PET-CT Research Articles

6504 Cerebellar Metastases from Papillary Thyroid Cancer; An Unusual Presentation

Abstract Disclosure: L.E. Chozet: None. A. Gilbert: None. M.A. Escobar Vasco: None. Background: Differentiated papillary thyroid cancer is known to have a very favorable prognosis. Brain metastases arising from papillary thyroid carcinoma are a very rare complication seen in approximately 1% of all cases of differentiated thyroid cancer with cerebellar metastases being even more uncommon. We present a case of a patient presenting with ataxia as the initial and only symptom of papillary thyroid carcinoma, found to have cerebellar metastases. Clinical Case: A 68-year-old man presented with ataxia for 1 week prior to arrival to hospital. CT head revealed hyperdense lesions in the right frontal lobe and left posterior cerebellar hemisphere. The patient underwent resection of left cerebellar mass with final pathology consistent with metastatic papillary thyroid carcinoma. Tumor cells were positive for TTF-1, thyroglobulin, CAM5.2, CK7, and PAX8, and negative for CK5/6, CK20, inhibin, and Napsin A. Ultrasound of the thyroid revealed multinodular goiter with dominant left thyroid lobe nodule 4 cm in size. PET CT showed left Thyroid mass with direct extension to adjacent lymph nodes, right anterior rib mass, left adrenal metastasis and right frontal lobe and left cerebellar metastasis. He received stereotactic radiosurgery with 5 out of 5 treatments completed. He subsequently underwent total thyroidectomy with left modified radical neck dissection, with pathology showing pT3bN1bM1. Next Generation Sequence positive for V600E, RADS1CR193, TERT PROMOTER -124C>T. After multidisciplinary team discussion, it was determined that the best course of action was to refer the patient to MD Anderson for evaluation, candidacy for prospective therapeutic clinical trials. Conclusion: This case demonstrates how differentiated papillary thyroid cancer, despite its favorable prognosis, can still prove to be a dangerous disease especially if undiagnosed for several years. This case also illustrates how papillary thyroid carcinoma can remain clinically silent for years and first present with atypical symptoms consistent with advanced metastases. Presentation: 6/2/2024

8282 A Diagnostically Challenging Case of Ectopic ACTH Secreting Pancreatic Neuroendocrine Tumor Presenting with Cushing’s Syndrome

Abstract Disclosure: O.A. Aluko: None. S. Patel: None. S.V. Silparshetty: None. T. Gallagher: None. Introduction: Ectopic ACTH mediated Cushing’s syndrome is an uncommon but treatable condition that poses time constrained diagnostic and therapeutic challenge due to severe morbidity as illustrated by our case below. Clinical case:A 65-year-old male was admitted with profound generalized weakness. He became restricted to wheelchair from being able to hike a trail at Yosemite national park 8 weeks prior. Recent history included hospitalization with uncontrolled diabetes and hypertension, new vertebral compression fractures, AKI, hypokalemia, proximal myopathy, anasarca, upper GI bleed and acute upper extremity DVT. Initial testing there revealed hypercortisolemia, elevated ACTH and a normal pituitary MRI. Further workup at our center revealed elevated 24hr urinary cortisol 2598 (n = 5 - 64 μg/24hr), random cortisol 55 (n= 4.2 -22.4 μg/dL) with elevated ACTH 194 (n= 7.2 - 63.3 pg/mL) consistent with ACTH dependent hypercortisolism. IPSS deferred due to AKI, underlying comorbidities and severe cervical stenosis with myelopathy. ACTH and cortisol remained elevated with an 8mg dexamethasone suppression test suggesting ectopic source ACTH. CT with contrast of chest, abdomen and pelvis showed 5mm right lower lobe lung nodule and bilateral adrenal nodularity. Bronchoscopic FNAC was negative for NET.Ketoconazole 400 mg twice daily was started pending localization of culprit lesion with improvement in 24 hr urinary cortisol to 554μg/24 hr however this was stopped within 4 weeks due to acute transaminasemia. Repeat imaging with Gallium-68 dotatate PET CT showed a 1.8 X 2.4 X 1.7 cm pancreatic mass. He underwent distal pancreatectomy with splenectomy. Pathology confirmed a 2.2cm well differentiated neuroendocrine tumor limited to the pancreas with immunohistochemistry strongly for ACTH and weakly for Gastrin. Postoperatively, patient was given hydrocortisone replacement. ACTH was 14.3 pg/mL and cortisol 6.2μg/dL a few weeks later. His diabetes, hypertension, hypokalemia, transaminasemia and proximal myopathy improved. Discussion:Ectopic ACTH mediated Cushing’s syndrome is responsible for about 5 - 20% of all Cushing’s syndrome cases. Pancreatic neuroendocrine tumor secreting Ectopic ACTH is rarer but can be aggressive. Clinical presentation can be confounding due to secretion of >1 neurohormone i.e ACTH and Gastrin in our patient. Gallium-DOTATATE PET/CT tracer has a very high sensitivity and specificity. Early use of this imaging may prevent comorbidity and mortality as surgical resection of ectopic ACTH secreting neuroendocrine tumor is first line therapy. Other diagnostic principles to consider are that severely elevated ACTH levels correlate only with a pituitary macroadenoma, IPSS is invasive and has relative contraindication in sick patients and Desmopressin stimulation test is not widely available. Presentation: 6/1/2024

7799 Nesidioblastosis Concurrent with Anatomically Confirmed Metastatic Gastric Cancer

Abstract Disclosure: Y. Cho: None. K. Jo: None. J. Han: None. S. Moon: None. E. Kim: None. Background: Nesidioblastosis is a rare condition that should be considered in cases of pancreatogenic hyperinsulinemic hypoglycemia without evidence of insulinoma on imaging. We present the first case of nesidioblastosis concomitant with anatomically confirmed metastatic gastric cancer of the pancreas. Case Report A 57-year-old male presented with recurrent episodes of loss of consciousness and hypoglycemia, with a glucose level of 26 mg/dl upon arrival at the emergency room. Despite a history of advanced gastric cancer and previous chemotherapy, the patient had not been diagnosed with diabetes and was not taking medications associated with hypoglycemia. Four months prior, he underwent total gastrectomy. The fasting plasma glucose levels was 38 mg/dl, accompanied by C-peptide levels of 6.10 ng/mL, insulin levels exceeding 1000 uIU/ml, and proinsulin levels at 8.8 pmol/L. The insulin antibody level was more than 100%, and the highest cortisol level reached 15.60 ug/dL during the rapid ACTH stimulation test. The patient's postprandial 2-hour glucose level reached 233 mg/dl during the 75g glucose tolerance test. Imaging studies, including whole-body PET CT and abdominal CT, showed no evidence of suspected metastatic lesions, and the pancreas appeared normal on MRI. Endoscopic ultrasound could not be performed due to anatomical changes following the surgery. A selective arterial calcium stimulation test demonstrated a substantial over twofold increase in insulin concentrations in the gastroduodenal artery, splenic artery, and superior mesenteric artery. The patient received methylprednisolone 125 mg once daily but insulin levels remained elevated, exceeding 1000 uIU/ml, requiring continuous dextrose infusion. Octreotide therapy was initiated, resulting in an improvement in insulin levels to 589 uIU/ml, although discontinuation of dextrose fluid remained unfeasible. After consultation with the surgeon, a open subtotal pancreatectomy was performed, allowing discontinuation of dextrose on the second post-surgery day, with improved glucose and insulin levels. Histological examination showed three clusters of atypical cells with perineural infiltration. Immunostaining indicated negative synaptophysin and positive CK20, suggesting possible gastric cancer metastasis, consistent with prior gastrectomy findings. Moreover, an increased number of variable-sized Langerhans islets exhibited positive insulin and glucagon immunostaining within the islets, indicative of nesidioblastosis. Conclusion: Nesidioblastosis should be considered in cases of unexplained post-surgery hypoglycemia following metastatic gastric cancer treatment. Furthermore, given the potential link with metastatic gastric cancer, which may elude detection via imaging alone, aggressive surgical intervention should be contemplated as a nesidioblastosis treatment strategy. Presentation: 6/3/2024

8477 Medullary Thyroid Carcinoma Masquerading as a Cold Nodule in a Patient With Graves' Disease

Abstract Disclosure: T. Umashree: None. K.J. Farooqui: None. A. Mithal: None. Background: Only a handful of cases of MTC have been reported in the setting of Graves’ disease. Clinical Case: A 38 year old lady presented with symptoms of significant weight loss and palpitations for past six months. Thyromegaly was present, with non tender left lobe enlargement of about 3x3 cm. On further probing it was found that her father had been operated for thyroid cancer 22 years ago, the type of which patient was not aware of. TFTs reflected a thyroxtoxic state (TSH -<0.01mIU/mL [0.34-5.6] FT4 - 3.38 ng/dL [0.58-1.64] FT3 - 8.46 pg/mL [2.6-4.2]) and TRAb was positive (8.74 IU/L [<1.22]). USG neck revealed a hypoechoic lesion of 18x18x13 mm in left lobe thyroid with internal calcifications, with multiple bilateral non-significant lymph nodes. Technetium99 (Tc99) scan showed an enlarged left lobe, with diffuse thyroid uptake at 20 minutes of 4%, and a well-defined photopenic area in left lobe, corresponding to the nodule seen on USG. FNAC of the nodule was suggestive of Hürthle cell neoplasm and patient underwent left hemithyroidectomy. Surprisingly, HPE was consistent with medullary thyroid cancer. Serum calcitonin was raised at 148 pg/mL (N<4.8 for females) and plasma free metanephrines and normetanephrine were normal. F-18 DOPA PET CT showed uptake in residual right lobe of thyroid only, no other abnormal uptake was seen. She underwent completion thyroidectomy with central compartment clearance and is now under regular follow up. Genetic analysis showed RET gene mutation of Cys634Ser, which is heterozygous for MTC. Cold nodules in Graves’ disease should be viewed with suspicion, and while PTC and FTC have been reported more commonly, MTC is extremely rare in this setting. A calcitonin washout of the FNAC may have prevented this patient from undergoing two surgeries. Moreover, Hürthle cell change can also occur in C-cells of the thyroid, not just the follicular cells. Lastly, given the history of thyroid cancer in her father, index of suspicion of MTC should have been higher in this patient. Conclusion: Cold nodules in Graves’ Disease may be malignant, and should always be examined by FNAC. Though MTC is rare, it is not unknown in Grave’s disease. Presentation: 6/3/2024

8104 Rare Case Of Ectopic Cushing’s Syndrome Secondary To Metastatic Parotid Pleomorphic Adenocarcinoma

Abstract Disclosure: B.S. Neutel: None. P. Manroa: None. Background: Pleomorphic adenocarcinoma of the parotid gland is a rare malignancy and ectopic ACTH secretion from these tumors is very rarely described. We report a case of ectopic Cushing’s syndrome (CS) in such a patient and describe the clinical course. Clinical Case: A 69-year-old female with left parotid pleomorphic adenocarcinoma status post surgery and adjuvant radiotherapy presented to her local hospital approximately 7 months after initial treatment with proximal muscle weakness and near-syncope. Workup revealed profound hypokalemia at 1.6 mmol/L (n 3.5-5.3 mmol/L) along with new-onset hypertension (BP 175/110 mm Hg) and hyperglycemia with a HbA1c 6.5 % (n <5.7%), as well as metabolic alkalosis with a bicarbonate level of >40 mmol/L (n 22-32 mmol/L). A CT scan showed multiple liver metastases and a biopsy confirmed metastatic parotid pleomorphic adenocarcinoma. She was then transferred to our comprehensive cancer center for further management. She reported muscle weakness, easy bruising, and facial edema. She denied acne, hirsutism, or abdominal striae. Endocrine workup revealed a random cortisol of 56 mcg/dL (n 3-18 mcg/dL) and ACTH of 378 pg/mL (n 7.2-63.3 pg/mL). Her AM cortisol level remained unsuppressed at 79.2 and 59.4 mcg/dL (n< 1.8 mcg/dL) after 1 mg and 8 mg overnight dexamethasone suppression tests respectively. Late-night salivary cortisol was 7.9 mcg/dL (n <0.112 mcg/dL). An MRI of the sella was negative for any pituitary lesions. After stabilizing her clinical condition and correcting electrolyte abnormalities, she was started on chemotherapy with paclitaxel and carboplatin by the oncologist. Based on clinical suspicion of ectopic CS, ketoconazole was started and titrated upwards with rapid improvement of blood pressure, hypokalemia, and hyperglycemia. She was discharged home and antihypertensives were tapered off. ACTH staining on the liver biopsy was unable to be performed due to paucity of the specimen. A Ga-68-DOTATATE PET CT revealed increased radiotracer uptake in the liver lesion suggestive of SSTR 2 receptor positivity. Despite initial clinical improvement, her disease progressed with widespread liver, lymph node, and osseous metastases within 3 months necessitating escalating doses of ketoconazole, spironolactone, and potassium supplementation. The patient elected to pursue hospice care due to intolerance to chemotherapy and passed away shortly afterward. Conclusion: Although ectopic CS caused by parotid pleomorphic adenocarcinoma is rare, prompt recognition and treatment is necessary because ectopic ACTH production is associated with poor prognosis in these patients. Presentation: 6/3/2024

Detection and Response Evaluation of Extramedullary and Medullary Blast Crisis in Chronic Myeloid Leukemia on 18F-FDG PET/CT.

FDG PET/CT imaging is usually not routinely undertaken in patients of chronic myeloid leukemia (CML). We present a case of CML on tyrosine kinase inhibitor treatment with disease control indicated by BCR-ABL1 quantitative reverse transcription-polymerase chain reaction, who underwent PET/CT for evaluation of recent onset vision deterioration with subretinal exudates on ophthalmological examination. PET CT detected FDG-avid sinonasal thickening and bilateral marrow lesions. These lesions on histopathological sampling, examination revealed extramedullary and intramedullary CML blast crisis. Patient was then treated with steroids and change of tyrosine kinase inhibitor for the CML blast crisis. FDG PET/CT done subsequently was able to demonstrate morphological and metabolic response in the lesions.

Prise en charge des cancers bronchiques à petites cellules de stade localisé i actualisation

Limited-stage small cell lung cancer (LS-SCLC) represents 15-20 % of all lung cancers, and because of its rapid tumor kinetics, less than a third of SCLC are discovered at limited stage. The different steps and modalities of its management are well defined and codified. They involve a comprehensive staging assessment using CT scans of the chest, abdomen, and pelvis, PET-CT scans, and ideally brain imaging using MRI to avoid missing a more extensive stage of the disease, which would significantly alter the treatment strategy. The treatment consists of a combination of chemotherapy with platinum/ etoposide and radiotherapy, possibly delivered in a hyperfractionated schedule with two daily sessions. SCLC is particularly both chemosensitive and radiosensitive, so that the initial evaluation shows frequently a complete response, and prophylactic cranial irradiation (PCI) is then recommended. Relapses are unfortunately frequent, less responsive to second line treatments, and therapeutic options are limited. No targeted agents or immunotherapy have robustly demonstrated efficacy in the treatment of LSSCLC. Even if hyperfractionated accelerated radiotherapy (HFART) at the dose of 45Gy in 30 fractions has given the best results, most clinicians use once-daily chemoradiation regimen (60-70Gy). Studies have evaluated dose escalation either with HFRAT or with conventional fractionation (66 to 70Gy). Several trials are currently investigating the addition of immunotherapy to chemoradiation, hippocampus sparing PCI or the omission of PCI. In rare cases of very early-stage SCLC, surgery or stereotactic radiotherapy may be envisaged.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

PET/CT Response Assessment in Pediatric Hodgkin Lymphoma: Does Deauville Score 3 Reflect Negativity?

FDG PET is required for the staging and response evaluation of pediatric Hodgkin lymphoma. This study aimed to evaluate the outcomes of pediatric patients with Hodgkin's lymphoma based on interim PET CT assessments of early response following second-cycle chemotherapy using the Deauville score (DS). It also determines whether DS-3 is providing an adequate or inadequate response. We conducted a retrospective cohort study including 504 pediatric patients with classic Hodgkin lymphoma who were treated with chemotherapy based on the Euro-Net protocol at the Children Cancer Hospital Egypt from March 2019 till the end of October 2022. Patients with adequate response DS 1/2 and DS 3 showed nearly the same 3-year event-free survival (EFS) of 91.9% and 91.5%, respectively, compared with those patients with inadequate response DS 4/5, who showed an EFS of 80.4% ( P =0.001). Patients with a DS 3 at interim PET evaluation were considered negative as DS 1/2. Patients of DS 3 group who did not receive radiotherapy had a much worse 3-year EFS by the existence of positive B symptoms, an ESR>30, or an advanced stage. Radiation therapy did not improve the 3-year EFS in patients with an inadequate response (DS4/5) and poor prognostic characteristics. They still need more advanced treatment. DS 1/2 and DS 3 had about the same 3-year EFS, which is better than the 3-year EFS of patients with DS 4/5. Therefore, we can classify DS 3 as having negative FDG PET CT uptake.

Fast vs slow rubidium-82 infusion profiles and test-retest precision of myocardial perfusion using contemporary 3D cardiac analog PET-CT imaging.

BackgroundOn legacy 2D PET systems utilizing a 50 mL/min Rb-82 profile, test-retest precision of quantitative perfusion is ∼10%. It is unclear whether Rb-82 infusion rate significantly impacts quantitative perfusion and/or image quality on modern analog 3D PET-CT systems. We aimed to determine whether the Rb-82 infusion profile significantly impacts test-retest precision of quantitative perfusion, perfusion metrics, and/or image quality on a modern analog 3D PET-CT scanner. MethodsNinety-eight volunteers from 3 distinct groups: healthy volunteers (Normals), patients with risk factors and/or coronary disease (Clinicals) and patients with prior transmural myocardial infarctions (Infarcts), underwent cardiac stress testing on an analog 3D PET-CT. Participants received 3 consecutive resting scans and 2 consecutive stress scans, minutes apart, with two randomly assigned Rb-82 infusion profiles: 50 mL/min (fast [F]) and 20 mL/min (slow [S]). Perfusion metrics (resting (rMBF) and stress myocardial blood flow (sMBF)) were calculated using HeartSee software. Coefficients of variance (COV), repeatability (RC), MBF and image quality metrics were compared. ResultsrMBF correlated well between F and S profiles, with intraclass correlation coefficients (ICC) ranging 0.91-0.93. sMBF was highly correlated between F and S profiles (ICC=0.97). Fast and slow profiles were associated with similar same-day test-retest precision (COV 11.5% vs. 11.3% (p=0.77); RC 21.5% vs. 22.6%, for F-F vs S-S). There were no clinically significant differences in MBF values between F and S profiles. Image quality metrics were similar between the 2 profiles. ConclusionsThere are no clinically significant differences in precision, perfusion metrics or image quality between Rb-82 fast and slow infusions using a contemporary analog 3D PET-CT.

Standardization of scan protocols for RT CT simulator from different vendors using quantitative image quality technique.

To investigate the feasibility of standardizing RT simulation CT scanner protocols between vendors using target-based image quality (IQ) metrics. A systematic assessment process in phantom was developed to standardize clinical scan protocols for scanners from different vendors following these steps: (a) images were acquired by varying CTDIvol and using an iterative reconstruction (IR) method (IR: iDose and model-based iterative reconstruction [IMR] of CTp-Philips Big Bore scanner, SAFIRE of CTs-Siemens biograph PETCT scanner), (b) CT exams were classified into body and brain protocols, (c) the rescaled noise power spectrum (NPS) was calculated, (d) quantified the IQ change due to varied CTDIvol and IR, and (e) matched the IR strength level. IQ metrics included noise and texture from NPS, contrast, and contrast-to-noise ratio (CNR), low contrast detectability (d'). Area under curve (AUC) of the receiver operation characteristic curve of d' was calculated and compared. The level of change in the IQ ratio was significant (>0.6) when using IMR. The IQ ratio change was relatively low to moderate when using either iDose in CTp (0.1-0.5) or SAFIRE in CTs (0.1-0.6). SAFIRE-2 in CTs showed a closer match to the reference body protocol when compared to iDose-3 in CTp. In the brain protocol, iDose-3 in CTp could be matched to the low to moderate level of SAFIRE in CTs. The AUC of d' was highest when using IMR in CTp with lower CTDIvol, and SAFIRE in CTs performed better than iDose in CTp CONCLUSION: It is possible to use target-based IQ metrics to evaluate the performance of the system and operations across various scanners in a phantom. This can serve as an initial reference to convert clinical scanned protocols from one CT simulation scanner to another.

A machine learning approach in a monocentric cohort for predicting primary refractory disease in Diffuse Large B-cell lymphoma patients.

Primary refractory disease affects 30-40% of patients diagnosed with DLBCL and is a significant challenge in disease management due to its poor prognosis. Predicting refractory status could greatly inform treatment strategies, enabling early intervention. Various options are now available based on patient and disease characteristics. Supervised machine-learning techniques, which can predict outcomes in a medical context, appear highly suitable for this purpose. Retrospective monocentric cohort study. Adult patients with a first diagnosis of DLBCL admitted to the hematology unit from 2017 to 2022. We evaluated in our Center five supervised machine-learning (ML) models as a tool for the prediction of primary refractory DLBCL. One hundred and thirty patients with Diffuse Large B-cell lymphoma (DLBCL) were included in this study between January 2017 and December 2022. The variables used for analysis included demographic characteristics, clinical condition, disease characteristics, first-line therapy and PET-CT scan realization after 2 cycles of treatment. We compared five supervised ML models: support vector machine (SVM), Random Forest Classifier (RFC), Logistic Regression (LR), Naïve Bayes (NB) Categorical classifier and eXtreme Gradient Boost (XGboost), to predict primary refractory disease. The performance of these models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, false positive rate, sensitivity, and F1-score to identify the best model. After a median follow-up of 19.5 months, the overall survival rate was 60% in the cohort. The Overall Survival at 3 years was 58.5% (95%CI, 51-68.5) and the 3-years Progression Free Survival was 63% (95%CI, 54-71) using Kaplan-Meier method. Of the 124 patients who received a first line treatment, primary refractory disease occurred in 42 patients (33.8%) and 2 patients (1.6%) experienced relapse within 6 months. The univariate analysis on refractory disease status shows age (p = 0.009), Ann Arbor stage (p = 0.013), CMV infection (p = 0.012), comorbidity (p = 0.019), IPI score (p<0.001), first line of treatment (p<0.001), EBV infection (p = 0.008) and socio-economics status (p = 0.02) as influencing factors. The NB Categorical classifier emerged as the top-performing model, boasting a ROC-AUC of 0.81 (95% CI, 0.64-0.96), an accuracy of 83%, a F1-score of 0.82, and a low false positive rate at 10% on the validation set. The eXtreme Gradient Boost (XGboost) model and the Random Forest Classifier (RFC) followed with a ROC-AUC of 0.74 (95%CI, 0.52-0.93) and 0.67 (95%CI, 0.46-0.88) respectively, an accuracy of 78% and 72% respectively, a F1-score of 0.75 and 0.67 respectively, and a false positive rate of 10% for both. The other two models performed worse with ROC-AUC of 0.65 (95%CI, 0.40-0.87) and 0.45 (95%CI, 0.29-0.64) for SVM and LR respectively, an accuracy of 67% and 50% respectively, a f1-score of 0.64 and 0.43 respectively, and a false positive rate of 28% and 37% respectively. Machine learning algorithms, particularly the NB Categorical classifier, have the potential to improve the prediction of primary refractory disease in DLBCL patients, thereby providing a novel decision-making tool for managing this condition. To validate these results on a broader scale, multicenter studies are needed to confirm the results in larger cohorts.

Case Series Analysis of Diagnosis and Treatment of Gastrointestinal Metastasis in Lung Cancer Patients.

This study was designed to investigate the clinical, pathological, endoscopic, and imaging characteristics of gastrointestinal metastasis in patients with lung cancer. The clinical data of 20 patients with primary lung cancer with gastrointestinal metastasis. This study included sixteen men and four women, ranging in age from 31 to 75 years. The time interval from the diagnosis of lung cancer to the detection of gastrointestinal metastasis ranged from 13 to 142 months. The most common sites of metastasis were the small intestine (eight cases), colon (four cases), and upper gastrointestinal tract (eight cases). The major symptoms included obstruction, perforation, abdominal pain, abdominal distension, anorexia, and anemia. The predominant pathological type was poorly differentiated adenocarcinoma (seventeen cases). A single ulcer was mostly seen on endoscopy, and some cases showed a slight depression of the intestinal wall. The CT and PET-CT scan revealed bowel wall thickening, intraluminal polypoid masses, and intestinal perforation. Gastrointestinal metastasis of lung cancer is mainly observed in the small intestine, colon, and stomach, and is often detected when severe complications such as gastrointestinal obstruction and perforation occurred. Regular evaluation of gastrointestinal conditions during lung cancer diagnosis and treatment is recommended to improve the diagnostic accuracy and prevent misdiagnosis.

Using Deauville Scoring to Guide Consolidative Radiotherapy in Diffuse Large B-Cell Lymphoma

Background: The most common aggressive lymphoma in adults is diffuse large B-cell lymphoma (DLBCL). Consolidative radiotherapy (RT) is often administered to DLBCL patients but guidelines remain unclear, which could lead to unnecessary RT. We aimed to evaluate the value of end-of-treatment PET-CT scans, interpreted using the Deauville score (DV), to guide the utilization of consolidative RT, which may help spare low-risk DLBCL patients from unnecessary RT. Methods: We included all DLBCL patients diagnosed between 2010 and 2022 at the National Cancer Centre Singapore with DV measured at the end of the first-line chemoimmunotherapy. The outcome measure was time-to-progression (TTP). The predictive value of DV for RT was assessed based on the interaction effect between the receipt of RT and DV in Cox regression models. Results: The data of 349 patients were analyzed. The median follow-up time was 38.1 months (interquartile range 34.0–42.3 months). RT was associated with a significant improvement in TTP amongst the DV4-5 patients (HR 0.33; 95%CI 0.13–0.88; p = 0.027) but not the DV1-3 patients (HR 0.85; 95%CI 0.40–1.81; p = 0.671) (interaction’s p = 0.133). Multivariable analysis reported that RT was again significantly associated with improved TTP among the DV4-5 patients (adjusted HR 0.29; 95%CI 0.10–0.80; p = 0.017) but not the DV1-3 group (HR 0.86; 95%CI 0.40–1.86; p = 0.707) (interaction’s p = 0.087). Conclusion: Our results suggests that DLBCL patients with end-of-treatment PET-CT DV1-3 may not need consolidative RT. Longer follow-up and prospective randomized trials are still necessary to investigate long-term outcomes.

Molecular imaging supports the development of multispecific cancer antibodies.

Multispecific antibodies are engineered antibody derivatives that can bind to two or more distinct epitopes or antigens. Unlike mixtures of monospecific antibodies, the binding properties of multispecific antibodies enable two specific molecules to be physically linked, a characteristic with important applications in cancer therapy. The field of multispecific antibodies is highly dynamic and expanding rapidly; to date, 15 multispecific antibodies have been approved for clinical use, of which 11 were approved for oncological indications, and more than 100 new antibodies are currently in clinical development. Nevertheless, substantial challenges limit the applications of multispecific antibodies in cancer therapy, particularly inefficient targeting of solid tumours and substantial adverse effects. Both PET and single photon emission CT imaging can reveal the biodistribution and complex pharmacology of radiolabelled multispecific antibodies. This Review summarizes the insights obtained from preclinical and clinical molecular imaging studies of multispecific antibodies, focusing on their structural properties, such as molecular weight, shape, target specificity, affinity and avidity. The opportunities associated with use of molecular imaging studies to support the clinical development of multispecific antibody therapies are also highlighted.

Non-Hodgkin lymphoma of vocal cord causing “pseudo-palsy”

Non epithelial lesion of vocal cord is identified as vocal cord palsy/ impaired movement without obvious mucosal ulceration. There are several nonepithelial lesions of vocal cord. Lymphoma, plasmacytoma, liposarcoma, lipoma, myxofibrolipoma, hemangioma, rhabdomyosarcoma are amongst the important differential diagnosis. These tumors occur in the submucosal layer of larynx and hence the mucosa appears intact at endoscopy. The lesions are typical non circumscribed, and invasion of adjoining structures helps in differentiating benign from malignant lesions. Presented here is a case of vocal cord (pseudo) palsy who underwent an 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET CT) scan which revealed a hypermetabolic trans glottic soft tissue lesion. Histology confirmed the diagnosis of Extra-nodal High Grade Diffuse Large B Cell Non-Hodgkin lymphoma (DLBCL NHL).

Neurologic Clinical, Electrophysiologic, and Pathologic Characteristics of Primary vs Secondary Neurolymphomatosis.

Neurolymphomatosis (NL) is characterized by lymphomatous infiltration of the peripheral nervous system presenting as the initial manifestation of a lymphoma (primary NL [PNL]) or in relapse of a known lymphoma (secondary NL [SNL]). This report details and compares the neurologic clinicopathologic characteristics of these 2 groups. This retrospective study was performed on patients diagnosed with pathologically confirmed NL in nerve between January 1, 1992, and June 31, 2020. Patient clinical characteristics, neurologic examination, imaging studies, EMG, and nerve biopsy data were collected, analyzed, and compared between PNL and SNL. A total of 58 patients were identified (34 PNL and 24 SNL). Time from neurologic symptom onset to diagnosis was longer in PNL at 18.5 months compared with 5.5 months in SNL (p = 0.01). Neurologic symptoms were similar in both patient groups and included primarily sensory loss (98%), severe pain (76%), and asymmetric weakness (76%). A wide spectrum of EMG-confirmed different neuropathy patterns were observed, but patients with SNL had increased numbers of mononeuropathies (n = 8) compared with PNL (n = 1, p = 0.01). MRI studies detected NL more frequently (86%) compared with fluorodeoxyglucose (FDG)-PET CT imaging studies (60%) (p = 0.007). Nerve biopsies revealed B-cell lymphoma (PNL n = 32, SNL n = 22), followed by T-cell lymphoma (PNL n = 2, SNL n = 2), with increased demyelination in both groups and increased axonal degeneration (p = 0.01) and multifocal myelinated fiber loss (p = 0.04) significant in SNL vs PNL. Identifying SNL resulted in patient treatment modifications but a worse prognosis compared with PNL (p = 0.025). While PNL and SNL are both primarily painful and asymmetric neuropathies with axonal and demyelinating features on EMG and nerve biopsy, SNL presents somewhat differently than PNL with fulminant, asymmetric often mononeuropathies better detected on MRI than FDG-PET/CT. The focal pattern of SNL is likely a result of residual cancer cells that evaded initial chemotherapy, which does not cross the blood-nerve barrier, and these cells can later recur and result in fulminant disease. Although still resulting in a poorer prognosis, identifying SNL is important because this changed treatment and management in every SNL case.

Impact of different parametric Patlak imaging approaches and comparison with a 2-tissue compartment pharmacokinetic model with a long axial field-of-view (LAFOV) PET/CT in oncological patients.

The recently introduced Long-Axial-Field-of-View (LAFOV) PET-CT scanners allow for the first-time whole-body dynamic- and parametric imaging. Primary aim of this study was the comparison of direct and indirect Patlak imaging as well as the comparison of different time frames for Patlak calculation with the LAFOV PET-CT in oncological patients. Secondary aims of the study were lesion detectability and comparison of Patlak analysis with a two-tissue-compartment model (2TCM). 50 oncological patients with 346 tumor lesions were enrolled in the study. All patients underwent [18F]FDG PET/CT (skull to upper thigh). Here, the Image-Derived-Input-Function) (IDIF) from the descending aorta was used as the exclusive input function. Four sets of images have been reviewed visually and evaluated quantitatively using the target-to-background (TBR) and contrast-to-noise ratio (CNR): short-time (30min)-direct (STD) Patlak Ki, short-time (30min)-indirect (STI) Patlak Ki, long-time (59.25min)-indirect (LTI) Patlak Ki, and 50-60min SUV (sumSUV). VOI-based 2TCM was used for the evaluation of tumor lesions and normal tissues and compared with the results of Patlak model. No significant differences were observed between the four approaches regarding the number of tumor lesions. However, we found three discordant results: a true positive liver lesion in all Patlak Ki images, a false positive liver lesion delineated only in LTI Ki which was a hemangioma according to MRI and a true negative example in a patient with an atelectasis next to a lung tumor. STD, STI and LTI Ki images had superior TBR in comparison with sumSUV images (2.9-, 3.3- and 4.3-fold higher respectively). TBR of LTI Ki were significantly higher than STD Ki. VOI-based k3 showed a 21-fold higher TBR than sumSUV. Parameters of different models vary in their differential capability between tumor lesions and normal tissue like Patlak Ki which was better in normal lung and 2TCM k3 which was better in normal liver. 2TCM Ki revealed the highest correlation (r = 0.95) with the LTI Patlak Ki in tumor lesions group and demonstrated the highest correlation with the STD Patlak Ki in all tissues group and normal tissues group (r = 0.93 and r = 0.74 respectively). Dynamic [18F]-FDG with the new LAFOV PET/CT scanner produces Patlak Ki images with better lesion contrast than SUV images, but does not increase the lesion detection rate. The time window used for Patlak imaging plays a more important role than the direct or indirect method. A combination of different models, like Patlak and 2TCM may be helpful in parametric imaging to obtain the best TBR in the whole body in future.

[89Zr]Zr-girentuximab for PET–CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial

With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect clear-cell renal cell carcinoma in patients with renal masses remain an unmet need. 89Zr-labelled monoclonal antibody ([89Zr]Zr-girentuximab) has high affinity for carbonic anhydrase 9, a tumour antigen highly expressed in clear-cell renal cell carcinoma. We aimed to evaluate [89Zr]Zr-girentuximab PET-CT imaging for detection and characterisation of clear-cell renal cell carcinoma. ZIRCON was a prospective, open-label, multicentre, phase 3 trial conducted at 36 research hospitals and practices across nine countries (the USA, Australia, Canada, the UK, Türkiye, Belgium, the Netherlands, Spain, and France). Patients aged 18 years or older with an indeterminate renal mass 7 cm or smaller (cT1) suspicious for clear-cell renal cell carcinoma and scheduled for nephrectomy received a single dose of [89Zr]Zr-girentuximab (37 MBq ±10%; 10 mg girentuximab) intravenously followed by abdominal PET-CT imaging 5 days (±2 days) later. Surgery was performed no later than 90 days after administration of [89Zr]Zr-girentuximab. Blinded central review, conducted by three independent readers, determined the histology from surgical samples. The coprimary endpoints, determined for each individual reader, were the sensitivity and specificity of [89Zr]Zr-girentuximab PET-CT imaging to detect clear-cell renal cell carcinoma, with histopathological confirmation as standard of truth. Analyses were on the full analysis set of patients, defined as patients who had evaluable PET-CT imaging and a confirmed histopathological diagnosis. The trial is registered with ClinicalTrials.gov, NCT03849118, and EUDRA Clinical Trials Register, 2018-002773-21, and is closed to enrolment. Between Aug 14, 2019, and July 8, 2022, 371 patients were screened for eligibility, 332 of whom were enrolled. 300 patients received [89Zr]Zr-girentuximab (214 [71%] male and 86 [29%] female). 284 (95%) evaluable patients were included in the primary analysis. The mean sensitivity was 85·5% (95% CI 81·5-89·6) and mean specificity was 87·0% (81·0-93·1). No safety signals were observed. Most adverse events were not or were unlikely to be related to [89Zr]Zr-girentuximab, with most (193 [74%] of 261 events) occurring during or after surgery. The most common grade 3 or worse adverse events were post-procedural haemorrhage (in six [2%] of 261 patients), urinary retention (three [1%]), and hypertension (three [1%]). In 25 (8%) of 300 patients, 52 serious adverse events were reported, of which 51 (98%) occurred after surgery. There were no treatment-related deaths. Our results suggest that [89Zr]Zr-girentuximab PET-CT has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma, which has the potential to be practice changing. Telix Pharmaceuticals.

EP362 - Small Cell Ca of the Gall Bladder: A rare tumour of the gall bladder

Abstract Small cell carcinoma (SCC) of the gallbladder is an extremely rare tumour. Despite aggressive and varied treatments, its prognosis is poor. A 53/F presented with complaints of pain in abdomen and fever since 3 days. Patient was vitally stable and tenderness present over the epigastric, Right hypochondrium and Right lumbar region. Except leucocytosis, all labs were WNL. CECT Abdomen pelvis was suggestive of suspicious Gall bladder perforation with necrotic lymph nodes in the peri-pancreatic region. The patient was taken for exploratory laparotomy and a perforated gall bladder was seen intra op and cholecystectomy was performed. Histopathology findings were suggestive of small cell carcinoma - gall bladder and IHC markers (Synaptophysin, CD56, Ki67, EMA, CK19) sent for confirmatory findings were raised. Post op PET CT shows periportal, paracaval and aortocaval metastatic lymph nodes. Chemotherapy regimen (cisplatin + itoposide) was started post op and patient is under follow up. The incidence of SCC of the GB is approximately 0.5% of all GB cancers. Among NETs of the gastrointestinal tract, SCC of the GB compromises 0.2%. Less than 100 cases of this tumour have been documented in the English literature. Surgery is the mainstay of GB cancer treatment. Due to poor prognosis of SCC of the GB, even when curative surgery is possible, additional treatment methods such as chemoradiation should be considered.

Prognostic nomogram combining 18F-FDG PET/CT radiomics and clinical data for stage III NSCLC survival prediction

The aim of this study was to establish and validate the precision of a novel radiomics approach that integrates 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scan data with clinical information to improve the prognostication of survival rates in patients diagnosed with stage III Non-Small Cell Lung Cancer (NSCLC) who are not candidates for surgery. We evaluated pretreatment 18F-FDG PET-CT scans from 156 individuals diagnosed with stage III inoperable NSCLC at Shandong Cancer Hospital. These individuals were divided into two groups: a training set comprising 110 patients and an internal validation set consisting of 46 patients. By employing random forest classifier and cox proportional hazards model , we identified and utilized relevant features to create predictive models and a nomogram. The effectiveness of these models was assessed through the use of the receiver operating characteristics(ROC) curves, Kaplan–Meier (KM) curves, and the application of the nomogram. Our findings showed that the combined model, which integrates both clinical and radiomic data, outperformed those based solely on clinical or radiomic features in predicting 3-year overall survival(OS). Furthermore, calibration plots revealed a high level of agreement between predicted and actual survival times. The research successfully established a predictive radiomics model that integrates 18F-FDG PET/CT imaging with clinical indicators to enhance survival predictions for patients with stage III inoperable NSCLC.