Janis O'Malley

A Phase I Clinical Trial of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Patients with Recurrent Gynecologic Cancer

Purpose: Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and a somatostatin receptor (SSTR) that allows for noninvasive gene transfer imaging. The purpose of this study was to identify the maximum tolerated dose (MTD), toxicities, clinical efficacy, and biologic effects of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Experimental Design: Eligible patients were treated intraperitoneally for 3 days with 1 × 109 to 1 × 1012 vp/dose of Ad5.SSTR/TK.RGD followed by intravenous ganciclovir for 14 days. Toxicity and clinical efficacy were assessed using Common Toxicity Criteria (CTC) Adverse Events grading and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Imaging using In-111 pentetreotide was obtained before and after treatment. Tissue samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding, and antibody response. Results: Twelve patients were treated in three cohorts. The most common vector-related clinical toxicities were grade I/II constitutional or pain symptoms, experienced most often in patients treated at the highest dose. MTD was not identified. Five patients showed stable disease; all others experienced progressive disease. One patient with stable disease experienced complete resolution of disease and normalization of CA125 on further follow-up. Imaging detected increased In-111 pentetreotide retention in patients treated at the highest dose. Ancillary studies showed presence of Ad5.SSTR/TK.RGD virus and HSV1-tk expression in ascites samples collected at various time points in most patients treated within the higher dose cohorts. Conclusions: This study shows the safety, potential efficacy, and possible gene transfer imaging capacity of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Further development of this novel gene therapeutic appears to be warranted. Clin Cancer Res; 18(12); 3440–51. ©2012 AACR.

Pilot trial of preoperative (neoadjuvant) letrozole in combination with bevacizumab in postmenopausal women with newly diagnosed estrogen receptor- or progesterone receptor-positive breast cancer.

INTRODUCTION Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of antiestrogen adjuvant therapy. We designed a pilot study to assess the feasibility and short-term efficacy of neoadjuvant letrozole and bevacizumab (anti-VEGF) in postmenopausal women with stage II and III estrogen receptor/progesterone receptor-positive breast cancer. PATIENTS AND METHODS Patients were treated with a neoadjuvant regimen of letrozole orally 2.5 mg/day and bevacizumab intravenously 15 mg/kg every 3 weeks for a total of 24 weeks before the surgical treatment of their breast cancer. Patients were followed for toxicity at 3-week intervals, and tumor assessment (a physical examination and ultrasound) was performed at 6-week intervals. Positron emission tomography (PET) scans were performed before therapy and 6 weeks after the initiation of therapy. RESULTS Twenty-five evaluable patients were treated. The regimen was well-tolerated, except in 2 patients who were taken off the study for difficulties controlling their hypertension. An objective clinical response occurred in 17 of 25 patients (68%), including 16% complete responses (CRs) and 52% partial responses. The 4 patients with clinical CRs manifested pathologic CRs in their breasts (16%), although 1 patient had residual tumor cells in her axillary nodes. Eight of 25 patients (32%) attained stage 0 or 1 status. The PET scan response at 6 weeks correlated with clinical CRs and breast pathologic CRs at 24 weeks (P < .0036). CONCLUSION Combination neoadjuvant therapy with letrozole and bevacizumab was well-tolerated and resulted in impressive clinical and pathologic responses. The Translational Breast Cancer Research Consortium has an ongoing randomized phase II trial of this regimen in this patient population.

¹⁸F-FDG PET and PET/CT patient preparation: a review of the literature.

For many types of cancer, 18F-FDG PET/CT is commonly used in evaluation and management, including tumor diagnosis, staging, restaging, treatment monitoring, and radiation therapy planning. Meticulous patient preparation including restrictions of diet and activity and management of blood glucose levels in diabetic patients, as well as an awareness of the effect of medications and environmental conditions, plays an important role toward obtaining good-quality images, which are essential for accurate interpretation. Protocol guidelines for performing PET/CT have been proposed by various societies and groups, including the Society of Nuclear Medicine and Molecular Imaging, the European Association of Nuclear Medicine, the American College of Radiology, and the National Cancer Institute. Standardization of the PET/CT procedure is necessary to enable use of metabolic parameters as imaging biomarkers in routine clinical decision making and to ensure reproducibility and allow comparison examinations across different sites. Though several published articles, including various society guidelines, have addressed the relevant patient preparation variables individually, we believe there is need for further clarification. This article summarizes existing data and proposes a standard patient preparation protocol.

99mTc-Tilmanocept: A Novel Molecular Agent for Lymphatic Mapping and Sentinel Lymph Node Localization

Preoperative lymphatic mapping in conjunction with intraoperative γ-probe detection is widely used for sentinel node localization in melanoma, breast cancer, and other malignancies. 99mTc-radiocolloids have been the standard radiotracers used for sentinel node mapping. 99mTc-tilmanocept is a receptor-binding molecular imaging agent approved by the U.S. Food and Drug Administration for lymphatic mapping and lymph node localization in breast cancer, melanoma, clinically node-negative squamous cell carcinoma of the oral cavity, and other solid tumors. It has several advantages over conventional radiocolloids, including rapid injection site clearance, high sentinel node extraction, and low distal node accumulation, which can lead to efficient resource use.

ABNM Position Statement: Nuclear Medicine Professional Competency and Scope of Practice

The purpose of this position statement is to define the scope of nuclear medicine practice and the professional competencies required now and for the future. Medical practice will change dramatically over the coming decades in ways no one can predict. The methodologies, technology, and radiotracers will certainly change. However, the core concepts and knowledge that were first required for nuclear medicine board certification in 1971 still hold true and will guide and sustain us into the future. The American Board of Nuclear Medicine (ABNM) is one of the 24 primary boards of the American Board of Medical Specialties (ABMS). This organizational structure provides an infrastructure that promotes transparency and accountability for all the member boards.

A Pilot Trial of Pre-Operative (Neoadjuvant) Letrozole in Combination with Bevacizumab in Post-Menopausal Women with Newly Diagnosed Estrogen and/or Progesterone Receptor Positive Breast Cancer.

Purpose Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of anti-estrogen adjuvant therapy. We designed a pilot study of neoadjuvant letrozole and bevacizumab (anti-VEGF) to assess feasibility and short term efficacy in post-menopausal women with stage II/III, ER/PR positive breast cancer. Patients and Methods Patients were treated with a neo-adjuvant regimen of letrozole, 2.5mg/day (P.O.) and bevacizumab 15mg/kg Q3 weeks (I.V.) for a total of 24 weeks prior to surgical treatment of their breast cancer. Patients were followed for toxicity at 3 week intervals and tumor assessment (physical exam and tumor ultrasound) at 6 week intervals. PET scans were carried out prior to therapy and 6 weeks after initiation of therapy. Surgery was done 4 weeks after the last dose of bevacizumab. Results Twenty five evaluable patients were treated. The regimen was well tolerated except for 2 patients who were taken off-study for difficult to control hypertension. Objective clinical response occurred in 17/25 patients (68%) including 16% CR and 52% PR. The 4 patients with clinical CR had pathologic CR in their breasts (16%) although one had residual tumor cells in axillary nodes. 8/25 patients (32%) attained stage 0 or 1 status. PET scan response at 6 weeks correlated with clinical CR and breast pathologic CR at 24 weeks (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1088.

A Guide to Writing Academic Portfolios for Radiologists

The academic educators portfolio is a collection of materials that document academic performance and achievements, supplementing the curriculum vitae, in order to showcase a faculty members most significant accomplishments. A decade ago, a survey of medical schools revealed frustration in the nonuniform methods of measuring facultys medical education productivity. A proposed solution was the use of an academic educators portfolio. In the academic medical community, compiling an academic portfolio is always a challenge because teaching has never been confined to the traditional classroom setting and often involves active participation of the medical student, resident, or fellow in the ongoing care of the patient. Diagnostic radiology in addition requires a knowledge base that encompasses basic sciences, imaging physics, technology, and traditional and molecular medicine. Teaching and performing research that involves this complex mix, while providing patient care that is often behind the scenes, provides unique challenges in the documentation of teaching, research, and clinical service for diagnostic radiology faculty. An academic portfolio is seen as a way to explain why relevant academic activities are significant to promotions committee members who may have backgrounds in unrelated academic areas and may not be familiar with a faculty members work. The academic portfolio consists of teaching, research, and service portfolios. The teaching portfolio is a collection of materials that document teaching performance and documents the educators transition to a more effective educator. A research portfolio showcases the most significant research accomplishments. The service portfolio documents service responsibilities and highlight any service excellence. All portfolios should briefly discuss the educators philosophy, activities, methods used to implement activities, leadership, mentoring, or committee roles in these respective areas. Recognizing that academic programs have differing needs, this article will attempt to provide some basic guidelines that may help junior faculty in diagnostic radiology develop their teaching, research, and service portfolios.

18F-FDG PET/CT Findings in Portal Vein Thrombosis and Liver Metastases

18F-FDG PET/CT is a valuable noninvasive tool in oncologic imaging, and its application in the diagnosis of liver metastases has been very convincing. Both the sensitivity and the specificity of 18F-FDG PET/CT are high for detecting liver metastases from various tumors including colorectal, breast, and lung. Such liver metastases are typically 18F-FDG–avid. We present atypical 18F-FDG PET findings in a lung cancer patient with known liver metastases and PVT.

All You Need to Know as an Authorized User

OBJECTIVE The purpose of this article is to review the training requirements for practicing nuclear radiology, the scope of licensing, how to start a new practice, and the key concepts an authorized user needs to know for responsible use of radiopharmaceuticals. CONCLUSION Physicians responsible for the daily operations of nuclear medicine clinics often find the regulations concerning the safe handling and administration of radiopharmaceuticals daunting. Even experienced authorized users have concerns about handling many new therapeutic agents. Those studying for certifying and subspecialty examinations or for maintenance of certification for the American Board of Nuclear Medicine and the American Board of Radiology must clearly understand the overall process for becoming an authorized user.

Abstract P1-15-02: Long term follow-up of the neo-adjuvant pilot trial evaluating activity of letrozole in combination with bevacizumab in post-menopausal women with newly diagnosed estrogen and/or progesterone receptor positive primary breast cancer

Introduction: Vascular endothelial growth factor overexpression has been associated with resistance to anti-estrogen therapy (Cancer Res 2008; 68: 6232); our preclinical data showed that anti-VEGF therapy reverse resistance to estrogen therapy. We postulated that anti-VEGF therapy would enhance anti-estrogen therapy and thus designed a pilot study to assess the feasibility and efficacy of neoadjuvant letrozole and bevacizumab in post-menopausal women with stage II/III, ER/PR positive breast cancer. Patients and Methods: Eligible patients were treated with a neo-adjuvant regimen of letrozole, 2.5 mg/day (PO) and bevacizumab 15 mg/kg every 3 weeks (IV) for a total of 24 weeks prior to surgical treatment of their breast cancer. Patients were followed for toxicity at three week intervals and for tumor assessment at 6 week intervals. Research tumor biopsies were taken before and 6 weeks after initiation of therapy. The primary endpoint was pathological complete remission (pCR). Patients with inflammatory breast cancer were excluded. Results: Twenty six patients were enrolled and 25 were treated (one patient had a TIA the day before initiation of therapy). The regimen was well tolerated with 2 patients taken off-study due to uncontrolled hypertension. Objective clinical response occurred in 68% of the patients (17/25), 16% with CR and 52% with partial response (PR). Sixteen percent of the patients (4/25) had clinical stable disease (SD) and 2 patients progressed (PD) while on therapy. Three patients had pCR and 1 patient had microscopic residual tumor cells in the LNs but not in the breast (pCR 16%). Thirty two percent of the patients attained stage 0 or 1 status. None of the pCR patients received adjuvant chemotherapy and none have relapsed after a median follow-up of 6.1 years (range, 5.8+ to 7.5+). Eight of the 13 patients with PR did not receive chemotherapy and only one relapsed with a median follow-up of 6.2 years (range, 3.7 to 7.7+). At a median follow-up of 6.4 years, 88% of the patients have not relapsed and 12% relapsed (1 PD [basal-like], 1 PR [Luminal B], 1 SD [HER2] relapsed at 1.7, 4, and 6.8 years respectively). Of the 17 patients with CR and PR, only 1 has relapsed (6%). Next Generation Sequencing Analysis and evaluation of markers of proliferation/apoptosis are underway. Conclusion: Combination neoadjuvant therapy with letrozole and bevacizumab was well tolerated and resulted in an impressive pCR of 16%. At a median of 6.4 years, the relapse free survival is 88% for all comers and 94% for responding patients (Luminal A and B). Full correlation of clinical and genomic/biomarker analysis will be presented at the time of the meeting. This encouraging data has led The Breast Cancer Translational Research Consortium to complete a randomized phase II trial (TBCRC002) of letrozole ± bevacizumab in this patient population. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-15-02.