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Anaplastic thyroid cancer (ATC), a rare and highly aggressive malignancy, is characterized by an exceptionally poor prognosis, where the majority of patients present with extensive local invasion and/or distant metastases. 20-30% of ATCs harbor the BRAF-V600E mutation. Neoadjuvant BRAF-targeted therapy may have the potential to downstage and facilitate surgical resection for patients with locally advanced and unresectable primary tumors with BRAF mutation and may convey a survival advantage in those with metastatic disease. There is emerging evidence to support the use of other targeted agents, including multikinase inhibitors, as well as the incorporation of immunotherapy into the treatment regimen. Rapid molecular and pathological diagnosis and expert multidisciplinary discussion at specialized treatment centers are critical to expedite investigations and initiate treatment for this complex and rapidly progressive disease.
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INTRODUCTION: In the current American Joint Committee on Cancer staging system, patients with pelvic nodal metastases are considered stage IV prostate cancer. This study aims to investigate whether men with prostate-specific membrane antigen positron emission tomography (PSMA PET)-detected pelvic node-positive prostate cancer at diagnosis have a better outcome compared to men with node-positive disease identified on conventional imaging. METHODS: This is a retrospective cohort study comparing the outcomes of men with node-positive prostate cancer and disease confined to the pelvis, staged with conventional versus PSMA PET imaging. Men had to be treated definitively with a combination of androgen deprivation therapy and radiation treatment to the prostate and pelvic lymph nodes. Kaplan-Meier and Cox regression analysis was used to compare biochemical failure-free survival (BFFS) and overall survival (OS). RESULTS: Seventy-six men with nodal metastases confined to the pelvis were identified. Fifty-one were detected with PSMA PET while 25 were staged with conventional imaging. PSMA PET staged patients had a lower proportion of Gleason 8-10 disease (78% vs. 96%) as well as a lower median prostate-specific antigen (11 ng/mL vs. 26 ng/mL). BFFS at 4 years was 72% with PSMA PET-detected node-positive disease vs. 38% with conventionally detected node-positive disease. Four-year OS was 93% with PSMA PET staged patients vs. 76% with conventionally staged patients. On multivariate analysis, the PSMA PET staged group was associated with improved BFFS (Adjusted HR = 3.00, 95% CI 1.43, 6.29, P = 0.004) and OS (Adjusted HR = 5.81, 95% CI 1.43, 23.7, P = 0.007). CONCLUSION: Men with PSMA PET-detected node-positive prostate cancer confined to the pelvis have significantly better biochemical control and survival compared to those with node-positive pelvic disease identified through conventional staging.
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Microcystic adenocarcinoma is an uncommon histologic variant of prostate carcinoma. Despite its rarity, it has gained increasing recognition over the past decade for its diagnostic challenges and unclear prognostic significance. Herein, we describe a rare case of metastatic microcystic prostate adenocarcinoma, presenting with discordance between imaging and histologic findings. This report highlights the diagnostic and therapeutic challenges of this pathological entity and the importance of multidisciplinary collaboration in the management of intermediate-risk prostate cancer.
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Background and purpose: Simulation-free radiotherapy, where diagnostic imaging is used for treatment planning, improves accessibility of radiotherapy for eligible palliative patients. Combining this pathway with online adaptive radiotherapy (oART) may improve accuracy of treatment, expanding the number of eligible patients. This study evaluated the adaptive process duration, plan dose volume histogram (DVH) metrics and geometric accuracy of a commercial cone-beam computed tomography (CBCT)-guided oART system for simulation-free, palliative radiotherapy. Materials and methods: Ten previously treated palliative cases were used to compare system-generated contours against clinician contours in a test environment with Dice Similarity Coefficient (DSC). Twenty simulation-free palliative patients were treated clinically using CBCT-guided oART. Analysis of oART clinical treatment data included; evaluation of the geometric accuracy of system-generated synthetic CT relative to session CBCT anatomy using a Likert scale, comparison of adaptive plan dose distributions to unadapted, using DVH metrics and recording the duration of key steps in the oART workflow. Results: Auto-generated contours achieved a DSC of higher than 0.85, excluding the stomach which was attributed to CBCT image quality issues. Synthetic CT was locally aligned to CBCT anatomy for approximately 80% of fractions, with the remaining suboptimal yet clinically acceptable. Adaptive plans achieved a median CTV V95% of 99.5%, compared to 95.6% for unadapted. The median overall oART process duration was found to be 13.2 mins, with contour editing being the most time-intensive adaptive step. Conclusions: The CBCT-guided oART system utilising a simulation-free planning approach was found to be sufficiently accurate for clinical implementation, this may further streamline and improve care for palliative patients.
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PURPOSE: Physical separation of healthy tissue and target volumes in prostate radiotherapy through the insertion of hydrogel can improve patient toxicity rates. An iodised hydrogel may provide anatomical separation of prostate and rectum while being easily visualised through radio-opacity. The aim of this study was to characterise SpaceOAR Vue™ in kilovoltage (kV) images and megavoltage (MV) radiotherapy treatment planning. METHODS: Two cassettes were 3D-printed, one filled with water and the other with SpaceOAR Vue™. Transmission dose through each cassette was measured in slab phantom geometry and compared for 6MV and 10MV photon energies. The SpaceOAR Vue™ slab phantom setup was simulated using computed tomography (CT) and a treatment plan created. The plan was calculated with the hydrogel segmented and material assignment set to water, and the resultant dose compared to corresponding measurement doses. The first 5 patients treated with SpaceOAR Vue™ were assessed with the volume and Hounsfield units (HU) of the hydrogel evaluated in CT and cone beam computed tomography (CBCT) imaging. RESULTS: Transmission through Water and SpaceOAR Vue™ agreed to within 0.5% for both photon energies. Furthermore, the segmentation of SpaceOAR Vue™ and material assignment to water, resulted in a plan dose that agreed to measurement to within 0.5%. Clinically, the SpaceOAR Vue™ volume and HU did not vary over patient treatment course, however was found to display differently on different kV imaging modalities. CONCLUSIONS: SpaceOAR Vue™ was found to be radio-opaque on kV images, but dosimetrically behaved similarly to water in MV treatment beams, making it suitable for clinical use.
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Hidrogeles , Neoplasias de la Próstata , Masculino , Humanos , Dosificación Radioterapéutica , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Próstata , Tomografía Computarizada de Haz Cónico/métodos , Fantasmas de Imagen , Agua , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In a randomized phase II clinical trial, the Trans Tasman Radiation Oncology Group compared single- versus multifraction stereotactic ablative body radiotherapy (SABR) in 90 patients with 133 oligometastases to the lung. The study found no differences in safety, efficacy, systemic immunogenicity, or survival between arms, with single-fraction SABR picked as the winner on the basis of cost-effectiveness. In this article, we report the final updated survival outcome analysis. The protocol mandated no concurrent or post-therapy systemic therapy until progression. Modified disease-free survival (mDFS) was defined as any progression not addressable by local therapy, or death. At a median follow-up of 5.4 years, the 3- and 5-year estimates for overall survival (OS) were 70% (95% CI, 59 to 78) and 51% (95% CI, 39 to 61). There were no significant differences between the multi- and single-fraction arms for OS (hazard ratio [HR], 1.1 [95% CI, 0.6 to 2.0]; P = .81). The 3- and 5-year estimates for disease-free survival were 24% (95% CI, 16 to 33) and 20% (95% CI, 13 to 29), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.6]; P = .92). The 3- and 5-year estimates for mDFS were 39% (95% CI, 29 to 49) and 34% (95% CI, 24 to 44), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.8]; P = .90). In this patient population, where patients receive SABR in lieu of systemic therapy, one-in-three patients are alive without disease in the long term. There were no differences in outcomes by fractionation schedule.
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Neoplasias Pulmonares , Radiocirugia , Humanos , Radiocirugia/efectos adversos , Radiocirugia/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Supervivencia sin Progresión , Supervivencia sin Enfermedad , PulmónRESUMEN
PURPOSE: Androgen deprivation therapy (ADT) combined with radiation treatment (RT) is recommended by the National Comprehensive Cancer Network guidelines for unfavorable intermediate and high-risk localized prostate cancer. Although there is a variable survival benefit conferred by ADT, there are potential side effects to consider for patient decision-making. We aimed to assess the side effects and bother of adding ADT to RT, the degree of regret, and what overall survival (OS) benefit men would want to justify adding or extending the duration of ADT, after their experience with this treatment. METHODS AND MATERIALS: Men receiving ADT with definitive RT completed a questionnaire asking about the side effects and degree of bother from ADT using a 4-point scale. They were also asked about regret, and what survival benefit would warrant ADT. RESULTS: In the study, 846 patients received definitive RT, of whom 356 received ADT and were asked about their experience with ADT. Of these, 234 responded (66%). In 54%, ADT caused some bother, most commonly hot flushes (32%), fatigue (29%), and sexual problems (29%). Five percent regretted receiving ADT "quite a lot" or "very much." Approximately one-third of men deemed a 1% OS benefit from ADT worthwhile, whereas one-third (34%) would want a >10% OS benefit enough to justify choosing ADT again. In addition, 49% of patients who received short-term ADT would accept longer duration ADT for a 6% OS benefit. CONCLUSIONS: Significant regret for ADT was low (5%). There was a clear dichotomy between those who deemed any OS benefit from ADT worthwhile versus those who needed a significant survival benefit to justify the side effects. Given that some men may change their opinion on the relative value of ADT after experiencing its effects, this study emphasizes the importance of revisiting patients after 6 months to given patients an opportunity to renegotiate their treatment.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Antagonistas de Andrógenos/uso terapéutico , Andrógenos/uso terapéutico , EmocionesRESUMEN
Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk stratification after surgery, but less data exist for patients treated with definitive radiation therapy (RT) or RT in oligo-/metastatic disease stages. To guide future perspectives of GCs for RT, we conducted (1) a systematic review on the evidence of GCs for patients treated with RT and (2) a survey of experts using the Delphi method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research. We performed a systematic review and screened ongoing clinical trials on ClinicalTrials.gov. Based on these results, a multidisciplinary international team of experts received an adapted Delphi method survey. Thirty-one and 30 experts answered round 1 and round 2, respectively. Questions with ≥75% agreement were considered relevant and included in the qualitative synthesis. Evidence for GCs as predictive biomarkers is mainly available to the postoperative RT setting. Validation of GCs as prognostic markers in the definitive RT setting is emerging. Experts used GCs in patients with PCa with extensive metastases (30%), in postoperative settings (27%), and in newly diagnosed PCa (23%). Forty-seven percent of experts do not currently use GCs in clinical practice. Expert consensus demonstrates that GCs are promising tools to improve risk-stratification in primary and oligo-/metastatic patients in addition to existing classifications. Experts were convinced that GCs might guide treatment decisions in terms of RT-field definition and intensification/deintensification in various disease stages. This work confirms the value of GCs and the promising evidence of GC utility in the setting of RT. Additional studies of GCs as prognostic biomarkers are anticipated and form the basis for future studies addressing predictive capabilities of GCs to optimize RT and systemic therapy. The expert consensus points out future directions for GC research in the management of PCa.
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Neoplasias de la Próstata , Masculino , Humanos , Consenso , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/tratamiento farmacológico , GenómicaRESUMEN
PURPOSE: Our objective is to describe the distribution of local recurrences after radical prostatectomy (RP) as delineated using 68-Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) to identify areas where current consensus guideline clinical target volumes (CTVs) are insufficient or excessive and to identify predictors of recurrence location within the fossa. METHODS AND MATERIALS: Retrospective review of databases from 2 tertiary referral centers was performed to identify patients who underwent 68Ga-PSMA PET/CT for biochemical recurrence after RP. Those with a component of local recurrence were included for further analysis. The epicenter of each recurrence was defined relative to reference points in 3 axes, categorized into 1 of 7 levels in the superior/inferior axis relative to the vesicourethral anastomosis, and recorded as within or outside the Faculty of Radiation Oncology Genito-urinary Group (FROGG) and Radiation Therapy Oncology Group consensus CTVs. Univariate and multivariate analysis was performed to identify predictors of recurrence location based on clinical and histopathologic variables. RESULTS: One thousand forty-nine 68Ga-PSMA PET/CT scans were reviewed. One hundred forty sites of local recurrence were identified on 132 scans. Relative to the vesicourethral anastomosis, 13 (9%), 31 (22%), 17 (12%), 24 (17%), 27 (19%), 20 (14%), and 8 (6%) recurrences occurred >5 mm inferior; within 5 mm above or below; and 6 to 15 mm, 16 to 25 mm, 26 to 35 mm, 36 to 45 mm, and >45 mm superiorly, respectively. Thirteen (9%) and 2 (1.4%) recurrences occurred beyond the FROGG and Radiation Therapy Oncology Group consensus CTVs, respectively, with all below the inferior CTV margin. CONCLUSIONS: In the largest study to date mapping local recurrences after RP in 3-dimensions, we provide several insights to inform future contouring guidelines; in particular, 9% of recurrences occurred inferior to the FROGG CTV.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Próstata/diagnóstico por imagen , Próstata/cirugía , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Recurrencia Local de Neoplasia/patología , Prostatectomía/métodos , Radioisótopos de Galio , Antígeno Prostático Específico , Estudios Retrospectivos , RecurrenciaRESUMEN
Background and purpose: Poor quality radiotherapy can detrimentally affect outcomes in clinical trials. Our purpose was to explore the potential of knowledge-based planning (KBP) for quality assurance (QA) in clinical trials. Materials and methods: Using 30 in-house post-prostatectomy radiation treatment (PPRT) plans, an iterative KBP model was created according to the multicentre clinical trial protocol, delivering 64 Gy in 32 fractions. KBP was used to replan 137 plans. The KB (knowledge based) plans were evaluated for their ability to fulfil the trial constraints and were compared against their corresponding original treatment plans (OTP). A second analysis between only the 72 inversely planned OTPs (IP-OTPs) and their corresponding KB plans was performed. Results: All dose constraints were met in 100% of KB plans versus 69% of OTPs. KB plans demonstrated significantly less variation in PTV coverage (Mean dose range: KB plans 64.1 Gy-65.1 Gy vs OTP 63.1 Gy-67.3 Gy, p < 0.01). KBP resulted in significantly lower doses to OARs. Rectal V60Gy and V40Gy were 17.7% vs 27.7% (p < 0.01) and 40.5% vs 53.9% (p < 0.01) for KB plans and OTP respectively. Left femoral head (FH) V45Gy and V35Gy were 0.4% vs 7.4% (p < 0.01) and 7.9% vs 34.9% (p < 0.01) respectively. In the second analysis plan improvements were maintained. Conclusions: KBP created high quality PPRT plans using the data from a multicentre clinical trial in a single optimisation. It is a powerful tool for utilisation in clinical trials for patient specific QA, to reduce dose to surrounding OARs and variations in plan quality which could impact on clinical trial outcomes.
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OBJECTIVE: To assess European Association of Urology (EAU) risk groups for biochemical recurrence (BCR) of prostate cancer relative to prostate-specific membrane antigen-positron emission tomography (PSMA-PET) status and oncological outcomes. PATIENTS AND METHODS: A retrospective analysis of a study that incorporated PSMA-PET for men with BCR after radical prostatectomy (RP) was undertaken. EAU risk groups were considered relative to clinical variables, PSMA-PET findings, and deployment of salvage radiotherapy (SRT). The primary oncological outcome was event-free survival (EFS) and this was analysed relative to clinical and imaging variables. An 'event' occurred if prostate-specific antigen (PSA) level rose >0.2 ng/mL above nadir or additional therapies were introduced. RESULTS: A total of 137 patients were included, most of whom had EAU high-risk disease (76%) and/or low PSA levels (80% <0.5 ng/mL) at the time of PSMA-PET. EAU risk group was not associated with regional nodal/distant metastasis on PSMA-PET. Regional nodal/distant metastasis on PSMA PET (compared to negative/local recurrence: hazard ratio [HR] 2.2; P = 0.002) and SRT use (vs no SRT: HR 0.44; P = 0.004) were associated with EFS. EAU high-risk status was not significantly associated with worse EFS (HR 1.7, P = 0.12) compared to EAU low-risk status. Among patients who received SRT, both regional/distant metastasis on PSMA-PET (HR 3.1; P < 0.001) and EAU high-risk status (HR 2.9; P = 0.04) were independently associated with worse EFS, which was driven by patients in the EAU high-risk group with regional/distant metastases (38%; HR 3.1, P = 0.001). CONCLUSIONS: In patients with post-RP BCR, PSMA-PET findings and receipt of SRT predicted EFS. In patients receiving SRT, PSMA status combined with EAU risk grouping was most predictive of EFS. These findings suggest that the EAU risk groups could be improved with the addition of PSMA-PET.
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Neoplasias de la Próstata , Urología , Masculino , Humanos , Antígeno Prostático Específico , Próstata/diagnóstico por imagen , Próstata/cirugía , Próstata/patología , Estudios Retrospectivos , Supervivencia sin Progresión , Radioisótopos de Galio , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Tomografía de Emisión de Positrones , Recurrencia Local de Neoplasia/patologíaAsunto(s)
Neoplasias de la Próstata , Radioterapia , Anciano , Exactitud de los Datos , Determinación de Punto Final , Humanos , Masculino , Metástasis de la Neoplasia/terapia , Estadificación de Neoplasias , Selección de Paciente , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radioterapia/métodos , Radioterapia/tendencias , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Mucinous prostate adenocarcinoma represents <0.1% of prostate cancers. To our knowledge, no previous report has described the 68 Ga-PSMA-PET characteristics of this entity at the primary site. We present a case of a fit 85-year-old with PSA 0.55 ng/mL and ISUP grade 4 acinar adenocarcinoma with mucinous features on biopsy. 68 Ga-PSMA-PET revealed an intensely avid primary lesion in the right prostate (SUVmax 10.9), concordant with biopsy findings and encompassing both the PI-RADS 5 lesion identified on MRI and a PI-RADS 1 lesion that presumably represented the mucinous component. The patient was treated with definitive radiotherapy to the prostate and lymph nodes with 6 months of androgen deprivation therapy.
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Adenocarcinoma , Neoplasias de la Próstata , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/radioterapia , Anciano de 80 o más Años , Antagonistas de Andrógenos , Ácido Edético , Radioisótopos de Galio , Humanos , Imagen por Resonancia Magnética , Masculino , Oligopéptidos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Próstata/patología , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapiaRESUMEN
INTRODUCTION: Aimed to develop a simple and robust volumetric modulated arc radiotherapy (VMAT) solution for comprehensive lymph node (CLN) breast cancer without increase in low-dose wash. METHODS: Forty CLN-breast patient data sets were utilised to develop a knowledge-based planning (KBP) VMAT model, which limits low-dose wash using iterative learning and base-tangential methods as benchmark. Another twenty data sets were employed to validate the model comparing KBP-generated ipsilateral VMAT (ipsi-VMAT) plans against the benchmarked hybrid (h)-VMAT (departmental standard) and bowtie-VMAT (published best practice) methods. Planning target volume (PTV), conformity/homogeneity index (CI/HI), organ-at-risk (OAR), remaining-volume-at-risk (RVR) and blinded radiation oncologist (RO) plan preference were evaluated. RESULTS: Ipsi- and bowtie-VMAT plans were dosimetrically equivalent, achieving greater nodal target coverage (P < 0.05) compared to h-VMAT with minor reduction in breast coverage. CI was enhanced for a small reduction in breast HI with improved dose sparing to ipsilateral-lung and humeral head (P < 0.05) at immaterial expense to spinal cord. Significantly, low-dose wash to OARs and RVR were comparable between all plan types demonstrating a simple VMAT class solution robust to patient-specific anatomic variation can be applied to CLN breast without need for complex beam modification (hybrid plans, avoidance sectors or other). This result was supported by blinded RO review. CONCLUSIONS: A simple and robust ipsilateral VMAT class solution for CLN breast generated using iterative KBP modelling can achieve clinically acceptable target coverage and OAR sparing without unwanted increase in low-dose wash associated with increased second malignancy risk.
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Oncología por Radiación , Radioterapia de Intensidad Modulada , Humanos , Bases del Conocimiento , Órganos en Riesgo , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodosRESUMEN
PURPOSE: Stereotactic body radiation therapy (SBRT) is a recognized treatment for low- and intermediate-risk prostate cancer, with 36.25 Gy in 5 fractions the most commonly used regimen. We explored the preliminary efficacy, patient recorded toxicity, and decision regret in intermediate- and high-risk prostate cancer receiving SBRT with prostate-specific membrane antigen (PSMA)/magnetic resonance imaging (MRI) guided focal gross tumor volume boost to 45 Gy. METHODS AND MATERIALS: Between July 2015 and June 2019, 120 patients received SBRT across 2 institutions with a uniform protocol. All patients had fiducial markers and hydrogel, MRI and PSMA positron emission tomography (PET) scan. All patients received a questionnaire asking the degree of urinary, bowel, and sexual bother experienced at set time points, including questions about treatment choice and decision regret. RESULTS: One hundred twelve of 120 patients consented. Their median age was 72 years and median follow-up was 2.3 years. As per National Comprehensive Cancer Network guidelines, 78% had intermediate risk and 20% high risk. Androgen deprivation was combined with radiation in 6 patients. Most patients (74%) reported that receiving SBRT significantly influenced their choice of treatment. Five men (4%) expressed "quite a lot" (n = 4) or "very much" regret (n = 1) regarding their choice of treatment, while 89% expressed "no regret." Similar to pretreatment levels, "quite a lot" or "very much" urinary or bowel bother was expressed in 8% and 6% of patients, respectively. Two patients experienced nadir +2 biochemical failure, both found to have bone metastases. A third patient underwent PSMA PET at nadir +1.7 and had disease at the penile bulb, which was out of field. Three year estimated freedom from biochemical failure was 99% for intermediate and 85% for high-risk groups. CONCLUSIONS: We have demonstrated promising efficacy and low toxicity with PSMA/MRI-guided SBRT focal boost. Less than 5% of patients expressed significant decision regret for their choice of treatment.
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Neoplasias de la Próstata , Radiocirugia , Anciano , Antagonistas de Andrógenos , Emociones , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radiocirugia/efectos adversos , Radiocirugia/métodosRESUMEN
Increasing evidence suggests that the gut microbiome is associated with both cancer chemotherapy (CTX) outcomes and adverse events (AEs). This review examines the relationship between the gut microbiome and CTX as well as the impact of CTX on the gut microbiome. A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for "cancer" and "chemotherapy" and "microbiome/microbiota". The relevant literature was selected for use in this article. Seventeen studies were selected on participants with colorectal cancer (CRC; n=5), Acute Myeloid Leukemia (AML; n=3), Non-Hodgkin's lymphoma (n=2), breast cancer (BCa; n=1), lung cancer (n=1), ovarian cancer (n=1), liver cancer (n=1), and various other types of cancers (n=3). Seven studies assessed the relationship between the gut microbiome and CTX with faecal samples collected prior to (n=3) and following CTX (n=4) showing that the gut microbiome is associated with both CTX efficacy and toxicity. Ten other prospective studies assessed the impact of CTX during treatment and found that CTX modulates the gut microbiome of people with cancer and that dysbiosis induced by the CTX is related to AEs. CTX adversely impacts the gut microbiome, inducing dysbiosis and is associated with CTX outcomes and AEs. Current evidence provides insights into the gut microbiome for clinicians, cancer survivors and the general public. More research is required to better understand and modify the impact of CTX on the gut microbiome.
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Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for "cancer" and "immunotherapy/immune checkpoint inhibitor" and "microbiome/microbiota" and/or "fecal microbiome transplant FMT". The relevant literature was selected for this article. Results: Ten studies examined patients diagnosed with advanced metastatic melanoma (n = 6), hepatocellular carcinoma (HCC) (n = 2), non-small cell lung carcinoma (NSCLC) (n = 1) and one study examined combination both NSCLC and renal cell carcinoma (RCC) (n = 1). These studies consistently reported that the gut microbiome profile prior to administering immune checkpoint inhibitors (ICIs) was related to clinical response as measured by progression-free survival (PFS) and overall survival (OS). Two studies reported that a low abundance of Bacteroidetes was associated with colitis. Two studies showed that patients with anti-PD-1 refractory metastatic melanoma experienced improved response rates and no added toxicity when receiving fecal microbiota transplant (FMT) from patients with anti-PD-1 responsive disease. Conclusions: Overall, significant differences in the diversity and composition of the gut microbiome were identified in ICIs responders and non-responders. Our findings provide new insights into the value of assessing the gut microbiome in immunotherapy. Further robust randomized controlled trials (RCTs) examining the modulatory effects of the gut microbiome and FMT on ICIs in patients not responding to immunotherapy are warranted.
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IMPORTANCE: Evidence is lacking from randomized clinical trials to guide the optimal approach for stereotactic ablative body radiotherapy (SABR) in patients with pulmonary oligometastases. OBJECTIVE: To assess whether single-fraction or multifraction SABR is more effective for the treatment of patients with pulmonary oligometastases. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, unblinded, phase 2 randomized clinical trial of 90 patients across 13 centers in Australia and New Zealand enrolled patients with 1 to 3 lung oligometastases less than or equal to 5 cm from any nonhematologic malignant tumors located away from the central airways, Eastern Cooperative Oncology Group performance status 0 or 1, and all primary and extrathoracic disease controlled with local therapy. Enrollment was from January 1, 2015, to December 31, 2018, with a minimum patient follow-up of 2 years. INTERVENTIONS: Single fraction of 28 Gy (single-fraction arm) or 4 fractions of 12 Gy (multifraction arm) to each oligometastasis. MAIN OUTCOMES AND MEASURES: The main outcome was grade 3 or higher treatment-related adverse events (AEs) occurring within 1 year of SABR. Secondary outcomes were freedom from local failure, overall survival, disease-free survival, and patient-reported outcomes (MD Anderson Symptom Inventory-Lung Cancer and EuroQol 5-dimension visual analog scale). RESULTS: Ninety participants were randomized, of whom 87 were treated for 133 pulmonary oligometastases. The mean (SD) age was 66.6 [11.6] years; 58 (64%) were male. Median follow-up was 36.5 months (interquartile range, 24.8-43.9 months). The numbers of grade 3 or higher AEs related to treatment at 1 year were 2 (5%; 80% CI, 1%-13%) in the single-fraction arm and 1 (3%; 80% CI, 0%-10%) in the multifraction arm, with no significant difference observed between arms. One grade 5 AE occurred in the multifraction arm. No significant differences were found between the multifraction arm and single-fraction arm for freedom from local failure (hazard ratio [HR], 0.5; 95% CI, 0.2-1.3; P = .13), overall survival (HR, 1.5; 95% CI, 0.6-3.7; P = .44), or disease-free survival (HR, 1.0; 95% CI, 0.6-1.6; P > .99). There were no significant differences observed in patient-reported outcomes. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, neither arm demonstrated evidence of superior safety, efficacy, or symptom burden; however, single-fraction SABR is more efficient to deliver. Therefore, single-fraction SABR, as assessed by the most acceptable outcome profile from all end points, could be chosen to escalate to future studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01965223.