Background: Medullary thyroid cancer (MTC) is a neuroendocrine tumour and a rare variant of thyroid cancer with different aetiology, presentation and treatment to differentiated thyroid cancer. Currently available thyroid cancer-specific quality of life (QoL) tools focus on issues and treatments more relevant to patients with differentiated thyroid cancer and therefore may not address issues specific to a MTC diagnosis and cancer journey. Method: This prospective multicentre randomised study involved 204 MTC patients completing four quality of life questionnaires (QOLQ) and stating their most and least preferred. The questionnaires were a general instrument, the EORTC QLQ-C30, two disease-specific tools, the MD Anderson Symptom Inventory (MDASI) thyroid module and the City of Hope Quality of Life Scale/THYROID (amended) and the neuroendocrine questionnaire, EORTC QLQ-GINET21. Patients were randomised to complete the four questionnaires in one of 24 possible orders and then answered questions about which tool they preferred. The primary outcome measure was patients’ preferred QoL instrument for describing their concerns and for facilitating communication with their healthcare professional. Secondary analyses looked at differences between preferred QOLQs amongst patient subgroups (WHO performance status [0 and 1+], disease stage: early [T1–3, N0 or N1A], metastatic [T4, any T N1b] and advanced [any T any N M1], and type of MTC [sporadic and inherited]), identification of MTC patients’ least preferred questionnaire and clinicians’ views on the QoL tools in terms of their ability to highlight problems not otherwise ascertained by a standard clinical review. Results: No evidence of a difference was observed for most preferred QOLQ (p = 0.650). There was however evidence of a difference in least preferred questionnaire in the cohort of 128 patients who stated their least preferred questionnaire (p = 0.042), with 36% (46/128) of patients choosing the EORTC QLQ-GI.NET21 questionnaire. Subgroup analyses showed that there was no evidence of a difference in patients’ most preferred questionnaire in sporadic MTC patients (p = 0.637), patients with WHO PS 0 or 1+ (p = 0.844 and p = 0.423) nor when comparing patients with early, advanced local or metastatic disease (p = 0.132, p = 0.463 and p = 0.506, respectively). Similarly, subgroup analyses on patients’ least preferred questionnaires showed no evidence of differences in sporadic MTC patients (p = 0.092), patients with WHO PS 0 or 1+ (p = 0.423 and p = 0.276), nor in early or metastatic disease patients (p = 0.682 and p = 0.345, respectively). There was however some evidence to suggest a difference in least preferred questionnaire in patients with advanced local stage disease (p = 0.059), with 43% (16/37) of these patients choosing the EORTC QLQ-GI.NET21 questionnaire. Conclusions: MTC patients regardless of their performance status, disease aetiology and disease burden did not express a preference for any one particular questionnaire suggesting any of the tools studied cou...
Purpose/Objective(s): Radiation therapy is commonly used for treatment of patients with intrathoracic malignancies, such as lung cancer, esophageal cancer, and lymphoma. Radiation-Induced Heart Disease (RIHD) is a major source of morbidity and mortality in patients receiving thoracic radiation. Therefore, there is an acute need for development of non-invasive approaches for detection of RIHD at a stage that offers potential for early intervention and reversibility. Cardiac mitochondrial dysfunction is a hallmark of radiation-induced cardiac injury. During aerobic respiration, pyruvate enters the tricarboxylic acid cycle and is metabolized into bicarbonate in mitochondria. We hypothesized that radiation-induced mitochondrial dysfunction results in decreased conversion of pyruvate to bicarbonate in the mitochondria and increased conversion to lactate in cytosol. We sought to non-invasively assess radiation-induced changes in mitochondrial myocardial metabolism by tracking the fate of hyperpolarized (HP) C-13 pyruvate utilization using Magnetic Resonance Spectroscopy (MRS). Materials/Methods: Sprague-Dawley rats (n = 10) underwent baseline echocardiography and HP C-13 pyruvate MRS. Rats in the cardiac radiation group (n = 5) underwent image-guided cardiac radiation with conebeam CT, to a total dose of 40 Gy in 5 fractions. All rats underwent repeat echocardiography and hyperpolarized C-13 pyruvate MRS one week later. Results: For the first time, we have demonstrated feasibility of employing HP C-13 pyruvate MRS for detecting radiation-induced myocardial mitochondrial metabolic changes in a pre-clinical rat model. In the cardiac radiation group, C-13 pyruvate MRS demonstrated a statistically significant decrease in cardiac bicarbonate-to-lactate ratio compared to pre-radiation baseline (P = 0.02, one-tailed paired t-test), suggesting increased metabolism of pyruvate into lactate in the cytoplasm (at the expense of metabolism into bicarbonate in the mitochondria) due to mitochondrial dysfunction. No significant decrease in this ratio was observed in the nonirradiated, age matched controls (P = 0.90). No significant changes in left ventricular ejection fraction or global longitudinal strain were observed in either the cardiac irradiation or control group of rats at this time point. Conclusion: Radiation-induced myocardial mitochondrial dysfunction is an early event and can be detected in vivo by hyperpolarized C-13 pyruvate MRS within 1 week after radiation, and prior to onset of echocardiographic changes. Due to its non-invasive nature, this technology has the potential to serve as a platform for building radiation-focused cardiooncology programs for early detection and mitigation of radiation-induced cardiac injury in hundreds of thousands of patients receiving thoracic radiation annually.
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