanced NSCLC. Methods: Were enrolled 451 patients with advanced NSCLC, stages IIIB and IV and treated with cisplatin and docetaxel. Blood was collected before chemotherapy. Plasma VEGF and bFGF levels were assessed by commercial ELISA (sensitivity 5 pg/ml). In parallel plasma from 32 age and gender-matched controls was used. Results: Median age was 61 years (35–82) and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Patient’s median plasma levels of VEGF (20 pg/ml, [6–203]) differ significantly (p = 0.04) from controls (14 pg/ml, [7–53]), but in contrast bFGF levels were not different, 14 pg/ml [5–960] vs 10 pg/ml [6–278] respectively. There were not differences in patients according to histology, site of metastasis and ECOG; however we could observe a tendency with stage for both factors: bFGF 9 pg/ml [5–24] in stage IIIB vs 15 pg/ml [6–960], p = 0.071 and VEGF 17 pg/ml [6–145] in IIIB vs 21 pg/ml [6–203] in IV, p = 0.086. It could not be observed any differences in response to therapy for both angiogenic factors; CR+PR patients presented median VEGF of 18 pg/ml [6–71] and bFGF 11 pg/ml [6–960] vs 20 pg/ml of VEGF [6–203] and 15 pg/ml of bFGF [5–395] in the SD+PD group. In the multivariate analysis we could not find that VEGF and bFGF plasma levels were predictors for time to progression (TTP) and overall survival (OS). Conclusions: VEGF but not bFGF levels in patients are significantly higher in patients than in controls. In our cohort of patients with advanced NSCLC we have not found any relationship between serum VEGF and bFGF levels with stage, histology, response, site of metastasis, TTP and OS. No significant financial relationships to disclose.

The quantification of epidermal growth factor receptor (EGFR) in plasma is a prognostic factor in advanced non-small cell lung cancer (NSCLC) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7597-7597
Author(s):  
C. Camps ◽  
R. Sirera ◽  
M. Muñoz-Navarro ◽  
G. Lopez-Vivanco ◽  
G. Alonso ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Complete Response ◽  
Binding Domain ◽  
Response To Therapy ◽  
First Line Therapy ◽  
Lower Egfr ◽  
Epidermal Growth ◽  
Nsclc Patients

7597 Background: EGFR has an extracellular ligand-binding domain that can be proteolitically cleaved from the cell surface and can be accurately quantified in blood by ELISA. We have investigated the usefulness of plasma EGFR measurements as prognostic marker in advanced NSCLC. Methods: The cohort consisted in 329 patients (p) with advanced NSCLC that received first-line therapy with cisplatin and docetaxel. The concentration levels of the EGFR extracellular binding domain were determined by a sandwich quantitative ELISA in the baseline, before therapy. Results: Median age was 61, range [39–80], 84% males, 100% caucasian, 68% stage IIIB and 32% IV and 99% PS 0–1. The histological subtypes were: 31% squamous cell carcinoma, 49% adenocarcinoma, 15% large cell, and 5% undifferentiated. 181 p achieved complete response (CR), partial response (PR) or stable disease (SD) and 109 p progressive disease (PD). Median patient's plasma levels of EGFR were 32.4 ng/ml. There were not differences in p according to histology, site of metastasis and ECOG. There were differences in response to therapy; CR+PR+SD p presented median EGFR of 31.97 ng/ml [13.2–48.6] vs 30 ng/ml [16.9–46.8] in the PD group (p=0.024). Dividing the cohort in two sets according to EGFR median we found two significantly different groups in terms of Overall Survival (OS) and Time To Progression (TTP). Patients with EGFR<32.4 ng/ml had a median TTP of 3.9 months (m) [3.3–4.6] while for EGFR>32.4 ng/ml was 4.7 m [4.0–5.4], (p=0.024). OS when EGFR<32.4 ng/ml was 6.9 m [5.9–7.8] and for EGFR>32.4 ng/ml was 9.1 m [8.2–10.1], (p=0.038). Conclusions: Patients with PD presented significantly lower levels of serum EGFR than those patients with CR+PR+SD. There is a relationship among lower EGFR concentration in serum with a worst prognosis in advanced NSCLC p in terms of TTP and OS. No significant financial relationships to disclose.

scholarly journals Complete Response of a Colonic High-Grade Neuroendocrine Carcinoma to Platinum-Based Therapy: Insights from Comprehensive Genomic Profiling

2021 ◽  
Author(s):  
Richard Wood ◽  
Daniel Rayson ◽  
Thomas Arnason ◽  
Ryan C DeCoste ◽  
Daniel Gaston ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Response To Therapy ◽  
Hereditary Cancer Syndrome ◽  
Genomic Profiling ◽  
Cancer Syndrome ◽  
Optimal Care ◽  
Comprehensive Genomic Profiling

Abstract Background Comprehensive genomic profiling (CGP) is an essential tool in precision medicine, providing diagnostic, prognostic, and predictive (therapeutic) information that enables personalized optimal care for cancer patients. We present the case of a 54-year-old woman with stage IV large-cell neuroendocrine carcinoma (LCNEC) of the colon with liver and nodal metastases with complete response to therapy and demonstrate the value of CGP in identifying potential targets for treatment in these tumors. Results CGP performed on the tumor showed pathogenic mutations in multiple oncogenes and tumor suppressor genes including BRCA1, BAP1, and BRAF, high tumor mutation burden (TMB), and high microsatellite instability (MSI-H). Treatment with platinum-based therapy resulted in a complete radiographic response of the metastases, with no evidence of recurrence after 6.5 years. Assessment by Medical Genetics did not identify any evidence of hereditary cancer syndrome. The dramatic response to therapy is likely due to loss of BRCA1 and/or BAP1 function, as deleterious mutations in both genes predict response to platinum-based therapy through exploitation of deficient homologous recombination repair (HRR). The information provided by CGP also suggested potential tumor sensitivity to poly(ADP-Ribose) polymerase inhibitors (PARPi), immunotherapy (IT) and BRAF/MEK inhibitor therapy, should the tumor recur. Conclusion This case highlights the value of CGP in guiding diagnosis and management of rare and aggressive tumors.

scholarly journals Complete response of a colonic high-grade neuroendocrine carcinoma to platinum-based therapy: Insights from comprehensive genomic profiling

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S143-S143
Author(s):  
R Wood ◽  
T Arnason ◽  
R DeCoste ◽  
D Gaston ◽  
M D Carter ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Systemic Therapy ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Response To Therapy ◽  
Genomic Profiling ◽  
High Grade ◽  
Cancer Management ◽  
Comprehensive Genomic Profiling

Abstract Introduction/Objective Comprehensive genomic profiling (CGP) is an essential tool in precision medicine, providing diagnostic, prognostic, and predictive (therapeutic) information to enable personalized and optimized care for cancer patients. We present the case of a patient with a metastatic high-grade tumor of the colon who showed an impressive response to systemic therapy and discuss the role of CGP in cancer management. Methods/Case Report A 54-year-old woman with was diagnosed with stage IV large-cell neuroendocrine carcinoma (LCNEC) of the colon with large volume liver and nodal metastases with imminent hepatic failure. CGP was performed on the resected tumor (TSO500 panel, 523 cancer-related genes, Illumina), showing pathogenic mutations in multiple oncogenes and tumor suppressor genes, including BRCA1, BAP1, and BRAF. Additionally, global parameters revealed a very high tumor mutation burden (TMB, 351 / Mb), and high-degree microsatellite instability (MSI-H). Treatment of the patient’s metastases with platinum-based systemic therapy resulted in a complete radiographic response, with no evidence of disease recurrence after 6.5 years. This type of complete response to therapy is rarely reported in colonic LCNEC. Assessment by Medical Genetics did not identify a germline mutation suggestive of hereditary breast/ovarian cancer or Lynch syndrome. Results (if a Case Study enter NA) NA Conclusion The patient’s extraordinary response to therapy is likely due to loss of BRCA1 and/or BAP1 function, as deleterious mutations in both genes predict sensitivity to platinum-based therapy through exploitation of deficient homologous recombination repair (HRR). The high TMB and MSI-H status suggest the immune system may have contributed to tumor clearance through neoantigen activation of T-cells. The information provided by CGP also suggested potential tumor sensitivity to poly(ADP-Ribose) polymerase inhibitors (PARPi), immunotherapy (IT), and BRAF/MEK inhibitor therapy, should the tumor recur. This case highlights the value of CGP in guiding management of rare and aggressive tumors.

T-cell lymphomas: immunologic, histologic, clinical, and therapeutic analysis of 63 cases.

1988 ◽  
Vol 6 (10) ◽  
pp. 1584-1589 ◽  
Author(s):  
B Coiffier ◽  
F Berger ◽  
P A Bryon ◽  
J P Magaud
Keyword(s):  
T Cell ◽  
Clinical Presentation ◽  
Performance Status ◽  
Stage Iv ◽  
Poor Performance ◽  
Large Cell ◽  
Response To Therapy ◽  
Poor Performance Status ◽  
T Cell Lymphomas ◽  
Stage Iv Disease

Sixty-three patients with T-cell lymphoma (TCL) were analyzed to correlate morphological and immunological features with clinical presentation, response to therapy, and survival. Clinical presentation was severe, with 59% of patients having stage IV disease, 60% B symptoms, 35% poor performance status, 44% large tumoral mass, and 40% a high number of extranodal localizations. Morphological subtypes were small-cell in four cases, diffuse-mixed in 29 cases, monomorphic medium-sized in two cases, immunoblastic in 21 cases, anaplastic large-cell in four cases, and unclassified in three cases. Immunological phenotypes were immature T in 11 cases, CD4 in 26 cases, CD8 in 13 cases, and undefined (CD4 + CD8) in ten cases. Response to therapy was poor except for the 39 patients treated by an intensive and sequential regimen (non-Hodgkin's lymphoma [LNH]-80 or LNH-84) that gave a 77% complete remission (CR) rate with a 23% relapse rate. Median survival was 35 months. No correlation was found between morphological subtypes and other variables. Helper (CD4) phenotype seemed to have a better prognosis than other phenotypes. Variables associated with long survival for all the patients were localized disease and absence of large tumoral mass and for the subgroup of patients treated by the LNH regimens CD4 phenotype, absence of B symptoms, absence of a large tumoral mass, and less than two extranodal sites of disease.

Extended administration of oral etoposide and oral cyclophosphamide for the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study.

1993 ◽  
Vol 11 (8) ◽  
pp. 1598-1601 ◽  
Author(s):  
S M Grunberg ◽  
J Crowley ◽  
R Livingston ◽  
I Gill ◽  
S K Williamson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Complete Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Southwest Oncology Group Study ◽  
The Mean

PURPOSE We designed an all-oral regimen of etoposide and cyclophosphamide for use in advanced non-small-cell lung cancer. PATIENTS AND METHODS Eligible patients were chemotherapy-naive and had histologically confirmed assessable or measurable stage IV non-small-cell lung cancer. Patients received etoposide 50 mg/m2/d orally days 1 through 14 and cyclophosphamide 50 mg/m2/d orally days 1 through 14 every 28 days. Doses on later cycles were adjusted for myelosuppression. RESULTS Sixty-six patients (64 eligible patients) received 192 cycles of oral extended etoposide/cyclophosphamide therapy (median, two cycles; range, zero to 15). Therapy was well tolerated with the mean dose per cycle being 104% of the originally scheduled dose. Two patients (3%) achieved a complete response and six (9%) achieved a partial response. Leukopenia, anemia, nausea/vomiting, and alopecia were the most common toxicities. Median survival was 6 months, and the 1-year survival rate was 25.6%, comparable to more intensive treatments. CONCLUSION Oral extended etoposide/cyclophosphamide is a well-tolerated alternative for the treatment of stage IV non-small-cell lung cancer and can be used as a basis for the design of further outpatient regimens.

Small noncleaved cell lymphoma in adults: superior results for stages I-III disease.

1990 ◽  
Vol 8 (4) ◽  
pp. 615-622 ◽  
Author(s):  
T M Lopez ◽  
F B Hagemeister ◽  
P McLaughlin ◽  
W S Velasquez ◽  
F Swan ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Stage Iv ◽  
Complete Response ◽  
Burkitt’S Lymphoma ◽  
Response To Therapy ◽  
Burkitt's Lymphoma ◽  
Disease Stage ◽  
Histologic Subtype ◽  
Ann Arbor ◽  
Stage Iv Disease

Small noncleaved cell lymphoma (SNCCL), a rare lymphoma in adults, is associated with not only a rapid complete response (CR) to chemotherapy but also with the potential to rapidly relapse both systemically and in the CNS. We treated 44 assessable adults with two similar protocols, consisting of three sequential chemotherapy combinations and intrathecal prophylaxis with methotrexate and cytarabine. The overall CR rate was 80%; it was 100% in patients with Ann Arbor (AA) stages I-III disease and 57% in those with stage IV disease. The overall survival (OS) rate at 5 years was 52%. The overall 5-year freedom from tumor mortality (FTM) rate was 63%; it was 95% for patients with AA stages I-III disease, and 29% for those with stage IV disease. Stepwise multivariate analysis of factors associated with remission duration and survival indicated that advanced-disease stage and age of 40 years or over were predictors of poor prognosis. Twelve patients with positive human immunodeficiency virus (HIV) serology were also included in this series. They had an 83% CR rate and an 83% 5-year FTM, but only a 36% 5-year OS; most deaths were secondary to opportunistic infection. Histologic subtype (Burkitt's lymphoma [BL] or non-Burkitt's lymphoma [NBL]) did not correlate with patient age, site of tumor presentation, response to therapy, or survival. Both protocols achieved comparable results. The approach used in these protocols is highly effective for patients with early staged disease, regardless of their HIV status; however, better therapy is necessary for those with SNCCL presenting in an advanced stage.

Observing patients with advanced non-small cell lung cancer (NSCLC): An overview of real world treatments and outcomes in Europe

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7626-7626
Author(s):  
H. G. Bischoff ◽  
H. Anderson ◽  
B. van den Borne ◽  
F. Langer ◽  
M. I. Leschinger ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Observational Study ◽  
Large Scale ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Complete Response ◽  
First Line ◽  
Best Response ◽  
Clinical Trial Results

7626 Background: ACTION (Assessment of Costs and ouTcomes of chemotherapy In an Observational setting in patients with advanced NSCLC) is a prospective, pan-European observational study. The objective of ACTION is to describe advanced NSCLC treatment in routine clinical practice. Methods: Chemonaive patients (pts) aged = 18 yrs with stage IIIb/IV NSCLC were observed for 18 months from presentation for initiation of chemotherapy (CT). All pt care, including CT given, was at the discretion of the pt/physician. Pts were excluded if participating in a clinical trial. Results: 975 pts [Germany (571), UK (193), Finland (99), Netherlands (76), Portugal (36)] were enrolled from April 2003 to September 2004 and observations completed June 2006. Median age was 65 yrs (32–90) with 28.3% of pts aged =70 yrs; 71.3% were male; 65.2% had stage IV disease. WHO performance status (PS) was 0/1 (86.2%), 2 (10.0%), 3/4 (3.8%). Of 487 pts who experienced weight loss, 172 (33.4%) lost >10% body weight in 4 weeks prior to start of CT. First-line CT given: gemcitabine (gem) 10.3%, vinorelbine (vin) 4.3%, gem+platinum 45.0%, vin+platinum 14.6%, taxane+platinum 11.7%, other 14.2%. Complete response (CR) to first-line CT was observed in 1.8% of pts, partial response (PR) 37.9%, stable disease (SD) 28.5%, progressive disease (PD) 17.8%, unknown 13.8%. Second-line CT was planned for 29.2% (285) pts. Median time from initiation of 1st-line to initiation of 2nd-line CT was 5.8 months. Median age was 62 yrs (32–84); 69.8% were male; WHO PS at initiation of 2nd line CT: 0/1 (79%), 2 (17%), 3/4 (4%). Best response to 2nd-line CT: CR 0.4%, PR 9.1%, SD 19.3%, PD 48.8%, unknown 14.3%. Unadjusted median survival time for all pts: 9.3 months (95% CI 8.6–10.3). Overall estimated 1-yr survival was 39.5%. Conclusions: ACTION was the first large-scale observational study in pts with advanced NSCLC in Europe. Overall response rates and survival were consistent with clinical trial results, even though approximately one- third of pts enrolled may have been excluded from clinical trials on the basis of their baseline demographics. No significant financial relationships to disclose.

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