Differences in Discounting Behavior and Brain Responses for Food and Money Reward.

Most neuroeconomic research seeks to understand how value influences decision-making. The influence of reward type is less well understood. We used functional magnetic resonance imaging (fMRI) to investigate delay discounting of primary (i.e., food) and secondary rewards (i.e., money) in 28 healthy, normal-weighted participants (mean age = 26.77; 18 females). To decipher differences in discounting behavior between reward types, we compared how well-different option-based statistical models (exponential, hyperbolic discounting) and attribute-wise heuristic choice models (intertemporal choice heuristic, dual reasoning and implicit framework theory, trade-off model) captured the reward-specific discounting behavior. Contrary to our hypothesis of different strategies for different rewards, we observed comparable discounting behavior for money and food (i.e., exponential discounting). Higher k values for food discounting suggest that individuals decide more impulsive if confronted with food. The fMRI revealed that money discounting was associated with enhanced activity in the right dorsolateral prefrontal cortex, involved in executive control; the right dorsal striatum, associated with reward processing; and the left hippocampus, involved in memory encoding/retrieval. Food discounting, instead, was associated with higher activity in the left temporoparietal junction suggesting social reinforcement of food decisions. Although our findings do not confirm our hypothesis of different discounting strategies for different reward types, they are in line with the notion that reward types have a significant influence on impulsivity with primary rewards leading to more impulsive choices.

Apical hypertrophic cardiomyopathy: A case series at a Brazilian referral center with a maximal follow-up of 15 years.

BACKGROUND: Apical hypertrophic cardiomyopathy (AHCM) is a rare cardiomyopathy, in which hypertrophy occurs predominantly in the ventricular apex, and in some cases with a high risk of sudden cardiac death. OBJECTIVE: The aim of this paper is to present a case series of patients with AHCM and describe their main clinical, echocardiographic and electrocardiographic characteristics, the recommendation for an implantable cardioverter-defibrillator (ICD) and the frequency of sudden cardiac death (SCD). METHODS: A retrospective case series was conducted at the referral center of a federal teaching hospital, between the years 2005 to 2020, involving patients with an echocardiographic diagnosis of AHCM. The parameters of the American College of Cardiology and the European Society of Cardiology were used to assess the risk of SCD. RESULTS: A total of 11 individuals were assessed with a mean age of 55.3 years, mean follow-up of 41.2 months, most of whom were symptomatic at diagnosis (72.7%). The most frequent symptom was dyspnea (27.3%). A family history of SCD was described in 45.5% of cases. Due to a high risk of SCD, four patients received ICDs. One patient presented sudden cardiac death after having refused the ICD. CONCLUSIONS: Symptoms and alterations in the imaging exams are significant factors in the clinical and prognostic assessment of patients with AHCM.

Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach.

This article reviews intravenous vitamin C (IV C) in cancer care and offers a rational approach to enable medical oncologists and integrative practitioners to safely provide IV C combined with oral vitamin C to patients. The use of IV C is a safe supportive intervention to decrease inflammation in the patient and to improve symptoms related to antioxidant deficiency, disease processes, and side effects of standard cancer treatments. A proposed rationale, together with relevant clinical safety considerations for the application of IV C in oncologic supportive care, is provided.

Platinum-Gemcitabine-Avastin (PGA) for platinum-resistant/refractory ovarian cancer.

OBJECTIVES: Synergism between gemcitabine and platinum is known clinically. Bevacizumab in combination with single-agent chemotherapy has demonstrated significant clinical activity in platinum-resistant recurrent ovarian cancer in AURELIA study. However, the efficacy of platinum-gemcitabine-bevacizumab (PGA) has not been investigated in the platinum-resistant population. MATERIALS AND METHODS: A retrospective chart review was conducted in all patients with platinum-resistant/refractory ovarian cancer treated with triplet combination therapy containing a platinum agent, gemcitabine, and bevacizumab between July 2011 and December 2013. RESULTS: In total, 13 patients met the selection criteria, including ten patients with resistant disease (10/13, 77%) and three patients with refractory disease (3/13, 23%). Most of the patients were heavily pre-treated, having received over three lines of prior chemotherapy regimens on average (range 1-11). All patients had previously received taxane therapy; four patients received gemcitabine, seven patients failed combination regimens including bevacizumab, and three patients progressed on chemotherapy including both gemcitabine and bevacizumab. Ten patients responded biochemically to the therapy (defined by CA-125 declined by at least 50%). Of ten responders, one patient achieved CR for 24 months (8%), six patients achieved PR for 6.8 months (46%), three had stable disease for 6.7 months (23%), and three patients had PD (23%) by RECIST 1.1 criteria. The regimen was well-tolerated. One patient (8%) developed grade 3 neutropenia and neutropenic fever, requiring hospitalization, two patients developed grade 3 thrombocytopenia, two patients (15%) developed thrombosis in internal jugular vein, requiring discontinuation of bevacizumab, one patient (8%) experienced skin ulcer, and two patients developed thrombosis in internal jugular vein, requiring discontinuation of bevacizumab. CONCLUSIONS: Combination of PGA appears to be safe and very active against platinum-resistant/refractory ovarian cancer and merits further evaluation prospectively. A randomized phase II study (NCTO 1936974) is currently under way to confirm this important finding.

Surgical intervention in relapsed ovarian cancer is beneficial: contra.

Secondary cytoreduction in the management of patients with recurrent ovarian cancer is a commonly employed strategy. Unfortunately, there remain 'no evidence-based phase III trial data' to demonstrate the survival benefits of this approach compared with the reintroduction of chemotherapy without surgery at the time of documented progression of the cancer. In the absence of such evidence, it is critical that gynecologic oncologists employ their best clinical judgment when deciding if an individual patient is an appropriate candidate for this as yet unproven strategy.

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy.

Bevacizumab is a biologically and clinically active antineoplastic agent in the management of epithelial ovarian cancer. While phase III trial data have revealed the favorable impact on progression-free survival associated with combining the agent with cytotoxic chemotherapy, at the current time a strong argument can be made (based on both efficacy and cost-effectiveness considerations) that a more rational approach to utilizing bevacizumab in ovarian cancer would be to administer the drug as a single agent in the platinum-resistant setting.

Role of chemotherapy in epithelial ovarian cancer.

Despite the fact the standard-of-care primary chemotherapy strategy in epithelial ovarian cancer has undergone very limited changes over the past decade there have been important advances in treatment outcomes resulting from data generated in evidence-based trials that has modified the paradigm for second-line disease management. Recently reported data suggest novel classes of agents, including anti-angiogenic drugs and PARP inhibitors may add to the established utility of standard cytotoxic chemotherapy.

Extended venous thromboembolism prophylaxis for high-risk patients undergoing surgery for malignancy.

BACKGROUND: In surgical patients with known malignancy, the odds ratio for an episode of a venous thromboembolism is approximately 6.5 compared to a group of patients without malignancy undergoing the same procedure [Heit et al.: Arch Intern Med 2000;160:809-815]. CASE REPORT: We present a case of a 46-year-old Caucasian male with a history of adenocarcinoma of the rectum. The patient received neoadjuvant treatment prior to low anterior resection with diverting colostomy. He received short-term prophylaxis for venous thrombosis, but unfortunately developed a blood clot in a lower extremity several weeks after surgery. CONCLUSION: There is a well-defined role in carefully selected patients for the use of extended prophylaxis to prevent venous thromboembolic complications following cancer surgery.

PET/CT scans in ovarian cancer: prognostic versus predictive utility?

The use of PET/CT has been advocated in the management of ovarian cancer as a diagnostic strategy to assist in patient management. To date, data in the peer reviewed literature support the argument that findings on PET/CT reveal evidence of the extent of disease and may be helpful in documenting disease recurrence. However, it remains to be determined through the conduct of phase 3 randomized trials if the information generated will be useful in predicting benefit of a management plan specifically selected based on the results of this expensive radiographic procedure.

Single-agent trabectedin as second-line therapy of persistent or recurrent endometrial cancer: results of a multicenter phase II study.

OBJECTIVE: To assess the efficacy and safety of single-agent trabectedin in women with persistent or recurrent endometrial cancer. METHODS: In this open-label, phase II multicenter trial, women with persistent or recurrent endometrial carcinoma were administered trabectedin as a 3-hour intravenous infusion every 21 days at a starting dose of 1.3 mg/m(2) with dexamethasone pretreatment. Clinical objective response was the primary efficacy endpoint. Secondary endpoints were time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: The median age of the 50 women entering the study was 63 years (range, 22-87), with all having history of prior chemotherapy (92% combination regimens) and the majority having undergone surgery (92%) or radiation therapy (68%). Patients received trabectedin for a median duration of 6.8 weeks (range, 3-20). A median of 2 cycles (range, 1-6) was administered, with a median dose intensity of 0.4 mg/m(2) per week (range, 0.27-0.43) and a median relative dose intensity of 92% (range, 61.5-100.2%). One patient exhibited a complete response for an objective response rate of 2.2% (95% confidence interval [CI]: 0.1%, 11.5%). Median TTP and PFS were both 1.8 months (95% CI: 1.4, 2.9), and median OS was 6.7 months (95% CI: 5.2, 13.9). Most frequent adverse events were nausea (62%), asthenia (50%), vomiting (42%), and increased alanine aminotransferase (40%). CONCLUSION: Single-agent trabectedin displayed minimal antitumor activity in this pretreated population of women with persistent or recurrent endometrial cancer.

Prevalence of pulmonary hypertension in patients with schistosomal liver fibrosis.

Between the April and July of 2007, patients undergoing treatment for schistosomal liver fibrosis, at a university hospital in north-eastern Brazil, were examined by transthoracic Doppler echocardiography (TTE). The main aim was to determine the prevalence of pulmonary hypertension in the patients. The thorax of each patient who had such hypertension, as indicated by an estimated pulmonary arterial systolic pressure (PASP) in excess of 35 mmHg, was then investigated by contrast-enhanced multidetector-row computed tomography (MDCT). The 84 patients (53 women and 31 men) enrolled in the study had a mean (S.D.) age of 50.06 (12.25) years. Nine (10.7%, with a 95% confidence interval of 5.0%-19.4%) of the patients were found to have pulmonary hypertension, with PASP ranging from 40-126 mmHg, and a median (S.D.) PASP of 58.78 (28.01) mmHg. The contrast-enhanced thoracic MDCT indicated that most of the patients with pulmonary hypertension had a pulmonary artery trunk that was unusually wide (67%) and more than 1.1-fold wider than the ascending aorta (56%), dilatation of the main pulmonary arteries (100%), a segmental artery that, in diameter, was more than 1.1-fold larger than the adjacent bronchi (89%), tapering of the peripheral pulmonary arteries (78%), and cardiac enlargement (78%). No patient suffered pulmonary embolism as a result of the investigations. The prevalence of pulmonary hypertension in the patients with schistosomal liver fibrosis (10.7%) justifies the screening of such patients by TTE.

What is the optimal approach to the administration of intraperitoneal chemotherapy in ovarian cancer?

Three well-designed and conducted randomized phase 3 trials have revealed that the intraperitoneal administration of cisplatin-based chemotherapy as primary treatment of small-volume residual advanced ovarian cancer improves both progression-free and overall survivals compared to an all intravenous cisplatin-based regimen. Based on very reasonable extrapolations from existing evidence-based data, a number of possible "options" can be proposed that use the intraperitoneal route for delivery of chemotherapy in this clinical setting.

Strategies to examine new compounds for intraperitoneal use in ovarian cancer.

The results of three large well-designed randomized trials demonstrating the favorable impact of primary cisplatin-based chemotherapy on survival in small-volume residual advanced ovarian cancer has stimulated considerable interest in exploration of this route of drug delivery for other antineoplastic agents. A number of relevant properties of both the drugs and the peritoneal cavity need to be considered in preclinical evaluation such that future clinical development will focus on strategies that have a realistic potential for being safe and effective when they enter the clinical arena.

Maintenance chemotherapy in advanced ovarian cancer: the US experience.

The somewhat controversial results of a Southwest Oncology Group/Gynecologic Oncology Group phase 3 randomized trial have revealed that a maintenance strategy consisting of 12 cycles of single-agent paclitaxel (175 mg/m(2) over 3 h every 28 days), delivered to women with advanced ovarian cancer who have achieved a clinically defined complete response to primary platinum-paclitaxel chemotherapy, significantly improves progression-free survival compared to delivery of three cycles of the same treatment regimen. While it is not possible to provide a definitive statement regarding the impact of this management approach on overall survival, in an exploratory analysis, patients who initiated this study with a baseline CA-125 level

Phase II trial of imatinib mesylate in recurrent, biomarker positive, ovarian cancer (Southwest Oncology Group Protocol S0211).

Platinum-resistant ovarian cancer continues to be a difficult therapeutic problem. Clearly, molecularly targeted agents should be evaluated in this patient population. Patients were eligible for this phase II study with stage III or IV ovarian cancer, whose tumor expressed Kit (CD117) or platelet-derived growth factor receptor (PDGFR) and with relapse of measurable disease within 6 months of completing frontline, platinum- and taxane-based chemotherapy. Patients were treated daily with 400 mg of imatinib mesylate orally. It was assumed that the agent would be of no further interest if the population response rate was less than 10%. A two-stage design was used for patient accrual. A total of 34 patients were registered to the study. Of these, 15 were found to be ineligible or not evaluable (8 because their tumor samples were negative for both DC117 and PDGFR). Of 19 evaluable patients, 2 (11%) tested positively for c-Kit and 17 (89%) tested positively for PDGFR. There were no objective responders. Thirteen patients (68%) had increasing disease or symptomatic deterioration, and six (32%) went off protocol during the first month due to adverse events. Median progression-free survival was 2 months (95% CI 1-3 months) and median overall survival was 10 months (95% CI 6-18 months). Eleven percent of patients experienced grade 4 hematologic/metabolic toxicity and 37% experienced grade 3 nonhematologic toxicity. We conclude that imatinib mesylate as a single agent does not appear to have useful clinical activity in c-Kit and/or PDGFR positive, recurrent ovarian cancer in heavily pretreated patients with ovarian cancer.

Principles and practice of intraperitoneal chemotherapy for ovarian cancer.

Intraperitoneal (IP) chemotherapy has been studied for years to improve the survival of patients with ovarian cancer. Recently, the result of Gynecologic Oncology Group 172 trial comparing IP versus intravenous administration of cisplatin-based chemotherapy was published, demonstrating the improvement of survival benefit in favor of the IP arm. This trial is the third trial that showed a survival benefit on IP chemotherapy. The National Cancer Institute (NCI) and Gynecologic Oncology Group have done a meta-analysis on the results of these three US trials and other phase III trials of IP versus intravenous chemotherapy, and significant improvement of survival was shown with IP therapy. Based on this meta-analysis, NCI has released a clinical announcement encouraging the gynecological oncology community to consider IP chemotherapy as the standard treatment for optimally debulked advanced ovarian cancer patients. However, there still are controversial issues regarding the use of IP chemotherapy. It is important to understand how IP chemotherapy works to solve those issues in the future. In this review article, we discuss the principles and clinical aspects of IP chemotherapy and also discuss the current problems and future perspectives in IP chemotherapy.

Proceedings of a GOG workshop on intraperitoneal therapy for ovarian cancer.

Ovarian cancer is the leading cause of gynecologic cancer deaths in the U.S. The concept of intraperitoneal drug delivery for therapy of intraperitoneal cancers, such as ovarian cancer, arose in the 1960s. The field of intraperitoneal cisplatin therapy for ovarian cancer was initiated in the late 1970s and early 1980s. The markedly improved survival data resulting from a phase III trial of intraperitoneal cisplatin for ovarian cancer in early 2006 led to an NCI Clinical Announcement and a Gynecologic Oncology Group-sponsored workshop on intraperitoneal therapy in January, 2006, in San Diego, California. The proceedings of this workshop summarize both research trial results and practical implementation issues associated with intraperitoneal therapy discussed at this workshop.