Yi-Jen Chen

Background/Objectives: Biology-guided radiotherapy (BgRT) is a novel technology utilizing PET radiotracer emissions to deliver image-guided adaptive RT. 18F-Fluorodeoxyglucose ([¹⁸F]FDG) is the most common PET radiotracer but has background in the liver and brain because it is taken up by viable tumor cells as well as inflammatory cells. Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts with minimal expression in normal tissues. FAP inhibitors (FAPIs) bind to FAP, and a FAPI labeled with Gallium-68 (68Ga) is a novel radiotracer with high tumor selectivity. Multiple studies have compared [⁶⁸Ga]Ga-FAPI-04 vs. [¹⁸F]FDG for diagnostic imaging, but [⁶⁸Ga]Ga-FAPI-04 vs. [¹⁸F]FDG have never been compared in terms of their utility for BgRT. Purpose: This study was designed to assess the utility of [⁶⁸Ga]Ga-FAPI-04 vs. [¹⁸F]FDG for BgRT used to treat pancreatic, liver, lung, head and neck, and cervical cancers. Methods: A radiation oncologist specializing in each cancer contoured the gross tumor volume (GTV) on [¹⁸F]FDG PET-CT and [⁶⁸Ga]Ga-FAPI-04 PET-CT images. Auto-contours were generated using an auto-threshold of 40% of the maximum Standardized Uptake Value (SUV). The suitability of [⁶⁸Ga]Ga-FAPI-04 vs. [¹⁸F]FDG for BgRT was evaluated by comparing Normalized Net Activity Concentration (NNA) and Normalized Target Signal (NTS) for each cancer. Results: NNA and NTS for [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG met the requirements for [¹⁸F]FDG-guided BgRT (NNA > 5.0 kBq/mL, NTS > 2.7) for all disease sites. NNAFAPI was significantly greater than NNAFDG for pancreatic, H&N, and cervical cancer. NTSFAPI was significantly greater than NTSFDG for pancreatic, liver, and lung cancer. Conclusions: [⁶⁸Ga]Ga-FAPI-04 is a novel radiotracer for BgRT and has the greatest potential impact in the treatment of pancreatic cancer.

Purpose: The standard of care for patients with locally advanced cervical cancer is definitive chemoradiation followed by a brachytherapy boost. This review describes the current status and future directions of image-guided adaptive brachytherapy for locally advanced cervical cancer. Methods: A systematic search of the PubMed and Clinicaltrials.gov databases was performed, focusing on studies published within the last 10 years. The search queried “cervical cancer [AND] image-guided brachytherapy [OR] magnetic resonance imaging (MRI) [OR] adaptive brachytherapy”. Discussion: The retroEMBRACE and EMBRACE-I trials have established the use of MRI as the standard imaging modality for brachytherapy application and planning. Quantitative imaging and radiomics have the potential to improve outcomes, with three ongoing prospective studies examining the use of radiomics to further risk-stratify patients and personalize brachytherapy. Another active area of investigation includes utilizing the superior soft tissue contrast provided by MRI to increase the dose per fraction and decrease the number of fractions needed for brachytherapy, with several retrospective studies demonstrating the safety and feasibility of three-fraction courses. For developing countries with limited access to MRI, trans-rectal ultrasound (TRUS) appears to be an effective alternative, with several retrospective studies demonstrating improved target delineation with the use of TRUS in conjunction with CT guidance. Conclusions: Further investigation is needed to continue improving outcomes for patients with locally advanced cervical cancer treated with image-guided brachytherapy.

This review aims to summarize the recent advances in radiation oncology for pancreatic cancer. A systematic search of the MEDLINE/PubMed database and Clinicaltrials.gov was performed, focusing on studies published within the last 10 years. Our search queried “locally advanced pancreatic cancer [AND] stereotactic body radiation therapy (SBRT) [OR] hypofractionation [OR] magnetic resonance guidance radiation therapy (MRgRT) [OR] proton” and “borderline resectable pancreatic cancer [AND] neoadjuvant radiation” and was limited only to prospective and retrospective studies and metanalyses. For locally advanced pancreatic cancers (LAPC), retrospective evidence supports the notion of radiation dose escalation to improve overall survival (OS). Novel methods for increasing the dose to high risk areas while avoiding dose to organs at risk (OARs) include SBRT or ablative hypofractionation using a simultaneous integrated boost (SIB) technique, MRgRT, or charged particle therapy. The use of molecularly targeted agents with radiation to improve radiosensitization has also shown promise in several prospective studies. For resectable and borderline resectable pancreatic cancers (RPC and BRPC), several randomized trials are currently underway to study whether current neoadjuvant regimens using radiation may be improved with the use of the multi-drug regimen FOLFIRINOX or immune checkpoint inhibitors.

Review Article Current landscape of radiation oncology in esophageal cancer: a narrative review Jason Liu, Colton Ladbury, Andrew Tam, Joseph Chao, Jae Kim, Heather M. McGee, Terence M. Williams, Arya Amini, Yi-Jen Chen

Portal vein tumor thrombosis (PVTT) from cancer involving the liver carries a dismal prognosis, with median overall survival (OS) ranging from 2 to 5 months. While treatment with yttrium-90 (⁹⁰Y) radioembolization alone may improve outcomes, overall prognosis remains poor. We hypothesize that the combination of ⁹⁰Y radioembolization to the parenchymal component of the tumor and stereotactic body radiation therapy (SBRT) to the vascular component is a safe and effective means of improving outcomes. A single center retrospective review identified 12 patients with cancers involving the liver who received both ⁹⁰Y radioembolization and SBRT to the PVTT between May 2015 to August 2020. Primary endpoint was the 90-day toxicity rate by the Common Terminology Criteria for Adverse Events version 5.0. Secondary endpoints were the best response rate based on the Response Evaluation Criteria in Solid Tumors v1.1, local control rate, portal vein (PV) patency rate, and median OS. Patients received a median ⁹⁰Y dose of 104.3 Gy (range, 83.3 to 131.7 Gy) and a median 5-fraction SBRT dose of 32.5 Gy (range, 27.5 to 50 Gy). There were no late toxicities reported, and only 7 acute grade 1 toxicities reported: elevation of liver function tests (17%), nausea (17%), fatigue (17%), and esophagitis (8%). Local control was 83%. 58% of patients had a patent PV after treatment. With a median follow-up time of 28 months, 1-year OS was 55% with a median OS of 14 months. Combination ⁹⁰Y radioembolization and SBRT appears to be safe and effective in the treatment of PVTT. Larger prospective studies are warranted to better evaluate this combination treatment approach.