Risk factors for synchronous brain metastases: A National Cancer Database analysis.

e13591 Background: Brain metastases (BM) are a significant source of disability and mortality in cancer patients. Investigations on the risk factors for their development are limited. We provide risk factors assessment using the largest cancer database. Methods: We analyzed the National Cancer Database from 2010-2014, for risk factors and survival outcomes in all patients with BM. Results: 4,650,963 tumor records were analyzed of which 88,274 were BM. Lung cancer accounted for 82.2%, breast cancer for 4.2%, melanoma for 3.5%, and urinary system tumors for 3.1% of cases. The majority of patients were males (51.6%), and whites (84.2%) with a median age of 65 years. A high index of comorbidities [Charlson-Deyo score (CDS) ≥3] was reported in 3.5% of patients. Lung primaries had the highest risk of BM (OR of 17.867), followed by melanoma (OR 1.946). Patients diagnosed at 70 years or older were less likely to present with BM, while patients diagnosed between 40 and 60 years were at increased risk. Other and unknown race were associated with an increased risk of BM compared to whites. Patients with a CDS of one or two had a decreased risk of presenting with BM compared to patients with scores greater or equal to three. Median overall survival was 5 months, with a 5-year survival rate of 5.2%. There was a decreasing risk of mortality, and increasing risk of receiving surgery, radiation, or chemotherapy per advancing year of diagnosis. Older age, white race, Hispanic origin, and higher CDS were risk factors for mortality. Conclusions: Higher number of comorbidities, younger age at diagnosis, and other races were associated with an higher risk of synchronous BM. The risk of mortality is decreasing, with a higher risk of receiving radiation, surgery, and/or chemotherapy. Median overall survival has increased in comparison to the Radiation Therapy Oncology Group Recursive Partitioning Analysis RPA studies (4.4 months).

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Outcome comparison of patients who develop leptomeningeal disease or distant brain recurrence after brain metastases resection cavity radiosurgery

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab036 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Achiraya Teyateeti ◽

Paul D Brown ◽

Anita Mahajan ◽

Nadia N Laack ◽

Bruce E Pollock

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Median Overall Survival ◽

Recursive Partitioning ◽

Leptomeningeal Disease ◽

Resection Cavity ◽

Whole Brain Radiation ◽

Class 1 ◽

Outcome Comparison ◽

Brain Radiation

Abstract Background To compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity. Methods Twenty-nine patients having single-fraction SRS after BM resection who developed either LMD (n = 11) or DBR (n = 18) as their initial and only site of intracranial progression were retrospectively reviewed. Results Patients developing LMD more commonly had a metachronous presentation (91% vs 50%, P = .04) and recursive partitioning class 1 status (45% vs 6%, P = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, P = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS (n = 4), whole-brain radiation therapy (WBRT; n = 5), resection + WBRT (n = 1), and no treatment (n = 1). Treatment for DBR was repeat SRS (n = 9), WBRT (n = 3), resection + resection cavity SRS (n = 1), and no treatment (n = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group (P = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group (P = .004) while 18.7 and 16.2 months in the DBR group (P = .30), respectively. Conclusions Following BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.

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Radiosurgery Followed by Planned Observation in Patients with One to Three Brain Metastases

Neurosurgery ◽

10.1093/neurosurgery/52.5.1066 ◽

2003 ◽

Vol 52 (5) ◽

pp. 1066-1074 ◽

Cited By ~ 1

Author(s):

Johannes Lutterbach ◽

Donatus Cyron ◽

Karl Henne ◽

Christoph B. Ostertag

Keyword(s):

Risk Factors ◽

Brain Metastasis ◽

Brain Metastases ◽

Local Control ◽

Cox Model ◽

Recursive Partitioning ◽

Radiation Therapy Oncology Group ◽

Recursive Partitioning Analysis ◽

Maximum Diameter ◽

Single Brain Metastasis

Abstract OBJECTIVE To analyze the role of radiosurgery alone in patients with brain metastases. There were three specific study goals: 1) to determine whether survival of patients selected for this treatment approach can be predicted successfully by use of the recursive partitioning analysis classification defined by the Radiation Therapy Oncology Group; 2) to evaluate local control; and 3) to identify risk factors of cerebral failure. METHODS A total of 101 patients with Karnofsky Performance Scale scores of at least 50 and up to three brain metastases, each 3 cm or less in maximum diameter, were treated with radiosurgery alone. Survival, local control, distant brain freedom from progression (FFP), and overall brain FFP were evaluated according the method of Kaplan and Meier. Risk factors for survival and overall brain FFP were analyzed using the Cox model. RESULTS Median survival was 13.4 months, 9.3 months, and 1.5 months for patients in recursive partitioning analysis Classes 1, 2, and 3, respectively (P< 0.0001). At 1 year, local control, distant brain FFP, and overall brain FFP were 91, 53, and 51%, respectively. An interval greater than 2 years between diagnosis of the primary tumor and diagnosis of brain metastases and the presence of a single brain metastasis were associated with significantly higher overall brain FFP. CONCLUSION Recursive partitioning analysis classification successfully predicted survival. Radiosurgery alone yielded high local control. Overall brain FFP was highest in patients with an interval greater than 2 years between primary diagnosis and diagnosis of a single brain metastasis.

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Validation of Recursive Partitioning Analysis and Diagnosis-Specific Graded Prognostic Assessment in patients treated initially with radiosurgery alone

Journal of Neurosurgery ◽

10.3171/2012.3.gks1289 ◽

2012 ◽

Vol 117 (Special_Suppl) ◽

pp. 38-44 ◽

Cited By ~ 25

Author(s):

Anna Likhacheva ◽

Chelsea C. Pinnix ◽

Neil Parikh ◽

Pamela K. Allen ◽

Nandita Guha-Thakurta ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Brain Metastases ◽

Median Overall Survival ◽

Recursive Partitioning ◽

Prognostic Index ◽

Survival Times ◽

Prognostic Assessment ◽

Whole Brain Radiation ◽

Brain Radiation

Object Brain metastases present a therapeutic challenge because patients with metastatic cancers live longer now than in the recent past due to systemic therapies that, while effective, may not penetrate the blood-brain barrier. In the present study the authors sought to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), a new prognostic index that takes into account the histological characteristics of the primary tumor, and the Radiation Therapy Ontology Group Recursive Partitioning Analysis (RPA) system by using a single-institution database of patients who were treated initially with stereotactic radiosurgery (SRS) alone for brain metastases. Methods Investigators retrospectively identified adult patients who had undergone SRS at a single institution, MD Anderson Cancer Center, for initial treatment of brain metastases between 2003 and 2010 but excluded those who had undergone craniotomy and/or whole-brain radiation therapy at an earlier time; the final number was 251. The Leksell Gamma Knife was used to treat 223 patients, and a linear accelerator was used to treat 28 patients. The patient population was grouped according to DS-GPA scores as follows: 0–0.5 (7 patients), 1 (33 patients), 1.5 (25 patients), 2 (63 patients), 2.5 (14 patients), 3 (68 patients), and 3.5–4 (41 patients). The same patients were also grouped according to RPA classes: 1 (24 patients), 2 (216 patients), and 3 (11 patients). The most common histological diagnoses were non–small cell lung cancer (34%), melanoma (29%), and breast carcinoma (16%). The median number of lesions was 2 (range 1–9) and the median total tumor volume was 0.9 cm3 (range 0.3–22.9 cm3). The median radiation dose was 20 Gy (range 14–24 Gy). Stereotactic radiosurgery was performed as the sole treatment (62% of patients) or combined with a salvage treatment consisting of SRS (22%), whole-brain radiation therapy (12%), or resection (4%). The median duration of follow-up was 9.4 months. Results In this patient group the median overall survival was 11.1 months. The DS-GPA prognostic index divided patients into prognostically significant groups. Median survival times were 2.8 months for DS-GPA Scores 0–0.5, 3.9 months for Score 1, 6.6 months for Score 1.5, 12.9 months for Score 2, 11.9 months for Score 2.5, 12.2 months for Score 3, and 31.4 months for Scores 3.5–4 (p < 0.0001). In the RPA groups, the median overall survival times were 38.8 months for Class 1, 9.4 months for Class 2, and 2.8 months for Class 3 (p < 0.0001). Neither the RPA class nor the DS-GPA score was prognostic for local tumor control or new lesion–free survival. A multivariate analysis revealed that patient age > 60 years, Karnofsky Performance Scale score ≤ 80%, and total lesion volume > 2 cm3 were significant adverse prognostic factors for overall survival. Conclusions Application of the DS-GPA to a database of patients with brain metastases who were treated with SRS appears to be valid and offers additional prognostic refinement over that provided by the RPA. The DS-GPA may also allow for improved selection of patients to undergo initial SRS alone and should be studied further.

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The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma

Neuro-Oncology Practice ◽

10.1093/nop/npz070 ◽

2019 ◽

Vol 7 (4) ◽

pp. 391-399

Author(s):

Roshan S Prabhu ◽

Christopher D Corso ◽

Matthew C Ward ◽

John H Heinzerling ◽

Reshika Dhakal ◽

...

Keyword(s):

Overall Survival ◽

Propensity Score ◽

Adjuvant Radiotherapy ◽

Subtotal Resection ◽

National Cancer Database ◽

Risk Of Death ◽

Increased Risk ◽

Intracranial Ependymoma ◽

Male Sex ◽

Grade 3

Abstract Background Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined. Methods We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post–subtotal resection only, (4) and grade 3 only. The association between adjuvant RT use and overall survival (OS) was assessed using multivariate Cox and propensity score matched analyses. Results A total of 1787 patients were included in cohort 1, of which 856 patients (48%) received adjuvant RT and 931 (52%) were observed. Approximately two-thirds of tumors were supratentorial and 80% were grade 2. Cohorts 2, 3, and 4 included 1471, 345, and 316 patients, respectively. There was no significant association between adjuvant RT use and OS in multivariate or propensity score matched analysis in any of the cohorts. Older age, male sex, urban location, higher comorbidity score, earlier year of diagnosis, and grade 3 were associated with increased risk of death. Conclusions This large NCDB study did not demonstrate a significant association between adjuvant RT use and OS for adults with intracranial ependymoma, including for patients with grade 2 ependymoma status post–subtotal resection. The conflicting results regarding the efficacy of adjuvant RT in this patient population highlight the need for high-quality studies to guide therapy recommendations in adult ependymoma.

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Undifferentiated Embryonal Sarcoma of the Liver in Children Versus Adults: A National Cancer Database Analysis

Cancers ◽

10.3390/cancers13122918 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2918

Author(s):

Ioannis A. Ziogas ◽

Irving J. Zamora ◽

Harold N. Lovvorn III ◽

Christina E. Bailey ◽

Sophoclis P. Alexopoulos

Keyword(s):

Surgical Treatment ◽

Cox Regression ◽

Clinicopathological Characteristics ◽

National Cancer Database ◽

Term Survival ◽

Long Term Survival ◽

Risk Of Mortality ◽

Increased Risk ◽

Embryonal Sarcoma

This study evaluates the clinicopathological characteristics and outcomes of children vs. adults with undifferentiated embryonal sarcoma of the liver (UESL). A retrospective analysis of 82 children (<18 years) and 41 adults (≥18 years) with UESL registered in the National Cancer Database between 2004–2015 was conducted. No between-group differences were observed regarding tumor size, metastasis, surgical treatment, margin status, and radiation. Children received chemotherapy more often than adults (92.7% vs. 65.9%; p < 0.001). Children demonstrated superior overall survival vs. adults (log-rank, p < 0.001) with 5-year rates of 84.4% vs. 48.2%, respectively. In multivariable Cox regression for all patients, adults demonstrated an increased risk of mortality compared to children (p < 0.001), while metastasis was associated with an increased (p = 0.02) and surgical treatment with a decreased (p = 0.001) risk of mortality. In multivariable Cox regression for surgically-treated patients, adulthood (p = 0.004) and margin-positive resection (p = 0.03) were independently associated with an increased risk of mortality. Multimodal treatment including complete surgical resection and chemotherapy results in long-term survival in most children with UESL. However, adults with UESL have poorer long-term survival that may reflect differences in disease biology and an opportunity to further refine currently available treatment schemas.

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Workload-indexed blood pressure response is superior to peak systolic blood pressure in predicting all-cause mortality

European Journal of Preventive Cardiology ◽

10.1177/2047487319877268 ◽

2019 ◽

Vol 27 (9) ◽

pp. 978-987 ◽

Cited By ~ 4

Author(s):

Kristofer Hedman ◽

Nicholas Cauwenberghs ◽

Jeffrey W Christle ◽

Tatiana Kuznetsova ◽

Francois Haddad ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Systolic Blood Pressure ◽

Exercise Testing ◽

Lower Risk ◽

Metabolic Equivalents ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality ◽

Clinical Exercise Testing

Aims The association between peak systolic blood pressure (SBP) during exercise testing and outcome remains controversial, possibly due to the confounding effect of external workload (metabolic equivalents of task (METs)) on peak SBP as well as on survival. Indexing the increase in SBP to the increase in workload (SBP/MET-slope) could provide a more clinically relevant measure of the SBP response to exercise. We aimed to characterize the SBP/MET-slope in a large cohort referred for clinical exercise testing and to determine its relation to all-cause mortality. Methods and results Survival status for male Veterans who underwent a maximal treadmill exercise test between the years 1987 and 2007 were retrieved in 2018. We defined a subgroup of non-smoking 10-year survivors with fewer risk factors as a lower-risk reference group. Survival analyses for all-cause mortality were performed using Kaplan–Meier curves and Cox proportional hazard ratios (HRs (95% confidence interval)) adjusted for baseline age, test year, cardiovascular risk factors, medications and comorbidities. A total of 7542 subjects were followed over 18.4 (interquartile range 16.3) years. In lower-risk subjects ( n = 709), the median (95th percentile) of the SBP/MET-slope was 4.9 (10.0) mmHg/MET. Lower peak SBP (<210 mmHg) and higher SBP/MET-slope (>10 mmHg/MET) were both associated with 20% higher mortality (adjusted HRs 1.20 (1.08–1.32) and 1.20 (1.10–1.31), respectively). In subjects with high fitness, a SBP/MET-slope > 6.2 mmHg/MET was associated with a 27% higher risk of mortality (adjusted HR 1.27 (1.12–1.45)). Conclusion In contrast to peak SBP, having a higher SBP/MET-slope was associated with increased risk of mortality. This simple, novel metric can be considered in clinical exercise testing reports.

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Risk Factors of SARS-CoV-2 Infection: Global Epidemiological Study

JMIRx Med ◽

10.2196/28843 ◽

2021 ◽

Vol 2 (3) ◽

pp. e28843 ◽

Cited By ~ 3

Author(s):

William Alphonse Barletta

Keyword(s):

Risk Factors ◽

Case Fatality ◽

Physiological Basis ◽

Public Health Agencies ◽

The Public ◽

Physical Conditions ◽

Clinical Observations ◽

Risk Of Mortality ◽

Increased Risk ◽

Cross Correlations

Background Since the first recognition of the pandemic characteristics of SARS-CoV-2 infection, and before substantial case fatality data were available worldwide, public health agencies warned the public about the increased dangers of SARS-CoV-2 to persons with a variety of underlying physical conditions, many of which are more commonly found in persons over 50 years of age or in certain ethnic groups. Objective To investigate the statistical rather than the physiological basis in support of the abovementioned warnings, this study examines correlations globally on a nation-by-nation basis between the statistical data concerning COVID-19 fatalities and the statistics of potential comorbidities that may influence the severity of infection. Methods This study considers the statistics describing the populations of the 99 countries with the greatest numbers of SARS-CoV-2 infections at the time of the data cutoff. As national compilations of direct measures of immune system strength are not publicly available, the frequency of fatalities in those countries due to a variety of serious diseases is used as a proxy for the susceptibility of those populations to those same diseases. Results The analysis produces plots and calculations of correlations and cross-correlations of COVID-19 case fatality rates and the risks of other potential cofactors. It exposes some reasons that may underlie the degree to which advanced age increases the risk of mortality of infection with SARS-CoV-2. In contrast with the strong influences of comorbidities on the seriousness of consequences of influenzas and their associated pneumonias, the correlations of the same set of risk factors with SARS-CoV-2 infection are considerably weaker. The general characteristics of the observed correlations strengthened through 3 cycles of analysis, starting in September 2020. The strongest correlations were with chronic kidney disease and coronary disease (approximately 0.28 and 0.20, respectively). Conclusions This study confirms early clinical observations that infection with SARS-CoV-2 presents an increased risk to persons over the age of 65 years. It does not support the suggestions presented by government agencies early in the pandemic that the risks are much greater for persons with certain common potential comorbidities.

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Stereotactic radiosurgery for brain metastases from pelvic gynecological malignancies: oncologic outcomes, validation of prognostic scores, and dosimetric evaluation

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002906 ◽

2021 ◽

pp. ijgc-2021-002906

Author(s):

Eva Meixner ◽

Tanja Eichkorn ◽

Sinem Erdem ◽

Laila König ◽

Kristin Lang ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Recursive Partitioning ◽

Whole Brain Radiotherapy ◽

Prognostic Scores ◽

Gynecologic Malignancies ◽

Whole Brain ◽

Brain Radiotherapy ◽

Cerebral Control

IntroductionStereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores.MethodsWe retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis.ResultsWith a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (p<0.0001). Radionecrosis was diagnosed in five women (16%); long-term neurotoxicity was significantly worse after whole-brain radiotherapy compared with radiosurgery (p=0.023).ConclusionStereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.

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Lower serum retinoic acid level for prediction of higher risk of mortality in ischemic stroke

Neurology ◽

10.1212/wnl.0000000000007261 ◽

2019 ◽

Vol 92 (15) ◽

pp. e1678-e1687 ◽

Cited By ~ 22

Author(s):

Wen-Jun Tu ◽

Han-Cheng Qiu ◽

Yiqun Zhang ◽

Jian-lei Cao ◽

Hong Wang ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Retinoic Acid ◽

Prognostic Significance ◽

Multivariable Analysis ◽

Net Reclassification Improvement ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality ◽

Cvd Mortality

ObjectiveTo explore the association between serum retinoic acid (RA) level in patients with acute ischemic stroke (AIS) and mortality risk in the 6 months after admission.MethodsFrom January 2015 through December 2016, patients admitted to 3 stroke centers in China for first-ever AIS were screened. The primary endpoint was all-cause mortality or cardiovascular disease (CVD) mortality in the 6 months after admission. The significance of serum RA level, NIH Stroke Scale score, and established risk factors in predicting mortality were determined. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in statistical analysis.ResultsOf the 1,530 patients enrolled, 325 died within 6 months of admission, with an all-cause mortality of 21.2% and CVD-related mortality of 13.1%. In multivariable analysis, RA levels were expressed as quartiles with the clinical variables. The results of the second to fourth quartiles (Q2–Q4) were compared with the first quartile (Q1); RA levels showed prognostic significance, with decreased all-cause and CVD mortality of 55% and 63%, respectively. After RA was added to the existing risk factors, all-cause mortality could be better reclassified, in association with only the NRI statistic (p = 0.005); CVD mortality could be better reclassified with significance, in association with both the IDI and NRI statistics (p < 0.01).ConclusionsLow circulating levels of RA were associated with increased risk of all-cause and CVD mortality in a cohort of patients with first-incidence AIS, indicating that RA level could be a predictor independent of established conventional risk factors.

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Association of Cardiovascular Risk Factors With Cardiac Events and Survival Outcomes Among Patients With Breast Cancer Enrolled in SWOG Clinical Trials

Journal of Clinical Oncology ◽

10.1200/jco.2017.77.4414 ◽

2018 ◽

Vol 36 (26) ◽

pp. 2710-2717 ◽

Cited By ~ 21

Author(s):

Dawn L. Hershman ◽

Cathee Till ◽

Sherry Shen ◽

Jason D. Wright ◽

Scott D. Ramsey ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Cardiovascular Disease ◽

Overall Survival ◽

Clinical Trials ◽

Survival Outcomes ◽

Cardiac Events ◽

Free Survival ◽

Increased Risk

Background Cardiovascular disease is the primary cause of death among patients with breast cancer. However, the association of cardiovascular-disease risk factors (CVD-RFs) with long-term survival and cardiac events is not well studied. Methods We examined SWOG (formerly the Southwest Oncology Group) breast cancer trials from 1999 to 2011. We identified baseline diabetes, hypertension, hypercholesterolemia, and coronary artery disease by linking trial records to Medicare claims. The primary outcome was overall survival. Patients with both baseline and follow-up claims were examined for cardiac events. Cox regression was used to assess the association between CVD-RFs and outcomes. Results We identified 1,460 participants older than 66 years of age from five trials; 842 were eligible for survival outcomes analysis. At baseline, median age was 70 years, and median follow-up was 6 years. Hypertension (73%) and hypercholesterolemia (57%) were the most prevalent conditions; 87% of patients had one or more CVD-RF. There was no association between any of the individual CVD-RFs and overall survival except for hypercholesterolemia, which was associated with improved overall survival (hazard ratio [HR], 0.73; 95% CI, 0.57 to 0.93; P = .01). With each additional CVD-RF, there was an increased risk of death (HR, 1.23; 95% CI, 1.08 to 1.40; P = .002), worse progression-free survival (HR, 1.12; 95% CI, 1.00 to 1.25; P = .05), and marginally worse cancer-free survival (HR, 1.15; 95% CI, 0.99 to 1.34; P = .07). The relationship between baseline CVD-RFs and cardiac events was analyzed in 736 patients. A strong linear association between the number of CVD-RFs and cardiac event was observed (HR per CVD-RF, 1.41; 95% CI, 1.17 to 1.69; P < .001). Conclusion Among participants in clinical trials, each additional baseline CVD-RF was associated with an increased risk of cardiac events and death. Efforts to improve control of modifiable CVD-RFs are needed, especially among those with multiple risk factors.

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