Business as unusual: medical oncology services adapt and deliver during COVID-19.

BACKGROUND: The COVID-19 pandemic has challenged cancer care globally, introducing resource limitations and competing risks into clinical practice. AIMS: To describe the COVID-19 impact on medical oncology care provision in an Australian setting. METHODS: Calvary Mater Newcastle and Newcastle Private Hospital medical oncology data from 1 February to 31 April 2019 versus 2020 were retrospectively analysed. RESULTS: Three hundred and sixty-four inpatient admissions occurred in 2020, 21% less than in 2019. Total inpatient days decreased by 22% (2842 vs 2203). April was most impacted (36% and 44% fewer admissions and inpatient days respectively). Mean length of stay remained unchanged (6.4 vs 6.2 days, P = 0.7). In all, 5072 outpatient consultations were conducted, including 417 new-patient consultations (4% and 6% increase on 2019 respectively). Telephone consultations (0 vs 1380) replaced one-quarter of face-to-face consultations (4859 vs 3623, -25%), with minimal telehealth use (6 vs 69). Day Treatment Centre encounters remained stable (3751 vs 3444, -8%). The proportion of new patients planned for palliative treatment decreased (35% vs 28%, P = 0.04), observation increased (16% vs 23%, P = 0.04) and curative intent treatment was unchanged (both 41%). Recruiting clinical trials decreased by one-third (45 vs 30), two trials were activated (vs 5 in 2019) and 45% fewer patients consented to trial participation (62 vs 34). CONCLUSION: Our medical oncology teams adapted rapidly to COVID-19 with significant changes to care provision, including fewer hospital admissions, a notable transition to telephone-based outpatient clinics and reduced clinical trial activity. The continuum of care was largely defended despite pandemic considerations and growing service volumes.

Phase 1 trial of olaparib and oral cyclophosphamide in BRCA breast cancer, recurrent BRCA ovarian cancer, non-BRCA triple-negative breast cancer, and non-BRCA ovarian cancer.

BACKGROUND: We conducted a Phase 1 study to evaluate safety and activity of olaparib tablets and oral cyclophosphamide. METHODS: Patients had metastatic breast cancer (BC) or recurrent high-grade serous ovarian cancer (HGSOC), performance status 0-2, and ≤3 lines of prior therapy. Patients were treated using a dose escalation strategy with cohort expansion once maximal tolerated dose (MTD) was determined. Dose level 1 (DL1): olaparib 300 mg bid, cyclophosphamide 50 mg on days 1, 3, and 5, weekly. DL2: olaparib 300 mg bid, cyclophosphamide 50 mg, days 1-5 weekly. RESULTS: Of 32 patients, 23 had HGSOC (germline BRCA mutation [gBRCAm] 70%) and 9 had BC (gBRCAm 67%). Four were treated at DL1 and 28 at DL2, the MTD. Haematological adverse events (AEs) were most common: grade 3/4 AEs: lymphopenia 75%, anaemia 31%, neutropenia 37%, thrombocytopenia 47%. Two permanently discontinued treatment due to haematological AEs. In BC, no objective response was reported. Unconfirmed objective response was 48% and 64% for all HGSOC and gBRCAm subset, respectively. CA125 responses were 70% (all HGSOC) and 92% (gBRCAm). CONCLUSIONS: In HGSOC and BC, olaparib 300 mg bid and cyclophosphamide 50 mg on days 1-5 weekly were tolerable and active, particularly in gBRCAm, and is worthy of further investigation.

Genetic testing in women with breast cancer: implications for treatment.

INTRODUCTION: Mutations in either the BRCA1 or BRCA2 genes are responsible for approximately 42,000 cases of breast cancer annually. Identifying these germline mutations in a woman with breast cancer is important because it can influence her immediate and long-term management and has important implications for other family members. Areas covered: This review highlights how treatment-focussed genetic testing for BRCA1 and BRCA2 mutations can potentially influence cancer treatment and secondary prevention decisions in women with breast cancer. Expert commentary: Testing women with breast cancer for BRCA1 and BRCA2 germline mutations has the potential to decrease cancer burden and improve cancer outcomes. It can help optimise surgical and systemic therapy approaches. Clinicians should actively consider whether genetic testing is appropriate for each woman with breast cancer, and if so should instigate it early in the treatment trajectory when it can most influence cancer care.

Optimisation of the superplastic forming of a dental implant for bone augmentation using finite element simulations.

OBJECTIVES: The phenomenon of superplasticity has made it possible to form complex shapes that require extremely high degrees of ductility in titanium alloy with minimal internal stresses. Combined with the use of an investment casting material as the die material, which makes possible the forming of re-entrant angles, it is possible to produce membranes for ridge augmentation. The aim is to characterise the metal alloy sheet and simulate the superplastic forming process in three dimensions to produce process parameters, namely gas pressure as a function of time, to accurately adapt the titanium sheet to the bone surface. METHOD: The surface of the die was digitised using a 3D laser scanning system (UBM-Keyence LC2450). Ti-6Al-4V sheet of 140 mm diameter was modelled using a grid of triangular membrane elements. This mesh was automatically refined during the simulations. Finite element simulation was carried out using the Superflag software program (University of Wales Swansea) Three different options for gas pressure control were adopted, namely, target flow stress, target strain rate and target energy dissipation. The pressure cycles produced from the simulation were used to form titanium alloy sheet at 900 degrees C using argon gas. The deformed regions of the formed sheet were then examined to determine the regions of contact with the die and to characterise surface damage. RESULTS: Comparison of the simulations with experiment showed that there was good agreement between simulated and experimental thickness distributions in most parts of the sheet that were examined. Interrupted tests showed that in the intermediate positions of the forming sheet the simulations were slightly ahead of the experiment. The target stress option was found to produce the best degree of adaptation and the sheet formed using this cycle showed good surface quality, whereas in highly deformed regions using the other target options, the sheet was found to have formed microcracks. The use of a solid lubricant on the surface of the forming sheet was not found to have a significant influence on the adaptation of the titanium alloy sheet except in areas of high deformation where the sheet perforated. SIGNIFICANCE: The finite element membrane formulation is well adapted to the superplastic forming of a ridge augmentation membrane prosthesis. The simulation accurately describes the evolution of the shape of the prosthesis and its thickness distribution with time, which allows the manufacturer to select an appropriate initial thickness of titanium alloy sheet prior to attempting to form the component. The investment dies are found to have sufficient strength to withstand the forming operation if a suitable orientation of the titanium sheet with respect to the die is adopted. A metal surface of good quality can be produced in the formed prosthesis using the appropriate gas control option.