Phase II Trial of Cisplatin, Gemcitabine, and Intensity-Modulated Radiation Therapy for Locally Advanced Vulvar Squamous Cell Carcinoma: NRG Oncology/GOG Study 279.

PURPOSE: To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery. METHODS: Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed. Sixty-four Gy IMRT was prescribed to the vulva, with 50-64 Gy delivered to the groins/low pelvis. Radiation therapy (RT) plans were quality-reviewed pretreatment. C 40 mg/m2 and G 50 mg/m2 were administered once per week throughout IMRT. Complete pathologic response (CPR) was the primary end point. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adverse events were assessed with Common Terminology Criteria for Adverse Events v 4.0. RESULTS: Fifty-seven patients enrolled, of which 52 were evaluable. The median age was 58 years (range, 25-58), and 94% were White. Forty (77%) had stage II or III disease, and all had squamous histology. A median of six chemotherapy cycles (range, 1-8) were received. Eighty-five percent of RT plans were quality-reviewed with 100% compliance to protocol. Seven patients came off trial because of toxicity or patient withdrawal. Of 52 patients available for pathologic assessment, 38 (73% [90% CI, 61 to 83]) achieved CPR. No pelvic exenterations were performed. With a median follow-up of 51 months, the 12-month PFS was 74% (90% CI, 62.2 to 82.7) and the 24-month OS was 70% (90% CI, 57 to 79). The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event unlikely related to treatment. CONCLUSION: Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.

Single-cell quantitative expression of nicotinic acetylcholine receptor mRNA in rat hippocampal interneurons.

Hippocampal interneurons are a very diverse population of cells. Using single-cell quantitative PCR to analyze rat CA1 hippocampal interneurons, we quantified neuronal nicotinic acetylcholine receptor (nAChR) mRNA subunit expression and detailed possible nAChR subtype combinations for the α2, α3, α4, α5, α7, ß2, ß3, and ß4 subunits. We also compared the expression detected in the stratum oriens and the stratum radiatum hippocampal layers. We show that the majority of interneurons in the CA1 of the rat hippocampus contain detectable levels of nAChR subunit mRNA. Our results highlight the complexity of the CA1 nAChR population. Interestingly, the α3 nAChR subunit is one of the highest expressed subunit mRNAs in this population, while the α4 is one of the least likely subunits to be detected in CA1 interneurons. The ß2 nAChR subunit is the highest expressed beta subunit mRNA in these cells. In addition, Pearson's correlation coefficient values are calculated to identify significant differences between the nAChR subunit combinations expressed in the CA1 stratum oriens and the stratum radiatum. Statistical analysis also indicates that there are likely over 100 different nAChR subunit mRNA combinations expressed in rat CA1 interneurons. These results provide a valid avenue for identifying nAChR subtype targets that may be effective hippocampus-specific pharmacological targets.

Distance to Burn Center Does Not Impact Long-term Anxiety and Depression Risk Following Burn Injury.

Burn injury predisposes patients to significant psychological morbidity, including anxiety, depression, and posttraumatic stress. Adding to the burden of injury, patients often require transfer to specialized burn centers located far from home. We hypothesized that greater distances between a patient's home address and the treating burn center would increase the rate of postinjury anxiety and depression. From January 2021 to June 2023, patients who were admitted to our American Burn Association verified center and seen for posthospitalization follow-up were identified. Demographics, burn characteristics, and follow-up anxiety (Generalized Anxiety Disorder-7) and depression (Patient Health Questionnaire-2) screening scores were reviewed. Comparisons between patients with positive and negative screens were performed using univariate analysis followed by logistic regression. Linear regression was used to evaluate the relationship between distance to the burn center and incremental screening scores. Of the 272 patients identified, 35.6% and 27.9% screened positive for anxiety and depression, respectively. The distance to burn center was not greater among patients with positive screens. Likewise, no statistically significant linear relationship was found between distance to the burn center and incremental screening scores. Morphine milligram equivalents on the last day of hospitalization (P = .04) and a prior psychiatric history (P < .001) all predicted postinjury anxiety. Total body surface area burned (P = .02) and a prior psychiatric history (P = .02) predicted postinjury depression. The distance between a patient's home and the treating burn center does not alter anxiety and depression rates following burn injury, further supporting the transfer of patients to specialized centers.

Dosimetric evaluation of the feasibility of utilizing a reduced number of interstitial needles in combined intracavitary and interstitial brachytherapy for cervical cancer.

PURPOSE: To evaluate the ability of the Venezia advanced multichannel tandem and ring applicator to consistently produce dosimetrically comparable plans utilizing a reduced number of needle channels, to reduce the risk of secondary complications when boosting cervical cancer treatments with high dose rate (HDR) brachytherapy. METHODS: We evaluated 26 fractions from 13 patients who were treated with HDR brachytherapy using the Venezia (Elekta) applicator. The original plans included a full load of 12-16 needles, including both parallel and 30-degree oblique needles. We replanned each original to nine new configurations, with a reduced number of two, three, four, or six needles. Comparisons included differences in percentage dose coverage to 90% of the high-risk clinical target volume, and percentage dose to 2 cm3 of the bladder, rectum, sigmoid, and bowel. We considered new plans "passing" if they remained within our standards (D90 > 100%; D2 cm3  < 85% bladder, <65% rectum, sigmoid, bowel) or did not perform worse than original. RESULTS: Removing only the two most anterior or the two most posterior needles from both sides showed 80.8% and 61.5% overall passing rate. Removal of the most anterior and posterior four needles together showed 65.4% overall passing rate. Removing all oblique needles showed 19.2% overall passing rate. Removing only left-sided or only right-sided oblique needles showed 46.2% and 23.1% overall passing, respectively. Removing only right-sided or only left-sided parallel needles separately showed 19.2% and 34.6% overall passing, respectively. Removing all parallel needles showed 11.5% overall passing rate. CONCLUSIONS: As only two replans required a full needle load to maintain dosimetric quality and 40 (76.9%), 36 (34.6%), 18 (69.2%), and 10 (19.2%) replans passed with 2, 3, 4, and 6 needles removed respectively, this indicates the potential for using a lesser number of interstitial needles during combined intracavitary and interstitial HDR brachytherapy while maintaining dosimetric quality.

Phase II trial of vaginal cuff brachytherapy followed by dose-dense chemotherapy in early stage endometrial cancer patients with enriched, high-intermediate risk factors for recurrence.

OBJECTIVE: To determine the feasibility of vaginal cuff brachytherapy (VCB) followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy (ddTC) in enriched, high-intermediate risk (H-IR) patients with early stage endometrial cancer following hysterectomy. METHODS: A phase II trial of early stage endometrial cancer patients treated with VCB (2100 cGy) followed by three cycles of carboplatin (AUC 6) and dose dense paclitaxel (80 mg/m2) weekly within 12-weeks of surgery was conducted. The primary endpoint was the proportion of patients completing both VCB and ddTC. Secondary outcomes include short and long-term toxicities, recurrence rate and sites, and progression free survival. Toxicity assessments were patient reported as well as those resulting in delays or dose modifications. RESULTS: A total of 32 evaluable patients with median age of 64.5 years were included. Most patients were endometrioid histology (18/32, 56.3%) and fully staged (21/32, 65.6%) to stage Ib (18/32, 56.3%). In total, 27/32 (84.4%) patients completed treatment per protocol. Protocol non-completion included renal insufficiency, paclitaxel reaction, and treatment refusal. Median time to VCB completion was 11 days with all patients completing three fractions of VCB. Acute toxicities with VCB included grade 1 and 2 gastrointestinal, genitourinary and fatigue symptoms. Acute toxicities associated with ddTC included infusion reaction and neutropenia. Most reported long-term toxicities were grade 1 or 2 and resolved with time. CONCLUSIONS: Treatment with VCB followed by three cycles of ddTC is well-tolerated with promising utility for treatment in enriched high-intermediate risk endometrial cancer patients. Recurrence-free and overall survival outcomes are not yet mature.

Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study.

PURPOSE: In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT). PATIENTS AND METHODS: Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar's test for rates > 0%. RESULTS: Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% (P < .0001), high-grade diarrhea 38.5% (P < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; P = .01), frequency of fecal incontinence (8.2% difference; P = .01), and interference of fecal incontinence (8.5% difference; P = .04). CONCLUSION: Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.

Dosimetric considerations when utilizing Venezia, Capri, Rotte double tandem, and tandem and ring with interstitial needles for the treatment of gynecological cancers with high dose rate brachytherapy.

This work evaluated the difference in dosimetry of high dose rate (HDR) brachytherapy treatments between plans using advanced multichannel applicators and simplified base versions. Eighteen HDR patients treated using Interstitial Ring CT/MR Applicator Set (Elekta Brachytherapy, Netherlands) (TRN) (21 plans), CapriTM Applicator Set (Varian Medical Systems, Inc., Palo Alto, CA) (CC) (19 plans), Rotte Endometrial Applicator Set (Elekta Brachytherapy, Netherlands) (RDT) (18 plans), and the Advanced Gynecological Applicator Venezia (Vz) (Elekta Brachytherapy, Netherlands) (6 plans) were retrospectively reviewed. For each plan, "advanced" channels including any interstitial channels, the 12 noncentral channels in the CC, and the lateral extending aspects of the RDT were removed and a new plan with the original inverse planning settings was optimized using only the remaining "simplified" applicator and compared to the original. The new plans were renormalized to match the original percent dose to 90% of the high-risk clinical target volume (HR-CTV). Critical structures included bladder, rectum, sigmoid colon, and small bowel. Comparisons were made utilizing dose volume histograms of HR-CTVs, conformation number (CN), and the equivalent total dose in 2 Gy fractions (EQD2) to 2 cm3 of the normal structures. Comparing simplified to advanced plans, the average percent differences in EQD2 to 2 cm3 for Vz, with 95% confidence interval, were 101.7 ± 85.9%, 147.8 ± 76.7%, 95.3 ± 61.6%, and 44.0 ± 12.4% for Rectum, Bladder, Sigmoid, and Bowel, respectively. For TRN: 36.9 ± 18.5%, 38.2 ± 14.5%, 20.3 ± 8.8%, and 15.3 ± 8.2%. For CC: 18.9 ± 3.7%, 12.3 ± 5.3%, 27.8 ± 7.1%, and 17.1 ± 3.6%. For RDT: 1.5 ± 6.8%, 7.4 ± 6.7%, 11.1 ± 4.4%, and 8.0 ± 8.7%. The CN was better in advanced applications by 0.024 for RDT, 0.104 for TRN, 0.043 for CC, and 0.251 for Vz (all p < 0.05). Advanced multichannel treatments allow better target dose conformation and normal tissue dose manipulation. The biggest factors influencing the brachytherapy dose distributions are the number of available channels and their separation from each other within the target.

Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy.

OBJECTIVE: Women with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT. METHODS: In addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed. RESULTS: Mean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT. CONCLUSION: Correlations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.

Computational Models of Polymer Synthesis Driven by Dehydration/Rehydration Cycles: Repurination in Simulated Hydrothermal Fields.

Cycles of biologically relevant reactions are an alternative to an origin of life emerging from a steady state away from equilibrium. The cycles involve a rate at which polymers are synthesized and accumulate in microscopic compartments called protocells, and two rates in which monomers and polymers are chemically degraded by hydrolytic reactions. Recent experiments have demonstrated that polymers are synthesized from mononucleotides and accumulate during cycles of hydration and dehydration, which means that the rate of polymer synthesis during the dehydrated phase of the cycle is balanced (but not dominated) by the rate of polymer hydrolysis during the hydrated phase of the cycle. Furthermore, depurination must be balanced by the reverse process of repurination. Here we describe a computational model that was inspired by experimental results, can be generalized to accommodate other reaction parameters, and has qualitative predictive power.

Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203.

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related 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.

A Systematic Review and Meta-Analysis on the Use of Repetitive Transcranial Magnetic Stimulation for Spasticity Poststroke.

BACKGROUND: Spasticity is a common and potentially debilitating complication that develops after stroke, arising in approximately 30% of patients. OBJECTIVE: To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in improving spasticity after stroke. DESIGN: Meta-analysis and systematic review. SETTING: Not applicable. PATIENTS: A total of 273 poststroke (hemorrhagic = 123, ischemic = 150) participants were included with sample sizes ranging from 5 to 80. The majority of participants were male (66.0%) with a mean age ranging from 55.0 to 64.6 years. Mean stroke duration ranged from 6 months to 10 years. METHODS: A literature search of multiple databases was conducted for articles published in English from January 1980 to April 2015 using select keywords. Studies were included if (1) the population included was >50% stroke patients; (2) the sample size included ≥4 subjects; (3) the intervention applied was rTMS; and (4) upper extremity spasticity was assessed pre- and postintervention. Randomized controlled trials (RCTs) were assessed for methodologic quality with the Physiotherapy Evidence Database tool. All research designs were given a level of evidence according to a modified Sackett Scale. MAIN OUTCOME MEASUREMENTS: Modified Ashworth Scale (MAS). RESULTS: Ten studies met the inclusion criteria: 2 RCTs (Physiotherapy Evidence Database scores 8-9) and 8 pre-post studies. Meta-analyses of primarily uncontrolled pre-post studies found significant improvements in MAS for elbow (P < .001), wrist (P < .001), and finger flexors (P < .001). However, a meta-analysis of the 2 available RCTs failed to find a significant rTMS treatment effect on MAS for the wrist (standardized difference = .34, P = .30). CONCLUSIONS: There is limited available evidence to support the use of rTMS in improving spasticity poststroke. Despite the positive findings reported, better powered and appropriately controlled trials are necessary. LEVEL OF EVIDENCE: II.

Hepatocytes Are the Principal Source of Circulating RBP4 in Mice.

RBP4 is produced mainly by hepatocytes. In type 2 diabetes and obesity, circulating RBP4 is increased and may act systemically to cause insulin resistance and glucose intolerance. Observations that adipocyte RBP4 mRNA increases in parallel with circulating RBP4 in these conditions, whereas liver RBP4 mRNA does not, led to a widely held hypothesis that elevated circulating RBP4 is a direct result of increased production by adipocytes. To test this, we generated mice with hepatocyte-specific deletion of RBP4 (liver RBP4 knockout or LRKO mice). Adipose tissue RBP4 expression and secretion remained intact in LRKO mice and increased as expected in the setting of diet-induced insulin resistance. However, circulating RBP4 was undetectable in LRKO mice. We conclude that adipocyte RBP4 is not a significant source of circulating RBP4, even in the setting of insulin resistance. Adipocyte RBP4, therefore, may have a more important autocrine or paracrine function that is confined within the adipose tissue compartment.

Repetitive Transcranial Magnetic Stimulation for Depression Due to Cerebrovascular Disease: A Systematic Review.

OBJECTIVE: This study aims to perform a systematic review evaluating the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in improving depression resulting from cerebrovascular disease including vascular depression (VD) and poststroke depression (PSD). METHODS: A literature search of multiple scientific databases was conducted for English studies published from January 1980 to June 2016. Studies were included if the sample consisted of 50% or more adult humans with VD or PSD and had 3 or more subjects, the intervention applied was rTMS, and depression was assessed pre- and post intervention using a formal outcome measure. Randomized controlled trials (RCTs) were assessed for methodological quality using the Physiotherapy Evidence Database (PEDro) tool. A level of evidence was assigned to each study according to the modified Sackett Scale. RESULTS: Five studies met the inclusion criteria including 3 RCTs (level 1b; PEDro range: 6-8) and 2 uncontrolled pre-post studies (level 4). There were 186 participants with either PSD (n = 40) or VD (n = 146); the majority of the participants were female (52.7%) and had a mean age ranging from 51.9 to 67.9 years. There were no adverse effects reported by any of the studies. Using clinically accepted criteria for the response rate, all studies reported a benefit from rTMS for the treatment of depression. Three studies also demonstrated a benefit on remission rates as well. CONCLUSIONS: rTMS was reported to be beneficial in treating depression among individuals with cerebrovascular disease over the short term. However, heterogeneous populations and variability in study design and protocol, as well as a limited number of studies to review, challenge the ability to form conclusions as to the effectiveness of rTMS.

Linear accelerator based intracranial and extracranial stereotactic radiation therapy at the University of Oklahoma.

PURPOSE: Review our institutional outcomes with linear accelerator based stereotactic radiation therapy at the University of Oklahoma. METHODS: We retrospectively reviewed all patients treated in our department with linear accelerator based stereotactic radiation therapy since we implemented this modality in 2008. Thirty-seven patients have been treated with a mean follow-up of 8.3 months. Seventeen patients had tumors near critical structures; ten had treatment sites not suited for gamma knife therapy. Outcomes are reviewed for efficacy and toxicity. RESULTS: Acute and long term complications reported are minimal. Stabilization of treatment sites was achieved in 96% of patients on follow-up imaging. Thirteen patients (35%) have died, of which eleven died to systemic disease progression outside of the treatment site. No treatment related deaths occurred. CONCLUSIONS: Stereotactic radiation therapy is a successful treatment modality to achieve local disease control with minimal toxicity. We plan to expand its use and applications in the future.

Radiotherapy in treatment of carcinoma of the parotid gland, an approach for the medically or technically inoperable patient.

INTRODUCTION: Initial surgical resection is considered the standard of care for patients diagnosed with tumours involving the salivary glands. We reviewed our institutional outcomes of patients treated with initial radiation therapy (RT) for diagnosed carcinoma of the parotid gland. METHODS: This review examined seventeen patients that received RT as initial therapy for tumours involving the parotid gland. Fifteen patients had primary salivary gland cancer, and two patients had metastatic carcinoma to the parotid gland. Sixteen patients (94.1%) following surgical evaluation had operative risk of facial nerve impairment or sacrifice with initial surgery, four (23.5%) had clinical objective evidence of nerve involvement at evaluation, five (29.4%) were poor surgical candidates and three (17.6%) refused initial surgery. Primary tumour stages ranged T2-T4b, and disease stages ranged II-IVb. RT median dose was 70 Gy, and median follow-up was 12 months. RESULTS: Eleven patients (64.7%) achieved a clinical complete response (CR) to therapy. Of these CR patients eight (72.7%) received definitive RT and three (27.3%) underwent surgery following RT. Two surgical patients avoided facial nerve impairment while one required nerve sacrifice. The other six patients (35.3%) achieved an unfavourable response to RT and had unresectable or metastatic disease at follow-up. No long-term complications were reported. CONCLUSION: Initial radiation therapy for tumours involving the parotid gland is effective to achieve clinical CR, eliminate surgical resection for many patients, and decrease risk of facial nerve impairment or sacrifice for those patients requiring surgery following RT.

Evaluation of the setup accuracy of a stereotactic radiotherapy head immobilization mask system using kV on-board imaging.

The purpose of this study was to evaluate setup accuracy and quantify random and systematic errors of the BrainLAB stereotactic immobilization mask and localization system using kV on-board imaging. Nine patients were simulated and set up with the BrainLAB stereotactic head immobilization mask and localizer to be treated for brain lesions using single and hypofractions. Orthogonal pairs of projections were acquired using a kV on-board imager mounted on a Varian Trilogy machine. The kV projections were then registered with digitally-reconstructed radiographs (DRR) obtained from treatment planning. Shifts between the kV images and reference DRRs were calculated in the different directions: anterior-posterior (A-P), medial-lateral (R-L) and superior-inferior (S-I). If the shifts were larger than 2mm in any direction, the patient was reset within the immobilization mask until satisfying setup accuracy based on image guidance has been achieved. Shifts as large as 4.5 mm, 5.0 mm, 8.0 mm in the A-P, R-L and S-I directions, respectively, were measured from image registration of kV projections and DRRs. These shifts represent offsets between the treatment and simulation setup using immobilization mask. The mean offsets of 0.1 mm, 0.7 mm, and -1.6 mm represent systematic errors of the BrainLAB localizer in the A-P, R-L and S-I directions, respectively. The mean of the radial shifts is about 1.7 mm. The standard deviations of the shifts were 2.2 mm, 2.0 mm, and 2.6 mm in A-P, R-L and S-I directions, respectively, which represent random patient setup errors with the BrainLAB mask. The Brain-LAB mask provides a noninvasive, practical and flexible immobilization system that keeps the patients in place during treatment. Relying on this system for patient setup might be associated with significant setup errors. Image guidance with the kV on-board imager provides an independent verification technique to ensure accuracy of patient setup. Since the patient may relax or move during treatment, uncontrolled and undetected setup errors may be produced with patients that are not well-immobilized. Therefore, the combination of stereotactic immobilization and image guidance achieves more controlled and accurate patient setup within 2mm in A-P, R-L and S-I directions.

Quantitative evaluation of increase in surface dose by immobilization thermoplastic masks and superficial dosimetry using Gafchromic EBT film and Monte Carlo calculations.

PURPOSE: To investigate the increase in surface dose under immobilization thermoplastic masks by measurements and calculation in the build-up region using Gafchromic films and Monte Carlo simulation. MATERIALS AND METHODS: Surface doses were measured underneath three thermoplastic masks in open fields using 6 and 18 MV photon beams. These masks are used to immobilize patients for head and neck (H&N), pelvis and thoracic treatment. Gafchromic EBT films were placed on the top of the flat surface of a phantom partially underneath the mask and exposed in open 10 x 10 cm2 photon fields. The depth doses were calculated using BEAMnrc Monte Carlo code for water-equivalent film detectors with different layers of thickness ranging from 50 microm to 2.5 mm and compared with film measurements. RESULTS: Surface dose increased by a factor of 3 to 4 underneath the mask relative to the open areas and 6 MV beam delivers more skin dose than 18 MV. H&N mask increased surface dose by a factor of 3 using 18 MV and a factor of 4 using 6 MV. In addition, increase in surface dose depended on the type of the mask, the size of openings, and the amount of stretching performed during the mask preparation. The measured depth doses were compared with BEAMnrc Monte Carlo calculation for water-equivalent detectors using different sizes. The calculated depth dose depended significantly on the thickness of film detector and varies by more than 15% using layer thickness of 2.5 mm compared to 50 microm. Surface doses measured by Gafchromic EBT films agreed within 3% with the Monte Carlo calculations using a small detector layer of 50 microm. CONCLUSION: Thermoplastic masks used for patient immobilization can significantly increase skin doses by up to a factor of 4 more than that without the mask using 6 MV beams. The skin reactions resulting from thermoplastic masks should be monitored and corrective measures should be taken during treatment such as partially removing the mask over skin areas with complications and optimizing the skin dose in IMRT planning. Gafchromic EBT films provide accurate skin dosimetry which agrees within 3% with Monte Carlo calculations. Gafchromic EBT film makes an excellent tool for measuring depth doses in the buildup region and these data can be applied for treatment planning calculations and IMRT optimization.

Using an advanced radiation therapy technique for T4 squamous cell carcinoma of the face.

BACKGROUND: Patients with locally advanced skin cancer often present an uncommon and unique treatment challenge. Surgical resection and reconstruction with an acceptable cosmetic outcome is difficult for larger lesions with deep infiltration into subcutaneous tissues. Radiation therapy has been shown to be an effective treatment modality for advanced non-melanoma skin cancers, with cure rates ranging 50-100%. In this case report, we discuss the efficacy and outcome of treatment using an advanced radiation therapy technique to a large T4 squamous cell carcinoma of the face. MAIN OBSERVATIONS: The patient responded favorably to the advanced radiation treatment course, and achieved a clinical complete response to therapy. No further intervention was required. Advanced radiation therapy techniques offered treatment advantages that resulted in greater tumor dose escalation and minimizing of patient morbidity. CONCLUSIONS: Patients with advanced skin cancers of the head and neck should be considered for definitive radiation therapy using advanced treatment techniques. The use of definitive RT only for tumors deemed unresectable, or for inoperable patients at presentation deserves reconsideration. Further investigation is warranted.

A comparative study of seed localization and dose calculation on pre- and post-implantation ultrasound and CT images for low-dose-rate prostate brachytherapy.

This work investigates variation in the volume of the prostate measured at different stages through the prostate brachytherapy procedure for 30 patients treated with I-125 radioactive seeds. The implanted seeds were localized on post-implantation ultrasound (US) images and the effect of prostate enlargement due to edema on dose coverage for 15 patients was studied. The volume of the prostate was measured at four stages as follows: (a) 2-3 weeks prior to implantation using US imaging, (b) then at the start of the intra-operative prostate brachytherapy procedure on the day of the implant, (c) immediately post-implantation using US imaging in the operating room and (d) finally by CT imaging at nearly 4 weeks post-implantation. Comparative prostate volume studies were performed using US imaging stepper and twister modes. For the purpose of this study, the implanted seeds were localized successfully on post-implant ultrasound twister images, retrospectively. The plans using post-implant US imaging were compared with intra-operative plans on US and plans created on CT images. The prostate volume increases about 10 cm(3) on average due to edema induced by needle insertion and seed loading during implantation. The visibility of the implanted seeds on US twister images acquired post-implantation is as good as those on CT images and can be localized and used for dose calculation. The dose coverage represented by parameters such as D90 (dose covering 90% of the volume) and V100 (volume covered by 100% dose) is poorer on plans performed on post-implantation twister US studies than on the intra-operative live plan or the CT scan performed 4 weeks post-operatively. For example, the mean D90 difference on post-implantation US is lower by more than 15% than that on pre-implantation US. The volume enlargement of the prostate due to edema induced by needle insertion and seed placement has a significant effect on the quality of dosimetric coverage in brachytherapy prostate seed implants. Here, we introduced a new approach based on the use of post-implant US twister images to correct for prostate enlargement intra-operatively. Besides the ability to localize the seeds and superior soft tissue visibility, the twister US images include effects of the enlargement of the prostate gland and seed migration during the implantation procedure.