Results from a global survey of clinical cancer researchers on clinical trial design and conduct during the COVID-19 pandemic and beyond.

e13576 Background: The COVID-19 pandemic has had profound detrimental consequences on cancer patient outcomes and clinical cancer research, with considerable adaptations made to both standard care and clinical research to optimise patient safety. Detailed perspectives of clinical researchers on such risk mitigation, and granular insight into which adaptions should persist long term, are required to inform future clinical trial design. Methods: We designed and performed an in depth, global survey (open between 04/22/20 and 06/10/2020) of cancer research professionals to assess the impact of the pandemic on clinical care and research, and how researchers prioritise and view clinical research methodologies. Results: 162 valid responses were received (58.7% oncologists, 14.8% research nurses; 69.1% working in academic centers) from six continents. There was significant heterogeneity in how the pandemic has affected healthcare workers, patients on standard of care or investigational trial treatments, and clinical trial recruitment. Our results detail how trial and non-trial patient care has altered in respondents’ centres and how respondents would prioritise specific trial designs while the pandemic continues. We show marked variance in the perceived value of specific trial protocol features and assessments (regardless of the pandemic). More respondents agreed than disagreed that trial eligibility criteria are too restrictive (48% agreed versus 28% disagreed), that screening assessments generally have unnecessary tests (51% versus 23%), that physical examination should only be performed when clinically indicated (43% versus 30%), that electronic patient outcomes/questionnaires are better at detecting adverse events that a consultation with a study doctor (33% versus 29%), that wearable technology/validated tools for patients to perform self-examination would provide more useful information than vital sign assessment in the study center (48% versus 13%), and that replacing routine in person visits with virtual visits would not significantly compromise patient safety (36% versus 28%). However, 65% of respondents indicated that fully virtual clinical trials (in the absence of reported clinically significant toxicities) would not be sufficiently safe (versus 15% who indicated that they would be). Conclusions: These detailed data provide further evidence of a significant adverse impact of the pandemic on cancer patient care and drug development, may help inform risk mitigation for studies in times of heightened infection risk, and aid with future clinical trial design.

Future Directions in the Treatment of Osteosarcoma

Osteosarcoma is the most common primary bone sarcoma and is often diagnosed in the 2nd–3rd decades of life. Response to the aggressive and highly toxic neoadjuvant methotrexate-doxorubicin-cisplatin (MAP) chemotherapy schedule is strongly predictive of outcome. Outcomes for patients with osteosarcoma have not significantly changed for over thirty years. There is a need for more effective treatment for patients with high risk features but also reduced treatment-related toxicity for all patients. Predictive biomarkers are needed to help inform clinicians to de-escalate or add therapy, including immune therapies, and to contribute to future clinical trial designs. Here, we review a variety of approaches to improve outcomes and quality of life for patients with osteosarcoma with a focus on incorporating toxicity reduction, immune therapy and molecular analysis to provide the most effective and least toxic osteosarcoma therapy.

Ultra-Minimally Invasive Sonographically Guided Trigger Digit Release: An External Pilot Study

Objective: The most common surgical option for releasing the first annular pulley in trigger digit is classic open surgery followed by blind percutaneous release. However, they have been related to major complications and incomplete releases, respectively. Classic. The intrasheath sonographically guided first annular pulley release has recently shown to be safe and effective in every digit. The objectives of this pilot study were to preliminary compare clinically an intrasheath sonographically-guided first annular pulley release versus a classic open technique and to evaluate the feasibility of a future clinical trial in patients with trigger digits. Methods: Thirty patients were 1:1 randomized in an external pilot study comparing the two surgical techniques: a percutaneous sonographically-guided release performed through a 1 mm incision using a hook knife versus a classic open surgery with a 1 cm incision. Inclusion criteria were primary trigger digit grade III (Froimson). We defined success if primary (safety and efficacy) and secondary objectives (recruitment rates, compliance, completion, treatment blinding, personnel resources and sample size calculation for the clinical trial) could be matched. We registered the grip strength, the Quick-DASH score and a set of clinical postoperative variables at 1, 3 and 6 weeks and at 3 months. We calculated the sample size for the clinical trial using the Quick-DASH at the end of the follow-up. Outcomes assessors were blinded. Results: All patients in both groups showed resolution of their symptoms with no associated complications or relapses. Secondary feasibility objectives were matched: 76.9% of eligible patients were included in the study, 3.3% refused randomization, 20 patients per month were recruited, 100% received blinded treatment, 98.5% showed compliance and 100% completed the study. The sample size for a future clinical trial was of 84 patients. There were no differences in grip strength. The intrasheath sonographically-guided first annular pulley release showed significantly better scores for the Quick-DASH, until the 6th postoperative week. Conclusions: The intrasheath sonographically-guided first annular pulley release is safe and efficacious and it shows a trend towards clinical superiority versus the classic open procedure, which should be confirmed with a clinical trial. Our study shows that a randomized clinical trial is feasible.

Flares in patients with systemic lupus erythematosus

Objective SLE is characterized by relapses and remissions. We aimed to describe the frequency, type and time to flare in a cohort of SLE patients. Methods SLE patients with one or more ‘A’ or ‘B’ BILAG-2004 systems meeting flare criteria (‘new’ or ‘worse’ items) and requiring an increase in immunosuppression were recruited from nine UK centres and assessed at baseline and monthly for 9 months. Subsequent flares were defined as: severe (any ‘A’ irrespective of number of ‘B’ flares), moderate (two or more ‘B’ without any ‘A’ flares) and mild (one ‘B’). Results Of the 100 patients, 94% were female, 61% White Caucasians, mean age (s.d.) was 40.7 years (12.7) and mean disease duration (s.d.) was 9.3 years (8.1). A total of 195 flares re-occurred in 76 patients over 781 monthly assessments (flare rate of 0.25/patient-month). There were 37 severe flares, 32 moderate flares and 126 mild flares. By 1 month, 22% had a mild/moderate/severe flare and 22% had a severe flare by 7 months. The median time to any ‘A’ or ‘B’ flare was 4 months. Severe/moderate flares tended to be in the system(s) affected at baseline, whereas mild flares could affect any system. Conclusion . In a population with active SLE we observed an ongoing rate of flares from early in the follow-up period with moderate–severe flares being due to an inability to fully control the disease. This real-world population study demonstrates the limitations of current treatments and provides a useful reference population from which to inform future clinical trial design.

EXPAREL® (Long-Acting Liposomal Bupivacaine) Use for Popliteal Nerve Block in Postoperative Pain Control after Ankle Fracture Fixation

EXPAREL® has been used successfully to prolong postoperative pain control when applied as a wound infiltrate. EXPAREL® has not yet been approved for use in regional anesthesia to prolong postoperative pain control. We conducted a clinical case series of 4 patients using EXPAREL® for sciatic blocks via the popliteal fossa approach. Our results suggested that there is a large degree of variability in response to the medication. These inconsistent results and the possibility of bimodal kinetics creating analgesic gaps as seen in two of our patients indicate that more studies with larger sample size are needed to better characterize these phenomena and determine if more consistent results can be obtained in a future clinical trial.