Noelle L. Williams

RB Loss Promotes Prostate Cancer Metastasis

RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that RB loss in multiple murine models of cancer produces a prometastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelial-mesenchymal transition, motility, and invasion by cancer cells. Genetic modulation or pharmacologic inhibition of RHAMM activity was sufficient and necessary for metastatic phenotypes induced by RB loss in prostate cancer. Mechanistic studies in this setting established that RHAMM stabilized F-actin polymerization by controlling ROCK signaling. Collectively, our findings show how RB loss drives metastatic capacity and highlight RHAMM as a candidate therapeutic target for treating advanced prostate cancer. Cancer Res; 77(4); 982-95. ©2016 AACR.

A pilot study to determine if the use of a virtual reality education module reduces anxiety and increases comprehension in patients receiving radiation therapy

ObjectivesPre-treatment patient education has been shown to decrease anxiety and enhance comprehension. Our pilot study evaluates the impact of VERT™, a virtual environment education tool, on these endpoints.MethodsTwenty-two patients with prostate cancer being treated with radiotherapy completed a 16-question comprehension/anxiety survey. Patients proceeded to VERT™, modeled after a flight simulator using realistic sounds and views. The test was then repeated. A power analysis determined that enrolling 20 patients achieves 80% power to detect an effect size of 0.89 with a Bonferroni-adjusted significance level of 0.003125 using a one-sided one-sample paired t test to analyze differences between individual pre/post-test scores. Descriptive statistics were reported and effect size was computed.ResultsPre/post-test measures for all questions were statistically significant, favoring our hypothesis of improved education and reduced anxiety following virtual simulation except three measures of anxiety (low in both assessments). Baseline anxiety was highest for treatment precision, which also demonstrated the most significant pre/post-intervention improvement.ConclusionDecreased anxiety and improved comprehension influence patient-reported satisfaction and can contribute to quality assurance. Implementation of virtual simulation was successful in improving comprehension and reducing anxiety. Development of personalized, site-specific, clinic-based virtual modules is a long-term goal of this pilot study.

Scalp-sparing total skin electron therapy in mycosis fungoides: Case report highlighting technique and outcome.

Among the classically described cutaneous T-cell lymphomas, mycosis fungoides (MF) is the most common. Patients typically present with pruritic patches or tumors of the skin. Prognosis relates to age, stage, and the presence of extracutaneous disease.1,2 Total skin electron therapy (TSET) has emerged as the single most effective targeted therapy for patients with MF. Historically, complete response rates improved with dose escalation from 8 Gy to 36 Gy. Also seen with dose escalation was an increase in toxicity including dry desquamation, skin erythema, alopecia, anhidrosis, and loss of fingernails.1,3 Therefore, more recent studies have focused on the impact of dose de-escalation on toxicity and response rates. A pooled analysis published by Hoppe et al. explored low-dose (12 Gy, 1 Gy per fraction) TSET for patients with stage IB to IIIA disease. Of the 33 evaluable patients, the majority experienced a rapid reduction of disease burden and minimal toxicities.1 Alopecia remains a common concern of patients preceding TSET. In the aforementioned study, 1 female patient with stage IIB

Brain Metastases in Patients with Gynecologic Cancers: A Single Institution Experience and Review of the Literature

Objective: Brain Metastasis (BM) from primary gynecologic cancers is a rare entity. The advances and successes in the treatment of primary gynecologic malignancies, have led to prolonged survival and, a higher incidence of BM. This study aims to report the experience at our institution in managing these patients, and provide possible data points that may be essential to note as prognostic factors, and see if our findings are consistent with the literature in this subject. We also aim to provide a brief literature review of patients with gynecologic cancers and BM. Methods: This is a small single institution retrospective study of 23 patients with a gynecologic malignancy and BM, identified between the years 2007–2015. Data were collected on variables including patient demographics, disease and treatment. Results: The median overall survival from the primary diagnosis was 28 months. Median time from diagnosis of BM to death was 9 months. Conclusion: The outcomes in our study are similar to what is stated in the current literature with regard to BM from gynecologic malignancies. Our literature search also revealed that the molecular analysis and treatment of the primary tumor remain important to prevent BMs. The tendency of tumors to metastasize varies for one tumor type to another for the same type of tumor. The tendency to develop BM may not only depend on risk factors such as stage, grade, and histology, but also on the genetic profile of the primary tumor. The study suggests that multimodal treatment of BM has better outcomes in managing BM from gynecologic cancers.

Radioisotopes in management of metastatic prostate cancer

Introduction: Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting. However, the first in class radiopharmaceutical radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival. Methods: Medline publications from 1990 to 2016 were searched and reviewed to assess the use of currently approved radioisotopes in the management of prostate cancer including emerging data regarding integration with novel systemic therapies. New positron emission tomography-based radiotracers for advanced molecular imaging of prostate cancer were also queried. Results: Radioisotopes play a crucial role in the diagnosis and treatment of prostate cancer in the definitive and metastatic setting. Molecular imaging of prostate cancer and theranostics are currently being investigated in the clinical arena. Conclusions: The use of modern radioisotopes in selected patients with mCRPC is associated with improvements in overall survival, pain control, and quality of life.

Radiation Therapy for Melanoma

Radiotherapy works by inducing DNA damage in cancer cells, and there are several different methods of radiotherapy delivery including external beam radiotherapy, stereotactic radiosurgery, stereotactic body radiotherapy, radiospheres, brachytherapy, and particle therapy. Historically, melanoma has been deemed a radioresistant tumor, due to early in vitro studies demonstrating a broad shoulder in cell survival curves as well as a high repair rate, inferring a better tumor response with higher radiation doses. For this reason, hypofractionated regimens have become commonplace in the treatment of melanoma given the tolerability, convenience, and low risk of late effects. Nonetheless, in the treatment of primary melanoma, maximal safe surgical resection offers the greatest likelihood of local control. Radiotherapy as a primary treatment is often offered in well-defined situations, such as medical inoperability due to patient comorbidities or tumor location. Clinically, radiation oncologists most frequently see patients with melanoma for consultation in regard to palliation of metastatic disease (for example, stereotactic radiosurgery for brain metastasis or stereotactic body radiotherapy for lung metastasis). The multiple advancements (including technological developments as well as evolution of systemic therapy and immunotherapy) in the treatment of patients with melanoma highlight the importance of multidisciplinary management in this disease.

Treatment recommendations for elderly patients with newly diagnosed glioblastoma lack worldwide consensus

BackgroundGlioblastoma predominantly occurs in the 6th and 7th decades of life. The optimal treatment paradigm for elderly patients is not well established. We sampled current worldwide management strategies for elderly patients with newly diagnosed glioblastoma.MethodsA web-based survey was developed and distributed to 168 radiation oncologists, neuro-oncologists and neurosurgeons identified through the United Council for Neurologic Subspecialties and the CNS committees for North American, European and Asian Organizations. Questions addressed treatment recommendations in order to determine whether management consensus exists in this patient subset.ResultsThere were 68 (40%) respondents. Across respondents, the most important factors directing treatment were KPS (94%) and MGMT methylation status (71%). Only 37% of respondents strictly factor in age when making treatment recommendations with 59% defining elderly as greater than 70 years-old. The most common treatment recommendations for MGMT-methylated elderly patients with KPS > 70 were as follows: standard chemoRT (49%), short course chemoRT (39%), and temozolomide alone (30%). The most common treatment recommendations for MGMT-unmethylated patients with KPS > 70 were as follows: short course RT alone (51%), standard chemoRT (38%), and short course chemoRT (28%). Treatment recommendations for patients with KPS < 50 were short course RT alone (40%), best supportive care (57%), or TMZ alone (17%). Individuals practicing in North America were significantly more likely to recommend standard chemoradiation for patients compared to their European counterparts.ConclusionWorldwide treatment recommendations for elderly patients with newly diagnosed GBM vary widely. Further randomized studies are needed to elucidate the optimal treatment strategy for this subset of patients.

Clinical Integration of Digital Solutions in Health Care: An Overview of the Current Landscape of Digital Technologies in Cancer Care

Digital health constitutes a merger of both software and hardware technology with health care delivery and management, and encompasses a number of domains, from wearable devices to artificial intelligence, each associated with widely disparate interaction and data collection models. In this review, we focus on the landscape of the current integration of digital health technology in cancer care by subdividing digital health technologies into the following sections: connected devices, digital patient information collection, telehealth, and digital assistants. In these sections, we give an overview of the potential clinical impact of such technologies as they pertain to key domains, including patient education, patient outcomes, quality of life, and health care value. We performed a search of PubMed ( www.ncbi.nlm.nih.gov/pubmed ) and www.ClinicalTrials.gov for numerous terms related to digital health technologies, including digital health, connected devices, smart devices, wearables, activity trackers, connected sensors, remote monitoring, electronic surveys, electronic patient-reported outcomes, telehealth, telemedicine, artificial intelligence, chatbot, and digital assistants. The terms health care and cancer were appended to the previously mentioned terms to filter results for cancer-specific applications. From these results, studies were included that exemplified use of the various domains of digital health technologies in oncologic care. Digital health encompasses the integration of a vast array of technologies with health care, each associated with varied methods of data collection and information flow. Integration of these technologies into clinical practice has seen applications throughout the spectrum of care, including cancer screening, on-treatment patient management, acute post-treatment follow-up, and survivorship. Implementation of these systems may serve to reduce costs and workflow inefficiencies, as well as to improve overall health care value, patient outcomes, and quality of life.

Management of Stage I Lung Cancer with Stereotactic Ablative Radiation Therapy

Early stage non-small cell lung cancer is a growing clinical entity with evolving standards of care. With the adoption of lung screening guidelines, the incidence of early stage disease is expected to increase. Surgical resection for early stage disease has been considered standard of care; however, there is evidence that stereotactic ablative radiation therapy (SABR) may be a viable alternate to surgery. In the last decade, advances in image guidance, treatment planning systems, and improved spatial accuracy of treatment delivery have converged to result in the effective use of SABR in the treatment of early stage lung cancer.

Radium-223 in Metastatic Castrate Resistant Prostate Cancer

Metastatic disease continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with metastatic castrate resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. These new agents include the incorporation of newer cytotoxics, next generation anti-androgens, immunotherapeutics, and radiopharmaceuticals. Of these available treatments, the first in class radiopharmaceutical Radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival. In this chapter we will discuss the development of Radium-223 in prostate cancer, its unique mechanism of action, clinical outcome data, practical use, and future directions.