abstract: Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias British Columbia, Canada

Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias.:

Diabetologia. 2011 Sep;54(9):2263-71

Abstract

AIMS/HYPOTHESIS:
Despite the vast body of epidemiological literature on the risk of cancer in people with diabetes, few studies have examined the pattern of cancer risk during different time windows following diabetes onset. The objective of the study was to examine the risks of site-specific cancer in people with incident type 2 diabetes during different time windows following diabetes onset.

METHODS: 

This was a population-based retrospective cohort study. The study period was 1 April 1994 to 31 March 2006; censoring occurred at 31 March 2006, at death or on departure from British Columbia, Canada. Using linked health databases, we identified incident cohorts with and without diabetes, who were matched by age, sex and index year. Following a minimum 2-year cancer washout period, first site-specific cancers were identified prospectively in both cohorts.

RESULTS: 

Within 3 months following diabetes onset, participants with diabetes had significantly increased risks of colorectal, lung, liver, cervical, endometrial, ovarian, pancreatic and prostate cancers. After the initial 3-month period, the risks for colorectal (HR 1.15, 95% CI 1.05, 1.25), liver (HR 2.53, 95% CI 1.93, 3.31) and endometrial (HR 1.58, 95% CI 1.28, 1.94) cancers remained significantly elevated compared with those without diabetes.

The diabetes cohort remained at increased risk of pancreatic cancer in later years, but followed a different pattern: HR 3.71 at 3 months-1 year, 2.94 at 1-2 years, 1.78 at 2-3 years and 1.65 at 3-10 years (p value for all <0.01). After an initial period of elevated risk, men with type 2 diabetes subsequently had a decreased risk of prostate cancer (HR 0.82, 95% CI 0.76, 0.88).

CONCLUSIONS/INTERPRETATION: 

People with type 2 diabetes are at increased risk of select cancers; this risk is particularly elevated at the time of diabetes onset, which is likely to be due to increased ascertainment.

open access: Medscape - How Would Physicians Die?

How Would Physicians Die?


"How do doctors prefer to die? This question was addressed in a recent article on the Website zocalopublicsquare.org. The article suggests that physicians eschew extraordinary measures to extend life; instead they put a priority on reducing the pain and maximizing the quality of any limited time remaining. In a discussion on Medscape Physician Connect, an all-physician discussion group, doctors evaluated the accuracy of this portrait.
Overwhelmingly, the respondents agreed with sentiments expressed in the article. They sought to avoid the agony of a lingering final illness for themselves and for those they love. The results of an accompanying poll were unanimous. When completing the thought, "If I or my family were faced with a terminal illness with great potential for a terrible course and reasonable options have failed," all 27 respondents chose, "I'd want the focus to be on quality of life and comfort, no CPR." Not one expressed a preference for life-extending measures. Several physicians shared wrenching stories from personal experience...........cont'd

open access: CA-125: To Monitor or Not to Monitor?: Evidence Against Monitoring CA-125 For Ovarian Cancer Patients in Remission (Dr's Rustin, Karlan, Markman)

CA-125: To Monitor or Not to Monitor?: Evidence Against Monitoring CA-125

 For Ovarian Cancer Patients in Remission

Gordon Rustin, MD; Beth Y. Karlan, MD; Maurie Markman, MD

Authors and Disclosures

Posted: 03/08/2012

Editor's Note:
 
CA-125 is the most useful tumor marker in ovarian cancer. Since 1981, measurement of the serum level of the CA-125 antigen has become a standard component of routine management of women with advanced ovarian cancer.^[1,2] CA-125 concentrations are used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients. However, the question remains as to whether routine monitoring of CA-125 in women with advanced ovarian cancer in complete remission is advantageous. Recently, Drs. Gordon Rustin and Beth Karlan -- experts in the treatment of ovarian cancer -- participated in a Medscape Virtual Debate via email addressing the question, "Should patients with advanced ovarian cancer in complete remission undergo routine CA-125 monitoring?" Dr. Maurie Markman served as moderator. What follows is their conversation..........cont'd

open access: Expert Reviews - Current developments in ovarian cancer screening (March 2012)

Expert Reviews - Expert Review of Obstetrics & Gynecology - 7(2):131 - Full Text

ABSTRACT

Over 150 delegates from the UK, USA and Europe with a core interest in risk prediction and screening for ovarian cancer attended the International Conference on Ovarian Cancer Screening held on 29–30 November 2011 in London, UK. The scientific program was driven by two experts in the field – Usha Menon and Ian Jacobs – with assistance from the scientific committee, which included Steve Skates, Jatinderpal Kalsi, Anna Lokshin, Uzi Beller, Tim Mould and Ranjit Manchanda. Over the 2 days, key opinion leaders and researchers reported on the latest developments, and debated the future of risk prediction and screening for ovarian cancer.

                                      ~~~~~~~~~~~~~

The conference started with a welcome from Ian Jacobs (University of Manchester, Manchester, UK), followed by an overview of the current management of ovarian cancer (OC) by Tim Mould (University College Hospitals NHS Trust, London, UK). Stuart Campbell (Create Health Ltd, London, UK), a stalwart in the field of pelvic ultrasonography, chaired the first session on differential diagnosis in symptomatic patients. Robert Bast (University of Texas MD Anderson Cancer Center, TX, USA), who in the early 1980s discovered CA125, discussed recent biomarker panels and algorithms (Risk of Malignancy Index [RMI], Risk of Ovarian Malignancy Algorithm [ROMA] and OVA1) for OC diagnosis. His view was that the current challenge, especially in the USA, was implementation so that OC patients could be operated on by trained gynecological oncologists. Of the many OC markers, CA125 and HE4 provided the greatest discrimination between malignant and benign adnexal masses, with the latter particularly useful in premenopausal women..........cont'd

open access: Expert Reviews - Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC paradigm (ovarian/breast)

Expert Reviews - Expert Review of Vaccines - 11(3):275 - Full Text
  
Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC paradigm

Key issues

	• Heterologous prime—boost regimen with antigenically diverse recombinant poxviruses encoding for tumor-associated antigens and B7.1/ICAM-1/LFA3 cassette represents a most promising vaccination schedule inducing clinical and immunological responses.
	• PANVAC shows clinical efficacy in patients with metastatic breast and ovarian cancers.
	•  Patients with limited tumor burden and minimal prior chemotherapy had a benefit from PANVAC vaccination.
	• PANVAC was demonstrated to be immunologically active in some of the patients who developed clinical responses.
	• Overall survival, rather than progression-free survival, may be more relevant for addressing the effects of therapeutic cancer vaccines.
	• PANVAC, as also other cancer vaccines, elicits a dynamic process of immune responses, which may be exploited in subsequent therapies.
	• Vaccines used in the adjuvant setting (i.e., in patients with low tumor burden following conventional treatment) may be more efficacious than in patients with more advanced disease having increased tumor load.
	• Immunological end points as intermediate markers are needed for assessing clinical efficacy shortly after vaccination. Five-year view "The ultimate goal of therapeutic cancer vaccines should be to reduce the risk of recurrences in cancer patients with minimal residual disease or with no evidence of disease. In this case, therapeutic cancer vaccines, such as PANVAC, should be applied in the adjuvant setting after conventional therapies. However, therapeutic vaccination may also be applied in the metastatic setting, albeit in this case, it will likely need to be combined with chemotherapy. Considering the time of translation of vaccination-induced immune responses into clinical efficacy, median OS in the group of vaccinated patients may be affected at much later time points after treatment initiation compared to the group of patients receiving chemotherapy. Therefore, it becomes mandatory to plan clinical trials in such a way as to include start of assessments of clinical efficacy at later time points, which will also allow a better planning for interim analyses. OS as an end point for clinical vaccine trials poses a problem for making decisions about treatment efficacy after short-term assessment. Thus, there is a need for standardized immunological biomarkers as intermediate end points, which will be useful to determine clinical benefit shortly after immunotherapy. Such immunological end points will be essential to demonstrate the development of vaccine-induced immune responses and their clinical relevance. Novel immune-related response criteria are also essential for assessing clinical activity of cancer vaccines. Thus, developing optimized cancer vaccines and combining those with modalities aimed at improving their anticancer activity in well-designed clinical trials will open new avenues for the design of clinically effective cancer vaccine strategies. In this scenario, PANVAC may play a significant role in cancer immunotherapy for appropriately selected patients with cancer." Financial & competing interests disclosure   The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter discussed in the article. This includes employment, consultancies, stock ownership or options, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this article.

abstract: Clinical Outcome Prediction by MicroRNAs in Human Cancer: A Systematic Review

Clinical Outcome Prediction by MicroRNAs in Human Cancer: A Systematic Review

Background
MicroRNA (miR) expression may have prognostic value for many types of cancers. However, the miR literature comprises many small studies. We systematically reviewed and synthesized the evidence.

. ........The median hazard ratio for poor outcome in externally validated studies was 2.52 (IQR = 2.26–5.40). For all classifier miRs in studies that evaluated overall survival across diverse malignancies, the miRs most frequently associated with poor outcome after accounting for differences in miR assessment due to platform type were let-7 (decreased expression in patients with cancer) and miR 21 (increased expression).

Conclusions MiR classifiers show promising prognostic associations with major cancer outcomes and specific miRs are consistently identified across diverse studies and platforms. These types of classifiers require careful external validation in large groups of cancer patients that have adequate protection from bias.

pdf: Summaries for Patients - Surrogate Decision Makers’ Interpretation of Prognostic Information

Surrogate Decision Makers’ Interpretation of Prognostic Information

What are the implications of the study?

Inaccurate interpretations of doctors’ prognostications arise partly from optimistic biases rather than simply from misunderstandings. Helping surrogates attain realistic expectations about patients’ likely outcomes is more complex than just giving clear information.

Weighing the Chances at Life's End - NYTimes.com

Weighing the Chances at Life's End - NYTimes.com


"........But the grimmer the prognosis, the more inaccurate and more optimistic the surrogates’ responses became. Only 22 percent correctly interpreted a statement about what a “5 percent chance of surviving” meant, while 65 percent answered with greater optimism.
“They clearly grasped the meaning of these statements,” Dr. White said. “They were not misunderstanding the numbers. They weren’t misunderstanding the language.” If that had been the case, you’d expect them to have been inaccurate about good news, too.
Instead, relatives hearing doctors deliver dire prognoses just didn’t accept or believe them. They displayed, in medspeak, “a systematic optimism bias.”
Such bias has shown up many times before in the medical literature. Cancer patients enrolled in early phases of clinical trials, for instance,....."

Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases. (300T>G mutation)

Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases.:
Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases.
Fam Cancer. 2012 Mar 1;


Abstract
It is estimated that about 5-10% of ovarian and 2-5% of all breast cancer patients are carriers of a germline BRCA1 or BRCA2 gene mutation. Most families with detected BRCA1 or BRCA2 gene mutation are qualified for molecular testing on the basis of family history of breast or ovarian cancers. The purpose of our study was to establish the frequency of positive family history of cancer in a series of Polish consecutive breast and ovarian cancer patients in two groups, with and without the BRCA1 gene mutations. We analysed the prevalence of four of the most common BRCA1 mutations: 5382insC (c.5266dupC), 300T>G (p.181T>G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5). The patient group consisted of 1,845 consecutive female breast and 363 ovarian cancer cases. 19 out of 37 (51%) of BRCA1-positive ovarian cancer patients and 21 out of 55 (39%) BRCA1-positive breast cancer had negative family history of breast and/or ovarian cancer among first- and second-degree relatives.

In ovarian cancer patients, negative family history was more frequent in those with 300T>G BRCA1 gene mutation than in 5382insC carriers. This finding indicates the necessity of searching for 300T>G mutation in families with a single diagnosis of ovarian cancer in family. The high frequency of mutations detected in breast cancer patients lacking obvious family history shows that breast cancer patients should be qualified for genetic testing on the basis of wide clinical and pathological criteria.

Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States

Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States: Publication year: 2012

Source:Cancer Epidemiology, Volume 36, Issue 1


Background: 
Cancer mortality statistics, an important indicator for monitoring cancer burden, are traditionally restricted to instances when cancer is determined to be the underlying cause of death (UCD) based on information recorded on standard certificates of death. This study's objective was to determine the impact of using multiple causes of death codes to compute site-specific cancer mortality statistics.

Methods:
The state cancer registries of California, Colorado and Idaho provided linked cancer registry and death certificate data for individuals who died between 2002 and 2004, had at least one cancer listed on their death certificate and were diagnosed with cancer between 1993 and 2004. These linked data were used to calculate the site-specific proportion of cancers not selected as the UCD (non-UCD) among all cancer-related deaths (any mention on the death certificate). In addition, the retrospective concordance between the death certificate and the population-based cancer registry, measured as confirmations rates, was calculated for deaths with cancer as the UCD, as a non-UCD, and for any mention.

Results: 
Overall, non-UCD deaths comprised 9.5 percent of total deaths; 11 of the 79 cancer sites had proportions greater than 3 standard deviations from 9.5 percent. The confirmation rates for UCD and for any mention did not differ significantly for any of the cancer sites.

Conclusion and impact:
The site-specific variation in proportions and rates suggests that for a few cancer sites, death rates might be computed for both UCD and any mention of the cancer site on the death certificate. Nevertheless, this study provides evidence that, in general, restricting to UCD deaths will not under report cancer mortality statistics.

(re: statistics) Comparison of methods for calculating relative survival in population-based studies

Comparison of methods for calculating relative survival in population-based studies: Publication year: 2012

Source:Cancer Epidemiology, Volume 36, Issue 1


Background: 

It is vital that unbiased estimates of relative survival are estimated and reported by cancer registries. A single figure of relative survival is often required to make reporting simpler. This can be obtained by pooling all ages or, more commonly, by using age-standardisation. The various methods for providing a single figure estimate of relative survival can give very different estimates.

Methods:

The problem is illustrated through an example using Finnish thyroid cancer data. The differences are further explored through a simulation study that investigates the effect of age on the estimates of relative survival.

Results: 

The example highlights that in practice the all-age estimates from the various methods can be substantially different (up to 6 percentage units at 15 years of follow-up). The simulation study confirms the finding that differing estimates for the all-age estimates of relative survival are obtained. Performing age-standardisation makes the methods more comparable and results in better estimation of the true net survival.

Conclusions: 

The all-age estimates of relative survival rarely give an appropriate estimate of net survival. We feel that modelling or stratifying by age when calculating relative survival is vitally important as the lack of homogeneity in the cohort of patients leads to potentially biased estimates. We feel that the methods using modelling provide a greater flexibility than life-table based approaches. The flexible parametric approach does not require an arbitrary splitting of the time-scale, which makes it more computationally efficient. It also has the advantage of easily being extended to incorporate time-dependent effects.

Postmenopausal hormone therapy and ductal carcinoma in situ: A population-based case–control study

Postmenopausal hormone therapy and ductal carcinoma in situ: A population-based case–control study: Publication year: 2012

Source:Cancer Epidemiology

Background and aim:

The relationship between hormone therapy (HT) and invasive breast cancer has been extensively investigated, but the relationship between HT and in situ breast cancer has received relatively little attention. We examined the relationship between HT and ductal carcinoma in situ (DCIS) among postmenopausal women who participated in a population-based case–control study in Connecticut, USA.

Methods: 

This analysis included 1179 post-menopausal women (603 controls and 576 cases), who comprised a subset of a population-based case–control study that included all incident cases of breast carcinoma in situ (BCIS) in Connecticut and frequency-matched controls by 5-year age intervals.

Results: 

We found no association between DCIS and ever use of any HT (adjusted odds ratio (OR)=0.85, 95% confidence interval (CI): 0.65–1.11); of estrogen alone (adjusted OR=0.93; 95% CI: 0.68–1.29) or of estrogen and progesterone (adjusted OR=0.75; 95% CI: 0.52–1.08). There was also no association between DCIS and current use of these hormones. In addition, estimated risk of DCIS did not increase with duration of use of these preparations. Conclusions: These results add to a small literature that remains inconclusive. To determine whether HT poses risk of in situ breast cancer, larger studies with greater power and precise control of important covariates (e.g., mammography screening) are needed, as are meta-analyses of available data.

Demanding dignity, and competence, in older people's care : The Lancet (several links of interest)

Demanding dignity, and competence, in older people's care : The Lancet

Other Articles of Interest

Articles Effect of dignity therapy on distress and end-of-life experience in terminally ill patients: a randomised controlled trial

Articles Dignity in the terminally ill: a cross-sectional, cohort study

Public Health Rediscovering human dignity

Comment Dignity and inequality

Commentary Death and dignity: dogma disputed

Cetuximab inhibits the growth of mucinous ovarian carcinoma tumor cells lacking... - Abstract - UK PubMed Central

Abstract

The purpose of this study was to explore the possibility of targeted molecular therapy with anti-epidermal growth factor receptor (anti-EGFR) antibody (cetuximab) for the treatment of mucinous ovarian carcinoma. ...............These results suggest the possibility of targeted molecular therapy with cetuximab for mucinous ovarian carcinoma cells lacking a KRAS gene mutation.

Activity and resistance of trastuzumab according to different clinical settings

Activity and resistance of trastuzumab according to different clinical settings: Publication year: 2012


Trastuzumab, a humanized monoclonal antibody directed against HER2, has shown efficacy in breast cancers; however many patients do not respond to this reagent. Here, we discuss the potential mechanisms of trastuzumab efficacy and resistance in different clinical settings as a step toward optimizing the appropriate application of this antibody. The three major antitumor mechanisms of trastuzumab, i.e., inhibition of proliferation, antibody-dependent cell cytotoxicity (ADCC) and inhibition of DNA repair, appear to be differentially operative in different clinical settings. ADCC appears to be the prevalent mechanism in trastuzumab neoadjuvant monotherapy, whereas in neoadjuvant, adjuvant or metastatic settings in which trastuzumab is combined with chemotherapy, the relative role of ADCC is probably small, considering the compromising effects of chemotherapy on the immune cells that mediate this mechanism. In neoadjuvant and adjuvant settings involving concomitant use of trastuzumab and chemotherapy, the primary mechanism at play is presumably inhibition of DNA repair by the antibody, while in sequential protocols, the antibody acts mostly by exerting cytostatic activity through inhibition of HER2-mediated tumor cell proliferation. According to the ability of the antibody to induce cytotoxic or cytostatic antitumor effects depending on the clinical setting, different criteria, i.e., RECIST for cytotoxic effect, OS, and DFS for cytostatic, must be considered in accurately estimating antibody efficacy. Moreover, since trastuzumab resistance likely depends directly on the mechanisms responsible for its antitumor activity, resistance mechanisms must also be considered with respect to the different clinical settings.

Importance of monitoring renal function in patients with cancer

Importance of monitoring renal function in patients with cancer: Publication year: 2012


Monitoring renal function in patients with solid tumors and hematologic malignancies is vital to the safe administration of therapeutic agents. Renal impairment is frequent in elderly patients (i.e., age⩾65) with cancer, despite normal serum creatinine levels in most patients. Because serum creatinine levels do not accurately reflect clearance rates, renal function should be estimated by calculation (either Cockcroft-Gault or abbreviated Modification of Diet in Renal Disease [aMDRD] equations) or by measuring creatinine clearance using a 24-h urine collection. Additionally, patients with cancer often have preexisting comorbidities or other risk factors that increase the probability of renal impairment before receiving potentially nephrotoxic therapies. Patient age, preexisting renal dysfunction, and chronic comorbidities (e.g., diabetes, kidney disease, hypertension, and cardiac insufficiency) all contribute to the risk of renal impairment. Furthermore, both cancer and its therapies may lead to renal impairment. A number of cancer therapy agents are nephrotoxic, including chemotherapy agents, molecular targeted agents, pain management agents, radiopharmaceuticals, contrast agents used in radiology, and antiresorptive agents, and contrast agents used in radiology are nephrotoxic as well. Undetected decreases in clearance rates by the kidneys can greatly increase exposure to treatment agents, possibly decreasing the safety of treatment and exacerbating renal impairment.
In conclusion, all cancer patients, not only those receiving potentially nephrotoxic agents, require renal monitoring.

Reliability, validity and feasibility of quality of life instruments for adult patients with cancer undergoing chemotherapy: result from a systematic review - 2012 - International Journal of Evidence-Based Healthcare

Abstract

Aim  The aim of this review was to analyse the literature critically and present the best available evidence related to quality of life (QoL) instruments that consists of all four subscales of physical, psychological, social and spiritual, which can be used in the clinical setting to assess adult patients with cancer on chemotherapy.

Inclusion criteria  This review included randomised control trials and observational studies without control group related to QoL instruments used for cancer chemotherapy. The types of participants for this review included all adults with cancer over the age of 18 years who have undergone chemotherapy. The QoL instruments for this review included instruments that consist of all subscales of physical, psychological, social and spiritual. In order to retrieve QoL instruments that were current and not outdated, this review included studies reported in the recent 10 years.

Results  A total of 3149 references was retrieved during the initial search. Only 13 articles with validation of the QoL instruments that contained all the four subscales of physical, psychological, social and spiritual were included in this review. Four QoL instruments were identified. These include the City of Hope QOL – Ovarian Cancer Tool (QOL-OVCA), QOL-Breast cancer version (QOL-BC) ........

Conclusion  In this review, there was one article on development of new QoL instrument, the New India QoL tool, which has comprehensive validity examinations – the least number of items that may be useful in the clinical setting but need further psychometric testing in different settings or languages. The QLI-CV instrument has had comprehensive intra- and inter-method validation on different languages, different cultural settings and various types of cancer. However, the instrument may not be feasible because the method to calculate the QoL score is not straightforward.