The objective of this study was to evaluate and understand the systematic error between the planned three-dimensional (3D) dose and the delivered dose to patient in scanning beam proton therapy for lung tumors. Single-field and multifield optimized scanning beam proton therapy plans were generated for ten patients with stage II-III lung cancer with a mix of tumor motion and size. 3D doses in CT datasets for different respiratory phases and the time-weighted average CT, as well as the four-dimensional (4D) doses were computed for both plans. The 3D and 4D dose differences for the targets and different organs at risk were compared using dose-volume histogram (DVH) and voxel-based techniques, and correlated with the extent of tumor motion. The gross tumor volume (GTV) dose was maintained in all 3D and 4D doses, using the internal GTV override technique. The DVH and voxel-based techniques are highly correlated. The mean dose error and the standard deviation of dose error for all target volumes were both less than 1.5% for all but one patient. However, the point dose difference between the 3D and 4D doses was up to 6% for the GTV and greater than 10% for the clinical and planning target volumes. Changes in the 4D and 3D doses were not correlated with tumor motion. The planning technique (single-field or multifield optimized) did not affect the observed systematic error. In conclusion, the dose error in 3D dose calculation varies from patient to patient and does not correlate with lung tumor motion. Therefore, patient-specific evaluation of the 4D dose is important for scanning beam proton therapy for lung tumors.
Rationale and Objectives: To investigate the diagnostic accuracy of ultrasound histogram features in the quantitative assessment of radiation-induced parotid gland injury and to identify potential imaging biomarkers for radiation-induced xerostomia (dry mouth)-the most common and debilitating side effect after head-and-neck radiotherapy (RT).
Materials and Methods: Thirty-four patients, who have developed xerostomia after RT for head-and-neck cancer, were enrolled. Radiation-induced xerostomia was defined by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity scale. Ultrasound scans were performed on each patient's parotids bilaterally. The 34 patients were stratified into the acute-toxicity groups (16 patients, ≤3months after treatment) and the late-toxicity group (18 patients, >3months after treatment). A separate control group of 13 healthy volunteers underwent similar ultrasound scans of their parotid glands. Six sonographic features were derived from the echo-intensity histograms to assess acute and late toxicity of the parotid glands. The quantitative assessments were compared to a radiologist's clinical evaluations. The diagnostic accuracy of these ultrasonic histogram features was evaluated with the receiver operating characteristic (ROC) curve.
Results: With an area under the ROC curve greater than 0.90, several histogram features demonstrated excellent diagnostic accuracy for evaluation of acute and late toxicity of parotid glands. Significant differences (P<.05) in all six sonographic features were demonstrated between the control, acute-toxicity, and late-toxicity groups. However, subjective radiologic evaluation cannot distinguish between acute and late toxicity of parotid glands.
Conclusions: We demonstrated that ultrasound histogram features could be used to measure acute and late toxicity of the parotid glands after head-and-neck cancer RT, which may be developed into a low-cost imaging method for xerostomia monitoring and assessment.
Magnetic resonance imaging (MRI) provides a number of advantages over computed tomography (CT) for radiation therapy treatment planning; however, MRI lacks the key electron density information necessary for accurate dose calculation. We propose a dictionary-learning-based method to derive electron density information from MRIs. Specifically, we first partition a given MR image into a set of patches, for which we used a joint dictionary learning method to directly predict a CT patch as a structured output. Then a feature selection method is used to ensure prediction robustness. Finally, we combine all the predicted CT patches to obtain the final prediction for the given MR image. This prediction technique was validated for a clinical application using 14 patients with brain MR and CT images. The peak signal-to-noise ratio (PSNR), mean absolute error (MAE), normalized cross-correlation (NCC) indices and similarity index (SI) for air, soft-tissue and bone region were used to quantify the prediction accuracy. The mean ± std of PSNR, MAE, and NCC were: 22.4±1.9dB, 82.6±26.1 HU, and 0.91±0.03 for the 14 patients. The SIs for air, soft-tissue, and bone regions are 0.98±0.01, 0.88±0.03, and 0.69±0.08. These indices demonstrate the CT prediction accuracy of the proposed learning-based method. This CT image prediction technique could be used as a tool for MRI-based radiation treatment planning, or for PET attenuation correction in a PET/MRI scanner.
by
Ann H. Klopp;
Anamaria R. Yeung;
Snehal Deshmukh;
Karen M. Gil;
Lari Wenzel;
Shannon N. Westin;
Kent Gifford;
David K. Gaffney;
William Small;
Spencer Thompson;
Desiree E. Doncals;
Guilherme H. C. Cantuaria;
Brian P. Yaremko;
Amy Chang;
Vijayananda Kundapur;
Dasarahally S. Mohan;
Michael L. Haas;
Yong Bae Kim;
Catherine L. Ferguson;
Stephanie L. Pugh;
Lisa A. Kachnic;
Deborah W. Bruner
Purpose: NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and healthrelated quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer.
Methods: Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index.
Results: From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group (P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group (P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group (P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea (P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04).
Conclusion: Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient's perspective.
by
James A. Kavanaugh;
Sarah Holler;
Todd A. DeWees;
Clifford G. Robinson;
Jeffey D. Bradley;
Puneeth Iyengar;
Kristin Higgins;
Sasa Mutic;
Lindsey A. Olsen
Purpose
To evaluate the feasibility of using a single-institution knowledge based planning (KBP) model as a dosimetric plan quality control (QC) for multi-institutional clinical trials. The efficacy of this QC tool was retrospectively evaluated using a subset of plans submitted to RTOG 0617.
Methods and Materials
A single KBP model was created utilizing a commercially available software (RapidPlan™, Varian Medical Systems, Palo Alto, CA) and data from 106 patients with non-small cell lung cancer (NSCLC) treated at a single institution. All plans had prescriptions ranging from 60Gy/30fx to 74Gy/37fx and followed planning guidelines from RTOG 0617. Two sets of optimization objectives were created to produce different trade-offs using the single KBP model predictions: one prioritizing target coverage (PC) and a second prioritizing lung sparing (LS) while allowing acceptable variation in target coverage. Three institutions that submitted a high volume of clinical plans to RTOG 0617 provided 25 patients which were replanned using both sets of optimization objectives. Model-generated dose volume histogram predictions were used to identify patients that exceeded Lungs-CTV V20Gy > 37% and would benefit from the LS objectives. Overall plan quality differences between KBP-generated plans and clinical plans were evaluated at RTOG 0617 defined dosimetric end-points.
Results
Target coverage and OAR sparing was significantly improved for most KBP generated plans compared to clinical trial data. The KBP model using PC objectives reduced heart Dmean and V40Gy by 2.1Gy and 5.2%, respectively. Similarly, utilizing LS objectives reduced the Lungs-CTV Dmean and V20Gy by 2.0Gy and 2.9% respectively. The KBP predictions correctly identified all patients with Lungs-CTV V20Gy>37% (5/25) and significantly reduced dose to Lungs-CTV by applying LS optimization objectives.
Conclusions
A single institution KBP model can be applied as a QC tool for multi-institutional clinical trials to improve overall plan quality and provide decision-support to determine the need for anatomy-based dosimetric trade-offs.
In vivo safety study using radiation at wavelengths and dosages relevant to intravascular imaging was conducted at varying power. According to the protocol and client communication, a total of 3 carotid arteries from swine were assigned to this study, in which there were seven total conditions (treatments). These consisted of two wavelengths of laser light with 3 different dosages of light at each wavelength, as well a negative control which was not irradiated with any light. After laser irradiation at several dosages, each artery was dissected into sixteen segments and placed in containers filled with 10% neutral buffered formalin. All collected samples were sent to for histology and microscopic evaluation. The pre-trimmed carotid artery segments were processed in a series of graded alcohols and xylene and paraffin wax embedded. The resulting paraffin blocks were sectioned twice serially, with an effort to capture the center of each segment, at an approximate 5 μm thickness and mounted to slide. One slide was stained with hematoxylin and eosin (H&E) and the other with Gomori’s Elastin Trichrome (GET).
Purpose: Cardiac radiation dose was a predictor of inferior overall survival in the Radiation Therapy Oncology Group 0617 non-small cell lung cancer trial. We examined the association between radiation therapy (RT) and cardiac events (CE) for patients with small cell lung cancer (SCLC).
Methods and Materials: The US population–based Surveillance, Epidemiology, and End Results Program and Medicare claims databases were queried for rates of CE among patients with SCLC treated with chemotherapy (CTX) ± RT. Propensity score matching (PSM) and multivariate analysis were conducted. Patients were matched for actual/theoretical RT start date (to prevent immortal time bias) and then full PSM balanced clinical characteristics. Cumulative incidence function curves were generated.
Results: From 2000 to 2011, 7060 patients were included: 2892 limited-stage SCLC (LS-SCLC) and 4168 extensive-stage SCLC. Grouping LS-SCLC and extensive-stage SCLC together, the incidence of CE for the CTX + RT and CTX-only groups was 44.1% versus 39% at 60 months (P =.008). After PSM (5286 patients), the incidence of CE for the CTX + RT and CTX-only groups was 43% versus 38.6% at 60 months (P =.033). Analysis of only LS-SCLC (2016 patients) demonstrated that the incidence of CE for CTX + RT versus CTX-only groups was 50.3% versus 42% at 60 months (P =.0231). Multivariate analysis again demonstrated an association between CE and RT (hazard ratio 1.20; 95% confidence interval 1.06-1.37; P =.005). After PSM (1614 patients), the incidence of CE for CTX + RT versus CTX-only groups was 51.7% versus 41.6% at 60 months (P =.0042).
Conclusions: Patients with SCLC are at significant risk of developing CE posttreatment; RT is associated with an absolute increase in the rate of CE at 5 years of approximately 5% for all patients with SCLC and up to 10% for patients with LS-SCLC. Cardiac risk management and cardiac-sparing RT techniques should be further evaluated for patients with SCLC.
by
Martin Sanda;
Bradford S. Hoppe;
Jeff M. Michalski;
Nancy P. Mendenhall;
Christopher G. Morris;
Randall H. Henderson;
Romaine C. Nichols;
William M. Mendenhall;
Christopher Williams;
Meredith M. Regan;
Jonathan Chipman;
Catrina Crociani;
Howard M. Sandler;
Daniel A. Hamstra
BACKGROUND Data continue to emerge on the relative merits of different treatment modalities for prostate cancer. The objective of this study was to compare patient-reported quality-of-life (QOL) outcomes after proton therapy (PT) and intensity-modulated radiation therapy (IMRT) for prostate cancer.
METHODS A comparison was performed of prospectively collected QOL data using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. QOL data were collected during the first 2 years after treatment for men who received PT and IMRT. PT was delivered to 1243 men at a single center at doses from 76 grays (Gy) to 82 Gy. IMRT was delivered to 204 men who were included in the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) study in doses from 75.6 Gy to 79.4 Gy. The Wilcoxon rank-sum test was used to compare EPIC outcomes by modality using baseline-adjusted scores at different time points. Individual questions were assessed by converting to binary outcomes and testing with generalized estimating equations.
RESULTS No differences were observed in summary score changes for bowel, urinary incontinence, urinary irritative/obstructive, and sexual domains between the 2 cohorts. However, more men who received IMRT reported moderate/big problems with rectal urgency (P = 0.02) and frequent bowel movements (P = 0.05) than men who received PT.
CONCLUSIONS There were no differences in QOL summary scores between the IMRT and PT cohorts during early follow-up (up to 2-years). Response to individual questions suggests possible differences in specific bowel symptoms between the 2 cohorts. These outcomes highlight the need for further comparative studies of PT and IMRT.
Administration of the bacterial protein flagellin to mice activates innate immune signaling that protects against an array of challenges, including ionizing radiation. Herein, we define the underlying mechanism for this protection. We report that flagellin treatment induces proliferation and mobilization of bone marrow cells that aid survival following irradiation. Specifically, treatment of mice or bone marrow cells ex vivo with flagellin induced Toll-like receptor 5 (TLR5)-dependent and NOD-like receptor C4-independent proliferation of Lin-Sca-1+Kit+ (LSK) cells, which includes both hematopoietic stem cells that provide long-term repopulation (LTR) and multipotent progenitor cells (MPPs) that transiently proliferate and differentiate into a range of blood cell types. TLR5 expression on bone marrow cells was necessary and sufficient for flagellin-induced LSK proliferation. Flagellin treatment stimulated LSK proliferation by inducing a 10-fold increase in type 3 MPP (MPP3) without a concomitant increase in LTR cells. Cotransfer of 5 × 103 fluorescence-activated cell sorted flagellin-induced MPP3 cells along with 1 × 105 whole bone marrow cells to lethally irradiated mice revealed that such cells predominantly repopulated the neutrophil compartment for up to 4 week, and dramatically increased the survival rate of the bone marrow transplantation procedure. Hence, we propose the administration of MPP3 cells, elicited by flagellin, as a novel approach to prevent life-threatening neutropenia that can accompany bone marrow transplant and other myeloablative therapeutic procedures.
by
Lene H. S. Veiga;
Parveen Bhatti;
Cecile M. Ronckers;
Alice J. Sigurdson;
Marilyn Stovall;
Susan A. Smith;
Rita Weathers;
Wendy Leisenring;
Ann Mertens;
Sue Hammond;
Joseph P. Neglia;
Anna T. Meadows;
Sarah S. Donaldson;
Charles A. Sklar;
Debra L. Friedman;
Leslie L. Robison;
Peter D. Inskip
Background: Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy.
Methods: The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose.
Results: Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0-1.6) for females and 0.6% (0.4-0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3-4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (P trend = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy.
Conclusions: Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing.
Impact: Our study adds to the evidence for chemotherapy agent-specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy.