Maximum SUV Research Articles

18F]FDG and [68Ga]Ga-FAPI-04-Directed Imaging for Outcome Prediction in Patients with High-Grade Neuroendocrine Neoplasms.

We aimed to quantitatively investigate the prognostic value of PET-based biomarkers on [18F]FDG and [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in patients with highly aggressive neuroendocrine neoplasms (NENs) and to compare the visually assessed differences in uptake on both examinations with progression-free survival (PFS). Methods: In this single-center retrospective analysis, 20 patients with high-grade NENs had undergone [18F]FDG and [68Ga]Ga-FAPI-04 PET. Both PET scans were visually compared, and the presence of [18F]FDG-positive, [68Ga]Ga-FAPI-04-negative (FDG+/FAPI-) lesions was noted. In addition, we assessed maximum, peak, and mean SUV; tumor volume (TV); and total lesion uptake (TLU = TV × SUVmean) for both radiotracers using a 40% lesion-based threshold. The results of quantitative and visual analysis were correlated with PFS using log-rank analysis or univariate Cox regression. PFS was defined radiographically using RECIST 1.1., clinically using signs of disease progression, or as death. Results: Most primary tumors were located in the gastrointestinal tract (13/20 patients, 65%) or were cancer of unknown primary (5/20 patients, 25%). FDG+/FAPI- lesions were found in 9 of 20 patients (45%). Patients with FDG+/FAPI- lesions had a significantly decreased PFS of 4 mo, compared with 9 mo for patients without FDG+/FAPI- metastases (P = 0.0063 [log-rank test]; hazard ratio [HR], 5.637; 95% CI 1.619-26.16; P = 0.0110 [univariate Cox regression]). On univariate analysis, a significant correlation was also found between PFS and TV for both radiotracers ([18F]FDG: mean TV, 258 ± 588 cm3; HR, 1.024 [per 10 cm3]; 95% CI, 1.007-1.046; P = 0.0204) ([68Ga]Ga-FAPI-04: mean TV, 130 ± 192 cm3; HR, 1.032 [per 10 cm3]; 95% CI, 1.001-1.062; P = 0.0277) and TLU on [18F]FDG PET (mean TLU, 1,931 ± 4,248 cm3; HR, 1.004 [per 10 cm3]; 95% CI, 1.001-1.007; P = 0.0135). Conclusion: The presence of discordant FDG+/FAPI- lesions is associated with a significantly shorter PFS, which might indicate more aggressive disease prone to early progression. Dual-tracer PET/CT of patients with highly aggressive NENs could help guide treatment decisions or identify high-risk lesions for additional local therapeutic approaches.

Clinical value of SUVpeak-to-tumor centroid distance on FDG PET/CT for predicting neoadjuvant chemotherapy response in patients with breast cancer

BackgroundSince it has been found that the maximum metabolic activity of a cancer lesion shifts toward the lesion edge during cancer progression, normalized distances from the hot spot of radiotracer uptake to tumor centroid (NHOC) and tumor perimeter (NHOP) have been suggested as novel F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters that can reflect cancer aggressiveness. This study aimed to investigate whether NHOC and NHOP parameters could predict pathological response to neoadjuvant chemotherapy (NAC) and progression-free survival (PFS) in breast cancer patients.MethodsThis study retrospectively enrolled 135 female patients with breast cancer who underwent pretreatment FDG PET/CT and received NAC and subsequent surgical resection. From PET/CT images, normalized distances of maximum SUV and peak SUV-to-tumor centroid (NHOCmax and NHOCpeak) and -to-tumor perimeter (NHOPmax and NHOPpeak) were measured, in addition to conventional PET/CT parameters.ResultsOf 135 patients, 32 (23.7%) achieved pathological complete response (pCR), and 34 (25.2%) had events during follow-up. In the receiver operating characteristic (ROC) curve analysis, NHOCmax showed the highest area under the ROC curve value (0.710) for predicting pCR, followed by NHOCpeak (0.694). In the multivariate logistic regression analysis, NHOCmax, NHOCpeak, and NHOPmax were independent predictors for pCR (p < 0.05). In the multivariate survival analysis, NHOCpeak (p = 0.026) was an independent predictor for PFS along with metabolic tumor volume, with patients having higher NHOCpeak showing worse PFS.ConclusionNHOCpeak on pretreatment FDG PET/CT could be a potential imaging parameter for predicting NAC response and survival in patients with breast cancer.

7242 Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) In A Patient With Recurrent Carcinoid

Abstract Disclosure: F. Woron: None. T.L. Anderson: None. P. Madhavan: None. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare generalized proliferation of pulmonary neuroendocrine cells. It is considered to be a pre-invasive lesion for pulmonary carcinoid, a rare neuroendocrine tumor (NET). DIPNECH is thought to be underdiagnosed, as patients can be asymptomatic or present with nonspecific cough and dyspnea, though it is also associated with fibrotic lung changes. Long-term annual surveillance imaging is recommended for due to the potential for development and metastasis of carcinoid tumors. We present a patient with recurrent pulmonary carcinoid later diagnosed with probable DIPNECH based on CT findings. The patient is a 72-year-old female with a prior 15 pack-year smoking history, who initially had a left lower lobe typical carcinoid tumor diagnosed and resected in 2018, with no evidence of lymph node metastasis. The patient’s medical history also includes pulmonary sarcoidosis, adrenal adenoma, thyroid nodule, hiatal hernia, and prediabetes. She has no family history of neuroendocrine tumors. Physical exam showed stable vitals with blood pressure of 112/70 mmHg in the right upper arm, heart rate of 84 bpm, and a body mass index of 39. Physical exam was unremarkable except for thyroid nodularity and obesity. Extensive biochemical evaluation for markers including chromogranin A and 24-hour urine 5-HIAA levels were within normal limits. In 2022, surveillance CT imaging showed a new 9 mm nodule in the right lobe within the bronchus, which was shown to be carcinoid on FNA. She complained of dyspnea and wheezing at this time, which has been managed with an albuterol inhaler. In 2023, PET/CT copper 64 dotatate scan showed a focal area of activity related to the nodule in the superior segment, also identified on recent CT scan, with the nodule measuring approximately 2.05 cm x 1.8 cm with a maximal SUV of 4.2. Interestingly, somatostatin receptor scintigraphy did not show any pick-up in the lung in 2018 or 2022. In 2023, the patient underwent right lower lobe superior segmentectomy after the nodule was found to have increased in size. Pathology showed G1, well-differentiated 1.1 cm typical carcinoid tumor with margins negative for invasive carcinoma. All 18 regional lymph nodes were negative for tumor. Immunohistochemical tests show that the tumor cells were positive for INSM1 and chromogranin with a low Ki-67 proliferation index (&amp;lt;2%), supporting the diagnosis. The patient is currently being monitored by yearly CT imaging and followed by both endocrinology and pulmonology. Given this case, we propose that DIPNECH should be considered as a differential in cases of pulmonary carcinoid, especially recurrent ones. Given that DIPNECH is thought to be underdiagnosed and a precursor for carcinoid associated with fibrotic lung changes, it is essential for this disease to be identified in order for patients to receive appropriate long-term monitoring. Presentation: 6/1/2024

18F]AlF-NOTA-FAPI-04 PET/CT for Predicting Pathologic Response of Resectable Esophageal Squamous Cell Carcinoma to Neoadjuvant Camrelizumab and Chemotherapy: A Phase II Clinical Trial.

This single-center, single-arm, phase II trial (ChiCTR2100050057) investigated the ability of 18F-labeled fibroblast activation protein inhibitor ([18F]AlF-NOTA-FAPI-04, denoted as 18F-FAPI) PET/CT to predict the response to neoadjuvant camrelizumab plus chemotherapy (nCC) in locally advanced esophageal squamous cell carcinoma (LA-ESCC). Methods: This study included 32 newly diagnosed LA-ESCC participants who underwent 18F-FAPI PET/CT at baseline, of whom 23 also underwent scanning after 2 cycles of nCC. The participants underwent surgery after 2 cycles of nCC. Recorded PET parameters included maximum, peak, and mean SUVs and tumor-to-background ratios (TBRs), metabolic tumor volume, and total lesion FAP expression. PET parameters were compared between patient groups with good and poor pathologic responses, and the predictive performance for treatment response was analyzed. Results: The good and poor response groups each included 16 participants (16/32, 50.0%). On 18F-FAPI PET/CT, the posttreatment SUVs were significantly lower in good responders than in poor responders, whereas the changes in SUVs with treatment were significantly higher (all P < 0.05). SUVmax (area under the curve [AUC], 0.87; P = 0.0026), SUVpeak (AUC, 0.89; P = 0.0017), SUVmean (AUC, 0.88; P = 0.0021), TBRmax (AUC, 0.86; P = 0.0031), and TBRmean (AUC, 0.88; P = 0.0021) after nCC were significant predictors of pathologic response to nCC, with sensitivities of 63.64%-81.82% and specificities of 83.33%-100%. Changes in SUVmax (AUC, 0.81; P = 0.0116), SUVpeak (AUC, 0.82; P = 0.0097), SUVmean (AUC, 0.81; P = 0.0116), and TBRmean (AUC, 0.74; P = 0.0489) also were significant predictors of the pathologic response to nCC, with sensitivities and specificities in similar ranges. Conclusion: 18F-FAPI PET/CT parameters after treatment and their changes from baseline can predict the pathologic response to nCC in LA-ESCC participants.

ASL, DSC, DCE perfusion MRI and 18F-DOPA PET/CT in differentiating glioma recurrence from post-treatment changes

ObjectivesTo discriminate between post-treatment changes and tumor recurrence in patients affected by glioma undergoing surgery and chemoradiation with a new enhancing lesion is challenging. We aimed to evaluate the role of ASL, DSC, DCE perfusion MRI, and 18F-DOPA PET/CT in distinguishing tumor recurrence from post-treatment changes in patients with glioma.Materials and methodsWe prospectively enrolled patients with treated glioma (surgery plus chemoradiation) and a new enhancing lesion doubtful for recurrence or post-treatment changes. Each patient underwent a 1.5T MRI examination, including ASL, DSC, and DCE PWI, and an 18F-DOPA PET/CT examination. For each lesion, we measured ASL-derived CBF and normalized CBF, DSC-derived rCBV, DCE-derived Ktrans, Vp, Ve, Kep, and PET/CT-derived SUV maximum. Clinical and radiological follow-up determined the diagnosis of tumor recurrence or post-treatment changes.ResultsWe evaluated 29 lesions (5 low-grade gliomas and 24 high-grade gliomas); 14 were malignancies, and 15 were post-treatment changes.CBF ASL, nCBF ASL, rCBV DSC, and PET SUVmax were associated with tumor recurrence from post-treatment changes in patients with glioma through an univariable logistic regression.Whereas the multivariable logistic regression results showed only nCBF ASL (p = 0.008) was associated with tumor recurrence from post-treatment changes in patients with glioma with OR = 22.85, CI95%: (2.28–228.77).ConclusionIn our study, ASL was the best technique, among the other two MRI PWI and the 18F-DOPA PET/CT PET, in distinguishing disease recurrence from post-treatment changes in treated glioma.

July 2024 Medical Image of the Month: Vocal Cord Paralysis on PET-CT

No abstract available. Article truncated after 150 words. A 60-year-old woman with a past medical history of hypertension, rheumatoid arthritis, and a significant smoking history (40+ pack-years) presented with a 3-month history of hoarseness of voice as well as a 10 lb weight loss over a 5-month period. Chest CT revealed a spiculated left upper lobe nodule (Figure 1A). Additionally, there was evidence of bulky mediastinal and left hilar lymphadenopathy (Figure 1B). A subsequent 17-FDG PET-CT (Figure 2) demonstrated marked metabolic activity in the left upper lobe nodule with an SUV maximum of 9.1. Metabolically active mediastinal and left hilar lymphadenopathy was also noted with an SUV maximum of 5.9. Interestingly, increased metabolic activity of the right vocal cord compared to the left was noted on the PET scan (Figure 2B). Direct laryngoscopy, performed during intubation for a diagnostic bronchoscopy and endobronchial ultrasound, confirmed left vocal cord paralysis. EBUS sampling of multiple mediastinal hilar lymph node stations, including …

Abstract PO2-20-08: Metastatic Lung Cancer Masquerading as Metaplastic Breast Cancer

Abstract Background Metaplastic breast carcinoma (MBC) is an unusual malignancy that presents a diagnostic challenge due to the presence of varying cytomorphologies that can be seen in benign and malignant tumors. We posit that metastatic disease to the breast, itself an uncommon entity, should be considered in the differential diagnosis of MBC. We report a unique case of metastatic non-small cell lung cancer (NSCLC) with an actionable driver mutation that presented as a symptomatic breast mass and was initially considered to represent MBC. Report A 74-year-old woman with a 22-pack-year smoking history presented to the breast clinic complaining of a palpable left breast mass that had grown rapidly over the previous month. Ultrasound-guided biopsy of the breast mass revealed high-grade poorly differentiated carcinoma. On immunohistochemical (IHC) evaluation, tumor cells were strongly positive for epithelial markers CAM5.2 and keratin AE1/AE3, weakly positive for breast cancer (BC) marker TRPS1, and negative for BC marker GATA3, squamous cell carcinoma markers p63 and CK5, and melanoma marker SOX10. Metaplastic triple-negative BC was diagnosed. However, concern remained for metastasis from a non-breast primary tumor due to the patient’s constitutional symptoms such as fatigue, night sweats, and 60-pound unintentional weight loss over the previous year, as well as interval development of a suspicious nodular rash on her right upper extremity. An FDG-PET-CT was obtained and demonstrated a hypermetabolic left lung consolidation (maximum SUV 33.3) measuring 7.2 cm, pulmonary nodules, and extensive thoracic lymphadenopathy. Due to rising suspicion for a primary lung tumor, additional IHC staining on the original breast biopsy was requested. Tumor cells were positive for TTF-1, consistent with metastatic lung adenocarcinoma. Tissue next-generation sequencing (NGS) identified a MET exon 14 skipping mutation, making the patient eligible for treatment with capmatinib, a first-line kinase inhibitor targeted therapy for metastatic NSCLC. At the time of this report, the patient has completed a course of palliative stereotactic body radiation therapy to the left lung and started capmatinib 400 mg BID, which she is tolerating well. Her first restaging scans after treatment initiation will be obtained one week after the time of this report. Conclusion In the absence of heightened suspicion for a non-breast primary tumor, our patient had initially received a diagnosis of triple-negative MBC. This diagnosis would have exposed her to increased treatment-related toxicities from cytotoxic chemotherapy and poor prognosis from MBC without survival benefit from targeted therapy for NSCLC. We advocate for the use of supplemental body imaging, expert and comprehensive IHC evaluation, and multidisciplinary discussion in cases of MBC and undifferentiated breast malignancy to facilitate accurate diagnosis and treatment. Citation Format: Tanmayi Pai, Marte Wasserman, Jason Lewis, Miglena Komforti, James Jakub, Augustine Lee, Yanyan Lou, Pooja Advani, Rohit Rao. Metastatic Lung Cancer Masquerading as Metaplastic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-08.

Synthesis and preclinical evaluation of 11C-labeled 7-Oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine radioligands for RIPK1 positron emission tomography imaging

Targeting receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic strategy for various neurodegenerative disorders. The development of a positron emission tomography (PET) probe for brain RIPK1 imaging could offer a valuable tool to assess therapeutic effectiveness and uncover the neuropathology associated with RIPK1. In this study, we present the development and characterization of two new PET radioligands, [11C]PB218 and [11C]PB220, which have the potential to facilitate brain RIPK1 imaging. [11C]PB218 and [11C]PB220 were successfully synthesized with a high radiochemical yield (34 % − 42 %) and molar activity (293 – 314 GBq/µmol). PET imaging characterization of two radioligands was conducted in rodents, demonstrating that both newly developed tracers have good brain penetration (maximum SUV = 0.9 – 1.0) and appropriate brain clearance kinetic profiles. Notably, [11C]PB218 has a more favorable binding specificity than [11C]PB220. A PET/MR study of [11C]PB218 in a non-human primate exhibited good brain penetration, desirable kinetic properties, and a safe profile, thus supporting the translational applicability of our new probe. These investigations enable further translational exploration of [11C]PB218 for drug discovery and PET probe development targeting RIPK1.

El papel de la PET/TC con 2-[18F]FDG en la enfermedad de Erdheim-Chester

ObjectiveTo analyze the body distribution of Erdheim-Chester disease (ECD) and determine the utility of 2-[18F]FDG PET/CT compared to other imaging techniques. Additionally, to assess the aggressiveness and extent of the disease based on the presence/absence of the BRAFV600E mutation. Materials and methodsThe 2-[18F]FDG PET/CT scans of all patients diagnosed with ECD between 2008 and 2021 were reviewed, including 19 patients. The affected territories were classified as detectable by PET/CT or detectable only by other imaging techniques (bone scintigraphy, contrast-enhanced CT, or MRI). Descriptive analysis and correlation of the BRAF mutation with the affected organs and maximum SUV were performed using the Student's t-test. ResultsOut of the 19 patients (14 males; mean age 60.3years), 11 had the BRAFV600E mutation. A total of 127 territories (64 organ-systems) affected were identified using different imaging modalities, of which 112 were detected by PET/CT, and an additional 15 territories were solely identified by cerebral and cardiac MRI. The presence of BRAFV600E mutation was associated with greater organ involvement (P<.05) without differences in SUVmax (P>.05). Conclusion2-[18F]FDG PET/CT is a highly effective diagnostic tool in patients with ECD, detecting the majority of affected territories. MRI was the only imaging modality with additional findings in territories showing high physiological uptake of 2-[18F]FDG (cerebral and cardiac). The presence of the BRAFV600E mutation correlated with a higher extent of the disease.

Genomic Correlates of Radiosensitivity in Diffuse Large B Cell Lymphoma

Introduction Radiotherapy (RT) is beneficial for select patients with localized diffuse large B cell lymphoma (DLBCL), in both the early stage and relapsed/refractory settings. Although molecular subtyping plays a key role in classification of DLBCL, genomic predictors of local response to RT have yet to be adequately explored. To our knowledge, there are no existing studies investigating the genomic landscape of DLBCL patients treated with RT. Therefore, we sought to identify genomic signatures of radiosensitivity in localized DLBCL patients. Methods We analyzed an institutional database of DLBCL patients treated with RT for localized measurable disease treated between 2007-2022. All patients underwent next-generation sequencing using an institutional 505-gene panel (MSK-Impact). Clinical and radiographic characteristics were obtained from chart and imaging review. All patients had measurable disease on CT scan at time of RT and included both Ann Arbor stage I/II patients referred for consolidative radiotherapy and those with isolated sites of relapsed/refractory disease. Patients did not receive any systemic therapy between RT start and time of response assessment. The public NCI LymphGen algorithm was used to further classify genomic subgroups. Using Fisher's exact test and logistic regression, we tested for univariable correlation between specific gene alterations and LymphGen subgroups with initial radiation response, defined by Lugano criteria and decrease in maximum SUV. Results We identified 46 patients including 15 (33%) tumors treated in the early-stage setting (13% definitively without prior chemotherapy, 87% as consolidation), while 31 (60%) were treated in the localized relapsed/refractory setting. The majority were GCB subtype (57%) while 28% were non-GCB and 15% had missing immunohistochemistry data. The median number of prior lines of systemic therapy was 1 (0-2) in early stage and 1 (1-7) in localized relapsed/refractory diseases. The median RT dose was 36 Gy (4-54), with 38 (83%) tumors receiving at least 30Gy. The median lesion SUV at the time of RT was 4.11 (1.1-46.0). Complete response (CR) was achieved in 41% of tumors at the time of first imaging assessment (median 3.1 months) with a median of 90.3% (42-100%) decrease in SUV. The most commonly altered individual genes were KMT2D (35%), MYD88 (28%), and TP53 (35%). LymphGen classified 22% of cases as EZB subtype, 13% as MCD, 2% as BN2, 2% as ST2, and the remaining 61% were unclassified. Mutations in ETV6 (13% of tumors) were associated with a higher CR rate in response to RT (83% mutated vs 35% wildtype, p=0.068). Lesions from ETV6 mutated cases had similar SUVs (p=0.74) and sizes (p=0.92) as wildtype cases. Alterations in genes from the LymphGen MCD subgroup were associated with greater reductions in SUV (ETV6 p&amp;lt;0.0001, PIM1 p&amp;lt;0.0001, MYD88 p&amp;lt;0.001, and TNFAIP3 p=0.02) The MCD subgroup trended towards increased odds of CR post-RT (log odds 1.9, p=0.08) and greater reduction of SUV (p=0.07) compared to the EZB subgroup. Conclusions To our knowledge this is the first study evaluating the role of LymphGen subgrouping on radiotherapy response, and the first study to examine genomic alterations in DLBCL patients treated with radiation. Genomic biomarkers of radiosensitivity are needed to identify radioresponsive tumors which may benefit from better integration of RT into existing salvage paradigms such as CAR T cells. Our data suggest that alterations in MCD LymphGen subgroup genes (ETV6, PIM1, MYD88, TNFAIP3) may be associated with better response to radiotherapy. ETV6 is a strong hematopoietic transcription factor known to be altered in many human leukemias and myelodysplastic syndromes. Its role in DLBCL is not well defined, with preclinical studies suggesting a distinct role compared to leukemias. Due to the limited sample size, these findings are hypothesis generating and warrant further study with larger, prospective cohorts to validate the ability of genomic signatures to predict RT response.

Genetic Alterations of Follicular Lymphoma Can Predict Response to Very Low Dose Radiotherapy

Introduction Follicular lymphoma (FL) is typically indolent, but relapses and transformation to higher grade disease are common. FL is often radiosensitive and can show complete response (CR) even to very low dose radiotherapy (VLDRT, 4Gy). There are no known genetic markers of FL radiosensitivity. We sought to identify molecular signatures of FL radiosensitivity to aid in patient selection for VLDRT. Methods We analyzed our institutional database and identified 110 FL patients with 113 tumors treated with radiotherapy (RT) and preexisting MSK-IMPACT, a targeted exon sequencing panel. For each patient, we collected key clinicodemographic information including pre- and post-RT treatment history, prior large cell lymphoma, and Ann Arbor stage at RT. For treated tumors, we obtained tumor site, grade, diameter, maximum SUV, BCL2 translocation (trans) status through fluorescence in situ hybridization, RT dose and fractionation, and the treatment strategy ( i.e. treating all sites of disease vs a subsite of disease). Tumor site was dichotomized by pelvic tumors vs all others, as this was the most frequently altered site. The presence of mutant (mut) genes compared to wild type (WT) were associated with RT response, measured by PET scan within 6 months of RT, using logistic regression. Log-rank testing and Cox proportional hazards models were used to analyze local progression free survival (LPFS), censored at start of unplanned therapy, with 2-year (2y) survival reported. Multivariate modeling was used to adjust gene associations with outcomes, controlling for the clinicodemographic and tumor characteristics mentioned above. Results The patient and tumor characteristics are summarized in table 1. We found CREBBP to be the most frequently altered gene (66% of tumors). We identified 5 signatures of altered genes, most of which showed altered CREBBP and relatively long LPFS (e.g. one signature showed CREBBP mut, TNFRSF14 mut and IRF8/STAT6 mut with a 2y LPFS 78%); however, one signature with concurrent KMT2D mut and altered BCL2 including trans and mut had significantly shorter LPFS than all other signatures (2y LPFS 47%, p &amp;lt; 0.01) and lower odds of CR relative to the other signatures (p= 0.03). CREBBP mut was the only alteration associated with increased odds of CR (Odds ratio: 2.39 (95% CI: 1.06-5.37, p = 0.04), and this effect remained significant after adjusting for pelvic disease site (p=0.04). Mutations of BCL2, IRF8, and KMT2D were associated with LPFS using log-rank testing (p&amp;lt;0.01, p=0.02, and p=0.04, respectively). BCL2 mut or concurrent BCL2 mut and BCL2 trans (mut/trans) had shorter LPFS for the overall cohort (p&amp;lt;0.01 for both), while for VLDRT, only BCL2 mut/trans was associated with shorter LPFS (p=0.02). In the VLDRT cohort, we found that CREBBP histone acetyltransferase (HAT) mut was associated with improved LPFS compared to WT (n=39, 2y LPFS 74% vs 52%, HR:0.41 (95% CI: 0.18-0.93, p=0.03)), but this was not observed for tumors receiving &amp;gt;4Gy (n=44, HR: 1.27 (95% CI: 0.32-5.08), p=0.74)). We observed that either BCL2 mut, BCL2 trans, or BCL2 mut/trans and CREBBP HAT WT had a 2y LPFS of 13% whereas BCL2 mut, BCL2 trans or BCL2 mut/trans and CREBBP HAT mut had a 2y LPFS of 83% (p&amp;lt;0.01), and this relationship persisted on multivariate analysis (Figure 1). Conclusions Incorporating genetic signatures associated with radiosensitivity, and specifically alterations involving BCL2 and CREBBP, may independently improve patient selection for RT. CREBBP HAT domain mutations are potentially targetable and may have important implications for augmenting radiosensitivity to VLDRT.

Treatment Outcomes of Limited Stage Grade 3A Follicular Lymphoma

Introduction While radiotherapy is the established standard of care for limited stage, grade 1-2 follicular lymphoma (FL), the management of localized grade 3A (FL3A) disease remains controversial. We reviewed the outcomes of grade 3A patients treated with definitive RT, systemic therapy (ST) alone or combined modality therapy (CMT) of RT plus ST. Methods We analyzed a single institution database to identify newly-diagnosed, FL3A patients with Ann Arbor stage I/II disease treated between 2000-2021. All cases were reviewed by the Hematopathology staff at the time of diagnosis. Patients were stratified by definitive treatment modality including RT monotherapy, CMT, or ST. Best post-RT imaging response was evaluated using Lugano criteria for all by CT, and by PET if available. Rate of complete response (CR), overall survival (OS), progression-free survival (PFS) and time to out-of-field progression were compared between the three treatment modalities. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan Meier from first day of treatment. Time to out-of-field progression was estimated via cumulative incidence function from treatment start date with competing events death without out-of-field progression of disease (PD) and in-field PD. Univariable Cox regression was used to assess possible clinicodemographic associations with PFS. Results 84 patients (median age 62, 38% male) were analyzed with median follow-up of 6.9 years from treatment. Patients were stage I (73%) or II (27%) and 92% were initially PET staged at diagnosis. 29 (35%) had extranodal disease. The most common site of extranodal disease was the head and neck (13% of patients). The median (IQR) baseline maximum SUV and maximum lesion size prior to treatment were 9.8 (5.4, 14.0) and 3.2 (2.0, 4.5) cm respectively, and did not differ between treatment groups. RT was the most commonly utilized treatment modality (n=48, 57%), followed by CMT (n=21, 25%), then ST (n=15, 18%). For RT/CMT patients the planned RT dose was most commonly 36 Gy (32%, range 4-40Gy). 2 patients (3%) received a very low dose program beginning with 4 Gy. Of the CMT/ST patients the most common regimen was 3-4 cycles of R-CHOP (53%). 3 patients (8%) received Rituximab alone. All ST patients were diagnosed after 2010. The ST subset had the highest proportion of patients with stage II disease (p&amp;lt;0.001), while CMT patients had the highest proportion of female patients (p=0.03) and grade 3 disease not further characterized (p=0.002). The rates of CR post-treatment were 88% for RT, 100% for CMT, and 87% for ST. Of the 22 patients who relapsed, only 1 suffered an infield relapse alone (4.5%) with the rest experiencing distant relapse (95.5%). The 5-year cumulative incidence of out-of-field progression was 32% (95%CI 18-46%) for RT, 11% (95%CI 1.7-30%) for CMT, and 17% (95%CI 2.3-43%) for ST. There were factors significantly associated with PFS univariably including the treatment modality (CMT vs. RT HR 0.30, 95% CI 0.10-0.91, p=0.03), and presence of low-grade FL component in the biopsy (HR 3.33, 95% CI 1.43-7.78, p=0.005). Age, sex, stage, extranodal status, Ki67 score, max pre-treatment size, and max pre-treatment SUV were not associated with PFS. The probability of transformation to DLBCL was 4.2% (95% CI 1.1-11%) at 5 years after treatment. Overall survival was excellent for all treatment modalities with median OS of 18 years for CMT, and not reached for RT or ST. Conclusion To our knowledge this is the largest study of the outcomes of early stage FL3A after therapy. CMT had the highest rate of CR in our cohort, and was associated with a statistically significantly lower hazard of PFS compared to RT. However, OS is excellent regardless of treatment modality suggesting all may be appropriate options.

The role of 2-[18F]FDG PET/CT in Erdheim-Chester disease

ObjectiveTo analyze the body distribution of Erdheim-Chester disease (ECD) and determine the utility of 2-[18 F]FDG PET/CT compared to other imaging techniques. Additionally, to assess the aggressiveness and extent of the disease based on the presence/absence of the BRAFV600E mutation. Materials and methodsThe 2-[18F]FDG-PET/CT scans of all patients diagnosed with ECD between 2008 and 2021 were reviewed, including 19 patients. The affected territories were classified as detectable by PET/CT or detectable only by other imaging techniques (bone scintigraphy, contrast-enhanced CT, or MRI). Descriptive analysis and correlation of the BRAF mutation with the affected organs and maximum SUV were performed using the Student's t-test. ResultsOut of the 19 patients (14 males; mean age 60.3 years), 11 had the BRAFV600E mutation. A total of 127 territories (64 organ-systems) affected were identified using different imaging modalities, of which 112 were detected by PET/CT, and an additional 15 territories were solely identified by cerebral and cardiac MRI. The presence of BRAFV600E mutation was associated with greater organ involvement (p < 0.05) without differences in SUVmax (p > 0.05). Conclusion2-[18F]FDG PET/CT is a highly effective diagnostic tool in patients with ECD, detecting the majority of affected territories. MRI was the only imaging modality with additional findings in territories showing high physiological uptake of 2-[18F]FDG (cerebral and cardiac). The presence of the BRAFV600E mutation correlated with a higher extent of the disease.

CT Based Tumor Radiomics with Machine Learning Classifiers for Molecular Subtyping of Diffuse Large B Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBL) has been classified into two distinct molecular subtypes based on their cell of origin- namely germinal center B-cell-like (GCB) and activated B-cell-subtype (ABC) based on Han's algorithm. These two entities are also prognostically distinct. We assessed CT based tumor radiomic features using machine learning classifiers to distinguish the two molecular subtypes. One hundred one patients were accrued in the study after institutional ethics committee approval. GCB subtype was diagnosed in 59 while 42 patients were ABC subtype. Lesion with maximum SUV was delineated using a semi-automated segmentation tool (3D slicer) and radiomic features were extracted using Pyradiomics. A total of 1030 features were extracted including Shape features, first, second, third, higher order and wavelet-based features. Recursive feature elimination was used for feature selection and optimal 10 features were selected. Five machine learning (ML) tools were used to build a model to sub- classify the two molecular subtypes. (Table -1) Model performance was assessed using Accuracy, Precision, Recall, F1 score and Area under curve of receiver operating characteristic curve. The models were constructed by two methods.1) A 5-fold internal cross validation strategy & 2) splitting the data into training (70%) and validation set (30%). Recursive feature elimination using a random forest algorithm method was used to select 7 radiomic features. These 7 features were then used to build the model using the 5 ML classifiers. Of the five classifiers, Random Forest Classifier (RFC) using a 70:30 training: test strategy was the best performer among all the ML models, with the highest accuracy of 80%, AUC of 0.87, recall(sensitivity), f1score(specificity) & precision (Positive Predictive value; PPV) or precision of 82% respectively. When an internal 5-fold cross validation strategy was used, RFC again performed better than other ML classifiers with an accuracy of 75%, AUC of 0.80, recall of 79%, PPV of 77% and specificity of 79%. The machine-learning based Radiomics features extracted from pre-treatment CT images can provide a simple and non-invasive method for the prediction of DLBL molecular subtypes with favorable predictive accuracy. The Random Forest Classifier was the most accurate in distinguishing GCB subtype from the ABC subtype.

Evaluation of 68Ga-Fibroblast Activation Protein Inhibitor vs. 18F-FDG as a Novel Radiotracer for Biologically Guided Radiation Therapy

Real-time biology guided radiation therapy (BgRT) uses real-time positron emissions from a PET tracer during treatment to guide targeted radiation to cancerous lesions. Fibroblast activation protein alpha (FAP) is highly expressed on cancer-associated fibroblasts in tumors with low expression in normal tissues. While 18F-FDG-PET requires fasting and has background in the liver and brain, 68-Gallium labeled FAP inhibitor (FAPI) does not require fasting and has less background uptake. The goal of this study was to investigate the utility of FAPI as a potential universal fiducial for BgRT. We hypothesized that 68Ga-FAPI would be a better radiotracer than 18F-FDG, as assessed by the Normalized Minimal kBq/mL and the Normal Target Signal (NTS), two parameters used to gauge the suitability of BgRT. PET-CTs were obtained for 50 patients with pancreatic, liver, lung, head & neck, and cervical cancer using 18F-FDG and 68Ga-FAPI (n = 10 for each). Four DICOM images were obtained per patient (FDG PET + CT, FAPI PET + CT). Radiation oncologists delineated the gross tumor volume (GTV) on PET images. A separate set of auto-contours were generated from the PET using an auto-threshold of 40% maximum SUV for all tumors. A 1 cm expansion was added to the GTV to create a ring around the physician-generated contours and auto-contours. The following parameters were measured: GTV volume, SUV max of GTV, SUV mean of GTV, Normalized Minimal kBq/mL within the GTV, and NTS (= SUV max/Ring SUV mean). Values were compared using paired t-test. For the BgRT product with similar calculations, the required Normalized Minimal kBq/mL is > 5 kBq/mL; the required NTS is > 2.7 for treatment planning and > 2.0 for BgRT delivery. The Normalized Minimal kBq/mL for FAPI was > 5 kBq/mL for all tumors and greater for auto-contoured GTVs compared to physician-contoured GTVs. The mean NTS for the auto-contours for all tumor sites was > 2.0. In addition, there was a statistically significant increase in the NTS for FAPI compared to FDG in pancreatic, liver and head & neck cancers. In pancreatic cancer, there was a statistically significant increase in Normalized Minimal kBq/mL for FAPI compared to FDG (26.0 vs 14.2) (p = 0.01) and the SUVmax of FAPI was almost double that of FDG (15.9 vs 8.2) (p = 0.01). FAPI had no background in the liver, but had high background in the uterus, suggesting it may have a role in liver cancer but not cervical cancer. This is the first study demonstrating the potential superiority of 68Ga-FAPI compared to 18F-FDG as a biologic fiducial for BgRT when treating pancreatic, liver and head & neck cancers, with a similar efficacy for lung cancer. Our results indicate that auto-contoured GTVs generate a higher NTS than physician-contoured GTVs but all are > 2.0. In addition, the Normalized Minimal kBq/mL for auto-contours is > 5 kBq/mL for all tumors. As hypothesized, FAPI-based BgRT is most likely to be successful when treating tumors with significant desmoplastic stroma, such as pancreatic cancer.

Threshold for defining PSMA-positivity prior to 177Lu-PSMA therapy: a comparison of [68Ga]Ga-PSMA-11 and [18F]F-DCFPyL in metastatic prostate cancer

BackgroundIn 2022, the American Food and Drug Administration and the European Medicines Agency approved [177Lu]Lu-PSMA-617 (PLUVICTO™, Novartis AG, Basel, Switzerland) for radionuclide therapy with prostate-specific membrane antigen (PSMA) ligands in metastatic prostate cancer. Theranostics require appropriate patients to be identified by positron emission tomography (PET) prior to radionuclide therapy, usually employing [68Ga]Ga-PSMA-11. Alternatively, several 18F-labelled PSMA-PET tracers are available and may increasingly replace 68Ga-labelled compounds, with respect to their image quality, availability and other practical advantages. However, alternative tracers may differ in uptake behaviour, and their comparability with regard to patient selection for [177Lu]Lu-PSMA therapy has not yet been established. Here, we analysed whether tumour-to-background ratios determined by PET using the 18F-labelled PSMA-specific radiopharmaceutical [18F]F-DCFPyL were comparable to those determined by PET using [68Ga]Ga-PSMA-11.ResultsNo differences could be observed between [68Ga]Ga-PSMA-11-PET and [18F]F-DCFPyL-PET regarding tumour-to-liver ratios or tumour-to-mediastinum ratios (e. g. tumour-to-liver ratios using maximum SUV of the tumour lesion for ultra-high definition reconstructed PET images with a median of 2.5 (0.6–9.0) on [68Ga]Ga-PSMA-11-PET vs. 2,0 (0.6–11.4) on [18F]F-DCFPyL-PET). However, significant differences were observed in terms of contrast-to-noise ratios, thereby demonstrating the better image quality obtained with [18F]F-DCFPyL-PET.ConclusionsOur data showed that [18F]F-DCFPyl-PET and [68Ga]Ga-PSMA-11-PET provide comparable tumour-to-liver and tumour-to-mediastinum ratios. Therefore, a tumour uptake of [18F]F-DCFPyL above the liver background, like using [68Ga]Ga-PSMA-11, can be considered as equally suitable for defining PSMA-positivity by a semiquantitative assessment based on the liver background, e. g. prior to radioligand therapy with 177Lu-labelled PSMA ligands. In addition, our data suggest a tending advantage of [18F]F-DCFPyL in terms of lesion detectability.

Direct Patlak Reconstruction of [68Ga]Ga-PSMA PET for the Evaluation of Primary Prostate Cancer Prior Total Prostatectomy: Results of a Pilot Study.

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3-130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [68Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa.

The value of baseline 18F-sodium fluoride and 18F-choline PET activity for identifying responders to radium-223 treatment in castration-resistant prostate cancer bone metastases

ObjectivesTo investigate whether baseline 18F-sodium fluoride (NaF) and 18F-choline PET activity is associated with metastatic castration-resistant prostate cancer (mCRPC) global and individual bone metastases’ DWI MR imaging response to radium-223 treatment.MethodsThirty-six bone-only mCRPC patients were prospectively recruited from three centers. Whole-body (WB)-MRI with DWI and 18F-NaF and 18F-choline PET/CT were performed at therapy baseline and 8-week intervals. In each patient, bone disease median global (g)ADC change between baseline and follow-up was calculated. Additionally, up to five bone target lesions per patient were delineated and individual median ADC change recorded. An ADC increase > 30% defined response per-patient and per-lesion. For the same targets, baseline 18F-NaF and 18F-choline PET SUVmax were recorded. Mean SUVmax across patient targets was correlated with gADC change and lesion SUVmax with per-lesion ADC change.ResultsA total of 133 lesions in 36 patients (14 responders) were analyzed. 18F-NaF PET per-patient mean SUVmax was significantly higher in responders (median = 56.0 versus 38.7 in non-responders; p = 0.008), with positive correlation between SUVmax and gADC increase (rho = 0.42; p = 0.015). A 48.7 SUVmax threshold identified responders with 77% sensitivity and 75% specificity. Baseline 18F-NaF PET per-lesion SUVmax was higher in responding metastases (median = 51.6 versus 31.8 in non-responding metastases; p = 0.001), with positive correlation between baseline lesion SUVmax and ADC increase (rho = 0.39; p < 0.001). A 36.8 SUVmax threshold yielded 72% sensitivity and 63% specificity. No significant association was found between baseline 18F-choline PET SUVmax and ADC response on a per-patient (p = 0.164) or per-lesion basis (p = 0.921).Conclusion18F-NaF PET baseline SUVmax of target mCRPC bone disease showed significant association with response to radium-223 defined by ADC change.Clinical relevance statement18F-sodium fluoride PET/CT baseline maximum SUV of castration-resistant prostate cancer bone metastases could be used as a predictive biomarker for response to radium-223 therapy.Key Points• 18F-sodium fluoride PET baseline SUVmax of castration-resistant prostate cancer bone metastases showed significant association with response to radium-223.• Baseline 18F-sodium fluoride PET can improve patient selection for radium-223 therapy.• Change in whole-body DWI parameters can be used for response correlation with baseline 18F-sodium fluoride PET SUVmax in castration-resistant prostate cancer bone metastases.

Comparison of Oral and IV 18 F-NaF PET/CT Administration in the Assessment of Bone Metastases in Patients With Breast or Prostate Cancers.

The aim of this study was to compare oral and IV administrations of 18 F-NaF PET/CT for detection of suspicious bone metastatic lesions of breast and prostate cancers. Thirty-six patients with breast (n = 23) or prostate (n = 13) cancers and high risk for bone metastases were prospectively evaluated. All patients underwent 2 PET/CT studies after IV and oral 18 F-NaF administration within a 2 to 23 days interval between them. The maximum SUVs from the same suspicious lesions (≤5 index lesions per patient) in both studies were measured. The target-to-background ratio (TBR), defined as the relation between the lesion maximum SUV and the whole skeletal mean SUV, was calculated for each lesion. The TBRs in the same lesion calculated using the 2 administration routes were compared. The agreements between 2 physicians in the definition of the number of lesions in both studies were also assessed using weighted κ. One hundred thirty-four pairs of lesions were analyzed. There was no significant statistical difference between the median TBRs ( P = 0.212) for IV (10.33) and oral (10.85). Excellent intraobserver agreement was observed between IV and oral routes: weighted κ of 1.0 (95% confidence interval, 0.92-1.0) and 0.92 (95% confidence interval, 0.81-0.99) for physicians 1 and 2, respectively. The interobserver coefficients were 0.82 and 0.87 for "oral versus oral" and "IV versus IV," respectively. 18 F-NaF PET/CT studies using oral and IV routes present comparable performance; thus, it is possible to use oral route in patients with difficult venous access.

68Ga]-DOTATATE PET/MR-based evaluation of physiologic somatostatin receptor 2 expression in the adult pituitary gland as a function of age and sex in a prospective cohort.

The pituitary gland has the fourth highest physiologic avidity of [68Ga]-DOTATATE. In order to guide our understanding of [68Ga]-DOTATATE PET in clinical contexts, accurate characterization of the normal pituitary gland is first required. This study aimed to characterize the normal pituitary gland using dedicated brain [68Ga]-DOTATATE PET/MRI as a function of age and sex. A total of 95 patients with a normal pituitary gland underwent brain [68Ga]-DOTATATE PET examinations for the purpose of diagnosing CNS SSTR2 positive tumors (mean age: 58.9, 73% female). Maximum SUV of the pituitary gland was obtained in each patient. SUV of superior sagittal sinus was obtained to calculate normalized SUV score (SUVR) of the gland. The anatomic size of the gland was collected as maximum sagittal height (MSH). Correlations with age and sex were analyzed. The mean SUV and SUVR of the pituitary gland were 17.6 (range: 7-59.5, SD = 7.1) and 13.8 (range: 3.3-52.6, SD = 7.2), respectively. Older females had significantly higher SUV of the pituitary gland compared to younger females. When stratified by age and sex, both older and younger females had significantly higher pituitary SUV than older males. SUVR did not differ significantly by age or sex. MSH of the pituitary gland in younger females was significantly greater than in younger males at all age cutoffs. This study provides an empiric profiling of the physiological [68Ga]-DOTATATE avidity of the pituitary gland. The findings suggest that SUV may vary by age and sex and can help guide the use of [68Ga]-DOTATATE PET/MRI in clinical and research settings. Future studies can build on these findings to investigate further the relationship between pituitary biology and demographic factors.