Development of a Margin Determination Framework for Tumor-Tracking Radiation Therapy With Intraoperatively Implanted Fiducial Markers

PurposeTo develop an internal target volume (ITV) margin determination framework (or decision-supporting framework) for treating multiple lung metastases using CyberKnife Synchrony with intraoperatively implanted fiducial markers (IIFMs). The feasibility of using non-ideally implanted fiducial markers (a limited number and/or far from a target) for tracking-based lung stereotactic ablative radiotherapy (SABR) was investigated.MethodsIn the developed margin determination framework, an optimal set of IIFMs was determined to minimize a tracking uncertainty-specific ITV (ITVtracking) margin (margin required to cover target-to-marker motion discrepancy), i.e., minimize the motion discrepancies between gross tumor volume (GTV) and the selected set of fiducial markers (FMs). The developed margin determination framework was evaluated in 17 patients with lung metastases. To automatically calculate the respiratory motions of the FMs, a template matching-based FM tracking algorithm was developed, and GTV motion was manually measured. Furthermore, during-treatment motions of the selected FMs were analyzed using log files and compared with those calculated using 4D CTs.ResultsFor 41 of 42 lesions in 17 patients (97.6%), an optimal set of the IIFMs was successfully determined, requiring an ITVtracking margin less than 5 mm. The template matching-based FM tracking algorithm calculated the FM motions with a sub-millimeter accuracy compared with the manual measurements. The patient respiratory motions during treatment were, on average, significantly smaller than those measured at simulation for the patient cohort considered.ConclusionUse of the developed margin determination framework employing CyberKnife Synchrony with a limited number of IIFMs is feasible for lung SABR.

MRI-guided Radiotherapy for PVTT in HCC Patients: Evaluation of the Efficacy and Safety

PurposeThis study aims to evaluate to efficacy, feasibility, and safety of the tumor tracking magnetic resonance imaging (MRI)-guided hypofractionated radiotherapy (HFRT) and stereotactic body radiation therapy (SBRT) for portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients.MethodsWe retrospectively reviewed the twelve cases of unresectable HCC with tumor thrombus in the main trunk or first branch of the portal vein that were treated with tumor tracking MRI-guided HFRT or SBRT using the ViewRay Linac MRIdian system between June 2019 and January 2021. The HFRT was performed with a total of 50 Gy in 10 fractions, and SBRT performed in a range of 36-50 Gy with 4-5 fractions. The median biologic effective dose (BED) with an a/b ratio of 10 was 75 Gy10 (range, 68.4–100 Gy10). ResultsThe median follow-up duration was 5.0 months (range, 1.7–12.8 months). Ten patients (83.3%) showed an objective response of PVTT. At the time of analysis, 10 patients (83.3%) showed local control. The median survival of these patients was 11.6 months (range, 1.9–12.8 months). Three patients (25%) showed mild gastrointestinal symptoms, and there were no cases of grade 3 or higher toxicity. For hepatic toxicity, there were no cases of Child-Puch score increased by more than 2 points after RT without disease progression. ConclusionTumor tracking MRI-guided HFRT and SBRT was a feasible, effective, and safe treatment option in HCC patients with tumor thrombi in the main trunk or first branch of the portal vein.

Review of MR-Guided Radiotherapy for Esophageal Cancer

In this review, we outline the potential benefits and the future role of MRI and MR-guided radiotherapy (MRgRT) in the management of esophageal cancer. Although not currently used in most clinical practice settings, MRI is a useful non-invasive imaging modality that provides excellent soft tissue contrast and the ability to visualize cancer physiology. Chemoradiation therapy with or without surgery is essential for the management of locally advanced esophageal cancer. MRI can help stage esophageal cancer, delineate the gross tumor volume (GTV), and assess the response to chemoradiotherapy. Integrated MRgRT systems can help overcome the challenge of esophageal motion due to respiratory motion by using real-time imaging and tumor tracking with respiratory gating. With daily on-table MRI, shifts in tumor position and tumor regression can be taken into account for online-adaptation. The combination of accurate GTV visualization, respiratory gating, and online adaptive planning, allows for tighter treatment volumes and improved sparing of the surrounding normal organs. This could lead to a reduction in radiotherapy induced cardiac toxicity, pneumonitis and post-operative complications. Tumor physiology as seen on diffusion weighted imaging or dynamic contrast enhancement can help individualize treatments based on the response to chemoradiotherapy. Patients with a complete response on MRI can be considered for organ preservation while patients with no response can be offered an earlier resection. In patients with a partial response to chemoradiotherapy, areas of residual cancer can be targeted for dose escalation. The tighter and more accurate targeting enabled with MRgRT may enable hypofractionated treatment schedules.

αPD-1-mesoCAR-T cells partially inhibit the growth of advanced/refractory ovarian cancer in a patient along with daily apatinib

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies in China. In particular, advanced/refractory ovarian cancer lacks effective targeted therapies due to the immunosuppressive and proangiogenic tumor microenvironment. Mesothelin (MSLN) has been found to be highly expressive in most EOC. Targeting MSLN by antibodies or chimeric antigen receptor-modified T (CAR-T) cells and immune checkpoint blockades as well as apatinib, an anti-angiogenic drug, have been used in patients with refractory ovarian cancer. Apatinib was reported to promote the infiltration of CD8+ T cells in lung cancer. However, the combination therapy of CAR-T secreting anti-PD-1 antibody with apatinib in EOC has not been reported.Case presentationHere we report a case of refractory EOC in a patient who had relapsed after multiline chemotherapy. The patient received autologous T cells that contained sequences encoding single-chain variable fragments specific for MSLN and full-length antibody for PD-1 (αPD-1). The modified T cells were called αPD-1-mesoCAR-T cells. After infusion, the copy number and PD-1 antibody secretion of the CAR-T cells were increased in the blood. By application of multimodality tumor tracking, MRI of the liver showed shrinkage of metastatic nodules from average diameter of 71.3–39.1 mm at month 2. The patient achieved partial response and survived more than 17 months. IL-6 levels in the patient fluctuated from the baseline to 2–4-folds after treatment, but side effects were mild with only grade 1 hypertension and fatigue.ConclusionαPD-1-mesoCAR-T cell therapy combined with apatinib demonstrates a potential therapeutic effect on advanced refractory ovarian cancer.Trial registration numberNCT03615313.