Radiation Dose and Cardiac Risk in Breast Cancer Treatment: An Analysis of Modern Radiotherapy Including Community Settings

Publication date: Available online 20 July 2017
Source:Practical Radiation Oncology
Author(s): Julian C. Hong, Elham Rahimy, Cary P. Gross, Timothy Shafman, Xin Hu, James B. Yu, Rudi Ross, Steven E. Finkelstein, Arie Dosoretz, Henry S. Park, Pamela R. Soulos, Suzanne B. Evans
PurposeAdjuvant radiotherapy (RT) for breast cancer improves outcomes, but prior studies have documented substantive cardiac dose and cardiac risk. We assessed mean heart dose (MHD) of RT, and estimated risk of RT-associated cardiac toxicity in women undergoing adjuvant RT for breast cancer in contemporary (predominantly) community practice.Methods and MaterialsWe identified women with left-sided breast cancer receiving adjuvant RT during 2012 through 2014 from 94 centers across 16 states. We used bivariate analyses and multivariable linear regression to assess associations between RT techniques and MHD. Excess RT-related cardiac risk by age 80 was estimated for women diagnosed at age 60 using previously reported relationship between MHD and cardiac risk.ResultsAmong 1161 women, 77.3% were treated in community practice and with breast-conservation (77.8%). The most common techniques were free-breathing (92.2%), supine (94.8%), and fixed gantry intensity modulated RT (FG-IMRT; 46.9%). Median MHD was 2.76Gy (IQR 1.47–5.03). In multivariable analyses, predicted median MHD with deep inspiration breath hold was 2.41Gy compared to 3.86Gy with free-breathing (p<0.001). Three-dimensional conformal RT (3D–CRT) was associated with lower predicted median MHD (2.78Gy) than FG-IMRT (4.02Gy) or rotational IMRT (R-IMRT, 6.60Gy, p<0.001). For 60-year old women with the median MHD of the study population (2.76Gy) and no cardiovascular risk factors, the 20-year predicted excess risk of death from ischemic heart disease attributable to radiation was 3.5 excess events/1000 patients, in contrast to estimates of 8 events/1000 from prior analyses. The predicted risk of cardiac events varied based on radiation technique, with 4 excess events/1000 with 3D–CRT, 5 excess events/1000 with FG-IMRT, and 8 excess events/1000 with R-IMRT.ConclusionsMHD varies substantially across patients and is influenced by technique in predominantly community settings. Overall risk of cardiac toxicity is modest.SummaryWe assessed mean heart dose of radiotherapy (RT), and estimated risk of RT-associated cardiac toxicity in women undergoing adjuvant RT for left-sided breast cancer in a large contemporary cohort. For 60-year old women without cardiovascular risk factors, the predicted excess risk of death from ischemic heart disease 20years post-radiation was 3.5 excess events/1000 patients, lower than estimates derived in prior studies (8 per 1000). Mean heart dose varied substantially and was influenced by technique.



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Prostate Cancer-Specific PET Radiotracers: A Review on the Clinical Utility in Recurrent Disease

Publication date: Available online 20 July 2017
Source:Practical Radiation Oncology
Author(s): Jaden D. Evans, Krishan R. Jethwa, Piet Ost, Scott Williams, Eugene D. Kwon, Val J. Lowe, Brian J. Davis
Prostate cancer-specific positron emission tomography (pcPET) has been shown to detect sites of disease recurrence at serum prostate specific antigen (PSA) levels that are lower than those levels detected by conventional imaging. Commonly used pcPET radiotracers in the setting of biochemical recurrence are reviewed including C-11/F-18 choline, Ga-68/F-18 PSMA, and F-18 fluciclovine. Review of the literature generally favors PSMA-based agents for the detection of recurrence as a function of low PSA levels. Positive Ga-68/F-18 PSMA PET/CT scans detected potential sites of recurrence in a median 51.5% of patients when PSA level is <1.0ng/mL, 74% of patients when PSA level is 1.0–2.0ng/mL, and 90.5% of patients when PSA level is >2.0ng/mL. Review of C-11/F-18 choline and F-18 fluciclovine data commonly demonstrated lower detection rates for each respective PSA cohort, although with some important caveats, despite having similar operational characteristics to PSMA-based imaging. Sensitive pcPET imaging has provided new insight into the early patterns of disease spread, which has prompted judicious re-consideration of additional local therapy either after prostatectomy, definitive radiotherapy or post-prostatectomy radiotherapy. This review discusses the literature, clinical utility, availability and fundamental understanding of pcPET imaging needed to improve clinical practice.



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Standardization of Nodal Radiation Therapy through Changes to a Breast Cancer Clinical Pathway throughout a Large, Integrated Cancer Center Network

Publication date: Available online 20 July 2017
Source:Practical Radiation Oncology
Author(s): Brian J. Gebhardt, Joel Thomas, Zachary D. Horne, Colin E. Champ, Gretchen M. Ahrendt, Emilia Diego, Dwight E. Heron, Sushil Beriwal
BackgroundStudies demonstrate safety of omitting axillary nodal dissection (ALND) for early-stage breast cancer with positive sentinel lymph node (+SLN) biopsy, though trial designs differed in radiotherapy (RT) fields. Regional nodal irradiation (RNI) was separately shown to improve outcomes in high-risk patients. This led to lack of consensus in RT volumes. Clinical pathways (CP) standardize care where practice varies unnecessarily. We evaluated the impact of changes to a CP guiding post-operative RT in women with +SLNs on practice patterns throughout a network.Methods/MaterialsWe implemented a CP for management of breast cancer with post-operative RT designed to promote uniform nodal treatment. The CP recommended modified tangents (MT) including level I/II nodes for women with micrometastases (pN1mi). For women with macrometastases (pN1a), CP recommended including level I/II LN in MT and a third supraclavicular (SCN) LN +/− internal mammary nodes for women with adverse factors present.ResultsRT fields of 233 women undergoing breast conserving surgery with +SLN but not ALND were retrospectively reviewed: 25% had pN1mi disease, and 75% pN1a. Of 127 women treated before CP changes, 35% with pN1mi and 22% with pN1a were treated with whole-breast irradiation (WBI) alone. Following CP changes, 106 women were treated: 5% with WBI alone, 58% with MT, and 38% with MT+SCN field. Utilization of MT was associated with CP changes. Utilization of a 3rd SCN field was associated with CP changes, pN-Stage, extracapsular extension, and total number of adverse factors.ConclusionCP's translate published data and institutional experience into management plans that promote evidence-based care and eliminate unnecessary practice variations. Recognizing that post-operative RT treatment volumes were heterogeneous, we modified the CP based upon the latest evidence for RNI, after which we found increased compliance and consistency with quality guidelines, which will also aid in tracking outcomes in future investigations.



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Recurrent triploid digynic conceptions and mature ovarian teratomas: Are they different manifestations of the same genetic defect?

Abstract

Miscarriages affect 15% of clinically recognized pregnancies. Recurrent miscarriage (RM) is defined by the occurrence of at least two consecutive pregnancy losses and affects 1% to 5% of couples trying to conceive. In an attempt to categorize patients with RM and identify the mechanisms leading to their miscarriages, we first used flow cytometry to assess the ploidy of 93 products of conception (POCs) from 53 patients with RM (≥ 3 miscarriages). We identified a single patient with four triploid POCs. We then used fluorescent in situ hybridization to confirm the triploidies and fluorescent microsatellite genotyping with distal and pericentromeric markers to determine their parental origin and the mechanisms leading to their formation. We found that all four triploidies were digynic and due to a failure in meiosis II (MII) suggesting a genetic predisposition. Upon further investigation into the family, we found a remarkable history of ovarian cysts and dysfunctions on the maternal side. Notably, one maternal cousin had a mature ovarian teratoma that we analyzed and found an identical mechanism at its origin, a failure in MII. The identification of two patients in the same family with two different manifestations, digynic triploid conceptions and mature ovarian teratomas, both resulting from the failure of MII, suggests an inherited genetic susceptibility towards an error in MII segregating in the family that may manifest in the form of a triploid digynic miscarriage as well as a mature ovarian teratoma. Our findings may facilitate the future identification of causative mutations for MII defects. This article is protected by copyright. All rights reserved.

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Analysis of clinical characteristics and efficacy of chronic myeloid leukemia onset with extreme thrombocytosis in the era of tyrosine kinase inhibitors

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Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer

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Circ-104916 is downregulated in gastric cancer and suppresses migration and invasion of gastric cancer cells

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