AI-Radiomics Can Improve Inclusion Criteria and Clinical Trial Performance.

Purpose: Success of clinical trials increasingly relies on effective selection of the target patient populations. We hypothesize that computational analysis of pre-accrual imaging data can be used for patient enrichment to better identify patients who can potentially benefit from investigational agents. Methods: This was tested retrospectively in soft-tissue sarcoma (STS) patients accrued into a randomized clinical trial (SARC021) that evaluated the efficacy of evofosfamide (Evo), a hypoxia activated prodrug, in combination with doxorubicin (Dox). Notably, SARC021 failed to meet its overall survival (OS) objective. We tested whether a radiomic biomarker-driven inclusion/exclusion criterion could have been used to improve the difference between the two arms (Evo + Dox vs. Dox) of the study. 164 radiomics features were extracted from 296 SARC021 patients with lung metastases, divided into training and test sets. Results: A single radiomics feature, Short Run Emphasis (SRE), was representative of a group of correlated features that were the most informative. The SRE feature value was combined into a model along with histological classification and smoking history. This model as able to identify an enriched subset (52%) of patients who had a significantly longer OS in Evo + Dox vs. Dox groups [p = 0.036, Hazard Ratio (HR) = 0.64 (0.42-0.97)]. Applying the same model and threshold value in an independent test set confirmed the significant survival difference [p = 0.016, HR = 0.42 (0.20-0.85)]. Notably, this model was best at identifying exclusion criteria for patients most likely to benefit from doxorubicin alone. Conclusions: The study presents a first of its kind clinical-radiomic approach for patient enrichment in clinical trials. We show that, had an appropriate model been used for selective patient inclusion, SARC021 trial could have met its primary survival objective for patients with metastatic STS.

Retropubic parasymphyseal cyst: A rare entity.

We report a case of a retropubic parasymphyseal cyst in a 69-year-old multiparous female with a protracted history of metastatic small bowel carcinoid (neuroendocrine) tumor. Cysts related to the pubic symphysis are uncommon, and mostly reported in subpubic location. They may be confused with primary vulvar masses, malignant bone tumors or metastatic disease. In our case, encapsulation, lack of solid components or diffusion restriction, communication with the symphysis, lack of activity on Gallium-68-Dotatate PET/CT and signal characteristics on MRI similar to those previously reported in literature for subpubic cysts all aided in eventual diagnosis. We aim to remind the reader of this rare entity and its distinguishing features on imaging.

Recurrent parachordoma of the lower back: A case report.

Parachordoma is a rare entity with less than 50 cases described in the literature. This soft-tissue tumor resembles chordomas as well as extraskeletal myxoid chondrosarcomas and has only recently been fully characterized. Here we describe the case of a patient with a lower back parachordoma and its subsequent postresection recurrence 9 years after the initial procedure, emphasizing the importance of long-term follow-up in individuals with this diagnosis.

Oncologic 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: What All Physicians Need to Know.

Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) hybrid examinations (PET/computed tomography, PET/magnetic resonance imaging) have become the most common PET imaging tools in the evaluation of the oncologic patient. Therefore it is of paramount importance that physicians who take care of oncology patients in any capacity are familiar with the basics of when these examinations are indicated, know how to best prepare the patients, and understand the benefits and limitations of the procedure. Additionally, it is important to understand which medical conditions and medications need to be controlled to maintain the diagnostic accuracy of these tests. In this article we aim to explain what 18F-FDG is, how to best prepare our patients, what PET is, and how these examinations are interpreted. Finally, we discuss some of the limitations of these examinations.

Langerhans cell histiocytosis of bone in an adult: A case report.

Langerhans cell histiocytosis (LCH) may clinically manifest in a variety of ways due to its ability to involve nearly every organ system. LCH may present as a single bone lesion, skin rash, or as invasive disseminated disease and occurs typically in the pediatric and adolescent population, affecting both males and females. Independent of its clinical presentation and severity, LCH lesions share the common histology of CD1a+/CD207+ dendritic cells along with an inflammatory infiltrate, and, based upon improved scientific understanding, is now classified as a myeloproliferative neoplasm. We present a case report of an adult diagnosed with LCH of the pelvis.

Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma.

RET fusions have been found in lung adenocarcinoma, of which KIF5B-RET is the most prevalent. We established inducible KIF5B-RET transgenic mice and KIF5B-RET-dependent cell lines for preclinical modeling of KIF5B-RET-associated lung adenocarcinoma. Doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET transgenic mice developed invasive lung adenocarcinoma with desmoplastic reaction. Tumors regressed upon suppression of KIF5B-RET expression. By culturing KIF5B-RET-dependent BaF3 (B/KR) cells with increasing concentrations of cabozantinib or vandetanib, we identified cabozantinib-resistant RETV804L mutation and vandetanib-resistant-RETG810A mutation. Among cabozantinib, lenvatinib, ponatinib, and vandetanib, ponatinib was identified as the most potent inhibitor against KIF5B-RET and its drug-resistant mutants. Interestingly, the vandetanib-resistant KIF5B-RETG810A mutant displayed gain-of-sensitivity (GOS) to ponatinib and lenvatinib. Treatment of doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET bitransgenic mice with ponatinib effectively induced tumor regression. These results indicate that KIF5B-RET-associated lung tumors are addicted to the fusion oncogene and ponatinib is the most effective inhibitor for targeting KIF5B-RET in lung adenocarcinoma. Moreover, this study finds a novel vandetanib-resistant RETG810A mutation and identifies lenvatinib and ponatinib as the secondary drugs to overcome this vandetanib resistance mechanism. Mol Cancer Ther; 15(10); 2521-9. ©2016 AACR.