PET-CT Research Articles

Management of Abdominal Paraganglioma: A Single Center's Experience.

Background and Objectives: Paragangliomas (PGLs) are rare neuroendocrine extra-adrenal tumors that could be secreting mass. The symptoms are the typical triad of paroxysmal headache, hypertension and sweating, but could also be accompanied by symptoms involving multiple organs. Surgery is the gold standard treatment for both PGLs and pheochromocytomas (PHEOs). Material and Methods: We used a computerized endocrine surgery registry to record the demographic and clinical data of 153 patients who underwent surgery for PPGL between 2010 and 2023 at our hospital. Results: Thirteen patients (8.43%) with paragangliomas underwent surgery at our institute. Five patients presented symptomatic syndrome. Preoperative investigations included enhanced abdominal CT (nine patients) and enhanced MRI (seven patients). In cases of suspicious mass, we performed 131I-MIBG scans (two patients) or 68GA-DOTATOC PET-CT scans (11 patients). Laparoscopic approach was used in four cases (30.7%) and abdominal laparotomy in the other nine (69.3%). Biochemical tests were performed on all patients. Conclusions: In this retrospective study, we discuss the multidisciplinary management in our institute of this rare disease, from its challenging diagnosis to the surgical strategy for PGLs. Laparoscopic surgery is the gold standard, but a tailored approach should be adopted for each patient.

Abstract LB236: Metabolically armed CD19 CAR-T cells for safe and effective treatment of relapsed or refractory CD19+ B cell hematological malignancies at extremely low doses

Abstract Background: The undeniable success of CD19 CAR-T cell therapy in managing relapsed or refractory (r/r) B-cell hematological malignancies, such as diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (B-ALL), underscores its significance. Despite the favorable complete remission (CR) rates of around 50% for r/r DLBCL and up to 90% for r/r B-ALL, a notable challenge persists as more than half of patients experiencing CR after CD19 CAR-T cells treatment encounter relapse within a year, attributed to inadequate CAR-T persistence in both indications. Urgent attention is required to devise innovative strategies to overcome these challenges. Recently, we developed metabolically armed CD19 CAR-T cells expressing IL-10 can enhance OXPHOS metabolism, proliferation, and persistence of CAR-T cells in vivo. Significantly, these IL-10-expressing CAR-T cells trigger stem-like memory responses in various lymphoid organs, leading to robust tumor eradication and durable protection. Motivated by these promising findings, an open-label, single arm, investigator-initiated trial (IIT, ClinicalTrials.gov identifier: NCT05715606, NCT05747157) was conducted to assess the safety and efficacy of newly developed metabolically armed IL-10-expressing CD19 CAR-T (product name: Meta10-19 infusion) for treating patients with r/r DLBCL or r/r B-ALL. Method: From Feb 2023 to Dec 2023, this IIT clinical trial evaluated Meta10-19 infusion in adult patients with r/r DLBCL or r/r B-ALL. The patients were recruited and treated at the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China. Patients in 3 dose cohorts (2.0 × 104, 5.0 × 104, or 1.0 × 105 CAR-T cells/kg, corresponding to 1%, 2.5%, or 5% doses of commercialized CAR-T infusion) underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine before Meta10-19 infusion. The primary endpoint was the incidence of dose-limiting toxicities. The secondary endpoint was the response and survival. Results: The treatment with Meta10-19 infusion has successfully induced CR in all 12 cases of r/r DLBCL (n=6) or r/r B-ALL (n=6), as evaluated by PET-CT scan, NMR spectroscopy or minimal residual disease assessment of bone marrow. No server cytokine storm syndrome or neurotoxicity was observed. All treated patients achieved CR at 3 months post treatment, with the first patient maintaining continuous remission up to 9 months until now. Notably, these metabolically armed CD19 CAR-T cells demonstrated efficacy even for patients with bulky mass (≥7.5 cm) of DLBCL at extremely low infusion dose (1~5% doses of commercialized CAR-T). Conclusion: Preliminary findings suggest that Meta10-19 infusion exhibits promising breakthrough efficacy and safety profile, and active enrollment is ongoing to validate the initial results. Citation Format: Yugang Guo, Qianwen Xu, Lei Xue, Erling Chen, Chonglin Liu, Min Gao, Youjia Li, Jingjing Ren, Jinping Li, Li Tang, Xingbing Wang. Metabolically armed CD19 CAR-T cells for safe and effective treatment of relapsed or refractory CD19+ B cell hematological malignancies at extremely low doses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB236.

Occult Breast Cancer Presenting as Sternum Pain.

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

An Unusual Presentation of Squamous Cell Carcinoma in a Never Smoker: A Case Report

Lung Cancer is one of the most common types of cancer found among smokers. However, approximately 10% of lung cancer patients are non-smokers. Non-smokers are frequently seen developing Adenocarcinoma, a type of non-small cell carcinoma with a female predominance. The incidence of Squamous cell carcinoma among non-smokers is very low. Moreover, studies have shown that tetra site metastasis in the case of Squamous cell carcinoma of the lung is almost as rare as 0.6% [1]. The authors report here in this article a case report of a rare and aggressive presentation of Squamous cell carcinoma in a non-smoker. This is a case of a 50-year-old male patient who is a non-smoker, presented with complaints of exertional dyspnoea and cough with expectoration for 3 months which had aggravated since 15 days, associated with hoarseness of voice and diffuse headache since 15 days. There was a history of significant weight loss and loss of appetite for 3 months. CECT thorax revealed a heterogeneously enhancing mass lesion in the anterior segment of the left upper lobe encasing the left pulmonary artery with evidence of liver, adrenal and vertebral metastasis. During the hospital stay, the patient developed complete ptosis of the right eye. MRI brain was done which showed features suggestive of metastasis involving bilateral cerebral and cerebellar hemispheres. USG guided lung biopsy was done and was suggestive of moderately differentiated Squamous cell carcinoma. The patient was planned to be further worked up for IHC markers and PET CT scan to determine the further line of treatment however, unfortunately, the patient succumbed to the disease within 1 week of histopathological diagnosis.

Use of Multimodality Imaging in the Evaluation of Patients With Spondyloarthropathies and Sacroiliitis.

Spondyloarthropathy (SpA) is one of the most common causes of low back pain. It is caused by inflammatory arthritis in the spine, manifesting in various forms such as psoriatic arthritis (PsA), ankylosing spondylitis (AS), and sacroiliitis. A comprehensive systematic literature search was done to evaluate and compare MRI, CT, single-photon emission CT, PET, ultrasound (US) imaging, low-dose CT, and diffusion-weighted imaging (DWI) techniques in assessing SpAs. The search strategy was constructed by an analysis of key terms from relevant articles in MEDLINE ProQuest, Embase, and PubMed. The key terms used to search for these articles were "SpA," "sacroiliitis," "spondylitis," "psoriatic arthritis," "MRI," "CT scan," "x-ray," "magnetic resonance imaging," "computed tomography," "bone density," and "ultrasound." A total of 1,131 articles published in English between January 1, 2003, and October 15, 2023 were identified and screened for eligibility by members of the research team, which resulted in 69 total articles selected for the final review. US has played an important role in visualizing joint inflammation and enthesitis (inflammation of the enthesis), which are common features of PsA. Although MRI and CT are considered more reliable modalities for diagnosing active sacroiliitis, US imaging with Doppler flow can also be useful in conjunction with CT images to visualize abnormal blood flow in the sacroiliac joints, as well as other joints affected by inflammatory arthritis. MRI provides increased diagnostic confidence in the diagnosis of sacroiliitis in active AS patients when compared to CT. CT is more sensitive than plain radiographs. The PET activity score showed a good correlation in diagnosing inflammatory sacroiliitis but lacked in identifying structural lesions. CT has high diagnostic accuracy, but it exposes patients to a high radiation dose. MRI visualizes joint and tissue inflammation, bone, and bone marrow change and can identify peripheral inflammation in soft tissue and joints in patients diagnosed with PsA. MRI can also visualize bone marrow changes and subchondral edema, which can aid in the early diagnosis of ankylosing SpA and gauge disease severity. DWI and short-tau inversion recovery imaging are both MRI techniques used in detecting sacroiliitis. MRI and CT are shown to be reliable imaging modalities for the diagnosis of sacroiliitis; however, it was found that Doppler US played an accurate role in the diagnosis as well. MRI visualizes joints and tissue with the most precision, making it useful in evaluating patients with PsA, while PET CT is useful in the diagnosis of inflammatory sacroiliitis patients. There is limited literature available comparing the multiple modalities of imaging available for each SpA. The review's objective is to analyze imaging findings in patients diagnosed with sacroiliitis and SpAs. The findings in this literature review are valuable for properly assessing and diagnosing patients suffering from SpAs.

Role of F-18 FDG PET-CT in neuropsychiatric systemic lupus erythematosus

BackgroundNeuropsychiatric systemic lupus erythematosus (NPSLE) is a major contributor to morbidity and mortality in systemic lupus erythematosus (SLE) patients. To date no single clinical, laboratory or imaging test has proven accurate for NPSLE diagnosis which is a testament to the intricate and multifactorial pathophysiological mechanisms suspected to exist. Functional imaging with FDG PET-CT has shown promise in NPSLE diagnosis, detecting abnormalities prior to changes evident on anatomical imaging. Research indicates that NPSLE may be more aggressive in people of African descent with higher mortality rates, making rapid and correct diagnosis even more important in the African context. MethodsIn this narrative review, we provide a thorough appraisal of the current literature on the role of FDG PET-CT in NPSLE. Large, well-known databases were searched using appropriate search terms. Manual searches of references of retrieved literature were also included. FindingsA total of 73 article abstracts were assessed, yielding 26 papers that were directly relevant to the topic of FDG PET-CT in NPSLE. Results suggest that FDG PET-CT is a sensitive imaging test for NPSLE diagnosis and may play a role in assessing treatment response. It is complementary to routine anatomical imaging, particularly in diffuse manifestations of the disease. Newer quantitative analyses are commonly used for interpretation and can detect even subtle abnormalities, missed on visual inspection. Findings of group-wise analyses of FDG PET-CT scans in NPSLE patients are important in furthering our understanding of the complicated pathophysiological mechanisms involved. Limitations of FDG PET-CT include its lack of specificity, high cost and poor access. ConclusionFDG PET-CT is a sensitive test for NPSLE diagnosis but is hampered by lack of specificity. It is a valuable tool for clinicians managing SLE patients, particularly when anatomical imaging is negative. Its exact application will depend on the local context and clinical scenario.

Warthin's Tumour as a Parotid Gland Incidentaloma Identified by PET-CT Scan in a Large Series of Cases.

Occasionally in imaging scans there are findings unrelated to the pathology for which the scan was indicated, findings that are called incidentalomas. Warthin tumors have a high glucose avidity, being one of the common incidentalomas in PET-CT scans. The aim of the present study is to analyze the frequency of occurrence of Warthin's tumor as an incidental finding in a large series of patients undergoing 18F-FDG PET-CT. Retrospective analysis of 18F-FDG PET-CT scans performed in our center during the period 2010-2021. Parotid hypermetabolic lesions were identified, as well as their SUVmax, size, smoking habit, BMI (body mass index), and otorhinolaryngology follow-up. 31,423 PET-CT-18FDG studies corresponding to 12,806 patients were analyzed. The frequency of incidentalomas at the parotid level with a diagnosis compatible with Warthin's tumor was 0.87% (n = 111). Eighty percent of the patients with incidentalomas accordant to Warthin's tumor had a history of tobacco use. The highest percentage of incidentalomas compatible with a Warthin tumor was found in patients in whom the indication for PET-CT was the study of a lung carcinoma (1.44%). Only 37% of patients with a PET-CT lesion compatible with a Warthin's tumor were referred for evaluation by the Otorhinolaryngology service. The incidence of Warthin's tumor in 18-FDG PET-CT scans in our center was 0.87%.

Abstract 1305: Comparison of HPV-DNA testing to PET-CT imaging as prognostic test following definitive treatment for cervical cancer: A retrospective proof-of-concept study

Abstract Cervical cancer is a significant global health issue, with oncogenic HPV-High Risk (HPV) responsible for over 99% of cases. Despite the prevalence of HPV-related malignancies, current guidelines by the National Comprehensive Cancer Center (NCCN) do not recommend post-treatment HPV-DNA testing. Instead, PET-CT imaging is recommended as a prognostic test. This retrospective proof-of-concept study aims to evaluate current NCCN guidelines and examines whether post-treatment HPV-HR DNA testing is a cost-effective, reliable alternative to PET-CT imaging in cervical cancer prognosis. Methods: The study included female patients diagnosed with cervical or vaginal carcinomas (2011-2021), ensuring comprehensive records of both pre-treatment and post-treatment high-risk HPV (HPV-HR) testing, alongside PET-CT imaging results. Utilizing the FDA-approved HPV-HR DNA test, capable of detecting 14 oncogenic HPV strains, the study conducted rigorous statistical analyses via STATA software to determine significance of the study results. Results: Our analysis of 53 patients who met the inclusion criteria demonstrated that post-treatment assessments using both HPV status and PET-CT imaging exhibited high levels of sensitivity and specificity, as well as impressive negative and positive predictive values (NPV and PPV, respectively). There was a statistically significant correlation between the likelihood of cancer recurrence and the results obtained from HPV status and PET-CT imaging post-treatment (p-value < 0.001). A critical observation was the superior sensitivity and improved NPV of post-treatment HPV status compared to PET-CT scans. Specifically, the sensitivity for HPV status post-treatment was quantified at 92.31, surpassing the 76.92 sensitivity rating of PET-CT scans. Furthermore, the NPV for post-treatment HPV status was measured at 97.44, which is better than the 92.31 NPV for PET-CT scans. Notably, no patients with negative post-treatment HPV-HR tests had a recurrence. Discussion: The results of this study underscore the clinical significance of assessing HPV-HR DNA status post-treatment, particularly when HPV-HR DNA is negative. If future prospective studies confirm these findings, it may eliminate the need for post-treatment PET-CT scans, providing significant survivorship benefits for patients by reducing follow-up visits and eliminating unnecessary imaging. This would also result in substantial financial savings, estimated to be over $75,000,000 per year in the US alone, based on 2023 data. The limitations of the study include small sample size, single-institution data, and biases associated with retrospective studies. Future multi-institutional prospective studies are necessary to improve current guidelines further and validate the findings of this study. Citation Format: Cameron Huddleston, Aya Bou Fakhreddine, Stephanie Stroever, Robert Young, Naresh Sah, Komaraiah Palle, Mark Reedy. Comparison of HPV-DNA testing to PET-CT imaging as prognostic test following definitive treatment for cervical cancer: A retrospective proof-of-concept study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1305.

Abstract 2585: First in human study with a novel peptide binder to glypican-3, demonstrates high specificity as a PET imaging agent in patients with hepatocellular carcinoma

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The American Association for the Study of Liver Disease recommends surveillance for high-risk individuals with abdominal ultrasound, triple phase contrast CT or MRI. However, these imaging techniques have limited sensitivity in classifying lesions smaller than 2 centimeters. The use of [18F]FDG Positron Emission Tomography (PET) is constrained due to insufficient uptake by HCC lesions over background liver uptake. Hence, there is an urgent need for more precise radiotracers for HCC. This study introduces the development of a novel radiotracer that binds to glypican-3 (GPC3), a cell membrane-anchored oncofetal protein overexpressed in HCC with minimal normal tissue expression. Methods: [68Ga]Ga-RYZ-GPC3 is composed of a small macrocyclic peptide binder with high affinity to GPC3 linked with a tetraxetan moiety capable of chelating a variety of radioisotopes including positron-emitting 68Ga and other radiometals. The unlabeled binder to GPC3 was synthesized by the sponsor and provided to three imaging centers in India as part of investigator-initiated trials reviewed and approved by each site’s institutional review board and ethics committee. Labeling with 68Ga and quality checks of the product was performed locally at each center. Patients with high clinical suspicion or with confirmed HCC who gave informed consent received injections of 1.5-5.5 mCi of [68Ga]Ga-RYZ-GPC3 and underwent PET-CT scanning at predetermined intervals. Some patients underwent companion [18F]FDG PET-CT scans in accordance with local guidelines. Results: A total of 64 patients underwent [68Ga]Ga-RYZ-GPC3 PET-CT scans. The median age within the cohort was 61 (41-83), 22% were female. Liver cirrhosis was present in 72% of patients, attributed to hepatitis B, hepatitis C or NASH in 17%, 13% and 20% of cases. Notably, 92% of patients exhibited at least one positive lesion on [68Ga]Ga-RYZ-GPC3 scans. The median SUVmax of GPC3-avid liver lesions was 15.5 (range 1.1 to 137.0) while the median liver SUVmean was 1.6 (0.3-7.9). Physiologic uptake was predominantly observed in the kidneys, the primary route of clearance, with a median SUVmean of 10.9 (2.2-20.7). Additionally, 20 patients underwent [18F]FDG PET-CT scan for comparison. The median SUVmax of lesions on 68Ga-RYZ-GPC3 vs [18F]FDG PET was 11.0 (1.1-137.0) vs 3.8 (1.2-12.2). Conclusion: Early human imaging results in patients with HCC indicate that [68Ga]Ga-RYZ-GPC3 has high tumor lesion specificity compared to normal liverand demonstrates the potential of [68Ga]Ga-RYZ-GPC3 to improve detection of HCC over conventional [18F]FDG PET-CT. In addition, the binder could be complexed with a therapeutic radioisotope as a novel targeted therapeutic option for HCC. Further investigation of this first-in-class binder to HCC is warranted. Citation Format: Chandresakhar Bal, Sanjana Ballal, Kumar Kallur, Anna Karmann, Ye Yuan, Jessica Rearden, Kathryn Shah, Charlotte Lorenz, Susan Moran, Ken Song, Ishita Sen. First in human study with a novel peptide binder to glypican-3, demonstrates high specificity as a PET imaging agent in patients with hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2585.

Checkpoint Inhibitors Prior to Autologous Stem Cell Transplantation for Relapsed/ Refractory Hodgkin Lymphoma

Aim: To present the evolution of our patients treated with checkpoint inhibitors before high-dose chemotherapy and autologous stem cell transplantation (ASCT) and to compare the results with data from the literature. Material and methods: We evaluate 3 patients with relapsed/refractory Hodgkin’s Lymphoma, who failed to achieve complete remission after 2 or more lines of salvage chemotherapy and were treated with anti PD1 inhibitors as a bridging therapy to autologous stem cell transplant. To evaluate the treatment response, we used PET CT scan before and 100 days after ASCT. Results: In our study, heavily pre-treated and chemo-refractory patients had increased response rates to conditioning chemotherapy followed by ASCT given after exposure to immune-checkpoint inhibitors. All 3 patients remain in complete response at 14 months, 20 months and respectively 32 months of follow-up. Conclusions: High-dose chemotherapy and ASCT can be curative for many patients with relapsed or refractory Hodgkin’s Lymphoma (HL), but the outcome depends on disease status at ASCT. Patients who have chemorefractory disease, particularly those who fail more than 2 lines of salvage therapy, are considered poor candidates for ASCT. Checkpoint inhibitors are routinely employed in relapsed/refractory classical Hodgkin lymphoma. The results from our center are similar with those from several studies which have suggested that treatment with anti PD1 can sensitize previously chemorefractory HL patients to subsequent high-dose therapy and ASCT.

Abstract 6294: Subclinical atherosclerosis in newly diagnosed colorectal cancer patients

Abstract Introduction: Recent advances in early detection and treatment have improved survival rates for patients with colorectal cancer (CRC), and emerging data suggests patients may be at elevated risk of cardiovascular disease (CVD). However, there are no standard recommendations for assessing CVD risk in patients with CRC. Coronary artery calcium (CAC) is a measure of the quantity of coronary artery calcification using noninvasive scanning and has been shown to be predictive of CVD risk. This prospective cohort study utilizes CAC to evaluate the occurrence of subclinical atherosclerosis at the time of CRC diagnosis and the risk of major adverse cardiovascular events (MACE). Methods: The ColoCare Study is a prospective cohort study across six U.S. and European sites. Data from one of the ColoCare consortium sites in Los Angeles, California was analyzed. Adults with newly diagnosed stage I- IV colorectal cancer and available non-contrast CT scans were included. Electronic medical records were reviewed for assessment of baseline cardiovascular risk factors and adverse events. Subclinical atherosclerosis was defined as the presence of CAC (CAC>0). CAC was manually measured from routine oncologic diagnostic CT and PET-CT scans at the time of cancer diagnosis using the Agatston method. MACE was defined as hospitalization due to heart failure, cardiomyopathy, ischemic heart disease, or ischemic stroke after the diagnosis of CRC cancer. Multivariable-adjusted Cox regression was used to evaluate the association between CAC at diagnosis and the risk of MACE. Results: Among 109 individuals with CAC measured at the time of CRC diagnosis, 41 (37.6%) had subclinical atherosclerosis (CAC=1-399 [n=29], CAC>400 [n=12]). Individuals with CAC>0 were older (67.0 vs. 51.9 years, p<0.01), more likely to be former or current smokers (48.0 vs. 29.0 years, p=0.04), and to have hypertension (61% vs. 23%, p<0.01) compared to those without CAC (CAC=0). Among individuals with CAC (n=41), 51.2% had scores >100, and 29.2% had scores >400, indicating moderate and severe atherosclerosis respectively. Among patients with moderate or greater CAC burden (>100; statin therapy indicated), 28.6% were not on statin therapy. CAC>0 was associated with an increased incidence of MACE (13% vs. 53%, p<0.01). Discussion: Subclinical atherosclerosis was observed in nearly 40% of patients with CRC at diagnosis and MACE occurred in 38.2% of patients. Most patients were under-optimized for CVD risk, with nearly 30% of statin-eligible patients with at least moderate CAC burden not prescribed statin therapy. These findings highlight an opportunity for improved CVD risk mitigation in patients with CRC, including guidelines-based CVD risk factor modification. Citation Format: Julia A. Levy, Maimoona Nadri, Elham Kazemian, Katelyn M. Atkins, Jordan O. Gasho, Katrina D. Silos, Cody Ramin, Andriana P. Nikolova, Erin M. Siegel, Biljana Gigic, Adetunji T. Toriola, Jennifer Ose, Christopher I. Li, David Shibata, Cornelia M. Ulrich, Jane C. Figueiredo. Subclinical atherosclerosis in newly diagnosed colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6294.

Antibiotic treatment modestly reduces protection against Mycobacterium tuberculosis reinfection in macaques.

Concomitant immunity is generally defined as an ongoing infection providing protection against reinfection . Its role in prevention of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is supported by epidemiological evidence in humans as well as experimental evidence in mice and non-human primates (NHPs). Whether the presence of live Mtb, rather than simply persistent antigen, is necessary for concomitant immunity in TB is still unclear. Here, we investigated whether live Mtb plays a measurable role in control of secondary Mtb infection. Using cynomolgus macaques, molecularly barcoded Mtb libraries, positron emission tomography-computed tomography (PET CT) imaging, flow cytometry, and cytokine profiling, we evaluated the effect of antibiotic treatment after primary infection on immunological response and bacterial establishment, dissemination, and burden post-secondary infection. Our data provide evidence that, in this experimental model, treatment with antibiotics after primary infection reduced inflammation in the lung but was not associated with a significant change in bacterial establishment, dissemination, or burden in the lung or lymph nodes. Nonetheless, treatment of the prior infection with antibiotics did result in a modest reduction in protection against reinfection: none of the seven antibiotic-treated animals demonstrated sterilizing immunity against reinfection, while four of the seven non-treated macaques were completely protected against reinfection. These findings support that antibiotic-treated animals were still able to restrict bacterial establishment and dissemination after rechallenge compared to naïve macaques, but not to the full extent of non-antibiotic-treated macaques.

Abstract 7582: Descriptive analysis of patients with mCRPC and liver metastases receiving alpha and beta PSMA targeted radionuclide therapy (PSMA-TRT)

Abstract Introduction: Predictors of outcomes after PSMA-TRT are still being established. Liver metastases (mets) have been associated with poor response. Mutations in genes encoding DNA damage repair (DDR) and TP53 affect radiosensitivity. Here we describe a cohort of patients with mCRPC and liver metastases treated on clinical trials of PSMA-TRT. Methods: 39 patients with liver mets were enrolled on phase I/II PSMA-TRT studies between Jan 2006 to Apr 2022. Patients received alpha therapy (225Ac-J591), beta therapy (fractionated 177Lu-PSMA-617, single-dose and fractionated 177Lu-J591) or a combination of both (225Ac-591 and 177Lu-PSMA-I&T). All patients included in this analysis had CT imaging; patients enrolled after 2017 had PSMA-PET imaging. 15 patients also had genomic analysis completed. Results: Median age was 69 (range 55-93), PSA 85.7 (2.45-9614). 39 (100%) bone mets, 33 (84.6%) LN, 9 (23.1%) lung. 22 (56.4%) greater than 1 ARPI, 23 (59.0%) greater thanc 1 chemo, 13 (33.3%) sip-T, 7 (17.9%) Ra-223, 4 (10.2%) prior TRT (with concurrent liver mets). Of the 19 with both CT and PSMA PET, 18 (94.7%) were identified on PSMA PET (including 8 PET only), 10 (55.6%) on CT (1 CT only, i.e. non-PSMA PET avid). Median whole body PSMA-imaging score (PSMA-IS) was 4 (range 1-4), with 7 (17.9%) 1-2 and 32 (82.1%) 3-4. 9 (23.0%) received alpha-TRT, 26 (66.7%) beta-TRT, and 4 (10.3%) combo-TRT. Somatic or germline analysis was completed in 15 (38.5%) of 39 patients. 8 (53.3%) had mutations in DNA repair pathways (3 in BRCA2, 3 in CHEK 2, 1 in FANC, 1 in MSH2). 7 (46.7%) had mutations in TP53. 31 patients (79.5%) had PSA decline, with 15 (38.5%) achieving PSA 50. 26 (66.7%) had baseline CTC measured; 19 (73.0%) had detectable CTC at baseline. Of these 19, 3 (15.8%) converted to undetectable after therapy and 2 (10.5%) converted to favorable CTC. PSA50 rate in alpha-TRT was 4 (44.4%), beta-TRT 8 (30.7%), combo-TRT 3 (75%). PSA50 in patients with PSMA-IS 1-2 was 1 (14.2%) compared to 14 (43.9%) in PSMA-IS 3-4. 3 (37.5%) of 8 patients with mutDDR achieved PSA50, compared to 3 (42.9%) with mutTP53. Conclusions: This dataset adds to the collective literature of two subgroups of patients with mCRPC receiving TRT: those with liver disease and those with mutations in DNA repair pathways. The results of this study suggest higher rates of response in patients receiving alpha therapy, either alone or in combination with beta therapy, and in patients with high radiotracer uptake on PSMA-PET, based on PSMA-imaging score of 3 or 4. Genomic alterations in DRR proteins did not have clear implications. Citation Format: Samuel Ruder, Michael Sun, Andres Ricaurte Fajardo, Jones Nauseef, Zachary Davidson, Joseph Thomas, Sandra Huicochea Castellanos, Ana Molina, Cora Sternberg, Amie Patel, Escarleth Fernandez, Sarah Yuan, Edward Fung, Vasilios Avlonitis, Elisabeth O'Dwyer, David Nanus, Joseph Osborne, Neil Bander, Scott Tagawa. Descriptive analysis of patients with mCRPC and liver metastases receiving alpha and beta PSMA targeted radionuclide therapy (PSMA-TRT) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7582.

Accuracy of positron emission tomography-computed tomography in the assessment of metabolically negative axillary lymph nodes in breast cancer

Background Breast cancer is a significant public health concern, and early detection of breast lesions is crucial for improved patient outcomes. Accurate assessment of axillary lymph node involvement in breast cancer is vital for staging and treatment decisions. The purpose of this study was to assess to what extent positron emission tomography (PET)-computed tomography (CT) can be used in the assessment of negative axillary lymph nodes in breast cancer and to determine if pathological variability can affect the result of the PET-CT. Patients and methods This prospective study was carried out on 50 female patients with locally advanced breast cancer and with negative PET-CT scans for active axillary lymph nodes. All studied cases underwent postoperative pathological examination to be compared with preoperative PET-CT results. Results Of the studied cases, 84% showed negative axillary lymph node involvement. PET/CT exhibited high sensitivity (95.24%) and specificity (87.5%) in predicting positive nodes, with an axillary maximum standardized uptake value cutoff value of 4.22 (area under the curve=0.923). Logistic regression revealed a significant association between higher T stage and positive lymph nodes (P<0.05). Conclusion PET/CT demonstrates strong predictive accuracy in detecting metabolically negative axillary lymph nodes in breast cancer patients.

Abstract 4784: PATHFINDER 2: A prospective study to evaluate safety and performance of a multi-cancer early detection test in a population setting

Abstract Background: Multi-cancer early detection (MCED) tests are being established as a novel approach to screen for multiple cancer types with one test. A blood-based MCED test using cell-free DNA targeted methylation patterns to detect a shared cancer signal and predict a cancer signal origin (CSO) has demonstrated feasibility. An initial return of results study (PATHFINDER; NCT04241796) reported performance of a refined version of the MCED test, including a 43.1% positive predictive value (PPV), 98.5% negative predictive value (NPV), 99.5% specificity, and 88.0% CSO accuracy. To build on this work, the PATHFINDER 2 study (NCT05155605) will evaluate safety and performance of the MCED test in larger, more diverse populations. Methods: PATHFINDER 2 is a prospective, multicenter, interventional study. Participants ≥50 years of age will be enrolled, with specific targets to improve diversity (age, sex, race/ethnicity) and few exclusions due to comorbid conditions. Exclusion criteria include current clinical suspicion of cancer or recent cancer/treatment (within 3 years). Participants will undergo blood draw for MCED testing, followed by return of results (cancer signal detection and CSO) to the investigator and diagnostic evaluations if a cancer signal is detected. A confirmatory PET-CT scan will be performed when CSO-directed workups do not result in a cancer diagnosis. Participants will be followed for approximately 3 years. Primary endpoints include 1) MCED test safety in terms of diagnostic testing triggered by a positive result (number/type of procedures and adverse events) and 2) test performance (PPV, NPV, specificity, sensitivity, CSO accuracy, cancer detection rate and number needed to screen). Secondary endpoints include participant reported outcomes (eg, anxiety), utilization of guideline-recommended cancer screening, and cancer detection rate of confirmatory PET-CT, amongst others. The study plans to enroll approximately 35,000 participants across North America. Sites were selected based on geographic location, catchment area demographics, and practice setting (academic vs non-academic). Enrollment targets for age, sex and race/ethnicity (White [non-Hispanic] 72%; Hispanic or Latino 11%; African American or Black 11%; Asian, Native Hawaiian or Other Pacific Islander 6%; American Indian/Alaska Native 1%) were derived from US Census data. Strategies to promote diverse recruitment include translation of participant-facing documents across multiple languages, participant and healthcare provider educational material, and site-led community outreach campaigns. MCED testing is an emerging, potentially paradigm-changing strategy in cancer screening, and PATHFINDER 2 is designed to characterize the safety, performance, and clinical implementation of the MCED test as a screening tool in a broad and representative population. Citation Format: Karthik V. Giridhar, Michael J. Demeure, Raymond H. Kim, Justin A. Chen, Shirish Gadgeel, Dax Kurbegov, Margarita Lopatin, Roland Matthews, Marc Matrana, Charles McDonnell, Donald Richards, Benjamin Rybicki, Gretchen Stipec, Nima Nabavizadeh. PATHFINDER 2: A prospective study to evaluate safety and performance of a multi-cancer early detection test in a population setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4784.

Neuropsychiatric Profiles and Cerebral Amyloid Burden in Adults without Dementia

Plain Language SummaryThis study examines how patients’ and their caregivers’ report of neuropsychiatric symptoms are associated with amyloid burden, of the primary markers of risk for amyloid burden, in older adults without dementia. Amyloid burden was measured using a PET-CT scan, and neuropsychological symptoms were measured with a self-reported and an informant-reported questionnaire. We found that neuropsychiatric symptoms were associated with amyloid burden in older adults without dementia, and these relationships were stronger in older adults with greater cognitive and functional impairment. In particular, caregivers’ report of anxiety, depression, and irritability and patients’ report of cognitive concerns were associated with greater amyloid burden. Neuropsychiatric symptoms, observed by both the patient and the informant, may be promising first identifiers of the neuropathology associated with Alzheimer’s disease and related dementias. Although neuropsychiatric symptoms have been characterized in persons with dementia, we do not yet have a clear understanding of how neuropsychiatric symptoms appear in non-dementia stages or which instruments may be the most sensitive screening tools for neuropsychiatric symptoms in older adults without dementia. These older adults without dementia may exist in a window of opportunity for behavioral and pharmacologic interventions that may prevent or slow clinical progression.

Sequential deep learning image enhancement models improve diagnostic confidence, lesion detectability, and image reconstruction time in PET

BackgroundInvestigate the potential benefits of sequential deployment of two deep learning (DL) algorithms namely DL-Enhancement (DLE) and DL-based time-of-flight (ToF) (DLT). DLE aims to enhance the rapidly reconstructed ordered-subset-expectation-maximisation algorithm (OSEM) images towards block-sequential-regularised-expectation-maximisation (BSREM) images, whereas DLT aims to improve the quality of BSREM images reconstructed without ToF. As the algorithms differ in their purpose, sequential application may allow benefits from each to be combined. 20 FDG PET-CT scans were performed on a Discovery 710 (D710) and 20 on Discovery MI (DMI; both GE HealthCare). PET data was reconstructed using five combinations of algorithms:1. ToF-BSREM, 2. ToF-OSEM + DLE, 3. OSEM + DLE + DLT, 4. ToF-OSEM + DLE + DLT, 5. ToF-BSREM + DLT. To assess image noise, 30 mm-diameter spherical VOIs were drawn in both lung and liver to measure standard deviation of voxels within the volume. In a blind clinical reading, two experienced readers rated the images on a five-point Likert scale based on lesion detectability, diagnostic confidence, and image quality.ResultsApplying DLE + DLT reduced noise whilst improving lesion detectability, diagnostic confidence, and image reconstruction time. ToF-OSEM + DLE + DLT reconstructions demonstrated an increase in lesion SUVmax of 28 ± 14% (average ± standard deviation) and 11 ± 5% for data acquired on the D710 and DMI, respectively. The same reconstruction scored highest in clinical readings for both lesion detectability and diagnostic confidence for D710.ConclusionsThe combination of DLE and DLT increased diagnostic confidence and lesion detectability compared to ToF-BSREM images. As DLE + DLT used input OSEM images, and because DL inferencing was fast, there was a significant decrease in overall reconstruction time. This could have applications to total body PET.

Loss of psoas muscle during neoadjuvant treatment for rectal cancer is associated with poor oncological and surgical outcomes.

Sarcopenia has been associated with poor outcomes in rectal cancer patients. This study aims to assess the degree of muscle loss during neoadjuvant therapy in patients with rectal cancer, and its relationship with tumour response, post-operative complications and long-term disease recurrence. The change in the psoas muscle area was determined by measuring the psoas muscle area at L4 on initial staging PET CT scans and comparing this with the restaging scan 8-10 weeks after radiation treatment had been completed. The average change in the psoas muscle area was compared between patients who had residual disease versus complete clinical/pathological response, anastomotic leak vs. no leak, and distant recurrence vs. no recurrence on follow-up imaging. Ninety-two patients were included in the study. The mean loss of psoas muscle area was 5%. Patients who had a complete response to chemoradiotherapy showed a statistically significant difference in muscle mass loss (2.8%) compared to those with residual tumour present after therapy (6.2%), P = 0.02 on multivariable analysis. There was a statistically significant greater loss of muscle in patients who had an anastomotic leak versus those that did not (10.2% vs. 4.1%) and in those who developed metastatic disease versus those that did not (10.7% vs. 4.1%) (P < 0.05). Our study adds to the growing body of evidence that sarcopenia is a predictor of poor surgical and oncological outcomes in rectal cancer patients. We postulate that the loss of muscle is an indication of disease burden and worse tumour biology.

Evaluating Outcome Prediction via Baseline, End-of-Treatment, and Delta Radiomics on PET-CT Images of Primary Mediastinal Large B-Cell Lymphoma.

Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression (TTP) of primary mediastinal large B-cell lymphoma (PMBCL) patients. Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans. Consequently, our radiomics analysis focused on these 31 patients who underwent [18F]FDG PET-CT scans before and after R-CHOP chemotherapy. Expert manual lesion segmentation was conducted on their scans for delta radiomics analysis, along with an additional 19 EoT scans, totaling 50 segmented scans for single time point analysis. Radiomics features (on PET and CT), along with maximum and mean standardized uptake values (SUVmax and SUVmean), total metabolic tumor volume (TMTV), tumor dissemination (Dmax), total lesion glycolysis (TLG), and the area under the curve of cumulative standardized uptake value-volume histogram (AUC-CSH) were calculated. We additionally applied longitudinal analysis using radial mean intensity (RIM) changes. For prediction of relapse/progression, we utilized the individual coefficient approximation for risk estimation (ICARE) and machine learning (ML) techniques (K-Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA), and Random Forest (RF)) including sequential feature selection (SFS) following correlation analysis for feature selection. For TTP, ICARE and CoxNet approaches were utilized. In all models, we used nested cross-validation (CV) (with 10 outer folds and 5 repetitions, along with 5 inner folds and 20 repetitions) after balancing the dataset using Synthetic Minority Oversampling TEchnique (SMOTE). To predict relapse/progression using Delta radiomics between the baseline (staging) and EoT scans, the best performances in terms of accuracy and F1 score (F1 score is the harmonic mean of precision and recall, where precision is the ratio of true positives to the sum of true positives and false positives, and recall is the ratio of true positives to the sum of true positives and false negatives) were achieved with ICARE (accuracy = 0.81 ± 0.15, F1 = 0.77 ± 0.18), RF (accuracy = 0.89 ± 0.04, F1 = 0.87 ± 0.04), and LDA (accuracy = 0.89 ± 0.03, F1 = 0.89 ± 0.03), that are higher compared to the predictive power achieved by using only EoT radiomics features. For the second category of our analysis, TTP prediction, the best performer was CoxNet (LASSO feature selection) with c-index = 0.67 ± 0.06 when using baseline + Delta features (inclusion of both baseline and Delta features). The TTP results via Delta radiomics were comparable to the use of radiomics features extracted from EoT scans for TTP analysis (c-index = 0.68 ± 0.09) using CoxNet (with SFS). The performance of Deauville Score (DS) for TTP was c-index = 0.66 ± 0.09 for n = 50 and 0.67 ± 03 for n = 31 cases when using EoT scans with no significant differences compared to the radiomics signature from either EoT scans or baseline + Delta features (p-value> 0.05). This work demonstrates the potential of Delta radiomics and the importance of using EoT scans to predict progression and TTP from PMBCL [18F]FDG PET-CT scans.

Diffusion models for medical image reconstruction

Abstract Better algorithms for medical image reconstruction can improve image quality and enable reductions in acquisition time and radiation dose. A prior understanding of the distribution of plausible images is key to realising these benefits. Recently, research into deep-learning image reconstruction has started to look into using unsupervised diffusion models, trained only on high-quality medical images (ie, without needing paired scanner measurement data), for modelling this prior understanding. Image reconstruction algorithms incorporating unsupervised diffusion models have already attained state-of-the-art accuracy for reconstruction tasks ranging from highly accelerated MRI to ultra-sparse-view CT and low-dose PET. Key advantages of diffusion model approach over previous deep learning approaches for reconstruction include state-of-the-art image distribution modelling, improved robustness to domain shift, and principled quantification of reconstruction uncertainty. If hallucination concerns can be alleviated, their key advantages and impressive performance could mean these algorithms are better suited to clinical use than previous deep-learning approaches. In this review, we provide an accessible introduction to image reconstruction and diffusion models, outline guidance for using diffusion-model-based reconstruction methodology, summarise modality-specific challenges, and identify key research themes. We conclude with a discussion of the opportunities and challenges of using diffusion models for medical image reconstruction.