Matthew C. Abramowitz

The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer

The American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (BF) incorporates backdating, resulting in an artificial flattening of Kaplan‐Meier curves and overly favorable estimates when follow‐up is short. The nadir + 2 ng/mL (Nadir + 2; Phoenix) definition reduces these artifacts. The objective of the current study was to compare ASTRO and Phoenix BF estimates as determinants of distant metastasis (DM), cause‐specific mortality (CSM), and overall mortality (OM).

Dermal Lymphatic Invasion and Inflammatory Breast Cancer Are Independent Predictors of Outcome After Postmastectomy Radiation

Objectives:Inflammatory breast cancer (IBC) is a clinical staging based on history and physical findings. Dermal lymphatic invasion (DLI) can occur with or without IBC. We examine how these independently affect outcome in women treated with postmastectomy radiation. Methods:Four hundred thirty-two patients treated with postmastectomy radiation for invasive mammary cancer were assessed. Kaplan-Meier methodology was used to calculate rates of locoregional recurrence (LRR), distant metastases (DM) and overall survival (OS). Variables entered into univariate and multivariate analysis included T stage, IBC, DLI, estrogen receptor/progesterone receptor status, HER-2/neu status, N stage, extracapsular node extension (ECE), and use of chemotherapy (CT). Median follow-up is 58 months. Results:For all 432 patients, the rate of LRR was 3% and DM 28%. Seven percent are alive with disease (AWD) and 26% are dead of disease (DOD). Thirty-one patients had IBC without DLI, 21 had DLI without IBC, and 18 had both IBC and DLI. For DLI 10% developed LRR, 45% DM, 7.5% are AWD and 50% are DOD. Of patients with IBC, 8% developed LRR, 44% DM, 8% are AWD and 48% DOD. DLI was the only significant independent predictor for LRR (HR 4.8, P < 0.05). Predictors of DM and OS were IBC, ≥4 positive nodes, and CT. Conclusions:DLI and IBC are independent predictors of poor outcome after postmastectomy radiation. DLI is associated with an increased risk for LRR, and IBC with worse rates of DM and OS. Patients with both features have worse outcome than those with either alone.

Ethnic heterogeneity and prostate cancer mortality in Hispanic/Latino men: a population-based study

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.BACKGROUNDnFew 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.nnnMETHODSnWe 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.nnnRESULTSnCompared 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.nnnCONCLUSIONSnOur findings indicate previously unknown disparities in PCSM for Puerto Rican and Mexican American men.

Dynamische kontrastmittelverstärkte MRT (DCE-MRI) zur automatischen Erkennung von residualen oder rezidivierenden Krebsherden nach Prostatektomie

PurposeThis study aimed to develop an automated procedure for identifying suspicious foci of residual/recurrent disease in the prostate bed using dynamic contrast-enhanced-MRI (DCE-MRI) in prostate cancer patients after prostatectomy.Materials and methodsData of 22xa0patients presenting for salvage radiotherapy (RT) with an identified gross tumor volume (GTV) in the prostate bed were analyzed retrospectively. An unsupervised pattern recognition method was used to analyze DCE-MRI curves from the prostate bed. Data were represented as axa0product of axa0number of signal-vs.-time patterns and their weights. The temporal pattern, characterized by fast wash-in and gradual wash-out, was considered the “tumor” pattern. The corresponding weights were thresholded based on the number (1, 1.5, 2, 2.5) of standard deviations away from the mean, denoted as DCE1.0,xa0…, DCE2.5, and displayed on the T2-weighted MRI. The resultant four volumes were compared with the GTV and maximum pre-RT prostate-specific antigen (PSA) level. Pharmacokinetic modeling was also carried out.ResultsPrincipal component analysis determined 2–4xa0significant patterns in patients’ DCE-MRI. Analysis and display of the identified suspicious foci was performed in commercial software (MIM Corporation, Cleveland, OH, USA). In general, DCE1.0/DCE1.5 highlighted larger areas than GTV. DCE2.0 and GTV were significantly correlated (rxa0= 0.60, pxa0< 0.05). DCE2.0/DCA2.5 were also significantly correlated with PSA (rxa0= 0.52, 0.67, pxa0< 0.05). Ktrans for DCE2.5 was statistically higher than the GTV’s Ktrans (pxa0< 0.05), indicating that the automatic volume better captures areas of malignancy.ConclusionAxa0software tool was developed for identification and visualization of the suspicious foci in DCE-MRI from post-prostatectomy patients and was integrated into the treatment planning system.ZusammenfassungZielEntwicklung eines automatischen Analyseverfahrens, um nach Prostatektomie mittels dynamischer kontrastmittelverstärkter Magnetresonanztomographie (DCE-MRT) residuelle/rezidivierende Krebsherde im Prostatabett zu identifizieren.Material und MethodenDaten von 22xa0Patienten mit einer Salvage-Strahlentherapie (RT) und einem makroskopischen Tumorvolumen (GTV) im Prostatabett wurden retrospektiv analysiert. Die DCE-MRT-Kurven vom Prostatabett wurden mit einer nichtüberwachten Mustererkennungsmethode analysiert. Die Datendarstellung erfolgte als Produkt aus Mustern von Signal-vs.-Zeitverläufen und deren Gewichtungen. Zeitmuster, charakterisiert durch schnelles Anreichern und langsames Auswaschen, galten als „Tumorgewebe“. Der Grenzwert für die entsprechenden Gewichtungen basierte auf dem Mehrfachen (1; 1,5; 2; und 2,5) der Standardabweichungen vom Mittelwert und wurde auf den T2-gewichteten Bildern als DCE1.0,xa0…, DCE2.5 angezeigt. Die resultierenden 4 verschiedenen Volumina wurden mit dem GTV und dem maximal Wert des prostataspezifischen Antigens vor RT (pre-RT PSA) verglichen. Außerdem erfolgte eine pharmakokinetische Modellierung.ErgebnisseDie Hauptkomponentenanalyse ermittelte anhand der DCE-MRT-Daten 2–4 signifikante Muster. Analyse und Darstellung der identifizierten, verdächtigen Krebsherde erfolgte mit einer kommerziellen Software. Gewöhnlich waren DCE1.0/DCE1.5 größer als das GTV. Eine starke Korrelation zeigte DCE2.0 und GTV (rxa0= 0,60; pxa0< 0,05) sowie DCE2.0/DCE2.5 mit dem PSA-Wert (rxa0= 0,52; rxa0= 0,67; pxa0< 0,05). Ktrans für DCE2.5 war signifikant größer als Ktrans für GTV (pxa0< 0,05), was belegt, dass die automatische Volumenerkennung bösartige Tumorareale besser identifiziert.SchlussfolgerungAnhand von DCE-MRT-Daten von Patienten nach Prostatektomie ließ sich ein Software-Programm zur Identifizierung und Darstellung verdächtiger Krebsherde entwickelt und in das Behandlungsplanungssystem integrieren.

Prostate cancer: Moderate hypofractionated radiotherapy — not yet a standard of care

A theoretical radiobiological rationale supports the use of hypofractionated radiotherapy (higher radiation doses per fraction over a shorter period of time compared with conventional fractionation) for the treatment of prostate cancer. The investigators of two recently published phase III clinical trials with different designs have come to opposing conclusions regarding whether hypofractionated radiotherapy should be considered a new standard of care.

Contemporary role of postoperative radiotherapy for prostate cancer

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.

Magnetic resonance imaging (MRI)-based radiomics for prostate cancer radiotherapy

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.

Towards a universal MRI atlas of the prostate and prostate zones : Comparison of MRI vendor and image acquisition parameters.

Background and purposeThe 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.MethodsT2-weighted (T2) and fat-saturated (T2FS) MRIs were acquired on 3Txa0GE (GE, Waukesha, WI, USA) and Siemens (Erlangen, Germany) systems. Manual prostate and PZ contours were used to create atlas libraries. As axa0test MRI is entered, the procedure for atlas segmentation automatically identifies the atlas subjects that best match the test subject, followed by axa0normalized 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.ResultsThree atlases were generated based on GE_T2 (nu202f=u200930), GE_T2FS (nu202f=u200930), and Siem_T2FS (nu202f=u200931). When test images matched the contrast and vendor of the atlas, DSCs of 0.81 and 0.83 for T2u202f±u2009FS were obtained (baseline performance). Atlases performed with higher accuracy when segmenting (i)xa0T2FS vs. T2 images, likely due to axa0superior 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.ConclusionThe 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.ZusammenfassungHintergrund und ZweckZiel der Studie war es, eine automatische multi-atlasbasierende Segmentierungsmethode zur Erzeugung von Prostata-, peripheren und Übergangszonenkonturen (PZ/TZ) auf Magnetresonanztomographie(MRT)-Bildern mit und ohne Fettsättigung (±FS) zu beurteilen und MRT-Systeme verschiedener Hersteller zu vergleichen.MethodenT2-gewichtete (T2) und fettgesättigte (T2FS) MRTs wurden auf 3T-Systemen von GE (GE, Waukesha, WI, USA) und Siemens (Erlangen, Deutschland) aufgenommen. Manuelle Prostata- und PZ-Konturen wurden verwendet, um Atlasbibliotheken zu erstellen. Nach dem Einlesen eines MRT-Testdatensatzes identifiziert das Verfahren zur Atlassegmentierung automatisch die Atlasobjekte, die am besten zum Testobjekt passen, gefolgt von einer normalisierten, intensitätsbasierenden, frei deformierbaren Registrierung. Die Konturen werden dem Testobjekt angepasst und die „Dice Similarity Coefficients“ (DSC) und der Hausdorff-Abstand zwischen atlasgenerierten und manuellen Konturen verwendet, um die Übereinstimmung zu beurteilen.ErgebnisseDrei Atlanten wurden basierend auf GE_T2 (nu202f=u200930), GE_T2FS (nu202f=u200930) und Siem_T2FS (nu202f=u200931) erstellt. Wenn die Testbilder mit dem gewählten Kontrast und Atlashersteller übereinstimmten, wurden DSC von 0,81 und 0,83 für T2u202f±u2009FS erzielt (Ausgangswert). Atlanten erreichten eine höhere Genauigkeit beim Segmentieren von: (i)xa0T2FS-Bildern verglichen mit T2-Bildern, wahrscheinlich aufgrund des besseren Kontrasts zwischen Prostata und umgebendem Gewebe auf T2FS-Bildern; (ii) Prostata verglichen mit zonaler Anatomie; (iii) der Drüsenmitte verglichen mit Basis und Apex. Die Qualität der Atlanten ging zurück, wenn sie mit Bildern mit unterschiedlichem Kontrast und MRT-Gerät getestet wurden. Umgekehrt zeigten kombinierte Atlanten eine ähnliche Übereinstimmung und Qualität wie der Ausgangswert.SchlussfolgerungDie atlasbasierende MRT-Segmentierungsmethode erzielte gute Ergebnisse für Prostata, PZ und TZ im Vergleich zu konturierten Volumina. Kombinierte Atlanten erreichten eine ähnliche Übereinstimmung und Genauigkeit wie passender Atlas- und Scan-Typ. Die Technik ist schnell, vollautomatisch und auf einer kommerziell erhältlichen klinischen Plattform integriert.

Hin zu einem universellen MRT-Atlas von Prostata und Prostatazonen: Vergleich von verschiedenen MRT-Herstellern und Bildaufnahmeparametern

Background and purposeThe 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.MethodsT2-weighted (T2) and fat-saturated (T2FS) MRIs were acquired on 3Txa0GE (GE, Waukesha, WI, USA) and Siemens (Erlangen, Germany) systems. Manual prostate and PZ contours were used to create atlas libraries. As axa0test MRI is entered, the procedure for atlas segmentation automatically identifies the atlas subjects that best match the test subject, followed by axa0normalized 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.ResultsThree atlases were generated based on GE_T2 (nu202f=u200930), GE_T2FS (nu202f=u200930), and Siem_T2FS (nu202f=u200931). When test images matched the contrast and vendor of the atlas, DSCs of 0.81 and 0.83 for T2u202f±u2009FS were obtained (baseline performance). Atlases performed with higher accuracy when segmenting (i)xa0T2FS vs. T2 images, likely due to axa0superior 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.ConclusionThe 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.ZusammenfassungHintergrund und ZweckZiel der Studie war es, eine automatische multi-atlasbasierende Segmentierungsmethode zur Erzeugung von Prostata-, peripheren und Übergangszonenkonturen (PZ/TZ) auf Magnetresonanztomographie(MRT)-Bildern mit und ohne Fettsättigung (±FS) zu beurteilen und MRT-Systeme verschiedener Hersteller zu vergleichen.MethodenT2-gewichtete (T2) und fettgesättigte (T2FS) MRTs wurden auf 3T-Systemen von GE (GE, Waukesha, WI, USA) und Siemens (Erlangen, Deutschland) aufgenommen. Manuelle Prostata- und PZ-Konturen wurden verwendet, um Atlasbibliotheken zu erstellen. Nach dem Einlesen eines MRT-Testdatensatzes identifiziert das Verfahren zur Atlassegmentierung automatisch die Atlasobjekte, die am besten zum Testobjekt passen, gefolgt von einer normalisierten, intensitätsbasierenden, frei deformierbaren Registrierung. Die Konturen werden dem Testobjekt angepasst und die „Dice Similarity Coefficients“ (DSC) und der Hausdorff-Abstand zwischen atlasgenerierten und manuellen Konturen verwendet, um die Übereinstimmung zu beurteilen.ErgebnisseDrei Atlanten wurden basierend auf GE_T2 (nu202f=u200930), GE_T2FS (nu202f=u200930) und Siem_T2FS (nu202f=u200931) erstellt. Wenn die Testbilder mit dem gewählten Kontrast und Atlashersteller übereinstimmten, wurden DSC von 0,81 und 0,83 für T2u202f±u2009FS erzielt (Ausgangswert). Atlanten erreichten eine höhere Genauigkeit beim Segmentieren von: (i)xa0T2FS-Bildern verglichen mit T2-Bildern, wahrscheinlich aufgrund des besseren Kontrasts zwischen Prostata und umgebendem Gewebe auf T2FS-Bildern; (ii) Prostata verglichen mit zonaler Anatomie; (iii) der Drüsenmitte verglichen mit Basis und Apex. Die Qualität der Atlanten ging zurück, wenn sie mit Bildern mit unterschiedlichem Kontrast und MRT-Gerät getestet wurden. Umgekehrt zeigten kombinierte Atlanten eine ähnliche Übereinstimmung und Qualität wie der Ausgangswert.SchlussfolgerungDie atlasbasierende MRT-Segmentierungsmethode erzielte gute Ergebnisse für Prostata, PZ und TZ im Vergleich zu konturierten Volumina. Kombinierte Atlanten erreichten eine ähnliche Übereinstimmung und Genauigkeit wie passender Atlas- und Scan-Typ. Die Technik ist schnell, vollautomatisch und auf einer kommerziell erhältlichen klinischen Plattform integriert.

A meta-analysis of health-related quality of life after primary treatment for prostate cancer as measured by the Expanded Prostate Cancer Index Composite.

39 Background: Health-related quality of life (HRQoL) outcomes are important in treatment selection for prostate cancer. The Expanded Prostate Cancer Index Composite (EPIC) is a validated and widely-utilized HRQoL survey which accounts for newer radiotherapeutic, surgical, and hormonal treatment methods. We present a meta-analysis of patient reported HRQoL outcomes collected with EPIC and compare HRQoL trends with radiation therapy, surgery, or active surveillance as primary treatment. Methods: The PubMed database was systematically searched for all studies which presented data directly derived from the use of EPIC on patients with prostate cancer prior to 07/09/2014. All eligible studies were selected for either inclusion and analysis or exclusion based on pre-determined criteria. The data from included studies was compiled and a simulation-based estimation method using Approximate Bayesian Computation was performed to obtain missing standard deviation estimate. A longitudinal meta-analysis was conducted...