C.E. Rutter

Adoption of hypofractionated whole-breast irradiation for early-stage breast cancer: a National Cancer Data Base analysis.

PURPOSE 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. METHODS AND MATERIALS 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). RESULTS 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). CONCLUSIONS 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.

Postoperative Radiation Therapy Is Associated With Improved Overall Survival in Incompletely Resected Stage II and III Non–Small-Cell Lung Cancer

PURPOSE To review trends in the use of postoperative radiotherapy (PORT) for stage II and III incompletely resected non-small-cell lung cancer (NSCLC) and evaluate the association between PORT and survival in such patients. PATIENTS AND METHODS We identified patients with pathologic stage N0-2, overall American Joint Committee on Cancer stage II or III NSCLC within the National Cancer Data Base who had undergone a lobectomy or pneumonectomy with positive surgical margins. Only patients coded as receiving external-beam PORT at 50 to 74 Gy or observation were included. To account for perioperative mortality, we excluded patients who survived less than 4 months after diagnosis. Multivariable logistic regression was used to determine factors associated with PORT receipt. Cox proportional hazards regression was performed for multivariable analyses of overall survival. RESULTS Among 3,395 included patients, 1,207 (35.6%) received PORT. Predictors for the use of PORT among this patient population included age less than 60 years, treatment in a nonacademic facility, earlier year of diagnosis, decreased travel distance, lower nodal stage, and chemotherapy receipt. On multivariable analysis adjusting for demographic and clinicopathologic covariates, PORT (hazard ratio, 0.80; 95% CI, 0.70 to 092) was associated with improved survival. Subset analysis by nodal stage showed that PORT improved survival across all nodal stages. CONCLUSION PORT is associated with improved overall survival in patients with incompletely resected stage II or III N0-2 NSCLC. The use of PORT for this population in more recent years has been declining. In the absence of randomized trials evaluating PORT utilization for this patient population, our findings strongly support the delivery of PORT in patients with incompletely resected NSCLC.

Assessment of National Practice for Palliative Radiation Therapy for Bone Metastases Suggests Marked Underutilization of Single-Fraction Regimens in the United States

PURPOSE To characterize temporal trends in the application of various bone metastasis fractionations within the United States during the past decade, using the National Cancer Data Base; the primary aim was to determine whether clinical practice in the United States has changed over time to reflect the published randomized evidence and the growing movement for value-based treatment decisions. PATIENTS AND METHODS The National Cancer Data Base was used to identify patients treated to osseous metastases from breast, prostate, and lung cancer. Utilization of single-fraction versus multiple-fraction radiation therapy was compared according to demographic, disease-related, and health care system details. RESULTS We included 24,992 patients treated during the period 2005-2011 for bone metastases. Among patients treated to non-spinal/vertebral sites (n=9011), 4.7% received 8 Gy in 1 fraction, whereas 95.3% received multiple-fraction treatment. Over time the proportion of patients receiving a single fraction of 8 Gy increased (from 3.4% in 2005 to 7.5% in 2011). Numerous independent predictors of single-fraction treatment were identified, including older age, farther travel distance for treatment, academic treatment facility, and non-private health insurance (P<.05). CONCLUSIONS Single-fraction palliative radiation therapy regimens are significantly underutilized in current practice in the United States. Further efforts are needed to address this issue, such that evidence-based and cost-conscious care becomes more commonplace.

Re-evaluation of the Role of Postoperative Radiotherapy and the Impact of Radiation Dose for Non–Small-Cell Lung Cancer Using the National Cancer Database

Background: The role of postoperative radiotherapy (PORT) after surgical resection of non–small-cell lung cancer (NSCLC) remains controversial. Although pertinent randomized evidence is lacking, historical studies have shown a survival detriment, partially attributed to antiquated radiotherapy techniques and supratherapeutic doses, whereas more recent nonrandomized data have suggested a survival benefit for PORT in appropriate patients. This analysis reassesses the impact of PORT in a modern cohort of patients with particular attention to radiotherapy details. Methods: Patients treated with margin-negative (R0) surgical resection of NSCLC with complete adjuvant treatment information were identified within the National Cancer Database. Overall survival (OS) was compared between patients based upon pathologic stage of disease, histologic subtype, and details of adjuvant therapy delivered. Results: We identified 30,552 patients treated for stages II–IIIA NSCLC in National Cancer Database between 1998 and 2006. Histology was adenocarcinoma in 16,482, squamous cell in 9847, large cell in 1715 and other in 2562. Overall, 3430 patients (11.2%) received PORT, and 23.8% of N2 patients received PORT. There was a detriment in 5-year OS with PORT for pathologically N0 (48 versus 37.7%, p < 0.001) and N1 patients (39.4 versus 34.8%, p < 0.001), although 5-year OS was improved with PORT in N2 patients (27.8 versus 34.1%, p < 0.001). Importantly, PORT dose was found to have a significant impact on OS. Patients who received 45 to 54 Gy demonstrated superior survival relative to patients without PORT (5-year OS 38 versus 27.8%, p < 0.001), although patients who received greater than 54 Gy had equivalent survival to patients treated without PORT (5-year OS 27.6 versus 27.8%, p = 0.784). PORT with doses of 45 to 54 Gy remained significantly associated with improved OS on multivariate analysis (hazard ratio for death 0.85, 95% confidence interval 0.76–0.94, p < 0.001). Conclusions: PORT delivered with modern techniques with appropriate doses continues to demonstrate a survival benefit in patients with positive mediastinal nodal metastases, and therefore should remain a standard of care for this population.

Patients Selected for Definitive Concurrent Chemoradiation at High-volume Facilities Achieve Improved Survival in Stage III Non–Small-Cell Lung Cancer

Background: The relationship between provider experience and clinical outcomes is poorly defined in radiation oncology. This study examined the impact of facility case volume on overall survival in patients with stage III non–small cell lung cancer (NSCLC) treated with definitive concurrent chemoradiation therapy (CCRT). Methods: Using the National Cancer Data Base, we identified clinical stage III NSCLC patients diagnosed in 2004 to 2006 who were treated with definitive CCRT to 59.4–74.0 Gy. High-volume facilities (HVF) were defined as those in the ninetieth percentile of annual CCRT volume (≥12 cases/year). Independent predictors of receiving CCRT at HVF were identified using multivariable logistic regression. Overall survival based on receiving CCRT at HVF was assessed using Kaplan–Meier analysis, Cox proportional hazards regression, and propensity score matching. Results: Among 10,072 included patients, 1207 (12.0%) were treated at HVF. Patients in HVF were more likely to have a higher Charlson–Deyo comorbidity score, more advanced nodal stage, higher doses, and 3D-conformal or intensity-modulated radiotherapy. When controlling for demographic and clinical covariates including academic affiliation, treatment at HVF was independently associated with a significantly decreased risk of death (hazards ratio = 0.93; 95% confidence interval: 0.87–0.99; p = 0.03). Propensity score matching showed that these findings were robust (hazards ratio = 0.91; 95% confidence interval: 0.84–0.99; p = 0.04). Conclusions: Our findings suggest that treatment at HVF is associated with improved overall survival among stage III NSCLC patients receiving definitive CCRT, independent of academic affiliation. Further research is needed to determine whether or not efforts supporting centralization of radiotherapy at HVF will improve population-based survival, toxicities, and costs.

Breast cancer laterality does not influence survival in a large modern cohort: implications for radiation-related cardiac mortality.

OBJECTIVES Radiation therapy for left-sided breast cancer has been associated with an elevated risk of cardiac mortality, based on studies predating treatment planning based on computed tomography. This study assessed the impact of tumor laterality on overall survival (OS) in a large cohort treated with modern techniques, to indirectly determine whether left-sided treatment remains associated with increased cardiac mortality. METHODS AND MATERIALS Patients treated for breast cancer with breast conserving surgery and adjuvant external beam radiation therapy were identified in the National Cancer Database, and OS was compared based on tumor laterality using Kaplan-Meier analysis. Separate analyses were performed for noninvasive and invasive carcinoma and for breast-only and breast plus regional nodal radiation therapy. Multivariate regression analysis of OS was performed with demographic, pathologic, and treatment variables as covariates to adjust for factors associated with breast cancer-specific survival. RESULTS We identified 344,831 patients whose cancer was diagnosed from 1998 to 2006 with a median follow-up time of 6.04 years (range, 0-14.17 years). Clinical, tumor, and treatment characteristics were similar between laterality groups. Regional nodal radiation was used in 14.2% of invasive cancers. No OS difference was noted based on tumor laterality for patients treated with breast-only (hazard ratio [HR] 0.984, P=.132) and breast plus regional nodal radiation therapy (HR 1.001, P=.957). In multivariate analysis including potential confounders, OS was identical between left and right sided cancers (HR 1.002, P=.874). No significant OS difference by laterality was observed when analyses were restricted to patients with at least 10 years of follow-up (n=27,725), both in patients treated with breast-only (HR 0.955, P=.368) and breast plus regional nodal radiation therapy (HR 0.859, P=.155). CONCLUSIONS Radiation therapy for left-sided breast cancer does not appear to increase the risk of death in this national database relative to right-sided tumors. Consequently, radiation therapy-induced cardiac disease may be less prominent than previously demonstrated.

Role of Chemoradiotherapy in Elderly Patients With Limited-Stage Small-Cell Lung Cancer

Purpose To investigate outcomes for elderly patients treated with chemotherapy (CT) alone versus chemoradiotherapy (CRT) in the modern era by using a large national database. Patients and Methods Elderly patients (age ≥ 70 years) with limited-stage small-cell lung cancer clinical stage I to III who received CT or CRT were identified in the National Cancer Data Base between 2003 and 2011. Hierarchical mixed-effects logistic regression with clustering by reporting facility was performed to identify factors associated with treatment selection. Overall survival (OS) of patients receiving CT versus CRT was compared by using the log-rank test, Cox proportional hazards regression, and propensity score matching. Results A total of 8,637 patients were identified, among whom 3,775 (43.7%) received CT and 4,862 (56.3%) received CRT. The odds of receiving CRT decreased with increasing age, clinical stage III disease, female sex, and the presence of medical comorbidities (all P < .01). Use of CRT was associated with increased OS compared with CT on univariable and multivariable analysis (median OS, 15.6 v 9.3 months; 3-year OS, 22.0% v 6.3%; log-rank P < .001; Cox P < .001). Propensity score matching identified a matched cohort of 6,856 patients and confirmed a survival benefit associated with CRT (hazard ratio, 0.52; 95% CI, 0.50 to 0.55; P < .001). Subset analysis of CRT treatment sequence showed that patients alive 4 months after diagnosis derived a survival benefit with concurrent CRT over sequential CRT (median OS, 17.0 v 15.4 months; log-rank P = .01). Conclusion In elderly patients with limited-stage small-cell lung cancer, modern CRT appears to confer an additional OS advantage beyond that achieved with CT alone in a large population-based cohort. Our findings suggest that CRT should be the preferred strategy in elderly patients who are expected to tolerate the toxicities of the combined approach.

Increase in the use of lung stereotactic body radiotherapy without a preceding biopsy in the United States

BACKGROUND Stereotactic body radiotherapy (SBRT) is an efficacious treatment for early stage non-small cell lung cancer (NSCLC). Patients with clinically suspected NSCLC may have medical comorbidities that increase biopsy risks, making them more likely to receive SBRT without biopsy. This study characterizes the pervasiveness of this management approach nationally. METHODS Patients with stage I NSCLC who received SBRT from 2003 to 2011 were identified within National Cancer Database. Changes in the proportion treated without biopsy were compared by year of diagnosis using binomial logistic regression. Demographics were compared between patients with and without biopsy with Chi-square and t-tests. Multivariate logistic regression was used to determine factors independently associated with SBRT delivery without biopsy. RESULTS We identified 6960 patients. Most had biopsy before SBRT (95.5%). Over time the proportion treated without biopsy increased (OR 1.11, p=0.038). Univariate comparisons demonstrated that older, medically inoperable patients treated at academic centers located in the New England or Pacific regions were less likely to have biopsy before SBRT. Facility type and location (p<0.001), medical inoperability (p<0.001), and smaller tumor size (p=0.013) were associated with odds of SBRT without biopsy in multivariate analyses. A trend toward increased use of SBRT with a biopsy with later year of diagnosis (p=0.093) was observed in multivariate analysis. CONCLUSIONS The percentage of patients nationally undergoing SBRT without biopsy has increased over time. The reasons for this trend and ramifications of this approach on cost-effectiveness of care must be studied.

Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: An analysis of the National Cancer Data Base.

The optimal treatment for resected pancreatic cancer is controversial because direct comparisons of adjuvant chemotherapy (CT) alone and chemotherapy and radiotherapy (CRT) are limited. This study assessed outcomes of CT versus CRT in a national cohort to provide a modern estimate of comparative effectiveness.

The evolving role of adjuvant radiotherapy for elderly women with early-stage breast cancer

Elderly patients with early‐stage breast cancer (ESBC) derive a local control benefit from radiotherapy (RT) after lumpectomy, without any apparent effect on overall survival. Therefore, the use of RT is controversial. In the current study, the authors characterized updated trends in RT for elderly patients with estrogen receptor (ER)‐positive ESBC.