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.

Diagnostic performance of F-18 FDG PET/CT in recurrent adenocarcinoma gallbladder and its impact on post-recurrence survival.

PURPOSE: To analyze diagnostic performance of F-18 FDG PET/CT in recurrent adenocarcinoma gallbladder (GBC) and to establish its possible impact on post-recurrence survival. METHOD: FDG PET/CT studies of suspected recurrent GBC were retrospectively analyzed alongside tumor markers serum CEA and CA 19-9. Abnormal FDG-avid lesions and abnormal morphological lesions were considered positive for recurrence, and were categorized as isolated abdominal wall recurrence, loco-regional recurrence, and distant metastatic disease. Histopathology, definite progression on imaging and positive response to treatment was considered as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were used as diagnostic performance parameters. Post-recurrence survival was calculated whenever appropriate follow-up was available, based on the abovementioned categories of sites of recurrence using survival curves and log-rank test. RESULTS: Out of 117 PET/CT studies, 93 (79.5%) were positive and 24 (20.5%) were negative for recurrence. 86 out of 93 were true positive and 23 of 24 were true negative. PET/CT demonstrated sensitivity, specificity, PPV, NPV and accuracy of 98.8%, 76.7%, 92.5%, 95.8% and 93.1%, respectively. Diagnostic performance of PET/CT was significantly better than combination tumor markers. Of 66 cases with available follow-up, isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence demonstrated significantly higher post-recurrence survival as compared to distant metastasis; median survival being 39, 25 and 12 months, respectively. CONCLUSION: F-18 FDG PET/CT has better diagnostic performance than tumor markers combination. Isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence on PET/CT demonstrated better survival than non-regional metastatic disease. These results suggest a possible role of PET/CT as a surveillance modality, as well as a guide to therapeutic decision-making in cases of recurrent GBC.

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.

Mebendazole plus lomustine or temozolomide in patients with recurrent glioblastoma: A randomised open-label phase II trial.

Background: Recurrent glioblastoma (GBM) has dismal outcomes and limited treatment options. Mebendazole (MBZ) has activity in glioma both in-vivo and in-vitro, and is well tolerated in combination with lomustine (CCNU) and temozolomide (TMZ). In this study, we sought to determine whether the addition of MBZ to CCNU or TMZ would improve overall survival (OS) in recurrent GBM. Methods: In this phase II randomized open-label trial, adult patients with ECOG PS 0-3, with recurrent GBM who were not eligible for re-radiation, were randomized 1:1 to the CCNU-MBZ and TMZ-MBZ arms. CCNU was administered at 110 mg/m2 every 6 weeks with MBZ 800 mg thrice daily and TMZ was administered at 200 mg/m2 once daily on days 1-5 of a 28 days cycle with MBZ 1600 mg thrice daily. The primary endpoint was OS at 9 months. A 9-month OS of 55% or more in any arm was hypothesized to warrant further evaluation and a value below 35% was too low to warrant further investigation. OS was analyzed using intention to treat (ITT) and per-protocol (PP) analyses. Per-protocol analysis was used for safety analysis. Clinical Trials Registry-India number, CTRI/2018/01/011542. Findings: Participants were recruited from 14th March 2019 to 18th June 2021, 44 patients were randomised on each arm. At 17.4 months, 68 events for OS analysis had occurred, 33 in the TMZ-MBZ and 35 in the CCNU-MBZ arm. The 9-month OS was 36.6% (95% CI 22.3-51.0) and 45% (95% CI 29.6-59.2) in the TMZ-MBZ and CCNU-MBZ arms respectively, in the ITT population. ECOG PS was the only independent prognostic factor impacting OS (HR-0.48, 95% CI 0.27-0.85; P = 0.012). Grade 3-5 adverse events were seen in 8 (18.6%; n = 43) and 4 (9.5%; n = 42) patients in the TMZ-MBZ and CCNU-MBZ arms respectively. There were no treatment related deaths. Interpretation: The addition of MBZ to TMZ or CCNU failed to achieve the pre-set benchmark of 55% 9-month OS. This was probably due to 28.6% of patients having poor PS of 2-3. Funding: Brain Tumor Foundation (BTF) of India, Indian Cooperative Oncology Network (ICON), and India Cancer Research Consortium (ICRC) under ICMR (Indian Council of Medical Research).

Prognostic value of lung shunt fraction in hepatocellular carcinoma and unresectable liver dominant metastatic colorectal cancer undergoing transarterial radioembolisation.

AIM: To assess the overall survival and determine whether pre-TARE shunt fraction, tumor volume and tumor marker impact the outcome. METHODS: This is a retrospective study of 75 patients who were referred for 90Y-glass microsphere radioembolisation by a joint clinic decision between 1 January 2010 and 31 December 2014. All patients underwent pre-TARE CECT and 99mTc-MAA lung shunt fraction (LSF) imaging. RESULTS: Overall survival was 19 months for hepatocellular carcinoma (HCC) and 24 months for metastatic colorectal carcinoma. For hepatocellular carcinoma-LSF higher than 6.51 % was predictive of significantly decreased survival (P value 0.00). A progressive disease in survival was observed as LSF increased from less than 6.51 % to more than 20%. Tumor volume and tumor marker did show correlation with patient outcomes. For metastatic colorectal carcinoma-LSF and tumor marker did not show significant correlation with survival and tumor volume showed significant correlation with survival with P value of 0.049.

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.

Pelvic Venous Thromboembolism Leading to Pulmonary Embolism in a Case of Chondroblastic Osteosarcoma Detected on FDG PET/CT.

Chondroblastic osteosarcoma is an uncommon subtype of osteosarcoma, constituting about 25% of all osteosarcoma cases. It has shown high propensity for developing tumor thrombi and thromboembolism, with poor overall survival rate. Differentiation between tumor thrombus and bland thrombus is an important factor in making treatment decisions. 18 F fluorodeoxyglucose positron emission tomography/computed tomography plays a very important role in detecting and differentiating bland thrombus from tumor thrombus.

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.

Target Heterogeneity in Oncology: The Best Predictor for Differential Response to Radioligand Therapy in Neuroendocrine Tumors and Prostate Cancer.

Tumor or target heterogeneity (TH) implies presence of variable cellular populations having different genomic characteristics within the same tumor, or in different tumor sites of the same patient. The challenge is to identify this heterogeneity, as it has emerged as the most common cause of 'treatment resistance', to current therapeutic agents. We have focused our discussion on 'Prostate Cancer' and 'Neuroendocrine Tumors', and looked at the established methods for demonstrating heterogeneity, each with its advantages and drawbacks. Also, the available theranostic radiotracers targeting PSMA and somatostatin receptors combined with targeted systemic agents, have been described. Lu-177 labeled PSMA and DOTATATE are the 'standard of care' radionuclide therapeutic tracers for management of progressive treatment-resistant prostate cancer and NET. These approved therapies have shown reasonable benefit in treatment outcome, with improvement in quality of life parameters. Various biomarkers and predictors of response to radionuclide therapies targeting TH which are currently available and those which can be explored have been elaborated in details. Imaging-based features using artificial intelligence (AI) need to be developed to further predict the presence of TH. Also, novel theranostic tools binding to newer targets on surface of cancer cell should be explored to overcome the treatment resistance to current treatment regimens.

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.

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.

Incidentally Detected COVID-19 Lung Changes during Oncologic Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography Studies: Experience from Tertiary Care Cancer Hospital.

OBJECTIVE: The objective is to evaluate incidental detection of COVID-19 lung involvement in asymptomatic individuals who undergo fluorodeoxyglucose (FDG) positron emission tomography-computerized tomography (PET/CT) scans for oncologic indications. PATIENTS AND METHODS: The study was conducted in a tertiary care oncology hospital and included patients who were asymptomatic for COVID-19 infection and underwent FDG PET/CT scans for standard oncologic indications between April 15, 2020, and September 30, 2020. Patients who showed CO-RADS category 4/5 changes (high level of suspicion) on the CT chest component of the PET/CT study were considered for analysis. CT severity score, presence of FDG uptake, and maximum standardized uptake value of FDG avid lung involvement were noted and correlated with reverse transcriptase-polymerase chain reaction (RT-PCR) test. RESULTS: 1982 PET/CT scans were performed, 78 (3.9%) patients showed lung changes with high degree of suspicion of COVID-19 pneumonia (CO-RADS 4/5). Hematolymphoid and head-neck cancer were the most common tumor types (23%), and restaging/response evaluation was the most common PET/CT indication. Of the patients who underwent RT-PCR testing, 70% showed a positive result. The mean CT severity score was 6 (standard deviation 5.9) with no significant difference seen between the RT-PCR positive and negative groups. FDG avidity in lung lesions was noted in 41 out 57 (72%) patients. A significant correlation was seen between the RT-PCR positivity and FDG uptake in lung lesions. CONCLUSION: A small but significant proportion of patients undergoing routine oncologic PET/CT scans showed incidental COVID-19 lung involvement. Lung involvement in these asymptomatic patients showed a low CT severity score in all patients and FDG avidity in majority. Timely detection of such incidental cases can initiate further confirmatory RT-PCR testing and isolation measures that not only influence patient's cancer treatment protocols but also have a larger community impact of limiting the spread of infection.

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.

Prognostic value of imaging-based parameters in patients with intermediate-stage hepatocellular carcinoma undergoing transarterial radioembolization.

OBJECTIVE: Patients with inoperable multilobar hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage B, who have failed other liver-directed treatment options, are ideal candidates for transarterial radioembolization (TARE) with Yttrium-90 (Y-90)-labeled glass spheres. There is limited data regarding variables that impact the prognosis and outcome in these patients. 99mTc-MAA scan for lung shunt fraction (LSF) and 18F-FDG PET/CT are performed during initial workup. We, therefore, decided to assess the prognostic impact of LSF and metabolic parameters, such as maximum SUVmax, MTV and TLG in patients undergoing TARE for HCC. METHODS: We retrospectively analyzed 64 patients of HCC, between January 2010 and December 2016, deemed suitable for TARE. Pre-TARE LSF was computed on 99mTc MAA scan, and SUVmax, MTV and TLG on fluoro-deoxyglucose positron emission tomography/computed tomography were measured using automated software by 3D region of interest. LSF and PET parameters were stratified using optimal cut-offs derived from receiver operating curve analysis. Survival curves for the groups were estimated using the Kaplan-Meier method and were compared using log-rank test. RESULTS: Overall survival (OS) was 15 months. In univariate analysis, high LSF (greater than 7.19), MTV and TLG were statistically significant and were associated with poor OS. In multivariate analysis, TLG (P value 0.044), MTV (P value 0.290) and LSF (P value 0.010) were independent predictors of outcome, after adjustment for significant univariate variables. However, SUVmax was not statistically significant for OS. CONCLUSIONS: LSF, MTV and TLG are significant independent prognostic indicators of outcome in patients undergoing TARE for HCC.

Regorafenib-Associated Acute Pancreatitis Diagnosed on 18F-FDG PET/CT.

ABSTRACT: A 23-year-old man with metastatic osteosarcoma, with disease progression on conventional chemotherapy, was treated with regorafenib, a multikinase inhibitor. After treatment for 6 months with regorafenib, 18F-FDG PET/CT scan demonstrated FDG uptake in a necrotic space-occupying lesion involving tail of pancreas. After imaging, patient described symptoms of epigastric pain with elevated serum amylase and lipase levels, confirming diagnosis of regorafenib-induced pancreatitis, because patient had no other causative factors of pancreatitis. Physicians should be aware of rare and possibly clinically silent adverse effects of tyrosine kinase inhibitors, like acute pancreatitis, and recognize the 18F-FDG PET/CT findings to guide appropriate clinical management.

Nuclear Medicine in India: Are We Pandemic Ready?

There is a sudden upsurge in the literature over the last fortnight on strategies to be followed by imaging services during this SARS-CoV-2 global pandemic. This compilation of strategies, experiences, and precautions is intended to support nuclear medicine departments, as they make decisions regarding patient care. These guidelines are a good resource to tackle the current crisis, however, situations such as these may occur again, and long-term readiness measures need to be discussed and implemented.

Reverse swing-M, phase 1 study of repurposing mebendazole in recurrent high-grade glioma.

BACKGROUND: Relapsed high-grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in-vitro and in-vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma. METHODS: We conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re-irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 day 1-5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination. FINDINGS: 11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%). INTERPRETATION: The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide-radiation combination while the dose of 800 mg TDS needs to be used with single-agent CCNU.