RESUMO
Magnetic resonance imaging (MRI) can facilitate accurate organ delineation and optimal dose distributions in high-dose-rate (HDR) MRI-Assisted Radiosurgery (MARS). Its use for this purpose has been limited by the lack of positive-contrast MRI markers that can clearly delineate the lumen of the HDR applicator and precisely show the path of the HDR source on T1- and T2-weighted MRI sequences. We investigated a novel MRI positive-contrast HDR brachytherapy or interventional radiotherapy line marker, C4:S, consisting of C4 (visible on T1-weighted images) complexed with saline. Longitudinal relaxation time (T1) and transverse relaxation time (T2) for C4:S were measured on a 1.5 T MRI scanner. High-density polyethylene (HDPE) tubing filled with C4:S as an HDR brachytherapy line marker was tested for visibility on T1- and T2-weighted MRI sequences in a tissue-equivalent female ultrasound training pelvis phantom. Relaxivity measurements indicated that C4:S solution had good T1-weighted contrast (relative to oil [fat] signal intensity) and good T2-weighted contrast (relative to water signal intensity) at both room temperature (relaxivity ratio > 1; r2/r1 = 1.43) and body temperature (relaxivity ratio > 1; r2/r1 = 1.38). These measurements were verified by the positive visualization of the C4:S (C4/saline 50:50) HDPE tube HDR brachytherapy line marker on both T1- and T2-weighted MRI sequences. Orientation did not affect the relaxivity of the C4:S contrast solution. C4:S encapsulated in HDPE tubing can be visualized as a positive line marker on both T1- and T2-weighted MRI sequences. MRI-guided HDR planning may be possible with these novel line markers for HDR MARS for several types of cancer.
RESUMO
Prostate cancer may recur several years after definitive treatment, such as prostatectomy or radiation therapy. A rise in serum prostate-specific antigen (PSA) level is the first sign of disease recurrence, and this is termed biochemical recurrence. Patients with biochemical recurrence have worse survival outcomes. Radiologic localization of recurrent disease helps in directing patient management, which may vary from active surveillance to salvage radiation therapy, androgen-deprivation therapy, or other forms of systemic and local therapy. The likelihood of detecting the site of recurrence increases with higher serum PSA level. MRI provides optimal diagnostic performance for evaluation of the prostatectomy bed. Prostate-specific membrane antigen (PSMA) PET radiotracers currently approved by the U.S. Food and Drug Administration demonstrate physiologic urinary excretion, which can obscure recurrence at the vesicourethral junction. However, MRI and PSMA PET/CT have comparable diagnostic performance for evaluation of local recurrence after external-beam radiation therapy or brachytherapy. PSMA PET/CT outperforms MRI in identifying recurrence involving the lymph nodes and bones. Caveats for use of both PSMA PET/CT and MRI do exist and may cause false-positive or false-negative results. Hence, these techniques have complementary roles and should be interpreted in conjunction with each other, taking the patient history and results of any additional prior imaging studies into account. Novel PSMA agents at various stages of investigation are being developed, and preliminary data show promising results; these agents may revolutionize the landscape of prostate cancer recurrence imaging in the future. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center. See the invited commentary by Turkbey in this issue. The slide presentation from the RSNA Annual Meeting is available for this article.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Antagonistas de Androgênios , Isótopos de Gálio , Radioisótopos de Gálio , Recidiva Local de Neoplasia/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated. PATIENTS AND METHODS: Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (Sâ +â R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGFR TT, and inclusion of cabozantinib in the post-ICT TT regimen. RESULTS: 29/57 patients had S dedifferentiation and 19 had R dedifferentiation. The most frequently used TT was cabozantinib (43.9%) followed by selective VEGFR TT (22.8%). The median time on TT was 6.4 months for all, 6.1 months for those with S dedifferentiation, 15.6 months for R dedifferentiation, and 6.1 months for Sâ +â R dedifferentiation. Median OS from initiation of TT was 24.9 months for the entire cohort, and the ORR was 20.0%. Patients with R dedifferentiation had significantly longer time on TT than those with S dedifferentiation (HR 0.44, 95% CI, 0.21-0.94). IMDC risk was associated with OS. CONCLUSIONS: A subset of patients with S/R dedifferentiation derive clinical benefit from TT after they have progressive disease on ICT. Patients with R dedifferentiation appeared to derive more benefit from TT than those with S dedifferentiation.
RESUMO
PURPOSE: The benefit of local consolidative therapy (LCT) for oligometastasis across histologies remains uncertain. EXTernal beam radiation to Eliminate Nominal metastatic Disease (EXTEND; NCT03599765) is a randomized phase 2 basket trial evaluating the effectiveness of LCT for oligometastatic solid tumors. We report here the prospective results of the single-arm "lead-in" phase intended to identify histologies most likely to accrue to histology-specific endpoints in the randomized phase. METHODS AND MATERIALS: Eligible histologies included colorectal, sarcoma, lung, head and neck, ovarian, renal, melanoma, pancreatic, prostate, cervix/uterine, breast, and hepatobiliary. Patients received LCT to all sites of active metastatic disease and primary/regional disease (as applicable) plus standard-of-care systemic therapy or observation. The primary endpoint in EXTEND was progression-free survival (PFS), and the primary endpoint of the lead-phase was histology-specific accrual feasibility. Adverse events were graded by Common Terminology Criteria for Adverse Events version 4.0. RESULTS: From August 2018 through January 2019, 50 patients were enrolled and 49 received definitive LCT. Prostate, breast, and kidney were the highest enrolling histologies and identified for independent accrual in the randomization phase. Most patients (73%) had 1 or 2 metastases, most often in lung or bone (79%), and received ablative radiation (62%). Median follow-up for censored patients was 38 months (range, 16-42 months). Median PFS was 13 months (95% confidence interval, 9-24), 3-year overall survival rate was 73% (95% confidence interval, 57%-83%), and local control rate was 98% (93 of 95 tumors). Two patients (4%) had Common Terminology Criteria for Adverse Events grade 3 toxic effects related to LCT; no patient had grade 4 or 5 toxic effects. CONCLUSIONS: The prospective lead-in phase of the EXTEND basket trial demonstrated feasible accrual, encouraging PFS, and low rates of severe toxic effects at mature follow-up. The randomized phase is ongoing with histology-based baskets that will provide histology-specific evidence for LCT in oligometastatic disease.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Feminino , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Intervalo Livre de ProgressãoRESUMO
Purpose Fluorine 18 (18F)-fluciclovine and prostate-specific membrane antigen (PSMA) tracers are commonly used for localizing biochemical recurrence of prostate cancer, but their accuracy in primary tumor detection in the initial staging of high-risk prostate cancer has not been established. Materials and Methods A systematic review was performed of the electronic databases for original studies published between 2012 and 2020. Included studies were those in which 18F-fluciclovine or PSMA PET was used for initial staging of patients with high-risk prostate cancer. The diagnostic performance data were collected for primary tumor with histopathologic results as reference standard. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used for quality appraisal. A random-effects model was used to summarize the effect sizes and to evaluate the difference between two groups. Results Overall, 28 studies met the eligibility criteria, and 17 were included in the meta-analysis (18F-fluciclovine = 4, PSMA = 13). Of these 17 studies, 12 (70%) were judged to have high risk of bias in one of the evaluated domains, and nine studies were deemed to have applicability concerns. The pooled sensitivity, specificity, and diagnostic odds ratio for 18F-fluciclovine versus PSMA were 85% (95% CI: 73%, 92%) versus 84% (95% CI: 77%, 89%) (P = .78), 77% (95% CI: 60%, 88%) versus 83% (95% CI: 76%, 89%) (P = .40), and 18.88 (95% CI: 5.01, 71.20) versus 29.37 (95% CI: 13.35, 64.60) (P = .57), respectively, with no significant difference in diagnostic test accuracy. Conclusion 18F-fluciclovine and PSMA PET demonstrated no statistically significant difference in diagnostic accuracy in primary tumor detection during initial staging of high-risk prostate cancer. Keywords: PET, Prostate, Molecular Imaging-Cancer, Staging Supplemental material is available for this article. © RSNA, 2022.
Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Compostos RadiofarmacêuticosRESUMO
Background Prostatic ductal adenocarcinoma (DAC) is an aggressive histologic variant of prostate cancer that often warrants multimodal therapy and poses a significant diagnostic challenge clinically and at imaging. Purpose To develop multiparametric MRI criteria to define DAC and to assess their diagnostic performance in differentiating DAC from prostatic acinar adenocarcinoma (PAC). Materials and Methods Men with histologically proven DAC who had multiparametric MRI before radical prostatectomy were retrospectively identified from January 2011 through November 2018. MRI features were predefined using a subset of nine DACs and then compared for men with peripheral-zone DACs 1 cm or greater in size and men with matched biopsy-confirmed International Society of Urological Pathology grade group 4-5 PAC, by four independent radiologists blinded to the pathologic diagnosis. Diagnostic performance was determined by consensus read. Patient and tumor characteristics were compared by using the Fisher test, t-tests, and Mann-Whitney U test. Agreement (Cohen κ) and sensitivity analyses were also performed. Results There were 59 men with DAC (median age, 63 years [interquartile range, 56, 67 years]) and 59 men with PAC (median age, 64 years [interquartile range, 59, 69 years]). Predefined MRI features, including intermediate T2 signal, well-defined margin, lobulation, and hypointense rim, were detected in a higher proportion of DACs than PACs (76% [45 of 59] vs 5% [three of 59]; P < .001). On consensus reading, the presence of three or more features demonstrated 76% sensitivity, 94% specificity, 94% positive predictive value [PPV], and 80% negative predictive value [NPV] for all DACs and 100% sensitivity, 95% specificity, 81% PPV, and 100% NPV for pure DACs. The DACs and PACs showed no difference in contrast enhancement (100% vs 100%; P >.99, median T2 signal intensity (254 vs 230; P = .99), or apparent diffusion coefficient (median, 677 10-6 mm2/sec vs 685 10-6 mm2/sec; P = .73). Conclusion The presence of intermediate T2 signal, well-defined margin, lobulation, and/or hypointense rim, together with restricted diffusion and contrast enhancement at multiparametric MRI of the prostate, suggests prostatic ductal adenocarcinoma rather than prostatic acinar adenocarcinoma. © RSNA, 2022 Online supplemental material is available for this article.
Assuntos
Adenocarcinoma , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Adenocarcinoma/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prostatectomia , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Integrated quality improvement (QI) and cost reduction strategies can help increase value in cancer care. Time-driven activity-based costing (TDABC) is a bottom-up costing tool that measures resource use over the full care cycle. We applied standard QI and TDABC methods to improve workflow efficiency and reduce costs for MRI-guided prostate brachytherapy. METHODS AND MATERIALS: We constructed process maps of the baseline prostate brachytherapy workflow from initial consultation through one year after treatment. Process maps reflected resources and time required at each step. TDABC costs were calculated by multiplying each process time by the cost per min of the resource(s) used at that step. We then used plan-do-study-act methodology to identify workflow inefficiencies and implement solutions to reduce resource consumption. RESULTS: The highest cost components at baseline were the operating room (OR) (40%), imaging (8.7%), and consultation (7.6%). Higher-than-expected costs (3%) were incurred during surgery scheduling. After targeted QI initiatives, OR time was reduced from 90 to 70 min, which reduced overall cost by 5%. Personnel task downshifting reduced costs by 10% at consultation and 77% at surgery scheduling. Re-engineering of follow-up protocols reduced costs by 8.4%. Costs under the new workflow decreased by 18.2%. CONCLUSIONS: TDABC complements traditional QI initiatives by quantifying the highest cost steps and focusing QI initiatives to reduce costs and improve efficiency. As payment reform evolves toward bundled payments, TDABC and QI initiatives will help providers understand, communicate, and improve the value of cancer care.
Assuntos
Braquiterapia , Braquiterapia/métodos , Custos de Cuidados de Saúde , Humanos , Imageamento por Ressonância Magnética , Masculino , Salas Cirúrgicas , Próstata , Fluxo de TrabalhoRESUMO
MRI features are presented in a multicenter retrospective series of five patients with a unilateral masslike lesion seen in the genitourinary diaphragm at MRI performed for known or suspected prostate cancer. In all cases, the lesion appeared as an encapsulated 1.3 to 3.0 cm mass of heterogeneous low or intermediate T2 signal intensity in the genitourinary diaphragm, and targeted biopsy demonstrated benign Cowper's gland tissue. This entity is a potential imaging pitfall that could result in a diagnosis of an exophytic nodule of benign prostatic hyperplasia or local spread of prostate cancer. We present these cases to facilitate correct identification of Cowper's gland hyperplasia as an occasional finding at MRI of the prostate.
Assuntos
Glândulas Bulbouretrais , Próstata , Glândulas Bulbouretrais/patologia , Humanos , Hiperplasia/diagnóstico por imagem , Hiperplasia/patologia , Imageamento por Ressonância Magnética , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Immune checkpoint therapy (ICT) prolongs survival in subsets of patients with cancer but can also trigger immune-related adverse events (irAEs) requiring treatment discontinuation. Recent studies have investigated safety of ICT rechallenge after irAEs, and evidence suggests that rechallenge may be associated with improved antitumor responses. However, data are limited on response duration after ICT rechallenge, particularly after severe irAEs. OBJECTIVE: To evaluate safety and efficacy of ICT rechallenge after moderate-to-severe irAEs in patients with renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer. METHODS: In this retrospective cohort study, medical records from September 25, 2013, to June 1, 2020, for patients with genitourinary (GU) cancers at MD Anderson Cancer Center who were rechallenged with the same or different ICT following irAEs were reviewed. Demographics, ICT exposure, irAEs (grade and treatment), ICT discontinuation or rechallenge, rates of subsequent irAEs (new or recurrent) and antitumor activity (objective response rates and response duration) were reviewed. RESULTS: Sixty-one patients with RCC, UC, and prostate cancer were rechallenged with ICT after experiencing 105 total irAEs. Objective response rates after rechallenge, that is, upgrade in response, were 14% in RCC (4/28), 21% in UC (3/14), and 0% in prostate cancer. All seven patients who achieved upgrade in response had initial grade 2 or 3 irAEs. Responses were durable among these seven patients, with median radiographic progression-free survival not reached (range: 3.7-66.4 months) as of the March 8, 2021, data cut-off (median follow-up 40.9 months (95% CI 35.3 to 46.5)). All achieved complete response except one patient who was lost to follow-up. The rate of subsequent grade 3 or 4 irAEs after rechallenge was 30%, with no fatal irAEs. The rate of recrudescence of the same irAE was 26% (16/61). 54% of patients received corticosteroids (33/61), and 21% received targeted immunosuppression (13/61) for the initial irAEs. CONCLUSIONS AND RELEVANCE: ICT rechallenge after moderate-to-severe irAEs was associated with deep and durable responses in a subset of patients with RCC and UC, with acceptable safety and no fatal events. Strategies to enable ICT resumption after moderate-to-severe irAEs, such targeted immunosuppression, warrant further study.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/métodos , Neoplasias Urogenitais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: The freehand (FH) technique of transperineal prostate biopsy using commercialized needle access systems facilitates a reduction in anesthesia requirements from general to local or local/sedation. We sought to compare the efficacy and complication rates of the FH method with those of the standard grid-based (GB) method. MATERIALS AND METHODS: The GB method was performed from 2014 to 2018, and the updated FH technique was performed from 2018 to 2020, yielding comparative cohorts of 174 and 304, respectively. RESULTS: The FH and GB techniques demonstrated equivalent yields of ≥Gleason grade group (GGG)-2 prostate cancer (PCa). The FH group had a significantly higher mean number of cores with ≥GGG-2 PCa involvement (p=0.011) but a significantly lower mean number of biopsy samples (p <0.01). The urinary retention rate of the GB group (10%) was significantly higher than that of the FH group (1%; p <0.01). The rates of ≥GGG-2 PCa involvement in the anterior (GB, 31%) and anteromedial (FH, 22%) sectors were higher than those in other sectors (range, 0%-9%). For multiparametric magnetic resonance imaging, the rate of ≥GGG-2 PCa detection in the anteromedial prostate (23%) was nearly half that in other locations (range, 38%-55%). CONCLUSIONS: Compared with GB transperineal biopsy, FH transperineal biopsy demonstrates an equivalent cancer yield with no risk of sepsis, a significantly reduced risk of urinary retention, and reduced anesthesia needs. The higher number of cores with ≥GGG-2 PCa involvement in the FH group suggests that FH transperineal biopsy can sample the prostate better than GB-transperineal biopsy can.
Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Biópsia Guiada por Imagem/métodos , Complicações Pós-Operatórias/epidemiologia , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Idoso , Biópsia com Agulha de Grande Calibre/efeitos adversos , Biópsia com Agulha de Grande Calibre/instrumentação , Biópsia com Agulha de Grande Calibre/estatística & dados numéricos , Marcadores Fiduciais , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/instrumentação , Biópsia Guiada por Imagem/estatística & dados numéricos , Imagem por Ressonância Magnética Intervencionista/instrumentação , Masculino , Pessoa de Meia-Idade , Períneo/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
PURPOSE: To assess the efficacy and safety of bevacizumab plus erlotinib in patients with RMC. METHODS: We retrospectively reviewed the records of patients with RMC treated with bevacizumab plus erlotinib at our institution. RESULTS: Ten patients were included in the study. Two patients achieved a partial response (20%) and seven patients achieved stable disease (70%). Tumor burden was reduced in seven patients (70%) in total, and in three out of five patients (60%) that had received three or more prior therapies. The median progression-free survival (PFS) was 3.5 months (95% CI, 1.8-5.2). The median overall survival (OS) from bevacizumab plus erlotinib initiation was 7.3 months (95% CI, 0.73-13.8) and the median OS from diagnosis was 20.8 months (95% CI, 14.7-26.8). Bevacizumab plus erlotinib was well tolerated with no grade ≥4 adverse events and one grade 3 skin rash. Dose reduction was required in one patient (10%). CONCLUSIONS: Bevacizumab plus erlotinib is clinically active and well tolerated in heavily pre-treated patients with RMC and should be considered a viable salvage strategy for this lethal disease.
RESUMO
The Coronavirus disease 2019 (COVID-19) pandemic has significantly affected health care systems throughout the world. A Qualtrics survey was targeted for radiologists around the world to study its effect on the operations of prostate MRI studies and biopsies. Descriptive statistics were reported. A total of 60 complete responses from five continents were included in the analysis. 70% of the responses were from academic institutions. Among all participants, the median (range) number of prostate MRI was 20 (0, 135) per week before the COVID-19 pandemic versus 10 (0, 30) during the lockdown period; the median (range) number of prostate biopsies was 4.5 (0, 60) per week before the COVID-19 versus 0 (0, 12) during the lockdown period. Among the 30% who used bowel preparation for their patients prior to MRI routinely, 11% stopped the bowel preparation due to the pandemic. 47% reported that their radiology departments faced staff disruptions, while 68% reported changes in clinic schedules in other clinical departments, particularly urology, genitourinary medical oncology, and radiation oncology. Finally, COVID-19 pandemic was found to disrupt not only the clinical prostate MRI operations but also impacted prostate MRI/biopsy research in up to 50% of institutions. The impact of this collateral damage in delaying diagnosis and treatment of prostate cancer is yet to be explored.
Assuntos
COVID-19 , Neoplasias da Próstata , Radioterapia (Especialidade) , Biópsia , Controle de Doenças Transmissíveis , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Masculino , Pandemias , Neoplasias da Próstata/diagnóstico por imagem , SARS-CoV-2RESUMO
INTRODUCTION: Lenvatinib (Len) plus everolimus (Eve) is an approved therapy for metastatic renal cell carcinoma (mRCC) after first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), but limited data exist on the efficacy of Len ± Eve after progression on immune checkpoint inhibitors (ICIs) and VEGFR-TKIs. METHODS: We retrospectively reviewed the records of patients with mRCC at our institution who were treated with Len ± Eve after ICI and VEGFR-TKI. A blinded radiologist assessed objective response as defined by RECIST version 1.1. Descriptive statistics and the Kaplan-Meier method were used. RESULTS: Fifty-five patients were included in the analysis. Of these patients, 81.8% had clear-cell histology (ccRCC), and 76.4% had International Metastatic RCC Database Consortium intermediate-risk disease. Median number of prior therapies was four (range, 2-10); all patients had prior ICIs and VEGFR-TKIs, and 80% were previously treated with ICI and at least two VEGFR-TKIs, including cabozantinib. One patient (1.8%) achieved a complete response, and 11 patients (20.0%) achieved a partial response, for an overall response rate (ORR) of 21.8%; 35 patients (63.6%) achieved stable disease. In all patients, median progression-free survival (PFS) was 6.2 months (95% confidence interval [CI], 4.8-9.4) and median overall survival (OS) was 12.1 months (95% CI, 8.8-16.0). In patients with ccRCC, ORR was 24.4%, PFS was 7.1 months (95% CI, 5.0-10.5), and OS was 11.7 months (95% CI, 7.9-16.1). 50.9% of patients required dose reductions and 7.3% discontinued treatment because of toxicity. CONCLUSION: Len ± Eve demonstrated meaningful clinical activity and tolerability in heavily pretreated patients with mRCC after disease progression with prior ICIs and VEGFR-TKIs. IMPLICATIONS FOR PRACTICE: As the therapeutic landscape for patients with metastatic renal cell carcinoma continues to evolve, this single-center, retrospective review highlights the real-world efficacy of lenvatinib with or without everolimus in heavily pretreated patients. This article supports the use of lenvatinib with or without everolimus as a viable salvage strategy for patients whose disease progresses after treatment with immune checkpoint inhibitors and vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies, including cabozantinib.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Everolimo/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Renais/tratamento farmacológico , Compostos de Fenilureia , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Estudos Retrospectivos , Fator A de Crescimento do Endotélio VascularRESUMO
INTRODUCTION: Metastatic renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is associated with poor survival outcomes. We aimed to analyze the efficacy and safety of immune checkpoint inhibitors (ICI) in patients with sRCC comparing clear-cell (sccRCC) to non-clear cell epithelial histology (snccRCC). METHODS: We performed retrospective analysis of sRCC patients who received ICI at MD Anderson Cancer Center (nâ¯=â¯48, 41 with ccRCC and 7 with nccRCC) to determine the overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additionally, we performed a prespecified multivariable Cox regression comparing survival outcomes between sccRCC and snccRCC. RESULTS: The ORR for the entire cohort was 35.4% (95% confidence interval [CI]: 23.4%, 49.6%), including 8 (16.7%) patients (95% CI: 8.7%, 29.6%) who achieved a complete remission. The disease control rate was 52% (95% CI: 38.3%, 65.5%). In patients with sccRCC, the ORR was 39% (95% CI: 25.7%, 54.3%) and disease control rate 58.5% (43.4%, 72.2%). Among 7 snccRCC patients, only one (14.3%) achieved an objective partial response. At a median follow-up of 51.1 months, the median PFS was 4.9 months (95% CI: 2.7, 16.3) and the median OS was 28.4 months (95% CI: 15.8, NA) for the entire cohort. For patients with sccRCC, the median PFS was 8.9 months, with median OS of 30.1 months, compared with median PFS of 2.3 months (HR 0.25 [95% CI: 0.08, 0.78]; P= 0.0145) and median OS of 6.7 months (HR 0.13 [95% CI 0.04, 0.44]; P=0.0009) for patients with snccRCC. CONCLUSION: ICIs appear to be effective in sccRCC while the treatment of snccRCC remains challenging.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Desdiferenciação Celular , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Adulto , Idoso , Carcinoma de Células Renais/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Sarcoma/patologia , Resultado do TratamentoRESUMO
PURPOSE: MRI-assisted radiosurgery (MARS) is a modern technique for prostate brachytherapy that provides superior soft tissue contrast. The purpose of this analysis was to evaluate treatment planning factors associated with urinary toxicity, particularly damage to the membranous urethra (MUL) and external urethral sphincter (EUS), after MARS. MATERIAL AND METHODS: We retrospectively reviewed 227 patients treated with MARS. Comparisons were made between several factors including preimplantation length of the MUL and EUS dosimetric characteristics after implantation with longitudinal changes in American Urological Association (AUA) urinary symptom score. RESULTS: Rates of grade 3 urinary incontinence and obstructive urinary symptoms were 4% and 2%. A piecewise mixed univariate model revealed that MUL and V200, V150, V125, and D5 to the EUS were all associated with increased rates of urinary toxicity over time. On univariate logistic regression, MUL >14.2 mm (odds ratio [OR] 2.03 per cm3, 95% confidence interval [CI] 1.10-3.77, p = 0.025), V125 to the EUS (OR 3.21 cm3, 95% CI 1.18-8.71, p = 0.022), and use of the I-125 isotope (OR 3.45, 95% CI 1.55-7.70, p = 0.001) were associated with subacute urinary toxicity (i.e., that occurring at 4-8 months). Optimal dose-constraint limits to the EUS were determined to be V200 < 0.04 cm3 (p = 0.002), V150 < 0.12 cm3 (p = 0.041), V125 < 0.45 cm3 (p = 0.033), D30 < 160 Gy (p = 0.004), and D5 < 218 Gy (p = 0.016). CONCLUSIONS: MARS brachytherapy provides detailed anatomic information for treatment planning, implantation, and quality assurance. Overall rates of urinary toxicity are low; however, several dosimetric variables associated with the EUS were found to correlate with urinary toxicity.
Assuntos
Braquiterapia/métodos , Sintomas do Trato Urinário Inferior/epidemiologia , Neoplasias da Próstata/radioterapia , Lesões por Radiação/epidemiologia , Radiocirurgia/métodos , Doenças Uretrais/epidemiologia , Adulto , Idoso , Humanos , Radioisótopos do Iodo/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Paládio/uso terapêutico , Radioisótopos/uso terapêutico , Radiometria , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem , Estudos Retrospectivos , Fatores de Risco , Uretra/anatomia & histologia , Uretra/diagnóstico por imagemRESUMO
PURPOSE: The purpose of this study was to compare an isotropic three-dimensional (3D) T2-weighted sequence sampling perfection with application-optimized contrasts by using flip angle evolution (SPACE) with an axial two-dimensional T2-weighted turbo spin echo (TSE) sequence with regard to overall image quality and the delineation of normal prostate and periprostatic anatomy for low-dose-rate prostate cancer brachytherapy planning evaluation. METHODS AND MATERIALS: Patients (n = 69) with prostate cancer who had pelvic magnetic resonance imaging (MRI) for low-dose-rate brachytherapy treatment planning were included. Three radiologists independently assessed the visibility of nine anatomic structures on each sequence by using a 5-point scale and overall image quality by using a 4-point scale. The significance of the differences in diagnostic performance was tested with a Wilcoxon signed rank test. RESULTS: No significant intersequence differences were found for most (7/9) anatomical structures and overall image quality. The mean scores for visibility of anatomical structures on the 3D SPACE and 2D TSE sequences, respectively, were as follows: the zonal anatomy (3.7; 3.9, p = 0.05), prostate capsule (3.9; 4.0, p = 0.08), neurovascular bundle (2.9; 2.9, p = 0.9), rectoprostatic angle (3.8; 3.8, p = 0.35), rectum (4.2; 4.3, p = 0.26), urethra (3.8; 3.9, p = 0.12), urinary bladder (4.6; 4.6, p = 0.61), and overall image quality (2.9; 2.9, p = 0.33). 3D SPACE was superior for delineation of the genitourinary diaphragm (3.8; 3.6, p = 0.003), whereas 2D TSE was superior for delineation of the seminal vesicles (3.5; 4.0, p < 0.0001). CONCLUSIONS: Anatomic delineation of the prostatic and periprostatic anatomy provided by the 3D SPACE sequence is as robust in quality as that provided by a conventional 2D TSE sequence with superior delineation of the genitourinary diaphragm. For MRI-based brachytherapy treatment planning, the 3D SPACE sequence with subcentimeter isotropic resolution can replace the 2D TSE sequence and be incorporated into standard MRI protocols.
Assuntos
Pontos de Referência Anatômicos/diagnóstico por imagem , Braquiterapia , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador , Idoso , Vasos Sanguíneos/diagnóstico por imagem , Meios de Contraste , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Nervos Periféricos/diagnóstico por imagem , Reto/diagnóstico por imagem , Estudos Retrospectivos , Glândulas Seminais/diagnóstico por imagem , Uretra/diagnóstico por imagem , Bexiga Urinária/diagnóstico por imagemRESUMO
PURPOSE: Patients with prostate cancer presenting with advanced T stage, mainly T4, might have a unique pattern of nodal failure and disease involvement that is not typically covered when local therapy is offered. We attempted to identify common sites of nodal disease presentation and failure for patients presenting with cT4 prostate cancer. METHODS AND MATERIALS: All patients with treatment-naïve cT4 prostate cancer were retrospectively identified. All patients were required to have a confirmed diagnosis reviewed by our genitourinary pathologist and completed baseline staging. Lymph node (LN) involvement and location at diagnosis were reviewed by a genitourinary radiologist. All patients' follow-up scans were also reviewed; based on LN size, imaging characteristics, and progression/regression characteristics on systemic therapy, the locations of sites of LN failure were recorded. For patients who underwent surgery, any pathologically involved LNs and their anatomic locations were recorded. A total of 103 patients met these criteria, with a median follow-up of 8 years (range, 0.5-14 years). RESULTS: Rectal involvement by the primary disease was associated with a higher risk of perirectal and mesorectal LN involvement (45%) relative to no rectal involvement (26%) (P < .05). These echelons are typically not covered with conventional pelvic external beam radiation therapy and are not routinely part of pelvic LN dissection in patients treated surgically. Conversely, bladder or pelvic side wall invasion did not correlate with increased frequency of involvement of perirectal/mesorectal LNs (P > .05). CONCLUSIONS: When offering local therapy, target modification to include the perirectal and mesorectal LNs should be considered for patients presenting with T4 prostate cancer with rectal involvement.
Assuntos
Neoplasias da Próstata/patologia , Reto , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The current study was conducted to investigate the patterns of metastases in men with metastatic prostatic ductal adenocarcinoma (DAC) and recurrence patterns after therapy. METHODS: All patients with a new diagnosis of DAC with de novo metastases and those with localized disease who developed metastases after treatment and were treated at the study institution from January 2005 to November 2018 were included. All patient and tumor characteristics and outcome data were collected. RESULTS: A total of 164 patients (37.7%) had metastatic DAC, including 112 with de novo metastases and 52 who developed metastases after treatment. Men with de novo metastases were found to have a significantly higher median prostate-specific antigen level and International Society of Urological Pathology grade but a lower cT3 and/or T4 classification compared with those with metastases that developed after treatment (all P < .05). Approximately 87% of men with de novo metastases progressed despite multiple systemic therapies, 37.6% required intervention for the palliation of symptoms, and 10.1% responded to systemic therapy and underwent treatment of the primary tumor. Men with de novo metastatic DAC and those who developed metastases after treatment had multiple metastatic sites (including bone and viscera), with higher rates of lung metastases noted in the posttreatment group (23.2% vs 44.2%; P = .01). A total of 45 patients who were treated with curative intent developed metastases at a median of 22 months (range, 0.9-74.8 months) after treatment, at low prostate-specific antigen levels (median, 4.4 ng/mL [interquartile range, 1.7-11.1 ng/mL]). CONCLUSIONS: The current study described the metastatic patterns of DAC in both patients with de novo metastatic disease and those who later progress to metastases. Men receiving treatment for DAC with curative intent require stringent long-term follow-up with imaging modalities, including chest imaging given the predilection toward lung metastases noted among these patients.
Assuntos
Adenocarcinoma/diagnóstico , Carcinoma Ductal/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Idoso , Carcinoma Ductal/diagnóstico por imagem , Carcinoma Ductal/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Tórax/diagnóstico por imagem , Tórax/patologiaRESUMO
Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.
Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Sistemas de Informação em Radiologia , Idoso , Estudos Transversais , Humanos , Masculino , Valor Preditivo dos Testes , Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sociedades MédicasRESUMO
PURPOSE: The aim of this study was to investigate the imaging diagnostic performance of F-fluciclovine PET/CT and pelvic multiparametric MRI (mpMRI) for prostate cancer in the setting of rising PSA after initial treatment, with a focus on detection of recurrent and metastatic prostate cancer in the pelvis. METHODS: Patients with prostate cancer who had fluciclovine PET and pelvic mpMRI between October 2017 and October 2018 in our center were retrospectively reviewed. Patients were included if they had fluciclovine PET/CT and mpMRI within a 3-month interval. Patients were excluded if they had separate concurrent cancer or if the PSA were more than 2-fold difference with an absolute difference more than 1 ng/mL between the 2 image studies. For each eligible patient, we compared all abnormal lesions identified on either scan. The findings were verified by pathology or other imaging techniques within minimal 10-month clinical follow-up. RESULTS: A total of 129 patients with 129 paired tests were included in this study. Fluciclovine PET/CT and pelvic MRI had a high degree of concordance (121/129, 93.8%). The sensitivity, specificity, positive predictive value, and negative predictive value for fluciclovine PET/CT and mpMRI were 96.6%, 94.3%, 93.4%, and 97%, and 91.5%, 95.7%, 94.7%, and 93%, respectively. There were no statistical significant differences in diagnostic performance between the 2 imaging tests. Among the 8/129 discordant cases, although fluciclovine PET/CT provided definitive diagnosis when mpMRI was equivocal due to paramagnetic artifacts from fiducial markers and detected normal-sized regional lymph nodes, mpMRI detected subcentimeter periurethral recurrence and clarified physiological urinary artifacts that was not appreciated on fluciclovine PET/CT. CONCLUSIONS: Our single-center study demonstrated that fluciclovine PET/CT has similar diagnostic performance with pelvic mpMRI in detecting recurrent/metastatic prostate disease in the pelvis in the setting of rising PSA after initial treatment. Moreover, fluciclovine PET/CT and mpMRI have different implications in different clinical scenario; each test has its own limitation and pitfalls, but can be complementary to each other.