Imaging of Neuroendocrine Neoplasms; Principles of Treatment Strategies. What Referring Clinicians Want to Know.

ABSTRACT: Neuroendocrine neoplasms (NENs) are a diverse group of tumors that express neuroendocrine markers and primarily affect the lungs and digestive system. The incidence of NENs has increased over time due to advancements in imaging and diagnostic techniques. Effective management of NENs requires a multidisciplinary approach, considering factors such as tumor location, grade, stage, symptoms, and imaging findings. Treatment strategies vary depending on the specific subtype of NEN. In this review, we will focus on treatment strategies and therapies including the information relevant to clinicians in order to undertake optimal management and treatment decisions, the implications of different therapies on imaging, and how to ascertain their possible complications and treatment effects.

Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.

Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms: Maximizing Strengths and Mitigating Weaknesses.

ABSTRACT: Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms.

An Illustrated Review of the Recent 2019 World Health Organization Classification of Neuroendocrine Neoplasms: A Radiologic and Pathologic Correlation.

ABSTRACT: Recent advances in molecular pathology and an improved understanding of the etiology of neuroendocrine neoplasms (NENs) have given rise to an updated World Health Organization classification. Since gastroenteropancreatic NENs (GEP-NENs) are the most common forms of NENs and their incidence has been increasing constantly, they will be the focus of our attention. Here, we review the findings at the foundation of the new classification system, discuss how it impacts imaging research and radiological practice, and illustrate typical and atypical imaging and pathological findings. Gastroenteropancreatic NENs have a highly variable clinical course, which existing classification schemes based on proliferation rate were unable to fully capture. While well- and poorly differentiated NENs both express neuroendocrine markers, they are fundamentally different diseases, which may show similar proliferation rates. Genetic alterations specific to well-differentiated neuroendocrine tumors graded 1 to 3 and poorly differentiated neuroendocrine cancers of small cell and large-cell subtype have been identified. The new tumor classification places new demands and creates opportunities for radiologists to continue providing the clinically most relevant report and on researchers to design projects, which continue to be clinically applicable.

State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

ABSTRACT: Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

Society of Radiologists in Ultrasound Consensus Conference Recommendations for Incidental Gallbladder Polyp Management: Interreader Agreement Among 10 Radiologists.

BACKGROUND. The 2022 Society of Radiologists in Ultrasound (SRU) consensus conference recommendations for small gallbladder polyps support management that is less aggressive than earlier approaches and may help standardize evaluation of polyps by radiologists. OBJECTIVE. The purpose of the present study was to assess the interreader agreement of radiologists in applying SRU recommendations for management of incidental gallbladder polyps on ultrasound. METHODS. This retrospective study included 105 patients (75 women and 30 men; median age, 51 years) with a gallbladder polyp on ultrasound (without features highly suspicious for invasive or malignant tumor) who underwent cholecystectomy between January 1, 2003, and January 1, 2021. Ten abdominal radiologists independently reviewed ultrasound examinations and, using the SRU recommendations, assessed one polyp per patient to assign risk category (extremely low risk, low risk, or indeterminate risk) and make a possible recommendation for surgical consultation. Five radiologists were considered less experienced (< 5 years of experience), and five were considered more experienced (≥ 5 years of experience). Interreader agreement was evaluated. Polyps were classified pathologically as nonneoplastic or neoplastic. RESULTS. For risk category assignments, interreader agreement was substantial among all readers (k = 0.710), less-experienced readers (k = 0.705), and more-experienced readers (k = 0.692). For surgical consultation recommendations, inter-reader agreement was substantial among all readers (k = 0.795) and more-experienced readers (k = 0.740) and was almost perfect among less-experienced readers (k = 0.811). Of 10 readers, a median of 5.0 (IQR, 2.0-8.0), 4.0 (IQR, 2.0-7.0), and 0.0 (IQR, 0.0-0.0) readers classified polyps as extremely low risk, low risk, and indeterminate risk, respectively. Across readers, the percentage of polyps classified as extremely low risk ranged from 32% to 72%; as low risk, from 24% to 65%; and as indeterminate risk, from 0% to 8%. Of 10 readers, a median of zero change to 0 (IQR, 0.0-1.0) readers recommended surgical consultation; the percentage of polyps receiving a recommendation for surgical consultation ranged from 4% to 22%. Of a total of 105 polyps, 102 were nonneo-plastic and three were neoplastic (all benign). Based on readers' most common assessments for nonneoplastic polyps, the risk category was extremely low risk for 53 polyps, low risk for 48 polyps, and indeterminate risk for one polyp; surgical consultation was recommended for 16 polyps. CONCLUSION. Ten abdominal radiologists showed substantial agreement for polyp risk categorizations and surgical consultation recommendations, although areas of reader variability were identified. CLINICAL IMPACT. The findings support the overall reproducibility of the SRU recommendations, while indicating opportunity for improvement.

Abdominal Positron Emission Tomography/Magnetic Resonance Imaging.

Hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) is highly suited for abdominal pathologies. A precise co-registration of anatomic and metabolic data is possible thanks to the simultaneous acquisition, leading to accurate imaging. The literature shows that PET/MRI is at least as good as PET/CT and even superior for some indications, such as primary hepatic tumors, distant metastasis evaluation, and inflammatory bowel disease. PET/MRI allows whole-body staging in a single session, improving health care efficiency and patient comfort.

Long-Term Outcomes of Tuberous Sclerosis Complex-Associated Non-functional Pancreatic Neuroendocrine Tumors: Should We Be More Conservative?

BACKGROUND: Hereditary syndromes such as tuberous sclerosis complex (TSC) account for 10% of pancreatic neuroendocrine tumors (PNETs). Surgical intervention is the current standard of care for sporadic PNETs (spPNETs) that are >2 cm in size. We compared the long-term outcomes of resected TSC-PNETs with patients with spPNETs. METHODS: We conducted a retrospective review of perioperative data and outcomes of TSC-PNETs compared with spPNETs. Inclusion criteria involved selecting patients whose tumors were no larger than 5.1 cm, the maximum size observed in the TSC-PNET group. RESULTS: Of the 347 patients resected for PNETs, 14 were TSC-PNETs and 241 were non-functional spPNETs. The median age for the whole cohort was 56 years (interquartile range [IQR] 21.0) and 47% were female. The median follow-up was 103.8 months (95% confidence interval [CI] 89.2-118.6). Specifically, 14 patients with TSC-PNETs and 194 patients with spPNETs were included. Compared with spPNETs, patients with TSC-PNETs were operated on at a younger age (24.0 vs. 57.5 years; p < 0.001), were more frequently multifocal (28.5% vs. 0.0%; p < 0.001), were more likely to undergo minimally invasive operations (78.6% vs. 24.3%; p < 0.001), and had more R1 resections (28.6% vs. 5.7%; p = 0.006). Local and distant tumor recurrence was only observed in the spPNET group. The 5-year mortality rates for the spPNET and TSC-PNET groups were 6.2% and 0.0%, respectively. No PNET-related deaths were observed among TSC-PNETs. CONCLUSION: None of the TSC-PNET patients recurred after a median follow-up of 78.0 months. The risk-benefit of aggressive pancreatic operations in TSC-PNET patients is still unclear and our findings suggest a conservative approach should be considered.

Non-exposed endoscopic wall-inversion surgery with one-step nucleic acid amplification for early gastrointestinal tumors: Personal experience and literature review.

BACKGROUND: Laparoscopic and endoscopic cooperative surgery is a safe, organ-sparing surgery that achieves full-thickness resection with adequate margins. Recent studies have demonstrated the safety and efficacy of these procedures. However, these techniques are limited by the exposure of the tumor and mucosa to the peritoneal cavity, which could lead to viable cancer cell seeding and the spillage of gastric juice or enteric liquids into the peritoneal cavity. Non-exposed endoscopic wall-inversion surgery (NEWS) is highly accurate in determining the resection margins to prevent intraperitoneal contamination because the tumor is inverted into the visceral lumen instead of the peritoneal cavity. Accurate intraoperative assessment of the nodal status could allow stratification of the extent of resection. One-step nucleic acid amplification (OSNA) can provide a rapid method of evaluating nodal tissue, whilst near-infrared laparoscopy together with indocyanine green can identify relevant nodal tissue intraoperatively. AIM: To determine the safety and feasibility of NEWS in early gastric and colon cancers and of adding rapid intraoperative lymph node (LN) assessment with OSNA. METHODS: The patient-based experiential portion of our investigations was conducted at the General and Oncological Surgery Unit of the St. Giuseppe Moscati Hospital (Avellino, Italy). Patients with early-stage gastric or colon cancer (diagnosed via endoscopy, endoscopic ultrasound, and computed tomography) were included. All lesions were treated by NEWS procedure with intraoperative OSNA assay between January 2022 and October 2022. LNs were examined intraoperatively with OSNA and postoperatively with conventional histology. We analyzed patient demographics, lesion features, histopathological diagnoses, R0 resection (negative margins) status, adverse events, and follow-up results. Data were collected prospectively and analyzed retrospectively. RESULTS: A total of 10 patients (5 males and 5 females) with an average age of 70.4 ± 4.5 years (range: 62-78 years) were enrolled in this study. Five patients were diagnosed with gastric cancer. The remaining 5 patients were diagnosed with early-stage colon cancer. The mean tumor diameter was 23.8 ± 11.6 mm (range: 15-36 mm). The NEWS procedure was successful in all cases. The mean procedure time was 111.5 ± 10.7 min (range: 80-145 min). The OSNA assay revealed no LN metastases in any patients. Histologically complete resection (R0) was achieved in 9 patients (90.0%). There was no recurrence during the follow-up period. CONCLUSION: NEWS combined with sentinel LN biopsy and OSNA assay is an effective and safe technique for the removal of selected early gastric and colon cancers in which it is not possible to adopt conventional endoscopic resection techniques. This procedure allows clinicians to acquire additional information on the LN status intraoperatively.

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe.

The 68Ga-Collagen Binding Probe #8, 68Ga-CBP8, is a peptide-based, type I collagen-targeted probe developed for imaging of tissue fibrosis. The aim of this study was to determine the biodistribution, dosimetry, and pharmacokinetics of 68Ga-CBP8 in healthy human subjects. Methods: Nine healthy volunteers (5 male and 4 female) underwent whole-body 68Ga-CBP8 PET/MRI using a Biograph mMR scanner. The subjects were imaged continuously for up to 2 h after injection of 68Ga-CBP8. A subset of subjects underwent an additional imaging session 2-3 h after probe injection. OLINDA/EXM software was used to calculate absorbed organ and effective dose estimates based on up to 17 regions of interest (16 for men) defined on T2-weighted MR images and copied to the PET images, assuming a uniform distribution of probe concentration in each region. Serial blood sampling up to 90 min after probe injection was performed to assess blood clearance and metabolic stability. Results: The mean injected activity (±SD) of 68Ga-CBP8 was 220 ± 100 MBq (range, 113-434 MBq). No adverse effects related to probe administration were detected. 68Ga-CBP8 demonstrated an extracellular distribution with predominantly rapid renal clearance. Doses on the urinary bladder were 0.15 versus 0.19 mGy/MBq for men versus women. The highest absorbed doses for the rest of the organs were measured in the kidneys (0.078 vs. 0.088 mGy/MBq) and the liver (0.032 vs. 0.041 mGy/MBq). The mean effective dose was 0.018 ± 0.0026 mSv/MBq using a 1-h voiding model. The 68Ga-CBP8 signal in the blood demonstrated biexponential pharmacokinetics with an initial distribution half-life of 4.9 min (95% CI, 2.4-9.4 min) and a 72-min elimination half-life (95% CI, 47-130 min). The only metabolite observed had a long blood plasma half-life, suggesting protein-bound 68Ga. Conclusion: 68Ga-CBP8 displays favorable in-human characteristics and dosimetry similar to that of other gallium-based probes. 68Ga-CBP8 could therefore be used for noninvasive collagen imaging across a range of human fibrotic diseases.

External validation of a machine learning based algorithm to differentiate hepatic mucinous cystic neoplasms from benign hepatic cysts.

PURPOSE: To externally validate an algorithm for non-invasive differentiation of hepatic mucinous cystic neoplasms (MCN) from benign hepatic cysts (BHC), which differ in management. METHODS: Patients with cystic liver lesions pathologically confirmed as MCN or BHC between January 2005 and March 2022 from multiple institutions were retrospectively included. Five readers (2 radiologists, 3 non-radiologist physicians) independently reviewed contrast-enhanced CT or MRI examinations before tissue sampling and applied the 3-feature classification algorithm described by Hardie et al. to differentiate between MCN and BHC, which had a reported accuracy of 93.5%. The classification was then compared to the pathology results. Interreader agreement between readers across different levels of experience was evaluated with Fleiss' Kappa. RESULTS: The final cohort included 159 patients, median age of 62 years (IQR [52.0, 70.0]), 66.7% female (106). Of all patients, 89.3% (142) had BHC, and the remaining 10.7% (17) had MCN on pathology. Agreement for class designation between the radiologists was almost perfect (Fleiss' Kappa 0.840, p < 0.001). The algorithm had an accuracy of 98.1% (95% CI [94.6%, 99.6%]), a positive predictive value of 100.0% (95% CI [76.8%, 100.0%]), a negative predictive value of 97.9% (95% CI [94.1%, 99.6%]), and an area under the receiver operator characteristic curve (AUC) of 0.911 (95% CI [0.818, 1.000]). CONCLUSION: The evaluated algorithm showed similarly high diagnostic accuracy in our external, multi-institutional validation cohort. This 3-feature algorithm is easily and rapidly applied and its features are reproducible among radiologists, showing promise as a clinical decision support tool.

Radiomics: A radiological evidence-based artificial intelligence technique to facilitate personalized precision medicine in hepatocellular carcinoma.

The high postoperative recurrence rates in hepatocellular carcinoma (HCC) remain a major hurdle in its management. Appropriate staging and treatment selection may alleviate the extent of fatal recurrence. However, effective methods to preoperatively evaluate pathophysiologic and molecular characteristics of HCC are lacking. Imaging plays a central role in HCC diagnosis and stratification due to the non-invasive diagnostic criteria. Vast and crucial information is hidden within image data. Other than providing a morphological sketch for lesion diagnosis, imaging could provide new insights to describe the pathophysiological and genetic landscape of HCC. Radiomics aims to facilitate diagnosis and prognosis of HCC using artificial intelligence techniques to harness the immense information contained in medical images. Radiomics produces a set of archetypal and robust imaging features that are correlated to key pathological or molecular biomarkers to preoperatively risk-stratify HCC patients. Inferred with outcome data, comprehensive combination of radiomic, clinical and/or multi-omics data could also improve direct prediction of response to treatment and prognosis. The evolution of radiomics is changing our understanding of personalized precision medicine in HCC management. Herein, we review the key techniques and clinical applications in HCC radiomics and discuss current limitations and future opportunities to improve clinical decision making.

Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Versus the Standard of Care Imaging in the Diagnosis of Peritoneal Carcinomatosis.

OBJECTIVE: To compare positron emission tomography (PET)/magnetic resonance imaging (MRI) to the standard of care imaging (SCI) for the diagnosis of peritoneal carcinomatosis (PC) in primary abdominopelvic malignancies. SUMMARY BACKGROUND DATA: Identifying PC impacts prognosis and management of multiple cancer types. METHODS: Adult subjects were prospectively and consecutively enrolled from April 2019 to January 2021. Inclusion criteria were: 1) acquisition of whole-body contrast-enhanced (CE) 18F-fluorodeoxyglucose PET/MRI, 2) pathologically confirmed primary abdominopelvic malignancies. Exclusion criteria were: 1) greater than 4 weeks interval between SCI and PET/MRI, 2) unavailable follow-up. SCI consisted of whole-body CE PET/computed tomography (CT) with diagnostic quality CT, and/or CE-CT of the abdomen and pelvis, and/or CE-MRI of the abdomen±pelvis. If available, pathology or surgical findings served as the reference standard, otherwise, imaging followup was used. When SCI and PET/MRI results disagreed, medical records were checked for management changes. Follow-up data were collected until August 2021. RESULTS: One hundred sixty-four subjects were included, 85 (52%) were female, and the median age was 60 years (interquartile range 50-69). At a subject level, PET/MRI had higher sensitivity (0.97, 95% CI 0.86-1.00) than SCI (0.54, 95% CI 0.37-0.71), P < 0.001, without a difference in specificity, of 0.95 (95% CI 0.90-0.98) for PET/MRI and 0.98 (95% CI 0.93-1.00) for SCI, P » 0.250. PET/MRI and SCI results disagreed in 19 cases. In 5/19 (26%) of the discordant cases, PET/MRI findings consistent with PC missed on SCI led to management changes. CONCLUSION: PET/MRI improves detection of PC compared with SCI which frequently changes management.

HER3 PET Imaging Predicts Response to Pan Receptor Tyrosine Kinase Inhibition Therapy in Gastric Cancer.

PURPOSE: New generation of receptor tyrosine kinase inhibitors (RTKIs) have shown to improve survival in many solid tumors. However, an imaging biomarker is needed for patient selection and prediction of treatment response. This study evaluates the use of quantitative changes of HER3 on 68 Ga-NOTA-HER3P1 PET/MRI for prediction of early response to pan-RTKIs in gastric cancer (GCa). PROCEDURES: GCa cell lines were evaluated for expression of RTKs, and downstream signaling pathways (AKT and MAPK). Cell viability was assessed following 24-72 h of treatment with 0.01-1 µmol/L of afatinib, a pan-RTKI. HER3-expressing afatinib-sensitive (NCI-N87) and resistant cells (SNU16) were selected for evaluation of changes in RTKs expression and downstream pathways, with 24-72 h of 0.1 µmol/L afatinib treatment. 68 Ga-NOTA-HER3P1 PET/MRI was performed in subcutaneous NCI-N87 and SNU16 xenografts (nu:nu, n = 12/group) at baseline and 4 days after afatinib treatment (10 mg/kg, PO, daily). Temporal changes in PET measures were correlated to HER3 expression in tumors, tumor growth rate, and treatment response. RESULTS: With afatinib therapy, NCI-N87 cells showed increased total HER3 expression, and reduction of other RTKs and downstream nodes within 72 h, while SNU16 cells showed no significant change in total HER3 and downstream nodes. 68 Ga-HER3P1 PET/MRI showed increased uptake in NCI-N87 and no significant change in SNU16 tumors (day 4 vs. baseline SUVmean: 3.8 ± 0.7 vs. 1.6 ± 0.6, p < 0.05 in NCI-N87, and 1.5 ± 0.7 vs. 1.7 ± 0.7, p > 0.05 in SNU16). These findings were in concordance with HER3 expression in histopathological analyses and tumor growth over 3 weeks of treatment (mean tumor volume in treated vs. control: 11 ± 17 mm3 vs. 293 ± 79 mm3, p < 0.001 in NCI-N87, and 238 ± 91 mm3 vs. 282 ± 35 mm3, p > 0.05 in SNU16). CONCLUSIONS: Quantitative changes in HER3 PET could be used to predict response to pan-RTKI within few days after initiation of treatment and can help with personalizing GCa management.

Introduction of a daily peer learning process with added value for faculty and trainees.

OBJECTIVE: To implement a new daily peer learning (PL) conference which incorporates faculty and trainees within the abdominal imaging division of a large academic medical center, and to determine participants' level of satisfaction and preference over the pre-existing peer review (PR) model. METHODS: We replaced our pre-existing PR-based tool with a daily hour-long case-based PL teaching conference over a 3-month pilot period. Faculty and trainees were surveyed about their experience at the end of the pilot period. RESULTS: A total of 711 cases were logged during the pilot period (median 9 cases per day). We received 30 survey responses from a total of 48 eligible participants. Survey responses from both faculty and trainees on the new PL conference were overwhelmingly favorable, including unanimous support for permanently replacing the existing PR tool with the new PL conference. CONCLUSION: Our successful pilot of a daily PL conference replacing an existing PR tool adds to the growing body of evidence of radiologists strongly supporting PL based processes over PR. Our paradigm of actively involving trainees within the process can serve as a model for other institutions.

Role of one-step nucleic acid amplification in colorectal cancer lymph node metastases detection.

Current histopathological staging procedures in colorectal cancer (CRC) depend on midline division of the lymph nodes (LNs) with one section of hematoxylin and eosin staining. Cancer cells outside this transection line may be missed, which could lead to understaging of Union for International Cancer Control Stage II high-risk patients. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid molecular diagnostic tool for LN metastases detection. It is a molecular technique that can analyze the entire LN tissue using a reverse-transcriptase loop-mediated isothermal amplification reaction to detect tumor-specific cytokeratin 19 mRNA. Our findings suggest that the OSNA assay has a high diagnostic accuracy in detecting metastatic LNs in CRC and a high negative predictive value. OSNA is a standardized, observer-independent technique, which may lead to more accurate staging. It has been suggested that in stage II CRC, the upstaging can reach 25% and these patients can access postoperative adjuvant chemotherapy. Moreover, intraoperative OSNA sentinel node evaluation may allow early CRC to be treated with organ-preserving surgery, while in more advanced-stage disease, a tailored lymphadenectomy can be performed considering the presence of aberrant lymphatic drainage and skip metastases.

FDG PET/CT radiomics as a tool to differentiate between reactive axillary lymphadenopathy following COVID-19 vaccination and metastatic breast cancer axillary lymphadenopathy: a pilot study.

OBJECTIVES: To evaluate if radiomics with machine learning can differentiate between F-18-fluorodeoxyglucose (FDG)-avid breast cancer metastatic lymphadenopathy and FDG-avid COVID-19 mRNA vaccine-related axillary lymphadenopathy. MATERIALS AND METHODS: We retrospectively analyzed FDG-positive, pathology-proven, metastatic axillary lymph nodes in 53 breast cancer patients who had PET/CT for follow-up or staging, and FDG-positive axillary lymph nodes in 46 patients who were vaccinated with the COVID-19 mRNA vaccine. Radiomics features (110 features classified into 7 groups) were extracted from all segmented lymph nodes. Analysis was performed on PET, CT, and combined PET/CT inputs. Lymph nodes were randomly assigned to a training (n = 132) and validation cohort (n = 33) by 5-fold cross-validation. K-nearest neighbors (KNN) and random forest (RF) machine learning models were used. Performance was evaluated using an area under the receiver-operator characteristic curve (AUC-ROC) score. RESULTS: Axillary lymph nodes from breast cancer patients (n = 85) and COVID-19-vaccinated individuals (n = 80) were analyzed. Analysis of first-order features showed statistically significant differences (p < 0.05) in all combined PET/CT features, most PET features, and half of the CT features. The KNN model showed the best performance score for combined PET/CT and PET input with 0.98 (± 0.03) and 0.88 (± 0.07) validation AUC, and 96% (± 4%) and 85% (± 9%) validation accuracy, respectively. The RF model showed the best result for CT input with 0.96 (± 0.04) validation AUC and 90% (± 6%) validation accuracy. CONCLUSION: Radiomics features can differentiate between FDG-avid breast cancer metastatic and FDG-avid COVID-19 vaccine-related axillary lymphadenopathy. Such a model may have a role in differentiating benign nodes from malignant ones. KEY POINTS: • Patients who were vaccinated with the COVID-19 mRNA vaccine have shown FDG-avid reactive axillary lymph nodes in PET-CT scans. • We evaluated if radiomics and machine learning can distinguish between FDG-avid metastatic axillary lymphadenopathy in breast cancer patients and FDG-avid reactive axillary lymph nodes. • Combined PET and CT radiomics data showed good test AUC (0.98) for distinguishing between metastatic axillary lymphadenopathy and post-COVID-19 vaccine-associated axillary lymphadenopathy. Therefore, the use of radiomics may have a role in differentiating between benign from malignant FDG-avid nodes.