Outcomes of Metastatic Brain Lesions Treated with Radioactive Cs-131 Seeds after Surgery: Experience from One Institution.

Introduction Brain metastases are common in patients with advanced systemic cancer and often recur despite treatment with surgical resection and radiotherapy. Whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) have significantly improved local control rates but are limited by complications including neurocognitive deficits and radiation necrosis. These risks can be higher in the re-irradiation setting. Brachytherapy may be an alternative method of additional targeted adjuvant radiotherapy with acceptable rates of toxicity. Methods A retrospective chart review of all patients undergoing resection for metastatic brain lesions and permanent low-dose rate Cs-131 brachytherapy was performed for one institution over a 10-year period. All patients had previous radiation therapy already and, after surgery, were followed with imaging every three months. Patient demographics, disease characteristics, intracranial disease, peri- and post-operative complications, and outcomes were recorded. The primary outcome of interest was local tumor recurrence at the site of brachytherapy while secondary outcomes included distant disease progression (within the brain) and complications such as radiation necrosis. Results During the study period, nine cases of individual patients met inclusion criteria. The median preoperative lesion diameter was 3 cm (0.8-4.1). The median overall survival after surgery and brachytherapy was 10.3 months, after excluding two patients who were lost to follow-up. Six of nine patients had no local recurrence, while three patients had development or progression of distant lesions. No patients experienced acute or delayed complications. Conclusion Cs-131 brachytherapy is a promising alternative method for controlling brain metastases after previous radiation interventions and surgical resection. In this case series, there were no incidences of local tumor recurrence or complications such as radiation necrosis.

Evaluating the Effectiveness of Neoadjuvant Chemotherapy in Reducing Mastectomy for Women With Breast Cancer.

BACKGROUND: Neoadjuvant chemotherapy in breast cancer reduced mastectomy rates by 7% to 13% in randomized trials. However, the differential effects for women with different stages, receptor subtypes, and ages are unknown. We compared mastectomy rates in women who did vs did not receive neoadjuvant chemotherapy in 18 patient subgroups. The main objective was to quantify the potential benefit from neoadjuvant chemotherapy in reducing mastectomy rates for each subgroup. METHODS: Our retrospective analysis used data from the National Cancer Data Base, which includes approximately 70% of incident cancers across the United States. Absolute risk reductions for mastectomy were determined for 18 subgroups of clinical stage, receptor subtype, and age group. In each subgroup, propensity score weighting balanced measured covariates between women treated with vs without neoadjuvant chemotherapy. RESULTS: A total of 55 709 patients were analyzed. In clinical stage IIA disease, only patients with human epidermal growth factor receptor 2 (HER2)-positive tumors had reduced mastectomy rates associated with neoadjuvant chemotherapy (age < 60 years, 12%; age ≥ 60 years, 12.6%). For stage IIB cancers, neoadjuvant chemotherapy was associated with an absolute reduction in mastectomy rates of 5.9% in women younger than age 60 years with hormone receptor-positive/HER2- disease, 8.2% to 10.7% for triple-negative disease, and 11.7% to 17.4% for HER2+ disease. For stage IIIA, the reductions in mastectomy rates ranged from 6.6% to 15.9%. CONCLUSIONS: In an analysis of patients treated across the United States, we found that neoadjuvant chemotherapy was associated with a reduction in mastectomy rates to a similar magnitude overall as shown in randomized trials, but this benefit varied widely by patient subgroup. This study provides novel information to help women make informed decisions regarding treatment.

Neoadjuvant Systemic Therapy Use for Younger Patients with Breast Cancer Treated in Different Types of Cancer Centers Across the United States.

BACKGROUND: Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. STUDY DESIGN: Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. RESULTS: Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69-0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74-0.83). CONCLUSIONS: Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment.

Use of stereotactic body radiotherapy for prostate cancer in the United States from 2004 through 2012.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is a newer treatment option for patients with localized prostate cancer. The rates of diffusion of this technology across the United States are unknown. The goal of the current study was to describe the use of SBRT among patients with prostate cancer based on different risk groups (low, intermediate, or high risk) and by type of facility (community cancer program, comprehensive community cancer program, or academic program) in which patients were treated. METHODS: Using the National Cancer Data Base, a national registry that contains approximately 70% of patients with cancer in the United States, the authors identified 274,466 men between the ages of 40 to 80 years who were diagnosed from 2004 to 2012 with localized prostate cancer and received radiation therapy (RT) as their initial treatment. The authors described the prevalence of SBRT use each year, and multivariable analysis was used to examine factors associated with the receipt of SBRT. RESULTS: In 2004, SBRT use was low (<1% in all patient groups), and was observed to increase steadily each year. By 2012, 8.8% of low-risk patients treated at academic centers with RT received SBRT. Uptake of SBRT was highest in patients with low-risk or intermediate-risk disease. Multivariable analysis demonstrated that year of diagnosis, type of center, risk group, and race were all significantly associated with the use of SBRT. CONCLUSIONS: To the authors' knowledge, the current study is the first report of the adoption of SBRT for localized prostate cancer across the United States. Diffusion was noted to be slowest at community cancer programs, reflecting potential barriers of cost or expertise for this new technology. Adoption of SBRT was found to be highest among patients with low-risk or intermediate-risk disease, in accordance with the bulk of patients included in published SBRT studies. Cancer 2016;122:2234-41. © 2016 American Cancer Society.

The role of radiotherapy in node-positive prostate cancer.

Node-positive prostate cancer represents 12% of newly diagnosed prostate cancer cases in the United States; with decreasing use of screening, this proportion is likely to increase. However, very few clinical trials have specifically compared treatment options for this group of patients. Radiotherapy has a potential role as both definitive therapy and adjuvant therapy for node-positive prostate cancer. In regard to definitive treatment, retrospective studies comparing androgen deprivation therapy (ADT) alone vs ADT plus radiotherapy consistently demonstrated better survival associated with radiotherapy. In addition, two secondary analyses of clinical trial data compared radiotherapy alone vs radiotherapy plus ADT in this setting, and showed combination treatment achieved better survival. In terms of adjuvant treatment after prostatectomy in the setting of pathologic node-positive disease, the Eastern Cooperative Oncology Group (ECOG) 3886 trial established ADT as a standard of care. Institutional retrospective studies showed that ADT plus radiotherapy was associated with improved overall survival compared with ADT alone, but an analysis of the population-based Surveillance, Epidemiology and End Results-Medicare linked data did not show a benefit from radiotherapy. Because current management is informed by mostly retrospective studies, clinical trials are needed to more definitively guide treatment decisions for patients with node-positive disease. Off trial, radiotherapy with ADT should be offered to patients with this very aggressive form of prostate cancer.

Radiotherapy for high-risk prostate cancer.

The combination of radiation treatment and long-term androgen deprivation therapy (ADT) has been shown in multiple clinical trials to prolong overall survival in men with high-risk prostate cancer compared with either treatment alone. New radiation technologies enable the safe delivery of high radiation doses that improve cancer control compared with lower radiation doses. Based on the results of multiple randomized trials, clinical practice guidelines for high-risk prostate cancer recommend total radiation doses of at least 75.6 Gy, with long-term (2-3 years) ADT. Ongoing research into hypofractionated radiation treatment, whole-pelvic radiation, and combinations of radiation with novel hormonal agents could further improve cancer control and survival outcomes for patients with high-risk prostate cancer.

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia.

RATIONALE: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized. OBJECTIVES: To use a standard protocol for measuring nNO to establish a disease-specific cutoff value at one site, and then validate at six other sites. METHODS: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. MEASUREMENTS AND MAIN RESULTS: At the lead site, nNO values in PCD (mean ± standard deviation, 20.7 ± 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 ± 118.8; 125.5-867.0 nl/min), asthma (267.8 ± 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 ± 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 ± 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD. CONCLUSIONS: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.