Publications by authors named "Kathryn E Huber"

12 Publications

  • Page 1 of 1

Hippocampal Dosimetry and the Necessity of Hippocampal-Sparing in Gamma Knife Stereotactic Radiosurgery for Extensive Brain Metastases.

Adv Radiat Oncol 2020 Mar-Apr;5(2):180-188. Epub 2019 Oct 30.

Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusettes.

Purpose: To characterize hippocampal dosimetry in Gamma Knife stereotactic radiosurgery (GK-SRS) for extensive brain metastases and evaluate the need for hippocampal-sparing in GK-SRS treatment planning.

Methods And Materials: We reviewed 75 GK-SRS plans for the treatment of 4 to 30 brain metastases generated without consideration of the hippocampi. The mean dose, maximum dose to 100% of the volume (D), maximum dose to 40% of the volume (D), and maximum point dose (D, 0.03 cm) were obtained for the unilateral and bilateral hippocampi and compared between plans with 4 to 9 and ≥10 lesions. The rate at which plans met hippocampal dose constraints (D ≤ 4.21 Gy, D ≤ 4.50 Gy, and D ≤ 6.65 Gy) was compared between groups, and each was examined for risk factors associated with excessive hippocampal dosing. For plans that exceeded constraints, we attempted replanning to spare the hippocampi.

Results: Compared with those for the treatment of 4 to 9 brain metastases, GK-SRS plans with ≥10 lesions were associated with significantly greater median bilateral mean dose (1.0 vs 2.0, = .001), D (0.4 vs 0.8, = .003), D (0.9 vs 1.9, = .001), and D (2.0 vs 4.9, = .0005). These plans also less frequently met hippocampal constraints, with this difference trending toward significance (80% vs 93%; = .1382; odds ratio 0.29; 95% CI, 0.06-1.4). Risk factors for exceeding constraints included greater total disease volume and closer approach of the nearest metastasis to the hippocampi, both of which depended upon the number of metastases present. Seven plans failed to meet constraints and were successfully replanned to spare the hippocampi with minimal increases in treatment time and without compromise to target coverage or conformity.

Conclusions: Patients with extensive brain metastases treated with GK-SRS are at increased risk for excessive hippocampal dosing when ≥10 lesions are present or when lesions are in close proximity to the hippocampi and may benefit from hippocampal-avoidant treatment planning.
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http://dx.doi.org/10.1016/j.adro.2019.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136666PMC
October 2019

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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http://dx.doi.org/10.1016/j.clbc.2019.12.006DOI Listing
June 2020

The Effectiveness of Intraoperative Clip Placement in Improving Radiation Therapy Boost Targeting After Oncoplastic Surgery.

Pract Radiat Oncol 2020 Sep - Oct;10(5):e348-e356. Epub 2019 Dec 19.

Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts. Electronic address:

Purpose: The role of surgical clips as markers of the tumor bed cavity for radiation therapy boost targeting after oncoplastic surgery is not well understood. Therefore, we sought to evaluate whether the placement of surgical clips can reduce interobserver variability in the delineation of the tumor bed cavities of oncoplastic surgery patients and ultimately determine an optimal number of clips to place.

Methods And Materials: We reviewed records of 39 women with breast cancer who underwent oncoplastic breast surgery and adjuvant radiation therapy at our institution. Three radiation oncologists contoured tumor bed cavity volumes on planning computed tomography simulation images. Interobserver variability was measured both by a coefficient of variation of radiation oncologists contour volume and a concordance index defined as the quotient of the intersecting and aggregated volume of the contours. Patients were stratified by the number of surgical clips placed and compared by 1-way analysis of variance. Simple linear regression was used to evaluate the relationship of total excised volume and interobserver variability in patients with a sufficient quantity of surgical clips.

Results: Interobserver variability in the delineation of the tumor bed cavity as measured by concordance index was significantly reduced in patients who received intraoperative surgical clips (F = 5.755; P = .001). A similar trend was seen in contour volume (F = 2.616; P = .052). Results of 1-way analysis of variance and post hoc analysis showed that 4 clips are effective and sufficient for reproducible delineation of the tumor bed cavity for the radiation therapy boost. Increasing excision volume does not result in an increase in interobserver variability (r = 0.00003).

Conclusions: In oncoplastic surgery patients, intraoperative placement of surgical clips is beneficial and effective in improving the delineation of the tumor bed cavity for the radiation therapy boost. Four clips are necessary and sufficient for accurate boost targeting after lumpectomy with oncoplastic reconstruction.
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http://dx.doi.org/10.1016/j.prro.2019.12.005DOI Listing
December 2019

Late complications of radiation therapy for breast cancer: evolution in techniques and risk over time.

Gland Surg 2018 Aug;7(4):371-378

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

Radiation therapy in combination with surgery, chemotherapy, and endocrine therapy as indicated, has led to excellent local and distant control of early stage breast cancers. With the majority of these patients surviving long term, mitigating the probability and severity of late toxicities is vital. Radiation to the breast, with or without additional fields for nodal coverage, has the potential to negatively impact long term cosmetic outcome of the treated breast as well as cause rare, but severe, complications due to incidental dosage to the heart, lungs and contralateral breast. The long-term clinical side-effects of breast radiation have been studied extensively. This review aims to discuss the risk of developing late complications following breast radiation and how modern techniques can be used to diminish these risks.
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http://dx.doi.org/10.21037/gs.2018.01.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107587PMC
August 2018

Capecitabine as a Radiosensitizer in Adjuvant Chemoradiotherapy for Pancreatic Cancer: A Retrospective Study.

Anticancer Res 2015 Dec;35(12):6901-7

Tufts University School of Medicine, Tufts Medical Center, Boston, MA, U.S.A.

Aim: Pancreatic cancer remains one of the deadliest cancer diagnoses and is the fourth leading cause of cancer-related deaths in the U.S. Surgery is the mainstay of treatment for the 20% for whom the tumor is resectable, however, controversy exists over the appropriate adjuvant therapy where local recurrence rates remain strikingly high (50-85%). We aimed to evaluate the safety and efficacy of adding capecitabine (a known radiosensitizer by direct and abscopal effects) to concurrent radiation in the adjuvant setting after resection of pancreatic adenocarcinoma.

Patients And Methods: We conducted a retrospective study of 63 patients diagnosed from 2004-2013 with histopathologically-confirmed stage I/II pancreatic cancer treated with a surgical resection followed by adjuvant concurrent chemoradiation to at least 45 Gy using 3D planning and capecitabine at 1,600 mg/m(2)/day (Monday-Friday) for 6 weeks. This was combined with either 4 months of gemcitabine at 1,000 mg/m(2) weekly for 3 out of 4 weeks or capecitabine at 2,000 mg/m(2) for 14 days every 3 weeks for a total of 4 months.

Results: The majority of patients were over 65 years old (71%), male (60%), had negative surgical margins (79%), had pancreatic head or neck involvement (71%), Eastern Cooperative Oncology Group performance score of 1 (71%), and a cancer antigen 19-9 in the range of 11-100 U/ml at the time of diagnosis (51%). Of the 63 patients reviewed, 61 patients (97%) completed concurrent chemoradiotherapy. Treatment was halted in one patient due to gastritis and a second for gastrointestinal bleeding. Otherwise, adverse reactions during concurrent chemoradiotherapy were well-tolerated and the majority were Common Terminology Criteria for Adverse Events grades 1 and 2. Grade 3 toxicity was anorexia (n=2) and hand and foot syndrome (n=2) and GI bleeding (n=1). The only grade 4 toxicities were anorexia (n=1) and fatigue (n=1). The median follow-up of patients at the time of analysis was 36 months. The median survival of the entire cohort was 23.5 (range=8.5-42) months. The 1-, 2- and 3-year survival rates were 80%, 35% and 25%, respectively.

Conclusion: Concurrent chemoradiation using capecitabine as a radiosensitizer in the adjuvant setting for pancreatic cancer was completed by the vast majority of patients in this series. Treatment was relatively well-tolerated, and its efficacy seems comparable to that for historical controls. This study probably represents the largest yet reported using capecitabine in this setting. Future studies including an increased sample size are required.
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December 2015

Patterns of care of radiation therapy in patients with stage IV rectal cancer: a Surveillance, Epidemiology, and End Results analysis of patients from 2004 to 2009.

Cancer 2014 Mar 13;120(5):731-7. Epub 2013 Nov 13.

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

Background: According to the 2013 National Comprehensive Cancer Network guidelines, pelvic radiation therapy (RT) is one of the preferred regimens for patients with metastatic rectal cancer (mRC). The objective of this study was to analyze patterns of care and outcomes data for the receipt of RT among patients with mRC using the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: Patients with stage IV rectal or rectosigmoid cancer were identified in the SEER database (2004-2009). Patients were stratified according to their primary disease site (rectum vs rectosigmoid), tumor (T) classification, and lymph node (N) classification. Treatment regimens (with or without surgical resection, with or without RT) were recorded. The Fisher exact test was used to compare RT rates based on stratified factors. Two and five-year survival rates were compared among treatment groups.

Results: In total, 6873 patients with stage IV rectal cancer and 3417 patients with rectosigmoid cancer were identified. Overall, 20.5% of patients with rectal cancer underwent surgery alone, whereas 38.7% received RT with or without surgery. Within the rectosigmoid group, 51.4% of patients underwent surgery alone, and 15.1% received RT with or without surgery. The use of RT differed significantly between patients with in situ (Tis) through T2 tumors versus T3/T4 tumors (P < .001) and between those with N0 disease versus N1/N2 disease (P < .001). The 2-year and 5-year survival rates differed between treatment groups, with the highest survival rates observed among those who received combined surgery and RT.

Conclusions: The primary treatments for patients with mRC include RT with or without surgery. RT is used more commonly in patients with primary rectal (vs rectosigmoid) tumors, N0 disease, or Tis-T2 tumors. Treatment with combination surgery and RT is associated with prolonged survival.
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http://dx.doi.org/10.1002/cncr.28467DOI Listing
March 2014

Locally advanced pancreatic cancer. Looking beyond traditional chemotherapy and radiation.

JOP 2013 Jul 10;14(4):337-9. Epub 2013 Jul 10.

Tufts Medical Center. Boston, MA 02111, USA.

About a third of all pancreatic cancer is found to be locally advanced at the time of diagnosis, where the tumor is inoperable but remains localized to the pancreas and regional lymphatics. Sadly, this remains a universally deadly disease with progression to distant disease being the predominant mode of failure and average survival under one year. Optimal treatment of these patients continues to be an area of controversy, with chemotherapy alone being the treatment preference in Europe, and chemotherapy followed by chemoradiation in selected patients, preferred in the USA. The aim of this paper is to summarize the key abstracts presented at the 2013 ASCO Annual Meeting that address evolving approaches to the management of locally advanced pancreatic cancer. The late breaking abstract (#LBA4003) provided additional European data showing non-superiority of chemoradiation compared to chemotherapy in locally advanced pancreatic cancer patients without distant progression following 4 months of chemotherapy. Another late breaking abstract, (#LBA4004), unfortunately showed a promising new complement to gemcitabine and capecitabine using immunotherapy in the form of a T-helper vaccine did not translate to improved survival in the phase III setting.
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http://dx.doi.org/10.6092/1590-8577/1677DOI Listing
July 2013

Locally advanced pancreatic cancer.

JOP 2013 Mar 10;14(2):126-8. Epub 2013 Mar 10.

Second Oncology Clinic, St. Savvas Anticancer Hospital, Athens, Greece.

Treatment of locally advanced pancreatic cancer is palliative, based on chemotherapy and according to response, chemoradiotherapy can be applied. The authors summarize three abstracts (#LBA146, #256 and #303) presented on the 2013 ASCO Gastrointestinal Cancers Symposium, which were focused on treatment of locally advanced pancreatic cancer. A discussion is presented about the different chemotherapy or chemoradiotherapy regimens, that move away from gemcitabine-based treatment, and the effort to find less toxic, but efficient therapeutic combinations.
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http://dx.doi.org/10.6092/1590-8577/1469DOI Listing
March 2013

BEDVH-A method for evaluating biologically effective dose volume histograms: application to eye plaque brachytherapy implants.

Med Phys 2012 Feb;39(2):976-83

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

Purpose: A method is introduced to examine the influence of implant duration T, radionuclide, and radiobiological parameters on the biologically effective dose (BED) throughout the entire volume of regions of interest for episcleral brachytherapy using available radionuclides. This method is employed to evaluate a particular eye plaque brachytherapy implant in a radiobiological context.

Methods: A reference eye geometry and 16 mm COMS eye plaque loaded with (103)Pd, (125)I, or (131)Cs sources were examined with dose distributions accounting for plaque heterogeneities. For a standardized 7 day implant, doses to 90% of the tumor volume ( (TUMOR)D(90)) and 10% of the organ at risk volumes ( (OAR)D(10)) were calculated. The BED equation from Dale and Jones and published α/β and μ parameters were incorporated with dose volume histograms (DVHs) for various T values such as T = 7 days (i.e.,  (TUMOR) (7)BED(10) and  (OAR) (7)BED(10)). By calculating BED throughout the volumes, biologically effective dose volume histograms (BEDVHs) were developed for tumor and OARs. Influence of T, radionuclide choice, and radiobiological parameters on  (TUMOR)BEDVH and  (OAR)BEDVH were examined. The nominal dose was scaled for shorter implants to achieve biological equivalence.

Results:  (TUMOR)D(90) values were 102, 112, and 110 Gy for (103)Pd, (125)I, and (131)Cs, respectively. Corresponding  (TUMOR) (7)BED(10) values were 124, 140, and 138 Gy, respectively. As T decreased from 7 to 0.01 days, the isobiologically effective prescription dose decreased by a factor of three. As expected,  (TUMOR) (7)BEDVH did not significantly change as a function of radionuclide half-life but varied by 10% due to radionuclide dose distribution. Variations in reported radiobiological parameters caused  (TUMOR) (7)BED(10) to deviate by up to 46%. Over the range of (OAR)α/β values,  (OAR) (7)BED(10) varied by up to 41%, 3.1%, and 1.4% for the lens, optic nerve, and lacrimal gland, respectively.

Conclusions: BEDVH permits evaluation of the relative biological effectiveness for brachytherapy implants. For eye plaques,  (TUMOR)BEDVH and  (OAR)BEDVH were sensitive to implant duration, which may be manipulated to affect outcomes.
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http://dx.doi.org/10.1118/1.3679010DOI Listing
February 2012

The implications of breast cancer molecular phenotype for radiation oncology.

Front Oncol 2011 28;1:12. Epub 2011 Jun 28.

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

The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.
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http://dx.doi.org/10.3389/fonc.2011.00012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355956PMC
August 2012

Breast cancer molecular subtypes in patients with locally advanced disease: impact on prognosis, patterns of recurrence, and response to therapy.

Semin Radiat Oncol 2009 Oct;19(4):204-10

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

Gene expression profiling has led to the discovery of 4 distinct molecular subtypes of breast cancer: luminal A, luminal B, basal like, and HER2 enriched. Investigation of these subtypes in women with breast cancer has given insight into the heterogeneous biology and outcomes in patients with locally advanced disease. These subtypes have been found to be predictors for survival, response to systemic therapy, and locoregional recurrence. This review discusses the biology of locally advanced breast cancer and the available data on how molecular subtype may provide information regarding response to treatment and prognosis of women with locally advanced breast cancer.
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http://dx.doi.org/10.1016/j.semradonc.2009.05.004DOI Listing
October 2009

Filamentous phage integration requires the host recombinases XerC and XerD.

Nature 2002 Jun;417(6889):656-9

Division of Geographic Medicine/Infectious Diseases, New England Medical Center and Department of Microbiology, Tufts University School of Medicine and Howard Hughes Medical Institute, 750 Washington Street, Boston, Massachusetts 02111, USA.

Many bacteriophages and animal viruses integrate their genomes into the chromosomal DNA of their hosts as a method of promoting vertical transmission. Phages that integrate in a site-specific fashion encode an integrase enzyme that catalyses recombination between the phage and host genomes. CTX phi is a filamentous bacteriophage that contains the genes encoding cholera toxin, the principal virulence factor of the diarrhoea-causing Gram-negative bacterium Vibrio cholerae. CTX phi integrates into the V. cholerae genome in a site-specific manner; however, the approximately 6.9-kilobase (kb) CTX phi genome does not encode any protein with significant homology to known recombinases. Here we report that XerC and XerD, two chromosome-encoded recombinases that ordinarily function to resolve chromosome dimers at the dif recombination site, are essential for CTX phi integration into the V. cholerae genome. The CTX phi integration site was found to overlap with the dif site of the larger of the two V. cholerae chromosomes. Examination of sequences of the integration sites of other filamentous phages indicates that the XerCD recombinases also mediate the integration of these phage genomes at dif-like sites in various bacterial species.
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http://dx.doi.org/10.1038/nature00782DOI Listing
June 2002