Ann C. Raldow

Assessing the Impact of a Cooperative Group Trial on Breast Cancer Care in the Medicare Population

PURPOSE The Cancer and Leukemia Group B (CALGB) C9343 trial found that adjuvant radiation therapy (RT) provided minimal benefits for older women with breast cancer. Although treatment guidelines were changed to indicate that some women could forego RT, the impact of the C9343 results on clinical practice is unclear. PATIENTS AND METHODS We used the Surveillance, Epidemiology, and End Results (SEER) -Medicare data set to assess the use of adjuvant RT in a sample of women ≥ 70 years old diagnosed with stage I breast cancer from 2001 to 2007 who fulfilled the C9343 inclusion criteria. We used log-binomial regression to estimate the relation between publication of C9343 and use of RT in the full sample and across strata of patient and health system characteristics. RESULTS Of the 12,925 Medicare beneficiaries in our sample (mean age, 77.7 years), 76.5% received RT. Approximately 79% of women received RT before study publication compared with 75% after (adjusted relative risk of receiving RT postpublication v prepublication: 0.97; 95% CI, 0.95 to 0.98). Although use of RT was lower after the trial within all strata of age and life expectancy, the magnitude of this decrease did not differ significantly by strata. For instance, among patients with life expectancy less than 5 years, RT use decreased by 3.7%, from 44.4% prepublication to 40.7% postpublication. Among patients with life expectancy ≥ 10 years, RT use decreased by 3.0%, from 92.0% to 89.0%. CONCLUSION The C9343 trial had minimal impact on the use of RT among older women in the Medicare population, even among the oldest women and those with shorter life expectancies.

Risk Group and Death From Prostate Cancer: Implications for Active Surveillance in Men With Favorable Intermediate-Risk Prostate Cancer

IMPORTANCE Active surveillance (AS), per the National Comprehensive Cancer Network (NCCN) guidelines, is considered for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, given the grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may be appropriate for men presenting with favorable intermediate-risk PC. OBJECTIVE To estimate and compare the risk of PC-specific mortality (PCSM) and all-cause mortality (ACM) following brachytherapy among men with low and favorable intermediate-risk PC. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 5580 consecutively treated men (median age, 68 years) with localized adenocarcinoma of the prostate treated with brachytherapy at the Prostate Cancer Foundation of Chicago between October 16, 1997, and May 28, 2013. INTERVENTION Standard of practice per the NCCN guidelines. MAIN OUTCOMES AND MEASURES Fine and Gray competing risks regression and Cox regression analyses were used to assess whether the risks of PCSM and ACM, respectively, were increased in men with favorable intermediate-risk vs low-risk PC. Analyses were adjusted for age at brachytherapy, year of treatment, and known PC prognostic factors. RESULTS After median follow-up of 7.69 years, 605 men had died (10.84% of total cohort), 34 of PC (5.62% of total deaths). Men with favorable intermediate-risk PC did not have significantly increased risk of PCSM and ACM compared with men with low-risk PC (adjusted hazard ratio [HR], 1.64; 95% CI, 0.76-3.53; P = .21 for PCSM; adjusted HR, 1.11; 95% CI, 0.88-1.39; P = .38 for ACM). Eight-year adjusted point estimates for PCSM were low: 0.48% (95% CI, 0.23%-0.93%) and 0.33% (95% CI, 0.19%-0.56%) for men with favorable intermediate-risk PC and low-risk PC, respectively. The respective estimates for ACM were 10.45% (95% CI, 8.91%-12.12%) and 8.68% (95% CI, 7.80%-9.61%). CONCLUSIONS AND RELEVANCE Men with low-risk PC and favorable intermediate-risk PC have similarly low estimates of PCSM and ACM during the first decade following brachytherapy. While awaiting the results of ProtecT, the randomized trial of AS vs treatment, our results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC.

Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases: an update.

Brain metastases are unfortunately a common occurrence in patients with cancer. Whole-brain radiation therapy (WBRT) is still considered the standard of care in the treatment of brain metastases. Stereotactic radiosurgery (SRS) offers the additional ability to treat tumors with relative sparing of normal brain tissue in a single fraction. While the addition of SRS to WBRT has been shown to improve survival and local tumor control in selected patients, the idea of deferring WBRT in order to avoid its effects on normal tissues and using SRS alone continues to generate significant discussion and interest. Three recent randomized trials from Japan, Europe and the MD Anderson Cancer Center (TX, USA) have attempted to address this issue. In this article, we update a previous review by discussing these trials to compare the outcomes for SRS alone versus SRS plus WBRT for limited metastases. We also discuss recent nonrandomized evidence for the use of SRS alone for oligometastatic disease.

Survival and intracranial control of patients with 5 or more brain metastases treated with gamma knife stereotactic radiosurgery.

Purpose:Limited data are available to help inform decisions about stereotactic radiosurgery for patients with ≥5 brain metastases. We therefore performed a retrospective analysis of patients treated for >5 brain metastases. Materials/Methods:Patients who underwent treatment for ≥5 brain metastases from October 2000 to September 2010 were identified. Overall survival (OS) for each patient was calculated from the date of first treatment of ≥5 metastases. Intracranial recurrence-free survival was defined when posttreatment magnetic resonance imaginag showed evidence for disease progression. Cox proportional hazards regression was performed for OS and intracranial recurrence free survival. Variables included sex, age, Karnofsky Performance Status (KPS), histology, prior whole-brain radiation treatment or Gamma Knife treatment, and number of metastases treated. Results:A total of 103 patients were identified. Median OS was 8.3 months. Median OS was 7.6 months and 8.3 months, for patients with 5 to 9 and ≥10 metastases, respectively. KPS was the only significant variable affecting OS (P <0.01). Forty-six patients had post–Gamma Knife surveillance imaging recorded. There was a trend towards a higher hazard for intracranial failure for patients with 10+ versus 5 to 9 metastases, however, the association did not reach statistical significance (univariate P=0.09, multivariate P=0.21). Conclusions:OS for carefully selected patients with 5 or more brain metastases treated with stereotactic radiosurgery alone is reasonable and compares well with historical controls. KPS is the most important factor predicting OS.

Cost Effectiveness of the Oncotype DX DCIS Score for Guiding Treatment of Patients With Ductal Carcinoma In Situ

Purpose The Oncotype DX DCIS Score short form (DCIS Score) estimates the risk of an ipsilateral breast event (IBE) in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery without adjuvant radiation therapy (RT). We determined the cost effectiveness of strategies using this test. Materials and Methods We developed a Markov model simulating 10-year outcomes for 60-year-old women eligible for the Eastern Cooperative Oncology Group E5194 study (cohort 1: low/intermediate-grade DCIS, ≤ 2.5 cm; cohort 2: high-grade DCIS, ≤ 1 cm) with each of five strategies: (1) no testing, no RT; (2) no testing, RT only for cohort 2; (3) no RT for low-grade DCIS, test for intermediate- and high-grade DCIS, RT for intermediate- or high-risk scores; (4) test all, RT for intermediate- or high-risk scores; and (5) no testing, RT for all. We used utilities and costs extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios and examined the number of women needed to irradiate per IBE prevented. Results No strategy using the DCIS Score was cost effective. The most cost-effective strategy (RT for none or RT for all) was sensitive to small differences between the utilities of receiving or not receiving RT and remaining without recurrence. The numbers needed to irradiate per IBE prevented were 10.5, 9.1, 7.5, and 13.1 for strategies 2 to 5, respectively, relative to strategy 1. Conclusion Strategies using the DCIS Score lowered the proportion of women undergoing RT per IBE prevented. However, no strategy incorporating the DCIS Score was cost effective. The cost effectiveness of RT was exquisitely utility sensitive, highlighting the importance of engaging patient preferences in this decision. Physicians should discuss trade-offs associated with omitting or adding adjuvant RT with each patient to maximize quality-of-life outcomes.

The Relationship Between Clinical Benefit and Receipt of Curative Therapy for Prostate Cancer

Ann C. Raldow, MD1,2, Carolyn J. Presley, MD1,3, James B. Yu, MD1,4, Richa Sharma, MPH1, Laura D. Cramer, PhD1, Pamela R. Soulos, MPH1,3, Jessica B. Long, MPH1,3, Danil V. Makarov, MD, MHS1,5, and Cary P. Gross, MD1,3 1Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Comprehensive Cancer Center and Yale University School of Medicine 2Department of Medicine, Memorial Sloan Kettering Cancer Center 3Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine 4Department of Therapeutic Radiology, Yale University School of Medicine 5Department of Urology, New York University School of Medicine and United States, Department of Veterans Affairs

Establishing Cost-Effective Allocation of Proton Therapy for Breast Irradiation

PURPOSE Cardiac toxicity due to conventional breast radiation therapy (RT) has been extensively reported, and it affects both the life expectancy and quality of life of affected women. Given the favorable oncologic outcomes in most women irradiated for breast cancer, it is increasingly paramount to minimize treatment side effects and improve survivorship for these patients. Proton RT offers promise in limiting heart dose, but the modality is costly and access is limited. Using cost-effectiveness analysis, we provide a decision-making tool to help determine which breast cancer patients may benefit from proton RT referral. METHODS AND MATERIALS A Markov cohort model was constructed to compare the cost-effectiveness of proton versus photon RT for breast cancer management. The model was analyzed for different strata of women based on age (40 years, 50 years, and 60 years) and the presence or lack of cardiac risk factors (CRFs). Model entrants could have 1 of 3 health states: healthy, alive with coronary heart disease (CHD), or dead. Base-case analysis assumed CHD was managed medically. No difference in tumor control was assumed between arms. Probabilistic sensitivity analysis was performed to test model robustness and the influence of including catheterization as a downstream possibility within the health state of CHD. RESULTS Proton RT was not cost-effective in women without CRFs or a mean heart dose (MHD) <5 Gy. Base-case analysis noted cost-effectiveness for proton RT in women with ≥1 CRF at an approximate minimum MHD of 6 Gy with a willingness-to-pay threshold of

Short-course androgen deprivation therapy and the risk of death from high-risk prostate cancer in men undergoing external beam radiation therapy and brachytherapy.

100,000/quality-adjusted life-year. For women with ≥1 CRF, probabilistic sensitivity analysis noted the preference of proton RT for an MHD ≥5 Gy with a similar willingness-to-pay threshold. CONCLUSIONS Despite the cost of treatment, scenarios do exist whereby proton therapy is cost-effective. Referral for proton therapy may be cost-effective for patients with ≥1 CRF in cases for which photon plans are unable to achieve an MHD <5 Gy.

Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) for Locally Advanced Pancreatic Cancer: A Promising Approach

PURPOSE We estimated the risks of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) in men with high-risk prostate cancer (PC) undergoing external beam radiation therapy and brachytherapy with short-course androgen deprivation therapy (ADT) (median 4 months) as compared with men with more favorable-risk PC undergoing standard of care as per the National Comprehensive Cancer Network guidelines. METHODS AND MATERIALS The prospective study cohort comprised 6595 consecutively treated men with T1-4 N0M0 PC whose treatment included brachytherapy between October 16, 1997, and May 28, 2013. Fine and Gray competing risk regression and Cox regression analyses were used to assess the risks of PCSM and ACM in men with high, unfavorable intermediate, and favorable intermediate risk as compared with low-risk PC. RESULTS After median followup of 7.76 years, 820 men died (12.43%): 72 of PC (8.78%). Men with favorable intermediate-risk PC did not have significantly increased PCSM risk as compared with men with low-risk PC (adjusted hazard ratio [AHR], 1.26; 95% confidence interval [CI] 0.56, 2.88; p-Value 0.58), whereas men with high-risk PC (AHR, 3.74; 95% CI 1.12, 12.53; p-Value 0.032) and unfavorable intermediate-risk PC (AHR, 3.10; 95% CI 1.43, 6.72; p-Value 0.004) did. Based on 10-year adjusted point estimates of PCSM and ACM for men with high-risk PC being 6.01% (95% CI 3.79%, 8.94%) and 21.30% (95% CI 17.45%, 25.42%), respectively, PCSM comprised 28% of ACM. CONCLUSIONS In the setting of external beam radiation therapy and brachytherapy, men with high-risk PC have low absolute adjusted estimates of PCSM (~6%) during the first decade after treatment despite receiving only short-course ADT. Whether long-term ADT can lower PCSM and improve survival in these men requires additional study.

Differences in Cancer-Specific Mortality of Right- Versus Left-Sided Colon Adenocarcinoma: A Surveillance, Epidemiology, and End Results Database Analysis

Locally advanced pancreatic cancer (LAPC) is characterized by poor prognosis and low response durability with standard-of-care chemotherapy or chemoradiotherapy treatment. Stereotactic body radiation therapy (SBRT), which has a shorter treatment course than conventionally fractionated radiotherapy and allows for better integration with systemic therapy, may confer a survival benefit but is limited by gastrointestinal toxicity. Stereotactic MRI-guided adaptive radiation therapy (SMART) has recently gained attention for its potential to increase treatment precision and thus minimize this toxicity through continuous real-time soft-tissue imaging during radiotherapy. The case presented here illustrates the promising outcome of a 69-year-old male patient with LAPC treated with SMART with daily adaptive planning and respiratory-gated technique.