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BACKGROUND - Planning and delivery of IMRT for locally advanced head and neck cancer (LAHNC) can be performed using sequential boost or simultaneous integrated boost (SIB). Whether these techniques differ in treatment-related outcomes including survival and acute and late toxicities remain largely unexplored.
METHODS - We performed a single institutional retrospective matched cohort analysis on patients with LAHNC treated with definitive chemoradiotherapy to 69.3 Gy in 33 fractions. Treatment was delivered via sequential boost (n = 68) or SIB (n = 141). Contours, plan evaluation, and toxicity assessment were performed by a single experienced physician. Toxicities were graded weekly during treatment and at 3-month follow up intervals. Recurrence-free survival, disease-free survival, and overall survival were estimated via Kaplan-Meier statistical method.
RESULTS - At 4 years, the estimated overall survival was 69.3% in the sequential boost cohort and 76.8% in the SIB cohort (p = 0.13). Disease-free survival was 63 and 69% respectively (p = 0.27). There were no significant differences in local, regional or distant recurrence-free survival. There were no significant differences in weight loss (p = 0.291), gastrostomy tube placement (p = 0.494), or duration of gastrostomy tube dependence (p = 0.465). Rates of acute grade 3 or 4 dysphagia (82% vs 55%) and dermatitis (78% vs 58%) were significantly higher in the SIB group (p < 0.001 and p = 0.012 respectively). Moreover, a greater percentage of the SIB cohort did not receive the prescribed dose due to acute toxicity (7% versus 0, p = 0.028).
CONCLUSIONS - There were no differences in disease related outcomes between the two treatment delivery approaches. A higher rate of grade 3 and 4 radiation dermatitis and dysphagia were observed in the SIB group, however this did not translate into differences in late toxicity. Additional investigation is necessary to further evaluate the acute toxicity differences.
PURPOSE - To report on radiosurgery delivery positioning accuracy in the treatment of tremor patients with frameless image guided radiosurgery using the linear accelerator (LINAC) based ExacTrac system and to describe quality assurance (QA) procedures used.
METHODS AND MATERIALS - Between 2010 and 2015, 20 patients underwent radiosurgical thalamotomy targeting the ventral intermediate nucleus for the treatment of severe tremor. The median prescription dose was 140 Gy (range, 120-145 Gy) in a single fraction. The median maximum dose was 156 Gy (range, 136-162 Gy). All treatment planning was performed with the iPlan system using a 4-mm circular cone with multiple arcs. Before each treatment, QA procedures were performed, including the imaging system. As a result of the extremely high dose delivered in a single fraction, a well-defined circular mark developed on the posttreatment magnetic resonance imaging (MRI). Eight of these 20 patients were selected to evaluate treatment localization errors because their circular marks were available in posttreatment MRI. In this study, the localization error is defined as the distance between the center of the intended target and the center of the posttreatment mark.
RESULTS - The mean error of distance was found to be 1.1 mm (range, 0.4-1.5 mm). The mean errors for the left-right, anteroposterior, and superoinferior directions are 0.5 mm, 0.6 mm, and 0.7 mm, respectively.
CONCLUSIONS - The result reported in this study includes all tremor patients treated at our institution when their posttreatment MRI data were available for study. It represents a direct confirmation of target positioning accuracy in radiosurgery with a LINAC-based frameless system and its limitations. This level of accuracy is only achievable with an appropriate QA program in place for a LINAC-based frameless radiosurgery system.
Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
OBJECTIVES/HYPOTHESIS - Dysphagia and esophageal stricture are frequent consequences of treatment for head and neck cancer. This study examines the effectiveness of the anterograde-retrograde rendezvous procedure and serial dilations in reestablishing esophageal patency to allow return to oral diet and gastrostomy tube removal in a cohort of patients with complete or near-complete esophageal stricture following nonsurgical cancer treatment.
STUDY DESIGN - Retrospective review of patients treated with radiation therapy with or without concurrent chemotherapy presented with complete or near-complete esophageal stricture. Patients underwent serial dilations using combined anterograde-retrograde dilation (rendezvous) techniques.
METHODS - Medical records of patients having undergone treatment between 2006 and 2012 were reviewed, and semistructured interviews were also conducted to determine current swallowing function and actual patient experience. The primary outcome was swallowing improvement that allowed for return to oral diet and/or gastrostomy tube removal. Outcomes were compared between patients with complete and near-complete (<5 mm in diameter) strictures and univariate analysis performed to identify associations between patient, cancer, and treatment characteristics on odds of gastrostomy tube removal.
RESULTS - Twenty-four patients (median age 59.5 years, 63% male, 91% Caucasian) underwent treatment. Fifty percent of patients had complete occlusion of the esophageal lumen. The majority of patients (92%) underwent either anterograde (54%) or combined antero-retrograde (38%) approach. Following a median (interquartile range) of 9 (6-20) dilation sessions, 42% of patients were able to return to an oral diet and/or had their gastrostomy tube removed. This outcome was independent of whether the stricture was complete or near complete (P = .67). Of patients who had their gastrostomy tubes removed, only 33.3% had ever smoked, compared to 92.3% of those whose tubes were not discharged (P = .007).
CONCLUSIONS - Recannulation is possible even in cases of complete or near-complete stricture. Several factors appear to impact the likelihood of successful outcome, but in this study, only patients with a history of smoking had a significantly lower likelihood of return to full oral diet.
© 2014 The American Laryngological, Rhinological and Otological Society, Inc.
BACKGROUND AND PURPOSE - To determine if dose and/or dose-volume parameters to anatomic swallowing structures are predictive of gastrostomy tube (PEG) dependence from chemotherapy-intensity modulated radiotherapy (IMRT) in locally advanced head and neck cancer (LAHNC).
METHODS AND MATERIALS - A retrospective study was performed on 141 consecutive patients with LAHNC (squamous cell) treated with definitive chemoIMRT with weekly concurrent carboplatin and paclitaxel. Late dysphagia was assessed by length of PEG requirement. Analysis of IMRT dose was retrospectively performed for critical swallowing structures.
RESULTS - Approximately 62% of patients required PEG, the majority placed during treatment. Mean and median time for PEG was 7.7 and 4.4 months respectively (range 1.4-43.8). Only IMRT dose to the inferior constrictor was significantly associated with length of PEG. Mean dose (of individual mean doses) was 47 Gy for prolonged PEG use versus 41 Gy for PEG ⩽ 12 months. V40 to the inferior constrictor also correlated with PEG >12 months (p = 0.02) with a mean V40 of 48% versus 41% for PEG ⩽ 12 months.
CONCLUSIONS - IMRT dose to the inferior constrictor correlated with persistent dysphagia requiring prolonged PEG use. Maintaining mean inferior constrictor dose to ⩽ 41 Gy and V40 to ⩽ 41% may help minimize gastrostomy tube dependence.
Copyright © 2014. Published by Elsevier Ireland Ltd.
UNLABELLED - Study Type - Therapy (phase 1) Level of Evidence 2a What's known on the subject? and What does the study add? High-risk and locally advanced prostate cancers are difficult to cure with the standard regimen of radiation therapy (RT) with concurrent androgen-deprivation therapy (ADT). Multiple studies have explored the addition of docetaxel chemotherapy in attempt to improve patient outcomes. Prior Phase I studies have shown that docetaxel 20 mg/m(2) is a safe dose, when given concurrently with 70 Gy of radiation. But current standard RT for prostate cancer uses higher doses, and it is unclear if concurrent chemotherapy is safe with modern RT. This is a Phase I study that explored the addition of concurrent docetaxel chemotherapy to modern RT (intensity-modulated RT to 78 Gy) plus ADT. The study showed that weekly docetaxel at 20 mg/m(2) is safe with modern RT. At a median follow-up of 2.2 years, biochemical progression-free survival was 94%. This triple-therapy regimen is safe and promising for further evaluation in prospective trials.
OBJECTIVE - • To evaluate in a phase I trial, the feasibility of adding concurrent weekly docetaxel chemotherapy to high-dose intensity modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for treatment of high-risk prostate cancer.
PATIENTS AND METHODS - • Patients with high-risk prostate cancer were treated with a luteinising hormone-releasing hormone agonist (starting 2-3 months before IMRT and lasting 2 years), IMRT of 78 Gy to the prostate and seminal vesicles, and weekly docetaxel during RT. • All patients had computed tomography and bone scans to exclude metastatic disease. • A standard 3 + 3 design was used for docetaxel dose escalation. Successive patients were treated on dose levels of 10, 15, and 20 mg/m(2) of weekly docetaxel.
RESULTS - • In all, 18 patients participated in the study: 15 (83%) had Gleason 8-10 disease; the other three had either clinical T3 disease and/or a prostate-specific antigen (PSA) level of >20 ng/mL. • Grade 3 diarrhoea (a defined dose-limiting toxicity, DLT) occurred in one patient in each of the first two dose levels. However, when the cohorts were expanded, no further DLT was seen. • Weekly docetaxel at 20 mg/m(2) (dose level 3) was successfully given without DLT. • No patient had grade 4 or 5 toxicity. • At a median follow-up of 2.2 years, all patients achieved a PSA nadir of <1 ng/mL, including 13 patients who had an undetectable PSA level. The 2-year biochemical progression-free survival was 94%.
CONCLUSION - • A dose of 20 mg/m(2) of weekly docetaxel given concurrently with high-dose IMRT and ADT appears safe for further study in patients with high-risk prostate cancer.
© 2012 BJU INTERNATIONAL.
PURPOSE - The purpose of this study was to examine factors associated with the presence of secondary external and internal lymphedema in patients with head-and-neck cancer (HNC).
METHODS AND MATERIALS - The sample included 81 patients ≥3 months after HNC treatment. Physical and endoscopic examinations were conducted to determine if participants had external, internal, and/or combined head-and-neck lymphedema. Logistic regression analysis was used to examine the factors associated with the presence of lymphedema.
RESULTS - The following factors were statistically significantly associated with presence of lymphedema: (1) location of tumor associated with presence of external (P=.009) and combined lymphedema (P=.032); (2) time since end of HNC treatment associated with presence of external (P=.004) and combined lymphedema (P=.005); (3) total dosage of radiation therapy (P=.010) and days of radiation (P=.017) associated with the presence of combined lymphedema; (4) radiation status of surgical bed was associated with the presence of internal lymphedema, including surgery with postoperative radiation (P=.030) and (salvage) surgery in the irradiated field (P=.008); and (5) number of treatment modalities associated with external (P=.002), internal (P=.039), and combined lymphedema (P=.004). No demographic, health behavior-related, or comorbidity factors were associated with the presence of lymphedema in the sample.
CONCLUSIONS - Select tumor and treatment parameters are associated with increased occurrence of lymphedema in patients with HNC. Larger and longitudinal studies are needed to identify adjusted effects and causative risk factors contributing to the development of lymphedema in patients with HNC.
Copyright © 2012 Elsevier Inc. All rights reserved.
BACKGROUND - Intensity-modulated radiation therapy (IMRT) and alternative chemotherapy regimens strive to maintain efficacy while minimizing toxicity in locally advanced head and neck cancer (LAHNC) treatment. Our experience with concurrent IMRT and taxane-based chemotherapy is presented.
METHODS - A retrospective review of 150 consecutive patients with LAHNC treated with IMRT and concurrent taxane-based chemotherapy with curative intent was performed. The IMRT fractionation regimen consisted of 69.3 Gy to gross disease (2.1 Gy/fraction) and 56.1 Gy to prophylactic nodal sites (1.7 Gy/fraction). Weekly paclitaxel (30 mg/m(2)) and carboplatin (area under the concentration-time curve [AUC], 1) were given concurrently to all patients, and 69% received weekly induction with paclitaxel (60 mg/m(2)) and carboplatin (AUC, 2).
RESULTS - Over 90% of patients received the prescribed radiation dose. Ninety-six percent completed five or more cycles of concurrent chemotherapy, with similar tolerability for induction chemotherapy. A percutaneous endoscopic gastrostomy (PEG) tube was required in 80 patients, with 10 maintaining PEG use >18 months. Acute grade 4 mucositis and dermatitis developed in 2.0% and 4.0% of patients, respectively. No patient experienced nadir sepsis, grade ≥3 late xerostomia, or significant nephropathy or gastrointestinal toxicity. Median follow-up was 30 months. The 3-year locoregional control rate was 83.2% with disease-free survival and overall survival rates of 78.8% and 76.5%, respectively.
CONCLUSION - Rates of acute and late toxicities were low, with excellent radiation dose delivery and impressive tumor control at 3 years, suggesting that concurrent carboplatin and paclitaxel with IMRT is a reasonable therapeutic option for the curative treatment of LAHNC.
PURPOSE - To estimate the possible radiation dose to other individuals from patients treated with yttrium-90 ((90)Y).
MATERIALS AND METHODS - Dosimetry data were analyzed after 143 consecutive administrations of (90)Y (124 resin, 19 glass) in 86 patients. External radiation exposure levels from patients were measured immediately after infusion. Total effective dose equivalent (TEDE) to maximally exposed individuals was calculated based on total body residence time and measured dose rate. These values were compared to Nuclear Regulatory Commission (NRC) regulations (maximum, 1 mSv) and other potential guidelines for caregivers, extensive caregivers, or pregnant contacts.
RESULTS - Mean administered activity for resin microspheres was 0.71 GBq ± 0.35 (range, 0.07-1.6GBq). Mean TEDE dose to the maximally exposed contact was 0.03 mSv (range, 0.0005-0.16 mSv). For glass microspheres, mean administered activity was 2.8 GBq ± 1.5 (range, 0.37-5.14 GBq). Mean TEDE dose to the maximally exposed contact was 0.06 mSv (range, 0.0023-0.23 mSv). All (90)Y treatments were within current NRC regulations for release without instructions. One, three, and one infusion were beyond potential thresholds for caregivers, extensive caregivers, or pregnant contacts, respectively. For any contact scenario, release without instruction was appropriate when administered activity was less than 3 GBq.
CONCLUSIONS - All patients treated with (90)Y hepatic radioembolization to a maximum administered activity of 5.14 GBq and maximum dose rate of 10 uSv/h were releasable without contact restrictions according to the NRC contact scenario. Patients who receive more than 3 GBq during infusion may require dose rate measurement if more restrictive contact scenarios are considered.
Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.
PURPOSE - Preconception radiation and chemotherapy have the potential to produce germ cell mutations leading to genetic disease in the next generation. Dose-response relationships were evaluated between cancer treatments and untoward pregnancy outcomes.
PATIENTS AND METHODS - A case-cohort study was conducted involving 472 Danish survivors of childhood and adolescent cancer and their 1,037 pregnancies. Adverse outcomes included 159 congenital malformations, six chromosomal abnormalities, seven stillbirths, and nine neonatal deaths. Preconception radiation doses to the gonads, uterus, and pituitary gland and administered chemotherapy were quantified based on medical records and related to adverse outcomes using a generalized estimating equation model.
RESULTS - No statistically significant associations were found between genetic disease in children and parental treatment with alkylating drugs or preconception radiation doses to the testes in male and ovaries in female cancer survivors. Specifically, the risk of genetic disease was similar among the children of irradiated survivors when compared with nonirradiated survivors (relative risk [RR], 1.02; 95% CI, 0.59 to 1.44; P = .94). A statistically significant association between abdomino-pelvic irradiation and malformations, stillbirths, and neonatal deaths was not seen in the children of female survivors overall (P = .07) or in the children of mothers receiving high uterine doses (mean, 13.5 Gy; max, 100 Gy; RR, 2.3; 95% CI, 0.95 to 5.56).
CONCLUSION - Mutagenic chemotherapy and radiotherapy doses to the gonads were not associated with genetic defects in children of cancer survivors. However, larger studies need to be conducted to further explore potential associations between high-dose pelvic irradiation and specific adverse pregnancy outcomes.
BACKGROUND - 25-hydroxyvitamin D insufficiency is common in healthy children and adolescents. There have been limited studies of the 25-hydroxyvitamin D status of survivors of pediatric and adolescent acute lymphoblastic leukemia (ALL).
PROCEDURE - In a cohort of 78 ALL survivors (52 chemotherapy-treated and 26 HCT-treated), we determined the prevalence of, and host, treatment and environmental risk factors for 25-hydroxyvitamin D insufficiency and deficiency.
RESULTS - There were no differences in serum 25-hydroxyvitamin D levels between ALL survivors treated with conventional chemotherapy and those treated with HCT (median 26.0 vs 25.5 ng/ml). Fifty-three percent of pediatric ALL survivors were 25-hydroxyvitamin D insufficient (15-29 ng/dl), and 12% were deficient (<15 ng/dl). Younger age, higher reported dietary vitamin D intake, use of vitamin D supplementation, and increased ambient ultraviolet light were associated with higher serum 25-hydroxyvitamin D levels. There was not enough evidence to suggest treatment type, gender, race, years since diagnosis or BMI were associated with serum 25-hydroxyvitamin D levels. Only 27% of conventional chemotherapy-treated ALL survivors and 8% of HCT-treated ALL survivors met RDA for dietary vitamin D intake.
CONCLUSIONS - The prevalence of vitamin D deficiency and insufficiency in ALL survivors is similar to that of the general pediatric population in the United States, and there is no difference in serum 25-hydroxyvitamin D status between chemotherapy-treated and HCT-treated ALL survivors. ALL survivors rarely meet the RDA requirements for vitamin D. Further studies are needed to determine whether dietary and behavioral interventions can improve the vitamin D status of ALL survivors.
Copyright © 2010 Wiley-Liss, Inc.