A novel body composition risk score (B-Score) and overall survival among patients with nonmetastatic breast cancer.

BACKGROUND & AIMS: Measurements (amount, distribution, and radiodensity) of muscle and adipose tissue were reported to be individually associated with overall survival in patients with breast cancer. However, they were not typically combined to develop an overall risk score, which can identify patients at high risk of death and prioritize patients in need of dietary and lifestyle interventions. Thus, we aimed to develop a novel composite body composition risk score (B-Score). METHODS: We included 3105 patients with stage II or III breast cancer at Kaiser Permanente Northern California and Dana Farber Cancer Institute. From CT scans at diagnosis, we assessed areas and radiodensity of muscle and adipose tissue at the third lumber vertebrae. We considered skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and SAT radiodensity as they were independent prognostic factors for overall survival. Each measurement was dichotomized using optimal stratification, with low SMI (<40.1 cm2/m2), high SATI (≥75.7 cm2/m2), and high SAT radiodensity (≥-97.2HU) considered risk factors. We calculated B-Score as the sum of these factors and estimated its association with overall survival using Cox proportional hazards regression with adjustment for clinicopathologic factors. RESULTS: Mean (standard deviation) age was 53.9 (11.8) years, 70.3% were Non-Hispanic White, and 60.5% were stage II. Most patients (60.6%) had only one body composition risk factor (B-Score = 1). Compared to those with no risk factors (B-Score = 0), the risk of death increased with more body composition risk factors: the adjusted hazard ratios were 1.10 (95% CI: 0.85, 1.42), 1.47 (95% CI: 1.12, 1.92), and 2.11 (95% CI: 1.26, 3.53) for B-Scores of 1, 2, and 3, respectively (Ptrend < 0.001). CONCLUSIONS: More unfavorable body composition characteristics were associated with increased risks of overall mortality in a dose-response manner. Considering body composition measurements together as a composite score (B-Score) may improve risk stratification and inform dietary and lifestyle interventions following breast cancer diagnosis.

Postoperative chemotherapy relative dose intensity and overall survival in patients with colon cancer.

PURPOSE: Quantifying the association of chemotherapy relative dose intensity (RDI) with overall survival may enable supportive care interventions that improve chemotherapy RDI to estimate their magnitude of potential clinical benefit. METHODS: This cohort study included 533 patients with stage II-III colon cancer who initiated a planned regimen of 12 cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. The primary exposure was chemotherapy RDI. The primary outcome was overall survival. Restricted cubic splines estimated hazard ratios (HR). RESULTS: Chemotherapy regimen RDI was associated with overall survival in an L-shaped pattern (linear P = 0.006; nonlinear P = 0.057); the risk of death was flat above 85% but increased linearly below 85%. For example, a decrease in RDI from 85 to 75% was associated with an increased risk of death [HR: 1.20 (95% CI: 1.08, 1.52)], whereas an increase in RDI from 85 to 95% was not associated with the risk of death [HR: 1.06 (95% CI: 0.82, 1.38)]. CONCLUSION: If chemotherapy RDI is considered a potential surrogate of overall survival, supportive care interventions that improve chemotherapy RDI might confer a potential clinical benefit in this population.

Differences in Smoking Behavior by Nativity, Race/Ethnicity, and Education among Women Diagnosed with Breast Cancer.

BACKGROUND: We evaluated smoking differences across nativity and race/ethnicity among women diagnosed with breast cancer. METHODS: In our Northern Californian pooled population of 5,653 [670 Asian, 690 Hispanic, and 4,300 non-Hispanic White (White)] women diagnosed with breast cancer, we evaluated smoking differences across nativity, race/ethnicity, and acculturation and effect modification of nativity by race/ethnicity and education. RESULTS: Foreign-born women currently smoked less than US-born women [odds ratio (OR) = 0.46, 95% confidence limit (CL): 0.29-0.72]. Hispanic (OR = 0.50; 95% CL: 0.32-0.78) women currently smoked less than White women. Among those who ever smoked (n = 2,557), foreign-born women smoked 5.23 fewer pack-years (PY) than US-born women (95% CL: -2.75 to -7.70). Furthermore, Asian (-4.60, 95% CL: -0.81 to -8.39) and Hispanic (-6.79, 95% CL: -4.14 to -9.43) women smoked fewer PY than White women. Associations were generally suggestive of greater smoking with greater acculturation (immigration age, US years, survey language). Finally, associations for nativity differed by education but not race/ethnicity, with a higher likelihood of smoking in US-born women only among those with less than a bachelor's degree (OR = 2.84, 95% CL: 2.15-3.77; current smoking: P = 0.01, PY: P = 0.05). CONCLUSIONS: Asian and Hispanic (vs. White) and foreign-born (vs. US-born) breast cancer survivors reported fewer smoking behaviors. Smoking differences across nativity and education were driven by higher rates of smoking in US-born women with lower educational attainment. IMPACT: Smoking behavioral patterns were similar among breast cancer survivors and the general population, informing potential smoking interventions.

Advances in Adherence Reporting of Resistance Training in a Clinical Trial during Adjuvant Chemotherapy for Colon Cancer.

PURPOSE: Detailed reporting of individually tailored exercise prescriptions (ExR x ) used in clinical trials is essential to describe feasibility, tolerability, and efficacy of the intervention and to inform translation to clinical care. This article outlines the methodology used to develop a resistance training (RT) ExR x for people with colon cancer receiving chemotherapy and reports adherence to the randomized controlled trial testing the impact of RT on relative dose intensity of chemotherapy and patient-reported toxicities. METHODS: Participants randomized to the exercise arm ( n = 90) were included. To promote muscle hypertrophy, the ExR x was twice-weekly, moderate to heavy loads (65%-85% one-repetition maximum), high sets (3-5), and intermediate repetitions (6-10) of five large multijoint movements with adjustable dumbbells. Attendance (achieved frequency) and adherence (achieved volume) were calculated. Group-based trajectory modeling was used to identify clusters of individuals with similar adherence patterns and compared baseline characteristics across adherence groups. RESULTS: The median attendance was 69.1%. Adherence was 60.6% but higher for those receiving 3 versus 6 months of chemotherapy (80.4 vs 47.4%; P < 0.05 ). Participants engaged in a median of 1.4 d of RT each week, lifting 62% of the one-repetition maximum load, for 3.0 sets and 7.5 repetitions per set. Three distinct adherence groups were identified: 13% "nonstarter," 37% "tapered off," and 50% "consistent exercisers." Females were more likely to be in the nonstarter and tapered-off groups. CONCLUSIONS: This article outlines suggested methods for reporting ExR x of RT in oncology clinical trials and provides insight into the tolerance of ExR x of RT during chemotherapy treatment for colon cancer. These findings aim to foster constructive dialogue and offer a premise for designing future research to elucidate the benefits of exercise during chemotherapy.

Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial.

BACKGROUND: Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients. METHODS: Multicenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program. RESULTS: Among 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06). CONCLUSIONS: Among patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity.

D3-creatine dilution, computed tomography and dual-energy X-ray absorptiometry for assessing myopenia and physical function in colon cancer: A cross-sectional study.

BACKGROUND: Low skeletal muscle mass (myopenia) is common in cancer populations and is associated with functional decline and mortality, but prior oncology studies did not assess total body skeletal muscle mass. Instead, they measured surrogates such as cross-sectional area (CSA) of skeletal muscle at L3 from computed tomography (CT) or appendicular lean mass (ALM) from dual-energy X-ray absorptiometry (DXA). D3-creatine (D3Cr) dilution is a non-invasive method to assess total body skeletal muscle mass, which has been examined in a variety of populations but not in cancer. To compare the associations of D3Cr muscle mass, CT CSA, and DXA ALM with myopenia and physical function, we conducted a cross-sectional study among 119 patients with colon cancer (2018-2022). METHODS: For each technique (D3Cr, CT and DXA), myopenia was defined as the lowest sex-specific quartile of its measurement. Physical function was measured by the short physical performance battery and grip strength. We calculated Pearson correlations (r) among three techniques, computed Cohen's kappa coefficients (κ) to assess the agreement of myopenia, and estimated Pearson correlations (r) of three techniques with physical function. All analyses were sex-specific. RESULTS: Sixty-one (51.3%) participants were male, the mean (standard deviation) age was 56.6 (12.9) years, and most (68.9%) had high physical function (short physical performance battery: ≥11 points). Correlations and myopenia agreement among three techniques were greater in men than women; for example, regarding D3Cr muscle mass versus CT CSA, r was 0.73 (P < 0.001) for men versus 0.45 (P < 0.001) for women, and κ was 0.82 (95% CI: 0.65, 0.99) for men versus 0.24 (95% CI: -0.08, 0.52) for women. Among men, higher D3Cr muscle mass was significantly correlated with faster gait speed (r = 0.43, P < 0.01) and stronger grip strength (r = 0.32, P < 0.05); similar correlations were observed for CT CSA and DXA ALM. However, among women, no measure of muscle or lean mass was significantly associated with physical function. CONCLUSIONS: This is the first study using D3-creatine dilution method to assess muscle mass in a cancer population. Regardless of the techniques used for muscle or lean mass assessment, we observed stronger correlations, greater myopenia agreement, and more significant associations with physical function in men with colon cancer than women. D3Cr, CT and DXA are not interchangeable methods for assessing myopenia and physical function, especially in women with colon cancer. Future studies should consider relative advantages of these techniques and examine the D3-creatine dilution method in other cancer types.

Alcohol consumption and prognosis and survival in breast cancer survivors: The Pathways Study.

BACKGROUND: The impact of alcohol consumption on breast cancer (BC) prognosis remains unclear. METHODS: The authors examined short-term alcohol intake in relation to recurrence and mortality in 3659 women who were diagnosed with stage I-IV BC from 2003 to 2013 in the Pathways Study. Alcohol drinking in the past 6 months was assessed at cohort entry (mean, 2 months postdiagnosis) and 6 months later using a food-frequency questionnaire. Study end points were recurrence and death from BC, cardiovascular disease, and all causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. RESULTS: Over an average follow-up of 11.2 years, 524 recurrences and 834 deaths (369 BC-specific and 314 cardiovascular disease-specific) occurred. Compared with nondrinkers (36.9%), drinkers were more likely younger, more educated, and current or past smokers. Overall, alcohol consumption was not associated with recurrence or mortality. However, women with higher body mass index (BMI ≥ 30 kg/m2 ) had lower risk of overall mortality with increasing alcohol consumption for occasional drinking (HR, 0.71; 95% CI, 0.54-0.94) and regular drinking (HR, 0.77; 95% CI, 0.56-1.08) around the time of diagnosis, along with 6 months later, in a dose-response manner (p < .05). Women with lower BMI (<30 kg/m2 ) were not at higher risk of mortality but were at possibly higher, yet nonsignificant, risk of recurrence for occasional drinking (HR, 1.29; 95% CI, 0.97-1.71) and regular drinking (HR, 1.19; 95% CI, 0.88-1.62). CONCLUSIONS: Alcohol drinking around the time of and up to 6 months after BC diagnosis was associated with lower risk of all-cause mortality in obese women. A possible higher risk of recurrence was observed in nonobese women.

Adipose tissue and skeletal muscle wasting precede clinical diagnosis of pancreatic cancer.

Patients with pancreatic cancer commonly develop weight loss and muscle wasting. Whether adipose tissue and skeletal muscle losses begin before diagnosis and the potential utility of such losses for earlier cancer detection are not well understood. We quantify skeletal muscle and adipose tissue areas from computed tomography (CT) imaging obtained 2 months to 5 years before cancer diagnosis in 714 pancreatic cancer cases and 1748 matched controls. Adipose tissue loss is identified up to 6 months, and skeletal muscle wasting is identified up to 18 months before the clinical diagnosis of pancreatic cancer and is not present in the matched control population. Tissue losses are of similar magnitude in cases diagnosed with localized compared with metastatic disease and are not correlated with at-diagnosis circulating levels of CA19-9. Skeletal muscle wasting occurs in the 1-2 years before pancreatic cancer diagnosis and may signal an upcoming diagnosis of pancreatic cancer.

Body Composition, Relative Dose Intensity, and Adverse Events among Patients with Colon Cancer.

BACKGROUND: Despite evidence that low muscle increases the risk of chemotoxicity, most chemotherapies are dosed on body surface area without considering body composition. Among 178 patients with colon cancer, we assessed muscle and adipose tissue with multiple techniques and examined their associations with relative dose intensity (RDI) and adverse events. METHODS: We estimated (i) cross-sectional skeletal muscle area (SMA) and total adipose tissue (TAT) area at L3 from computed tomography (CT); (ii) appendicular lean mass (ALM) and total body fat (TBF) mass from dual-energy X-ray absorptiometry (DXA); and (iii) total body skeletal muscle mass using D3-creatine (D3Cr) dilution. We standardized each measurement by its sex-specific standard deviation (SD). The primary outcome was reduced RDI (RDI <85%). The secondary outcome was the number of moderate and severe adverse events during each cycle of chemotherapy. We estimated the associations of muscle and adipose tissue measurements (per SD increase) with reduced RDI using logistic regression and adverse events using generalized estimating equations for repeated measures. RESULTS: Higher CT SMA and DXA ALM were significantly associated with a lower risk of reduced RDI [odds ratios: 0.56 (0.38-0.81) for CT SMA; 0.56 (0.37-0.84) for DXA ALM]. No measurements of muscle or adipose tissue were associated with adverse events. CONCLUSIONS: More muscle was associated with improved chemotherapy completion among patients with colon cancer, whereas muscle and adipose tissue were not associated with adverse events. IMPACT: Considering body composition may help personalize dosing for colon cancer chemotherapy by identifying patients at risk for poor chemotherapy outcomes.

Pre-diagnosis lipid levels and mortality after obesity-related cancer diagnosis in the Women's Health Initiative cardiovascular disease biomarker cohort.

BACKGROUND: Published studies have demonstrated inconclusive relationships between serum lipid levels and mortality after cancer. METHODS: The primary objective was to evaluate the relationship between fasting lipid levels and mortality after cancer. Data were obtained on baseline lipids and outcomes after cancer from 1263 postmenopausal women diagnosed with 13 obesity-related cancers who were part of the Women's Health Initiative (WHI) lipid biomarkers cohort. Obesity-related cancers included incident invasive cancers of the breast, colorectum, endometrium, esophagus (adenocarcinoma), kidney, liver, gallbladder, pancreas, ovaries, small intestine, thyroid, stomach, as well as multiple myeloma. Baseline lipid measurements included high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and non-HDL-cholesterol. Outcomes were all cause, cancer-specific, and CVD mortality. Multivariable Cox proportional hazards models were used to measure associations between lipid levels and mortality (all cause, cancer, and CVD) after a cancer diagnosis, with lipids analyzed as continuous variables. RESULTS: Among women with obesity-related cancer, there were 707 deaths, of which 379 (54%) were due to cancer and 113 (16%) were due to CVD. Mean time from blood draw to cancer diagnosis was 5.1 years (range: 0.05-10 years). LDL-C values above the 95th percentile were associated with higher risk of all-cause mortality (p < 0.001), and cancer-specific mortality (p < 0.001), but not mortality due to CVD. Non-HDL-C values above the 65th percentile were associated with higher risk of all-cause mortality (p = 0.01) and mortality due to CVD (p = 0.003), but not cancer-specific mortality (p = 0.37). HDL-C values above the 95th percentile were associated with lower all-cause mortality (p = 0.002), and above the 65th percentile with lower cancer-specific mortality (p = 0.003), but no significant relationship with mortality due to CVD was observed. CONCLUSIONS: The relationship between pre-diagnosis fasting lipid levels and mortality after cancer diagnosis is complex. These results suggest that improved lipid control through lifestyle and anti-lipid medications could have a meaningful impact on outcomes after cancer.

Development and testing of a polygenic risk score for breast cancer aggressiveness.

Aggressive breast cancers portend a poor prognosis, but current polygenic risk scores (PRSs) for breast cancer do not reliably predict aggressive cancers. Aggressiveness can be effectively recapitulated using tumor gene expression profiling. Thus, we sought to develop a PRS for the risk of recurrence score weighted on proliferation (ROR-P), an established prognostic signature. Using 2363 breast cancers with tumor gene expression data and single nucleotide polymorphism (SNP) genotypes, we examined the associations between ROR-P and known breast cancer susceptibility SNPs using linear regression models. We constructed PRSs based on varying p-value thresholds and selected the optimal PRS based on model r2 in 5-fold cross-validation. We then used Cox proportional hazards regression to test the ROR-P PRS's association with breast cancer-specific survival in two independent cohorts totaling 10,196 breast cancers and 785 events. In meta-analysis of these cohorts, higher ROR-P PRS was associated with worse survival, HR per SD = 1.13 (95% CI 1.06-1.21, p = 4.0 × 10-4). The ROR-P PRS had a similar magnitude of effect on survival as a comparator PRS for estrogen receptor (ER)-negative versus positive cancer risk (PRSER-/ER+). Furthermore, its effect was minimally attenuated when adjusted for PRSER-/ER+, suggesting that the ROR-P PRS provides additional prognostic information beyond ER status. In summary, we used integrated analysis of germline SNP and tumor gene expression data to construct a PRS associated with aggressive tumor biology and worse survival. These findings could potentially enhance risk stratification for breast cancer screening and prevention.

Cachexia: A systemic consequence of progressive, unresolved disease.

Cachexia, a systemic wasting condition, is considered a late consequence of diseases, including cancer, organ failure, or infections, and contributes to significant morbidity and mortality. The induction process and mechanistic progression of cachexia are incompletely understood. Refocusing academic efforts away from advanced cachexia to the etiology of cachexia may enable discoveries of new therapeutic approaches. Here, we review drivers, mechanisms, organismal predispositions, evidence for multi-organ interaction, model systems, clinical research, trials, and care provision from early onset to late cachexia. Evidence is emerging that distinct inflammatory, metabolic, and neuro-modulatory drivers can initiate processes that ultimately converge on advanced cachexia.

Association of Inflammatory Biomarkers With Survival Among Patients With Stage III Colon Cancer.

Importance: The association of chronic inflammation with colorectal cancer recurrence and death is not well understood, and data from large well-designed prospective cohorts are limited. Objective: To assess the associations of inflammatory biomarkers with survival among patients with stage III colon cancer. Design, Setting, and Participants: This cohort study was derived from a National Cancer Institute-sponsored adjuvant chemotherapy trial Cancer and Leukemia Group B/Southwest Oncology Group 80702 (CALGB/SWOG 80702) conducted between June 22, 2010, and November 20, 2015, with follow-up ending on August 10, 2020. A total of 1494 patients with plasma samples available for inflammatory biomarker assays were included. Data were analyzed from July 29, 2021, to February 27, 2022. Exposures: Plasma inflammatory biomarkers (interleukin 6 [IL-6], soluble tumor necrosis factor α receptor 2 [sTNF-αR2], and high-sensitivity C-reactive protein [hsCRP]; quintiles) that were assayed 3 to 8 weeks after surgery but before chemotherapy randomization. Main Outcomes and Measures: The primary outcome was disease-free survival, defined as time from randomization to colon cancer recurrence or death from any cause. Secondary outcomes were recurrence-free survival and overall survival. Hazard ratios for the associations of inflammatory biomarkers and survival were estimated via Cox proportional hazards regression. Results: Of 1494 patients (median follow-up, 5.9 years [IQR, 4.7-6.1 years]), the median age was 61.3 years (IQR, 54.0-68.8 years), 828 (55.4%) were male, and 327 recurrences, 244 deaths, and 387 events for disease-free survival were observed. Plasma samples were collected at a median of 6.9 weeks (IQR, 5.6-8.1 weeks) after surgery. The median plasma concentration was 3.8 pg/mL (IQR, 2.3-6.2 pg/mL) for IL-6, 2.9 × 103 pg/mL (IQR, 2.3-3.6 × 103 pg/mL) for sTNF-αR2, and 2.6 mg/L (IQR, 1.2-5.6 mg/L) for hsCRP. Compared with patients in the lowest quintile of inflammation, patients in the highest quintile of inflammation had a significantly increased risk of recurrence or death (adjusted hazard ratios for IL-6: 1.52 [95% CI, 1.07-2.14]; P = .01 for trend; for sTNF-αR2: 1.77 [95% CI, 1.23-2.55]; P < .001 for trend; and for hsCRP: 1.65 [95% CI, 1.17-2.34]; P = .006 for trend). Additionally, a significant interaction was not observed between inflammatory biomarkers and celecoxib intervention for disease-free survival. Similar results were observed for recurrence-free survival and overall survival. Conclusions and Relevance: This cohort study found that higher inflammation after diagnosis was significantly associated with worse survival outcomes among patients with stage III colon cancer. This finding warrants further investigation to evaluate whether anti-inflammatory interventions may improve colon cancer outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT01150045.

Long-term Trajectories of Physical Function Decline in Women With and Without Cancer.

Importance: Patients with cancer experience acute declines in physical function, hypothesized to reflect accelerated aging driven by cancer-related symptoms and effects of cancer therapies. No study has examined long-term trajectories of physical function by cancer site, stage, or treatment compared with cancer-free controls. Objective: Examine trajectories of physical function a decade before and after cancer diagnosis among older survivors and cancer-free controls. Design, Setting, and Participants: This prospective cohort study enrolled patients from 1993 to 1998 and followed up until December 2020. The Women's Health Initiative, a diverse cohort of postmenopausal women, included 9203 incident cancers (5989 breast, 1352 colorectal, 960 endometrial, and 902 lung) matched to up to 5 controls (n = 45 358) on age/year of enrollment and study arm. Exposures: Cancer diagnosis (site, stage, and treatment) via Medicare and medical records. Main Outcomes and Measures: Trajectories of self-reported physical function (RAND Short Form 36 [RAND-36] scale; range: 0-100, higher scores indicate superior physical function) estimated from linear mixed effects models with slope changes at diagnosis and 1-year after diagnosis. Results: This study included 9203 women with cancer and 45 358 matched controls. For the women with cancer, the mean (SD) age at diagnosis was 73.0 (7.6) years. Prediagnosis, physical function declines of survivors with local cancers were similar to controls; after diagnosis, survivors experienced accelerated declines relative to controls, whose scores declined 1 to 2 points per year. Short-term declines in the year following diagnosis were most severe in women with regional disease (eg, -5.3 [95% CI, -6.4 to -4.3] points per year in regional vs -2.8 [95% CI, -3.4 to -2.3] for local breast cancer) or who received systemic therapy (eg, for local endometrial cancer, -7.9 [95% CI, -12.2 to -3.6] points per year with any chemotherapy; -3.1 [95% CI, -6.0 to -0.3] with radiation therapy alone; and -2.6 [95% CI, -4.2 to -1.0] with neither, respectively). While rates of physical function decline slowed in the later postdiagnosis period (eg, women with regional colorectal cancer declined -4.3 [95% CI, -5.9 to -2.6] points per year in the year following diagnosis vs -1.4 [95% CI, -1.7 to -1.0] points per year in the decade thereafter), survivors had estimated physical function significantly below that of age-matched controls 5 years after diagnosis. Conclusions and Relevance: In this prospective cohort study, survivors of cancer experienced accelerated declines in physical function after diagnosis, and physical function remained below that of age-matched controls even years later. Patients with cancer may benefit from supportive interventions to preserve physical functioning.

Metabolic abnormalities and survival among patients with non-metastatic breast cancer.

BACKGROUND: Research on the impact of metabolic abnormalities on breast cancer prognosis is limited by small samples and assessment of laboratory values at a single time point, often prior to cancer diagnosis and treatment. In this population-based cohort, time-updated laboratory values were adjusted for cancer treatment to assess the association between metabolic risk factors (glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides) and breast cancer survival. METHODS: 13,434 women diagnosed with stage I-III breast cancer from 2005-15 at Kaiser Permanente were included. All outpatient fasting glucose, HDL-C, LDL-C, and triglyceride values from diagnosis through 2019 or death were extracted from electronic medical records. Risk of breast cancer-specific mortality was evaluated with Cox proportional hazards models adjusted for metabolic labs, demographics, body mass index, diabetes, dyslipidemia and anti-hypertensive medications, tumor characteristics (stage, ER and HER2 receptor status) and cancer treatment (use of chemotherapy, tamoxifen, and aromatase inhibitors). RESULTS: Mean (SD) age at diagnosis was 62.3 (11.8) years. Over a median follow-up of 8.6 years, 2,876 patients died; 1,080 of breast cancer. Patients with low HDL-C (≤ 45 vs. > 45 mg/dL) had higher breast cancer-specific mortality (HR, 1.77; 95% CI, 1.53-2.05), as did those with elevated fasting glucose (> 99 vs. 60-99 mg/dL) (HR, 1.19; 95% CI, 1.03-1.37). Elevated levels of triglycerides and LDL-C were not associated with breast cancer-specific mortality. CONCLUSIONS: High fasting glucose and low HDL-C evaluated over time after cancer diagnosis were associated with higher breast cancer mortality independent of cancer treatments and changes in other metabolic risk factors. Future studies should address whether pharmacologic or lifestyle treatment of glucose and lipids after breast cancer diagnosis can optimize survival outcomes.

Adipose tissue radiodensity and mortality among patients with nonmetastatic breast cancer.

BACKGROUND & AIMS: Computed tomography (CT) scans can measure quantity and distribution of adipose tissue, which are associated with breast cancer prognosis. As a novel prognostic marker, radiodensity of adipose tissue has been examined in multiple cancer types, but never in breast cancer. Lower density indicates larger adipocytes with greater lipid content, whereas higher density can reflect inflammation, fibrosis, vascularity, or even metabolic changes; and both may impact breast cancer prognosis. METHODS: We included 2868 nonmetastatic patients with breast cancer diagnosed between January 2005 and December 2013 at Kaiser Permanente Northern California, an integrated healthcare system. From CT scans at diagnosis, we assessed the radiodensity of subcutaneous (SAT) and visceral adipose tissue (VAT) at the third lumbar vertebra and categorized their radiodensity into three levels: low (<1 standard deviation [SD] below the mean), middle (mean ± 1 SD), and high (>1 SD above the mean). Using multivariable Cox proportional hazards regression with adjustment for clinicopathological characteristics including body mass index, we calculated hazard ratios (HRs [95% confidence intervals]) for the associations of adipose tissue radiodensity with overall mortality and breast-cancer-specific mortality. RESULTS: Median age at diagnosis of breast cancer was 56.0 years, most (63.3%) were non-Hispanic White and nearly half (45.6%) were stage II. Compared to middle SAT radiodensity, high SAT radiodensity was significantly associated with increased risk of overall mortality (HR: 1.45 [1.15-1.81]), non-significantly with breast-cancer-specific mortality (HR: 1.32 [0.95-1.84]). Neither low SAT radiodensity nor high or low VAT radiodensity was significantly associated with overall or breast-cancer-specific mortality. CONCLUSIONS: High radiodensity of SAT at diagnosis of nonmetastatic breast cancer was associated with increased risk of overall mortality, independent of adiposity and other prognostic factors. Considering both radiodensity and quantity of adipose tissue at different locations could deepen understanding of the role of adiposity in breast cancer survival.

Adiposity and cancer survival: a systematic review and meta-analysis.

PURPOSE: The increasing availability of clinical imaging tests (especially CT and MRI) that directly quantify adipose tissue has led to a rapid increase in studies examining the relationship of visceral, subcutaneous, and overall adiposity to cancer survival. To summarize this emerging body of literature, we conducted a systematic review and meta-analysis of imaging-measured as well as anthropometric proxies for adipose tissue distribution and cancer survival across a wide range of cancer types. METHODS: Using keywords related to adiposity, cancer, and survival, we conducted a systematic search of the literature in PubMed and MEDLINE, Embase, and Web of Science Core Collection databases from database inception to 30 June 2021. We used a random-effect method to calculate pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) within each cancer type and tested for heterogeneity using Cochran's Q test and the I2 test. RESULTS: We included 203 records for this review, of which 128 records were utilized for quantitative analysis among 10 cancer types: breast, colorectal, gastroesophageal, head and neck, hepatocellular carcinoma, lung, ovarian, pancreatic, prostate, and renal cancer. We found that imaging-measured visceral, subcutaneous, and total adiposity were not significantly associated with increased risk of overall mortality, death from primary cancer, or cancer progression among patients diagnosed with these 10 cancer types; however, we found significant or high heterogeneity for many cancer types. For example, heterogeneity was similarly high when the pooled HRs (95% CI) for overall mortality associated with visceral adiposity were essentially null as in 1.03 (0.55, 1.92; I2 = 58%) for breast, 0.99 (0.81, 1.21; I2 = 71%) for colorectal, versus when they demonstrated a potential increased risk 1.17 (0.85, 1.60; I2 = 78%) for hepatocellular carcinoma and 1.62 (0.90, 2.95; I2 = 84%) for renal cancer. CONCLUSION: Greater adiposity at diagnosis (directly measured by imaging) is not associated with worse survival among cancer survivors. However, heterogeneity and other potential limitations were noted across studies, suggesting differences in study design and adiposity measurement approaches, making interpretation of meta-analyses challenging. Future work to standardize imaging measurements and data analyses will strengthen research on the role of adiposity in cancer survival.

The association of abdominal adiposity with premature discontinuation of postoperative chemotherapy in colon cancer.

BACKGROUND & AIMS: Patients with colon cancer who prematurely discontinue postoperative chemotherapy may have an increased risk of disease recurrence and death. This study tested the hypothesis that the quantity and distribution of abdominal adipose tissue predict premature chemotherapy discontinuation. METHODS: This cohort study included 533 patients with stage II-III colon cancer who initiated a planned regimen of 24-weeks of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. The primary exposures were body mass index (BMI) and computed tomography-derived abdominal adiposity measures (e.g., visceral, subcutaneous, and intramuscular adipose tissue). The primary endpoint was premature chemotherapy discontinuation, defined as receiving <6 cycles of FOLFOX. Generalized linear models quantified the relative risk (RR) of premature chemotherapy discontinuation adjusted for age, sex, cancer stage, height, and muscle area, using two-sided statistical tests. RESULTS: Forty-two patients [7.9% (95% CI: 5.7, 10.5)] prematurely discontinued chemotherapy. Visceral adipose tissue [RR: 3.27 (95% CI: 1.26, 8.49)] and intramuscular adipose tissue [RR: 2.79 (95% CI: 1.09, 7.12)] were statistically significantly associated with an increased risk of premature chemotherapy discontinuation. BMI [RR: 2.07 (95% CI: 0.75, 5.73)] and subcutaneous adipose tissue [RR: 2.32 (95% CI: 0.91, 5.94)] were not statistically significantly associated with premature chemotherapy discontinuation. CONCLUSION: Among patients with stage II-III colon cancer who initiate postoperative chemotherapy, excess visceral and intramuscular adiposity may be risk factors for the premature discontinuation of chemotherapy.

Effect of Lifestyle Coaching or Enhanced Pharmacotherapy on Blood Pressure Control Among Black Adults With Persistent Uncontrolled Hypertension: A Cluster Randomized Clinical Trial.

Importance: Greater difficulty in controlling blood pressure (BP) and adverse lifestyle practices such as higher salt intake or less physical activity may account for some of the differences between BP control rates in Black vs White adults, thereby exposing Black adults to a higher risk of vascular events. Objective: To determine whether a lifestyle coaching intervention or an enhanced pharmacotherapy protocol is more effective than usual care in improving BP control rates in Black adults treated within an integrated health care delivery system. Design, Setting, and Participants: Shake, Rattle & Roll, a cluster randomized clinical trial, was conducted from June 5, 2013, to June 11, 2018, in a large integrated health care delivery system. Enrollment was completed during a 12-month period and interventions were implemented for 12 months. Follow-up lasted 48 months after enrollment. Panels of Black adult members of the health care delivery system with BP of at least 140/90 mm Hg from 98 adult primary care physicians were randomly assigned at the primary care physician level to usual care (UC group [n = 1129]), enhanced pharmacotherapy monitoring (EP group [n = 346]) of current BP management protocol, or diet and lifestyle coaching consisting of photographs, stories, and recipes, for example, that are appropriate for Black adults (LC group [n = 286]) focused on the Dietary Approaches to Stop Hypertension (DASH) diet. Data were analyzed from June 1, 2016, to March 25, 2022. Interventions: The UC group received care per customary protocol. The EP group was contacted by a research nurse and/or a clinical pharmacist to discuss barriers to hypertension control, and drug therapy emphasized the use of thiazide diuretic intensification and addition of spironolactone as needed. The LC group received as many as 16 telephone sessions with a lifestyle coach and an emphasis on implementing reduction of sodium intake and the DASH diet. Main Outcomes and Measures: Intention-to-treat analysis of BP control rates at end of the 12-month intervention. Results: Among the 1761 participants, the mean (SD) age was 61 (13) years, and 1214 (68.9%) were women. At the end of the 12-month intervention period, there was no significant difference in BP control rate among study groups (UC, 61.8% [95% CI, 58.8%-64.9%]; EP, 64.5% [95% CI, 59.0%-69.4%]; LC, 67.8% [95% CI, 62.1%-73.2%]; LC vs EP, P = .07). However, greater BP control was present in the LC group vs UC at 24 months (UC, 61.2% [95% CI, 57.3%-64.7%]; EP, 67.6% [95% CI, 61.9%-72.8%]; LC, 72.4% [95% CI, 66.9%-78.1%]; LC vs UC, P = .001), and 48 months (UC, 64.5% [95% CI, 61.6%-67.2%]; EP, 66.5% [95% CI, 61.3%-71.3%]; LC, 73.1% [95% CI, 67.6%-77.9%]; LC vs UC, P = .006) after enrollment. The contribution of BP medication adherence to explain group differences was inconclusive. Conclusions and Relevance: In this cluster randomized clinical trial including Black adults with persistent uncontrolled hypertension, a 12-month LC intervention was more effective at controlling BP than UC at 24 and 48 months after enrollment. Further research is needed to explore the potential implementation of this intervention into clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT01892592.

American Cancer Society nutrition and physical activity guideline for cancer survivors.

The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.