Elizabeth R. Kessler

Local control rates of metastatic renal cell carcinoma (RCC) to the bone using stereotactic body radiation therapy: Is RCC truly radioresistant?

PURPOSE We report the radiographic and clinical response rate of stereotactic body radiation therapy (SBRT) compared with conventional fractionated external beam radiation therapy (CF-EBRT) for renal cell carcinoma (RCC) bone lesions treated at our institution. METHODS AND MATERIALS Forty-six consecutive patients were included in the study, with 95 total lesions treated (50 SBRT, 45 CF-EBRT). We included patients who had histologic confirmation of primary RCC and radiographic evidence of metastatic bone lesions. The most common SBRT regimen used was 27 Gy in 3 fractions. RESULTS Median follow-up was 10 months (range, 1-64 months). Median time to symptom control between SBRT and CF-EBRT were 2 (range, 0-6 weeks) and 4 weeks (range, 0-7 weeks), respectively. Symptom control rates with SBRT and CF-EBRT were significantly different (P = .020) with control rates at 10, 12, and 24 months of 74.9% versus 44.1%, 74.9% versus 39.9%, and 74.9% versus 35.7%, respectively. The median time to radiographic failure and unadjusted pain progression was 7 months in both groups. When controlling for gross tumor volume, dose per fraction, smoking, and the use of systemic therapy, biologically effective dose ≥80 Gy was significant for clinical response (hazard ratio [HR], 0.204; 95% confidence interval [CI], 0.043-0.963; P = .046) and radiographic (HR, 0.075; 95% CI, 0.013-0.430; P = .004). When controlling for gross tumor volume and total dose, biologically effective dose ≥80 Gy was again predictive of clinical local control (HR, 0.140; 95% CI, 0.025-0.787; P = .026). Toxicity rates were low and equivalent in both groups, with no grade 4 or 5 toxicity reported. CONCLUSIONS SBRT is both safe and effective for treating RCC bone metastases, with rapid improvement in symptoms after treatment and more durable clinical and radiographic response rate. Future prospective trials are needed to further define efficacy and toxicity of treatment, especially in the setting of targeted agents.

Distress among caregivers of phase I trial participants: a cross-sectional study

PurposeThe number of patients with cancer enrolling in phase I trials is expected to increase as these trials incorporate patient selection and exhibit greater efficacy in the era of targeted therapies. Despite the fact that people with advanced cancer often require a caregiver, little is known about the experience of caregivers of people enrolling in oncology phase I clinical trials. We conducted a cross-sectional study assessing the distress and emotion regulation of caregivers of phase I trial participants to inform the design of future interventions targeting the unique needs of this population.MethodsCaregivers of oncology patients were approached at the patient’s phase I clinical trial screening visit. Caregiver participants completed a one-time survey incorporating validated instruments to comprehensively assess distress and emotion regulation. Basic demographic information about both the caregiver and patient was collected.ResultsCaregivers exhibited greater distress than population norms. Emotion regulation was also moderately impaired. Respondents identified positive aspects of caregiving despite exhibiting moderate distress.ConclusionEnrollment of a patient in a phase I clinical trial is a time of stress for their caregivers. This pilot study demonstrates the feasibility of engaging caregivers of phase I trial participants and the need to better support them through this component of their caregiving experience.

Geriatric considerations in the treatment of advanced prostate cancer

Prostate cancer is the most common non-cutaneous cancer in US men and mainly affects elderly patients, with most new diagnoses occurring in those over 65. As the geriatric population in the US continues to grow, the incidence of this disease is likewise expected to rise. Many older patients are diagnosed with advanced disease or are treated only when their disease becomes symptomatic or metastatic. The treatment options for advanced prostate cancer have increased dramatically in the last decade. It is important to understand the nuances of caring for an elderly cancer patient in order to optimally treat prostate cancer, such as the importance of using a geriatric assessment to uncover overlooked or under-reported vulnerabilities. In addition, many of the newly approved agents for the treatment of advanced prostate cancer have a unique mechanism of action and toxicities that warrant consideration when choosing therapies for older patients. This review focuses on the importance of a geriatric assessment as well as the considerations of treating elderly patients with the newer agents approved for prostate cancer.

Patient characterization and usage trends of proton beam therapy for localized prostate cancer in the United States: A study of the National Cancer Database

PURPOSE To evaluate usage trends and identify factors associated with proton beam therapy (PBT) compared to alternative forms of external beam radiation therapy (RT) (EBRT) for localized prostate cancer. PATIENTS AND METHODS The National Cancer Database was queried for men with localized (N0, M0) prostate cancer diagnosed between 2004 and 2013, treated with EBRT, with available data on EBRT modality (photon vs. PBT). Binary multiple logistic regression identified variables associated with EBRT modality. RESULTS In total, 143,702 patients were evaluated with relatively few men receiving PBT (5,709 [4.0%]). Significant differences in patient and clinical characteristics were identified between those men treated with PBT compared to those treated with photon (odds ratio [OR]; 95% CI). Patients treated with PBT were generally younger (OR = 0.73; CI: 0.67-0.82), National Comprehensive Cancer Network low-risk compared to intermediate (0.71; 0.65-0.78) or high (0.44; 0.38-0.5) risk, white vs. black race (0.66; 0.58-0.77), with less comorbidity (Charlson-Deyo 0 vs. 2+; 0.70; 0.50-0.98), live in higher income counties (1.55; 1.36-1.78), and live in metropolitan areas compared to urban (0.21; 0.18-0.23) or rural (0.14; 0.10-0.19) areas. Most patients treated with PBT travelled more than 100 miles to the treatment facility. Annual PBT utilization significantly increased in both total number and percentage of EBRT over time (2.7%-5.6%; P<0.001). PBT utilization increased mostly in men classified as National Comprehensive Cancer Network low-risk (4%-10.2%). CONCLUSION PBT for men with localized prostate cancer significantly increased in the United States from 2004 to 2013. Significant demographic and prognostic differences between those men treated with photons and protons were identified.

Renal cell carcinoma: a review of biology and pathophysiology

Over the past decade, our understanding of the biology and pathophysiology of renal cell carcinoma (RCC) has improved significantly. Insight into the disease process has helped us in developing newer therapeutic approaches toward RCC. In this article, we review the various genetic and immune-related mechanisms involved in the pathogenesis and development of this cancer and how that knowledge is being used to develop therapeutic targeted drugs for the treatment of RCC. The main emphasis of this review article is on the most common genetic alterations found in clear cell RCC and how various drugs are currently targeting such pathways. This article also looks at the role of the immune system in allowing the growth of RCC and how the immune system can be manipulated to reactivate cytotoxic immunity against RCC.

Treatment of Metastatic Prostate Cancer in Older Adults

The aging of the population, along with rising life expectancy, means that increasing numbers of older men will be diagnosed with prostate cancer, and a large proportion of these men will present with metastatic disease. In this paper, we discuss recent advances in prostate cancer treatment. In particular, we review management approaches for older patients with metastatic prostate cancer based on the decision tree developed by the International Society of Geriatric Oncology, which categorized older men as “fit,” “vulnerable,” and “frail” according to comprehensive geriatric assessment.

Capsule commentary on Tomko et al., A comparison of web- versus print-based decision AIDS for prostate cancer screening: participants' evaluation and utilization.

C. Tomko et al.1 compares web-based and print-based decision tools for prostate cancer screening. Using an already supported prostate cancer screening decision aid, they asked the practical question of how these tools are best implemented. In their cohort of 1,235 adults, decision aid use was independently influenced by race, education, and the decision aid medium. The best choice based on preference and utilization was print medium. Thus, in an increasingly digitized age, there is still a role for paper and pencil. Decision aids are helpful when patients are faced with complex decisions with no clear-cut “best answer” and uncertain ramifications. There has been much discussion regarding the utility of prostate cancer screening with digital rectal exam and a serum prostate specific antigen (PSA), with most organizations recommending against routine screening.2 However, patients are still being screened under the rubric that this should be a shared decision thaht occurs after discussion between patient and provider. However, this decision has been shown to be biased by multiple factors on the part of the provider and patients,3 and the accuracy and amount of information provided is variable.4 Decision tools may be helpful and effective in these situations, by providing accurate evidence-based information to support decision-making. The current study is interesting not so much in that it adds to the support of using decision aids, but that it addresses how best to implement these effective tools. If we are to work to impact patient experience, we need to understand how best to apply evidence-supported methodology to real-world scenarios.5 Our medical systems have turned increasingly to electronic health records, and informational web portals; yet, this study concludes that print may be a preferred medium for many patients. An important factor for some patients is still internet access and computer skills. The “digital divide” still exists and requires recognition as these tools are implemented. The clearest implication from this study is that in an age of patient choice, even the format of the decision aid should be up to the patient.

Resistance to HER2-Targeted Therapy in HER2+ Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women and one of the earliest tumor types for which we have used molecular characterization of the tumor to guide treatment. Approximately one quarter of breast tumors show overexpression of HER2, a transmembrane receptor tyrosine kinase. This review focuses on the HER2 pathway and consequences of overexpression, or activation, of this signal. Trastuzumab, the first line monoclonal antibody directed at HER2 will also be described in terms of mechanism of action and influence on patient care. Additional focus will be paid to understanding mechanisms of primary and secondary resistance to the agent. We then attempt to describe the current milieu of therapeutic options for patients resistant or refractory to trastuzumab. There are certainly many new targeted agents as well as exciting preclinical data which may offer some direction for treatment of patients in whom trastuzumab is not an effective targeted agent.

Molecular Targeted Therapy of Bladder Cancer

The modern treatment of advanced urothelial carcinoma has been built on the foundation of platinum-containing combination chemotherapy. This therapeutic approach has been in place with little change in several decades. Urothelial carcinoma possesses a high prevalence of therapeutic targets including: Vascular Endothelial Growth Factor Receptor (VEGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Fibroblast Growth Factor Receptor (FGFR), among other pathways. Despite this target-rich environment, there are currently no molecularly targeted therapies in regular clinical use for the treatment of advanced urothelial carcinoma. Active clinical investigations, including randomized, phase 3 trials targeting these pathways are underway and will provide definitive results to these approaches. Recent genetic characterization of bladder cancer has provided new insights into the molecular-drivers of the disease and established new classification schemas, which may aid in our improved understanding of the disease and provide additional molecular targets. These newly characterized molecularly derived subtypes show similarities between subsets of bladder cancer patients and other cancer types such as lung and breast cancer. Several predictive biomarkers have been developed in bladder cancer including those based on gene expression signatures and single nucleotide polymorphisms (SNP), with the application of these approaches currently in active clinical investigation. With the recent approval of immune checkpoint inhibitor therapy for advanced bladder cancer, more attention is now being paid to therapeutic needs and opportunities in this disease. This, coupled with advances in molecular characterization of bladder cancer, presents a great opportunity for drug development and the rational integration of targeted agents in the care of bladder cancer patients.

Phase II Trial of Acai Juice Product in Biochemically Recurrent Prostate Cancer

Background: Plant derivatives have been studied as therapies for prostate cancer based on their purported anti-inflammatory and antioxidant properties and low toxicities. The acai berry is an example of a plant rich in phytochemicals, which may slow the growth of prostate cancer. Methods: This was a phase II, Simon 2-stage clinical trial in patients with biochemically recurrent prostate cancer with a primary endpoint of prostate-specific antigen (PSA) response. Patients were asymptomatic, with a rising PSA of at least 0.2 ng/mL, and were treated with twice daily intake of Acai Juice Product until PSA progression, with a primary endpoint of PSA response. Results: Twenty-one patients were enrolled in the first stage of the trial. One of those patients had a PSA response within the study time period. The PSA doubling time was lengthened in 71% of patients (95% confidence interval = 48% to 89%) on the trial, and in a small number of responders, this was sustained over an extended time. Conclusions: This study did not meet its primary endpoint of 50% PSA response. Nevertheless, the overall tolerability and effects on PSA stabilization warrant further exploration in a biochemically recurrent population.