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1.
Impacto de la medicina nuclear en el diagnóstico y tratamiento del cáncer diferenciado de tiroides.
Medina-Ornelas, S, García-Pérez, F, Granados-García, M
Gaceta medica de Mexico. 2018;(4):509-519
Abstract
Los pacientes afectados por el cáncer diferenciado de tiroides habitualmente presentan un curso clínico favorable, ya que la piedra angular del tratamiento es la cirugía; a pesar de esto, algunos pueden desarrollar un ominoso desenlace, debido a las características clinico-patológicas de esta enfermedad. El tratamiento óptimo aún es controvertido, en especial respecto a la extensión de la cirugía, indicaciones de radioyodo y la supresión de la hormona estimulante de la tiroides. La correcta evaluación de los riesgos, antes y después de la cirugía, facilita un selectivo enfoque del tratamiento; destacando la relevancia de revisar el impacto de la medicina nuclear en la correcta evaluación, tratamiento y seguimiento de los pacientes que padecen esta neoplasia. Patients affected by differentiated thyroid cancer usually have a favorable clinical course, since the cornerstone of treatment is surgery; despite this, some patients may develop an ominous outcome, due to the clinical-pathological features of this disease. Optimal treatment remains controversial, especially regarding the extent of surgery, indications for radioiodine and thyroid-stimulating hormone. The correct evaluation of risks before and after surgery facilitates a selective treatment approach; highlighting the importance of reviewing the impact of nuclear medicine on the correct evaluation, treatment and follow-up of patients suffering from this neoplasm.
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2.
Long term quality of life in differentiated thyroid cancer patients after thyroidectomy and high doses of 131I with or without suppressive treatment.
Giannoula, E, Iakovou, I, Verburg, FA
Hellenic journal of nuclear medicine. 2018;(1):69-73
Abstract
According to international guidelines, the most frequently applied diagnostic procedures and therapeutic interventions for differentiated thyroid cancer (DTC) patients are those of nuclear medicine. Differentiated thyroid cancer is the most common endocrine malignancy and over the past decades has shown the fastest increasing incidence of all malignancies. This cancer has a detrimental impact on a patients' quality of life (QoL), not very well considered in general practice. In this paper we aimed to review the QoL of DTC patients who received high doses of 131I and had (or not) a supplementary treatment. Our review includes physical, mental and social well-being and emotional and physical discomfort. Quality of life is related to the diagnostic and therapeutic procedures which DTC patients still have to undergo. Nuclear medicine physicians can maintain or restore the highest achievable QoL of these patients based on guidelines as well as individualized patient centered practice.
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3.
Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial.
Schlumberger, M, Leboulleux, S, Catargi, B, Deandreis, D, Zerdoud, S, Bardet, S, Rusu, D, Godbert, Y, Buffet, C, Schvartz, C, et al
The lancet. Diabetes & endocrinology. 2018;(8):618-626
Abstract
BACKGROUND In ESTIMABL1, a randomised phase 3 trial of radioactive iodine (131I) administration after complete surgical resection in patients with low-risk thyroid cancer, 92% of patients had complete thyroid ablation at 6-10 months, defined as a recombinant human thyroid-stimulating hormone (rhTSH)-stimulated serum thyroglobulin concentration of 1 ng/mL or less and normal findings on neck ultrasonography. Equivalence was shown between low-activity (1·1 GBq) and high-activity (3·7 GBq) radioactive iodine and also between the use of rhTSH injections and thyroid hormone withdrawal. Here, we report outcomes after 5 years of follow-up. METHODS This multicentre, randomised, open-label, equivalence trial was done at 24 centres in France. Between March 28, 2007, and Feb 25, 2010, we randomly assigned (1:1:1:1) adults with low-risk differentiated thyroid carcinoma who had undergone total thyroidectomy to one of four strategies, each combining one of two methods of thyrotropin stimulation (rhTSH or thyroid hormone withdrawal) and one of two radioactive iodine activities (1·1 GBq or 3·7 GBq). Randomisation was by computer-generated sequence, with variable block size. Follow-up consisted of a yearly serum thyroglobulin measurement on levothyroxine treatment. Measurement of rhTSH-stimulated thyroglobulin and neck ultrasonography were done at the discretion of the treating physician. No evidence of disease was defined as serum thyroglobulin of 1 ng/mL or less on levothyroxine treatment and normal results on neck ultrasonography, when performed. This study was registered with ClinicalTrials.gov, number NCT00435851. FINDINGS 726 patients (97% of the 752 patients originally randomised) were followed up. At a median follow-up since randomisation of 5·4 years (range 0·5-9·2), 715 (98%) had no evidence of disease. The other 11 had either structural disease (n=4), raised serum thyroglobulin concentration (n=5), or indeterminate findings on neck ultrasonography (n=2). At ablation, six of these patients had received 1·1 GBq radioactive iodine (five after rhTSH and one after withdrawal) and five had received 3·7 GBq (two after rhTSH and three after withdrawal). TSH-stimulated (either after rhTSH injections or thyroid hormone withdrawal according to the treatment group) thyroglobulin concentration measured at the time of ablation was prognostic for structural disease status at ablation, ablation status at 6-10 months, and the final outcome. INTERPRETATION Our findings suggest that disease recurrence was not related to the strategy used for ablation. These data validate the use of 1·1 GBq radioactive iodine after rhTSH for postoperative ablation in patients with low-risk thyroid cancer. FUNDING French National Cancer Institute (INCa), French Ministry of Health, and Sanofi Genzyme.
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4.
Lenvatinib - A multikinase inhibitor for radioiodine-refractory differentiated thyroid cancer.
Hewett, Y, Ghimire, S, Farooqi, B, Shah, BK
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2018;(1):28-32
Abstract
Lenvatinib, an oral multikinase inhibitor, was approved by the US Food and Drug Administration in February 2015. In a pivotal phase III study of 392 patients with progressive radioiodine-refractory thyroid cancer, the overall response rate of patients receiving lenvatinib was 64.8%, with complete response in four patients. The median progression-free survival was 18.3 months in the lenvatinib arm versus 3.6 months in patients receiving placebo. Median overall survival was not reached in either arm. Lenvatinib is a promising new treatment for patients with radioiodine (iodine-131)-refractory differentiated thyroid cancer.
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5.
Optimisation of treatment with lenvatinib in radioactive iodine-refractory differentiated thyroid cancer.
Capdevila, J, Newbold, K, Licitra, L, Popovtzer, A, Moreso, F, Zamorano, J, Kreissl, M, Aller, J, Grande, E
Cancer treatment reviews. 2018;:164-176
Abstract
Lenvatinib has been approved for the treatment of advanced differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) following the results of the SELECT trial which demonstrated a significant increase in progression-free survival and a high response rates. The data reported for lenvatinib in RAI-refractory DTC (RAI-R DTC) are the most significant to date in this patient population, with a RECIST objective response rate above 60% and almost 80% reduction in the risk of disease progression. Because the first indication in oncology for lenvatinib is specifically in RAI-R DTC, a period of familiarisation with its safety and efficacy profile is required. This review includes a series of specific recommendations for optimising the management of RAI-R DTC with lenvatinib, as well as specific guidelines for minimising the incidence and severity of adverse events (AEs), which enable dose intensity to be increased and this way maximise the benefits of the drug in the patient population treated. These recommendations were defined at a meeting of experts of different specialities, reviewing available scientific evidence on the drug, as well as their own direct personal experience in daily clinical practice. For toxicity to be properly managed, a multidisciplinary approach is required in which the different medical services, nursing staff and the patient and their careers are all involved. It is essential to assess the suitability of patients who are candidates for lenvatinib, as well as their clinical and physiological status prior to treatment. They must then be closely monitored to prevent and detect possible AEs. The main objective should be to maintain the dose that obtains the maximum therapeutic effect, discontinuing the treatment only if the toxicity becomes unmanageable or there is no clinical benefit.
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6.
Brachytherapy of Intracranial Gliomas.
Nachbichler, SB, Kreth, FW
Progress in neurological surgery. 2018;:72-86
Abstract
Interstitial implantation of radioactive materials (brachytherapy [BT]) has been designed to protractedly deliver a high radiation dose to a well-defined target volume, while minimizing irradiation of the adjacent normal tissues. Even though promising results have been reported over time, the role of this treatment modality in the management of brain tumors is still poorly defined, and only a few centers worldwide apply it in clinical practice. Nevertheless, temporary or permanent interstitial implantation of low activity (<20 mCi) and low dose rate (≤10 cGy/h) iodine-125 (125I) seeds as possible therapy of intracranial gliomas is currently undergoing a definite revival, and several indications for its use have been identified. Generally, 125I-BT may be considered a reasonable option in cases of unresectable, well-circumscribed, either newly diagnosed or recurrent tumors with a diameter of ≤4 cm, virtually in any location within the brain. Importantly, this treatment does not narrow down the spectrum of the possible subsequent salvage therapeutic options, since neither repeated interstitial nor additional external beam irradiation at the time of tumor progression after BT is associated with a significantly increased risk of radiogenic complications. Using correct patient selection criteria, appropriate surgical technique, and established treatment parameters, would make BT a truly minimally invasive procedure with a low risk of complications and reasonable efficacy.
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7.
Enhanced activated T cell subsets in prostate cancer patients receiving iodine-125 low-dose-rate prostate brachytherapy.
Kubo, M, Satoh, T, Ishiyama, H, Tabata, KI, Tsumura, H, Komori, S, Iwamura, M, Baba, S, Hayakawa, K, Kawamura, T, et al
Oncology reports. 2018;(1):417-424
Abstract
Radiotherapy (RT) is one of the most important treatments for prostate cancer. Although RT can kill cancer cells through direct and indirect effects of radiation, it occasionally induces an abscopal effect whereby localized radiation treatment is associated with elimination of metastatic cancer at a distance from the irradiated area. Thus, RT may induce an effective antitumor immune response, although the mechanism involved has remained unclear. The present was designed to evaluate this effect of RT in 36 patients with prostate cancer who provided informed consent prior to enrollment in this clinical trial. Peripheral blood samples were collected periodically after low-dose-rate (LDR) prostate brachytherapy, and lymphocyte subsets were analyzed by flow cytometry. The proportion of activated T cells (CD3+HLA-DR+, CD4+HLA-DR+ and CD8+HLA-DR+) in peripheral blood revealed a gradual and bimodal increase after LDR brachytherapy, whereas memory CD8+ T cells bimodally decreased after treatment. The ratios of activated T cells and regulatory T cells gradually increased after the treatment. Thus, LDR brachytherapy was demonstrated to induce effective immune responses in patients. This increase of activated T cells may contribute to maintenance of remission and reduction of relapse rates.
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8.
RADIATION AND THYROID CANCER-AN OVERVIEW.
Thomas, G
Radiation protection dosimetry. 2018;(1):53-57
Abstract
It has long been known that the thyroid is a radiosensitive organ. It is the only organ in the body to both take up and bind iodine, and therefore exposure to radioiodine in fallout from nuclear power plants poses an increased danger to the thyroid. Studies following the Chernobyl accident have shown that children are most at risk from the development of thyroid cancer following exposure to radioactive iodine in fallout. This article reviews what we know so far about the type of thyroid cancer induced by radiation, its molecular biology and clinical outcome.
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9.
Selective use of radioactive iodine (RAI) in thyroid cancer: No longer "one size fits all".
Marti, JL, Morris, LGT, Ho, AS
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2018;(3):348-356
Abstract
A remarkable, evidence-based trend toward de-escalation has reformed the practice of radioactive iodine (RAI) administration for thyroid cancer patients. Updated guidelines have supported both decreased RAI doses for select populations, as well as expanded definitions of low-risk and intermediate-risk patients that may not require RAI. Correspondingly, there is now increased flexibility for hemithyroidectomy without need for RAI, and relaxed TSH suppression targets for low-risk thyroidectomy patients. Clinical judgment remains indispensable where multiple risk factors co-exist that individually are not indications for RAI. This is especially salient in intermediate-risk patients with a less than excellent response to therapy, determined through thyroglobulin and ultrasound surveillance. Such judgment, however, may lead to patterns of inappropriate RAI practices or overuse with little benefit to the patient and unnecessary harm. A multidisciplinary, risk-adapted approach is ever more important and obliges the surgeon to understand the likelihood that their patients will receive RAI. The risks and benefits of RAI, its evolved role in contemporary guidelines, and current patterns of use among endocrinologists are reviewed, as well as the practical implications for thyroid surgeons.
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10.
A phase II study of radioimmunotherapy with intraventricular 131 I-3F8 for medulloblastoma.
Kramer, K, Pandit-Taskar, N, Humm, JL, Zanzonico, PB, Haque, S, Dunkel, IJ, Wolden, SL, Donzelli, M, Goldman, DA, Lewis, JS, et al
Pediatric blood & cancer. 2018;(1)
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Abstract
BACKGROUND High-risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell-surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular 131 I-labeled 3F8 in patients with MB on a phase II clinical trial. METHODS Patients with histopathologically confirmed high-risk or recurrent MB were eligible for cRIT. After determining adequate cerebrospinal fluid (CSF) flow, patients received 2 mCi (where Ci is Curie) 124 I-3F8 or 131 I-3F8 with nuclear imaging for dosimetry, followed by up to four therapeutic (10 mCi/dose) 131 I-3F8 injections. Dosimetry estimates were based on serial CSF and blood samplings over 48 hr plus region-of-interest analyses on serial imaging scans. Disease evaluation included pre- and posttherapy brain/spine magnetic resonance imaging approximately every 3 months for the first year after treatment, and every 6-12 months thereafter. RESULTS Forty-three patients received a total of 167 injections; 42 patients were evaluable for outcome. No treatment-related deaths occurred. Toxicities related to drug administration included acute bradycardia with somnolence, headache, fatigue, and CSF pleocytosis consistent with chemical meningitis and dystonic reaction. Total CSF absorbed dose was 1,453 cGy (where Gy is Gray; 350.0-2,784). Median overall survival from first dose of cRIT was 24.9 months (95% confidence interval [CI]:16.3-55.8). Patients treated in radiographic and cytologic remission were at a lower risk of death compared to patients with radiographically measurable disease (hazard ratio: 0.40, 95% CI: 0.18-0.88, P = 0.024). CONCLUSIONS cRIT with 131 I-3F8 is safe, has favorable dosimetry to CSF, and when added to salvage therapy using conventional modalities, may have clinical utility in maintaining remission in high-risk or recurrent MB.