Post-therapy Scan Research Articles

6918 A Unique Case of Oncocytic Thyroid Cancer with an NBN Gene Pathogenic Variant

Abstract Disclosure: A. Grover: None. S. Jhawar: None. S. Shekhar: None. S.A. Avadhanula: None. G. Al-Naqeeb: None. G. Thota: None. P. Veeraraghavan: None. C. Cochran: None. M.Y. Kao-Hsieh: None. A. Gharib: None. F.E. Escorcia: None. J. Del Rivero: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Oncocytic thyroid carcinoma (OTC), previously known as “Hürthle cell” carcinoma, makes up less than 5% of all thyroid cancers. OTCs are often aggressive with a high risk of metastasis, and a poorer prognosis compared to other forms of differentiated thyroid carcinoma (DTC). Molecular drivers of OTC include pathogenic variants (PVs) in NRAS, DAXX, CDKN1A, the mitochondrial genome and chromosomal alterations. PVs in the NBN gene in OTC have not been previously reported. Case: A 53-year-old male was noted to have a thyroid nodule on a routine physical examination. Patient denied any hyper/hypothyroid or compressive symptoms, and family history was unremarkable. Cytopathologic analysis of the fine needle aspiration biopsy of the nodule was consistent with a thyroid follicular neoplasm (Bethesda IV). A total thyroidectomy with central compartment neck dissection was performed. Histopathologic examination demonstrated a 7 cm x 4 cm x 4 cm OTC with capsular and lymphovascular invasion, but without extra-thyroidal extension or lymph node metastasis (pT3aN0Mx). Subsequently, adjuvant radioiodine (RAI) I131 therapy with 165 mCi was administered and post-therapy scan revealed neck uptake. One-year post-therapy RAI diagnostic scan was negative. Three years following the initial thyroid surgery, elevated serum thyroglobulin (Tg) levels were noted. A computed tomogram of the chest revealed multiple bilateral lung nodules. Further imaging ruled out involvement of other distant sites. A diagnostic lower lung wedge resection demonstrated metastatic OTC. The tumor stained positive for CK7, PAX8, TG, TTF-1 and negative for CK20 on immunohistochemistry. Next-generation sequencing of the tumor tissue (Oncomine Comprehensive Assay v3) revealed a PV in the NBN gene (c.2166_2167delGCinsAT; p.Trp722Ter). A year later, the serum Tg levels continued to rise, and the lung nodules had increased in size. Due to disease progression, lenvatinib was initiated. A [F18]-fluorodeoxyglucose positron emission tomography performed one year later demonstrated persistent pulmonary tumor burden with new osseous metastasis in the right scapula, left acetabulum, and the sternum. Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain. Conclusion: The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course. Identification of this novel PV therefore adds to the current knowledge of the molecular landscape of OTC. Presentation: 6/3/2024

Gold nanoshells for prostate cancer treatment: evidence for deposition in abdominal organs.

Gold-silica nanoshell therapy [AuroShells with subsequent focal laser therapy (AuroLase)] is an emerging targeted treatment modality for prostate cancer. We reviewed pre- and post-treatment unenhanced CT imaging to assess for retained gold-silica nanoshells in the abdomen and pelvis. This single-institution retrospective study identified patients in the AuroLase pilot who underwent pre- and post-treatment unenhanced abdominopelvic CT. The attenuation, before and after gold-silica nanoshell administration, of the liver, spleen, pancreas, kidneys, prostate, blood pool, paraspinal musculature, and abnormal lymph nodes were manually measured by two readers. After inter-reader agreement was calculated using intraclass correlation (ICC), a permutation test was used to assess pre- and post-therapy attenuation differences. Four patients met the inclusion criteria. Mean age was 72.3 ± 5.9years. Median time interval between pre-treatment CT and treatment, and between treatment and post-treatment CT, was 232days and 236.5days, respectively. The two readers' attenuation measurements had very high agreement (ICC = 0.99, p < 0.001). The highest differences in organ attenuation between pre- and post-therapy scans were seen in all four patients in the liver and spleen (liver increased by an average of 28.9 HU, p = 0.010; spleen increased by an average of 63.7 HU, p = 0.012). A single measured lymph node increased by an average of 58.9 HU. In the remainder of the measured sites, the change in attenuation from pre- to post-therapy scans ranged from -0.1 to 3.8 HU (p > 0.05). Increased attenuation of liver and spleen at CT can be an expected finding in patients who have received gold-silica nanoshell therapy.

Real life experience of compassionate use of 177Lu-PSMA-1 for metastatic castration-resistant prostate cancer patients in Leon Berard Cancer Centre

PurposeWe present a retrospective feedback of PSMA-targeted radioligands therapy (PRLT) using onsite radiolabeled 177Lu-PSMA-1 to treat metastatic castration-resistant prostate cancer patients (mCRPC) progressing after conventional treatments. MethodsOnsite radiolabeling of the PSMA-1 with 177Lu was authorized by the National Agency for the Safety of Medicines and Health Products (ANSM) after IMPD (Investigational Medicinal Product Dossier) approval allowing to treat patients before 177Lu-PSMA-617 national agreement. Patients were screened on 68Ga-PSMA and 18F-FDG PET-CTs and would be included in case of significant PSMA uptake in the majority of known lesions without mismatch between FDG and PSMA especially in liver metastases, following the THERAP trial procedure. Treatments would consist in 6 injections of 7.4GBq of 177Lu-PSMA-1 every 6 weeks following the VISION phase III trial. A clinical, biological and radiological follow-up during the treatment allowed the detection of possible adverse effects or tumor progression that should lead to treatment discontinuation, and the monitoring and characterization of the expected benefits, according to PCWG3 criteria. Whole-body SPECT-CT was performed in all patients 24hours after injection at each cycle using the VERITON® - Spectrum Dynamics to monitor lesions 177Lu-PSMA-1 uptake. ResultsBetween April 2021 and July 2022, 21 of the 24 patients screened could be included after clinical, biological and imaging screening. Ten received at least 4 injections, and 6 received all 6 injections. Three patients demonstrated a 50% reduction in PSA (PSA50), and 3 others any significant PSA evolution. The safety profile was favorable, with however grade 3 toxicities leading to permanent discontinuation of the treatment. ConclusionOn-site radiolabeled 177Lu-PSMA-1 appeared safe and lead to clinical benefit in most patients. The benefit-risk balance seems to be favorable for these multitreated mCRPC progressive patients in the absence of therapeutic alternatives. It requires a close multidisciplinary and multiprofessional collaboration within the nuclear medicine department. Further studies are necessary to specify the modalities of scans analysis, the impact of post-therapy scans, the length of the benefits observed, and the position of PRLT in the management of prostate cancers.

SAT562 Metastatic Oncocytic (Formerly Hürthle Cell) Thyroid Carcinoma in a Patient With Birt-Hogg-Dubé Syndrome

Abstract Disclosure: S. Vaid: None. R. Klein: None. P. Veeraraghavan: None. D.M. Blakaj: None. A. Agrawal: None. J. Sipos: None. S.I. Sherman: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Birt-Hogg-Dubé syndrome (BHD) is a rare, autosomal dominant disorder due to a germline loss-of-function mutation in the folliculin (FLCN) gene. Clinical manifestations include pulmonary cysts, renal cell carcinoma, and skin tumors, while tumors of other sites such as thyroid are uncommon. Here, we report an extremely rare case of oncocytic thyroid carcinoma (OTC) in a patient with BHD. Clinical case: A 55-year-old male with BHD noted a lump in his neck which was identified as a 3 cm right thyroid nodule on sonogram. Medical history only included BHD, which was diagnosed based on the presence of pulmonary cysts and two family members with BHD. No family members had thyroid tumors, and the patient denied any history of radiation exposure. Fine needle aspiration biopsy was indeterminate (Bethesda III). A total thyroidectomy and central lymph node (LN) dissection was performed as LN metastases were identified on intraoperative frozen section. Histopathology revealed 3 foci of OTC, largest being 3.8 cm, with extrathyroidal extension into fibroadipose tissue, 3/31 LN metastases with the largest deposit of 0.5 cm without extranodal extension. A 156.6 mCi dose of I-131 radioiodine (RAI) was administered. No uptake was noted on the post-therapy scan. Four months later, new right lateral cervical lymphadenopathy was noted on computed tomogram (CT). A right lateral selective neck dissection was performed, which identified 3/28 metastatic LNs without extranodal extension. Next generation gene sequencing testing of the metastatic tumor revealed the pathogenic FLCN (H429fs*27) variant, along with TP53 (R248Q), and DAXX (L666fs*29) pathogenic variants. Over the next 20 months, serum thyroglobulin increased from 1.8 ng/ml to 121 ng/mL (normal: 1.6 - 59.9 ng/mL). Several sub-centimeter lung nodules and new right cervical lymphadenopathy were noted on CT, and these lesions demonstrated increased uptake on fluorodeoxyglucose positron emission tomography (PET/CT) and on Ga-68 DOTATATE PET/CT scans. Due to close proximity to the right internal jugular vein, the cervical lymphadenopathy was deemed to be inoperable. Stereotactic radiation was administered to the neck, which resulted in substantial shrinkage of the neck metastases. The patient continues to be on active surveillance, with tyrosine kinase inhibitors or peptide receptor radionuclide therapy being potential future systemic therapy options in case of disease progression. Conclusion: Thyroid tumors have been occasionally reported in BHD. While most of them are papillary or follicular tumors, only one case of OTC in BHD has been previously reported in the literature [1]. This report underscores the importance of screening for thyroid neoplasms in patients with BHD. Reference: 1. Panagiotidis et al. World J Nucl Med. 2018;17(2):123-125 Presentation Date: Saturday, June 17, 2023

Do radioiodine-avid lymph nodes from differentiated thyroid cancer on the initial posttherapy scan need repeated 131I therapy?

Residual/recurrent lymph node metastase (LNM) is often found after differentiated thyroid cancer (DTC) surgery. This study aimed to investigate whether patients complicated with radioiodine-avid (131I+) lymph nodes from DTC on the initial posttherapy scan (PTS) need repeated 131I therapy. From June 2013 to August 2022, DTC patients with 131I+ lymph nodes on the initial PTS who received at least two cycles of 131I therapy were retrospectively enrolled. They were divided into a complete response (CR) group and an incomplete response (IR) group according to their response to the initial 131I therapy based on the 2015 American Thyroid Association (ATA) guidelines. A total of 170 DTC patients with 131I+ lymph nodes on the initial PTS were included; 42/170 (24.7%) patients were classified into the CR group and 128/170 (75.9%) were classified into the IR group according to their response to the initial 131I therapy. None of the 42 CR patients had disease progression at the subsequent follow-up, and 37/170 (21.8%) IR patients improved after repeated therapy. Univariate analysis showed that N stage (P=0.002), stimulated thyroglobulin (sTg) level before initial 131I therapy (P<0.001), LNM size (P<0.001), number of total residual/recurrent LNM (P=0.021), radioiodine-nonavid (131I-) LNM (P=0.002) and ultrasound features (P<0.001) were related to the initial treatment response. On multivariate analysis, sTg level (OR=1.186, P<0.001) and LNM size (OR=1.533, P=0.004) were independent risk factors for IR after initial 131I therapy. The optimal sTg level and LNM size cutoff value for predicting the treatment response after initial 131I therapy were 18.2 µg/l and 5mm. This study suggested that approximately one-quarter of patients with 131I+ lymph nodes on initial PTS, especially those with N0 or N1a stage, lower sTg level, smaller LNM size, ≤2 residual/recurrent LNMs, negative ultrasound features and no 131I- LNM, remain stable after one cycle of 131I therapy and do not need repeated therapy.

A192 EFFICACY OF USTEKINUMAB IN SMALL BOWEL STRICTURES OF FIBROSTENOTIC CROHN'S DISEASE AS ASSESSED BY INTESTINAL ULTRASOUND

Abstract Background Small bowel Crohn’s disease (CD) strictures can lead to debilitating obstructive symptoms and the deterioration of quality of life. Imaging modalities such as intestinal ultrasound (IUS) are invaluable in the diagnosis of strictures. The use of IUS in CD is rapidly growing, is cost-effective, easily repeatable, and similar in accuracy to magnetic resonance enterography. Evidence for medical management of fibrostenotic CD has been limited to anti-tumor necrosis factor biologics. Studies on the efficacy of other biologic therapies for strictures such as ustekinumab, a p40/interleukin 12 and 23 inhibitor, are lacking. Purpose The objective of this study was to evaluate the efficacy of ustekinumab in the treatment of small bowel strictures on IUS. Method This retrospective cohort study evaluated the IUS changes of terminal ileal (TI) CD strictures at baseline and 12 months following ustekinumab initiation from 2016 to 2020 at a single tertiary care center. Strictures identified were defined as 1) increased bowel wall thickness (BWT) &amp;gt; 3mm, 2) narrowed luminal apposition, and 3) presence of pre-stenotic dilation (PSD) or the inability to pass the colonoscope through the narrowed area. Changes in sonographic parameters (BWT, luminal size, PSD, length, hyperemia, inflammatory fat, dysfunctional peristalsis) were recorded at baseline prior to initiation of ustekinumab and compared 12 months after treatment. Differences from baseline to 12 months were paired within-person and statistical analysis was performed using paired T-tests for continuous variables and McNemar’s test for categorical variables. Result(s) Of the 18 patients identified, 55% (n = 10) were male, median age was 49 years (Q1-Q3: 33-63 years) at initial scan, with median CD duration of 10 years (Q1-Q3: 8-20 years). The majority of TI strictures were surgically naïve (67%, n = 12). Between pre- and 12-month post ustekinumab therapy scans, there was significant improvement in BWT [8.2 mm vs 7.2 mm, p = 0.048], however there was no significant difference in the presence of peri-enteric inflammatory fat (p = 0.10), mean stricture length (17.7 vs 21.7 cm, p = 0.18), and mean stricture lumen diameter (3.3 mm vs 2.7 mm, p = 0.44) (Table 1). There was also no significant difference in the presence of stricture-associated peri-enteric fat (89% vs 67%, p = 0.10), stricture-associated hyperemia (83% vs 89%, p = 0.65) or dysfunctional peristalsis (50% vs 61%, p = 0.41) (Table 1). Image Conclusion(s) Our study is the first to report the efficacy of ustekinumab in small bowel CD strictures using IUS at baseline and 12 months. This study shows that although ustekinumab leads to improvement in overall sonographic appearance of bowel thickness, it does not improve luminal narrowing nor PSD, two hallmark criteria of fibrostenosis. More extensive studies with larger sample sizes evaluating ustekinumab, or combination therapies, are required to identify their role in stricturing CD. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

SPECT at the speed of PET: a feasibility study of CZT-based whole-body SPECT/CT in the post 177Lu-DOTATATE and 177Lu-PSMA617 setting.

To evaluate the feasibility of using the StarGuide (General Electric Healthcare, Haifa, Israel), a new generation multi-detector cadmium-zinc-telluride (CZT)-based SPECT/CT, for whole-body imaging in the setting of post-therapy imaging of 177Lu-labeled radiopharmaceuticals. Thirty-one patients (34-89 years old; mean ± SD, 65.5 ± 12.1) who were treated with either 177Lu-DOTATATE (n=17) or 177Lu-PSMA617 (n=14) as part of standard of care were scanned post-therapy with the StarGuide; some were also scanned with the standard GE Discovery 670 Pro SPECT/CT. All patients had either 64Cu-DOTATATE or 18F-DCFPyL PET/CT prior to first cycle of therapy for eligibility check. The detection/targeting rate (lesion uptake greater than blood pool uptake) of large lesions meeting RECIST 1.1 size criteria on post-therapy StarGuide SPECT/CT was evaluated and compared to the standard design GE Discovery 670 Pro SPECT/CT (when available) and pre-therapy PET by two nuclear medicine physicians with consensus read. This retrospective analysis identified a total of 50 post-therapy scans performed with the new imaging protocol from November 2021 to August 2022. The StarGuide system acquired vertex to mid-thighs post-therapy SPECT/CT scans with 4 bed positions, 3 min/bed and a total scan time of 12 min. In comparison, the standard GE Discovery 670 Pro SPECT/CT system typically acquires images in 2 bed positions covering the chest, abdomen, and pelvis with a total scan time of 32 min. The pre-therapy 64Cu-DOTATATE PET takes 20 min with 4 bed positions on GE Discovery MI PET/CT, and 18F-DCFPyL PET takes 8-10 min with 4-5 bed positions on GE Discovery MI PET/CT. This preliminary evaluation showed that the post-therapy scans acquired with faster scanning time using StarGuide system had comparable detection/targeting rate compared to the Discovery 670 Pro SPECT/CT system and detected large lesions defined by RECIST criteria on the pre-therapy PET scans. Fast acquisition of whole-body post-therapy SPECT/CT is feasible with the new StarGuide system. Short scanning time improves the patients' clinical experience and compliance which may lead to increased adoption of post-therapy SPECT. This opens the possibility to offer imaged-based treatment response assessment and personalized dosimetry to patients referred for targeted radionuclide therapies.

Equivocal end-of-therapy imaging findings do not predict a higher risk of local relapse after definitive radiotherapy in pediatric Ewing sarcoma and rhabdomyosarcoma.

Posttherapy imaging studies can provide reassurance or induce anxiety regarding risk of recurrence for patients and their families. In some cases, it is difficult to determine if imaging findings represent posttreatment changes or residual disease. Equivocal radiographic findings can occur due to therapy-related inflammation or residual, inactive soft tissue masses, but it is unknown if such findings indicate an increased likelihood of local recurrence. The aim of this study was to assess the value of initial posttherapy scans for predicting local relapse in patients with Ewing sarcoma (EWS) or rhabdomyosarcoma (RMS) who received radiotherapy (RT) for local control. These findings are critical to inform clinicians' surveillance recommendations and ability to accurately counsel patients and their families. The primary endpoint was time to local progression (LP). Patients were classified as having posttherapy scans that were "positive" (residual disease within the RT field), "negative" (no evidence of residual disease within the RT field), or "equivocal" (no determination could be made). The value of initial posttreatment scans for predicting LP was assessed using positive predictive value (PPV) and negative predictive value (NPV). Negative imaging findings (n=51) had an NPV of 88%, and positive imaging findings (n=1) had a PPV of 100%. When equivocal findings (n=16) were categorized with negative results (i.e., positive vs. equivocal/negative), the NPV was 90%. When equivocal findings were categorized with positive results (equivocal/positive vs. negative), the PPV was 12%. Equivocal findings within the RT field on end-of-therapy imaging studies indicate no higher risk of local recurrence than negative findings. These results may contribute to appropriate surveillance schedules and accurate counseling of patients with RMS and EWS who have received RT for local control.

Increased PSMA Expression in 177 Lu-PSMA-617 Scan in Metastatic Castrate-Resistant Prostate Cancer Patient Treated With PSMA Radioligand Therapy and Enzalutamide : A Potential Game-Changer.

Androgen deprivation therapy plays an integral role in the treatment algorithm of advanced prostate cancer. Enzalutamide has shown great benefit in castrate-sensitive as well as resistant prostate cancer. Few studies have shown that enzalutamide can potentially increase the PSMA expression on 68 Ga-PSMA-11 PET/CT imaging in patients with metastatic castrate-resistant prostate cancer. We present an interesting case where addition of short course of enzalutamide resulted in increased localization of 177 Lu-PSMA-617 in metastatic lesions on posttherapy scan pointing to the added benefit of PSMA RLT.

PSAT285 A Rare Case of Co-Existing Papillary Thyroid Cancer with Lung Metastasis and Lung Adenocarcinoma

Abstract Introduction Multiple primary tumors are defined as the presence of two primary tumors of different histologies in the same individual, which can be diagnosed at the same time or at different times. We present a rare case of papillary thyroid cancer (PTC) with pulmonary metastasis and lung adenocarcinoma diagnosed simultaneously and highlight the importance of identifying multiple primary cancers to guide management and improve patient outcomes. Clinical Case A 57-year-old female with no prior history of malignancy was found to have a 12 mm left upper lobe lung nodule on CT chest as a part of evaluation of worsening cough. A fluorodeoxyglucose PET scan showed increased uptake in the left upper lobe nodule as well as a hypermetabolic thyroid nodule in the right thyroid lobe. She underwent a thoracoscopy, wedge resection, and left lung lobectomy with lymph node dissection, and pathology revealed adenocarcinoma of the lung as well as incidentally found PTC. Subsequently, thyroid ultrasound was obtained which showed a right upper mid-pole thyroid nodule measuring 1.7 cm. She underwent a total thyroidectomy, and pathology showed PTC, tall cell variant in the right lobe, with largest tumor dimension 1.5 cm with no extrathyroidal extension, no lymphatic, and no vascular invasion. A nuclear uptake scan post thyroidectomy showed focal uptake in the thyroid corresponding to residual thyroid tissue, without evidence of metastatic disease. She subsequently received 152.6 mCi of radioactive iodine (RAI). A post-therapy scan obtained one week later showed no new uptake. After RAI, her thyroglobulin antibody remained negative and thyroglobulin became undetectable. She remains on levothyroxine therapy with her TSH at target of 0.1-0.4 U/L. However, she unfortunately had recurrent disease of her lung adenocarcinoma and is continuing to undergo treatment with chemotherapy Conclusion PTC is the most common type of differentiated thyroid cancer and generally has a better prognosis than other types of thyroid cancer given its indolent course. Histologic subtype, presence of extra thyroidal extension, lymph node involvement, and distant metastasis play a role in prognosis, and PTC metastasizes to the lungs in about 5% of cases. Clinicians should be aware of the possibility of multiple primary tumors, and the use of diagnostic modalities like FDG-PET and tissue biopsy can help differentiate a second primary tumor from metastatic disease. Radioactive iodine therapy (RAI) for management of differentiated thyroid carcinoma has been linked to predisposition to other primary malignancies such as leukemia and lymphoma, however our patient was found to have both malignancies simultaneously prior to receiving RAI. This suggests the possibility of genetic susceptibility or alterations in the immune constituency. Further studies are needed to analyze the genetic and environmental factors that lead to development of two primary tumors in certain individuals. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Initial Post-Therapy Imaging as a Predictor of Local Relapse after Radiotherapy in Pediatric Sarcomas

<h3>Purpose/Objective(s)</h3> To assess the value of initial post-therapy scans for predicting local relapse in patients with Ewing sarcoma (EWS) and rhabdomyosarcoma (RMS) who received radiotherapy (RT) for local control. <h3>Materials/Methods</h3> This single-center study included all patients who were diagnosed with EWS or RMS at <22 years of age, completed RT for local control and underwent post-treatment diagnostic imaging evaluations from 2007-2020. Radiologists' impressions of the primary tumor site were categorized as "positive" (residual disease within RT field), "negative" (no residual disease within RT field), or "equivocal." Each patient was assigned to one of these categories, based on the radiologists' overall impression of all off-therapy scans. The primary endpoint was local progression (LP), defined as disease progression within the RT field. Positive predictive value (PPV) and negative predictive value (NPV) quantified the ability of off-therapy imaging studies to predict LP. Actuarial rates of LP were calculated using Kaplan-Meier methods. <h3>Results</h3> Sixty-eight patients were eligible (29 EWS, 39 RMS). The median age at diagnosis was 8 years (range 0-21). All patients received chemotherapy and RT based on disease histology and risk group, per Children's Oncology Group protocols. RT was to a median dose of 50.4 Gy (range 36-55.8); 19 patients (28%) underwent surgery and RT for local control, and 49 (72%) received RT alone. Post-treatment imaging was performed 3 weeks (range <1- 13) after completion of chemotherapy and 17 weeks (range 4-52) after completion of RT. Post-treatment imaging of the primary site included PET in 51 patients (75%), MRI in 54 (79%), and CT in 5 (7%). Radiologists' overall impressions were that 1 patient's (1%) scans were positive, 50 (74%) were negative, and 17 (25%) were equivocal. 4-year LP was 100% for patients with positive scans, 12% for patients with negative scans, and 5.9% for patients with equivocal scans. The difference in the percentages of LP for patients with negative vs. equivocal scans did not reach significance (p= 0.5). Positive scans had a PPV of 100%, and negative scans an NPV of 88%. When equivocal results were considered positive (positive/equivocal vs. negative), the PPV was 11%. When equivocal results were considered negative (positive vs. equivocal/negative), the NPV was 90%. Five patients (29%) with equivocal results underwent short-term surveillance imaging at a median of 7 weeks (range 6-9) after the equivocal studies. No short-term follow-up scan demonstrated local progression. <h3>Conclusion</h3> Equivocal findings on initial post-treatment diagnostic imaging studies did not indicate a higher risk of local recurrence after RT than negative findings. These results may influence the interpretation of initial post-therapy scans and contribute to accurate counseling of patients and families.

Non-Iodine-Avid Disease Is Highly Prevalent in Distant Metastatic Differentiated Thyroid Cancer With Papillary Histology.

Patients with radioactive iodine (RAI) refractory metastatic differentiated thyroid cancer (DTC) have poor prognosis. Early identification of RAI refractoriness may improve care. This work aimed to characterize DTC patients with distant metastases (DM) at diagnosis who presented with non-iodine-avid disease. Retrospective analyses of DTC patients with DM at diagnosis who presented between 2012 and 2020 were performed. Iodine uptake in DM was correlated with tumor histology and mutational profile. The difference in uptake between BRAFV600E-like (BVL) and RAS-like (RL) cancers based on insights from The Cancer Genome Atlas was evaluated. Among 78 patients, 48.7% had negative uptake in DM on the first posttherapy scan. Negative scans were highly prevalent in papillary thyroid carcinoma (PTC) with papillary architecture, PTC with BRAFV600E mutation, and PTC with both BRAFV600E and TERT promoter mutations (71.1%, 80.9%, and 100%, respectively). BVL and RL tumors exhibited distinct uptake patterns with negative scan prevalence of 76.9% and 14.3% (P = .005). Multivariate logistical regression confirmed high odds of negative uptake in BVL tumors with either BVL mutations or papillary architecture, 19.8 (95% CI, 2.72-144), and low odds of negative uptake in RL tumors with either RL mutations or follicular architecture, 0.048 (95% CI, 0.006-0.344), after adjusting for age, sex, race, RAI preparation method, bone metastases, and RAI dose. Patients with negative scans were significantly older (62.4 vs 47.0 years, P = .03). Among DTC patients with DM at diagnosis, non-iodine-avid disease is highly prevalent in patients with BVL cancers, particularly with BRAFV600E and TERT promoter mutations, and is associated with an older age. Better strategies are needed to improve RAI treatment response for these patients.

CT-Based Definition and Structured Reporting of Abdominal Lymph Node Stations.

Background Meticulous evaluation of abdominal lymph nodes on computed tomography (CT) is a fundamental task in radiological practice especially in oncological reporting. Although various reporting systems exist to define abdominal nodal stations for malignancies of individual abdominal organs, a complete and uniform framework for radiological reporting of abdominal lymph nodes does not exist in the literature. Purpose The goal of this review was to provide a step-wise reporting template and precise definitions of the radiological anatomy of abdominal lymph nodes and to generate a CT-based illustration of the lymph node stations of the abdomen. Conclusion This CT-based illustration and reporting template will help the radiologists to aptly describe the extent of the lymph nodal diseases and will help in comparison with posttherapy scans.

Preparation of 177Lu-PSMA-617 in Hospital Radiopharmacy: Convenient Formulation of a Clinical Dose Using a Single-Vial Freeze-Dried PSMA-617 Kit Developed In-House.

Objective In the recent time, endoradionuclide therapy for metastatic castration-resistant prostate carcinoma employing 177Lu-PSMA-617 has yielded encouraging results and several clinical trials with the agent are currently ongoing. Routine preparation of 177Lu-PSMA-617 patient doses can be made simpler and convenient, if the ingredients essential for radiolabeling are made available in a ready-to-use lyophilized form. Methods PSMA-617 freeze-dried kit was formulated and used for the preparation of 177Lu-PSMA-617 clinical dose with high radiochemical purity using low/medium specific activity 177Lu. Detailed radiochemical studies were performed to determine the maximum activity and volume of 177LuCl3, which can be added in the kit for the formulation of 177Lu-PSMA-617. Studies were also performed to determine the shelf life of the kit to ensure its long-term usage. Studies were performed in buffer as well as human serum medium to determine the stability of the 177Lu-PSMA-617 complex after storing in respective media up to 7 days postpreparation. About ten patient doses of 177Lu-PSMA-617 were administered, and posttherapy scans were acquired. Results The formulated freeze-dried kit of PSMA-617 could be radiolabeled with an average percentage radiochemical purity > 98.53 ± 0.38. The freeze-dried kit was found suitable for tolerating up to 0.5 mL of 177LuCl3 (in 0.01 N HCl) and specific activity of 555 MBq/μg (15 mCi/μg) for the preparation of the patient dose of 177Lu-PSMA-617. The 177Lu-PSMA-617 complex prepared using the freeze-dried kit of PSMA-617 was observed to maintain % radiochemical purity (RCP) of 96.74 ± 0.87 and 94.81 ± 2.66, respectively, even after storing up to 7 days in buffer and human serum, respectively. 177Lu-PSMA-617 prepared using the in-house formulated freeze-dried kit of PSMA-617 exhibited accumulation in metastatic lesions picked up in a pretherapy PET scan. Reduction in number as well as size of lesions was observed in posttherapy scans acquired after two months of administering the first therapeutic dose of 177Lu-PSMA-617. Conclusions The freeze-dried kit of PSMA-617 could be used for the preparation of 177Lu-PSMA-617 with high radiochemical purity (>98%) in a reproducible manner. 177Lu-PSMA-617 prepared using the developed kit was successfully evaluated in patients suffering from metastatic prostate cancer.

CTNI-53. RADIATION TREATMENT VOLUMES BEFORE AND AFTER BRAF/MEK THERAPY IN NEWLY DIAGNOSED PAPILLARY CRANIOPHARYNGIOMAS: A CORRELATIVE ANALYSIS OF THE ALLIANCE A071601 PHASE II TRIAL

Abstract PURPOSE Standard of care for craniopharyngiomas is surgery with or without radiotherapy (RT). Cohort A of Alliance A071601 evaluated the efficacy of BRAF/MEK inhibition with vemurafenib/cobimetinib in patients with previously untreated papillary craniopharyngiomas (PCP), which carry the BRAF V600E mutation. Cohort B is currently enrolling patients with recurrence after RT. In a correlative analysis, we examined changes in RT volumes after BRAF/MEK therapy in Cohort A. METHODS Previously unirradiated patients with BRAF-mutated PCP were treated with vemurafenib/cobimetinib. Sixteen patients had scans available before starting vemurafenib/cobimetinib (“pre-therapy”) and after completing therapy (“post-therapy”). Two patients went off study treatment after 8 and 9 days due to side-effects and were excluded for this analysis. Gross target volumes (GTV) were contoured on pre-therapy and post-therapy scans. On post-therapy scans, an additional target comprising gross disease and at-risk regions for microscopic residual disease (GTV-micro) was defined and considered the treatment volume. Clinical target volume (CTV) was a 5-mm uniform expansion on pre-therapy GTV and post-therapy GTV-micro. Volumes were independently reviewed by two radiation oncologists. Changes in volumes from pre- versus post-therapy were compared using the Wilcoxon signed rank test. RESULTS In 14 patients evaluated, 57% were female and median age at enrollment was 49.5 years (range 33-83). Median time on treatment was 8.9 months (range 4.0-18.0). Median GTV pre-therapy was 3.8 mL (range 0.2-23.4) versus 0.3 mL (range 0.0-3.2) post-therapy (p=0.0001) and 1.7 mL (range 0.1-8.0) post-therapy GTV-micro (p=0.0001). Median CTV pre-therapy was 13.7 mL (range 2.8-51.8) versus 9.1 mL (range 2.2-27.5) post-therapy (p=0.0001). All tumors abutted the optic chiasm pre-therapy, only 6 did post-therapy. CONCLUSIONS Vemurafenib/cobimetinib resulted in smaller RT volumes. BRAF/MEK inhibitors could reduce RT volumes and spare dose to surrounding normal structures. Enrollment to Cohort B of Alliance A071601 should be considered for patients with recurrent tumors after RT. SUPPORT https://acknowledgments.alliancefound.org

Incidental Muscle Uptake of 177Lu-DOTATATE in Peripheral Vascular Disease

Somatostatin receptor (SSTR)-based imaging and therapy has emerged as well-established modality in neuroendocrine tumors. However, its role in inflammation imaging is still evolving. We present a 48-year-old male with metastatic neuroendocrine tumor who underwent lutetium-177-based somatostatin receptor-based therapy. The post-therapy scan showed a focal tracer uptake in the left calf muscle in addition to the expected tracer uptake at the primary and metastatic sites. Further, cross-sectional imaging and biochemical investigations revealed peripheral vascular disease (PVD). The incidental tracer uptake in the calf on post-therapy scan potentiates the role of somatostatin receptor scintigraphy in identifying macrophage-specific inflammatory reactions.

Metastatic Malignant Phosphaturic Mesenchymal Tumor of Mandibular Alveolus: a Rare Case Report and Review of Literature.

Malignant phosphaturic mesenchymal tumors (PMT) of the head and neck region are extremely rare, which cause paraneoplastic syndrome characterized by hypophosphatemia and osteomalacia. We report a 48-year-old gentleman who had persistent knee and calf pain associated with weakness in lower limbs on presentation. He had hypophosphatemia and elevated FGF-23 and 68Ga-DOTANOC PET scan showed soft tissue density mass with increased peripheral radiotracer uptake in the left mandibular alveolus and adjoining floor of the mouth, revealing the primary tumor. It also showed a non-avid, histological inconclusive nodule of 17 × 12mm in size in the lower lobe of the right lung. The patient was treated with composite resection and bilateral level I-III neck dissection with microvascular free fibula osteocutaneous flap mandibular reconstruction. Histopathological examination showed malignant PMT with positive soft tissue margins and bilateral metastatic cervical lymphadenopathy. The patient received adjuvant radiation therapy and sequential post therapy scans showed no evidence of locoregional disease, however showed progressive functional pulmonary metastatic disease which did not respond to chemotherapy. We also made a brief review of literature of head and neck malignant PMT focusing on presentation, primary and adjuvant treatment, and response to treatment.

Responses to the First Radioactive Iodine Treatment After Targeted Therapy for Aggressive Papillary Thyroid Cancers

Introduction: Tall cell variant (TCV) and columnar cell variant (CCV) are aggressive variants of papillary thyroid cancer (PTC) and they are overrepresented in radioactive iodine (RAI) refractory cases. Studies have reported using BRAF and/or MEK inhibitors to restore iodine avidity in patients with iodine refractory disease. There is much less experience of using targeted therapy pre-emptively to enhance iodine uptake for aggressive variants and advanced disease prior to the first RAI treatment (RAI-T). We present three patients with these variants and describe their responses to the first RAI-T after targeted therapy. Case 1: 64-year-old male with CCV-PTC and areas of poor differentiation (pT3aN1bM1) has somatic BRAF V600E, TERT and AJUBA mutations. Thyroglobulin (TG) 6 weeks post surgery was 21 ug/L, with negative TG antibodies (TGAb). PET-CT revealed FDG avid superior mediastinal lymphadenopathy and lung metastases. He received dabrafenib for 6 weeks followed by his first RAI -T(153 mCi) after thyroid hormone withdrawal (THW). Pre- and post-therapy scans showed uptake in the neck, right superior mediastinum and lung metastases. Three months post RAI, TG decreased to 5.1 ug/L. Chest CT revealed stable mediastinal lymphadenopathy and decreased size of lung metastases. Case 2: 41-year-old male with TCV-PTC containing areas of focal squamous differentiation and poor differentiation (pT4aN1bM1) has somatic BRAF V600E and TP53 mutations. PET-CT showed FDG avid neck lymph nodes and lung metastases. TG 8 weeks after surgery was 1.5 ug/L, TGAb 31.19 IU/L. He was treated with dabrafenib and trametinib for 4 weeks followed by his first RAI-T (150mCi) after THW. Pretreatment scan showed uptake in the thyroid bed and cervical lymph nodes. Post-therapy scan revealed additional uptake in the lung metastases. Chest CT 3 and 9 months after RAI-T revealed stable paratracheal lymph node and lung metastases. TGAb decreased to 7.04 IU/L; TG was 2.2 ug/L. Case 3: 33-year-old female with invasive TCV-PTC (pT3bN1aM1) has a somatic BRAF V600E mutation. CT chest showed multiple scattered lung nodules up to 4mm. Ten weeks post surgery, TG was 0.1 ug/L, TGAb 5.21 IU/ml. Patient received 1 month of dabrafenib and trametinib followed by his first RAI-T(125 mCi) after THW. Pre- and post-therapy scans revealed uptake in the neck and left supraclavicular areas, without uptake in lung nodules. Three months post RAI, chest CT revealed stable lung nodules. TG was 0.1 ug/L, and TGAb was 5.16 IU/L. Neck ultrasound showed no disease. Conclusion: These three patients with aggressive variants of PTC have advanced disease, and all were found to have a BRAFV600E mutation on genomic analysis. They tolerated BRAF targeted inhibition as an attempt to enhance iodine uptake preemptively with various responses to their first RAI-T. More studies will be needed to determine if this strategy will improve outcomes for these patients.

Predictive factors of tumor sink effect: Insights from 177Lu-Prostate-specific membrane antigen therapy.

Tumor sink effect (TSE) has been defined as; decreased uptake in healthy tissue with increased tumor sequestration of the radiopharmaceuticals. It enables us to give high tumoral radiation doses while resulting in lower absorbed radiation to critical organs. However, the factors which influence this effect are yet to be defined. In this study, we have investigated the predictive factors of the tumor sink effect in a group of patients who received 177Lu-Prostate-specific membrane antigen (PSMA) therapy due to progressive metastatic castration-resistant prostate cancer (mCRPC). We have retrospectively analyzed the pre-therapy 68Ga-PSMA positron-emission tomography (PET)-computed tomography (CT) and post-therapy planar whole-body scans of 65 patients who received at least two cycles of 7.4GBq of 177Lu-PSMA therapy. All patients with mCRPC were referred to our department after multiple treatment lines. Age, previous therapies, International Society of Urological Pathology (ISUP) score, and pre-therapy serum tumor marker levels were recorded. Post 177Lu-PSMA therapy images were analyzed for TSE. 68Ga-PSMA PET-CT images were used for the calculation of SUVmax in malignant and healthy tissues as well as metabolic tumor volume (MTV) and total lesion PSMA index (TLPI). Based on the post-therapy scans, TSE was seen in 17/65 (26.2%) patients. In univariate analysis, patients with TSE had higher pre-therapy PSA, PSA velocity, and ALP (p < 0.0001). In relation to PET parameters, patients with TSE had higher 68Ga-PSMA MTV, 68Ga-PSMA TLPI and lower pretherapy renal SUVmax (p < 0.0001)), pretherapy liver SUVmax (p:0.012), pretherapy parotid gland SUVmax (p:0.032), and pretherapy parotid gland SUVmean (p:0.038). In the multivariant analysis, 68Ga-PSMA TLPI, pre-therapy PSA, and PSA velocity were found to be statistically significant. When analyzed according to Youden index, pretherapy PSA level of 133ng/ml (sensitivity 0.765 and 0.875), PSA velocity of 246ng/ml/year (sensitivity 0.765 and 0.833), and 68Ga-PSMA TLPI of 2969g (sensitivity 0.765 and 0.875) was found to be the best cut-off points to predict TSE. The tumor sink effect was seen in 26.2% of patients. 68Ga- PSMA TLPI, pre-therapy PSA, and PSA velocity was found to be the predictors of TSE. Accurate prediction of TSE may lead to increased tumoral doses while sparing healthy organs. Clinical trials that consider this effect as a part of a dose algorithm may further increase therapeutic efficacy.

Early Quantification of Salivary Gland Function after Radioiodine Therapy.

Purpose of the Study:Radioiodine (I-131) is used as an effective noninvasive treatment for thyroid malignancies. Salivary gland is one of the most affected nontarget organs. The present study aims to perform early quantification of salivary gland function after I-131 therapy (RIT) for thyroid cancer considering I-131 down-scatter in the Tc-99m window.Materials and Methods:A total of 20 patients (6 males and 14 females) with differentiated thyroid carcinoma were enrolled in the study. Baseline dynamic salivary scintigraphy was performed in all patients using 185–370 MBq (5–10 mCi) Tc-99m pertechnetate. Posttherapy, salivary scintigraphy was performed 10–25 days after RIT in the range of 1.85–7.4 GBq (50–200 mCi). Time–activity curves obtained from the pre- and posttherapy dynamic salivary scintigraphy were used for semi-quantitative analysis. Uptake ratio (UR), ejection fraction (EF%), and maximum accumulation (MA%) were calculated by drawing regions of interest of individual parotid and submandibular glands over a composite image, after correcting for down-scatter from I-131 in the Tc-99m window. A paired t-test was used for comparison of the parameters obtained.Results:Significant changes were observed in UR and EF% of both parotid and submandibular glands (P < 0.05). No significant changes were found in the value of MA% of left parotid gland and both submandibular glands in the posttherapy scans in comparison to pretherapy scans (P > 0.05). However, significant difference was observed in the MA% of the right parotid gland (P = 0.025).Conclusion:Salivary gland function was found to deteriorate after RIT, with the parotid glands affected more than the submandibular glands.