Search Results (20)

Poorly differentiated thyroid malignancy, a rare histological type of aggressive thyroid malignancy with associated difficulties and gaps in its histological and molecular characterization, might lead to challenging clinical presentations that require a prompt multimodal approach. This case study involved a 56-year-old, non-smoking male with a rapidly developing goiter (within 2–3 months) in association with mild, non-specific neck compressive symptoms. His medical history was irrelevant. A voluminous goiter with substernal and posterior extension up to the vertebral bodies was detected using an ultrasound and computed tomography (CT) scan and required emergency thyroidectomy. He had normal thyroid function, as well as negative thyroid autoimmunity and serum calcitonin. The surgery was successful upon “Y” incision, which was used to give better access to the retrosternal component in order to avoid a sternotomy. Post-operatively, the subject developed hypoparathyroidism-related hypocalcemia and showed a very high serum thyroglobulin level (>550 ng/mL). The pathological report confirmed poorly differentiated, multifocal thyroid carcinoma (with an insular, solid, and trabecular pattern) against a background of papillary carcinoma (pT3b, pN0, and pM1; L1; V2; Pn0; R1; and stage IVB). The subject received 200 mCi of radioiodine therapy for 6 weeks following the thoracic surgery. Whole-body scintigraphy was performed before radioiodine therapy and showed increased radiotracer uptake at the thyroid remnants and pre-tracheal levels. Additionally, single-photon emission computed tomography combined with CT (SPECT/CT) was performed, and confirmed the areas of intense uptake, in addition to a moderate uptake in the right and left pulmonary parenchyma, suggesting lung metastasis. To conclude, an overall low level of statistical evidence exists regarding poorly differentiated malignancy in substernal goiters, and the data also remains scarce regarding the impact of genetic and molecular configurations, such as the BRAF-positive profile, in this specific instance. Furthermore, multimodal management includes additional diagnosis methods such as SPECT/CT, while long-term multilayered therapy includes tyrosine kinase inhibitors if the outcome shows an iodine-resistant profile with a poor prognosis. Awareness remains a key factor in cases of a poorly differentiated carcinoma presenting as a rapidly growing goiter with substernal extension in an apparently healthy adult. A surgical approach, while varying with the surgeon’s skills, represents a mandatory step to ensure a better prognosis. In addition to a meticulous histological characterization, genetic/molecular features provide valuable information regarding the outcome and can further help with the decision to use new anti-cancer drugs if tumor response upon radioiodine therapy is no longer achieved; such a development is expected in this disease stage in association with a BRAF-positive configuration. Full article

Background: Radioactive iodine (RAI) ablation therapy is a common minimally invasive treatment for patients diagnosed with differentiated thyroid cancer (DTC). Although previous studies have identified a link between RAI and the mortality from secondary solid cancers, the connection between RAI and leukemia remains under-researched. This study investigated the differential risk of leukemia and its subtypes in DTC patients following RAI treatment. Methods: DTC patients from the Surveillance, Epidemiology, and End Results (SEER) Registry 17 (2000–2019) were analyzed. The standard incidence ratio (SIR) and excess risk (ER) compared to the reference population were calculated. Results: Out of 196,569 DTC patients, 1381 patients developed various types of hematological malignancies. Leukemia was diagnosed in 508 of these patients, and it had the highest risk among the malignancies studied, with an SIR of 1.74 (95%CI: 1.59–1.9). The RAI group had an SIR of 2.12 (95%CI: 1.87–2.39), while the non-RAI group had an SIR was 1.45 (95%CI: 1.37–1.52) (p < 0.001). Those diagnosed before the age of 55 years had a conspicuously elevated risk (SIR 2.74) compared to those diagnosed at 55 years or older (SIR 1.53). American Indian/Alaska Native survivors manifested a pronounced leukemia risk with an SIR of 7.63 (95%CI: 2.46–17.8). Conclusions: RAI treatment increased the risk of developing leukemia when serving as adjuvant therapy in surgical patients (SIR 2.12). There exists a significant association between RAI treatment in DTC patients and the incidence of leukemia. This susceptibility seems to be modulated by factors including time since diagnosis, age, gender, and racial background. Full article

Selective RET inhibitors, such as selpercatinib and pralsetinib, have revolutionized the treatment of cancers with RET gene alterations. These inhibitors have shown remarkable clinical efficacy, particularly in RET-driven lung cancer, medullary thyroid cancer, and other solid tumors driven by RET gene fusions. The assessment of treatment response in oncology has been greatly enhanced by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), a valuable tool that measures tumor metabolism and provides early indicators of treatment effectiveness. This work explores the effectiveness of selective RET inhibitors in targeting RET-positive cancers and investigates the utility of FDG-PET in assessing treatment response. The paper includes insightful case studies that highlight the successful application of RET inhibitors in the treatment of RET-positive cancers. The findings suggest that FDG-PET has the potential to serve as a non-invasive biomarker for monitoring treatment response in patients with RET-positive cancers. However, further research is required to establish standardized criteria for interpreting FDG-PET scans in the context of selective RET inhibitors and to uncover the broader applications of FDG-PET in precision oncology. Full article

Background: Glioblastoma (GBM) is a highly aggressive, invasive, and growth factor-independent grade IV glioma. Survival following the diagnosis is generally poor, with a median survival of approximately 15 months, and it is considered the most aggressive and lethal central nervous system tumor. Conventional treatments based on surgery, chemotherapy, and radiation therapy only delay progression, and death is inevitable. Malignant glioma cells are resistant to traditional therapies, potentially due to a subpopulation of glioma stem cells that are invasive and capable of rapid regrowth. Methods: This is a literature review. The systematic retrieval of information was performed on PubMed, Embase, and Google Scholar. Specified keywords were used in PubMed and the articles retrieved were published in peer-reviewed scientific journals and were associated with brain GBM cancer and the sodium iodide symporter (NIS). Additionally, the words ‘radionuclide therapy OR mesenchyma, OR radioiodine OR iodine-131 OR molecular imaging OR gene therapy OR translational imaging OR targeted OR theranostic OR symporter OR virus OR solid tumor OR combined therapy OR pituitary OR plasmid AND glioblastoma OR GBM OR GB OR glioma’ were also used in the appropriate literature databases of PubMed and Google Scholar. A total of 68,244 articles were found in this search on Mesenchymal Stem Cell Sodium Iodide Symporter and GBM. These articles were found till 2024. To study recent advances, a filter was added to include articles only from 2014 to 2024, duplicates were removed, and articles not related to the title were excluded. These came out to be 78 articles. From these, nine were not retrieved and only seven were selected after the removal of keyword mismatched articles. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. Results: As a result of their natural capacity to identify malignancies, MSCs are employed as tumor therapy vehicles. Because MSCs may be transplanted using several methods, they have been proposed as the ideal vehicles for NIS gene transfer. MSCs have been used as a delivery vector for anticancer drugs in many tumor models due to their capacity to move precisely to malignancies. Also, by directly injecting radiolabeled MSCs into malignant tumors, a therapeutic dosage of beta radiation may be deposited, with the added benefit that the tumor would only localize and not spread to the surrounding healthy tissues. Conclusion: The non-invasive imaging-based detection of glioma stem cells presents an alternate means to monitor the tumor and diagnose and evaluate recurrence. The sodium iodide symporter gene is a specific gene in a variety of human thyroid diseases that functions to move iodine into the cell. In recent years, an increasing number of studies related to the sodium iodide symporter gene have been reported in a variety of tumors and as therapeutic vectors for imaging and therapy. Gene therapy and nuclear medicine therapy for GBM provide a new direction. In all the preclinical studies reviewed, image-guided cell therapy led to greater survival benefits and, therefore, has the potential to be translated into techniques in glioblastoma treatment trials. Full article

Background: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed on the surface of tumor cells in most of the patients affected by prostate adenocarcinoma (PCa). However, PSMA expression has also been demonstrated in the endothelial cells of newly formed vessels of various solid tumors, suggesting a role for PSMA in neoangiogenesis. In this scenario, gallium-68 (⁶⁸Ga) or fluoro-18 (¹⁸F)-labeled PSMA positron emission tomography (PET) may play a role in tumors other than PCa, generally evaluated employing other radiopharmaceuticals targeting different pathways. This review aims to investigate the detection rate of PSMA-PET compared to other radiopharmaceuticals (especially [¹⁸F]FDG) in non-prostate tumors to identify patients who may benefit from the use of such a theragnostic agent. Methods: We performed a bibliographic search on three different databases until February 2024 using the following terms: “positron emission tomography”, “PET”, “PET/CT”, “Prostate-specific membrane antigen”, “PSMA”, “non-prostate”, “not prostate cancer”, “solid tumor”, “FDG”, “Fluorodeoxyglucose”, “FAPi”, “FET”, “MET”, “DOPA”, “choline”, “FCH”, “FES”, “DOTATOC”, “DOTANOC”, and “DOTATATE”. Only original articles edited in English with at least 10 patients were included. Results: Out of a total of 120 articles, only 25 original articles comparing PSMA with other radiotracers were included in this study. The main evidence was demonstrated in renal cell carcinoma, where PSMA showed a higher detection rate compared to [¹⁸F]FDG PET/CT, with implications for patient management. PSMA PET may also improve the assessment of other entities, such as gliomas, in defining regions of early neoangiogenesis. Further data are needed to evaluate the potential role of PSMA-PET in triple-negative breast cancer as a novel therapeutic vascular target. Finally, unclear applications of PSMA-PET include thyroid and gastrointestinal tumors. Conclusions: The present review shows the potential use of PSMA-labeled PET/CT in solid tumors beyond PCa, underlining its value over other radiopharmaceuticals (mainly [¹⁸F]FDG). Prospective clinical trials with larger sample sizes are crucial to further investigate these possible clinical applications. Full article

Selpercatinib is indicated for locally advanced/metastatic RET-activated solid tumors after progression or following prior systemic therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing selpercatinib with other first-line treatments in RET-activated non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {TTP}, and the objective response rate {ORR}) of first-line selpercatinib (selpercatinib arm) use with the outcomes of first-line standard therapies in patients who then received selpercatinib in later lines of treatment (comparator arm). Overall, the first-line selpercatinib arm had a longer TTD, TTNT-D, and TTP versus the first-line comparator arm. The hazard ratios (HRs) for TTD were 0.29 (NSCLC), 0.15 (MTC), 0.08 (TC); for TTNT-D, the HRs were 0.48 (NSCLC), 0.11 (MTC), 0.09 (TC); and for TTP, the HRs were 0.54 (NSCLC), 0.15 (MTC), and 0.12 (TC). The ORR was higher for first-line selpercatinib versus the first-line comparator (NSCLC: 85.3% vs. 39.7%; MTC: 82.6% vs. 15.2%; and TC: 81.8% vs. 31.8%). First-line selpercatinib use is associated with improved outcomes compared to first-line comparator therapies for patients with advanced/metastatic RET-activated cancers. Full article

Background: A BRAF V600E mutation in papillary thyroid cancer (PTC) has been shown to be associated with aggressive behavior. Nevertheless, not all BRAF V600E PTCs behave aggressively. Allele frequency (AF) is the number of mutated molecules divided by the total number of wild-type molecules at a specific location in the genome. The relationship between BRAF V600E AF and the histopathological features of thyroid malignancies is not well understood. We hypothesized that the BRAF V600E AF will correlate directly with aggressive histopathological behavior. The aim of this study was to examine this relationship. Methods: A retrospective chart review was performed for patients treated for BRAF V600E thyroid malignancies from 2019 to 2022 at McGill University tertiary care hospitals (n = 317). Patients with BRAF V600E-positive malignancies that included information on AF were included (n = 44). The correlation between AF and tumor histopathological features was analyzed. Results: Out of the 44 nodules with a BRAF V600E mutation, those with aggressive features of PTC had a mean AF of 25.8%, which was significantly higher than the non-aggressive group with a mean AF of 10.25% (p = 0.020). Additionally, there was a statistically significant difference in mean AF between patients with a positive sentinel LN (29%) and those with a negative sentinel LN (17.8%) (p = 0.021). Classical PTC was present in 29.5% (13/44) of nodules, with a mean AF of 15.6%. The tall cell subtype was found in 64% (28/44) of nodules, with a mean AF of 23%. Solid and hobnail subtypes were less common in this study, and there was no statistically significant relationship between AF and histopathological subtypes (p = 0.107). Nodules smaller than 1cm had a mean AF of 13.3%, while nodules ranging from 1 2cm had a mean AF of 20.6%, and those larger than 2cm had a mean AF of 27.7%. However, no statistical difference was observed between AF and nodule size (p = 0.160). Conclusion: In this study, BRAF V600E mutations in conjunction with AF help to determine whether thyroid malignancies will display aggressive behavior. This pre-operative finding can help thyroid specialists to determine the extent of thyroidectomy and whether lymph node dissection is required. Full article

Background: Cancer treatments have gradually evolved into targeted molecular therapies characterized by a unique mechanism of action instead of non-specific cytotoxic chemotherapies. However, they have unique safety concerns. For instance, endocrinopathies, which are defined as unfavorable metabolic alterations including thyroid disorders, hyperglycemia, dyslipidemia, and adrenal insufficiency necessitate additional monitoring. The aim of this study was to assess the prevalence of monitoring errors and develop strategies for monitoring cancer patients who receive targeted therapies. Method: A retrospective chart review was used to assess the prevalence of monitoring errors of endocrinopathies among cancer patients who received targeted therapies over one year. All of the adult cancer patients diagnosed with a solid tumor who received targeted therapies were included. The primary outcome was to determine the prevalence of monitoring errors of endocrinopathies. The secondary outcomes were to assess the incidences of endocrinopathies and referral practice to endocrinology services. Results: A total of 128 adult patients with solid tumors were involved. The primary outcome revealed a total of 148 monitoring errors of endocrinopathies. Monitoring errors of the lipid profile and thyroid functions were the most common error types in 94% and 92.6% of the patients treated with novel targeted therapies, respectively. Subsequently, 57% of the monitoring errors in the blood glucose measures were identified. Targeted therapies caused 63 events of endocrinopathies, hyperglycemia in 32% of the patients, thyroid disorders in 15.6% of them and dyslipidemia in 1.5% of the patients. Conclusion: Our study showed a high prevalence of monitoring errors among the cancer patients who received targeted therapies which led to endocrinopathies. It emphasizes the importance of adhering to monitoring strategies and following up on the appropriate referral process. Full article

Due to its overexpression on the surface of prostate cancer cells, prostate-specific membrane antigen (PSMA) is a relatively novel effective target for molecular imaging and radioligand therapy (RLT) in prostate cancer. Recent studies reported that PSMA is expressed in the neovasculature of various types of cancer and regulates tumour cell invasion as well as tumour angiogenesis. Several authors explored the role of diagnostic and therapeutic PSMA radioligands in various malignancies. In this narrative review, we describe the current status of the literature on PSMA radioligands’ application in solid tumours other than prostate cancer to explore their potential role as diagnostic or therapeutic agents, with particular regard to the relevance of PSMA radioligand uptake as neoangiogenetic biomarker. Hence, a comprehensive review of the literature was performed to find relevant articles on the applications of PSMA radioligands in non-prostate solid tumours. Data on the general, methodological and clinical aspects of all included studies were collected. Forty full-text papers were selected for final review, 8 of which explored PSMA radioligand PET/CT performances in gliomas, 3 in salivary gland malignancies, 6 in thyroid cancer, 2 in breast cancer, 16 in renal cell carcinoma and 5 in hepatocellular carcinoma. In the included studies, PSMA radioligand PET showed promising performance in patients with non-prostate solid tumours. Further studies are needed to better define its potential role in oncological patients management, especially in those undergoing antineoangiogenic therapies, and to assess the efficacy of PSMA-RLT in this clinical context. Full article

Hypothyroidism in patients with solid non-thyroid cancer is a tantalizing entity, integrating an intriguing thyroid hormones (THs)–cancer association with the complexity of hypothyroidism itself. The present narrative review provides a comprehensive overview of the clinical relevance of hypothyroidism in solid non-thyroid cancer. Hypothyroidism in patients with solid non-thyroid cancer is reminiscent of hypothyroidism in the general population, yet also poses distinct challenges due to the dual role of THs in cancer: promoting versus inhibitory. Close collaboration between oncologists and endocrinologists will enable the prompt and personalized diagnosis and treatment of hypothyroidism in patients with solid non-thyroid cancer. Clinical data indicate that hypothyroidism is a predictor of a decreased or increased risk of solid non-thyroid cancer and is a prognostic factor of favorable or unfavorable prognosis in solid non-thyroid cancer. However, the impact of hypothyroidism with respect to the risk and/or prognosis of solid non-thyroid cancer is not a consistent finding. To harness hypothyroidism, or THs replacement, as a personalized anticancer strategy for solid non-thyroid cancer, four prerequisites need to be fulfilled, namely: (i) deciphering the dual THs actions in cancer; (ii) identifying interventions in THs status and developing agents that block tumor-promoting THs actions and/or mimic anticancer THs actions; (iii) appropriate patient selection; and (iv) counteracting current methodological limitations. Full article

The aim of the study was to validate thyroid US malignancy features, especially the nodule’s shape, and selected Thyroid Imaging Reporting and Data Systems (EU-TIRADS; K-TIRADS; ACR-TIRADS, ATA guidelines) in patients with or without Hashimoto’s thyroiditis (HT and non-HT groups). The study included 1188 nodules (HT: 358, non-HT: 830) with known final diagnoses. We found that the strongest indications of nodule’s malignancy were microcalcifications (OR: 22.7) in HT group and irregular margins (OR:13.8) in non-HT group. Solid echostructure and macrocalcifications were ineffective in patients with HT. The highest accuracy of nodule’s shape criterion was noted on transverse section, with the cut-off value of anteroposterior to transverse dimension ratio (AP/T) close to 1.15 in both groups. When round nodules were regarded as suspicious in patients with HT (the cut-off value of AP/T set to ≥1), it led to a three-fold increase in sensitivity of this feature, with a disproportionally lower decrease in specificity and similar accuracy. Such a modification was effective also for cancers other than PTC. The diagnostic effectiveness of analyzed TIRADS in patients with HT and without HT was similar. Changes in the threshold for AP/T ratio influenced the number of nodules classified into the category of the highest risk, especially in the case of EU-TIRADS. Full article

Childhood papillary thyroid carcinoma (PTC) diagnosed after the Chernobyl accident in Belarus displayed a high frequency of gene rearrangements and low frequency of point mutations. Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have not been reported. Here, we determine the major oncogenic events in PTC from non-exposed Belarusian children and assess their clinicopathological correlations. Among the 34 tumors, 23 (67.6%) harbored one of the mutually exclusive oncogenes: 5 (14.7%) BRAF^V600E, 4 (11.8%) RET/PTC1, 6 (17.6%) RET/PTC3, 2 (5.9%) rare fusion genes, and 6 (17.6%) ETV6ex4/NTRK3. No mutations in codons 12, 13, and 61 of K-, N- and H-RAS, BRAF^K601E, or ETV6ex5/NTRK3 or AKAP9/BRAF were detected. Fusion genes were significantly more frequent than BRAF^V600E (p = 0.002). Clinicopathologically, RET/PTC3 was associated with solid growth pattern and higher tumor aggressiveness, BRAF^V600E and RET/PTC1 with classic papillary morphology and mild clinical phenotype, and ETV6ex4/NTRK3 with follicular-patterned PTC and reduced aggressiveness. The spectrum of driver mutations in sporadic childhood PTC in Belarus largely parallels that in Chernobyl PTC, yet the frequencies of some oncogenes may likely differ from those in the early-onset Chernobyl PTC; clinicopathological features correlate with the oncogene type. Full article

Background: Precision medicine is based on molecular and genotypic patient characterization to define specific target treatment. BRAF mutation is an oncogenic driver, and the Cancer Genome Atlas has identified BRAF mutations in different cancer types. Tumor type agnostic therapy is based on targeting genomic alterations, regardless of tumor origin. In this context, novel therapeutic agents including BRAF and MEK inhibitors based on the molecular landscape in solid tumors have been investigated. Case presentation, Case 1: The first case is chemotherapy-refractory, BRAF V600E mutated intrahepaticcholangiocarcinoma treated with vemurafenib and cobimetinib as third line therapy. In this setting the dual BRAF and MEK inhibition resulted in improved progression-free survival and quality of life; Case 2: The second case shows aBRAF G466A mutated Bellini duct carcinoma (BDC), treated with dabrafenib and trametinib in second line therapy. The disease remained under control for 11 months after the first relapse. Discussion: In the literature there is strong evidence that melanoma, colorectal cancer, non small cell lung cancer and anaplastic thyroid cancer with BRAF mutations are good targets for BRAF/MEK pathway inhibitors. The VE-BASKET and ROAR basket trials explored the efficacy of vemurafenib and the combination of dabrafenib/trametinib, respectively, in BRAF V600 mutation-positive cancers other than melanoma, papillary thyroid cancer, colorectal cancer and non small cell lung cancer. Within the concept of tumor type agnostic therapy, we decided to treat our BRAF-mutated tumors with the association of BRAF and MEK inhibitors. Conclusions: Our results confirm the emerging importance of molecular tumor profiling for the successful management of cancer, and the potential of BRAF-targeted therapy in the treatment of rare solid tumors with poor prognosis and no clinical benefit from systemic therapies with. Full article

The tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib were recently approved in Canada for the treatment of solid tumours harbouring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. These NTRK gene fusions are oncogenic drivers found in most tumour types at a low frequency (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., secretory carcinoma of the salivary gland and of the breast). They are generally mutually exclusive of other common oncogenic drivers. Larotrectinib and entrectinib have demonstrated impressive overall response rates and tolerability in Phase I/II trials in patients with TRK fusion cancer with no other effective treatment options. Given the low frequency of TRK fusion cancer and the heterogeneous molecular testing landscape in Canada, identifying and optimally managing such patients represents a new challenge. We provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor. We focus on five tumour types: thyroid carcinoma, colorectal carcinoma, non-small cell lung carcinoma, soft tissue sarcoma, and salivary gland carcinoma. Based on the probability of the tumour harbouring an NTRK gene fusion, we also suggest a tumour-agnostic consensus for NTRK gene fusion testing and treatment. We recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options. Full article

Neurotrophic tyrosine receptor kinase gene fusions (NTRK) are oncogenic drivers present at a low frequency in most tumour types (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive with other common oncogenic drivers. Health Canada recently approved two tyrosine receptor kinase (TRK) inhibitors, larotrectinib (for adults and children) and entrectinib (for adults), for the treatment of solid tumours harbouring NTRK gene fusions. In Phase I/II trials, these TRK inhibitors have demonstrated promising overall response rates and tolerability in patients with TRK fusion cancer who have exhausted other treatment options. In these studies, children appear to have similar responses and tolerability to adults. In this report, we provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor for pediatric patients with solid tumours. We focus on three pediatric tumour types: non-rhabdomyosarcoma soft tissue sarcoma/unspecified spindle cell tumours including IFS, differentiated thyroid carcinoma, and glioma. We also propose a tumour-agnostic consensus based on the probability of the tumour harbouring an NTRK gene fusion. For children with locally advanced or metastatic TRK fusion cancer who have either failed upfront therapy or lack satisfactory treatment options, TRK inhibitor therapy should be considered. Full article