Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations.

Outdoor air pollution is a major contributor to the burden of disease worldwide. Most of the global population resides in places where air pollution levels, because of emissions from industry, power generation, transportation, and domestic burning, considerably exceed the World Health Organization's health-based air-quality guidelines. Outdoor air pollution poses an urgent worldwide public health challenge because it is ubiquitous and has numerous serious adverse human health effects, including cancer. Currently, there is substantial evidence from studies of humans and experimental animals as well as mechanistic evidence to support a causal link between outdoor (ambient) air pollution, and especially particulate matter (PM) in outdoor air, with lung cancer incidence and mortality. It is estimated that hundreds of thousands of lung cancer deaths annually worldwide are attributable to PM air pollution. Epidemiological evidence on outdoor air pollution and the risk of other types of cancer, such as bladder cancer or breast cancer, is more limited. Outdoor air pollution may also be associated with poorer cancer survival, although further research is needed. This report presents an overview of outdoor air pollutants, sources, and global levels, as well as a description of epidemiological evidence linking outdoor air pollution with cancer incidence and mortality. Biological mechanisms of air pollution-derived carcinogenesis are also described. This report concludes by summarizing public health/policy recommendations, including multilevel interventions aimed at individual, community, and regional scales. Specific roles for medical and health care communities with regard to prevention and advocacy and recommendations for further research are also described.

Do age at diagnosis, tumour thickness and tumour site explain sex differences in melanoma survival? A causal mediation analysis using cancer registry data.

Women diagnosed with melanoma have better survival than men, but little is known about potential intervention targets to reduce this survival gap by sex. We conducted a population-based study using Victorian Cancer Registry data including 5833 women and 6780 men aged 15 to 70 years when diagnosed with first primary melanoma between 2007 and 2015. Deaths to the end of 2020 were identified through linkage to the Victorian and national death registries. We estimated the effect of age at diagnosis, tumour thickness and tumour site on reducing the melanoma-specific survival gap by sex (ie, interventional indirect effects [IIEs]) on risk difference (RD) scale. Compared to women, there were 211 (95% CI: 145-278) additional deaths per 10 000 in men within 5 years following diagnosis. We estimated that 44% of this gap would be reduced by a hypothetical intervention shifting the distribution of melanoma thickness in men to be the same as that observed for women (IIEthickness RD 93 [95% CI: 75-118] per 10 000) and 20% by an intervention on tumour site (head and neck/trunk vs upper limb/lower limb; IIEsite RD 42 [95% CI: 15-72] per 10 000), while an intervention on age at diagnosis would have a negligible effect. Tumour thickness, tumour site and age at diagnosis mediated 65% of the effect of sex on 5-year melanoma survival in Victoria. Of these factors, tumour thickness had the most considerable mediating effect, suggesting that effective promotion of earlier detection of melanoma in men could potentially nearly halve the gap in melanoma-specific survival by sex.

Healthy lifestyle and cancer survival: A multinational cohort study.

Lifestyle factors after a cancer diagnosis could influence the survival of cancer 60 survivors. To examine the independent and joint associations of healthy lifestyle factors with mortality outcomes among cancer survivors, four prospective cohorts (National Health and Nutrition Examination Survey [NHANES], National Health Interview Survey [NHIS], UK Biobank [UKB] and Kailuan study) across three countries. A healthy lifestyle score (HLS) was defined based on five common lifestyle factors (smoking, alcohol drinking, diet, physical activity and body mass index) that related to cancer survival. We used Cox proportional hazards regression to estimate the hazard ratios (HRs) for the associations of individual lifestyle factors and HLS with all-cause and cancer mortality among cancer survivors. During the follow-up period of 37,095 cancer survivors, 8927 all-cause mortality events were accrued in four cohorts and 4449 cancer death events were documented in the UK and US cohorts. Never smoking (adjusted HR = 0.77, 95% CI: 0.69-0.86), light alcohol consumption (adjusted HR = 0.86, 95% CI: 0.82-0.90), adequate physical activity (adjusted HR = 0.90, 95% CI: 0.85-0.94), a healthy diet (adjusted HR = 0.69, 95% CI: 0.61-0.78) and optimal BMI (adjusted HR = 0.89, 95% CI: 0.85-0.93) were significantly associated with a lower risk of all-cause mortality. In the joint analyses of HLS, the HR of all-cause and cancer mortality for cancer survivors with a favorable HLS (4 and 5 healthy lifestyle factors) were 0.55 (95% CI 0.42-0.64) and 0.57 (95% CI 0.44-0.72), respectively. This multicohort study of cancer survivors from the United States, the United Kingdom and China found that greater adherence to a healthy lifestyle might be beneficial in improving cancer prognosis.

Post-diagnosis dietary factors, supplement use and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.

Post-diagnosis physical activity and sedentary behaviour and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

Low physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post-diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post-diagnosis physical activity, and/or sedentary behaviour in relation to all-cause and cause-specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non-linear dose-response random-effects meta-analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non-overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%-60% estimated reductions in risk. Sedentary behaviour was positively associated with all-cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited-suggestive evidence for recreational physical activity with all-cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited-no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders.

Three-year survival of breast cancer patients attending a one-stop breast care clinic nested within a primary care health facility in sub-Saharan Africa-Zambia.

In Zambia, women with breast symptoms travel through multiple levels of the healthcare system before obtaining a definitive diagnosis. To eradicate this critical barrier to care, we nested a novel breast specialty service platform inside a large public-sector primary healthcare facility in Lusaka, Zambia to offer clinical breast examination, breast ultrasound, and ultrasound-guided core needle biopsy in a one-stop format, tightly linked to referral for treatment. The objective of the study was to determine the life expectancy and survival outcomes of a prospective cohort of women diagnosed with breast cancer who were attended to and followed up at the clinic. The effect of breast cancer stage on prognosis was determined by estimating stage-specific crude survival using the Kaplan-Meier method. Survival analysis was used to estimate mean lifespan according to age and stage at diagnosis. We enrolled 302 women with histologically confirmed breast cancer. The overall 3-year survival was 73%. An increase in patients presenting with early breast cancer and improvements in their survival were observed. Women with early-stage breast cancer had a lifespan similar to the general population, while loss of life expectancy was significant at more advanced stages of disease. Our findings suggest that implementing efficient breast care services at the primary care level can avert a substantial proportion of breast cancer-related deaths. The mitigating factor appears to be stage of disease at the time of diagnosis, the cause of which is multifactorial, with the most influential being delays in the referral process.

Breast cancer survival in India across 11 geographic areas under the National Cancer Registry Programme.

BACKGROUND: Population-based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5-year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population-Based Cancer Registries (PBCRs) in India. METHODS: In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer-II approach, respectively. RESULTS: The 5-year age-standardized relative survival (95% confidence interval [CI]) of patients with breast cancer was 66.4% (95% CI, 65.5%-67.3%). Mizoram (74.9%; 95% CI, 68.1%-80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%-74.9%), Kollam (71.5%; 95% CI, 69.2%-73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%-71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%-68.6%). The 5-year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively. CONCLUSIONS: The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country.

Survival Outcomes in Patients with Resectable Gastric Cancer Treated with Total Neoadjuvant Therapy.

BACKGROUND: Perioperative chemotherapy has become the standard of care for locally advanced gastric cancer. Total neoadjuvant therapy (TNT), including both chemotherapy and chemoradiation, is utilized in other gastrointestinal malignancies. We determined survival in a contemporary cohort of gastric cancer patients treated with TNT. METHODS: Using a prospective institutional database, patients diagnosed with cT2-4 or cN+ gastric adenocarcinoma (January 2012 to June 2022) who underwent staging laparoscopy, received TNT, and underwent gastrectomy were identified. Overall survival (OS) and disease-specific survival (DSS) were determined using standard statistical methods. RESULTS: The study included 203 patients. The most common TNT sequence was induction chemotherapy followed by chemoradiation (n = 186 [91.6%]). A total of 195 (96.1%) patients completed planned neoadjuvant treatments. Surgery included total gastrectomy in 108 (53.2%), extended (D1+/D2) lymphadenectomy in 193 (95.1%), and adjacent organ resection in 19 (9.4%) patients. Pathologic complete response (pCR) was achieved in 32 (15.8%) patients. The 5-year OS rate was 65.2% (95% confidence interval [CI] 57.8-73.5%), and the 5-year DSS rate was 70.8% (95% CI 63.6-78.9%) in the study cohort. Among patients with pCR, the 5-year OS rate was 89.1% (95% CI 78.1-100.0%), and the 5-year DSS rate was 96.9% (95% CI 91-100%). Posttreatment pathologic N and M stages were the strongest prognostic indicators associated with both OS and DSS. CONCLUSIONS: Total neoadjuvant therapy for resectable gastric cancer is associated with a high rate of treatment completion and promising survival outcomes. Prospective comparisons with perioperative treatment are needed to identify patients most likely to benefit from TNT.

Should Palpable Nodes Be Exclusionary in Patients Who Are Otherwise Candidates for ACOSOG Z0011-Type Trials?

BACKGROUND: Palpable nodes were exclusionary in American College of Surgeons Oncology Group (ACOSOG) Z0011, while SINODAR-ONE excluded those with positive axillary nodes by palpation and ultrasound. To determine whether clinical nodal status should be exclusionary in those fulfilling pathologic criteria for ACOSOG Z0011 and similar trials, this study analyzed the accuracy and implications of clinical nodal positivity. METHODS: Patients ≥ 18 years old with cT1-T2, cN0-cN1, M0 breast cancer were identified in the National Cancer Database between 2004 and 2019. Subset characteristics of cN1 and cN0 were compared with respect to final pathologic nodal status and overall survival (OS). RESULTS: Of 57,823 patients identified, 77.0% were cT1 and 23.0% were cT2. Of the 93.9% of patients who were staged as cN0, 16.7% were pN1; of the remaining 6.1% staged as cN1, 9.6% were found to be pN0. Among cN1/pN0 patients, 14.9% underwent axillary dissection without sentinel node biopsy. There was no difference in adjusted OS for patients staged as cN0 versus cN1 who were found to be pN1 (HR 1.13, 95% CI 0.93-1.37, p = 0.22), a finding that persisted on subset analysis in those with two positive nodes (HR 0.91, 95% CI 0.62-1.33, p = 0.63). CONCLUSIONS: Clinical nodal stage does not affect OS in pN1 patients. Clinical nodal assessment can both overstage patients and result in unnecessary axillary surgery. These data suggest that cN1 patients who are otherwise candidates for a Z0011-like paradigm should still be considered eligible. Their final candidacy should be determined by surgical lymph node pathology and not preoperative clinical status.

Understanding the Quality of Life Among Patients With Cancer in Saudi Arabia: Insights From a Cross-Sectional Study.

INTRODUCTION: Cancer patients' quality of life (QoL) significantly influences treatment response and mortality rates. Understanding QoL domains among patients with cancer and what affects it can help create interventions that improve QoL and ease patients' experience. This study measures the OoL among patients with cancer and influencing factors. METHODS: A prospective cross-sectional questionnaire-based study included cancer patients aged >18 currently receiving treatment. The questionnaire collected social and economic data, followed by the validated Arabic version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Means and standard deviations for described numeric variables and frequencies and percentages described categorical variables. Analysis of variance, F-tests, and P-values were reported. RESULTS: Among 182 cancer patients, 60% were female. Younger patients exhibited higher QoL in physical and role functioning (P = .016 and .03) and experienced more significant financial impact (P = .0144). Females reported more adverse effects from cancer symptoms, including fatigue, nausea, vomiting, and pain (36.7% vs 25.5%, P = .005; 20.6% vs 11.5%, P = .0186; 34.7% vs 25.1%, P = .0281). Single patients had superior QoL in physical functioning compared to others (P = .0127). Patients traveling long distances were more likely to face adverse financial consequences (P = .007). Asthmatic patients exhibited lower QoL in physical, role, and cognitive functioning (72.3 vs 37.8, P = .0147; 76.4 vs 22.2, P = .0024; 84.7 vs 44.4, P = .0038) and reported increased dyspnea and appetite loss (16 vs 55.6 and 26.1 vs 66.7, both P < .05). CONCLUSION: Factors influencing QoL in Saudi cancer patients include age, marital status, gender, hospital distance, and chronic conditions. Thus emphasizing the necessity for personalized care strategies to enhance outcomes and alleviate the overall burden of cancer care.

Racial disparities in the incidence and survival outcomes in diffuse large B-cell lymphoma in adolescents and young adults.

Diffuse large B-cell Lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL). The disease generally occurs in older patients. Although at a lower prevalence, the disease also occurs in the adolescent and young adult group (AYA). There is paucity of data in the literature on racial and ethnic disparities in the incidence and survival outcomes of DLBCL in the AYA group. The objective of our study is to demonstrate the disparities in these outcomes. Utilizing SEER, we obtained data on patient demographics, incidence, and survival from 2000 to 2020. We observed statistically significant reduced incidence of DLBCL in all racial groups, except the non-Hispanic Asian and Pacific Islander group (NHAPI). The non-Hispanic Black group (NHB) had one of the lowest survival despite showing the largest decrease in incidence in DLBCL. The differences in the survival could be secondary to socioeconomic factors, however other reasons need to be explored. The increased incidence among the NHAPI group mirrors that of large population-based studies in East Asian countries, however, underlying reasons have not been elucidated.

Comprehensive analysis of the prognostic value of glutathione S-transferases Mu family members in breast cancer.

Breast cancer (BC) remains a significant public health concern globally, with a high number of reported cases and a substantial number of deaths every year. Accumulating reactive oxygen species (ROS) and oxidative stress are related to BC and the Glutathione S-transferases Mu (GSTM) family is one of the most important enzymatic detoxifiers associated with many cancers. In this study, UALCAN, Kaplan-Meier plotter, bc-GenExMiner, cBioPortal, STRING, Enrichr, and TIMER databases were employed to carry out a comprehensive bioinformatic analysis and provide new insight into the prognostic value of GSTMs in BC. GSTM2-5 genes in mRNA and protein levels were found to be expressed at lower levels in breast tumors compared to normal tissues, and reduction in mRNA levels is linked to shorter overall survival (OS) and relapse-free survival (RFS). The lower mRNA levels of GSTMs were strongly associated with the worse Scarff-Bloom-Richardson (SBR) grades (p < 0.0001). The mRNA levels of all five GSTMs were substantially higher in estrogen receptor (ER)-positive and progesterone receptor (PR)-positive compared to ER-negative and PR-negative BC patients. As well, when nodal status was compared, GSTM1, GSTM3, and GSTM5 were significantly higher in nodal-positive BC patients (p < .01). Furthermore, GSTM4 had the most gene alteration (4%) among other family members, and GSTM5 showed the strongest correlation with CD4+ T cells (Cor= .234, p = 2.22e-13). In conclusion, our results suggest that GSTM family members may be helpful as biomarkers for prognosis and as therapeutic targets in BC.

Integrative Oncology Approaches to Reduce Recurrence of Disease and Improve Survival.

PURPOSE OF REVIEW: After a cancer diagnosis, patients ask what they can do in addition to the recommended treatments to increase their survival. Many turn to integrative medicine modalities and lifestyle changes to improve their chances of survival. Numerous studies have demonstrated that lifestyle changes can significantly improve survival rates for cancer patients. Less support exists for the use of natural products or supplements to improve cancer survival. In this manuscript, we review key findings and evidence in the areas of healthy eating habits, physical activity, stress management and social support, and sleep quality, as well as natural products and supplements as they relate to the cancer recurrence and survival. RECENT FINDINGS: While more research is needed to fully understand the mechanisms underlying the associations between lifestyle changes and cancer survival, findings suggest that lifestyle modifications in the areas of diet, physical activity, stress management and social support, and sleep quality improve clinical cancer outcomes. This is especially true for programs that modify more than one lifestyle habit. To date, outside of supplementing with vitamin D to maintain adequate levels, conflicting conclusion within the research remain regarding the efficacy of using natural products or supplement to improve cancer recurrence of disease or cancer survival. A call for further research is warranted. Lifestyle screening and counseling should be incorporated into cancer treatment plans to help improve patient outcomes. While the scientific community strives for the pursuit of high-quality research on natural products to enhance cancer survival, transparency, dialogue, and psychological safety between patients and clinicians must continue to be emphasized. Proactive inquiry by clinicians regarding patients' supplement use will allow for an informed discussion of the benefits and risks of natural products and supplements, as well as a re-emphasis of the evidence supporting diet and other lifestyle habits to increase survival.

Evaluation of antihypertensive medications use and survival in patients with ovarian cancer: a population-based retrospective cohort study.

BACKGROUND: Despite declining mortality in most countries and in Lithuania, ovarian cancer burden has remained high. Studies have indicated that antihypertensive medications use may help to improve ovarian cancer survival, however findings remain controversial. The aim of the study was to analyse the association between post-diagnosis antihypertensive medications intake and cancer-specific survival in ovarian cancer patients. METHODS: This retrospective cohort study included 588 ovarian cancer cases diagnosed between 2013 and 2015. Hazard ratios (HR) and corresponding 95% confidence intervals (95%CI) were estimated using multivariable Cox proportional hazards models to assess associations between antihypertensive medications and ovarian cancer-specific mortality. RESULTS: In total, 279 (47%) patients died during the follow-up; 242 (87%) of them died due to ovarian cancer. The risk of ovarian cancer death was reduced in angiotensin-converting enzyme inhibitors (ACE inhibitors) users vs. non-users (HR 0.55, 95% CI: 0.36-0.83). Subgroup analysis showed better ovarian cancer survival in higher dose ACE inhibitors users (HR 0.46, 95% CI: 0.28-0.77, p for trend 0.002); the effect was also stronger in age 51-65 years, stage I-III, surgery or chemotherapy treatment, pre-diagnosis ACE inhibitor users' and pre-diagnosis hypertension subgroups. The risk of cancer-specific death was slightly lower among calcium-channel blocker and angiotensin-receptor blocker users and higher among beta-blocker users as compared to non-users, however chance and confounding could not be ruled out. We found no association between the use of centrally and peripherally acting antiadrenergic agents and diuretics and risk of ovarian cancer-specific mortality. CONCLUSIONS: Our findings imply that post-diagnosis use of ACE inhibitors may be associated with reduced ovarian cancer-specific mortality; however, further research is needed for the comprehensive assessment.

'I Do It All Alone': The Burdens and Benefits of Being Diagnosed With, and Treated for, Colorectal Cancer During the Covid-19 Pandemic.

INTRODUCTION: The Covid-19 pandemic dramatically altered the way cancer care services were accessed and delivered, including for colorectal cancer (CRC). In the United Kingdom, patients were discouraged from presenting in primary care, many consultations took place remotely, investigative procedures and screening programmes were temporarily suspended, and fewer operations and treatments were delivered. People had to face the practical consequences of having cancer during a pandemic and navigate never before seen pathways, often alone. We examined the experience of being diagnosed and treated for CRC during the pandemic, and the implications of this on people's cancer journeys. METHODS: Semi-structured interviews were undertaken with people diagnosed with CRC during the Covid-19 pandemic (January 2020-May 2021), in the North East of England. An iterative topic guide was used during interviews, which took place remotely (telephone or Zoom), were audio recorded, pseudo-anonymised and transcribed. Initial transcripts were independently coded by two researchers, and a code 'bank' developed for application across transcripts. Development of themes and overarching analytical constructs was undertaken collaboratively by the research team. RESULTS: Interviews were conducted with 19 participants, analysed and four key themes identified: (1) The relative threats of Covid-19 and Cancer were not comparable, with cancer seen as posing a far greater risk than Covid-19; (2) Remote consultations were problematic, affecting patients' abilities to build rapport and trust with clinicians, assess nonverbal communication, and feel able to disclose, comprehend and retain information; (3) Stoma follow-up care was seen to be lacking, with long wait times for stoma reversal experienced by some; Finally, (4) Being alone during consultations negatively impacted some peoples' abilities to absorb information, and left them without the support of loved ones at an emotionally vulnerable time. However, some participants preferred being alone at certain points in their pathways, including receiving a diagnosis, and most frequently when receiving in-patient treatment. CONCLUSION: Being alone brought unexpected benefits, absolving people from undertaking emotions work for others, and instead focus on their recovery, however, remote consultations negatively impacted patients' experiences. This study highlights the complex benefits and burdens of pandemic-located cancer journeys, including how these shifted at different points across cancer pathways. PATIENT OR PUBLIC CONTRIBUTION: Lorraine Angell, a cancer survivor, has been central to this study from idea conception, contributing to: development of study focus and design; securing funding; production of patient-facing materials; development of interview topic guides; analysis and interpretation of data; and drafting of key findings and manuscripts.

Trident cold atmospheric plasma blocks three cancer survival pathways to overcome therapy resistance.

Therapy resistance is responsible for most cancer-related death and is mediated by the unique ability of cancer cells to leverage metabolic conditions, signaling molecules, redox status, and other pathways for their survival. Interestingly, many cancer survival pathways are susceptible to disturbances in cellular reactive oxygen species (ROS) and may therefore be disrupted by exogenous ROS. Here, we explore whether trident cold atmospheric plasma (Tri-CAP), a gas discharge with exceptionally low-level ROS, could inhibit multiple cancer survival pathways together in a murine cell line model of therapy-resistant chronic myeloid leukemia (CML). We show that Tri-CAP simultaneously disrupts three cancer survival pathways of redox deregulation, glycolysis, and proliferative AKT/mTOR/HIF-1α signaling in this cancer model. Significantly, Tri-CAP blockade induces a very high rate of apoptotic death in CML cell lines and in primary CD34+ hematopoietic stem and progenitor cells from CML patients, both harboring the therapy-resistant T315I mutation. In contrast, nonmalignant controls are minimally affected by Tri-CAP, suggesting it selectively targets resistant cancer cells. We further demonstrate that Tri-CAP elicits similar lethality in human melanoma, breast cancer, and CML cells with disparate, resistant mechanisms and that it both reduces tumor formation in two mouse models and improves survival of tumor-bearing mice. For use in patients, administration of Tri-CAP may be extracorporeal for hematopoietic stem cell transplantation therapy, transdermal, or through its activated solution for infusion therapy. Collectively, our results suggest that Tri-CAP represents a potent strategy for disrupting cancer survival pathways and overcoming therapy resistance in a variety of malignancies.

Cancer survival prediction by learning comprehensive deep feature representation for multiple types of genetic data.

BACKGROUND: Cancer is one of the leading death causes around the world. Accurate prediction of its survival time is significant, which can help clinicians make appropriate therapeutic schemes. Cancer data can be characterized by varied molecular features, clinical behaviors and morphological appearances. However, the cancer heterogeneity problem usually makes patient samples with different risks (i.e., short and long survival time) inseparable, thereby causing unsatisfactory prediction results. Clinical studies have shown that genetic data tends to contain more molecular biomarkers associated with cancer, and hence integrating multi-type genetic data may be a feasible way to deal with cancer heterogeneity. Although multi-type gene data have been used in the existing work, how to learn more effective features for cancer survival prediction has not been well studied. RESULTS: To this end, we propose a deep learning approach to reduce the negative impact of cancer heterogeneity and improve the cancer survival prediction effect. It represents each type of genetic data as the shared and specific features, which can capture the consensus and complementary information among all types of data. We collect mRNA expression, DNA methylation and microRNA expression data for four cancers to conduct experiments. CONCLUSIONS: Experimental results demonstrate that our approach substantially outperforms established integrative methods and is effective for cancer survival prediction. AVAILABILITY AND IMPLEMENTATION: https://github.com/githyr/ComprehensiveSurvival .

Postdiagnosis circulating osteoprotegerin and TRAIL concentrations and survival and recurrence after a breast cancer diagnosis: results from the MARIE patient cohort.

BACKGROUND: Experimental studies suggest a role for osteoprotegerin (OPG) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in mammary tumor development and progression. These biomarkers have been minimally investigated with respect to outcomes in breast cancer patients. METHODS: OPG and TRAIL were evaluated in blood samples collected from 2459 breast cancer patients enrolled in the MARIE study, a prospective population-based patient cohort, at median of 129 days after diagnosis. Participants were between ages 50 and 74 at diagnosis and recruited from 2002 to 2005 in two regions of Germany. Follow-up for recurrence and mortality was conducted through June 2015. Delayed-entry Cox proportional hazards regression was used to assess associations between OPG and TRAIL with all-cause and breast cancer-specific mortality, and recurrence, both overall and by tumor hormone receptor status. RESULTS: Median follow-up time was 11.7 years, with 485 deaths reported (277 breast cancer-specific). Higher OPG concentrations were associated with a higher risk of all-cause mortality (hazard ratio for 1-unit log2-transformed concentration (HRlog2) = 1.24 (95% confidence interval 1.03-1.49). Associations were observed in women diagnosed with ER-PR- tumors or discordant hormone receptor status (ER-PR-, HRlog2 = 1.93 (1.20-3.10); discordant ERPR, 1.70 (1.03-2.81)), but not for women with ER + PR + tumors (HRlog2 = 1.06 (0.83-1.35)). OPG was associated with a higher risk of recurrence among women with ER-PR- disease (HRlog2 = 2.18 (1.39-3.40)). We observed no associations between OPG and breast cancer-specific survival, or for TRAIL and any outcome. CONCLUSIONS: Higher circulating OPG may be a biomarker of a higher risk of poor outcome among women diagnosed with ER- breast cancer. Further mechanistic studies are warranted.

Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.

Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.

Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis.

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2  = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.