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1.
Med Dosim ; 44(4): 405-408, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30928177

RESUMO

For early-stage glottic cancers, intensity-modulated radiation therapy (IMRT) has been shown to have comparable local control to 3D-conformal radiotherapy with the advantage of decreased dose to the carotid arteries. The planning target volume (PTV) for early glottic cancers typically includes the entire larynx, plus a 3 to 5 mm uniform margin. The air cavity within the larynx creates a challenge for the inverse optimization process as the software attempts to "build up" dose within the air. This unnecessary attempt at dose build-up in air can lead to hot spots within the rest of the PTV and surrounding soft tissue. We hypothesized that removal of the air from the PTV would decrease hot spots and allow for a more homogeneous plan while still maintaining adequate coverage of the PTV. We analyzed 20 consecutive patients with early-stage glottic cancer, T1-2N0, who received IMRT at our institution from April 2015 to December 2016. Each patient received 63 to 65.25 Gy in 2.25 Gy per fraction. Two plans were created for each case: one in which the PTV included the laryngeal air cavity and one in which the air cavity was subtracted from the PTV to create a new PTV-air structure. Dosimetric variables were collected for PTV-air structure from both IMRT plans, including V100%, D98% D2%, and D0.2%. Dosimetric variables for spinal cord and the carotid arteries were also recorded. Homogeneity index (HI) defined as D98/D2 was calculated. Two-sided t-tests were used to compare dosimetric variables. The median PTV volume was 69.9 cc (standard deviation [SD] ± 28.7 cc) and the median air cavity volume removed was 11.0 cc (SD ± 3.4 cc). A 2-sided t-test revealed a statistically significant decrease in max dose (112.7% vs 108.8%, p value = 0.0002) and improvement of HI (0.93 vs 0.91, p value = 0.0023) for the PTV air in the IMRT plan optimized for PTV air, which had air excluded, compared to the IMRT plan optimized for PTV with air included. There was no significant worsening of PTV-air coverage or significant increase in doses to the organs at risk (OARs). The removal of the air cavity from the PTV for early-stage glottic cancers does not compromise PTV coverage or sparing of OARs and can result in a more homogeneous IMRT plan. A more homogeneous plan has the potential to reduce treatment morbidity, although further study is warranted to investigate the clinical impact of air cavity removal from the PTV.

2.
Sci Rep ; 8(1): 16801, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30429515

RESUMO

A procedure for identification of optimal Apparent Diffusion Coefficient (ADC) thresholds for automatic delineation of prostatic lesions with restricted diffusion at differing risk for cancer was developed. The relationship between the size of the identified Volumes of Interest (VOIs) and Gleason Score (GS) was evaluated. Patients with multiparametric (mp)MRI, acquired prior to radical prostatectomy (RP) (n = 18), mpMRI-ultrasound fused (MRI-US) (n = 21) or template biopsies (n = 139) were analyzed. A search algorithm, spanning ADC thresholds in 50 µm2/s increments, determined VOIs that were matched to RP tumor nodules. Three ADC thresholds for both peripheral zone (PZ) and transition zone (TZ) were identified for estimation of VOIs at low, intermediate, and high risk of prostate cancer. The determined ADC thresholds for low, intermediate and high risk in PZ/TZ were: 900/800; 1100/850; and 1300/1050 µm2/s. The correlation coefficients between the size of the high/intermediate/low risk VOIs and GS in the three cohorts were 0.771/0.778/0.369, 0.561/0.457/0.355 and 0.423/0.441/0.36 (p < 0.05). Low risk VOIs mapped all RP lesions; area under the curve (AUC) for intermediate risk VOIs to discriminate GS6 vs GS ≥ 7 was 0.852; for high risk VOIs to discriminate GS6,7 vs GS ≥ 8 was 0.952. In conclusion, the automatically delineated volumes in the prostate with restricted diffusion were found to strongly correlate with cancer aggressiveness.

3.
Strahlenther Onkol ; 2018 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30140944

RESUMO

BACKGROUND AND PURPOSE: The aim of this study was to evaluate an automatic multi-atlas-based segmentation method for generating prostate, peripheral (PZ), and transition zone (TZ) contours on MRIs with and without fat saturation (±FS), and compare MRIs from different vendor MRI systems. METHODS: T2-weighted (T2) and fat-saturated (T2FS) MRIs were acquired on 3T GE (GE, Waukesha, WI, USA) and Siemens (Erlangen, Germany) systems. Manual prostate and PZ contours were used to create atlas libraries. As a test MRI is entered, the procedure for atlas segmentation automatically identifies the atlas subjects that best match the test subject, followed by a normalized intensity-based free-form deformable registration. The contours are transformed to the test subject, and Dice similarity coefficients (DSC) and Hausdorff distances between atlas-generated and manual contours were used to assess performance. RESULTS: Three atlases were generated based on GE_T2 (n = 30), GE_T2FS (n = 30), and Siem_T2FS (n = 31). When test images matched the contrast and vendor of the atlas, DSCs of 0.81 and 0.83 for T2 ± FS were obtained (baseline performance). Atlases performed with higher accuracy when segmenting (i) T2FS vs. T2 images, likely due to a superior contrast between prostate vs. surrounding tissue; (ii) prostate vs. zonal anatomy; (iii) in the mid-gland vs. base and apex. Atlases performance declined when tested with images with differing contrast and MRI vendor. Conversely, combined atlases showed similar performance to baseline. CONCLUSION: The MRI atlas-based segmentation method achieved good results for prostate, PZ, and TZ compared to expert contoured volumes. Combined atlases performed similarly to matching atlas and scan type. The technique is fast, fully automatic, and implemented on commercially available clinical platform.

4.
Transl Androl Urol ; 7(3): 399-413, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30050800

RESUMO

While radical prostatectomy (RP) has provided long-term disease control for the majority of patients with localized prostate cancer (CaP), nearly 30% of all surgical patients have disease progression. For high-risk patients, more than half of men experience disease recurrence within 10 years. Postoperative radiotherapy is the only known potentially curative treatment for a large number of patients following prostatectomy. Lately, there have been several advances with the potential to improve outcomes for patients undergoing postoperative radiotherapy. This article will give an overview of the existing literature and current controversies on: (I) timing of postoperative radiation; (II) use of concomitant androgen deprivation therapy; (III) optimal dose to the prostate bed; (IV) use of hypofractionation; (V) elective treatment of the pelvic lymph nodes; (VI) novel imaging modalities, and (VII) genomic biomarkers.

5.
Transl Androl Urol ; 7(3): 445-458, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30050803

RESUMO

In radiotherapy (RT) of prostate cancer, dose escalation has been shown to reduce biochemical failure. Dose escalation only to determinate prostate tumor habitats has the potential to improve tumor control with less toxicity than when the entire prostate is dose escalated. Other issues in the treatment of the RT patient include the choice of the RT technique (hypo- or standard fractionation) and the use and length of concurrent/adjuvant androgen deprivation therapy (ADT). Up to 50% of high-risk men demonstrate biochemical failure suggesting that additional strategies for defining and treating patients based on improved risk stratification are required. The use of multiparametric MRI (mpMRI) is rapidly gaining momentum in the management of prostate cancer because of its improved diagnostic potential and its ability to combine functional and anatomical information. Currently, the Prostate Imaging, Reporting and Diagnosis System (PIRADS) is the standard of care for region of interest (ROI) identification and risk classification. However, PIRADS was not designed for 3D tumor volume delineation; there is a large degree of subjectivity and PIRADS does not accurately and reproducibly elucidate inter- and intra-lesional spatial heterogeneity. "Radiomics", as it refers to the extraction and analysis of large number of advanced quantitative radiological features from medical images using high throughput methods, is perfectly suited as an engine to effectively sift through the multiple series of prostate mpMRI sequences and quantify regions of interest. The radiomic efforts can be summarized in two main areas: (I) detection/segmentation of the suspicious lesion; and (II) assessment of the aggressiveness of prostate cancer. As related to RT, the goal of the latter is in particular to identify patients at high risk for metastatic disease; and the aim of the former is to identify and segment cancerous lesions and thus provide targets for radiation boost. The article is structured as follows: first, we describe the radiomic approach; and second, we discuss the radiomic pipeline as tailored for RT of prostate cancer. In this process we summarize the current efforts and progress in integrating mpMRI radiomics into the radiotherapeutic management of prostate cancer with emphasis placed on its role in treatment target definition, treatment plan strategizing, and prognostic assessment. The described concepts, methods and tools are not currently applicable to the radiation oncology practice outside of the research setting. More data are required in the form of clinical trials to assess the robustness of radiomics-based predictive models, and to maximize the efficacy of these models.

6.
Int J Radiat Oncol Biol Phys ; 102(4): 821-829, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29908220

RESUMO

PURPOSE: To develop a prostate tumor habitat risk scoring (HRS) system based on multiparametric magnetic resonance imaging (mpMRI) referenced to prostatectomy Gleason score (GS) for automatic delineation of gross tumor volumes. A workflow for integration of HRS into radiation therapy boost volume dose escalation was developed in the framework of a phase 2 randomized clinical trial (BLaStM). METHODS AND MATERIALS: An automated quantitative mpMRI-based 10-point pixel-by-pixel method was optimized to prostatectomy GSs and volumes using referenced dynamic contrast-enhanced and apparent diffusion coefficient sequences. The HRS contours were migrated to the planning computed tomography scan for boost volume generation. RESULTS: There were 51 regions of interest in 12 patients who underwent radical prostatectomy (26 with GS ≥7 and 25 with GS 6). The resultant heat maps showed inter- and intratumoral heterogeneity. The HRS6 level was significantly associated with radical prostatectomy regions of interest (slope 1.09, r = 0.767; P < .0001). For predicting the likelihood of cancer, GS ≥7 and GS ≥8 HRS6 area under the curve was 0.718, 0.802, and 0.897, respectively. HRS was superior to the Prostate Imaging, Reporting and Diagnosis System 4/5 classification, wherein the area under the curve was 0.62, 0.64, and 0.617, respectively (difference with HR6, P < .0001). HRS maps were created for the first 37 assessable patients on the BLaStM trial. There were an average of 1.38 habitat boost volumes per patient at a total boost volume average of 3.6 cm3. CONCLUSIONS: An automated quantitative mpMRI-based method was developed to objectively guide dose escalation to high-risk habitat volumes based on prostatectomy GS.

7.
JAMA Oncol ; 4(5): e175230, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29372236

RESUMO

Importance: Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. Objective: To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. Design, Setting, and Participants: This multi-institutional, propensity score-matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. Main Outcomes and Measures: Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. Results: Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. Conclusions and Relevance: Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

8.
Eur Urol ; 74(1): 99-106, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29128208

RESUMO

BACKGROUND: Outcomes with postprostatectomy salvage radiation therapy (SRT) are not ideal. Little evidence exists regarding potential benefits of adding whole pelvic radiation therapy (WPRT) alone or in combination with androgen deprivation therapy (ADT). OBJECTIVE: To explore whether WPRT and/or ADT added to prostate bed radiation therapy (PBRT) improves freedom from biochemical failure (FFBF) or distant metastases (DM). DESIGN, SETTING, AND PARTICIPANTS: A database was compiled from 10 academic institutions of patients with postprostatectomy prostate-specific antigen (PSA) >0.01 ng/ml; pT1-4, Nx/0, cM0; and Gleason score (GS) ≥7 treated between 1987 and 2013. Median follow-up was 51 mo. INTERVENTIONS: WPRT and/or ADT in addition to PBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: FFBF and DM were calculated using cumulative incidence estimation. Multivariable analysis (MVA) utilized cumulative incidence regression. RESULTS AND LIMITATION: Median pre-SRT PSA was 0.5 ng/ml for 1861 patients. Median follow-up for patients not experiencing biochemical failure (BF) was 55 mo. MVA showed increased BF for PBRT versus WPRT (hazard ratio [HR] 1.82, p<0.001) and no ADT versus ADT (HR 1.70, p<0.001). WPRT was associated with a 5-yr FFBF of 62% versus 49% (p<0.001) for PBRT. ADT use was associated with improved 5-yr FFBF (55% vs 50%, p=0.012). No significant differences in DM cumulative incidence were found. CONCLUSIONS: For patients with GS ≥7 receiving SRT, clinicians should weigh FFBF benefits of WPRT and ADT against toxicities. Future studies should explore the impact of WPRT on quality of life, clinical progression, and overall survival. PATIENT SUMMARY: We evaluated patients with prostate cancer treated with radiation after surgery to remove the prostate. Both radiation to the pelvic lymph nodes and suppression of testosterone lowered the chance of increasing prostate-specific antigen (a marker for cancer returning).

9.
Front Oncol ; 7: 259, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29177134

RESUMO

Purpose: To develop a robust and clinically applicable automated method for analyzing Dynamic Contrast Enhanced (DCE-) MRI of the prostate as a guide for targeted biopsies and treatments. Materials and methods: An unsupervised pattern recognition (PR) method was used to analyze prostate DCE-MRI from 71 sequential radiotherapy patients. Identified regions of interest (ROIs) with increased perfusion were assigned either to the peripheral (PZ) or transition zone (TZ). Six quantitative features, associated with the washin and washout part of the weighted average DCE curve from the ROI, were calculated. The associations between the assigned DCE-scores and Gleason Score (GS) were investigated. A heatmap of tumor aggressiveness covering the entire prostate was generated and validated with histopathology from MRI-ultrasound fused (MRI-US) targeted biopsies. Results: The volumes of the PR-identified ROI's were significantly correlated with the highest GS from the biopsy session for each patient. Following normalization (and only after normalization) with gluteus maximus muscle's DCE signal, the quantitative features in PZ were significantly correlated with GS. These correlations straightened in subset of patients with available MRI-US biopsies when GS from the individual biopsies were used. Area under the receiver operating characteristics curve for discrimination between indolent vs aggressive cancer for the significant quantitative features reached 0.88-0.95. When DCE-scores were calculated in normal appearing tissues, the features were highly discriminative for cancer vs no cancer both in PZ and TZ. The generated heatmap of tumor aggressiveness coincided with the location and GS of the MRI-US biopsies. Conclusion: A quantitative approach for DCE-MRI analysis was developed. The resultant map of aggressiveness correlated well with tumor location and GS and is applicable for integration in radiotherapy/radiology imaging software for clinical translation.

10.
Oncotarget ; 8(41): 69709-69721, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-29050235

RESUMO

BACKGROUND: Few studies focus on prostate cancer (PCa) outcomes in Hispanic/Latino men. Our study explores whether Hispanic/Latino subgroups demonstrate significantly different prostate cancer-specific mortality (PCSM) relative to Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) men. METHODS: We extracted a population-based cohort of men diagnosed with local-regional PCa from 2000-2013 (n= 486,865). PCSM was measured in racial/ethnic groups: NHW (n=352,886), NHB (n= 70,983), Hispanic/Latino (n= 40,462), and Asian American/Pacific Islander (n= 22,534). PCSM was also measured in Hispanic/Latino subgroups: Mexican (n= 8,077), Puerto Rican (n= 1,284), South or Central American (n= 3,021), Cuban (n= 788), and Dominican (n= 300). We conducted univariable and multivariable analyses (MVA) to compare risk for PCSM. RESULTS: Compared to NHW men, results showed worse outcomes for NHB men with similar outcomes for Hispanic/Latino men. In MVA with NHW men as a reference, NHB (HR= 1.15, p <0.001) men had significantly worse PCSM and Hispanic/Latino (HR= 1.02, p= 0.534) men did not show a significant difference. In a second MVA, Puerto Rican (HR= 1.71, p <0.001) and Mexican (HR= 1.21, p= 0.008) men had significantly higher PCSM. With NHB men as a reference, the MVA showed Puerto Rican (HR= 1.50, p= 0.006) men with higher PCSM and Mexican (HR= 1.08, p= 0.307) men with no significant difference. CONCLUSIONS: Our findings indicate previously unknown disparities in PCSM for Puerto Rican and Mexican American men.

11.
Radiother Oncol ; 121(2): 294-298, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27890426

RESUMO

BACKGROUND AND PURPOSE: Evaluate changes in bowel, urinary and sexual patient-reported quality of life following treatment with moderately hypofractionated radiotherapy (<5Gray/fraction) or stereotactic body radiation therapy (SBRT;5-10Gray/fraction) for prostate cancer. MATERIALS AND METHODS: In a pooled multi-institutional analysis of men treated with moderate hypofractionation or SBRT, we compared minimally detectable difference in bowel, urinary and sexual quality of life at 1 and 2years using chi-squared analysis and logistic regression. RESULTS: 378 men received moderate hypofractionation compared to 534 men who received SBRT. After 1year, patients receiving moderate hypofractionation were more likely to experience worsening in bowel symptoms (39.5%) compared to SBRT (32.5%; p=.06), with a larger difference at 2years (37.4% versus 25.3%, p=.002). Similarly, patients receiving moderate fractionation had worsening urinary symptom score compared to patients who underwent SBRT at 1 and 2years (34.7% versus 23.1%, p<.001; and 32.8% versus 14.0%, p<.001). There was no difference in sexual symptom score at 1 or 2years. After adjusting for age and cancer characteristics, patients receiving SBRT were less likely to experience worsening urinary symptom scores at 2years (odds ratio: 0.24[95%CI: 0.07-0.79]). CONCLUSIONS: Patients who received SBRT or moderate hypofractionation have similar patient-reported change in bowel and sexual symptoms, although there was worse change in urinary symptoms for patients receiving moderate hypofractionation.


Assuntos
Neoplasias da Próstata/radioterapia , Qualidade de Vida , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Humanos , Intestinos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Órgãos em Risco/efeitos da radiação , Neoplasias da Próstata/patologia , Neoplasias da Próstata/reabilitação , Hipofracionamento da Dose de Radiação , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Disfunções Sexuais Fisiológicas/etiologia , Sistema Urinário/efeitos da radiação
12.
Int J Radiat Oncol Biol Phys ; 96(5): 1046-1053, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27745980

RESUMO

PURPOSE: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. METHODS AND MATERIALS: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. RESULTS: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. CONCLUSIONS: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/radioterapia , Terapia de Salvação/métodos , Idoso , Distribuição de Qui-Quadrado , Bases de Dados Factuais/estatística & dados numéricos , Relação Dose-Resposta à Radiação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Prostatectomia , Neoplasias da Próstata/cirurgia , Tamanho da Amostra , Glândulas Seminais/patologia , Fatores de Tempo , Falha de Tratamento , Estados Unidos
13.
J Clin Oncol ; 34(30): 3648-3654, 2016 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-27528718

RESUMO

PURPOSE: We aimed to update a previously published, multi-institutional nomogram of outcomes for salvage radiotherapy (SRT) following radical prostatectomy (RP) for prostate cancer, including patients treated in the contemporary era. METHODS: Individual data from node-negative patients with a detectable post-RP prostate-specific antigen (PSA) treated with SRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 10 academic institutions. Freedom from biochemical failure (FFBF) and distant metastases (DM) rates were estimated, and predictive nomograms were generated. RESULTS: Overall, 2,460 patients with a median follow-up of 5 years were included; 599 patients (24%) had a Gleason score (GS) ≤ 6, 1,387 (56%) had a GS of 7, 244 (10%) had a GS of 8, and 230 (9%) had a GS of 9 to 10. There were 1,370 patients (56%) with extraprostatic extension (EPE), 452 (18%) with seminal vesicle invasion (SVI), 1,434 (58%) with positive surgical margins, and 390 (16%) who received ADT (median, 6 months). The median pre-SRT PSA was 0.5 ng/mL (interquartile range, 0.3 to 1.1). The 5-yr FFBF rate was 56% overall, 71% for those with a pre-SRT PSA level of 0.01 to 0.2 ng/mL (n = 441), 63% for those with a PSA of 0.21 to 0.50 ng/mL (n = 822), 54% for those with a PSA of 0.51 to 1.0 ng/mL (n = 533), 43% for those with a PSA of 1.01 to 2.0 ng/mL (n = 341), and 37% for those with a PSA > 2.0 ng/mL (n = 323); P < .001. On multivariable analysis, pre-SRT PSA, GS, EPE, SVI, surgical margins, ADT use, and SRT dose were associated with FFBF. Pre-SRT PSA, GS, SVI, surgical margins, and ADT use were associated with DM, whereas EPE and SRT dose were not. The nomogram concordance indices were 0.68 (FFBF) and 0.74 (DM). CONCLUSION: Early SRT at low PSA levels after RP is associated with improved FFBF and DM rates. Contemporary nomograms can estimate individual patient outcomes after SRT in the modern era.

14.
Oncotarget ; 7(33): 53362-53376, 2016 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-27438142

RESUMO

Standard clinicopathological variables are inadequate for optimal management of prostate cancer patients. While genomic classifiers have improved patient risk classification, the multifocality and heterogeneity of prostate cancer can confound pre-treatment assessment. The objective was to investigate the association of multiparametric (mp)MRI quantitative features with prostate cancer risk gene expression profiles in mpMRI-guided biopsies tissues.Global gene expression profiles were generated from 17 mpMRI-directed diagnostic prostate biopsies using an Affimetrix platform. Spatially distinct imaging areas ('habitats') were identified on MRI/3D-Ultrasound fusion. Radiomic features were extracted from biopsy regions and normal appearing tissues. We correlated 49 radiomic features with three clinically available gene signatures associated with adverse outcome. The signatures contain genes that are over-expressed in aggressive prostate cancers and genes that are under-expressed in aggressive prostate cancers. There were significant correlations between these genes and quantitative imaging features, indicating the presence of prostate cancer prognostic signal in the radiomic features. Strong associations were also found between the radiomic features and significantly expressed genes. Gene ontology analysis identified specific radiomic features associated with immune/inflammatory response, metabolism, cell and biological adhesion. To our knowledge, this is the first study to correlate radiogenomic parameters with prostate cancer in men with MRI-guided biopsy.


Assuntos
Regulação Neoplásica da Expressão Gênica , Imagem por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos
15.
J Appl Clin Med Phys ; 17(3): 304-312, 2016 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-27167286

RESUMO

Advances in magnetic resonance imaging (MRI) sequences allow physicians to define the dominant intraprostatic lesion (IPL) in prostate radiation therapy treat-ments allowing for dose escalation and potentially increased tumor control. This work quantifies the margin required around the MRI-defined IPL accounting for both prostate motion and deformation. Ten patients treated with a simultaneous integrated intraprostatic boost (SIIB) were retrospectively selected and replanned with incremental 1 mm margins from 0-5 mm around the IPL to determine if there were any significant differences in dosimetric parameters. Sensitivity analysis was then performed accounting for random and systematic uncertainties in both prostate motion and deformation to ensure adequate dose was delivered to the IPL. Prostate deformation was assessed using daily CBCT imaging and implanted fiducial markers. The average IPL volume without margin was 2.3% of the PTV volume and increased to 11.8% with a 5 mm margin. Despite these changes in vol-ume, the only statistically significant dosimetric difference was found for the PTV maximum dose, which increased with increasing margin. The sensitivity analysis demonstrated that a 3.0 mm margin ensures > 95% IPL coverage accounting for both motion and deformation. We found that a margin of 3.0 mm around the MRI defined IPL is sufficient to account for random and systematic errors in IPL posi-tion for the majority of cases.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias da Próstata/patologia , Radioterapia Guiada por Imagem/métodos , Fracionamento da Dose de Radiação , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
17.
Head Neck ; 38 Suppl 1: E873-83, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-25966421

RESUMO

BACKGROUND: Patients with head and neck cancer are at high risk for second primary malignancies. Human papillomavirus (HPV)-driven tumors are generally high-grade oropharyngeal cancers. We analyzed the incidence of second primary malignancy of the head and neck in patients with primary squamous cell carcinoma (SCC) of the head and neck and temporal trends in the HPV era. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with SCC of the head and neck (range, 1973-2008). Cumulative incidence rates of second primary malignancy of the head and neck were compared based on competing risk analysis. RESULTS: A total of 104,639 cases were included in this study, of which 4616 patients had second primary malignancy of the head and neck. Oropharyngeal cancer incidence increased over time. Estimated incidence rate/10,000 person-years (105.5, 80.6, and 50.2 for 1973-1989, 1990-1999, and 2000-2008, respectively) and cumulative incidence rates (10-year rates of 6.68%, 5.72%, and 4.59% for 1973-1989, 1990-1999, and 2000-2008, respectively) of second primary malignancies of the head and neck for patients with oropharyngeal cancer decreased over time (p < .001). The second primary malignancy of the head and neck incidence rate was significantly lower in patients with high-grade oropharyngeal cancer from 2000 to 2008 (30.3 vs 65.5 and 54.6 from 1973-1989 and 1990-1999, respectively; p < .001). CONCLUSION: The incidence of second primary malignancy of the head and neck in patients with head and neck cancer has decreased over time. This is driven by lower rates in patients with high-grade oropharyngeal cancer, is temporally related with increases in HPV-associated oropharyngeal cancer, and suggests that incidence rates of second primary malignancy of the head and neck may be lower for HPV-associated cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E873-E883, 2016.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Infecções por Papillomavirus/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/virologia , Feminino , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/virologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Programa de SEER , Adulto Jovem
18.
Clin Genitourin Cancer ; 13(4): 378-384.e1, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25907230

RESUMO

BACKGROUND: Neoadjuvant radiotherapy (NART) for muscle-invasive bladder cancer (MIBC) is currently underused. However, the outcomes for MIBC have remained suboptimal. We investigated the relationship of NART to cause-specific mortality (CSM) and overall mortality (OM) among patients with a diagnosis of MIBC. MATERIALS AND METHODS: The patients diagnosed with primary invasive urothelial carcinoma of the bladder from 1983 to 2008 with localized disease were included. Patients aged > 90 years, those diagnosed with T1 or T4 BC, and those with no information on tumor grade were excluded from the analysis. Kaplan-Meier, Cox regression, and competing risk methods were used in the analysis of OM and CSM. RESULTS: A total of 5562 patients were included in the cohort (115 NART and 5447 surgery alone). On univariate analysis, NART significantly decreased the OM for patients with high-grade BC (hazard ratio [HR], 0.8), stage T2b (HR, 0.74), and stage T2b/T3 (HR, 0.74). CSM was also lower for those with stage T2b disease (HR, 0.63). Multivariable analysis revealed that NART was associated with a significant decrease in CSM (P = .043) and OM (P = .0462) for those with T2b. Likewise, an improvement was seen in OM (P = .0337) for patients with T2b/T3 who had received NART. CONCLUSION: NART was significantly associated with decreased CSM and OM in patients with clinical T2b/T3 BC and OM for patients with T2b/T3. These data suggest that NART could be beneficial in patients with T2b/T3 BC. In the modern era, the greatest utility would potentially be for patients with an incomplete response to neoadjuvant chemotherapy or as an adjunct to chemotherapy to improve the complete response rates.


Assuntos
Carcinoma de Células de Transição/terapia , Neoplasias da Bexiga Urinária/terapia , Adulto , Idoso , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Programa de SEER , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
19.
Front Oncol ; 4: 165, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25072020

RESUMO

BACKGROUND: Cetuximab (Cx) + radiation therapy (RT) is well-tolerated and has improved survival in patients (pts) with locoregionally advanced head and neck squamous cell carcinomas (LA-HNSCC). However, its efficacy when compared to HD-DDP + RT has been questioned. At our institution, low-dose weekly carboplatin is added to Cx + RT for patients unsuitable for HD-DDP. METHODS: We reviewed records of 16 patients with LA-HNSCC treated with definitive Cx + carboplatin + RT at the University of Miami from 2007 to 2011. Median follow-up was 24 months (range: 1-69 months). RESULTS: Median age: 71.5 years (range: 57-90 years); 15 male, 1 female. ECOG PS 0 = 15, 1 = 1. TNM staging was: T 1 = 1, T 2 = 5, T 3 = 8, T 4 = 2; N stage: N 0 = 8, N 1 = 5, N 2a = 2, N 2b = 1. All patients received weekly carboplatin (AUC 1.5-2), Cx given conventionally and daily conventionally fractionated RT. Median total weeks of concurrent systemic therapy = 7 (range: 3-8 weeks). RT was delivered to a median total dose of 70 Gy (range 30-74 Gy). Of the 15 evaluable patients, there were: 12 CR, 2 PR, and 1 PD. There were three local in-field failures, two regional failures, and three distant failures. At last follow-up, 8/15 patients remained with NED. Three-year locoregional recurrence was 28.3% (95% CI: 7.7-53.9%). Mean percentage of weight loss was 14% (range: 6-26%). Two patients required systemic therapy dose reduction. Three patients experienced a treatment delay and three did not finish RT as planned including a patient who received only 30 Gy due to death secondary to MI during treatment. CONCLUSION: In this small retrospective series, carboplatin/Cx/RT was well-tolerated and efficacious in patients unsuitable for HD-DDP having LA-HNSCC. Acute toxicities were similar to Cx + RT, likely due to the non-overlapping toxicity profiles of the two systemic agents. We hypothesize that the addition of a well-tolerated cytotoxic chemotherapy agent may improve the therapeutic ratio of Cx + RT in patients who are poor candidates for more aggressive therapies and warrants evaluation in a prospective manner.

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