Three weekly versus weekly concurrent cisplatin: safety propensity score analysis on 166 head and neck cancer patients

Background Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m2/q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m2/q1. Methods Patients were treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules. Results Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule. Conclusions 3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients.

Evaluation of Treatment Outcome and Acute Toxicity in Patients Undergoing Adjuvant Therapy in Ductal Carcinoma Pancreas: A Prospective Observational Study

Ductal adenocarcinoma of the pancreas is one of the commonly diagnosed cancers and is a leading cause of cancer mortality in the population. The prognosis of patients even after undergoing a complete resection is generally poor, with a median survival of 13–20 months and a 3-year survival of 30%. Therefore, adjuvant therapies including adjuvant chemoradiation and adjuvant chemotherapy are given in an effort to improve survival. In the authors’ centre, all patients undergoing resection are given adjuvant chemoradiation followed by adjuvant chemotherapy. This study was conducted to evaluate the acute toxicity and treatment outcome (patterns of failure, overall and disease-free survival) of patients undergoing adjuvant therapy in resected carcinoma pancreas. Adjuvant chemoradiation was well tolerated by most patients with resected carcinoma pancreas and all patients completed chemoradiation. Adjuvant chemotherapy was associated with high haematological toxicity, similar to previously published literature. However, treatment interruptions were higher and only 77% patients completed adjuvant chemotherapy. The adjuvant gemcitabine, given on Days 1, 8, and 15, for a 4-weekly schedule was poorly tolerated by the authors’ patient population and there were only fewer interruptions in patients who were switched to the 3-weekly schedule. Inclusion of a greater number of patients and longer follow-up of this study is required to clearly assess the patterns of failure and survival outcomes.

164 Potent tumor organoid infiltration and killing by PBMC-derived effector cells

BackgroundAlloplex Biotherapeutics has developed a novel autologous cellular therapy for cancer that uses ENgineered Leukocyte ImmunoSTimulatory cell lines called ENLIST cells to activate and expand a heterogeneous population of tumor killing effector cells from human peripheral blood mononuclear cells (PBMCs). The 2-week manufacturing process from PBMCs consistently results 300-fold expansion of NK cells, CD8+ T cells, gamma/delta T cells, NKT cells and some CD4+ T cells, collectively called SUPLEXA therapeutic cells. SUPLEXA cells will be delivered back to cancer patients via intravenous administrations on a weekly schedule as an autologous adoptive cellular immunotherapy for cancer. In this study, we tested SUPLEXA cells developed from normal healthy volunteer PBMCs for their ability to infiltrate and kill patient-derived tumor organoids (PDO) as a pre-clinical assessment for potency against 2 different types of tumor organoids.MethodsTumor organoids derived from colorectal cancer (CRC) or non-small cell lung carcinoma (NSCLC) patients were labeled with cell-trace red dye and plated at equal density in a 96-well plate. After 3 days culture, SUPLEXA cells were thawed (82.8% viable), labeled with cell-trace violet dye, and added to PDO at 1:2 serial diluted numbers ranging from 2 million to 7,800 cells per well. Fluorescent images were captured at 24 hours after adding SUPLEXA cells to PDO models to measure PDO size, tumor infiltration, and PDO killing.ResultsAdding SUPLEXA cells to PDO from CRC and NSCLC resulted in significant infiltration and killing of organoids by 24 hours as shown by the fluorescent images and the organoid size plot for the CRC PDO model (figure 1). Significant reduction in PDO size was observed by adding 31,240 SUPLEXA cells. Similar results were observed with the NSCLC PDO model with significant reduction in PDO size by adding 15,600 SUPLEXA cells. Obvious organoid infiltration was observed in both PDO models and organoid fluorescence was significantly reduced by addition of SUPLEXA cells in both PDO models to suggest that SUPLEXA cells were able to reduce tumor burden (figure 2).Abstract 164 Figure 1CRC organoid infiltration and killing by SUPLEXA. A representative fluorescent image of CRC organoid killing with addition of increasing SUPLEXA cell numbers and a plot showing statistical analysis of 6 replicate wells for changes in CRC organoid size in relation to SUPLEXA cell number additionsAbstract 164 Figure 2Dose-dependent killing in CRC and NSCLC PDO models. CRC and NSCLC organoids were detected by total red fluorescence at 24 hours after adding the indicated numbers of SUPLEXA cells. Loss of red fluorescence after adding SUPLEXA is a measure of overall tumor cell killing/burden in organoids. Data is plotted as mean ± SEM for n=6 replicates per group.ConclusionsSUPLEXA cells infiltrated and killed tumor cells in patient-derived organoids within 24 hours of culture at low cell concentrations indicating potent tumor killing activity. The observed activity in both colorectal and lung cancer organoid models support broad anti-tumor killing activity by SUPLEXA. These results provide further evidence that PBMCs from cancer patients can be activated and expanded by our approach as a novel autologous cellular immunotherapy for cancer.

Lighting Solutions to Improve the Valorisation and Fruition of the Parque del Retiro in Madrid

The lighting design of public spaces, and in particular of green areas, is becoming a growing interest in the contemporary culture, as more and more people are starting to enjoy cities at nighttime. In this study, the lighting design for two main areas of the Parque del Retiro in Madrid (Spain), the Puerta de España and the Paseo de las Estatuas de Reyes, is discussed. Two different lighting scenarios have been designed by means of the software DIALux evo, the first one with the aim of maximise the lighting effect and the second one with the aim to optimize the energy consumption while still allowing for the enhancement of the key characteristics of the two areas. A combined lighting design solution, obtained by using the two scenarios in a weekly schedule, allowed to achieve adequate levels of illumination, an improvement in the feeling of safety in visitors while optimizing energy consumption.

Habitat characteristics and animal management factors associated with habitat use by bottlenose dolphins in zoological environments

The way an animal uses its habitat can serve as an indicator of habitat appropriateness for the species and individuals. Bottlenose dolphins (Tursiops truncatus and Tursiops aduncus) in accredited zoos and aquariums experience a range of habitat types and management programs that provide opportunities for dolphins to engage in species-appropriate behaviors and potentially influence their individual and group welfare. Data in the present study were collected as part of a larger study titled “Towards understanding the welfare of cetaceans in zoos and aquariums” (colloquially called the Cetacean Welfare Study). Non-invasive bio-logging devices (Movement Tags) recorded the diving behavior and vertical habitat movements of 60 bottlenose dolphins at 31 zoos and aquariums that were accredited by the Alliance for Marine Mammal Parks and Aquariums and/or the Association of Zoos & Aquariums. Bottlenose dolphins wore a Movement Tag one day per week for two five-week data collection periods. Demographic variables, environmental enrichment programs, training programs, and habitat characteristics were associated with habitat usage. Longer dive durations and use of the bottom third of the habitat were associated with higher enrichment program index values. Dolphins receiving new enrichment on a monthly/weekly schedule also used the bottom third of the habitat more often than those receiving new enrichment on a yearly/year+ schedule. Dolphins that were managed in a group that was split into smaller subgroups during the day and were reunited into one group at night spent less time in the top third of the habitat than those who remained in a single group with consistent members at all times. Dolphins that were managed as subgroups with rotating members but were never united as one group spent less time in the bottom third of the habitat than those who remained in a single group with consistent members at all times. Taken together, the results suggested that management practices, such as enrichment and training programs, played a greater role in how dolphins interacted with their environment relative to the physical characteristics of the habitat.

Sea Surface Salinity and Wind Speed Retrievals Using GNSS-R and L-Band Microwave Radiometry Data from FMPL-2 Onboard the FSSCat Mission

The Federated Satellite System mission (FSSCat), winner of the 2017 Copernicus Masters Competition and the first ESA third-party mission based on CubeSats, aimed to provide coarse-resolution soil moisture estimations and sea ice concentration maps by means of the passive microwave measurements collected by the Flexible Microwave Payload-2 (FMPL-2). The mission was successfully launched on 3 September 2020. In addition to the primary scientific objectives, FMPL-2 data are used in this study to estimate sea surface salinity (SSS), correcting for the sea surface roughness using a wind speed estimate from the L-band microwave radiometer and GNSS-R data themselves. FMPL-2 was executed over the Arctic and Antarctic oceans on a weekly schedule. Different artificial neural network algorithms have been implemented, combining FMPL-2 data with the sea surface temperature, showing a root-mean-square error (RMSE) down to 1.68 m/s in the case of the wind speed (WS) retrieval algorithms, and RMSE down to 0.43 psu for the sea surface salinity algorithm in one single pass.

Impaired Performance on a Cognitively-Based Instrumental Activities of Daily Living Task, the 10-Item Weekly Calendar Planning Activity, in Individuals With Stroke Undergoing Acute Inpatient Rehabilitation

Performance-based, functionally relevant, and standardized measures of cognitive-instrumental activities of daily living (C-IADL) can complement neuropsychological tests of cognitive impairment and provide valuable clinical information to inform rehabilitation planning. Existing measures have been validated in the outpatient setting. Here, we sought to evaluate a 10-item, short-form of a C-IADL measure, Weekly Calendar Planning Activity (WCPA-10), in inpatients with stroke undergoing acute rehabilitation. The specific goal was to determine if the WCPA-10 could differentiate between stroke patients undergoing acute inpatient rehabilitation and healthy control individuals. We also explored whether the WCPA-10 would identify C-IADL limitations in stroke patients screened as having intact cognition. Seventy-seven stroke inpatients undergoing rehabilitation and 77 healthy control participants completed the WCPA-10, which involves entering a list of simulated, fictional appointments into a weekly schedule while keeping track of and adhering to multiple task rules and ignoring built-in obstacles and distractions. Compared to the control group, stroke patients had significantly worse accuracy, made more errors, used fewer cognitive strategies, followed fewer rules, took more time to complete the task, and were less efficient. 83% of stroke patients were less accurate than predicted by their age, and 64% used less strategies than their age prediction. Among 28 participants who screened as having “normal” cognitive function on the Montreal Cognitive Assessment, the majority had deficits on the WCPA-10. Our results provide initial support for use of a brief C-IADL assessment, WCPA-10, for individuals with stroke undergoing inpatient rehabilitation. They indicate that stroke patients have deficits in C-IADL accuracy, efficiency, and strategy use at this stage of stroke recovery. Results highlight the need to use performance based, functional cognitive assessments, even for those who perform well on cognitive screening tools.

Weekly chemotherapy as first line treatment in frail head and neck cancer patients in the immunotherapy era

Objective First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, which have shown a significant improvement in overall survival (OS) gaining approval in a first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to 3-weeks treatment, was retrospectively evaluated in a frail patient population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach. Methods A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in a first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities were analysed. Results Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients in weekly group (21) were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35% (36 patients) and 34% (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%). Conclusion The weekly schedule appears to be an active and safe strategy in frail patients with R/M HNSCC. Based on these data, a weekly schedule could be considered as a first line treatment in all frail patients excluded from pembrolizumab treatment and a study on the combination of weekly chemotherapy and immunotherapy should be performed.

Impact of additional intravenous methylprednisolone pulse therapy on the quality of life in patients with dysthyroid optic neuropathy

Introduction. Dysthyroid optic neuropathy (DON) is a severe complication of Graves’ orbitopathy (GO). Treatment of DON should involve immediate administration of intravenous methylprednisolone (ivMP) in very high doses. It is recommended to include additional 12 pulses of ivMP according to a weekly schedule as a further step of the treatment process. The purpose of this study was to evaluate the influence of a 12-week ivMP treatment on the quality of life (QoL) in DON patients. Material and Methods. A retrospective study was conducted on 6 patients (the tests involved 8 individual eyes) with DON and treated with ivMP in very high doses, followed by orbital decompression in one patient. All patients were qualified for additional treatment with ivMP in a 12-week protocol and completed the Polish version of the GOQoL questionnaire before and after the therapy. Visual acuity (VA) and diplopia were examined prior to the administration of ivMP pulses for DON, as well as before and after the additional ivMP treatment. Results. A minimal clinically important difference in QoL was observed in four patients at the end of the additional ivMP therapy. A significant increase in VA was observed following additional pulses of ivMP compared to the evaluation at the time of the DON diagnosis (p=0.04). Conclusions. Applying additional 12 pulses of ivMP following DON therapy may impact QoL. Performing QoL assessment throughout the entire therapy in patients with DON is particularly important in the clinical practice. Final evaluation of QoL should be performed after completing the entire therapeutic process, which involves surgical treatment to correct diplopia.

COORDINATING THE INSTRUCTION OF FOUR ONLINE COURSES

The University of British Columbia Vantage College offers a pathway for academically qualified international students who do not yet meet the English language admission requirements fordirect entry into UBC. In the summer of 2020, during the COVID-19 pandemic, we taught four courses to a cohort of 64 students scattered across the globe. The courses were taught online and asynchronously, raising coordination challenges in terms of class schedule and delivery, assessment, and student support. To address those challenges, we developed a highly structured weekly schedule, specifying lecture and assessment days, as well as regular, synchronous office hours. We met weekly to keep each other updated about the progress of students. Students falling behind in multiple courses were reported in an “early alert” system: a university-specific resource through which students are contacted by health and wellness staff. A midterm survey was conducted and the feedback was generally positive. Final results in the courses were varied, with some comparable