Initial clinical outcomes of audiovisual-assisted therapeutic ambience in radiation therapy (AVATAR).

PURPOSE: Radiation therapy is an important component of treatment for many childhood cancers. Depending upon the age and maturity of the child, pediatric radiation therapy often requires general anesthesia for immobilization, position reproducibility, and daily treatment delivery. We designed and clinically implemented a radiation therapy-compatible audiovisual system that allows children to watch streaming video during treatment, with the goal of reducing the need for daily anesthesia through immersion in video. METHODS AND MATERIALS: We designed an audiovisual-assisted therapeutic ambience in radiation therapy (AVATAR) system using a digital media player with wireless streaming and pico projector, and a radiolucent display screen positioned within the child's field of view to him or her with sufficient entertainment and distraction for the duration of serial treatments without the need for daily anesthesia. We piloted this system in 25 pediatric patients between the ages of 3 and 12 years. We calculated the number of fractions of radiation for which this system was used successfully and anesthesia avoided and compared it with the anesthesia rates reported in the literature for children of this age. RESULTS: Twenty-three of 25 patients (92%) were able to complete the prescribed course of radiation therapy without anesthesia using the AVATAR system, with a total of 441 fractions of treatment administered when using AVATAR. The median age of patients successfully treated with this approach was 6 years. Seven of the 23 patients were initially treated with daily anesthesia and were successfully transitioned to use of the AVATAR system. Patients and families reported an improved treatment experience with the use of the AVATAR system compared with anesthesia. CONCLUSIONS: The AVATAR system enables a high proportion of children to undergo radiation therapy without anesthesia compared with reported anesthesia rates, justifying continued development and clinical investigation of this technique.

Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal.

PURPOSE: To compare the toxicity and treatment outcomes in human immunodeficiency virus (HIV)-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal who underwent definitive concurrent chemoradiation at a single institution. MATERIALS AND METHODS: Fifty-three consecutive HIV-positive patients treated between 1987 and 2013 were compared with 205 consecutive HIV-negative patients treated between 2003 and 2013. All patients received radiotherapy at a single regional facility. The median radiation dose was 54 Gy (range, 28 to 60 Gy). Concurrent chemotherapy consisted of 2 cycles 5-FU with mitomycin-C given on day 1±day 29). After treatment, patients were closely followed with imaging studies, clinical examinations, and rigid proctoscopies. Outcomes assessed were toxicity rates, progression-free survival, colostomy-free survival, cancer-specific survival, and overall survival. RESULTS: Median follow-up was 34 months. Compared with HIV-negative patients, HIV-positive patients were younger (median age, 48 vs. 62 y) and predominantly male sex (98% of HIV-positive patients were male vs. 22% of HIV-negative patients). Of the HIV-positive patients, 37 (70%) were on highly active antiretroviral therapy, 26 (65%) had an undetectable viral load at the time of treatment, and 36 (72%) had a CD4 count>200 (mean CD4 count, 455). There were no significant differences in acute or late nonhematologic or hematologic toxicity rates between the 2 groups. At 3 years, there was no significant difference between HIV-positive and HIV-negative patients in regards to progression-free survival (75% vs. 76%), colostomy-free survival (85% vs. 85%), or cancer-specific survival (79% vs. 88%, P=0.36), respectively. On univariate analysis, there was a trend toward worse overall survival in HIV-positive patients (72% vs. 84% at 3 y, P=0.06). For the entire cohort, on multivariate analysis only male sex and stage were predictive of worse survival outcomes. HIV status was not associated with worse outcomes in Cox models. CONCLUSIONS: In the highly active antiretroviral therapy era, HIV-positive patients with anal cancer treated with standard definitive chemoradiation have equivalent toxicity and cancer-specific survival compared with HIV-negative patients.

Posttreatment FDG-PET-CT response is predictive of tumor progression and survival in anal carcinoma.

PURPOSE: We hypothesize that posttreatment F-18 fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) metabolic response predicts clinical outcomes in patients with anal cancer treated with chemoradiation. METHODS AND MATERIALS: This was a single-institution retrospective review of 148 patients treated definitively for anal squamous cell carcinoma between 2005 and 2012. All patients were followed with posttreatment PET-CT scans and clinical examinations. Progression-free survival (PFS), cause-specific survival, and overall survival (OS) estimates were calculated using the Kaplan-Meier method. RESULTS: The median follow-up was 34 months (range, 5-89 months). Pretreatment PET was successful in detecting the primary tumor in 140 cases (95%). Computed tomography (CT) alone was able to detect primary tumors in 78 of 122 patients who had pretreatment CT scans (64%). Inguinal or pelvic lymph nodes were FDG avid in 68 patients, with only 41 of these patients having enlarged lymph nodes by CT criteria (60.3%). Initial posttreatment PET-CT was obtained on average 12.7 ± 4.3 weeks after the last day of radiation (range, 5-25 weeks). Overall complete metabolic response (CR) on initial PET-CT was found in 82 patients (58%). Partial metabolic response was noted in 52 (36.9%) and progression in 7 patients (5%). Only 12/82 patients (14.6%) with a FDG-PET CR eventually recurred. The negative predictive value of a PET-CT scan performed between 13 and 25 weeks posttreatment was 92.9%. The 2-year PFS for patients with CR versus non-CR was 89.8% and 69.2%, respectively (P = .004). The 2-year OS for CR versus non-CR patients was 94.8% and 79.3% (P = .036). CONCLUSIONS: Complete metabolic response on posttreatment FDG PET-CT is highly predictive of increased PFS and OS in patients treated with chemoradiation for anal carcinoma. In addition to close clinical surveillance, we recommend obtaining posttreatment PET-CT scans >12 weeks following definitive treatment for anal cancer.

Chemoradiotherapy for squamous cell carcinoma of the anal canal: Comparison of one versus two cycles mitomycin-C.

BACKGROUND AND PURPOSE: Concurrent chemoradiotherapy with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is standard treatment for anal cancer. Randomized clinical trials in Europe have used 1 cycle MMC, while North American studies use 2 cycles. We compared treatment outcomes between patients treated with either 1 or 2 cycles of concurrent MMC. MATERIAL AND METHODS: 217 consecutive patients were treated definitively with chemoradiation from 2004 to 2012 in an integrated health system. Concurrent chemotherapy regimen depended on individual practice, and consisted of 2 cycles 5-FU (1000 mg/m(2)/day on days 1-4 and 29-32), along with MMC (10-15 mg/m(2)), given on either day 1 alone (n = 154), or days 1 and 29 (n = 63). Outcomes included progression-free (PFS), cancer-specific (CSS), overall (OS), and colostomy-free survival (CFS), as well as toxicity criteria. RESULTS: Median age 60 years, 70% female, 52% T3-T4, and 40% node-positive. Median follow-up 26 months. At 2 years, outcomes were: PFS 80%, CSS 89%, OS 86%, and CFS 88%. There was no difference in PFS (HR 0.85, 95% CI 0.37-1.92), CSS (HR 0.32, 95% CI 0.07-1.42), OS (HR 0.67, 95% CI 0.25-1.83), or CFS (HR 0.91, 95% CI 0.31-2.67) between the MMC1 and MMC2 groups. Stage and male gender were predictive of worse outcomes. Acute grade ⩾ 2 toxicities were worse in the MMC2 group. There were 3 treatment-related deaths, all in the MMC2 group. CONCLUSIONS: This study suggests that MMC1 is efficacious and may be an alternative to MMC2 in patients with anal cancer treated with definitive chemoradiation, with the potential for less acute treatment-related toxicity. Randomized trials comparing these two regimens could be considered.

Low Toxicity in Inflammatory Bowel Disease Patients Treated With Abdominal and Pelvic Radiation Therapy.

OBJECTIVE: To determine the short-term and long-term toxicity of abdominal and pelvic radiation therapy in a cohort of patients with inflammatory bowel disease (IBD). We hypothesize that with newer techniques, such as intensity-modulated radiation therapy (IMRT) and 3-dimensional conformal radiotherapy (3D-CRT), patients with IBD can safely undergo abdominal and pelvic radiation, with low risk for major acute or late toxicity. MATERIALS AND METHODS: Nineteen consecutive patients with IBD (14 with ulcerative colitis, 5 with Crohn disease) who were treated with abdominal or pelvic external beam radiation therapy at Stanford University from 1997 to 2011 were identified. Fourteen patients were treated with IMRT and 5 were treated with 3D-CRT. Treated sites included prostate (n=8), gastric/esophageal (n=5), rectal/anal (n=3), and liver (n=3) tumors. Charts were reviewed and toxicity was graded according to the Common Terminology Criteria for Acute Events version 4.0. Median follow-up was 32.5 months. Fisher exact test was used to determine if any clinical and/or treatment factors were associated with toxicity outcomes. RESULTS: Acute grade ≥3 toxicity occurred in 2 patients (11%). Late grade ≥3 toxicity occurred in 1 patient (6%). Acute grade ≥2 toxicity occurred in 28% of patients treated with IMRT versus 100% of patients treated with 3D-CRT (P=0.01). Acute grade ≥2 gastrointestinal toxicity was lower in patients treated with IMRT versus 3D-CRT (14% vs. 100%, respectively, P=0.002). Late grade ≥2 toxicity occurred in 21% of patients. Higher total dose (Gy) and biologically effective dose (Gy) were associated with increased rates of late grade ≥2 toxicity (P=0.02 and 0.03, respectively). CONCLUSIONS: These data suggest that select patients with IBD can safely undergo abdominal and pelvic radiation therapy. The use of IMRT was associated with decreased acute toxicity. Acute and late severe toxicity rates were low in this patient population with the use of modern radiation techniques.

High-dose-rate prostate brachytherapy consistently results in high quality dosimetry.

PURPOSE: We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy. METHODS AND MATERIALS: Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size. RESULTS: The mean prostate ultrasound volume was 38.7 ± 13.4 cm(3) (range: 11.7-108.6 cm(3)). The mean CTV was 75.1 ± 20.6 cm(3) (range: 33.4-156.5 cm(3)). The mean D90 was 109.2% ± 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% ± 0.05%, 99.5% ± 0.8%, 25.4% ± 4.2%, and 7.8% ± 1.4%. The mean dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) for organs at risk were: Urethra: 107.3% ± 3.0%, 101.1% ± 14.6%, and 47.9% ± 34.8%; bladder wall: 79.5% ± 5.1%, 69.8% ± 4.9%, and 64.3% ± 5.0%; bladder balloon: 70.3% ± 6.8%, 59.1% ± 6.6%, and 52.3% ± 6.2%; rectum: 76.3% ± 2.5%, 70.2% ± 3.3%, and 66.3% ± 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size. CONCLUSIONS: HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes.

Does preoperative immunosuppression influence unplanned hospital readmission after surgery in patients with Crohn's disease?

BACKGROUND: Steroids, immunomodulators, and biologics, often in combination with one another, are frequently used in the treatment of Crohn's disease. Retrospective studies have yielded conflicting results regarding the influence of preoperative immunosuppressive therapy on postoperative complications after surgery in Crohn's disease. Unplanned hospital readmission is considered to be an index of quality surgical care. OBJECTIVE: The aim of this study was to examine the association, if any, between the number of preoperative immunosuppressive therapies and unplanned hospital readmission after surgery in patients with Crohn's disease. DESIGN: Consecutive patients with Crohn's disease requiring abdominal surgery were identified from a prospectively maintained database. Preoperative immunosuppressive therapy within 3 months before surgery was categorized into 3 classes: steroids, immunomodulators, and biologics. MAIN OUTCOME MEASURES: Unplanned readmission occurring within 30 days of hospital discharge was assessed. Trend analysis was performed with the use of the Cochrane-Armitage test. RESULTS: The study group included 338 patients. Preoperative medical therapy included steroids (n = 199; 59%), immunomodulators (n = 162; 48%), and biologics (n = 59; 18%). Sixty-three patients (19%) were not treated with any immunosuppressive medications preoperatively, whereas 148 patients (44%), 108 patients (32%), and 19 patients (6%) were treated with 1, 2, or 3 classes of immunosuppressive medications. Twenty-eight patients (8.3%) had an unplanned readmission. The incidence of unplanned readmission was similar among patients treated with steroids (11%), immunomodulators (9%), and biologics (12%). The incidence of unplanned readmission was 3%, 7%, 11%, and 16% in patients treated with 0, 1, 2, or 3 preoperative medication classes (trend analysis p = 0.02). No significant differences were observed between patient groups treated with 0, 1, 2, or 3 preoperative immunosuppressive therapies with respect to patient, disease, or surgical factors. CONCLUSIONS: Unplanned hospital readmission occurs frequently (8.3%) after surgery for Crohn's disease. Combination immunosuppressive therapy before surgery in patients with Crohn's disease appears to be associated with an increased incidence of postoperative unplanned hospital readmission.