Chemotherapy or Targeted Therapy as Second-Line Treatment of Advanced Gastric Cancer. A Systematic Review and Meta-Analysis of Published Studies

Chemotherapy is a cornerstone in treatments of gastric cancer, but despite its benefit, less than 60% of patients receive salvage therapy in clinical practice. We performed a systematic review and meta-analysis based on trial data on the role of second-line treatment of advanced gastric cancer. MEDLINE/PubMed and Cochrane Library were searched for randomized phase III trials that compared active therapy to best supportive care in advanced gastric cancer. Data extraction was conducted according to the PRISMA statement. Summary HR for OS was calculated using a hierarchical Bayesian model and subgroup analysis was performed based on baseline Eastern Cooperative Oncology Group Performance Status (ECOG) performance status (0 vs. 1 or more). A total of 1,407 patients were evaluable for efficacy, 908 were treated in the experimental arms, with chemotherapy (231 pts) or with targeted therapies (677 pts). The risk of death was decreased by 18% (HR = 0.82; 95% CI, 0.79–0.85; posterior probability HR≥1: <0.00001) with active therapies. Chemotherapy and ramucirumab were able to decrease this risk by 27% and 22%, respectively. No differences were found between chemotherapy and ramucirumab. In patients with ECOG = 0 a greater benefit was found for chemotherapy with a reduction of the risk of death by 43% and no benefits were found for ramucirumab or everolimus. In patients with ECOG = 1 or more a significant reduction of the risk of death by 32% was reported in patients treated with ramucirumab, even if no significant difference was reported between chemotherapy and ramucirumab. This analysis reports that active and available therapies are able to prolong survival in patients with advanced gastric cancer with a different outcome based on initial patient’s performance status. New trials based on a better patient stratification are awaited.     

Mediated speculations in the genomics futures markets

This article examines the interactions between the media and genomics, with particular reference to the case of deCODE Genetics in Iceland. It focuses on the role of "forward-looking statements" and other forms of speculation as they operate in the science of genomics, in the social relations that happen around genomics, and in the commercial genomics economy. The article discusses how these fundamentally anticipatory speech acts uttered or written by genomic corporate executives, journalists, or social scientists are simultaneously volatile, exceeding any formal practices of accounting or analysis, and demanding to be accounted for, analysed, or valued. The article discusses four speculative events or cases in the genomics economy: the March 2000 bursting out of the genomics bubble, prompted in part by remarks by President Clinton and Prime Minister Blair to the media concerning gene patenting; the new disclosure requirements of the US Securities and Exchange Commission (SEC) regarding "forward-looking statements" as they appear in genomics press releases; deCODE Genetics' registration statement with the SEC that discloses a settlement of a dispute over the ownership of a fragment of DNA; and the entanglement between the author's ethnographic fieldwork and the breaking news story of reported payoffs from deCODE to the Icelandic political parties.     

Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. The Scottish Breast Cancer Committee.

OBJECTIVE--To investigate the incidence of fatal myocardial infarction in women in the two randomised arms of the Scottish adjuvant tamoxifen trial. DESIGN--Retrospective review of hospital notes to determine with the greatest possible certainty women who had died of an acute myocardial infarction. SETTING--Scottish Cancer Trials Office, the University of Edinburgh. PATIENTS--1070 postmenopausal women with operable breast cancer who were randomised to receive either adjuvant tamoxifen for five years or until relapse (539 patients) or tamoxifen for at least six weeks on the confirmation of first recurrence (531 patients). MAIN OUTCOME MEASURES--Incidence of fatal myocardial infarction in women with no known or suspected systemic cancer. RESULTS--Of the 200 women who died in the adjuvant tamoxifen arm of the trial, 44 were free of cancer at death and 10 of these died of myocardial infarction. In the observation arm 251 women died, of whom 61 showed no evidence of systemic cancer and 25 had a fatal myocardial infarction. The incidence of fatal myocardial infarction in the two groups was significantly different (chi 2 = 6.88, p = 0.0087). CONCLUSION--Tamoxifen given for at least five years as adjuvant therapy for breast cancer seems to have a cardioprotective oestrogen-like effect in postmenopausal women.     

The Association of Socioeconomic Status and Access to Low-Volume Service Providers in Breast Cancer

Background

No large-scale study has explored the combined effect of patients’ individual and neighborhood socioeconomic status (SES) on their access to a low-volume provider for breast cancer surgery. The purpose of this study was to explore under a nationwide universal health insurance system whether breast cancer patients from a lower individual and neighborhood SES are disproportionately receiving breast cancer surgery from low-volume providers.

Methods

5,750 patients who underwent breast cancer surgery in 2006 were identified from the Taiwan National Health Insurance Research Database. The Cox proportional hazards model was used to compare the access to a low-volume provider between the different individual and neighborhood SES groups after adjusting for possible confounding and risk factors. Hosmer-Lemeshow goodness-of-fit statistic was used to determine how well the model fit the data.

Results

Univariate analysis data shows that patients in disadvantaged neighborhood were more likely to receive breast cancer surgery at low-volume hospitals; and lower-SES patients were more likely to receive surgery from low-volume surgeons. In multivariate analysis, after adjusting for patient characteristics, the odds ratios of moderate- and low-SES patients in disadvantaged neighborhood receiving surgery at low-volume hospitals was 1.47 (95% confidence interval=1.19-1.81) and 1.31 (95% confidence interval=1.05-1.64) respectively compared with high-SES patients in advantaged neighborhood. Moderate- and low-SES patients from either advantaged or disadvantaged neighborhood had an odds ratios ranging from 1.51 to 1.80 (p<0.001) to receiving surgery from low-volume surgeons. In Hosmer-Lemeshow goodness-of-fit test, p>0.05 that shows the model has a good fit.

Conclusions

In this population-based cross-sectional study, even under a nationwide universal health insurance system, disparities in access to healthcare existed. Breast cancer patients from a lower individual and neighborhood SES are more likely to receive breast cancer surgery from low-volume providers. The authorities and public health policies should keep focusing on these vulnerable groups.     

The United States and the new law of the sea

Abstract

The official U.S. statement on the 32nd meeting of the International Whaling Commission (IWC termed the outcome a “modest success.”; However, from the point of view of conservationists—i.e., governments and private groups seeking greater protection for the world's endangered whales—the results of the 1980 IWC session can be described at best as satisfactory. The disappointing U.S. performance at this and other recent Commission proceedings strongly suggests the need for a reassessment of American cetacean policy and the way in which we pursue this policy in the IWC.

The discussion will begin with a review of U.S. objectives in the IWC in relation to national and international law governing cetaceans. The focus will then turn to the role played by the United States in the Commission's deliberations on selected issues in 1980. The conclusion will set forth recommendations for improvements in American policy and strategy in the IWC.     

Carcinomatous Neuromyopathy—The Non-Metastatic Effects of Cancer on the Nervous System

Cancer can produce a variety of effects on the nervous system either by direct compression or invasion, or remotely by some as yet unknown metabolic, toxic, viral or immunologic effect on the nervous system. The neurologic effects associated with cancer that does not directly involve neural tissue have distinctive features that can give the first clue to a previously undiagnosed neoplasm. Physicians who see patients with neurologic illness should be aware that there may be an underlying malignant lesion giving rise to the neurologic syndrome; and conversely they should be on the alert for neurologic complications in patients with known cancer even though the lesion does not directly press upon or invade nerve tissue.     

Cancer prevention: setting the scene.

Each year in the United Kingdom there are over 300,000 new cases of cancer and nearly 165,000 deaths from cancer. It is widely believed that as many as four fifths of all cancers are preventable by means that are already available. The Health of the Nation and the Europe Against Cancer programme have set targets and strategies for reducing the risk of cancer. An approach based on the whole population will achieve the greatest reductions in morbidity and mortality. Complementary to this is the individual approach, which can be based in primary care and targeted at high risk subjects. Health promotion and screening in primary care are not in themselves self evidently valuable. Their effectiveness must be tested rigorously and scientifically. Furthermore, because of limited time and resources, health education in primary care should be focused on interventions that are likely to achieve the greatest benefit, such as helping people to stop smoking.     

Cancer predisposition in Bloom's syndrome.

This article focuses upon defining those factors which may contribute to the pathogenesis of cancer. The molecular basis of tumour etiology is discussed with reference to cancer predisposing syndromes, and in particular to the human inherited disease, Bloom's syndrome. In Bloom's syndrome, patients are predisposed to a wide variety of malignant disease. We propose a model in which overexpression of the ubiquitous c-myc proto-oncogene contributes to this process.     

A plea for ‘genealogical thinking’ in comparative biology – a rebuttal to the reply of Szucsich,Wirkner, and Pass to my article ‘Deconstructing Morphology’

Scholtz G. in press. A plea for ‘genealogical thinking’ in comparative biology – a rebuttal to the reply of Szucsich, Wirkner, and Pass to my article ‘Deconstructing Morphology’. —Acta Zoologica (Stockholm) 00 : 1–4. Szucsich et al. (in press) claim that – in contrast to my statement – morphological thinking has to be ‘cladistic.’ Based on this premise, they stress the difference between the relationships among states of characters versus those among structures assigned to the same character state as implemented in numerical cladistic reasoning. SEA claim that my approach to the homology concept only deals with the problem of the integration of various character states into the same character, whereas the necessary relationships among structures assigned to the same state are not covered. Based on this distinction, SEA also criticise the application of similarity in my definition of homology. Furthermore, they address the issue of evolutionarily independent units.     

Impact of Pelvic Radiotherapy on Gut Microbiota of Gynecological Cancer Patients Revealed by Massive Pyrosequencing

Although pelvic irradiation is effective for the treatment of various cancer types, many patients who receive radiotherapy experience serious complications. Gut microbial dysbiosis was hypothesized to be related to the occurrence of radiation-induced complications in cancer patients. Given the lack of clinical or experimental data on the impact of radiation on gut microbiota, a prospective observational study of gut microbiota was performed in gynecological cancer patients receiving pelvic radiotherapy. In the current study, the overall composition and alteration of gut microbiota in cancer patients receiving radiation were investigated by 454 pyrosequencing. Gut microbial composition showed significant differences (P < 0.001) between cancer patients and healthy individuals. The numbers of species-level taxa were severely reduced after radiotherapy (P < 0.045), and the abundance of each community largely changed. In particular, the phyla Firmicutes and Fusobacterium were significantly decreased by 10% and increased by 3% after radiation therapy, respectively. In addition, overall gut microbial composition was gradually remolded after the full treatment course of pelvic radiotherapy. In this set of cancer patients, dysbiosis of the gut microbiota was linked to health status, and the gut microbiota was influenced by pelvic radiotherapy. Although further studies are needed to elucidate the relationship between dysbiosis and complications induced by pelvic radiotherapy, the current study may offer insights into the treatment of cancer patients suffering from complications after radiation therapy.     

Recent Trends in Computer Assisted Diagnosis (CAD) System for Breast Cancer Diagnosis Using Histopathological Images

Breast cancer is one of the common type of cancer in females across the world. An early detection and diagnosis of breast cancer may reduce the mortality rate to a great extent. To diagnose breast cancer, different types of imaging modalities are used to collect samples like mammography, Computerized Tomography, Magnetic Resonance Imaging, Ultrasound and Biopsy. Histopathological images obtained from biopsy may influence how and at which stage the cancer is being diagnosed. The Computer Assisted Diagnosis (CAD) system helps the pathologists in early diagnosis of breast cancer. In this survey, the recently reported techniques for breast cancer diagnosis using histopathological images have been summarized. This study could be beneficial for: (i) Clinicians to receive second opinion from the CAD system for early diagnosis, and (ii) Researchers to analyze and enhance the existing state-of-art techniques used in CAD system, which may further reduce the gap of variability between intra and inter observer.     

Prioritising health services in an era of limits: the Oregon experience.

How do we decide who should receive the benefits that medical science has to offer? One approach to this decision process, that used by the state of Oregon, is described: who and what are covered, and how health care is financed and delivered, are considered. Oregon''s priorities were set on the basis of broad consensus. The objective of health care reform, it was agreed, is to improve, maintain, or restore health--not universal coverage, access to health care, or cost containment. A Health Services Commission was created to consider clinical effectiveness and, through public involvement, to attempt to integrate social values into the priority list. Oregon''s legislature can use the list to develop an overall health policy which recognises that health can be maintained only if investments in several related areas are balanced.     

Cancer screening in older adults.

Adults aged 65 and older represent an increasingly important segment of the US population. Cancer is an important cause of death in this group. Screening for cancer can significantly reduce cancer incidence and mortality. In this review I address screening for breast, cervical, prostate, lung, colorectal, and ovarian cancer in older Americans. Decisions about screening for cancer must consider the effects of screening, diagnostic evaluations, and treatments on the quality of life of each person.     

Biological response modifiers of cancer-related neuroendocrine disorders: efficacy of the long-term dopaminergic agonist cabergoline in the treatment of breast cancer-induced hyperprolactinemia

The evaluation of the biological status of cancer patients should not be limited only to investigation of immune reactivity, but should also include analysis of the endocrine condition, namely concerning those hormones which have appeared to be tumor growth factors, such as prolactin (PRL) for breast and prostate carcinomas. This statement is justified by the fact that the evidence of abnormally high serum concentrations of PRL has been proven to be associated with poor prognosis in breast and prostate cancer patients. Moreover, since hyperprolactinemia negatively influences the efficacy of anticancer therapies in breast cancer, it could be fundamental to achieve a normalization of PRL levels by long-acting dopaminergic agents, such as cabergoline. On this basis, a study was planned to evaluate the effect of cabergoline on PRL levels in hyperprolactinemic metastatic breast cancer subjects. The study included 20 hyperprolactinemic metastatic breast cancer subjects, who were randomized to receive no therapy or cabergoline at 0.5 mg/week orally for 4 consecutive weeks. Cabergoline therapy induced a normalization in all patients, whereas no spontaneous normalization of PRL levels occured in the control group. These results show that a weekly oral administration of the long-acting dopaminergic agent cabergoline is a well tolerated and effective treatment of metastatic breast cancer-related hyperprolactinemia. The possible prognostic impact of PRL normalization needs to be established by successive studies.     

Country profile: Australia,New South Wales. From validation to implementation: Progressing tobacco smoking cessation among people with cancer and beyond via relevant authorities

This paper delineates how a program of tobacco smoking cessation after a cancer diagnosis was achieved by engagement of multiple stakeholders, government, and non-government authorities in one jurisdiction in Australia, New South Wales. While it had become increasingly obvious that smoking cessation imparts benefits akin to other known treatment modalities, knowledge of this generalisation is without benefit unless this information is delivered in a trusted context and means to quit are made available. Against a backdrop of little enthusiasm among clinicians, the Cancer Institute NSW, charged with implementing tobacco control strategies, decided to focus its 2017 annual colloquium on the topic. While the evidence was unequivocal, better clarity was needed that this was indeed a clinical responsibility, and on the resources needed. The Clinical Oncology Society of Australia, (COSA) a non-governmental peak national body representing cancer care professionals, addressed this challenge. The society’s governing body resolved to develop a position statement indicating how smoking cessation might be integrated within hospital-based cancer care. The position statement, endorsed by nineteen other cancer and non-cancer organisations, provided reassurance to the Institute to improve record capture of hospital smoking information; upskill all clinical staff and develop an automatic “patient opt out” referral to existing resources such as the Quitline. Early pilot work shows that people newly diagnosed with cancer who smoke and who were advised at that time to quit increased from 55% in 2016 to 72% in 2019.     

CALIFORNIA MEDICAL ASSOCIATION: TRANSFER OF PATIENTS FOR THERAPY

The following statement regarding requests for transfer of patients from one county to another for certain types of therapy not available locally, was prepared by the Cancer Commission of the California Medical Association.     

Factors Influencing Patient Pathways for Receipt of Cancer Care at an NCI-Designated Comprehensive Cancer Center

Background

Within the field of oncology, increasing access to high quality care has been identified as a priority to reduce cancer disparities. Previous research reveals that the facilities where patients receive their cancer care have implications for cancer outcomes. However, there is little understanding of how patients decide where to seek cancer care. This study examined the factors that shape patients’ pathways to seek their cancer care at a National Cancer Institute-designated comprehensive cancer center (NCI-CCC), and differences in these factors by race, income and education.

Methods

In-depth interviews and survey questionnaires were administered to a random sample of 124 patients at one NCI-CCC in the Northeast US. In-depth interview data was first analyzed qualitatively to identify themes and patterns in patients’ pathways to receive their cancer care at an NCI-CCC. Logistic Regression was used to examine if these pathways varied by patient race, income, and education.

Results

Two themes emerged: following the recommendation of a physician and following advice from social network members. Quantitative data analysis shows that patient pathways to care at an NCI-CCC varied by education and income. Patients with lower income and education most commonly sought their cancer care at an NCI-CCC due to the recommendation of a physician. Patients with higher income and education most commonly cited referral by a specialist physician or the advice of a social network member. There were no statistically significant differences in pathways to care by race.

Conclusions

Our findings show that most patients relied on physician recommendations or advice from a social network member in deciding to seek their cancer care at an NCI-CCC. Due to the role of physicians in shaping patients’ pathways to the NCI-CCC, initiatives that strengthen partnerships between NCI-CCCs and community physicians who serve underserved communities may improve access to NCI-CCCs.     

Cancer patterns in Canada.

Cancer is diagnosed in about 70 000 Canadians each year and is the leading cause of the loss of potential years of life before age 75 among women. Life-threatening forms of cancer will develop in at least one of every three Canadian newborns during their lifetimes if current cancer risks are not reduced. Lung and breast cancers are, respectively, the leading causes of premature death due to cancer among men and women. Compared with other countries Canada has low death rates for stomach cancer but high rates for certain smoking-related cancers (those of the lung and of the mouth and throat), leukemia and cancers of the colon, breast and lymphatic tissues. Newfoundland has the highest rates of death from stomach cancer and the lowest rates of death from prostatic cancer, whereas the western provinces have the opposite pattern. The rates of death from lung cancer among men are highest in Quebec, the province with the highest prevalence of smoking. In Canada the overall rates of death from cancer increased by 32% among men from 1951 to 1983. However, among women they declined by 12% from 1951 to 1976 and increased from 1976 to 1983, particularly among those aged 55 to 74. The rising rates of death due to lung cancer were primarily responsible for these increases. Lung cancer will likely displace breast cancer as the leading cancer killer of Canadian women by 1990. Given the relatively low survival rates for cancers caused by smoking and the lack of substantial improvement in rates for the most frequent types of cancer, preventive strategies that include effective measures to reduce tobacco consumption are urgently required.     

Family Physicians' Barriers to Cancer Screening in Extremely Obese Patients

Extremely obese women are less likely than nonobese women to receive breast and cervical cancer screening examinations. Reasons for this disparity are unclear and may stem from patient and/or physician barriers. This sequential mixed‐methods study used individual in‐depth interviews of 15 family physicians followed by a mail survey of 255 family physicians (53% response rate) to understand the barriers they faced in performing cancer screening examinations in extremely obese women. Barriers fell into three main areas: (i) difficulty doing pelvic and breast exams; (ii) inadequate equipment; and (iii) challenges overcoming patient barriers and refusal. This led some physicians to avoid performing breast and pelvic examinations on extremely obese women. Having more knowledge about specific examination techniques was associated with less difficulty in palpating lumps on breast and pelvic examinations (P < 0.005). Physicians perceived that embarrassment, aversion to undressing, and avoidance of discussions related to their weight were the most frequent barriers extremely obese women had with getting physical examinations. Educating and/or motivating patients and addressing fears were strategies used most frequently when patients refused mammograms or Pap smears. Interventions focusing on physician barriers, such as educating them on specific examination techniques, obtaining adequate equipment and supplies, and providing resources to assist physicians in dealing with patient barriers and refusal, may be fruitful in increasing cancer screening rates in extremely obese patients. Future research studies testing the effectiveness of these strategies are needed to improve cancer outcomes in this high‐risk population.