Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma.

BACKGROUND: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent. A significant improvement in disease-free survival according to investigator assessment (the primary end point) was shown previously. Overall survival was the key secondary end point. Safety was a secondary end point. RESULTS: A total of 496 participants were assigned to receive pembrolizumab and 498 to receive placebo. As of September 15, 2023, the median follow-up was 57.2 months. The disease-free survival benefit was consistent with that in previous analyses (hazard ratio for recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87). A significant improvement in overall survival was observed with pembrolizumab as compared with placebo (hazard ratio for death, 0.62; 95% CI, 0.44 to 0.87; P = 0.005). The estimated overall survival at 48 months was 91.2% in the pembrolizumab group, as compared with 86.0% in the placebo group; the benefit was consistent across key subgroups. Pembrolizumab was associated with a higher incidence of serious adverse events of any cause (20.7%, vs. 11.5% with placebo) and of grade 3 or 4 adverse events related to pembrolizumab or placebo (18.6% vs. 1.2%). No deaths were attributed to pembrolizumab therapy. CONCLUSIONS: Adjuvant pembrolizumab was associated with a significant and clinically meaningful improvement in overall survival, as compared with placebo, among participants with clear-cell renal-cell carcinoma at increased risk for recurrence after surgery. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).

Clinical Evidence for the Benefits of Neoadjuvant Chemotherapy and Immunotherapy in Colon Cancer: A Concise Review.

Neoadjuvant chemotherapy (NAC) has long been considered technically difficult in locally advanced colon cancer (LACC). However, the introduction of oxaliplatin-based regimens led to a growing interest in NAC for patients with LACC. Several cohort studies showed that NAC was safe and reduced the rate of incomplete resection in patients with LACC. This was followed by the pivotal phase III FOxTROT trials, which showed significant benefits of NAC in this population. However, in patients with deficient mismatch repair (dMMR), the response to a neoadjuvant fluoropyrimidine regimen may be poor, limiting the benefit of NAC in this subset of patients. Neoadjuvant immunotherapy is a potential alternative for NAC in LACC patients with dMMR. In this concise review, we present the published clinical evidence evaluating the efficacy and safety of NAC and/or neoadjuvant immunotherapy in patients with LACC. Overall, the evidence suggests that NAC can be associated with significant downstaging and tumor regression, which facilitate surgical resection. However, the impact of NAC on long-term survival is still under investigation. Despite the promising results of NAC in LACC, several concerns still exist that necessitate further evidence. On the other hand, LACC patients with dMMR can benefit from neoadjuvant immunotherapy; however, further trials are still needed to confirm its effectiveness, as well as biomarkers that can predict response.

Novel findings from determination of common expressed plasma exosomal microRNAs in patients with psoriatic arthritis, psoriasis vulgaris, rheumatoid arthritis, and gouty arthritis.

Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy. Localized tumors can be treated successfully with surgical excision, but the presence of micrometastases, recurrence, and advanced disease are associated with high mortality rates, despite the use of chemotherapy with etoposide, doxorubicin, cisplatin (EDP), and mitotane. During the past decade, the characterization of ACC using genomic profiling and next-generation sequencing (NGS) has resulted in the proposed new targeted therapies for patients with advanced ACC. In 2018, the European Society of Endocrinology in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT) published clinical practice guidelines for the management of ACC. However, the authors of these new guidelines concluded that the evidence to support clinical management recommendations remains weak, as there remains a requirement for large-scale controlled clinical trials to support new targeted therapies. This review discusses the recent developments in the diagnosis, staging, and management of ACC, and the molecular changes that may be the basis for future personalized or targeted therapy, if supported by data from clinical trials.

Accreditation Standard Guideline Initiative for Tai Chi and Qigong Instructors and Training Institutions.

Evidence of the health and wellbeing benefits of Tai Chi and Qigong (TQ) have emerged in the past two decades, but TQ is underutilized in modern health care in Western countries due to lack of promotion and the availability of professionally qualified TQ instructors. To date, there are no government regulations for TQ instructors or for training institutions in China and Western countries, even though TQ is considered to be a part of Traditional Chinese medicine that has the potential to manage many chronic diseases. Based on an integrative health care approach, the accreditation standard guideline initiative for TQ instructors and training institutions was developed in collaboration with health professionals, integrative medicine academics, Tai Chi and Qigong master instructors and consumers including public safety officers from several countries, such as Australia, Canada, China, Germany, Italy, Korea, Sweden and USA. In this paper, the rationale for organizing the Medical Tai Chi and Qigong Association (MTQA) is discussed and the accreditation standard guideline for TQ instructors and training institutions developed by the committee members of MTQA is presented. The MTQA acknowledges that the proposed guidelines are broad, so that the diversity of TQ instructors and training institutions can be integrated with recognition that these guidelines can be developed with further refinement. Additionally, these guidelines face challenges in understanding the complexity of TQ associated with different principles, philosophies and schools of thought. Nonetheless, these guidelines represent a necessary first step as primary resource to serve and guide health care professionals and consumers, as well as the TQ community.

Development and Application of a Machine Learning Approach to Assess Short-term Mortality Risk Among Patients With Cancer Starting Chemotherapy.

Importance: Patients with cancer who die soon after starting chemotherapy incur costs of treatment without the benefits. Accurately predicting mortality risk before administering chemotherapy is important, but few patient data-driven tools exist. Objective: To create and validate a machine learning model that predicts mortality in a general oncology cohort starting new chemotherapy, using only data available before the first day of treatment. Design, Setting, and Participants: This retrospective cohort study of patients at a large academic cancer center from January 1, 2004, through December 31, 2014, determined date of death by linkage to Social Security data. The model was derived using data from 2004 through 2011, and performance was measured on nonoverlapping data from 2012 through 2014. The analysis was conducted from June 1 through August 1, 2017. Participants included 26 946 patients starting 51 774 new chemotherapy regimens. Main Outcomes and Measures: Thirty-day mortality from the first day of a new chemotherapy regimen. Secondary outcomes included model discrimination by predicted mortality risk decile among patients receiving palliative chemotherapy, and 180-day mortality from the first day of a new chemotherapy regimen. Results: Among the 26 946 patients included in the analysis, mean age was 58.7 years (95% CI, 58.5-58.9 years); 61.1% were female (95% CI, 60.4%-61.9%); and 86.9% were white (95% CI, 86.4%-87.4%). Thirty-day mortality from chemotherapy start was 2.1% (95% CI, 1.9%-2.4%). Among the 9114 patients in the validation set, the most common primary cancers were breast (21.1%; 95% CI, 20.2%-21.9%), colorectal (19.3%; 95% CI, 18.5%-20.2%), and lung (18.0%; 95% CI, 17.2%-18.8%). Model predictions were accurate for all patients (area under the curve [AUC], 0.940; 95% CI, 0.930-0.951). Predictions for patients starting palliative chemotherapy (46.6% of regimens; 95% CI, 45.8%-47.3%), for whom prognosis is particularly important, remained highly accurate (AUC, 0.924; 95% CI, 0.910-0.939). To illustrate model discrimination, patients were ranked initiating palliative chemotherapy by model-predicted mortality risk, and observed mortality was calculated by risk decile. Thirty-day mortality in the highest-risk decile was 22.6% (95% CI, 19.6%-25.6%); in the lowest-risk decile, no patients died. Predictions remained accurate across all primary cancers, stages, and chemotherapies, even for clinical trial regimens that first appeared in years after the model was trained (AUC, 0.942; 95% CI, 0.882-1.000). The same model also performed well for prediction of 180-day mortality (AUC for all patients, 0.870 [95% CI, 0.862-0.877]; highest- vs lowest-risk decile mortality, 74.8% [95% CI, 72.7%-77.0%] vs 0.2% [95% CI, 0.01%-0.4%]). Predictions were more accurate than estimates from randomized clinical trials of individual chemotherapies or the Surveillance, Epidemiology, and End Results data set. Conclusions and Relevance: A machine learning algorithm using electronic health record data accurately predicted short-term mortality among patients starting chemotherapy. Further research is necessary to determine the generalizability and feasibility of applying this algorithm in clinical settings.

Applied Informatics Decision Support Tool for Mortality Predictions in Patients With Cancer.

PURPOSE: With rapidly evolving treatment options in cancer, the complexity in the clinical decision-making process for oncologists represents a growing challenge magnified by oncologists' disposition of intuition-based assessment of treatment risks and overall mortality. Given the unmet need for accurate prognostication with meaningful clinical rationale, we developed a highly interpretable prediction tool to identify patients with high mortality risk before the start of treatment regimens. METHODS: We obtained electronic health record data between 2004 and 2014 from a large national cancer center and extracted 401 predictors, including demographics, diagnosis, gene mutations, treatment history, comorbidities, resource utilization, vital signs, and laboratory test results. We built an actionable tool using novel developments in modern machine learning to predict 60-, 90- and 180-day mortality from the start of an anticancer regimen. The model was validated in unseen data against benchmark models. RESULTS: We identified 23,983 patients who initiated 46,646 anticancer treatment lines, with a median survival of 514 days. Our proposed prediction models achieved significantly higher estimation quality in unseen data (area under the curve, 0.83 to 0.86) compared with benchmark models. We identified key predictors of mortality, such as change in weight and albumin levels. The results are presented in an interactive and interpretable tool ( www.oncomortality.com ). CONCLUSION: Our fully transparent prediction model was able to distinguish with high precision between highest- and lowest-risk patients. Given the rich data available in electronic health records and advances in machine learning methods, this tool can have significant implications for value-based shared decision making at the point of care and personalized goals-of-care management to catalyze practice reforms.

Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically Recurrent Prostate Cancer: A Phase II Randomized Trial.

Purpose: STAND, a randomized, phase II, open-label trial (NCT01431391), assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC) patients at high risk for metastasis.Experimental Design: Men with BRPC following prostatectomy and/or radiotherapy, a PSA doubling time ≤12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms. The primary endpoint was PA2024-specific T-cell response [enzyme-linked immunospot (ELISPOT)] over time.Results: PA2024-specific ELISPOT responses over time were similar between groups, except at week 6, where responses were higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P = 0.013). PA2024-specific T-cell proliferation responses, averaged across time points, were approximately 2-fold higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P = 0.001). PA2024-specific cellular and humoral responses and prostatic acid phosphatase-specific humoral responses increased significantly versus baseline (P < 0.001) and were maintained for 24 months (both arms). Median time-to-PSA recurrence was similar between arms (21.8 vs. 22.6 months, P = 0.357). Development of a PA2024-specific humoral response correlated with prolonged time-to-PSA progression (HR, 0.22; 95% CI, 0.08-0.67; P = 0.007). Sipuleucel-T with ADT was generally well tolerated.Conclusions: Sipuleucel-T→ADT appears to induce greater antitumor immune responses than the reverse sequence. These results warrant further investigation to determine whether this sequence leads to improved clinical outcomes, as well as the independent contribution of ADT alone in terms of immune activation. Clin Cancer Res; 23(10); 2451-9. ©2016 AACR.

Oxidative stress in prostate cancer patients: A systematic review of case control studies.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men in Western countries. In-vitro and in-vivo studies suggest that oxidative stress (OS) and antioxidants play a key role in the pathogenesis of chronic diseases including PCa, which is promoted by the production of reactive oxygen species and impaired antioxidant defense mechanisms. This study evaluates the association between OS and men with PCa. METHODS: A literature search was carried out on Medline, PubMed, and ScienceDirect databases, as well as manual searches from inception up to August 2015 using the keywords "Oxidative stress" or "Reactive oxygen species" or "Lipid peroxidation" AND "Prostate cancer." All studies including data on the measurement of OS biomarkers in PCa were included. RESULTS: Twenty-three case control studies were retrieved with sample sizes ranging from 15 to 3,613 (6,439 participants in total). Markers of OS were significantly higher in patients with PCa compared with control groups in 21 studies. Two self-controlled case studies comparing OS between PCa cells and non-PCa cells in tissue biopsies found OS to be statistically higher in PCa cancer cells. Results on markers of antioxidant capacity (superoxide dismutase, catalase, glutathione, glutathione reductase, glutathione peroxidase, uric acid, lutein, lycopene, beta carotein, vitamin A, vitamin C, vitamin E, and total antioxidants) were not completely consistent in their association with PCa. CONCLUSIONS: Upregulated OS profiles and impairment of antioxidant defense systems may play a role in men with PCa. To confirm these findings, robust clinical trials utilizing a personalized approach which monitors both OS and antioxidant markers during therapy are warranted.

Assessment and management of advanced adrenocortical carcinoma using a precision oncology care model.

Within the category of orphan diseases and rare malignancies, adrenocortical carcinoma (ACC) represents an aggressive entity with high mortality and morbidity. While localized tumors which are diagnosed early can be cured with surgical intervention, there are prognostic factors which predict for micrometastases and consequent recurrent and advanced disease. In such cases, cytotoxic chemotherapy and mitotane have been utilized with a very modest degree of benefit. The poor prognosis of recurrent and advanced ACC has underscored the interest in nuanced characterization of ACC cases using next-generation sequencing (NGS)-based genomic and other '-omic' profiling to guide the precision medicine approach and personalized use of targeted and novel therapies.

Duration of Androgen Deprivation Therapy for High-Risk Prostate Cancer: Application of Randomized Trial Data in a Tertiary Referral Cancer Center.

INTRODUCTION: We evaluated the incidence and predictors of the use of long-term (2-3 years) versus shorter term androgen deprivation therapy (ADT) in radiation-managed men with high-risk prostate cancer. PATIENTS AND METHODS: We identified 302 patients from the Dana-Farber Cancer Institute patient registry who had been diagnosed with high-risk prostate cancer (T3a or prostate-specific antigen [PSA] > 20 ng/mL or Gleason score 8-10) from 1993 to 2015. We assessed the intended duration of ADT and used multivariable Cox regression to evaluate the predictors of receiving a shorter course of ADT than recommended by the guidelines (< 2 years). RESULTS: The course of ADT intended by physicians increased after the 2008/2009 publication of trials showing the superiority of long-term versus short-term ADT, with 43.5% intending ≥ 2 years before versus 61.4% after (P = .014). Starting in 2010, 49.4% of patients actually received < 2 years of ADT. The most common reasons for receipt of shorter course ADT were intolerance of ADT side effects, patient comorbidity/age, the presence of T3a on magnetic resonance imaging only as the sole high-risk feature, or participation in a clinical trial. Moderate to severe comorbidity assessed using the Adult Comorbidity Evaluation-27 (adjusted hazard ratio [AHR] = 2.94), Gleason score < 8 (AHR = 5.66), and PSA < 20 ng/mL (AHR = 4.19) all predicted for receipt of shorter course ADT (P < .05 for all). CONCLUSION: In a tertiary-care setting, the rates of long-course ADT for high-risk disease have increased since the 2008/2009 trials supporting its use. However, approximately one half of patients continued to receive shorter course ADT, often because of intolerance of side effects, underlying comorbidity, or physician judgment about the aggressiveness of the disease.

Adrenocortical Carcinoma: A Clinician's Perspective.

Within the category of orphan diseases and rare malignancies, adrenocortical carcinoma (ACC) represents an aggressive entity with high mortality and morbidity. While localized tumors which are diagnosed early can be cured with surgical intervention, there are prognostic factors which predict for micrometastases and consequent recurrent and advanced disease. In such cases, mitotane and cytotoxic chemotherapy have been utilized with a modest degree of benefit. The poor prognosis of recurrent and advanced ACC has underscored the interest in nuanced characterization of ACC cases to guide the personalized use of immunotherapeutic and novel targeted therapies.

Practice innovation: the need for nimble data platforms to implement precision oncology care.

Given the drive toward personalized, value-based, and coordinated cancer care delivery, modern knowledge-based practice is being shaped within the context of an increasingly technology-driven healthcare landscape. The ultimate promise of 'precision medicine' is predicated on taking advantage of the range of new capabilities for integrating disease- and individual-specific data to define new taxonomies as part of a systems-based knowledge network. Specifically, with cancer being a constantly evolving complex disease process, proper care of an individual will require the ability to seamlessly integrate multi-dimensional 'omic' and clinical data. Importantly, however, the challenges of curating knowledge from multiple dynamic data sources and translating to practice at the point-of-care highlight parallel needs. As patients, caregivers, and their environments become more proactive in clinical care and management, practical success of precision medicine is equally dependent on the development of proper infrastructures for evolving data integration, platforms for knowledge representation in a clinically-relevant context, and implementation within a provider's work-life and workflow.

The effect of technology-based interventions on pain, depression, and quality of life in patients with cancer: a systematic review of randomized controlled trials.

BACKGROUND: The burden of cancer is increasing; projections over the next 2 decades suggest that the annual cases of cancer will rise from 14 million in 2012 to 22 million. However, cancer patients in the 21st century are living longer due to the availability of novel therapeutic regimens, which has prompted a growing focus on maintaining patients' health-related quality of life. Telehealth is increasingly being used to connect with patients outside of traditional clinical settings, and early work has shown its importance in improving quality of life and other clinical outcomes in cancer care. OBJECTIVE: The aim of this study was to systematically assess the literature for the effect of supportive telehealth interventions on pain, depression, and quality of life in cancer patients via a systematic review of clinical trials. METHODS: We searched PubMed, EMBASE, Google Scholar, CINAHL, and PsycINFO in July 2013 and updated the literature search again in January 2015 for prospective randomized trials evaluating the effect of telehealth interventions in cancer care with pain, depression, and quality of life as main outcomes. Two of the authors independently reviewed and extracted data from eligible randomized controlled trials, based on pre-determined selection criteria. Methodological quality of studies was assessed by the Cochrane Collaboration risk of bias tool. RESULTS: Of the 4929 articles retrieved from databases and relevant bibliographies, a total of 20 RCTs were included in the final review. The studies were largely heterogeneous in the type and duration of the intervention as well as in outcome assessments. A majority of the studies were telephone-based interventions that remotely connected patients with their health care provider or health coach. The intervention times ranged from 1 week to 12 months. In general, most of the studies had low risk of bias across the domains of the Cochrane Collaboration risk of bias tool, but most of the studies had insufficient information about the allocation concealment domain. Two of the three studies focused on pain control reported significant effects of the intervention; four of the nine studies focus on depression reported significant effects, while only the studies that were focused on quality of life reported significant effects. CONCLUSIONS: This systematic review demonstrates the potential of telehealth interventions in improving outcomes in cancer care. However, more high-quality large-sized trials are needed to demonstrate cogent evidence of its effectiveness.

Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory biomarker study.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor in which prognostic factors are still not well established. Programmed Death Ligand-1 (PD-L1) expression in ACC and its association with clinico-pathological features and survival outcomes are unknown. METHODS: Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 28 patients with ACC. PD-L1 expression was evaluated by immunohistochemistry (IHC) in both tumor cell membrane and tumor infiltrating mononuclear cells (TIMC). PD-L1 positivity on tumor cells was defined as ≥5% tumor cell membrane staining. TIMC were evaluated by IHC using a CD45 monoclonal antibody. For PD-L1 expression in TIMC, a combined score based on the extent of infiltrates and percentage of positive cells was developed. Any score greater that zero was considered PD-L1 positive. Baseline clinico-pathological characteristics and follow up data were retrospectively collected. Comparisons between PD-L1 expression and clinico-pathological features were evaluated using unpaired t-test and Fisher's exact test. Kaplan-Meier method and log-rank test were used to assess association between PD-L1 expression and 5-year overall survival (OS). RESULTS: Among 28 patients with surgically treated ACC, 3 (10.7%) were considered PD-L1 positive on tumor cell membrane. On the other hand, PD-L1 expression in TIMC was performed in 27 specimens and PD-L1 positive staining was observed in 19 (70.4%) patients. PD-L1 positivity in either tumor cell membrane or TIMC was not significantly associated with higher stage at diagnosis, higher tumor grade, excessive hormone secretion, or OS. CONCLUSIONS: PD-L1 expression can exist in ACC in both tumor cell membrane and TIMC with no relationship to clinico-pathologic parameters or survival.

Income inequality and treatment of African American men with high-risk prostate cancer.

PURPOSE: Definitive treatment of high-risk prostate cancer with radical prostatectomy or radiation improves survival. We assessed whether racial disparities in the receipt of definitive therapy for prostate cancer vary by regional income. PATIENTS AND METHODS: A cohort of 102,486 men (17,594 African American [AA] and 84,892 non-Hispanic white) with localized high-risk prostate cancer (prostate-specific antigen >20 ng/ml or Gleason ≥ 8 or stage ≥ cT2c) diagnosed from 2004 to 2010 was identified in the Surveillance, Epidemiology, and End Results database. Income was measured at the census-tract-level. We used multivariable logistic regression to assess patient and cancer characteristics associated with the receipt of definitive therapy for prostate cancer. Multivariable Fine and Gray competing risks analysis was used to evaluate factors associated with prostate cancer death. RESULTS: Overall, AA men were less likely to receive definitive therapy than white men (adjusted odds ratio [AOR] = 0.51; 95% CI: 0.49-0.54; P<0.001), and there was a significant race/income interaction (Pinteraction = 0.016) such that there was a larger racial treatment disparity in the bottom income quintile (AOR = 0.49; 95% CI: 0.45-0.55; P<0.001) than in the top income quintile (AOR = 0.60; 95% CI: 0.51-0.71; P<0.001). After a median follow-up of 35 months, AA men in the bottom income quintile suffered the greatest prostate cancer mortality (adjusted hazard ratio = 1.47; 95% CI: 1.17-1.84; P = 0.001), compared with white men in the top income quintile. CONCLUSIONS: Racial disparities in the receipt of definitive therapy for high-risk prostate cancer are greatest in low-income communities, suggesting that interventions to reduce racial disparities should target low-income populations first.

A phase I study of everolimus and docetaxel in patients with castration-resistant prostate cancer.

BACKGROUND: The PTEN tumor suppressor is frequently lost in CRPC, with activation of Akt-mTOR signaling, driving growth. We conducted a phase I trial of the mTOR inhibitor, everolimus, and docetaxel in CRPC. PATIENTS AND METHODS: Eligible patients had progressive, metastatic, chemotherapy-naive CRPC. Patients received everolimus 10 mg daily for 2 weeks and underwent a restaging FDG-PET/computed tomography scan. Patient cohorts were subsequently treated at 3 dose levels of everolimus with docetaxel: 5 mg to 60 mg/m(2), 10 mg to 60 mg/m(2), and 10 mg to 70 mg/m(2). The primary end point was the safety and tolerability of combination therapy. RESULTS: Accrual was 4 patients at level 1, 3 patients at level 2, and 8 patients at level 3. Common toxicities were hematologic and fatigue. Serum concentrations of everolimus when administered with docetaxel were 1.5 to 14.8 ng/mL in patients receiving 5 mg everolimus and 4.5 to 55.4 ng/mL in patients receiving 10 mg everolimus. Four patients had partial metabolic response (PMR) using FDG-PET, 12 had stable metabolic disease, and 2 had progressive metabolic disease after a 2-week treatment with everolimus alone. Five of 12 evaluable patients experienced a prostate-specific antigen (PSA) reduction ≥ 50% during treatment with everolimus together with docetaxel. All 4 patients with a PMR according to PET imaging experienced a PSA reduction in response to everolimus with docetaxel, and 3 of 4 had PSA declines ≥ 50%. CONCLUSION: Everolimus 10 mg daily and docetaxel 60 mg/m(2) was safe in CRPC patients and these were the recommended doses in combination. FDG-PET response might serve as a biomarker for target inhibition by mTOR inhibitors.

Improving outcomes in cancer patients on oral anti-cancer medications using a novel mobile phone-based intervention: study design of a randomized controlled trial.

BACKGROUND: The widespread and increasing use of oral anti-cancer medications has been ushered in by a rapidly increasing understanding of cancer pathophysiology. Furthermore, their popular ease of administration and potential cost savings has highlighted their central position in the health care system as a whole. These facts have heightened appreciation of the unique challenges associated with the use of oral anti-cancer medications; especially in the long-term use of these medications and the associated side effects that may impede optimal adherence to their use. Therefore, we developed ChemOtheRapy Assistant, CORA, a personalized mobile phone-based self-management application to help cancer patients on oral anti-cancer medications. OBJECTIVE: Our objective is to evaluate the effect of CORA on adherence to oral anti-cancer medications and other clinically relevant outcomes in the management of patients with renal and prostate cancer. METHODS: The study will be implemented as a 2-parallel group randomized controlled trial in 104 patients with renal or prostate cancer on oral anti-cancer medications over a 3-month study period. The intervention group will use CORA in addition to usual care for self-management while the control group will continue care as usual. Medication adherence will be measured objectively by a Medication Event Monitoring System device and is defined as the percentage of prescribed doses taken. We will also assess the effect of the intervention on cancer-related symptoms measured by the MD Anderson Symptom Inventory and unplanned hospital utilizations. Other outcomes that will be measured at study start, midpoint, and endpoint are health-related quality of life, cancer-related fatigue, and anxiety. Group differences in medication adherence will be examined by t tests or by non-parametric Mann-Whitney tests if the data are not normally distributed. Logistic regression will be used to identify potential predictors of adherence. RESULTS: We expect to have results for this study before the end of 2016. CONCLUSIONS: This novel mobile phone-enabled, multimodal self-management and educational intervention could lead to improvements in clinical outcomes and serve as a foundation for future mHealth research in improving outcomes for patients on oral anti-cancer medications.

Cabozantinib in chemotherapy-pretreated metastatic castration-resistant prostate cancer: results of a phase II nonrandomized expansion study.

PURPOSE: Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: Patients received open-label cabozantinib at daily starting doses of 100 mg or 40 mg until disease progression or unacceptable toxicity. The primary end point was bone scan response, defined as ≥ 30% reduction in bone scan lesion area. Other efficacy end points included overall survival, pain, analgesic use, and biomarkers. RESULTS: One hundred forty-four patients sequentially enrolled in either a 100-mg (n = 93) or 40-mg (n = 51) study cohort. Ninety-one patients (63%) had a bone scan response, often by week 6. Treatment resulted in clinically meaningful pain relief (57% of patients) and reduction or discontinuation of narcotic analgesics (55% of patients), as well as improvements in measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Improvements in each of these outcomes were observed in both cohorts: bone scan response in 73% and 45%, respectively; reductions in measurable soft tissue disease in 80% and 79%, respectively. Median overall survival was 10.8 months for the entire population. Most common grade 3 or 4 adverse events were fatigue (22%) and hypertension (14%). Fewer dose reductions because of toxicity were required in the 40-mg group. CONCLUSION: The evidence suggests that cabozantinib has clinically meaningful activity in CRPC. Cabozantinib resulted in improvements in bone scans, pain, analgesic use, measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Taken together, these phase II observations warrant further development of cabozantinib in prostate cancer.

Adrenocortical carcinoma: the management of metastatic disease.

Adrenocortical cancer is a rare malignancy. While surgery is the cornerstone of the management of localized disease, metastatic disease is hard to treat. Cytotoxic chemotherapy and mitotane have been utilized with a variable degree of benefit and few long-term responses. A growing understanding of the molecular pathogenesis of this malignancy as well as multidisciplinary and multi-institutional collaborative efforts will result in better defined targets and subsequently, effective novel therapies.