Association of cognitive function with increased risk of cancer death and all-cause mortality: Longitudinal analysis, systematic review, and meta-analysis of prospective observational studies

Background Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not been extensively investigated yet. We aimed to evaluate the association of cognitive function with the risk of cancer death and all-cause mortality in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) and Leiden 85-plus Study. Additionally, a systematic review and meta-analysis of longitudinal studies were conducted to evaluate the association of cognitive function and risk of cancer death. Methods Risk of cancer death and all-cause mortality were reported using hazard ratios (HRs) with 95% confidence interval (CI) in tertiles of cognitive function of PROSPER and Leiden85-Plus Study. Additionally, PubMed, Embase, Web of Science, Cochrane, PsycINFO, Academic Search Premier, CINHAL, and Emcare were searched up to November 1st, 2020 to perform a systematic review and meta-analysis. The relative risks (RRs) with 95%CI of cancer death per each standard deviation lower performance in cognitive measurements were calculated. Results Participants of PROSPER had 1.65-fold (95%CI 1.11–2.47) greater risk of cancer death (P for trend = 0.016) and 1.85-fold (95%CI 1.46–2.34) higher risk of all-cause mortality (P for trend<0.001), in multivariable models. Results of the Leiden-85 Plus Study showed that subjects with MMSE score below 24 had a lower chance of cancer death (HR 0.79, 95%CI 0.36–1.70, P for trend = 0.820) but had 2.18-fold (95%CI 1.57–3.02) higher risk of all-cause mortality compared to the reference group (P for trend<0.001). Besides, the results of systematic review and meta-analysis showed that per each standard deviation lower performance in cognitive function, individuals were at a 10% higher chance of cancer death (RR 1.10, 95%CI 1.00–1.20, P-value = 0.044). Conclusions Lower cognitive function performance is associated with a marginally increased risk of cancer death, in line with a significantly greater risk of all-cause mortality.

Auranofin and its analogs as prospective agents for the treatment of colorectal cancer

Today colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. This disease is poorly chemo-sensitive toward the existing medical treatments so that new and more effective therapeutic agents are urgently needed and intensely sought. Platinum drugs, oxaliplatin in particular, were reported to produce some significant benefit in CRC treatment, triggering the general interest of medicinal chemists and oncologists for metal-based compounds as candidate anti-CRC drugs. Within this frame, gold compounds and, specifically, the established antiarthritic drug auranofin with its analogs, form a novel group of promising anticancer agents. Owing to its innovative mechanism of action and its favorable pharmacological profile, auranofin together with its derivatives are proposed here as novel experimental agents for CRC treatment, capable of overcoming resistance to platinum drugs. Some encouraging results in this direction have already been obtained. A few recent studies demonstrate that the action of auranofin may be further potentiated through the preparation of suitable pharmaceutical formulations capable of protecting the gold pharmacophore from unselective reactivity or through the design of highly synergic drug combinations. The perspectives of the research in this field are outlined.

Lung cancer attracts greater stigma than other cancer types in Aotearoa New Zealand

Introduction: Lung cancer is the leading cause of cancer death in Aotearoa New Zealand, killing over 1,700 people each year. Despite the burden of lung cancer, a recent stuff.co.nz article called lung cancer deaths ‘the cancer disgrace that no-one-talks about’. When asked about this Professor Ross Lawrenson hypothesized that the low survival rate meant that few people made the transition from patient to advocate. Here, we investigate another, lung-cancer stigma.Method: Participants completed the Cancer Stigma Scale (CSS) for one of five cancer types (lung, cervical, breast, skin, or bowel). The CSS is a 25-item scale, with items that tap awkwardness, avoidance, severity, policy opposition, personal responsibility, and financial discrimination.Results: Relative to most other cancer types included, people were more likely to avoid someone with lung cancer, view interacting with someone with lung cancer as more awkward, and view people with lung cancer as being responsible for their condition.Conclusion: Lung cancer is the leading cause of cancer death in Aotearoa New Zealand. Unfortunately, the current study suggests that lung cancer also leads the way with respect to stigma, with patients not only attracting higher levels of blame but also higher levels of ostracism.

Association of bilateral salpingo-oophorectomy with all cause and cause specific mortality: population based cohort study

Objectives To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery. Design Population based cohort study. Setting Ontario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017. Participants 200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (<45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17). Exposures Bilateral salpingo-oophorectomy versus ovarian conservation. Main outcomes measures The primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P<0.0125 was considered statistically significant. Results Bilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged <45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged <45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P<0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged <50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter. Conclusion In this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged <50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.

The prostate tissue-based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy

ABSTRACTPurposeCurrent biomarkers are inadequate prognostic predictors in localized prostate cancer making treatment decision-making challenging. Previously, we observed that the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer-associated stromal cells – the telomere biomarker – is strongly associated with progression to metastasis and prostate cancer death after prostatectomy independent of currently used pathologic indicators.Experimental DesignWe optimized our method allowing for semi-automated telomere length determination in single cells in fixed tissue, and tested the telomere biomarker in tissue microarrays from five cohort studies of men surgically treated for clinically localized disease (N=2,255). We estimated the relative risk (RR) of progression to metastasis (N=311) and prostate cancer death (N=85) using models appropriate to each study’s design adjusting for age, prostatectomy stage, and tumor grade, which then we meta-analyzed using inverse variance weights.ResultsCompared with men who had less variable telomere length among prostate cancer cells and longer telomere length in prostate cancer-associated stromal cells, men with the combination of more variable and shorter telomere length, had 3.76-times the risk of prostate cancer death (95% CI 1.37-10.3; p=0.01) and had 2.23-times the risk of progression to metastasis (95% CI 0.99-5.02, P=0.05). The telomere biomarker was associated with prostate cancer death in men with intermediate risk disease (Grade Groups 2/3: RR=9.18, 95% CI 1.14- 74.0, p=0.037) and with PTEN intact tumors (RR=6.74, 95% CI 1.46-37.6, p=0.015).ConclusionsThe telomere biomarker is robust and associated with poor outcome independent of current pathologic indicators in surgically-treated men.Translational RelevanceCurrent prognostic biomarkers in localized prostate cancer are inadequate imperfect predictors; therefore, new biomarkers are needed to improve the prognostic classification and management of these patients. In a five-cohort study, we confirmed that the tissue-based telomere biomarker – the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer-associated stromal cells – was associated with progression to metastasis and prostate cancer death independent of currently used prognostic indicators after prostatectomy for clinically-localized disease. Importantly, the telomere biomarker was associated with poor outcome in men with intermediate risk disease, as well as in men with intact PTEN tumors. Thus, this tissue-based telomere biomarker has the translational potential to improve treatment and surveillance decision-making.

Adjuvant Breast Radiotherapy Improve Survival in Women With Heart Failure

BACKGROUND To date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast intraductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). PATIENTS AND METHODS : We enrolled 294 women with left-breast IDC at clinical stages IA–IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs). RESULTS In the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44–0.94) was a significant independent prognostic factor for all-cause death (P = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24–0.71; P = 0.0017) and 0.37 (0.22–0.63; P = 0.0004), respectively, compared with the no adjuvant WBRT group. The aHR (95% CI) of breast cancer death for adjuvant WBRT was 0.54 (0.44–0.85; P = 0.0201) compared with no adjuvant WBRT group. CONCLUSION Adjuvant WBRT was associated with a decrease in all-cause death, breast cancer death, LRR, and DM in women with left IDC and HFrEF compared with no adjuvant WBRT.

Lobular Mammary Carcinoma Presenting as an Obstructing Rectal Mass

Breast cancer is the leading cause of cancer death in women, and while metastasis is common to areas like the bone, lungs, and brain, it is rare to metastasize to the gastrointestinal tract and especially to the rectum. Due to the rarity of this condition and its resemblance clinically and radiologically to primary gastrointestinal tract tumors, diagnosis and treatment are challenging. We present a case of metastatic lobular mammary carcinoma in a 52-year-old Bahraini woman who presented with an obstructing rectal mass.

Oxidative Stress and Autophagy as Key Targets in Melanoma Cell Fate

Melanoma originates from the malignant transformation of melanocytes and is one of the most aggressive forms of cancer. The recent approval of several drugs has increased the chance of survival although a significant subset of patients with metastatic melanoma do not show a long-lasting response to these treatments. The complex cross-talk between oxidative stress and the catabolic process autophagy seems to play a central role in all aspects of melanoma pathophysiology, from initiation to progression and metastasis, including drug resistance. However, determining the fine role of autophagy in cancer death and in response to redox disruption is still a fundamental challenge in order to advance both basic and translational aspects of this field. In order to summarize the interactions among reactive oxygen and nitrogen species, autophagy machinery and proliferation/growth/death/apoptosis/survival, we provide here a narrative review of the preclinical evidence for drugs/treatments that modulate oxidative stress and autophagy in melanoma cells. The significance and the potential for pharmacological targeting (also through multiple and combination approaches) of these two different events, which can contribute independently or simultaneously to the fate of melanoma, may help to define new processes and their interconnections underlying skin cancer biology and unravel new reliable approaches.

A Double-Edged Sword Role of Cytokines in Prostate Cancer Immunotherapy

Prostate cancer (PC) is one of the most common malignancies among men and is the second leading cause of cancer death. PC immunotherapy has taken relatively successful steps in recent years, and these treatments are still being developed and tested. Evidence suggests that immunotherapy using cytokines as essential mediators in the immune system may help treat cancer. It has been shown that cytokines play an important role in anti-tumor defense. On the other hand, other cytokines can also favor the tumor and suppress anti-tumor responses. Moreover, the dose of cytokine in cancer cytokine-based immunotherapy, as well as the side effects of high doses, can also affect the outcomes of treatment. Cytokines can also be determinative in the outcome of other immunotherapy methods used in PC. In this review, the role of cytokines in the pathogenesis of cancer and their impacts on the main types of immunotherapies in the treatment of PC are discussed.