Integrative analysis identifies an older female-linked AML patient group with better risk in ECOG-ACRIN Cancer Research Group's clinical trial E3999.
Ontology highlight
ABSTRACT:
SUBMITTER: Rapaport F
PROVIDER: S-EPMC9508258 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
Publications
Integrative analysis identifies an older female-linked AML patient group with better risk in ECOG-ACRIN Cancer Research Group's clinical trial E3999.
Rapaport Franck F Seier Kenneth K Neelamraju Yaseswini Y Hassane Duane D Baslan Timour T Gildea Daniel T DT Haddox Samuel S Lee Tak T Murdock H Moses HM Sheridan Caroline C Thurmond Alexis A Wang Ling L Carroll Martin M Cripe Larry D LD Fernandez Hugo H Mason Christopher E CE Paietta Elisabeth E Roboz Gail J GJ Sun Zhuoxin Z Tallman Martin S MS Zhang Yanming Y Gönen Mithat M Levine Ross R Melnick Ari M AM Kleppe Maria M Garrett-Bakelman Francine E FE
Blood cancer journal 20220923 9
Similar Datasets
Project description: Not available
| S-EPMC10322919 | biostudies-literature
Project description:BackgroundUncertainty regarding the reproducibility of the apparent diffusion coefficient (ADC) hampers the use of quantitative diffusion-weighted imaging (DWI) in evaluation of the prostate with magnetic resonance imaging MRI. The quantitative imaging biomarkers alliance (QIBA) profile for quantitative DWI claims a within-subject coefficient of variation (wCV) for prostate lesion ADC of 0.17. Improved understanding of ADC reproducibility would aid the use of quantitative diffusion in prostate MRI evaluation.PurposeEvaluation of the repeatability (same-day) and reproducibility (multi-day) of whole-prostate and focal-lesion ADC assessment in a multi-site setting.Study typeProspective multi-institutional.SubjectsTwenty-nine males, ages 53 to 80 (median 63) years, following diagnosis of prostate cancer, 10 with focal lesions.Field strength/sequence3T, single-shot spin-echo diffusion-weighted echo-planar sequence with four b-values.AssessmentSites qualified for the study using an ice-water phantom with known ADC. Readers performed DWI analyses at visit 1 ("V1") and visit 2 ("V2," 2-14 days after V1), where V2 comprised scans before ("V2pre") and after ("V2post") a "coffee-break" interval with subject removal and repositioning. A single reader segmented the whole prostate. Two readers separately placed region-of-interests for focal lesions.Statistical testsReproducibility and repeatability coefficients for whole prostate and focal lesions derived from median pixel ADC. We estimated the wCV and 95% confidence interval using a variance stabilizing transformation and assessed interreader reliability of focal lesion ADC using the intraclass correlation coefficient (ICC).ResultsThe ADC biases from b0 -b600 and b0 -b800 phantom scans averaged 1.32% and 1.44%, respectively; mean b-value dependence was 0.188%. Repeatability and reproducibility of whole prostate median pixel ADC both yielded wCVs of 0.033 (N = 29). In 10 subjects with an evaluable focal lesion, the individual reader wCVs were 0.148 and 0.074 (repeatability) and 0.137 and 0.078 (reproducibility). All time points demonstrated good to excellent interreader reliability for focal lesion ADC (ICCV1 = 0.89; ICCV2pre = 0.76; ICCV2post = 0.94).Data conclusionThis study met the QIBA claim for prostate ADC. Test-retest repeatability and multi-day reproducibility were largely equivalent. Interreader reliability for focal lesion ADC was high across time points.Level of evidence1 TECHNICAL EFFICACY: Stage 2 TOC CATEGORY: Pelvis.
| S-EPMC9363527 | biostudies-literature
Project description:This study examines the long-term OS of relapsed AML patients who were enrolled to 9 successive ECOG-ACRIN trials for newly diagnosed AML, during 1984-2008. The objectives were to examine whether there is a trend of improvement in the survival of relapsed AML patients in the more recent studies and to search for prognostic factors that are associated with long-term OS after relapse. A total of 3012 patients were enrolled, 1779 (59.1%) achieved CR1 and of these, 58.9% relapsed. The median follow-up was 9.7 years. The median OS from relapse was 0.5 years and the 5-year OS was 10 (±1)%. These results were similar even for the most recent studies. A multivariate model showed that age, cytogenetics at diagnosis, duration of CR1 and undergoing allogeneic transplantation were significantly associated with OS from relapse. Even among patients who relapsed with better prognostic factors; age < 40 and CR1 > 12 months, there was no significant OS difference between the studies. In conclusion, this large cohort appears to confirm that the survival of AML patients postrelapse continues to be dismal and has not improved during the past quarter of a century.
| S-EPMC6699929 | biostudies-literature
Project description:ObjectivesTo assess the long-term outcomes and objective response (OR) to preradiation chemotherapy and radiation in adult high-risk medulloblastoma.Materials and methodsIn this prospective phase II trial, adults with high-risk medulloblastoma were treated with 3 cycles of preradiation cisplatin, etoposide, cyclophosphamide, and vincristine followed by craniospinal radiation (CSI). OR, progression-free survival (PFS), overall survival (OS), and toxicities were assessed.ResultsEleven patients were enrolled over a 6-year period. Six (55%) had subarachnoid metastases. Two (18%) had an OR to preradiation chemotherapy. Two (18%) progressed while on chemotherapy. Completion of CSI was not compromised. The OR rate after chemotherapy and radiation was 45% (5/11). Nonevaluable patients at both time-points weakened the response data conclusions. Median PFS was 43.8 months. Five-year PFS was 27%. Five-year OS was 55%. Nonmetastatic (M0) and metastatic (M+) patients had similar outcomes.ConclusionsThe OR to this preradiation chemotherapy regimen is lower than anticipated from the adult and pediatric literature raising a question about comparative efficacy of chemotherapy in different age groups. The OS achieved is similar to retrospective adult series, but worse than pediatric outcomes. Although this regimen can be administered without compromising delivery of CSI, our results do not provide support for the use of this neoadjuvant chemotherapy for adult medulloblastoma.
| S-EPMC5352534 | biostudies-literature
Project description:Racial disparity in breast cancer outcomes exists between African American and Caucasian women in the United States. We have evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for breast cancer patients in the context of a randomized, phase III adjuvant trial.This study compared outcomes between 386 patients of African ancestry (AA) and 2473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial; ECOG-ACRIN-E5103. The primary efficacy endpoint, invasive disease free survival (DFS) and clinically significant toxicities were compared including: anthracycline-induced congestive heart failure (CHF), taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension.Overall, AAs had significantly inferior DFS (p=0.002; HR=1.5) compared with EAs. This was significant in the estrogen receptor-positive subgroup (p=0.03); with a similar, non-significant trend for those who had triple negative breast cancer (TNBC; p=0.12). AAs also had significantly more grade 3-4 TIPN (OR=2.9; p=2.4 ×10-11) and grade 3-4 bevacizumab-induced hypertension (OR=1.6; p=0.02), with a trend for more CHF (OR=1.8; p=0.08). AAs had significantly more dose reductions for paclitaxel (p=6.6 ×10-6). In AAs, dose reductions in paclitaxel had a significant negative impact on DFS (p=0.03); whereas in EAs, dose reductions did not impact outcome (p=0.35).AAs had inferior DFS with more clinically important toxicities in ECOG-ACRIN-E5103. The altered risk to benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus centered on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions for paclitaxel, especially due to TIPN, are warranted for this population.
| S-EPMC5765553 | biostudies-other
Project description:BackgroundThe optimal surveillance strategy for pancreatic cysts, which occur in up to 20% of the adult population, is ill defined. The risk of malignant degeneration of these cysts is low, however the morbidity and mortality associated with pancreatic cancer are high. Two clinical surveillance guidelines are in regular use. Both the Fukuoka and American Gastroenterological Association (AGA) guidelines rely on radiographic and endoscopic imaging. They differ primarily in their recommended frequencies of interval surveillance imaging. While evidence driven clinical guidelines should promote higher quality care, competing guidelines on the same topic may provide discordant recommendations and potential reduction in the quality and/or value of care.ObjectivesThe primary objective is to compare the clinical effectiveness of the two surveillance guidelines to identify patients most likely to benefit from pancreatic resection. Secondary objectives include comparison of resource utilization, patient reported outcomes, incidental findings are other clinical outcomes.Methods4606 asymptomatic patients with newly identified pancreatic cysts ≥1 cm in diameter will be randomized 1:1 to high intensity (Fukuoka) or low intensity (AGA) surveillance. All participants will be followed prospectively for 5 years.ConclusionDiffering guidelines confuse providers, patients and policymakers. This large, prospective, randomized trial will compare the clinical effectiveness and resource allocation requirements of two guidelines addressing a common clinical entity. CLINICALTRIALS.Gov identifierNCT04239573.
| S-EPMC7686040 | biostudies-literature
Project description:BackgroundAtrasentan, an oral endothelin receptor A antagonist, demonstrated phase 1 activity in patients with renal cell carcinoma (RCC). A phase 2 study was undertaken in patients with measurable or bone-only metastatic RCC in the pre-VEGF/TKI era.Methods and materialsPatients were stratified by disease status and prior immunotherapy. Eligible patients had no prior chemotherapy, 0 to 1 prior immunotherapies, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received atrasentan 10 mg per day until progression. The primary end point was progression-free (PF) rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A 2-stage design was used for cohorts without prior immunotherapy.ResultsFrom 2003 to 2005, 98 patients were registered. Median treatment duration was 9.9 weeks (range, 0.3-107 weeks). Toxicities were mild; 71% of patients reported no grade 3 or higher treatment-related events. Grade 4 events included neutropenia (n = 3), dyspnea (n = 2), thrombosis (n = 1), and arrhythmia (n = 1). Two grade 5 events (dyspnea and constitutional) were possibly treatment related. Six-month PF rates (90% confidence interval) were 14% (6-25), 0% (0-39), 8% (1-23), and 22% (8-44), respectively, for patients with prior immunotherapy/measurable disease (n = 44), prior immunotherapy/bone metastases (n = 6), no prior immunotherapy/measurable disease (n = 25), and no prior immunotherapy/bone metastases (n = 18). Median PF survival was 2.3 months (95% confidence interval, 2.0-3.5 months).ConclusionAlthough well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC.
| S-EPMC4637227 | biostudies-literature
Project description:BackgroundBlockade of human epidermal growth factor receptor type 2 (HER2) has dramatically improved outcome for patients with HER2-positive breast cancer. Trastuzumab, an anti-HER2 monoclonal antibody, has previously demonstrated improvement in overall survival (OS) in patients with metastatic and early stage HER2-positive breast cancer. However, trastuzumab can cause congestive heart failure (CHF) with an increased frequency for patients who have also received an anthracycline. The current trial was designed to evaluate the impact of the duration of trastuzumab on CHF.MethodsE2198 included 227 eligible women with histologically confirmed stage II or IIIA HER2-positive breast cancer. The patients were randomised to receive 12 weeks of paclitaxel and trastuzumab followed by four cycles of doxorubicin and cyclophosphamide (abbreviated Arm) or the aforementioned treatment with additional 1 year of trastuzumab (conventional Arm). The primary end point was to evaluate the safety of this variable duration of trastuzumab therapy, particularly cardiac toxicity defined as CHF or left ventricular ejection fraction decrease >10%. Secondary end points included disease-free survival (DFS) and OS.ResultsCompared with 12-week treatment with trastuzumab, 1 year of trastuzumab-based therapy did not increase the frequency or severity of cardiac toxicity: three patients on the abbreviated Arm and four on the conventional Arm experienced CHF. The 5-year DFS was 76% and 73% for the abbreviated and conventional Arms, respectively, with a hazard ratio (HR) of 1.3 (95% CI: 0.8-2.1; P=0.3). There was also no statistically significance difference in OS (HR, 1.4; P=0.3).ConclusionsCompared with 12 weeks of treatment, 1 year of treatment with trastuzumab did not significantly increase the risk of cardiac toxicity. Although not powered for efficacy comparisons, the longer duration of trastuzumab therapy did not demonstrate a signal for marked superiority.
| S-EPMC4701997 | biostudies-literature
Project description:PurposeUnderstanding the role of transoral surgery in oropharyngeal cancer (OPC) requires prospective, randomized multi-institutional data. Meticulous evaluation of surgeon expertise and surgical quality assurance (QA) will be critical to the validity of such trials. We describe a novel surgeon credentialing and QA process developed to support the ECOG-ACRIN Cancer Research Group E3311 (E3311) and report outcomes related to QA.Patients and methodsE3311 was a phase II randomized clinical trial of transoral surgery followed by low- or standard-dose, risk-adjusted post-operative therapy with stage III-IVa (AJCC 7th edition) HPV-associated OPC. In order to be credentialed to accrue to this trial, surgeons were required to demonstrate active hospital credentials and technique-specific surgical expertise with ≥20 cases of transoral resection for OPC. In addition, 10 paired operative and surgical pathology reports from the preceding 24 months were reviewed by an expert panel. Ongoing QA required <10% rate of positive margins, low oropharyngeal bleeding rates, and accrual of at least one patient per 12 months. Otherwise surgeons were placed on hold and not permitted to accrue until re-credentialed using a new series of transoral resections.Results120 surgeons trained in transoral minimally invasive surgery applied for credentialing for E3311 and after peer-review, 87 (73%) were approved from 59 centers. During QA on E3311, positive final pathologic margins were reported in 19 (3.8%) patients. Grade III/IV and grade V oropharyngeal bleeding was reported in 29 (5.9%) and 1 (0.2%) of patients.ConclusionsWe provide proof of concept that a comprehensive credentialing process can support multicenter transoral head and neck surgical oncology trials, with low incidence of positive margins and *grade III/V oropharyngeal bleeding.
| S-EPMC7771718 | biostudies-literature
Project description:t(8;21) is one of the most frequent chromosomal abnormalities observed in acute myeloid leukemia (AML). However, expression of AML1-ETO is not sufficient to induce transformation in vivo. Consistent with this observation, patients with this translocation harbor additional genetic abnormalities, suggesting a requirement for cooperating mutations. To better define the genetic landscape in AML and distinguish driver from passenger mutations, we compared the mutational profiles of AML1-ETO-driven mouse models of leukemia with the mutational profiles of human AML patients. We identified TET2 and PTPN11 mutations in both mouse and human AML and then demonstrated the ability of Tet2 loss and PTPN11 D61Y to initiate leukemogenesis in concert with expression of AML1-ETO in vivo. This integrative genetic profiling approach allowed us to accurately predict cooperating events in t(8;21)(+) AML in a robust and unbiased manner, while also revealing functional convergence in mouse and human AML.
| S-EPMC4710200 | biostudies-literature