Citations

75 Background: Combined radiotherapy (RT) and long-term hormonal therapy (HT) is a standard treatment option for high-risk prostate cancer. Dose escalated RT alone has been shown to improve disease free survival. Increased sensitivity of prostate cancer to high doses per fraction has led to hypofractionation as a method to radiobiologically escalate dose.We report on the quality of life of patients treated with combined hypofractionated RT and HT. Methods: A prospective phase I/II study enrolling patients with any of: clinical T3, PSA ≥20, or Gleason 8-10. Forty-five Gy (1.8 Gy/fraction) was delivered to the pelvic nodes with a concomitant 22.5 Gy intensity-modulated RT boost to the prostate, for a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions over 5 weeks. Hormonal therapy was administered for 2-3 years. Patient reported outcomes were measured at baseline and every 6 months using the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire, which measures urinary, bowel, sexual, and hormonal domains. Results: Sixty patients with a minimum 24 months of patient-reported outcomes were analyzed. Mean scores comparing baseline to 24 month values are reported. There were no statistically significant changes in the urinary summary scores (86.3 vs. 86.0, p=0.45) or any of the urinary subscales (function, bother, incontinence, irritative/obstructive). Domain summary score decreases were observed in: bowel by 4.4% (94.7 vs. 90.3, p<0.01), sexual by 27% (44.5 vs. 17.5, p<0.01), and hormonal by 11.9% (93.1 vs. 81.2, p<0.01). Examining time trends in outcomes, most changes occurred within the first 6 months with smaller changes thereafter. Conclusions: Hypofractionated RT combined with long-term HT is associated with good patient-reported urinary and bowel outcomes at 24 months. Sexual and hormonal summary scores are affected, largely due to continued androgen deprivation therapy. Further follow-up is needed to document patient reported outcomes after testosterone recovery. No significant financial relationships to disclose.

327 Background: To report long-term outcomes of patients (pts) treated with radiotherapy (RT) for stage II testicular seminoma. Methods: Between 1974 and 2007, 52 pts received RT for clinical stage II testicular seminoma after radical inguinal orchiectomy; 3 pts were excluded due to no clinical follow-up. CT staging was used for 46 pts (94%). Estimates of overall (OS), relapse-free (RFS), and cause-specific (CSS) survival were determined using the Kaplan-Meier technique. Major cardiac event (MCE) was defined as myocardial infarction, coronary artery bypass grafting or stenting, or valve replacement. Second malignancy (SM) was defined as biopsy-confirmed malignancy occurring in the RT field. Results: The median pt age was 35 years. AJCC stage was IIA (n=23), IIB (n=7), IIC (n=15), and unknown (n=4). Three pts were treated for paraortic recurrence during surveillance for stage I seminoma. Four pts with IIB (n=1) or IIC (n=3) disease were treated with chemotherapy in addition to RT. The median total RT dose was 30.4 Gy. Prophylactic mediastinal/supraclavicular (MSCV) RT was given to 24 pts (49%). The median follow-up was 18 years (range 0.4-37). Estimates of OS, RFS, and CSS at 10 and 20 years were 94% and 81%, 79% and 70%, and 96% and 96%, respectively. OS, RFS, and CSS were not significantly different between stage groups. Recurrence occurred in 9 pts (18%); sites were MSCV (n=6), para-aortic (n=1), lung (n=1), and peritoneal cavity (n=1). Seven pts were successfully salvaged, while 2 pts died of seminoma. No patient with stage IIA/B that received prophylactic MSCV RT (n=11) experienced MSCV relapse. Among patients that did not receive prophylactic MSCV RT, 2 of 13 (15%) with stage IIA and 3 of 6 (50%) with stage IIB experienced MSCV relapse. MCE occurred in 10 pts (20%) at a median of 18 years (range 7-30) after RT. SM occurred in 5 pts (10%) at a median of 27 years (range 20-34) after RT. Conclusions: Infradiaphragmatic RT alone was associated with a significant risk of MSCV failure, particularly in patients with stage IIB disease, suggesting that chemotherapy may be the optimal treatment in this patient cohort. Most MCE and SM events occurred more than 20 years after RT, highlighting the importance of vigilant long-term follow-up.

367 Background: On initial publication of GI Intergroup RTOG 98-11, concurrent chemoradiation with 5FU+mitomycin (MMC) decreased colostomy failure (CF) vs induction plus concurrent 5FU+cisplatin (CDDP), but did not significantly impact disease free or overall survival (DFS, OS). The intent of the current analysis is to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free [CFS]), CF and relapse (local-regional [LRF], distant [DM]) in this patient group. Methods: Stratification factors included gender, clinical node status, and primary size. DFS/OS were estimated univariately by Kaplan-Meier method and treatment arms compared by log-rank test. Time to relapse/CF were estimated by cumulative incidence method and treatment arms compared by Gray's test. Multivariate analyses were done with Cox proportional hazard models to test for treatment differences, adjusting for stratification factors. Results: Of 682 patients accrued, 649 were analyzable for outcomes. As seen in the table, 5-yr DFS and OS were statistically better for RT+5FU/MMC vs RT+5FU/CDDP (67.7 v 57.6%, p=.0.0045; 78.2 v 70.5%, p=0.021) with trends toward statistical significance for CFS, LRF, and CF (71.8 v 64.9%, p=0.053; 20 v 26.5%, 11.9 v 17.3%, p=0.092 and 0.075). Similar results were seen in multivariate analysis. Conclusions: Concurrent chemoradiation with 5FU-MMC has a statistically significant impact on DFS and OS vs induction + concurrent 5FU-CDDP and borderline significance for CFS, CF and LRF. Therefore, RT+5FU/MMC remains the preferred standard of care. Potential strategies to improve outcomes include treatment intensification and individualized molecular-based treatment. Supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). [Table: see text] No significant financial relationships to disclose.

LBA2000 Background: Formalin-fixed, paraffin embedded GBM tumor tissue, adequate for conventional MGMT methylation analyses, was required for entry onto the RTOG 0525 clinical trial. Methods: Four prognostic biomarkers were evaluated on a training set of 220 retrospectively obtained GBM samples, consisting of IDH1 mutation, the glioma-CpG island methylator phenotype (G-CIMP), a microarray-based mRNA panel and a novel MGMT promoter methylation assay. For each biomarker, 2 (IDH1 and mRNA) or 3 subgroups (G-CIMP and MGMT) were defined based on associations with overall survival. All combinations (36 possible) of each of the 4 biomarker-derived subgroups were then defined and compared with survival data and then consolidated into 4 risk groups. Once created in the training set, this model was applied to the RTOG 0525 samples (n=763) for external validation. Results: Application of the molecular risk classification to RTOG 0525 samples (left table) showed a highly significant survival association (p<0.001). When compared to the recursive partitioning analysis (RPA, table on right), this composite molecular classifier better identified patients with long term survival and appears to improve resolution by revealing an additional distinct risk group. The molecular classifier was prognostic in each of the treatment arms individually. Conclusions: Four distinct biomarkers or biomarker panels were tested in GBM. These biomarkers were compared with clinical outcome in a training set to optimize a method to combine them into a classifier. This classifier was then validated on a large sample set from a large phase III clinical trial. This composite panel may represent an improvement over the existing RPA with respect to risk stratification of patients for GBM. Additionally, it has the potential to impact future clinical trial designs and provide enhanced opportunities for personalization of therapy for GBM. Support: NCI U10 CA2121661, U10 CA37422, P50 CA127001. [Table: see text]

SummaryBackgroundClostridium difficile infection (CDI) is associated with increased mortality in inflammatory bowel disease (IBD), but the risk of colectomy is variable and has not been adequately studied.AimTo perform a systematic review and meta‐analysis to assess the impact of CDI on colectomy risk in IBD.MethodsMultiple databases were searched systematically for observational studies reporting colectomy risk in IBD, stratified by the presence of CDI, and the duration of follow‐up (short term 3 months, and long term at least 1 year). Weighted summary estimates were calculated using generalised inverse variance with random‐effects model. Study quality was assessed using the Newcastle–Ottawa scale.ResultsTwelve observational studies were identified and included 35 057 IBD patients with CDI, and 929 259 without CDI. CDI did not increase the short‐term colectomy risk in IBD patients overall (10 studies) (OR: 1.35; 95% CI: 0.68–2.67), or in patients with ulcerative colitis (nine studies) (OR: 1.20; 95% CI: 0.39–3.76). In contrast, CDI was associated with higher long‐term colectomy risk in patients with IBD overall (five studies) (OR: 2.23; 95% CI: 1.18–4.21), and in patients with ulcerative colitis (four studies) (OR: 2.96; 95% CI: 1.19–7.34). The results were stable in subgroups stratified by recruitment period, hospitalisation status and geographical location. All studies were at least of moderate quality. The results were limited in the ability to compare IBD severity and the type of anti‐microbial therapy.ConclusionBased on 12 observational studies with at least moderate quality, Clostridium difficile infection appears to increase colectomy risk in IBD in the long‐ but not short‐ term.

Background: Total knee arthroplasty (TKA) with a rotating-hinge prosthesis is considered a salvage procedure. While excellent immediate stability is achieved, the historically high failure rate has tempered its use. The goal of this study was to determine clinical outcomes, radiographic results, and survivorship after TKA with contemporary rotating-hinge components. Methods: We identified 408 consecutive TKAs performed with rotating-hinge components for nononcologic indications from 2002 to 2012 at a single academic institution. Two hundred and sixty-four knees (65%) had rotating-hinge TKA components implanted for aseptic etiologies, while 144 knees (35%) were managed with the components in 2-stage reimplantation following infection. Rotating-hinge TKA implants were used for complex primary procedures in 74 knees (18%) and as a revision construct in 334 knees (82%). Clinical outcomes were assessed with the Knee Society scoring system, survivorship analyses, and cumulative incidence of revision. The mean age of the patients at the time of the index arthroplasty was 69 years, and the mean duration of follow-up was 4 years (range, 2 to 12 years). Results: At the most recent follow-up, the mean Knee Society knee score had increased from 51 points preoperatively to 81 points (p < 0.0001), and the mean Knee Society functional score had increased from 26 to 36 points (p < 0.0001). At a mean of 4 years, loosening of components was observed in 13 (3.7%) of 349 knees. At the most recent follow-up, 59 revision procedures and 25 reoperations had been performed. The cumulative incidence of any revision was 9.7% at 2 years and 22.5% at 10 years. The cumulative incidence of revision for aseptic loosening was 1.7% at 2 years and 4.5% at 10 years. Metaphyseal cones were used in 114 knees (28%). Survivorship analysis revealed a trend toward a lower risk of revision (hazard ratio [HR] = 0.69; 95% confidence interval [CI] = 0.39 to 1.22; p = 0.20) and reoperation (HR = 0.51; 95% CI = 0.22 to 1.19; p = 0.12) in patients with metaphyseal cones, despite their use in the most severe of bone defects. Conclusions: Contemporary rotating-hinge TKA implants had a low 10-year cumulative incidence of revision for aseptic loosening of 4.5%. Greater use of metaphyseal fixation has aided this improvement. Patients can expect substantial improvements in clinical outcomes with this revision strategy. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

ObjectivesIdiopathic subglottic stenosis (iSGS) is rare, and its cause remains elusive. Treatment options include empiric medical therapy and endoscopic or open surgery. We present our results for open surgical technique.Study DesignCase series with chart review (1978‐2015).SettingTertiary academic center.Subjects/MethodsThirty‐three patients (32 female; median age, 51 years) met inclusion criteria and underwent cricotracheal resection with thyrotracheal anastomosis, tracheal resection with primary anastomosis, or laryngotracheoplasty with rib grafting. Continuous variables were summarized using medians and ranges while categorical features are presented using frequency counts and percentages.ResultsSixteen patients (48%) underwent a single‐stage approach with immediate extubation or temporary intubation following surgery (median, 1 day; range, 1‐3 days). Seventeen patients (52%) underwent a double‐staged approach with a median time to decannulation of 35 days (range, 13‐100 days). Twenty‐four (73%) patients underwent a previous intervention. Median stay in the intensive care unit was 1 day (range, 0‐3 days), with a median hospital stay of 4 days (range, 2‐7 days). Recurrence requiring further surgical intervention was observed in 12 patients (36%). The median time to recurrence was 8 years over an average follow‐up of 9.7 years. The most common complaint following surgery was change in voice quality (fair to poor; n = 10; 30%).ConclusionsOpen surgery should be reserved for refractory cases of iSGS; cricotracheal resection with thyrotracheal anastomosis is the preferred open technique. Recurrence may occur after open treatment, highlighting the importance of long‐term follow‐up. Patients should be counseled about the potential for worsening voice quality with the open approach.

Abstract BACKGROUND: Early and mid-term safety and efficacy of aneurysm treatment with the Pipeline Embolization Device (PED) has been well demonstrated in prior studies. OBJECTIVE: To present 5-yr follow-up for patients treated in the Pipeline for Uncoilable or Failed Aneurysms clinical trial. METHODS: In our prospective, multicenter trial, 109 complex internal carotid artery (ICA) aneurysms in 107 subjects were treated with the PED. Patients were followed per a standardized protocol at 180 d and 1, 3, and 5 yr. Aneurysm occlusion, in-stent stenosis, modified Rankin Scale scores, and complications were recorded. RESULTS: The primary endpoint of complete aneurysm occlusion at 180 d (73.6%) was previously reported. Aneurysm occlusion for those patients with angiographic follow-up progressively increased over time to 86.8% (79/91), 93.4% (71/76), and 95.2% (60/63) at 1, 3, and 5 yr, respectively. Six aneurysms (5.7%) were retreated. New serious device-related events at 1, 3, and 5 yr were noted in 1% (1/96), 3.5% (3/85), and 0% (0/81) of subjects. There were 4 (3.7%) reported deaths in our trial. Seventy-eight (96.3%) of 81 patients with 5-yr clinical follow-up had modified Rankin Scale scores ≤2. No delayed neurological deaths or hemorrhagic or ischemic cerebrovascular events were reported beyond 6 mo. No recanalization of a previously occluded aneurysm was observed. CONCLUSION: Our 5-yr findings demonstrate that PED is a safe and effective treatment for large and giant wide-necked aneurysms of the intracranial ICA, with high rates of complete occlusion and low rates of delayed adverse events.