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Purpose: The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and <20% rate of acute grade ≥3 toxicity, and secondary endpoints included cancer-specific outcomes and toxicities. Patients were followed with magnetic resonance imaging or computed tomography at 3-month intervals. Proton beam therapy was delivered with doses up to 79.2 Gy using protons only, combination protons/intensity modulated radiation therapy (IMRT), or IMRT only. Results: Feasibility endpoints were met, with only 2 out of 54 patient radiation therapy plans failing to meet dosimetric constraints with protons, and 4 out of 54 experiencing a delay or treatment break >5 days, none for toxicities related to treatment. There were no grade 4 acute toxicities and 1 grade 3 acute toxicity (sensory neuropathy). The only 2 grade 3 late toxicities recorded, osteoradionecrosis and intranasal carotid blowout (mild and not emergently treated), occurred in a single patient. We report overall survival as 83% at 5 years, with local failure-free survival and progression-free survival rates of 72% and 68%, respectively. Five patients developed distant disease, and among the 9/54 patients who died, 4 deaths were not attributed to treatment or recurrence. Conclusions: Our findings suggest that high-dose proton therapy alone or in combination with IMRT is a safe and effective treatment option for chordomas and chondrosarcomas of the skull base and spine.
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PURPOSE: Radiopharmaceutical therapy (RPT) is a rapidly growing treatment modality. Though uncommon, patients may experience complications during their RPT treatment, which may trigger a rapid response from the hospital team. However, members of this team are typically not familiar with precautions for radiation safety. During these events, it is important to prioritize the patient's health over all else. There are some practices that can help minimize the risk of radiation contamination spread and exposure to staff while tending to the patient. METHODS AND MATERIALS: We formed a team to develop a standard protocol for handling patient emergencies during RPT treatment. This team consisted of an authorized user, radiation safety officer, medical physicist, nurse, RPT administration staff, and a quality/safety coordinator. The focus for developing this standardized protocol for RPT patient emergencies was 3-fold: (1) stabilize the patient; (2) reduce radiation exposure to staff; and (3) limit the spread of radiation contamination. RESULTS: We modified our hospital's existing rapid response protocol to account for the additional staff and tasks needed to accomplish all 3 of these goals. Each team member was assigned specific responsibilities, which include serving as a gatekeeper to restrict traffic, managing the crash cart, performing chest compressions, timing chest compressions, documenting the situation, and monitoring/managing radiation safety in the area. We developed a small, easy-to-read card for rapid response staff to read while they are en route to the area so they can be aware of and prepare for the unique circumstances that RPT treatments present. CONCLUSIONS: Though rapid response events with RPT patients are uncommon, it is important to have a standardized protocol for how to handle these situations beforehand rather than improvise in the moment. We have provided an example of how our team adapted our hospital's current rapid response protocol to accommodate RPT patients.
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BACKGROUND: Cardiovascular (CV) disease is common among men with prostate cancer and the leading cause of death in this population. There is a need for CV risk assessment tools that can be easily implemented in the prostate cancer treatment setting. METHODS: Consecutive patients who underwent positron emission tomography/computed tomography (PET/CT) for recurrent prostate cancer at a single institution from 2012 to 2017 were identified retrospectively. Clinical data and coronary calcification on nongated CT imaging were obtained. The primary outcome was major adverse CV event (MACE; myocardial infarction, coronary or peripheral revascularization, stroke, heart failure hospitalization, or all-cause mortality) occurring within 5 years of PET/CT. RESULTS: Among 354 patients included in the study, there were 98 MACE events that occurred in 74 patients (21%). All-cause mortality was the most common MACE event (35%), followed by coronary revascularization/myocardial infarction (26%) and stroke (19%). Coronary calcification was predictive of MACE (HR = 1.9, 95% CI: 1.1-3.4, P = .03) using adjusted Kaplan-Meier analysis. As a comparator, the Framingham risk score was calculated for 198 patients (56%) with complete clinical and laboratory data available. In this subgroup, high baseline Framingham risk (corresponding to 10-year risk of CV disease > 20%) was not predictive of MACE. CONCLUSIONS: MACE was common (21%) in men with recurrent prostate cancer undergoing PET/CT over 5 years of follow-up. Incidental coronary calcification on PET/CT was associated with increased risk of MACE and may have utility as a CV risk predictor that is feasible to implement among all prostate cancer providers.
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Doenças Cardiovasculares , Infarto do Miocárdio , Neoplasias da Próstata , Acidente Vascular Cerebral , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Estudos Retrospectivos , Recidiva Local de Neoplasia/complicações , Medição de Risco , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Fatores de Risco de Doenças Cardíacas , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/complicações , Prognóstico , Valor Preditivo dos TestesRESUMO
BACKGROUND: In select patients, pancreatic adenocarcinoma remains a local disease, yet there are no validated biomarkers to predict this behavior and who may benefit from aggressive local treatments. This study sought to determine if SMAD4 (mothers against decapentaplegic homolog 4) messenger RNA-sequencing (RNA-seq) expression is a robust method for predicting overall survival (OS) and distant metastasis-free survival (DMFS) in patients with resected pancreatic adenocarcinoma. METHODS: Utilizing The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), 322 patients with resected stage I-III pancreatic adenocarcinoma were identified. In TCGA, multivariable proportional hazards models were used to determine the association of SMAD4 genomic aberrations and RNA-seq expression with OS and DMFS. In the ICGC, analysis sought to confirm the predictive performance of RNA-seq via multivariable models and receiver operator characteristic curves. RESULTS: In TCGA, the presence of SMAD4 genomic aberrations was associated with worse OS (hazard ratio [HR], 1.55; 95% CI, 1.00-2.40; p = .048) but not DMFS (HR, 1.33; 95% CI, .87-2.03; p = .19). Low SMAD4 RNA-seq expression was associated with worse OS (HR, 1.83; 95% CI, 1.17-2.86; p = .008) and DMFS (HR, 1.70; 95% CI, 1.14-2.54; p = .009). In the ICGC, increased SMAD4 RNA-seq expression correlated with improved OS (area under the curve [AUC], .92; 95% CI, .86-.94) and DMFS (AUC, .84; 95% CI, .82-.87). CONCLUSIONS: In patients with resected pancreatic adenocarcinoma, SMAD4 genomic aberrations are associated with worse OS but do not predict for DMFS. Increased SMAD4 RNA-seq expression is associated with improved OS and DMFS in patients with resected pancreatic adenocarcinoma. This reproducible finding suggests SMAD4 RNA-seq expression may be a useful marker to predict metastatic spread.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Proteína Smad4/genética , Modelos de Riscos Proporcionais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , PrognósticoRESUMO
α-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the α-particle pathlength. We sought to determine the distribution of clinically approved [223Ra]RaCl2 in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. 223Ra activity in each sample was recorded, and the microstructure of biopsy specimens was analyzed by micro-CT. Quantitative autoradiography and histopathology were segmented and registered with an automated procedure. Activity distributions by tissue compartment and dosimetry calculations based on the MIRD formalism were performed. Results: We revealed the activity distribution differences across and within patient samples at the macro- and microscopic scales. Microdistribution analysis confirmed localized high-activity regions in a background of low-activity tissue. We evaluated heterogeneous α-particle emission distribution concentrated at bone-tissue interfaces and calculated spatially nonuniform absorbed-dose profiles. Conclusion: Primary patient data of radiopharmaceutical therapy distribution at the small scale revealed that 223Ra uptake is nonuniform. Dose estimates present both opportunities and challenges to enhance patient outcomes and are a first step toward personalized treatment approaches and improved understanding of α-particle radiopharmaceutical therapies.
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Neoplasias Ósseas , Neoplasias da Próstata , Masculino , Humanos , Compostos Radiofarmacêuticos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Autorradiografia , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundárioRESUMO
BACKGROUND: Non-muscle invasive bladder cancer (non-MIBC) that is high-grade and confined to the lamina propria (HGT1) often has an aggressive clinical course. Currently, there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT in HGT1 bladder cancer. METHODS: Patients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. Inverse probability of treatment weighting (IPTW) was employed and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. OS was the primary endpoint, and was estimated using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio [HR]: 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Four-year OS for the CRT vs. RT alone was 36% and 19%, respectively (log-rank P <.008). CONCLUSION: For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone in a retrospective cohort. These results are hypothesis-generating. The NRG is currently developing a phase II randomized clinical trial comparing CRT to other novel, bladder preservation strategies.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/terapia , Bexiga Urinária/cirurgia , Bexiga Urinária/patologia , Quimiorradioterapia/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Introduction: Our institution was the first in the world to clinically implement MR-guided adaptive radiotherapy (MRgART) in 2014. In 2021, we installed a CT-guided adaptive radiotherapy (CTgART) unit, becoming one of the first clinics in the world to build a dual-modality ART clinic. Herein we review factors that lead to the development of a high-volume dual-modality ART program and treatment census over an initial, one-year period. Materials and Methods: The clinical adaptive service at our institution is enabled with both MRgART (MRIdian, ViewRay, Inc, Mountain View, CA) and CTgART (ETHOS, Varian Medical Systems, Palo Alto, CA) platforms. We analyzed patient and treatment information including disease sites treated, radiation dose and fractionation, and treatment times for patients on these two platforms. Additionally, we reviewed our institutional workflow for creating, verifying, and implementing a new adaptive workflow on either platform. Results: From October 2021 to September 2022, 256 patients were treated with adaptive intent at our institution, 186 with MRgART and 70 with CTgART. The majority (106/186) of patients treated with MRgART had pancreatic cancer, and the most common sites treated with CTgART were pelvis (23/70) and abdomen (20/70). 93.0% of treatments on the MRgART platform were stereotactic body radiotherapy (SBRT), whereas only 72.9% of treatments on the CTgART platform were SBRT. Abdominal gated cases were allotted a longer time on the CTgART platform compared to the MRgART platform, whereas pelvic cases were allotted a shorter time on the CTgART platform when compared to the MRgART platform. Our adaptive implementation technique has led to six open clinical trials using MRgART and seven using CTgART. Conclusions: We demonstrate the successful development of a dual platform ART program in our clinic. Ongoing efforts are needed to continue the development and integration of ART across platforms and disease sites to maximize access and evidence for this technique worldwide.
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Single-photon emission-computed tomography (SPECT) provides a mechanism to estimate regional isotope uptake in lesions and at-risk organs after administration of α-particle-emitting radiopharmaceutical therapies (α-RPTs). However, this estimation task is challenging due to the complex emission spectra, the very low number of detected counts (~20 times lower than in conventional SPECT), the impact of stray-radiation-related noise at these low counts, and the multiple image-degrading processes in SPECT. The conventional reconstruction-based quantification methods are observed to be erroneous for α-RPT SPECT. To address these challenges, we developed a low-count quantitative SPECT (LC-QSPECT) method that directly estimates the regional activity uptake from the projection data (obviating the reconstruction step), compensates for stray-radiation-related noise, and accounts for the radioisotope and SPECT physics, including the isotope spectra, scatter, attenuation, and collimator-detector response, using a Monte Carlo-based approach. The method was validated in the context of 3-D SPECT with 223Ra, a commonly used radionuclide for α-RPT. Validation was performed using both realistic simulation studies, including a virtual clinical trial, and synthetic and 3-D-printed anthropomorphic physical-phantom studies. Across all studies, the LC-QSPECT method yielded reliable regional-uptake estimates and outperformed the conventional ordered subset expectation-maximization (OSEM)-based reconstruction and geometric transfer matrix (GTM)-based post-reconstruction partial-volume compensation methods. Furthermore, the method yielded reliable uptake across different lesion sizes, contrasts, and different levels of intralesion heterogeneity. Additionally, the variance of the estimated uptake approached the Cramér-Rao bound-defined theoretical limit. In conclusion, the proposed LC-QSPECT method demonstrated the ability to perform reliable quantification for α-RPT SPECT.
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Radiation oncology (RO) has seen declines in Medicare reimbursement (MCR) in the past decade under the current fee-for-service model. Although studies have explored decline in reimbursement at a per-code level, to our knowledge there are no recent studies analyzing changes in MCR over time for common RO treatment courses. By analyzing changes in MCR for common treatment courses, our study had 3 objectives: (1) to provide practitioners and policymakers with estimates of recent reimbursement changes for common treatment courses; (2) to provide an estimate of how reimbursement will change in the future under the current fee-for-service model if current trends continue; and (3) to provide a baseline for treatment episodes in the event that the episode-based Radiation Oncology Alternative Payment Model is eventually implemented. Specifically, we quantified inflation- and utilization-adjusted changes in reimbursement for 16 common radiation therapy (RT) treatment courses from 2010 to 2020. Centers for Medicare & Medicaid Services Physician/Supplier Procedure Summary databases were used to obtain reimbursement for all RO procedures in 2010, 2015, and 2020 for free-standing facilities. Inflation-adjusted average reimbursement (AR) per billing instance was calculated for each Healthcare Common Procedure Coding System code using 2020 dollars. For each year, the billing frequency of each code was multiplied by the AR per code. Results were summed per RT course per year, and AR for RT courses were compared. Sixteen common RO courses for head and neck, breast, prostate, lung, and palliative RT were analyzed. AR decreased for all 16 courses from 2010 to 2020. From 2015 to 2020, the only course that increased in AR was palliative 2-dimensional 10-fraction 30 Gy, which increased by 0.4%. Courses using intensity modulated RT saw the largest AR decline from 2010 to 2020, ranging from 38% to 39%. We report significant declines in reimbursement from 2010 to 2020 for common RO courses, with the largest declines for intensity modulated RT. Policymakers should consider the significant cuts to reimbursement that have already occurred when considering future reimbursement adjustment under the current fee-for-service model or when considering mandatory adoption of a new payment system with further cuts and the negative effect of such cuts on quality and access to care.
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Medicare , Radioterapia (Especialidade) , Idoso , Masculino , Humanos , Estados Unidos , BenchmarkingRESUMO
Introduction Stereotactic body radiation therapy (SBRT) for prostate adenocarcinoma (PCa) has demonstrated excellent biochemical recurrence-free survival, with studies showing improved BRFS with higher-dose SBRT. However, current studies have been underpowered to evaluate the relationship of SBRT dose to overall survival (OS). In this retrospective study using the National Cancer Database (NCDB), we hypothesize that, given the low alpha/beta ratio of PCa, a relatively small increase in the dose-per-fraction would be associated with improved survival outcomes for intermediate-risk PCa (IR-PCa) comparing 36.25 Gy/5 fx [biologically equivalent dose (BEDα/ß = 1.5 = 211.46 Gy vs. 35 Gy (BED1.5 = 198.33 Gy)]. Materials and methods We queried records from the NCDB from 2005 to 2015 for men receiving prostate SBRT for IR-PCa (n=2673). 82% were treated using either 35 Gy/5 fx or 36.25 Gy/5 fx. We compared OS in men receiving 35 Gy versus 36.25 Gy. Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalances. Unweighted- and weighted-multivariable analysis (MVA) using Cox regression was used to compare OS hazard ratios, accounting for age, race, Charlson-Deyo comorbidity score, treatment facility type, prostate-specific antigen (PSA), clinical T-stage, Gleason Score, and use of androgen deprivation therapy (ADT). Kaplan-Meier analysis was performed. Results Seven hundred and eighty men (35%) were treated with 35 Gy/5 fx and 1434 men (65%) were treated with 36.25 Gy/5 fx (n=2214). Compared to 35 Gy, treatment with 36.25 Gy was associated with significantly improved OS (hazard ratio [HR]: 0.61 [95% CI: 0.43-0.89], P=0.009) on MVA. On Kaplan-Meier analysis, 36.25 Gy was associated with improved survival (p=0.034), with a five-year OS of 92% and 88%, respectively. Conclusions In a multi-institutional retrospective database of 2,214 IR patients treated with prostate SBRT, a prescription dose of 36.25 Gy/5 fx was associated with improved OS vs. 35 Gy/5 fx. Results are hypothesis-generating but do lend support to the current National Comprehensive Cancer Network (NCCN) guidelines that the minimum recommended dose for prostate SBRT is 36.25 Gy/5 fx.
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BACKGROUND: Bladder-sparing chemoradiation therapy (CRT) is a definitive first-line treatment for muscle-invasive bladder cancer. The optimal radiotherapy target volume, either bladder-only (BO) or bladder plus pelvic lymph nodes (BPN), remains unclear. METHODS: We identified 2,104 patients in the National Cancer Database with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with CRT following maximal transurethral resection of bladder tumor from 2004 to 2016. The exposure of interest was BO vs. BPN treatment volume. The primary outcome was overall survival (OS), compared between groups using Kaplan-Meier and multivariable Cox proportional hazards. Sensitivity analysis tested an interaction term for clinical T stage (T2 vs. T3-4) and radiation modality (3-dimensional conformal radiotherapy vs. intensity modulated radiotherapy or proton therapy). Annual use of BO vs. BPN from 2004 to 2016 was compared using Cochran-Armitage test. RESULTS: A total of 578 patients were treated with BO and 1,526 patients treated with BPN CRT. There was a significant increase in BPN use from 2004 to 2016 (66.9%-76.8%, P < 0.0001). With a median follow-up of 6.2 years, there was no survival difference between groups: 5- and 10-year OS 27.4% (95% CI 23.4%-31.4%) in the BO group vs. 31.9% (95% CI 29.3%-34.6%) in the BPN group, and 13.1% (95% CI 9.7%-17.1%) in the BO group vs. 13.2% (95% CI 10.6%-16.0%) in the BPN group, respectively (log-rank Pâ¯=â¯0.10). On multivariable analysis, there was no significant association between BPN and OS (adjusted HR 0.90, 95% CI 0.81-1.02, Pâ¯=â¯0.09). On sensitivity analysis, we found no differential effect by T stage or radiation modality. CONCLUSION: Use of pelvic lymph node radiation has risen in the US but may not impact long-term survival outcomes for patients with node-negative muscle-invasive bladder cancer (MIBC). Optimizing radiation treatment volumes for CRT for MIBC will be important to study under prospective trials, such as the SWOG/NRG 1806.
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Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Bexiga Urinária/cirurgia , Bexiga Urinária/patologia , Estudos Prospectivos , Cistectomia/métodos , Neoplasias da Bexiga Urinária/patologia , Linfonodos/patologia , Músculos/patologiaRESUMO
Circulating tumor DNA (ctDNA) sensitivity remains subpar for molecular residual disease (MRD) detection in bladder cancer patients. To remedy this problem, we focused on the biofluid most proximal to the disease, urine, and analyzed urine tumor DNA in 74 localized bladder cancer patients. We integrated ultra-low-pass whole genome sequencing (ULP-WGS) with urine cancer personalized profiling by deep sequencing (uCAPP-Seq) to achieve sensitive MRD detection and predict overall survival. Variant allele frequency, inferred tumor mutational burden, and copy number-derived tumor fraction levels in urine cell-free DNA (cfDNA) significantly predicted pathologic complete response status, far better than plasma ctDNA was able to. A random forest model incorporating these urine cfDNA-derived factors with leave-one-out cross-validation was 87% sensitive for predicting residual disease in reference to gold-standard surgical pathology. Both progression-free survival (HR = 3.00, p = 0.01) and overall survival (HR = 4.81, p = 0.009) were dramatically worse by Kaplan-Meier analysis for patients predicted by the model to have MRD, which was corroborated by Cox regression analysis. Additional survival analyses performed on muscle-invasive, neoadjuvant chemotherapy, and held-out validation subgroups corroborated these findings. In summary, we profiled urine samples from 74 patients with localized bladder cancer and used urine cfDNA multi-omics to detect MRD sensitively and predict survival accurately.
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Prostate-specific membrane antigen (PSMA) is a cell surface protein highly expressed in nearly all prostate cancers, with restricted expression in some normal tissues. The differential expression of PSMA from tumor to non-tumor tissue has resulted in the investigation of numerous targeting strategies for therapy of patients with metastatic prostate cancer. In March of 2022, the FDA granted approval for the use of lutetium-177 PSMA-617 (Lu-177-PSMA-617) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Therefore, the use of Lu-177-PSMA-617 is expected to increase and become more widespread. Herein, we describe logistical, technical, and radiation safety considerations for implementing a radiopharmaceutical therapy program, with particular focus on the development of operating procedures for therapeutic administrations. Major steps for a center in the U.S. to implement a new radiopharmaceutical therapy (RPT) program are listed below, and then demonstrated in greater detail via examples for Lu-177-PSMA-617 therapy.
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Lutécio , Neoplasias de Próstata Resistentes à Castração , Compostos Radiofarmacêuticos , Humanos , Masculino , Lutécio/uso terapêutico , Próstata , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Compostos Radiofarmacêuticos/uso terapêutico , Resultado do TratamentoRESUMO
PURPOSE: The addition of a brachytherapy (BT) boost to external beam radiotherapy (EBRT) reduces recurrence risk in men with high-risk prostate cancer (PCa) and may reduce PCa-mortality for Gleason grade group 5 (GG5). Whether the extent of pattern five, a risk factor for distant metastases, impacts the benefit of a BT boost is unclear. METHODS: Men with localized GG5 PCa treated with (1) EBRT or (2) EBRT+BT between 2010 and 2016 were identified in the National Cancer Database. EBRT monotherapy group received conventionally fractionated (1.8-2.0 Gy per fraction) ≥74 Gy or moderately hypofractionated (2.5-3.0 Gy per fraction) ≥60 Gy. EBRTâ¯+â¯BT group received conventionally fractionated ≥45 Gy or moderately hypofractionated ≥37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT; none received chemotherapy, immunotherapy, or surgery. OS was compared using Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards in the overall cohort, followed by subgroups based on primary versus secondary pattern 5. Propensity score- and exact-matching was used to corroborate results. RESULTS: A total of 8260 men were eligible: EBRT alone (89%) versus EBRTâ¯+â¯BT (11%). 5-year OS for EBRT versus EBRTâ¯+â¯BT was 76.3% and 85.0%, respectively (pâ¯=â¯0.002; multivariable adjusted HR 0.84, 95% CI 0.65-0.98; pâ¯=â¯0.04). These results remained consistent after propensity score and exact matching. The OS advantage of a BT boost was more prominent in men with Gleason 4â¯+â¯5 PCa (pâ¯=â¯0.001) and not observed in men with Gleason 5â¯+â¯5 or 5â¯+â¯4 PCa. CONCLUSIONS: Extent of pattern five may be useful in appropriately selecting men for EBRT+BT and should be considered as a pre-randomization stratification variable for future clinical trial design.
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Braquiterapia , Neoplasias da Próstata , Masculino , Humanos , Braquiterapia/métodos , Estudos Retrospectivos , Neoplasias da Próstata/patologia , Fatores de RiscoRESUMO
There are limited data regarding the optimal management of patients with pelvic node-positive, but non-metastatic, bladder cancer. Increasing data demonstrate that this is a distinct clinical entity with outcomes bridging between bladder-confined muscle-invasive bladder cancer and metastatic advanced bladder cancer. Guidelines and staging systems have formalized the need to incorporate the unique considerations of management of pelvic node-positive bladder cancer. However, there remains an absence of a definite standard of care. Treatment options include systemic therapy alone, neoadjuvant chemotherapy followed by radical cystectomy, or bladder-preserving trimodality therapy. Furthermore, ongoing studies aim to determine the benefit of incorporating immunotherapy into these treatment paradigms. In this review article, we will discuss the key considerations for management of patients with pelvic node-positive bladder cancer.
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Neoplasias da Bexiga Urinária , Humanos , Terapia Combinada , Estadiamento de Neoplasias , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/radioterapia , Cistectomia , Terapia NeoadjuvanteRESUMO
The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways-such as those induced by irradiation. Here, we used a third-generation PARP1-specific radiotracer, [18F]-PARPZ, to delineate castrate resistant prostate cancer xenografts. Following treatment with the clinically applied [225Ac]-PSMA-617, positron emission tomography was performed and correlative autoradiography and histology acquired. [18F]-PARPZ was able to distinguish treated from control (saline) xenografts by increased uptake. Kinetic analysis of tracer accumulation also suggests that the localization of the agent to sites of increased PARP-1 expression is a consequence of DNA damage response. Together, these data support expanded investigation of [18F]-PARPZ to facilitate clinical translation in the âº-therapy space.
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Radioisótopos de Flúor , Neoplasias da Próstata , Partículas alfa/uso terapêutico , Humanos , Cinética , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: We evaluated if proton therapy is associated with decreased acute toxicities compared to intensity-modulated radiation therapy (IMRT) in patients receiving concurrent chemoradiotherapy for head and neck cancers. METHODS: We analyzed 580 patients with nonmetastatic head and neck cancers. Primary endpoint was any 90-day grade ≥3 toxicity, prospectively collected and graded per CTCAEv4. Modified Poisson regression models were used. RESULTS: Ninety-five patients received proton and 485 IMRT. The proton group had more HPV-positive tumors (65.6 vs. 58.0%, p = 0.049), postoperative treatment (76.8 vs. 62.1%, p = 0.008), unilateral neck treatment (18.9 vs. 6.6%, p < 0.001) and significantly lower doses to organs-at-risk compared to IMRT group. Adjusted for patient and treatment characteristics, the proton group had decreased grade 2 dysgeusia (RR0.67, 95%CI 0.53-0.84, p = 0.004) and a trend toward lower grade ≥3 toxicities (RR0.60, 95%CI 0.41-0.88, p = 0.06). CONCLUSIONS: Proton therapy was associated with significantly reduced grade 2 dysgeusia and nonstatistically significant decrease in acute grade ≥3 toxicities compared to IMRT.
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Neoplasias de Cabeça e Pescoço , Terapia com Prótons , Radioterapia de Intensidade Modulada , Quimiorradioterapia/efeitos adversos , Disgeusia/etiologia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Terapia com Prótons/efeitos adversos , Prótons , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversosRESUMO
Prostate-specific membrane antigen is a transmembrane protein found predominately on prostate epithelium and is expressed at high levels in prostate cancer. In this review, we discuss the background, clinical data, patient selection, side effects, and necessary resources to deliver lutetium-177 prostate-specific membrane antigen in the research setting, or as standard of care if approved by the United States Food and Drug Administration. Targeted radionuclide therapeutics require understanding of fundamental principles of radiobiology and physics, and radiation oncologists and medical physicists are well-suited to play an integral role in their delivery and treatment response monitoring as key components of a multidisciplinary care team.