Publications by authors named "Santino S Butler"

18 Publications

  • Page 1 of 1

Risk of cardiovascular mortality with androgen deprivation therapy in prostate cancer: A secondary analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Randomized Controlled Trial.

Cancer 2021 Jul 27;127(13):2213-2221. Epub 2021 Apr 27.

Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, Massachusetts.

Background: For men with radiation-managed prostate cancer, there is conflicting evidence regarding the association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM), particularly among those who have with preexisting comorbidities. The objective of this study was to analyze the association between ADT and CVM across patient comorbidity status using prospectively collected data from a large clinical trial.

Methods: In total, 1463 men were identified who were diagnosed with clinically localized, intermediate-risk/high-risk prostate cancer (T2b-T4, Gleason 7-10, or prostate-specific antigen >10 ng/mL) from 1993 to 2001 and managed with either radiation therapy (RT) alone or RT plus ADT during the randomized Prostate, Lung, Colon, and Ovarian (PLCO) Cancer Screening Trial. Adjusted hazard ratios (aHRs) for cause-specific mortality (prostate cancer-specific mortality vs other-cause mortality-including the primary end point of CVM [death from ischemic heart disease, cerebrovascular accident, or other circulatory disease]) were determined using Fine and Gray competing-risk regression analysis and stratified by comorbidity history.

Results: There was no difference in the risk of 5-year CVM between ADT plus RT and RT alone (2.3% vs 3.3%, respectively; aHR, 0.69; 95% CI, 0.38-1.24; P = .21) overall or on subgroup analysis among men with a history of ≥1 preexisting comorbidities (3.2% vs 5.3%, respectively; aHR, 0.83; 95% CI, 0.43-1.60; P = .58), ≥2 preexisting comorbidities (6.9% vs 8.3%, respectively; aHR, 0.95; 95% CI, 0.40-2.25; P = .90), or cardiovascular disease/risk factors (3.6% vs 4.3%, respectively; aHR, 0.85; 95% CI, 0.44-1.65; P = .63). These results were all similar when each component of CVM was analyzed separately-either cardiac, stroke, or other vascular mortality (P > .05).

Conclusions: This study provides prospectively collected evidence that the use of ADT plus RT, compared with RT alone, is not associated with an increased risk of CVM, even among subgroups of men who have preexisting comorbidities and cardiovascular disease.
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http://dx.doi.org/10.1002/cncr.33486DOI Listing
July 2021

Financial worry and psychological distress among cancer survivors in the United States, 2013-2018.

Support Care Cancer 2021 Sep 16;29(9):5523-5535. Epub 2021 Mar 16.

Department of Radiation Oncology, University of Texas Southwestern, Dallas, TX, USA.

Background: A growing proportion of cancer survivors experience financial toxicity. However, the psychological burden of cancer costs and associated mental health outcomes require further investigation. We assessed prevalence and predictors of self-reported financial worry and mental health outcomes among cancer survivors.

Patients And Methods: Data from the 2013-2018 National Health Interview Survey (NHIS) for adults reporting a cancer diagnosis were used. Multivariable ordinal logistic regressions defined adjusted odds ratios (AORs) of reporting financial worry by relevant sociodemographic variables, and sample weight-adjusted prevalence of financial worry was estimated. The association between financial worry and psychological distress, as defined by the six-item Kessler Psychological Distress Scale was also assessed.

Results: Among 13,361 survey participants (median age 67; 60.0% female), 9567 (71.6%) self-reported financial worry, including worries regarding costs of paying for children's college education (62.7%), maintaining one's standard of living (59.7%), and medical costs due to illness or accident (58.3%). Female sex, younger age, and Asian American race were associated with increased odds of financial worry (P < 0.05 for all). Of 13,218 participants with complete responses to K6 questions, 701 (5.3%) met the threshold for severe psychological distress. Participants endorsing financial worry were more likely to have psychological distress (6.6 vs. 1.2%, AOR 2.89, 95% CI 2.03-4.13, P< 0.001) with each additional worry conferring 23.9% increased likelihood of psychological distress.

Conclusions: A majority of cancer survivors reported financial worry, which was associated with greater odds of reporting psychological distress. Policies and guidelines are needed to identify and mitigate financial worries and psychologic distress among patients with cancer, with the goal of improving psychological well-being and overall cancer survivorship care.
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http://dx.doi.org/10.1007/s00520-021-06084-1DOI Listing
September 2021

Disparities in Refusal of Locoregional Treatment for Prostate Adenocarcinoma.

JCO Oncol Pract 2021 Feb 25:OP2000839. Epub 2021 Feb 25.

Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Purpose: We assessed sociodemographic factors associated with and survival implications of refusal of potentially survival-prolonging locoregional treatment (LT, including radiotherapy and surgery) despite provider recommendation among men with localized prostate adenocarcinoma.

Methods: The National Cancer Database (2004-2015) identified men with TxN0M0 prostate cancer who either received or refused LT despite provider recommendation. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of refusing LT, with sociodemographic and clinical covariates. Models were stratified by low-risk and intermediate- or high-risk (IR or HR) disease, with a separate interaction analysis between race and risk group. Multivariable Cox proportional hazard ratios compared overall survival (OS) among men who received versus refused LT.

Results: Of 887,839 men (median age 64 years, median follow-up 6.14 years), 2,487 (0.28%) refused LT. Among men with IR or HR disease (n = 651,345), Black and Asian patients were more likely to refuse LT than White patients (0.35% 0.29% 0.17%; Black White AOR, 1.75; 95% CI, 1.52 to 2.01; < .001; Asian White AOR, 1.47; 95% CI, 1.05 to 2.06; = .027, race * risk group interaction < .001). Later year of diagnosis, community facility type, noninsurance or Medicaid, and older age were also associated with increased odds of LT refusal, overall and when stratifying by risk group. For men with IR or HR disease, LT refusal was associated with worse OS (5-year OS 80.1% 91.5%, HR, 1.65, < .001).

Conclusion: LT refusal has increased over time; racial disparities were greater in higher-risk disease. Refusal despite provider recommendation highlights populations that may benefit from efforts to assess and reduce barriers to care.
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http://dx.doi.org/10.1200/OP.20.00839DOI Listing
February 2021

Association Between Travel Distance and Use of Postoperative Radiation Therapy Among Men With Organ-Confined Prostate Cancer: Does Geography Influence Treatment Decisions?

Pract Radiat Oncol 2021 Jul-Aug;11(4):e426-e433. Epub 2021 Feb 6.

Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: After radical prostatectomy, men with adverse pathologic features or a persistent postoperative detectable prostate-specific antigen (PSA) are candidates for postoperative radiation therapy (PORT). Previous data have suggested disparities in receipt of adjuvant radiation therapy for adverse pathologic features according to travel distance. Among patients without adverse pathologic features (pT2 disease and negative margins), the main indication for PORT is a persistent postoperative detectable PSA. However, it remains unknown whether the rate of receipt of PORT in this cohort of men with persistently detectable PSA is related to travel distance from the treating facility.

Methods And Materials: Using the National Cancer Database, we identified 170,379 men with prostate cancer diagnosed from 2004 to 2015 managed with upfront surgery who were found to have pT2 disease with negative surgical margins. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% confidence intervals (CIs) of receiving PORT as the primary dependent variable and distance (<5, 5-10, 10-20, ≥20 miles from the treatment facility) as the primary independent variable.

Results: Within our cohort, progressively farther distance from the treatment facility was associated with lower rates of PORT. In patients living <5 miles, 5 to 10 miles, 10 to 20 miles, and >20 miles from the treating facility, rates of PORT of were 1.37% (referent), 1.16% (AOR, 0.90; 95% CI, 0.79-1.04; P = .158), 0.98% (AOR, 0.80; 95% CI, 0.70-0.93; P = .003), and 0.64% (AOR, 0.47; 95% CI, 0.41-0.54; P < .001), respectively.

Conclusions: For men with localized prostate cancer without adverse pathologic features managed with surgery, increasing distance from treatment facility was associated with lower receipt of PORT. Given that the rate of a persistent postoperative detectable PSA is unlikely to depend on the distance to the treatment facility, these findings raise the possibility that the geographic availability of radiation treatment facilities influences the decision to undergo PORT for patients with persistent postoperative detectable PSA.
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http://dx.doi.org/10.1016/j.prro.2020.12.002DOI Listing
February 2021

Factors Influencing Noncompletion of Radiation Therapy Among Men With Localized Prostate Cancer.

Int J Radiat Oncol Biol Phys 2021 04 1;109(5):1279-1285. Epub 2020 Dec 1.

Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida; Office of Community Outreach and Engagement, Sylvester Comprehensive Cancer Center, Miami, Florida. Electronic address:

Purpose: Treatment noncompletion may occur with radiation therapy (RT), especially with protracted treatment courses such as RT for prostate cancer, and may affect the efficacy of RT. For men with localized prostate cancer managed with primary RT, we evaluated associations between rates of treatment noncompletion and RT fractionation schedules.

Methods And Materials: The National Cancer Database identified men diagnosed from 2004 to 2014 treated with primary RT. Patients receiving 180 cGy/fraction or 200 cGy/fraction were defined as having completed radiation therapy if they received ≥41 fractions of 180 cGy/fraction or ≥37 fractions of 200 cGy/fraction. Stereotactic body radiation therapy (SBRT) was defined as 5 to 8 fractions of 600 to 800 cGy/fraction. Odds ratios compared rates of treatment noncompletion, adjusting for sociodemographic covariates. A propensity-adjusted multivariable Cox regression assessed the association between treatment completion and overall survival.

Results: Of 157,657 patients, 95.7% (n = 150,847) received conventional fractionation and 4.3% (n = 6810) received SBRT. Rates of noncompletion were 12.5% (n = 18,803) among patients who received conventional fractionation and 1.9% (n = 131) among patients who received SBRT (odds ratio [OR] versus conventional, 0.21; 95% confidence interval [CI], 0.18-0.26; P < .001). The rate of noncompletion among 25,727 African American patients was 12.8%, compared with 11.8% among 126,199 white patients (OR, 1.14; 95% CI, 1.09-1.19; P < .001). In a subgroup analysis, the disparity in noncompletion persisted for conventional fractionation (13.2% vs 12.3%, respectively; OR, 1.09; 95% CI, 1.05-1.13; P < .001), but not for SBRT (2.2% vs 1.8%, respectively; OR, 1.26; 95% CI, 0.79-2.00; P = .34). Noncompletion was associated with worse survival in a propensity-adjusted multivariable analysis (hazard ratio, 1.25; 95% CI, 1.22-1.29; P < .001).

Conclusions: SBRT was associated with lower rates of RT noncompletion among men with localized prostate cancer. African American race was associated with greater rates of treatment noncompletion, although the disparity may be decreased among men receiving SBRT.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.064DOI Listing
April 2021

General and Health-Related Internet Use Among Cancer Survivors in the United States: A 2013-2018 Cross-Sectional Analysis.

J Natl Compr Canc Netw 2020 11 2;18(11):1468-1475. Epub 2020 Nov 2.

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.

Background: A significant proportion of cancer survivors endorse ongoing health information needs and may use the internet to access information. We assessed patterns and predictors of general and health-specific internet use among cancer survivors.

Methods: Using data from the National Health Interview Survey (NHIS), which was administered in 2013 through 2018, for adults reporting a cancer diagnosis, sample weight-adjusted estimates defined prevalence and multivariable logistic regressions defined adjusted odds ratios (aORs) of general and health-specific internet use, adjusting for relevant sociodemographic covariates, including healthcare satisfaction as the primary independent variable. The analysis for health-specific internet use was also repeated including a sex (female vs male)*healthcare satisfaction (very satisfied/somewhat satisfied vs somewhat dissatisfied/very dissatisfied) interaction term.

Results: Among 12,970 survivors of cancer, general and health-specific internet use increased from 2013 to 2018 (from 63.2% to 70.8% and from 46.8% to 52.2%, respectively; P<.05 for both). Survivors who were very dissatisfied with healthcare were more likely to use the internet for health information compared with those who were very satisfied (59.5% vs 48.0%; aOR, 1.78; 95% CI, 1.20-2.64; P=.004). Younger age, female sex, higher educational attainment, and higher socioeconomic status were all associated with increased reported use of the internet for both general and health-specific purposes (P<.001 for all). There was a significant sex*healthcare satisfaction interaction (P=.009) such that for female survivors, healthcare dissatisfaction was associated with higher odds of health-specific internet use (61.4% vs 52.5%; P<.001; men, P=.97). No association was found between healthcare satisfaction and general internet use (P=.42).

Conclusions: The increasing proportion of survivors of cancer using the internet for health-specific information may be associated with self-reported dissatisfaction with healthcare. Efforts are needed to improve both access to the internet and the quality of cancer-relevant online health information, and to enhance patients' online health literacy.
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http://dx.doi.org/10.6004/jnccn.2020.7591DOI Listing
November 2020

Prostate cancer-specific mortality burden by risk group among men with localized disease: Implications for research and clinical trial priorities.

Prostate 2020 09 13;80(13):1128-1133. Epub 2020 Jul 13.

Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Objective: To estimate contemporary population-based patterns of the relative burden of prostate cancer-specific mortality (PCSM) attributable to each N0M0 prostate cancer risk-group, that may guide prioritization in research, trial design, and clinical practice.

Methods: We categorized 2004-2015 Surveillance, Epidemiology, and End Results database patients by risk group (low, favorable intermediate, unfavorable intermediate, high, and very highrisk). Using the Fine-Gray method, we calculated the relative burden of 10-year PCSM attributable to each risk group.

Results: Among N = 337 162 men (6.8-year median follow-up; median age 65 years), the relative proportion of low-, favorable intermediate-, unfavorable intermediate-, high-, and very high-risk diagnoses were 29.9% (N = 100 969), 31.1% (N = 104 696), 17.9% (N = 60 360), 18.1% (N = 61 023), and 3.0% (N = 10 114). Within 10 years of diagnosis, among patients who died of prostate cancer (N = 15 064), 5.0% (N = 746) had low-risk, 13.7% (N = 2060) had favorable intermediate-risk, 16.1% (N = 2429) had unfavorable intermediate-risk, 47.8% (N = 7196) had high-risk, and 17.5% (N = 2633) had very high-risk disease at diagnosis. Patients aged 65 and older accounted for 51.9% of all diagnoses and 72.3% of 10-year PCSM. Although black patients accounted for 15.0% of low-risk diagnoses, they accounted for 20.6% of 10-year PCSM. White patients accounted for 80.3% of low-risk diagnoses and 75.7% of 10-year PCSM.

Conclusion: Although high-risk and very high-risk disease account for one-fifth of diagnoses, they account for two-thirds of 10-year PCSM. Older patients and black patients with low-risk disease accounted for a disproportionately large proportion of deaths. These findings support targeting research toward high-risk disease and ensuring adequate representation of older and black men in clinical trials.
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http://dx.doi.org/10.1002/pros.24041DOI Listing
September 2020

Validation of a subclassification for high-risk prostate cancer in a prospective cohort.

Cancer 2020 05 19;126(10):2132-2138. Epub 2020 Feb 19.

Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: A subgroup of men with favorable high-risk prostate cancer (T1c with either a Gleason score of 4 + 4 = 8 and a prostate-specific antigen [PSA] level <10 ng/mL or a Gleason score of 6 and a PSA level >20 ng/mL) has been associated with improved outcomes in comparison with other standard high-risk patients. This study was designed to validate the prognostic utility of a subclassification for high-risk disease with a prospectively collected data set.

Methods: This study identified 3033 men from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had been diagnosed from 1993 to 2001 with clinically localized prostate cancer-either intermediate-risk disease (clinical stage T2b-c, a Gleason score of 7, or a PSA level of 10 to 20 ng/mL) or high-risk disease (clinical stage T3-T4, a Gleason score of 8-10, or a PSA level >20 ng/mL)-that was managed with radical prostatectomy or radiation therapy. Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) for pathological T3 to T4 or N1 (pT3-T4/pN1) disease. Fine and Gray competing risks regression was used to determine adjusted hazard ratios (aHRs) of prostate cancer-specific mortality (PCSM).

Results: The median follow-up was 5.7 years. Patients with favorable high-risk disease had lower 8-year PCSM in comparison with patients with standard high-risk disease (2.2% vs 10.8%; aHR, 0.26; 95% confidence interval [CI], 0.09-0.73; P = .01) but similar PCSM in comparison with patients with intermediate-risk disease (2.2% vs 2.2%; aHR, 0.90; 95% CI, 0.32-2.54; P = .84). Among those who underwent surgery, those with favorable high-risk disease had lower odds of pT3-T4/pN1 disease than those with standard high-risk disease (46.2% vs 63.3%; aOR, 0.50; 95% CI, 0.27-0.94; P = .03).

Conclusions: This study validates the prognostic utility of a subclassification for high-risk disease in a prospectively collected patient cohort. Patients with favorable high-risk disease have PCSM similar to that of patients with intermediate-risk disease and significantly better than that of patients with standard high-risk disease. Future trials are needed to assess possible de-intensification of therapy for favorable high-risk disease.
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http://dx.doi.org/10.1002/cncr.32778DOI Listing
May 2020

Reply to Obesity and aggressive prostate cancer and the golden rule: Do not do to others what you do not want done to yourself.

Cancer 2020 05 5;126(10):2321-2322. Epub 2020 Feb 5.

Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1002/cncr.32758DOI Listing
May 2020

Short-term mortality risks among patients with oropharynx cancer by human papillomavirus status.

Cancer 2020 04 13;126(7):1424-1433. Epub 2020 Jan 13.

Harvard Medical School, Boston, Massachusetts.

Background: There is substantial variation in head and neck cancer (HNC) mortality and competing mortality among patients with HNC. In this study, the authors characterize the causes and risks of short-term mortality among patients with oropharynx cancer (OPC) and how these risks differ by human papillomavirus (HPV) status.

Methods: A custom Surveillance, Epidemiology, and End Results (SEER) data set with HPV status was used to identify 4930 patients with OPC who were diagnosed with nonmetastatic (M0) disease from 2013 to 2014, including 3560 (72.2%) HPV-positive patients and 1370 HPV-negative patients. Causes of death and cumulative incidence estimates for HNC-specific mortality, competing mortality, second-cancer mortality, and noncancer mortality were analyzed by HPV status. Risk factors for mortality events were determined using multivariable competing risk regression models.

Results: Compared with HPV-negative patients, HPV-positive patients had a lower risk of 2-year cumulative incidence of all-cause mortality (10.4% vs 33.3%; P < .0001) and a lower risk of both HNC-specific mortality (4.8% vs 16.2%; P < .0001) and competing-cause mortality (5.6% vs 16.8%; P < .0001). Second-cancer mortality was the most common cause of non-HNC mortality among HPV-negative patients. Both second-cancer mortality and noncancer mortality were significantly higher among patients who had HPV-negative OPC (10.8% and 6.1%, respectively) compared with those who had HPV-positive OPC (2.4% and 3.2%, respectively; both P < .0001). The median follow-up was 11 months (range 1-23 months) in this cohort with known HPV-status.

Conclusions: Patients with HPV-positive and HPV-negative OPC have significantly different rates of both HNC mortality and competing mortality. HPV-negative patients are at substantial risk of competing mortality, even within 2 years of cancer diagnosis. These differences can inform power calculations for clinical trials and patient management in the acute and survivorship settings.
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http://dx.doi.org/10.1002/cncr.32652DOI Listing
April 2020

Prostate cancer incidence across stage, NCCN risk groups, and age before and after USPSTF Grade D recommendations against prostate-specific antigen screening in 2012.

Cancer 2020 02 3;126(4):717-724. Epub 2019 Dec 3.

Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: We sought to determine the extent to which US Preventive Services Task Force (USPSTF) 2012 Grade D recommendations against prostate-specific antigen screening may have impacted recent prostate cancer disease incidence patterns in the United States across stage, National Comprehensive Cancer Network (NCCN) risk groups, and age groups.

Methods: SEER*Stat version 8.3.4 was used to calculate annual prostate cancer incidence rates from 2010 to 2015 for men aged ≥50 years according to American Joint Committee on Cancer stage at diagnosis (localized vs metastatic), NCCN risk group (low vs unfavorable [intermediate or high-risk]), and age group (50-74 years vs ≥75 years). Age-adjusted incidences per 100,000 persons with corresponding year-by-year incidence ratios (IRs) were calculated using the 2000 US Census population.

Results: From 2010 to 2015, the incidence (per 100,000 persons) of localized prostate cancer decreased from 195.4 to 131.9 (P  < .001) and from 189.0 to 123.4 (P  < .001) among men aged 50-74 and ≥75 years, respectively. The largest relative year-by-year decline occurred between 2011 and 2012 in NCCN low-risk disease (IR, 0.77 [0.75-0.79, P < .0001] and IR 0.68 [0.62-0.74, P < .0001] for men aged 50-74 and ≥75 years, respectively). From 2010-2015, the incidence of metastatic disease increased from 6.2 to 7.1 (P  < .001) and from 16.8 to 22.6 (P  < .001) among men aged 50-74 and ≥75 years, respectively.

Conclusions: This report illustrates recent prostate cancer "reverse migration" away from indolent disease and toward more aggressive disease beginning in 2012. The incidence of localized disease declined across age groups from 2012 to 2015, with the greatest relative declines occurring in low-risk disease. Additionally, the incidence of distant metastatic disease increased gradually throughout the study period.
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http://dx.doi.org/10.1002/cncr.32604DOI Listing
February 2020

United States trends in active surveillance or watchful waiting across patient socioeconomic status from 2010 to 2015.

Prostate Cancer Prostatic Dis 2020 03 7;23(1):179-183. Epub 2019 Oct 7.

Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Prospective evidence supports active surveillance/watchful waiting (AS/WW) as an efficacious management option for low-risk prostate cancer that avoids potential treatment toxicity. AS/WW schedules require regular follow-up and adherence, and it is unknown to what extent patient socioeconomic status (SES) may impact management decisions for AS/WW. We sought to determine whether AS/WW use in the United States differs according to patient SES.

Design: Using the Surveillance, Epidemiology, and End Results Prostate with AS/WW Database, all adult men diagnosed with localized low-risk prostate cancer (clinical T1-T2a, Gleason 6, and prostate-specific antigen <10 ng/mL) and managed with either AS/WW, radical prostatectomy, or radiotherapy were identified between 2010 and 2015. SES tertile was measured by the validated Yost Index (low: 0-10,901; middle: 10,904-11,469; high: 11,470-11,827). AS/WW trends were defined across SES tertiles from 2010 to 2015. Logistic multivariable regression defined adjusted odds ratios (aOR) for receipt of AS/WW by SES tertile.

Results: In 50,302 men, AS/WW use was higher with increasing SES tertile (24.6, 25.3, and 30.5% for low, middle, and high SES tertiles, respectively; P <0.001). From 2010 to 2015, AS/WW use in the low, middle, and high SES tertiles increased from 11.2 to 37.3%, 14.1 to 45.8%, and 17.6 to 46.4%, respectively (P <0.001). By 2015, likelihood of AS/WW became comparable among the middle vs. high SES tertiles (aOR 0.96, 95% confidence interval (CI): 0.83-1.11, P = 0.55), but remained lower among the low vs. high SES tertile (aOR 0.73, 95% CI: 0.64-0.83, P < 0.001).

Conclusions: AS/WW use for low-risk prostate cancer in the US differs by SES. Despite increases in AS/WW across SES from 2010 to 2015, patients from low SES received significantly lower rates of AS/WW compared with higher SES groups. SES may therefore influence management decisions, where factors associated with low SES might act as a barrier to AS/WW, and may need to be addressed to reduce any disproportionate risk of unnecessary treatment to lower SES patients.
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http://dx.doi.org/10.1038/s41391-019-0175-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202379PMC
March 2020

Prevalence of chronic pain among cancer survivors in the United States, 2010-2017.

Cancer 2019 12 22;125(23):4310-4318. Epub 2019 Aug 22.

McGraw/Patterson Center for Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: There are a growing number of cancer survivors in the United States who are at risk for chronic pain due to cancer disease and treatments. The prevalence of chronic pain among cancer survivors has not been comprehensively reported.

Methods: This study used data from the National Health Interview Survey (2010-2017) to compare the prevalence of chronic pain between participants with a cancer diagnosis and participants without one. Adjusted odds ratios (AORs) of having chronic pain were assessed by multivariable logistic regression, which included an age (less than the median age vs greater than or equal to the median age) × cancer diagnosis (yes vs no) interaction term. Among cancer survivors, multivariable logistic regression defined the odds of feeling depressed, feeling worried/nervous/anxious, being unable to work, and needing assistance for activities of daily living (ADLs) and instrumental activities of daily living (IADLs).

Results: Among 115,091 participants, a cancer diagnosis was associated with an increased AOR of chronic pain in comparison with the general population (30.8% vs 15.7%; AOR, 1.48; 95% confidence interval, 1.38-1.59). Older age was associated with higher odds of chronic pain (P < .001 across all increasing age categories); however, the positive association between older age and chronic pain was seen only in participants without cancer and was not seen in those with a cancer diagnosis (P  < .001). Among patients reporting a cancer diagnosis, chronic pain was associated with greater odds of feeling depressed, feeling worried/nervous/anxious, being unable to work, and needing assistance with ADLs or IADLs (P < .001 for all).

Conclusions: Cancer survivors appear to have a high prevalence of chronic pain, which is associated with worse mental, functional, and employment outcomes. Screening and management of chronic pain should be addressed by policymakers to improve cancer survivorship care.
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http://dx.doi.org/10.1002/cncr.32450DOI Listing
December 2019

Genomic Validation of 3-Tiered Clinical Subclassification of High-Risk Prostate Cancer.

Int J Radiat Oncol Biol Phys 2019 11 2;105(3):621-627. Epub 2019 Jul 2.

Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts.

Purpose: Recent data and National Comprehensive Cancer Network (NCCN) guidelines suggest that high-risk prostate cancer (cT3-4, Gleason score ≥8, or prostate-specific antigen [PSA] >20 ng/mL) is a heterogenous group in terms of long-term patient outcomes. We sought to determine whether subclassification of high-risk prostate cancer based on clinical factors correlates with genomic markers of risk.

Methods And Materials: We identified 3220 patients with NCCN unfavorable intermediate-risk (n = 2000) or high-risk (n = 1220) prostate cancer from a prospective multi-institutional registry cohort. We defined the following subclassification of high-risk prostate cancer based on previously published data: favorable high risk (cT1c, Gleason 6, and PSA >20 ng/mL or cT1c, Gleason 4 + 4 = 8, PSA <10 ng/mL); very high risk (cT3b-T4 or primary Gleason pattern 5); and standard high risk (all others with cT3a, Gleason score ≥8, or PSA >20 ng/mL). We used a set of 33 previously developed genomic classifiers, including Decipher, to determine whether high-risk genomic features correlate with clinical subclasses of high-risk prostate cancer.

Results: Among those with favorable high-risk, standard high-risk, and very high-risk prostate cancer, 50.4%, 64.2%, and 81.6% had a high-risk Decipher score, respectively (P < .001). Among 32 other genomic signatures, 29 had a similar trend of increasing risk scores across the 3 subclasses of high-risk disease (P < .05 after correction for multiple hypothesis testing). Patients in the 3 subclasses of high-risk disease had a median of 4, 6, and 13 high-risk signatures, respectively. In comparison, among those with unfavorable intermediate-risk prostate cancer, 38.2% had a high-risk Decipher score, and the median number of high-risk signatures was 3.

Conclusions: Although NCCN guidelines currently use a 2-tiered system for high-risk prostate cancer, genomic markers of risk correlate with the clinically validated subclassification of high-risk prostate cancer into favorable high-risk, standard high-risk, and very high-risk disease, further confirming the prognostic utility of this 3-tiered stratification.
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http://dx.doi.org/10.1016/j.ijrobp.2019.06.2510DOI Listing
November 2019

Use and early mortality outcomes of active surveillance in patients with intermediate-risk prostate cancer.

Cancer 2019 09 31;125(18):3164-3171. Epub 2019 May 31.

Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts.

Background: Certain patients with intermediate-risk prostate cancer (PCa) may be appropriate candidates for active surveillance (AS). In the current study, the authors sought to characterize AS use and early mortality outcomes for patients with intermediate-risk PCa in the United States.

Methods: The novel Surveillance, Epidemiology, and End Results Active Surveillance/Watchful Waiting database identified 52,940 men diagnosed with National Comprehensive Cancer Network intermediate-risk PCa (cT2b-c, Gleason score of 7, or a prostate-specific antigen level of 10-20 ng/mL) and actively managed (AS, radiotherapy, or radical prostatectomy) from 2010 through 2015. The Cuzick test assessed AS time trends, and logistic multivariable regression characterized features associated with AS. Fine-Gray and Cox modeling determined PCa-specific mortality (PCSM) and overall survival, respectively.

Results: The rate of AS increased from 3.7% in 2010 to 7.3% in 2015, and from 7.2% to 11.7% among men aged ≥70 years. Among men with favorable and unfavorable intermediate-risk disease, the use of AS increased from 7.2% to 14.9% and from 2.2% to 3.8%, respectively (all P value for trend, <.001). The mean age of those patients managed with AS decreased from 69.9 years to 67.9 years (P = .0004). Factors found to be associated with AS included favorable risk disease; black race; higher socioeconomic status; older age; and diagnosis in the West, Northwest, or Midwest regions of the United States. The 5-year PCSM rate was comparable to AS versus treatment among patients with low-risk and favorable intermediate-risk disease, but was worse with AS among those with unfavorable intermediate-risk disease (PCSM, 1.3% vs 0.5%; adjusted hazard ratio, 2.48 [95% CI, 1.11-5.50; P = .026]) and intermediate-risk disease overall (PCSM, 1.1% vs 0.4%; adjusted hazard ratio, 2.34 [95% CI, 1.25-4.37; P = .008]).

Conclusions: The use of AS for patients with intermediate-risk PCa is increasing across the United States, particularly for older men and those with favorable intermediate-risk disease. Early estimates of cancer-specific and overall mortality rates are low with AS, although significantly higher compared with treatment.
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http://dx.doi.org/10.1002/cncr.32202DOI Listing
September 2019

Self-reported Reasons and Patterns of Noninsurance Among Cancer Survivors Before and After Implementation of the Affordable Care Act, 2000-2017.

JAMA Oncol 2019 Oct 10;5(10):e191973. Epub 2019 Oct 10.

Dana-Farber Cancer Institute McGraw/Patterson Center for Population Sciences, Boston, Massachusetts.

Importance: Cancer survivors experience difficulties in maintaining health care coverage, but the reasons and risk factors for lack of insurance are poorly defined.

Objective: To assess self-reported reasons for not having insurance and demographic and socioeconomic factors associated with uninsured status among cancer survivors, before and after implementation of the Affordable Care Act (ACA) in 2014.

Design, Setting, And Participants: This survey study analyzes National Health Interview Survey (NHIS) data from January 1, 2000, through December 31, 2017. Included were adult participants (age, 18-64 years) reporting a cancer diagnosis; however, those with a diagnosis of nonmelanoma skin cancer were excluded.

Exposures: Insurance status.

Main Outcomes And Measures: Multivariable logistic regression was used to define the association between demographic and socioeconomic variables and odds of being uninsured. The prevalence of the most common self-reported reasons for not having insurance (cost, unemployment, employment-related reason, family-related reason) were estimated, with adjusted odds ratios (aORs) for each of the reasons defined by multivariable logistic regression.

Results: Among 17 806 survey participants, the mean (SD) age was 50.9 (10.8) years, and 6121 (34.4%) were men. A total of 1842 participants (10.3%) reported not having health insurance. Individuals surveyed in 2000 to 2013 had higher odds of not having insurance than those surveyed in 2014 to 2017 (10.6% vs 6.2%; aOR 1.75; 95% CI 1.49-2.08). Variables associated with higher odds of uninsured status included younger age (14.2% for age younger than mean vs 6.5% for age older than mean; aOR, 1.84; 95%, CI, 1.62-2.10), annual family income below the poverty threshold (21.4% vs 8.0%; aOR, 1.97; 95%, CI, 1.69-2.30), Hispanic ethnicity (18.8% vs 9.0%; aOR, 1.87; 95% CI, 1.51-2.33), noncitizen status (24.3% vs 9.2%; aOR, 2.38; 95% CI, 1.69-3.34), and current smoking (18.6% vs. 6.7%; aOR, 2.65; 95% CI, 2.32-3.02). Before the ACA, increasing interval from cancer diagnosis was associated with not having insurance (12.3% for ≥6 years vs 8.9% for 0-5 years; aOR, 1.47; 95% CI 1.26-1.70) as was black race (13.9% for black patients vs 10.4% for nonblack patients; AOR, 1.29; 95% CI, 1.04-1.61), but after the ACA, they no longer were (6.8% for ≥6 years vs 5.6% for 0-5 years; aOR, 1.12; 95% CI, 0.82-1.54; and 6.9% for black patients vs 6.2% for nonblack patients; aOR, 0.81; 95% CI, 0.46-1.43). The most commonly cited reason for not having insurance was cost, followed by unemployment, both of which decreased after ACA implementation (cost, 49.6% vs 37.6%, aOR [pre-ACA vs post-ACA], 0.62; 95% CI, 0.46-0.85; unemployment, 37.1% vs 28.5%; aOR 0.62; 95% CI, 0.45-0.87).

Conclusions And Relevance: The proportion of uninsured cancer survivors decreased after implementation of the ACA, but certain subgroups remained at greater risk of being uninsured. Cost was identified as the primary barrier to obtaining insurance, although more than half of cancer survivors reported other barriers to coverage.
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http://dx.doi.org/10.1001/jamaoncol.2019.1973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537771PMC
October 2019
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