Prevalence and Subtype Distribution of High-Risk Human Papillomavirus Among Women Presenting for Cervical Cancer Screening at Karanda Mission Hospital.

PURPOSE: High-risk human papillomaviruses (hrHPV) are the primary cause of cervical cancer. Human papillomavirus (HPV) vaccination is expected to prevent cervical cancers caused by the HPV types included in vaccines and possibly by cross-protection from other types. This study sought to determine the hrHPV type distribution in women at a rural Zimbabwe hospital. METHODS: We implemented a cross-sectional study at the Karanda Mission Hospital. Using the Visual Inspection with Acetic Acid Cervicography technique, clinicians collected cervical swabs from 400 women presenting for screening for cervical cancer. Samples were initially analyzed by Cepheid GeneXpert; candidate hrHPV genotypes were further characterized using the Anyplex II HPV28 Detection Kit. RESULTS: Twenty-one percent of the 400 women were positive for a high-risk genotype when using the GeneXpert analyzer; 17% were positive when using the multiplex analysis. Almost two thirds of the hrHPV women had a single DNA type identified, whereas one third had multiple genotypes, ranging from 2 to 5. hrHPV was observed more frequently in HIV-positive than in HIV-negative women (27% v 15%). Of the 113 isolates obtained, 77% were hrHPV genotypes not included in the bivalent or quadrivalent vaccines, and 47% represented DNA types not covered in the nonavalent vaccine. Forty-seven percent of the women with hrHPV harbored a single genotype that was not covered by the nonavalent vaccine. CONCLUSION: A large fraction of hrHPV isolates from women participating in a cervical cancer screening program in northern Zimbabwe are DNA types not covered by the bivalent, quadrivalent, or nonavalent vaccines. These findings suggest the importance of characterizing the hrHPV DNA types isolated from cervical neoplasia in this population and determining whether cross-immunization against these genotypes develops after administration of the vaccines in current use.

All Men Are Created Equal: Addressing Disparities in Prostate Cancer Care.

The global cancer burden is estimated to have risen to 18.1 million new cases and 9.6 million deaths in 2018. By 2030, the number of cancer cases is projected to increase to 24.6 million and the number of cancer deaths, to 13 million. Global data mask the social and health disparities that influence cancer incidence and survival. Inequality in exposure to carcinogens, education, access to quality diagnostic services, and affordable treatments all affect the probability of survival. Worryingly, despite the fact that many cancers could be prevented by stronger public health actions and many others could be largely cured by better access to diagnostics and affordable treatments, the international community has yet to make a substantial move to tackle this challenge. In prostate cancer, studies show that there are geographic and racial/ethnic distribution differences as well as a number of other variables, including environmental factors, limited access to standard cancer treatments, reduced probability to be included in trials, and the financial burden of cancer treatments. Financial burden for the patients can result in poor adherence, increased debt, and poor long-term outcomes. The following article will discuss some of the important causes for disparity in prostate cancer and prostate cancer care, focused on the current situation in the United States, as well as possible remedies to address these causes.

Comparative Assessment of Clinical Benefit Using the ESMO-Magnitude of Clinical Benefit Scale Version 1.1 and the ASCO Value Framework Net Health Benefit Score.

PURPOSE: To better understand the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) and the ASCO Value Framework Net Health Benefit score version 2 (ASCO-NHB v2), ESMO and ASCO collaborated to evaluate the concordance between the frameworks when used to assess clinical benefit attributable to new therapies. METHODS: The 102 randomized controlled trials in the noncurative setting already evaluated in the field testing of ESMO-MCBS v1.1 were scored using ASCO-NHB v2 by its developers. Measures of agreement between the frameworks were calculated and receiver operating characteristic curves used to define thresholds for the ASCO-NHB v2 corresponding to ESMO-MCBS v1.1 categories. Studies with discordant scoring were identified and evaluated to understand the reasons for discordance. RESULTS: The correlation of the 102 pairs of scores for studies in the noncurative setting is estimated to be 0.68 (Spearman's rank correlation coefficient; overall survival, 0.71; progression-free survival, 0.67). Receiver operating characteristic curves identified thresholds for ASCO-NHB v2 for facilitating comparisons with ESMO-MCBS v1.1 categories. After applying pragmatic threshold scores of 40 or less (ASCO-NHB v2) and 2 or less (ESMO-MCBS v1.1) for low benefit and 45 or greater (ASCO-NHB v2) and 4 to 5 (ESMO-MCBS v1.1) for substantial benefit, 37 discordant studies were identified. Major factors that contributed to discordance were different approaches to evaluation of relative and absolute gain for overall survival and progression-free survival, crediting tail of the curve gains, and assessing toxicity. CONCLUSION: The agreement between the frameworks was higher than observed in other studies that sought to compare them. The factors that contributed to discordant scores suggest potential approaches to improve convergence between the scales.

American Society of Clinical Oncology's Global Oncology Leadership Task Force: Findings and Actions.

In response to rising cancer incidence and mortality rates in low- and middle-income countries and the increasingly global profile of ASCO's membership, the ASCO Board of Directors appointed the Global Oncology Leadership Task Force (Task Force) to provide recommendations on ASCO's engagement in global oncology. To accomplish its work, the Task Force convened meetings of global oncology experts, conducted focus group discussions with member groups, did site visits to South America and India, and met regularly to analyze the findings and develop recommendations. Task Force findings included global concerns, such as access to care, and specific concerns of middle- and low-resource settings. The need to strengthen health systems and the importance of alliances with a range of international cancer stakeholders were emphasized. Task Force recommendations to the ASCO Board of Directors were based on a three-part global oncology strategy of professional development, improvement of access to quality care, and acceleration of global oncology research. Specific areas of focus within each of these strategic pillars are provided along with an update on areas of ASCO activity as these recommendations are implemented.

Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred.

PURPOSE: Members of a family with hereditary gastrointestinal stromal tumors (GISTs) and a germline KIT oncogene mutation were evaluated for other potential syndrome manifestations. A tumor from the proband was analyzed to compare features with sporadic GISTs. PATIENTS AND METHODS: Members of a kindred in which six relatives in four consecutive generations comprised an autosomal dominant pattern of documented GISTs and cutaneous lesions underwent physical examination, imaging studies, and germline KIT analysis. A recurrent GIST from the proband was studied using microarray, karyotypic, immunohistochemical, and immunoblotting techniques. RESULTS: In addition to evidence of multiple GISTs, lentigines, malignant melanoma, and an angioleiomyoma were identified in relatives. A previously reported gain-of-function missense mutation in KIT exon 11 (T --> C) that results in a V559A substitution within the juxtamembrane domain was identified in three family members. The proband's recurrent gastric GIST had a 44,XY-14,-22 karyotype and immunohistochemical evidence of strong diffuse cytoplasmic KIT expression without expression of actin, desmin, or S-100. Immunoblotting showed strong expression of phosphorylated KIT and downstream signaling intermediates (AKT and MAPK) at levels comparable with those reported in sporadic GISTs. cDNA array profiling demonstrated clustering with sporadic GISTs, and expression of GIST markers comparable to sporadic GISTs. CONCLUSION: These studies provide the first evidence that gene expression and mechanisms of cytogenetic progression and cell signaling are indistinguishable in familial and sporadic GISTs. Current investigations of molecularly targeted therapies in GIST patients provide opportunities to increase the understanding of features of the hereditary syndrome, and risk factors and molecular pathways of the neoplastic phenotypes.

In vitro and in vivo induction of antiangiogenic activity by plasminogen activators and captopril.

BACKGROUND: Many antiangiogenic molecules are proteolytically cleaved from larger plasma proteins. For example, plasminogen activators cleave plasminogen into plasmin, and plasmin is converted into angiostatin in the presence of sulfhydryl donors. We thus investigated whether the antiangiogenic activity in plasma could be increased by treatment with recombinant tissue plasminogen activator (rt-PA) and the sulfhydryl donor captopril. METHODS: Human plasma was treated with rt-PA (10 micro g/mL) and/or captopril (1 micro M). Angiogenesis was measured in vitro by human endothelial cell tube formation and endothelial cell proliferation and in vivo in mice with the Matrigel plug assay. Angiostatin was removed from treated plasma by affinity chromatography, immunoprecipitation, or ion-exchange chromatography, and the antiangiogenic activity of the depleted plasma was assessed by tube formation. Three cancer patients were treated with rt-PA and captopril, and their pretreatment and post-treatment plasmas were tested for antiangiogenic activity in vitro. RESULTS: Angiogenesis in vitro was stimulated by untreated plasma and inhibited by plasma that had been treated with rt-PA and captopril but was not affected by treatment with rt-PA and/or captopril alone. In vivo angiogenesis in Matrigel plugs was substantially lower in mice treated with rt-PA and captopril than in untreated control mice. Antiangiogenic activity in treated plasma was largely retained after angiostatin was removed: treated plasma inhibited angiogenesis by 64.3% (95% confidence interval [CI] = 46.4% to 82.2%), relative to untreated plasma, and treated plasma depleted of angiostatin by affinity chromatography or immunoprecipitation inhibited angiogenesis by 65.1% (95% CI = 53.8% to 76.4%) or 63.7% (95% CI = 50.9% to 76.5%), respectively. Antiangiogenic activity of plasma from three cancer patients was higher after treatment with rt-PA and captopril than before such treatment. CONCLUSION: Treatment with rt-PA and captopril induced antiangiogenic activity in vitro and in vivo that appears to be independent of angiostatin.

The costs of conducting clinical research.

PURPOSE: Physicians frequently receive payment for enrolling subjects onto clinical trials. Some view these payments as conflicts of interest. Others contend that these payments are necessary reimbursements for conducting clinical research. We evaluated the clinical and nonclinical hours and costs associated with conducting a mock phase III clinical research trial. METHODS: We collected data from representatives of 21 clinical sites, on the numbers of hours associated with 13 activities necessary to the conduct of clinical research. The hours were based on enrolling 20 patients in a 12-month randomized placebo-controlled trial of a new chemotherapeutic agent. The outcome measures were disease progression and quality-of-life reports. These costs were evaluated for both government and pharmaceutical industry-sponsored trials. RESULTS: On average, 4,012 hours (range, 1,512 to 13,319 hours) were required for a government-sponsored trial, and 3,998 hours (range: 1735 to 15,699) were required for a pharmaceutical industry-sponsored trial involving 20 subjects with 17 office visits, or approximately 200 hours per subject. Thirty-two percent of the hours were devoted to nonclinical activities, such as institutional review board submission and completion of clinical reporting forms. On average, excluding overhead expenses, it cost slightly more than 6,094 dollars (range, 2,098 dollars to 19,285 dollars) per enrolled subject for an industry-sponsored trial, including 1,999 dollars devoted to nonclinical costs. CONCLUSION: Based on the results of our mock trial, the time required for nontreatment trial activities is considerable, and the associated costs are substantial.

American society of clinical oncology statement: toward individualized care for patients with advanced cancer.

Patients with advanced incurable cancer face complex physical, psychological, social, and spiritual consequences of disease and its treatment. Care for these patients should include an individualized assessment of the patient's needs, goals, and preferences throughout the course of illness. Consideration of disease-directed therapy, symptom management, and attention to quality of life are important aspects of quality cancer care. However, emerging evidence suggests that, too often, realistic conversations about prognosis, the potential benefits and limitations of disease-directed therapy, and the potential role of palliative care, either in conjunction with or as an alternative to disease-directed therapy, occur late in the course of illness or not at all. This article addresses the American Society of Clinical Oncology's (ASCO's) vision for improved communication with and decision making for patients with advanced cancer. This statement advocates an individualized approach to discussing and providing disease-directed and supportive care options for patients with advanced cancer throughout the continuum of care. Building on ASCO's prior statements on end-of-life care (1998) and palliative care (2009), this article reviews the evidence for improved patient care in advanced cancer when patients' individual goals and preferences for care are discussed. It outlines the goals for individualized care, barriers that currently limit realization of this vision, and possible strategies to overcome these barriers that can improve care consistent with the goals of our patients and evidence-based medical practice.

Value and cancer care: toward an equitable future.

Health care expenses in the United States are increasing inexorably. At the current rate of growth, it is anticipated that 20% of the gross national product will consist of health-related expenditures within the next decade. Cancer is the second leading cause of death in the United States, and it is increasing in prevalence because of the aging of the population and the limited number of successful prevention strategies. As the biological characteristics of cancer come into sharper focus, targeted therapies are being developed that offer the promise of increased clinical benefit with fewer toxicities than are associated with conventional treatment. Although spectacular successes are infrequent with this approach, to date, the majority of targeted therapies are modestly effective at best, and extremely costly. This observation suggests that a broadly acceptable definition of value in a cancer therapeutic agent is not at hand, but is sorely needed from the vantage points of the patient and society. A corollary issue of enormous import is how to equitably distribute the health care dollar in the service of achieving the greatest good for the greatest number. Although cancer is responsible for only 5% of the health care budget, its cost is increasing and it can be viewed as paradigmatic when contemplating the problem of equity in health care. Here, a number of concepts are discussed that focus on this goal and its implications for the cancer patient and society at large.