Conservative management of Paget disease of the breast with radiotherapy

BACKGROUND At 5-year follow-up, patients with Paget disease of the breast who were treated with breast-conserving surgery (BCS) and radiotherapy (RT) had excellent results. The current report provides 10- and 15-year rates of tumor control in the breast, as well as disease-free and overall survival rates following BCS and RT in a cohort of patients with Paget disease presenting without a palpable mass or mammographic density. METHODS Through a collaborative review of patients treated with BCS and RT from seven institutions, 38 cases of Paget disease of the breast presenting without a palpable mass or mammographic density were identified. All patients had pathologic confirmation of typical Paget cells at time of diagnosis. Thirty-six of 38 patients had a minimum follow-up greater than 12 months and constitute the study cohort. Ninety-four percent of patients underwent complete or partial excision of the nipple-areola complex and all patients received a median external beam irradiation dose of 50 Gy (range, 45–54 Gy) to the whole breast. Ninety-seven percent of patients also received a boost to the remaining nipple or tumor bed, a median total dose of 61.5 Gy (range, 50.4–70 Gy). RESULTS With median follow-up of 113 months (range, 18–257 months), 4 of 36 patients (11%) developed a first recurrence of disease in the treated breast only. Two of the four recurrences in the breast were ductal carcinoma in situ (DCIS) only and two were invasive with DCIS. Two additional patients had a recurrence in the breast as a component of first failure. Actuarial local control rates for the breast as the only site of first recurrence were 91% at 5 years (95% confidence interval [CI], 80–100%) and 87% (95% CI, 75–99%) at both 10 and 15 years. Actuarial local control rates for breast recurrence, as a component of first failure, were 91% (95% CI, 80–100%), 83% (95% CI, 69–97%), and 76% (95% CI, 58–94%) at 5, 10, and 15 years, respectively. No clinical factors were identified as significant predictors for breast recurrence. Five-, 10- and 15-year actuarial rates for survival without disease of 97% (95% CI, 90–100%) and 5-, 10-, and 15-year actuarial rates of overall survival of 93% (95% CI, 84–100%) at 5 years and 90% (95% CI, 78–100%) at 10 and 15 years were reported. CONCLUSIONS These data confirm excellent rates of local control, disease-free survial, and overall survival at 10 and 15 years following BCS and RT for Paget disease of the breast. This study continues to support the recommendation of local excision and definitive breast irradiation as an alternative to mastectomy in the treatment of patients with Paget disease presenting without a palpable mass or mammographic density. Cancer 2003;97:2142–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11337Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34369/1/11337_ftp.pd

Core curriculum online lecture series in musculoskeletal imaging: initial results.

ObjectiveTo augment the educational resources available to training programs and trainees in musculoskeletal (MSK) radiology by creating a comprehensive series of Web-based open-access core curriculum lectures.Materials and methodsSpeakers with recognized content and lecturing expertise in MSK radiology were invited to create digitally recorded lecture presentations across a series of 42 core curriculum topics in MSK imaging. Resultant presentation recordings, organized under curriculum subject headings, were archived as open-access video file recordings for online viewing on a dedicated Web page (http://radiologycorelectures.org/msk/). Information regarding the online core curriculum lecture series was distributed to members of the International Skeletal Society, Society of Skeletal Radiology, Society of Chairs of Academic Radiology Departments, and the Association of Program Directors in Radiology. Web page and online lecture utilization data were collected using Google Analytics (Alphabet, Mountain View, CA, USA).ResultsForty-two lectures, by 38 speakers, were recorded, edited and hosted online. Lectures spanned ACGME curriculum categories of musculoskeletal trauma, arthritis, metabolic diseases, marrow, infection, tumors, imaging of internal derangement of joints, congenital disorders, and orthopedic imaging. Online access to the core curriculum lectures was opened on March 4, 2018. As of January 20, 2019, the core curriculum lectures have had 77,573 page views from 34,977 sessions.ConclusionsTo date, the MSK core curriculum lecture series lectures have been widely accessed and viewed. It is envisioned that the initial success of the project will serve to promote ongoing content renewal and expansion to the lecture materials over time

Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Onartuzumab Plus Bevacizumab Versus Placebo Plus Bevacizumab in Patients With Recurrent Glioblastoma: Efficacy, Safety, and Hepatocyte Growth Factor and O(6)-Methylguanine-DNA Methyltransferase Biomarker Analyses

Purpose Bevacizumab regimens are approved for the treatment of recurrent glioblastoma in many countries. Aberrant mesenchymal-epithelial transition factor (MET) expression has been reported in glioblastoma and may contribute to bevacizumab resistance. The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma. Methods At first recurrence after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once every 3 weeks) or Pla + Bev until disease progression. The primary end point was progression-free survival by response assessment in neuro-oncology criteria. Secondary end points were overall survival, objective response rate, duration of response, and safety. Exploratory biomarker analyses correlated efficacy with expression levels of MET ligand hepatocyte growth factor, O6-methylguanine–DNA methyltransferase promoter methylation, and glioblastoma subtype. Results Among 129 patients enrolled (Ona + Bev, n = 64; Pla + Bev, n = 65), baseline characteristics were balanced. The median progression-free survival was 3.9 months for Ona + Bev versus 2.9 months for Pla + Bev (hazard ratio, 1.06; 95% CI, 0.72 to 1.56; P = .7444). The median overall survival was 8.8 months for Ona + Bev and 12.6 months for Pla + Bev (hazard ratio, 1.45; 95% CI, 0.88 to 2.37; P = .1389). Grade ≥ 3 adverse events were reported in 38.5% of patients who received Ona + Bev and 35.9% of patients who received Pla + Bev. Exploratory biomarker analyses suggested that patients with high expression of hepatocyte growth factor or unmethylated O6-methylguanine–DNA methyltransferase may benefit from Ona + Bev. Conclusion There was no evidence of further clinical benefit with the addition of onartuzumab to bevacizumab compared with bevacizumab plus placebo in unselected patients with recurrent glioblastoma in this phase II study; however, further investigation into biomarker subgroups is warranted. </jats:sec