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BACKGROUND: Salvage radiotherapy (SRT) and androgen-deprivation therapy (ADT) are widely used in routine clinical practice to treat patients with prostate cancer who develop biochemical recurrence (BCR) after radical prostatectomy (RP). However, there is no standard-of-care consensus on optimal duration ADT. Investigators propose three distinct risk groups in patients with prostate cancer treated with SRT in order to better define the indications and duration of ADT combined with SRT. STUDY DESIGN: The URONCOR 06-24 trial (ClinicalTrials.gov identifier NCT05781217) is a prospective, multicentre, randomised, open-label, phase III, clinical trial. The aim of the trial is to determine the impact of short-term (6 months) vs long-term (24 months) ADT in combination with SRT on distant metastasis-free survival (MFS) in patients with prostate cancer with BCR after RP (intermediate and high risk). ENDPOINTS: The primary endpoint is 5-year MFS rates in patients with prostate cancer treated with long- vs short-term ADT in combination with SRT. Secondary objectives are biochemical-relapse free interval, pelvic progression-free survival, time to start of systemic treatment, time to castration resistance, cancer-specific survival, overall survival, acute and late toxicity, and quality of life. METHODS AND ANALYSIS: Total of 534 patients will be randomised 1:1 to ADT 6 months or ADT 24 months with a luteinizing hormone-releasing hormone analogue in combination with SRT, stratified by risk group and pathological lymph node status. ETHICS AND DISSEMINATION: The study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT number 2021-006975-41.
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Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumor's anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.
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In recent years, several systemic therapies have been introduced for metastatic hormone-sensitive prostate cancer, including androgen deprivation therapy (ADT) combined with docetaxel (Doc) and/or new-generation androgen receptor signaling inhibitors (ARSI). Trials evaluating ADT + ARSI have consistently demonstrated an overall survival (OS) benefit for doublet therapy over ADT alone. Similarly, the STOPCaP meta-analysis showed an OS benefit in favor of ADT + Doc versus ADT alone. ARSI, Doc, and ADT have different antitumor mechanisms, thus potentiating the effect of combination therapy. Two randomized trials showed that the addition of ARSI to ADT + Doc improves OS, especially for synchronous high-volume disease. However, the real question about triplet therapy remains unanswered: whether combining Doc with ARSI improves outcomes compared to ADT + ARSI. As there are no head-to-head comparisons, this narrative review aims to summarize the current evidence regarding triplet therapy versus doublet therapy including ADT+ ARSI.
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Neoplasias da Próstata , Masculino , Humanos , Docetaxel/uso terapêutico , Neoplasias da Próstata/patologia , Receptores Androgênicos , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
PURPOSE: To compare the long-term oncologic outcomes of intermediate risk (IR) prostate cancer (PCa) patients treated with low dose-rate brachytherapy (LDR-BT) or moderate hypofractionated external beam radiotherapy (HF-EBRT). METHODS AND MATERIALS: Patients diagnosed with IR PCa and treated with LDR-BT or HF-EBRT between January 2005 and December 2013 were included. Brachytherapy treatment involved a transperineal implant of iodine-125 to a dose of 145 Gy to the PTV, while HF-EBRT was delivered using intensity modulated radiotherapy with 60 Gy in 20 fractions. The Phoenix ''nadir +2'' threshold was used to define biochemical relapse (BR). The cumulative incidence function (CIF) of BR and metastases was reported for each group and compared using the Gray's test to account for the competing risk of death. The Kaplan-Meier (KM) method was used to estimate overall survival (OS) and prostate cancer specific survival (PCSS). Univariate (UVA) and multivariable (MVA) analysis of the CIF of BR and metastases were performed. A 2-tailed p-value ≤ 0.05 was considered statistically significant. RESULTS: Overall, 122 and 124 patients were treated with LDR-BT and HF-EBRT respectively. Median follow-up was 95 months [interquartile range (IQR): 79-118] in the LDR-BT group and 96 months (IQR: 63-123) in the HF-EBRT group. BR was observed in 5 patients treated with LDR-BT and 34 treated with HF-EBRT. At 60 and 90 months, the CIF of BR was 0.9% and 3.5% in the LDR-BT group vs. 16.6% and 23.7% in the HF-EBRT (p < 0.001). The CIF of metastases at 90 and 108 months, was 0% and 1.6% vs. 3.4% and 9.1% in the LDR-BT and HF-EBRT groups (pâ¯=â¯0.003), respectively. At the last follow-up, 3 patients treated with HF-EBRT died from their cancer [PCSS of 97.5% at 8 years and none died in the LDR-BT group (pâ¯=â¯0.09). On UVA and MVA risk group and treatment modality were independently associated with CIF of BR. On UVA HF-EBRT and ISUP grade group 3 were associated with metastases. CONCLUSION: LDR-BT was associated with higher biochemical and metastases control in our cohort when compared to moderately HF-EBRT. In the absence of a randomized trial, LDR-BT when feasible should be offered to patients with a life expectancy of >8 years.
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Braquiterapia , Neoplasias da Próstata , Masculino , Humanos , Braquiterapia/métodos , Estudos Retrospectivos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/etiologia , Neoplasias da Próstata/patologia , Dosagem RadioterapêuticaRESUMO
PURPOSE: To report acute toxicity and health-related quality of life (HRQoL) outcomes of a phase II clinical trial of magnetic resonance imaging (MRI)-guided prostate high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy. METHODS AND MATERIALS: Patients with intermediate- and high-risk prostate cancer (PCa) were eligible. Treatment consisted of a single 15 Gy MRI-guided HDR-BT followed by external beam radiotherapy (37.5-46 Gy depending on their risk category). Dosimetry, toxicity and HRQoL outcomes were collected prospectively at baseline, 1 and 3 months using Common Terminology Criteria for Adverse Events Version 4.0 and the expanded PCa index composite, respectively. General linear mixed modeling was conducted to assess the changes in expanded PCa index composite domain scores over time. A minimally important difference was defined as a deterioration of HRQoL scores at 3 months compared to baseline ≥ 0.5 standard deviation. A p value ≤ 0.05 was considered statistically significant. RESULTS: Sixty-one patients were included. Acute grade (G)2 urinary toxicity was observed in 18 (30%) patients while 1 (2%) patient had G3 toxicity, and none had G4 toxicity. Two patients had an acute urinary retention. G2 gastrointestinal toxicity was reported by 5 (8%) patients with no G3-4. Compared to baseline, urinary HRQoL scores significantly declined at 1 month (p < 0.001) but recovered at 3 months (p > 0.05). Bowel (p < 0.001) and sexual (p < 0.001) domain scores showed a significant decline over the 3-month follow-up period. At 3 months, 44%, 49% and 57% of patients reported a minimally important difference respectively in the urinary bowel and sexual domains. CONCLUSION: MRI-guided HDR-BT boost is a safe and well tolerated treatment of intermediate- and high-risk PCa in the acute setting. A longer follow-up and a comparison to ultrasound-based HDR-BT are needed to assess the potential benefit of MRI-guided prostate HDR-BT.
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Braquiterapia , Neoplasias da Próstata , Lesões por Radiação , Masculino , Humanos , Braquiterapia/métodos , Qualidade de Vida , Estudos Prospectivos , Dosagem Radioterapêutica , Lesões por Radiação/etiologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND AND PURPOSE: To evaluate the results of low-dose radiation therapy (LD-RT) to lungs in the management of patients with COVID-19 pneumonia. MATERIAL AND METHODS: We conducted a prospective phase I-II trial enrolling COVID-19 patients ≥50 years-old, with bilateral lung involvement at imaging study and oxygen requirement (oxygen saturation ≤93% on room air). Patients received 1 Gy to whole lungs in a single fraction. Primary outcome was a radiological response assessed as severity and extension scores at days +3 and +7. Secondary outcomes were toxicity (CTCAE v5.0), days of hospitalization, changes in inflammatory blood parameters (ferritin, lymphocytes, C-reactive protein, d-dimer and LDH) and SatO2/FiO2 index (SAFI), at day +3 and +7. Descriptive analyses were summarized as means with standard deviation (SD) and/or medians with interquartile ranges (IQR). A Wilcoxon sign rank test for paired data was used to assess the CT scores and Chi Square was used to assess for comparison of categorical variables. RESULTS: Forty-one patients were included. Median age was 71 (IQR 60-84). Eighteen patients (44%) previously received an anti-COVID treatment (tocilizumab, lopinavir/ritonavir, remdesivir) and thirty-two patients (84%) received steroids during LD-RT. The extension score improved significantly (p = 0.02) on day +7. Mean baseline extension score was 13.7 (SD ± 4.9) with a score of 12.2 (±5.2) at day 3, and 12.4 ± 4.7 at day 7. No differences were found in the severity score. SAFI improved significantly on day +3 and +7 (p < 0.01). Median SAFI on day 0 was 147 (IQR 118-264), 230 (IQR 120-343) on day +3 and 293 (IQR 121-353) on day +7. Significant decrease was found in C-reactive protein on day +7 (p = 0.02) and in lymphocytes counts on day +3 and +7 (p = 0.02). The median number of days in hospital after RT was 11 (range 4-78). With a median follow-up of 60 days after LD-RT, 26 (63%) patients were discharged, 11 (27%) died because of COVID respiratory failure and 4 (10%) died of other causes. CONCLUSIONS: LD-RT is a feasible and well-tolerated treatment that could lead to rapid clinical improvement. Large randomized trials would be required to establish the efficacy of LD-RT to treat COVID-19 pneumonia.
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COVID-19 , Idoso , Proteína C-Reativa , COVID-19/radioterapia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , Resultado do TratamentoRESUMO
PURPOSE: Low-dose radiation therapy (LD-RT) has been shown to have an anti-inflammatory effect, and preliminary results suggest it is feasible to treat patients with coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: We conducted a prospective, single-arm, phase 1/2 clinical trial enrolling patients aged ≥50 years, who were coronavirus disease 2019 (COVID-19) positive, at phase 2 or 3 with lung involvement at imaging study and oxygen requirement. Patients received 100 cGy to total lungs in a single fraction. Primary outcome was radiologic response using severity and extension score on baseline computed tomography (CT), at days 3 and 7 after LD-RT. Secondary outcomes were toxicity using Common Terminology Criteria for Adverse Events v.5.0, duration of hospitalization, blood work evolution, and oxygen requirements using SatO2/FiO2 index (SAFI), at days 3 and 7 after LD-RT. RESULTS: Nine patients were included. Median age was 66 (interquartile range, 57-77). Severity score was stable or decreased in the third CT but was not statistically significant (P = .28); however, there were statistically significant changes in the extension score (P = .03). SAFI index significantly improved 72 hours and 1 week after LD-RT (P = .01). Inflammatory blood parameters decreased 1 week after RT compared with baseline; only lactate dehydrogenase decreased significantly (P = .04). Two patients presented grade 2 lymphopenia after RT and another (with baseline grade 3) worsened to grade 4. Overall, the median number of days of hospitalization was 59 (range, 26-151). After RT the median number of days in the hospital was 13 (range, 4-77). With a median follow-up after RT of 112 days (range, 105-150), 7 patients were discharged and 2 patients died, 1 due to sepsis and the other with severe baseline chronic obstructive pulmonary disease from COVID-19 pneumonia. CONCLUSIONS: Our preliminary results show that LD-RT was a feasible and well-tolerated treatment, with potential clinical improvement. Randomized trials are needed to establish whether LD-RT improves severe pneumonia.
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COVID-19/radioterapia , Doses de Radiação , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Dosagem Radioterapêutica , Resultado do TratamentoRESUMO
PURPOSE: To assess the impact of RTOG-9601 and GETUG-AFU-16 on the routine use of combination androgen deprivation therapy (ADT) with postoperative radiotherapy (PORT) for prostate cancer (CaP). MATERIAL AND METHODS: Patients with localized CaP treated with radical prostatectomy (RP) and PORT with or without ADT at a comprehensive cancer center from January 2006 to June 2007 (Period 1â¯=â¯P1), July 2011 to December 2012 (Period 2â¯=â¯P2), and January 2017 to June 2018 (Period 3â¯=â¯P3) were included. Clinicopathologic features and treatment characteristics were analyzed and compared. Multivariable logistic regression was used to assess prognostic factors and association with ADT use. Statistical tests were two-sided and a P value <0.05 was considered significant. To validate the findings, United States National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results (SEER) data were collected to assess rates of combined ADT and PORT from 2004 to 2015. RESULTS: Five hundred and two patients were included: 152 (P1), 185 (P2), and 165 (P3). PORT was most commonly delivered as early SRT (delivered >1 year post-RP with undetectable PSA or PSA >0.05 and ≤0.5 ng/ml) in all periods. The use of combination PORT and ADT increased over time: 14.5% (P1), 32% (P2), and 41% (P3) (P < 0.001). The proportion of patients that met eligibility criteria for either GETUG-AFU-16 or RTOG-9601 decreased from 47% (P1) to 35% (P3) (Pâ¯=â¯0.04). International Society of Urological Pathology grade ≥4 (P < 0.002) and pre-PORT PSA >0.5 ng/ml (P < 0.001) were associated with use of ADT. Positive surgical margin status had a negative association (RR 0.5, P < 0.002). The NCDB demonstrated similar trends for use of combined ADT with PORT, increasing from 37% to 49% from 2004 to 2015. CONCLUSION: The use of combined ADT with PORT increased over time. However, only a third of contemporary patients undergoing PORT are represented in the major trials supporting the evidence for combination treatment, highlighting the need to characterize the modern impact of this intensification strategy.
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Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Idoso , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prostatectomia , Neoplasias da Próstata/cirurgia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: To report dosimetry, preliminary toxicity and health-related quality of life (HRQoL) outcomes of tumor-targeted dose-escalation delivered by integrated boost volumetric arc therapy (IB-VMAT) or MR-guided HDR brachytherapy (HDR) boost for prostate cancer. MATERIALS AND METHODS: Patients diagnosed with localized prostate cancer, with at least 1 identifiable intraprostatic lesion on multiparametric MRI (mpMRI) were enrolled in a prospective non-randomized phase II study. All patients received VMAT to the prostate alone (76 Gy in 38 fractions) plus a GTV boost: IB-VMAT (95 Gy in 38 fractions) or MR-guided HDR (10 Gy single fraction). GTV was delineated on mpMRI and deformably registered to planning CT scans. Comparative dosimetry using EQD2 assuming α/ß 3 Gy was performed. Toxicity and health-related quality of life data (HRQoL) data were collected using CTCAE v.4.0, International Prostate Symptom Score (IPSS) and the Expanded Prostate Index Composite (EPIC). RESULTS: Forty patients received IB-VMAT and 40 HDR boost. Organs at risk and target minimal doses were comparable between the two arms. HDR achieved higher mean and maximal tumor doses (p < 0.05). Median follow-up was 31 months (range 25-48); Acute grade G2 genitourinary (GU) toxicity was 30% and 37.5% in IB-VMAT and HDR boost, while gastrointestinal (GI) toxicity was 7.5% and 10%, respectively. Three patients developed acute G3 events, two GU toxicity (one IB-VMAT and one HDR boost) and one GI (IB-VMAT). Late G2 GU toxicity was 25% and 17.5% in the IB-VMAT and HDR boost arm and G2 GI was 5% and 7.5%, respectively. Two patients, both on the IB-VMAT arm, developed late G3 toxicity: one GI and one GU. No statistically significant difference was found in HRQoL between radiotherapy techniques (p > 0.2). Urinary and bowel HRQoL domains in both groups declined significantly by week 6 of treatment in both arms (p < 0.05) and recovered baseline scores at 6 months. CONCLUSION: Intraprostatic tumor dose escalation using IB-VMAT or MR-guided HDR boost achieved comparable OAR dosimetry, toxicity and HRQOL outcomes, but higher mean and maximal tumor dose were achieved with the HDR technique. Further follow-up will determine long-term outcomes including disease control.
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Braquiterapia , Neoplasias da Próstata , Lesões por Radiação , Braquiterapia/efeitos adversos , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Dosagem RadioterapêuticaRESUMO
OBJECTIVES: To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT). PATIENTS AND METHODS: A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes. RESULTS: In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high-intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T-stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow-up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR-free survival (hazard ratio 6.624, 95% confidence interval 2.243-19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5-9.5) and 23.5 (15.75-25) respectively, while in the final follow-up the median (IQR) values were 7 (3.5-11) and 6 (5-12.25), respectively (P = 0.088 and P < 0.001). At last follow-up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter. CONCLUSIONS: sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.
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Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Idoso , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Terapia de Salvação , Resultado do TratamentoRESUMO
PURPOSE: To assess the impact of the dose to the bladder neck (BN) on acute urinary toxicity (AUT) and health-related quality of life (uHRQoL) in patients with prostate cancer treated with MRI-guided high-dose-rate brachytherapy combined to external beam radiotherapy. METHODS AND MATERIALS: Sixty-one patients were treated with a single 15-Gy MRI-guided high-dose-rate brachytherapy followed by external beam radiotherapy as part of a prospective Phase II trial. The BN was delineated in retrospect on T2-weighted images. AUT and uHRQoL data were collected prospectively using Common Terminology Criteria for Adverse Events version 4.0 and the expanded prostate index composite. A minimally important difference (MID) was defined as a deterioration of uHRQoL scores at 3 months ≥ 0.5 standard deviation of baseline score. Linear and logistic regression models were used. RESULTS: The median BN volume was 0.6 cc. The median BN and urethral maximum dose (BNDmax and UDmax) were 22 Gy and 20 Gy, respectively. BNDmax was significantly associated with UDmax (p = 0.03). AUT Grade 2 + was observed in 32% of patients. Among those, 4 patients had an acute urinary retention (AUR). No Grade 4 + toxicity was reported. At 3 months, 47% of patients reported an MID in urinary uHRQoL. None of the dosimetric parameters including BNDmax was associated with acute Grade 2 + urinary toxicity or MID. However, 3 of 4 patients with AUR had a BNDmax in the highest quartile; >175% of prescription dose. CONCLUSIONS: Although a high BN dose was observed in patients who had an AUR, the predictive value of this parameter is yet to be determined in a larger cohort.
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Braquiterapia/efeitos adversos , Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Lesões por Radiação/etiologia , Bexiga Urinária/efeitos da radiação , Idoso , Terapia Combinada , Fracionamento da Dose de Radiação , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Órgãos em Risco/efeitos da radiação , Estudos Prospectivos , Doses de Radiação , Lesões por Radiação/diagnóstico por imagem , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/efeitos adversos , Uretra/efeitos da radiação , Bexiga Urinária/diagnóstico por imagem , Retenção Urinária/etiologiaRESUMO
PURPOSE: Neoadjuvant radiation therapy (RT) improves disease control in various cancers and has become an established oncologic treatment strategy. During 2001 to 2004, we conducted a phase 1 pilot study assessing the role of short-course preoperative RT (PreORT) for men with unfavorable intermediate- and high-risk localized prostate cancer. Herein, we present long-term follow-up toxicity and oncologic outcomes. METHODS AND MATERIALS: Eligible patients had histologically proven prostate cancer, cT1-T2N0M0 disease, prostate-specific antigen >15 to 35 ng/mL regardless of Gleason score, or prostate-specific antigen 10 to 15 ng/mL with Gleason score ≥7. Patients received 25 Gy in 5 consecutive daily fractions (5 Gy per fraction) to the prostate only, followed by radical prostatectomy within 14 days after RT completion. Primary outcomes were intraoperative morbidity and late genitourinary (GU) and gastrointestinal toxicities. RESULTS: In total, 15 patients were enrolled; 14 patients completed PreORT followed by radical prostatectomy, which also included bilateral lymph node dissections in 13 cases. Median follow-up was 12.2 years (range, 6.7-16.3). Late GU toxicity was common, with 2 patients (13.3%) experiencing G2 toxicity and 6 patients (40%) G3 toxicity. There were no patients with G4 to G5 late GU toxicity. Late gastrointestinal toxicity was infrequent, with only 1 patient (6.7%) experiencing transient G2 proctitis. At last follow-up, 8 (53.3%) and 6 (40%) patients experienced biochemical and metastatic disease recurrence, respectively. CONCLUSIONS: The use of PreORT in men with high-risk prostate cancer is associated with unexpected high rates of late GU toxicity. Future studies examining the role of RT preradical prostatectomy must cautiously select RT technique and dose schedule. Importantly, long-term follow-up data are essential to fully determine the therapeutic index of PreORT in the management of localized disease.
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Neoplasias da Próstata/radioterapia , Idoso , Fracionamento da Dose de Radiação , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Projetos Piloto , Cuidados Pré-Operatórios , Proctite/etiologia , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia Conformacional , Fatores de Tempo , Resultado do Tratamento , Sistema Urogenital/efeitos da radiaçãoRESUMO
PURPOSE: The NCCN Guidelines® recently endorsed a subclassification of intermediate risk prostate cancer into favorable and unfavorable subgroups. However, this subclassification was developed in a treatment heterogeneous cohort. Thus, to our knowledge the natural history of androgen deprivation treatment naïve favorable and unfavorable intermediate risk prostate cancer cases remains unknown. MATERIALS AND METHODS: Groups at 3 academic centers pooled data on patients with intermediate risk prostate cancer treated with radical monotherapy (dose escalated external beam radiotherapy, brachytherapy or radical prostatectomy) without combined androgen deprivation treatment. We used the cumulative incidence with competing risk analysis to estimate biochemical recurrence, distant metastasis and prostate cancer specific mortality. RESULTS: A total of 2,550 men at intermediate risk were included in study, of whom 1,063 and 1,487 were at favorable and unfavorable risk, respectively. Of the men 1,149 underwent radical prostatectomy, 1,143 underwent dose escalated external beam radiotherapy and 258 underwent brachytherapy. Median followup after the different treatments ranged from 60.4 to 107.4 months. The 10-year cumulative incidence of distant metastasis in the favorable vs unfavorable risk groups was 0.2% (95% CI 0.2-0.2) vs 11.6% (95% CI 7.7-15.5) for radical prostatectomy (p <0.001), 2.8% (95% CI 0.8-4.8) vs 13.5% (95% CI 9.6-17.4) for dose escalated external beam radiotherapy (p <0.001) and 3.5% (95% CI 0-7.4) vs 10.2% (95% CI 4.3-16.1) for brachytherapy (p = 0.063). The 10-year rate of prostate cancer specific mortality in the favorable vs unfavorable risk groups was 0% (95% CI 0-0) vs 3.7% (95% CI 1.7-5.7) for radical prostatectomy (p = 0.016), 0.5% (95% CI 0.5-0.5) vs 5.6% (95% CI 3.6-7.6) for dose escalated external beam radiotherapy (p = 0.015) and 0% (95% CI 0-0) vs 2.5% (95% CI 0.5-4.5) for brachytherapy (p = 0.028). CONCLUSIONS: This multicenter international effort independently validates the prognostic value of the intermediate risk prostate cancer subclassification in androgen deprivation treatment naïve cases across all radical treatment modalities. It is unlikely that treatment intensification would meaningfully improve oncologic outcomes in men at favorable intermediate risk.
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Braquiterapia , Recidiva Local de Neoplasia/diagnóstico , Prostatectomia , Neoplasias da Próstata/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Próstata/patologia , Próstata/cirurgia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: The risk of gastrointestinal (GI) toxicity may limit the use of curative-intent radical radiotherapy (RT) for prostate cancer (PCa) in circumstances where morbidity of treatment may exceed an acceptable threshold. Rectal spacers are used to expand the distance between the anterior rectal wall and the prostate, consequently sparing the rectum from the high-dose region. CASE PRESENTATIONS: We report three clinical scenarios of PCa patients treated at our institution, where risk of RT-associated rectal toxicity may be increased: inflammatory bowel disease (IBD), salvage brachytherapy (BT) after previous external beam RT (EBRT), and tailored dose-escalation with focal BT to the gross tumor volume followed by stereotactic body RT. Prior to RT, a polyethylene glycol (PEG) hydrogel spacer was successfully placed in all cases. Treatment comprised magnetic resonance (MR) guided high dose-rate BT ± EBRT. All patients completed treatment uneventfully, without any significant GI toxicity at last follow-up. CONCLUSIONS: These cases illustrate the utility of PEG hydrogel spacer, where concerns of radiation induced toxicity may have previously limited the application of radiotherapy. The synergistic use of these novel devices together with MR-guided BT may expand the indications and therapeutic index of curative-intent RT-based treatments, while minimizing the risks of GI toxicity.
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Management options for locally recurrent sarcoma of the pelvis in patients previously treated with external beam radiation and surgery are limited. Pelvic exenteration is often the only viable but unattractive option. We present a patient with recurrent myxoid round cell liposarcoma of the ischiorectal fossa treated in 2013 with preoperative radiation (50 Gy in 25 fractions) and subsequent wide local resection. Four years later, a follow-up magnetic resonance imaging (MRI) scan demonstrated a 1 x 1 cm T2 hypointense soft tissue pre-sacral nodule consistent with local recurrence (LR). The patient declined posterior pelvic exenteration and was treated with 12 Gy using high dose rate brachytherapy (BT) under MRI-guidance followed by a further external beam radiation to a dose of 30 Gy in 15 fractions.