Citations

Abstract Abstract 687 Background: A persistently positive PET scan after just a few cycles of therapy is predictive of a poor clinical outcome in diffuse large B-cell lymphoma (DLBCL). Prior data suggested that about one third of patients remain PET positive after 2–4 cycles, with ≤ 20% 2 year progression-free survival (PFS) for such patients. A response-adapted strategy was studied in E3404 to test the hypothesis that an early treatment change to four cycles of R-ICE might reduce the treatment failure rate of patients whose PET scan remained positive after an initial 3 cycles of R-CHOP. Study Design: Previously untreated patients with DLBCL stage III, IV, or bulky II, with measurable disease, HIV negative, and with adequate organ reserve, were eligible. PET/CT scan was performed before treatment and again after 3 cycles of R-CHOP. A fourth cycle of R-CHOP was given while the scan was centrally reviewed and scored as either positive or negative for FDG-avid tumor by a single reviewer using criteria based on modifications of the Harmonization Criteria. Persistently PET-positive patients received 4 cycles of R-ICE, while PET-negative patients received 2 more cycles of R-CHOP, for a total of 6 cycles. PET/CT was performed again at the end of treatment. A ≥45% 2 year PFS for mid-treatment PET- positive patients was viewed as a promising result, with 88% power if 33 such patients were accrued. Total accrual of 99 patients was therefore planned. Results: Of 100 patients accrued, 78 were eligible; all but 1 ineligibility was based on central pathology review. Fifty-eight were male; median age was 62 years (20–74); 13% IPI 0–1, 31% IPI 2, 37% IPI 3, and 19% IPI 4–5. Seventy-four of 78 (95%) patients completed the first 3 cycles of R-CHOP. Of 72 patients continuing treatment, 67 (93%) completed protocol treatment: 83% of mid-treatment PET-positive and 93% of PET-negative patients. Of 74 patients undergoing mid-treatment PET scan, 12 (16%) were scored as positive, and 62 (84%) as negative. At the end of treatment, 13% were scored as positive, and 87% as negative. Two-year PFS, from the time of study entry, was 72% among all eligible patients. Two year PFS from the time of mid-treatment PET scan was 45% (90% CI, 21–67%) for patients scored as mid-treatment PET-positive, and 77% (90% CI 67–85%) for patients scored as mid-treatment PET-negative. The 80% confidence interval (corresponding to a test with a one-sided type I error of 10%) did not include the null hypothesis of 25%, implying that the results met the pre-specified threshold. Among all 78 eligible patients, 10 have died (13%); 5-year overall survival was 87% (90% CI 78–92%) Three-year overall survival was 67% (90% CI 40–84%) for mid-treatment PET-positive patients, and 93% (90% CI 85–97%) for mid-treatment PET-negative patients. Conclusions: The 2-year PFS for mid-treatment PET-positive patients met the threshold to be considered promising, but the confidence interval was wider than expected due to the small patient number. In addition, the inter-observer variability in the interpretation of mid-treatment PET scans as a binary variable in this study (studied and reported separately in Horning SJ et al. Blood 2010) implies that treatment modification based on early PET scanning should remain confined to clinical trials. Disclosures: Swinnen: Celgene: Consultancy; Genentech: Research Funding. Quon:Genentech: Research Funding. Advani:Pharmacyclics: Research Funding. Kahl:Roche/Genentech: Consultancy; Celgene: Consultancy; Cell Therapeutics: Consultancy; Janssen: Consultancy; GSK: Consultancy; Gilead: Consultancy. Horning:Genentech: Employment; Roche: stock, stock Other.

Abstract Background A cluster of severe lung disease occurred at a manufacturing facility making industrial machines. We aimed to describe disease features and workplace exposures. Methods Clinical, functional, radiologic, and histopathologic features were characterized. Airborne concentrations of thoracic aerosol, metalworking fluid, endotoxin, metals, and volatile organic compounds were measured. Facility airflow was assessed using tracer gas. Process fluids were examined using culture, polymerase chain reaction, and 16S ribosomal RNA sequencing. Results Five previously healthy male never‐smokers, ages 27 to 50, developed chest symptoms from 1995 to 2012 while working in the facility's production areas. Patients had an insidious onset of cough, wheeze, and exertional dyspnea; airflow obstruction (mean FEV 1 = 44% predicted) and reduced diffusing capacity (mean = 53% predicted); and radiologic centrilobular emphysema. Lung tissue demonstrated a unique pattern of bronchiolitis and alveolar ductitis with B‐cell follicles lacking germinal centers, and significant emphysema for never‐smokers. All had chronic dyspnea, three had a progressive functional decline, and one underwent lung transplantation. Patients reported no unusual nonoccupational exposures. No cases were identified among nonproduction workers or in the community. Endotoxin concentrations were elevated in two air samples; otherwise, exposures were below occupational limits. Air flowed from areas where machining occurred to other production areas. Metalworking fluid primarily grew Pseudomonas pseudoalcaligenes and lacked mycobacterial DNA, but 16S analysis revealed more complex bacterial communities. Conclusion This cluster indicates a previously unrecognized occupational lung disease of yet uncertain etiology that should be considered in manufacturing workers (particularly never‐smokers) with airflow obstruction and centrilobular emphysema. Investigation of additional cases in other settings could clarify the cause and guide prevention.

6511 Background: Conventional adverse event (AE) analysis (ToxC) focuses on incidence of grade (gr) 3+ toxicities, and fails to capture AE time profile. Novel metrics that reflect chronic low gr and overall AE burden are needed. We applied the Toxicity over Time (ToxT) approach to ECOG-ACRIN 2408 to depict time-dependent toxicity of lenalidomide (L) with rituximab maintenance (MR) in follicular lymphoma (FL), and we developed a novel summary metric of symptomatic AE burden, the maximum gr over time (MGOT). Methods: In E2408, high risk FL patients (pts) were randomized (1:2:2) to: A) bendamustine-rituxumab (BR) x 6 then MR x 2 years (yrs) vs B) BR-bortezomib x 6 then MR x 2 yrs vs C) BR x 6 then MR x 2 yrs + L x 1 yr (MRL). Analysis included 3 laboratory and 5 symptomatic AEs of highest incidence during maintenance on arms A and C. Treatment-related AEs of any gr were analyzed by ToxC and ToxT. Repeated measures, time-to-event (TTE) and area under the curve (AUC) analyses capture trends over time in ToxT. MGOT combines the 5 symptomatic AEs. Results: 104 randomized pts (30 MR, 74 MRL) were included. For the laboratory AEs, by ToxC, neutropenia incidence was significantly higher in MRL (84%) than MR (47%, p < .001). ToxT additionally shows neutropenia does not worsen over time (10/14/20% gr 1/2/3+ at c1, 6/21/12% gr 1/2/3+ at c12). For the symptomatic AEs, ToxC indicates 2% gr 3+ GI AEs. However, gr 1-2 GI AEs are more common on MRL (59%) than MR (26%, p < .001). ToxT AUC captures a higher burden of GI AEs over time on MRL(2.8) vs MR(1.4, p = .002). TTE depicts sooner GI AE onset in MRL (10% vs 0% gr 2+ GI by day 50, p = 0.03). Bar charts of incidence and grade by cycle illustrate this improves over time (34/7/4% gr 1/2/3+ at c1, 13/0/0% gr 1/2/3+ at c12). ToxT MGOT analyses demonstrate earlier time to gr 2+ symptomatic AE on MRL vs MR (63% vs 31% by day 50, p < .001) and suggest that overall AE burden over time is higher for patients on MRL(AUC 18.2) than MR(11.8, p < .001). Conclusions: ToxT depicts AE time profile and can guide AE interventions. Summary metrics suggest that symptomatic AEs occur earlier and their burden over time is higher on MRL. We are implementing ToxT in patient-reported AE data to better characterize pt tolerability.

ABSTRACT Introduction Scrotoplasty has become a common practice during insertion of penile prosthesis, improving patient perception of penile length. Previous reports on scrotoplasty outcomes have only focused on the perceived benefits. The risk of wound complications after scrotoplasty is unknown. Aim Identify wound complications and associated risk factors of scrotoplasty with insertion of penile prosthesis. Methods A retrospective review of a single-surgeon series (T.S.K.) of patients who underwent scrotoplasty with initial insertion of inflatable penile prosthesis (IPP) was performed from 2009–2014. Surgical outcomes and wound complications after scrotoplasty were examined, along with patient information, including basic demographics, medical comorbidities, and perioperative data. Main Outcome Measures Studied outcomes included rate of wound complications after scrotoplasty and IPP insertion and identification of risk factors for wound dehiscence. Results Of the 103 scrotoplasties performed during the study period, a total of 15 had mild, moderate, or major wound dehiscence. Of these 15 cases, 9 had mild dehiscence and 5 cases had moderate dehiscence and required stitches to be placed in clinic to reinforce the closure. 1 patient had a major dehiscence requiring a return to the operating room for a washout, with exchange of IPP to malleable prosthesis. Multiple risk factors for wound dehiscence were found, including diabetes (odds ratio 6.1, CI 1.5, 25.0, P = .0129) and scrotoplasty technique (odds ratio 4.9, CI 1.2, 8.6, P = .003). Other examined variables, including patient age, Peyronie’s disease, hypertension, intraoperative penile modeling, smoking, and device manufacturer, were not associated with wound dehiscence. Clinical Implications Patients with diabetes and scrotoplasties performed via V-Y plasty are more likely to experience wound dehiscence. Strengths & Limitations Strengths include a single surgeon, thus lending continuity of skill and technique, a consecutive series, and 100% short-term follow-up. Limitations include retrospective design, single institution series, and lack of long-term follow-up. Conclusion Although scrotoplasty can improve patient satisfaction with IPP, scrotoplasty can lead to increased patient morbidity. Diabetic patients are at increased risk for wound complication after scrotoplasty.

OBJECTIVE Papers from 2002 to 2017 have highlighted consistent unique socioeconomic challenges and opportunities facing military neurosurgeons. Here, the authors focus on the reserve military neurosurgeon who carries the dual mission of both civilian and military responsibilities. METHODS Survey solicitation of current active duty and reserve military neurosurgeons was performed in conjunction with the AANS/CNS Joint Committee of Military Neurosurgeons and the Council of State Neurosurgical Societies. Demographic, qualitative, and quantitative data points were compared between reserve and active duty military neurosurgeons. Civilian neurosurgical provider data were taken from the 2016 NERVES (Neurosurgery Executives Resource Value and Education Society) Socio-Economic Survey. Economic modeling was done to forecast the impact of deployment or mobilization on the reserve neurosurgeon, neurosurgery practice, and the community. RESULTS Seventy-five percent (12/16) of current reserve neurosurgeons reported that they are satisfied with their military service. Reserve neurosurgeons make significant contributions to the military’s neurosurgical capabilities, with 75% (12/16) having been deployed during their career. No statistically significant demographic differences were found between those serving on active duty and those in the reserve service. However, those who served in the reserves were more likely to desire opportunities for improvement in the military workflow requirements compared with their active duty counterparts (p = 0.04); 92.9% (13/14) of current reserve neurosurgeons desired more flexible military drill programs specific to the needs of practicing physicians. The risk of reserve deployment is also borne by the practices, hospitals, and communities in which the neurosurgeon serves in civilian practice. This can result in fewer new patient encounters, decreased collections, decreased work relative value unit generation, increased operating costs per neurosurgeon, and intangible limitations on practice development. However, through modeling, the authors have illustrated that reserve physicians joining a larger group practice can significantly mitigate this risk. What remains astonishing is that 91.7% of those reserve neurosurgeons who were deployed noted the experience to be rewarding despite seeing a 20% reduction in income, on average, during the fiscal year of a 6-month deployment. CONCLUSIONS Reserve neurosurgeons are satisfied with their military service while making substantial contributions to the military’s neurosurgical capabilities, with the overwhelming majority of current military reservists having been deployed or mobilized during their reserve commitments. Through the authors’ modeling, the impact of deployment on the military neurosurgeon, neurosurgeon’s practice, and the local community can be significantly mitigated by a larger practice environment.