Publications by authors named "Jill S Gluskin"

6 Publications

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Accuracy of Magnetic Resonance Imaging-Guided Biopsy to Verify Breast Cancer Pathologic Complete Response After Neoadjuvant Chemotherapy: A Nonrandomized Controlled Trial.

JAMA Netw Open 2021 01 4;4(1):e2034045. Epub 2021 Jan 4.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: After neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) is an optimal outcome and a surrogate end point for improved disease-free and overall survival. To date, surgical resection remains the only reliable method for diagnosing pCR.

Objective: To evaluate the accuracy of magnetic resonance imaging (MRI)-guided biopsy for diagnosing a pCR after NAC compared with reference-standard surgical resection.

Design, Setting, And Participants: Single-arm, phase 1, nonrandomized controlled trial in a single tertiary care cancer center from September 26, 2017, to July 29, 2019. The median follow-up was 1.26 years (interquartile range, 0.85-1.59 years). Data analysis was performed in November 2019. Eligible patients had (1) stage IA to IIIC biopsy-proven operable invasive breast cancer; (2) standard-of-care NAC; (3) MRI before and after NAC, with imaging complete response defined as no residual enhancement on post-NAC MRI; and (4) definitive surgery. Patients were excluded if they were younger than 18 years, had a medical reason precluding study participation, or had a prior history of breast cancer.

Interventions: Post-NAC MRI-guided biopsy without the use of intravenous contrast of the tumor bed before definitive surgery.

Main Outcomes And Measures: The primary end point was the negative predictive value of MRI-guided biopsy, with true-negative defined as negative results of the biopsy (ie, no residual cancer) corresponding to a surgical pCR. Accuracy, sensitivity, positive predictive value, and specificity were also calculated. Two clinical definitions of pCR were independently evaluated: definition 1 was no residual invasive cancer; definition 2, no residual invasive or in situ cancer.

Results: Twenty of 23 patients (87%) had evaluable data (median [interquartile range] age, 51.5 [39.0-57.5] years; 20 women [100%]; 13 White patients [65%]). Of the 20 patients, pre-NAC median tumor size on MRI was 3.0 cm (interquartile range, 2.0-5.0 cm). Nineteen of 20 patients (95%) had invasive ductal carcinoma; 15 of 20 (75%) had stage II cancer; 11 of 20 (55%) had ERBB2 (formerly HER2 or HER2/neu)-positive cancer; and 6 of 20 (30%) had triple-negative cancer. Surgical pathology demonstrated a pCR in 13 of 20 (65%) patients and no pCR in 7 of 20 patients (35%) when pCR definition 1 was used. Results of MRI-guided biopsy had a negative predictive value of 92.8% (95% CI, 66.2%-99.8%), with accuracy of 95% (95% CI, 75.1%-99.9%), sensitivity of 85.8% (95% CI, 42.0%-99.6%), positive predictive value of 100%, and specificity of 100% for pCR definition 1. Only 1 patient had a false-negative MRI-guided biopsy result (surgical pathology showed <0.02 cm of residual invasive cancer).

Conclusions And Relevance: This study's results suggest that the accuracy of MRI-guided biopsy to diagnose a post-NAC pCR approaches that of reference-standard surgical resection. MRI-guided biopsy may be a viable alternative to surgical resection for this population after NAC, which supports the need for further investigation.

Trial Registration: ClinicalTrials.gov Identifier: NCT03289195.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.34045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811182PMC
January 2021

Immunomodulatory Activity of a Colony-stimulating Factor-1 Receptor Inhibitor in Patients with Advanced Refractory Breast or Prostate Cancer: A Phase I Study.

Clin Cancer Res 2020 Nov 26;26(21):5609-5620. Epub 2020 Aug 26.

Cedars-Sinai Medical Center, Los Angeles, California.

Purpose: Tumor-associated macrophages correlate with increased invasiveness, growth, and immunosuppression. Activation of the colony-stimulating factor-1 receptor (CSF-1R) results in proliferation, differentiation, and migration of monocytes/macrophages. This phase I study evaluated the immunologic and clinical activity, and safety profile of CSF-1R inhibition with the mAb LY3022855.

Patients And Methods: Patients with advanced refractory metastatic breast cancer (MBC) or metastatic castration-resistant prostate cancer (mCRPC) were treated with LY3022855 intravenously in 6-week cycles in cohorts: (A) 1.25 mg/kg every 2 weeks (Q2W); (B) 1.0 mg/kg on weeks 1, 2, 4, and 5; (C) 100 mg once weekly; (D)100 mg Q2W. mCRPC patients were enrolled in cohorts A and B; patients with MBC were enrolled in all cohorts. Efficacy was assessed by RECIST and Prostate Cancer Clinical Trials Working Group 2 criteria.

Results: Thirty-four patients (22 MBC; 12 mCRPC) received ≥1 dose of LY3022855. At day 8, circulating CSF-1 levels increased and proinflammatory monocytes CD14CD16 decreased. Best RECIST response was stable disease in five patients with MBC (23%; duration, 82-302 days) and three patients with mCRPC (25%; duration, 50-124 days). Two patients with MBC (cohort A) had durable stable disease >9 months and a third patient with MBC had palpable reduction in a nontarget neck mass. Immune-related gene activation in tumor biopsies posttreatment was observed. Common any grade treatment-related adverse events were fatigue, decreased appetite, nausea, asymptomatic increased lipase, and creatine phosphokinase.

Conclusions: LY3022855 was well tolerated and showed evidence of immune modulation. Clinically meaningful stable disease >9 months was observed in two patients with MBC.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0855DOI Listing
November 2020

PET-CT for Evaluating Breast Cancer Yields Incidental Finding in the Lung.

Radiol Technol 2019 Nov;91(2):120-125

Background: A woman aged 75 years presented with a palpable left axillary lymph node. Mammography showed a spiculated mass in the left breast, demonstrated by biopsy to be triple-negative breast cancer. A positron emission tomography-computed tomography (PET-CT) scan was performed to evaluate the extent of the cancer and revealed an unrelated nonmetastatic, synchronous carcinoid in the left lung. The patient was a nonsmoker and presented with no symptoms of lung disease.

Discussion: Advanced imaging modalities used to evaluate the extent of locally advanced breast cancer have been a keystone in decreasing cancer mortality rates. Mammography is considered the gold standard for breast disease evaluation, but sonography is a valuable modality for correlating suspicious findings and evaluating lesions that might not be visible on mammograms. When a breast biopsy confirms metastasis to the axillary lymph nodes, PET-CT is the modality of choice for cancer staging and ruling out distant metastases.

Conclusion: Imaging tools used to evaluate breast cancer can help determine whether distant metastasis has occurred and in rare cases can help discover other primary cancers. The patient in this case study was 1 of the few patients with an incidental finding of a second nonmetastatic primary malignancy in the lung detected using PET-CT. The risks associated with advanced imaging include exposing patients to additional tests and potentially invasive procedures based on the results. However, in some instances, imaging results can alter the treatment plan and increase survival rates. Further empirical research and case studies are needed to identify clinical outcomes for patients with a second primary cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561062PMC
November 2019

Thyroid neoplasms: incidental findings on extent of disease evaluation CT for other pediatric malignancies.

J Pediatr Surg 2017 Jun 15;52(6):938-943. Epub 2017 Mar 15.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Purpose: We performed a retrospective analysis to evaluate the risk of thyroid cancer in incidental thyroid nodules (ITNs) discovered on CT in patients with a history of pediatric cancer.

Methods: With IRB approval we reviewed the records of pediatric oncology patients age ≤21y with newly detected thyroid nodules on surveillance CT of the neck, chest, chest/abdomen/pelvis, or PET/CT performed between April 2008 and March 2015. Patients with <6months of follow-up after incidental findings, a history of primary thyroid malignancy, or incomplete records were excluded.

Results: The final cohort (N=68) included 35 females and 33 males (mean age 16.0±4.3[SD] years) with a mean follow-up time of 3.7±1.9[SD] years after CT detection of ITN(s). Twenty patients (29.4%) received a follow-up thyroid ultrasound, eleven (16.2%) of whom underwent fine needle aspiration (FNA) for cytopathologic diagnosis. Among these, six (8.8%) underwent thyroid resection, with final pathology demonstrating papillary carcinoma in five (7.4%) and benign pathology in one.

Conclusions: Despite the low incidence of thyroid nodules and low risk of thyroid malignancy in the general pediatric population, we found a significant rate of malignancy in CT-detected ITNs in our pediatric oncology patients, and recommend ultrasound and FNA of these nodules in this high-risk population.

Level Of Evidence: Level IV, retrospective study with no comparison group.
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http://dx.doi.org/10.1016/j.jpedsurg.2017.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466891PMC
June 2017

Response rates of hepatic arterial infusion pump therapy in patients with metastatic colorectal cancer liver metastases refractory to all standard chemotherapies.

J Surg Oncol 2016 Nov 26;114(6):655-663. Epub 2016 Aug 26.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Background And Objectives: To evaluate the role of hepatic arterial infusion (HAI) in patients with metastatic colorectal cancer (mCRC) liver metastases (LM) refractory to oxaliplatin, irinotecan, and fluorouracil-based treatments.

Methods: A search identified patients with mCRC treated after tumor progression on at least three standard systemic therapies.

Results: One hundred and ten patients met criteria for inclusion (i.e., progression on at least three standard agents). Fifty seven patients had LM-only and 53 patients had LM and low volume extrahepatic metastases (LME). Patients with LM-only and LME had a response rate (RR) of 33% and 36%, median survival of 20 months and 11.4 months, respectively. Patients with LM-only had progression free survival of 6 months and hepatic progression free survival of 7.56 months. In a secondary analysis, 46 patients were RECIST-refractory to all standard therapies: LM-only (n = 24) and LME (n = 22). LM-only and LME had a RR of 29% and 36%, and median survival 17.2 months and 9.1 months, respectively.

Conclusions: Patients with refractory mCRC LM can achieve a response to HAI resulting in antitumor activity and improvement in survival. Responses are rarely seen in such heavily treated patients with systemic therapy alone, suggesting a regional directed approach is useful. J. Surg. Oncol. 2016;114:655-663. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jso.24399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570459PMC
November 2016

Hepatocellular Carcinoma and Diffusion-Weighted MRI: Detection and Evaluation of Treatment Response.

J Cancer 2016 13;7(11):1565-70. Epub 2016 Jul 13.

1. Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C276, New York, NY 10065, USA.

Differentiating between cancerous tissue and healthy liver parenchyma could represent a challenge with the only conventional Magnetic Resonance (MR) imaging. Diffusion weighted imaging (DWI) exploits different tissue characteristics to conventional Magnetic Resonance Imaging (MRI) sequences that enhance hepatocellular carcinoma (HCC) detection, characterization, and post-treatment evaluation. Detection of HCC is improved by DWI, infact this technology increases conspicuity of lesions that might otherwise not be identified due to obscuration by adjacent vessels or due to low contrast between the lesion and background liver. It is important to remember that DWI combined with contrast-enhanced MRI has higher sensitivity than DWI alone, and that some patients are not eligible for use of contrast on CT and MRI; in these patients DWI has a prominent role. MRI has advanced beyond structural anatomic imaging to now showing pathophysiologic processes. DWI is a promising way to characterize lesions utilizing the inherent contrast within the liver and has the benefit of not requiring contrast injection. DWI improves detection and characterization of HCC. Proposed clinical uses for DWI include: assessing prognosis, predicting response, monitoring response to therapy, and distinguishing tumor recurrence from treatment effect. Ideally, DWI will help risk stratify patients and will participate in prognostic modeling.
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http://dx.doi.org/10.7150/jca.14582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964141PMC
July 2016