Search

A 65-year-old patient presented with recurrent, locally advanced poorly differentiated thyroid cancer despite 2 neck surgeries, and with newly diagnosed brain and skull base metastases. He was treated with palliative stereotactic radiosurgery to the brain and skull base lesions. Thereafter, as no targetable genetic alteration was identified and antiangiogenic multikinase inhibitors were deemed at high risk of hemorrhagic complications, off-label systemic therapies were considered. The mechanistic target of rapamycin (mTOR) inhibitor everolimus could not be obtained due to lack of insurance coverage, so the patient was treated with single-agent pembrolizumab. He showed an initial remarkable response, but unfortunately had disease progression in the neck and upper mediastinum after 1 year of therapy. At that time, he was treated with external beam radiotherapy, with concomitant pembrolizumab. He was then found to have an CTSB::ALK fusion, which has previously been described in 2 cases of thyroid cancer. However, as he showed a positive response to radiation with pembrolizumab, he continued single-agent immune checkpoint inhibition and had a persistent marked response almost a year after completing radiation. The patient was then followed at an outside institution and was transitioned to hospice at time of progression per his preference. He died 4 years after his initial diagnosis., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.)

Importance: Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors., Objective: To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS)., Design, Setting, and Participants: A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023., Interventions: Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab., Main Outcomes and Measures: The primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months., Results: Forty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively., Conclusions and Relevance: In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS., Trial Registration: ClinicalTrials.gov Identifier: NCT03181100.

Background and Purpose: This retrospective study evaluated the utility of contrast-enhanced (CE) T1-weighted 3D fast spinecho-based SPACE sequences for brain metastasis detection on 3T MRI compared to gradient recalled-echo-based 3D fast low-angle shot (FLASH) sequence., Materials and Methods: We identified all patients at a single institution who underwent SPACE and 3D FLASH sequences as part of a practice quality improvement project. Their medical records were retrospectively reviewed. Five certified neuroradiologists reviewed the images, with at least 2 weeks separation between scoring sequences for the same patient. The following parameters were evaluated: number of metastatic lesions, number of indeterminate lesions, lesion margin, contrast-to-noise ratio (CNR), extent of image artifacts, and overall image quality. CNR was also quantified for solidly enhancing lesions > 1 cm., Results: We identified 220 patients who underwent SPACE and 3D FLASH sequences (the order of the sequences was equally distributed). Of these, 79 had brain metastases on imaging, and 7 were excluded; thus, 72 patients were included in the study. Twenty patients were scored by 2 radiologists. Out of the 92 evaluations, SPACE detected more lesions than did 3D FLASH in 35, while 3D FLASH detected more lesions in 10. More indeterminate lesions were seen on 3D FLASH (27) than on SPACE (9). For lesion margin, CNR, and overall image quality on a Likert scale, SPACE performed significantly better than did 3D FLASH, with less image artifacts ( P < 0.00001). Higher quantitative CNRs were found on SPACE than on 3D FLASH images, although this result was not statistically significant (median = 22.9 vs. 15.5, respectively, P = 0.134). There was a high inter-reader lesion detection concordance with Krippendorf's alpha ordinals at 0.962 for SPACE, 0.870 for 3D FLASH, and 0.918 for the two sequences combined., Conclusions: Compared with 3D FLASH, the SPACE sequence detected more metastatic lesions and was rated higher for image quality, lesion margin, and CNR, with fewer artifacts. Importantly, the SPACE sequence resulted in increased reader confidence, with fewer indeterminate lesions detected., Abbreviations: FLASH = fast low-angle shot; FSE = fast spin-echo; GRE = gradient-recalled echo; MP-RAGE = magnetization-prepared rapid gradient echo; SPACE = Sampling Perfection with Application-optimized Contrasts using different flip angle Evolution; VIBE = volumetric interpolated breath-hold examination., (© 2024 by American Journal of Neuroradiology.)

BACKGROUND. Advanced MRI-based neuroimaging techniques, such as perfusion and spectroscopy, have been increasingly incorporated into routine follow-up protocols in patients treated for high-grade glioma (HGG), to help differentiate tumor progression from treatment effect. However, these techniques' influence on clinical management remains poorly understood. OBJECTIVE. The purpose of this article was to evaluate the impact of MRI-based advanced neuroimaging on clinical decision-making in patients with HGG after treatment. METHODS. This prospective study, performed at a comprehensive cancer center from March 1, 2017, to October 31, 2020, included adult patients treated by chemoradiation for WHO grade 4 diffuse glioma who underwent MRI-based advanced neuroimaging (comprising multiple perfusion imaging sequences and spectroscopy) to further evaluate findings on conventional MRI equivocal for tumor progression versus treatment effect. The ordering neurooncologists completed surveys before and after each advanced neuroimaging session. The percent of episodes of care with a change between the intended and actual management plan on the surveys conducted before and after advanced neuroimaging, respectively, was computed and compared with a published percent using the Wald test for independent samples proportions. RESULTS. The study included 63 patients (mean age, 54.6 ± 12.9 [SD] years; 36 women, 27 men) who underwent 70 advanced neuroimaging sessions. Ordering neurooncologists' intended and actual management plans on the surveys completed before and after advanced neuroimaging, respectively, differed in 44% (31/70; 95% CI: 33-56%) of episodes, which differed from the published frequency of 8.5% (5/59) ( p < .001). These management plan changes included selection of a different plan for six of eight episodes with an intended plan to enroll patients in a clinical trial, 12 of 19 episodes with an intended plan to change chemotherapeutic agents, four of eight episodes with an intended plan of surgical intervention, and one of two episodes with an intended plan of reirradiation. The ordering neurooncologists found advanced neuroimaging to be helpful in 93% (65/70; 95% CI: 87-99%) of episodes. CONCLUSION. Neurooncologists' management plans changed in a substantial fraction of adult patients with HGG who underwent advanced neuroimaging to further evaluate conventional MRI findings equivocal for tumor progression versus treatment effect. CLINICAL IMPACT. The findings support incorporation of advanced neuroimaging into HGG posttreatment monitoring protocols.

Background: The dabrafenib plus trametinib combination (DT) has revolutionized the treatment of BRAF V600E -mutated anaplastic thyroid carcinoma (BRAFm-ATC). However, patients eventually develop resistance and progress. Single-agent anti-PD-1 inhibitor spartalizumab has shown a median overall survival (mOS) of 5.9 months. Combination of immunotherapy with BRAF/MEK inhibitors (BRAF/MEKi) seems to improve outcomes compared with BRAF/MEKi alone, although no direct comparison is available. BRAF-targeted therapy before surgery (neoadjuvant approach) has also shown improvement in survival. We studied the efficacy and safety of DT plus pembrolizumab (DTP) compared with current standard-of-care DT alone as an initial treatment, as well as in the neoadjuvant setting. Methods: Retrospective single-center study of patients with BRAFm-ATC treated with first-line BRAF-directed therapy between January 2014 and March 2023. Three groups were evaluated: DT, DTP (pembrolizumab added upfront or at progression), and neoadjuvant (DT before surgery, and pembrolizumab added before or after surgery). The primary endpoint was mOS between DT and DTP. Secondary endpoints included median progression-free survival (mPFS) and response rate with DT versus DTP as initial treatments, and the exploratory endpoint was mOS in the neoadjuvant group. Results: Seventy-one patients were included in the primary analysis: n  = 23 in DT and n  = 48 in DTP. Baseline demographics were similar between groups, including the presence of metastatic disease at start of treatment ( p  = 0.427) and prior treatments with surgery ( p  = 0.864) and radiation ( p  = 0.678). mOS was significantly longer with DTP (17.0 months [confidence interval CI, 11.9-22.1]) compared with DT alone (9.0 months [CI, 4.5-13.5]), p  = 0.037. mPFS was also significantly improved with DTP as the initial treatment (11.0 months [CI, 7.0-15.0]) compared with DT alone (4.0 months [CI, 0.7-7.3]), p  = 0.049. Twenty-three patients were in the exploratory neoadjuvant group, where mOS was the longest (63.0 months [CI, 15.5-110.5]). No grade 5 adverse events (AEs) occurred in all three cohorts, and 32.4% had immune-related AEs, most frequently hepatitis and colitis. Conclusions: Our results show that in BRAFm-ATC, addition of pembrolizumab to dabrafenib/trametinib may significantly prolong survival. Surgical resection of the primary tumor after initial BRAF-targeted therapy in selected patients may provide further survival benefit. However, conclusions are limited by the retrospective nature of the study. Additional prospective data are needed to confirm this observation.

Background: There is a paucity of literature regarding the clinical characteristics and management of subependymomas of the fourth ventricle due to their rarity. Here, we describe the operative and non-operative management and outcomes of patients with such tumors., Methods: This retrospective single-institution case series was gathered after Institutional Review Board (IRB) approval. Patients diagnosed with a subependymoma of the fourth ventricle between 1993 and 2021 were identified. Clinical, radiology and pathology reports along with magnetic resonance imaging (MRI) images were reviewed., Results: Patients identified (n = 20), showed a male predominance (n = 14). They underwent surgery (n = 9) with resection and histopathological confirmation of subependymoma or were followed with imaging surveillance (n = 11). The median age at diagnosis was 51.5 years. Median tumor volume for the operative cohort was 8.64 cm 3 and median length of follow-up was 65.8 months. Median tumor volume for the non-operative cohort was 0.96 cm 3 and median length of follow-up was 78 months. No tumor recurrence post-resection was noted in the operative group, and no tumor growth from baseline was noted in the non-operative group. Most patients (89 %) in the operative group had symptoms at diagnosis, all of which improved post-resection. No patients were symptomatic in the non-operative group., Conclusions: Surgical resection is safe and is associated with alleviation of presenting symptoms in patients with large tumors. Observation and routine surveillance are warranted for smaller, asymptomatic tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Imaging of head and neck cancer at initial staging and as part of post-treatment surveillance is a key component of patient care as it guides treatment strategy and aids determination of prognosis. Head and neck cancer includes a heterogenous group of malignancies encompassing several anatomic sites and histologies, with squamous cell carcinoma the most common. Together this comprises the seventh most common cancer worldwide. At initial staging comprehensive imaging delineating the anatomic extent of the primary site, while also assessing the nodal involvement of the neck is necessary. The treatment of head and neck cancer often includes a combination of surgery, radiation, and chemotherapy. Post-treatment imaging is tailored for the evaluation of treatment response and early detection of local, locoregional, and distant recurrent tumor. Cross-sectional imaging with CT or MRI is recommended for the detailed anatomic delineation of the primary site. PET/CT provides complementary metabolic information and can map systemic involvement. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Tinnitus is abnormal perception of sound and has many subtypes. Clinical evaluation, audiometry, and otoscopy should be performed before ordering any imaging, as the choice of imaging will depend on various factors. Type of tinnitus (pulsatile or nonpulsatile) and otoscopy findings of a vascular retrotympanic lesion are key determinants to guide the choice of imaging studies. High-resolution CT temporal bone is an excellent tool to detect glomus tumors, abnormal course of vessels, and some other abnormalities when a vascular retrotympanic lesion is seen on otoscopy. CTA or a combination of MR and MRA/MRV are used to evaluate arterial or venous abnormalities like dural arteriovenous fistula, arteriovenous malformation, carotid stenosis, dural sinus stenosis, and bony abnormalities like sigmoid sinus wall abnormalities in cases of pulsatile tinnitus without a vascular retrotympanic lesion. MR of the brain is excellent in detecting mass lesions such as vestibular schwannomas in cases of unilateral nonpulsatile tinnitus. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to report outcomes for 19 consecutive patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma. Patients were treated from 2014 to 2021 and followed for a median of 22.3 months. The median overall survival (OS) and disease-free survival (DFS) were 31.8 and 9.9 months, respectively. Patients with nasal cavity or maxillary sinus tumors had 84% better disease-specific survival (DSS) (hazard ratio [HR], 0.136; 95% confidence interval [CI], 0.028-0.66; p = .005) and 71% better DFS (HR, 0.29; 95% CI, 0.097-0.84; p = .041) than patients with other sinonasal sites. Patients who received induction chemotherapy were 76% less likely to die of disease (DSS HR, 0.241; 95% CI, 0.058-1.00; p = .047). In the largest single-institution study of SMARCB1-deficient sinonasal carcinoma to date, OS and DFS approached 3 years and 1 year, respectively, but were better for nasal cavity and maxillary sinus tumors. Patients may benefit from induction chemotherapy., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Medulloblastoma in adults is rare and treatment decisions are largely driven from pediatric literature. We sought to characterize recurrent medulloblastoma in adults., Methods: From a single-institution dataset of 200 adult patients diagnosed with medulloblastoma during 1978-2017, those with recurrence were analyzed for clinical features, treatment, and outcome., Results: Of the 200 patients, 82 (41%) with median age of 29 years (18-59) had recurrence after a median follow-up time of 8.4 years (95% CI = 7.1, 10.3). Of these, 30 (37%) were standard-risk, 31 (38%) were high-risk, and 21 (26%) had unknown-risk diseases at the time of initial diagnosis. Forty-eight (58%) presented with recurrence outside the posterior fossa, of whom 35 (43%) had distant recurrence only. Median Progression-free survival (PFS) and OS from initial surgery were 33.5 and 62.4 months, respectively. Neither PFS nor OS from initial diagnosis differed between the standard-risk and high-risk groups in those who experience recurrence ( P = .505 and .463, respectively). Median OS from first recurrence was 20.3 months, also with no difference between the standard-risk and high-risk groups ( P = .518). Recurrences were treated with combinations of re-resection (20 patients; 25%), systemic chemotherapy (61 patients; 76%), radiation (29 patients; 36%), stem cell transplant (6 patients; 8%), and intrathecal chemotherapy (4 patients; 5%). Patients who received radiation at recurrence had better OS (32.9 months) than those who did not (19.2 months) ( P = .034)., Conclusions: Recurrent medulloblastoma in adults has a poor prognosis irrespective of initial risk stratification. Recurrence commonly arises outside the posterior fossa years after initial diagnosis., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background and Purpose: Brain tumors are the most common cause of cancer-related deaths among the pediatric population. Among these, pediatric glioblastomas (GBMs) comprise 2.9% of all central nervous system tumors and have a poor prognosis. The purpose of this study is to determine whether the imaging findings can be a prognostic factor for survival in children with GBMs., Materials and Methods: The imaging studies and clinical data from 64 pediatric patients with pathology-proven GBMs were evaluated. Contrast enhancement patterns were classified into focal, ring-like, and diffuse, based on preoperative postcontrast T1-weighted magnetic resonance images. We used the Kaplan-Meier method and Cox proportional hazard regression to evaluate the prognostic value of imaging findings., Results: Patients with ring-enhanced GBMs who underwent gross total resection or subtotal resection were found to have a significantly shorter progression-free survival ( P = 0.03) comparing with other enhancing and nonenhancing glioblastomas., Conclusions: In this study, we analyzed survival factors in children with pediatric glioblastomas. In the group of patients who underwent gross total resection or subtotal resection, those patients with focal-enhanced GBMs had significantly longer progression-free survival ( P = 0.03) than did those with other types of enhancing GBMs (diffuse and ring-like)., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Cranial neuropathy can result from pathology affecting the nerve fibers at any point and requires imaging of the entire course of the nerve from its nucleus to the end organ in order to identify a cause. MRI with and without intravenous contrast is often the modality of choice with CT playing a complementary role. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: Subependymomas located within the 4th ventricle are rare, and the literature describing imaging characteristics is sparse. Here, we describe the clinical and radiological characteristics of 29 patients with 4th ventricle subependymoma., Methods: This is a retrospective multi-center study performed after Institutional Review Board (IRB) approval. Patients diagnosed with suspected 4th ventricle subependymoma were identified. A review of clinical, radiology, and pathology reports along with magnetic resonance imaging (MRI) images was performed., Results: Twenty-nine patients, including 6 females, were identified. Eighteen patients underwent surgery with histopathological confirmation of subependymoma. The median age at diagnosis was 52 years. Median tumor volume for the operative cohort was 9.87 cm 3 , while for the non-operative cohort, it was 0.96 cm 3 . Thirteen patients in the operative group exhibited symptoms at diagnosis. For the total cohort, the majority of subependymomas (n = 22) were isointense on T1, hyperintense (n = 22) on T2, and enhanced (n = 24). All tumors were located just below the body of the 4th ventricle, terminating near the level of the obex. Fourteen cases demonstrated extension of tumor into foramen of Magendie or Luschka., Conclusion: To the best of our knowledge, this is the largest collection of 4th ventricular subependymomas with imaging findings reported to date. All patients in this cohort had tumors originating between the bottom of the body of the 4th ventricle and the obex. This uniform and specific site of origin aids with imaging diagnosis and may infer possible theories of origin., (© 2022. The Author(s).)

This article presents guidelines for initial imaging utilization in patients presenting with sinonasal disease, including acute rhinosinusitis without and with suspected orbital and intracranial complications, chronic rhinosinusitis, suspected invasive fungal sinusitis, suspected sinonasal mass, and suspected cerebrospinal fluid leak. CT and MRI are the primary imaging modalities used to evaluate patients with sinonasal disease. Given its detailed depiction of bony anatomy, CT can accurately demonstrate the presence of sinonasal disease, bony erosions, and anatomic variants, and is essential for surgical planning. Given its superior soft tissue contrast, MRI can accurately identify clinically suspected intracranial and intraorbital complications, delineate soft tissue extension of tumor and distinguish mass from obstructed secretions.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Maxillofacial trauma patients comprise a significant subset of patients presenting to emergency departments. Before evaluating for facial trauma, an emergency or trauma physician must perform a primary survey to ensure patient stabilization. Following this primary survey, this document discusses the following clinical scenarios for facial trauma: tenderness to palpation or contusion or edema over frontal bone (suspected frontal bone injury); pain with upper jaw manipulation or pain overlying zygoma or zygomatic deformity or facial elongation or malocclusion or infraorbital nerve paresthesia (suspected midface injury); visible nasal deformity or palpable nasal deformity or tenderness to palpation of the nose or epistaxis (suspected nasal bone injury); and trismus or malocclusion or gingival hemorrhage or mucosal hemorrhage or loose teeth or fractured teeth or displaced teeth (suspected mandibular injury). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Glioblastomas are malignant, often incurable brain tumors. Reliable discrimination between recurrent disease and treatment changes is a significant challenge. Prior work has suggested glioblastoma FDG PET conspicuity is improved at delayed time points vs. conventional imaging times. This study aimed to determine the ideal FDG imaging time point in a population of untreated glioblastomas in preparation for future trials involving the non-invasive assessment of true progression vs. pseudoprogression in glioblastoma. Methods: Sixteen pre-treatment adults with suspected glioblastoma received FDG PET at 1, 5, and 8 h post-FDG injection within the 3 days prior to surgery. Maximum standard uptake values were measured at each timepoint for the central enhancing component of the lesion and the contralateral normal-appearing brain. Results: Sixteen patients (nine male) had pathology confirmed IDH-wildtype, glioblastoma. Our results revealed statistically significant improvements in the maximum standardized uptake values and subjective conspicuity of glioblastomas at later time points compared to the conventional (1 h time point). The tumor to background ratio at 1, 5, and 8 h was 1.4 ± 0.4, 1.8 ± 0.5, and 2.1 ± 0.6, respectively. This was statistically significant for the 5 h time point over the 1 h time point ( p > 0.001), the 8 h time point over the 1 h time point ( p = 0.026), and the 8 h time point over the 5 h time point ( p = 0.036). Conclusions: Our findings demonstrate that delayed imaging time point provides superior conspicuity of glioblastoma compared to conventional imaging. Further research based on these results may translate into improvements in the determination of true progression from pseudoprogression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Johnson, Chen, Rohren, Prabhu, Chasen, Mawlawi, Liu and Gule-Monroe.)

Hyperparathyroidism is defined as excessive parathyroid hormone production. The diagnosis is made through biochemical testing, in which imaging has no role. However, imaging is appropriate for preoperative parathyroid gland localization with the intent of surgical cure. Imaging is particularly useful in the setting of primary hyperparathyroidism whereby accurate localization of a single parathyroid adenoma can facilitate minimally invasive parathyroidectomy. Imaging can also be useful to localize ectopic or supernumerary parathyroid glands and detail anatomy, which may impact surgery. This document summarizes the literature and provides imaging recommendations for hyperparathyroidism including primary hyperparathyroidism, recurrent or persistent primary hyperparathyroidism after parathyroid surgery, secondary hyperparathyroidism, and tertiary hyperparathyroidism. Recommendations include ultrasound, CT neck without and with contrast, and nuclear medicine parathyroid scans. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively ( p  = 0.20). On multivariable analysis, LTD, receipt of SCT, and response after RT were associated with better OS and CNS-disease-free survival. Patients with localized secondary CNS DLBCL may benefit from RT serving as a bridge to SCT.

Parathyroid carcinoma is a rare neuroendocrine tumor. Non-functional parathyroid carcinomas are exceedingly rare neoplasms which generally present at an advanced disease stage, and occasionally can masquerade as medullary thyroid carcinoma., (Published by Elsevier Inc.)

Background: Adult medulloblastoma (MB) is rare, and management guidelines are largely based on pediatric clinical trials and retrospective series. Limited data exist with respect to clinical characteristics, prognostic factors, and outcomes based on first-line treatments., Methods: Two hundred adults with MB seen at a single institution from January 1978 to April 2017 were identified and followed for a median of 8.4 y (7.1, 10.3)., Results: Patient's median age at diagnosis was 29 y (18, 63). One hundred eleven (55.5%) were standard-risk, 59 (29.5%) were high-risk, and 30 (15.0%) were indeterminate. Most received post-operative radiation (RT) (184 [92.0%]), and 105 (52.5%) received first-line chemotherapy. Median overall survival (OS) was 8.8 y (7.2, 12.2) and median progression-free survival (PFS) was 6.6 y (4.9, 11.2). High-risk patients had inferior OS (Hazard ratio [HR] = 2.5 [1.5, 4.2], P = .0006) and PFS (HR = 2.3 [1.3, 3.9], P = .002) compared to standard-risk patients. Age, sex, and metastatic disease were not associated with survival. After adjusting for risk status, those who received RT plus adjuvant chemotherapy had superior PFS compared to RT plus neoadjuvant chemotherapy [HR = 0.46 (0.22, 0.95), P = .0357]. Within a subgroup for whom detailed clinical data were available, those who received RT plus adjuvant chemotherapy had improved PFS compared to RT only [HR = 0.24 (0.074-0.76), P = .016]. The substitution of cisplatin for carboplatin and the elimination of vincristine did not negatively affect outcomes., Conclusion: This is the largest single-institution retrospective study of adult MB to our knowledge and identifies standard-risk status, first-line RT and adjuvant chemotherapy as factors associated with improved outcomes., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Targeted kinase inhibitors have been increasingly utilized in the treatment of advanced medullary thyroid cancer (MTC) over the last decade. Recently, highly potent next generation selective RET inhibitors have been clinically validated, and selpercatinib was recently Food and Drug Administration (FDA)-approved for advanced MTC. The advent of highly selective, potent RET inhibitors is broadening the treatment options for patients with RET-mutated cancers., Methods: We report the first published case of neoadjuvant selpercatinib followed by surgery for a patient with initially unresectable, widely metastatic, RET-mutated MTC who was treated on a single patient protocol., Results: After greater than 50% RECIST response, the patient underwent complete surgical resection followed by selpercatinib resumption. He remains locoregionally disease-free 21 months after starting therapy with stable metastatic disease (after initial partial response); and calcitonin/CEA continue to decline., Conclusion: This novel treatment strategy for locoregionally advanced RET-mutated MTC warrants further study in clinical trials., (© 2020 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Purpose: Brain metastases are manually contoured during stereotactic radiosurgery (SRS) treatment planning, which is time-consuming, potentially challenging, and laborious. The purpose of this study was to develop and investigate a 2-stage deep learning (DL) approach (MetNet) for brain metastasis segmentation in pre-treatment magnetic resonance imaging (MRI)., Materials and Methods: We retrospectively analyzed postcontrast 3D T1-weighted spoiled gradient echo MRIs from 934 patients who underwent SRS between August 2009 and August 2018. Neuroradiologists manually identified brain metastases in the MRIs. The treating radiation oncologist or physicist contoured the brain metastases. We constructed a 2-stage DL ensemble consisting of detection and segmentation models to segment the brain metastases on the MRIs. We evaluated the performance of MetNet by computing sensitivity, positive predictive value (PPV), and Dice similarity coefficient (DSC) with respect to metastasis size, as well as free-response receiver operating characteristics., Results: The 934 patients (mean [±standard deviation] age 59 ± 13 years, 474 women) were randomly split into 80% training and 20% testing groups (748:186). For patients with metastases 1-52 mm (n = 766), 648 (85%) were detected and segmented with a mean segmentation DSC of 81% ± 15%. Patient-averaged sensitivity was 88% ± 19%, PPV was 58% ± 25%, and DSC was 85% ± 13% with 3 ± 3 false positives (FPs) per patient. When considering only metastases ≥6 mm, patient-averaged sensitivity was 99% ± 5%, PPV was 67% ± 28%, and DSC was 87% ± 13% with 1 ± 2 FPs per patient., Conclusion: MetNet can segment brain metastases across a broad range of metastasis sizes with high sensitivity, low FPs, and high segmentation accuracy in postcontrast T1-weighted MRI, potentially aiding treatment planning for SRS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The BRAF V600E mutation is the most common driver mutation in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC). This mutation is considered actionable and, for BRAF V600E -mutated ATC, a BRAF inhibitor (dabrafenib) in combination with an MEK inhibitor (trametinib) is FDA approved. BRAF inhibitors have also shown efficacy in BRAF V600E -mutated PTC. However, as with all targeted therapies, resistance to these drugs eventually develops. It is essential that we understand the mechanisms of resistance to the BRAF inhibitors in thyroid cancer to develop future strategies to effectively treat these patients and improve survival. Patients: Herein, we describe four patients with thyroid cancer treated with selective BRAF inhibitors, who developed a RAS mutation in addition to the BRAF V600E mutation at progression. Results: Patients 1 and 3 acquired a KRAS G12V mutation in the progressive tumor, patient 2 acquired a NRAS Q61K mutation in a progressive lymph node, and patient 4 acquired NRAS G13D mutation on liquid biopsy performed at the time of radiographic disease progression. Conclusion: Similar to the melanoma experience, the emergence of RAS mutations appears to act as a mechanism of resistance to BRAF inhibitors in thyroid cancers.

We report a case of a 77-year-old female with purulent chondritis of the thyroid cartilage who was initially referred for laryngeal neoplasm. Purulent chondritis of the laryngeal cartilage is a rare entity with three reports in the literature. The unique CT imaging features of expansile laryngeal cartilage with peripheral rim enhancement and central fluid-attenuation correlate to the abscess formation between the inner and outer perichondria. The correct imaging assessment prompts surgical management and avoid misdiagnosis., (© 2020 The Authors. Published by the British Institute of Radiology.)

Background Brain metastases are manually identified during stereotactic radiosurgery (SRS) treatment planning, which is time consuming and potentially challenging. Purpose To develop and investigate deep learning (DL) methods for detecting brain metastasis with MRI to aid in treatment planning for SRS. Materials and Methods In this retrospective study, contrast material-enhanced three-dimensional T1-weighted gradient-echo MRI scans from patients who underwent gamma knife SRS from January 2011 to August 2018 were analyzed. Brain metastases were manually identified and contoured by neuroradiologists and treating radiation oncologists. DL single-shot detector (SSD) algorithms were constructed and trained to map axial MRI slices to a set of bounding box predictions encompassing metastases and associated detection confidences. Performances of different DL SSDs were compared for per-lesion metastasis-based detection sensitivity and positive predictive value (PPV) at a 50% confidence threshold. For the highest-performing model, detection performance was analyzed by using free-response receiver operating characteristic analysis. Results Two hundred sixty-six patients (mean age, 60 years ± 14 [standard deviation]; 148 women) were randomly split into 80% training and 20% testing groups (212 and 54 patients, respectively). For the testing group, sensitivity of the highest-performing (baseline) SSD was 81% (95% confidence interval [CI]: 80%, 82%; 190 of 234) and PPV was 36% (95% CI: 35%, 37%; 190 of 530). For metastases measuring at least 6 mm, sensitivity was 98% (95% CI: 97%, 99%; 130 of 132) and PPV was 36% (95% CI: 35%, 37%; 130 of 366). Other models (SSD with a ResNet50 backbone, SSD with focal loss, and RetinaNet) yielded lower sensitivities of 73% (95% CI: 72%, 74%; 171 of 234), 77% (95% CI: 76%, 78%; 180 of 234), and 79% (95% CI: 77%, 81%; 184 of 234), respectively, and lower PPVs of 29% (95% CI: 28%, 30%; 171 of 581), 26% (95% CI: 26%, 26%; 180 of 681), and 13% (95% CI: 12%, 14%; 184 of 1412). Conclusion Deep-learning single-shot detector models detected nearly all brain metastases that were 6 mm or larger with limited false-positive findings using postcontrast T1-weighted MRI. © RSNA, 2020 See also the editorial by Kikinis and Wells in this issue.

Background: The cyclin-dependent-kinase inhibitor/retinoblastoma pathway has been implicated in sporadic medullary thyroid carcinoma tumorigenesis. Somatic CDKN2C loss has been associated with decreased overall survival in medullary thyroid carcinoma patients. We evaluated CDKN2C loss in a prospective clinical environment using a novel Clinical Laboratory Improvement Amendments-certified assay to confirm its association with aggressive disease and to interrogate response to targeted therapy., Methods: Patients with advanced sporadic medullary thyroid carcinoma underwent tumor genotyping for the purpose of management of targeted therapy and prognostication., Results: Of patients with informative CDKN2C assay results, 30 (51.8%) were haploinsufficient/1N and 28 (48.3%) were 2N. Forty patients (69.0%) had a somatic RET mutation, and 36.9% had alterations of both genes. Thirty patients (51.7%) were treated with systemic therapy. Presence of genetic alterations in CDKN2C or RET did not predict treatment response. Patients with 1N CDKN2C loss had significantly shorter time-to-distant-metastasis than patients with normal copy number (P = .03)., Conclusion: This is the first evaluation in the clinical setting of CDKN2C haploinsufficiency in sporadic medullary thyroid carcinoma. Although a larger cohort and longer follow-up will be required, loss seems to be associated with more aggressive disease and may indicate patients that might receive benefit from treatment with a CDK inhibitor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Subclassification of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is encouraged in the Bethesda System. In our practice, we subclassified AUS/FLUS into 3 subcategories: atypical follicular cells of undetermined significance (ACUS) for cases with cytologic atypia; follicular lesion (FL) for cellular cases with follicular cells with-minimal or no atypia, arranged in a macro- and micro-follicular pattern with scant colloid; and indeterminate follicular lesion, favor benign (IFL-FB) for cases with few clusters of follicular cells without atypia associated with minimal or no colloid. The objective of our study was to evaluate the prevalence, clinical management, and risk of malignancy for each subcategory., Materials and Methods: We retrospectively identified ultrasound-guided fine-needle aspiration (US-FNA) of thyroid cases that were subcategorized as ACUS, IFL-FB, and FL at our-institution during 2014-2016. The results of US-FNA were correlated with clinical outcome in the subsequent 2 years including repeat US-FNA, thyroid surgery, and clinical/imaging follow-up., Results: Of 3207 thyroid US-FNA cases, 718 (22.4%) cases were included in the study. Of these 718 cases, 104 (14.5%) were subcategorized as ACUS, 166 (23.1%) as FL, and 448 (62.4%) as IFL-FB. The surgery rate was 39.4% (41 of 104) for ACUS, 13.6% (61 of 448) for IFL-FB, and 27.1% (45 of 166) for FL. The risk of malignancy (ROM) was 25% (26 of 104) for ACUS, and 2.9% (13 of 448) for IFL-FB, 6.0% (10 of 166) for FL. The surgery rate and ROM was significantly higher for ACUS in comparison to IFL-FB (P < 0.05) and FL (P < 0.05)., Conclusions: Subclassification of AUS/FLUS into 3 groups based on cytopathologic findings alone not only improved the triage of patients for subsequent clinical management but also effectively stratified the risk of malignancy., (Copyright © 2019 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Study Design: A case series of dual time-point F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) for the diagnosis of spinal cord sarcoidosis., Objective: The aim of this study was to illustrate three cases of spinal sarcoidosis with occult presentation and subsequent identification with the use of dual time-point F-FDG PET/CT., Summary of Background Data: Sarcoidosis of the spinal cord is very rare and when it occurs without systemic manifestations of disease can be a challenging diagnostic dilemma frequently resulting in the need for spinal cord biopsy in order to establish a diagnosis., Methods: Case series presentation and report., Results: This manuscript presents a case series experience of dual time-point F-FDG PET/CT for the diagnosis of spinal cord sarcoidosis. We review the cases of three patients who presented with myelopathy and underwent F-FDG DTPI as part of the evaluation for enhancing spinal cord lesions of unknown etiology for 2 years at a university-based cancer hospital. F-FDG DTPI was vital in making the diagnosis of sarcoidosis, and in two of the cases, the patients were able to avoid biopsy, thereby avoiding potential morbidity from an invasive procedure., Conclusion: F-FDG PET/CT imaging is a noninvasive imaging technique that can be crucial in the diagnosis of sarcoidosis of the spinal cord and help avoid unnecessary procedures., Level of Evidence: 4.

Background: When achieved, complete surgical resection improves outcomes in anaplastic thyroid carcinoma (ATC). However, most ATC patients present with advanced inoperable disease, often with impending airway obstruction, increased hemorrhage risk, and significant dysphagia. Novel treatment strategies are critically needed to improve disease control and decrease locoregional morbidity. The objective of this study was to determine the feasibility and effectiveness of a neoadjuvant regimen by using dabrafenib with trametinib followed by surgical resection in patients with initially unresectable BRAF V600E -mutated ATC. Methods: Case series of six consecutive patients with BRAF V600E -mutated ATC diagnosed between January 2017 and February 2018. Pathologic confirmation of ATC was obtained before treatment. BRAF V600E status was ascertained via immunohistochemistry or sequencing of circulating tumor DNA. All patients received dabrafenib and trametinib (DT) followed by surgical resection and adjuvant chemoradiation. Three patients also received pembrolizumab. Results: Complete surgical resection was achieved in all patients. Histopathologic analyses of resected specimens showed high pathologic response rates with significantly decreased ATC viability and residual papillary thyroid carcinoma components. Overall survival at six months and one year was 100% and 83%, respectively. Locoregional control rate was 100%. Two patients died of distant metastases without evidence of locoregional disease at 8 and 14 months from diagnosis. The remaining four patients had no evidence of disease at the last follow-up. Conclusions: We report the first series in the literature of BRAF V600E -mutated ATC patients with locoregionally advanced disease treated with DT followed by surgical resection. We demonstrated feasibility of complete resection, decreased need for tracheostomy, high pathologic response rates, and durable locoregional control with symptom amelioration.

Background: Fluorine-18-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (fluciclovine) is a synthetic amino acid radiopharmaceutical initially developed to improve noninvasive diagnosis of gliomas and currently FDA approved for prostate cancer imaging. Although fluciclovine positron emission tomography (PET) has proven to be efficacious in detecting multiple types of cancer, its ability to detect oropharyngeal squamous cell carcinoma (OPSCC) is largely unknown., Methods: We describe a case of incidental OPSCC detection with fluciclovine PET in a 66-year old male patient during workup for recurrent prostate adenocarcinoma., Results: Fluciclovine PET detected a left base of tongue (BOT) lesion, which was subsequently confirmed as invasive SCC on surgical pathology., Conclusion: Given these findings, we discuss potential future directions for research with fluciclovine to overcome some of the known limitations of 18 [F]fluorodeoxyglucose in oncological imaging., (© 2019 Wiley Periodicals, Inc.)

Distant metastatic disease from gliomas is extremely rare. We report the case of a 17-year-old female with an H3F3A G34R mutated infiltrative glioma who developed painful osseous metastases to her pelvis and spine within 3 months of clinical presentation. The presence of an H3F3A mutation in these patients may indicate further work-up to include intensive staging examination.

Purpose: Anaplastic thyroid cancer (ATC) is a deadly form of thyroid cancer. BRAF V600E is the only actionable mutation for which there is a Food and Drug Administration-approved drug combination. Rapid detection of BRAF V600E and initiation of therapy is critical. We explored the ability of droplet digital polymerase chain reaction (ddPCR) to identify this mutation in circulating cell-free DNA (cfDNA) in plasma., Materials and Methods: The ddPCR assay was evaluated for its sensitivity, specificity for detection of BRAF V600E cfDNA, and concordance with tumor tissue. The assay also was used to evaluate its potential role as a biomarker of response., Results: Forty-four patients with ATC who were tested for the BRAF mutation by tumor tissue DNA sequencing or immunohistochemistry were included. Sixteen BRAF V600E-positive patients had treatment samples to evaluate cfDNA levels as a biomarker of response in correlation with restaging scans. Concordance of ddPCR with tumor tissue was 93%, with a sensitivity of 85% and specificity of 100%. Area under the curve by Wilcoxon rank sum test was 0.9 (95% CI, 0.80 to 0.99; P < .001). As a biomarker of response to treatment, 94% of ddPCR samples were concordant with tumor shrinkage in restaging scans, and 47% were concordant with tumor growth (Fisher's exact test P = .0061). In addition, cfDNA levels by ddPCR were predictive of treatment response in 71% of samples., Conclusion: cfDNA detection by ddPCR is highly sensitive, specific, and concordant with mutation status on ATC tumors. ddPCR also can be used for monitoring cfDNA levels in conjunction with imaging scans in patients with ATC., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Priyanka C. IyerNo relationship to discloseGilbert J. CoteNo relationship to discloseTao HaiNo relationship to discloseMaria Gule-MonroeNo relationship to discloseJacquelin Bui-GriffithNo relationship to discloseMichelle D. WilliamsNo relationship to discloseKenneth HessNo relationship to discloseMarie-Claude HofmannNo relationship to discloseRamona DaduResearch Funding: AstraZeneca, Merck, Eisai, Genentech, Bristol-Myers SquibbMark ZafereoNo relationship to discloseNaifa L. BusaidyConsulting or Advisory Role: Loxo Oncology, Eisai Research Funding: GlaxoSmithKline, NovartisRenata FerrarottoConsulting or Advisory Role: AYALA Research Funding: OncoMed Pharmaceuticals (Inst), G1 Therapeutics (Inst), AstraZeneca (Inst), MedImmune (Inst), EMD Serono (Inst), Genentech (Inst), Roche (Inst), Merck Serono (Inst)Vivek SubbiahConsulting or Advisory Role: MedImmune Research Funding: Novartis (Inst), GlaxoSmithKline (Inst), NanoCarrier (Inst), Northwest Biotherapeutics (Inst), Genentech (Inst), Roche (Inst), BERG (Inst), Bayer AG (Inst), Incyte (Inst), Fujifilm (Inst), PharmaMar (Inst), D3 Oncology Solutions (Inst), Pfizer (Inst), Amgen (Inst), AbbVie (Inst), MultiVir (Inst), Blueprint Medicines (Inst), Loxo Oncology (Inst), Vegenics (Inst), Takeda Pharmaceuticals (Inst), Alfasigma (Inst), Agensys (Inst), Idera (Inst), Boston Biomedical (Inst), Inhibrx (Inst), Exelixis (Inst) Travel, Accommodations, Expenses: PharmaMar, Bayer AGNeil GrossHonoraria: Intuitive Surgical Consulting or Advisory Role: PDS Biotechnology, Verb Surgical (Inst) Research Funding: Regeneron Pharmaceuticals, MedImmune (Inst), Genentech (Inst)Brandon G. GunnNo relationship to discloseHeath D. SkinnerNo relationship to discloseAdam S. GardenConsulting or Advisory Role: Galera TherapeuticsMaria E. CabanillasConsulting or Advisory Role: Loxo Oncology, Blueprint Medicines Research Funding: Kura Oncology, Eisai, Roche, Genentech, Exelixis, (© 2018 by American Society of Clinical Oncology.)

Background: Anaplastic thyroid carcinoma (ATC) is a rare but deadly form of thyroid cancer. Kinase inhibitors kinase inhibitors have shown clinical efficacy in the management of ATC, however, eventually these tumors acquire resistance to KI and patients succumb to their disease. Salvage therapy in this setting is limited. As ATC tumors diffusely express the programmed cell death protein ligand (PD-L1), anti- programmed cell death protein (PD-1) drugs such as pembrolizumab offer therapeutic potential. We sought to explore the efficacy of adding pembrolizumab to kinase inhibitors at progression in ATC., Methods: We retrospectively reviewed the charts of ATC patients initiated on pembrolizumab in combination with KI at the time of progression on kinase inhibitors at MD Anderson Cancer Center between August 2016 and August 2017. Efficacy was evaluated with best overall response (BOR) using RECISTv1.1 criteria. Progression free survival (PFS) from the start of pembrolizumab and overall survival (OS) from the start of kinase inhibitors, as well as from the time of addition of pembrolizumab were calculated., Results: Twelve patients were treated with combination kinase inhibitors plus pembrolizumab at the time of progression on their KI therapy. Median age at initiation of pembrolizumab was 60 years (range 47-84 years). BOR was as follows: 5/12 (42%) had partial response, 4/12 (33%) had stable disease and 3/12 (25%) had progressive disease. Median OS from the start of kinase inhibitor was 10.43 months (95% CI = 6.02, 14.83, range 5.4-40 months). Median OS and PFS from the addition of pembrolizumab were 6.93 months (95% CI = 1.7, 12.15, range 3-15.9 months) and 2.96 months (95% CI = 2.2, 3.7, range 0.57-13.14 months), respectively. Fatigue, anemia and hypertension were the most common AEs encountered on these combinations. Therapy had to be discontinued in 2 patients due to drug induced rash and altered mental status likely from progression of disease., Conclusion: In a subset of ATC patients, pembrolizumab may be an effective salvage therapy added to kinase inhibitors at the time of progression on these drugs. However, better treatment strategies aimed at incorporating immunotherapy in patients with ATC should be explored. Frontline combination of KI with immunotherapy should be studied in prospective clinical trials.

Background: Patients with anaplastic thyroid cancer (ATC) have a dismal prognosis, despite systemic cytotoxic chemotherapy. The objective of this study was to investigate the efficacy and safety of targeted therapy in ATC patients when used outside of a clinical trial., Methods: This is a retrospective review from April 2015 to May 2016 at a single academic institution where 16 ATC patients receiving targeted therapy outside of a clinical trial were studied. Ten patients (eight BRAF wild type and two BRAF V600E mutant tumors) were started on lenvatinib, and six with BRAF V600E -mutated tumors received a combination of dabrafenib plus trametinib. Best response evaluated by RECIST v1.1, progression-free survival, and overall survival were determined. Adverse events were evaluated for safety., Results: The majority of patients (63%) were men, and all had distant metastases or radiation-resistant primary disease at the time of treatment. In the entire cohort, 6/16 (38%) had a partial response, 6/16 (38%) had stable disease, and 2/16 (12%) had progressive disease. Two (12%) patients died before restaging. Median follow-up time was 11.8 months. Median progression-free survival was 3.7 months [confidence interval 1.8-7.6] in the entire cohort, 2.7 months for lenvatinib, and 5.2 months for dabrafenib plus trametinib. Median OS was 6.3 months [confidence interval 1.8-7.6] for the entire cohort, 3.9 months for lenvatinib, and 9.3 months for dabrafenib plus trametinib. Adverse events were as expected and manageable., Conclusions: Targeted therapies, lenvatinib, and dabrafenib plus trametinib (for BRAF V600E mutants) may provide clinical benefit in ATC patients who are unable to participate in clinical trials, and toxicities are manageable.