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Cancer Journal

Daniel H Hovelson, Scott A Tomlins
Molecular biomarkers play little role in the current treatment of metastatic castration-resistant prostate cancer (CRPC). The advent of next-generation sequencing (NGS) has enabled the comprehensive molecular characterization of the genomic and transcriptomic landscape of both untreated primary prostate cancer and CRPC. Recent studies demonstrating the feasibility of interinstitution studies obtaining and NGS profiling of metastatic biopsies, targeted NGS approaches applicable to routine formalin-fixed, paraffin-embedded specimens, and NGS approaches applicable to circulating DNA and circulating tumor cells portend near-term adoption of NGS approaches in the management and treatment of CRPC...
September 2016: Cancer Journal
Elena Castro, Joaquin Mateo, David Olmos, Johann S de Bono
Several genomic studies have identified DNA repair gene defects in prostate cancer in the last 5 years. The mechanisms by which these DNA repair defects promote carcinogenesis and tumor progression in the prostate have not been fully elucidated, but their presence in at least 20-25% of metastatic castration-resistant prostate cancers (CRPCs) provides an opportunity for a therapeutic strategy that turns a tumor strength into its weakness and may lead to arguably the first molecularly stratified treatment for this disease...
September 2016: Cancer Journal
Min Yuen Teo, Michael J Morris
Prostate-specific membrane antigen (PSMA) is highly expressed on both benign and malignant prostatic tissue. Prostate-specific membrane antigen-directed therapy is conceptually promising, with a potential to additionally serve as a theranostic model in management of advanced prostate cancer. To date, various approaches have been devised and tested, including radiolabeled PSMA antibodies and inhibitor and antibody-drug conjugates. However, development and progress have faced challenges in determining the optimal combination of payload, PSMA-binding moiety, and linker technology...
September 2016: Cancer Journal
Oliver Sartor
Radiopharmaceuticals used in the treatment of castrate-resistant prostate cancer are reviewed herein with an emphasis on sequential and combination therapies. Four bone-seeking radiopharmaceuticals had been approved in the United States. Three of these are β-emitters (phosphorus-32, strontium-89, samarium-153-ethylenediaminetetramethylene-phosphonic acid) that are approved for palliative purposes. One α-emitter (radium-223 [Ra]) is approved for prolongation of survival in bone metastatic castrate-resistant prostate cancer...
September 2016: Cancer Journal
Oladapo Yeku, Susan F Slovin
Immunotherapy for castration-resistant prostate cancer has continued to be an area of active research over the last several years. The enthusiasm of this approach has been based on the assumption of better tolerability and that using the body's own immune system may be more effective than either hormonal or chemotherapy. Sipuleucel-T, a dendritic cell-based vaccine, is the only approved agent in this class for the management of castrate-resistant prostate cancer. Although sipuleucel-T increases overall survival without any significant changes in progression-free survival, other forms of immunotherapy such as PSA-TRICOM, ipilimumab, and chimeric antigen receptor T cell therapy are in advanced stages of clinical development...
September 2016: Cancer Journal
Michael W Drazer, Walter M Stadler
Most men with metastatic prostate cancer who are treated with androgen deprivation therapy will eventually develop castration-resistant disease. In this review, we examine the molecular mechanisms that constitute castration resistance and how these processes may be exploited using testosterone-based therapies. We detail how the utilization of superphysiologic doses of testosterone at regular intervals, followed by a rapid clearance of testosterone through continued chemical castration, also known as bipolar androgen therapy, offers an especially promising therapeutic approach...
September 2016: Cancer Journal
Zachery R Reichert, Maha Hussain
The development of metastatic castration-resistant prostate cancer (mCRPC) signals the terminal disease phase. The preceding hormone-dependent disease setting is effectively managed with androgen deprivation therapy. This foundation of treatment has a high rate of biochemical and clinical response and meaningful clinical benefit but is finite in duration as most cancers will progress to castration resistance. Historically, treatment for mCRPC entailed androgen receptor (AR) inhibitors (nilutamide, flutamide, bicalutamide), nonspecific steroidal biosynthesis inhibitors (ketoconazole, itraconazole), steroids (prednisone, diethylstilbesterol, dexamethasone), or palliative chemotherapy (mitoxantrone, estramustine), but none of these strategies impacted survival...
September 2016: Cancer Journal
Christos E Kyriakopoulos, Glenn Liu
Ever since the critical role of androgen deprivation therapy for the treatment of metastatic prostate cancer was established, several trials aimed to show an improved outcome with the early introduction of chemotherapy in metastatic disease. Until recently, all these trials-including the GETUG-AFU 15 trial-failed to confirm an improvement in survival. The recently published CHAARTED and STAMPEDE trials showed a striking benefit and changed the standard of care for patients with newly diagnosed metastatic prostate cancer...
September 2016: Cancer Journal
Daniel P Petrylak
No abstract text is available yet for this article.
September 2016: Cancer Journal
Daniel C Danila, Aliaksandra Samoila, Chintan Patel, Nicole Schreiber, Amrita Herkal, Aseem Anand, Diogo Bastos, Glenn Heller, Martin Fleisher, Howard I Scher
Circulating tumor cell (CTC) number measured with the CellSearch assay is prognostic for survival in metastatic castration-resistant prostate cancer before and after therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch performed using US Food and Drug Administration-cleared methodology with a second positive selection assay, AdnaTest, and a nonselection polymerase chain reaction (PCR)-based (direct detection PCR [DDPCR]) assay in 55 blood samples from 47 men with progressive metastatic castration-resistant prostate cancer...
September 2016: Cancer Journal
Jonathan W Lischalk, Irving D Kaplan, Sean P Collins
Stereotactic body radiation therapy (SBRT) has become a viable treatment option for the many patients who receive a diagnosis of localized prostate cancer each year. Technological advancements have led to tight target conformality, allowing for high-dose-per-fraction delivery without untoward normal tissue toxicity. Biochemical control, now reported up to 5 years, appears to compare favorably with dose-escalated conventionally fractionated radiotherapy. Moreover, toxicity and quality of life follow-up data indicate genitourinary and gastrointestinal toxicities are likewise comparable to conventional radiation therapy...
July 2016: Cancer Journal
Diane C Ling, John A Vargo, Dwight E Heron
Stereotactic body radiation therapy (SBRT) offers a promising opportunity for cure and/or palliation to patients with recurrent head and neck cancer whose comorbidities, performance status, and history of prior treatment may preclude many other salvage options. Stereotactic body radiation therapy appears to have a favorable response and toxicity profile compared with other nonoperative salvage options for recurrent head and neck cancer. However, the risk of severe toxicity remains, with carotid blowout syndrome a unique concern, although the incidence of this complication may be minimized with alternating-day fractionation...
July 2016: Cancer Journal
Andrew J McPartlin, Laura A Dawson
Hepatocellular carcinoma (HCC) is a leading cause of cancer death. Experience with radiotherapy for HCC is increasing. Stereotactic body radiotherapy allows the delivery of tumoricidal doses in 3 to 6 treatments to focal HCC with low rates of toxicity and excellent local control. Stereotactic body radiotherapy can be used to control disease in patients unsuitable for other conventional therapies. How it might optimally be used to improve outcomes, including its use in combination with other therapies, is an area of active research, and further randomized studies are needed...
July 2016: Cancer Journal
Karyn A Goodman
The role of radiation therapy in the management of pancreatic cancer represents an area of some controversy. However, local disease progression remains a significant cause of morbidity and even mortality for patients with this disease. Stereotactic body radiotherapy (SBRT) is an emerging treatment option for pancreatic cancer, primarily for locally advanced (unresectable) disease as it can provide a therapeutic benefit with significant advantages for patients' quality of life over standard conventional chemoradiation...
July 2016: Cancer Journal
Siavash Jabbari, Peter C Gerszten, Mark Ruschin, David A Larson, Simon S Lo, Arjun Sahgal
Spine metastases can be a debilitating and difficult therapeutic challenge for a significant number of cancer patients. Surgical management of spine metastases is often limited because of the complexity, risks, and recovery delays associated with open invasive surgical procedures. Conventional palliative external beam radiation therapy is the most common treatment modality. However, it is associated with limited palliative efficacy and local tumor control, including in the postoperative setting. In the era of improving systemic disease control, spine stereotactic body radiotherapy is fast emerging as the therapeutic modality of choice for selected de novo, postoperative, and salvage reirradiation spine metastases patients...
July 2016: Cancer Journal
Genevieve Maquilan, Robert Timmerman
Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy, is a technique of external beam radiation that delivers precisely targeted, ablative doses to extracranial sites. It has become an integral component of the management of early-stage non-small cell lung cancer (NSCLC). In this review, we discuss the technology and techniques used in treatment planning and delivery, the efficacy and toxicity of SBRT for medically inoperable early-stage NSCLC, and the preliminary investigations into the role of SBRT for operable early-stage NSCLC...
July 2016: Cancer Journal
Everett J Moding, Yvonne M Mowery, David G Kirsch
Stereotactic body radiation therapy (SBRT) utilizing a small number of high-dose radiation therapy fractions continues to expand in clinical application. Although many approaches have been proposed to radiosensitize tumors with conventional fractionation, how these radiosensitizers will translate to SBRT remains largely unknown. Here, we review our current understanding of how SBRT eradicates tumors, including the potential contributions of endothelial cell death and immune system activation. In addition, we identify several new opportunities for radiosensitization generated by the move toward high dose per fraction radiation therapy...
July 2016: Cancer Journal
Eric D Brooks, Jonathan E Schoenhals, Chad Tang, Goran Micevic, Daniel R Gomez, Joe Y Chang, James W Welsh
Immunotherapy, particularly immune-checkpoint inhibition, is producing encouraging clinical responses and affecting the way numerous cancers are treated. Yet immune-checkpoint therapy is not effective for many patients, and even those who initially respond can experience relapse, fueling interest in finding new processes or tools to improve the effectiveness of these novel therapeutics. One such tool is radiation. Both preclinical and clinical studies have demonstrated that the systemic effects of immunotherapy can be amplified when it is used in combination with radiation and, conversely, that the immunogenic effects of local irradiation can be amplified and extended to distant sites when used with immunotherapy...
July 2016: Cancer Journal
Rohann J M Correa, Joseph K Salama, Michael T Milano, David A Palma
Oligometastasis refers to a state of limited metastatic disease burden, in which surgical or ablative treatment to all known visible metastases holds promise to extend survival or even effect cure. Stereotactic body radiotherapy is a form of radiation treatment capable of delivering a high biologically effective dose of radiation in a highly conformal manner, with a favorable toxicity profile. Enthusiasm for oligometastasis ablation, however, should be counterbalanced against the limited supporting evidence...
July 2016: Cancer Journal
Brian D Kavanagh
No abstract text is available yet for this article.
July 2016: Cancer Journal
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