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.
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.
Rak tijela maternice, prema zadnjim podatcima Registra za rak iz 2017. godine u Republici Hrvatskoj, nalazi se na četvrtom mjestu po učestalosti, a na osmom mjestu po smrtnosti. Najčešće se ...dijagnosticira u postmenopauzalnih žena, većinom u dobi od 50. do 79. godine života. Dijagnoza karcinoma endometrija utvrđuje se patohistološkom analizom kiretmana ili bioptata sluznice maternice, a stupanj proširenosti bolesti primjenom slikovnih metoda. U većine bolesnica bolest se otkriva u lokaliziranom stadiju te se uspješno liječi operativno, a ovisno o patohistološkom nalazu i primjenom odgovarajuće adjuvantne terapije. Lokalno uznapredovala bolest najčešće se liječi operativno uz adjuvantnu terapiju, a metastatska primjenom kemoterapije ili hormonske terapije. Mezenhimalni tumori tijela maternice liječe se operativno uz dodatak sistemske terapije adjuvantno ili samo sistemskom terapijom u slučaju diseminirane bolesti. Ove kliničke upute pisane su u cilju postizanja najviših standarda i ujednačenja postupaka u dijagnosticiranju, liječenju i praćenju bolesnica sa zloćudnim tumorima tijela maternice u Republici Hrvatskoj.
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.
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. Key words: prostate IMRT, patient specific QA Radioterapija moduliranog intenziteta (eng intensity modulated radiotherapy -IMRT) u posljednjem desetljecu je postala uobicajena radioterapijska metoda za terapiju lokaliziranih karcinoma prostate. Prelazak s konformalne radioterapije na napredniju i tehnicki slozeniju IMRT tehniku, donio je i potrebu za detaljnijom i sveobuhvatnom provjerom tocnosti isporuke doze zracenja. U ovom radu predstavljamo provodenje postupaka dozimetrijske verifikacije radio terapijskih planova poznatih pod engleskim nazivom patient specific QA (PSQA) te rezultate za 40 bolesnika s karcinomom prostate koji su primili IMRT terapiju. U tu svrhu koristimo posebni dozimetrijski sustav s rotacijskim fantomom i visoko razlucivom detektorskom matricom, Octavius 4D (PTW Freiburg). Pokazalo se kako su sva dobivena odstupanja izmedu planirane i mjerene trodimenzionalne raspodjele doze bila unutar preporucenih tolerancija (1) sto nam daje povjerenje u sigurnost provodenja ovakve terapije te otvara mogucnost za primjenu strozijih ogranicenja u buducnosti. Kljucne rijeci: radioterapija moduliranog intenziteta (IMRT) karcinoma prostate, dozimetrijska verifikacija plana, patient specific QA (PSQA)
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