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.
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.
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.
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.
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.
Objective
To assess efficiency of various I-131 activities on thyroid remnant ablation in thyroid cancer patients. The significance of patients’ characteristics, pathologic features and levels of Tg ...were analyzed.
Patients and methods
This study included 259 consecutive differentiated thyroid cancer patients, with disease confined to the thyroid, treated with I-131 after total thyroidectomy. Patients were divided into the three groups: 80 patients receiving low 1110–1850 MBq (30–50 mCi), 121 intermediate 2775 MBq (75 mCi) and 58 high 3700 MBq (100 mCi) postoperative I-131 activities. Six to eight months after the application of radioiodine, measurements of TSH, Tg, anti-Tg antibodies (in hypothyroid state) together with ultrasound exam and whole-body scintigraphy were performed.
Results
The ablation was significantly more effective (after the first application) in patients receiving 100 mCi of I-131—89.7 % than in patients receiving lower activities (
P
= 0.016). There was no significant difference in ablation rate between the 30–50 mCi (77.5 %) and 75 mCi (70.2 %) groups. In the group receiving 30–50 mCi, patients with solitary tumors had significantly higher ablation rate (
P
= 0.038). In patients receiving 75 mCi ablation rates were higher among older patients (
P
= 0.005), with infiltration of the single lobe (
P
= 0.005), and with solitary tumor (
P
= 0.012). The rates of successful ablation after the second application of I-131 (after 12–16 months) amounted to 96, 97 and 96 % in the 30–50, 75 and 100 mCi groups, respectively. The activity of I-131 and age were independent factors for thyroid ablation failure after the first application of I-131 (model of binary logistic regression).
Conclusion
The results of remnant ablation were satisfactory with all activities applied. Although after the first application of I-131 the activity of 100 mCi is significantly more effective in thyroid ablation than the administration of 30–50 mCi and 75 mCi, the ablation rates between all the three groups are similar (almost equal) after the second application. Thus, the activity to be administered may depend on patients’ characteristics and a detailed consideration of the merits and demerits of each I-131 activity.
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.
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.
- 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.
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 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, chi square-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. Key words: Subclinical hypothyroidism; Prevalence; Elderly; Thyroid gland; Thyroid dysfunction; Thyrotropin; Cholesterol
Tyrosine kinase inhibitors are standard treatment in patients with metastatic renal cell carcinoma (mRCC). Several studies have indicated that side-effects including hypothyroidism may serve as ...potential predictive biomarkers of treatment efficacy.
All patients with clear cell mRCC treated with sunitinib in the first-line setting in our Center between November 2008 and October 2013 were included. Thyroid function was assessed after every 2 cycles. Prognostic factors were tested using Cox proportional hazards model for univariate analysis.
During treatment, 29.3% developed hypothyroidism, with a median of peak TSH values of 34.4 mIU/L. Patients who had both TSH >4 mIU/L and were receiving substitution therapy with levothyroxine had prolonged PFS compared to all other patients (25.3 months vs. 9.0 months; p=0.042).
The rate of hypothyroidism as a side-effect of sunitinib in patients with mRCC is significant. Patients with symptomatic hypothyroidism experienced significantly longer PFS, but without difference in OS.
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