Dosimetric comparison of magnetic resonance-guided radiation therapy, intensity-modulated proton therapy and volumetric-modulated arc therapy for distal esophageal cancer.

Advances in radiotherapy (RT) technologies permit significant decreases in the dose delivered to organs at risk (OARs) for patients with esophageal cancer (EC). Novel RT modalities such as proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT), as well as motion management techniques including breath hold (BH) are expected to further improve the therapeutic ratio. However, to our knowledge, the dosimetric benefits of PBT vs MRgRT vs volumetric-modulated arc therapy (VMAT) have not been directly compared for EC. We performed a retrospective in silico evaluation using the images and datasets of nine distal EC patients who were treated at our institution with a 0.35-Tesla MR linac to 50.4 Gy in 28 fractions in mid-inspiration BH (BH-MRgRT). Comparison free-breathing (FB) intensity-modulated PBT (FB-IMPT) and FB-VMAT plans were retrospectively created using the same prescription dose, target volume coverage goals, and OAR constraints. A 5 mm setup margin was used for all plans. BH-IMPT and BH-VMAT plans were not evaluated as they would not reflect our institutional practice. Planners were blinded to the results of the treatment plans created using different radiation modalities. The primary objective was to compare plan quality, target volume coverage, and OAR doses. All treatment plans met pre-defined target volume coverage and OAR constraints. The median conformity and homogeneity indices between FB-IMPT, BH-MRgRT and FB-VMAT were 1.13, 1.25, and 1.43 (PITV) and 1.04, 1.15, 1.04 (HI), respectively. For FB-IMPT, BH-MRgRT and FB-VMAT the median heart dose metrics were 52.8, 79.3, 146.8 (V30Gy, cc), 35.5, 43.8, 77.5 (V40Gy, cc), 16.9, 16.9, 32.5 (V50Gy, cc) and 6.5, 14.9, 17.3 (mean, Gy), respectively. Lung dose metrics were 8.6, 7.9, 18.5 (V20Gy, %), and 4.3, 6.3, 11.2 (mean, Gy), respectively. The mean liver dose (Gy) was 6.5, 19.6, 22.2 respectively. Both FB-IMPT and BH-MRgRT achieve substantial reductions in heart, lung, and liver dose compared to FB-VMAT. We plan to evaluate dosimetric outcomes across these RT modalities assuming consistent use of BH.

A Multicenter Prospective Trial of Electronic Skin Surface Brachytherapy for Keratinocyte Carcinoma: Early Cosmesis, Quality of Life, and Adverse Events.

PURPOSE: Keratinocyte carcinomas are amenable to many treatments, including radiation therapy (RT). Electronic skin surface brachytherapy (ESSB) enables the precise delivery of radiation without radioisotopes. In this prospective multicenter clinical trial, we characterized early outcomes of ESSB prospectively through both patient- and clinician-reported measures. To corroborate the cosmesis observations, we also assessed patient-reported quality of life (QoL) and adverse events. METHODS AND MATERIALS: Patients ≥60 years old with stage T1N0M0 keratinocyte carcinoma were treated with ESSB. At 2-, 6-, and 12-weeks post-treatment, cosmesis from ESSB was assessed by both the patient and a clinician study investigator as either "good," "fair," or "bad." The Skindex-16 and the Skin Cancer Index (SCI) were used to assess patient QoL before and after treatment. Adverse events were assessed using the Common Toxicity Criteria for Adverse Events, version 4.0. RESULTS: Cosmesis and QoL were collected at 97% (99/102) of possible patient follow-up times. By 12 weeks post-treatment, 93.9% (31/33) of patient-reported and 96.9% (31/32) of clinician-reported cosmesis outcomes were "good." Compared with baseline, total Skindex-16 score significantly deteriorated at 2 weeks post-treatment (10.5 vs 24.5, P <.001), but significantly improved at 6 weeks (10.5 vs 4.7, P = .014) and 12 weeks (10.5 vs 2.1, P = .001) post-treatment. The total SCI score significantly improved from baseline to 6 weeks (78.4 vs 89.0, P = .001) post-treatment. The most frequent adverse events were radiation dermatitis, skin pain, and pruritus. All adverse events resolved to Grade ≤1 by 12 weeks post-treatment. CONCLUSIONS: This prospective, multicenter study demonstrated that ESSB is associated with a high rate of "good" early patient-reported cosmesis and increasing QoL and satisfaction with time. Validated assessments demonstrated a significant improvement in quality of life and resolution of moderate early adverse events by 6 to 12 weeks after treatment and corroborate the observation of favorable cosmesis.

American College of Radiology-American Brachytherapy Society practice parameter for electronically generated low-energy radiation sources.

BACKGROUND: This collaborative practice parameter technical standard has been created between the American College of Radiology and American Brachytherapy Society to guide the usage of electronically generated low energy radiation sources (ELSs). It refers to the use of electronic X-ray sources with peak voltages up to 120 kVp to deliver therapeutic radiation therapy. MAIN FINDINGS: The parameter provides a guideline for utilizing ELS, including patient selection and consent, treatment planning, and delivery processes. The parameter reviews the published clinical data with regard to ELS results in skin, breast, and other cancers. CONCLUSIONS: This technical standard recommends appropriate qualifications of the involved personnel. The parameter reviews the technical issues relating to equipment specifications as well as patient and personnel safety. Regarding suggestions for educational programs with regard to this parameter,it is suggested that the training level for clinicians be equivalent to that for other radiation therapies. It also suggests that ELS must be done using the same standards of quality and safety as those in place for other forms of radiation therapy.

Novel treatment options for nonmelanoma skin cancer: focus on electronic brachytherapy.

Nonmelanoma skin cancer (NMSC) is an increasing health care issue in the United States, significantly affecting quality of life and impacting health care costs. Radiotherapy has a long history in the treatment of NMSC. Shortly after the discovery of X-rays and (226)Radium, physicians cured patients with NMSC using these new treatments. Both X-ray therapy and brachytherapy have evolved over the years, ultimately delivering higher cure rates and lower toxicity. Electronic brachytherapy for NMSC is based on the technical and clinical data obtained from radionuclide skin surface brachytherapy and the small skin surface applicators developed over the past 25 years. The purpose of this review is to introduce electronic brachytherapy in the context of the history, data, and utilization of traditional radiotherapy and brachytherapy.

Complete response of endemic Kaposi sarcoma lesions with high-dose-rate brachytherapy: treatment method, results, and toxicity using skin surface applicators.

PURPOSE: To analyze the clinical outcome of Kaposi sarcoma skin lesions treated with high-dose-rate (HDR) brachytherapy in patients with a minimum of 2 years of followup. METHODS AND MATERIALS: Between February 2006 and July 2008, all patients with Kaposi sarcoma who received (192)Ir HDR brachytherapy using a skin surface applicator were evaluated for clinical response. Responses to treatment and toxicity were scored using standard criteria. RESULTS: Sixteen cases were collected. Treatment was delivered in four to six fractions, over a period of approximately 12 days. The specified dose ranged from 24 to 35Gy. Median followup the lesion was 41.4 months. No lesion was greater than 2cm. All patients had a complete response to treatment, with no evidence of local recurrence or tumor progression. Thirteen lesions developed Grade 1 and two lesions had Grade 2 acute skin reactions. One patient developed late skin changes with telangiectasias and hypopigmentation. CONCLUSIONS: HDR brachytherapy treatment seems to be an effective noninvasive option for patients with small cutaneous Kaposi sarcoma lesions, delivering excellent cosmesis and local control in our small series. Fewer fractions over a shorter period used in our group offer patients more convenience compared with other common regimens. Although HDR is being used more frequently for many surface applications, additional clinical studies with larger numbers of patients and longer followup are needed to confirm the general impression that it is an excellent option for many patients.

Differential effects of carvedilol and metoprolol succinate on plasma norepinephrine release and peak exercise heart rate in subjects with chronic heart failure.

Dosing equivalency of carvedilol and metoprolol remains a debate. Degree of beta 1-blockade is best assessed by blunting of the exercise-induced heart rate. Accordingly, the authors have investigated dosing equivalency by examining baseline and peak exercise heart rates and norepinephrine levels in subjects with chronic heart failure treated with carvedilol or metoprolol. Thirty-seven subjects treated with carvedilol (32.9 +/- 3.5 mg; n = 23) or metoprolol succinate (XL) (96.4 +/- 15.9 mg; n = 14) referred for cardiopulmonary exercise testing were studied prospectively. Carvedilol versus metoprolol XL subjects did not differ with respect to baseline heart rate (73 +/- 2 vs 70 +/- 3 bpm), or baseline plasma norepinephrine levels (597.5 +/- 78.3 vs 602.1 +/- 69.6 pg/mL), P = NS. However, despite similar peak exercise norepinephrine levels (2735.8 +/- 320.1 vs 2403.1 +/- 371.6 pg/mL), heart rate at peak exercise was higher in subjects receiving carvedilol (135 +/- 4 bpm) than those receiving metoprolol XL (117 +/- 6 bpm), P = 0.02. Similar norepinephrine release and more complete beta 1-blockade is observed in well-matched subjects with chronic heart failure treated with a mean daily dose of metoprolol XL 96.4 mg compared with carvedilol 32.9 mg.

Chronotropic incompetence, beta-blockers, and functional capacity in advanced congestive heart failure: time to pace?

BACKGROUND: Chronotropic incompetence (CI) is often seen in subjects with chronic congestive heart failure (CHF). The prevalence of CI, its mechanisms and association with beta-blocker use as well as exercise capacity have not been clearly defined. METHODS AND RESULTS: Cardiopulmonary exercise tolerance testing data for 278 consecutive patients with systolic CHF was analyzed. CI, defined as the inability to reach 80% of maximally predicted heart rate was present in 128 of 278 subjects (46%). The prevalence of CI was highest in those with most impaired exercise capacity (72, 48, and 24% for subjects with a VO(2) of <14.0, 14.0-20.0, and >20.0 ml/kg/min respectively; p=0.001). While subjects with CI had lower peak exercise heart rate (114 vs. 152 bpm), and lower peak VO(2) (15.4 vs. 19.9 ml/kg/min), they were equally likely to be on chronic beta-blocker therapy (74% vs. 71%; p=0.51). Heart rate and norepinephrine (NE) levels were measured during exercise in a separate cohort of 24 subjects with CHF. There was no difference in beta-blocker dose between subjects with and without CI, however, exercise induced NE release and Chronotropic Responsiveness Index, a measure of post-synaptic beta-receptor sensitivity to NE, were lower in subjects with CI (1687+/-911 vs. 2593+/-1451 pg/ml p=0.08; CRI 12.7+/-5.7 vs. 22.1+/-4.7, p=0.002). CONCLUSIONS: CI occurs in >70% of subjects with advanced systolic CHF irrespective of beta-blocker use and is associated with a trend toward impaired NE release, post-synaptic beta-receptor desensitization and reduced exercise capacity.