David J. Sher

Ambient Pollution and Blood Pressure in Cardiac Rehabilitation Patients

Background—Multiple studies have demonstrated a consistent association between ambient particulate air pollution and increased risk of hospital admissions and deaths for cardiovascular causes. We investigated the associations between fine particulate pollution (PM2.5) and blood pressure during 631 repeated visits for cardiac rehabilitation in 62 Boston residents with cardiovascular disease. Methods and Results—Blood pressure, cardiac risk factor, and exercise data were abstracted from records of rehabilitation visits between 1999 and 2001. We applied mixed-effect models, controlling for body mass index, age, gender, number of visits, hour of day, and weather variables. For an increase from the 10th to the 90th percentile in mean PM2.5 level during the 5 days before the visit (10.5 &mgr;g/m3), there was a 2.8-mm Hg (95% CI, 0.1 to 5.5) increase in resting systolic, a 2.7-mm Hg (95% CI, 1.2 to 4.3) increase in resting diastolic, and a 2.7-mm Hg (95% CI, 1.0 to 4.5) increase in resting mean arterial blood pressure. The mean PM2.5 level during the 2 preceding days (13.9 &mgr;g/m3) was associated with a 7.0-mm Hg (95% CI, 2.3 to 12.1) increase in diastolic and a 4.7-mm Hg (95% CI, 0.5 to 9.1) increase in mean arterial blood pressure during exercise in persons with resting heart rate ≥70 bpm, but it was not associated with an increase in blood pressure during exercise in persons with heart rate <70 bpm. Conclusions—In patients with preexisting cardiac disease, particle pollution may contribute to increased risk of cardiac morbidity and mortality through short-term increases in systemic arterial vascular narrowing, as manifested by increased peripheral blood pressure.

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

PURPOSEnThe 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.nnnMETHODS AND MATERIALSnTen 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.nnnRESULTSnWe 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).nnnCONCLUSIONSnIn 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.

Efficacy and Toxicity of Reirradiation Using Intensity-Modulated Radiotherapy for Recurrent or Second Primary Head and Neck Cancer

Patients with locally recurrent squamous cell cancer of the head and neck (SCCHN) are reported to have a poor prognosis and limited therapeutic options. Optimal management is selectively applied and morbid. Both surgical resection and chemoradiotherapy are reported to result in median survivals of approximately 12 months. Intensity‐modulated radiotherapy (IMRT) is a highly conformal approach for delivering RT. This study reported the experience of the Dana‐Farber Cancer Institute (DFCI) with IMRT‐based chemoradiotherapy with or without surgery for locally recurrent SCCHN.

PARTIAL-BREAST IRRADIATION VERSUS WHOLE-BREAST IRRADIATION FOR EARLY-STAGE BREAST CANCER: A COST-EFFECTIVENESS ANALYSIS

PURPOSEnAccelerated partial-breast irradiation (PBI) is a new treatment paradigm for patients with early-stage breast cancer. Although PBI may lead to greater local recurrence rates, it may be cost-effective because of better tolerability and lower cost. We aim to determine the incremental cost-effectiveness of PBI compared with whole-breast radiation therapy (WBRT) for estrogen receptor-positive postmenopausal women treated for early-stage breast cancer.nnnMETHODS AND MATERIALSnWe developed a Markov model to describe health states in the 15 years after radiotherapy for early-stage breast cancer. External beam (EB) and MammoSite (MS) PBI were considered and assumed to be equally effective, but carried different costs. Patients received tamoxifen, but not chemotherapy. Utilities, recurrence risks, and costs were adapted from the literature; the baseline utility for no disease after radiotherapy was set at 0.92. Probabilistic sensitivity analyses were performed to model uncertainty in the PBI hazard ratio, recurrence pattern, and patient utilities. Costs (in 2004 US dollars) and quality-adjusted life-years were discounted at 3%/y.nnnRESULTSnThe incremental cost-effectiveness ratio for WBRT compared with EB-PBI was

Cost-effectiveness of CT and PET-CT for determining the need for adjuvant neck dissection in locally advanced head and neck cancer

630,000/quality-adjusted life-year; WBRT strongly dominated MS-PBI. One-way sensitivity analysis found that results were sensitive to PBI hazard ratio, recurrence pattern, baseline recurrence risk, and no evidence of disease PBI utility values. Probabilistic sensitivity showed that EB-PBI was the most cost-effective technique over a wide range of assumptions and societal willingness-to-pay values.nnnCONCLUSIONSnEB-PBI was the most cost-effective strategy for postmenopausal women with early-stage breast cancer. Unless the quality of life after MS-PBI proves to be superior, it is unlikely to be cost-effective.

Relationship between serum adiponectin and prostate cancer grade

BACKGROUNDnPatients with node-positive head and neck squamous cell carcinomas (HNC) have a significant risk of residual disease (RD) in the neck after treatment, despite optimal chemoradiotherapy (CRT). Adjuvant neck dissection (ND) after CRT has been considered standard treatment, but its morbidity has led investigators to consider using post-CRT imaging to determine the need for surgery. We analyzed the cost-effectiveness of computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) as predictors of the need for ND compared with ND for all patients.nnnMATERIALS AND METHODSnWe developed a Markov model to describe health states in the 5 years after CRT for HNC in a 50-year-old man. We compared three strategies: dissect all patients, dissect patients with RD on CT, and dissect patients with RD on PET-CT. Probabilistic sensitivity analyses were carried out to model uncertainty in PET-CT performance, up-front and salvage dissection costs, and patient utilities.nnnRESULTSnND only for patients with RD on PET-CT was the dominant strategy over a wide range of realistic and exaggerated assumptions. Probabilistic sensitivity analyses confirmed that the PET-CT strategy was almost certainly cost-effective at a societal willingness-to-pay threshold of

Absence of Relationship Between Steroid Hormone Levels and Prostate Cancer Tumor Grade

500,000/quality-adjusted life year.nnnCONCLUSIONnAdjuvant ND reserved for patients with RD on PET-CT is the dominant and cost-effective strategy.

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

Obesity is associated with prostate cancer (PCA) grade, but the mechanism behind this relationship is not understood. Adiponectin is an adipokine that has been linked with the development of hormonally sensitive carcinomas, including prostate cancer. We evaluated the relationship between serum adiponectin and Gleason score (GS) in a prospective series of patients seen in a single institution.

The added value of concurrently administered temozolomide versus adjuvant temozolomide alone in newly diagnosed glioblastoma.

OBJECTIVESnTo analyze the relationship between plasma testosterone and estradiol levels on prostate biopsy and radical prostatectomy Gleason scores in a cohort of patients with newly diagnosed prostate cancer.nnnMETHODSnPatients with prostate cancer evaluated at the Dana-Farber Cancer Institute from 2001 to 2005 who were enrolled in a prospective sample banking protocol were eligible for this study. Stored plasma was processed for total testosterone, total estradiol, and sex hormone-binding globulin levels using enzyme-linked immunosorbent assays. The frequency of high-grade biopsy and radical prostatectomy Gleason scores (>6) was the primary endpoint. Univariate and multivariate logistic regression analyses were performed to determine the relationship between the hormone levels and high-grade Gleason scores while adjusting for sex hormone-binding globulin, age, body mass index, and prostate-specific antigen.nnnRESULTSnA total of 539 patients were included in this study, 199 of whom underwent radical prostatectomy. The median prostate-specific antigen level was 5.1 ng/dL, and 67% of the cancers were not palpable. The Gleason score was 2-6, 7, and 8-10 in 53%, 37%, and 10% of the cancers, respectively. On univariate analysis of the high-grade biopsy and radical prostatectomy Gleason score, the total testosterone, total estradiol, and estradiol-to-testosterone ratio were not significant as continuous or categorical variables. Adjusting these results for sex hormone-binding globulin level, body mass index, age, and prostate-specific antigen level did not change the conclusions, and these results were unchanged when categorizing high-grade prostate cancer as Gleason score 8-10.nnnCONCLUSIONSnNo relationship was found between the circulating steroid hormone levels and the Gleason score in this cohort.

Cost-effectiveness studies in radiation therapy

PURPOSEnThe 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).nnnMETHODS AND MATERIALSnUsing 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.nnnRESULTSnThree 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.nnnCONCLUSIONSnThe 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.