Intra-arterial PRRT with Lu-177 DOTATATE in Liver-dominant Metastatic Neuroendocrine Tumors: Early Assessment of Efficacy and Toxicity.

Purpose: We proposed to administer Lu-177-DOTATATE in intra-arterial (IA) mode for higher first-pass localization to somatostatin receptors, higher residence time in liver metastases, and more radiation to tumor. This study aimed at assessing early hematological, renal and hepatotoxicity; and objective response to IA peptide receptor radionuclide therapy (PRRT). Materials and Methods: Fourteen patients (4 females and 10 males) were prospectively assessed. 5/14 patients underwent 2 cycles, whereas 3/14 underwent 3 cycles, and 6/14 received 1 cycle of IA PRRT. 200 mCi of Lu-177-DOTATATE was administered in 15-20 min by IA route under angiographic guidance. Patients were asked to follow-up at 4 and 8 weeks with hematological, liver, and renal functional parameters, and Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) after 8 weeks. Response was assessed using RECIST 1.1 and EORTC PET criteria. Results: Safety: 2/14 patients had high total and direct bilirubin, which reverted to normal after IA PRRT. Three patients had low albumin, which improved after 1 cycle. Nine patients showed no worsening of liver function. Two patients showed Grade 1 hematotoxicity which reverted to normal. Five patients showed high creatinine, but preserved glomerular filtration rate and EC clearance. On follow-up at 8 weeks, serum creatinine reverted to normal. Efficacy: In five patients who underwent 2 cycles of IA PRRT, 3 showed partial response (PR) on RECIST 1.1 and partial metabolic response (PMR) on EORTC criteria, whereas 2 showed stable disease (SD). In patients who underwent 3 cycles, 1 showed SD, whereas other patient showed PMR on DOTANOC PET/CT, with PR in size. Among the remaining seven patients, 5 showed PMR, whereas the other 2 showed SD. Thus 9/14 patients showed PR, whereas 5 showed SD on metabolic and size criteria. Conclusions: IA PRRT is a safe and efficacious approach for the treatment of liver dominant metastatic neuroendocrine tumors.

Factors Predicting Prognosis in Metastatic Grade 1 Gastro-entero-pancreatic Neuroendocrine Tumors.

INTRODUCTION: The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NET) has steadily increased. These tumors are considered relatively indolent even when metastatic. What determines survival outcomes in such situations is understudied. MATERIALS AND METHODS: Retrospective analysis of a prospectively maintained NET clinic database, to include patients of metastatic grade 1 GEP-NET, from January 2018 to December 2021, to assess factors affecting progression-free survival (PFS). RESULTS: Of the 589 patients of GEP-NET treated during the study period, 100 were grade 1, with radiological evidence of distant metastasis. The median age was 50 years, with 67% being men. Of these, 15 patients were observed, while 85 patients received treatment in the form of surgery (n = 32), peptide receptor radionuclide therapy (n = 50), octreotide LAR (n = 22), and/or chemotherapy (n = 4), either as a single modality or multi-modality treatment. The median (PFS) was 54.5 months. The estimated 3-year PFS and 3-year overall survival rates were 72.3% (SE 0.048) and 93.4% (SE 0.026), respectively. On Cox regression, a high liver tumor burden was the only independent predictor of PFS (OR 3.443, p = 0.014). The 5-year OS of patients with concomitant extra-hepatic disease was significantly lower than that of patients with liver-limited disease (70.7% vs. 100%, p = 0.017). CONCLUSION: A higher burden of liver disease is associated with shorter PFS in patients with metastatic grade I GEP-NETs. The OS is significantly lower in patients with associated extrahepatic involvement. These parameters may justify a more aggressive treatment approach in metastatic grade 1 GEP-NETs.

PRRT with Lu-177 DOTATATE in Treatment-Refractory Progressive Meningioma: Initial Experience from a Tertiary-Care Neuro-Oncology Center.

PURPOSE: Refractory and/or recurrent meningiomas have poor outcomes, and the treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been used in this setting with promising results. We have documented our experience of using intravenous (IV) and intra-arterial (IA) approaches of Lu-177 DOTATATE PRRT. METHODS: Eight patients with relapsed/refractory high-grade meningioma received PRRT with Lu-177 DOTATATE by IV and an IA route. At least 2 cycles were administered. Time to progression was calculated from the first PRRT session to progression. The response was assessed on MRI using RANO criteria, and visual analysis of uptake was done on Ga-68 DOTANOC PET/CT. Post-therapy dosimetry calculations for estimating the absorbed dose were performed. RESULTS: Median time to progression was 8.9 months. One patient showed disease progression, whereas seven patients showed stable disease at 4 weeks following 2 cycles of PRRT. Dosimetric analysis showed higher dose and retention time by IA approach. No significant peri-procedural or PRRT associated toxicity was seen. CONCLUSION: PRRT is a safe and effective therapeutic option for relapsed/refractory meningioma. The IA approach yields better dose delivery and should be routinely practised.

Can 18 F FDG PET/CT metabolic parameters be used to noninvasively differentiate between different histopathological subtypes and Fuhrman grades of renal cell cancer?

AIM: To evaluate relationship between metabolic PET metabolic parameters and size of the primary tumor, various histopathological subtypes of renal cell carcinoma (RCC) and Fuhrman grade of the tumors. MATERIAL AND METHODS: Retrospective analysis of 93 biopsy-proven RCC patients who underwent pretreatment flourine 18 flourodeoxyglucose PET/computed tomography ( 18 F FDG PET/CT) was performed. Quantitative PET parameters, size of the primary tumor, histopathological subtypes and Fuhrman grades of the tumor were extracted. We tried to assess if there was any significant difference in the metabolic patterns of various histopathological subtypes of RCCs, Fuhrman grade of the tumors and size of the primary tumor. RESULTS: A significant correlation was noted between the size of primary tumor and maximum standardized uptake value (SUV max ), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) ( P  < 0.01, P  < 0.001 and P  < 0.001, respectively). SUV max values correlated significantly with the histopathological subtype ( P  < 0.001). Further sub-analyses was also done by segregating the patients into Low grade (Fuhrman grade 1 and 2) vs. High grade (Fuhrman grade 3 and 4). SUV max , MTV and TLG were significantly different between high grade vs. low grade tumors. ROC analysis yielded cut off values for SUV max , MTV and TLG to differentiate between high grade from low grade tumors. CONCLUSION: FDG PET/CT with the use of metabolic PET parameters can differentiate between different histopathological subtypes of RCC. Incorporation of metabolic parameters into clinical practice can potentially noninvasively identify patients with low-grade vs. high-grade RCC.

Tata Memorial Centre Evidence Based Use of Nuclear medicine diagnostic and treatment modalities in cancer.

ABSTRACT: PET/CT and radioisotope therapy are diagnostic and therapeutic arms of Nuclear Medicine, respectively. With the emergence of better technology, PET/CT has become an accessible modality. Diagnostic tracers exploring disease-specific targets has led the clinicians to look beyond FDG PET. Moreover, with the emergence of theranostic pairs of radiopharmaceuticals, radioisotope therapy is gradually making it's way into treatment algorithm of common cancers in India. We therefore would like to discuss in detail the updates in PET/CT imaging and radionuclide therapy and generate a consensus-driven evidence based document which would guide the practitioners of Oncology.

Primary Neuroendocrine Tumor of Prostate in a Case of Metastatic Adenocarcinoma of Lung: Rare Entity with Histopathological and Gallium 68 DOTANOC Positron Emission Tomography Correlation.

Neuroendocrine tumor (NET) of the prostate is an extremely rare entity which represents <1% of the prostatic cancers, but with increasing incidence. Its spectrum encompasses several histological variants ranging from well-differentiated tumor which are often indolent in nature; to aggressive neuroendocrine carcinoma which portends aggressive management. Hence, such rare entities are to be characterized and treated accordingly. We report an unusual case of well-differentiated NET of prostate which was flagged on fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) performed for other indication and confirmed on Gallium-68 DOTANOC PET/CT. Histopathology and immunohistochemistry confirmed the findings subsequently.

Imaging-Based Patterns of Failure following Re-Irradiation for Recurrent/Progressive High-Grade Glioma.

BACKGROUND: Re-irradiation (ReRT) is an effective treatment modality in appropriately selected patients with recurrent/progressive high-grade glioma (HGG). The literature is limited regarding recurrence patterns following ReRT, which was investigated in the current study. METHODS: Patients with available radiation (RT) contours, dosimetry, and imaging-based evidence of recurrence were included in the retrospective study. All patients were treated with fractionated focal conformal RT. Recurrence was detected on imaging with magnetic resonance imaging (MRI) and/ or amino-acid positron emission tomography (PET), which was co-registered with the RT planning dataset. Failure patterns were classified as central, marginal, and distant if >80%, 20-80%, or <20% of the recurrence volumes were within 95% isodose lines, respectively. RESULTS: Thirty-seven patients were included in the current analysis. A total of 92% of patients had undergone surgery before ReRT, and 84% received chemotherapy. The median time to recurrence was 9 months. Central, marginal, and distant failures were seen in 27 (73%), 4 (11%), and 6 (16%) patients, respectively. None of the patient-, disease-, or treatment-related factors were significantly different across different recurrence patterns. CONCLUSION: Failures are seen predominantly within the high-dose region following ReRT in recurrent/ progressive HGG.

Sporadic Cerebellar Hemangioblastoma With Strong SSTR Expression on 68 Ga-DOTANOC PET/CT.

ABSTRACT: Sporadic cerebellar hemangioblastomas are rare with majority of these tumors presenting as a part of von Hippel-Lindau syndrome. We demonstrate an unusual case of a symptomatic sporadic cerebellar hemangioblastoma mimicking a meningioma on MRI and 68 Ga-DOTANOC PET imaging.

Ga-68 Prostate-Specific Membrane Antigen PET/CT: Imaging and Clinical Perspective in Prostate Cancer: Imaging and Clinical Perspective in Prostate Cancer.

Imaging in prostate cancer has become increasingly important over time, as the incidence of prostate cancer has been on the rise and better screening techniques have emerged. The development of personalized systemic therapies highlights the unmet need for whole-body imaging. Prostate-specific membrane antigen (PSMA) PET, with its ease of performance and mechanism of localization to prostatic tumor cells, has now emerged as a preferred modality for diagnosis, staging, and treatment response assessment. In this context, PSMA PET can help in mapping the disease extent, both the skeletal and visceral spread, to plan targeted therapeutic approaches.

Congenital Melanocytic Nevi Syndrome With Leptomeningeal Melanoma.

ABSTRACT: The incidence of congenital melanocytic nevi (CMNs) is 1% to 6% for small- to intermediate-size nevi to 1 in 500,000 for giant size nevi. Large and satellite CMNs are known to be associated with neurocutaneous melanosis and central nervous system malformations such as Dandy-Walker malformation, defects of the vertebra-skull, and intraspinal lipomas. We hereby present a case of CMN syndrome in an 18-year-old girl with leptomeningeal melanoma, evaluated with MRI, adequately staged, and screened with FDG PET.

Prospective study to assess the role of FDG PET/CT in detecting systemic metastatic spread in rectal cancers with lateral pelvic lymph nodes.

INTRODUCTION: The utility of positron emission tomography (PET) in detecting additional M1 patients over conventional staging modalities is not known in rectal cancer patients with enlarged lateral pelvic nodes. METHODS: Prospective, single center, single-arm interventional study of consecutive rectal cancer patients that had baseline lateral pelvic nodes on MRI (>10 mm) between February 2017 to December 2018. Such patients underwent PET after confirming non-metastatic status on CT of thorax and abdomen. Primary outcome measure was additional M1 sites detected on PET. A 10% distant metastasis rate was expected with 80% confidence interval (CI) set at 5% as the lower limit. RESULTS: 44 patients were included and the concordance between MRI and PET in detection of lateral nodes was 97.7% (43 patients). Additional sites of metastasis were detected in 5 patients (11.36%; 80% CI - 5.63%-20.6%), and there was a change in treatment plan in 7 (15.9%). The number needed to treat (NNT) for PET scans to detect additional metastatic sites and change treatment were 9 and 6 respectively. There was a change in treatment intent (curative to palliative) in 2 patients (4.5%, NNT - 22). CONCLUSION: In rectal cancer patients with LPLN, the use of FDG-PET-CT over conventional staging studies led to the detection of additional extra-pelvic metastasis in 11.4% and changed the treatment plan in 15.9%. This met the pre-defined threshold to endorse the use of PET-CT in patients that match the study characteristics.

Radiation-Induced Meningioma in a Case of Medulloblastoma Treated 11 Years Ago-Detected on 68Ga-DOTANOC PET/CT.

ABSTRACT: Medulloblastomas, especially the sonic hedgehog subgroup, are treated aggressively with surgery and chemoradiotherapy, as they are associated with high local site recurrence rate and poor overall survival. Radiation-induced meningioma is the most common delayed complication of craniospinal irradiation. This needs to be differentiated from meningeal or ependymal metastases as the later need aggressive management. We report one such rare case, in a patient who completed treatment for medulloblastoma 11 years ago, was in remission, and now presented with dural-based lesions.

All that Glitters on PSMA is Not a Lesion: An Unusual Artifact on PSMA PET/CT.

Nonspecific uptake of prostate-specific membrane antigen (PSMA) on PSMA positron-emission tomography/computed tomography (CT) is normally encountered in benign conditions, which is detected on morphological changes on CT component. However, having a site of uptake without any CT finding is a rare occurrence. We herewith report one such rare case of a 66-year-old male with metastatic prostatic adenocarcinoma, who demonstrated an incidental finding of intense focal PSMA uptake in the lung parenchyma.

Brain FET PET tumor-to-white mater ratio to differentiate recurrence from post-treatment changes in high-grade gliomas.

BACKGROUND AND PURPOSE: Highergrade glial neoplasms undergo standard treatment with surgery, radiotherapy, and alkylating agents. There is often a clinical/neuroimaging dilemma in the post-treatment setting to differentiate disease recurrence from treatment-related changes. FET (fluoro-ethyl-tyrosine) PET has emerged as a molecular imaging modality for cases where MR imaging is inconclusive. This study aims to develop a cutoff on FET PET for differentiating true recurrence from post-treatment changes. METHODS: We retrospectively analyzed72 patientswith post-treatment grade 3 or 4 brain gliomas. Five to six mCi of 18 F-FET was injected and static imaging of the brain was performed at 20 min. A tumor-to-white matter (T/Wm) ratio was used as semiquantitative parameter. A T/Wm cutoff of 2.5 was used for image interpretation. Imaging findings were confirmed by either histopathologic diagnosis in a multidisciplinary joint clinic or based on follow-up of clinical and neuroimaging findings. RESULTS: Forty-one of 72 patients (57%) showed recurrent disease on FET PET. Thirty-five of them were confirmed to have tumor recurrence; six patients showed post-treatment changes. Thirty-one of 72 patients (43%) showed post-treatment changes on FET PET; 27 were confirmed as post-treatment change and four patients had tumor recurrence on subsequent MR imaging. An optimum T/Wm cutoff of 2.65 was derived based on receiver operating characteristic analysis with a sensitivity of 80% and specificity of 87.5%. CONCLUSION: Static FET PET can be used as problem-solving imaging modality with a T/Wm cutoff of 2.65 to differentiate late recurrence from post-treatment changes in grade 3 or 4 brain gliomas with equivocal MR features.

Unusual Variant of Breast Cancer Presenting With Pituitary Symptoms Detected on 68Ga-DOTATATE PET/CT.

ABSTRACT: Carcinoma of breast with neuroendocrine differentiation is an extremely rare entity, especially in male population. Although the "garden variety" of male breast cancers is often metastatic at presentation, with an aggressive course, there is hardly any literature about neuroendocrine variants. We report a case of a 57-year-old man who had pituitary symptoms, which on 68Ga-DOTANOC PET/CT imaging turned out to be a metastatic lesion, with somatostatin expressing primary in breast and other sites, with histopathological confirmation of neuroendocrine differentiation in breast cancer.

Prognostic significance of 18F-FDG PET/CT parameters in IDH-1 wild-type GBM and correlation with molecular markers.

AIM: To assess the prognostic role of metabolic parameters on 18F-FDG PET/CT & correlation with molecular markers in IDH-1 wild-type GBM. METHODS: A total of 129 patients with brain lesions showing equivocal findings on baseline MRI who were referred for fluoro-deoxy-glucose PET/CT were analyzed. Of these, 50 underwent surgery/biopsy and postoperative histopathological diagnosis of IDH-1 wild-type GBM. SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG) & T/w ratio was calculated. Median metabolic parameters were used for stratification. Overall survival was calculated using Kaplan-Meier method and was compared using log rank test. P value < 0.05 was considered significant. Multivariate analysis was done using Cox proportional hazard model. Correlation between metabolic parameters and molecular markers was done using Mann-Whitney U test. RESULTS: Median of SUVmax, T/w ratio, MTV, TLG, 18.3, 2.09, 61, 409. Average overall survival (OS) for T/w ratio >2.08 was 5 months, <2.08 was 18 months (P value 0.001). For MTV >61 was 4 months, <61 was 18 months (P value 0.001). Similarly, for TLG >409 was 5 months while for <409 was 19 months (P value 0.001). SUVmax was not significant for OS. In multivariate analysis, age was the statistically significant independent prognostic factor. CONCLUSION: Metabolic parameters of fluoro-deoxy-glucose PET/CT help in prognosticating IDH-1 wild-type GBM. Higher MiB-1 index correlates with higher T/w ratio and is associated with poor overall survival.

Rare Presentation of Radiation-induced Sarcoma Detected on F-18 FDG Positron Emission Tomography/Computed Tomography in a Treated Case of Giant Cell Tumor.

Giant cell tumors (GCTs) are benign bone lesions which are treated with curettage and bone grafting. Infrequently, GCTs show local site recurrences which are then treated with either surgical excision or radiation therapy. Radiation-induced sarcoma is rarely seen as a late complication of radiation therapy which needs to be differentiated from recurrent GCT. We report one such rare case of radiation-induced sarcoma detected on Flourine-18 fluorodeoxyglucose (18F FDG) positron emission tomography/computed tomography in a 40-year-old male who was treated with radiation therapy for recurrent GCT 9 years ago.

Utility of FET-PET in detecting high-grade gliomas presenting with equivocal MR imaging features.

High-grade gliomas, metastases, and primary central nervous system lymphoma (PCNSL) are common high-grade brain lesions, which may have overlapping features on magnetic resonance (MR) imaging. Our objective was to assess the utility of 18-fluoride-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) in reliably differentiating between these lesions, by studying their metabolic characteristics. Patients with high-grade brain lesions suspicious for glioma, with overlapping features for metastases and PCNSL were referred for FET-PET by Neuroradiologists from Multidisciplinary Neuro-Oncology Joint Clinic. Tumor-to-contralateral white mater ratio (T/Wm) at 5 and 20 min was derived and compared to histopathology. Receiver operating characteristic curve analysis was used to find the optimal T/Wm cutoff to differentiate between the tumor types. T/Wm was higher for glial tumors compared to nonglial tumors (metastases, PCNSL, tuberculoma, and anaplastic meningioma). A cutoff of 1.9 was derived to reliably diagnose a tumor of glial origin with a sensitivity and specificity of 93.8% and 91%, respectively. FET-PET can be used to diagnose glial tumors presenting as high-grade brain lesions when MR findings show overlapping features for other common high-grade lesions.