The rates of septicemia in older adults with prostate cancer treated with abiraterone or enzalutamide: A population-based study.

INTRODUCTION: Prostate cancer (PCa) is the most common non-cutaneous tumor among American men. Androgen receptor signaling inhibitors such as abiraterone and enzalutamide have been approved for similar disease states among patients with advanced PCa. Existing data suggest using steroids is associated with an increased risk of infection. Because abiraterone is usually prescribed with prednisone, we sought to compare the risk of septicemia in patients using abiraterone vs. enzalutamide. MATERIALS AND METHODS: We utilized the SEER-Medicare-linked data and used negative binomial regression models to compare the changes in the rates of septicemia-related hospitalizations six months pre- and post-abiraterone and enzalutamide initiation. RESULTS: We found that the incidence of septicemia-related hospitalizations increased 2.77 fold within six months of initiating abiraterone (incidence rate ratio [IRR]: 2.77, 95% confidence interval [CI]: 2.17-3.53) 1.97 fold within six months of starting enzalutamide (IRR: 1.97, 95% CI: 1.43-2.72). However, the difference in the changes did not reach statistical significance (interaction IRR: 0.71, 95% CI: 0.48-1.06). DISCUSSION: The findings suggest that both abiraterone and enzalutamide are associated with an increased risk of septicemia-related hospitalizations. However, the difference in the increase of septicemia risk following the two treatments did not reach statistical significance. Further studies are warranted to understand the mechanisms at play.

Prognostic Value of Fibroblast Growth Factor Receptor Genetic Alterations in Metastatic Urothelial Carcinoma.

INTRODUCTION: Evidence is limited on whether fibroblast growth factor receptor gene alterations (FGFRalt) impact clinical outcomes in patients with locally advanced or metastatic urothelial cancer (mUC). This study evaluated progression-free survival (PFS) in patients with mUC based on FGFRalt status in the first-line setting (1L). PATIENTS AND METHODS: Data on mUC patients were retrieved via convenience sampling of oncologists/urologists surveyed between August and September 2020 who treated at least 1 FGFRalt patient between July 2017 and June 2019. The questionnaire included information on patient demographics, FGFR status, treatment, and clinical and radiographic measures of progression. Primary endpoint was time from metastatic diagnosis to disease progression from initial treatment for FGFRalt and FGFRwt (wild-type) mUC. Cox proportional hazards models quantified adjusted risk of FGFR status relating to PFS. RESULTS: A total of 414 patients were analyzed. Mean age was 64.5 years, 73.9% were male, and 52.7% had an FGFRalt. Among FGFRalt, 47.2% received chemotherapy, 27.5% immune checkpoint inhibition (ICI), 11.5% chemotherapy+ICI, and 13.8% other treatments in 1L. FGFR status did not influence PFS from time of mUC diagnosis or among 224 stratified patients receiving either chemotherapy or chemotherapy+ICI. However, among 97 patients with an FGFRalt receiving 1L ICI therapy only, adjusted risk of progression was twice that of FGFRwt (HR: 2.12; 95% CI: 1.13-4.00). CONCLUSION: Although FGFRalt did not predict outcomes in the overall cohort, for patients treated with 1L ICI, FGFRalt had significantly higher rates of progression than FGFRwt patients. Further validation is needed to determine whether FGFRalt has a decreased benefit from ICI therapy.

Prostein expression on circulating tumor cells as a prognostic marker in metastatic castration-resistant prostate cancer.

BACKGROUND: Identification of emerging molecular biomarkers on circulating tumor cells (CTCs) represents an attractive feature of liquid biopsy that facilitates precision and tailored medicine in the management of metastatic castration-resistant prostate cancer (mCRPC). Prostein is an androgen-regulated transmembrane protein with high prostate specificity. Prostein-positive circulating tumor cell (CTC) was recently suggested to have diagnostic potential; however, no study has been conducted to evaluate its prognostic value in mCRPC. METHODS: CTCs from mCRPC patients were enumerated using the CellSearch System. Prostein-positive CTCs were identified by immunostaining results. The relationships between prostein expression on CTCs and PSA response rate, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (PFS), and overall survival (OS) were tested by Fisher's exact test or evaluated using Kaplan-Meier and multivariate Cox analyses. RESULTS: Prostein-positive CTCs were identified in 31 of 87 baseline samples from mCRPC patients and 16 of 51 samples collected at the first follow-up visit. PSA response rates were significantly lower in baseline prostein-positive patients (0%, 0/31) than in prostein-negative patients (19.6%, 11/56) (p = 0.007). The 31 prostein-positive patients had significantly shorter PSA-PFS (p < 0.001), radiographic PFS (p < 0.001), and OS (p = 0.018), compared to the 56 prostein-negative patients at baseline. The association with PSA-PFS maintained its significance (p = 0.028) in multivariate analyses. Analyzing prostein expression at the first follow-up as well as the conversion of prostein expression from baseline to follow-up samples not only confirmed the association with PSA-PFS, but also demonstrated prognostic significance with OS. CONCLUSION: Our study provides the first evidence to support the potential of prostein expression on CTCs to serve as a novel prognostic marker in mCRPC patients. Future large-scale prospective studies are needed to validate our findings.

Positive and negative psychosocial impacts on cancer survivors.

The purpose of this study is to understand psychosocial impacts on cancer survivors using the patient-reported outcomes measurement information system (PROMIS) Psychosocial Illness Impact banks. Cancer survivors (n = 509; age: 59.5 ± 1.4; 51.5% men) completed the PROMIS positive and negative illness impact items consisting of four sub-domains: self-concept (SC), social impact (SI), stress response (SR), and spirituality (Sp). Illness impact was defined as changed scores from items measuring "current" experiences to recalled experiences prior to cancer diagnosis. Descriptive statistics, effect sizes (ES), and coefficient of variation (CV) were calculated at item and sub-domain levels. Analysis of variance was used to identify potentially influential factors on the impacts. Our study found survivors reported stronger positive than negative impacts (overall ES mean: 0.30 vs. 0.23) in general; and more moderate (ES ≧ 0.30) positive than negative impacts at the item level, 54.3% (25 of 46) and 40% (16 of 40) for positive and negative items, respectively. Participants reported more positive impacts on SI and Sp but more negative impacts on SR. The CV results showed more individual differences appeared on positive SC items. Younger survivors reported stronger positive and negative impacts. Women reported higher positive impacts. Survivors with higher education levels tended to have higher positive SI impacts, while those with a lower family income reported higher negative SI and negative SR impacts. We conclude positive and negative psychosocial impacts coexisted-the strength of impacts varied across sub-domains. Age, gender, education, and family income influenced the psychosocial impacts reported by survivors. These findings provide a foundation to develop interventions to strengthen positive and minimize negative impacts and improve cancer survivors' overall well-being.

Review of Cardiovascular Risk of Androgen Deprivation Therapy and the Influence of Race in Men with Prostate Cancer.

Androgen deprivation therapy is the cornerstone of prostate cancer therapy. Recent studies have revealed an association between androgen deprivation therapy and cardiovascular adverse effects such as myocardial infarction and stroke. This review summarizes the available research on the cardiovascular risk of men using androgen deprivation therapy. We also discuss racial disparities surrounding both prostate cancer and cardiovascular disease, emphasizing the importance of biological/molecular and socioeconomic factors in assessing baseline risk in patients beginning androgen ablation. Based on the literature, we provide recommendations for monitoring patients who are at high risk for a cardiovascular adverse event while being treated on androgen deprivation therapy. This review aims to present the current research on androgen deprivation therapy and cardiovascular toxicity with an emphasis on racial disparities and provides a framework for clinicians to decrease the cardiovascular morbidity in men that are being treated with hormone therapy.

Three Ways to Improve Arm Function in the Chronic Phase After Stroke by Robotic Priming Combined With Mirror Therapy, Arm Training, and Movement-Oriented Therapy.

OBJECTIVE: To examine the effects of bilateral robotic priming combined with mirror therapy (R-mirr) vs bilateral robotic priming combined with bilateral arm training (R-bilat), relative to the control approach of bilateral robotic priming combined with movement-oriented training (R-mov) in patients with stroke. DESIGN: A single-blind, preliminary, randomized controlled trial. SETTING: Four outpatient rehabilitation settings. PARTICIPANTS: Outpatients with stroke and mild to moderate motor impairment (N=63). INTERVENTIONS: Patients received 6 weeks of clinic-based R-mirr, R-bilat, or R-mov for 90 min/d, 3 d/wk, plus a transfer package at home for 5 d/wk. MAIN OUTCOME MEASURES: Fugl-Meyer Assessment Upper Extremity subscale (FMA-UE), ABILHAND, and Stroke Impact Scale v3.0 scores before, immediately after, and 3 months after treatment as well as lateral pinch strength and accelerometry before and immediately after treatment. RESULTS: The posttest results favored R-mirr over R-bilat and R-mov on the FMA-UE score (P<.05). Follow-up analysis revealed that significant improvement in FMA-UE score was retained at the 3-month follow-up in the R-mirr over R-bilat or R-mov (P<.05). Significant improvements were not observed in the R-mirr over R-bilat and R-mov on other outcomes. CONCLUSIONS: Between-group differences were only detected for the primary outcome, FMA-UE. R-mirr was more effective at enhancing upper limb motor improvement, and the effect has the potential to be maintained at 3 months of follow-up.

Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease.

BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. RESULTS: The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. CONCLUSIONS: Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Epigenetic Dysregulations in Arsenic-Induced Carcinogenesis.

Arsenic is a crucial environmental metalloid whose high toxicity levels negatively impact human health. It poses significant health concerns to millions of people in developed and developing countries such as the USA, Canada, Bangladesh, India, China, and Mexico by enhancing sensitivity to various types of diseases, including cancers. However, how arsenic causes changes in gene expression that results in heinous conditions remains elusive. One of the proposed essential mechanisms that still has seen limited research with regard to causing disease upon arsenic exposure is the dysregulation of epigenetic components. In this review, we have extensively summarized current discoveries in arsenic-induced epigenetic modifications in carcinogenesis and angiogenesis. Importantly, we highlight the possible mechanisms underlying epigenetic reprogramming through arsenic exposure that cause changes in cell signaling and dysfunctions of different epigenetic elements.

A scoping review protocol to elucidate outcomes following abiraterone versus enzalutamide for prostate cancer.

INTRODUCTION: Abiraterone acetate and enzalutamide are commonly employed in prostate cancer therapy in an interchangeable manner. These drugs are highly efficacious in androgen antagonism to improve patient outcomes, but they also carry noteworthy risk of adverse effects. Common toxicities vary amongst the two drugs and may have differential interactions with patient co-morbidities, but these patterns are unclear as co-morbidities typically serve as exclusion criteria in clinical trials. Hence, there is no existing guidance on how clinicians may tailor treatment based on patient-specific factors. Analysis of differential patient outcomes between these two drugs can inform future systematic reviews, new clinical studies, and clinical decision making. METHOD AND ANALYSIS: The framework for this methodology was informed by the Joanna Briggs Institute methodology for scoping reviews. Title and abstract screening will be performed by two independent researchers to create an initial study inventory. This will be followed by full-text screening for study inclusion. Population-based studies describing patient outcomes, common toxicities, and associations with patient co-morbidities following abiraterone or enzalutamide therapy will be included. After data is extracted, it will be summarized for presentation. ETHICS AND DISSEMINATION: The findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on patient-specific factors informing treatment choice between abiraterone and enzalutamide for castration-resistant prostate cancer. All data are from published openly accessible sources, and therefore, no ethical clearance is necessary. The protocol is also registered at https://doi.org/10.6084/m9.figshare.19149227.

Outcomes Following Abiraterone versus Enzalutamide for Prostate Cancer: A Scoping Review.

Abiraterone acetate (AA) and enzalutamide (ENZ) are commonly used for metastatic prostate cancer. It is unclear how their outcomes and toxicities vary with patient-specific factors because clinical trials typically exclude patients with significant comorbidities. This study aims to fill this knowledge gap and facilitate informed treatment decision making. A registered protocol utilizing PRISMA scoping review methodology was utilized to identify real-world studies. Of 433 non-duplicated publications, 23 were selected by three independent reviewers. ENZ offered a faster and more frequent biochemical response (30-50% vs. 70-75%), slowed progression (HR 0.66; 95% CI 0.50-0.88), and improved overall survival versus AA. ENZ was associated with more fatigue and neurological adverse effects. Conversely, AA increased risk of cardiovascular- (HR 1.82; 95% CI 1.09-3.05) and heart failure-related (HR 2.88; 95% CI 1.09-7.63) hospitalizations. Ultimately, AA was associated with increased length of hospital stay, emergency department visits, and hospitalizations (HR 1.26; 95% CI 1.04-1.53). Accordingly, total costs were higher for AA, although pharmacy costs alone were higher for ENZ. Existing data suggest that AA and ENZ have important differences in outcomes including toxicities, response, disease progression, and survival. Additionally, adherence, healthcare utilization, and costs differ. Further investigation is warranted to inform treatment decisions which optimize patient outcomes.

Understanding the role of sex on outcomes for the cancer patient undergoing treatment with immune checkpoint inhibitors: a scoping review protocol.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for multiple cancer types. Sex plays an important role in both the development of cancer as well as the functioning of the immune system. Though a difference in response to immune therapy is emerging between men and women it is unclear how this difference affects cancer outcomes and what the potential underlying mechanisms are for those effects. The objective of this study is to describe the influence that sex has on the outcomes experienced by cancer patients on ICI therapy and to identify and analyse any knowledge gaps in the field. METHOD AND ANALYSIS: The framework for this methodology was guided by the Joanna Briggs Institute Manual for Evidence Synthesis. The search and review will be conducted from January 2022 to June 2022. Two independent researchers will screen titles and abstracts followed by full-text screening for manuscript inclusion. Full length studies published between 2010 and December 2021 found in PubMed, Cochrane, CINAHL, and Scopus describing the influence of sex differences on cancer outcomes in patients treated with ICIs will be included. After data are extracted it will be summarised for presentation. ETHICS AND DISSEMINATION: The findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on the potential differential impacts of ICIs. All data are from published openly accessible sources and therefore no ethical clearance is necessary.

Race-specific prostate cancer outcomes in a cohort of military health care beneficiaries undergoing surgery: 1990-2017.

BACKGROUND: There is substantial variability in prostate cancer (PCa) mortality rates across Caucasian American (CA), African American (AA), Asian, and Hispanic men; however, these estimates are unable to disentangle race or ethnicity from confounding factors. The current study explores survival differences in long-term PCa outcomes between self-reported AA and CA men, and examines clinicopathologic features across self-reported CA, AA, Asian, and Hispanic men. METHODS: This retrospective cohort study utilized the Center for Prostate Disease Research (CPDR) Multi-center National Database from 1990 to 2017. Subjects were consented at military treatment facilities nationwide. AA, CA, Asian, or Hispanic men who underwent radical prostatectomy (RP) for localized PCa within the first year of diagnosis were included in the analyses. Time from RP to biochemical recurrence (BCR), BCR to metastasis, and metastasis to overall death were evaluated using Kaplan-Meier unadjusted estimation curves and adjusted Cox proportional hazards regression. RESULTS: This study included 7067 men, of whom 5155 (73%) were CA, 1468 (21%) were AA, 237 (3%) were Asian, and 207 (3%) were Hispanic. AA men had a significantly decreased time from RP to BCR compared to CA men (HR = 1.25, 95% CI = 1.06-1.48, p = 0.01); however, no difference was observed between AA and CA men for a time from BCR to metastasis (HR = 0.73, 95% CI = 0.39-1.33, p = 0.302) and time from metastasis to overall death (HR = 0.67, 95% CI = 0.36-1.26, p = 0.213). CONCLUSIONS: In an equal access health care setting, AA men had a shorter survival time from RP to BCR, but comparable survival time from BCR to metastasis and metastasis to overall death.

Race-specific prostate cancer outcomes in a cohort of low and favorable-intermediate risk patients who underwent external beam radiation therapy from 1990 to 2017.

BACKGROUND: Previous research exploring the role of race on prostate cancer (PCa) outcomes has demonstrated greater rates of disease progression and poorer overall survival for African American (AA) compared to Caucasian American (CA) men. The current study examines self-reported race as a predictor of long-term PCa outcomes in patients with low and favorable-intermediate risk disease treated with external beam radiation therapy (EBRT). METHODS: This retrospective cohort study examined patients who were consented to enrollment in the Center for Prostate Disease Research Multicenter National Database between January 01, 1990 and December 31, 2017. Men self-reporting as AA or CA who underwent EBRT for newly diagnosed National Comprehensive Cancer Network-defined low or favorable-intermediate risk PCa were included. Dependent study outcomes included: biochemical recurrence-free survival, (ii) distant metastasis-free survival, and (iii) overall survival. Each outcome was modeled as a time-to-event endpoint using race-stratified Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis. RESULTS: Of 840 men included in this study, 268 (32%) were AA and 572 (68%) were CA. The frequency of biochemical recurrence, distant metastasis, and deaths from any cause was 151 (18.7%), 29 (3.5%), and 333 (39.6%), respectively. AA men had a significantly younger median age at time of EBRT and slightly higher biopsy Gleason scores. Multivariable Cox proportional hazards analyses demonstrated no racial differences in any of the study endpoints. CONCLUSIONS: These findings reveal no racial disparity in PCa outcomes for AA compared to CA men, in a long-standing, longitudinal cohort of patients with comparable access to cancer care.

Current and projected number of years of life lost due to prostate cancer: A global study.

BACKGROUND: Prostate cancer is an important cause of death worldwide. The number of years of life lost (YLL) due to prostate cancer is a metric of the toll of prostate cancer and using projections of demographic changes, can be used to measure future burden. METHODS: Prostate cancer mortality data by country and world region was retrieved from the Global Cancer Observatory and the World Health Organization mortality data set, and life expectancy was from the United Nations Department of Economic and Social Affairs. We estimated YLL as the difference between age at death in people with prostate cancer and remaining life expectancy for people of the same age in the general population. We also estimated the age-standardized YLL rates per 100,000 males over 50 and the average annual percentage change in YLL rates over the period 2000-2019 and the number of YLL for the year 2040 by applying population projections to the 2020 YLL rates. RESULTS: In 2020, 3.5 million person-years of life were lost due to prostate cancer in males over 50, and 40% of YLL were in those aged over 75. Age-standardized rates varied greatly between and within regions. Over the last two decades, rates of YLL have increased in many Asian and African countries while they have decreased in northern American and European countries. Globally, YLL are anticipated to double by 2040 to reach 7.5 million, with the greatest increases in Africa, Asia, and Latin America and the Caribbean. CONCLUSION: There are wide variations in the burden of prostate cancer globally as measured by YLL. The burden of prostate cancer is projected to increase over time and appears to be highest in Sub-Saharan Africa, Eastern Europe, and Latin America and the Caribbean. It will be critical to plan and implement programs to reduce the burden of prostate cancer globally.

Is Timing of Steroid Exposure Prior to Immune Checkpoint Inhibitor Initiation Associated with Treatment Outcomes in Melanoma? A Population-Based Study.

Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after ICIs. Modifications of the Cox proportional hazards model were used to calculate time-dependent hazards. Of 1671 patients with melanoma receiving ICIs, 907 received steroids. Compared with no steroids, last steroid exposures ≤1 month and 1-3 months prior to ICIs were associated with a 126% and 51% higher ACM within 3 months post ICI initiation, respectively (hazard ratio (HR): 2.26, 95% CI: 1.65-3.08; and HR: 1.51, 95% CI: 1.01-2.27). Steroid exposure within 3 months of initiating ICIs was associated with increased mortality up to 6 months after ICI. Further investigation is warranted to elucidate mechanisms affecting outcomes due to steroids.

Substantial Gleason reclassification in Black men with national comprehensive cancer network low-risk prostate cancer - A propensity score analysis.

BACKGROUND: Emerging evidence suggests that a subset of Black men with National Comprehensive Cancer Network (NCCN) low-risk prostate cancer (PCa) may harbor high volume and genomically aggressive disease. However, limited, and ambiguous research exist to evaluate the risk of extreme Gleason reclassification in Black men with low-risk PCa. METHODS: This retrospective cohort study included 45,674 low-risk PCa patients who underwent prostatectomy and were not on active surveillance, from National Cancer Database (NCDB). A propensity score matched-pair design was employed, and the final cohort was limited to 1:1 matched 12,340 patients. Gleason score reclassification was used as primary endpoint. As such, any migration to pathologic Gleason score ≥7(3 + 4) was identified as overall, whereas migration to ≥7(4 + 3) was defined as extreme reclassification. A conditional Poisson regression model was used to estimate the risk of reclassification. Whereas spline model was used to estimate the impact of increasing time to treatment as a non-linear function on Gleason reclassification between race group. RESULTS: Upon matching there were no differences in the baseline characteristics between race groups. In a matched cohort, higher proportion of low-risk Black men (6.6%) reported extreme reclassification to pathologic Gleason score than White men (5.0%), p < 0.001. In a conditional Poisson regression model adjusted for time to treatment, the risk of overall (RR = 1.09, 95% CI, 1.05-1.13, p < 0.001) and extreme (RR = 1.30, 95% CI, 1.12-1.50, p = 0.004) reclassification was significantly higher in Black men as compared to their White counterpart. In spline model, the probability of Gleason reclassification in Black men was elevated with increasing time to treatment, especially after 180 days (53% vs. 43% between Black and White men). CONCLUSION: Risk of Gleason score reclassification is disparately elevated in Black men with low-risk PCa. Furthermore, time to treatment can non-linearly impact Gleason reclassification in Black men.

International trends in cancer incidence in middle-aged and older adults in 44 countries.

OBJECTIVE: We examine international incidence trends of lung, colorectal, prostate, and breast cancers, as well as all cancers combined excluding non-melanoma skin cancer (NMSC) in adults aged 50 and older, over a fifteen-year period using data from 113 high quality population-based cancer registries included in the Cancer in Five Continents (CI5) series and NORDCAN. MATERIALS AND METHODS: We calculated annual incidence rates between 1998 and 2012 for ages 50-64, 65-74, and 75+, by sex and both sexes combined. We estimated average annual percentage change (AAPC) in rates using quasi-Poisson regression models. RESULTS: From 1998 to 2012, incidence trends for all cancers (excluding NMSC) have increased in most countries across all age groups, with the greatest increase observed in adults aged 75+ in Ecuador (AAPC = +3%). Colorectal cancer incidence rates increased in the majority of countries, across all age groups. Lung cancer rates among females have increased but decreased for males. Prostate cancer rates have sharply increased in men aged 50-64 with AAPC between 5% and 15% in 24 countries, while decreasing in the 75+ age group in 21 countries, by up to -7% in Bahrain. Female breast cancer rates have increased across all age groups in most countries, especially in the 65-74 age group and in Asia with AAPC increasing to 7% in the Republic of Korea. CONCLUSIONS: These findings assist with anticipating changing patterns and needs internationally. Due to the specific needs of older patients, it is urgent that cancer systems adapt to address their growing number.

Association Between Sex and Immune Checkpoint Inhibitor Outcomes for Patients With Melanoma.

Importance: Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment and are now standard of care. Although sex is associated with immune function and immune-related diseases, the interaction between sex and ICIs is understudied. Objective: To examine whether cancer immunotherapy effectiveness varies between female and male patients with advanced melanoma treated with either nivolumab plus ipilimumab combination therapy or anti-programmed cell death protein 1 (PD-1) therapy (namely, pembrolizumab or nivolumab). Design, Setting, and Participants: The study population consisted of 1369 older adults (aged ≥65 years) with a record of melanoma diagnosis from January 1, 1991, to December 31, 2015, in the Surveillance, Epidemiology, and End Results-Medicare linked database. Patients with a diagnosis of stage III or stage IV melanoma and a claims record showing nivolumab plus ipilimumab combination therapy or anti-PD-1 therapy (ie, pembrolizumab or nivolumab) as their last type of ICI prescribed were included in the analyses. Patients were followed up through December 31, 2017, for the overall survival analysis. Statistical analysis was performed from September 19, 2019, to February 20, 2021. Exposures: Sex, last prescribed ICI, and prior use of ipilimumab. Main Outcomes and Measures: The primary outcome was overall survival, defined as time from the index date until death from any cause, with patients censored at the end of the study (December 31, 2017). Cox proportional hazards regression modeling was used to examine the association of sex with ICI outcomes while adjusting for prior use of ipilimumab, age at ICI initiation, Charlson Comorbidity Index, cancer stage at the time of diagnosis, and autoimmune disease diagnosis. Results: Among the 1369 patients in the study (982 men [71.7%]; median age, 75 years [IQR, 69-82 years]), the outcome of nivolumab plus ipilimumab combination therapy depended on sex (Wald χ2 = 9.48; P = .009 for interaction). The mortality hazard ratio (HR) for women with prior ipilimumab use receiving combination therapy was 2.06 times (95% CI, 1.28-3.32; P = .003) higher than their male counterparts. No significant difference was observed between women and men receiving anti-PD-1 therapy with (HR, 0.97 [95% CI, 0.68-1.38]; P = .85) or without prior ipilimumab use (HR, 0.85 [95% CI, 0.67-1.07]; P = .16). For women with prior ipilimumab use, combination therapy was associated with 2.82 times higher mortality hazards than anti-PD-1 therapy (95% CI, 1.73-4.60). No statistically significant difference was seen in mortality risk between anti-PD-1 therapy and combination therapy for men. Conclusions and Relevance: This cohort study suggests that female patients with advanced melanoma may not benefit as much from combination ICIs as male patients would. Tumor mutation burden or estrogen level may serve as an important biomarker associated with ICI response in metastatic melanoma.

A Metabolomics Approach to Increasing Chinese Hamster Ovary (CHO) Cell Productivity.

Much progress has been made in improving the viable cell density of bioreactor cultures in monoclonal antibody production from Chinese hamster ovary (CHO) cells; however, specific productivity (qP) has not been increased to the same degree. In this work, we analyzed a library of 24 antibody-expressing CHO cell clones to identify metabolites that positively associate with qP and could be used for clone selection or medium supplementation. An initial library of 12 clones, each producing one of two antibodies, was analyzed using untargeted LC-MS experiments. Metabolic model-based annotation followed by correlation analysis detected 73 metabolites that significantly correlated with growth, qP, or both. Of these, metabolites in the alanine, aspartate, and glutamate metabolism pathway, and the TCA cycle showed the strongest association with qP. To evaluate whether these metabolites could be used as indicators to identify clones with potential for high productivity, we performed targeted LC-MS experiments on a second library of 12 clones expressing a third antibody. These experiments found that aspartate and cystine were positively correlated with qP, confirming the results from untargeted analysis. To investigate whether qP correlated metabolites reflected endogenous metabolic activity beneficial for productivity, several of these metabolites were tested as medium additives during cell culture. Medium supplementation with citrate improved qP by up to 490% and more than doubled the titer. Together, these studies demonstrate the potential for using metabolomics to discover novel metabolite additives that yield higher volumetric productivity in biologics production processes.

The Effects of Physical Activity on Cancer Patients Undergoing Treatment with Immune Checkpoint Inhibitors: A Scoping Review.

BACKGROUND: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy. METHOD: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results. RESULTS: In literature published from January 2010 through to August 2021, only one human study and three pre-clinical studies met inclusion criteria. CONCLUSION: Existing evidence supports that physical activity is associated with decreased treatment-related toxicities such as CRF. However, further investigation is warranted. The dearth of clinical studies illustrates the need for more research to address this question, to guide patients and their providers in the application of appropriate physical activity interventions in those patients undergoing ICI.