Jordan A. Holmes

Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer

CONTEXT There has been rapid adoption of newer radiation treatments such as intensity-modulated radiation therapy (IMRT) and proton therapy despite greater cost and limited demonstrated benefit compared with previous technologies. OBJECTIVE To determine the comparative morbidity and disease control of IMRT, proton therapy, and conformal radiation therapy for primary prostate cancer treatment. DESIGN, SETTING, AND PATIENTS Population-based study using Surveillance, Epidemiology, and End Results-Medicare-linked data from 2000 through 2009 for patients with nonmetastatic prostate cancer. MAIN OUTCOME MEASURES Rates of gastrointestinal and urinary morbidity, erectile dysfunction, hip fractures, and additional cancer therapy. RESULTS Use of IMRT vs conformal radiation therapy increased from 0.15% in 2000 to 95.9% in 2008. In propensity score-adjusted analyses (N = 12,976), men who received IMRT vs conformal radiation therapy were less likely to receive a diagnosis of gastrointestinal morbidities (absolute risk, 13.4 vs 14.7 per 100 person-years; relative risk [RR], 0.91; 95% CI, 0.86-0.96) and hip fractures (absolute risk, 0.8 vs 1.0 per 100 person-years; RR, 0.78; 95% CI, 0.65-0.93) but more likely to receive a diagnosis of erectile dysfunction (absolute risk, 5.9 vs 5.3 per 100 person-years; RR, 1.12; 95% CI, 1.03-1.20). Intensity-modulated radiation therapy patients were less likely to receive additional cancer therapy (absolute risk, 2.5 vs 3.1 per 100 person-years; RR, 0.81; 95% CI, 0.73-0.89). In a propensity score-matched comparison between IMRT and proton therapy (n = 1368), IMRT patients had a lower rate of gastrointestinal morbidity (absolute risk, 12.2 vs 17.8 per 100 person-years; RR, 0.66; 95% CI, 0.55-0.79). There were no significant differences in rates of other morbidities or additional therapies between IMRT and proton therapy. CONCLUSIONS Among patients with nonmetastatic prostate cancer, the use of IMRT compared with conformal radiation therapy was associated with less gastrointestinal morbidity and fewer hip fractures but more erectile dysfunction; IMRT compared with proton therapy was associated with less gastrointestinal morbidity.

Impact of Distance to a Urologist on Early Diagnosis of Prostate Cancer Among Black and White Patients

PURPOSE We examined whether an increased distance to a urologist is associated with a delayed diagnosis of prostate cancer among black and white patients, as manifested by higher risk disease at diagnosis. MATERIALS AND METHODS North Carolina Central Cancer Registry data were linked to Medicare claims for patients with incident prostate cancer diagnosed in 2004 to 2005. Straight-line distances were calculated from the patient home to the nearest urologist. Race stratified multivariate ordinal logistic regression was used to examine the association between distance to a urologist and prostate cancer risk group (low, intermediate, high or very high/metastasis) at diagnosis for black and white patients while accounting for age, comorbidity, marital status and diagnosis year. An overall model was then used to examine the distance × race interaction effect. RESULTS Included in analysis were 1,720 white and 531 black men. In the overall cohort the high risk cancer rate increased monotonically with distance to a urologist, including 40% for 0 to 10, 45% for 11 to 20 and 57% for greater than 20 miles. Correspondingly the low risk cancer rate decreased with longer distance. On race stratified multivariate analysis longer distance was associated with higher risk prostate cancer for white and black patients (p = 0.04 and <0.01, respectively) but the effect was larger in the latter group. The distance × race interaction term was significant in the overall model (p = 0.03). CONCLUSIONS Longer distance to a urologist may disproportionally impact black patients. Decreasing modifiable barriers to health care access, such as distance to care, may decrease racial disparities in prostate cancer.

Quality of care received and patient-reported regret in prostate cancer: Analysis of a population-based prospective cohort

Meeting quality of care standards in oncology is recognized as important by physicians, professional organizations, and payers. Data from a population‐based cohort of patients with prostate cancer were used to examine whether receipt of care was consistent with published consensus metrics and whether receiving high‐quality care was associated with less patient‐reported treatment decisional regret.

National study to determine the comfort levels of radiation therapists and medical dosimetrists to report errors.

PURPOSE Better understanding of the error reporting culture in radiation oncology treatment facilities, and obstacles to reporting, can provide insight into potential areas for improvement. We conducted a survey of radiation therapists and dosimetrists to examine the error reporting cultures in radiation oncology facilities across the United States and staff comfort in reporting errors. METHODS AND MATERIALS In 2011, a national sample of 1500 radiation therapists and 528 dosimetrists was mailed a 27-item survey assessing perceptions regarding communication among staff, comfort in error reporting, and associated obstacles. Survey results were summarized using descriptive statistics, and factors associated with discomfort with error reporting analyzed using multivariate logistic regression. RESULTS A total of 356 radiation therapists from 47 states (24% response rate) and 190 dosimetrists from 35 states (36% response rate) responded to the survey. Almost all (87% of therapists and 88% of dosimetrists) reported that there is an error reporting system in their treatment facility. Most feel that communication between them and physicians and dosimetrists or physicists (81% and 88% of therapists, and 89% and 88% of dosimetrists, respectively) is good, but only 65% of therapists and 66% of dosimetrists agree that communication with administrators is good. Obstacles to reporting errors included hierarchy within the treatment facility, poor communication, and fear of reprimand. On multivariate analysis, previous personal reprimand for reporting errors (odds ratio, 4.13, P = .001) and reprimand of other therapists and dosimetrists (odds ratio, 2.55, P = .03) were significantly associated with discomfort in error reporting. CONCLUSIONS The majority of therapists and dosimetrists feel communication in their treatment facilities is good and that there are systems in place to report errors. A sizable minority reported experience with reprimand for error reporting that significantly reduced their comfort level with reporting errors. Obstacles identified in this study represent opportunities for future research and potential ways for improvement in radiation oncology treatment facilities.

Is primary prostate cancer treatment influenced by likelihood of extraprostatic disease? A surveillance, epidemiology and end results patterns of care study

PURPOSE To examine the patterns of primary treatment in a recent population-based cohort of prostate cancer patients, stratified by the likelihood of extraprostatic cancer as predicted by disease characteristics available at diagnosis. METHODS AND MATERIALS A total of 157,371 patients diagnosed from 2004 to 2008 with clinically localized and potentially curable (node-negative, nonmetastatic) prostate cancer, who have complete information on prostate-specific antigen, Gleason score, and clinical stage, were included. Patients with clinical T1/T2 disease were grouped into categories of <25%, 25%-50%, and >50% likelihood of having extraprostatic disease using the Partin nomogram. Clinical T3/T4 patients were examined separately as the highest-risk group. Logistic regression was used to examine the association between patient group and receipt of each primary treatment, adjusting for age, race, year of diagnosis, marital status, Surveillance, Epidemiology and End Results database region, and county-level education. Separate models were constructed for primary surgery, external-beam radiotherapy (RT), and conservative management. RESULTS On multivariable analysis, increasing likelihood of extraprostatic disease was significantly associated with increasing use of RT and decreased conservative management. Use of surgery also increased. Patients with >50% likelihood of extraprostatic cancer had almost twice the odds of receiving prostatectomy as those with <25% likelihood, and T3-T4 patients had 18% higher odds. Prostatectomy use increased in recent years. Patients aged 76-80 years were likely to be managed conservatively, even those with a >50% likelihood of extraprostatic cancer (34%) and clinical T3-T4 disease (24%). The proportion of patients who received prostatectomy or conservative management was approximately 50% or slightly higher in all groups. CONCLUSIONS There may be underutilization of RT in older prostate cancer patients and those with likely extraprostatic disease. Because more than half of prostate cancer patients do not consult with a radiation oncologist, a multidisciplinary consultation may affect the treatment decision-making process.

Impact of timing of radiotherapy in patients with newly diagnosed glioblastoma

OBJECTIVE To further evaluate if a delay in the start of radiation therapy (RT) affects patient outcomes for glioblastoma (GBM). PATIENTS AND METHODS From May 1999 to May 2010, a total of 161 patients underwent surgery followed by RT for GBM. We assessed overall survival (OS) and progression free survival (PFS), stratified by extent of surgical resection. Included in the analysis were genomic predictors of progression. RESULTS Median time from surgery to start of RT was 20days for biopsy alone, 28days for subtotal resection (STR) and 28days for gross total resection (GTR). For all patients, a delay >28days did not result in a difference in PFS when compared to no delay (6.7 vs. 6.9 months, p=0.07). PFS was improved in biopsy or STR patients with a >28day delay to start of RT (4.2 vs. 6.7 months, p=0.006). OS was also improved in patients receiving biopsy or STR with a >28day delay to start of RT (12.3 vs. 7.8 months, p=0.005). Multivariable analysis (MVA) demonstrated an improvement in OS and PFS with time to RT >28days for biopsy or STR patients (HR 0.52 p=0.008 and HR 0.48 p=0.02, respectively). CONCLUSION In this retrospective review of GBM patients treated at a single institution, OS and PFS were not different between time to RT >28days compared to <28 days. There was a modest improvement in both PFS and OS in patients who received biopsy or STR with time to RT >28 days.

Acute Mania Associated With Levetiracetam Treatment

Levetiracetamisanovelantiepilepticdrugusedfor the treatment of partial and generalized epilepsy. Its mechanism of action is unclear, though it is thought to bind to a presynaptic vesicle protein that ultimately reduces the synaptic release of glutamate, impeding conduction of epileptic action potentials across the synapse. 1 Levetiracetam is frequently used owing to its ease of oral administration, excellent bioavailability, and low rate of drug interactions as it is not metabolized by the liver or bound significantly to serum proteins. 2,3 Adverse cognitive effects are atypical; however, adverse effects in the central nervous system (CNS) are relatively common, with behavioral symptoms occurring in up to 16% of patients in randomized controlled trials. 4 Frequently reported behavioral symptoms include depression, hostility, agitation, emotional lability, anger, nervousness, and depersonalization. Nonbehavioral CNS effects include sedation,headache,andasthenia. 5 Psychosisisinfrequently associated with levetiracetam, occurring in approximately 1% of patients, but well described in multiple case reports. 6,7 Researchers have explored the use of levetiracetam as a mood stabilizer for treatment of both depressive and manic phases of bipolar disorder with mixed results. 8–10 Despite the known association between levetiracetam and aggression and irritability, there are no reported cases in the literature of levetiracetam precipitating manic symptoms. In the following case report, we describe the acute onset of mania after levetiracetam therapy in a woman with no history of mania or hypomania.

Adoption of Stereotactic Body Radiotherapy for Stage IA Non–Small Cell Lung Cancer Across the United States

Abstract Background Stereotactic body radiotherapy (SBRT) is a treatment option for stage I non–small cell lung cancer (NSCLC), providing a potentially curative therapy for patients who are nonsurgical candidates. This study describes the adoption of SBRT vs other treatment options across the United States, as well as commonly used dose-fractionation regimens. Methods We analyzed patients in the National Cancer Data Base. A total of 107 233 stage IA NSCLC patients diagnosed from 2008 to 2013 were included. We described the proportions of patients who received different surgical and radiation treatment options by year. A multivariable model was constructed to assess factors associated with patients receiving SBRT. In patients who received SBRT, we described the proportion of patients who received common dose/fractionation regimens. Results Use of SBRT increased from 6.7% to 16.3% from 2008 to 2013, with a corresponding decrease in lobectomy/pneumonectomy (49.5% to 43.7%). The rates of wedge resection, conventional radiotherapy, and no treatment remained relatively constant. Adoption of SBRT was lowest in small community centers (8.6% of patients by 2013). On multivariable analysis, older age and treatment at larger centers were associated with higher SBRT receipt, and black race and higher comorbidity were associated with lower SBRT receipt. There was statistically significant geographic variation. Common SBRT schemes were 10 Gy × 5 (19%), 18–20 Gy × 3 (31%), and 12 Gy × 4 (16%). Conclusions SBRT adoption has been modest over time and has not substantially replaced less curative treatments. Lack of access to this technology in smaller cancer centers may have partly contributed to the slow adoption.

Comparative effectiveness of intensity modulated radiation therapy (IMRT), proton therapy (PT), and conformal radiation therapy (CRT) in the treatment of localized prostate cancer.

3 Background: Comparative effectiveness research is urgently needed in prostate cancer because of the rapid adoption of newer and costlier radiation treatments such as IMRT and PT despite limited demonstrated benefit compared to prior technologies. We compared the morbidity and disease control outcomes of IMRT, PT and the older CRT for primary prostate cancer treatment. METHODS Population-based study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2000 through 2009 for patients with non-metastatic prostate cancer. Propensity score adjustment was used to balance demographic, disease and institutional characteristics. Rates of morbidity (gastrointestinal, urinary, erectile dysfunction, hip fractures) and additional cancer therapy (surrogate for recurrence) were calculated. RESULTS IMRT use increased from 0.15% in 2000 to 95.9% in 2008. In propensity score-adjusted analyses, men who received IMRT vs. CRT were less likely to be diagnosed with GI morbidity (13.4 vs. 14.7 per 100 person-years, p<0.001) and hip fractures (0.8 vs. 1.0, p=0.006), but more likely to be diagnosed with erectile dysfunction (5.9 vs. 5.3, p=0.006). IMRT patients were less likely to receive additional cancer therapy (2.5 vs. 3.1, p<0.001). In a propensity-score matched comparison between PT and IMRT, PT patients had a higher rate of GI morbidity (17.8 vs. 12.2 per 100 person-years, p<.001). No significant differences in rates of other morbidities or additional therapies between PT and IMRT. CONCLUSIONS IMRT vs. CRT was associated with less GI morbidity and hip fractures, more erectile dysfunction, and less need for additional cancer therapy. This large-scale population-based study is the first to suggest a simultaneous reduction in disease recurrence and morbidity in patients treated with IMRT vs. CRT for localized prostate cancer. Proton therapy did not significantly improve outcomes compared to IMRT, but had increased GI morbidity. These results provide new and long-needed information to decision-makers regarding the currently available evidence on the comparative effectiveness of different RT techniques.

Racial Disparities in Time From Diagnosis to Treatment for Stage I Non–Small Cell Lung Cancer

Abstract Background Delay in lung cancer treatment is associated with worse survival outcomes. We examined whether there are racial disparities in time from diagnosis to treatment initiation for stage I non–small cell lung cancer (NSCLC) using data from the National Cancer Data Base, which includes approximately 70% of incident cancer patients across the United States. Methods We analyzed 119 184 patients diagnosed with stage I NSCLC from 2008 to 2013. Median times (in days) from diagnosis to treatment initiation for external beam radiation (EBRT), stereotactic body radiotherapy (SBRT), and surgery (inclusive of wedge resection, lobectomy, and pneumonectomy) were calculated separately and compared among white vs African American (AA) patients using the Wilcoxon rank-sum test. Multivariable linear regression assessed racial differences in days to treatment while adjusting for sex, age, insurance status, regional income, Charlson-Deyo comorbidity score, region, facility type, and treatment. Statistical tests were two-sided. Results AA patients had a statistically significantly longer median time to treatment for all three treatment modalities: EBRT 54 days (AA) vs 48 days (white, P < .001); SBRT 66 days vs 55 days (P < .001); surgery 31 vs 26 days (P < .001). In addition, 34% AA vs 24% white patients (P ≤ .001) had treatment initiation eight or more weeks after diagnosis. In multivariable analysis, AA patients experienced an average 8.2-day delay compared with white patients (P < .001). Conclusions These results shed light on one possible mechanism of the observed racial disparity in mortality outcomes in NSCLC. Future studies are needed to determine if interventions to reduce treatment delays can reduce racial disparities in this disease.