Optimizing Regulatory Reviews for Clinical Protocols that Use Radiopharmaceuticals: Findings of the University of Pennsylvania Radiation Research Safety Committee.

ABSTRACT: Institutional radiation safety committees review research studies with radiation exposure. However, ensuring that the potential patient benefit and knowledge gained merit the radiation risks involved often necessitates revisions that inadvertently delay protocol activations. This quality-improvement study analyzed protocols, identified factors associated with approval time by a radiation safety committee, and developed guidelines to expedite reviews without compromising quality. Clinical protocols submitted to the University of Pennsylvania's Radiation Research Safety Committee (RRSC) for review between 2017 and 2021 were studied. Protocol characteristics, review outcome, stipulations, and approval times were summarized. Statistical analysis (Spearman's rho) was used to investigate stipulations and approval time; rank-sum analysis (Kruskal-Wallis or Wilcoxon) was used to determine whether approval time differed by protocol characteristics. One hundred ten (110) protocols were analyzed. Approximately two-thirds of protocols used approved radiopharmaceuticals to aid investigational therapy trials. Twenty-three percent (23%) of protocols received RRSC approval, and 73% had approval withheld with stipulations, which included requests for edits or additional information. Submissions had a median of three stipulations. Median and mean RRSC approval times were 62 and 80.1 d, and 41% of protocols received RRSC approval after IRB approval. RRSC approval time was positively correlated with stipulations (Spearman's rho = 0. 632, p < 0.001). RRSC approval time was longer for studies using investigational new drugs (median 80 d) than approved radiopharmaceuticals (median 57 d, p = 0.05). The review process is lengthy and may benefit from changes, including publishing standardized radiation safety language and commonly required documents and encouraging timely response to stipulations.

Update on Quantitative Imaging for Predicting and Assessing Response in Oncology.

Molecular imaging has revolutionized clinical oncology by imaging-specific facets of cancer biology. Through noninvasive measurements of tumor physiology, targeted radiotracers can serve as biomarkers for disease characterization, prognosis, response assessment, and predicting long-term response/survival. In turn, these imaging biomarkers can be utilized to tailor therapeutic regimens to tumor biology. In this article, we review biomarker applications for response assessment and predicting long-term outcomes. 18F-fluorodeoxyglucose (FDG), a measure of cellular glucose metabolism, is discussed in the context of lymphoma and breast and lung cancer. FDG has gained widespread clinical acceptance and has been integrated into the routine clinical care of several malignancies, most notably lymphoma. The novel radiotracers 16α-18F-fluoro-17ß-estradiol and 18F-fluorothymidine are reviewed in application to the early prediction of response assessment of breast cancer. Through illustrative examples, we explore current and future applications of molecular imaging biomarkers in the advancement of precision medicine.

Advances in PET Diagnostics for Guiding Targeted Cancer Therapy and Studying In Vivo Cancer Biology.

Purpose of the Review: We present an overview of recent advances in positron emission tomography (PET) diagnostics as applied to the study of cancer, specifically as a tool to study in vivo cancer biology and to direct targeted cancer therapy. The review is directed to translational and clinical cancer investigators who may not be familiar with these applications of PET cancer diagnostics, but whose research might benefit from these advancing tools. Recent Findings: We highlight recent advances in 3 areas: (1) the translation of PET imaging cancer biomarkers to clinical trials; (2) methods for measuring cancer metabolism in vivo in patients; and (3) advances in PET instrumentation, including total-body PET, that enable new methodologies. We emphasize approaches that have been translated to human studies. Summary: PET imaging methodology enables unique in vivo cancer diagnostics that go beyond cancer detection and staging, providing an improved ability to guide cancer treatment and an increased understanding of in vivo human cancer biology.

Precise Localization of Occult Gastrointestinal Hemorrhage Using Dynamic SPECT/CT.

Active but intermittent gastrointestinal (GI) bleeding can be readily detected with dynamic planar scintigraphic imaging. This is a case of a 48-year-old woman who presented from an outside institution with active GI bleeding on 99mTc-labeled RBC (99mTc-RBC) scintigraphy, but the upper and lower GI evaluations failed to subsequently localize the site of persistent bleeding. Repeat 99mTc-RBC planar scintigraphy identified a focus of active extravasation in the right lower quadrant of the abdomen. Dynamic SPECT/CT imaging was immediately performed and further identified the ileocecal valve region as the precise site of active extravasation, which was confirmed at surgery.

How Imaging Can Impact Clinical Trial Design: Molecular Imaging as a Biomarker for Targeted Cancer Therapy.

The ability to measure biochemical and molecular processes to guide cancer treatment represents a potentially powerful tool for trials of targeted cancer therapy. These assays have traditionally been performed by analysis of tissue samples. However, more recently, functional and molecular imaging has been developed that is capable of in vivo assays of cancer biochemistry and molecular biology and is highly complementary to tissue-based assays. Cancer imaging biomarkers can play a key role in increasing the efficacy and efficiency of therapeutic clinical trials and also provide insight into the biologic mechanisms that bring about a therapeutic response. Future progress will depend on close collaboration between imaging scientists and cancer physicians and on public and commercial sponsors, to take full advantage of what imaging has to offer for clinical trials of targeted cancer therapy. This review will provide examples of how molecular imaging can inform targeted cancer clinical trials and clinical decision making by (1) measuring regional expression of the therapeutic target, (2) assessing early (pharmacodynamic) response to treatment, and (3) predicting therapeutic outcome. The review includes a discussion of basic principles of molecular imaging biomarkers in cancer, with an emphasis on those methods that have been tested in patients. We then review clinical trials designed to evaluate imaging tests as integrated markers embedded in a therapeutic clinical trial with the goal of validating the imaging tests as integral markers that can aid patient selection and direct response-adapted treatment strategies. Examples of recently completed multicenter trials using imaging biomarkers are highlighted.

131I therapy using rhTSH stimulation and dosimetry in metastatic malignant struma ovarii.

A 38-year-old woman with metastatic malignant struma ovarii, including massive liver metastases and retroperitoneal lymphadenopathy, underwent ovarian resection and retroperitoneal lymph nodes excision, partial hepatectomy, and radiofrequency ablation for liver metastases. She underwent thyroidectomy and received three I treatments using recombinant human thyrotropin stimulation and radioiodine dosimetry. posttherapy I imaging, anatomic images, and thyroglobulin levels showed significant diminution in the tumor burdens and remarkable decline in thyroglobulin levels. This case provided valuable information on recombinant human thyrotropin-assisted I ablation in conjunction with dosimetry in an unusual presentation of iodine-avid malignant struma ovarii with bulky metastases.