Pakistan Journal of Nuclear Medicine

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Novel targeted therapies tailored to the molecular profile of tumors have revolutionized the treatment landscape for advanced radioiodine-refractory differentiated thyroid cancer (RAI-R DTC), showcasing notable progression-free survival rates. These emerging therapies, leveraging kinase inhibitors, exhibit a remarkable capacity to restore iodide uptake in RAI-R thyroid cancer cells. However, successful implementation relies on crucial factors like adopting a multidisciplinary team approach and timely initiation of targeted therapies.

Radioactive iodine therapy is non-invasive, well established and effective treatment for hyperthyroidism. However, there are concerns about its potential to cause thyroid cancer when used for benign thyroid diseases. While studies show mixed results, our observations indicate that the risk of cancer after RAI therapy for benign conditions is very low, given that pre-therapy nodules have been confirmed as benign either through sonographic examination or fine-needle aspiration cytology (FNAC). This perspective is grounded because the iodine dose used for benign thyroid diseases is low and causes cell death rather than cancer.

This commentary delves into the significance of molecular markers, specifically BRAF and TERT mutations, in refining risk stratification and management strategies for thyroid cancer, with a focus on optimizing radioactive iodine (RAI) doses. BRAFV600E mutation notably impacts risk classification in papillary thyroid cancer (PTC), elevating it to intermediate-risk status and affecting recurrence rates. Additionally, the inclusion of TERT promoter mutation in risk assessment categorizes PTC larger than 1cm as high-risk. The initial maximum permissible RAI dose, tailored to the respective risk group, targets heterogeneous tumor cell populations, including those with poor RAI uptake due to mutations, by utilizing the cross-fire effect of radiation, thereby reducing the risk of recurrence. BRAF mutational analysis aids in ruling out follicular neoplasms, while TERT mutational analysis facilitates tailored management, particularly in follicular tumors of uncertain malignant potential (FT-UMP). Although current guidelines don't advocate RAI dose modification based solely on molecular markers, ongoing research emphasizes the need for exploration. Proactive integration of BRAF and TERT mutational analysis pre-RAI therapy enhances risk stratification, facilitating personalized treatment decisions. It's recommended to conduct mutational analysis for BRAF and TERT genes before initiating RAI therapy in PTC and RAS+TERT in FTC for improved risk assessment and tailored RAI administration. As molecular insights advance, personalized approaches are vital for optimizing patient outcomes in thyroid cancer management

Background: Thyroid cancer recurrence poses a significant challenge in oncology, necessitating effective tools for early prediction. Machine learning models offer the potential to improve prognostic accuracy and guide clinical decision-making. Aim and Objective: This study aims to investigate the efficacy of machine learning models in predicting thyroid cancer recurrence using a publicly available dataset comprising 17 features. Methods: We explored multiple machine learning algorithms, including Logistic Regression, K-Nearest Neighbors (KNN), Random Forest, and AdaBoost, to develop predictive models. The target variable was the "Recurred" column, indicating whether a patient experienced recurrence. Performance evaluation was conducted using metrics such as Accuracy, Precision, Recall, F1 Score, and ROC AUC. A correlation heatmap was generated to assess relationships between features and detect multicollinearity, while feature importance analysis using the Random Forest model identified key predictors. Results: Among the models, the Random Forest classifier achieved the highest performance on the test dataset, with an Accuracy of 0.9818, Precision of 0.9623, Recall of 1.0000, F1 Score of 0.9808, and ROC AUC of 0.9831. The feature importance analysis highlighted critical factors influencing recurrence prediction, while the correlation heatmap provided insights into feature interactions. Conclusion: This study demonstrates the effectiveness of machine learning models, particularly the Random Forest classifier, in predicting thyroid cancer recurrence. The insights gained from feature analysis and correlation studies contribute to model interpretability and future feature selection strategies. These findings emphasize the potential of machine learning in improving patient outcomes through early and accurate recurrence prediction.

Objectives: This study aimed at correlation of ultrasound findings with fine needle aspiration cytology (FNAC) results using the Bethesda system, providing insights into thyroid nodule pathology. Material and Methods: A retrospective analysis involving 104 patients was performed at Punjab Institute of Nuclear Medicine (PINUM) between July 5, 2023, and July 1, 2024. The study encompassed patients of all ages and genders diagnosed with cold thyroid nodules (solitary and with multinodular goiter) through thyroid nuclear scans. The exclusion criteria included diffuse goiter, hot nodules, recurrent thyroid cancers, and metastases. Ultrasound evaluations included the assessment of nodule composition and FNAC outcomes were classified according to the Bethesda system. Statistical analysis was conducted using SPSS version 24, with a significance threshold set at a P-value of less than 0.05. Results: The majority of patients were female (94%); and the right side being the most frequently affected (57%). Benign cases dominated in all nodule categories. Solid single nodules demonstrated an increased risk of follicular neoplasm and malignancy. Spongiform nodules were primarily benign. Ultrasound findings demonstrated an 80% correlation with fine needle aspiration cytology outcomes. Conclusion: Ultrasound, in conjunction with FNAC as reported on the Bethesda system, is highly useful in discriminating benign and malignant thyroid nodules, and it is suggested as a primary screening method for patients with thyroid nodules. Keywords: Ultrasound (US), Fine Needle Aspiration Cytology (FNAC), Thyroid Nodule (TN).

ABSTRACT Thyroid cancer is the most frequent endocrine cancer worldwide. Early-stage thyroid cancer is commonly asymptomatic but can proceed to cause major symptoms like neck swelling which lead to difficulty in swallowing. Thyroid glands are necessary for hormone production and for managing multiple bodily processes but malfunctioning may lead to thyroid malignancy. Precise diagnosis, typically, the foundation of affective treatment and restoration of normal body functions. Focusing on radiopharmaceuticals, this review outlines the recent developments as well as the promising prospects for thyroid cancer diagnostics and treatment. In addition to enhancing patient's treatment outcomes, the targeted diagnosis and medications makes possible more effective individualized treatment plans. Examining current advancements in radiopharmaceuticals that improve treatment efficacy and diagnostic accuracy, the review also addresses potential future prospects for this field of study and clinical practice.

Historically, dosimetry has been conducted with varying degrees of sophistication. A broad and general approach involves computing organ-specific time-integrated activity multiplied by S-factors, as defined by the Medical Internal Radiation Dose (MIRD) Committee. This method uses a standard human body phantom as a reference for mass density distribution. More advanced methods, such as the voxel dose approach, estimate absorbed dose by linearly superimposing contributions from each voxel in the spatial activity distribution, treating each voxel as a radiation point source. The energy dose from a radiation point source with isotropic unit activity in an infinite homogeneous medium is known as a dose point kernel (DPK). Previously, DPKs were calculated using Monte Carlo techniques for tissues like bone, lung, soft tissue, and water, primarily for isotopes such as Iodine-131 and Yttrium-90. Later, continuous DPKs were discretized into dose voxel kernels (DVKs) that can be arbitrarily scaled. The absorbed dose distribution is then derived by convolving the time-integrated spatial activity distribution with the Monte Carlo-based DVK, based on the patient's anatomy. Due to the computational expense of this process, various methods have been explored to estimate approximate DVKs. The highest level of sophistication is achieved with full Monte Carlo simulations of radiation transport inside the patient's body, providing reference results for benchmarking other approaches. The network is trained with DVKs obtained from dedicated Monte Carlo simulations using equally sized kernels of specified tissue density and a specified radioisotope. This method is intermediate between the canonical MIRD protocol and deep neural network approaches that predict whole-body absorbed dose distributions from individual mass density and activity distributions. In this paper, we have discussed and compared all the commonly employed dosimetric method along with new approaches using artificial intelligence.

ABSTRACT External Beam Radiation Therapy (EBRT) involves using high-energy x-rays or particle beams targeted at malignant tissues, with the goal of destroying tumor cells while minimizing damage to healthy surrounding structures. However, the indication and timing of EBRT vary considerably depending on the specific histological subtype of thyroid cancer, the presence of metastatic or unresectable lesions, and individual patient factors such as comorbidities and prior treatments. Moreover, the therapeutic benefit of EBRT must be balanced against potential side effects, making patient selection and protocol design pivotal components in managing advanced thyroid cancer. This article explores the role of EBRT in thyroid cancer, with particular attention to when it is recommended, the patient populations that benefit most, and how to optimize treatment protocols. By illuminating current best practices and emerging evidence, we aim to guide clinicians in deciding when and how to incorporate EBRT into a multidisciplinary treatment plan for thyroid cancer.

Background: Patients having papillary thyroid malignancy along with lymph adenopathy may cause diagnostic dilemmas. It is important to characterize these lymph nodes as metastasic or concomitant lymphoproliferative disease. The development of papillary thyroid carcinoma (PTC) as the second malignancy has been reported frequently after neck irradiation for lymphoma treatment but their coexistence in patients without any history of radiotherapy is very unusual and has been reported only in a few cases. Case Presentation: We present a 56-year-old female patient having thyroid nodule and cervical lymphadenopathy. The patient did not have significant past medical history, or history of neck irradiation but have intermittent signs of compression, including dysphagia and dysphonia. A neck ultrasound revealed a 3 cm solid hypoechoic nodule with suspicious features in the right lobe of the thyroid gland along with bilateral jugulodigastric and left supraclavicular lymphadenopathy. Ultrasound-guided fine-needle aspiration biopsy of the right-sided thyroid nodule revealed PTC, while supraclavicular lymph node biopsy surprisingly revealed classical Hodgkin's lymphoma with nodular sclerosis. Conclusion: Although in patients with cervical lymphadenopathy and concomitant thyroid carcinoma, lymphatic metastasis is the most common diagnosis, but the possibility of synchronous thyroid cancer and lymphoma should not be ignored to optimize the management.

Background: Thyroid nodules are frequently encountered, with 5%-10% being malignant. Follicular thyroid carcinoma (FTC) is a differentiated thyroid malignancy, known for hematogenous spread to distant sites such as lungs, bones, and less commonly, soft tissues. We report a rare case of FTC with isolated metastasis to the scapula. Case Description: A 55-year-old female initially presented with a thyroid mass. A diagnostic workup followed by FNAC revealed follicular neoplasm. The patient underwent a right lobectomy and then a total thyroidectomy. The patient was diagnosed with follicular carcinoma on biopsy and was given radioactive iodine (RAI) therapy. The patient was on regular yearly follow-up for 6 years and then lost to follow-up for 3 years due to the corona pandemic. Despite initial treatment and maintenance on levothyroxine, she presented nine years later with a painful, enlarging mass in her right shoulder. Imaging (X-ray, CT, and MRI) and ultrasound-guided core biopsy were performed to diagnose the lesion. Results: Imaging revealed a large, infiltrative malignant lesion in the right scapula, causing extensive bone and muscle destruction. Biopsy confirmed metastatic FTC. The second therapeutic dose of 200 mCi of radio-iodine (I-131) was given. Post therapy scan showed significant radioiodine uptake in the scapula, indicating active metastatic disease. The patient was then treated with monthly injections of Zometa for bone strengthening and continues to be monitored. Conclusion: This case underscores the necessity for vigilant long-term follow-up in FTC patients due to the potential for late metastatic presentations. The multidisciplinary approach, involving imaging, pathology, and nuclear medicine, is crucial for accurate diagnosis and effective management of metastatic FTC. This case highlights the role of appropriate counseling of the patient regarding the need for long-term follow-ups, keeping in mind the possibility of distant metastasis late after the initial presentation.

About the Cover (PJNM_14(2)) Thyroid Insights This special issue explores the essential role of nuclear medicine in thyroid disorder management. It showcases advanced imaging technologies that enable precise diagnosis and highlights innovative targeted therapies transforming treatment strategies. Additionally, it emphasizes nuclear medicine's impact on treatment accuracy and improved patient outcomes. This issue offers valuable insights for enhancing clinical practice and advancing thyroid care.