RESUMEN
Prostate cancer has substantial heterogeneity in clinical outcomes and therapeutic responses, posing challenges in predicting disease progression and tailoring treatment strategies. Recent studies have highlighted the potential prognostic value of evaluating the tumor microenvironment, including the presence of a histologically overt stromal response (HOST-response) characterized by peri-glandular stromal changes and architectural distortions. This retrospective study examined patient records from The Cancer Genome Atlas database to identify genomic alterations associated with the HOST-response in prostate cancer. Among 348 patients who underwent radical prostatectomy, 160 (45.98%) were identified as having a HOST-response. A gene expression analysis revealed 1263 genes with significantly higher expression in patients with a HOST-response. A protein-protein interaction network analysis identified seven hub genes (KIF2C, CENPA, CDC20, UBE2C, ESPL1, KIF23, and PLK1) highly interconnected in the network. A functional enrichment analysis revealed alterations in the cell division, cytoskeletal organization, cytokinesis, and interleukin-16 signaling pathways in patients with a HOST-response, suggesting dysregulated proliferation and inflammation. The distinct molecular signature associated with the HOST-response provides insights into the tumor-stroma interactions driving adverse outcomes and potential targets for tailored therapeutic interventions in this subset of patients with prostate cancer.
Asunto(s)
Neoplasias de la Próstata , Microambiente Tumoral , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Microambiente Tumoral/genética , Mapas de Interacción de Proteínas/genética , Regulación Neoplásica de la Expresión Génica , Células del Estroma/metabolismo , Células del Estroma/patología , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Prostatectomía , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , PronósticoRESUMEN
This Viewpoint discusses the clinical vs economic success of magnetic resonance imaging combined with linear accelerator technology and its impact on patients.
RESUMEN
BACKGROUND: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear. METHODS: The ADT & Metabolism Study was a single-center, 24-week, prospective observational study that enrolled ADT-naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non-ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks. RESULTS: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], -2.10 to 4.43; p = .47) or skeletal muscle (-3.2; 95% CI, -7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non-ADT group. Men undergoing ADT gained 3.7 kg of fat mass. CONCLUSIONS: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short-term ADT.
RESUMEN
Objective.We aim to: (1) quantify the benefits of lung sparing using non-adaptive magnetic resonance guided stereotactic body radiotherapy (MRgSBRT) with advanced motion management for peripheral lung cancers compared to conventional x-ray guided SBRT (ConvSBRT); (2) establish a practical decision-making guidance metric to assist a clinician in selecting the appropriate treatment modality.Approach.Eleven patients with peripheral lung cancer who underwent breath-hold, gated MRgSBRT on an MR-guided linear accelerator (MR linac) were studied. Four-dimensional computed tomography (4DCT)-based retrospective planning using an internal target volume (ITV) was performed to simulate ConvSBRT, which were evaluated against the original MRgSBRT plans. Metrics analyzed included planning target volume (PTV) coverage, various lung metrics and the generalized equivalent unform dose (gEUD). A dosimetric predictor for achievable lung metrics was derived to assist future patient triage across modalities.Main results.PTV coverage was high (median V100% > 98%) and comparable for both modalities. MRgSBRT had significantly lower lung doses as measured by V20 (median 3.2% versus 4.2%), mean lung dose (median 3.3 Gy versus 3.8 Gy) and gEUD. Breath-hold, gated MRgSBRT resulted in an average reduction of 47% in PTV volume and an average increase of 19% in lung volume. Strong correlation existed between lung metrics and the ratio of PTV to lung volumes (RPTV/Lungs) for both modalities, indicating that RPTV/Lungsmay serve as a good predictor for achievable lung metrics without the need for pre-planning. A threshold value of RPTV/Lungs< 0.035 is suggested to achieve V20 < 10% using ConvSBRT. MRgSBRT should otherwise be considered if the threshold cannot be met.Significance.The benefits of lung sparing using MRgSBRT were quantified for peripheral lung tumors; RPTV/Lungswas found to be an effective predictor for achievable lung metrics across modalities. RPTV/Lungscan assist a clinician in selecting the appropriate modality without the need for labor-intensive pre-planning, which has significant practical benefit for a busy clinic.
Asunto(s)
Tomografía Computarizada Cuatridimensional , Neoplasias Pulmonares , Pulmón , Imagen por Resonancia Magnética , Radiocirugia , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Humanos , Radiocirugia/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Pulmón/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada Cuatridimensional/métodos , Masculino , Femenino , Radioterapia Guiada por Imagen/métodos , Contencion de la Respiración , Anciano , Persona de Mediana Edad , Tratamientos Conservadores del Órgano/métodos , Órganos en RiesgoRESUMEN
PURPOSE: Given the variable clinical course of prostate cancer and the limitations of current prognostic factors, this study was conducted to investigate the impact of a histologically overt stromal response (HOST-response) to prostate cancer on clinical outcomes after radical prostatectomy. METHODS: This retrospective analysis utilized The Cancer Genome Atlas (TCGA) to evaluate data from individuals with a confirmed diagnosis of prostate cancer who underwent radical prostatectomy and had available pathology slides. These slides were assessed for the presence of a HOST-response, similar to desmoplasia. The primary endpoint was progression-free survival (PFS). A multivariable competing risk regression analysis was used to assess whether a significant association existed between HOST-response and PFS, adjusting for known prostate cancer prognostic factors. RESULTS: Among the 348 patients analyzed, 166 (47.70%) demonstrated a HOST-response. After a median follow-up of 37.87 months (IQR: 21.20, 65.50), the presence of a HOST-response was significantly associated with a shorter PFS (SDHR, 2.10; 95% CI, 1.26 to 3.50; p = 0.004), after adjusting for covariates. CONCLUSIONS: HOST-response in prostate cancer patients treated with radical prostatectomy is significantly associated with reduced PFS, suggesting a potential benefit from adjuvant therapy and highlighting the need for further investigation in a prospective randomized clinical trial.
RESUMEN
PURPOSE: Given the diverse clinical progression of prostate cancer (PC) and the evolving significance of histopathological factors in its management, this study aimed to explore the impact of cribriform pattern 4 (CP4) on clinical outcomes in PC patients and examine its molecular characteristics. METHODS: This retrospective study analyzed data from The Cancer Genome Atlas (TCGA) database and included PC patients who underwent radical prostatectomy (RP) and had pathology slides available for the assessment of CP4. A multivariable competing risk regression analysis was used to assess the association between CP4 and progression-free survival (PFS) while adjusting for established PC prognostic factors. The frequency of genomic alterations was compared between patients with and without CP4 using the Fisher's exact test. RESULTS: Among the 394 patients analyzed, 129 (32.74%) had CP4. After a median follow-up of 40.50 months (IQR: 23.90, 65.60), the presence of CP4 was significantly associated with lower PFS (AHR, 1.84; 95% CI, 1.08 to 3.114; p = 0.023) after adjusting for covariates. Seven hub genes-KRT13, KRT5, KRT15, COL17A1, KRT14, KRT16, and TP63-had significantly lower mRNA expression levels in patients with CP4 compared to those without. CONCLUSIONS: PC patients with CP4 have distinct genomic alterations and are at a high risk of disease progression following RP. Therefore, these patients may benefit from additional post-RP treatments and should be the subject of a prospective randomized clinical trial.
RESUMEN
Stereotactic magnetic resonance (MR)-guided adaptive radiotherapy (SMART) for renal cell carcinoma may result in more precise treatment delivery through the capabilities for improved image quality, daily adaptive planning, and accounting for respiratory motion during treatment with real-time MR tracking. In this study, we aimed to characterize the safety and feasibility of SMART for localized kidney cancer. Twenty patients with localized kidney cancer (ten treated in a prospective phase 1 trial and ten in the supplemental cohort) were treated to 40 Gy in five fractions on a 0.35 T MR-guided linear accelerator with daily adaptive planning and a cine MR-guided inspiratory breath hold technique. The median follow-up time was 17 mo (interquartile range: 13-20 months). A single patient developed local failure at 30 mo. No grade ≥3 adverse events were reported. The mean decrease in estimated glomerular filtration rate was -1.8 ml/min/1.73 m2 (95% confidence interval or CI [-6.6 to 3.1 ml/min/1.73 m2]), and the mean decrease in tumor diameter was -0.20 cm (95% CI [-0.6 to 0.2 cm]) at the last follow-up. Anterior location and overlap of the 25 or 28 Gy isodose line with gastrointestinal organs at risk were predictive of the benefit from online adaptive planning. Kidney SMART is feasible and, at the early time point evaluated in this study, was well tolerated with minimal decline in renal function. More studies are warranted to further evaluate the safety and efficacy of this technique. PATIENT SUMMARY: For patients with localized renal cell carcinoma who are not surgical candidates, stereotactic magnetic resonance--guided adaptive radiotherapy is a feasible and safe noninvasive treatment option that results in minimal impact on kidney function.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Radiocirugia , Humanos , Carcinoma de Células Renales/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Estudios Prospectivos , Radiocirugia/métodos , Neoplasias Renales/radioterapia , Riñón , Espectroscopía de Resonancia MagnéticaRESUMEN
PURPOSE: Fatigue is among the most common but most poorly understood radiation therapy-associated toxicities. This prospective study sought to investigate whether cardiorespiratory fitness, an integrative measure of whole-body cardiopulmonary function, is associated with patient-reported fatigue in women with early-stage breast cancer undergoing radiation therapy. METHODS AND MATERIALS: Patients with stage Tis-T2N0M0 breast cancer and an Eastern Cooperative Oncology Group performance status of 0 to 1 undergoing breast radiation therapy performed a symptom-limited cardiopulmonary exercise test (CPET) on a motorized treadmill to assess cardiorespiratory fitness as measured by peak oxygen uptake (VO2peak). Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. Both assessments were performed during or immediately after radiation therapy completion. All patients were treated with an opposed tangent technique to a dose of 4240 cGy in 16 fractions with or without a lumpectomy bed boost. Patients receiving cytotoxic chemotherapy were excluded. Pearson correlation coefficients and univariate linear regression were used to assess associations amongVO2peak, fatigue, and patient characteristics. RESULTS: Twenty-eight patients (median age, 52 years; range, 31-71) completed a CPET and FACIT-Fatigue assessment. Median VO2peak was 25.1 mL O2.kg-1.min-1 (range, 16.7-41.7). The majority of patients (78.6%) displayed a VO2peak lower than their age-predicted VO2peak. Both age and body mass index were significantly associated with VO2peak levels. The median FACIT-Fatigue score was 41.5 (range, 10-52), with lower values indicating more fatigue. VO2peak was not significantly associated with FACIT-Fatigue score (P = .20). CONCLUSIONS: VO2peak was not a significant predictor of radiation therapy-related fatigue. Most patients with breast cancer had marked impairments in cardiorespiratory fitness as determined by VO2peak. Larger prospective studies are needed to further investigate this novel finding and evaluate the effects of interventions aimed at improving cardiorespiratory fitness and their ability to potentially prevent fatigue.
Asunto(s)
Neoplasias de la Mama , Capacidad Cardiovascular , Humanos , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Proyectos Piloto , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/tratamiento farmacológico , Consumo de Oxígeno , Fatiga/etiologíaRESUMEN
BACKGROUND/PURPOSE: Central/ultra-central thoracic tumors are challenging to treat with stereotactic radiotherapy due potential high-grade toxicity. Stereotactic MR-guided adaptive radiation therapy (SMART) may improve the therapeutic window through motion control with breath-hold gating and real-time MR-imaging as well as the option for daily online adaptive replanning to account for changes in target and/or organ-at-risk (OAR) location. MATERIALS/METHODS: 26 central (19 ultra-central) thoracic oligoprogressive/oligometastatic tumors treated with isotoxic (OAR constraints-driven) 5-fraction SMART (median 50 Gy, range 35-60) between 10/2019-10/2022 were reviewed. Central tumor was defined as tumor within or touching 2 cm around proximal tracheobronchial tree (PBT) or adjacent to mediastinal/pericardial pleura. Ultra-central was defined as tumor abutting the PBT, esophagus, or great vessel. Hard OAR constraints observed were ≤ 0.03 cc for PBT V40, great vessel V52.5, and esophagus V35. Local failure was defined as tumor progression/recurrence within the planning target volume. RESULTS: Tumor abutted the PBT in 31 %, esophagus in 31 %, great vessel in 65 %, and heart in 42 % of cases. 96 % of fractions were treated with reoptimized plan, necessary to meet OAR constraints (80 %) and/or target coverage (20 %). Median follow-up was 19 months (27 months among surviving patients). Local control (LC) was 96 % at 1-year and 90 % at 2-years (total 2/26 local failure). 23 % had G2 acute toxicities (esophagitis, dysphagia, anorexia, nausea) and one (4 %) had G3 acute radiation dermatitis. There were no G4-5 acute toxicities. There was no symptomatic pneumonitis and no G2 + late toxicities. CONCLUSION: Isotoxic 5-fraction SMART resulted in high rates of LC and minimal toxicity. This approach may widen the therapeutic window for high-risk oligoprogressive/oligometastatic thoracic tumors.
Asunto(s)
Neoplasias Pulmonares , Traumatismos por Radiación , Radiocirugia , Neoplasias Torácicas , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Recurrencia Local de Neoplasia , Radiocirugia/métodos , Neoplasias Torácicas/radioterapia , Imagen por Resonancia Magnética/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologíaRESUMEN
BACKGROUND: Recent data have found an overall survival benefit from prostate-directed radiotherapy in patients with low-volume metastatic prostate cancer. Prostate SBRT is an attractive treatment in this setting and may be optimised with MR-guided adaptive treatment. Here, we share our institutional experience delivering stereotactic MR-guided adaptive prostate SBRT (SMART) for patients with low-volume metastatic disease. METHODS: We reviewed patients with low-volume metastatic disease who received prostate SMART from October 2019 to December 2021 on a 0.35T MR-Linac. The cohort included 14 patients. Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed using CTCAE v 5.0. Progression was defined as a change in systemic or hormonal therapy regimen as a result of PSA rise or disease progression. RESULTS: The median follow-up time was 29 months. Seven patients had hormone sensitive prostate cancer and 7 had castrate resistant prostate cancer (CRPC). 13 patients received 36.25 Gy in 5 fractions and one patient received 33 Gy in 5 fractions. At the time of last follow-up, 11 patients had not experienced progression and three patients, all with CRPC, had experienced progression. No patients developed local progression in the prostate after SMART. One patient experienced acute grade 2 urinary toxicity (7%) and no patients experienced acute grade 2 GI toxicity (0%). No grade 3 + acute toxicities were observed. CONCLUSIONS: Prostate SMART was found to be well tolerated and all patients had local control of disease within the prostate at the time of last follow-up. Prostate SMART may represent a low-risk and well-tolerated approach for delivering prostate-directed radiotherapy for patients with limited metastatic disease.
Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Radiocirugia , Humanos , Masculino , Próstata/patología , Antígeno Prostático Específico , Neoplasias de la Próstata/patología , Sistema UrogenitalRESUMEN
BACKGROUND: Stereotactic body radiotherapy (SBRT) is gaining wider adoption for prostate cancer management but there remain significant toxicity risks when delivering prostate SBRT with standard techniques. Magnetic resonance-guided daily adaptive SBRT (MRg-A-SBRT) offers technological advantages in precision of radiation dose delivery, but the toxicity profile associated with MRg-A-SBRT compared to more standardly used fiducial or computed tomography-guided non-adaptive prostate SBRT (CT-SBRT) remains unknown. METHODS: A meta-analysis to compare acute toxicity rates associated with MRg-A-SBRT and CT-SBRT for prostate cancer was performed in compliance with PRISMA guidelines. MEDLINE (PubMed) and Google Scholar were searched for prospective studies of prostate SBRT that were published between January 1, 2018 and August 31, 2022. Random effects and fixed effects models were used to estimate pooled toxicity rates, and meta-regression was performed to compare toxicity between MRg-A-SBRT and CT-SBRT study groups. RESULTS: Twenty-nine prospective studies were identified that met the inclusion criteria and included a total of 2547 patients. The pooled estimates for acute grade 2 or higher (G2+) genitourinary (GU) and gastrointestinal (GI) toxicity for MRg-A-SBRT were 16% (95% confidence interval [CI], 10%-24%) and 4% (95% CI, 2%-7%) and for CT-SBRT they were 28% (95% CI, 23%-33%) and 9% (95% CI, 6%-12%), respectively. On meta-regression, the odds ratios for acute G2+ GU and GI toxicities comparing MRg-A-SBRT and CT-SBRT were 0.56 (95% CI, 0.33-0.97, p = .04) and 0.40 (95% CI, 0.17-0.96, p = .04), respectively. CONCLUSION: MRg-A-SBRT is associated with a significantly reduced risk of acute G2+ GU or GI toxicity compared to CT-SBRT. Longer follow-up will be needed to evaluate late toxicity and disease control outcomes. PLAIN LANGUAGE SUMMARY: Magnetic resonance imaging-guided daily adaptive prostate stereotactic radiation (MRg-A-SBRT) is a treatment that may allow for delivery of prostate radiation more precisely than other radiotherapy techniques, but it is unknown whether this reduces side effects compared to standardly used computed tomography-guided SBRT (CT-SBRT). In this systematic review and meta-analysis combining data from 29 clinical trials including 2547 patients, it was found that the risk of short-term urinary side effects was reduced by 44% and the risk of short-term bowel side effects was reduced by 60% with MRg-A-SBRT compared to CT-SBRT.
Asunto(s)
Enfermedades Gastrointestinales , Neoplasias de la Próstata , Radiocirugia , Masculino , Humanos , Radiocirugia/efectos adversos , Radiocirugia/métodos , Próstata/patología , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Imagen por Resonancia Magnética , Espectroscopía de Resonancia MagnéticaRESUMEN
Initial studies of radiotherapy in renal cell carcinoma (RCC) failed to demonstrate significant clinical impact. With the advent of stereotactic body radiotherapy (SBRT) that allows for delivery of more effective radiation doses in a precise fashion, radiotherapy has become an essential component in the multidisciplinary management of patients with RCC both in the setting of localized and metastatic disease beyond the traditional role of palliative treatment. Recent evidence has demonstrated high rates of long-term local control (â¼95%) when SBRT is delivered to kidney tumors with limited toxicity risks and only minor impact on renal function.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Radiocirugia , Humanos , Carcinoma de Células Renales/radioterapia , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/secundario , Neoplasias Renales/radioterapia , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Radiocirugia/efectos adversos , Cuidados PaliativosRESUMEN
Renal cell carcinoma (RCC) has historically been considered resistant to radiotherapy. However, advances in the field of radiation oncology have led to safe delivery of higher radiation doses through the use of stereotactic body radiotherapy (SBRT) that have shown significant activity against RCC. SBRT has now been shown to be a highly effective modality for management of localized RCC for nonsurgical candidates. Increasing evidence also points to a role for SBRT in the management of oligometastatic RCC as a means for not only providing palliation but prolonging time to progression and potentially improving survival.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Radiocirugia , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patologíaRESUMEN
PURPOSE: The role of biliary stents in image-guided localization for pancreatic cancer has been inconclusive. To date, stent accuracy has been largely evaluated against implanted fiducials on cone beam computed tomography. We aim to use magnetic resonance (MR) soft tissue as a direct reference to examine the geometric and dosimetric impacts of stent-based localization on the newly available MR linear accelerator. METHODS: Thirty pancreatic cancer patients (132 fractions) treated on our MR linear accelerator were identified to have a biliary stent. In our standard adaptive workflow, patients were set up to the target using soft tissue for image registration and structures were re-contoured on daily MR images. The original plan was then projected on treatment anatomy and dose predicted, followed by plan re-optimization and treatment delivery. These online predicted plans were soft tissue-based and served as reference plans. Retrospective image registration to the stent was performed offline to simulate stent-based localization and the magnitude of shifts was taken as the geometric accuracy of stent localization. New predicted plans were generated based on stent-alignment for dosimetric comparison. RESULTS: Shifts were within 3 mm for 90% of the cases (mean = 1.5 mm); however, larger shifts up to 7.2 mm were observed. Average PTV coverage dropped by 1.1% with a maximum drop of 26.8%. The mean increase in V35Gy was 0.15, 0.05, 0.02, and 0.02 cc for duodenum, stomach, small bowel and large bowel, respectively. Stent alignment was significantly worse for all metrics except for small bowel (p = 0.07). CONCLUSIONS: Overall discrepancy between stent- and soft tissue-alignment was modest; however, large discrepancies were observed for select cases. While PTV coverage loss may be compensated for by using a larger margin, the increase in dose to gastrointestinal organs at risk may limit the role of biliary stents in image-guided localization.
Asunto(s)
Neoplasias Pancreáticas , Radiocirugia , Radioterapia Guiada por Imagen , Humanos , Radiocirugia/métodos , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirugía , Stents , Espectroscopía de Resonancia Magnética , Planificación de la Radioterapia Asistida por Computador/métodos , Dosificación Radioterapéutica , Radioterapia Guiada por Imagen/métodos , Neoplasias PancreáticasRESUMEN
Current MRI-guided adaptive radiotherapy (MRgART) workflows require fraction-specific electron and/or mass density maps, which are created by deformable image registration (DIR) between the simulation CT images and daily MR images. Manual density overrides may also be needed where DIR-produced results are inaccurate. This approach slows the adaptive radiotherapy workflow and introduces additional dosimetric uncertainties, especially in the presence of the magnetic field. This study investigated a method based on a conditional generative adversarial network (cGAN) with a multi-planar method to generate synthetic CT images from low-field MR images to improve efficiency in MRgART workflows for prostate cancer. Fifty-seven male patients, who received MRI-guided radiation therapy to the pelvis using the ViewRay MRIdian Linac, were selected. Forty-five cases were randomly assigned to the training cohort with the remaining twelve cases assigned to the validation/testing cohort. All patient datasets had a semi-paired DIR-deformed CT-sim image and 0.35T MR image acquired using a true fast imaging with steady-state precession (TrueFISP) sequence. Synthetic CT images were compared with deformed CT images to evaluate image quality and dosimetric accuracy. To evaluate the dosimetric accuracy of this method, clinical plans were recalculated on synthetic CT images in the MRIdian treatment planning system. Dose volume histograms for planning target volumes (PTVs) and organs-at-risk (OARs) and dose distributions using gamma analyses were evaluated. The mean-absolute-errors (MAEs) in CT numbers were 30.1 ± 4.2 HU, 19.6 ± 2.3 HU and 158.5 ± 26.0 HU for the whole pelvis, soft tissue, and bone, respectively. The peak signal-to-noise ratio was 35.2 ± 1.7 and the structural index similarity measure was 0.9758 ± 0.0035. The dosimetric difference was on average less than 1% for all PTV and OAR metrics. Plans showed good agreement with gamma pass rates of 99% and 99.9% for 1%/1 mm and 2%/2 mm, respectively. Our study demonstrates the potential of using synthetic CT images created with a multi-planar cGAN method from 0.35T MRI TrueFISP images for the MRgART treatment of prostate radiotherapy. Future work will validate the method in a large cohort of patients and investigate the limitations of the method in the adaptive workflow.
RESUMEN
Purpose: Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for prostate cancer allows for MR-based contouring, real-time MR motion management, and daily plan adaptation. The clinical and dosimetric benefits associated with prostate SMART remain largely unknown. Methods and Materials: A phase 1 trial of prostate SMART was conducted with primary endpoints of safety and feasibility. An additional cohort of patients similarly treated with prostate SMART were included in the analysis. SMART was delivered to 36.25 Gy in 5 fractions to the prostate ± seminal vesicles using the MRIdian linear accelerator system (ViewRay, Inc). Rates of urinary and gastrointestinal toxic effects and patient-reported outcome measures were assessed. Dosimetric analyses were conducted to evaluate the specific benefits of daily plan adaptation. Results: The cohort included 22 patients (n = 10 phase 1, n = 12 supplemental) treated in 110 fractions. Median follow-up was 7.9 months. Acute grade 2 urinary and gastrointestinal toxic effects were observed in 22.7% and 4.5%, respectively, and 4.5% and 0%, respectively, at last follow-up. No grade 3+ events were observed. Expanded Prostate Cancer Index-26 urinary obstructive scores decreased during SMART (mean, 9.3 points; P = .03) and returned to baseline by 3 months. No other significant changes in patient-reported outcome measures were observed. One-hundred percent of fractions required plan adaptation owing to exceeding organ-at-risk metrics (68%) or suboptimal target coverage (33%) resulting from anatomic changes. Minimum acceptable planning target volume, rectal, bladder, and urethra/bladder neck metrics were violated in 24%, 20%, 24%, and 33% of predicted plans, respectively; 0% of reoptimized plans violated metrics. Underlying causes for deficient dosimetry before reoptimization included changes in bladder filling, seminal vesicle position, prostate volume (median 4.7% increase by fraction 3; range, 0%-56%), and hotspots shifting into urethra/bladder neck. Conclusions: Prostate SMART results in low risk of acute toxic effects with improvements in target and organ-at-risk dosimetry. The clinical benefits resulting from daily plan adaptation, including urethra/bladder neck protection, warrant further investigation.
RESUMEN
BACKGROUND: Whole pelvic radiation therapy (WPRT) may improve outcomes compared with prostate only radiation therapy (PORT) in some subsets of men with prostate cancer, as in the POP-RT trial. However, there is concern about increased risk of adverse effects with WPRT, including the development of radiation-induced second malignancies (SM). Given the rarity of SM, little is known about relative rates of SM between WPRT and PORT. METHODS: A retrospective cohort analysis was performed of men with nonmetastatic, node-negative prostate cancer with at least 60 months of follow-up using a national database. SM probabilities were compared in men receiving either WPRT or PORT using multivariable logistic models adjusting for clinical and sociodemographic factors. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up were also conducted. RESULTS: Of 50,237 patients in the study, 39,338 (78.4%) received PORT, and 10,899 (21.7%) received WPRT. Median follow-up was 106.2 months (interquartile range 82.32-132.25). Crude probabilities of SM were 9.16% for WPRT and 8.88% for PORT. The adjusted odds ratio (AOR) for development of SM with PORT versus WPRT was 1.046 (95% confidence interval 0.968-1.130). Temporal sensitivity analyses by stratifying by year of diagnosis and follow-up length also did not demonstrate any significant difference in rates of SM between WPRT and PORT using AORs with WPRT as the referent. CONCLUSIONS: Retrospective analysis of over 50,000 patients did not demonstrate an association between WPRT and an increased probability of SM compared to PORT. Given the findings of POP-RT, the use of WPRT may become widespread for certain subsets of men. Thus, our findings could help guide how we counsel patients deciding between WPRT and PORT and suggest the need for prospective assessment of SM risk with WPRT and PORT.
Asunto(s)
Neoplasias Primarias Secundarias , Neoplasias de la Próstata , Antagonistas de Andrógenos/uso terapéutico , Humanos , Masculino , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Pelvis/patología , Probabilidad , Estudios Prospectivos , Próstata/patología , Antígeno Prostático Específico , Neoplasias de la Próstata/patología , Estudios RetrospectivosRESUMEN
PURPOSE: Stereotactic body radiation therapy can be an effective treatment for oligometastases. However, safe delivery of ablative radiation is frequently limited by the proximity of mobile organs sensitive to high radiation doses. The goal of this study was to determine the feasibility, safety, and disease control outcomes of stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) in patients with abdominopelvic oligometastases. METHODS AND MATERIALS: We identified 101 patients with abdominopelvic oligometastases, including 20 patients enrolled on phase 1 protocols, who were consecutively treated with SMART on a 0.35T magnetic resonance linear accelerator (MR linac) at a single institution from October 2019 to September 2021. Local control and overall survival were analyzed using the Kaplan-Meier method. RESULTS: Overall, 114 tumors were treated. The most common histology was prostate adenocarcinoma (60 tumors [53.5%]), and 65 sites (57.0%) were centered in the pelvis. Ninety-one sites (79.8%) were treated to 8 Gy × 5, and 49 (43.0%) were treated with breath-hold respiratory gating. Online adaptation resulted in a clinically significant improvement in coverage or organ sparing in 86.6% of delivered fractions. The median time required for adaptation was 24 minutes, and the median time in the treatment room was 58 minutes. With median follow-up of 11.4 months, the 12-month local control was 93% and was higher for prostate adenocarcinoma versus other histologies (100% vs 84%; P = .009). The 12-month overall survival was 96% and was higher for prostate adenocarcinoma versus other histologies (100% vs 91%; P = .046). Three patients (3.0%) developed grade 3 toxic effects (colonic hemorrhage at 3.4 months and urinary tract obstructions at 10.1 and 18.4 months, respectively). CONCLUSIONS: In this study, SMART was feasible, safe, and effective for delivering ablative radiation therapy to abdominopelvic metastases. Adaptive planning was necessary in the large majority of cases. The advantages of SMART warrant its further investigation as a standard option for the treatment of abdominopelvic oligometastases.
Asunto(s)
Adenocarcinoma , Neoplasias de la Próstata , Radiocirugia , Masculino , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Estudios Retrospectivos , Radiocirugia/efectos adversos , Radiocirugia/métodos , Neoplasias de la Próstata/radioterapia , Espectroscopía de Resonancia Magnética , Adenocarcinoma/radioterapiaRESUMEN
PURPOSE: Internal motion of the larynx can cause normal tissue toxicity and/or tumor underdosage during radiotherapy. MR-guided radiation therapy (MRgRT) provides improved soft-tissue contrast for patient setup and real-time gating of radiation based on cine imaging of tumor motion, potentially making it an advantageous modality for laryngeal treatments. However, there are potential concerns regarding the small target size, proximity to heterogeneous tissue interfaces in the airway that may cause dosimetric errors in the presence of the magnetic field, and uncertainty about the ability of MR-linear accelerator (MR-Linac) systems to visualize and track laryngeal motion. To date, there have been no reports of the use of MRgRT for laryngeal treatments. METHODS: A healthy volunteer was imaged on a ViewRay MRIdian MR-Linac. Organs-at-risk and a laryngeal pseudo target were contoured and used to generate a stereotactic body radiotherapy plan. A custom phantom was created using 3D-printing based on structures delineated on the volunteer images to construct an enclosure containing the target and airway anatomy, with a gap for radiochromic film, and filled with gelatin . The treatment plan was mapped onto the phantom and delivered dose assessed on radiochromic film with global normalization and a 10% dose threshold. A cine MR of the volunteer was acquired to assess the magnitude of larynx motion with speaking and swallowing, and system's ability to gate radiation. RESULTS: A clinically acceptable laryngeal treatment plan and larynx phantom that was MR and computed tomography-visible were successfully created. The delivered dose had good agreement with the treatment plan with a gamma passing rate of 96.5% (3%/2 mm). The MR-Linac was able to visualize, track, and gate larynx motion. CONCLUSIONS: The MRgRT workflow for laryngeal treatments was assessed and performed in preparation for clinical implementation on the MR-Linac, demonstrating that it is feasible to treat laryngeal cancer patients on the MR-Linac.
Asunto(s)
Neoplasias Laríngeas , Laringe , Radioterapia Guiada por Imagen , Voluntarios Sanos , Humanos , Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/radioterapia , Laringe/diagnóstico por imagen , Imagen por Resonancia Magnética , Aceleradores de Partículas , Fantasmas de Imagen , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: Clinical trials assessing evaluation prostate stereotactic body radiation therapy (SBRT) have used a wide range of allowed doses to the intraprostatic urethra, but the relationship between urethral dose and urinary toxicity has not been thoroughly evaluated. The goal of this study was to characterize urinary toxicity outcomes according to urethral dose administered during prostate SBRT. METHODS AND MATERIALS: The MEDLINE (PubMed) database was searched for published prospective studies of prostate SBRT through August 2020 that documented a maximum urethral dose metric (MUDM). Reported acute and late urinary toxicity rates were collected. Logistic regression and weighted Pearson correlation models were used to assess associations between urinary toxicity rates and MUDM. RESULTS: Twenty-three unique studies (n = 2232 patients) met the inclusion criteria and included a wide range of MUDMs (equivalent dose in 2 Gy fractions [EQD2]: 69-141.75 Gy; α/ß = 3 Gy). The median follow-up ranged from 3 to 67 months (median, 32 months). On logistic regression analysis, the MUDM EQD2 was significantly associated with multiple urinary toxicity endpoints, including acute grade (G) 2+ (odds ratio [OR], 1.02; P < .001), late G2+ (OR, 1.03; P < .0001), and late G3+ (OR, 1.04; P = .003) urinary toxicity. On weighted Pearson correlation analysis, the MUDM was more closely associated with all evaluated urinary toxicity endpoints than prescription dose, including acute G2+ (r = 0.51; P = .02), late G2+ (r = 0.9; P < .0001), and late G3+ toxicity (r = 0.7; P = .003). Multivariate analysis accounting for age, prostate size, bladder dosimetry, and baseline urinary function confirmed associations between urinary outcomes and MUDM. Within the studied dose range, each increase of 1 Gy to the MUDM corresponded to a 0.8% and 1.0% increase in acute G2+ and late G2+ toxicity, respectively. CONCLUSIONS: Radiation dose to the urethra correlates closely with urinary toxicity in patients with prostate cancer treated with SBRT. Attention should be paid to the urethral dose when delivering prostate SBRT to high doses, and approaches for urethral dose reduction warrant further investigation.