Daniel M. Trifiletti

Leukoencephalopathy After Stereotactic Radiosurgery for Brain Metastases

PURPOSEnAlthough the use of stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases has increased dramatically during the past decade to avoid the neurocognitive dysfunction induced by whole brain radiation therapy (WBRT), the cumulative neurocognitive effect of numerous SRS sessions remains unknown. Because leukoencephalopathy is a sensitive marker for radiation-induced central nervous system damage, we studied the clinical and dosimetric predictors of SRS-induced leukoencephalopathy.nnnMETHODS AND MATERIALSnPatients treated at our institution with at least 2 sessions of SRS for brain metastases from 2007 to 2013 were reviewed. The pre- and post-SRS magnetic resonance imaging sequences were reviewed and graded for white matter changes associated with radiation leukoencephalopathy using a previously validated scale. Patient characteristics and SRS dosimetric parameters were reviewed for factors that contributed to leukoencephalopathy using Cox proportional hazards modeling.nnnRESULTSnA total of 103 patients meeting the inclusion criteria were identified. The overall incidence of leukoencephalopathy was 29% at year 1, 38% at year 2, and 53% at year 3. Three factors were associated with radiation-induced leukoencephalopathy: (1) the use of WBRT (P=.019); (2) a higher SRS integral dose to the cranium (P=.036); and (3) the total number of intracranial metastases (P=.003).nnnCONCLUSIONSnOur results have established that WBRT plus SRS produces leukoencephalopathy at a much higher rate than SRS alone. In addition, for patients who did not undergo WBRT before SRS, the integral dose was associated with the development of leukoencephalopathy. As the survival of patients with central nervous system metastases increases and as the neurotoxicity of chemotherapeutic and targeted agents becomes established, these 3 potential risk factors will be important to consider.

Leptomeningeal disease following stereotactic radiosurgery for brain metastases from breast cancer

Leptomeningeal disease (LMD) is a highly aggressive and usually rapidly fatal condition. The purpose of this study is to identify clinical factors that can serve to predict for LMD at the time of stereotactic radiosurgery (SRS) for brain metastases from breast carcinoma. We conducted a retrospective review of patients with brain metastases from breast cancer treated with SRS from 1995 to 2014 at our institution. Clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cerebrospinal fluid (CSF) cytology or MRI demonstrating CSF seeding. Comparative statistical analyses were conducted using Cox proportional hazards regression, binary logistic regression, and/or log-rank test. 126 patients met inclusion criteria. Eighteen patients (14xa0%) developed LMD following SRS. From the time of SRS, the actuarial rate of LMD at 12xa0months from diagnosis of brain metastasis was 9xa0% (11 patients). Active disease in the chest at the time of SRS was associated with development of LMD (pxa0=xa00.038). Factors including receptor status, tumor size, number of intra-axial tumors, cystic tumor morphology, prior WBRT, active bone metastases, and active liver metastases were not significantly associated with the development of LMD. In patients with brain metastasis from breast cancer that undergo SRS, there is a relatively low rate of LMD. We found that while tumor hormonal status, bone metastases, and hepatic metastases were not associated with the development of LMD, active lung metastases at SRS was associated with LMD. Further research may help to delineate a causative relationship between metastatic lung disease and LMD.

Stereotactic radiosurgery in the treatment of brain metastases from gastrointestinal primaries

Brain metastases from gastrointestinal (GI) primary malignancies are generally less common than those arising from other primary locations. Our purpose was to analyze the efficacy of stereotactic radiosurgery (SRS) in the treatment of patients with brain metastases from GI malignancies in the modern radiosurgical and systemic therapy era. A review of patients treated with SRS to brain metastases from GI primaries treated from 1996 to 2015 at our institution was conducted. Clinical, therapeutic, dosimetric and radiographic characteristics were collected and analyzed for an association with brain tumor local control (LC) and overall survival (OS) following SRS using univariate and multivariate (MVA) analyses. 261 brain metastases were identified from 86 patients meeting inclusion criteria. The most common primary location was rectum (nxa0=xa036). LC was 94.1xa0% at last follow up and margin dose ≥20xa0Gy was associated with improved LC on MVA (pxa0=xa00.038). Median OS was 6.2xa0months and was improved with higher performance score and luminal primary location on MVA (pxa0=xa00.002 and 0.015, respectively). Tumor histology, whole brain irradiation, targeted therapies, and antineoplastic therapies were not associated with improved LC or OS on MVA. SRS provides favorable LC of brain metastases of GI origin, and margin doses of at least 20xa0Gy should be considered when clinically appropriate. Compared to non-luminal primaries, patients with brain metastases from a luminal primary demonstrate improved OS.

Parallelized patient-specific quality assurance for high-dose-rate image-guided brachytherapy in an integrated computed tomography–on-rails brachytherapy suite

PURPOSEnTo describe a parallelized patient-specific quality assurance (QA) program designed to ensure safety and quality in image-guided high-dose-rate brachytherapy in an integrated computed tomography (CT)-on-rails brachytherapy suite.nnnMATERIALS AND METHODSnA patient-specific QA program has been modified for the image-guided brachytherapy (IGBT) program in an integrated CT-on-rails brachytherapy suite. In the modification of the QA procedures of Task Group-59, the additional patient-specific QA procedures are included to improve rapid IGBT workflow with applicator placement, imaging, planning, treatment, and applicator removal taking place in one room.nnnRESULTSnThe IGBT workflow is partitioned into two groups of tasks that can be performed in parallel by two or more staff members. One of the unique components of our implemented workflow is that groups work together to perform QA steps in parallel and in series during treatment planning and contouring. Coordinating efforts in this systematic way enable rapid and safe brachytherapy treatment while incorporating 3-dimensional anatomic variations between treatment days.nnnCONCLUSIONSnImplementation of these patient-specific QA procedures in an integrated CT-on-rails brachytherapy suite ensures confidence that a rapid workflow IGBT program can be implemented without sacrificing patient safety or quality and deliver highly-conformal dose to target volumes. These patient-specific QA components may be adapted to other IGBT environments that seek to provide rapid workflow while ensuring quality.

Development of a novel remote-controlled and self-contained audiovisual-aided interactive system for immobilizing claustrophobic patients

In radiotherapy, only a few immobilization systems, such as open‐face mask and head mold with a bite plate, are available for claustrophobic patients with a certain degree of discomfort. The purpose of this study was to develop a remote‐controlled and self‐contained audiovisual (AV)‐aided interactive system with the iPad mini with Retina display for intrafractional motion management in brain/H&N (head and neck) radiotherapy for claustrophobic patients. The self‐contained, AV‐aided interactive system utilized two tablet computers: one for AV‐aided interactive guidance for the subject and the other for remote control by an operator. The tablet for audiovisual guidance traced the motion of a colored marker using the built‐in front‐facing camera, and the remote control tablet at the control room used infrastructure Wi‐Fi networks for real‐time communication with the other tablet. In the evaluation, a programmed QUASAR motion phantom was used to test the temporal and positional accuracy and resolution. Position data were also obtained from ten healthy volunteers with and without guidance to evaluate the reduction of intrafractional head motion in simulations of a claustrophobic brain or H&N case. In the phantom study, the temporal and positional resolution was 24 Hz and 0.2 mm. In the volunteer study, the average superior–inferior and right–left displacement was reduced from 1.9 mm to 0.3 mm and from 2.2 mm to 0.2 mm with AV‐aided interactive guidance, respectively. The superior–inferior and right–left positional drift was reduced from 0.5 mm/min to 0.1 mm/min and from 0.4 mm/min to 0.04 mm/min with audiovisual‐aided interactive guidance. This study demonstrated a reduction in intrafractional head motion using a remote‐controlled and self‐contained AV‐aided interactive system of iPad minis with Retina display, easily obtainable and cost‐effective tablet computers. This approach can potentially streamline clinical flow for claustrophobic patients without a head mask and also allows patients to practice self‐motion management before radiation treatment delivery. PACS number: 87.55.Gh

How dose sparing of cardiac structures correlates with in‐field heart volume and sternal displacement

Cardiac irradiation increases the risk of coronary artery disease in patients with left‐sided breast cancer. Techniques exist to reduce cardiac irradiation, but the optimum technique depends on individual patient anatomy and physiology. We investigated the correlation of delta heart volume in field (dHVIF) and sternal excursion with dose sparing in heart and left anterior descending artery (LAD) to develop quantitative predictive models for expected dose to heart and LAD. A treatment planning study was performed on 97 left‐breast cancer patients who underwent whole breast radiotherapy (prescription doseu2009=u200950u2009Gy) under deep inspiratory breath hold (DIBH). Two CT datasets, free breathing (FB) and DIBH, were utilized for treatment planning and for determination of the internal anatomy‐based DIBH amplitude. The mean heart and LAD dose were compared between FB and DIBH plans and dose to the heart and LAD as a function of dHVIF and sternal excursion were determined. The [Average (STD); Range] mean heart doses from free breathing and DIBH are [120.5(65.2);u200928.9u2009~u2009393.8]u2009cGy and [67.5(25.1);u200919.7u2009~u2009145.6]u2009cGy, respectively. The mean LAD doses from free breathing and DIBH are [571.0(582.2);u200942.2u2009~u20092332.2]u2009cGy and [185.9(127.0);u200941.2u2009~u2009898.4]u2009cGy, respectively. The mean dose reductions with DIBH are [53.1(50.6);u2009‐15.4u2009~u2009295.1]u2009cGy for the heart and [385.1(513.4);u2009‐0.6u2009~u20092105.8]u2009cGy for LAD. Percent mean dose reductions to the heart and LAD with DIBH are 44% (pu2009<u20090.0001) and 67% (pu2009<u20090.0001), respectively, compared to FB. The dHVIF mean dose reduction correlation is 8.1u2009cGy/cc for the heart and 81.6u2009cGy/cc for LAD (with linear trend and y intercept: 26.0 cGy for the heart, 109.1 cGy for LAD). DIBH amplitude using sternal position was [1.3(4.8);u2009.38u2009~2.5]u2009cm. The DIBH amplitude mean dose reduction correlation is 14u2009cGy/cm for the heart and 212u2009cGy/cm for LAD (with linear trend with y intercept: 35.6 cGy for the heart, 102.4 cGy for LAD). The strong correlation of dose sparing to the heart and LAD with dHVIF and sternal excursion suggests that mean dose sparing to heart and LAD can be predicted with either dHVIF or sternal excursion equally well. The metrics proposed could be utilized to allow providers to determine the relative dosimetric benefits of different heart‐sparing techniques as early as time of consultation. PACS number(s): 87.53.TfCardiac irradiation increases the risk of coronary artery disease in patients with left-sided breast cancer. Techniques exist to reduce cardiac irradiation, but the optimum technique depends on individual patient anatomy and physiology. We investigated the correlation of delta heart volume in field (dHVIF) and sternal excursion with dose sparing in heart and left anterior descending artery (LAD) to develop quantitative predictive models for expected dose to heart and LAD. A treatment planning study was performed on 97 left-breast cancer patients who underwent whole breast radiotherapy (prescription doseu2009=u200950u2009Gy) under deep inspiratory breath hold (DIBH). Two CT datasets, free breathing (FB) and DIBH, were utilized for treatment planning and for determination of the internal anatomy-based DIBH amplitude. The mean heart and LAD dose were compared between FB and DIBH plans and dose to the heart and LAD as a function of dHVIF and sternal excursion were determined. The [Average (STD); Range] mean heart doses from free breathing and DIBH are [ 120.5(65.2);u200928.9u2009~u2009393.8 ]u2009cGy and [ 67.5(25.1);u200919.7u2009~u2009145.6 ]u2009cGy, respectively. The mean LAD doses from free breathing and DIBH are [ 571.0(582.2);u200942.2u2009~u20092332.2 ]u2009cGy and [ 185.9(127.0);u200941.2u2009~u2009898.4 ]u2009cGy, respectively. The mean dose reductions with DIBH are [ 53.1(50.6);u2009-15.4u2009~u2009295.1 ]u2009cGy for the heart and [ 385.1(513.4);u2009-0.6u2009~u20092105.8 ]u2009cGy for LAD. Percent mean dose reductions to the heart and LAD with DIBH are 44% (pu2009<u20090.0001) and 67% (pu2009<u20090.0001), respectively, compared to FB. The dHVIF mean dose reduction correlation is 8.1u2009cGy/cc for the heart and 81.6u2009cGy/cc for LAD (with linear trend and y intercept: 26.0 cGy for the heart, 109.1 cGy for LAD). DIBH amplitude using sternal position was [ 1.3(4.8);u2009.38u2009~2.5 ]u2009cm. The DIBH amplitude mean dose reduction correlation is 14u2009cGy/cm for the heart and 212u2009cGy/cm for LAD (with linear trend with y intercept: 35.6 cGy for the heart, 102.4 cGy for LAD). The strong correlation of dose sparing to the heart and LAD with dHVIF and sternal excursion suggests that mean dose sparing to heart and LAD can be predicted with either dHVIF or sternal excursion equally well. The metrics proposed could be utilized to allow providers to determine the relative dosimetric benefits of different heart-sparing techniques as early as time of consultation. PACS number(s): 87.53.Tf.

Breast Brachytherapy and Clinical Appendix

Breast brachytherapy delivers partial breast irradiation after breast-conserving surgery. The goal is to reduce local recurrence while minimizing dose to normal tissue. The majority of ipsilateral breast tumor recurrences occur within the index quadrant. It provides options for shorter treatment duration compared to traditional whole breast external beam radiation therapy (5 days vs. 5 weeks). Guidelines from several groups exist with recommendations for selecting appropriate patients. Multiple imaging modalities may be used to identify the lumpectomy cavity and confirm applicator placement. Cross-sectional imaging allows for evaluation of the implant (confirms placement, adjustment, manipulation). HDR or LDR can be utilized to deliver dose: 34 Gy in 10 fractions over 5 days (HDR), 32 Gy in 8 fractions over 4 days (HDR), 10 Gy in 2 fractions over 1–2 days (HDR boost), 45–50 Gy/0.50 Gy per hour (LDR), or 15–20 Gy/0.50 Gy per hour (LDR boost). NSABP B-39/RTOG 0413 will allow for comparison of treatment-related toxicity and cosmesis between accelerated partial breast irradiation and whole breast irradiation (results pending). Good to excellent cosmetic and high treatment-related satisfaction have been reported in many series.

Fractionation trends in breast cancer and implications in partial breast irradiation

Purpose/objectivesThe aim of this study is to analyze the national trends in breast radiotherapy fractionation over the past decade.Methods/materialsThe National Cancer Database was queried for women with pTis-pT3pN0, cM0 breast carcinoma (ductal or lobular) treated with breast conserving surgery and radiotherapy (RT) from 1998 to 2012. Patients were grouped by number of radiotherapy fractions into four groups: conventional fractionation (ConvFx, 25–33 fractions), hypofractionation (HypoFx, 15–24 fractions), accelerated partial breast RT (APBI, 10 fractions), and intraoperative RT (IORT, 1 fraction on the day of surgery). Patients with alternative schedules were excluded. Trends were analyzed graphically, and univariable and multivariable (MVA) analyses were performed to investigate factors associated with the receipt of APBI or IORT.ResultsA total of 371,145 patients met inclusion criteria. Trends analysis demonstrates a clear increase in APBI from 1998 to 2008, at which point hypofractionation became increasingly popular and APBI stabilized. Among APBI patients (nxa0=xa05787), the predominant RT modality was HDR brachytherapy (71%). On MVA, several factors were associated with APBI over other fractionations (all pxa0<xa00.001): later year of diagnosis, older age, ductal histology, smaller tumors, estrogen receptor positivity, lower grade, and increased patient distance from treating facility (OR 2.16 if over 100xa0mi). Similar factors were associated with the receipt of IORT, including patients living a further distance from the hospital (OR 8.18 if over 100xa0mi).ConclusionsWhile APBI utilization increased sharply from 2000 to 2008, the use of APBI has stabilized since 2008 with a concomitant increase in use of hypofractionation. The causes of these trends are unknown but should be the focus of future research.