DOSIMETRIC VERIFICATION OF INTENSITY MODULATED RADIOTHERAPY (IMRT) TREATMENT PLANS FOR PROSTATE CANCER PATIENTS.

Intensity modulated radiotherapy (IMRT) has become widely used as a standard radiation therapy technique for the treatment of localized prostate cancer. The transition from conformal radiotherapy (3D CRT) to a more complex IMRT technique triggered the need for more thorough verification of the accuracy in the dose delivery. In this work we present the clinical workflow and the results of patient specific quality assurance (PSQA) procedures for 40 prostate cancer patients who have been treated with step and shot IMRT ever since its implementation in our routine clinical practice. PSQA procedures include dosimetric verification of each treatment plan with dedicated rotational phantom and high-resolution matrix detector system Octavius 4D (PTW Freiburg) that allows three-dimensional comparison of the calculated and delivered radiation dose distribution. Our results proved the compliance with the universal tolerance limits recommended for those procedures (1), assuring the safety of the treatment and providing the possibility for the adoption of more stringent constraints in the future.

THE PREVALENCE OF SUBCLINICAL HYPOTHYROIDISM IN THE POPULATION OF ELDERLY NURSING HOME RESIDENTS IN ZAGREB.

The aim of the study was to investigate the prevalence of thyroid dysfunction, positive thyroid peroxidase antibodies (TPOAb) and hypercholesterolemia in elderly and younger subjects, and the association of subclinical hypothyroidism with hypercholesterolemia. The study included 204 elderly (136 females and 68 males, age median 71, range 60-92 years), and 83 younger control subjects (63 females and 20 males, age median 45, range 19-55 years). Subjects with prior thyroid dysfunction were excluded. Serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), TPOAb, total cholesterol, height and weight were measured. Mann-Whitney, χ2-test and Student's t-test were used on statistical analysis. The prevalence of subclinical hypothyroidism (TSH >5 mU/L) in elderly was 7.4% vs. 3.6% in younger subjects, with the highest prevalence of 8.8% in elderly women vs. 4.8% in younger women, and 4.4% in elderly men. The prevalence of hypothyroidism and subclinical hyperthyroidism in elderly subjects was 0.5% and 1.5%, respectively. In women with subclinical hypothyroidism, the prevalence of TPOAb was 77% in elderly women and 67% in younger women (overall 19.9% in elderly and 14.3% in younger women). The mean FT3 level was lower in elderly women as compared with elderly men (p<0.01) and younger women (p<0.05). The mean cholesterol level was higher in elderly subjects in comparison with younger ones (p<0.01), and in elderly women vs. elderly men (p<0.01), but without difference between subclinical hypothyroidism and euthyroid subjects (6.0 mmol/L). In conclusion, subclinical hypothyroidism is the most prevalent thyroid dysfunction in elderly, with the highest prevalence in elderly women, and autoimmune thyroiditis is the most common etiology. Hypercholesterolemia was more related to older age, especially elderly females, but not influenced by subclinical hypothyroidism.

Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer.

The activity of nicotinamide N-methyltransferase (NNMT) is tightly linked to the maintenance of the nicotinamide adenine dinucleotide (NAD+) level. This enzyme catalyzes methylation of nicotinamide (NAM) into methyl nicotinamide (MNAM), which is either excreted or further metabolized to N1-methyl-2-pyridone-5-carboxamide (2-PY) and H2O2. Enzymatic activity of NNMT is important for the prevention of NAM-mediated inhibition of NAD+-consuming enzymes poly-adenosine -diphosphate (ADP), ribose polymerases (PARPs), and sirtuins (SIRTs). Inappropriately high expression and activity of NNMT, commonly present in various types of cancer, has the potential to disrupt NAD+ homeostasis and cellular methylation potential. Largely overlooked, in the context of cancer, is the inhibitory effect of 2-PY on PARP-1 activity, which abrogates NNMT's positive effect on cellular NAD+ flux by stalling liberation of NAM and reducing NAD+ synthesis in the salvage pathway. This review describes, and discusses, the mechanisms by which NNMT promotes NAD+ depletion and epigenetic reprogramming, leading to the development of metabolic plasticity, evasion of a major tumor suppressive process of cellular senescence, and acquisition of stem cell properties. All these phenomena are related to therapy resistance and worse clinical outcomes.

DIFFERENTIATED THYROID CANCER IN PEDIATRIC POPULATION (≤18 YEARS): POSTOPERATIVE TREATMENT WITH RADIOACTIVE IODINE (I-131).

The aim is to present data on the treatment and follow-up in a cohort of patients with pediatric thyroid cancer who underwent total thyroidectomy and received postoperative radioactive iodine (I-131) therapy. The study was conducted in a tertiary high-volume thyroid center, in pediatric patients with differentiated thyroid cancer who were consecutively treated during the 1965-2015 period. A total of 45 patients aged ≤18 years having undergone total thyroidectomy with or without selective neck dissection were included in the study. Decision on postoperative I-131 ablation was based on tumor characteristics, postoperative thyroglobulin level, preablative whole body scintigraphy, and/or neck ultrasound. Median age at diagnosis was 15 years. The presence of cervical lymph node metastases was significantly associated with papillary thyroid cancer, larger tumor size, involvement of two thyroid lobes, and multifocal disease. The presence of distant metastases was significantly associated with larger tumor size. None of the patients died during follow-up period, and the 5-year and 10-year overall survival rates were 100%. The 5-year and 10-year progression-free survival (PFS) rates were 87% and 73%, respectively. Male gender (p=0.046), age ≤15 years (p=0.029) and tumor size >15 mm (p=0.042) were significantly associated with inferior PFS. A significant positive trend of increase in the number of newly diagnosed patients was observed over time (p=0.011). Clinical management of pediatric thyroid cancer is challenging, especially in the light of increasing incidence in this population. Male patients younger than 15 years and with tumors of more than 15 mm in size require additional caution due to lower PFS observed.

THYROGLOBULIN AS A TUMOR MARKER IN DIFFERENTIATED THYROID CANCER - CLINICAL CONSIDERATIONS.

- Initial treatment of the majority of patients with differentiated thyroid cancer (DTC) includes total thyroidectomy. Postoperative ablation therapy with radioactive iodine (I-131) is indicated in all high-risk patients, however, there is disagreement regarding its use in low- and intermediate-risk patients. Over the last few decades, thyroglobulin (Tg) has been established as the primary biochemical tumor marker for patients with DTC. Thyroglobulin can be measured during thyroid hormone therapy or after thyroid-stimulating hormone (TSH) stimulation, through thyroid hormone withdrawal or the use of human recombinant TSH. In many studies, the cut-off value for adequate Tg stimulation is a TSH value ≥30 mIU/L. However, there is an emerging body of evidence suggesting that this long-established standard should be re-evaluated, bringing this threshold into question. Recently, a risk stratification system of response to initial therapy (with four categories) has been introduced and Tg measurement is one of the main components. The relationship between the Tg/TSH ratio and the outcome of radioiodine ablation has also been studied, as well as clinical significance of serum thyroglobulin doubling-time. The postoperative serum Tg value is an important prognostic factor that is used to guide clinical management, and it is the most valuable tool in long term follow-up of patients with DTC.

Dermatomyositis as paraneoplastic syndrome of peritoneal and ovarian relapse after long-term complete remission in patient with metastatic bilateral breast cancer.

Dermatomyositis is a rare disease characterised by inflammatory muscle affection and characteristic cutaneous changes. When occuring in a patient with cancer, dermatomyositis may indicate recurrence or progression and poor outcome. Herein, the treatment of metastatic breast cancer, metastatic pattern, characteristics of long-term survivors, and link between dermatomyositis and breast cancer are discussed and the literature reviewed. We report a 57-year old female patient with metastatic bilateral breast cancer whose ovarian and peritoneal relapse after long-term remission was disclosed by occurence of paraneoplastic dermatomyositis. The patient previously had a 15-year long disease free-period after primary treatment for breast cancer before onset of pulmonary dissemination. Following antracycline-based chemotherapy, the complete remission lasting another 15 years was accomplished. Dermatomyositis had been resolved upon induction of second-line taxane-based chemotherapy. After completion of six cycles of gemcitabine and paclitaxel chemotherapy, check-up revealed further progression. The patient subsequently underwent six cycles of third-line CAP chemotherapy (cyclofosfamide, doxorubicine, cisplatin) but disease progressed and oral capecitabine chemotherapy was initiated. The patient received four cycles of capecitabine followed by further vast progression and finally expired following massive pulmonary embolism. Our case stresses the need of thorough staging and check-up when dermatomyositis arises in patients with breast cancer, regardless of previous stable long-term complete remission. Furthermore, we believe that treatment with curative intent in young patients with metastatic breast cancer, who have good performance statuses and no comorbidities is required, because it is more likely to produce long-term complete remission. However, following disease relapse a poor outcome can be expected.

Alpha Satellite RNA Levels Are Upregulated in the Blood of Patients with Metastatic Castration-Resistant Prostate Cancer.

The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker.

Postoperative use of radioiodine (131-I): review of recommendations and guidelines.

In the management of large number of patients with differentiated thyroid cancer, the radioactive iodine (131-I) administration plays an important role. The guidelines of numerous international and national medical societies regarding the issue of postoperative 131-I administration have been published and updated in the last few years. The guidelines differ in the shape and content, and contain some specific features. The different methods for evaluation and analysis of clinical evidence level and resulting grades of recommendations have been used in line with the very guidelines. The postoperative 131-I administration refers to the radioiodine ablation as a form of adjuvant treatment and radioiodine therapy in the management of patients with recurrent cancer, persistent disease and regional or distant metastases. According to the indications for the postoperative 131-I administration, the patients could be divided into the three risk groups: the very low risk group in which there is no indication for the postoperative 131-I administration, the low risk group in which the indication could be considered, and the high risk group in which there is a clear indication for the 131-I administration. The different criteria for distribution of patients into these three groups are expressed in a certain guidelines. There are different opinions about the necessary dosage of 131-I for the efficient ablation in the low risk group. Moreover, the opinions are also divided regarding the conduction of postoperative (preablative or pretherapeutic) scintigraphy with 131-I. As regards the instructions on preparation of patients for the radioiodine ablation and therapy, all the guidelines recommend the low iodine diet and endogenous or exogenous stimulation of TSH. The endogenous stimulation is accomplished by the withdrawal of thyroid hormones, whereas the recombinant human TSH (rhTSH) is used for exogenous stimulation. For conducting the therapy with 131-I the level of TSH has to be > 25-30 mU/L.

Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience.

BACKGROUND: Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it's use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. METHODS: Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan-Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. RESULTS: Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58-106 months, range, 8-106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41-72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0-4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0-4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0-1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2-8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37-6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6-12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03-1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26-9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96-25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03-7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00-1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08-16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. CONCLUSIONS: In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.

Oncologist Burnout Syndrome in Eastern Europe: Results of the Multinational Survey.

PURPOSE: Burnout is defined as a three-dimensional syndrome-emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA)-caused by chronic occupational stress. The aim of the current study was to investigate the prevalence of burnout among oncologists in Eastern Europe and to identify the contributing factors. METHODS: The study was conducted as an online survey between October 2017 and March 2018. Oncologists (including medical, radiation, clinical, and surgical oncologists) from 19 countries were invited to participate. The survey consisted of 30 questions, including the standardized burnout instrument, Maslach Burnout Inventory, and eight demographic questions. Burnout risk was scored according to the scoring manual for health care workers. RESULTS: The study included 637 oncologists. Overall, 28% were at low or intermediate risk and 72% were at high risk for burnout. Forty-four percent of participants were at high risk for EE, 28.7% for DP, and 47.3% for PA. EE risk was associated with female sex. DP risk was highest among clinical and radiation oncologists, whereas PA risk was positively correlated with years of service, percentage of cancer deaths, and availability of the number of oncologists. In multivariate logistic regression analysis, burnout was significantly associated with standardized cancer mortality and fewer years of practice. CONCLUSION: Burnout among oncologists in Eastern Europe is high, and younger oncologists are the most vulnerable group. Preventive measures should be taken to address this issue, which negatively affects optimal care delivery and poses a threat to oncologists' health and well-being.

Dose-volume derived nomogram as a reliable predictor of radiotherapy-induced hypothyroidism in head and neck cancer patients.

Background The aim of this study was to determine the possible predictive value of various dosimetric parameters on the development of hypothyroidism (HT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. Patients and methods This study included 156 patients with HNSCC who were treated with (chemo)radiotherapy in a primary or postoperative setting between August 2012 and September 2017. Dose-volume parameters as well as V10 toV70, D02 to D98, and the VS10 to VS70 were evaluated. The patients' hormone status was regularly assessed during follow-up. A nomogram (score) was constructed, and the Kaplan-Maier curves and Log-Rank test were used to demonstrate the difference in incidence of HT between cut-off values of specific variables. Results After a median follow-up of 23.0 (12.0-38.5) months, 70 (44.9%) patients developed HT. In univariate analysis, VS65, Dmin, V50, and total thyroid volume (TTV) had the highest accuracy in predicting HT. In a multivariate model, HT was associated with lower TTV (OR 0.31, 95% CI 0.11-0.87, P = 0.026) and Dmin (OR 9.83, 95% CI 1.89-108.08, P = 0.042). Hypothyroidism risk score (HRS) was constructed as a regression equation and comprised TTV and Dmin. HRS had an AUC of 0.709 (95% CI 0.627-0.791). HT occurred in 13 (20.0%) patients with a score < 7.1 and in 57 (62.6%) patients with a score > 7.1. Conclusions The dose volume parameters VS65, Dmin, V50, and TTV had the highest accuracy in predicting HT. The HRS may be a useful tool in detecting patients with high risk for radiation-induced hypothyroidism.

Clinical guidelines development and usage: a critical insight and literature review: thyroid disease diagnostic algorithms.

Clinical guidelines have been increasingly used in medicine. They represent a system of recommendations for the conduction of specific procedures used in fields from public health to different diagnostic and therapeutic procedures in clinical medicine. Guidelines are designed to facilitate to medical practitioners the adoption, evaluation and application of an increasing body of evidence and arising number of expert opinions regarding the presently best treatment and to help in delivering proper decision for the management of a patient or condition. Clinical guidelines represent a part of complementary activity by which research is implemented into praxis, standards are defined and clinical excellence is promoted in all health care fields. There are specific conditions which quality guidelines should meet. First of all, they need to be founded on comprehensive literature review, apart from clinical studies and trials in the target field. Also, there are more systems for analyzing and grading the strength of clinical evidence and the level of recommendation emerging from it. Algorithms are used to organize and summarize guidelines. The algorithm itself has a form of an informatic record and a logical flow. Algorithms, especially in case of clinical uncertainty, must be used for the improvement of health care, increasing it's availability and integration of the newest scientific knowledge. They should have an important role in the health care rationalisation, fight against non-rational diagnostics manifested as diagnostic procedures with no clinical indications, it's unnecessary repetition and wrong sequence. Several diagnostic algorithms used in the field of thyroid diseases are presented, since they have been proved to be of great use.

Outcomes for patients with second primary malignancy after primary surgical treatment for early-stage squamous cell carcinoma of the oral cavity.

BACKGROUND: The purpose of our article was to describe a tertiary center's experience with patients with primarily surgically treated early-stage intraoral cancer with a second primary malignancy confirmed during follow-up. METHODS: A total of 183 patients were primarily surgically treated for oral cancer between 2000 and 2004. Among these, 24 patients (13.1% (24/183)) met inclusion criteria. RESULTS: There were 22 men (91.7%) and 2 women (8.3%) with a median age of 59.5 years. Patients with head and neck cancer with a second primary malignancy had significantly higher survival compared to nonhead and neck cancer with a second primary malignancy. Patients with head and neck cancer with second primary malignancy were diagnosed during the period of 14 to 45 months (median 29 months), whereas nonhead and neck cancer with second primary malignancy occurred in a period of 7 to 46 months (median 19 months). CONCLUSION: This study highlights the importance of optimizing screening strategies for second primary malignancies. In order to improve the survival of patients with head and neck squamous cell carcinoma (HNSCC), effective programs of screening and/or chemoprevention of second primary malignancies are essential.

Prediction of radioactive iodine remnant ablation failure in patients with differentiated thyroid cancer: A cohort study of 740 patients.

BACKGROUND: The purpose of this study was to detect parameters that could serve as predictors of radioactive iodine (I-131) ablation failure in patients with low-risk and intermediate-risk differentiated thyroid carcinoma (DTC). METHODS: Our cohort study included 740 patients with DTC who received postoperative I-131 remnant ablation. Anthropometric, biochemical, and pathohistological parameters were analyzed and correlated with ablation outcome using multivariable logistic regression models. RESULTS: Treatment failure rates were higher in patients <53 years, with N1a classification, and lymph node capsular invasion. In patients with N1a disease, thyroglobulin (Tg) > 2.4 ng/mL predicted treatment failure with 93.8% sensitivity and 52.5% specificity, and in patients with N1b disease, Tg > 14.9 ng/mL with 77.8% sensitivity and 92.9% specificity. I-131 activity was not associated with treatment outcome. CONCLUSION: Patients < 53 years old, with higher Tg levels, N1a classification, and lymph node capsular invasion have a higher risk of ablation failure. Stimulated Tg is an excellent predictor of treatment failure in patients with N1 disease. © 2016 Wiley Periodicals, Inc. Head Neck 39: 109-115, 2017.

Neurosyphilis in Anglo-American Composers and Jazz Musicians.

Syphilis is a sexually transmitted, systemic disease caused by the spirochete bacterium Treponema pallidum. The most common mechanism of transmission is sexual intercourse. Although there are several hypotheses, the exact origin of the disease remains unknown. Newly published evidence suggests that the hypothesis supporting the theory of the American origin of the disease is the valid one. Among 1500 analyzed pathographies of composers and musicians, data on ten Anglo-American composers and jazz musicians having suffered from neurosyphilis (tertiary stage of the disease) were extracted for this report. In this group of Anglo-American composers and musicians, most of them died from progressive paralysis while still in the creative phase of life. Additionally, diagnoses of eleven other famous neurosyphilitic composers, as well as basic biographic data on ten less known composers that died from neurosyphilis-progressive paralysis are also briefly mentioned. In conclusion, neurosyphilis can cause serious neurological damage, as well as permanent disability or death, preventing further work and skill improvement.

Clinical and prognostic significance of anisocytosis measured as a red cell distribution width in patients with colorectal cancer.

PURPOSE: : colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and detection of new prognostic markers is mandatory for patients to receive optimal oncological treatment. The aim of the study was to assess clinical and prognostic value of red cell distribution width (RDW) in patients with CRC. METHODS: : RDW values in 90 patients with CRC undergoing surgery for primary disease were analyzed in pre- and postoperative setting, and correlated with clinical and hematological parameters. RESULTS: : Both pre- and postoperative RDW measurements were found to be associated with features of iron deficiency anemia, inflammatory response to tumor, advanced age and depth of tumor invasion. Optimal cutoff points were calculated to be 14% for preoperative and 13.6% for postoperative RDW measurements. Elevations in both pre- and postoperative RDW values had significant effects on survival in univariate and multivariate analyses. Effects were found to be independent of tumor related features, stage of the disease, development of anemia and aberrant inflammatory response to tumor. CONCLUSIONS: : RDW is an integrative parameter reflecting tumor specific features and shows significant association with overall survival in patients with CRC. This is especially important in patients with stage 2 disease where elevation in preoperative RDW values can contribute to recognition of higher risk patients.

Pleural and pericardial effusions combined with ascites in a patient with severe sunitinib-induced hypothyroidism.

To best of our knowledge, this is the first reported case of pericardial and pleural effusions combined with ascites, precipitated with severe sunitinib-induced hypothyroidism. A 58-year-old man presented in our emergency department due to dyspnoea and dry cough. Sixteen months earlier, the patient underwent left nephrectomy due to metastatic renal cell adenocarcinoma (RCC), and therapy with sunitinib was initiated postoperatively. Thyroid function was not assessed during the therapy. On admission, all laboratory findings were within normal range. Computed tomography of the chest detected voluminous bilateral pleural effusions and mild pericardial effusion, and echocardiography revealed pericardial effusion. Thoracocentesis was carried out three times, and cytological examination showed no signs of malignant cells. After assessment of the thyroid function, neglected hypothyroidism was registered. Substitution therapy with levothyroxine was initiated, and thyroid function normalised 2 weeks later. Few days after the last thoracocentesis, his condition suddenly got worse. Thoracocentesis was repeated, and microbiological analysis of the exudate came positive for Klebsiella pneumoniae and Streptococcus pneumoniae. Despite the implemented therapeutic measures, his clinical condition progressively deteriorated. The patient died 27 days after the admission, hospital-acquired pneumonia was identified as the cause of death. Our case emphasises the necessity of careful monitoring and management of side-effects in patients who receive sunitinib. Hypothyroidism is a known cause of pleural, pericardial and abdominal effusions, as reported in several case reports. Timely initiation of substitution levothyroxine therapy can decrease unnecessary pauses in the therapy with sunitinib, as well as prevent development of severe symptoms.

Re-ablation I-131 activity does not predict treatment success in low- and intermediate-risk patients with differentiated thyroid carcinoma.

The aim of this study was to evaluate the efficacy of different radioactive iodine (I-131) activities used for re-ablation, to compare various combinations of treatment activities, and to identify predictors of re-ablation failure in low- and intermediate-risk differentiated thyroid carcinoma (DTC) patients. The study included 128 consecutive low- and intermediate-risk patients with DTC with ablation failure after total thyroidectomy. Patient characteristics, T status, tumor size, lymph node involvement, postoperative remnant size on whole-body scintigraphy, serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), anti-Tg antibody (TgAb), and Tg/TSH ratio were analyzed as potential predictors of the re-ablation success. Re-ablation was successful in 113 out of 128 patients (88.3 %). Mean first I-131 activity was 2868 ± 914 MBq (77.5 ± 24.7 mCi) and mean second I-131 activity 3004 ± 699 MBq (81.2 ± 18.9 mCi). There was no association between the first, second, and cumulative activity with re-ablation treatment outcome. Treatment failure was associated with higher Tg levels prior to re-ablation (Tg2) (OR 1.16, 95 % CI 1.05-1.29, P = 0.003) and N1a status (OR 3.89, 95 % CI 1.13-13.41, P = 0.032). After excluding patients with positive-to-negative TgAb conversion, Tg2 level of 3.7 ng/mL predicted treatment failure with a sensitivity of 75.0 %, specificity of 80.5 %, and a negative predictive value of 97.1 %. Patients with positive-to-negative TgAb conversion had higher failure rates (OR 2.96, 95 % CI 0.94-9.29). Re-ablation success was high in all subgroups of patients and I-131 activity did not influence treatment outcome. Tg may serve as a good predictor of re-ablation failure. Patients with positive-to-negative TgAb conversion represent a specific group, in whom Tg level should not be used as a predictive marker of treatment outcome.

INITIAL SYMPTOMATIC PITUITARY METASTASIS IN A PATIENT WITH PROSTATE FOAMY GLAND CARCINOMA: TAILORING SAFE AND EFFECTIVE THERAPY.

Metastases to pituitary gland are unusual and mostly asymptomatic, presenting with local symptoms in one of ten patients, and only 3%-5% of them are of prostate origin. Here we report and evaluate the effectiveness and safety of multimodal treatment in a patient with pituitary metastasis of a prostate foamy gland carcinoma. A 78-year-old male patient presented with blurred vision and headache without a previous history of malignancy. Magnetic resonance imaging scans revealed a large sellar mass, with infiltration of the surrounding structures. Maximal transsphenoidal reduction of pituitary metastasis was performed, with a histologic finding of metastatic prostate foamy gland adenocarcinoma. Evaluation of the prostate specific antigen revealed a very high level (1461 ng/mL) and foamy gland carcinoma was found on prostate needle biopsy. The patient received 3D conformal external beam radiotherapy with 6 MV photons to the sellar and parasellar region with a tumor dose of 44 Gy, followed by androgen deprivation therapy. Follow up magnetic resonance imaging done after radiotherapy showed shrinkage of the tumor process, with rapid prostate specific antigen decline to 0.3 ng/mL. The visual function was fully established and headache resolved. On the last follow up 14 months after the diagnosis, the patient was alive and free from clinical signs of disease. Tailored treatment, including limited radiotherapy in a higher palliative dose, in a patient with foamy gland symptomatic pituitary metastatic disease resulted in good local and systemic control of the disease. In older male patients with clinical and/or radiologic characteristics suggestive of metastatic pituitary disease, the prostate specific antigen test should be included as part of the work-up.