Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial

PURPOSE: This randomized, open -label trial compared the efficacy and safety of adjuvant nabpaclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430). METHODS: We assigned 866 treatment -naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m(2)) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28 -day cycles. The primary end point was independently assessed disease -free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS: Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nabpaclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 (nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P =.18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P=.02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P =.045). At a 16 -month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 (nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P =.0232). At the 5 -year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P =.0091). Eighty-six percent (nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade >= 3 treatment -emergent adverse events. Two patients per study arm died of treatment -emergent adverse events. CONCLUSION: The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Assessing quality of life (QoL) of patients and their caregivers on phase I clinical trials.

e23130 Background: Patients on Phase I trials help advance science through their participation but there is a paucity of data regarding QoL of patients and their caregivers. Methods: Phase I trial patients from a single Asian centre were assessed at baseline and at 3 time intervals after treatment initiation with EORTC-core (QLQ-C30) and Comprehensive Score for Financial Toxicity (COST) questionnaires. Caregivers’ QoL were assessed with Zarit-Burden Interview (ZBI). Paired-sample t-tests were used to test for QoL differences at different time intervals. Results: 35 patients have been recruited with 70 individual visits so far. 60% of patients were female, 74% were Chinese. The most common cancer types were gastrointestinal (51.5%) and gynaecological (25.7%). Patients had a median of 3 lines of prior treatment (range: 0-9). QLQ-C30 scores range from 0 to 100, higher scores represent a high level of QoL/functioning. At baseline, the mean global QoL score was 51.9 (range: 16.7-100). The mean physical, role, cognitive, emotional and social functioning scores (FS) were 74.1 64.7, 86.6, 78.8 and 69.5 respectively. Patients were most bothered by fatigue and pain. 65.7% experienced grade 1 or 2 financial toxicities based on COST. There were significant improvements in physical (14.5 +/- 16.7, p &lt; 0.001), cognitive (18.1 +/- 25.0, p = 0.002) and emotional (10.5 +/- 18.4, p = 0.012) FS at baseline and 1-month post treatment. Patients experienced a reduction in fatigue, but no change in pain or financial concerns. Only 28.6% of patients were referred to palliative care medicine. Of 19 caregivers surveyed with ZBI, 10 experienced little/no burden, 8 had mild-moderate levels of burden and 1 reported severe burden. Conclusions: This is the first Asian study reporting QoL of cancer patients and their caregivers in Phase I clinical trials. In this group of heavily pre-treated patients, Phase I options can result in QoL improvement. Two-thirds of caregivers had minimal burden. Identifying QoL issues of patients and their caregivers will improve supportive care rendered to them. </jats:p

Maximising Capacity and Saving Cost in an Outpatient Chemotherapy Centre during a Pandemic: A Quality Improvement Project

Introduction Blood transfusion is an integral part of routine outpatient Haematology-Oncology care. Blood product administration requires the concerted effort of nursing and laboratory staff in accredited institutions. One of the challenges with scheduling transfusions is the unpredictability surrounding transfusion requirements and the amount of time required to administer blood products. This mismatch between capacity availability for ad hoc transfusions and clinical need has resulted in physicians pre-booking transfusion slots so patients can be transfused if needed. However, when patients do not require transfusions, their cancelled slots represent capacity which could have otherwise been used to administer chemotherapy. This problem is exacerbated in a pandemic, where demand for inpatient beds necessitates the transition of elective chemotherapy to the outpatient setting insofar as is possible. Aim We hypothesized that reducing the number of transfusion slots booked could help to save healthcare-related costs and improve capacity utilisation. We also sought to right-site blood transfusions away from the chemotherapy infusion unit and to an acute cancer care unit (ACCU). Methods On 1 May 2020, two simple workflow changes were made. First, we introduced a policy where transfusions could not be pre-booked. Physicians were reassured that their patients would be transfused before their patient's crossmatch sample expired and that urgent transfusions would be done on the same day. The only exceptions to this policy were regularly transfused patients (e.g. thalassaemia major patients on chronic transfusions) and infirm patients. Secondly, ad hoc blood transfusions were moved from the chemotherapy unit to the acute cancer care unit. Ad hoc transfusion timing was prioritised according to clinical need. Consecutive patients treated at the National University Cancer Institute, Singapore, from 1 July 2019 to 31 July 2020 were included. Scheduled appointments were extracted from the hospital's scheduling system and analysed. Patients who had appointments booked for blood product transfusions were included. Data was extracted from drug ordering systems to determine the number of blood products administered. Patients were divided into a historical control group (before 1 May) and a study group (after 1 May). The primary outcome measures were cancellation rate (defined as the number of cancellations over total number of slots booked for transfusion) and number of chair hours wasted. Secondary outcome measures included the number of patients who had to be admitted for blood transfusion due to lack of slot availability and cost savings reflected in unit chair hours made available. Categorical data were analysed by the chi-square test. Analysis was done with SPSS v22 (IBM, USA). Results Between 1 July 2019 and 31 July 2020, a total of 3144 slots were booked for transfusion. Each slot was booked for four hours. 1548 blood products were administered. In the control group, there were 1630 cancellations. This equated to 6520 hours of chemotherapy chair time (average of 652 hours/month). There were no nett cancellations in the study group, as total number transfused exceeded the number booked. Assuming the booking rate would have been similar without our intervention, the study resulted in 1956 unutilised chair hours saved. This reflects capacity created for administration of chemotherapy, and cost savings of 1956x, where x is the unit cost of one chair hour. The cancellation rate was 58.3% (1630 cancelled, 2800 booked) in the control group. This decreased to -9.9% in the study group (378 administered (i.e., no nett cancellations), 344 booked, p&amp;lt;0.001, Figure 1). No patients had to be admitted for elective blood transfusion after 1 May 2020. One patient had to be admitted emergently for blood transfusion because of concurrent cardiac failure. The primary reason for admission was intravenous diuresis. All ad hoc transfusions were administered in ACCU. Conclusion Efficient utilisation brought about by two simple workflow changes can help to create capacity and save costs. Such strategies are especially critical in a pandemic, where healthcare resources are under major strain and existing capacity must be maximised. Disclosures No relevant conflicts of interest to declare. </jats:sec

Functional Precision in Pancreatic Cancer: Redefining Biomarkers with Patient-Derived Organoids

Pancreatic cancer remains a lethal disease despite advances in surgery and systemic treatment in the last two decades, underscoring the urgent need to better understand its biological underpinnings. Despite remarkable advances in the molecular characterization of pancreatic ductal adenocarcinoma (PDAC), clinically actionable biomarkers remain scarce, and current treatment remains empiric. Transcriptomic subtypes such as &ldquo;classical&rdquo; and &ldquo;basal-like&rdquo; offer some prognostic value, but their ability to guide real-time treatment decisions is limited. In this review, we explore the limitations of current biomarker strategies, in particular subtype-based classifications, and argue for a functional reframing of biomarker development in PDAC, centered on patient-derived organoids (PDOs). We explore four key domains in which PDOs deepen our understanding of therapeutic response and resistance, namely, drug response phenotyping, modeling chemoresistance, incorporating tumor microenvironmental complexity through co-culture systems, and more functional profiling through proteomic and metabolomic approaches. Together, these applications move PDOs beyond static avatars of the tumor to dynamic platforms capable of capturing clinically relevant biology. As functional precision medicine gains traction, PDOs may offer a path to more tailored, responsive treatment strategies in a cancer where new options are urgently needed

Reducing Chemotherapy Waiting Times in the Ambulatory Setting of a Tertiary Cancer Centre Using a Design Thinking Approach

Introduction: Chemotherapy is complex. We hypothesized that a design thinking approach could redesign preparatory processes and reduce wait times. Methods: A multidisciplinary process mapping exercise was undertaken to understand the current processes, followed by proposing and testing solutions. Proposals were selected based on desirability and feasibility. These focused on starting the morning treatments on time and scheduling pre-made regimens in these slots. The primary outcome measure was the time from the appointment to starting treatment. Treatments in the post-intervention study group were compared against a historical control group. Results: The median time to start morning treatment decreased by 46%, from 83 min (with an interquartile range 50–127) in the control group to 45 min (with an interquartile range of 24–81 min) in the study group (p p p p < 0.001). Conclusion: We have shown that a data-driven, design thinking approach can improve waiting times. This can be adapted to improve other processes in an empathetic, sustainable manner