Search

Purpose To determine the effect of biologically effective dose (BED 10 ) 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 10 and radiation treatment schedule. The linear-quadratic equation was used to calculate BED 10 and to generate a dichotomous dose variable of 10 . 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 10 was associated with OS. Results We identified 747 patients who met inclusion criteria. The median BED 10 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 10 had a median survival of 28 months, whereas the 166 patients receiving 10 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 10 ≥105 Gy versus 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 10 and beyond may improve survival in NSCLC patients treated with SBRT.

Purpose Intensity modulated radiation therapy (IMRT) is a newer method of radiation therapy (RT) that has been increasingly adopted as an adjuvant treatment after breast-conserving surgery (BCS). IMRT may result in improved cosmesis compared to standard RT, although at greater expense. To investigate the adoption of IMRT, we examined trends and factors associated with IMRT in women under the age of 65 with early stage breast cancer. Methods and Materials We performed a retrospective study of early stage breast cancer patients treated with BCS followed by whole-breast irradiation (WBI) who were ≤65 years old in the National Cancer Data Base from 2004 to 2011. We used logistic regression to identify factors associated with receipt of IMRT (vs standard RT). Results We identified 11,089 women with early breast cancer (9.6%) who were treated with IMRT and 104,448 (90.4%) who were treated with standard RT, after BCS. The proportion of WBI patients receiving IMRT increased yearly from 2004 to 2009, with 5.3% of WBI patients receiving IMRT in 2004 and 11.6% receiving IMRT in 2009. Further use of IMRT declined afterward, with the proportion remaining steady at 11.0% and 10.7% in 2010 and 2011, respectively. Patients treated in nonacademic community centers were more likely to receive IMRT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.30-1.43 for nonacademic vs academic center). Compared to privately insured patients, the uninsured patients (OR, 0.81; 95% CI, 0.70-0.95) and those with Medicaid insurance (OR, 0.87; 95% CI, 0.79-0.95) were less likely to receive IMRT. Conclusions The use of IMRT rose from 2004 to 2009 and then stabilized. Important nonclinical factors associated with IMRT use included facility type and insurance status.

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.

To evaluate the relationship of patient, hospital, and cancer characteristics with the adoption of hypofractionation in a national sample of patients diagnosed with early-stage breast cancer.We performed a retrospective study of breast cancer patients in the National Cancer Data Base from 2004-2011 who were treated with radiation therapy and met eligibility criteria for hypofractionation. We used logistic regression to identify factors associated with receipt of hypofractionation (vs conventional fractionation).We identified 13,271 women (11.7%) and 99,996 women (88.3%) with early-stage breast cancer who were treated with hypofractionation and conventional fractionation, respectively. The use of hypofractionation increased significantly, with 5.4% of patients receiving it in 2004 compared with 22.8% in 2011 (P.001 for trend). Patients living ≥50 miles from the cancer reporting facility had increased odds of receiving hypofractionation (odds ratio 1.57 [95% confidence interval 1.44-1.72], P.001). Adoption of hypofractionation was associated with treatment at an academic center (P.001) and living in an area with high median income (P.001). Hypofractionation was less likely to be used in patients with high-risk disease, such as increased tumor size (P.001) or poorly differentiated histologic grade (P.001).The use of hypofractionation is rising and is associated with increased travel distance and treatment at an academic center. Further adoption of hypofractionation may be tempered by both clinical and nonclinical concerns.

Purpose New radiation therapy modalities have broadened treatment options for older women with breast cancer, but it is unclear how clinical factors, geographic region, and physician preference affect the choice of radiation therapy modality. Methods and Materials We used the Surveillance, Epidemiology, and End Results-Medicare database to identify women diagnosed with stage I-III breast cancer from 1998 to 2007 who underwent breast-conserving surgery. We assessed the temporal trends in, and costs of, the adoption of intensity modulated radiation therapy (IMRT) and brachytherapy. Using hierarchical logistic regression, we evaluated the relationship between the use of these new modalities and patient and regional characteristics. Results Of 35,060 patients, 69.9% received conventional external beam radiation therapy (EBRT). Although overall radiation therapy use remained constant, the use of IMRT increased from 0.0% to 12.6% from 1998 to 2007, and brachytherapy increased from 0.7% to 9.0%. The statistical variation in brachytherapy use attributable to the radiation oncologist and geographic region was 41.4% and 9.5%, respectively (for IMRT: 23.8% and 22.1%, respectively). Women undergoing treatment at a free-standing radiation facility were significantly more likely to receive IMRT than were women treated at a hospital-based facility (odds ratio for IMRT vs EBRT: 3.89 [95% confidence interval, 2.78-5.45]). No such association was seen for brachytherapy. The median radiation therapy cost per treated patient increased from $5389 in 2001 to $8539 in 2007. Conclusions IMRT and brachytherapy use increased substantially from 1998 to 2007; overall, radiation therapy costs increased by more than 50%. Radiation oncologists played an important role in treatment choice for both types of radiation therapy, whereas geographic region played a bigger role in the use of IMRT than brachytherapy.

Purpose To evaluate the influence of immortal time bias on observational cohort studies of postoperative radiotherapy (PORT) and the effectiveness of sequential landmark analysis to account for this bias. Methods and Materials First, we reviewed previous studies of the Surveillance, Epidemiology, and End Results (SEER) database to determine how frequently this bias was considered. Second, we used SEER to select three tumor types (glioblastoma multiforme, Stage IA–IVM0 gastric adenocarcinoma, and Stage II–III rectal carcinoma) for which prospective trials demonstrated an improvement in survival associated with PORT. For each tumor type, we calculated conditional survivals and adjusted hazard ratios of PORT vs. postoperative observation cohorts while restricting the sample at sequential monthly landmarks. Results Sixty-two percent of previous SEER publications evaluating PORT failed to use a landmark analysis. As expected, delivery of PORT for all three tumor types was associated with improved survival, with the largest associated benefit favoring PORT when all patients were included regardless of survival. Preselecting a cohort with a longer minimum survival sequentially diminished the apparent benefit of PORT. Conclusions Although the majority of previous SEER articles do not correct for it, immortal time bias leads to altered estimates of PORT effectiveness, which are very sensitive to landmark selection. We suggest the routine use of sequential landmark analysis to account for this bias.

Purpose Intensity-modulated radiation therapy (IMRT) requires a high degree of expertise compared with standard radiation therapy (RT). We performed a retrospective cohort study of Medicare patients treated with IMRT compared with standard RT to assess outcomes in national practice. Methods and Materials Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database, we identified patients treated with radiation for cancer of the head and neck from 2002 to 2005. We used multivariate Cox models to determine whether the receipt of IMRT was associated with differences in survival. Results We identified 1613 patients, 33.7% of whom received IMRT. IMRT was not associated with differences in survival: the 3-year overall survival was 50.5% for IMRT vs. 49.6% for standard RT ( p = 0.47). The 3-year cancer-specific survival was 60.0% for IMRT vs. 58.8% ( p = 0.45). Conclusion Despite its complexity and resource intensive nature, IMRT use seems to be as safe as standard RT in national community practice, because the use of IMRT did not have an adverse impact on survival.

To perform a national survey of radiation oncologists and urologists about the type of resources used and the level of evidence needed to change clinical practice in localized prostate cancer.From a random sample, 1422 physicians were mailed a survey assessing the types of information used and what level of evidence could alter their clinical practice in prostate cancer. Multivariable logistic regression models were used to identify differences in physician characteristics for each outcome.Survey response rates were similar for radiation oncologists and urologists (44% vs 46%; P=.46). Specialty-specific journals represented the most commonly used resource for informing the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to report utilizing top-tier medical journals (25% vs 39%; adjusted odds ratio [OR] 0.50; P=.01) or cancer journals (22% vs 51%; adjusted OR 0.50; P.001) but more likely to rely on clinical guidelines (46% vs 38%; adjusted OR 1.6; P=.006). Both radiation oncologists and urologists most commonly reported large randomized, clinical trials as the level of evidence to change treatment recommendations for localized prostate cancer (85% vs 77%; P=.009).Both specialties rely on their own specialty-specific journals and view randomized, clinical trials as the level of evidence needed to change clinical practice. Our study provides a context on meaningful ways of disseminating evidence for localized prostate cancer.

To evaluate trends in the geographic distribution of the radiation oncology (RO) workforce.We used the 1995 and 2007 versions of the Area Resource File to map the ratio of RO to the population aged 65 years or older (ROR) within different health service areas (HSA) within the United States. We used regression analysis to find associations between population variables and 2007 ROR. We calculated Gini coefficients for ROR to assess the evenness of RO distribution and compared that with primary care physicians and total physicians.There was a 24% increase in the RO workforce from 1995 to 2007. The overall growth in the RO workforce was less than that of primary care or the overall physician workforce. The mean ROR among HSAs increased by more than one radiation oncologist per 100,000 people aged 65 years or older, from 5.08 per 100,000 to 6.16 per 100,000. However, there remained consistent geographic variability concerning RO distribution, specifically affecting the non-metropolitan HSAs. Regression analysis found higher ROR in HSAs that possessed higher education (p = 0.001), higher income (p0.001), lower unemployment rates (p0.001), and higher minority population (p = 0.022). Gini coefficients showed RO distribution less even than for both primary care physicians and total physicians (0.326 compared with 0.196 and 0.292, respectively).Despite a modest growth in the RO workforce, there exists persistent geographic maldistribution of radiation oncologists allocated along socioeconomic and racial lines. To solve problems surrounding the RO workforce, issues concerning both gross numbers and geographic distribution must be addressed.

Introduction The successful treatment of prostate cancer depends on the accurate estimation of the risk of regional lymph node (LN) involvement. The Roach formula (RF) has been criticized as overestimating LN risk. A modification of the RF has been attempted by other investigators using simplified adjustment ratios: the Nguyen formula (NF). Methods and Materials The National Cancer Institute Surveillance, Epidemiology, and End Results database was investigated for patients treated in 2004 through 2006 for whom at least 10 LN were examined at radical prostatectomy, cT1c or cT2 disease, and prostate-specific antigen (PSA) N = 2,930). The Yale formula (YF) was derived from half of the sample ( n = 1,460), and validated in the other half ( n = 1,470). Results We identified 2,930 patients. Only 4.6% of patients had LN+, and 72.6% had cT1c disease. Gleason (GS) 8–10 histology was found in 14.4% of patients. The YF for prediction of %LN+ risk is [GS – 5] × [PSA/3 + 1.5 × T], where T = 0, 1, and 2 for cT1c, cT2a, and cT2b/cT2c. Within each strata of predicted %LN+ risk, the actual %LN+ was closest to the YF. Using a >15% risk as an indicator of high-risk disease, the YF had increased sensitivity (39.0% vs. 13.6%) compared with the NF, without a significant reduction in specificity (94.9% vs. 98.8%). The NF was overly restrictive of the high-risk group, with only 2% of patients having a >15% risk of LN+ by that formula. Conclusion The YF performed better than the RF and NF and was best at differentiating patients at high risk for LN+ disease.

The United States spends almost 2.5 times more per capita on health care than other developed countries (1), yet produces comparably poor outcomes on measures such as life expectancy and disease specific mortality (2). Overutilization of expensive health care technology is a principal driver of this disparity (3). Radiation oncology will increasingly be under scrutiny as a significant contributor to this problem given the high cost of the technology and paucity of data supporting the use of newer, more expensive modalities (4). One analysis estimates that small-scale reform designed to restrict inappropriate use of radiotherapy could save the Medicare fee-for-service program $5.3 billion over 10 years (5). Although many factors influence the use of health care resources, ownership of expensive technology by referring physicians is known to substantially increase expenditures (6). A 1993 New England Journal of Medicine study found that joint ventures in which a non-radiation oncologist refers patients for radiation therapy on equipment in which they have an ownership interest perform 58% more procedures and bill 48% more than non-conflicted practices (7). These data are problematic, considering the new wave of integrated prostate cancer centers in which urologists acquire an ownership interest in the intensity-modulated radiation therapy (IMRT) equipment to which they refer patients. At least two companies, UroRad Healthcare and American Kidney Stone Management, are helping to drive the trend by marketing turnkey IMRT centers to urologists. In the traditional UroRad model, a group of urologists invests $3 million in equipment, information technology, and supplies; hires a salaried radiation oncologist for onsite work; and makes use of the company’s centralized, remote dosimetry (8). Because the technical and professional fees combine to approach $50,000 per patient treated with IMRT, there is a clear incentive to refer patients for radiation therapy who might be better served by prostatectomy, brachytherapy, or active

Purpose Clinical trials and guidelines published between 1997 and 2001 concluded that postmastectomy radiotherapy (PMRT) improves overall survival for women with high-risk breast cancer. However, the effect of these findings on current practice is not known. Using the Surveillance, Epidemiology, and End Results-Medicare cohort, we sought to characterize the adoption of PMRT from 1992 to 2002 and identify risk factors for PMRT omission among high-risk older patients. Methods and Materials We identified 28,973 women aged ≥66 years who had been treated with mastectomy for invasive breast cancer between 1992 and 2002. Trends in the adoption of PMRT for low- (T1-T2N0), intermediate- (T1-T2N1), and high- (T3-T4 and/or N2-N3) risk patients were characterized using a Monte Carlo permutation algorithm. Multivariate logistic regression identified the risk factors for PMRT omission and calculated the adjusted use rates. Results Postmastectomy radiotherapy use increased gradually and consistently for low-risk (+2.16%/y) and intermediate-risk (+7.20%/y) patients throughout the study interval. In contrast, PMRT use for high-risk patients increased sharply between 1996 and 1997 (+30.99%/y), but subsequently stabilized. Between 1998 and 2002, only 53% of high-risk patients received PMRT. The risk factors for PMRT omission included advanced age, moderate to severe comorbidity, smaller tumor size, fewer positive lymph nodes, and geographic region, with adjusted use rates ranging from 63.5% in San Francisco to 44.9% in Connecticut. Conclusion Among the high-risk patients, PMRT use increased sharply in 1997 after the initial clinical trial publication. Despite subsequent guidelines recommending the use of PMRT, no further increase in PMRT use has occurred, and nearly 50% of high-risk patients still do not receive PMRT.

Purpose/Objective(s): The clinical benefit of intensity-modulated (IMRT) compared to 3D conformal radiation (3D-RT) has not been wellestablished for locally advanced non-small cell lung cancer (NSCLC). We evaluated trends in use of IMRT for stage III lung NSCLC and compared survival and hospitalization outcomes. Materials/Methods: Using SEER-Medicare data, we identified use of IMRT or 3D-RT among 7061 Medicare beneficiaries diagnosed with stage III NSCLC from 2002-2009. Factors associated with use of IMRT versus 3D-RT were identified using multivariable logistic regression. Overall survival and number of hospital days within 90 days of radiation were analyzed using Cox proportional hazard and negative binomial regression models, respectively. Propensity score adjustment was used to control for clinical and demographic variables. Results: IMRT comprised an increasing proportion of conformal treatments for NSCLC, rising from 3.0% in 2002 to 26.8% in 2009. Patients treated at freestanding versus hospital-based facilities were twice as likely to receive IMRT (17.3% vs 9.5%, adj ORZ 2.0, p < 0.01). IMRT use varied by region, with higher rates in the South (12.8%, adj OR Z 1.13) and West (14.2%, adj ORZ 1.25), compared to theNortheast (9.9%, ref) andMidwest (9.1%, adjOR Z 0.88) (overall pZ 0.03) and in urban versus rural areas (12.5% vs 9.9%, adj OR Z 1.52, p < 0.01). Patients with more comorbidities were more likely to receive IMRT, 11.3% (ref) vs 11.7% (adj OR Z 1.03) vs 14.7% (adj OR Z 1.35) for modified Charlson score 0, 1, and 2+, respectively (overall pZ 0.03). We did not find a difference in IMRT use between stage IIIA and stage IIIB patients (11.8% vs 12.4%, adj OR Z 1.11, p Z 0.19). Patients receiving chemotherapy were more likely to receive IMRT (12.8% vs 10.4%, adj ORZ 1.24, p Z 0.02), though there was no difference in IMRT use among patients having surgery (11.4% vs 12.2%, adj ORZ 0.95, pZ 0.68). With propensity score adjustment, IMRTwas associatedwith greater overall survival (adj HRZ 0.91, pZ 0.03) compared to 3D-RT, though there was no difference in survival among patients receiving at least 25 fractions of radiation (adj HRZ 0.99, pZ 0.83). There was no significant difference in number of hospital days in the 90 days following radiation start (mean 5 days, adj HR Z 1.01, p Z 0.89). Conclusions: When radiation is used to treat locally advanced NSCLC, IMRT is increasingly preferred to 3D-RT. However, among patients receiving potentially curative radiation ( 25 fractions) there was no significant difference in overall survival or time spent hospitalized following treatment compared to 3D-RT. Author Disclosure: A.B. Chen: None. L. Li: None. A. Cronin: None. D. Schrag: None.

1522 Background: Ideally, screening detects cancer at a more curable stage, and as a result decreases the incidence of subsequent diagnosis at a late stage. Whereas breast cancer screening is suggested to have led to a substantial increase in the number of early-stage cancers diagnosed in the United States with only marginal reductions in the number of late stage cancers, the impact of colorectal cancer screening on cancer incidence is unknown. Methods: Colorectal cancer incidence data spanning over three decades, 1976—2009, were collected from the Surveillance, Epidemiology, and End Result (SEER) database. Screening utilization data spanning 1986—2010 were collected from the National Health Survey (NHS) progress reports. We examined trends in the incidence of early-stage (in situ, local) and late-stage (regional, distant) colorectal cancer among adults 50 years or older. Results: Over the past three decades, the incidence of late-stage colorectal cancer decreased significantly, from 118 to 74 cases per 100,000 people—a 37% decrease. The incidence of early-stage colorectal cancer also decreased, from 77 to 67 cases per 100,000 people. There was also an associated increase in the utilization rates of screening colonoscopy. From 1987 to 2010—the years for which NHS data were available—the percentage of adults 50 and older who received screening colonoscopy rose from 27% to 63%. After adjusting for trends in cancer incidence in non-screened populations, we estimated that colorectal screening was associated with a reduction of approximately 550,000 cases of colorectal cancer over the past three decades in the United States. Using the most conservative assumption of constant cancer incidence during the past three decades, 235,000 cases of colorectal cancer were prevented. Conclusions: There has been a significant decline in both early and late stage colorectal cancer diagnoses, during a time of increasing rates of increased screening.

Materials/Methods: The NCCN Breast Outcomes Database was used to identify women 70 and over with T1, cN0, hormone receptor positive breast cancers from 2000-2009 receiving care at 13 participating NCCN cancer centers. Factors considered to be potentially associated with use of RT a priori were evaluated in univariate and multivariable models, including year of diagnosis, tumor size, grade, histology, multicentric/ multifocal disease, Her2neu status, triggering event, patient age, race/ ethnicity, body mass index (BMI), Charlson/Katz co-morbidity score, type of biopsy, use of axillary surgery, and treating institution. Date of diagnosis was classified as 2000-2004 versus 2005-2009, reflecting the date of guideline change. Results: One thousand, five hundred forty-three women met study criteria; overall 1292 women (84%) had BCS. Among these, 1,005 (78%) received adjuvant breast RT; standard whole breast RT technique was used in 98.5%. ET without or with chemotherapy was used in 83% of all women. In a multivariable analysis, diagnosis year prior to 2005 (p Z 0.0003), younger age (p < 0.0001), lower co-morbidity score (p Z 0.0006), and larger tumor sizes (p Z 0.0146) were all significant predictors of use of RT. For example, 94% of women ages 70-74 received RT in 2000, compared with 88% in 2009; for the same time intervals in the 80 or above age group, usage was 80% versus 38%. Women who had axillary surgery as well were significantly more likely to receive RT (p < 0.0001). In addition, treating institution was a statistically significant factor associated with use of RT (p < 0.0001). Conclusions: Following the change in the NCCN guideline recommendations for elderly women with Stage I, estrogen receptor positive BC, the use of RT with BCS decreased over time in NCCN centers; however most women still received RT. Patient characteristics such as age and comorbidity impacted the use of RT. In addition, a key factor significantly affecting treatment use of RT was the institution where a woman received her treatment. Author Disclosure: B. McCormick: K. Stock; Varian. R. Ottesen: None. M. Hughes: None. S. Javid: None. S. Khan: None. J. Mortimer: None. J. Niland: None. J. Weeks: None. S. Edge: None.