scholarly journals Survival of patients with melanoma metastatic brain metastases in the era of novel systemic therapies in Cardiff, Wales

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv13-iv13
Author(s):  
Joseph Pasquale ◽  
Joanita Ocen ◽  
James Powell ◽  
Satish Kumar
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Small Sample Size ◽  
Brain Lesion ◽  
Small Sample ◽  
Simultaneous Treatment ◽  
Local Progression ◽  
Significant Difference ◽  
Retrospective Nature ◽  
The Uk

Abstract The incidence of malignant melanoma (MM) is increasing in the UK; it’s projected to rise by 7% by 2035. MM has high predisposition to developing brain metastases (BM) with 50–60% of patients being affected. Stereotactic radiosurgery (SRS) and surgery, key interventions in managing patients with BM, have been shown to improve survival outcomes of patients. Patients’ prognosis and survival has also significantly improved with the advent of novel therapies in the last few years. It was noted that the Cardiff Neuro-Oncology multidisciplinary team were receiving increasing amount of referrals for consideration of surgery or SRS in patients with MM. 106 MDT referrals were retrospectively reviewed. 31 patients had surgery, 20 patients had SRS and the remaining 54 patients had WBRT. There was no significant difference in the patient distribution. The majority of patients had 1 brain lesion in both groups (in similar proportions). The 12 month survival for the surgical cohort was 65% for immunotherapy group, 55%- targeted therapy and 30%- no therapy. For the SRS group the 12 month survival for immunotherapy was 45%, targeted therapy- 40% and 20%- no therapy. The median OS for surgery versus SRS was 8 and 7 months respectively. The results suggest that simultaneous treatment with surgery or SRS in conjunction with SACT does improve survival. Interpretation of results will have to be taken with caution due to the retrospective nature and the small sample size. Going forward, we will delve deeper and review local progression rates and SACT timing/sequencing in our practice.

scholarly journals NI-19 Use of 11C-methionine PET for decision of discontinuation of adjuvant chemotherapy with temozolomide

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii14-ii14
Author(s):  
Takaaki Beppu ◽  
Yuichi Sato ◽  
Toshiaki Sasaki ◽  
Kazunori Terasaki ◽  
Kuniaki Ogasawara
Keyword(s):  
Adjuvant Chemotherapy ◽  
Small Sample Size ◽  
Standardized Uptake Value ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Small Sample ◽  
Tumor Type ◽  
Diffuse Astrocytoma ◽  
Significant Difference ◽  
Met Pet

Abstract Background: The aim was to clarify whether positron emission tomography with 11C-methyl-L-methionine (met-PET) is useful to decide on discontinuation of TMZ-adjuvant therapy in patients with residual diffuse astrocytic tumor. Methods: Subjects were 44 patients with residual tumor comprising 17 with IDH1-mutant diffuse astrocytoma (DA), 13 with IDH1-mutant anaplastic astrocytoma (AA), and 14 with IDH1-wild glioblastoma (GB). All patients received TMZ-adjuvant chemotherapy (median, 12 courses), and whether to discontinue or continue TMZ-adjuvant chemotherapy was decided on the basis of the tumor-to-normal ratio in standardized uptake value from met-PET (T/N); patients with T/N < 1.6 immediately discontinued TMZ, and patients with T/N > 1.6 were either to continued or discontinued TMZ. Progression-free survival (PFS) was compared between patients with T/N > 1.6 and T/N < 1.6 in each tumor type. Median observation period was 434 days after met-PET scanning. Results: The number of patient who underwent recurrence was 10 in DA, 7 in AA, and 11 in GB. All patients showing T/N > 1.6 underwent tumor recurrence. PFS was significantly longer in patients with T/N < 1.6 than T/N > 1.6 in DA and AA (p < 0.01 in both types), but was no significant difference between 2 groups in GB (p = 0.06). Sixteen of 17 patients (94%) in DA and AA showed recurrence from residual tumor, whereas 4 of 11 patients (36%) in GB showed recurrent tumor at remote regions which were different from residual tumor. Conclusions: The present study suggested that met-PET is beneficial to decide to discontinue adjuvant chemotherapy with TMZ in patients with residual tumors of DA and AA, but not useful for patients with GB. Reasons for unsuccessful results in GB might have been small sample size, failure of establishing the cut off value in T/N, recurrences at remote regions where not be assessed by met-PET.

scholarly journals 1611. Evaluating Clinical Outcomes and Efficacy of Daptomycin in Combination with a Beta-Lactam for the Treatment of Vancomycin-Resistant Enterococcus (VRE) Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S799-S800
Author(s):  
Nerea Irusta ◽  
Ana Vega ◽  
Yoichiro Natori ◽  
Lilian M Abbo ◽  
Lilian M Abbo ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Primary Outcome ◽  
Small Sample Size ◽  
Univariate Analysis ◽  
Small Sample ◽  
Significant Difference ◽  
Vancomycin Resistant ◽  
Secondary Outcomes ◽  
Related Mortality

Abstract Background In-vitro studies have shown synergistic bactericidal activity with daptomycin (DAP) plus β-lactam antimicrobials against vancomycin resistant enterococci (VRE). There is a paucity of data regarding clinical outcomes with this combination in VRE bloodstream infections (BSI). The purpose of this study was to assess the efficacy of DAP plus a β-lactam with in-vitro activity vs. other therapies for treatment of VRE BSI. Methods IRB-approved, single-center, retrospective study of patients with VRE BSI from 01/2018-09/2019. Patients were excluded if < 18 years old, pregnant, or incarcerated. The primary outcome was time-to-microbiological clearance. Secondary outcomes included infection-related mortality, 30-day all-cause mortality, and incidence of recurrent BSI within 30 days of index culture. Targeted DAP doses were ≥ 8mg/kg and based on MIC. Factors associated with significance for outcomes, via univariate analysis, were evaluated with multivariable logistic regression (MLR), removed in a backward-step approach. Results A total of 85 patients were included, 23 of which received DAP plus a β-lactam. The comparator arm included linezolid or DAP monotherapy. Patients with combination therapy had significantly higher Charlson Comorbidity Index (CCI) (p=0.013) and numerically higher Pitt Bacteremia scores (PBS) (p=0.087) (Table 1). There was no difference seen in the primary outcome (Table 2). Secondary outcomes are provided in Table 2. The presence of polymicrobial infection and higher PBS were significantly associated with infection-related mortality (p=0.008 and p=0.005, respectively) by MLR. A Mann Whitney U test indicated that presence of infection-related mortality was greater for patients with higher MICS (U=20.5, p=0.06). The presence of an underlying source may be related to recurrence of BSI (p=0.075). Table 1: Patient Characteristics Table 2. Primary and Secondary Outcomes Conclusion We did not find a significant difference in time-to-microbiological clearance, although patients treated with DAP and a β-lactam had higher CCI and PBS. These results are limited by retrospective design, small sample size, and potential selection bias. Prospective randomized studies are needed to further validate these findings. Disclosures All Authors: No reported disclosures

scholarly journals Perioperative Outcomes Following Kidney-Pancreas Transplantation in Alberta, Canada: Research Letter

2021 ◽  
Vol 8 ◽  
pp. 205435812110293
Author(s):  
Danielle E. Fox ◽  
Robert R. Quinn ◽  
Paul E. Ronksley ◽  
Tyrone G. Harrison ◽  
Hude Quan ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Postoperative Care ◽  
Pancreas Transplantation ◽  
Type I Diabetes ◽  
Small Sample Size ◽  
Small Sample ◽  
Perioperative Outcomes ◽  
Type I ◽  
Patient Safety Indicators ◽  
Significant Difference

Background: Simultaneous kidney-pancreas transplantation (SPK) has benefits for patients with kidney failure and type I diabetes mellitus, but is associated with greater perioperative risk compared with kidney-alone transplantation. Postoperative care settings for SPK recipients vary across Canada and may have implications for patient outcomes and hospital resource use. Objective: To compare outcomes following SPK transplantation between patients receiving postoperative care in the intensive care unit (ICU) compared with the ward. Design: Retrospective cohort study using administrative health data. Setting: In Alberta, the 2 transplant centers (Calgary and Edmonton) have different protocols for routine postoperative care of SPK recipients. In Edmonton, SPK recipients are routinely transferred to the ICU, whereas in Calgary, SPK recipients are transferred to the ward. Patients: 129 adult SPK recipients (2002-2019). Measurements: Data from the Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD) were used to identify SPK recipients (procedure codes) and the outcomes of inpatient mortality, length of initial hospital stay (LOS), and the occurrence of 16 different patient safety indicators (PSIs). Methods: We followed SPK recipients from the admission date of their transplant hospitalization until the first of hospital discharge or death. Unadjusted quantile regression was used to determine differences in LOS, and age- and sex-adjusted marginal probabilities were used to determine differences in PSIs between centers. Results: There were no perioperative deaths and no major differences in the demographic characteristics between the centers. The majority of the SPK transplants were performed in Edmonton (n = 82, 64%). All SPK recipients in Edmonton were admitted to the ICU postoperatively, compared with only 11% in Calgary. There was no statistically significant difference in the LOS or probability of a PSI between the 2 centers (LOS for Edmonton vs Calgary:16 vs 13 days, P = .12; PSIs for Edmonton vs Calgary: 60%, 95% confidence interval [CI] = 0.50-0.71 vs 44%, 95% CI = 0.29-0.59, P = .08). Limitations: This study was conducted using administrative data and is limited by variable availability. The small sample size limited precision of estimated differences between type of postoperative care. Conclusions: Following SPK transplantation, we found no difference in inpatient outcomes for recipients who received routine postoperative ICU care compared with ward care. Further research using larger data sets and interventional study designs is needed to better understand the implications of postoperative care settings on patient outcomes and health care resource utilization.

scholarly journals Nutritional Support and Clinical Outcome of Severe and Critical Patients With COVID-19 Pneumonia

2020 ◽  
Vol 7 ◽  
Author(s):  
Xiangfeng Yue ◽  
Min Li ◽  
Yu Wang ◽  
Jing Zhang ◽  
Xinyi Wang ◽  
...  
Keyword(s):  
Protein Intake ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Antiviral Treatment ◽  
Small Sample ◽  
Nutrition Support ◽  
Calorie Intake ◽  
Viral Shedding ◽  
Significant Difference ◽  
Critical Patients

Background: In 2020, a novel coronavirus has spread throughout the world. More than four hundred thousand people have died of SARS-CoV-2 pneumonia, most of which were severe and critical patients. No effective antiviral treatment has been verified thus far. Nutrition support has become one of the important treatments for severe and critical patients.Methods: In this retrospective study, 26 severe patients and 22 critical patients with laboratory confirmed COVID-19 were enrolled. We recorded the diet and nutritional treatments in severe and critical patients. Baseline characteristics and clinical outcomes of severe and critical patients were also collected.Results: Average calorie intake of severe patients (19.3 kcal/kg/d) was higher than critical patients (15.3 kcal/kg/d) (P = 0.04). Protein intake was similar in the two groups (0.65 and 0.62 g/kg per day, respectively; P = 0.29). There was no significant difference in the median duration of viral shedding between the severe and critical patients (P = 0.354).Conclusions: A permissive underfeeding strategy that restricts non-protein calories but preserves protein intake is feasible for critical patients with SARS-CoV-2 pneumonia. Viral shedding duration of critical patients was the same as severe patients who received standard feeding. Nevertheless, evidence of the conclusion is not sufficient because of small sample size. To show the real clinical benefit of permissive low-calorie and adequate protein intake in critical SARS-CoV-2 pneumonia patients, a large and pragmatic randomized controlled trial is needed.

scholarly journals Acupuncture for Chronic Pain-Related Insomnia: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Fushui Liu ◽  
Jianyu You ◽  
Qi Li ◽  
Ting Fang ◽  
Mei Chen ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sample Size ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Sham Acupuncture ◽  
Small Sample ◽  
Control Group ◽  
Large Sample Size ◽  
Cure Rate ◽  
Significant Difference

Objectives. Acupuncture has been widely used to relieve chronic pain-related insomnia (CPRI). However, the efficacy of acupuncture for CPRI is uncertain. The purpose of this study was to evaluate the efficacy of acupuncture for CPRI. Methods. Seven electronic databases were searched from inception to December 2018. Randomized controlled trials (RCTs) were included if acupuncture was compared to sham acupuncture or conventional drug therapies for treating CPRI. Two reviewers screened each study and extracted data independently. Statistical analyses were conducted by RevMan 5.3 software. Results. A total of nine studies involving 944 patients were enrolled. The pooled analysis indicated that acupuncture treatment was significantly better than control group in improving effective rate (OR = 8.09, 95%CI = [4.75, 13.79], P < 0.00001) and cure rate (OR = 3.17, 95%CI = [2.35, 4.29], P < 0.00001), but subgroup analysis showed that there was no statistically significant difference between acupuncture and sham acupuncture in improving cure rate (OR =10.36, 95% CI [0.53, 201.45], P=0.12) based on one included study. In addition, meta-analysis demonstrated that acupuncture group was superior to control group in debasing PSQI score (MD = -2.65, 95%CI = [-4.00, -1.30], P = 0.0001) and VAS score (MD = -1.44, 95%CI = [-1.58, -1.29], P < 0.00001). And there was no significant difference in adverse events (OR =1.73, 95%CI = [0.92, 3.25], P =0.09) between the two groups. Conclusions. Acupuncture therapy is an effective and safe treatment for CPRI, and this treatment can be recommended for the management of patients with CPRI. Due to the low quality and small sample size of the included studies, more rigorously designed RCTs with high quality and large sample size are recommended in future.

scholarly journals Interfraction Variation and Dosimetric Changes in Patients With Cervical Cancer Treated With Intracavitary Brachytherapy

2018 ◽  
pp. 1-7
Author(s):  
Jayson L. Co ◽  
Maureen R. Bojador ◽  
Michael Benedict A. Mejia ◽  
Teresa T. Sy Ortin ◽  
Domingo E. Ganzon
Keyword(s):  
Cervical Cancer ◽  
Dwell Time ◽  
Small Sample Size ◽  
Three Dimensional ◽  
Small Sample ◽  
Intracavitary Brachytherapy ◽  
Source Position ◽  
Current Standard ◽  
Planning Software ◽  
Significant Difference

Purpose Intracavitary brachytherapy is integral in the treatment of cervical cancer. Because of interfraction variation, the current standard is replanning with every fraction. This study aimed to determine whether there was a difference in relative dosimetry if the source position and dwell time of the first fraction were applied to subsequent fractions. Materials and Methods The authors performed a retrospective review of charts and films from 2007 to 2012. Eligible cases were patients with cervical cancer treated with brachytherapy with the same dose prescription to point A. Replanning was done on the first set of orthogonal plates. Source position and dwell time were subsequently applied to the remaining fractions using actual films. Results Twenty-nine patients were included in this study. The results showed that cervical, rectal, and bladder dose between the actual plan and the hypothetical plan were not statistically different. In the hypothetical plan, the source activity and dwell time of the first plan were applied to the orthogonal films of the subsequent fractions and showed no significant difference in all dose points. Conclusion The results of this study showed proof of concept of the safety of using the source position and dwell time of the first plan for subsequent fractions. Until further studies are performed (also using three-dimensional planning software), the concept should be considered investigational because of the small sample size of the study. Until such research is performed, it is still strongly recommended that replanning be performed with every fraction whenever it is feasible.

scholarly journals Comparison of total joint arthroplasty outcomes between renal transplant patients and dialysis patients—a meta-analysis and systematic review

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jiayi Li ◽  
Mingyang Li ◽  
Bo-qiang Peng ◽  
Rong Luo ◽  
Quan Chen ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Sample Size ◽  
Total Joint Arthroplasty ◽  
Small Sample Size ◽  
Joint Arthroplasty ◽  
Small Sample ◽  
Dialysis Patients ◽  
Transplant Patients ◽  
Significant Difference ◽  
Renal Transplant Patients

Abstract Objectives End-stage renal disease (ESRD) patients are at an increased risk of needing total joint arthroplasty (TJA); however, both dialysis and renal transplantation might be potential predictors of adverse TJA outcomes. For dialysis patients, the high risk of blood-borne infection and impaired muscular skeletal function are threats to implants’ survival, while for renal transplant patients, immunosuppression therapy is also a concern. There is still no high-level evidence in the published literature that has determined the best timing of TJA for ESRD patients. Methods A literature search in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (up to November 2019) was performed to collect studies comparing TJA outcomes between renal transplant and dialysis patients. Two reviewers independently conducted literature screening and quality assessments with the Newcastle-Ottawa Scale (NOS). After the data were extracted, statistical analyses were performed. Results Compared with the dialysis group, a lower risk of mortality (RR = 0.56, Cl = [0.42, 0.73], P < 0.01, I2 = 49%) and revision (RR = 0.42, CI = [0.30, 0.59], P < 0.01, I2 = 43%) was detected in the renal transplant group. Different results of periprosthetic joint infection were shown in subgroups with different sample sizes. There was no significant difference in periprosthetic joint infection in the small-sample-size subgroup, while in the large-sample-size subgroup, renal transplant patients had significantly less risk (RR = 0.19, CI = [0.13, 0.23], P < 0.01, I2 = 0%). For dislocation, venous thromboembolic disease, and overall complications, there was no significant difference between the two groups. Conclusion Total joint arthroplasty has better safety and outcomes in renal transplant patients than in dialysis patients. Therefore, delaying total joint arthroplasty in dialysis patients until renal transplantation has been performed would be a desirable option. The controversy among different studies might be partially accounted for that quite a few studies have a relatively small sample size to detect the difference between renal transplant patients and dialysis patients.

scholarly journals ESD with double-balloon endoluminal intervention platform versus standard ESD for management of colon polyps

2020 ◽  
Vol 08 (10) ◽  
pp. E1273-E1279
Author(s):  
Mohamed Saleh Ismail ◽  
Firas Bahdi ◽  
Michael Oliver Mercado ◽  
Randa Habazi ◽  
Angel Alexander ◽  
...  
Keyword(s):  
Postoperative Complications ◽  
Curative Resection ◽  
Small Sample Size ◽  
Small Sample ◽  
Colon Polyps ◽  
Procedure Time ◽  
Polyp Size ◽  
En Bloc ◽  
Double Balloon ◽  
Significant Difference

Abstract Background and study aims Endoscopic submucosal dissection (ESD) with the double-balloon endoluminal intervention platform (DEIP) is a novel technique for removal of complex colon polyps (> 2 cm) or those located in anatomically difficult positions. DEIP helps create a therapeutic zone with improved visualization and stability, facilitating polyp removal. We aimed to compare the outcomes of DEIP with the conventional cap-assisted ESD (standard ESD) technique for colon polyp resection, in particular, the ability to complete the ESD procedure without resorting to hybrid ESD or piecemeal resection. Patients and methods This was a retrospective cohort of all patients who underwent colon ESD in a single large tertiary referral center between September 2016 and October 2019. Information was collected on patient demographics and study outcomes including procedure time, rates of en bloc and curative resection, operative and postoperative complications. All patients were followed up for 1 month after the procedure. Results 111 patients were included in the study (DEIP 60, standard ESD 51). There was no statistically significant difference between mean procedures time (± SD) in the two groups, mean (81.9 ± 35.4 min standard vs. 96.4 ± 42.2 min in DEIP). Mean polyp size (± SD) was similar between the two groups (7.6 ± 6.0 cm2 vs. 6.2 ± 5.5 cm2, P = .2). There were no significant differences in en bloc and curative resection rates or operative and postoperative complications between the two techniques. Conclusion Procedure time was similar using both techniques. However, DEIP enabled the entire procedure to be performed using the ESD technique without resorting to snare resection, which may affect the en bloc and curative resection rate. There were no significant differences in en bloc and curative resection rates between the two groups, probably due to the small sample size.

ABCA3 Expression Predicts Response to Gemtuzumab Ozogamicin in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3946-3946 ◽  
Author(s):  
Antony Ceraulo ◽  
Aminetou Mint-Mohamed ◽  
Delphine Maucort-Boulch ◽  
Etienne Paubelle ◽  
Xavier Thomas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Relapse Rate ◽  
Small Sample Size ◽  
Univariate Analysis ◽  
Gemtuzumab Ozogamicin ◽  
Small Sample ◽  
Control Group ◽  
Prognostic Impact ◽  
Significant Difference

Abstract Background. The ATP binding cassette transporter 3 (ABCA3) has been recently found to induce a significant reduction in cytotoxicity following exposure to anthracyclines, mitoxantrone, etoposide, Ara-C, vincristine, and rituximab. ABCA3 acts through the modulation of multivesicular bodies (MVB) and contributes to drug sequestration in late endosomal organelles, i.e. MVB and lysosomes. Studies having investigated the prognostic impact of ABCA3 expression in AML have yielded conflicting results as ABCA3 expression has both been reported to exert unfavorable or neutral effects on patient outcomes. In addition, the small sample size of these studies precluded the use of multivariate analyses. Methods. Our goal was to investigate the prognostic impact of ABCA3 expression in adult patients with AML treated with IC with or without gemtuzumab ozogamicin (GO). To this end we investigated the relationship between ABCA3 expression and EFS in a representative series of 221 AML homogeneously treated in the ALFA-0701 trial. qRTPCR amplification of conserved ABCA3 mRNA sequences, as identified with FasterDB database, was performed with GUS and ABL as reference genes. Primer sets were complementary to conserved ABCA3 exons 6-7 and exon 19-20 junctions. Patients were given a 3+7 induction course without (control group, n=110) or with fractionated intravenous GO (n=111) (Castaigne S, Lancet 2012; 379:1508-1516). Results. Among the 278 randomized patients, 221 had available bone-marrow diagnostic samples with high-quality RNA. The same benefits associated with GO were observed in the 221 patients from the present study as in the entire trial population. Overall, median age, CR rate, relapse rate, median follow-up, 3-years EFS were 62.1 years, 76.5%, 66%, 47.45 months, 28±3%, respectively. There was no significant difference in the level of ABCA3 expression between responders and non-responders. In the 169 responders, ABCA3 expression at diagnosis was more than 3-fold higher in the 111 remitters who subsequently relapsed than in the 58 patients who remained in persistent CR (p=0.033). The level of ABCA3 expression was significantly lower in ELN favorable group than in intermediate and adverse risk AML (p= 0.004) and negatively correlated with CD33 expression (R=-0.272, p<10-4). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±3 vs 45±7 % p=0.002). Multivariate analysis identified age, treatment arm, and ELN risk group as independent prognostic factors for EFS. In the control group, there was no significant association between ABCA3 expression and CR rate, relapse rate, and EFS. In the 111 patients within the GO arm, there was no significant difference in the level of ABCA3 expression between responders and non-responder whereas in the 89 responders, ABCA3 expression at diagnosis was more than 7-fold higher in the 53 remitters who subsequently relapsed than in the 36 patients who remained in persistent CR (p=0.006). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±5 vs 64±9 % p=0.0002). Multivariate analysis identified ABCA3 expression, cytogenetics, CD33 expression, and ECOG as independent prognostic factors for EFS (Figure 1). Conclusion. WhileABCB1 has been previously found to attenuate GO-induced cytotoxicity in AML cells (Walter RB, Blood 2003; 102:1466-1473), present results indicate that higher ABCA3 expression independently predicts poor outcome in AML patients treated with fractionated GO and intensive chemotherapy (IC). GO is an anti-CD33 antibody carrying a toxic calicheamicin derivative that, after hydrolytic release within lysosomal vesicles, induces DNA strand breaks, apoptosis, and cell death. Whether the clinical effect of ABCA3 expression relies on the modulation of CD33 internalization, calicheamicin release or combination thereof is under investigation. Finally our results encourage inhibiting ABCA3, such as with indomethacin, in order to overcome drug resistance in AML treated with GO-IC. Figure 1 Figure 1. Disclosures Thomas: Pfizer: Consultancy.

Cell cycle and apoptosis regulatory protein (CARP)-1 expression in neuroblastoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9578-9578
Author(s):  
Santosh S. Hanmod ◽  
Samantha Siegel ◽  
James Hatfield ◽  
Edi Levi ◽  
Marwan Zidan ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Regulatory Protein ◽  
Tumor Biology ◽  
Progression Free Survival ◽  
Small Sample ◽  
Immune Histochemistry ◽  
Formalin Fixed Paraffin ◽  
Number Of Patients ◽  
Significant Difference ◽  
Formalin Fixed Paraffin Embedded

9578 Background: Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. The prognosis for patients with high risk NB is still poor. Study of additional prognostic factors will enhance current understanding of the tumor biology and risk stratification. CARP-1 is a recently identified molecule mediating apoptosis signaling by agents like doxorubicin and etoposide. Since these agents are used in the front line treatment of NB, we tested whether CARP-1 expression could be another prognostic factor in NB. Methods: CARP-1 expression was examined by Western blot in a pair of NB cell lines, SK-N-SH and SK-N-SH Dox. We reviewed medical records of patients with NB at Children’s Hospital of Michigan from 2000-2009 and examined CARP-1 expression by immune-histochemistry in the archived, formalin fixed paraffin embedded NB tissues. CARP-1 expression was recorded as positive or negative. Correlation of CARP-1 expression and progression free survival (PFS) was calculated. Results: CARP-1 expression was detected in SK-N-SH but not SK-N-SH Dox, a doxorubicin-resistant derivative of SK-N-SH, suggesting that resistance to doxorubicin is associated with decreased level of CARP-1 expression in NB cells. Of the 30 cases studied, 53 % (16/30) expressed CARP-1. There was no significant difference in N-myc amplification status (13% vs.14%, p=0.3), or proportion of unfavorable Shimada histology (60% vs. 64%, p=0.5) between CARP-1 positive vs. negative groups. Twenty three percent (7/22) patients progressed or relapsed, including 2/16 (13%) in CARP-1 positive group vs. 5/14 (36%) in CARP-1 negative group (p=0.1). There was no significant difference in the PFS at 1 year (94% vs.79%, p=0.2) and 3 year (86% vs.71%, p=0.2) between CARP-1 positive vs. negative groups. Conclusions: CARP-1 expression was decreased in doxorubicin resistant NB cell line. CARP-1 expression was detected in approximately half (53%) of NB tumors. Patients with NB who expressed CARP-1 showed trend towards better 1- & 3-year PFS as compared to those who did not express CARP-1, however, the results are not statistically significant which could be due to the small sample size. Further study with a larger number of patients is warranted to clarify these findings.

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