Correlation between F18-FDG PET/CT Imaging and BRAF V600E Genetic Mutation for the Early Assessment of Treatment Response in Papillary Thyroid Cancers.

In thyroid neoplastic pathology, the BRAF V600E mutation is shown to be involved in the oncogenesis of papillary thyroid cancer and its subtypes. The purpose of this study is to evaluate the correlation between the mutation of the BRAF V600E oncogene and the pathological standardized uptake values (SUV) at the F18-fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography (PET/CT) evaluation, for a group of 20 patients with radically treated (total thyroidectomy and radioiodine therapy) papillary thyroid cancer, with subclinical persistent disease, at 6 months after the initial treatment. We analyzed the correlations between the values of SUV and the presence of the BRAF mutation as well with other prognostic factors such as stage, age, specific tumor markers (thyroglobulin and anti-thyroglobulin), extrathyroid extension, the presence of metastatic lymph nodes or distant metastasis. The value of SUV in the case of BRAF+ (positive) patients was higher than in the negative ones, but without statistical significance, thus, the values of the SUV cannot be a predictable factor for the presence of the genetic mutation. There was a statistically significant correlation in BRAF+ subgroup between the SUV values and the positive resection limit following surgery, showing a higher SUV value in the PET/CT evaluation. No correlation was observed between the aforementioned prognostic factors involved in papillary thyroid cancer and the BRAF V600E mutation.

Post-Treatment Thyroid Diseases in Children with Brain Tumors: A Single-Center Experience at "Prof. Dr. Ion Chiricuța" Institute of Oncology, Cluj-Napoca.

AIM OF STUDY: The purpose of the study was to evaluate the association of thyroid dysfunction occurring in pediatric patients treated for brain tumors. PATIENTS AND METHODS: A total of 255 patients with brain tumors were treated between 2001 and 2018 at the "Prof. Dr. Ion Chiricuța" Institute of Oncology, Cluj-Napoca. Due to a minimum follow-up of 4 years, we studied 184 out of the 255 patients. The cohort included 69 girls (37.5%) and 109 boys (62.5%), with a median age of 8.4 years. The evaluated tumors included medulloblastomas (47 patients), astrocytomas (44 patients), ependymomas (22 patients), gliomas (20 patients), germ cell tumors (12 patients), primitive neuroectodermal tumors (4 patients), as well as other types of tumors (15 patients); in 20 of the cases, biopsy could not be performed. RESULTS: There was a 60% overall survival rate; among the 120 surviving patients, 11 (9.1%) were diagnosed with iatrogenic thyroid disease. We observed an important number of iatrogenic thyroid disease cases in this group of patients, thus revealing the importance of long-term thyroid function evaluation in all children who finalized their treatment for brain tumors. Through this study, we aimed to provide an accurate image of the methodology of monitoring for thyroid dysfunction in childhood brain tumor survivors. CONCLUSION: Given the fact that the probability of developing thyroid dysfunction in the pediatric population treated for brain tumors is not rare, we recommend that childhood brain tumor survivors be monitored for iatrogenic thyroid disease, in order to provide early diagnosis and treatment.

Current evidence on thyroid related adverse events in patients treated with protein tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKI) are gaining more ground in oncology, they are widely used in the treatment of multiple types of cancers; still important side effects limit their efficacy. The aim of this study is to evaluate the existing medical literature on TKI induced thyroid dysfunction, to assess the adverse effects of targeted therapy on thyroid function in oncological patients and to evaluate the effects of thyroid dysfunction on disease prognosis. We included in this review 22 original studies published between 2010 and 2019. We used the PubMed database to search for articles upon the development of hypothyroidism and hyperthyroidism in TKI treated patients. After a careful review of the existing literature, we selected the relevant studies and cross-referenced the bibliography of each paper. A number of 1641 patients were included in our review. We found that thyroid dysfunction is not a rare side effect of TKI treatment, approximately 33% of the total number of patients presented clinical hypothyroidism. We also studied the necessity of thyroid hormone substitution treatment, a quarter of evaluated patients needed substitution therapy. Multiple studies showed that there is a link between a patient developing hypothyroidism and progression free survival. Hypothyroidism is a frequent side effect of TKI treatment, which affects the quality of life, sometimes even determines physicians to stop TKI treatment altogether. Our study underlines the necessity of TSH baseline testing and monitoring in patients treated with TKI agents.

Evaluation of Malignancy Risk in 18F-FDG PET/CT Thyroid Incidentalomas.

Thyroid incidentalomas detected by 18 fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography/computed tomography (PET/CT) are a real challenge for nuclear medicine physicians and clinicians. This study aimed to evaluate the risk of malignancy for patients with focal thyroid incidentalomas (TIs) diagnosed through FDG PET/CT. Data from 6900 patients, with a known primary tumor, who had an FDG PET/CT investigation performed were analyzed for the presence of incidental thyroid uptake. The focal TIs were reported, and the patients were referred for further investigation to the endocrinology department. There were 126 patients (1.82%) who presented with focal thyroid uptake, and for 87 of them, investigations were completed with ultrasonography (US), and for 29 with a fine needle aspiration biopsy (FNAB) procedure. Malignancy was detected in 7.93% (10/126) of cases. An arbitrary cutoff value of four was established for the standard uptake value lean body mass (SUVlbm Max) to differentiate the malignant nodules from the benign ones, and this value was significantly associated with malignancy (p = 0.0168). TIs are not so frequent, but they have a potential malignancy risk, and a proper evaluation is required. Even though SUVlbm Max is a predictive factor for malignancy, the FNAB remains the main diagnostic method for the therapeutic management of these patients.

Radiation induced thyroid carcinoma in Romania - effects of the Chernobyl fallout, a systematic review of observational studies.

INTRODUCTION: The development of thyroid carcinoma is a complex process, in which both genetic and environmental factors play an important role. The rising incidence of thyroid neoplasm determines researchers to investigate factors implicated in this phenomenon. This article aims to elucidate the effects of the Chernobyl nuclear disaster on the Romanian population, studying the existing literature on radiation induced thyroid carcinoma. We analyzed the main studies published on this matter. METHODS: We used the PubMed and Google Scholar databases to search for articles upon the effects of the Chernobyl nuclear disaster on the incidence of thyroid carcinoma in the Romanian population. After a careful review of the existing literature, we selected the relevant and accessible studies, the first observation being that data on thyroid related effects of the Chernobyl nuclear disaster are scarce. RESULTS: From the selected studies, results show that there is a possible link between the Chernobyl fallout and the incidence of thyroid carcinoma. Multiple factors have been studied that play an important role in the increasing number of thyroid carcinoma cases, such as: better diagnostic techniques, incidentalomas, microcarcinomas and radiation exposure. In consequence it is difficult to measure the influence that the Chernobyl nuclear fallout has on thyroid carcinoma incidence. CONCLUSION: Especially in pediatric patients, there seems to be a convincing evidence of radiation related thyroid carcinoma, while in adult patients the rising incidence due exclusively to nuclear fallout is not that clear. Further studies must be done on this matter to clearly see the influence radiation has on the incidence of thyroid cancer.

Psychological impact of 131I radioprotection measures on thyroid cancer patients.

BACKGROUND AND AIMS: It is very well know nowadays that despite all the good and qualitative information available, the patients who are supposed to be treated with radioiodine for differentiated thyroid cancer suffer from a lot of concerns prior the treatment. The aim of our study is to investigate the level of anxiety and lessening of the concerns pre and post RIT (radioiodine therapy) using a dedicated, special designed questionnaire. METHODS: A cross-sectional study of 54 differentiated thyroid cancer patients was conducted. Patients who met the inclusion criteria were invited to complete the radioprotection questionnaire pre and post RIT. The questionnaire comprises two sections (pre and post radioiodine treatment) with specific questions regarding aspects of radioprotection measures and the impact on the overall well-being. For uniform distribution of variables we used Pearson correlation and for monotonic relationship between variables, Spearman correlation. RESULTS: The pre-treatment questionnaire reported a strong confidence of the patients in the medical team, good and accurate information regarding the treatment, >50 % suffering from anxiety and concerns before the radioiodine treatment. The post treatment questionnaire revealed no fear of isolation, a lot of useful information and most of the patients would undergo another treatment, if necessary and also recommend it to others. CONCLUSION: The milestone in having a good and compliant patient remains a very good communication between the medical team and the patient. We are able to influence and change things and have fewer patients with fear from radioactivity and treatment concerns if we dedicate enough time to give them the adequate information in the best way so it will be correctly received.

Quantification of Radiation Exposure of Non-Dominant Index for the Surgeon Performing Sentinel Lymph-Node Removal Procedure.

BACKGROUND: Sentinel lymph-node scintigraphy is a useful method for accurate staging of different tumors and a helpful tool in personalized therapy for oncological patients. The radiation exposure for surgical staff has been a concern since the sentinel lymph-node detection method was developed. OBJECTIVE: The objective of the study was to determine and quantify the exposure to radiation of the non-dominant index for the surgeon performing sentinel lymph-node removal and to determine, if there is an irradiation risk imposed during the surgical procedure. METHOD: We performed a study over a period of one year, where we evaluated the exposure of surgeon's non-dominant index during 196 sentinel lymph-node removal procedures. The pharmaceutical was administrated via subcutaneous injection in four peritumoral or perilesional injection sites. The equipment we used consisted of EuroProbe3 for sentinel lymph-node detection and ring TLD dosimeter placed on the surgeon's non-dominant index. RESULTS: The clinical distribution was: 104 melanomas, 84 breast carcinomas, 6 vulvar carcinomas and 2 penial carcinomas. The administered activity showed an average of 39.55 MBq (SD ± 1.96) Tc-99m nanoalbumin compound. The non-dominant index exposure ranged between 0.10 mSv and 0.13 mSv/month with a cumulative dose of 1.31 mSv/year, thus 6.69 µSv per procedure. CONCLUSION: The surgeon received a minimal dose for the non-dominant index. The values we recorded did not pose any additional concerns or restrictions, the exposure being under the limits and constraints established by regulations, close to the detectability limit of the dosimeter. The procedure is safe in terms of radiation protection, respecting the limitation and optimization principles.

Quality of life in thyroid cancer patients: a literature review.

INTRODUCTION: Quality of life (QoL) has received increasing interest in the last years, especially in patients with cancer. This article aims to analyze a selection of medical research papers regarding the quality of life in patients with thyroid carcinoma. We overviewed the main QoL aspects derived from several studies and highlighted those less researched issues, which could represent a solid base for future clinical studies. METHOD: We used an integrative selection method of medical literature, choosing mostly "free access" studies, as it was considered that they could be easily viewed, searched and researched including by patients. RESULTS: After an integrative literature review, we selected 16 relevant studies. Patients with thyroid cancer have several factors influencing their QoL, with both physical and psychological impact. The decisive factors are the quality of the surgical act, radioiodine therapy, follow-up using rh-TSH vs. hormonal withdrawal, access to behavioral help and the relationship with their physician. CONCLUSION: We must understand the emotional impact of the cancer diagnosis on the patient and we must collaborate in order to help the patient restore the psychosomatic balance and to recover the quality of life.

Sentinel lymph node scintigraphy in cutaneous melanoma using a planar calibration phantom filled with Tc-99m pertechnetate solution for body contouring.

BACKGROUND AND AIMS: Melanoma is a disease that has an increasing incidence worldwide. Sentinel lymph node scintigraphy is a diagnostic tool that offers important information regarding the localization of the sentinel lymph nodes offering important input data to establish a pertinent and personalized therapeutic strategy. The golden standard in body contouring for sentinel lymph node scintigraphy is to use a planar flood source of Cobalt-57 (Co-57) placed behind the patients, against the gamma camera. The purpose of the study was to determine the performance of the procedure using a flood calibration planar phantom filled with aqueous solution of Technetion-99m (Tc-99m) in comparison with the published data in literature where the gold standard was used. METHODS: The study was conducted in the Department of Nuclear Medicine of Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca in 95 patients, 31 males and 64 females. The localization of the lesions was grouped by anatomical regions as follows: 23 on lower limbs, 17 on upper limbs, 45 on thorax and 10 on abdomen. The calibration flood phantom containing aqueous solution of Tc-99m pertechnetate was used as planar source to visualize the body contour of the patients for a proper anatomic localization of detected sentinel lymph nodes. The radiopharmaceutical uptake in sentinel lymph nodes has been recorded in serial images following peritumoral injection of 1 ml solution of Tc-99m albumin nanocolloids with an activity of 1 mCi (37 MBq). The used protocol consisted in early acquired planar images within 15 minutes post-injection and delayed images at 2-3 hours and when necessary, additional images at 6-7 hours. The acquisition matrix used was 128×128 pixels for an acquisition time of 5 - 7 minutes. The skin projection of the sentinel lymph nodes was marked on the skin and surgical removal of detected sentinel lymph nodes was performed the next day using a gamma probe for detection and measurements. RESULTS: The sentinel lymph nodes were detected in 92 cases and confirmed with the gamma probe during the surgical procedure. The localization of the lymph nodes was as follows: for the tumors localized on lower limb 23 lymph nodes were localized in inguinal region, for the tumors localized on upper limb, 17 lymph nodes were localized in axilla, for the tumors localized on the thorax, 40 lymph nodes were localized in axilla and 3 were localized in the inguinal region; for the tumors localized on the abdomen, 1 lymph node was localized in axilla and 8 lymph nodes was localized in inguinal region. Regarding the negative sentinel lymph node cases, 2 cases were registered for primarily lesions localized on thorax and 1 for a lesion localized on abdomen. According to histology, 26 cases revealed lymphatic metastatic invasion. Dose rates measured at 1m from the calibrator phantom had an average value of 3.46 µSv/h (SD 0.19) and at 1.4m, the value was 2.57 µSv/h (SD 0.22). Dose rates measured at the same distances from the Co-57 planar flood source had a average values of 32.5µSv/h (SD 0.11) respectively 24.1 µSv/h (SD 0.14). CONCLUSION: The planar calibration flood phantom is an effective tool for body contouring in sentinel lymph node scintigraphy and offers accurate anatomical information to efficiently localize the detected sentinel lymph nodes in melanoma, being for the first time used and mentioned as a pertinent alternative in our department.

Primary hyperparathyroidism-jaw tumor syndrome: a confusing and forgotten diagnosis.

BACKGROUND: Primary hyperparathyroidism is caused by the excessive growth of parathormone secretion, its consequence being hypercalcemia. The parathyroid adenoma is responsible for over half of primary hyperparathyroidism cases. The mandibular tumor can be the initial sign in the case of primary hyperparathyroidism. CASE PRESENTATION: We present the case of a 33 year old patient with history of a mandibular operated tumor, repetitive pathological fractures and hypercalcemia manifestations. The level of the parathormone at the first measurement indicated a very high value. The parathyroid scintigraphy with 99mTc-MIBI (methoxy-isobutyl-isonitrile) evidenced a high uptake of the tracerin the superior mediastinum, suggestive for an ectopic parathyroid adenoma. The histopathological examination after surgery leads to the diagnosis of parathyroid adenoma. The association between the primary hyperparathyroidism, the mandibular tumour, the clinical history and the nuclear imaging lead to the diagnosis of primary hyperparathyroidism - Jaw tumor syndrome. CONCLUSION: The hyperparathyroidism - Jaw tumor syndrome has a special clinical importance because of the severe and progressive symptomatology, and because of the risk of developing neoplasia of parathyroid glands, which have a reserved prognosis.

Second malignancies in patients with differentiated thyroid carcinoma treated with low and medium activities of radioactive I-131.

BACKGROUND AND AIM: This study aimed at determining whether there is a risk regarding the development of second primary malignancies after patient exposure to the low and medium radioiodine activity used during the treatment of differentiated thyroid cancers (DTC). METHODS: Second primary malignancies that occurred after DTC were detected in 1,990 patients treated between 1970 and 2003. The mean long-term follow-up period was 182 months. RESULTS: Radioiodine I-131was administrated at a mean dose of 63.2 mCi. There were 93 patients with at least one second primary malignancy. The relative risk of development of second malignancy in DTC patients was increased (p<0.0001) for breast, uterine and ovarian cancers compared with the general population. CONCLUSIONS: The overall risk concerning the development of second primary malignancies was related to the presence of DTC, but not to exposure to the low and medium activities of radioiodine administered as adjuvant therapy.