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Pilot study of rapid MR pancreas screening for patients with BRCA mutation.

ABSTRACT: PURPOSE:To develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in breast cancer susceptibility gene (BRCA)-positive individuals. METHODS:An IRB-approved prospective study was conducted. The rapid screening pancreatic MR protocol was designed to be less than 10 min to be performed after a standard breast MRI protocol. Protocol consisted of coronal NT T2 SSFSE, axial NT T2 SSFSE and axial NT rFOV FOCUS DWI, and axial T1. Images were acquired with the patient in the same prone position of breast MRI using the built-in body coil. Image quality was qualitatively assessed by two radiologists with 12 and 13 years of MRI experience, respectively. The imaging protocol was modified until an endpoint of five consecutive patients with high-quality diagnostic images were achieved. Signal-to-noise ratio and contrast-to-noise ratio were assessed. RESULTS:The rapid pancreas MR protocol was successfully completed in all patients. Diagnostic image quality was achieved for all patients. Excellent image quality was achieved for low b values; however, image quality at higher b values was more variable. In one patient, a pancreatic neuroendocrine tumor was found and the patient was treated surgically. In four patients, small pancreatic cystic lesions were detected. In one subject, a hepatic mass was identified and confirmed as adenoma by liver MRI. CONCLUSION:Rapid MR protocol for pancreatic cancer screening is feasible and has the potential to play a role in screening BRCA patients undergoing breast MRI. KEY POINT:• Develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in BRCA mutation positive individuals.

SUBMITTER: Corrias G

PROVIDER: S-EPMC6609466 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Pilot study of rapid MR pancreas screening for patients with BRCA mutation.

Corrias Giuseppe G Raeside Mitchell C MC Agostini Andrea A Huicochea-Castellanos Sandra S Aramburu-Nunez David D Paudyal Ramesh R Shukla-Dave Amita A Smelianskaia Olga O Capanu Marinela M Zheng Junting J Fung Maggie M Kelsen David P DP Mangino Debra A DA Robson Mark E ME Goldfrank Deborah J DJ Carter Jean J Allen Peter J PJ Conti Bettina B Monti Serena S Do Richard K G RKG Mannelli Lorenzo L

European radiology 20190128 8

<h4>Purpose</h4>To develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in breast cancer susceptibility gene (BRCA)-positive individuals.<h4>Methods</h4>An IRB-approved prospective study was conducted. The rapid screening pancreatic MR protocol was designed to be less than 10 min to be performed after a standard breast MRI protocol. Protocol consisted of coronal NT T2 SSFSE, axial NT T2 SSF ...[more]

PMID: 30689033

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Project description:BackgroundPatients with germline/somatic BRCA1/BRCA2 mutations (g/sBRCA1/2) comprise a distinct biologic subgroup of pancreas ductal adenocarcinoma (PDAC).MethodsInstitutional databases were queried to identify patients who had PDAC with g/sBRCA1/2. Demographics, clinicopathologic details, genomic data (annotation sBRCA1/2 according to a precision oncology knowledge base for somatic mutations), zygosity, and outcomes were abstracted. Overall survival (OS) was estimated using the Kaplan-Meier method.ResultsIn total, 136 patients with g/sBRCA1/2 were identified between January 2011 and June 2020. Germline BRCA1/2 (gBRCA1/2) mutation was identified in 116 patients (85%). Oncogenic somatic BRCA1/2 (sBRCA1/2) mutation was present in 20 patients (15%). Seventy-seven patients had biallelic BRCA1/2 mutations (83%), and 16 (17%) had heterozygous mutations. Sixty-five patients with stage IV disease received frontline platinum therapy, and 52 (80%) had a partial response. The median OS for entire cohort was 27.6 months (95% CI, 24.9-34.5 months), and the median OS for patients who had stage IV disease was 23 months (95% CI, 19-26 months). Seventy-one patients received a poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor (PARPi), and 52 received PARPi monotherapy. For maintenance PARPi, 10 patients (36%) had a partial response, 12 (43%) had stable disease, and 6 (21%) had progression of disease as their best response. Six patients (21%) received maintenance PARPi for >2 years. For those with stage IV disease who received frontline platinum, the median OS was 26 months (95% CI, 20-52 months) for biallelic patients (n = 39) and 8.66 months (95% CI, 6.2 months to not reached) for heterozygous patients (n = 4). The median OS for those who received PARPi therapy was 26.5 months (95% CI, 24-53 months) for biallelic patients (n = 25) and 8.66 months (95% CI, 7.23 months to not reached) for heterozygous patients (n = 2).Conclusionsg/sBRCA1/2 mutations did not appear to have different actionable utility. Platinum and PARPi therapies offer therapeutic benefit, and very durable outcomes are observed in a subset of patients who have g/sBRCA1/2 mutations with biallelic status.

Project description:PurposeFive percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (gBRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in gBRCA/PALB2+ PDAC.Patients and methodsEligible patients had untreated gBRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses.ResultsFifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B (P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B (P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia.ConclusionCisplatin and gemcitabine is an effective regimen in advanced gBRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in gBRCA/PALB2+ PDAC.

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Pilot study of rapid MR pancreas screening for patients with BRCA mutation.

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Pilot study of rapid MR pancreas screening for patients with BRCA mutation.

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