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.

Clinical Concept-Based Radiology Reports Classification Pipeline for Lung Carcinoma.

Rising incidence and mortality of cancer have led to an incremental amount of research in the field. To learn from preexisting data, it has become important to capture maximum information related to disease type, stage, treatment, and outcomes. Medical imaging reports are rich in this kind of information but are only present as free text. The extraction of information from such unstructured text reports is labor-intensive. The use of Natural Language Processing (NLP) tools to extract information from radiology reports can make it less time-consuming as well as more effective. In this study, we have developed and compared different models for the classification of lung carcinoma reports using clinical concepts. This study was approved by the institutional ethics committee as a retrospective study with a waiver of informed consent. A clinical concept-based classification pipeline for lung carcinoma radiology reports was developed using rule-based as well as machine learning models and compared. The machine learning models used were XGBoost and two more deep learning model architectures with bidirectional long short-term neural networks. A corpus consisting of 1700 radiology reports including computed tomography (CT) and positron emission tomography/computed tomography (PET/CT) reports were used for development and testing. Five hundred one radiology reports from MIMIC-III Clinical Database version 1.4 was used for external validation. The pipeline achieved an overall F1 score of 0.94 on the internal set and 0.74 on external validation with the rule-based algorithm using expert input giving the best performance. Among the machine learning models, the Bi-LSTM_dropout model performed better than the ML model using XGBoost and the Bi-LSTM_simple model on internal set, whereas on external validation, the Bi-LSTM_simple model performed relatively better than other 2. This pipeline can be used for clinical concept-based classification of radiology reports related to lung carcinoma from a huge corpus and also for automated annotation of these reports.

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.

An Audit of Systemic Therapy in Medullary Carcinoma Thyroid.

There is a paucity of evidence of the impact of sorafenib on MCT and it is the preferred therapy used in India. We decided to do an audit of all patients of MCT who were referred to us for systemic therapy. The objective of this exercise was to identify the treatment pattern, outcomes, and adverse events with therapy in MCT. Baseline demographics (age, gender, ECOG PS, comorbidities, habits), tumor details (site of metastasis), previous treatment details, clinical features at metastasis (symptomatic or asymptomatic), the pattern of treatment, adverse events (CTCAE version 4.02), date of progression, date of death and status, and follow-up were extracted from the rare tumor database and electronic medical records. Out of 75 patients referred for therapy for MCT, 47 (62.7%) patients were considered for immediate tyrosine kinase inhibitors as they had symptomatic status and 28 (37.3%) patients were kept on observation due to the asymptomatic nature of the disease. Out of the 28 patients, 15 (53.6%, n = 28) patients were subsequently started on TKI while in 13 (46.4%, n = 28) patients observation was continued. In the overall cohort, the median PFS was 18.9 months (95% CI 11.9-29.9) and OS was 26.6 months (95% CI 14.4-39.0). Among variables tested, only female gender had an impact on PFS (hazard ratio = 0.364 95% CI 0.148-0.895; P = 0.028) and the absence of lung metastasis had a positive impact on OS (hazard ratio = 0.443 95% CI 0.207-0.95; P = 0.037). Most commonly used TKI was sorafenib (n = 61) and sunitinib in 1 patient. The most common adverse events with TKI were palmo-plantar dysesthesia (50, 80.6%) and oral mucositis (25, 40.2%). The strategy of treating symptomatic MCT and observing in asymptomatic MCT is associated with reasonable PFS and OS. Sorafenib is the most commonly used TKI in our setup and provides similar outcomes as globally.

Benign Metastasizing Leiomyoma and Findings on Fluorodeoxyglucose Positron Emission Tomography/Contrast-Enhanced Computed Tomography.

Benign metastasizing leiomyoma is a rare condition where benign smooth muscle tumors having a histological appearance similar to uterine leiomyoma are present at distant sites. This entity is commonly associated with a past history of hysterectomy done for uterine fibroids. The knowledge of the presence of significant fluorodeoxyglucose uptake in leiomyoma helped in the diagnosis of this condition in a 47-year-old patient who being evaluated for multiple unusual sites of metastases; this was further confirmed on histopathology.

Radiomics: a quantitative imaging biomarker in precision oncology.

Cancer treatment is heading towards precision medicine driven by genetic and biochemical markers. Various genetic and biochemical markers are utilized to render personalized treatment in cancer. In the last decade, noninvasive imaging biomarkers have also been developed to assist personalized decision support systems in oncology. The imaging biomarkers i.e., radiomics is being researched to develop specific digital phenotype of tumor in cancer. Radiomics is a process to extract high throughput data from medical images by using advanced mathematical and statistical algorithms. The radiomics process involves various steps i.e., image generation, segmentation of region of interest (e.g. a tumor), image preprocessing, radiomic feature extraction, feature analysis and selection and finally prediction model development. Radiomics process explores the heterogeneity, irregularity and size parameters of the tumor to calculate thousands of advanced features. Our study investigates the role of radiomics in precision oncology. Radiomics research has witnessed a rapid growth in the last decade with several studies published that show the potential of radiomics in diagnosis and treatment outcome prediction in oncology. Several radiomics based prediction models have been developed and reported in the literature to predict various prediction endpoints i.e., overall survival, progression-free survival and recurrence in various cancer i.e., brain tumor, head and neck cancer, lung cancer and several other cancer types. Radiomics based digital phenotypes have shown promising results in diagnosis and treatment outcome prediction in oncology. In the coming years, radiomics is going to play a significant role in precision oncology.

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.

Spectrum of Flurodeoxyglucose Positron Emission Tomography/Computerized Tomography Findings in Tumors and Tumor-Like Conditions of the Musculoskeletal System.

Bone and soft-tissue tumors display a wide range of metabolic activity on flurodeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT) imaging due to their varying histopathological features. Several benign tumors show high FDG uptake similar to that seen in malignant lesions and their metabolic characteristics can overlap. Certain benign tumors can potentially undergo malignant transformation and FDG PET/CT can play an important role in detecting malignant change. The intensity of metabolic activity on FDG PET/CT correlates with histological grade of malignant tumors and also acts as a valuable prognostic factor. FDG PET/CT plays an important role in the staging work up of bone and soft-tissue malignancies. It has been found to be superior to conventional imaging techniques primarily for detecting distant metastatic disease. Because of its ability to detect metabolic changes, FDG PET/CT is a very useful in assessing response to treatment. Metabolic response seen on FDG PET is a powerful surrogate marker of histopathological response to chemotherapy. The purpose of this article is to study the variable patterns of FDG uptake in tumors of the musculoskeletal system, describe the clinical utility of FDG PET/CT in predicting malignant change in benign tumors and discuss its role in staging, response assessment, and prognostication of malignant lesions.

Myeloid Sarcoma of the Prostatic Tissue Diagnosed on 18F-FDG PET/CT in Treated Case of Acute Myeloid Leukemia.

Myeloid sarcoma is a rare extramedullary manifestation of acute myeloid leukemia (AML) that often presents during remission or disease relapse. The most common site of relapse being, however, many rare sites has been reported in the existing literature. We are herewith presenting the case of a 27-year-old patient of AML who showed an unusual site of relapse on fluorodeoxyglucose positron emission tomography/computed tomography scan.

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.

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.

Improving accuracy of 18F-fluorodeoxyglucose PET computed tomography to diagnose nodal involvement in non-small cell lung cancer: utility of using various predictive models.

PURPOSE: To determine predictive models (PM) that could improve the accuracy for identifying metastatic regional nodes in non-small cell lung cancer based on both PET and CT findings seen on 18F-FDG PET CT. METHODS: Three hundred thirty-nine biopsy-proven NSCLC patients who underwent surgical resection and had a staging 18F-FDG PET CT were enrolled. PET parameters obtained were (1) presence of visual PET positive nodes, (2) SUVmax of nodes (NSUV), (3) ratio of node to aorta SUVmax (N/A ratio) and (4) ratio of node to primary tumour SUVmax (N/T ratio). CT parameters obtained were (1) short-axis diameter and (2) Hounsfield units (HU) of PET-positive nodes. PET and CT parameters were correlated with nodal histopathology to find out the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy. Different PM combining these parameters were devised and the incremental improvement in accuracy was determined. RESULTS: Visual PET positivity showed sensitivity, specificity, PPV, NPV and accuracy of 72.4, 76.1, 30.1, 95.1 and 75.6, respectively. PM2 which combined visual PET positivity, NSUV and HU appears more clinically relevant and showed sensitivity, specificity, PPV, NPV and accuracy of 53.5, 96.5, 68.9, 93.6 and 91.2, respectively. PM6 which combined visual PET positivity, NSUV, N/A ratio and HU showed the maximum PPV (80.0%), specificity (98.3%) and accuracy of (91.9%). CONCLUSION: PM combining parameters like nodal SUVmax, N/A ratio, N/T ratio and HU values have shown to improve the PPV, specificity and overall accuracy of 18FDG PET CT in the preoperative diagnosis of nodal metastases.

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.