Aileen B. Chen

Patient and Treatment Factors Associated With Complications After Prostate Brachytherapy

PURPOSE To assess the prevalence and predictors of complications after prostate brachytherapy in a population-based sample of older men. PATIENTS AND METHODS We analyzed claims for Medicare-enrolled men older than age 65 years living in Surveillance, Epidemiology, and End Results (SEER) surveillance areas diagnosed with prostate cancer from 1991 to 1999 who underwent brachytherapy as initial treatment. RESULTS There were 5,621 men who had brachytherapy with at least 2 years of follow-up. A complication diagnosis or invasive procedure occurred in 54.5% of men within 2 years, with 14.1% undergoing an invasive procedure. Urinary, bowel, and erectile morbidity rates were 33.8%, 21.0%, and 16.7%, respectively, and invasive procedure rates were 10.3%, 0.8%, and 4.0%, respectively. On multivariable analysis, combined urinary diagnoses and invasive procedures (obstruction, incontinence, bleeding, fistula) were associated with older age (P < .01), nonwhite race (odds ratio [OR], 1.30; P = .01), low income (OR, 1.74; P < .01), external-beam radiotherapy (EBRT; OR, 0.85; P = .01), androgen deprivation (OR, 1.31; P < .01), later year of brachytherapy (OR, 1.03/yr; P = .02), higher Charlson comorbidity score (P < .01), and prior transurethral resection of the prostate (OR, 1.65; P < .01). Bowel morbidity (bleeding/proctitis, injury) was associated with older age (P = .04), EBRT (OR, 1.46; P < .01), later year (OR, 1.04/yr; P < .01), higher Charlson score (P = .01), and inflammatory bowel disease (OR, 2.60; P < .01). Erectile morbidity was associated with younger age (P < .01), nonwhite race (OR, 1.37; P < .01), AD (OR, 1.18; P = .04), and later year (OR, 1.08/yr; P < .01). Invasive procedure rates declined with later year of brachytherapy (OR, 0.93/yr; P < .01). CONCLUSION Morbidity after prostate brachytherapy was common, though invasive procedures were required infrequently. Invasive procedures for complications declined during the 1990s, suggesting technical improvement with experience.

Carboplatin and Paclitaxel With vs Without Bevacizumab in Older Patients With Advanced Non–Small Cell Lung Cancer

CONTEXT A previous randomized trial demonstrated that adding bevacizumab to carboplatin and paclitaxel improved survival in advanced non-small cell lung cancer (NSCLC). However, longer survival was not observed in the subgroup of patients aged 65 years or older. OBJECTIVE To examine whether adding bevacizumab to carboplatin and paclitaxel chemotherapy is associated with improved survival in older patients with NSCLC. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 4168 Medicare beneficiaries aged 65 years or older with stage IIIB or stage IV non-squamous cell NSCLC diagnosed in 2002-2007 in a Surveillance, Epidemiology, and End Results (SEER) region. Patients were categorized into 3 cohorts based on diagnosis year and type of initial chemotherapy administered within 4 months of diagnosis: (1) diagnosis in 2006-2007 and bevacizumab-carboplatin-paclitaxel therapy; (2) diagnosis in 2006-2007 and carboplatin-paclitaxel therapy; or (3) diagnosis in 2002-2005 and carboplatin-paclitaxel therapy. The associations between carboplatin-paclitaxel with vs without bevacizumab and overall survival were compared using Cox proportional hazards models and propensity score analyses including information about patient characteristics recorded in SEER-Medicare. MAIN OUTCOME MEASURE Overall survival measured from the first date of chemotherapy treatment until death or the censoring date of December 31, 2009. RESULTS The median survival estimates were 9.7 (interquartile range [IQR], 4.4-18.6) months for bevacizumab-carboplatin-paclitaxel, 8.9 (IQR, 3.5-19.3) months for carboplatin-paclitaxel in 2006-2007, and 8.0 (IQR, 3.7-17.2) months for carboplatin-paclitaxel in 2002-2005. One-year survival probabilities were 39.6% (95% CI, 34.6%-45.4%) for bevacizumab-carboplatin-paclitaxel vs 40.1% (95% CI, 37.4%-43.0%) for carboplatin-paclitaxel in 2006-2007 and 35.6% (95% CI, 33.8%-37.5%) for carboplatin-paclitaxel in 2002-2005. Neither multivariable nor propensity score-adjusted Cox models demonstrated a survival advantage for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel cohorts. In propensity score-stratified models, the hazard ratio for overall survival for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel in 2006-2007 was 1.01 (95% CI, 0.89-1.16; P = .85) and compared with carboplatin-paclitaxel in 2002-2005 was 0.93 (95% CI, 0.83-1.06; P = .28). The propensity score-weighted model and propensity score-matching model similarly failed to demonstrate a statistically significant superiority for bevacizumab-carboplatin-paclitaxel. Subgroup and sensitivity analyses for key variables did not change these findings. CONCLUSION Adding bevacizumab to carboplatin and paclitaxel chemotherapy was not associated with better survival among Medicare patients with advanced NSCLC.

Clinical Utility of 4D FDG-PET/CT Scans in Radiation Treatment Planning

PURPOSE The potential role of four-dimensional (4D) positron emission tomography (PET)/computed tomography (CT) in radiation treatment planning, relative to standard three-dimensional (3D) PET/CT, was examined. METHODS AND MATERIALS Ten patients with non-small-cell lung cancer had sequential 3D and 4D [(18)F]fluorodeoxyglucose PET/CT scans in the treatment position prior to radiation therapy. The gross tumor volume and involved lymph nodes were contoured on the PET scan by use of three different techniques: manual contouring by an experienced radiation oncologist using a predetermined protocol; a technique with a constant threshold of standardized uptake value (SUV) greater than 2.5; and an automatic segmentation technique. For each technique, the tumor volume was defined on the 3D scan (VOL3D) and on the 4D scan (VOL4D) by combining the volume defined on each of the five breathing phases individually. The range of tumor motion and the location of each lesion were also recorded, and their influence on the differences observed between VOL3D and VOL4D was investigated. RESULTS We identified and analyzed 22 distinct lesions, including 9 primary tumors and 13 mediastinal lymph nodes. Mean VOL4D was larger than mean VOL3D with all three techniques, and the difference was statistically significant (p < 0.01). The range of tumor motion and the location of the tumor affected the magnitude of the difference. For one case, all three tumor definition techniques identified volume of moderate uptake of approximately 1 mL in the hilar region on the 4D scan (SUV maximum, 3.3) but not on the 3D scan (SUV maximum, 2.3). CONCLUSIONS In comparison to 3D PET, 4D PET may better define the full physiologic extent of moving tumors and improve radiation treatment planning for lung tumors. In addition, reduction of blurring from free-breathing images may reveal additional information regarding regional disease.

A multi-region algorithm for markerless beam's-eye view lung tumor tracking

Methods that allow online lung tumor tracking during radiotherapy are desirable for a variety of applications that have the potential to vastly improve treatment accuracy, dose conformity and sparing of healthy tissue. Several publications have proposed the use of an on-board kV x-ray imager to assess the tumor location during treatment. However, there is some concern that this strategy may expose the patient to a significant amount of additional dose over the course of a typical radiotherapy treatment. In this paper we present an algorithm that utilizes the on-board portal imager of the treatment machine to track lung tumors. This does not expose the patient to additional dose, but is somewhat more challenging as the quality of portal images is inferior when compared to kV x-ray images. To quantify the performance of the proposed algorithm we retrospectively applied it to portal image sequences retrieved from a dynamic chest phantom study and an SBRT treatment performed at our institution. The results were compared to manual tracking by an expert. For the phantom data the tracking error was found to be smaller than 1 mm and for the patient data smaller than 2 mm, which was in the same range as the uncertainty of the gold standard.

Expectations About the Effectiveness of Radiation Therapy Among Patients With Incurable Lung Cancer

PURPOSE Although radiation therapy (RT) can palliate symptoms and may prolong life, it is not curative for patients with metastatic lung cancer. We investigated patient expectations about the goals of RT for incurable lung cancers. PATIENTS AND METHODS The Cancer Care Outcomes Research and Surveillance Consortium enrolled a population- and health system-based cohort of patients diagnosed with lung cancer from 2003 to 2005. We identified patients with stage wet IIIB or IV lung cancer who received RT and answered questions on their expectations about RT. We assessed patient expectations about the goals of RT and identified factors associated with inaccurate beliefs about cure. RESULTS In all, 384 patients completed surveys on their expectations about RT. Seventy-eight percent of patients believed that RT was very or somewhat likely to help them live longer, and 67% believed that RT was very or somewhat likely to help them with problems related to their cancer. However, 64% did not understand that RT was not at all likely to cure them. Older patients and nonwhites were more likely to have inaccurate beliefs, and patients whose surveys were completed by surrogates were less likely to have inaccurate beliefs. Ninety-two percent of patients with inaccurate beliefs about cure from RT also had inaccurate beliefs about chemotherapy. CONCLUSION Although patients receiving RT for incurable lung cancer believe it will help them, most do not understand that it is not at all likely to cure their disease. This indicates a need to improve communication regarding the goals and limitations of palliative RT.

Palliative Radiation Therapy Practice in Patients With Metastatic Non–Small-Cell Lung Cancer: A Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) Study

PURPOSE Randomized data suggest that single-fraction or short-course palliative radiation therapy (RT) is sufficient in the majority of patients with metastatic cancer. We investigated population-based patterns in the use of palliative RT among patients with metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS From patients diagnosed with lung cancer from 2003 to 2005 at a participating geographic or organizational site and who consented to the Cancer Care Outcomes Research and Surveillance Consortium study, we identified patients with metastatic NSCLC who had complete medical records abstractions. Patient characteristics and clinical factors associated with receipt of palliative RT and RT intensity (total dose and number of treatments) were evaluated with multivariable regression. RESULTS Of 1,574 patients with metastatic NSCLC, 780 (50%) received at least one course of RT, and 21% and 12% received RT to the chest and bone, respectively. Use of palliative RT was associated with younger age at diagnosis and receipt of chemotherapy and surgery to metastatic sites. Among patients receiving palliative bone RT, only 6% received single-fraction treatment. Among patients receiving palliative chest RT, 42% received more than 20 fractions. Patients treated in integrated networks were more likely to receive lower doses and fewer fractions to the bone and chest. CONCLUSION When palliative RT is used in patients with metastatic NSCLC, a substantial proportion of patients receive a greater number of treatments and higher doses than supported by current evidence, suggesting an opportunity to improve care delivery.

Survival Outcomes After Radiation Therapy for Stage III Non–Small-Cell Lung Cancer After Adoption of Computed Tomography–Based Simulation

PURPOSE Technical studies suggest that computed tomography (CT) -based simulation improves the therapeutic ratio for thoracic radiation therapy (TRT), although few studies have evaluated its use or impact on outcomes. METHODS We used the Surveillance, Epidemiology and End Results (SEER) -Medicare linked data to identify CT-based simulation for TRT among Medicare beneficiaries diagnosed with stage III non-small-cell lung cancer (NSCLC) between 2000 and 2005. Demographic and clinical factors associated with use of CT simulation were identified, and the impact of CT simulation on survival was analyzed by using Cox models and propensity score analysis. RESULTS The proportion of patients treated with TRT who had CT simulation increased from 2.4% in 1994 to 34.0% in 2000 to 77.6% in 2005. Of the 5,540 patients treated with TRT from 2000 to 2005, 60.1% had CT simulation. Geographic variation was seen in rates of CT simulation, with lower rates in rural areas and in the South and West compared with those in the Northeast and Midwest. Patients treated with chemotherapy were more likely to have CT simulation (65.2% v 51.2%; adjusted odds ratio, 1.67; 95% CI, 1.48 to 1.88; P < .01), although there was no significant association between use of surgery and CT simulation. Controlling for demographic and clinical characteristics, CT simulation was associated with lower risk of death (adjusted hazard ratio, 0.77; 95% CI, 0.73 to 0.82; P < .01) compared with conventional simulation. CONCLUSION CT-based simulation has been widely, although not uniformly, adopted for the treatment of stage III NSCLC and is associated with higher survival among patients receiving TRT.

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.

Predictors of IMRT and Conformal Radiotherapy Use in Head and Neck Squamous Cell Carcinoma: A SEER-Medicare Analysis

PURPOSE The extent to which new techniques for the delivery of radiotherapy for head and neck squamous cell carcinoma (HNSCC) have diffused into clinical practice is unclear, including the use of 3-dimensional conformal RT (3D-RT) and intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 2,495 Medicare patients with Stage I-IVB HNSCC diagnosed at age 65 years or older between 2000 and 2005 and treated with either definitive (80%) or adjuvant (20%) radiotherapy. Our primary aim was to analyze the trends and predictors of IMRT use over this time, and the secondary aim was a similar description of the trends and predictors of conformal radiotherapy (CRT) use, defined as treatment with either 3D-RT or IMRT. RESULTS Three hundred sixty-four (15%) patients were treated with IMRT, and 1,190 patients (48%) were treated with 3D-RT. Claims for IMRT and CRT rose from 0% to 33% and 39% to 86%, respectively, between 2000 and 2005. On multivariable analysis, IMRT use was associated with SEER region (West 18%; Northeast 11%; South 12%; Midwest 13%), advanced stage (advanced, 21%; early, 9%), non-larynx site (non-larynx, 23%; larynx, 7%), higher median census tract income (highest vs. lowest quartile, 18% vs. 10%), treatment year (2003-2005, 31%; 2000-2002, 6%), use of chemotherapy (26% with; 9% without), and higher radiation oncologist treatment volume (highest vs. lowest tertile, 23% vs. 8%). With CRT as the outcome, only SEER region, treatment year, use of chemotherapy, and increasing radiation oncologist HNSCC volume were significant on multivariable analysis. CONCLUSIONS The use of IMRT and CRT by Medicare beneficiaries with HNSCC rose significantly between 2000 and 2005 and was associated with both clinical and non-clinical factors, with treatment era and radiation oncologist HNSCC treatment volume serving as the strongest predictors of IMRT use.

Provider Case Volume and Outcomes Following Prostate Brachytherapy

PURPOSE We assessed the relationship between provider volume and outcomes following brachytherapy in a population based cohort of men. MATERIALS AND METHODS We analyzed the claims of Medicare enrolled men older than 65 years living in Surveillance, Epidemiology and End Results surveillance areas who were diagnosed with prostate cancer from 1991 to 1999 and underwent brachytherapy as initial treatment. Case volume was calculated for each physician and hospital from 1991 to 2001 from Medicare claims. Outcomes of interest were recurrence, prostate cancer death, all deaths and 2-year complications. Analyses were adjusted by patient and treatment characteristics. RESULTS We identified 5,595 men for whom a radiation oncologist and a hospital provider could be identified. Men who were older, nonwhite, lower income, unmarried, living in nonurban areas or had more comorbidities were more likely to see lower volume physicians. Physician volume was not associated with the complication rate after brachytherapy. However, men treated at higher volume hospitals had a slightly lower rate of combined complication diagnoses and procedures (OR 0.94/100 cases, p <0.01). Patients treated by higher volume physicians had a lower recurrence rate (HR 0.89/100 cases, p = 0.01) and rate of prostate cancer death (HR 0.80/100 cases, p = 0.03) with a borderline significant decrease in all deaths (HR 0.95/100 cases, p = 0.05). There was no significant association between hospital volume and recurrence, prostate cancer death or all deaths. CONCLUSIONS Men treated with brachytherapy by higher volume physicians were at lower risk for recurrence and prostate cancer death, and showed a borderline decrease in total deaths. We did not observe a clear relationship between provider volume and complications following treatment.