Publications by authors named "Pamela R Soulos"

72 Publications

Post-operative radiation therapy for non-small cell lung cancer: A comparison of radiation therapy techniques.

Lung Cancer 2021 11 20;161:171-179. Epub 2021 Sep 20.

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA; Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, CT, USA.

Objectives: Post-operative radiation therapy (PORT) in locally advanced non-small cell lung cancer (LA-NSCLC) has historically been associated with toxicity. Conformal techniques like intensity modulated radiation therapy (IMRT) have the potential to reduce acute and long-term toxicity from radiation therapy. Among patients receiving PORT for LA-NSCLC, we identified factors associated with receipt of IMRT and evaluated the association between IMRT and toxicity.

Methods: We queried the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between January 1, 2006 to December 31, 2014 to identify patients diagnosed with Stage II or III NSCLC and who received upfront surgery and subsequent PORT. Baseline differences between patients receiving 3-dimentional conformal radiation therapy (3D-CRT) and IMRT were assessed using the chi-squared test for proportions and the t-test for means. Multivariable logistic regression was used to identify predictors of receipt of IMRT and pulmonary, esophageal, and cardiac toxicity. Propensity-score matching was employed to reduce the effect of known confounders.

Results: A total of 620 patients met the inclusion criteria, among whom 441 (71.2%) received 3D-CRT and 179 (28.8%) received IMRT. The mean age of the cohort was 73.9 years and 54.7% were male. The proportion of patients receiving IMRT increased from 6.2% in 2006 to 41.4% in 2014 (P < 0.001). IMRT was not associated with decreased pulmonary (OR 0.89; 95% CI, 0.62-1.29), esophageal (OR 1.09; 95% CI, 0.0.75-1.58), or cardiac toxicity (OR 1.02; 95% CI, 0.69-1.51). These findings held on propensity-score matching. Clinical risk factors including comorbidity and prior treatment history were associated with treatment toxicity.

Conclusion: In a cohort of elderly patients, the use of IMRT in the setting of PORT for LA-NSCLC was not associated with a difference in toxicity compared to 3D-CRT. This finding suggests that outcomes from PORT may be independent of radiotherapy treatment technique.
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http://dx.doi.org/10.1016/j.lungcan.2021.09.010DOI Listing
November 2021

Physician trajectories of abandoning long-course breast radiotherapy and their cost impact.

Health Serv Res 2021 06 18;56(3):497-506. Epub 2020 Oct 18.

Yale Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut, USA.

Objective: To examine variation in trajectories of abandoning conventionally fractionated whole-breast irradiation (CF-WBI) for adjuvant breast radiotherapy among physician peer groups and the associated cost implications.

Data Sources: Medicare claims data were obtained from the Chronic Conditions Data Warehouse for fee-for-service beneficiaries with breast cancer in 2011-2014.

Study Design: We used social network methods to identify peer groups of physicians that shared patients. For each physician peer group in each time period (T1 = 2011-2012 and T2 = 2013-2014), we calculated a risk-adjusted rate of CF-WBI use among eligible women, after adjusting for patient clinical characteristics. We applied a latent class growth analysis to these risk-adjusted rates to identify distinct trajectories of CF-WBI use among physician peer groups. We further estimated potential savings to the Medicare program by accelerating abandonment of CF-WBI in T2 using a simulation model.

Data Collection/extraction Methods: Use of conventionally fractionated whole-breast irradiation was determined from Medicare claims among women ≥ 66 years of age who underwent adjuvant radiotherapy after breast conserving surgery.

Principal Findings: Among 215 physician peer groups caring for 16 988 patients, there were four distinct trajectories of abandoning CF-WBI: (a) persistent high use (mean risk-adjusted utilization rate: T1 = 94.3%, T2 = 90.6%); (b) decreased high use (T1 = 81.3%, T2 = 65.3%); (c) decreased medium use (T1 = 60.1%, T2 = 44.0%); and (d) decreased low use (T1 = 31.6%, T2 = 23.6%). Peer groups with a smaller proportion of patients treated at free-standing radiation facilities and a larger proportion of physicians that were surgeons tended to follow trajectories with lower use of CF-WBI. If all physician peer groups had practice patterns in T2 similar to those in the "decreased low use" trajectory, the Medicare program could save $83.3 million (95% confidence interval: $58.5 million-$112.2 million).

Conclusions: Physician peer groups had distinct trajectories of abandoning CF-WBI. Physician composition and setting of radiotherapy were associated with the different trajectories. Distinct practice patterns across the trajectories had important cost implications.
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http://dx.doi.org/10.1111/1475-6773.13572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143683PMC
June 2021

Temporal Trends in Opioid Prescribing Patterns Among Oncologists in the Medicare Population.

J Natl Cancer Inst 2021 03;113(3):274-281

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.

Background: In the wake of the US opioid epidemic, there have been efforts to curb opioid prescribing. However, it is unknown whether these efforts have affected prescribing among oncologists, whose patients often require opioids for symptom management. We investigated temporal patterns in opioid prescribing for Medicare beneficiaries among oncologists and nononcologists.

Methods: We queried the Centers for Medicare and Medicaid Services Part D prescriber dataset for all physicians between January 1, 2013, and December 31, 2017. We used population-averaged multivariable negative binomial regression to estimate the association between time and per-provider opioid and gabapentinoid prescribing rate, defined as the annual number of drug claims (original prescriptions and refills) per beneficiary, among oncologists and nononcologists on a national and state level.

Results: From 2013 to 2017, the national opioid-prescribing rate declined by 20.7% (P < .001) among oncologists and 22.8% (P < .001) among non oncologists. During this time frame, prescribing of gabapentin increased by 5.9% (P < .001) and 23.1% (P < .001) among oncologists and nononcologists, respectively. Among palliative care providers, opioid prescribe increased by 15.3% (P < .001). During the 5-year period, 43 states experienced a decrease (P < .05) in opioid prescribing among oncologists, and in 5 states, opioid prescribing decreased more among oncologists than nononcologists (P < .05).

Conclusions: Between 2013 and 2017, the opioid-prescribing rate statistically significantly decreased nationwide among oncologists and nononcologists, respectively. Given similar declines in opioid prescribing among oncologists and nononcologists, there is concern that opioid-prescribing guidelines intended for the noncancer population are being applied inappropriately to patients with cancer and cancer survivors.
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http://dx.doi.org/10.1093/jnci/djaa110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936059PMC
March 2021

Association of Programmed Cell Death Ligand 1 Expression Status With Receipt of Immune Checkpoint Inhibitors in Patients With Advanced Non-Small Cell Lung Cancer.

JAMA Netw Open 2020 06 1;3(6):e207205. Epub 2020 Jun 1.

Department of Urology, Yale University School of Medicine, New Haven, Connecticut.

Importance: Initial approval for immune checkpoint inhibitors (ICIs) for treatment of advanced non-small cell lung cancer (NSCLC) was limited to patients with high levels of programmed cell death ligand 1 (PD-L1) expression. However, in the period after approval, it is not known how new evidence supporting efficacy of these treatments in patients with low or negative PD-L1 expression was incorporated into real-world practice.

Objective: To evaluate the association between PD-L1 testing and first-line ICI use.

Design, Setting, And Participants: This retrospective cohort study (January 1, 2011, to December 31, 2018) used a deidentified nationwide electronic health record-derived database reflecting real-world care at more than 280 US community and academic cancer clinics (approximately 800 sites of care). Patients included those with advanced NSCLC without other identifiable variations diagnosed in the period after the US Food and Drug Administration's initial first-line approval of ICIs for patients with high PD-L1 expression (≥50%).

Exposure: First-line ICI treatment.

Main Outcomes And Measures: Patterns of PD-L1 testing and first-line ICI treatment among all patients and patients stratified by tumor histologic type (squamous vs nonsquamous).

Results: A total of 45 631 patients (mean [SD] age, 68.4 [9.6] years; 21 614 [47.4%] female) with advanced NSCLC were included in the study. PD-L1 testing increased from 468 (7.2%) in 2015 to 4202 (73.2%) in 2018. Within a subset of 7785 patients receiving first-line treatment in the period after first-line approval of pembrolizumab, those who received PD-L1 testing had a greater odds of receiving an ICI (odds ratio, 2.11; 95% CI, 1.89-2.36). Among patients with high PD-L1 expression (≥50%), 1541 (83.5%) received first-line ICI treatment; 776 patients (40.3%) with low PD-L1 expression (1%-49%) and 348 (32.3%) with negative PD-L1 expression (0%) also received ICIs. In addition, 755 untested patients (32.8%) were treated with a first-line ICI. The proportion of patients who received ICIs without PD-L1 testing increased during the study period (59 [17%] in quarter 4 of 2016 to 141 [53.8%] in quarter 4 of 2018).

Conclusions And Relevance: In this study, use of first-line ICI treatment increased among patients with advanced NSCLC with negative, low, or untested PD-L1 expression status in 2016 through 2018. These findings suggest that national practice was rapidly responsive to new clinical evidence rather than adhering to regulatory guidance in place at the time.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.7205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280954PMC
June 2020

Income disparities in needle biopsy patients prior to breast cancer surgery across physician peer groups.

Breast Cancer 2020 May 2;27(3):381-388. Epub 2019 Dec 2.

Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale Cancer Center, Yale School of Medicine, 333 Cedar Street, 208025, New Haven, CT, USA.

Objective: Evaluate income disparities in receipt of needle biopsy among Medicare beneficiaries and describe the magnitude of this variation across physician peer groups.

Methods: The Surveillance, Epidemiology and End Results (SEER)-Medicare database was queried from 2007-2009. Physician peer groups were constructed. The magnitude of income disparities and the patient-level and physician peer group-level effects were assessed.

Results: Among 9770 patients, 65.4% received needle biopsy. Patients with low income (median area-level household income < $33K) were less likely to receive needle biopsy (58.5%) compared to patients with high income (≥ $50K) (68.6%; adjusted odds ratio 0.77; 95% confidence interval (CI) 0.65-0.91). Needle biopsy varied substantially across physician peer groups (interquartile range 43.4-81.9%). The magnitude of the disparity ranged from an odds ratio (OR) of 0.50 (95% CI 0.23-1.07) for low vs. high income patients to 1.27 (95% CI 0.60-2.68). The effect of being treated by a physician peer group that treated mostly low-income patients on receipt of needle biopsy was nearly three times the effect of being a low-income patient.

Conclusions: Needle biopsy continues to be underused and disparities by income exist. The magnitude of this disparity varies substantially across physician peer groups, suggesting that further work is needed to improve quality and reduce inequities.
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http://dx.doi.org/10.1007/s12282-019-01028-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7512133PMC
May 2020

Peer Influence on Physician Use of Shorter Course External Beam Radiation Therapy for Patients with Breast Cancer.

Pract Radiat Oncol 2020 Mar - Apr;10(2):75-83. Epub 2019 Nov 27.

Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center at Yale, New Haven, Connecticut; Yale Cancer Center, New Haven, Connecticut.

Purpose: Social contagion among physicians may affect the dissemination of innovative and high-value cancer care. We applied social contagion theory to investigate the role of physician peer influence on the use of short courses of external beam radiation therapy (EBRT) for patients with breast cancer.

Methods And Materials: Using a cohort of Medicare beneficiaries with breast cancer, we constructed physician peer groups based on patient-sharing relationships. Outcomes were a patient's receipt of (1) moderately hypofractionated adjuvant EBRT after breast-conserving surgery and (2) short-course palliative EBRT for bone metastases. Using a longitudinal design, we used mixed-effects logistic regression to examine the association between physician peer group rate of short-course EBRT in 2011 to 2012 (T1) and patients' receipt of short-course EBRT in 2013 to 2014 (T2).

Results: During T2, a total of 17,248 patients received adjuvant therapy (32.3% moderately hypofractionated) from 3235 physicians in 1202 physician peer groups. Compared with patients treated within peer groups in which no moderately hypofractionated adjuvant EBRT was used in T1, patients treated by a physician in a peer group with higher T1 use of moderately hypofractionated adjuvant EBRT were more likely to receive moderately hypofractionated adjuvant EBRT in T2 (adjusted odds ratio = 2.03; 95% confidence interval, 1.62-2.54, vs adjusted odds ratio = 2.61; 95% confidence interval, 2.04-3.35, for peer groups where 21%-46% and 47%-100% of radiation oncologists used moderately hypofractionated adjuvant EBRT in T1, respectively, compared with peer groups with no use of moderately hypofractionated adjuvant EBRT). In contrast, there was no significant relationship between T1 peer group use and T2 receipt of short-course palliative EBRT for bone metastases.

Conclusions: Physician peer groups significantly influenced use of short-course EBRT in adjuvant therapy but not in palliative therapy for patients with breast cancer.
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http://dx.doi.org/10.1016/j.prro.2019.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061062PMC
October 2020

Utilization, duration, and outcomes of neoadjuvant endocrine therapy in the United States.

Breast Cancer Res Treat 2019 Nov 10;178(2):419-426. Epub 2019 Aug 10.

Yale Cancer Center, Yale New Haven Hospital, 20 York Street, Ste North Pavilion 1, New Haven, CT, 06510, USA.

Purpose: To evaluate if real-world utilization of neoadjuvant endocrine therapy (NET) is associated with similar rates of response and breast conservation surgery (BCS) compared to neoadjuvant chemotherapy (NAC).

Methods: Our population-based assessment used the National Cancer Data Base to identify women diagnosed with stage II-III, hormone receptor (HR)-positive BC who underwent surgery and received endocrine therapy from 2004 to 2014. Women were categorized by receipt of NET, NAC or no neoadjuvant therapy. We used logistic regression to assess differences in outcomes between therapies using inverse propensity score weighting to adjust for potential selection bias.

Results: In our sample of 211,986 women, 6584 received NET, 52,310 received NAC, and 153,092 did not receive any neoadjuvant therapy. After adjusting for multiple relevant covariates and cofounders, there was no significant difference between NET and NAC with regard to BCS [odds ratio (OR) 0.91; 95% confidence interval (CI) (0.82-1.01)]; however, women who received NET were significantly less likely to achieve pCR [OR 0.34; 95% CI (0.23-0.51)] or a decrease in T stage [OR 0.39; CI (0.34-0.44)] compared to women treated with NAC. Patients who received NET for ≥ 3 months had higher odds of BCS (OR 1.59; 95% CI 1.46-1.73) and downstaging (OR 1.79; 95% CI 1.63-1.97) compared to patients who did not receive neoadjuvant therapy.

Conclusions: Women who received NET had similar rates of BCS compared to women who received NAC. Those who received NET for longer treatment durations had increased odds of BCS and downstaging compared to women who did not receive neoadjuvant therapy.
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http://dx.doi.org/10.1007/s10549-019-05397-4DOI Listing
November 2019

Hospital Variation in Spending for Lung Cancer Resection in Medicare Beneficiaries.

Ann Thorac Surg 2019 12 7;108(6):1710-1716. Epub 2019 Aug 7.

National Clinician Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut; Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; Yale University Cancer Center, New Haven, Connecticut. Electronic address:

Background: As cancer payment models transition from fee for service toward payment "bundles" based on episodes of care, a deeper understanding of the costs associated with stage I lung cancer treatment becomes increasingly relevant. To better understand costs in early lung cancer care, we sought to characterize hospital-level variation in Medicare expenditure after lobectomy for stage I non-small cell lung carcinoma.

Methods: Patients who were diagnosed with stage I non-small cell lung carcinoma from 2006 through 2011 and undergoing lobectomy were selected from the Surveillance, Epidemiology and End Results-Medicare linked database. We used Medicare claims to estimate costs of care in the 90 days after initial surgical hospitalization. Hospitals were grouped into quintiles of mean excess cost, calculated as the mean difference between observed costs and risk-adjusted predicted costs. The association between hospital factors and mean excess cost were compared across hospitals, including complication rates and hospital volume.

Results: A total of 3530 patients underwent lobectomy at 156 hospitals. Hospitals in the lowest cost quintile had index hospitalizations $6226 less costly than predicted. Conversely, the most expensive hospital quintile had index hospital costs that were $6151 costlier than predicted. Increased costs were positively associated with the number of complications per patient (P < .001), but not hospital volume (P = .85).

Conclusions: Among Medicare beneficiaries undergoing lobectomy for stage I non-small cell lung carcinoma, the cost of perioperative care varied substantially across hospitals and was strongly associated with complication rate, but not hospital volume.
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http://dx.doi.org/10.1016/j.athoracsur.2019.06.048DOI Listing
December 2019

Persistent Use of Extended Fractionation Palliative Radiotherapy for Medicare Beneficiaries With Metastatic Breast Cancer, 2011 to 2014.

Am J Clin Oncol 2019 06;42(6):493-499

Yale Cancer Center.

Introduction: With no evidence to support extended radiation courses for the palliation of bone metastases, multiple guidelines were issued discouraging its use. We assessed contemporary use and cost of prolonged palliative radiotherapy in Medicare beneficiaries with bone metastases from breast cancer.

Methods: We conducted a retrospective, longitudinal study of palliative radiotherapy use among fee-for-service Medicare beneficiaries with bone metastasis from breast cancer who underwent palliative radiotherapy during 2011 to 2014. Patients were categorized according to the number of days (fractions) on which they received palliative radiotherapy: 1, 2 to 10, 11 to 19, or 20 to 30. We examined the association of clinical, demographic, and provider characteristics with the use of extended (≥11 fractions) or very extended (≥20 fractions) fractionation with logistic regression models. We also compared the cost of different fractionation schemes from the payer perspective.

Results: Of the 7547 patients in the sample (mean age, 71 y), 3084 (40.8%) received extended fractionation. The proportion of patients receiving 11 to 19 (34.7% in 2011 and 28.1% in 2014, trend P<0.001) and 20 to 30 treatments (10.3% in 2011 to 9.0% in 2014, trend P=0.07) decreased modestly over time. Patients with comorbidities were less likely to undergo extended fractionation (34.4% for ≥3 comorbidities vs. 44.9% for 0 comorbidities; adjusted odds ratio 0.67 [95% confidence interval, 0.58-0.76]). Patients treated at free-standing practices were more likely to undergo extended fractionation (47.9%) compared with those treated at hospital-based practices (37.3%, P<0.001; adjusted odds ratio, 1.49 [95% confidence interval, 1.35-1.65]). The mean cost of treatment varied from $633 (SD $240) for single-fraction treatment, to $3566 (SD $1349) for 11 to 19 fractions, to $6597 (SD $2893) for 20 to 30 fractions.

Conclusion: The use of prolonged courses of palliative radiotherapy among Medicare beneficiaries with breast cancer remained high in 2011 to 2014. The association between free-standing facility status and use of extended fractionation suggests that provider financial incentives may impact choice of treatment.
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http://dx.doi.org/10.1097/COC.0000000000000548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538429PMC
June 2019

Association Between Degrees of Separation in Physician Networks and Surgeons' Use of Perioperative Breast Magnetic Resonance Imaging.

Med Care 2019 06;57(6):460-467

Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale Cancer Center and Yale School of Medicine.

Background: Perioperative magnetic resonance imaging (MRI) is frequently used in breast cancer despite unproven benefits. It is unclear whether surgeons' use of breast MRI is associated with the practices of other surgeons to whom they are connected through shared patients.

Methods: We conducted a retrospective study using Medicare data to identify physicians providing breast cancer care during 2007-2009 and grouped them into patient-sharing networks. Physician pairs were classified according to their "degree of separation" based on patient-sharing (eg, physician pairs that care for the same patients were separated by 1 degree; pairs that both share patients with another physician but not with each other were separated by 2 degrees). We assessed the association between the MRI use of a surgeon and the practice patterns of surgical colleagues by comparing MRI use in the observed networks with networks with randomly shuffled rates of MRI utilization.

Results: Of the 15,273 patients who underwent surgery during the study period, 28.8% received perioperative MRI. These patients received care from 1806 surgeons in 60 patient-sharing networks; 55.1% of surgeons used MRI. A surgeon was 24.5% more likely to use MRI if they were directly connected to a surgeon who used MRI. This effect decreased to 16.3% for pairs of surgeons separated by 2 degrees, and 0.8% at the third degree of separation.

Conclusions: Surgeons' use of perioperative breast MRI is associated with the practice of surgeons connected to them through patient-sharing; the strength of this association attenuates as the degree of separation increases.
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http://dx.doi.org/10.1097/MLR.0000000000001123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522278PMC
June 2019

Association of State Dense Breast Notification Laws With Supplemental Testing and Cancer Detection After Screening Mammography.

Am J Public Health 2019 05 21;109(5):762-767. Epub 2019 Mar 21.

Susan H. Busch is with the Department of Health Policy and Management, Yale School of Public Health, New Haven, CT. Jessica R. Hoag, Jenerius A. Aminawung, Pamela R. Soulos, and Cary P. Gross are with Department of Internal Medicine, Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven. Xiao Xu is with the Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine. Ilana B. Richman is with the Department of Internal Medicine, Yale School of Medicine. Kelly A. Kyanko is with the Department of Population Health, New York University School of Medicine, New York, NY.

Objectives: To evaluate the association of state dense breast notification (DBN) laws with use of supplemental tests and cancer diagnosis after screening mammography.

Methods: We examined screening mammograms (n = 1 441 544) performed in 2014 and 2015 among privately insured women aged 40 to 59 years living in 9 US states that enacted DBN laws in 2014 to 2015 and 25 US states with no DBN law in effect. DBN status at screening mammography was categorized as no DBN, generic DBN, and DBN that mandates notification of possible benefits of supplemental screening (DBN+SS). We used logistic regression to examine the change in rate of supplemental ultrasound, magnetic resonance imaging, breast biopsy, and breast cancer detection.

Results: DBN+SS laws were associated with 10.5 more ultrasounds per 1000 mammograms (95% CI = 3.0, 17.6 per 1000; P = .006) and 0.37 more breast cancers detected per 1000 mammograms (95% CI = 0.05, 0.69 per 1000; P = .02) compared with no DBN law. No significant differences were found for generic DBN laws in either ultrasound or cancer detection.

Conclusions: DBN legislation is associated with increased use of ultrasound and cancer detection after implementation only when notification of the possible benefits of supplemental screening is required.
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http://dx.doi.org/10.2105/AJPH.2019.304967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459654PMC
May 2019

Disparities in broad-based genomic sequencing for patients with advanced non-small cell lung cancer.

J Geriatr Oncol 2019 07 2;10(4):669-672. Epub 2019 Feb 2.

Yale Cancer Center, 333 Cedar Street, New Haven, CT 06510, United States; Cancer Outcomes, Public Policy and Effectiveness Research Center, 367 Cedar Street, New Haven, CT 06510, United States.

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http://dx.doi.org/10.1016/j.jgo.2019.01.016DOI Listing
July 2019

An empiric approach to identifying physician peer groups from claims data: An example from breast cancer care.

Health Serv Res 2019 02 28;54(1):44-51. Epub 2018 Nov 28.

Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Objective: To develop an empiric approach for evaluating the performance of physician peer groups based on patient-sharing in administrative claims data.

Data Sources: Surveillance, Epidemiology and End Results-Medicare linked dataset.

Study Design: Applying social network theory, we constructed physician peer groups for patients with breast cancer. Under different assumptions of key parameter values-minimum patient volume for physician inclusion and minimum number of patients shared between physicians for a connection-we compared agreement in group membership between split samples during 2004-2006 (T1) (reliability) and agreement in group membership between T1 and 2007-2009 (T2) (stability). We also compared the results with those derived from randomly generated groups and to hospital affiliation-based groups.

Principal Findings: The sample included 142 098 patients treated by 43 174 physicians in T1 and 136 680 patients treated by 51 515 physicians in T2. We identified parameter values that resulted in a median peer group reliability of 85.2 percent (Interquartile range (IQR) [0 percent, 96.2 percent]) and median stability of 73.7 percent (IQR [0 percent, 91.0 percent]). In contrast, stability of randomly assigned peer groups was 6.2 percent (IQR [0 percent, 21.0 percent]). Median overlap of empirical groups with hospital groups was 32.2 percent (IQR [12.1 percent, 59.2 percent]).

Conclusions: It is feasible to construct physician peer groups that are reliable, stable, and distinct from both randomly generated and hospital-based groups.
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http://dx.doi.org/10.1111/1475-6773.13095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338298PMC
February 2019

Surgeon peer network characteristics and adoption of new imaging techniques in breast cancer: A study of perioperative MRI.

Cancer Med 2018 12 15;7(12):5901-5909. Epub 2018 Nov 15.

Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale Cancer Center and Yale School of Medicine, New Haven, Connecticut.

Background: Perioperative MRI has disseminated into breast cancer practice despite equivocal evidence. We used a novel social network approach to assess the relationship between the characteristics of surgeons' patient-sharing networks and subsequent use of MRI.

Methods: We identified a cohort of female patients with stage 0-III breast cancer from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We used claims data from these patients and non-cancer patients from the 5% Medicare sample to identify peer groups of physicians who shared patients during 2004-2006 (T1). We used a multivariable hierarchical model to identify peer group characteristics associated with uptake of MRI in T2 (2007-2009) by surgeons who had not used MRI in T1.

Results: Our T1 sample included 15 149 patients with breast cancer, treated by 2439 surgeons in 390 physician groups. During T1, 9.1% of patients received an MRI; the use of MRI varied from 0% to 100% (IQR 0%, 8.5%) across peer groups. After adjusting for clinical characteristics, patients treated by surgeons in groups with a higher proportion of primary care physicians (PCPs) in T1 were less likely to receive MRI in T2 (OR = 0.81 for 10% increase in PCPs, 95% CI = 0.71, 0.93). Surgeon transitivity (ie, clustering of surgeons) was significantly associated with MRI receipt (P = 0.013); patients whose surgeons were in groups with higher transitivity in T1 were more likely to receive MRI in T2 (OR = 1.29 for 10% increase in clustering, 95% CI = 1.06, 1.58).

Conclusion: The characteristics of a surgeon's peer network are associated with their patients' subsequent receipt of perioperative MRI.
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http://dx.doi.org/10.1002/cam4.1821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308117PMC
December 2018

Association of Broad-Based Genomic Sequencing With Survival Among Patients With Advanced Non-Small Cell Lung Cancer in the Community Oncology Setting.

JAMA 2018 08;320(5):469-477

Yale School of Medicine, New Haven, Connecticut.

Importance: Broad-based genomic sequencing is being used more frequently for patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the association between broad-based genomic sequencing and treatment selection or survival among patients with advanced NSCLC in a community oncology setting.

Objective: To compare clinical outcomes between patients with advanced NSCLC who received broad-based genomic sequencing vs a control group of patients who received routine testing for EGFR mutations and/or ALK rearrangements alone.

Design, Setting, And Participants: Retrospective cohort study of patients with chart-confirmed advanced NSCLC between January 1, 2011, and July 31, 2016, and who received care at 1 of 191 oncology practices across the United States using the Flatiron Health Database. Patients were diagnosed with stage IIIB/IV or unresectable nonsquamous NSCLC who received at least 1 line of antineoplastic treatment.

Exposures: Receipt of either broad-based genomic sequencing or routine testing (EGFR and/or ALK only). Broad-based genomic sequencing included any multigene panel sequencing assay examining more than 30 genes prior to third-line treatment.

Main Outcomes And Measures: Primary outcomes were 12-month mortality and overall survival from the start of first-line treatment. Secondary outcomes included frequency of genetic alterations and treatments received.

Results: Among 5688 individuals with advanced NSCLC (median age, 67 years [interquartile range, 41-85], 63.6% white, 80% with a history of smoking); 875 (15.4%) received broad-based genomic sequencing and 4813 (84.6%) received routine testing. Among patients who received broad-based genomic sequencing, 4.5% received targeted treatment based on testing results, 9.8% received routine EGFR/ALK targeted treatment, and 85.1% received no targeted treatment. Unadjusted mortality rates at 12 months were 49.2% for patients undergoing broad-based genomic sequencing and 35.9% for patients undergoing routine testing. Using an instrumental variable analysis, there was no significant association between broad-based genomic sequencing and 12-month mortality (predicted probability of death at 12 months, 41.1% for broad-based genomic sequencing vs 44.4% for routine testing; difference -3.6% [95% CI, -18.4% to 11.1%]; P = .63). The results were consistent in the propensity score-matched survival analysis (42.0% vs 45.1%; hazard ratio, 0.92 [95% CI, 0.73 to 1.11]; P = .40) vs unmatched cohort (hazard ratio, 0.69 [95% CI, 0.62 to 0.77]; log-rank P < .001).

Conclusions And Relevance: Among patients with advanced non-small cell lung cancer receiving care in the community oncology setting, broad-based genomic sequencing directly informed treatment in a minority of patients and was not independently associated with better survival.
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http://dx.doi.org/10.1001/jama.2018.9824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142984PMC
August 2018

Physician peer group characteristics and timeliness of breast cancer surgery.

Breast Cancer Res Treat 2018 Aug 24;170(3):657-665. Epub 2018 Apr 24.

Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale Cancer Center and Yale School of Medicine, New Haven, CT, USA.

Purpose: Little is known about how the structure of interdisciplinary groups of physicians affects the timeliness of breast cancer surgery their patients receive. We used social network methods to examine variation in surgical delay across physician peer groups and the association of this delay with group characteristics.

Methods: We used linked Surveillance, Epidemiology, and End Results-Medicare data to construct physician peer groups based on shared breast cancer patients. We used hierarchical generalized linear models to examine the association of three group characteristics, patient racial composition, provider density (the ratio of potential vs. actual connections between physicians), and provider transitivity (clustering of providers within groups), with delayed surgery.

Results: The study sample included 8338 women with breast cancer in 157 physician peer groups. Surgical delay varied widely across physician peer groups (interquartile range 28.2-50.0%). For every 10% increase in the percentage of black patients in a peer group, there was a 41% increase in the odds of delayed surgery for women in that peer group regardless of a patient's own race [odds ratio (OR) 1.41, 95% confidence interval (CI) 1.15-1.73]. Women in physician peer groups with the highest provider density were less likely to receive delayed surgery than those in physician peer groups with the lowest provider density (OR 0.65, 95% CI 0.44-0.98). We did not find an association between provider transitivity and delayed surgery.

Conclusions: The likelihood of surgical delay varied substantially across physician peer groups and was associated with provider density and patient racial composition.
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http://dx.doi.org/10.1007/s10549-018-4789-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048589PMC
August 2018

Quality Of Breast Cancer Care In The US Territories: Insights From Medicare.

Health Aff (Millwood) 2018 03;37(3):421-428

Cary P. Gross is a professor of medicine in the Department of Internal Medicine, director of COPPER Center, and director of the National Clinician Scholars Program, all at the Yale School of Medicine.

The quality of breast cancer care among Medicare beneficiaries in the US territories-where federal spending for health care is lower than in the continental US-is unknown. We compared female Medicare beneficiaries who were residents of the US territories and had surgical treatment for breast cancer in 2008-14 to those in the continental US in terms of receipt of recommended breast cancer care (diagnostic needle biopsy and adjuvant radiation therapy [RT] following breast-conserving surgery) and the timeliness (time from needle biopsy to surgery and from surgery to adjuvant RT) of that care. Residents of the US territories were less likely to receive recommended care (24 percent lower odds of receiving diagnostic needle biopsy and 34 percent lower odds of receiving adjuvant RT) and to receive timely care (45 percent lower odds of receiving surgery and 82 percent lower odds of receiving adjuvant RT, both within three months). Further research is needed to identify barriers to the provision of adequate and timely breast cancer care in this unique population.
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http://dx.doi.org/10.1377/hlthaff.2017.1045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081152PMC
March 2018

Regional Medicare Expenditures and Survival Among Older Women With Localized Breast Cancer.

Med Care 2017 12;55(12):1030-1038

*Yale School of Medicine†Section of General Internal Medicine, Department of Internal Medicine, Yale School of Medicine‡Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale University§Division of Cardiology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT∥Health Research and Educational Trust, Chicago, IL¶Section of Medical Oncology, Department of Internal Medicine, Yale School of Medicine#Department of Chronic Disease Epidemiology, Yale School of Public Health**Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT.

Background: Despite evidence on large variation in breast cancer expenditures across geographic regions, there is little understanding about the association between expenditures and patient outcomes.

Objectives: To examine whether Medicare beneficiaries with nonmetastatic breast cancer living in regions with higher cancer-related expenditures had better survival.

Research Design: A retrospective cohort study of women with localized breast cancer from the Surveillance, Epidemiology, and End Results-Medicare linked database. Hospital referral regions (HRR) were categorized into quintiles based on risk-standardized per patient Medicare expenditures on initial phase of breast cancer care. Hierarchical generalized linear models were estimated to examine the association between patients' HRR quintile and survival.

Subjects: In total, 12,610 Medicare beneficiaries diagnosed with stage II-III breast cancer during 2005-2008 who underwent surgery.

Measures: Outcome measures for our analysis were 3- and 5-year overall survival.

Results: Risk-standardized per patient Medicare expenditures on initial phase of breast cancer care ranged from $13,338 to $26,831 across the HRRs. Unadjusted 3- and 5-year survival varied from 66.7% to 92.2% and 50.0% to 84.0%, respectively, across the HRRs, but there was no significant association between HRR quintile and survival in bivariate analysis (P=0.08 and 0.28, respectively). After adjustment for sociodemographic and clinical characteristics, quintiles of regional cancer expenditures remained unassociated with patients' 3-year (P=0.35) and 5-year survival (P=0.20). Further analysis adjusting for treatment factors (surgery type and receipt of radiation and systemic therapy) and stratifying by cancer stage showed similar results.

Conclusions: For Medicare beneficiaries with nonmetastatic breast cancer, residence in regions with higher breast cancer-related expenditures was not associated with better survival. More attention to value in breast cancer care is warranted.
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http://dx.doi.org/10.1097/MLR.0000000000000822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863278PMC
December 2017

Radiation dose and cardiac risk in breast cancer treatment: An analysis of modern radiation therapy including community settings.

Pract Radiat Oncol 2018 May - Jun;8(3):e79-e86. Epub 2017 Jul 20.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut; Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine, New Haven, Connecticut. Electronic address:

Purpose: Adjuvant radiation therapy (RT) for breast cancer improves outcomes, but prior studies have documented substantive cardiac dose and cardiac risk. We assessed the mean heart dose (MHD) of RT and estimated the risk of RT-associated cardiac toxicity in women undergoing adjuvant RT for breast cancer in contemporary (predominantly) community practice.

Methods And Materials: We identified women with left-sided breast cancer receiving adjuvant RT between 2012 and 2014 from 94 centers across 16 states. We used bivariate analyses and multivariable linear regression to assess associations between RT techniques and MHD. Excess RT-related cardiac risk by age 80 was estimated for women diagnosed at age 60 using the previously reported relationship between MHD and cardiac risk.

Results: Among 1161 women, 77.3% were treated in community practice and with breast conservation (77.8%). The most common techniques were free-breathing (92.2%), supine (94.8%), and fixed gantry intensity modulated RT (FG-IMRT; 46.9%). The median MHD was 2.76 Gy (interquartile range, 1.47-5.03). In multivariable analyses, the predicted median MHD with deep inspiration breath hold was 2.41 Gy compared with 3.86 Gy with free-breathing (P < .001). Three-dimensional conformal RT (3D-CRT) was associated with a lower predicted median MHD (2.78 Gy) than FG-IMRT (4.02 Gy) or rotational IMRT, 6.60 Gy, P < .001). For 60-year-old women with the median MHD of the study population (2.76 Gy) and no cardiovascular risk factors, the 20-year predicted excess risk of death from ischemic heart disease attributable to radiation was 3.5 excess events/1000 patients, in contrast to estimates of 8 events/1000 from prior analyses. The predicted risk of cardiac events varied based on radiation technique, with 4 excess events/1000 with 3D-CRT, 5 excess events/1000 with FG-IMRT, and 8 excess events/1000 with rotational IMRT.

Conclusions: MHD varies substantially across patients and is influenced by technique in predominantly community settings. Overall risk of cardiac toxicity is modest.
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http://dx.doi.org/10.1016/j.prro.2017.07.005DOI Listing
September 2018

Increased Number of Beam Angles Is Associated With Higher Cardiac Dose in Adjuvant Fixed Gantry Intensity Modulated Radiation Therapy of Left-Sided Breast Cancer.

Int J Radiat Oncol Biol Phys 2017 12 27;99(5):1137-1145. Epub 2017 Jun 27.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut; Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine, New Haven, Connecticut.

Purpose: To analyze the relationship between angle number and mean heart dose (MHD) in adjuvant fixed gantry intensity modulated radiation therapy (FG-IMRT) treatment of left-sided breast cancer as is currently practiced in the community.

Methods And Materials: We performed a retrospective, multi-institutional review of women with left-sided breast cancer receiving adjuvant FG-IMRT between 2012 and 2014, encompassing 85 centers in 15 states. Bivariate and multivariate regression analyses were done to identify factors associated with MHD. Long-term cardiac risk was estimated according to a previously published model.

Results: Of the 538 women included, 284 had >2 gantry angle treatment plans (multi-angle), and 254 had 2 gantry angle (standard) plans. Median MHD was higher in patients with multi-angle plans compared with standard (median 475 vs 203 cGy). Number of gantry angles was significantly associated with MHD, with multi-angle plans independently increasing MHD by 229 cGy. Absolute risk of acute coronary events 20 years after treatment was estimated as 7 excess events per 1000 women for standard plans, compared with 12 excess events for multi-angle plans.

Conclusions: Fixed gantry IMRT breast treatment plans with >2 gantry angles were associated with increased MHD, which translated to an increased cardiac risk. Clinicians should account for this potential drawback in treatment technique when assessing overall plan quality.
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http://dx.doi.org/10.1016/j.ijrobp.2017.06.2451DOI Listing
December 2017

The Impact of Social Contagion on Physician Adoption of Advanced Imaging Tests in Breast Cancer.

J Natl Cancer Inst 2017 08;109(8)

Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale Cancer Center and Yale School of Medicine, New Haven, CT, USA.

Background: Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans are widely used in breast cancer practice despite unproven benefits. We examined the extent to which social contagion is associated with adoption of these imaging modalities.

Methods: We used Surveillance, Epidemiology, and End Results-Medicare to construct peer groups of physicians who shared patients during a baseline period when these imaging modalities were starting to disseminate into practice (2004-2006) and determined the potential impact of these peer groups during a follow-up period (2007-2009). For non-early-adopting surgeons (whose patients did not receive MRI/PET during baseline), we used hierarchical logistic regression models to examine the effect of their peer group's baseline use on their use of MRI/PET during the follow-up period, adjusting for patient characteristics and hospital MRI/PET use.

Results: For MRI, there were 6424 women diagnosed in the follow-up period assigned to 986 non-early-adopting surgeons. During baseline, 9.3% of women received an MRI, varying across peer groups from 0% to 81%. Women assigned to surgeons whose peers had the highest rate of baseline MRI use were more likely to receive MRI compared with women whose surgeons' peers did not use MRI (24.9% vs 10.1%, adjusted odds ratio [OR] = 2.47, 95% confidence interval [CI] = 1.39 to 4.39). Physician peers were associated with uptake of PET imaging (OR for highest vs lowest baseline peer group PET use = 2.04, 95% CI = 1.24 to 3.36).

Conclusions: The phenomenon of social contagion may offer opportunities to better understand how new approaches to cancer care disseminate into clinical practice.
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http://dx.doi.org/10.1093/jnci/djw330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059114PMC
August 2017

Bone Density Screening in Postmenopausal Women With Early-Stage Breast Cancer Treated With Aromatase Inhibitors.

J Oncol Pract 2017 05 7;13(5):e505-e515. Epub 2017 Mar 7.

Yale University School of Medicine; and Yale Cancer Outcomes Public Policy and Effectiveness Research (COPPER) Center, New Haven, CT.

Purpose: In postmenopausal women with breast cancer treated with aromatase inhibitors (AIs), most expert panels advise baseline bone mineral density testing with a dual-energy x-ray absorptiometry (DXA) scan repeated every 1 to 2 years. How often this recommendation is followed is unclear.

Methods: We performed a retrospective analysis of women with stage I to III breast cancer who started AI therapy from January 1, 2008, to December 31, 2010, with follow-up through December 31, 2012, by using the SEER-Medicare database. Selection criteria included AI use for ≥ 6 months and no recent osteoporosis diagnosis or bisphosphonate use. We used multivariable logistic regression to investigate associations between patient characteristics and receipt of a baseline DXA scan. In patients who continued AI treatment, we assessed rates of follow-up scans.

Results: In the sample of 2,409 patients (median age, 74 years), 51.0% received a baseline DXA scan. Demographic characteristics associated with the absence of a baseline DXA scan were older age (85 to 94 years v 67 to 69 years; odds ratio [OR], 0.62; 95% CI, 0.42 to 0.92) and black v white race (OR, 0.68; 95% CI, 0.47 to 0.97). Among patients who underwent a baseline DXA scan and continued AI for 3 years, 28.0% had a repeat DXA scan within 2 years and 65.9% within 3 years. In aggregate, of the 1,164 patients who continued with AI treatment for 3 years, only 34.5% had both a baseline and at least one DXA scan during the 3-year follow-up period.

Conclusion: The majority of older Medicare beneficiaries with breast cancer treated with AIs do not undergo appropriate bone mineral density evaluation.
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http://dx.doi.org/10.1200/JOP.2016.018341DOI Listing
May 2017

Longer Periods Of Hospice Service Associated With Lower End-Of-Life Spending In Regions With High Expenditures.

Health Aff (Millwood) 2017 02;36(2):328-336

Cary P. Gross is a professor of medicine and epidemiology in the Department of Internal Medicine, Yale University School of Medicine.

Hospice use is expected to decrease end-of-life expenditures, yet evidence for its financial impact remains inconclusive. One potential explanation is that the use of hospice may produce differential cost-savings effects by region because of geographic variation in end-of-life spending patterns. We examined 103,745 elderly Medicare fee-for-service beneficiaries in the Surveillance, Epidemiology, and End Results Program Medicare database who died from cancer in 2004-11. We created quintiles by the adjusted mean end-of-life expenditures per hospital referral region (HRR), and we examined HRR-level variation in the association between length of hospice service and expenditures across quintiles. Longer periods of hospice service were associated with decreased end-of-life expenditures for patients residing in regions with high average expenditures but not for those in regions with low average expenditures. Hospice use accounted for 8 percent of the expenditure variation between the highest and the lowest spending quintiles, which demonstrates the powers and limitations of hospice use for saving on costs.
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http://dx.doi.org/10.1377/hlthaff.2016.0683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972542PMC
February 2017

Treatment Burden of Medicare Beneficiaries With Stage I Non-Small-Cell Lung Cancer.

J Oncol Pract 2017 02 20;13(2):e98-e107. Epub 2016 Dec 20.

Yale University School of Medicine, New Haven, CT; and Mayo Clinic, Rochester, MN.

Purpose: To quantify the burden and complexity associated with treatment of Medicare beneficiaries with stage I non-small-cell lung cancer (NSCLC).

Methods: Using the SEER-Medicare database, we conducted a retrospective cohort study of Medicare beneficiaries who were diagnosed with stage I NSCLC from 2007 to 2011 and who were treated with surgery, stereotactic body radiation therapy, or external beam radiation therapy. Main outcome measures were the number of days a patient was in contact with the health care system (encounter days), the number of physicians involved in a patient's care, and the number of medications prescribed. Logistic regression modeled the association between patient characteristics, treatment type, and high treatment burden (defined as ≥ 66 encounter days).

Results: On average, 7,955 patients spent 1 in 3 days interacting with the health care system during the initial 60 days of treatment. Patients experienced a median of 44 encounter days with high variability (interquartile range [IQR], 29 to 66) in the 12 months after treatment initiation. The median number of physicians involved was 20 (IQR, 14 to 28), and the median number of medications prescribed was 12 (IQR, 8 to 17). Patients who were treated with surgery had high treatment burden (predicted probability, 21.6%; 95% CI, 20.2 to 23.1) compared with patients who were treated with stereotactic body radiation therapy (predicted probability, 16.1%; 95% CI, 12.9 to 19.3), whereas patients who were treated with external beam radiation therapy had the highest burden (predicted probability, 46.8%; 95% CI, 43.3 to 50.2).

Conclusion: The treatment burden imposed on patients with early-stage NSCLC was substantial in terms of the number of encounters, physicians involved, and medications prescribed. Because treatment burden varied markedly across patients and treatment types, future work should identify opportunities to understand and ameliorate this burden.
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http://dx.doi.org/10.1200/JOP.2016.014100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659117PMC
February 2017

Patient-reported quality of life after stereotactic body radiation therapy versus moderate hypofractionation for clinically localized prostate cancer.

Radiother Oncol 2016 11 24;121(2):294-298. Epub 2016 Nov 24.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, United States; Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, United States. Electronic address:

Background And Purpose: Evaluate changes in bowel, urinary and sexual patient-reported quality of life following treatment with moderately hypofractionated radiotherapy (<5Gray/fraction) or stereotactic body radiation therapy (SBRT;5-10Gray/fraction) for prostate cancer.

Materials And Methods: In a pooled multi-institutional analysis of men treated with moderate hypofractionation or SBRT, we compared minimally detectable difference in bowel, urinary and sexual quality of life at 1 and 2years using chi-squared analysis and logistic regression.

Results: 378 men received moderate hypofractionation compared to 534 men who received SBRT. After 1year, patients receiving moderate hypofractionation were more likely to experience worsening in bowel symptoms (39.5%) compared to SBRT (32.5%; p=.06), with a larger difference at 2years (37.4% versus 25.3%, p=.002). Similarly, patients receiving moderate fractionation had worsening urinary symptom score compared to patients who underwent SBRT at 1 and 2years (34.7% versus 23.1%, p<.001; and 32.8% versus 14.0%, p<.001). There was no difference in sexual symptom score at 1 or 2years. After adjusting for age and cancer characteristics, patients receiving SBRT were less likely to experience worsening urinary symptom scores at 2years (odds ratio: 0.24[95%CI: 0.07-0.79]).

Conclusions: Patients who received SBRT or moderate hypofractionation have similar patient-reported change in bowel and sexual symptoms, although there was worse change in urinary symptoms for patients receiving moderate hypofractionation.
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http://dx.doi.org/10.1016/j.radonc.2016.10.013DOI Listing
November 2016

The Effect of Biologically Effective Dose and Radiation Treatment Schedule on Overall Survival in Stage I Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy.

Int J Radiat Oncol Biol Phys 2016 12 31;96(5):1011-1020. Epub 2016 Aug 31.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut. Electronic address:

Purpose: To determine the effect of biologically effective dose (BED) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT).

Methods And Materials: Using data from 65 treatment centers in the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC patients undergoing SBRT alone from 2006 to 2014. Biologically relevant covariates, including dose per fraction, number of fractions, and time between fractions, were used to quantify BED and radiation treatment schedule. The linear-quadratic equation was used to calculate BED and to generate a dichotomous dose variable of <105 Gy versus ≥105 Gy BED. The primary outcome was OS. We used the Kaplan-Meier method, the log-rank test, and Cox proportional hazards regression with propensity score matching to determine whether prescription BED was associated with OS.

Results: We identified 747 patients who met inclusion criteria. The median BED was 132 Gy, and 59 (7.7%) had consecutive-day fractions. Median follow-up was 41 months, and 452 patients (60.5%) had died by the conclusion of the study. The 581 patients receiving ≥105 Gy BED had a median survival of 28 months, whereas the 166 patients receiving <105 Gy BED had a median survival of 22 months (log-rank, P=.01). Radiation treatment schedule was not a significant predictor of OS on univariable analysis. After adjusting for T stage, sex, tumor histology, and Eastern Cooperative Oncology Group performance status, BED ≥105 Gy versus <105 Gy remained significantly associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables within high- and low-dose cohorts confirmed a survival benefit with higher prescription dose.

Conclusions: We found that dose escalation to 105 Gy BED and beyond may improve survival in NSCLC patients treated with SBRT.
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http://dx.doi.org/10.1016/j.ijrobp.2016.08.033DOI Listing
December 2016

Myelodysplastic Syndromes and Acute Myeloid Leukemia After Radiotherapy for Prostate Cancer: A Population-Based Study.

Prostate 2017 04 21;77(5):437-445. Epub 2016 Nov 21.

Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.

Background: To understand the impact of radiotherapy on the development of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) among elderly prostate cancer patients.

Methods: We performed a retrospective cohort study of elderly prostate cancer patients diagnosed during 1999-2011 by using the National Cancer Institute's Surveillance, Epidemiology and End Results-Medicare linked database. Competing risk analyses adjusting for patient characteristics were conducted to assess the impact of radiotherapy on the development of subsequent MDS/AML, compared with surgery.

Results: Of 32,112 prostate cancer patients, 14,672 underwent radiotherapy, and 17,440 received surgery only. The median follow-up was 4.68 years. A total of 157 (0.47%) prostate cancer patients developed subsequent MDS or AML, and the median time to develop MDS/AML was 3.30 (range: 0.16-9.48) years. Compared with prostate cancer patients who received surgery only, patients who underwent radiotherapy had a significantly increased risk of developing MDS/AML (hazard ratio [HR] =1.51, 95% confidence interval [CI]: 1.07-2.13). When radiotherapy was further categorized by modalities (brachytherapy, conventional conformal radiotherapy, and intensity-modulated radiotherapy [IMRT]), increased risk of second MDS/AML was only observed in the IMRT group (HR = 1.66, 95% CI: 1.09-2.54).

Conclusions: Our findings suggest that radiotherapy for prostate cancer increases the risk of MDS/AML, and the impact may differ by modality. Additional studies with longer follow-up are needed to further clarify the role of radiotherapy in the development of subsequent myeloid malignancies. A better understanding may help patients, physicians, and other stakeholders make more informed treatment decisions. Prostate 77:437-445, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/pros.23281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785924PMC
April 2017

Association between access to accelerated partial breast irradiation and use of adjuvant radiotherapy.

Cancer 2017 02 22;123(3):502-511. Epub 2016 Sep 22.

Yale School of Medicine, Yale University, New Haven, Connecticut.

Background: The current study was performed to determine whether access to facilities performing accelerated partial breast irradiation (APBI) is associated with differences in the use of adjuvant radiotherapy (RT).

Methods: Using the National Cancer Data Base, the authors performed a retrospective study of women aged ≥50 years who were diagnosed with early-stage breast cancer between 2004 and 2013 and treated with breast-conserving surgery (BCS). Facilities performing APBI in ≥10% of their eligible patients within a given year were defined as APBI facilities whereas those not performing APBI were defined as non-APBI facilities. All other facilities were excluded. The authors identified independent factors associated with RT use using multivariable logistic regression with clustering in the overall sample as well as in subsets of patients with standard-risk invasive cancer, low-risk invasive cancer, and ductal carcinoma in situ.

Results: Among 222,544 patients, 76.6% underwent BCS plus RT and 23.4% underwent BCS alone. The likelihood of RT receipt in the overall sample did not appear to differ significantly between APBI and non-APBI facilities (adjusted odds ratio [AOR], 1.02; P = .61). Subgroup multivariable analysis demonstrated that among patients with standard-risk invasive cancer, there was no association between evaluation at an APBI facility and receipt of RT (AOR, 0.98; P = .69). However, patients with low-risk invasive cancer were found to be significantly more likely to receive RT (54.4% vs 59.5%; AOR, 1.22 [P<.001]), whereas patients with ductal carcinoma in situ were less likely to receive RT (56.9% vs 55.3%; AOR, 0.89 [P = .04]) at APBI facilities.

Conclusions: Patients who were eligible for observation were more likely to receive RT in APBI facilities but no difference was observed among patients with standard-risk invasive cancer who would most benefit from RT. Cancer 2017;123:502-511. © 2016 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30356DOI Listing
February 2017

Surveillance Practice Patterns after Curative Intent Therapy for Stage I Non-Small-Cell Lung Cancer in the Medicare Population.

Lung Cancer 2016 09 19;99:200-7. Epub 2016 Jul 19.

Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine, Yale Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, New Haven, CT, United States. Electronic address:

Objectives: Recurrence after treatment for non-small cell lung cancer (NSCLC) is common, and routine imaging surveillance is recommended by evidence-based guidelines. Little is known about surveillance patterns after curative intent therapy for early stage NSCLC. We sought to understand recent practice patterns for surveillance of stage I NSCLC in the first two years after curative intent therapy in the Medicare population.

Materials And Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database we selected patients diagnosed with stage I NSCLC between 1998 and 2008. We studied adherence to surveillance guidelines based on specialty society recommendations for chest radiography and computed tomography (CT) scanning. We also tracked the use of Positron Emission Tomography (PET) scans, which are not recommended for surveillance. We calculated the percent of patients who received guideline-adherent surveillance imaging and used logistic regression to determine associations between patient and provider factors and guideline adherence.

Results: Overall, 61.4% of patients received guideline-adherent surveillance during the initial 2 years after treatment. Use of CT scans in the first year after treatment increased from 47.4% in 1998-78.5% in 2008, and PET use increased from 5.8% to 28.9%. Adherence with surveillance imaging was associated with younger age, higher income, more comorbidities, access to primary care, and receipt of SBRT as the primary treatment.

Conclusions: Adherence to specialty society guidelines for surveillance after treatment for stage I NSCLC was poor in this population of Medicare beneficiaries, with less than two-thirds of patients receiving recommended imaging, and almost 30% receiving non-recommended PET scans.
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http://dx.doi.org/10.1016/j.lungcan.2016.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003420PMC
September 2016

Contrary To Conventional Wisdom, Physicians Abandoned A Breast Cancer Treatment After A Trial Concluded It Was Ineffective.

Health Aff (Millwood) 2016 07;35(7):1309-15

Cary P. Gross is a professor of medicine in the Section of General Internal Medicine at the Yale University School of Medicine.

Conventional wisdom holds that physicians are slow to abandon ineffective medical practices. We evaluated this theory in the case of axillary lymph node dissection, a procedure to remove the lymph nodes near the breast to prevent the spread of breast cancer following breast-conserving surgery. A major trial conducted from 1999 to 2004, with results presented in 2010 and published in 2011, found that patients who met certain criteria could forgo axillary lymph node dissection. Using cancer registry data, we estimated that the proportion of patients undergoing axillary dissection declined by 32.6 percentage points after the trial was published. The decline began immediately after the trial was presented at a medical conference. The rapid decline in the use of axillary dissection belies the common belief that practice patterns are slow to change in response to new evidence, and it highlights the value of trials of established medical practices to patients and the health system.
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http://dx.doi.org/10.1377/hlthaff.2015.1490DOI Listing
July 2016
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