Outcomes Following SBRT vs. IMRT and 3DCRT for Older Patients with Stage IIA Node-Negative Non-Small Cell Lung Cancer > 5 cm.

BACKGROUND: To describe outcomes and compare the effectiveness of stereotactic body radiotherapy (SBRT) versus 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in patients with stage IIA lymph node-negative (N0) non-small cell lung cancer (NSCLC) tumors > 5 cm. METHODS: We used the SEER-Medicare database (2005-2015) to identify patients > 65 years with stage IIA (AJCC TNM7) N0 NSCLC > 5 cm tumors who were treated with SBRT, IMRT, and 3DCRT. We used propensity score methods with inverse probability weighting to compare lung cancer-specific survival (LCSS), overall survival (OS), and toxicity. RESULTS: Of 584 patients, 88 (15%), 140 (24%), and 356 (61%) underwent SBRT, IMRT, and 3DCRT, respectively. The SBRT group was older (P = .004), had more comorbidities (P = .02), smaller tumors (P = .03), and more adenocarcinomas (P < .0001). We found a trend towards higher median unadjusted OS with SBRT compared to IMRT and 3DCRT (19 vs. 13 and 14 months, respectively, P = .37). In our propensity score-adjusted analyses, SBRT was significantly associated with better OS and LCSS compared to IMRT (HROS: 0.78, 95% CI: 0.68-0.89, HRLCSS: 0.70, 95% CI: 0.60-0.81) and 3DCRT (HROS: 0.81, 95% CI: 0.72-0.93, HRLCSS: 0.80, 95% CI: 0.68-0.93). SBRT-treated patients also had lower overall adjusted complication rates compared to IMRT (OR: 0.74, 95% CI: 0.55-0.99) and 3DCRT (OR: 0.53, 95% CI: 0.40-0.71). CONCLUSION: For patients with NSCLC tumors > 5 cm, SBRT trends towards fewer toxicities and improved survival compared to other forms of radiotherapy. Our findings support SBRT as an appropriate treatment strategy for older patients with larger inoperable NSCLC tumors.

Risk of Cardiovascular Toxicity According to Tumor Laterality Among Older Patients With Early Stage Non-small Cell Lung Cancer Treated With Radiation Therapy.

BACKGROUND: The long-term risk of cardiovascular outcomes from either stereotactic body radiation therapy (SBRT) or three-dimensional conformal radiation therapy (3DCRT) plus intensity-modulated radiation therapy (IMRT) to treat early stage non-small cell lung cancer (NSCLC) is largely unknown. As continued adoption of SBRT accelerates, it is important to delineate unforeseen cardiovascular risks associated with treatment. RESEARCH QUESTION: Does the long-term risk of cardiovascular outcomes for patients with early stage NSCLC treated with either SBRT or 3DCRT plus IMRT differ by tumor laterality? STUDY DESIGN AND METHODS: Data from the Surveillance, Epidemiology, and End Results registry linked to Medicare was analyzed to identify a sample of 3,256 patients (1,506 treated with SBRT and 1,750 treated with 3DCRT plus IMRT) with node-negative stage I or IIA NSCLC. Cardiovascular events were identified using diagnosis codes, and outcomes were compared between left- and right-sided tumors. We assumed that tumor laterality was random and that the radiation field for left-sided tumors likely would result in greater dose to cardiac tissues. Cox regression models were fit to quantify the association of laterality on outcomes. RESULTS: Patients were followed up for a median of 2 years. Those treated with SBRT showed no difference in hazard of any cardiovascular outcomes by tumor laterality, including the cardiovascular composite (hazard ratio [HR] comparing left- vs right-sided tumors, 0.98; 95% CI, 0.84-1.15). In contrast, patients treated with 3DCRT plus IMRT showed a greater risk of congestive heart failure (HR, 1.23; 95% CI, 1.01-1.48) and percutaneous coronary artery intervention (HR, 2.24; 95% CI, 1.12-4.47). INTERPRETATION: Patients with left- vs right-sided early stage NSCLC showed similar rates of cardiovascular events when treated with SBRT. However, these patients also showed higher rates of select cardiac events when they were treated with 3DCRT plus IMRT. This study provides evidence that SBRT may provide a safer option over 3DCRT plus IMRT for patients with left-sided early stage NSCLC and underscores the need for long-term follow-up for patients treated with radiation therapy.

Cost of Intensity-modulated Radiation Therapy for Older Patients with Stage III Lung Cancer.

RATIONALE: In the treatment of stage III non-small cell lung cancer (NSCLC), three-dimensional conformal radiotherapy (3D-RT) is the standard method for radiation delivery; however, intensity-modulated radiotherapy (IMRT) has been rapidly adopted. These two modalities may lead to similar survival, warranting a closer scrutiny of the costs involved. OBJECTIVES: The purpose of this study is to compare radiotherapy-related and total costs of older patients with NSCLC treated with 3D-RT versus IMRT. METHODS: We conducted a population-based study of all Medicare beneficiaries aged 65 years or older in a Surveillance, Epidemiology and End Results region. Patients were diagnosed with stage III NSCLC diagnosed between 2002 and 2009. Patients received IMRT or 3D-RT in combination with chemotherapy within 4 months of diagnosis. Radiotherapy-related and total adjusted cost and survival of patients receiving 3D-RT versus IMRT were compared using propensity scores methods. MEASUREMENTS AND MAIN RESULTS: Of the 2,418 patients in study, 314 (13%) received IMRT. Adjusted analyses showed no difference in overall survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.85-1.12) in patients treated with 3D-RT versus IMRT. After adjusting for propensity scores, RT-related costs (estimated difference, $6,850; 95% CI, $5,532-$8,168) and total costs (estimated difference, $8,713; 95% CI, $4,376-$13,051) were significantly higher among patients undergoing IMRT. CONCLUSIONS: The rapid adoption of IMRT for the treatment of stage III NSCLC has occurred in the absence of evidence from prospective randomized trials. Our results show that IMRT is associated with similar survival but increased costs, underscoring the need for continued research in IMRT and other new technologies.

Affluence and Breast Cancer.

High income, high socioeconomic status, and affluence increase breast cancer incidence. Socioeconomic status in USA breast cancer studies has been assessed by block-group socioeconomic measures. A block group is a portion of a census tract with boundaries that segregate, as far as possible, socioeconomic groups. In this study, we used US Census income data instead of block groups to gauge socioeconomic status of breast cancer patients in relationship with incidence, prognostic markers, and survival. US state breast cancer incidence and mortality data are from the U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2011. Three-Year-Average Median Household Income by State, 2010 to 2012, is from the U.S. Census Bureau, Current Population Survey, 2011 to 2013 Annual Social and Economic Supplements. County incomes are from the 2005-2009 American Community Survey of the U.S. Census Bureau. The American Community Survey is an ongoing statistical survey that samples a small percentage of the population yearly. Its purpose is to provide communities the information they need to plan investments and services. Breast cancer county incidence and survival data are from the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) data base. We analyzed SEER data from 198 counties in California, Connecticut, Georgia, Hawaii, Iowa, New Mexico, Utah, and Washington. SEER uses the Collaborative Stage (CS) Data Collection System. We have retained the SEER CS variables. There was a significant relationship of income with breast cancer incidence in 50 USA states and the District of Columbia in White women (r = 0.623, p < 0.001). There was a significant relationship between node involvement and income in Whites in 198 USA counties. Income was significantly correlated with 5-year relative survival in Whites with localized breast cancer. Income was not correlated with 5-year survival of Black race (p = 0.364) or other races (p = 0.624). The multivariate general linear model with income as covariate, 5-year survival by race as a dependent variable, showed a significant effect of income and White race on 5-year survival (p < 0.001), unrelated to Black race (p = 0.780) or other races (p = 0.618). In men, we found a nonsignificant positive correlation between county breast cancer incidence and income (r = 0.098, p = 0.168). Breast cancer risk factors, such as delayed childbirth, less breast-feeding, and use of hormone supplements, are more common in affluent women. Affluent women are more likely to have mammograms, which detect many cancers that might not otherwise be diagnosed. In addition, women in certain affluent ethnic groups-Ashkenazi Jews, Icelanders and the Dutch-are more likely to carry genetic mutations known to predispose to breast cancer. We hypothesize that women with more income can afford better cancer care and survive longer than poorer women. But our hypothesis does not explain why this effect should be limited to White women; or why node involvement increased with income in White women but not in Blacks or Hispanics. Further studies may be worthwhile.

(18)F-fluorodeoxyglucose positron emission tomography-based assessment of local failure patterns in non-small-cell lung cancer treated with definitive radiotherapy.

PURPOSE: To assess the pattern of local failure using (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans after radiotherapy (RT) in non-small-cell lung cancer (NSCLC) patients treated with definitive RT whose gross tumor volumes (GTVs) were defined with the aid of pre-RT PET data. METHOD AND MATERIALS: The data from 26 patients treated with involved-field RT who had local failure and a post-RT PET scan were analyzed. The patterns of failure were visually scored and defined as follows: (1) within the GTV/planning target volume (PTV); (2) within the GTV, PTV, and outward; (3) within the PTV and outward; and (4) outside the PTV. Local failure was also evaluated as originating from nodal areas vs. the primary tumor. RESULTS: We analyzed 34 lesions. All 26 patients had recurrence originating from their primary tumor. Of the 34 lesions, 8 (24%) were in nodal areas, 5 of which (63%) were marginal or geographic misses compared with only 1 (4%) of the 26 primary recurrences (p = 0.001). Of the eight primary tumors that had received a dose of <60 Gy, six (75%) had failure within the GTV and two (25%) at the GTV margin. At doses of > or = 60 Gy, 6 (33%) of 18 had failure within the GTV and 11 (61%) at the GTV margin, and 1 (6%) was a marginal miss (p < 0.05). CONCLUSION: At lower doses, the pattern of recurrences was mostly within the GTV, suggesting that the dose might have been a factor for tumor control. At greater doses, the treatment failures were mostly at the margin of the GTV. This suggests that visual incorporation of PET data for GTV delineation might be inadequate, and more sophisticated approaches of PET registration should be evaluated.

Evaluation of deep inspiration breath-hold lung treatment plans with Monte Carlo dose calculation.

PURPOSE: To evaluate dosimetry of deep inspiration breath-hold (DIBH) relative to free breathing (FB) for three-dimensional conformal radiation therapy of lung cancer with 6-MV photons and Monte Carlo (MC) dose calculations. METHODS AND MATERIALS: Static three-dimensional conformal radiation therapy, 6-MV plans, based on DIBH and FB CT images for five non-small-cell lung cancer patients, were generated on a clinical treatment planning system with equivalent path length tissue inhomogeneity correction. Margins of gross to planning target volume were not reduced for DIBH plans. Cord and lung toxicity determined the maximum treatment dose for each plan. Dose distributions were recalculated for the same beams with an MC dose calculation algorithm and electron density distributions derived from the CT images. RESULTS: MC calculations showed decreased target coverage relative to treatment-planning system predictions. Lateral disequilibrium caused more degradation of target coverage for DIBH than for FB (approximately 4% worse than expected for FB vs. 8% for DIBH). However, with DIBH higher treatment doses could be delivered without violating normal tissue constraints, resulting in higher total doses to gross target volume and to >99% of planning target volume. CONCLUSIONS: If DIBH enables prescription dose increases exceeding 10%, MC calculations indicate that, despite lateral disequilibrium, higher doses will be delivered to medium-to-large, partly mediastinal gross target volumes, providing that 6-MV photons are used and margins are not reduced.