Impact of the COVID-19 Pandemic and Vaccine Availability on Utilization of Breast Imaging in a Multistate Radiology Practice.

Method: Data were obtained from medical health records across 77 Radiology Partners practices in the US. The data provided us with the total monthly mammography, breast ultrasound, and breast MRI procedures from January 2019 to September 2022. An interrupted time-series (ITS) analysis was conducted to evaluate the effect of the COVID-19 pandemic and the COVID-19 vaccination. We chose March 2020 and December 2020 as critical time points in the pandemic and analyzed trends before and after these dates. Results: The starting level (at baseline in January 2019) of the total breast imaging procedure volume was estimated at 114,901.5, and this volume appeared to significantly increase every month prior to March 2020 by 4,864.0 (p < 0.0001, CI = [3,077.1, 6,650.9]). In March 2020, there appeared to be a significant decrease in volume by 104,446.3 (p=0.003, CI = [-172,063.1, -36,829.5]), followed by a significant increase in the monthly trend of service volume (relative to the pre-COVID trend) of 20,660.7 per month (p=0.001, CI = [8,828.5, 32,493.0]). In December 2020, there appeared to be a significant decrease in service volume by 69,791.2 (p=0.012, CI = [-123,602.6, -15,979.7]). Compared to the period from March to November 2020, there was a decrease in the monthly trend of service volumes per month by 24,213.9 (p < 0.0001, CI = [-36,027.6, -12,400.2]). After March 2020, the total service volume increased at the rate of 25,524.7 per month (p < 0.0001, CI = [13,828.2, 37,221.2]). In contrast, the service volumes after December 2020 appeared to grow steadily and slowly at a rate of 1,310.8 per month (p=0.118, CI = [-348.8, 2970.3]). Conclusion: Our study revealed that there has been a recovery and a further increase in breast imaging service volumes compared to prepandemic levels. The increase can be best explained by vaccination rollout, reopening of elective/nonemergency healthcare services, insurance coverage expansion, the decline in the US uninsured rate due to government interventions and policies, and the recovery of jobs with employer-provided medical insurance post-pandemic.

Social Determinants of Health Framework to Identify and Reduce Barriers to Imaging in Marginalized Communities.

Social determinants of health (SDOH) are conditions influencing individuals' health based on their environment of birth, living, working, and aging. Addressing SDOH is crucial for promoting health equity and reducing health outcome disparities. For conditions such as stroke and cancer screening where imaging is central to diagnosis and management, access to high-quality medical imaging is necessary. This article applies a previously described structural framework characterizing the impact of SDOH on patients who require imaging for their clinical indications. SDOH factors can be broadly categorized into five sectors: economic stability, education access and quality, neighborhood and built environment, social and community context, and health care access and quality. As patients navigate the health care system, they experience barriers at each step, which are significantly influenced by SDOH factors. Marginalized communities are prone to disparities due to the inability to complete the required diagnostic or screening imaging work-up. This article highlights SDOH that disproportionately affect marginalized communities, using stroke and cancer as examples of disease processes where imaging is needed for care. Potential strategies to mitigate these disparities include dedicating resources for clinical care coordinators, transportation, language assistance, and financial hardship subsidies. Last, various national and international health initiatives are tackling SDOH and fostering health equity.

Radiation Dosimetry, Artificial Intelligence and Digital Twins: Old Dog, New Tricks.

Developments in artificial intelligence, particularly convolutional neural networks and deep learning, have the potential for problem solving that has previously confounded human intelligence. Accurate prediction of radiation dosimetry pre-treatment with scope to adjust dosing for optimal target and non-target tissue doses is consistent with striving for improved the outcomes of precision medicine. The combination of artificial intelligence and production of digital twins could provide an avenue for an individualised therapy doses and enhanced outcomes in theranostics. While there are barriers to overcome, the maturity of individual technologies (i.e. radiation dosimetry, artificial intelligence, theranostics and digital twins) places these approaches within reach.

An Unusual Case of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Introduction: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare disease entity associated with textured breast implants. Though the clinical course is typically indolent, BIA-ALCL can occasionally invade through the capsule into the breast parenchyma with spread to the regional lymph nodes and beyond including chest wall invasive disease. Case: We present the case of a 51-year-old female with a history of bilateral silicone breast implants placed approximately twenty years ago who presented with two months of progressively enlarging right breast mass. Ultrasound-guided biopsy of right breast mass and right axillary lymph node showed CD 30-positive ALK-negative anaplastic large cell lymphoma, and staging work up showed extension of the tumor to chest wall and ribs consistent with advanced disease. She received CHP-BV (cyclophosphamide, doxorubicin, prednisone, and brentuximab vedotin) for six cycles with complete metabolic response. This was followed by extensive surgical extirpation and reconstruction, radiation for residual disease and consolidation with autologous stem cell transplant. She is currently on maintenance brentuximab vedotin with no evidence of active disease post autologous stem cell transplant. Conclusion: Treatment guidelines for advanced chest wall invasive BIA-ALCL are not well defined. Lack of predictive factors warrants mutation analysis and genetic sequencing to identify those at highest risk of progression to chest wall invasive disease. This rare case highlights the need for definitive consensus on the optimal management of chest wall invasive BIA-ALCL.

DOTATATE Uptake in an Axillary Lymph Node After COVID-19 Vaccination.

ABSTRACT: A 58-year-old man underwent DOTATATE PET/CT scan for follow-up of pulmonary neuroendocrine tumor after resection and adjuvant chemotherapy. On screening paperwork, the patient indicated having received the Johnson & Johnson/Janssen COVID-19 vaccine (Janssen Biotech, Inc) 1 day previously, administered in the right deltoid muscle. Reactive changes in regional lymph nodes is a known response for all 3 currently Food and Drug Administration-approved COVID-19 vaccines. Recent published data have demonstrated FDG PET-avid axillary lymphadenopathy subsequent to COVID-19 vaccination, and included here is a report of DOTATATE PET-avid axillary lymph node after injection of the Johnson & Johnson COVID-19 vaccine.

Pitfalls in Interpretation of PET/CT in the Chest.

Whole body positron emission tomography (PET)/computed tomography (CT) imaging with [18F]-fluoro-2-deoxy-D-glucose (FDG) is widely used in oncologic imaging. In the chest, common PET/CT applications include the evaluation of solitary pulmonary nodules, cancer staging, assessment of response to therapy, and detection of residual or recurrent disease. Knowledge of the technical artifacts and potential pitfalls that radiologists may encounter in the interpretation of PET/CT in the thorax is important to avoid misinterpretation and optimize patient management. This article will review pitfalls in the interpretation of PET/CT in the chest related to technical factors, physiologic uptake, false positive findings, false negative findings, and iatrogenic conditions.

Delayed FDG PET Provides Superior Glioblastoma Conspicuity Compared to Conventional Image Timing.

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.

ACR-ACNM-ASTRO-SNMMI Practice Parameter for the Performance of Therapy With Radium-223.

AIM/OBJECTIVES/BACKGROUND: The goal of therapy with unsealed radiopharmaceutical sources is to provide either cure or significant prolongation of disease-specific survival, and effective reduction and/or prevention of adverse disease-related symptoms or untoward events while minimizing treatment-associated side effects and complications. Radium-223 dichloride (radium-223) is an alpha particle-emitting isotope used for targeted bone therapy. This practice parameter is intended to guide appropriately trained and licensed physicians performing therapy with radium-223. Such therapy requires close cooperation and communication between the physicians who are responsible for the clinical management of the patient and those who administer radiopharmaceutical therapy and manage the attendant side effects. Adherence to this parameter should help to maximize the efficacious use of radium-223, maintain safe conditions, and ensure compliance with applicable regulations. METHODS: This practice parameter was developed according to the process described on the American College of Radiology (ACR) website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the American College of Nuclear Medicine (ACNM), the American Society for Radiation Oncology (ASTRO), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). All these societies contributed to the development of the practice parameter and approved the final document. RESULTS: This practice parameter addresses the many factors which contribute to appropriate, safe, and effective clinical use of radium-223. Topics addressed include qualifications and responsibilities of personnel, specifications of patient examination and treatment; documentation, radiation safety, quality control/improvement, infection control, and patient education. CONCLUSIONS: This practice parameter is intended as a tool to guide clinical use of radium-223 with the goal of facilitating safe and effective medical care based on current knowledge, available resources and patient needs. The sole purpose of this document is to assist practitioners in achieving this objective.

Low-dose versus High-dose Carfilzomib with Dexamethasone (S1304) in Patients with Relapsed-Refractory Multiple Myeloma.

PURPOSE: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits. PATIENTS AND METHODS: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m2; arm 1) to high-dose carfilzomib (56 mg/m2; arm 2), both with dexamethasone, administered for 12 cycles (11 months) for relapsed and/or refractory multiple myeloma with up to six prior lines of therapy (NCT01903811). The primary endpoint was progression-free survival (PFS), and patients on arm 1 could cross-over to arm 2 after progression on treatment. RESULTS: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (P = 0.113). Also, neither the median PFS [5 months and 8 months, respectively; HR, 1.061; 80% Wald confidence interval (CI), 0.821-1.370; P = 0.384] nor the median overall survival were significantly different (26 and 22 months, respectively; HR, 1.149, 80% Wald CI, 0.841-.571; P = 0.284). Sixteen patients crossed over to arm 2 with a median PFS benefit of 3 months. Certain adverse events (AE) were more frequent in arm 2, including fatigue, thrombocytopenia, and peripheral neuropathy, but there was no significant difference in cardiopulmonary AEs. CONCLUSIONS: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m2 dosing of carfilzomib over the 27 mg/m2 dose for the treatment of relapsed and/or refractory multiple myeloma. However, treatment to progression in earlier patient populations with high-dose carfilzomib using different schedules should still be considered as part of the standard of care.

Development of sodium fluoride PET response criteria for solid tumours (NAFCIST) in a clinical trial of radium-223 in osteosarcoma: from RECIST to PERCIST to NAFCIST.

PURPOSE: The development of osteosarcoma therapeutics has been challenging, in part because of the lack of appropriate criteria to evaluate responses. We developed a novel criteria in a clinical trial of radium-223 dichloride (223RaCl2) for response assessment in osteosarcoma, NAFCIST (Na18F PET response Criteria in Solid Tumors). EXPERIMENTAL DESIGN: Patients received one to six cycles of 223RaCl2, and cumulative doses varied from 6.84 MBq to 57.81 MBq. Molecular imaging with technetium-99m phosphonate scintigraphy, fluorine-18-fluorodeoxyglucose (18FDG) positron emission tomography (PET) or sodium fluoride-18 (Na18F) PET was used to characterise the disease. Correlation of biomarkers and survival was analysed with NAFCIST measure from Na18F PET. RESULTS: Of the 18 patients, 17 had bone lesions visible in at least one of the imaging studies. In four of seven patients with multiple skeletal lesions (>5), FDG PET and NaF PET studies could be compared. The skeletal tumour locations varied in our patient population: cranium=2, extremities=7, pelvis=10, spine=12 and thorax=9. The 18F-FDG PET and Na18F PET studies could be compared in all four patients who had multiple lung lesions (>5). Overall the Response Evaluation Criteria in Solid Tumors response was seen in one patient, but four patients experienced mixed responses better defined by Na18F PET. Changes in NAFCIST were correlated with changes in bone alkaline phosphatase levels (r=0.54) and negatively with cumulative dose of 223RaCl2 (r=- 0.53). NAFCIST correlated with overall survival (p value of 0.037) while the PERCIST (PET Response Criteria in Solid Tumors) did not (p value of 0.19). CONCLUSIONS: Our results indicate that Na18F PET should be further studied in osteosarcoma staging. NAFCIST may be a promising criteria for high-risk osteosarcoma response evaluation and correlates with survival. Further validation studies are needed.

Final Outcome of 223Ra-therapy and the Role of 18F-fluoride-PET in Response Evaluation in Metastatic Castration-resistant Prostate Cancer-A Single Institution Experience.

BACKGROUND: 223Ra was the first therapeutic alpha-emitting radionuclide registered for clinical practice. This radionuclide is targeting actively bone-forming cells, and it is approved for treating metastatic skeletal disease in prostate cancer. 18F-PET is used to detect skeletal metastatic disease based on osteoblastic activity. The aim of this study was to analyze, if 18F-PET can be used assessing the results of 223Ra therapy, and to report final median overall survival in a total of 773 therapy cycles. METHODS: A 161 men with castration-resistant prostate cancer were included in a single institution study (Protocol#: PA14-0848) and they received a total of 773 223Ra therapy cycles. RESULTS: The median overall survival (95% CI) was 12.4 (9.1, 16.1) months in patient population. Interim Na18F-PET imaging was applied in 14 patients at baseline, after 3 cycles and after 6 cycles. TLF10 (skeletal disease burden at SUV-values >10 on Na18F -PET) were calculated in all these PET studies, and there was no significant association between change in TLF10 after 3 cycles and TLF10 after 6 cycles (p=0.20). CONCLUSION: From these results, we conclude that interim imaging does not help in assessing the final outcome of 223Ra therapy. The survival benefit of 223Ra therapy alone is more than a year in a high-risk group of advanced prostate cancer.

Hematologic Toxicity From Radium-223 Therapy for Bone Metastases in Castration-Resistant Prostate Cancer: Risk Factors and Practical Considerations.

Radium-223 dichloride is an α-emitting radiopharmaceutical that localizes to bone matrix and is approved for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. The cumulative impact of Ra-223 and other therapeutic agents for metastatic CRPC on myelosuppression in bone marrow is unknown. The phase 3 randomized, double-blind, placebo-controlled ALSYMPCA trial of Ra-223 in patients with CRPC and symptomatic bone metastases demonstrated a significant improvement in overall survival. Of the 571 patients subsequently followed for 3 years, few in either the Ra-223 or placebo arm experienced hematologic adverse events. Little evidence shows secondary malignancies associated with Ra-223 treatment; only 2 cases of secondary leukemia after Ra-223 treatment were found in the literature. The goals of this review were to summarize safety and efficacy results from clinical trials and institutional safety data pertaining to hematologic adverse events occurring with Ra-223, and to discuss practical management issues.

Spectrum of Benign Bone Conditions on NaF-PET.

Fluoride imaging with 18F (NaF-PET), although not a new technique, is becoming increasingly utilized for evaluation of skeletal metastatic disease using PET/CT. As its use becomes more widespread, a variety of nonmalignant bone disorders will be encountered by the interpreting physician. It is important, therefore, to recognize these nonmalignant conditions to avoid errors in interpretation. Beyond this, there is increasing evidence in the literature that NaF-PET/CT imaging may provide valuable information for the primary diagnosis of these nonmalignant conditions, and furthermore may provide insight into the underlying biology leading to management decisions. In this article, we review a spectrum of benign bone conditions that can be visualized on NaF-PET.

Refining prognosis in patients with hepatocellular carcinoma through incorporation of metabolic imaging biomarkers.

PURPOSE: 18F-fluorodeoxyglucose positron emission tomopraphy/computed tomography (FDGPET/CT) has been proven to be useful for imaging many types of cancer; however, its role is not well defined in hepatocellular carcinoma (HCC). We assessed the prognostic value of metabolic imaging biomarkers as established by baseline pretreatment FDG PET/CT in patients with HCC. METHODS: We retrospectively analyzed the records of patients with HCC who underwent FDG PET/CT before initial treatment from May 2013 through May 2014. Four PET/CT parameters were measured: maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and tumor-to-normal-liver SUV ratio (TNR). Optimal cut-off values for the PET/CT parameters to stratify patients in terms of overall survival (OS) were determined. Multivariate analysis was performed to determine whether the PET/CT parameters could add to the prognostic value of the Cancer of the Liver Italian Program (CLIP) scoring system and the Barcelona-Clinic Liver Cancer (BCLC) staging system. RESULTS: The analysis included 56 patients. Univariate analysis of the association between OS and continuous variables, including the PET/CT parameters SUVmax, TLG, tumor size, total bilirubin level, and alkaline phosphatase level were significant predictors of OS. SUVmax ≥ 11.7, TLG ≥ 1,341, MTV ≥ 230 mL, and TNR ≥ 4.8 were identified as cut-off values. Multivariate analysis revealed that SUVmax ≥ 11.7 and TNR ≥ 4.8 were independent factors predicting a poor prognosis in both the CLIP scoring system and the BCLC staging system, as was TLG in the BCLC staging system. CONCLUSION: Pretreatment FDG PET/CT in patients with HCC can add to the prognostic value of standard clinical measures. Incorporation of imaging biomarkers derived from FDG PET/CT into HCC staging systems should be considered.

IGF-1R and mTOR Blockade: Novel Resistance Mechanisms and Synergistic Drug Combinations for Ewing Sarcoma.

BACKGROUND: Therapies cotargeting insulin-like growth factor receptor 1 (IGF-1R) and mammalian target of rapamycin (mTOR) have demonstrated remarkable, albeit short-lived, clinical responses in a subset of Ewing sarcoma (ES) patients. However, the mechanisms of resistance and applicable strategies for overcoming drug resistance to the IGF-1R/mTOR blockade are still undefined. METHODS: To elucidate predominant mechanism(s) of acquired drug resistance while identifying synergistic drug combinations that improve clinical efficacy, we generated more than 18 ES cell lines resistant to IGF-1R- or mTOR-targeted therapy. Two small-molecule inhibitors of IGF-1R were chosen, NVP-ADW-742 (IGF-1R-selective) and OSI-906 (a dual IGF-1R/insulin receptor alpha [IR-α] inhibitor). Reverse-phase protein lysate arrays (RPPAs) revealed proteomic changes linked to IGF-1R/mTOR resistance, and selected proteins were validated in cell-based assays, xenografts, and within human clinical samples. All statistical tests were two-sided. RESULTS: Novel mechanisms of resistance (MOR) emerged after dalotuzumab-, NVP-ADW-742-, and OSI-906-based targeting of IGF-1R. MOR to dalotuzumab included upregulation of IRS1, PI3K, and STAT3, as well as p38 MAPK, which was also induced by OSI-906. pEIF4E(Ser209), a key regulator of Cap-dependent translation, was induced in ridaforolimus-resistant ES cell lines. Unique drug combinations targeting IGF-1R and PI3K-alpha or Mnk and mTOR were synergistic in vivo and vitro (P < .001) as assessed respectively by Mantel-Cox and isobologram testing. CONCLUSIONS: We discovered new druggable targets expressed by chemoresistant ES cells, xenografts, and relapsed human tumors. Joint suppression of these newfound targets, in concert with IGF-1R or mTOR blockade, should improve clinical outcomes.