RESUMEN
PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly used for prostate cancer, but has morbidity as both the bladder and rectum are radiated during treatment. Our goal was to document and compare lower urinary tract symptoms (LUTS) among men who underwent SBRT with and without SpaceOAR hydrogel (Augmenix, Inc., Bedford, MA). METHODS: We performed a retrospective analysis of 87 men (50 SpaceOAR and 37 non-SpaceOAR) who underwent SBRT. Primary outcomes were patient reported symptoms during radiation therapy, pharmacotherapy usage, and urologic and bowel survey scores up to 6-months post-SBRT. RESULTS: 78% of men were on α-inhibitors at the end of SBRT, an increase from 27.6% baseline usage (p < 0.001). Post-SBRT urinary frequency was more common in the non-SpaceOAR group versus the SpaceOAR group (68% versus 38%, p = 0.006), as was nocturia (35% vs. 8%, p = 0.002). Acute gastrointestinal symptoms did not differ. 58.8% of men were on α-inhibitors at 6-months of follow-up post-SBRT, an increase from 27.6% baseline usage (p < 0.001). Importantly, there was a difference of α-inhibitor use between non-SpaceOAR and SpaceOAR groups at the end of SBRT and at 1.5-, 3-, and 6-months follow up (86% vs. 53% [p = 0.002], 83% vs. 53% [p = 0.005], 72% vs. 49% [p = 0.038], respectively). CONCLUSION: LUTS after SBRT remains a significant problem for men undergoing treatment for prostate cancer. LUTS affects men during and up to 6-months following SBRT. Owing to these increased LUTS, preemptive minimally invasive solutions and their mechanisms of protection, including the SpaceOAR, should be further investigated.
Asunto(s)
Síntomas del Sistema Urinario Inferior , Neoplasias de la Próstata , Radiocirugia , Humanos , Hidrogeles/uso terapéutico , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/cirugía , Masculino , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Dosificación Radioterapéutica , Recto , Estudios RetrospectivosRESUMEN
PURPOSE: To investigate the impact of rectal spacing on inter-fractional rectal and bladder dose and the need for adaptive planning in prostate cancer patients undergoing SBRT with a 0.35 T MRI-Linac. MATERIALS AND METHODS: We evaluated and compared SBRT plans from prostate cancer patients with and without rectal spacer who underwent treatment on a 0.35 T MRI-Linac. Each group consisted of 10 randomly selected patients that received prostate SBRT to a total dose of 36.25 Gy in five fractions. Dosimetric differences in planned and delivered rectal and bladder dose and the number of fractions violating OAR constraints were quantified. We also assessed whether adaptive planning was needed to meet constraints for each fraction. RESULTS: On average, rectal spacing reduced the maximum dose delivered to the rectum by more than 8 Gy (p < 0.001). We also found that D3cc received by the rectum could be 12 Gy higher in patients who did not have rectal spacer (p < 9E-7). In addition, the results show that a rectal spacer can reduce the maximum dose and D15cc to the bladder wall by more than 1 (p < 0.004) and 8 (p < 0.009) Gy, respectively. Our study also shows that using a rectal spacer could reduce the necessity for adaptive planning. The incidence of dose constraint violation was observed in almost 91% of the fractions in patients without the rectal spacer and 52% in patients with implanted spacer. CONCLUSION: Inter-fractional changes in rectal and bladder dose were quantified in patients who underwent SBRT with/without rectal SpaceOAR hydrogel. Rectal spacer does not eliminate the need for adaptive planning but reduces its necessity.
Asunto(s)
Neoplasias de la Próstata , Radiocirugia , Humanos , Hidrogeles , Imagen por Resonancia Magnética , Masculino , Órganos en Riesgo , Próstata , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Recto/diagnóstico por imagen , Vejiga Urinaria/diagnóstico por imagenRESUMEN
BACKGROUND: Stereotactic body radiotherapy (SBRT) for localized prostate cancer has potential advantages over traditional radiotherapies. Herein, the authors compared national trends in use, complications, and costs of SBRT with those of traditional radiotherapies. METHODS: The authors identified men who underwent SBRT, intensity-modulated radiotherapy (IMRT), brachytherapy, and proton beam therapy as primary treatment of prostate cancer between 2004 and 2011 from Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked data. Temporal trend of therapy use was assessed using the Cochran-Armitage test. Two-year outcomes were compared using the chi-square test. Median treatment costs were compared using the Kruskal-Wallis test. RESULTS: A total of 542 men received SBRT, 9647 received brachytherapy, 23,408 received IMRT, and 800 men were treated with proton beam therapy. There was a significant increase in the use of SBRT and proton beam therapy (P<.001), whereas brachytherapy use decreased (P<.001). A higher percentage of patients treated with SBRT and brachytherapy had low-grade cancer (Gleason score ≤ 6 vs ≥ 7) compared with individuals treated with IMRT and proton beam therapy (54.0% and 64.2% vs 35.2% and 49.6%, respectively; P<.001). SBRT compared with brachytherapy and IMRT was associated with equivalent gastrointestinal toxicity but more erectile dysfunction at 2-year follow-up (P<.001). SBRT was associated with more urinary incontinence compared with IMRT and proton beam therapy but less compared with brachytherapy (P<.001, respectively). The median cost of SBRT was $27,145 compared with $17,183 for brachytherapy, $37,090 for IMRT, and $54,706 for proton beam therapy (P<.001). CONCLUSIONS: The use of SBRT and proton beam therapy for localized prostate cancer has increased over time. Despite men of lower disease stage undergoing SBRT, SBRT was found to be associated with greater toxicity but lower health care costs compared with IMRT and proton beam therapy. Cancer 2016;122:2496-504. © 2016 American Cancer Society.
Asunto(s)
Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/radioterapia , Radiocirugia , Anciano , Anciano de 80 o más Años , Braquiterapia , Terapia Combinada , Análisis Costo-Beneficio , Costos de la Atención en Salud , Encuestas de Atención de la Salud , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/epidemiología , Terapia de Protones , Radiocirugia/efectos adversos , Radiocirugia/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Factores de Riesgo , Programa de VERFRESUMEN
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations identify a unique biological subtype of non-small cell lung cancer (NSCLC). Treatment outcomes for EGFR-mutant locally advanced NSCLC patients have not been well described. METHODS: We retrospectively examined outcomes after combined modality therapy including thoracic radiation therapy (RT) in 123 patients with locally advanced NSCLC and known EGFR mutation status. Outcomes were compared using Kaplan-Meier analysis, the log-rank test, and multivariate Cox regression models. RESULTS: All 123 patients underwent thoracic RT; 25% had tumors with EGFR mutations and 94% had stage III disease. Overall, 81% received chemotherapy concurrent with RT and 55% underwent surgical resection. With a median follow-up of 27.5 months, the overall survival (OS) rate was significantly higher in patients with EGFR-mutant tumors than in those with wild-type EGFR tumors (2-year estimate: 92.6% versus 69.0%; p = .04). The 2-year relapse-free survival and distant recurrence rates did not differ significantly by genotype. The 2-year locoregional recurrence rate (LRR) was significantly lower in EGFR-mutant than in wild-type EGFR patients (17.8% versus 41.7%; p = .005). EGFR-mutant genotype was associated with a lower risk for LRR on multivariate analysis, but not OS, after adjusting for surgery and other potential confounders. CONCLUSION: We observed that EGFR-mutant patients with locally advanced NSCLC treated with RT had lower rates of LRR than wild-type EGFR patients, raising the hypothesis that EGFR mutations may confer sensitivity to RT and/or chemotherapy. The association between mutation status and OS after combined modality therapy was less robust. Our data may serve as a useful baseline estimate of outcomes by EGFR genotype for future prospective studies.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Terapia Combinada , Determinación de Punto Final , Receptores ErbB/antagonistas & inhibidores , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Importance: Stereotactic body radiotherapy is a hypofractionated, cost-effective treatment option for localized prostate cancer. Objective: To characterize US national trends and the clinical and socioeconomic factors associated with the use of stereotactic body radiotherapy in prostate cancer. Design, Setting, and Participants: This retrospective cohort study used data collected by the National Cancer Database to assess the clinical and socioeconomic factors among 106â¯926 men diagnosed as having prostate cancer from 2010 to 2015 who underwent definitive radiotherapy and the trends in the use of this therapy. The initial analysis was performed between January and February 2018, with final updates performed August 2019. Exposure: Stereotactic body radiotherapy, defined as 5 fractions of radiotherapy. Main Outcomes and Measures: Temporal trends and clinical and sociodemographic factors associated with stereotactic body radiotherapy use. Results: In total, 106â¯926 patients diagnosed as having localized prostate cancer between 2010 and 2015 and receiving definitive radiotherapy were identified. White patients composed 77.3% of this cohort, whereas black patients composed 18.7%. Government-issued insurance was used by 61.2% of patients. More than 80% of patients had a Charlson-Deyo Comorbidity Index score of 0 (range, 0 to ≥3, with lower numbers indicating fewer comorbidities). In the study population, 25.7% had low-risk disease; 26.3%, favorable intermediate-risk disease; 23.3%, unfavorable intermediate-risk disease; and 24.7%, high-risk disease. The proportion of patients who underwent radiotherapy and received stereotactic body radiotherapy (a total of 5395 patients) increased from 3.1% in 2010 to 7.2% in 2015 (odds ratio, 0.36; 95% CI, 0.33-0.40; P < .001). Among the entire cohort, patients received a median dose of 36.25 Gy (range, 30.00-50.00 Gy). Androgen deprivation therapy use increased significantly as disease risk level increased among all patients receiving radiotherapy (9.5% with low risk to 76.6% with high risk; P = .02) and among those receiving stereotactic body radiotherapy (4.1% with low risk to 33.2% with high risk; P = .04) or not receiving stereotactic body radiotherapy (9.9% with low risk to 77.6% with high risk; P = .04). Patients treated at an academic center, living in an urban area, or possessing higher incomes and those who were healthier, white individuals, or were diagnosed as having lower-risk prostate cancer had higher odds of receiving stereotactic body radiotherapy. Conclusions and Relevance: This study found that stereotactic body radiotherapy use in prostate cancer more than doubled from 2010 to 2015 but accounted for less than 10% of all patients undergoing radiotherapy. Androgen deprivation therapy use increased with disease risk among patients overall, regardless of receiving stereotactic body radiotherapy. Socioeconomic and clinical determinants of stereotactic body radiotherapy included risk category, Charlson-Deyo Comorbidity Index score, facility type and location, income, race/ethnicity, and year of diagnosis. These results are hypothesis generating; further studies evaluating potential disparities in stereotactic body radiotherapy use in localized prostate cancer are warranted.
Asunto(s)
Disparidades en Atención de Salud/tendencias , Aceptación de la Atención de Salud/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Neoplasias de la Próstata/terapia , Radiocirugia/tendencias , Negro o Afroamericano/estadística & datos numéricos , Antagonistas de Andrógenos/uso terapéutico , Humanos , Masculino , Neoplasias de la Próstata/etnología , Estudios Retrospectivos , Factores Socioeconómicos , Resultado del Tratamiento , Estados Unidos , Población Blanca/estadística & datos numéricosRESUMEN
CONTEXT: Immunotherapy drugs, particularly checkpoint inhibitors, have recently been approved by the Food and Drug Administration for various malignancies. Preclinical and early clinical data show that combining these agents with radiotherapy may produce an even more potent antitumor effect in the treatment of cancer. OBJECTIVE: To describe the rationale, available data, and emerging data on the use of combined immunotherapy and radiation therapy in the setting of genitourinary (GU) malignancies. EVIDENCE ACQUISITION: We performed a search of primary studies from PubMed/Medline that included combinations of the search terms "radiation therapy," "radiotherapy," "abscopal effect," "immunotherapy," "combined," and "combination." EVIDENCE SYNTHESIS: Preclinical and clinical data support both immune-stimulating and immune-suppressing effects of radiotherapy. Preclinical and clinical studies investigating the combination of radiotherapy with immunotherapy, primarily in the setting of non-GU malignancies, have suggested efficacy and tolerability. Early randomized trials combining radiotherapy and immunotherapy have demonstrated success in lung cancer. Although a trial investigating combined immunotherapy and radiotherapy use for prostate cancer did not clearly improve survival, trials are ongoing in multiple GU malignancies to identify synergy between immunotherapy and radiotherapy. Several practical and technical questions remain about the optimal combination of radiotherapy and immunotherapy. CONCLUSIONS: Preclinical and clinical trials show that the combination of the immunotherapy and radiation therapy has the potential to provide a synergistic effect in treating cancer, including GU malignancies, although more work is needed to uncover the mechanism and determine the optimal delivery of this treatment. PATIENT SUMMARY: This paper reviews evidence that immunotherapy drugs can be given together with radiation therapy to improve outcomes in cancers of the genitourinary tract. We find promising initial results and raise important questions that need to be answered before this type of treatment can be utilized successfully.
Asunto(s)
Inmunoterapia/métodos , Neoplasias Urogenitales/tratamiento farmacológico , Neoplasias Urogenitales/radioterapia , Femenino , Humanos , Masculino , Neoplasias Urogenitales/patologíaRESUMEN
Orthologs of RecG and RuvABC are highly conserved among prokaryotes; in Escherichia coli, they participate in independent pathways that branch migrate Holliday junctions during recombinational DNA repair. RecG also has been shown to directly convert stalled replication forks into Holliday junctions. The bacterium Helicobacter pylori, with remarkably high levels of recombination, possesses RecG and RuvABC homologs, but in contrast to E. coli, H. pylori RecG limits recombinational repair. We now show that the RuvABC pathway plays the prominent, if not exclusive, repair role. By introducing an E. coli resolvase (RusA) into H. pylori, the repair and recombination phenotypes of the ruvB mutant but not the recG mutant were improved. Our results indicate that RecG and RuvB compete for Holliday junction structures in recombinational repair, but since a classic RecG resolvase is absent from H. pylori, deployment of the RecG pathway is lethal. We propose that evolutionary loss of the H. pylori RecG resolvase provides an "antirepair" pathway allowing for selection of varied strains. Such competition between repair and antirepair provides a novel mechanism to maximize fitness at a bacterial population level.
Asunto(s)
Proteínas Bacterianas/genética , ADN Helicasas/genética , Reparación del ADN , Helicobacter pylori/genética , Proteínas Bacterianas/metabolismo , ADN Helicasas/metabolismo , Endodesoxirribonucleasas/genética , Endodesoxirribonucleasas/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Prueba de Complementación Genética , Helicobacter pylori/enzimología , Resolvasas de Unión Holliday/genética , Resolvasas de Unión Holliday/metabolismo , Modelos Genéticos , Recombinación GenéticaRESUMEN
Helicobacter pylori, bacteria that colonize the human gastric mucosa, are naturally competent for transformation by exogenous DNA, and show a panmictic population structure. To understand the mechanisms involved in its horizontal gene transfer, we sought to define the interval required from exposure to substrate DNA until DNA uptake and expression of a selectable phenotype, as well as the relationship of transforming fragment length, concentration, homology, symmetry, and strandedness, to the transformation frequency. We provide evidence that natural transformation in H. pylori differs in efficiency among wild-type strains but is saturable and varies with substrate DNA length, symmetry, strandedness, and species origin. We show that H. pylori cells can be transformed within one minute of contact with DNA, by DNA fragments as small as 50 bp, and as few as 5 bp on one flank of a selectable single nucleotide mutation is sufficient substrate for recombination of a transforming fragment, and that double-stranded DNA is the preferred (1000-fold >single-stranded) substrate. The high efficiency of double-stranded DNA as transformation substrate, in conjunction with strain-specific restriction endonucleases suggests a model of short-fragment recombination favoring closest relatives, consistent with the observed H. pylori population biology.
Asunto(s)
Variación Genética , Genoma Bacteriano , Helicobacter pylori/fisiología , ADN Bacteriano/genética , Transferencia de Gen Horizontal , Helicobacter pylori/genética , Mutación Puntual , Transformación BacterianaRESUMEN
Environmental stresses may lead to selection for hypermutator bacterial cells, which have an increased chance of generating beneficial variants. With stress removal, cost of mutation exceeds the fitness advantage, selecting against hypermutators. Hypermutators arise through several mechanisms, including inactivation of mismatch repair genes (MMR) or induction of error-prone polymerases. Helicobacter pylori may provide an alternative mechanism of stress-induced mutagenesis, since it lacks the MMR genes and error-prone polymerases found in other bacterial species, and possesses an endogenously high mutation frequency. In this study, we expose H. pylori strains to reactive oxygen species and reactive nitrogen species, stressors found in their natural environment. These exposures directly resulted in elevated rates of spontaneous point mutation, deletion between direct repeats, and intergenomic recombination. We demonstrate that these effects are transient and do not involve selection for hypermutator strains. That H. pylori possesses direct repeats in regions where potential gene rearrangements can occur suggests a mechanism for targeted mutation in response to stress that avoids the deleterious fitness costs of fixed hypermutation. These studies provide a new paradigm for adaptation under increased selective pressures that may be present in other prokaryotes.
Asunto(s)
Helicobacter pylori/genética , Mutagénesis , Mutación/genética , Estrés Oxidativo/genética , Daño del ADN/efectos de los fármacos , ADN Bacteriano/química , ADN Bacteriano/efectos de los fármacos , ADN Bacteriano/genética , Eliminación de Gen , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/metabolismo , Mutagénesis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Especies de Nitrógeno Reactivo/metabolismo , Especies de Nitrógeno Reactivo/farmacología , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/farmacologíaRESUMEN
Metastatic disease to the bone is a common manifestation of advanced cancer, and can result in pain, pathologic fractures, hypercalcemia, and overall functional compromise. External beam radiation is a proven, highly efficacious, and noninvasive therapy that can provide symptomatic relief from painful osseous lesions. When deciding upon the best treatment regimen, it is important to consider patient factors such as overall life expectancy, performance status, disease burden, and site of osseous metastatic pain. Determination of best treatment ideally requires multidisciplinary input from radiologists, medical oncologists, surgeons, pain management, and palliative care specialists together with radiation oncologists.
RESUMEN
CONTEXT: Radiation therapy (RT) is used with palliative intent in patients with advanced stage cancer. Prior studies, primarily in patients with poor performance status (PS), suggest that RT is associated with aggressive medical care, which may impact patients' quality of life near death (QoD) adversely. OBJECTIVE: This study examines associations between RT use and patients' receipt of aggressive care and QoD based on patients' PS. METHODS: This is a multi-institutional, prospective cohort study of patients with end-stage cancers (N = 312) who were identified as terminally ill at study enrollment. RT use (n = 24; 7.7%) and Eastern Cooperative Oncology Group (ECOG) PS were assessed at study entry (median = 3.8 months before death). Aggressive care near death was operationalized as use of mechanical ventilation and/or resuscitation in the last week of life. QoD was determined using validated caregiver ratings of patients' physical and mental distress in their final week. RESULTS: RT use was associated with higher QoD (8/8, 100.0%, vs. 58/114, 50.9%; P = 0.006) among patients with good PS (ECOG = 1), more aggressive care near death (3/9, 33.3%, vs. 6/107, 5.6%; P = 0.020) among patients with moderate PS (ECOG = 2), and lower QoD (1/7, 14.3%, vs. 28/51, 54.9%; P = 0.046) among patients with poor PS (ECOG = 3). CONCLUSIONS: Targeted use of RT in end-of-life cancer care may benefit patients with good PS, but its use may adversely affect patients with poorer PS. Decisions about RT use in this setting should consider likely end-of-life outcomes based on patients' current PS.
Asunto(s)
Cuidados Paliativos/métodos , Calidad de Vida , Radioterapia/métodos , Cuidado Terminal/métodos , Enfermo Terminal , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
INTRODUCTION: In recent years, major changes in health care policy have affected oncology practice dramatically. In this context, we examined the effect of practice structure on volume and payments for radiation oncology services using the 2013 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF) for New York State radiation oncologists. METHODS: The Medicare POSPUF data was queried, and individual physicians were classified into freestanding office-based and hospital-based practices. Freestanding practices were further subdivided into urology, hematology-oncology, and other ownership structures. Additional variables analyzed included gender, year of medical school graduation, and Herfindahl-Hirschman Index (HHI). Statistical analyses were performed to assess the impact of the above-mentioned variables on reimbursements. RESULTS: There were 236 New York State radiation oncologists identified in the 2013 Medicare POSPUF dataset, with a total reimbursement of $91,525,855. Among freestanding centers, the mean global Medicare reimbursement was $832,974. Global Medicare reimbursement was $1,328,743 for urology practices, compared to $754,567 for hematology-oncology practices and $691,821 for other ownership structures (p < 0.05). The mean volume of on-treatment visits (OTVs) was 240.5 per year, varying by practice structure. The mean annual OTV volumes for urology practices, hematology-oncology practices, other freestanding practices, and hospital-based programs were 424.6, 311.5, 247.5, and 209.3, respectively. After correcting for gender, physician experience, and HHI, practice structure was predictive of freestanding reimbursement and on treatment visit volume. CONCLUSION: Higher Medicare payment was significantly predicted by the type of practice structure, with urology-based and hematology-oncology practices accounting for the highest total reimbursement and OTV volume.
RESUMEN
Increasing evidence demonstrates that radiation acts as an immune stimulus, recruiting immune mediators that enable anti-tumor responses within and outside the radiation field. There has been a rapid expansion in the number of clinical trials harnessing radiation to enhance antitumor immunity. If positive, results of these trials will lead to a paradigm shift in the use of radiotherapy. In this review, we discuss the rationale for trials combining radiation with various immunotherapies, provide an update of recent clinical trial results and highlight trials currently in progress. We also address issues pertaining to the optimal incorporation of immunotherapy with radiation, including sequencing of treatment, radiation dosing and evaluation of clinical trial endpoints.
RESUMEN
BACKGROUND AND PURPOSE: To determine appropriate risk-stratification factors for prostate cancer patients undergoing stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Between 2006 and 2010, 515 patients with organ-confined prostate cancer were treated with a regimen of five-fraction SBRT to dose of 35-36.25 Gy. By NCCN criteria, 324 patients were low risk, 153 were intermediate risk, and 38 were high risk. Patients were defined as unfavorable intermediate risk if Gleason 4 + 3 = 7 or >1 intermediate-risk factors (cT2b, c, PSA 10-20, Gleason 3 + 4 = 7). Cox regression analysis was used to determine risk factors significantly associated biochemical failure, and patterns of failure analyzed. RESULTS: With median follow-up of 84 months, the 8-year disease-free survival was 93.6, 84.3, and 65.0% for low, intermediate, and high-risk group patients, respectively. Based on the above definition, 106 favorable intermediate-risk patients had excellent outcomes, with no significant difference compared to low-risk patients (7-year DFS 95.2 vs. 93.2%, respectively). The 47 unfavorable intermediate-risk patients had worse outcomes, similar to high-risk patients (7-year DFS 68.2 vs. 65.0%, respectively). Gleason score was the only significant factor associated with biochemical failure on multivariate analysis (p = 0.0003). CONCLUSION: Patients with favorable intermediate-risk disease have excellent outcomes, comparable to low-risk patients. Patients with unfavorable intermediate-risk disease have significantly worse outcomes after SBRT, and should be considered for clinical trials or treatment intensification.
RESUMEN
BACKGROUND: Stereotactic Body Radiotherapy (SBRT) has excellent control rates for low- and intermediate-risk prostate carcinoma.The role of SBRT for high-risk disease remains less studied. We present long-term results on a cohort of patients with NCCN-defined high-risk disease treated with SBRT. METHODS: We retrospectively studied 97 patients treated as part of prospective trial from 2006-2010 with SBRT alone (n = 52) to dose of 35-36.25 Gy in 5 fractions, or pelvic radiation to 45 Gy followed by SBRT boost of 19-21 Gy in 3 fractions (n = 45). 46 patients received Androgen Deprivation Therapy. Quality of life and bladder/bowel toxicity was assessed using the Expanded Prostate Index Composite (EPIC) and RTOG toxicity scale. RESULTS: Median followup was 60 months. 6-year biochemical disease-free survival (bDFS) was 69%. On multivariate analysis, only PSA remained significant (P < 0.01) for bDFS. Overall toxicity was mild, with 5% Grade 2-3 urinary and 7% Grade 2 bowel toxicity. Use of pelvic radiotherapy was associated with significantly higher bowel toxicity (P = .001). EPIC scores declined for the first six months and then returned towards baseline. CONCLUSIONS: SBRT appears to be a safe and effective treatment for high-risk prostate carcinoma. Our data suggests that SBRT alone may be the optimal approach. Further followup and additional studies is required to corroborate our results.
Asunto(s)
Carcinoma/radioterapia , Carcinoma/cirugía , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Radiocirugia/métodos , Radioterapia Conformacional , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/patología , Terapia Combinada , Fraccionamiento de la Dosis de Radiación , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Radioterapia Conformacional/métodos , Estudios Retrospectivos , Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: Stereotactic body radiation therapy (SBRT) takes advantage of the prostate's low α/ß ratio to deliver a large radiation dose in few fractions. Initial studies on small groups of low-risk patients support SBRT's potential for clinical efficacy while limiting treatment-related morbidity and maintained quality of life. This prospective study expands upon prior studies to further evaluate SBRT efficacy for a large patient population with organ confined, low- and intermediate-risk prostate cancer patients. METHODS: Four hundred seventy-seven patients with prostate cancer received CyberKnife SBRT. The median age was 68.6 years and the median PSA was 5.3 ng/mL. Three hundred twenty-four patients were low-risk (PSA <10 ng/mL and Gleason <7), 153 were intermediate-risk (PSA 10-20 ng/mL or Gleason = 7). Androgen deprivation therapy was administered to 51 patients for up to 6 months. One hundred fifty-four patients received 35 Gy delivered in five daily fractions; the remaining patients received a total dose of 36.25 Gy in five daily fractions. Biochemical failure was assessed using the phoenix criterion. RESULTS: Median follow-up was 72 months. The median PSA at 7 years was 0.11 ng/mL. Biochemical failures occurred for 11 low-risk patients (2 locally), 14 intermediate-risk patients (3 locally). The actuarial 7-year freedom from biochemical failure was 95.6 and 89.6% for low- and intermediate-risk groups, respectively (p < 0.012). Among patients with intermediate-risk disease, those considered to have low intermediate-risk (Gleason 6 with PSA >10, or Gleason 3 + 4 with PSA <10; n = 106) had a significantly higher bDFS than patients with high intermediate-risk (Gleason 3 + 4 with PSA 10-20 or Gleason 4 + 3; n = 47), with bDFS of 93.5 vs. 79.3%, respectively. For the low-risk and low intermediate-risk groups, there was no difference in median PSA nadir or biochemical disease control between doses of 35 and 36.25 Gy. CONCLUSION: CyberKnife SBRT produces excellent biochemical control rates. Median PSA levels compare favorably with other radiation modalities and strongly suggest durability of response. These results also strongly suggest that 35 Gy is as effective as 36.25 Gy for low- and intermediate-risk patients.
RESUMEN
OBJECTIVES: Stereotactic body radiation therapy (SBRT) yields excellent disease control for low- and intermediate-risk prostate cancer by delivering high doses of radiation in a small number of fractions. Our report presents a 7-year update on treatment toxicity and quality of life (QOL) from 515 patients treated with prostate SBRT. METHODS: From 2006 to 2009, 515 patients with clinically localized, low-, intermediate-, and high-risk prostate cancer were treated with SBRT using Cyberknife technology. Treatment consisted of 35-36.25 Gy in 5 fractions. Seventy-two patients received hormone therapy. Toxicity was assessed at each follow-up visit using the expanded prostate cancer index composite (EPIC) questionnaire and the radiation therapy oncology group urinary and rectal toxicity scale. RESULTS: Median follow-up was 72 months. The actuarial 7-year freedom from biochemical failure was 95.8, 89.3, and 68.5% for low-, intermediate-, and high-risk groups, respectively (p < 0.001). No patients experienced acute Grade 3 or 4 acute complications. Fewer than 5% of patients had any acute Grade 2 urinary or rectal toxicity. Late toxicity was low, with Grade 2 rectal and urinary toxicity of 4 and 9.1%, respectively, and Grade 3 urinary toxicity of 1.7%. Mean EPIC urinary and bowel QOL declined at 1 month post-treatment, returned to baseline by 2 years and remained stable thereafter. EPIC sexual QOL declined by 23% at 6-12 months and remained stable afterwards. Of patients potent at baseline evaluation, 67% remained potent at last follow-up. CONCLUSION: This study suggests that SBRT, when administered to doses of 35-36.25 Gy, is efficacious and safe. With long-term follow-up in our large patient cohort, we continue to find low rates of late toxicity and excellent rates of biochemical control.
RESUMEN
Locally ablative therapies have an increasing role in the effective multidisciplinary approach towards the treatment of both primary and metastatic liver tumors. In patients who are not considered surgical candidates and have low volume disease, these therapies have now become established into consensus practice guidelines. A large range of therapeutic options exist including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, percutaneous laser ablation (PLA), irreversible electroporation (IRE), stereotactic body radiation therapy (SBRT) and high intensity focused ultrasound (HIFU); each having benefits and drawbacks. The greatest body of evidence supporting clinical utility in the liver currently exists for RFA, with PEI having fallen out of favor. MWA, IRE, SBRT and HIFU are relatively nascent technologies, and outcomes data supporting their use is promising. Future directions of ablative therapies include tandem approaches to improve efficacy in the treatment of liver tumors.
Asunto(s)
Técnicas de Ablación/métodos , Neoplasias Hepáticas/cirugía , Guías de Práctica Clínica como Asunto , Animales , Ablación por Catéter/métodos , Criocirugía/métodos , Electroquimioterapia/métodos , Etanol/administración & dosificación , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Humanos , Terapia por Láser/métodos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Radiocirugia/métodosRESUMEN
BACKGROUND: This study analyzed whether socio-economic factors affect the cause specific survival of soft tissue sarcoma (STS). METHODS: Surveillance, Epidemiology and End Results (SEER) soft tissue sarcoma (STS) data were used to identify potential socio-economic disparities in outcome. Time to cause specific death was computed with Kaplan-Meier analysis. Kolmogorov-Smirnov tests and Cox proportional hazard analysis were used for univariate and multivariate tests, respectively. The areas under the receiver operating curve were computed for predictors for comparison. RESULTS: There were 42,016 patients diagnosed STS from 1973 to 2009. The mean follow up time (S.D.) was 66.6 (81.3) months. Stage, site, grade were significant predictors by univariate tests. Race and rural-urban residence were also important predictors of outcome. These five factors were all statistically significant with Cox analysis. Rural and African-American patients had a 3-4% disadvantage in cause specific survival. CONCLUSIONS: Socio-economic factors influence cause specific survival of soft tissue sarcoma. Ensuring access to cancer care may eliminate the outcome disparities.
Asunto(s)
Sarcoma/mortalidad , Sarcoma/patología , Factores Socioeconómicos , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Área Bajo la Curva , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Curva ROC , Población Rural/estadística & datos numéricos , Programa de VERF , Sarcoma/etnología , Neoplasias de los Tejidos Blandos/etnología , Estados Unidos/epidemiología , Población Urbana/estadística & datos numéricos , Adulto JovenRESUMEN
AIM: This study employed public use National Health and Nutrition Examination Survey (NHANES III) data to investigate the association between urinary cadmium (UDPSI) and all cause, all cancer and prostate cancer mortalities in men. PATIENTS AND METHODS: NHANES III household adult, laboratory and mortality data were merged. The sampling weight used was WTPFEX6, with SDPPSU6 applied for the probability sampling unit and SDPSTRA6 to designate the strata for the survey analysis. RESULTS: For prostate cancer death, the significant univariates were UDPSI, age, weight, and drinking. Under multivariate logistic regression, the significant covariates were age and weight. For all cause mortality in men, the significant covariates were UDPSI, age, and poverty income ratio. For all cancer mortality in men, the significant covariates were UDPSI, age, black and Mexican race. CONCLUSIONS: UDPSI was a predictor of all cause and all cancer mortalities in men as well as prostate cancer mortality.