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At least 487 records · Page 27
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

E-cigarettes as a source of toxic and potentially carcinogenic metals

Background and aims: The popularity of electronic cigarette devices is growing worldwide. The health impact of e-cigarette use, however, remains unclear. E-cigarettes are marketed as a safer alternative to cigarettes. The aim of this research was the characterization and quantification of toxic metal concentrations in five, nationally popular brands of cig-a-like e-cigarettes. Methods: We analyzed the cartomizer liquid in 10 cartomizer refills for each of five brands by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results: All of the tested metals (cadmium, chromium, lead, manganese and nickel) were found in the e-liquids analyzed. Across all analyzed brands, mean (SD) concentrations ranged from 4.89 (0.893) to 1970 (1540) μg/L for lead, 53.9 (6.95) to 2110 (5220) μg/L for chromium and 58.7 (22.4) to 22,600 (24,400) μg/L for nickel. Manganese concentrations ranged from 28.7 (9.79) to 6910.2 (12,200) μg/L. We found marked variability in nickel and chromium concentration within and between brands, which may come from heating elements. Conclusion: Additional research is needed to evaluate whether e-cigarettes represent a relevant exposure pathway for toxic metals in users. - Highlights: • Certain brands of cig-a-like e-cigarettes contain high levels of nickel and chromium. • Cig-a-likes contain low levels of cadmium, compared to tobacco cigarettes. • Nickel and chromium in the e-liquid of cig-a-likes may come from nichrome heating coils.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Toxics (Pb, Cd) and trace elements (Zn, Cu, Mn) in women during pregnancy and at delivery, South Benin, 2014–2015

Highlights: • Lack of data on maternal exposure to toxic and trace elements in Africa. • Longitudinal blood measurements of Pb, Cd, Zn, Cu and Mn during pregnancy in Benin. • Evidence of maternal exposure to Pb and Cd. • Identification of potential sources for Pb exposure during pregnancy. During pregnancy, fetal development can be hindered by maternal exposure to toxic elements and abnormal concentrations of trace elements. Few data are available in African countries. Our goal was to assess the body burden of lead (Pb), cadmium (Cd), manganese (Mn), zinc (Zn) and copper (Cu) in pregnant women in Benin. The study was carried out in Sô-Ava district, from November 2015 to April 2016. Sixty women were recruited from the RECIPAL pre-conceptional cohort study. In all women, blood samples were collected during the first trimester of pregnancy. Thirty-two women had additional maternal and cord blood samples collected at delivery. Blood samples were analyzed by inductively coupled plasma mass spectrometry. At delivery, Cd median (IQR) concentration in maternal blood was 0.34 µg/L (0.24–0.46) in this non-smoking population. Pb median (IQR) concentration in maternal blood at delivery was 37.4 µg/L (30.5–52.0), with 31.3% of blood Pb levels above the 50 μg/L threshold. These pregnant women lived in semi-rural lakeside villages. Potential sources of Pb exposure identified during pregnancy were having water supply by drill pump and activities such as smoking fish by the woman and fishing by the household head. At delivery, Zn, Cu, and Mn median (IQR) concentrations in maternal blood were, respectively, 5415 μg/L (4894–5822), 1609 μg/L (1295–1771) and 16.0 μg/L (12.5–20.8). Pb, Cd, Mn and Cu blood concentrations were significantly higher at delivery than during the first trimester of pregnancy. Pb, Cd, Zn and Cu concentrations were significantly lower in cord blood than in maternal blood, contrary to Mn concentration, which was significantly higher in cord blood than in maternal blood at delivery. This exploratory study is the first one performed in Benin, and warns us about exposition of women from Sô-Ava district to Pb and Cd during pregnancy.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2011

Late Patient-Reported Toxicity After Preoperative Radiotherapy or Chemoradiotherapy in Nonresectable Rectal Cancer: Results From a Randomized Phase III Study

Purpose: Preoperative chemoradiotherapy (CRT) is superior to radiotherapy (RT) in locally advanced rectal cancer, but the survival gain is limited. Late toxicity is, therefore, important. The aim was to compare late bowel, urinary, and sexual functions after CRT or RT. Methods and Materials: Patients (N = 207) with nonresectable rectal cancer were randomized to preoperative CRT or RT (2 Gy Multiplication-Sign 25 {+-} 5-fluorouracil/leucovorin). Extended surgery was often required. Self-reported late toxicity was scored according to the LENT SOMA criteria in a structured telephone interview and with questionnaires European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), International Index of Erectile Function (IIEF), and sexual function -vaginal changes questionnaire (SVQ). Results: Of the 105 patients alive in Norway and Sweden after 4 to 12 years of follow-up, 78 (74%) responded. More patients in the CRT group had received a stoma (73% vs. 52%, p = 0.09). Most patients without a stoma (7 of 12 in CRT group and 9 of 16 in RT group) had incontinence for liquid stools or gas. No stoma and good anal function were seen in 5 patients (11%) in the CRT group and in 11 (30%) in the RT group (p = 0.046). Of 44 patients in the CRT group, 12 (28%) had had bowel obstruction compared with 5 of 33 (15%) in the RT group (p = 0.27). One-quarter of the patients reported urinary incontinence. The majority of men had severe erectile dysfunction. Few women reported sexual activity during the previous month. However, the majority did not have concerns about their sex life. Conclusions: Fecal incontinence and erectile dysfunction are frequent after combined treatment for locally advanced rectal cancer. There was a clear tendency for the problems to be more common after CRT than after RT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Acute Toxicity of Radiochemotherapy in Rectal Cancer Patients: A Risk Particularly for Carriers of the TGFB1 Pro25 variant

Purpose: Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of neoadjuvant radiochemotherapy under clinical trial conditions. Methods and Materials: Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.4 Gy combined with 5-fluorouracil-based chemotherapy. Toxicity was monitored according to Common Terminology Criteria for Adverse Events. QAOT was defined as a CTCAE grade {>=}2 for at least one case of enteritis, proctitis, cystitis, or dermatitis. Nine germline polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped. Results: In both cohorts, all patients carrying the TGFB1 Pro25 variant experienced QAOT (positive predictive value of 100%, adjusted p = 0.0006). In a multivariate logistic regression model, gender, age, body mass index, type of chemotherapy, or disease state had no significant impact on QAOT. Conclusion: The TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification and carriers may benefit from adaptive clinical care or specific radiation techniques.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

A Treatment Planning and Acute Toxicity Comparison of Two Pelvic Nodal Volume Delineation Techniques and Delivery Comparison of Intensity-Modulated Radiotherapy Versus Volumetric Modulated Arc Therapy for Hypofractionated High-Risk Prostate Cancer Radiotherapy

Purpose: To perform a comparison of two pelvic lymph node volume delineation strategies used in intensity-modulated radiotherapy (IMRT) for high risk prostate cancer and to determine the role of volumetric modulated arc therapy (VMAT). Methods and Materials: Eighteen consecutive patients accrued to an ongoing clinical trial were identified according to either the nodal contouring strategy as described based on lymphotropic nanoparticle-enhanced magnetic resonance imaging technology (9 patients) or the current Radiation Therapy Oncology Group (RTOG) consensus guidelines (9 patients). Radiation consisted of 45 Gy to prostate, seminal vesicles, and lymph nodes, with a simultaneous integrated boost to the prostate alone, to a total dose of 67.5 Gy delivered in 25 fractions. Prospective acute genitourinary and gastrointestinal toxicities were compared at baseline, during radiotherapy, and 3 months after radiotherapy. Each patient was retrospectively replanned using the opposite method of nodal contouring, and plans were normalized for dosimetric comparison. VMAT plans were also generated according to the RTOG method for comparison. Results: RTOG plans resulted in a significantly lower rate of genitourinary frequency 3 months after treatment. The dosimetric comparison showed that the RTOG plans resulted in both favorable planning target volume (PTV) coverage and lower organs at risk (OARs) and integral (ID) doses. VMAT required two to three arcs to achieve adequate treatment plans, we did not observe consistent dosimetric benefits to either the PTV or the OARs, and a higher ID was observed. However, treatment times were significantly shorter with VMAT. Conclusion: The RTOG guidelines for pelvic nodal volume delineation results in favorable dosimetry and acceptable acute toxicities for both the target and OARs. We are unable to conclude that VMAT provides a benefit compared with IMRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Glioblastoma Treatment: Bypassing the Toxicity of Platinum Compounds by Using Liposomal Formulation and Increasing Treatment Efficiency With Concomitant Radiotherapy

Purpose: Treatments of glioblastoma with cisplatin or oxaliplatin only marginally improve the overall survival of patients and cause important side effects. To prevent adverse effects, improve delivery, and optimize the tumor response to treatment in combination with radiotherapy, a potential approach consists of incorporating the platinum agent in a liposome. Methods and Materials: In this study, cisplatin, oxaliplatin, carboplatin, Lipoplatin (the liposomal formulation of cisplatin), and Lipoxal (the liposomal formulation of oxaliplatin) were tested on F98 glioma orthotopically implanted in Fischer rats. The platinum compounds were administered by intracarotid infusion and were assessed for the ability to reduce toxicity, improve cancer cell uptake, and increase survival of animals when combined or not combined with radiotherapy. Results: The tumor uptake was 2.4-fold more important for Lipoxal than the liposome-free oxaliplatin. Lipoxal also improved the specificity of oxaliplatin as shown by a higher ratio of tumor to right hemisphere uptake. Surprisingly, Lipoplatin led to lower tumor uptake compared with cisplatin. However, Lipoplatin had the advantage of largely reducing the toxicity of cisplatin and allowed us to capitalize on the anticancer activity of this agent. Conclusion: Among the five platinum compounds tested, carboplatin showed the best increase in survival when combined with radiation for treatment of glioma implanted in Fischer rats.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Patients Treated With Intensity-Modulated Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal

Purpose: To identify dosimetric parameters that correlate with acute hematologic toxicity (HT) in patients with squamous cell carcinoma of the anal canal treated with definitive chemoradiotherapy (CRT). Methods and Materials: We analyzed 33 patients receiving CRT. Pelvic bone (PBM) was contoured for each patient and divided into subsites: ilium, lower pelvis (LP), and lumbosacral spine (LSS). The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. Endpoints included grade {>=}3 HT (HT3+) and hematologic event (HE), defined as any grade {>=}2 HT with a modification in chemotherapy dose. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT and dosimetric/clinical parameters. Results: Nine patients experienced HT3+ and 15 patients experienced HE. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.175, n = 1, and TD{sub 50} = 32 Gy. With this model, mean PBM doses of 25 Gy, 27.5 Gy, and 31 Gy result in a 10%, 20%, and 40% risk of HT3+, respectively. Compared with patients with mean PBM dose of <30 Gy, patients with mean PBM dose {>=}30 Gy had a 14-fold increase in the odds of developing HT3+ (p = 0.005). Several low-dose radiation parameters (i.e., PBM-V10) were associated with the development of HT3+ and HE. No association was found with the ilium, LP, or clinical factors. Conclusions: LKB modeling confirms the expectation that PBM acts like a parallel organ, implying that the mean dose to the organ is a useful predictor for toxicity. Low-dose radiation to the PBM was also associated with clinically significant HT. Keeping the mean PBM dose <22.5 Gy and <25 Gy is associated with a 5% and 10% risk of HT, respectively.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

A New Model for Predicting Acute Mucosal Toxicity in Head-and-Neck Cancer Patients Undergoing Radiotherapy With Altered Schedules

Purpose: One of the worst radiation-induced acute effects in treating head-and-neck (HN) cancer is grade 3 or higher acute (oral and pharyngeal) mucosal toxicity (AMT), caused by the killing/depletion of mucosa cells. Here we aim to testing a predictive model of the AMT in HN cancer patients receiving different radiotherapy schedules. Methods and Materials: Various radiotherapeutic schedules have been reviewed and classified as tolerable or intolerable based on AMT severity. A modified normal tissue complication probability (NTCP) model has been investigated to describe AMT data in radiotherapy regimens, both conventional and altered in dose and overall treatment time (OTT). We tested the hypothesis that such a model could also be applied to identify intolerable treatment and to predict AMT. This AMT NTCP model has been compared with other published predictive models to identify schedules that are either tolerable or intolerable. The area under the curve (AUC) was calculated for all models, assuming treatment tolerance as the gold standard. The correlation between AMT and the predicted toxicity rate was assessed by a Pearson correlation test. Results: The AMT NTCP model was able to distinguish between acceptable and intolerable schedules among the data available for the study (AUC = 0.84, 95% confidence interval = 0.75-0.92). In the equivalent dose at 2 Gy/fraction (EQD2) vs OTT space, the proposed model shows a trend similar to that of models proposed by other authors, but was superior in detecting some intolerable schedules. Moreover, it was able to predict the incidence of {>=}G3 AMT. Conclusion: The proposed model is able to predict {>=}G3 AMT after HN cancer radiotherapy, and could be useful for designing altered/hypofractionated schedules to reduce the incidence of AMT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Predictor of Severe Gastroduodenal Toxicity After Stereotactic Body Radiotherapy for Abdominopelvic Malignancies

Purpose: To identify the predictors for the development of severe gastroduodenal toxicity (GDT) in patients treated with stereotactic body radiotherapy (SBRT) using 3 fractionations for abdominopelvic malignancies. Methods and Materials: From 2001 to 2011, 202 patients with abdominopelvic malignancies were treated with curative-intent SBRT. Among these patients, we retrospectively reviewed the clinical records of 40 patients with the eligibility criteria as follows: 3 fractionations, follow-up period {>=}1 year, absence of previous radiation therapy (RT) history or combination of external-beam RT and the presence of gastroduodenum (GD) that received a dose higher than 20% of prescribed dose. The median SBRT dose was 45 Gy (range, 33-60 Gy) with 3 fractions. We analyzed the clinical and dosimetric parameters, including multiple dose-volume histogram endpoints: V{sub 20} (volume of GD that received 20 Gy), V{sub 25}, V{sub 30}, V{sub 35}, and D{sub max} (the maximum point dose). The grade of GDT was defined by the National Cancer Institute Common Toxicity Criteria version 4.0, and GDT {>=}grade 3 was defined as severe GDT. Results: The median time to the development of severe GDT was 6 months (range, 3-12 months). Severe GDT was found in 6 patients (15%). D{sub max} was the best dosimetric predictor for severe GDT. D{sub max} of 35 Gy and 38 Gy were respectively associated with a 5% and 10% probability of the development of severe GDT. A history of ulcer before SBRT was the best clinical predictor on univariate analysis (P=.0001). Conclusions: We suggest that D{sub max} is a valuable predictor of severe GDT after SBRT using 3 fractionations for abdominopelvic malignancies. A history of ulcer before SBRT should be carefully considered as a clinical predictor, especially in patients who receive a high dose to GD.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Meningioma Causing Visual Impairment: Outcomes and Toxicity After Intensity Modulated Radiation Therapy

Purpose: To evaluate ophthalmologic outcomes and toxicity of intensity modulated radiation therapy (IMRT) in patients with meningiomas causing visual deficits. Methods and Materials: A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway (including 3 optic nerve sheath meningiomas); 4 were posterior to the chiasm. Results: Vision improved objectively in 12 patients (40%). Improvements were in visual field (5/16 patients), color vision (4/9 patients), acuity (1/15 patients), extraocular movements (3/11 patients), ptosis (1/5 patients), and proptosis (2/6 patients). No predictors of clinical response were found. Two patients had minor reductions in tumor dimensions on magnetic resonance imaging, 1 patient had radiological progression, and the other patients were stable. One patient experienced grade 2 keratitis, 1 patient had a minor visual field loss, and 5 patients had grade 1 dry eye. Conclusion: IMRT is an effective method for treating meningiomas causing ophthalmologic deficits, and toxicity is minimal. Thorough ophthalmologic assessment is important because clinical responses often occur in the absence of radiological change.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Proton Beam Craniospinal Irradiation Reduces Acute Toxicity for Adults With Medulloblastoma

Purpose: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma. Methods and Materials: Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at the University of Texas MD Anderson Cancer Center from 2003 to 2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4-103) for x-CSI patients and 26 months (range 11-63) for p-CSI. Results: p-CSI patients lost less weight than x-CSI patients (1.2% vs 5.8%; P=.004), and less p-CSI patients had >5% weight loss compared with x-CSI (16% vs 64%; P=.004). p-CSI patients experienced less grade 2 nausea and vomiting compared with x-CSI (26% vs 71%; P=.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, P<.001). p-CSI patients had a smaller reduction in peripheral white blood cells, hemoglobin, and platelets compared with x-CSI (white blood cells 46% vs 55%, P=.04; hemoglobin 88% vs 97%, P=.009; platelets 48% vs 65%, P=.05). Mean vertebral doses were significantly associated with reductions in blood counts. Conclusions: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

Purpose: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m{sup 2}). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P=.049). Conclusions: Pelvic IMRT with weekly cisplatin is associated with low rates of HT and high rates of weekly cisplatin use. The volume of bone marrow receiving 40 Gy and the median dose to bone marrow correlated with higher rates of grade ≥2 toxicity among patients receiving weekly cisplatin (cervical cancer patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Prospective Study of Local Control and Late Radiation Toxicity After Intraoperative Radiation Therapy Boost for Early Breast Cancer

Purpose: To report the local recurrence rate and late toxicity of intraoperative radiation therapy (IORT) boost to the tumor bed using the Intrabeam System followed by external-beam whole-breast irradiation (WBI) in women with early-stage breast cancer in a prospective single-institution study. Methods and Materials: Women with breast cancer ≤3 cm were recruited between February 2003 and May 2005. After breast-conserving surgery, a single dose of 5 Gy IORT boost was delivered using 50-kV x-rays to a depth of 10 mm from the applicator surface. This was followed by WBI to a total dose of 50 Gy in 25 fractions. Patients were reviewed at regular, predefined intervals. Late toxicities were recorded using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring systems. Results: Fifty-five patients completed both IORT boost and external-beam WBI. Median follow-up was 3.3 years (range, 1.4-4.1 years). There was no reported locoregional recurrence or death. One patient developed distant metastases. Grade 2 and 3 subcutaneous fibrosis was detected in 29 (53%) and 8 patients (15%), respectively. Conclusions: The use of IORT as a tumor bed boost using kV x-rays in breast-conserving therapy was associated with good local control but a clinically significant rate of grade 2 and 3 subcutaneous fibrosis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

[{sup 18}F]FDG-PET Standard Uptake Value as a Metabolic Predictor of Bone Marrow Response to Radiation: Impact on Acute and Late Hematological Toxicity in Cervical Cancer Patients Treated With Chemoradiation Therapy

Purpose: To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using {sup 18}F-labeled fluorodeoxyglucose positron emission tomography [{sup 18}F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT). Methods and Materials: Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [{sup 18}F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BM{sub TOT}). Active bone marrow (BM{sub ACT}) was contoured based on SUV greater than the mean SUV of BM{sub TOT}. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V{sub 10}, V{sub 20}, V{sub 30}, and V{sub 40}, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models. Results: Mean relative pre-post-therapy SUV reductions in BM{sub TOT} and BM{sub ACT} were 27% and 38%, respectively. BM{sub ACT} volume was significantly reduced after treatment (from 651.5 to 231.6 cm{sup 3}, respectively; P<.0001). BM{sub ACT} V{sub 30} was significantly correlated with a reduction in BM{sub ACT} SUV (R{sup 2}, 0.14; P<.001). The reduction in BM{sub ACT} SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R{sup 2}, 0.27; P=.04) and at last follow-up (R{sup 2}, 0.25; P=.04). Different dosimetric parameters of BM{sub TOT} and BM{sub ACT} correlated with long-term hematological outcome. Conclusions: The volumes of BM{sub TOT} and BM{sub ACT} that are exposed to even relatively low doses of radiation are associated with a decrease in WBC counts following CRT. The loss in proliferative BM SUV uptake translates into low WBC nadirs after treatment. These results suggest the potential of intensity modulated radiation therapy to spare BM{sub TOT} to reduce long-term hematological toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Toxicity After Central versus Peripheral Lung Stereotactic Body Radiation Therapy: A Propensity Score Matched-Pair Analysis

Purpose: To compare toxicity after stereotactic body radiation therapy (SBRT) for “central” tumors—within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum—versus noncentral (“peripheral”) lung tumors. Methods and Materials: From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non–small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/β=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up using Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ{sup 2} and 2-tailed t tests, adverse events with χ{sup 2} test-for-trend, and cumulative incidence using competing risks analysis (Gray's test). Results: With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral tumors, respectively. Pooled 2-year incidences of grades 4 and 5 AEs were <1% and 0%, respectively, in both the prematched and matched groups. Conclusion: Moderate-dose SBRT with these techniques yields a similarly safe toxicity profile for both central and peripheral lung tumors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Modelling the Impact of Fractionation on Late Urinary Toxicity After Postprostatectomy Radiation Therapy

Purpose: To fit urinary toxicity data of patients treated with postprostatectomy radiation therapy with the linear quadratic (LQ) model with/without introducing a time factor. Methods and Materials: Between 1993 and 2010, 1176 patients were treated with conventional fractionation (1.8 Gy per fraction, median 70.2 Gy, n=929) or hypofractionation (2.35-2.90 Gy per fraction, n=247). Data referred to 2004-2010 (when all schemes were in use, n=563; conventional fractionation: 316; hypofractionation: 247) were fitted as a logit function of biological equivalent dose (BED), according to the LQ model with/without including a time factor γ (fixing α/β = 5 Gy). The 3-year risks of severe urethral stenosis, incontinence, and hematuria were considered as endpoints. Best-fit parameters were derived, and the resulting BEDs were taken in multivariable backward logistic models, including relevant clinical variables, considering the whole population. Results: The 3-year incidences of severe stenosis, incontinence, and hematuria were, respectively, 6.6%, 4.8%, and 3.3% in the group treated in 2004-2010. The best-fitted α/β values were 0.81 Gy and 0.74 Gy for incontinence and hematuria, respectively, with the classic LQ formula. When fixing α/β = 5 Gy, best-fit values for γ were, respectively, 0.66 Gy/d and 0.85 Gy/d. Sensitivity analyses showed reasonable values for γ (0.6-1.0 Gy/d), with comparable goodness of fit for α/β values between 3.5 and 6.5 Gy. Likelihood ratio tests showed that the fits with/without including γ were equivalent. The resulting multivariable backward logistic models in the whole population included BED, pT4, and use of antihypertensives (area under the curve [AUC] = 0.72) for incontinence and BED, pT4, and year of surgery (AUC = 0.80) for hematuria. Stenosis data could not be fitted: a 4-variable model including only clinical factors (acute urinary toxicity, pT4, year of surgery, and use of antihypertensives) was suggested (AUC = 0.73). Conclusions: The unexpected impact of moderate hypofractionation on severe incontinence and hematuria after postprostatectomy radiation therapy may be explained by a bladder α/β value <1 Gy or, radiobiologically more plausible, by introducing a time factor likely to represent a previously hypothesized consequential component of late effect.

62 RADIOLOGY AND NUCLEAR MEDICINE↗