OBJECTIVE: Routine use of face masks for patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the COVID-19 pandemic. This study evaluates the impact of physician, ancillary staff, and patient face use on rates and outcomes of post-injection endophthalmitis. DESIGN: Retrospective, multicenter, comparative cohort study PARTICIPANTS: Eyes receiving intravitreal anti-VEGF injections from 10/1/2019 to 7/31/2020 at twelve centers from the United States of America. INTERVENTION: Cases were divided into a face mask group if no face masks were worn by the physician or patient during intravitreal injections or a universal face mask group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections. MAIN OUTCOME MEASURES: Rate of endophthalmitis, microbial spectrum, and visual acuity. RESULTS: Of 505,968 intravitreal injections from 110,547 eyes administered, 85 of 294,514 (0.0289%; 1 in 3,464 injections) cases of presumed endophthalmitis occurred in the face mask group, and 45 of 211,454 (0.0213%; 1 in 4,699) cases occurred in the universal face mask group (odds ratio [OR], 0.74; 95%CI, 0.51-1.18; p=0.097). In the face mask group, there were 27 cases (0.0092%; 1 in 10,908 injections) of culture-positive endophthalmitis compared to 9 cases (0.004%; 1 in 23,494) in the universal face mask group (OR, 0.46; 95%CI, 0.22-0.99; p=0.041). Three cases of oral flora-associated endophthalmitis occurred in the face mask group (0.001%; 1 in 98,171 injections) compared to one (0.0005%; 1 in 211,454) in the universal face mask group (p=0.645). Patients presented a mean (range) 4.9 (1-30) days after the causative injection, and mean logMAR visual acuity at endophthalmitis presentation was 2.04 [∼20/2200] for face mask group compared to 1.65 [∼20/900] for the universal face mask group (p=0.022), although no difference was observed three months after treatment (p=0.764). CONCLUSION: In a large, multicenter, retrospective study, physician and patient face use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months following presentation, there was no difference in visual acuity between the groups.

Summary We sought to develop a safe and effective outpatient salvage regimen by replacing ifosfamide within the (R) ICE (rituximab, ifosfomide, carboplatin, etoposide) regimen with bendamustine (T(R) EC ) via a multicentre phase I/ II study for patients with relapsed or refractory diffuse large B cell lymphoma ( DLBCL ) and classic Hodgkin lymphoma ( HL ). Therapy consisted of 60–120 mg/m 2 per day bendamustine on days 1 and 2 in combination with carboplatin, etoposide and rituximab (only for CD 20 + lymphoma) used in the (R) ICE regimen for up to 2 cycles. The objectives were to define a maximally tolerated dose ( MTD ) of bendamustine, determine safety and toxicity, assess efficacy, and evaluate impact on stem cell collection. Forty‐eight patients were treated of which 71% had refractory disease. No dose‐limiting toxicities were observed. The recommended phase II dose of bendamustine was 120 mg/m 2 per day on days 1 and 2. Response rates were 85% (70% complete response, CR ) in HL , and 65% (40% CR ) in DLBCL . Stem cell collection was successful in 30 of 32 patients. The most common non‐haematological toxicities ≥grade 3 were febrile neutropenia (8%) and dehydration (8%). The T(R) EC regimen safely yields high response rates, successfully mobilizes peripheral blood stem cells and compares favourably to RICE , offering an effective outpatient treatment option for patients with relapsed or refractory DLBCL and HL .

34 Background: In the context of many initiatives aimed at measuring quality and value in cancer care, the Hutchinson Institute for Cancer Outcomes Research (HICOR), partnered with community members to launch a regional, stakeholder-driven initiative to define and report value metrics for cancer care for Washington State. Region-wide Summits were held in 2014 and 2015. Participants included local healthcare delivery organizations, patient advocacy groups, payers, and policymakers. The 2014 Summit identified priority metrics; these metrics were reported at the 2015 Summit. Methods: For the 2015 Summit, HICOR staff developed algorithms to measure adherence to the community-prioritized metrics using a claims-registry linked database. Metrics spanned diagnosis, treatment, continuing, and end-of-life (EOL) phases of care. After reviewing adherence at the clinic-level and for the region, attendees were invited to attend break-out sessions for metrics where there was the largest variation: hospital and ED use during treatment, hospital and ED use at EOL, and breast cancer surveillance. Within the breakout sessions, participants were asked to identify barriers to adherence and possible interventions to improve care. After discussion, participants individually ranked the top 3 interventions and estimated expected improvement to be gained by successful implementation of the intervention Results: Table. Working groups were formed to develop detailed protocols for implementable interventions. Conclusions: Using an iterative, transparent, multi-stakeholder process, it is feasible build regional consensus to identify and prioritize value metrics in cancer care, and to develop consensus regarding approaches to improve adherence to those metrics. [Table: see text]

39 Background: In the context of many initiatives aimed at measuring quality and value in cancer care, the Hutchinson Institute for Cancer Outcomes Research (HICOR) has adopted a multi-stakeholder approach to characterize oncology care, prioritize areas for improvement, design programs, and evaluate outcomes. Beginning in 2014, HICOR initiated a process to move towards data transparency in the reporting of regional quality and value metrics. Methods: The HICOR team constructed clinic-level adherence reports for community-prioritized metrics and the 2012 ASCO Choosing Wisely recommendations using a registry-claims linked database. In the fall of 2014, a national external advisory board reviewed methodology for measuring adherence. De-identified regional results were presented at a provider meeting in late 2014 to elicit provider feedback on methodology and on strategies for reporting clinic-identified adherence. Clinics were privately given their own adherence data. In 2015, revised de-identified regional reports were presented at a Value in Cancer Care Summit poster session and made available through HICOR IQ, a regional oncology informatics platform, for further discussion. Results: Results show that no clinic was also the best or worst performing clinic. The table shows the performance by clinic for the 5 Choosing Wisely recommendations. There is now increased demand by clinics to view their own adherence benchmarked with the region as a next step in moving towards full data transparency. Additionally, there is support from provider members in the community to re-identify clinics in order to compare results against their peers. Conclusions: Using an iterative, transparent, multi-stakeholder process, it is feasible build regional consensus towards releasing clinic-level adherence to quality and value metrics. By consulting trusted experts in the field and allowing multiple opportunities to provide feedback, providers are requesting even more transparency in order use the oncology measures to improve care in their practice and the region. [Table: see text]

4 Background: People with cancer increasingly wish to discuss cancer care costs with clinicians. In our organization all price questions go to a central customer service line with limited capacity to address oncology-specific questions. We aimed to improve clinician access to treatment prices to assist them in responding to patient concerns about prices. Methods: We developed, launched, and evaluated a pilot tool and accompanying workflow for four oncology clinics in an integrated delivery system in WA. The online tool included a series of 50 printable worksheets for the most commonly ordered cancer treatment protocols accessible directly from the electronic health record. The worksheets included codes and prices for all drugs, supportive medications, tests, and professional services for one treatment cycle presented in patient-friendly language. We audited the accuracy of the cost information against patient bills. The worksheets did not provide patient-level cost-shares. We evaluated the resource’s launch, initial use, and acceptability through a convenience survey of initial users. Results: The project was successfully launched. Initial web traffic to price sheets exceeded the number of treatments being ordered during the launch period. A third of survey respondents (33%) reported using the cost sheets at least once a week. Reported most useful features were improved access to cost information, treatment protocol-based layout, and the service of previously unmet patient needs. Seventy percent (70%) reported that the resource had no impact on their workload. The mean value of the resource (1 lowest and 10 highest value) was 7.9 (value to patients); 7.8 (to oncology service line), 7.7 (to Group Health) and 6.5 (to own work or practice). Staff reporting of patient response was generally positive. Suggested improvements included provide patient-level cost share (63%) followed by expanding the project to include more protocols (33%). Conclusions: The pilot was feasible, built capacity to locate price data, and did not adversely impact staff workload. It addressed a clear need and demonstrated high potential overall value, especially its protocol-based format. The resource’s lack of personalized estimates of out-of-pocket charges was the biggest gap reported.

PURPOSEPatients with cancer increasingly wish to discuss cancer care costs with clinicians. We aimed to improve clinician access to treatment prices.METHODSWe developed a pilot tool and accompanying workflow for four oncology clinics in an integrated care system. The online tool included 50 printable worksheets for cancer treatment protocols and was accessible directly from the electronic health record. Each sheet included codes and prices for all drugs and services for one treatment cycle in patient-friendly language. The worksheets did not provide patient-level cost-shares. We evaluated the resource's launch, initial use, and acceptability through a convenience survey of initial users.RESULTSThe project was successfully launched. Initial Web traffic to price sheets exceeded the number of treatments ordered during the launch period. One third of survey respondents reported use of the cost sheets at least once a week. The most useful features were improved access to cost information, treatment protocol-based layout, and ability to meet patient needs. The resource was rated as generally high value to patients, staff, and the organization. Suggested improvements included provision of patient-level cost sharing (63%) followed by expansion of the project to include more protocols (33%). These improvements are in progress.CONCLUSIONThe pilot was feasible, built capacity to locate price data, and did not adversely affect staff workload. It addressed a clear need and demonstrated high potential overall value, especially with its protocol-based format. The resource's lack of personalized estimates of out-of-pocket charges was the biggest gap reported.

e20703 Background: Over the last decade, the use of oral oncolytics has increased dramatically. In 2011, Group Health Oncology recognized the need for management of complex high-risk and high-cost medication therapies in patients who often have comorbidities. In response to the demand, Group Health pharmacy designed a clinical oral chemotherapy management program aligned with our existing primary care medical home model. The program’s goal is to integrate oncology trained clinical pharmacists (OTP) into the medical oncology care team to provide comprehensive medication management for cancer patients. This abstract describes our training, design, and implementation of our oral chemotherapy program. Methods: Three clinical pharmacists with 30 years of combined primary care experience received ten intensive weeks of oncology training outlined below. Results: After completing training, pharmacists received referrals from oncologists and managed patients on oral oncolytics. A comprehensive evaluation of disease states, labs, and drug interactions was conducted before the onboarding office visit. During this face to face visit, OTP provided education about cancer therapy, supportive care, and side effect management. OTP also managed drug therapy for other chronic diseases. In addition, OTP helped expedite the start of therapy by removing barriers, such as insurance authorization, financial burden, and procurement of drug therapy. Follow up appointments were scheduled throughout the course of therapy to ensure safety, tolerability, adherence, and efficacy. Conclusions: Group Health has integrated clinical pharmacists successfully into our oncology medical home model. It is possible to develop a training program for general practice clinical pharmacists to become proficient in comprehensive cancer care management. Based on three months of data, over 40 significant and cost saving interventions were made by our three OTP. Our future direction is to expand pharmaceutical care to all oncology patients beyond oral oncolytics management. Didactic Training Focus Areas Common oncology disease states, drug therapy, supportive care Experiential Training Work shadow with oncology team members: providers, nurses, social workers, pharmacists

Tripod configurations of plane curves, formed by certain triples of normal lines coinciding at a point, were introduced by Tabachnikov, who showed that C2 closed convex curves possess at least two tripod configurations. Later, Kao and Wang established the existence of tripod configurations for C2 closed locally convex curves. In this paper we generalize these results, answering a conjecture of Tabachnikov on the existence of tripod configurations for all closed plane curves by proving existence for a generalized notion of tripod configuration. We then demonstrate the existence of the natural extensions of these tripod configurations to the spherical and hyperbolic geometries for a certain class of convex curves, and discuss an analogue of the problem for regular plane polygons.

8533 Background: Traditional multi-agent salvage strategies for lymphoma are less effective after failed modern front line therapies. Bendamustine (Treanda, T) has considerable anti-lymphoma activity and a favorable toxicity profile. We hypothesized that bendamustine could replace ifosfamide within the (R)ICE regimen yielding a feasible and effective salvage strategy (TREC). Methods: This multicenter phase I study used a two stage design followed by 2 expansion cohorts for patients with diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). Eligibility included measurable relapsed/refractory lymphoma, ECOG performance status ≤ 2, adequate blood counts and organ function. The primary objective was to define a maximally tolerated dose (MTD) of bendamustine associated with a dose limiting toxicity (DLT) rate of ≤ 25%. Therapy consisted of bendamustine ranging from 60 mg/m2 to 120 mg/m2 daily on days 1 and 2 with standard doses of carboplatin, etoposide, and rituximab (CD20+ disease only) used in the RICE regimen every 21 days for 2 cycles. Results: A total of 46 treated patients with median age of 58 years and median of 1 prior therapy, were enrolled with 3 at the dose escalation cohorts and 43 at the recommended phase 2 dose (RP2D). MTD was not reached. Primary refractory disease or early relapse was seen in 13 (65%) patients with HL (n = 20) and 14 (74%) patients with DLBCL (n = 19). All cycles were successfully given in the outpatient setting. Fourteen patients suffered ≥ grade 3 non-hematologic adverse events but without DLTs. The most common ones were febrile neutropenia (n = 4, 9%) and rash (n = 3, 4%). Per Cheson 2007 criteria overall response rates were 67% with 84% (14 CR, 2 PR) in HL, and 63% (8 CR, 4 PR) in DLBCL. Mobilization of peripheral blood stem cells (PBSC) was successful in all attempts immediately following the treatment with a median collection of 5.9 x 106CD34/kg. To date, 16 of 22 (77%) CR patients underwent transplant. Conclusions: The outpatient administration, manageable toxicity profile, and high response rate in HL and DLBCL of the TREC regimen are encouraging. These data support future evaluation of TREC. Clinical trial information: NCT01165112.

25 Background: In the context of numerous national initiatives aimed at measuring quality and value in cancer care, the Hutchinson Institute for Cancer Outcomes Research, in partnership with local healthcare delivery organizations, patient advocacy groups, payers, and policymakers launched a regional, stakeholder-driven initiative to define 3-5 “value-based metrics” for cancer care for Washington State. Methods: Representatives from major cancer care delivery organizations, patient advocacy groups, payers, and policymakers were invited to participate in a day-long Value Summit. Attendees were tasked with identifying metrics that considered both costs and outcomes. Trained facilitators helped participants identify metrics for 9 domains: appropriate use of effective therapies, adherence to best practices, survival, comprehensive disease management, efficiency of care, hospice/palliative care, patient and family satisfaction with care, patient reported outcomes/preferences and safety. After the initial list was generated, attendees were then asked to rank the metrics on the basis of feasibility to collect, clinical relevance, ability to act on, meaningfulness to multiple stakeholders, and willingness to report statewide. Attendees were then asked to participate in 3 domain-specific facilitated breakout sessions to prioritize the top metrics for each domain. Breakout sessions reported top metrics for a final group prioritization exercise. Following the Summit, attendees provided feedback on the final rankings. The metrics were then presented at a Town Hall style meeting for public comment. Results: Over 70 participants, representing 20 different organizations, identified 750 unique metrics from 9 domains. The prioritization process yielded 3 areas of interest, with 2 specific metrics within each: end of life and palliative care (metric 1, metric 2); adherence to best practices (metric 3, metric 4); and coordinated and efficient care (metric 5, metric 6). Follow-up surveys of Summit attendees and the Town Hall forum showed widespread support for these metrics Conclusions: Using an iterative, transparent, multi-stakeholder process, it is feasible build regional consensus around value metrics in cancer care.

207 Background: ASCO launched the Choosing Wisely campaign to reduce the use of interventions that lack evidence for their use in clinical cancer care. The recommendations have strong support, but lack an implementation plan. The objective of this project is to develop a stakeholder-informed process to improve adherence to ASCO Choosing Wisely within an experimental context. Methods: Participants include Medical Directors from 7 oncology clinics and 1 commercial insurer within the Puget Sound region, and the SEER Puget Sound Cancer Registry. The project consists of 3 phases (1) prioritization, (2) design, (3) implementation and monitoring. For phase 1, Medical Directors were surveyed via e-mail to prioritize the recommendations with the following criteria: importance for improving the value of cancer care; impact of adherence; urgency; and feasibility of implementing an intervention. Participants met via teleconference to discuss survey results, review regional utilization data, and design of interventions. Participants were surveyed again for a final ranking. In phase 2, participants discussed options for interventions and study designs. Results: Initially, the highest ranked recommendations were advanced imaging in staging of local stage prostate cancer, surveillance of local and regional stage breast cancer, and colony stimulating factor (CSF) use for low risk chemotherapy. After discussion, breast cancer surveillance and CSF prescribing ranked the highest. Participants requested utilization and cost-impact data from the health insurer for the top 2 choices. Conclusions: Using a transparent, multi-stakeholder process, it is feasible to implement programs to improve adherence to ASCO Choosing Wisely.

We answer a question of Niederreiter concerning the enumeration of a class of subspaces of finite dimensional vector spaces over finite fields by proving a conjecture of Ghorpade and Ram.

Adoptive immunotherapy with T cells expressing a tumor-specific chimeric T-cell receptor is a promising approach to cancer therapy that has not previously been explored for the treatment of lymphoma in human subjects. We report the results of a proof-of-concept clinical trial in which patients with relapsed or refractory indolent B-cell lymphoma or mantle cell lymphoma were treated with autologous T cells genetically modified by electroporation with a vector plasmid encoding a CD20-specific chimeric T-cell receptor and neomycin resistance gene. Transfected cells were immunophenotypically similar to CD8(+) effector cells and showed CD20-specific cytotoxicity in vitro. Seven patients received a total of 20 T-cell infusions, with minimal toxicities. Modified T cells persisted in vivo 1 to 3 weeks in the first 3 patients, who received T cells produced by limiting dilution methods, but persisted 5 to 9 weeks in the next 4 patients who received T cells produced in bulk cultures followed by 14 days of low-dose subcutaneous interleukin-2 (IL-2) injections. Of the 7 treated patients, 2 maintained a previous complete response, 1 achieved a partial response, and 4 had stable disease. These results show the safety, feasibility, and potential antitumor activity of adoptive T-cell therapy using this approach. This trial was registered at www.clinicaltrials.gov as #NCT00012207.

Follicular Lymphoma (FL) is the second most common type of non-Hodgkin's Lymphoma (NHL) in the United States, accounting for approximately 20% of NHL cases. FL is considered incurable with conventional therapies, and novel therapies are therefore urgently needed. Long-term remissions using allogeneic stem cell transplantation and donor lymphocyte infusion suggest curability using cellular therapy, but these approaches are limited by significant toxicity. We have initiated a pilot Phase I clinical trial testing the feasibility, safety, and toxicity of treating patients with relapsed FL with autologous T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) recognizing the CD20 antigen present on B cell lymphomas. Nine patients have been registered to the protocol to date. Peripheral blood mononuclear cells were obtained from patients by apheresis, activated with anti-CD3 monoclonal antibody (OKT3) and interleukin-2 (IL-2) and transfected by electroporation with a plasmid encoding a CD20-specific scFvFc:ζ CAR as well as a neomycin-resistance selection gene. Transfectants were selected using G418 and expanded ex vivo. For the first 5 patients, cytotoxic CD8+ T cells were cloned by limiting dilution, but this process proved to be laborious and inefficient. Two patients' clones failed to expand adequately and are off-study, and 2 additional patients received cell doses below the target level. Therefore, subsequent patients underwent oligoclonal expansion of T cells in bulk culture. T cells expressing the CAR and manifesting CD20-specific cytotoxicity were identified by flow cytometry and standard chromium release assays. Patients underwent three infusions of modified T cells at escalating doses (108, 109 and 3.3 × 109 cells/m2) over a period of 7–10 days. The 4 patients who received oligoclonal T cells also received 14 days of low-dose subcutaneous IL-2 injections (500,000 U/m2 twice daily) to prolong in vivo persistence. Seven patients underwent a total of 20 T cell infusions, and no significant toxicities attributable to the T cell infusions were observed. Cellular and immune response assays have not detected any immune responses to the genetically modified T cells in any of the treated patients, although the seventh patient has not yet been evaluated for immune responses. T cells expressing the CAR were detectable in the peripheral blood of patients by PCR for ∼14 days after infusions in the first three patients who received T cell clones, and 4–8 weeks in patients receiving oligoclonal T cells and IL-2 injections. One patient was maintained in complete remission for over a year after T cell infusions, and a second patient achieved a partial remission lasting three months. A third patient had a partial PET response. The remaining 3 patients maintained stable disease for 3–12 months. These results suggest that adoptive cellular therapy with genetically modified CD20-specific T cells is a safe and feasible approach to treating FL that warrants further investigation.

We previously demonstrated the feasibility of generating therapeutic numbers of cytotoxic T lymphocyte (CTL) clones expressing a CD20-specific scFvFc:CD3zeta chimeric T cell receptor (cTCR), making them specifically cytotoxic for CD20+ B lymphoma cells. However, the process of generating and expanding he CTL clones was laborious, the CTL clones expressed the cTCR at low surface density, and they exhibited suboptimal proliferation and cytotoxicity. To improve the performance of the CTLs in vitro and in vivo, we engineered "second-generation'' plasmid constructs containing a translational enhancer (SP163) and CD28 and CD137 costimulatory domains in cis with the CD3zeta intracellular signaling domain of the cTCR gene. Furthermore, we verified the superiority of generating genetically modified polyclonal T cells expressing the second-generation cTCR rather than T cell clones. Our results demonstrate that SP163 enhances the surface expression of the cTCR; that the second-generation cTCR improves CTL activation, proliferation, and cytotoxicity; and that polyclonal T cells proliferate rapidly in vitro and mediate potent CD20-specific cytotoxicity. This study provides the preclinical basis for a clinical trial of adoptive T cell immunotherapy for patients with relapsed CD20+ mantle cell lymphoma and indolent lymphomas.

Follicular Lymphoma (FL) is the second most common type of Non-Hodgkin's Lymphoma (NHL) in the United States, with over 120,000 Americans living with the disease. FL is considered incurable with conventional therapies and innovative new approaches are needed. We have initiated a pilot Phase I clinical trial to test the feasibility, safety, toxicity, and efficacy of treating patients with relapsed indolent B cell lymphomas with autologous CD8+ cytotoxic T lymphocytes (CTL) that have been genetically modified to express a chimeric T cell receptor (cTCR) recognizing the CD20 antigen present on B cell lymphomas. Five patients have been registered to the protocol to date. Peripheral blood mononuclear cells were obtained from patients by apheresis, activated with anti-CD3 monoclonal antibody and interleukin 2 and transfected by electroporation with a plasmid encoding a CD20-specific scFvFc:zeta chimeric immunoreceptor as well as a neomycin-resistance selection gene. Transfectants were selected using G418, and cloned by limiting dilution. CD8+ clones expressing the cTCR and manifesting CD20-specific cytotoxicity were identified by flow cytometry and chromium-51 cytotoxicity assays. Selected clones were expanded and infused into two of the patients at escalating doses (108, 109, and 3.3 × 109 cells/m2) on three occasions over a period of 10 days. Two additional patients are scheduled for T cell infusions in the near future. One patient is now off study because the clones failed to expand sufficiently to numbers required for therapy. No significant toxicities attributable to the T cell infusions were observed. There have been no cellular or humoral immune responses to the genetically modified T cells in the two treated patients. T cells expressing the cTCR were detectable in the peripheral blood of patients by PCR for 14 days after infusions. One patient was maintained in complete remission for over a year after T cell infusions, and a second patient was maintained in a partial remission for four months. Future planned interventions include infusion of polyclonal populations of transfected CD4 helper T cells with cytotoxic CD8 T cells rather than CD8 clones, subcutaneous administration of low dose interleukin 2, and introduction of a modified plasmid containing CD28 and CD137 co-stimulatory domains in addition to the CD3 zeta chain.