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Background: This study aimed to develop an artificial intelligence-based computer-aided diagnosis system (AI-CAD) emulating the diagnostic logic of radiologists for lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) patients, which contributed to clinical treatment decision-making. Methods: A total of 689 ESCC patients with PET/CT images were enrolled from three hospitals and divided into a training cohort and two external validation cohorts. 452 CT images from three publicly available datasets were also included for pretraining the model. Anatomic information from CT images was first obtained automatically using a U-Net-based multi-organ segmentation model, and metabolic information from PET images was subsequently extracted using a gradient-based approach. AI-CAD was developed in the training cohort and externally validated in two validation cohorts. Results: The AI-CAD achieved an accuracy of 0.744 for predicting pathological LNM in the external cohort and a good agreement with a human expert in two external validation cohorts (kappa = 0.674 and 0.587, p < 0.001). With the aid of AI-CAD, the human expert's diagnostic performance for LNM was significantly improved (accuracy [95% confidence interval]: 0.712 [0.669-0.758] vs. 0.833 [0.797-0.865], specificity [95% confidence interval]: 0.697 [0.636-0.753] vs. 0.891 [0.851-0.928]; p < 0.001) among patients underwent lymphadenectomy in the external validation cohorts. Conclusions: The AI-CAD could aid in preoperative diagnosis of LNM in ESCC patients and thereby support clinical treatment decision-making.
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Background: Biology-guided radiotherapy (BgRT) is a novel treatment where the detection of positron emission originating from a volume called the biological tracking zone (BTZ) initiates dose delivery. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a novel imaging technique that may improve patient selection for metastasis-directed therapy in renal cell carcinoma (RCC). This study aims to determine the feasibility of BgRT treatment for RCC. Material and methods: All consecutive patients that underwent PSMA PET/CT scan for RCC staging at our institution between 2014 and 2020 were retrospectively considered for inclusion. GTVs were contoured on the CT component of the PET/CT scan. The tumor-to-background ratio was quantified from the normalized standardized uptake value (nSUV), defined as the ratio between SUVmax inside the GTV and SUVmean inside the margin expansion. Tumors were classified suitable for BgRT if (1) nSUV was greater or equal to an nSUV threshold and (2) if the BTZ was free of any PET-avid region other than the tumor. Results: Out of this cohort of 83 patients, 47 had metastatic RCC and were included in this study. In total, 136 tumors were delineated, 1 to 22 tumors per patient, mostly in lung (40%). Using a margin expansion of 5 mm/10 mm/20 mm and nSUV threshold = 3, 66%/63%/41% of tumors were suitable for BgRT treatment. Uptake originating from another tumor, the kidney, or the liver was typically inside the BTZ in tumors judged unsuitable for BgRT. Conclusions: More than 60% of tumors were found to be suitable for BgRT in this cohort of patients with RCC. However, the proximity of PET-avid organs such as the liver or the kidney may affect BgRT delivery.
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Introduction: Meningiomas are the most common central nervous system tumor in adults. Knowledge of the tumor grade can guide optimal treatment timing and shape personalized follow-up strategies. Positron emission tomography (PET) has been utilized for the metabolic assessment of various intracranial space-occupying lesions. Herewith, we set out to evaluate the diagnostic accuracy of PET for the noninvasive assessment of meningioma's grade. Materials and methods: The Medline, Scopus and Cochrane databases were systematically searched in March 2022 for studies that evaluated the sensitivity and specificity of PET compared to the gold standard of histological diagnosis in the grading of meningiomas. Summary statistics will be calculated and scatter plots, summary curve from the HSROC model and posterior predictions by empirical Bayes estimates will be presented. Results: Five studies consisting of 242 patients with a total of 196 low-grade (Grade 1) and 46 high grade (Grade 2/3) meningiomas were included in our analysis. Three of the included studies used 18F-FDG, one study used 18F-FLT and one used(Whiting et al., 2011) 18 F-FET as PET tracers. The pooled sensitivity was 76% (95% CI: 52%-91%) and the pooled specificity was 89% (95% CI: 83%-93%). The diagnostic odds ratio was 27.17 (95% CI: 9.22-80.06), the positive likelihood ratio was 7.18 (95% CI: 4.54-11.34) and the negative likelihood ratio was 0.26 (95% CI: 0.11-0.61). Conclusion: PET is a promising and viable option as a noninvasive imaging tool to differentiate the meningioma grades. However, currently it cannot overtake the gold standard of histological grade confirmation. More studies are required for further validation and refinement of this imaging technique and assessment of other radiotracers as well.
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In the treatment of Non-Hodgkin lymphoma (NHL), multiple therapeutic options are available. Improving outcome predictions are essential to optimize treatment. The metabolic active tumor volume (MATV) has shown to be a prognostic factor in NHL. It is usually retrieved using semi-automated thresholding methods based on standardized uptake values (SUV), calculated from 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) images. However, there is currently no consensus method for NHL. The aim of this study was to review literature on different segmentation methods used, and to evaluate selected methods by using an in house created software tool. A software tool, MUltiple SUV Threshold (MUST)-segmenter was developed where tumor locations are identified by placing seed-points on the PET images, followed by subsequent region growing. Based on a literature review, 9 SUV thresholding methods were selected and MATVs were extracted. The MUST-segmenter was utilized in a cohort of 68 patients with NHL. Differences in MATVs were assessed with paired t-tests, and correlations and distributions figures. High variability and significant differences between the MATVs based on different segmentation methods (p < 0.05) were observed in the NHL patients. Median MATVs ranged from 35 to 211 cc. No consensus for determining MATV is available based on the literature. Using the MUST-segmenter with 9 selected SUV thresholding methods, we demonstrated a large and significant variation in MATVs. Identifying the most optimal segmentation method for patients with NHL is essential to further improve predictions of toxicity, response, and treatment outcomes, which can be facilitated by the MUST-segmenter.
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Background: Prostate Specific Membrane Antigen (PSMA) - positron emission tomography (PET) guides metastasis-directed radiotherapy (MDRT) in prostate cancer (PrCa). However, its value as a treatment response assessment tool after MDRT remains unclear. Importantly, there is limited understanding of the potential of radiotherapy (RT) to alter PSMA gene (folate hydrolase 1; FOLH1) expression. Methodology: We reviewed a series of 11 men with oligo-metastatic PrCa (25 metastasis sites) treated with MDRT before re-staging with 18F-DCFPyL (PSMA) PET upon secondary recurrence. Acute effects of RT on PSMA protein and mRNA levels were examined with qPCR and immunoblotting in human wild-type androgen-sensitive (LNCap), castrate-resistant (22RV1) and castrate-resistant neuroendocrine (PC3 and DU145) PrCa cell lines. Xenograft tumors were analyzed with immunohistochemistry. Further, we examined PSMA expression in untreated and irradiated radio-resistant (RR) 22RV1 (22RV1-RR) and DU145 (DU145-RR) cells and xenografts selected for survival after high-dose RT. Results: The majority of MDRT-treated lesions showed lack of PSMA-PET/CT avidity, suggesting treatment response even after low biological effective dose (BED) MDRT. We observed similar high degree of heterogeneity of PSMA expression in both human specimens and in xenograft tumors. PSMA was highly expressed in LNCap and 22RV1 cells and tumors but not in the neuroendocrine PC3 and DU145 models. Single fraction RT caused detectable reduction in PSMA protein but not in mRNA levels in LNCap cells and did not significantly alter PSMA protein or mRNA levels in tissue culture or xenografts of the other cell lines. However, radio-resistant 22RV1-RR cells and tumors demonstrated marked decrease of PSMA transcript and protein expression over their parental counterparts. Conclusions: PSMA-PET may be a promising tool to assess RT response in oligo-metastatic PrCa. However, future systematic investigation of this concept should recognize the high degree of heterogeneity of PSMA expression within prostate tumors and the risk for loss of PSMA expression in tumor surviving curative courses of RT.
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Introduction and importance: Pulmonary sclerosing pneumocytoma (PSP) is a rare tumor thought to originate from respiratory epithelial cells. It is usually benign, but may rarely metastasize to lymph nodes. Surgeons face unique challenges in diagnosis and management of this condition, and ideal surgical management is yet to be established. Case presentation: 48-year-old woman with a 7 × 7 mm pulmonary lesion discovered incidentally on computerized tomography (CT) imaging, which grew to 9 mm over the following year. Seven years later, follow-up imaging revealed that the mass had grown to 1.3 cm in largest dimension. Surgery was recommended and the mass was resected via a right video-assisted thoracic surgery (VATS) middle lobectomy with mediastinal lymph node dissection. All lymph nodes were negative and the patient's postoperative course was unremarkable. Clinical discussion: There are few evidence-based guidelines available on the treatment and postoperative surveillance of PSP. Research has shown comparable recurrence-free survival rates for sublobar resection and lobectomy, though recurrence can occur, especially following sublobar resection in larger or more centrally-located tumors. In absence of established guidelines, it was decided to follow this patient according to NCCN guidelines for surveillance of early-stage non-small cell lung cancer due to potential risk of recurrence. Conclusion: This case report adds to the limited literature on PSP and depicts a possible treatment and postoperative follow-up plan. Right VATS middle lobectomy can effectively treat some cases of central PSP. In absence of established guidelines for postoperative follow-up of PSP, NCCN guidelines may outline one possible strategy for postoperative management.
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Endometrial cancer, also known as uterine cancer, is the second most common cancer affecting women globally and the fourth most prevalent in the United States (US). Treatment often involves a combination of surgery, radiotherapy and chemotherapy depending on the severity. In this case report, we present two patients with relapsed endometrial carcinomas, who responded positively to combined radiotherapy and immunotherapy followed by maintenance immunotherapy. Given the worsening prognoses associated with recurrent endometrial cancers, these two cases warrant the further exploration of the concurrent administration of immunotherapy and radiation therapy in the context of clinical trials.
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Chordoma is a rare tumor, often occurring in the cervical spine and sacrococcygeal spine with a lytic appearance, but rarely in the thoracolumbar spine. Chordomas can occasionally be sclerotic and are included in the differential diagnosis for an ivory vertebra. We present a case of a sclerotic chordoma in an upper lumbar vertebral body with corresponding multimodality imaging. This case demonstrates that chordoma should be a concern for an older adult with a sclerotic vertebral lesion, particularly if it is a solitary lesion. Knowledge of the variable location and appearance of chordomas is critical so it is not mistaken for a metastasis.
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Background: Biology-guided radiotherapy (BgRT) delivers dose to tumours triggered from positron emission tomography (PET) detection. Prostate specific membrane antigen (PSMA) PET uptake is abundant in the dominant intraprostatic lesion (DIL). This study investigates the feasibility of BgRT to PSMA-avid subvolume in the prostate region. Methods: Patients enrolled in the prospective randomized trial ProPSMA at our institution were included (ID: ANZCTR12617000005358). Gross tumour volumes (GTVs) were delineated on the PET component of a PET/CT scan from a standardized uptake value (SUV) threshold technique. Suitability for BgRT requires a strong signal-to-background ratio with a surrounding tissue free of significant PSMA uptake. The signal-to-background ratio was quantified from the calculation of the normalized SUV (nSUV), defined as the ratio between SUVmax within the GTV and SUVmean inside a 3D margin expansion of the GTV. The PSMA distribution surrounding the tumour was quantified as a function of the distance from the GTV. Results: In this cohort of 84 patients, 83 primary tumours were included. Prostate volume ranged from 19 cm3 to 148 cm3 (median = 52 cm3; IQR = 39 cm3 - 63 cm3). SUVmax inside the prostate was between 2 and 125 (median = 19; IQR = 11 - 30). More than 50% of GTVs generated with threshold between 25%SUVmax (median volume = 10.0 cm3; IQR = 4.5 cm3 - 20.0 cm3) and 50%SUVmax (median volume = 1.9 cm3; IQR = 1.1 cm3 - 3.8 cm3) were suitable for BgRT by using nSUV ≥ 3 and a margin expansion of 5 mm. Conclusions: It is feasible to identify GTVs suitable for BgRT in the prostate. These GTVs are characterized by a strong signal-to-background ratio and a surrounding tissue free of PSMA uptake.
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A healthy 49-year-old nonsmoker lady, who was found to have an incidental finding of a lung lesion on a chest X-ray. A Chest CT scan was performed and revealed left upper lobe, 1.5 cm solitary nodule with ground glass borders that highly suspicious for Bronchioloalveolar carcinoma and warranted further investigation to rule out malignancy. The FDG PET and/or CT scan was performed for staging and further evaluation and it displayed avidity of the nodule with a standardized uptake value (SUV) of 6.2, no abnormal uptake elsewhere in the body. CT guided biopsy was arranged and the histopathology result revealed eosinophilic pneumonia.
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Cardiovascular diseases such as myocardial infarction (MI) are among the major causes of death worldwide. Although intramyocardial injection of hydrogels can effectively enhance the ventricular wall, this approach is limited because of its restriction to the poor vascularization in the infarcted myocardium. Here, we reported a new type of hydrogel composed of alginate (ALG) and hyaluronic acid (HA) with lyophilized platelet-rich fibrin (Ly-PRF) for releasing abundant growth factors to realize their respective functions. The results of in vitro studies demonstrated favorable mechanical property and release ability of ALG-HA with Ly-PRF. When injected into the infarcted myocardium, this composite hydrogel preserved heart function and the Ly-PRF within the hydrogel promoted angiogenesis and increased vascular density in both infarcted and border zone, which rescued the ischemic myocardium. These beneficial effects were also accompanied by macrophage polarization and regulation of myocardial fibrosis. Moreover, the autologous origin of Ly-PRF with ALG-HA hydrogel offers myriad advantages including safety profile, easiness to obtain and cost-effectiveness. Overall, this study demonstrated the versatile therapeutic effects of a novel composite hydrogel ALG-HA with Ly-PRF, which optimizes a promising vascularized substitution strategy for improving cardiac function after MI.
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INTRODUCTION: Pulmonary nodules are a frequent finding on chest imaging studies, with differential including multiple benign entities, but malignancy is often also a concern. Computed Tomography (CT) and Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) scans have improved the characterization of pulmonary nodules. However, many nodules remain indeterminate and require periodic monitoring. Here we report two nodular pulmonary amyloidosis cases as a rare etiology of enlarging pulmonary nodules with FDG avidity. CASE PRESENTATION: Case 1: 75-year-old woman with a history of asthma, emphysema, bronchiectasis, and a 48 pack-year smoking history was found to have subcentimeter groundglass pulmonary nodules in the right lower lobe (RLL). Follow-up imaging demonstrated an increased solid component of a RLL bulla associated with mild FDG uptake on PET scan. A CT-guided biopsy revealed amyloid deposition. Case 2: 77-year-old man with a history of interstitial lung disease, asbestos exposure, prior tobacco use, and atrial fibrillation treated with amiodarone was found to have a 1.6cm RLL nodule. Follow-up imaging identified an interval increase to 2.0cm associated with moderate FDG uptake on PET scan. Transthoracic biopsy identified amyloid deposition. DISCUSSION: Nodular pulmonary amyloidosis is a rare form of amyloidosis which may present as an enlarging pulmonary nodule with FDG avidity, raising concern for malignancy. A CT-guided biopsy is a safe way to establish a diagnosis. Recent studies have demonstrated an association between nodular pulmonary amyloidosis and marginal zone lymphomas, which warrants longitudinal follow-up for evolution to lymphoproliferative disorder.
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Assessment of absolute myocardial hydroxydimethylene diphosphonate-technetium-99m uptake using standardized uptake value with a single-photon emission computed tomography-computed tomography cadmium zinc telluride camera (Discovery NM/CT 670CZT, GE Healthcare, Chicago, Illinois) in a patient with cardiac transthyretin-related amyloidosis treated with tafamidis showed a decrease in hydroxydimethylene diphosphonate cardiac uptake. This imaging technique should be helpful in monitoring therapy and evaluating prognosis. (Level of Difficulty: Intermediate.).
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We report a patient with an optic nerve sheath meningioma whose diagnosis and management were guided by using Gallium-68 DOTA-Tyr3-octreotatate (68Ga-DOTATATE). Positron Emission Tomography-Computed Tomography (PET-CT).
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Lung cancer is a leading cause of cancer mortality worldwide. As the incidence of lung cancer increases in recent years, the number of patients diagnosed with synchronous multiple primary lung cancers (SMPLC) is also rising. SMPLC diagnosis is often made based on the clinical course, imaging findings, and histologic and molecular features. Standard lobectomy is the main therapeutic modality for SMPLC. Because maximum retention of lung function is essential, sublobectomy is also a commonly used surgical strategy when appropriate. The question is how to optimize the sequence of lobectomy and sublobectomy for patients with SMPLC. Thoracoscope lobectomy for the primary lesion plus sublobectomy for the secondary lesions is the most commonly used approach. Here we present a case of SMPLC with sublobectomy followed by lobectomy.
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BACKGROUND: Both bone metastases and multiple myeloma (MM) are malignant diseases that can appear osteolytic on imaging and are difficult to differentiate. While positron emission tomography/computed tomography (PET/CT) has been demonstrated useful for the diagnosis of various bone lesions, correlations between PET/CT and histopathology and these diseases are unclear. This retrospective study investigated the optimal cutoff standardized uptake value (SUV) to differentiate MM and bone metastasis. METHODS: Patients with newly diagnosed osteolytic lesions (n = 344) and suspected malignancy underwent both fluorodeoxyglucose (FDG) PET/CT and biopsy/surgery. FDG uptake and morphologic changes (e.g., soft tissue mass formation) were compared with pathological results. RESULTS: A total of 8896 osteolytic lesions were evaluated. The SUVmax of MM osteolytic lesions (1.6 ± 0.7) was significantly lower than that of bone metastases (5.5 ± 2.7; p = 0.000). The best cutoff SUVmax for differentiating MM and bone metastasis was 2.65 (sensitivity 86.1%, specificity 94.7%; p = 0.000). The SUVmax of bone lesions of soft tissue mass was higher than that for pure osteolytic lesions (p = 0.000). A greater percentage of patients with bone metastasis had a soft tissue mass (7%) than did patients with MM (2%). The mean SUVmax of bone metastases was 5.5 ± 2.7 (0.4-30.4); that of primary tumors was 7.5 ± 4.2 (1.0-28.5). The SUVmax of bone metastases significantly correlated with the SUVmax of primary tumors (r = 0.532; p = 0.000). CONCLUSIONS: FDG PET/CT is a valuable tool to differentiate osteolytic lesions. The best cutoff value of SUVmax for differentiating MM from bone metastasis is 2.65. The significant correlation between the SUVmax of bone metastasis and that of primary tumors is helpful for detecting primary tumors.
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Cancer cells reprogram their gene expression to promote growth, survival, proliferation, and invasiveness. The unique expression of certain uptake transporters in cancers and their innate function to concentrate small molecular substrates in cells make them ideal targets for selective delivering imaging and therapeutic agents into cancer cells. In this review, we focus on several solute carrier (SLC) transporters known to be involved in transporting clinically used radiopharmaceutical agents into cancer cells, including the sodium/iodine symporter (NIS), norepinephrine transporter (NET), glucose transporter 1 (GLUT1), and monocarboxylate transporters (MCTs). The molecular and functional characteristics of these transporters are reviewed with special emphasis on their specific expressions in cancers and interaction with imaging or theranostic agents [e.g., I-123, I-131, 123I-iobenguane (mIBG), 18F-fluorodeoxyglucose (18F-FDG) and 13C pyruvate]. Current clinical applications and research areas of these transporters in cancer diagnosis and treatment are discussed. Finally, we offer our views on emerging opportunities and challenges in targeting transporters for cancer imaging and treatment. By analyzing the few clinically successful examples, we hope much interest can be garnered in cancer research towards uptake transporters and their potential applications in cancer diagnosis and treatment.
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BACKGROUND: There is evidence that metabolic disease burden in lymphoma influences patient outcome. However, the impact of disease severity on the cardiovascular system is unknown. OBJECTIVES: The aim of this study was to examine whether lymphoma is associated with arterial inflammation by investigating the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake. METHODS: Sixty-two chemotherapy-naïve patients with active Hodgkin's or non-Hodgkin's lymphoma were matched (2:1) to individual control groups of lymphoma patients previously treated and free of active disease. All groups underwent 18F-FDG position emission tomography-computed tomography imaging. Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis corresponding to standardized uptake values (SUVs) ≥41% or ≥2.5 of the maximum SUV within lymphoma regions, and aortic FDG uptake was quantified through the target-to-background ratio (TBR). Inflammatory and disease severity biomarkers were also measured. RESULTS: MTV and total lesion glycolysis measurements were significantly correlated with inflammatory and disease biomarkers. Aortic TBR was higher in patients with active non-Hodgkin's lymphoma compared with control subjects (median difference 0.51; 95% confidence interval [CI]: 0.28 to 0.78; p < 0.001). Similarly, patients with active Hodgkin's lymphoma had higher values of aortic TBR compared with control subjects (median difference 0.31; 95% CI: 0.15 to 0.49; p < 0.001). In addition, aortic TBR was modestly increased in patients with stage III to IV disease compared with those with stage I to II disease (median aortic TBR: 2.23 [interquartile range: 2.01 to 2.54] vs. 2.06 [interquartile range: 1.83 to 2.27; p = 0.050). In multivariable analysis, aortic FDG uptake and MTV≥2.5 values were independently associated (ß = 0.425; 95% CI: 0.189 to 0.662; p = 0.001; R2 = 0.208), as were aortic FDG uptake and MTV≥41% (ß = 0.407; 95% CI: 0.167 to 0.649, p = 0.001; R2 = 0.191). CONCLUSIONS: Aortic wall FDG uptake is related with disease severity indicative of a possible vascular effect of lymphoma. This work highlights a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences on the vasculature.