Publications by authors named "Kara Lynne Leonard"

9 Publications

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New Cardiac Abnormalities After Radiotherapy in Breast Cancer Patients Treated With Trastuzumab.

Clin Breast Cancer 2020 06 19;20(3):246-252. Epub 2019 Dec 19.

Department of Radiation Oncology, Rhode Island Hospital, Providence, RI.

Purpose: To evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients.

Patients And Methods: All patients treated with trastuzumab and radiotherapy for breast cancer between 2006 and 2014 with available cardiac imaging (echocardiogram or multigated acquisition scan) were retrospectively analyzed. Cardiac abnormalities included myocardial abnormalities (atrial or ventricular dilation, hypertrophy, hypokinesis, and impaired relaxation), decreased ejection fraction > 10%, and valvular abnormalities (thickening or stenosis of the valve leaflets). Breast laterality (left vs. right) and heart radiation dose volume parameters were analyzed for association with cardiac imaging abnormalities.

Results: A total of 110 patients with 57 left- and 53 right-sided breast cancers were evaluated. Overall, 37 patients (33.6%) developed a new cardiac abnormality. Left-sided radiotherapy was associated with an increase in new cardiac abnormalities (relative risk [RR] = 2.51; 95% confidence interval [CI], 1.34-4.67; P = .002). Both myocardial and valvular abnormalities were associated with left-sided radiotherapy (myocardial: RR = 2.21; 95% CI, 1.06-4.60; P = .029; valvular: RR = 3.30; 95% CI, 0.98-10.9; P = .044). There was no significant difference in decreased ejection fraction between left- and right-sided radiotherapy (9.6% vs. 2.1%; P = .207). A mean heart dose > 2 Gy as well as volume of the heart receiving 20 Gy (V20), V30, and V40 correlated with cardiac abnormalities (mean heart dose > 2 Gy: RR = 2.00; P = .040).

Conclusion: New cardiac abnormalities, including myocardial and valvular dysfunction, are common after trastuzumab and radiotherapy. The incidence of new abnormalities correlates with tumor laterality and cardiac radiation dose exposure. Long-term follow-up is needed to understand the clinical significance of these early imaging abnormalities.
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June 2020

Tolerability of ADXS11-001 Lm-LLO Listeria-Based Immunotherapy With Mitomycin, Fluorouracil, and Radiation for Anal Cancer.

Int J Radiat Oncol Biol Phys 2018 04 31;100(5):1175-1178. Epub 2018 Jan 31.

The Department of Medicine, The Brown University Oncology Research Group, Providence, Rhode Island.

Purpose: To obtain safety and preliminary efficacy data of the combination of ADXS11-001, live attenuated Listeria monocytogenes bacterium, with mitomycin, 5-fluorouracil (5-FU), and intensity modulated radiation therapy in locally advanced anal cancer.

Patients And Methods: Eligibility included patients with previously untreated, nonmetastatic anal cancer with a primary tumor >4 cm or node-positive disease. Patients received 2 cycles of mitomycin and 5-FU concurrent with 54.0 Gy intensity modulated radiation therapy. One intravenous dose of ADXS11-001 (1 × 10 colony-forming units) was administered before chemoradiation; 3 additional monthly doses were given after chemoradiation.

Results: Ten patients were treated, including 1 with N2 and 4 with N3 disease. Two patients had grade 3 acute toxicities after the initial dose of ADXS11-001, including chills/rigors (n = 2), back pain (n = 1), and hyponatremia (n = 1). All ADXS11-001 toxicities occurred within 24 hours of administration. There was no apparent increase in chemoradiation toxicities or myelosuppression. One patient had a grade 5 cardiopulmonary event shortly after beginning 5-FU treatment. All 9 assessable patients had complete clinical responses by sigmoidoscopy. Eight of 9 patients (89%) are progression-free at a median follow-up of 42 months.

Conclusions: Preliminary data show that ADXS11-001 can be safely administered with standard chemoradiation for anal cancer. Further studies of listeria-based immunotherapy with radiation are warranted.
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April 2018

Genomic Assays and Individualized Treatment of Ductal Carcinoma In Situ in the Era of Value-Based Cancer Care.

J Clin Oncol 2016 11 31;34(33):3953-3955. Epub 2016 Oct 31.

Kara-Lynne Leonard and David E. Wazer, Alpert Medical School of Brown University, Providence, RI.

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November 2016

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study.

Int J Radiat Oncol Biol Phys 2016 12 31;96(5):1021-1027. Epub 2016 Aug 31.

Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts.

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD).

Methods And Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated.

Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively.

Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.
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December 2016

Prescription dose evaluation for APBI with noninvasive image-guided breast brachytherapy using equivalent uniform dose.

Brachytherapy 2015 Jul-Aug;14(4):496-501. Epub 2015 Apr 18.

Department of Radiation Oncology, Rhode Island Hospital, Brown Alpert Medical School, Providence, RI; Department of Radiation Oncology, Tufts Medical Center, Boston, MA; Department of Radiation Oncology, Tufts University School of Medicine, Boston, MA.

Purpose: Noninvasive image-guided breast brachytherapy (NIBB) is an attractive novel approach to deliver accelerated partial breast irradiation (APBI). Calculations of equivalent uniform dose (EUD) were performed to identify the appropriate APBI dose for this technique.

Methods And Materials: APBI plans were developed for 15 patients: five with three-dimensional conformal APBI (3D-CRT), five with multi-lumen intracavitary balloons (m-IBB), and five simulating NIBB treatment. Prescription doses of 34.0 and 38.5 Gy were delivered in 10 fractions for m-IBB and 3D-CRT, respectively. Prescription doses ranging from 34.0 to 38.5 Gy were considered for NIBB. Dose-volume histogram data from all 3D-CRT, m-IBB, and NIBB plans were used to calculate the biologically effective EUD and corresponding EUD to the PTV_eval using the following equation: EUD = EUBED/(n [1 + EUD/α/β]). An α/β value of 4.6 Gy was assumed for breast tumor. EUD for varying NIBB prescription doses were compared with EUD values for the other APBI techniques.

Results: Mean PTV_eval volume was largest for 3D-CRT (372.9 cm(3)) and was similar for NIBB and m-IBB (88.7 and 87.2 cm(3), respectively). The EUD value obtained by prescribing 38.5 Gy with 3D-CRT APBI was 38.6 Gy. The EUD value of 34.0 Gy prescribed with m-IBB was 34.4 Gy. EUD values for NIBB ranged from 33.9 to 38.2 Gy for prescription doses ranging from 34.0 to 38.5 Gy.

Conclusions: Using EUD calculations to compare APBI techniques and treatment doses, a prescription dose of 36.0 Gy in 10 fractions using NIBB has a comparable biologic equivalent dose to other established brachytherapy techniques.
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February 2016

Breast boost using noninvasive image-guided breast brachytherapy vs. external beam: a 2:1 matched-pair analysis.

Clin Breast Cancer 2013 Dec 4;13(6):455-9. Epub 2013 Oct 4.

Department of Radiation Oncology, Rhode Island Hospital, Brown Alpert Medical School, Providence, RI; Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA. Electronic address:

Background: To compare clinical outcomes and toxicity in patients treated with NIBB boost with those in patients treated with external beam (EB) boost.

Patients And Methods: Women with early stage breast cancer treated with WBI and NIBB boost were identified. Control subjects treated with EB boost identified as the best possible match with respect to age, stage, chemotherapy use, and fractionation were chosen for a 2:1 comparison. Acute toxicity, late toxicity, and oncologic outcomes were reviewed. The McNemar nonparametric test was used to evaluate marginal homogeneity between matched pairs.

Results: One hundred forty-one patients were included in the analysis: 47 patients treated with NIBB boost and 94 matched control subjects treated with EB boost (electron, n = 93) or 3-D conformal radiation (n = 1). Grade 2+ desquamation developed in 18 patients (39%) treated with NIBB boost and in 49 patients (52%) treated with EB boost (P = .07). Breast size, electron energy, and fractionation predicted for acute desquamation (P < .0001, P < .001, and P = .006). Median follow-up was 13.6 months. One patient (2%) who received NIBB had Grade 2+ skin/subcutaneous fibrosis 15 months after completion of treatment. Among those treated with EB, 9 patients (9.5%) developed Grade 2+ subcutaneous fibrosis, and 1 patient had recurrent cellulitis. There was statistically significantly less combined skin/subcutaneous toxicity in those treated with NIBB than in those treated with EB (P = .046).

Conclusion: NIBB boost is associated with favorable short-term clinical outcomes compared with EB.
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December 2013

The effect of dose-volume parameters and interfraction interval on cosmetic outcome and toxicity after 3-dimensional conformal accelerated partial breast irradiation.

Int J Radiat Oncol Biol Phys 2013 Mar 4;85(3):623-9. Epub 2012 Aug 4.

Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts, USA.

Purpose: To evaluate dose-volume parameters and the interfraction interval (IFI) as they relate to cosmetic outcome and normal tissue effects of 3-dimensional conformal radiation therapy (3D-CRT) for accelerated partial breast irradiation (APBI).

Methods And Materials: Eighty patients were treated by the use of 3D-CRT to deliver APBI at our institutions from 2003-2010 in strict accordance with the specified dose-volume constraints outlined in the National Surgical Adjuvant Breast and Bowel Project B39/Radiation Therapy Oncology Group 0413 (NSABP-B39/RTOG 0413) protocol. The prescribed dose was 38.5 Gy in 10 fractions delivered twice daily. Patients underwent follow-up with assessment for recurrence, late toxicity, and overall cosmetic outcome. Tests for association between toxicity endpoints and dosimetric parameters were performed with the chi-square test. Univariate logistic regression was used to evaluate the association of interfraction interval (IFI) with these outcomes.

Results: At a median follow-up time of 32 months, grade 2-4 and grade 3-4 subcutaneous fibrosis occurred in 31% and 7.5% of patients, respectively. Subcutaneous fibrosis improved in 5 patients (6%) with extended follow-up. Fat necrosis developed in 11% of women, and cosmetic outcome was fair/poor in 19%. The relative volume of breast tissue receiving 5%, 20%, 50%, 80%, and 100% (V5-V100) of the prescribed dose was associated with risk of subcutaneous fibrosis, and the volume receiving 50%, 80%, and 100% (V50-V100) was associated with fair/poor cosmesis. The mean IFI was 6.9 hours, and the minimum IFI was 6.2 hours. The mean and minimum IFI values were not significantly associated with late toxicity.

Conclusions: The incidence of moderate to severe late toxicity, particularly subcutaneous fibrosis and fat necrosis and resulting fair/poor cosmesis, remains high with continued follow-up. These toxicity endpoints are associated with several dose-volume parameters. Minimum and mean IFI values were not associated with late toxicity.
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March 2013

Axillary lymph node dose with tangential whole breast radiation in the prone versus supine position: a dosimetric study.

Radiat Oncol 2012 May 18;7:72. Epub 2012 May 18.

Department of Radiation Oncology, Tufts Medical Center, Box #593 800, Washington St, Boston, MA 02111, USA.

Background: Prone breast positioning reduces skin reaction and heart and lung dose, but may also reduce radiation dose to axillary lymph nodes (ALNs).

Methods: Women with early stage breast cancer treated with whole breast irradiation (WBI) in the prone position were identified. Patients treated in the supine position were matched for treating physician, laterality, and fractionation. Ipsilateral breast, tumor bed, and Level I, II, and III ALNs were contoured according to the RTOG breast atlas. Clips marking surgically removed sentinel lymph nodes (SLN)s were contoured. Treatment plans developed for each patient were retrospectively analyzed. V90% and V95% was calculated for each axillary level. When present, dose to axillary surgical clips was calculated.

Results: Treatment plans for 46 women (23 prone and 23 supine) were reviewed. The mean V90% and V95% of ALN Level I was significantly lower for patients treated in the prone position (21% and 14%, respectively) than in the supine position (50% and 37%, respectively) (p < 0.0001 and p < 0.0001, respectively). Generally, Level II & III ALNs received little dose in either position. Sentinel node biopsy clips were all contained within axillary Level I. The mean V95% of SLN clips was 47% for patients treated in the supine position and 0% for patients treated in the prone position (p < 0.0001). Mean V90% to SLN clips was 96% for women treated in the supine position but only 13% for women treated in the prone position.

Conclusions: Standard tangential breast irradiation in the prone position results in substantially reduced dose to the Level I axilla as compared with treatment in the supine position. For women in whom axillary coverage is indicated such as those with positive sentinel lymph node biopsy who do not undergo completion axillary dissection, treatment in the prone position may be inappropriate.
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May 2012

A novel ytterbium-169 brachytherapy source and delivery system for use in conjunction with minimally invasive wedge resection of early-stage lung cancer.

Brachytherapy 2011 Mar-Apr;10(2):163-9. Epub 2010 Aug 12.

Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.

Purpose: To describe a novel source-delivery system for intraoperative brachytherapy in patients with early-stage lung cancer that is readily adaptable to a video-assisted thoracoscopic surgery approach and can be precisely delivered to achieve optimal dose distribution.

Methods And Materials: Radioactive ytterbium-169 ((169)Yb) was sealed within a titanium tube 0.28 mm in diameter and then capped and resealed by titanium wires laser welded to the tube to serve as the legs of a tissue-fastening system. Dose simulations were performed using Monte Carlo computer code (Los Alamos National Laboratory, Los Alamos, NM) to mimic the geometric and elemental compositions of the source, fastening apparatus, and surroundings.

Results: Five test source capsules were subjected to a tensile load to failure. Failure in each capsule occurred in the wire of the fastener leg; there were no weld failures. Monte Carlo simulations and subsequent dose measurement showed the perturbation by the source legs in the deployed (bent over) position to be small (4-5%) for (169)Yb and much less than that for iodine-125 (32%).

Conclusion: We have developed a (169)Yb brachytherapy source-delivery system that can be used in conjunction with commercially available surgical stapling instruments, facilitates the precise placement of brachytherapy sources relative to the surgical margin, assures the seeds remain fixed in their precise position for the duration of the treatment, overcomes the technical difficulties of manipulating the seeds through the narrow surgical incision associated with video-assisted thoracoscopic surgery, and reduces the radiation dose to the clinicians.
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June 2011