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Androgen deprivation therapy (ADT) is a mainstay of treatment for metastatic prostate cancer, while additional salvage radiotherapy may offer prolonged remission for patients with regional node relapses. We report 5-yr outcomes from OLIGOPELVIS (GETUG-P07), an open-label phase 2 trial assessing long-term outcomes and patterns of relapse after 6-mo ADT and elective nodal radiotherapy (ENRT) in men with pelvic nodal oligorecurrence (<6 lesions) of prostate cancer. Progression was defined as two consecutive prostate-specific antigen (PSA) levels above the level at inclusion and/or clinical progression according to Response Evaluation Criteria in Solid Tumors v1.1 and/or death from any cause. Sixty-seven patients were recruited. Median follow-up was 6.1 yr (95% confidence interval 5.9-6.3). Rates of grade 2+ toxicities among patients without progression at 3, 4, and 5 yr were 15%, 9%, and 4% for genitourinary toxicities, and 2%, 3%, and 4% for gastrointestinal toxicities, respectively. The 5-yr progression-free, biochemical relapse-free, and ADT-free survival rates were 39%, 31%, and 64%, respectively. In total, 45 patients experienced progression, which was PSA-only progression in seven cases. Among the other 38 patients, local clinical progression occurred in 18%, progression to N1 stage in 29%, to M1a stage in 50%, to M1b stage in 32%, and to M1c stage in 11%. Finally, combined ENRT and ADT appeared to prolong tumor control with limited toxicity. At 5 yr, one-third of the patients had not experienced biochemical relapse. The major site of relapse was the para-aortic lymph nodes. PATIENT SUMMARY: We evaluated long-term results for high-dose radiotherapy in patients with recurrence of prostate cancer in pelvic lymph nodes. We found that this treatment provided prolonged tumor control without significant toxicity. One-third of the patients were still in complete remission after 5 years.
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Introduction: Delayed surgical management of spinal metastases (SMs) can have detrimental effects on patient survival and quality of life, leading to pain and potential neurological impairment. This study aimed to assess the impact of delayed referral for SMs on clinical outcomes by analyzing patients managed in emergency situations. Methods: We retrospectively reviewed the data of all patients admitted on either emergency or elective basis who underwent surgery for the treatment of neoplastic spine lesions at our two institutions (tertiary referral neurosurgical units) between January 2008 and December 2019. Results: We analyzed 210 elective (EGp) and 323 emergency patients (UGp); emergencies increased significantly over the 12-year period, with a Friday peak (39.3%) and frequent neurological impairment (61.6% vs. 20%). Among the UGp patients, 186 (7.5%) had a previously monitored primitive cancer, including 102 (31.6%) with known SMs. On admission, 71 of the 102 (69.9%) patients presented with neurological deficits. UGp patients were more likely to undergo a single decompression without fixation. Outcomes at the 3-month follow-up were significantly worse for UGp patients ([very] poor, 29.2 vs. 13.8%), and the median overall survival for UGp patients was statistically lower. Risk factors for patients with SM undergoing emergency management included short delay between onset of symptoms and first contact with a spine surgeon, and an initial motor deficit. Conclusion: Many patients with previously identified metastases, including those with neurological deficits, are urgently referred. Optimization is needed in the oncology pathway, and all stakeholders must be made aware of the factors contributing to the improvement in the clinical and radiological identification of potential complications affecting patient survival and quality of life.
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Purpose: High-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer. Methods: Patients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed. Results: We recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p < 0.01 for both GU and GI). Medians of OS, bRFS, LRRFS, MFS and DFS were not reached. At 60 months, OS, bRFS, LRRFS, MFS and DFS were 88.2 % [82.1; 94.7], 86.0 % [79.4 %;93.2 %], 95.8 % [91.8 %;99.9 %], 87.2 % [80.9 %;94.0 %] and 84.1 % [77.2 %;91.6 %] respectively. Conclusion: SIB RT at a dose of 54.4 Gy to the pelvis and 74.8 Gy to the prostate is feasible, leading to satisfying tumor control and reasonable toxicity in HR and VHR prostate cancer.
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CONTEXT: Erectile dysfunction represents a major side effect of prostate cancer (PCa) treatment, negatively impacting men's quality of life. While radiation therapy (RT) advances have enabled the mitigation of both genitourinary and gastrointestinal toxicities, no significant improvement has been showed in sexual quality of life over time. OBJECTIVE: The primary aim of this review was to assess sexual structures' dose-volume parameters associated with the onset of erectile dysfunction. EVIDENCE ACQUISITION: We searched the PubMed database and ClinicalTrials.gov until January 4, 2023. Studies reporting the impact of the dose delivered to sexual structures on sexual function or the feasibility of innovative sexual structure-sparing approaches were deemed eligible. EVIDENCE SYNTHESIS: Sexual-sparing strategies have involved four sexual organs. The mean penile bulb doses exceeding 20 Gy are predictive of erectile dysfunction in modern PCa RT trial. Maintaining a D100% of ≤36 Gy on the internal pudendal arteries showed preservation of erectile function in 88% of patients at 5 yr. Neurovascular bundle sparing appears feasible with magnetic resonance-guided radiation therapy, yet its clinical impact remains unanswered. Doses delivered to the testicles during PCa RT usually remain <2 Gy and generate a decrease in testosterone levels ranging from -4.6% to -17%, unlikely to have any clinical impact. CONCLUSIONS: Current data highlight the technical feasibility of sexual sparing for PCa RT. The proportion of erectile dysfunction attributable to the dose delivered to sexual structures is still largely unknown. While the ability to maintain sexual function over time is impacted by factors such as age or comorbidities, only selected patients are likely to benefit from sexual-sparing RT. PATIENT SUMMARY: Technical advances in radiation therapy (RT) made it possible to significantly lower the dose delivered to sexual structures. While sexual function is known to decline with age, the preservation of sexual structures for prostate cancer RT is likely to be beneficial only in selected patients.
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PURPOSE: Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF). MATERIALS AND METHODS: A 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus. RESULTS: Limits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes. CONCLUSION: New recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected.
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Neoplasias Meníngeas , Meningioma , Radioterapia de Intensidade Modulada , Humanos , Meningioma/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/patologiaRESUMO
BACKGROUND: Management of macroscopic local recurrence (MLR) after radical prostatectomy is a challenging situation with no standardized approach. OBJECTIVE: The objective of our study was to assess the efficacy and safety of functional image-guided salvage radiotherapy (SRT) in patients with MLR in the prostate bed. DESIGN, SETTING, AND PARTICIPANTS: In this international multicenter retrospective study across 16 European centers, eligible patients were initially treated by radical prostatectomy (RP) with or without pelvic lymph node dissection for localized or locally advanced adenocarcinoma of the prostate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate-specific antigen (PSA) measured 4 wk after RP was <0.1 ng/ml. All patients presented a biochemical relapse after RP defined by an increase in PSA level of ≥0.2 ng/ml on two successive measures. Only patients with an MLR lesion in the prostatectomy bed visualized on functional imaging (multiparametric magnetic resonance imaging, positron emission tomography/computed tomography [PET/CT] choline, or PET/CT prostate-specific membrane antigen) were eligible. Patients with lymph node, bone, or visceral dissemination at restaging imaging (CT and/or bone scintigraphy and/or magnetic resonance imaging and/or PET) were excluded. Dose escalation was defined as a dose of >66 Gy prescribed to the prostate bed or to MLR. Toxicities were classified using the Common Terminology Criteria for Adverse Events scale, version 4.03. The primary endpoint was progression-free survival (PFS). Secondary outcomes were metastasis-free survival (MPFS), biochemical progression-free survival, and overall survival. Genitourinary (GU) and gastrointestinal (GI) toxicities were analyzed. RESULTS AND LIMITATIONS: Between January 2000 and December 2019, 310 patients received at least one dose escalation on MLR and 25 patients did not receive any dose escalation. The median PSA level before SRT was 0.63 ng/ml (interquartile range [IQR], 0.27-1.7). The median follow-up was 54 mo (IQR, 50-56). Five-year PFS and MPFS were 70% (95% confidence interval [CI]: [64; 75]) and 84% (95% CI: [78; 88]), respectively. Grade ≥2 GU and GI late toxicities were observed in 43 (12%) and 11 (3%) patients, respectively. When the prescribed dose on the MLR lesion was ≥72 Gy, an improvement in 5-yr PFS was found for patients received at least one dose escalation (73% [95% CI: 65-79]) vs 60% [95% CI: 48; 70]; p = 0.03). CONCLUSIONS: In this contemporary study integrating functional imaging data, we found potential efficacy of SRT with dose escalation ≥72 Gy for patients with MLR in the prostate bed and with an acceptable toxicity profile. Prospective data exploring this MLR dose escalation strategy are awaited. PATIENT SUMMARY: In this report, we looked at the outcomes from salvage radiotherapy for prostate cancer and macroscopic relapse in a large European population. We found that outcomes varied with prostate-specific antigen at relapse, Gleason score, and dose escalation. We found potential efficacy of salvage radiotherapy with dose escalation for macroscopic relapse in the prostate bed, with an acceptable toxicity profile.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Estudos Prospectivos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Prostatectomia/métodosRESUMO
Background: As in other solid tumors, increasing evidence indicates that patients diagnosed with a limited number of prostate cancer metastases, so-called oligometastases, have a better prognosis than patients with extensive metastatic disease. Stereotactic body radiotherapy (SBRT) is now considered an option in this population.Programmed death-1 (PD-1) and its ligands (PD-L1) are targeted by immune checkpoint inhibitors. Preclinical studies have shown that the tumor immune microenvironment changes when combining radiotherapy with immunotherapy, especially with hypofractionated radiotherapy.The oligometastatic setting appears to be the most relevant clinical situation for evaluating the immune response generated by radiotherapy and immune checkpoint inhibitors in patients with an intact immune system.We hypothesize that durvalumab will enhance the immune response following SBRT targeting oligometastatic lesions. Our purpose is to demonstrate, via a randomized 2:1 phase II trial, that SBRT (3 fractions) with durvalumab in oligometastatic hormone-sensitive prostate cancer patients would improve progression-free survival in patients with prostate cancer with up to 5 metastases compared to patients who exclusively received SBRT. Methods: This is a multicentric randomized phase II study in French academic hospitals. Patients with prostate cancer and up to 5 metastases (lymph node and/or bone) were randomized into a 2:1 ratio between Arm A (experimental group), corresponding to durvalumab and SBRT to the metastases, and Arm B (control group), corresponding to SBRT alone to the metastases. The study aims to accrue a total of 96 patients within 3 years. The primary endpoint is two-year progression-free survival and secondary endpoints include androgen deprivation therapy-free survival, quality of life, toxicity, prostate cancer specific survival, overall survival, and immune response. Discussion: The expected benefit for the patients in the experimental arm is longer life expectancy with acceptable toxicity. We also expect our study to provide data for better understanding the synergy between immunotherapy and radiotherapy in oligometastatic prostate cancer.
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PURPOSE OF REVIEW: During decades, adjuvant radiotherapy (ART) has been the standard of care after surgery, based on four randomized clinical trials (RCTs). As early salvage radiotherapy (SRT) recently challenged the ART paradigm, the optimal timing to initiate radiotherapy remains a matter of debate. RECENT FINDINGS: Three RCTs evaluated ART or SRT for postprostatectomy patients, with pathological risk factors (Gleason score > 8, pT3, positive margins). The ARTISTIC meta-analysis demonstrated similar 5-year biochemical recurrence-free survival for ART and SRT (89 vs. 88%). Lower rates of late genitourinary toxicity were demonstrated within the SRT arm, favouring early SRT in clinical practice.The addition of pelvic lymph node radiotherapy recently demonstrated an improvement in freedom from progression within the randomized RTOG 0534 trial, especially for patients with pretreatment prostate serum antigen (PSA) levels more than 0.35âng/ml. The most appropriate androgen deprivation therapy duration remains a point of controversy. SUMMARY: The SRT approach can be favoured for the vast majority of patients, provided close monitoring of PSA and early treatment in the event of biochemical recurrence. Radiotherapy dose and volumes and ADT use might be correlated to SRT timing (early vs. late). Results from trials including genomic tests and metabolic imaging will probably help to refine these criteria.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Próstata/patologia , Radioterapia Adjuvante/métodos , Prostatectomia , Recidiva Local de NeoplasiaRESUMO
In the case of synchronous metastatic disease, the local treatment of primary tumors by radiotherapy has long been reserved for palliative indications. The emergence of the concept of oligometastatic and oligopersistent diseases, the advent of new systemic therapies enabling longer overall survival with an enhanced quality of life, a better understanding of the biologic history of metastatic spread, and technical advances in radiation therapy are revolutionizing the management of patients with de novo metastatic cancer. The prognosis of these patients has been markedly improved and many studies have investigated the survival benefits from the local treatment of various primary tumors in cases of advanced disease at the time of diagnosis or in the case of oligopersistence. This article provides an update on the place of irradiation of the primary tumor in cancer with synchronous metastases, and discusses its interest through published or ongoing trials.
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OBJECTIVE: Dosimetric radiosurgery incidents are rare and probably insufficiently reported in scientific publications. After a long follow-up (FU), the authors studied the outcomes of patients treated with overexposure radiation for arteriovenous malformation (AVM) administered via stereotactic radiosurgery (SRS) at their department. METHODS: Between May 2006 and June 2007, 22 patients were treated for AVM with SRS. The mean (range) patient age was 43.5 (11.8-78) years. Previous treatments were embolization (n = 10), SRS (1), and surgery (1). The average (range) volume was 2.1 (0.2-6.4) cm3. The median prescribed minimal dose was 18.0 Gy. An initial error in the estimation of scatter factors led to overexposure to radiation. Due to this incident, the median delivered minimum dose was 25.0 Gy. All patients were prospectively followed with clinical examination and imaging. RESULTS: The mean (range) clinical FU was 14.5 (12.0-15.2) years. AVM obliteration after SRS was completed in 90.9% of patients at a mean (range) of 39.4 (24.4-70.4) months. No patient had post-SRS AVM bleeding. Three patients (13.6%) had new permanent deficits due to radiation-induced changes (RICs). Obliteration without new deficits was achieved in 18 patients (81.8%). Two patients had new epilepsy that was probably due to RIC but well controlled. The median (range) MRI FU was 13.8 (2.5-14.9) years. During MRI FU, two RIC periods were observed: one classic period during the first 3 years showed T1-weighted annular irregular enhancement (13%), and the other period between 5 and 15 years after SRS showed the occurrence of cystic and hemorrhagic lesions (22.7%). There were no cases of radiation-induced tumor. CONCLUSIONS: The present long-term report showed that this overexposure incident probably increased the AVM obliteration rate. This overexposure seems to have induced RIC and in particular a higher rate of cystic and hemorrhagic late lesions with nevertheless moderate clinical consequences. Long-term FU for AVM is mandatory due to the risk of late RIC.
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BACKGROUND: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care. METHODS: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436. FINDINGS: Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone. INTERPRETATION: Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients. FUNDING: Janssen-Cilag, Ipsen, Sanofi, and the French Government.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Próstata , Antagonistas de Androgênios , Androgênios , Androstenos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Castração , Docetaxel/uso terapêutico , Feminino , Humanos , Hipertensão/etiologia , Masculino , Prednisona/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologiaRESUMO
Magnetic resonance imaging (MRI) is being increasingly used for imaging suspected recurrence in prostate cancer therapy. Functional MRI with diffusion and perfusion imaging has the potential to demonstrate local recurrence even at low PSA value. Detection of recurrence can modify the management of postprostatectomy biochemical recurrence. MRI scan acquired before salvage radiotherapy is useful for the localization of recurrent tumors and also in the delineation of the target volume. The objective of this review is to assess the role and potential impact of MRI in targeting local recurrence after surgery for prostate cancer in the setting of salvage radiation therapy.
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Approximately 30% of patients treated with radical prostatectomy (RP) for prostate cancers experience biochemical recurrence (BCR). Post-operative radiation therapy (RT) can be either offered immediately after the surgery in case of aggressive pathological features or proposed early if BCR occurs. Until recently, little data were available regarding the optimal RT timing, protocol, volumes to treat, and the benefit of adding androgen deprivation therapies to post-operative RT. In this review, we aim to pragmatically discuss current literature data on these points. Early salvage RT appears to be the optimal post-operative approach, improving oncological outcomes especially with low prostate-specific antigen (PSA) levels, as well as sparing several unnecessary adjuvant treatments. The standard RT dose is still 64-66 Gy to the prostate bed in conventional fractionation, but hypofractionation protocols are emerging pending on late toxicity data. Several scientific societies have published contouring atlases, even though they are heterogeneous and deserve future consensus. During salvage RT, the inclusion of pelvic lymph nodes is also controversial, but preliminary data show a possible benefit for PSA > 0.34 ng/ml at the cost of increased hematological side effects. Concomitant ADT and its duration are also discussed, possibly advantageous (at least in terms of metastasis-free survival) for PSA rates over 0.6 ng/ml, taking into account life expectancy and cardiovascular comorbidities. Intensified regimens, for instance, with new-generation hormone therapies, could further improve outcomes in carefully selected patients. Finally, recent advances in molecular imaging, as well as upcoming breakthroughs in genomics and artificial intelligence tools, could soon reshuffle the cards of the current therapeutic strategy.
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BACKGROUND/PURPOSE: Dose-escalated external beam radiotherapy (RT) is effective in the control of prostate cancer but is associated with a greater incidence of rectal adverse events. We assessed the dosimetric gain and safety profile associated with implantation of a new biodegradable rectal spacer balloon. MATERIALS/METHODS: Patients scheduled for image-guided, intensity-modulated RT for intermediate-risk prostate cancer were prospectively included in the French multicenter BioPro-RCMI-1505 study (NCT02478112). We evaluated the dosimetric gain, implantation feasibility, adverse events (AEs), and prostate-cancer-specific quality of life associated with use of the balloon spacer. RESULTS: After a scheduled review of the initial recruitment target of 50 patients by the study's independent data monitoring committee (IDMC), a total of 24 patients (including 22 with dosimetry data) were included by a single center between November 2016 and May 2018. The interventional radiologist who implanted the balloons considered that 86% of the procedures were easy. 20 of the 24 patients (83.3%) received IMRT and 4 (16.7%) received volumetric modulated arc therapy (78-80 Gy delivered in 39 fractions). The dosimetric gains associated with spacer implantation were highly significant (p<0.001) for most variables. For the rectum, the median (range) relative gain ranged from 15.4% (-9.2-47.5) for D20cc to 91.4% (36.8-100.0) for V70 Gy (%). 15 patients (62%) experienced an acute grade 1 AE, 8 (33%) experienced a late grade 1 AE, 1 (4.2%) experienced an acute grade 2 AE, and 3 experienced a late grade 2 AE. No grade 3 AEs were reported. Quality of life was good at baseline (except for sexual activity) and did not markedly worsen during RT and up to 24 months afterwards. CONCLUSION: The use of a biodegradable rectal spacer balloon is safe, effective and associated with dosimetric gains in modern RT for intermediate-risk prostate cancer.
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Biochemical recurrence is a clinical situation experienced by 20 to 40% of prostate cancer patients treated with radical prostatectomy (RP). Prostate bed (PB) radiation therapy (RT) remains the mainstay salvage treatment, although it remains non-curative for up to 30% of patients developing further recurrence. Positron emission tomography with computed tomography (PET/CT) using prostate cancer-targeting radiotracers has emerged in the last decade as a new-generation imaging technique characterized by a better restaging accuracy compared to conventional imaging. By adapting targeting of recurrence sites and modulating treatment management, implementation in clinical practice of restaging PET/CT is challenging the established therapeutic standards born from randomized controlled trials. This article reviews the potential impact of restaging PET/CT on changes in the management of recurrent prostate cancer after RP. Based on PET/CT findings, it addresses potential adaptation of RT target volumes and doses, as well as use of androgen-deprivation therapy (ADT). However, the impact of such management changes on the oncological outcomes of PET/CT-based salvage RT strategies is as yet unknown.
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PURPOSE: To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS: The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p < 0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p < 0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p = 0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities. CONCLUSIONS: The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Mama , Neoplasias da Mama/radioterapia , Feminino , Humanos , Hipertrofia , Planejamento da Radioterapia Assistida por ComputadorRESUMO
Metastatic melanoma patients are at high risk of brain metastases (BM). Although intracranial control is a prognostic factor for survival, impact of local (intracranial) treatment (LT), surgery and/or radiotherapy (stereotactic or whole brain) in the era of novel therapies remains unknown. We evaluated BM incidence in melanoma patients receiving immune checkpoint inhibitors (ICI) or anti-BRAF therapy and identified prognostic factors for overall survival (OS). Clinical data and treatment patterns were retrospectively collected from all patients treated for newly diagnosed locally advanced or metastatic melanoma between May 2014 and December 2017 with available BRAF mutation status and receiving systemic therapy. Prognostic factors for OS were analyzed with univariable and multivariable survival analyses. BMs occurred in 106 of 250 eligible patients (42.4%), 64 of whom received LT. Median OS in patients with BM was 7.8 months (95% CI [5.4-10.4]). In multivariable analyses, LT was significantly correlated with improved OS (HR 0.21, p < 0.01). Median OS was 17.3 months (95% CI [8.3-22.3]) versus 3.6 months (95% CI [1.4-4.8]) in patients with or without LT. LT correlates with improved OS in melanoma patients with BM in the era of ICI and anti-BRAF therapy. The use of LT should be addressed at diagnosis of BM while introducing systemic treatment.
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INTRODUCTION: Late gastro-intestinal toxicities (LGIT) secondary to pelvic radiotherapy (RT) are well described in the literature. LGIT are mainly related to rectal or ano-rectal irradiation; however, involvement of the anal canal (AC) in the occurrence of LGIT remains poorly described and understood. MATERIALS AND METHODS: The aim of this work was to explore the potential role of the AC in the development of LGIT after prostate irradiation and identify predictive factors that could be optimized in order to limit these toxicities. This narrative literature review was realized using the Pubmed database. We identified original articles published between June 1997 and July 2019, relating to LGIT after RT for localized prostate cancer and for which AC was identified independently. Articles defining the AC as part of an anorectal or rectal volume only were excluded. RESULTS: A history of abdominal surgery or cardio-vascular risk, anticoagulant or tobacco use, and the occurrence of acute GIT during RT increases the risk of LGIT. A dose-effect relationship was identified between dose to the AC and development of LGIT. Identification and contouring of the AC and adjacent anatomical structures (muscles or nerves) are justified to apply specific dose constraints. As a limitation, our review mainly considered on 3DCRT which is no longer the standard of care nowadays; we did not identify any reports in the literature using moderately hypofractionated RT for the prostate and AC specific dosimetry. CONCLUSION: These results suggest that the AC may have an important role in the development of LGIT after pelvic RT for prostate cancer. The individualization of the AC during planning should be recommended in prospective studies.
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BACKGROUND: Oligorecurrent pelvic nodal relapse in prostatic cancer is a challenge for regional salvage treatments. Androgen depriving therapies (ADTs) are a mainstay in metastatic prostate cancer, and salvage pelvic radiotherapy may offer long ADT-free intervals for patients harboring regional nodal relapses. OBJECTIVE: To assess the efficacy of the combination of ADT and salvage radiotherapy in men with oligorecurrent pelvic node relapses of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We performed an open-label, phase II trial of combined high-dose intensity-modulated radiotherapy and ADT (6 mo) in oligorecurrent (five or fewer) pelvic node relapses in prostate cancer, detected by fluorocholine positron-emission tomography computed tomography imaging. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 2-yr progression-free survival defined as two consecutive prostate-specific antigen levels above the level at inclusion and/or clinical evidence of progression as per RECIST 1.1 and/or death from any cause. RESULTS AND LIMITATIONS: Between August 2014 and July 2016, 67 patients were recruited in 15 centers. Half of the patients had received prior prostatic irradiation. The median age was 67.7 yr. After a median follow-up of 49.4 mo, 2- and 3-yr progression-free survival rates were 81% and 58%, respectively. Median progression-free survival was 45.3 mo. The median biochemical relapse-free survival (BRFS) was 25.9 mo. At 2 and 3 yr, the BRFS rates were 58% and 46%, respectively. Grade 2 + 2-yr genitourinary and gastrointestinal toxicities were 10% and 2%, respectively. CONCLUSIONS: Combined high-dose salvage pelvic radiotherapy and ADT appeared to prolong tumor control in oligorecurrent pelvic node relapses in prostate cancer with limited toxicity. After 3 yr, nearly half of patients were in complete remission. Our study showed initial evidence of benefit, but a randomized trial is required to confirm this result. PATIENT SUMMARY: In this report, we looked at the outcomes of combined high-dose salvage pelvic radiotherapy and 6-mo-long hormone therapy in oligorecurrent pelvic nodal relapse in prostatic cancer. We found that 46% of patients presenting with oligorecurrent pelvic node relapses in prostate cancer were in complete remission after 3 yr following combined treatment at the cost of limited toxicity.