Marinela Capanu

Marinela Capanu
Memorial Sloan Kettering Cancer Center | MSKCC · Bioinformatics Core

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371
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Publications

Publications (371)
Article
Background Adjuvant mFOLFIRINOX (mFFX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). There are limited data on adjuvant mFFX outcomes outside clinical trials. Methods Institutional databases queried to identify patients with resected PDAC who received ≥1 dose adjuvant mFFX. Primary endpoints: recurr...
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The genomic features of pancreatic ductal adenocarcinoma (PDAC) have been well described, yet the evolutionary contexts within which those features occur remains unexplored. We studied the genome landscapes, phylogenies and clonal compositions of 91 PDACs in relation to clinicopathologic features. There was no difference in the number of driver mut...
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Introduction Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes. Methods The primary objective of this retrospective study...
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TPS4630 Background: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer with poor prognosis. While pembrolizumab is a NCCN recommended treatment, our prior study showed no benefit in patients with liver metastases (NCT02673333). ¹ Preclinical evidence suggests combining liver-directed radiation therapy (RT) with pembrolizumab might enhan...
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4170 Background: Adjuvant chemotherapy with mFFX is the standard for pts with ECOG 0-1 (1) after pancreatectomy for resectable PC. Herein, we report long-term survival data on an expanded cohort and present comprehensive genomic analyses. Methods: Pts with resected PC who received >1 dose of adjuvant mFFX identified from institutional databases. Pr...
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4041 Background: ecDNA-enabled amplification of oncogenes is associated with increased expression and poor prognosis and is believed to contribute to treatment resistance. However, the prognostic implications of ecDNA amplification on specific targeted therapy outcomes remains unknown. We investigated whether ERBB2ecDNA positivity (+) in EGC is ass...
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e16384 Background: Fibrolamellar carcinoma (FLC) is a rare form of primary liver cancer which affects young adults and adolescents without underlying liver disease or cirrhosis. The tumors are typically well circumscribed masses characterized pathologically by well differentiated polygonal hepatic cells with eosinophilic and granular cytoplasm surr...
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e16193 Background: Common risk factors for hepatocellular carcinoma (HCC) include viral hepatitis (hepatitis B and hepatitis C), alcoholic liver disease, and metabolic dysfunction-associated steatohepatitis (MASH). Non-risk factored HCC has been suggested where patients who do not have common risk factors develop HCC (Journal of Clinical Oncology V...
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Background Mutated KRAS is the most common oncogene alteration in pancreatic cancer (PDAC), and KRAS G12C mutations (KRAS G12Cmut) are observed in 1-2%. Several inhibitors of KRAS G12C have recently demonstrated promise in solid tumors, including PDAC. Little is known regarding clinical, genomics and outcome data of this population. Methods Patien...
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Anti-programmed death 1 (PD-1) inhibitors are the standard of care for advanced gastroesophageal cancer. Although recommendations and approval by regulatory agencies are often based on programmed death ligand 1 (PD-L1) expression, pathologic assessments of PD-L1 status have several limitations. Single-site biopsies do not adequately capture disease...
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Purpose Targeted therapies have improved outcomes for patients with metastatic colorectal cancer, but their impact is limited by rapid emergence of resistance. We hypothesized that an understanding of the underlying genetic mechanisms and intrinsic tumor features that mediate resistance to therapy will guide new therapeutic strategies and ultimatel...
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Purpose To investigate the differences in baseline staging of anal squamous cell carcinoma based on CT, MRI, and PET/CT, and the resultant impact on the radiation plan. Methods This retrospective study included consecutive patients with anal squamous cell carcinoma who underwent baseline pelvic MRI, CT, and PET/CT (all examinations within 3 weeks...
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Purpose To investigate the prevalence of FLCN, BAP1, SDH, and MET mutations in an oncologic cohort and determine the prevalence, clinical features, and imaging features of renal cell carcinoma (RCC) associated with these mutations. Secondarily, to determine the prevalence of encountered benign renal lesions. Materials and Methods From 25 220 patien...
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In advanced pancreatic neuroendocrine neoplasms (PanNEN), there is little data detailing the frequency of genetic alterations identified in cell free DNA (cfDNA), plasma-tissue concordance of detected alterations, and clinical utility of cfDNA. Patients with metastatic PanNENs underwent cfDNA collection in routine practice. Next-generation sequenci...
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37 Background: Colitis-associated cancer (CAC) is a devastating complication of inflammatory bowel disease. CAC tumor biology differs from that of sporadic colorectal cancer (CRC). Patients (pts) with (w/) metastatic CAC (mCAC) treated w/ 1st line (1L) chemotherapy have worse outcomes than pts w/ sporadic metastatic CRC (mCRC). EGFR inhibitor (EGFR...
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409 Background: PD-1 inhibitors are now standard in advanced EG cancer, with approval often based on PD-L1 CPS. However, single site biopsies are inadequate due to disease heterogeneity, dynamic changes over time, and variability due to operator, choice of assay, and tumor content. Better methods of non-invasive, comprehensive PD-L1 evaluation are...
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Background: Most pancreatic cancers (PC) are resistant to immunotherapy and have a poor prognosis with advanced stage (III/IV, 80%). However, recent cancer vaccine trials have demonstrated that long-term host anti-cancer immunity can improve outcomes of patients (pts) with resectable PC (stage I/II, 20%), harboring high-quality neoantigens or selec...
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The benefit of primary tumor resection in distant metastatic small bowel neuroendocrine tumors (SBNETs) is controversial, with treatment-based morbidity not well-defined. We aimed to determine the impact of primary tumor resection on development of disease-specific complications in patients with metastatic well-differentiated SBNETs. A retrospectiv...
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Background: The addition of nivolumab to chemotherapy improves survival in patients with advanced oesophagogastric (oesophageal, gastric, or gastro-oesophageal junction) adenocarcinoma; however, outcomes remain poor. We assessed the safety and activity of regorafenib in combination with nivolumab and chemotherapy in the first-line treatment of adv...
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PURPOSE Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors. METHODS An open forum for HCC-experienced health care workers...
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Background: Cancers with non-V600 BRAF-activating alterations have no matched therapy. Preclinical data suggest that these tumors depend on ERK signaling; however, clinical response to MEK/ERK inhibitors has overall been low. We hypothesized that a narrow therapeutic index, driven by ERK inhibition in healthy (wild-type) tissues, limits the effica...
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Purpose: To determine the genetic predisposition underlying pancreatic acinar cell carcinoma (PACC) and characterize its genomic features. Methods: Both somatic and germline analyses were performed using an Food and Drug Administration-authorized matched tumor/normal sequencing assay on a clinical cohort of 28,780 patients with cancer, 49 of who...
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Background Diffusion-weighted (DW) imaging is useful in detecting tumor in the primary tumor bed in locally advanced rectal cancer (LARC) after neoadjuvant therapy, but its value in detecting extramural venous invasion (EMVI) and tumor deposit is not well validated. Purpose To evaluate diagnostic accuracy and association with patient prognosis of...
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BACKGROUND: Imaging reports that consistently document all disease sites with potential to increase surgical complexity or morbidity can facilitate ovarian cancer treatment planning. OBJECTIVES: To compare simple structured reports and synoptic reports for pre-treatment CT examinations in patients with advanced ovarian cancer in terms of completene...
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Purpose: We report updated clinical outcomes from a phase II study of pembrolizumab, trastuzumab, and chemotherapy (PTC) in metastatic esophagogastric (EG) cancer in conjunction with outcomes from an independent MSK cohort. Experimental design: The significance of pre-treatment 89Zr-trastuzumab PET, plasma circulating tumor DNA (ctDNA) dynamics,...
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4164 Background: Pancreatic cancer (PC) is largely refractory to immune checkpoint blockade (ICB) in genomically unselected patients (pts). Synergistic effects of combined ICB and radiotherapy have been suggested in varied solid tumors. Few studies have evaluated this approach in pts with PC. We sought to evaluate the safety and efficacy of PD-L1 i...
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4140 Background: Maintenance olaparib improves PFS in g BRCA1/2m (core HRD) in mPDAC (Golan, NEJM 2019). Whether other HRD indicators, such as gene mutations other than g BRCA1/2m (non-Core HRD, Cohort B) and exceptional platinum responders (Cohort C, response > 6 months) may benefit from PARPi in mPDAC remains unanswered. We hypothesized that pemb...
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4154 Background: ctDNA provides opportunities for identifying targeted therapies, a source to conduct NGS when tissue acquisition is infeasible, detection of minimal residual disease (MRD), and identification of resistance mutations. There are limited large data sets to inform clinical utility and limited correlation of NGS of ctDNA and tumor in PC...
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e16024 Background: In DESTINY-Gastric01/02, T-DXd improved objective response rates (ORR) and overall survival (OS) relative to chemotherapy in patients (pts) with trastuzumab-refractory HER2+ EGC. We sought to identify clinicopathologic features that predict response and resistance to T-DXd, in a cohort from Memorial Sloan Kettering Cancer Center...
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Background: Perioperative chemotherapy is standard of care management for locally advanced gastric cancer (GC), but a substantial proportion of patients do not complete adjuvant therapy due to postoperative complications and prolonged recovery. Administration of all chemotherapy prior to surgery in the form of total neoadjuvant therapy (TNT) may o...
Article
Most pancreatic ductal adenocarcinomas (PDAC) are lethal and resistant to immunotherapy. Thus, identifying the immunogenic subgroup (iPDAC) and therapeutic targets can save lives. Herein, we present molecular features of iPDAC. 3 cohorts (A, B, C) from 288 patients whose sequenced tumors (MSK-IMPACT) were classified by homologous recombination defi...
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A novel variable selection method for low-dimensional generalized linear models is introduced. The new approach called AIC OPTimization via STABility Selection (OPT-STABS) repeatedly subsamples the data, minimizes Akaike's Information Criterion (AIC) over a sequence of nested models for each subsample, and includes in the final model those predicto...
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Objective: To determine the safety and efficacy of adding the anti-PD-1 antibody durvalumab to induction FOLFOX and preoperative chemotherapy in locally advanced esophageal adenocarcinoma. Background: Neoadjuvant induction FOLFOX followed by PET directed chemoradiation has demonstrated improved survival for esophageal adenocarcinoma. There is cl...
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685 Background: Adjuvant mFFX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) is a standard-of-care for fit patients (pts) with resected PDAC, owing to the immediate practice-changing PRODIGE 24/CCTG PA6 trial (2018). Five-year follow-up: median overall survival (mOS) 53.3 months (m) and median disease-free survival (mDFS) 21.4 m for mFFX vs...
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653 Background: PanNENs represent 1-2% of all pancreatic neoplasms. The genomic landscape derived from PanNEN tumor tissue has been described previously. There are little data detailing the frequency of genetic alterations identified in cfDNA in an advanced PanNEN population, the plasma-tissue concordance of detected alterations, and the clinical u...
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Importance: Clonal hematopoiesis (CH) has been associated with development of atherosclerosis and leukemia and worse survival among patients with cancer; however, the association with cancer therapy efficacy, in particular immune checkpoint blockade (ICB), and toxicity has not yet been established. Given the widespread use of ICB and the critical...
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Variations in HER2 expression between the primary tumor and metastases may contribute to drug resistance in HER2-positive metastatic esophagogastric cancer (mEGC). 89Zr-trastuzumab positron emission tomography (HER2 PET) holds promise for noninvasive assessment of variations in HER2 expression and target engagement. The aim of this study is to desc...
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Background and Objective Pancreatic ductal adenocarcinoma (PDAC) is characterized by the occurrence of pathogenic variants in BRCA1/2 in 5–6% of patients. Biallelic loss of BRCA1/2 enriches for response to platinum agents and poly (ADP-ribose) polymerase 1 inhibitors. There is a dearth of evidence on the mechanism of inactivation of the wild-type B...
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Purpose: Characterizing germline and somatic ATM variants (gATMm, sATMm), zygosity and their contribution to homologous recombination deficiency (HRD) is important for therapeutic strategy in pancreas ductal adenocarcinoma (PDAC). Methods: Clinico-genomic data for patients with PDAC and other cancers with ATM variants was abstracted. Genomic ins...
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Importance: Brain metastasis (BrM) in gastroesophageal adenocarcinoma (GEA) is a rare and poorly understood phenomenon associated with poor prognosis. Objectives: To examine the clinical and genomic features of patients with BrM from GEA and evaluate factors associated with survival. Design, setting, and participants: In this single-institutio...
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Purpose To evaluate an MRI-based radiomic texture classifier alone and combined with radiologist qualitative assessment in predicting pathological complete response (pCR) using restaging MRI with internal training and external validation. Methods Consecutive patients with locally advanced rectal cancer (LARC) who underwent neoadjuvant therapy foll...
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Objective: To evaluate the efficacy of chemotherapy in patients with microsatellite instability-high (MSI-high) gastric cancer. Summary background data: Although MSI-high gastric cancer is associated with superior prognosis, recent studies question the benefit of perioperative chemotherapy in this population. Methods: Locally advanced gastric...
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Patients with high-grade serous ovarian cancer suffer poor prognosis and variable response to treatment. Known prognostic factors for this disease include homologous recombination deficiency status, age, pathological stage and residual disease status after debulking surgery. Recent work has highlighted important prognostic information captured in c...
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Background: Cutaneous metastases in pancreatic cancer (PC) are rare. Herein, we evaluate the clinical, genomic, and other descriptors of patients with PC and cutaneous metastases. Methods: Institutional databases were queried, and clinical history, demographics, PC cutaneous metastasis details, and overall survival (OS) from cutaneous metastasis...
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Background Pancreatic adenocarcinoma (PDAC) remains a refractory disease; however, modern cytotoxic chemotherapeutics can induce tumor regression and extend life. A blood‐based, pharmacogenomic, chemosensitivity assay using gene expression profiling of circulating tumor and invasive cells (CTICs) to predict treatment response was previously develop...
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4110 Background: HCC is often diagnosed based on high-quality cross-sectional imaging, and when a biopsy is pursued, acquisition of tissue may be of limited quantity and quality or complicated by underlying medical comorbidities. NGS of tumor derived circulating cfDNA represents an investigational tool for non-invasive molecular profiling, that has...
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4029 Background: Induction FOLFOX followed by PET-directed CRT prior to surgery demonstrated positive results in the CALGB 80803 study. We investigated the safety and efficacy of adding D, an anti-PD-L1 antibody, to PET-directed CRT. Methods: Patients (pts) with locally advanced esophageal/GEJ adenocarcinoma were enrolled. Pts received 2 cycles of...
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Introduction: Lutetium-177 (177Lu)-DOTATATE received FDA approval in 2018 to treat somatostatin receptor (SSTR) positive gastroenteropancreatic neuroendocrine tumors (NETs). Little data are available on response and outcomes for well differentiated (WD) high grade (HG) NETs treated with 177Lu-DOTATATE. Materials and methods: Patients with WD HG...
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Background It is unknown how body fat distribution modulates the cardiometabolic risk of testicular cancer survivors (TCSs) after cisplatin-based chemotherapy. Methods For 455 patients enrolled in The Platinum Study at Memorial Sloan Kettering Cancer Center, visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified on pre-chemotherapy CT...
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Background: A biologic, degradable extracellular matrix (ECM) has been shown to support esophageal tissue remodeling, which could reduce the risk of anastomotic leak following total gastrectomy and esophagectomy. We evaluated the safety and efficacy of reinforcing the anastomosis with ECM in reducing anastomotic leak as compared to a matched cohor...
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PURPOSE Subset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with...
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Objectives: Describe the cumulative incidence (CUIN) of peritoneal carcinomatosis (PC) and survival in patients presenting with advanced rectal cancer at staging pelvic MRI. Methods: From 2013 to 2018, clinicopathologic records of patients with pretreatment rectal MRI clinical (c)T3c, cT3d, cT4a, and cT4b primary rectal adenocarcinoma were retro...
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506 Background: Immune checkpoint inhibitors (ICIs) have antitumor activity in some solid tumors, however a role for ICI’s in the treatment of neuroendocrine neoplasms (NENs) is uncertain. We analyzed response and outcomes of NENs, both well differentiated neuroendocrine tumors (WDNET) and poorly differentiated neuroendocrine carcinomas (PDNEC), tr...
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347 Background: Brain metastases (BrM) rarely occur in patients with metastatic gastroesophageal adenocarcinoma (GEA) and represent a unique therapeutic challenge. We describe the unique clinical, molecular, and genomic factors associated with mGEA cancer and BrM development in order to help guide future clinical management. Methods: Patients (pts)...
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437 Background: TACE is a standard of care for liver limited HCC and impacts the immune microenvironment, potentially augmenting the effects of immune checkpoint inhibitors. Methods: This is a multicenter phase 1 study of NIVO and deb-TACE in unresectable HCC pts and Child Pugh A cirrhosis (NCT03143270). The primary objective is to assess safety. S...
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615 Background: The occurrence of cutaneous metastasis from pancreatic cancer (PC) is rare, and the exact incidence is unknown. The literature to date is primarily limited to isolated case reports. Herein, we evaluate the clinical, genomic, and other descriptors of patients with PC and cutaneous metastases. Methods: Institutional databases were que...
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Purpose: Paclitaxel plus ramucirumab is a standard second-line regimen for patients with advanced gastric adenocarcinoma, but clinical benefit remains modest. One potential resistance mechanism to VEGFR2 inhibition is activation of the PDGF/PDGFR pathway, which can be blocked by the selective inhibitor crenolanib. Therefore, we performed a phase I...
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Background Hepatocellular carcinoma (HCC) patient-derived xenograft (PDX) models hold potential to advance knowledge in HCC biology to help improve systemic therapies. Beside hepatitis B virus-associated tumors, HCC is poorly established in PDX. Methods PDX formation from fresh HCC biopsies were obtained and implanted intrahepatically or in subren...
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Objectives To investigate the inter- and intra-reader agreement of immune Response Evaluation Criteria in Solid Tumors (iRECIST) and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in patients with lung cancer treated with immunotherapy. Materials and Methods This retrospective study included 85 patients with lung cancer trea...
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Background: Radiation therapy (RT) for breast cancer increases risk of coronary artery disease (CAD). Women treated for left- vs right-sided breast cancer receive greater heart radiation exposure, which may further increase this risk. The risk of radiation-associated CAD specifically among younger breast cancer survivors is not well defined. Obje...
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Background Patients with germline/somatic BRCA1/BRCA2 mutations (g/sBRCA1/2) comprise a distinct biologic subgroup of pancreas ductal adenocarcinoma (PDAC). Methods Institutional databases were queried to identify patients who had PDAC with g/sBRCA1/2. Demographics, clinicopathologic details, genomic data (annotation sBRCA1/2 according to a precis...
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Purpose: The LI-RADS Treatment Response (LR-TR) algorithm was introduced in 2017 to assist radiologists in assessing hepatocellular carcinoma (HCC) response following locoregional therapy. The objective of this study was to evaluate the associations between pre-treatment LI-RADS diagnostic categories, post-treatment LR-TR categories, and mRECIST r...
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Importance Among patients with esophagogastric cancers, only individuals who present with known features of heritable cancer syndromes are referred for genetic testing. Broader testing might identify additional patients with germline alterations. Objectives To examine the prevalence of likely pathogenic or pathogenic (LP/P) germline alterations am...
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Purpose To assess the value of diffusion-weighted MRI (DW-MRI) in the non-invasive prediction of blastemal remnant after neoadjuvant chemotherapy in nephroblastoma. Methods This IRB-approved study included 32 pediatric patients with 35 tumors who underwent DW-MRI prior and after completion of neoadjuvant chemotherapy and subsequent surgical resect...
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A T1 sequence on routine baseline staging rectal magnetic resonance imaging (MRI) is thought to help detect bone lesions. Our primary aim was to evaluate the incidence of bone lesions encountered on baseline staging rectal MRI, particularly the prevalence of bone metastases. This retrospective study included patients with rectal adenocarcinoma who...
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Purpose The safety of multiple doses of gadolinium-based MRI IV contrast has recently been called in to question. While the long-term safety is being investigated, here, we seek to determine if there is added value to the use of IV contrast for improving detection of tumoral recurrences in children with a history of abdominal neuroblastoma. Method...
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5019 Background: Preferential fat accumulation in the visceral compartment (i.e. central adiposity) increases cardiovascular risk in the general population independent of body mass index (BMI). We investigated how body fat distribution modulates the cardiometabolic risk of male germ cell tumor (GCT) survivors after cisplatin-based chemotherapy. Met...
Article
e16204 Background: The somatostatin analogs (SSAs) octreotide LAR and lanreotide are equally acceptable in the NCCN guidelines to treat WDNETs. Average Sales Price for 1 year of lanreotide at 120mg is $106,802 versus $53,471 for 1 year of octreotide LAR 20mg and $80,206 for 1 year of 30mg. Lanreotide is given by “deep subcutaneous injection” while...
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Objective/background: The purpose was to determine whether adding Pmab versus no Pmab to an adjuvant regimen of HAI of floxuridine (FUDR) plus systemic (SYS) leucovorin, fluorouracil, and irinotecan (FOLFIRI) improves 15-month recurrence-free survival (RFS) for patients with RAS wild-type (WT) colorectal cancer. Secondary endpoints included overal...
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Background Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Methods PDAC patients who underwent surgical resection between 01/2012–06/2014 were identified....
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Purpose: To evaluate the associations between computed tomography (CT) imaging features extracted from the structured American Pancreatic Association (APA)/Society of Abdominal Radiology (SAR) template and overall survival in patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods: This retrospective analysis included consecutive...
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Background Recent evidence suggests a rising incidence of cancer in younger individuals. Herein, we report