Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients.

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease.

The Impact of Metastasis Histopathology on Oncologic Outcomes for Patients With Surgically Resected Metastatic Renal Cell Carcinoma.

Purpose: Multiple prognostic models exist to assess survival among patients with metastatic clear cell renal cell carcinoma. However, the relative contribution of histopathological features of the metastasis has not been extensively studied. Herein, we compared models using clinical, primary tumor, and metastatic features to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma.

Dynamic assessment of serum chromogranin A and treatment response with abiraterone acetate in metastatic castration-resistant prostate cancer.

Objective: Elevated serum chromogranin A (CGA) is associated with intrinsic or treatment-related neuroendocrine differentiation (NED) in men with metastatic castration-resistant prostate cancer (mCRPC). Fluctuations in serum CGA during treatment of mCRPC have had conflicting results. We analyzed the impact of (i) rising serum CGA and (ii) baseline CGA/PSA ratio during treatment to identify associations with abiraterone acetate (AA) therapy.

Radiation Therapy in Oligometastatic Prostate Cancer.

Prostate cancer ranges from localized, low risk to metastatic, morbid disease. Although radiation therapy (RT) is commonly incorporated in the treatment of early disease or for palliation of symptomatic lesions, its role in extending survival in metastatic disease is less well-established. Here, we review the available evidence surrounding localized RT in the presence of oligometastatic disease and metastasis-directed therapy in both hormone-sensitive and hormone-resistant prostate cancer.

The impact of genetic aberrations on response to radium-223 treatment for castration-resistant prostate cancer with bone metastases.

Background: Radium (Ra)-223 is an established treatment option for patients with metastatic castrate-resistant prostate cancer (mCRPC) who have symptomatic bone metastases without soft tissue disease. Studies have indicated genetic aberrations that regulate DNA damage response (DDR) in prostate cancer can increase susceptibility to treatments such as poly ADP-ribose polymerase inhibitors and platinum-based therapies. This study aims to evaluate mCRPC response to Ra-223 stratified by tumor genomics.

Rational Second-Generation Antiandrogen Use in Prostate Cancer.

The second-generation antiandrogens have achieved an ever-growing list of approvals and indications in subsets of prostate cancer. Here, we provide an overview of second-generation antiandrogen trials and FDA approvals and outline a rational sequencing approach for the use of these agents as they relate to chemotherapy and other available treatment modalities in advanced prostate cancer. All published phase II-III randomized controlled trials reporting outcomes with the use of second-generation antiandrogens in prostate cancer are included as well as all published trials and retrospective studies of second-generation antiandrogen sequencing and/or combinations.

Path Planner for UAV Applications with Curvature Constraints: A Comparative Analysis with Other Planning Approaches.

This paper studies the Fast Marching Square (FM2) method as a competitive path planner for UAV applications. The approach fulfills trajectory curvature constraints together with a significantly reduced computation time, which makes it overperform with respect to other planning methods of the literature based on optimization. A comparative analysis is presented to demonstrate how the FM2 approach can easily adapt its performance thanks to the introduction of two parameters, saturation α and exponent β, that allow a flexible configuration of the paths in terms of curvature restrictions, among others.

Multi UAV Coverage Path Planning in Urban Environments.

Coverage path planning (CPP) is a field of study which objective is to find a path that covers every point of a certain area of interest. Recently, the use of Unmanned Aerial Vehicles (UAVs) has become more proficient in various applications such as surveillance, terrain coverage, mapping, natural disaster tracking, transport, and others. The aim of this paper is to design efficient coverage path planning collision-avoidance capable algorithms for single or multi UAV systems in cluttered urban environments.

Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer.

Purpose: Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking.

Patients And Methods: Eighty-nine patients with oligometastatic CRPC were identified by C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR.

Chemotherapy with atezolizumab for small cell or neuroendocrine carcinoma of the prostate: A single institution experience.

Introduction: Chemotherapy in combination with immunotherapy has a proven survival benefit compared to chemotherapy alone in extensive stage small cell lung cancer (SCLC) and is the new standard of care. Since extrapulmonary small cell carcinomas (SCCs) are less common, treatment paradigms are reasonably extrapolated from SCLC regimens. We examined our institution's experience utilizing the combination of chemotherapy and immunotherapy (as used in SCLC) for SCC and neuroendocrine carcinoma of the prostate.

Chemoimmunotherapy after progression on single-agent pembrolizumab for metastatic urothelial carcinoma: a case series.

Those with metastatic urothelial carcinoma generally respond more poorly to chemotherapy after they have progression on a checkpoint inhibitor (CPI). There is interest in combining CPIs with conventional cytotoxic chemotherapies as a strategy to exploit the efficacy and immunomodulatory effects of chemotherapy. We conducted a single institution, retrospective analysis including all patients treated between May 2018 and May 2020 with carboplatin and paclitaxel, concurrently or sequential with pembrolizumab, after having progression on a CPI alone.

Path Planning and Collision Risk Management Strategy for Multi-UAV Systems in 3D Environments.

Multi-UAV systems are attracting, especially in the last decade, the attention of researchers and companies of very different fields due to the great interest in developing systems capable of operating in a coordinated manner in complex scenarios and to cover and speed up applications that can be dangerous or tedious for people: search and rescue tasks, inspection of facilities, delivery of goods, surveillance, etc. Inspired by these needs, this work aims to design, implement and analyze a trajectory planning and collision avoidance strategy for multi-UAV systems in 3D environments. For this purpose, a study of the existing techniques for both problems is carried out and an innovative strategy based on Fast Marching Square-for the planning phase-and a simple priority-based speed control-as the method for conflict resolution-is proposed, together with prevention measures designed to try to limit and reduce the greatest number of conflicting situations that may occur between vehicles while they carry out their missions in a simulated 3D urban environment.

Predictors of Locoregional Recurrence and Delineation of Adjuvant Radiation Therapy Fields for Patients With Upper Tract Urothelial Carcinoma Receiving Nephroureterectomy.

Purpose: To identify factors predictive of locoregional recurrence (LRR) in upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy and to propose adjuvant radiation therapy (ART) fields.

Methods And Materials: Clinical and pathologic variables for patients receiving nephroureterectomy for UTUC between 1995 and 2009 were analyzed for associations with outcomes. Sites of LRR from all patients with available imaging (39) were contoured on computed tomography image sets of patients with representative anatomy, and ART fields were proposed based on these distributions.

Changes in Frequency of Surveillance Imaging of Survivors of Diffuse Large B-Cell Lymphoma After the American Society of Hematology Choosing Wisely Recommendations.

In 2013, the American Society of Hematology (ASH) published recommendations with Choosing Wisely to limit surveillance imaging in aggressive lymphoma. We studied surveillance imaging practice patterns for diffuse large B-cell lymphoma (DLBCL) before and after the ASH Choosing Wisely campaign. We used OptumLabs Data Warehouse, a national insurance claims database, to retrospectively study imaging frequency in survivors of DLBCL from 2008 to 2016.

Penile cancer with visceral metastasis and p16/human papillomavirus positivity: An unusual case of long-term survival.

Squamous cell carcinoma (SCC) of the penis is a rare cancer in the industrialized countries, including the United States. Risk factors for these cancers include inflammatory conditions as well as infection with the human papilloma virus (HPV). Treatment modalities are based on TNM staging and may include surgical management or chemoradiation.

Use of Imaging During Staging and Surveillance of Localized Colon Cancer in a Large Insured Population.

Background: Adherence to surveillance guidelines in resected colon cancer has significant implications for patient morbidity, cost of care, and healthcare utilization. This study measured the underuse and overuse of imaging for staging and surveillance in stage I-II colon cancer.

Methods: The OptumLabs database was queried for administrative claims data on adult patients with stage I-II colon cancer who underwent surgery alone in 2008 through 2016.

C-Choline PET Guided Salvage Radiation Therapy for Isolated Pelvic and Paraortic Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Rationale and Early Genitourinary or Gastrointestinal Toxicities.

Purpose: To assess gastrointestinal (GI) and genitourinary (GU) adverse events (AEs) of C-choline-positron emission tomography (CholPET) guided lymph node (LN) radiation therapy (RT) in patients who experience biochemical failure after radical prostatectomy.

Methods And Materials: From 2013 to 2016, 107 patients experienced biochemical failure of prostate cancer, had CholPET-detected pelvic and/or paraortic LN recurrence, and were referred for RT. Patients received androgen suppression and CholPET guided LN RT (median dose, 45 Gy) with a simultaneous integrated boost to CholPET-avid sites (median dose, 56.

Delaying Radical Cystectomy After Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer is Associated with Adverse Survival Outcomes.

Background: Delaying radical cystectomy (RC) after a diagnosis of muscle-invasive bladder cancer (MIBC) has been associated with adverse survival. However, data are lacking regarding the impact of RC delay in patients receiving neoadjuvant chemotherapy (NAC).

Objectives: To assess whether the time from last cycle of NAC to RC (time to cystectomy, TTC) is associated with survival among MIBC patients.

Clinical predictors and survival outcome of patients receiving suboptimal neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer: a single-center experience.

Purpose: To investigate the prevalence of and factors' association with receiving suboptimal neoadjuvant chemotherapy (NAC) and its impact on survival outcomes in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC).

Methods: We reviewed 1119 patients treated with NAC and/or RC for cT2-cT4N0M0 BC. Patients were segregated into three groups: (i) suboptimal NAC (received < 3 cycles of cisplatin-based NAC or non-cisplatin-based regimen), (ii) optimal NAC and (iii) no NAC.

Cigarette smoking is associated with adverse pathological response and increased disease recurrence amongst patients with muscle-invasive bladder cancer treated with cisplatin-based neoadjuvant chemotherapy and radical cystectomy: a single-centre experience.

Objective: To investigate the association between smoking status and pathological response to cisplatin-based neoadjuvant chemotherapy (NAC) and survival outcomes in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC).

Patients And Methods: We reviewed 201 patients treated with NAC and RC for cT2-cT4N0M0 BC between 01/1999 and 01/2015. Smoking status was categorised as: 'never', 'former', and 'current' smoker.

Serum chromogranin-A-based prognosis in metastatic castration-resistant prostate cancer.

Objective: To determine the prognostic value of serum chromogranin-A (CGA) in a two-cohort study of men with metastatic castrate resistant prostate cancer (mCRPC) and to compare with circulating tumor cells (CTCs)-based prognosis.

Patients And Methods: A two-cohort-based evaluation for serum CGA for prognostication in CRPC stage was performed using a screening cohort of 256 men with mCRPC and an independent validation cohort of 92 men with mCRPC. In both cohorts, men receiving proton pump inhibitors and those with non-castrate levels of testosterone (>50 ng/dl) were excluded.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma.

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance.

Low hypoxia inducible factor-1α (HIF-1α) expression in testicular germ cell tumors - a major reason for enhanced chemosensitivity?

The molecular basis for enhanced chemosensitivity of testicular germ cell tumors (GCT) has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of GCT has been variously attributed to multiple factors - an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology leading to the aforementioned processes and having a translational implication has so far been elusive. Herein, we offer evidence to support a potential significant role for the previously demonstrated low hypoxia inducible factor-1α (HIF-1α) expression in mediating the general exquisite chemosensitivity of testicular GCT, through the aforementioned processes.

Identification of Recurrence Sites Following Post-Prostatectomy Treatment for Prostate Cancer Using C-Choline Positron Emission Tomography and Multiparametric Pelvic Magnetic Resonance Imaging.

Purpose: We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging.

Materials And Methods: After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features.