P-L13 Proposed sampling methodology for improved accuracy of hepatic burden assessment in neuroendocrine tumours

Background Hepatic burden is a significant confounder in the assessment of impact of primary tumour resection in metastatic small bowel neuroendocrine tumours (SI-NET). For SI-NET metastatic hepatic burden >10% disease replacement or > 5 hepatic metastases are known prognostic markers, though nomograms and scores do not adequately account for this. Most trials do not adequately account for hepatic burden when assessing the survival difference between SI-NET primary tumour resection and no resection. We propose a sampling methodology to more accurately assess metastatic liver burden in SI-NET and correlate with delayed resection vs. upfront primary tumour resection at a specialist NET surgical unit. Methods Patients referred for metastatic SI-NET between January 2003 and February 2020 were identified from a prospective dataset. The earliest CT scan after diagnosis was used. The axial, coronal and sagittal slice position limits of the whole liver were recorded. These limits allowed equitable slice position of the liver, with 8 equally distributed axial, 4 equally distributed coronal and 4 equally distributed sagittal slices. Each slice was used to define the liver and metastatic area as assessed using liver CT windows. Liver burden was estimated as percentage total metastatic area summed from all 8 axial, 4 coronal and 4 sagittal slices. Results 157 total patients were on the collated data base and 46 patients were identified with an appropriate CT. Liver burden was positively skewed. Liver burden was significantly higher for delayed resection vs. upfront resection in all planes of assessment (axial: 11.61% vs. 0.14%, p = 0.003; coronal: 13.46% vs. 0.33%, p = 0.006; sagittal: 10.46% vs. 0.16%, p = 0.008). All planar assessments correlated well with one another (all Kendall’s tau ≥0.851, all p < 0.001). Liver metastatic burden correlated with total liver volume (Kendall’s tau 0.549-0.573, all p < 0.001). Conclusions Hepatic burden differs between resection groups in a small sample at our centre, highlighting the unmeasured confounders favouring primary tumour resection via positive bias. Therefore, hepatic burden needs quantifying in prospective studies that assess primary tumour resection in SI-NET. This is to ensure comparable groups after randomisation. Our method provides an assessment of this metastatic SI-NET liver burden.

Pitfalls of using denosumab preoperatively to treat refractory severe hypercalcaemia

A 40-year-old man, with a history of metastatic parathyroid carcinoma, status post primary tumour resection and lung metastasectomy, was hospitalised for persistent severe hypercalcaemia and elevated parathyroid hormone levels despite conventional management and escalating doses of cinacalcet. A single dose (120 mg) of denosumab was given and his calcium level plummeted from 14.8 mg/dL to 5.5 mg/dL. After second lung metastasectomy, he developed prolonged hypocalcaemia that required calcium and vitamin D supplements for more than 3 years. In patients with severe hypercalcaemia refractory to conventional therapies, denosumab has been used off-label with some success. A known side effect of denosumab is hypocalcaemia, which is often short-lived. The risk of prolonged hypocalcaemia should be fully evaluated before using denosumab preoperatively, especially in patients with renal insufficiency, prolonged hyperparathyroidism or anticipated tumour debulking surgery.

Bipolar hemiarthroplasty versus total hip arthroplasty in allograft-prosthesis composite reconstruction of the proximal femur following primary bone tumour resection

Aims The consensus is that bipolar hemiarthroplasty (BHA) in allograft-prosthesis composite (APC) reconstruction of the proximal femur following primary tumour resection provides more stability than total hip arthroplasty (THA). However, no comparative study has been performed. In this study, we have compared the outcome and complication rates of these two methods. Methods In a retrospective study, 57 patients who underwent APC reconstruction of proximal femur following the primary tumour resection, either using BHA (29) or THA (28), were included. Functional outcome was assessed using the Musculoskeletal Tumour Society (MSTS) scoring system and Harris Hip Score (HHS). Postoperative complications of the two techniques were also compared. Results The mean follow-up of the patients was 8.3 years (standard deviation (SD) 5.5) in the BHA and 6.9 years (SD 4.7) in the THA group. The mean HHS was 65 (SD 16.6) in the BHA group and 88 (SD 11.9) in the THA group (p = 0.036). The mean MSTS score of the patients was 73.3% (SD 16.1%) in the BHA and 86.7% (SD 12.2%) in the THA group (p = 0.041). Limping was recorded in 19 patients (65.5%) of the BHA group and five patients (17.8%) of the THA group (p < 0.001). Dislocation occurred in three patients (10.3%) of the BHA group and two patients (7.1%) of the THA group. Conclusion While the dislocation rate was not higher in THA than with BHA, the functional outcome was significantly superior. Based on our results, we recommend THA in APC reconstruction of the proximal femur. Cite this article: Bone Joint J 2020;102-B(4):524–529.

A randomized controlled trial comparing primary tumour resection plus chemotherapy with chemotherapy alone in incurable stage IV colorectal cancer: JCOG1007 (iPACS study)

It is controversial whether chemotherapy with or without primary tumour resection is effective for the patients with incurable Stage IV colorectal cancer. A randomized controlled trial, initiated in Japan in 2012, is being conducted to evaluate the survival benefit and safety of primary tumour resection plus chemotherapy compared with chemotherapy alone in asymptomatic Stage IV colorectal cancer patients with unresectable metastatic disease. Patients are randomly assigned to either chemotherapy alone or primary tumour resection followed by chemotherapy. The primary endpoint is overall survival. Secondary endpoints are progression-free survival, incidence of adverse events, proportion of patients with R0 resection and proportion of palliative surgery for the chemotherapy-alone group. This trial was registered in June 2012 with the UMIN Clinical Trials Registry as UMIN000008147 [http://www.umin.ac.jp/ctr/index-j.htm]. In December 2017, the study protocol was amended for reducing sample size. A total of 280 patients will be enrolled over the course of 8.5 years.