Copper transporter CTR1 expression and tissue platinum concentration in NSCLC.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2601-2601
Author(s):  
Deepak Kilari ◽  
XiMing Tang ◽  
Chi-Wan Chow ◽  
Junya Fujimoto ◽  
Neda Kalhor ◽  
...  
Keyword(s):  
Tumor Response ◽  
Causative Factor ◽  
Cancer Center ◽  
Nsclc Tissue ◽  
Copper Transporter ◽  
Md Anderson ◽  
Nsclc Patients ◽  
The Relationship ◽  
Larger Sample ◽  
Expression Score

2601 Background: Platinum (Pt) resistance is a major limitation in the treatment of advanced non-small cell lung cancer (NSCLC). We previously demonstrated that low tissue Pt concentration in NSCLC tumor specimens was significantly associated with reduced tumor response and worse survival. Furthermore, low expression of the copper transporter CTR1, a transporter of Pt uptake is reported to be associated with poor clinical outcome following Pt-based therapy in NSCLC patients. However, a defect in CTR1expression as a causative factor in reduced Pt accumulation in NSCLC tissues is not well-established. We investigated the relationship between tissue Pt concentrations and CTR1 expression in NSCLC specimens. Methods: We identified paraffin-embedded NSCLC tissue blocks from 30 patients who underwent neoadjuvant Pt-based chemotherapy with known tissue Pt concentrations at MD Anderson Cancer Center. Expression of CTR1 was determined by immunohistochemistry with adequate controls; 0 = undetectable; 1+ = barely detectable staining; 2+ = readily appreciable staining; and 3+ = dark brown staining. Pt concentration was compared between different CTR1 expression groups. Results: Tissue Pt concentration significantly correlated with tumor response in 30 patients who received neoadjuvant Pt-based chemotherapy (P<0.001). There was an uneven distribution of CTR1 expression scores with a majority of specimens demonstrating scores of 2+ (N=15, 50%). There were 2 specimens with no detectable CTR1 expression (score of 0) and 6 patients with a score of 3+. Patients with undetectable CTR1 expression in their tumors had significantly lower Pt concentrations compared to those with scores of 3+ (P=0.014). Furthermore, those with undetectable CTR1 expression had reduced tumor response compared to those with scores of 3+ following Pt-based chemotherapy (P=0.039). Conclusions: To the best of our knowledge, this is the first study to correlate CTR1 expression in clinical specimens to both tumor Pt uptake and response. Patients with undetectable CTR1 expression in their tumors had significantly lower Pt concentration and reduced tumor response. Further evaluation with a larger sample size is required. (Supported by 2012 ASCO Young Investigator Award)

Association of cfDNA androgen receptor amplifications with BRAF alterations in mCRPC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 234-234
Author(s):  
Elisa M. Ledet ◽  
Joshua Schiff ◽  
Patrick Cotogno ◽  
Charlotte Manogue ◽  
Emma M. Ernst ◽  
...  
Keyword(s):  
Point Mutations ◽  
Response To Therapy ◽  
Cancer Center ◽  
Therapeutic Implications ◽  
Heterogenous Group ◽  
Somatic Alterations ◽  
The Common ◽  
The Relationship ◽  
Larger Sample ◽  
Redwood City

234 Background: Cell free DNA (cfDNA) present in plasma of cancer pts can reflect tumoral alterations. Genomic alterations in cfDNA alter prognosis and abiraterone/enzalutamide resistance in mCRPC. The goal of this evaluation was to characterize AR amplifications (Amps) and various somatic point mutations (Muts) detected in mCRPC cfDNA and to relate those changes to other common alterations in the cfDNA landscape. Methods: A heterogenous group of 46 mCRPC patients (pts) with evidence of clinical progression from Tulane Cancer Center underwent cfDNA analysis using Guardant360 test (Guardant Health, Redwood City, CA). This evaluation included full exonic coverage of 70 genes and amplifications in 18 genes. Mutations reported herein include both known pathogenic mutations as well as mutations uncharacterized for functional importance. Results: 69.5% (n = 32) of the mCRPC pts evaluated had an AR alteration. Of the pts with AR alterations, 46.8% (n = 16) had AR Amps, 43.7% (n = 14) had AR Muts, and only 6.25% (n = 2) had both. In this cohort, AR alterations were the most commonly observed aberration. In addition to amplifications, 12 different AR Muts were detected. AR Muts included: T878A (n = 9), H875Y (n = 5), W742C (n = 4), AR L702H (n = 3), and others. To better understand the relationship between AR alteration and other commonly detected cfDNA aberrations, association between BRAF (35.5%), TP53 (46.7%), and MYC (22.2%) alterations and AR were assessed. Among these genes, TP53 alterations were all Muts and MYC alterations were all Amps. BRAF alterations were predominantly Amps (N = 15) though Muts were also detected (N = 6). Neither TP53 Muts or MYC Amps were significantly associated with AR alterations. On the other hand, BRAF alterations were significantly associated with AR Amps (p = 0.041); 60% (9/15) pts with AR Amps also had BRAF alteration (Odds ratio = 7.71, 95% CI 1.284- 46.366). Conclusions: AR alterations in cfDNA impact both disease progression and response to therapy. Co-segregation of AR and BRAF alterations may have significant prognostic and therapeutic implications. Further research and larger sample size is needed to further elucidate associations between the common somatic alterations detected in mCRPC.

The clinical impact and prognostic value of 18F-fluorodeoxyglucose PET/CT in the initial staging non-small cell lung cancer at MD Anderson Cancer Center.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11079-11079
Author(s):  
Satoshi Takeuchi ◽  
Benjapa Khiewvan ◽  
Stephen Swisher ◽  
Eric Rohren ◽  
Homer A. Macapinlac
Keyword(s):  
Fdg Pet ◽  
Small Cell ◽  
Cancer Center ◽  
Stage Migration ◽  
Conventional Imaging ◽  
Small Cell Lung ◽  
Pet Ct ◽  
Md Anderson ◽  
Fdg Pet Ct ◽  
Nsclc Patients

11079 Background: 18F-fluorodeoxyglucosePositron Emission Tomography/Computed Tomography (FDG-PET/CT) has an important role for Non-Small Cell lung cancer (NSCLC) management, especially in staging. Our objective was to assess stage migration, the clinical impact, and prognostic value of PET/CT in patients with NSCLC at MD Anderson Cancer Center (MDACC). Methods: We retrospectively reviewed the database from MDACC, and identified 729 NSCLC patients referred for staging between 2006 and 2011. Stage was classified using TNM classification. FDG-PET/CT and conventional imaging staging were compared with all-cause mortality and the survival rates of the respective clinical stage. The management impact of FDG-PET/CT was determined based on conventional imaging and PET/CT management plans. A change in stage was confirmed by histopathology and/or further imaging. Results: We identified 598 NSCLC patients with FDG-PET/CT and conventional imaging performed. FDG-PET/CT changed stage in 28.1 % (16.4 % upstaged, 11.7 % downstaged). Based on FDG-PET/CT, treatment plans were modified in 38 % of patients. Median progression free survival (PFS) and overall survival (OS) was significantly worse in patients with management impact of FDG-PET/CT than patients without impact (PFS, 24.9 v 60.6 months, P < 0.001; OS, 66.7 v 115.9 months, P < 0.001). Multivariate analysis showed that the impact of FDG-PET/CT impact on management was an independent prognostic factor for DFS (hazard ratio [HR] = 2.08; 95 % CI, 1.63 to 2.65; P < 0.001) and OS (HR = 2.16; 95 % CI, 1.56 to 2.99; P < 0.001). Stage migration from stage I (40/249 patients) showed worse outcome than those without change (PFS, 21.0 v 60.0 months, P < 0.001; OS, 64.7 v 115.9 months, P = 0.003). Conclusions: FDG-PET/CT has major role in NSCLC management. The added staging information provided by FDG-PET/CT as compared to conventional imaging resulted in a change in management in more than one third NSCLC patients. FDG-PET/CT is also a powerful tool for outcome prediction. Even in patients diagnosed as stage I by conventional method, FDG-PET/CT at initial diagnosis may have an impact on survival.

scholarly journals The relationship between lymphedema severity and awareness of lymphedema surgery

2021 ◽  
Vol 48 (5) ◽  
pp. 534-542
Author(s):  
Hyun Seung Lee ◽  
Yong Chan Bae ◽  
Su Bong Nam ◽  
Chang Ryul Yi ◽  
Jin A Yoon ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Surgical Technique ◽  
Indocyanine Green ◽  
Upper Extremity ◽  
Surgical Techniques ◽  
Cancer Center ◽  
Limited Knowledge ◽  
Early Stages ◽  
Md Anderson ◽  
The Relationship

Background During the early stages of lymphedema, active physiologic surgical treatment can be applied. However, lymphedema patients often have limited knowledge and misconceptions regarding lymphedema and surgical treatment. We analyzed the correlations between lymphedema severity and surgical technique according to patients’ awareness of surgical treatment for secondary upper extremity lymphedema (UEL).Methods Patients with UEL diagnosed between December 2017 and December 2019 were retrospectively evaluated. At the time of their presentation to our hospital for the treatment of lymphedema, they were administered a questionnaire about lymphedema and lymphedema surgery. Based on the results, patients were classified as being aware or unaware of surgical treatment. Lymphedema severity was classified according to the arm dermal backflow (ADB) stage and the MD Anderson Cancer Center (MDACC) stage based on indocyanine green lymphography conducted at presentation. Surgical techniques were compared between the two groups.Results Patients who were aware of surgical treatment had significantly lower initial ADB and MDACC stages (P<0.05) and more frequently underwent physiologic procedures than excisional procedures (P=0.003).Conclusions If patients are actively educated regarding surgical treatment of lymphedema, physiologic procedures may be performed during the early stages of UEL.

The relationship between pemetrexed exposure (AUC) and clinical outcome in Japanese NSCLC patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18041-18041
Author(s):  
S. Adachi ◽  
T. Tamura ◽  
K. Nakagawa ◽  
C. Falcoz ◽  
L. Musib ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Tumor Response ◽  
Single Agent ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Clinical Findings ◽  
Randomized Phase Ii ◽  
Previously Treated ◽  
Nsclc Patients ◽  
The Relationship

18041 Background: The efficacy of pemetrexed (PEM) 500 mg/m2 administered with vitamin B12 and folic acid (FS) has been established in previously treated NSCLC. The 500 mg/m2 dose is based on the MTD determined for PEM without FS. Recently completed phase I studies have shown the recommended dose of PEM single agent with FS to be 900–1,000 mg/m2. A randomized phase II study conducted in Japan (ASCO 2007) showed PEM 500 mg/m2 and 1,000 mg/m2 with FS to have similar efficacy for patients with 2nd and 3rd line NSCLC. PEM is renally excreted and a PK model characterizing the relationship between CrCL and PEM AUC has been previously established. The exposure response relationships (ERRs) between AUC and progression free survival (PFS), individual patient’ tumor response, and toxicity were explored in these analyses. Methods: Eligible patients had a histologic or cytologic diagnosis of NSCLC, had been previously treated by 1 or 2 chemotherapy regimens, and were randomized to 500 mg/m2 (N = 108 pts) or 1,000 mg/m2 (N = 108 pts) of PEM once every 3 weeks. A previously established PK model was used to estimate AUC based on patient CrCL and dose administered. AUCs were linked to clinical outcome to identify ERRs. Efficacy models assumed a distribution of events with hazard dependent on prognostic factors and mean AUC at cycle over the treatment period. The AE model assumed probability of toxicity as a function of AUC at each cycle. Results: Median CrCL for patients in 500 mg/m2 and 1,000 mg/m2 groups were 85 ml/min (42–167) and 83 ml/min (38–146), respectively; median estimated PEM AUCs were 158 mg.h/L (107–221) and 318 mg.h/L (215–468). The relationship between model-estimated AUC and PFS was not significant. This is consistent with the clinical findings: PFS for the 500 mg/m2 and 1,000 mg/m2 groups of 3.0 months and 2.4 months, respectively; overall response rate (RR) of 18.5% and 14.8%, respectively. ERR analyses for individual patient tumor response, neutropenia and thrombocytopenia are ongoing at this time. Conclusions: Estimated PEM AUCs, based on CrCL, does not correlate with PFS for pretreated NSCLC at 500 mg/m2 and 1,000 mg/m2. The ERRs for individual tumor response and toxicity are ongoing and will be presented at the meeting. No significant financial relationships to disclose.

XIST: A Meaningful Long Noncoding RNA in NSCLC Process

2020 ◽  
Vol 26 ◽  
Author(s):  
Yujie Shen ◽  
Yexiang Lin ◽  
Kai Liu ◽  
Jinlan Chen ◽  
Juanjuan Zhong ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Critical Role ◽  
Biological Functions ◽  
Potential Therapeutic Target ◽  
Considerable Evidence ◽  
Lncrna Xist ◽  
Nsclc Patients ◽  
The Relationship

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.

657 Interleukin-6 receptor blockade for management of immune checkpoint inhibitor related adverse events in patients with melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A694-A694
Author(s):  
Chantal Saberian ◽  
Faisal Fa’ak ◽  
Jean Tayar ◽  
Maryam Buni ◽  
Sang Kim ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Activity ◽  
Median Time ◽  
Interleukin 6 ◽  
Immune Checkpoint ◽  
Activity Index ◽  
Critical Role ◽  
Cancer Center ◽  
Interleukin 6 Receptor ◽  
Md Anderson

BackgroundManagement of certain immune mediated adverse events (irAEs) can be challenging and may require prolonged/chronic immune suppression with corticosteroids or other immunosuppressant which could compromise and even reverse the efficacy of immune checkpoint inhibitors (ICI). While the exact immunobiology of irAEs is not fully understood there is enough evidence that IL-6 induced Th-17 that may play critical role in the pathogenesis. Herein, we describe our clinical experience using interleukin-6 receptor (IL-6R) blockade in management of irAEs in melanoma patients.MethodsWe searched MD Anderson databases to identify cancer patients who had received ICIs between January 2004 and March 2020. Of 11,391 ICI-treated patients, 21 patients with melanoma who received IL-6R blockade after ICI infusion were identified and their medical records were reviewed.ResultsMedian age was 61 years (41–82), 52% were females, 90% received anti-programmed cell death-1 antibodies. Fourteen patients (67%) had de novo onset irAEs (11 had arthritis, and 1 each with polymyalgia rheumatica, oral mucositis, and CNS vasculitis), and 7 patients (33%) had flare of their pre-existing autoimmune diseases (5 had had rheumatoid arthritis, and 1 each with myasthenia gravis and Crohn’s disease). Median time from ICI initiation to irAEs was 91 days (range, 1–496) and to initiation of IL-6R blockade was 6.6 months (range, 0.6–24.3). Median number of IL-6R blockade was 12 (range, 1–35), and 16 patients (76%) were concomitantly receiving corticosteroids of median dose of 10 mg (range, 5–20 mg). Of the 21 patients, irAEs improved in 14 (67%) (95% CI: 46%-87%). Of 13 evaluable patients with arthritis, 11 (85%) achieved remission or minimal disease activity as defined by the clinical disease activity index. Median time from initiation of IL-6R blockade till improvement of irAEs was 2.9 months (range, 1.5–36.9). Nineteen patients tolerated well IL-6R blockade, while two patients stopped treatment due to abdominal pain and sinus tachycardia. The median CRP levels at irAEs was 84 mg/L (0.6–187) and decreased to 1.9 mg/L (0.56–12) at 10 weeks after initiation of IL-6R blockade (P=0.02). Of the 17 evaluable patients, the overall tumor response rate by RECIST-1.1 criteria was similar before and after IL-6R blockade initiation (41% vs. 53%).ConclusionsOur data demonstrated that IL-6R blockade could be an effective therapy for irAEs management without dampening the efficacy of ICIs. Prospective clinical trials with longitudinal blood, tumor, and inflamed tissue biopsies are planned to accurately validate these findings and better study the immunobiology of irAEs.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition’s Ethics Board, approval number PA19-0089

scholarly journals 0570 Apnea-Hypopnea Index is Positively Correlated with Mood Disturbance

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A218-A219
Author(s):  
K M Stubbers ◽  
S S Thosar ◽  
M P Butler ◽  
N P Bowles ◽  
A W McHill ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Mood State ◽  
Mood Disturbance ◽  
Apnea Hypopnea Index ◽  
Uncomplicated Hypertension ◽  
Total Mood Disturbance ◽  
Obstructive Sleep ◽  
Sleep Schedule ◽  
The Relationship ◽  
Larger Sample

Abstract Introduction The prevalence of mood disorders such as depression is higher in individuals with obstructive sleep apnea (OSA). Previous studies have found no significant correlation between the apnea-hypopnea index (AHI) and measures of mood and have only included participants who met diagnostic criteria for OSA. The current analysis sought to determine whether mood correlated with AHI in individuals with any AHI values including those that did not meet diagnostic criteria for OSA. Methods 31 volunteers were studied (BMI=29.2±1.0 kg/m2, mean±SE), free from medication and without psychiatric illness or chronic medical conditions with the exception of untreated OSA, uncomplicated hypertension (BP&lt;160/100), or obesity. Following 1-3 weeks of an 8h habitual at home sleep schedule, participants completed the POMS-Brief questionnaire (POMS-B) to assess mood after undergoing overnight polysomnography to determine AHI. Total mood disturbance (TMD) scores were calculated by adding the scores on the POMS-B for each mood state subscale and subtracting the score for vigor-activity. Results The average AHI was 15.3±3.1 (range of 1.1-74.1) events per hour. The average POMS-B TMD score was 21±1.5 (range of 4-46). There was a significant correlation between the POMS-B TMD score and AHI (p=0.037, r2=0.14). This result was also seen in only those individuals with AHI scores &gt;5 (p=0.002, r2=0.4). Conclusion In this sample, individuals with higher AHI values displayed higher TMD scores. These results differ from previous data that showed no significant correlation between AHI and TMD. This is the first analysis to demonstrate a correlation between TMD and AHI while including individuals who didn’t meet diagnostic criteria for OSA. However, the relationship between AHI and TMD was also significant in those with AHI&gt;5. More data on these measures with larger sample sizes and a more equal representation of AHI values should be gathered to provide additional evidence for this relationship. Support: Support NIH R01-HL125893; CTSA UL1TR000128, R21HL140377

Sequential monitoring of PD-L1 on circulating stromal cells in blood predicts PFS in NSCLC patients undergoing immunotherapy after definitive chemoradiation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8534-8534
Author(s):  
Daniel L Adams ◽  
Alexander Augustyn ◽  
Jianzhong He ◽  
Yawei Qiao ◽  
Ting Xu ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Progression Free Survival ◽  
Free Survival ◽  
Hazard Ratios ◽  
Fda Approval ◽  
Inflammatory State ◽  
Nsclc Patients ◽  
Tumor Biopsies ◽  
Relationship Of ◽  
The Relationship

8534 Background: Cancer Associated Macrophage-Like cells (CAMLs) are circulating stromal cells in the blood of patients (pts) with solid tumors that are phagocytic macrophages that may represent the inflammatory state of the tumor microenvironment. Previously, we demonstrated CAMLs ≥50µm after chemo-radiation therapy (CRT) in NSCLC is associated with worse progression free survival (PFS) and overall survival (OS). We also showed that PDL1 expression in CAMLs is dynamic & can change with CRT, difficult to assess with repeat biopsies, but possible with liquid biopsy. For this study we evaluated whether CAML properties can predict response to CRT with/without immunotherapy (IMT) agents in unresectable NSCLC. Methods: A single blind multi-year prospective study was undertaken to test the relationship of PDL1 expression and ≥50µm CAML size to PFS/OS in NSCLC, pre and post CRT with (n = 96) and without (n = 72) anti-PDL1/PD1 IMT. This included atezolizumab (prospective single arm NCT02525757) n = 39, durvalumab n = 52 or pembrolizumab n = 5 both after 2018 FDA approval. We recruited 168 pts with pathologically confirmed unresectable NSCLC prior to CRT. Blood samples 15 mL were taken at baseline (BL), CRT completion (T1), and ̃1 month after CRT (T2) (with n = 96 or without n = 72 IMT). Blood was filtered by CellSieve filtration and CAMLs quantified for size ( < 49 µm or ≥50 µm) and PDL1 expression to evaluate PFS and OS hazard ratios (HRs) by censored univariate and multivariate analysis at 24 months. Results: CAMLs were found in 90% of all samples, average 5.8 CAMLs/15mL. At BL, ≥50µm CAMLs did not predict PFS in CRT/IMT pts (HR 1.6, p = 0.220) nor CRT alone (HR 1.3, p = 0.593). However, after completion of CRT (T1) ≥50µm CAMLs predicted PFS in CRT/IMT pts (HR 2.7, p = 0.003) and CRT alone (HR 2.5, p = 0.015). In primary tumor biopsies, PDL1 expression > 1% did not predict CRT/IMT response (PFS HR 1.8, p = 0.262 & OS HR 2.3, p = 0.158). At BL, high CAML PDL1 did not predict PFS in CRT/IMT pts (HR 1.4, p = 0.427) nor CRT alone (HR 1.1, p = 0.982). Further, at CRT completion (T1), high CAML PDL1 only trended for better PFS in CRT/IMT pts (HR 1.7, p = 0.137), but not CRT alone (HR 1.1, p = 0.972). At T2, however, pts with continuously high CAML PDL1 had significantly better PFS with IMT (HR 3.2, p = 0.002) vs CRT alone (HR 1.4, p = 0.616). While ≥50µm CAMLs at BL did not predict 24 month progression, ≥50 µm CAMLs after CRT (with or without 1 cycle of anti-PDL1 IMT) was 84% accurate at predicting progression. Further subtyping and analysis is ongoing to evaluate OS and PDL1 in the CAML populations. Conclusions: Our data suggests that in unresectable NSCLC, ≥50 µm CAMLs after completion of CRT is prognostic regardless of IMT use. PDL1 expression in CAMLs also appears to predict for response to consolidated IMT after CRT. Additional studies are needed to validate these findings.

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