Rechallenge of denosumab in advanced giant cell tumor of the bone after atypical femur fracture: A case report and review of literature.

Giant cell tumor of the bone (GCTB) is a locally aggressive neoplasm where surgery is often curative. However, it can rarely give rise to distant metastases. Currently, the only available active therapeutic option for unresectable GCTB is denosumab, an anti-RANKL monoclonal antibody that dampens the aggressive osteolysis typically seen in this disease. For advanced/metastatic GCTB, denosumab should be continued lifelong, and although it is usually well tolerated, important questions may arise about the long-term safety of this drug. In fact, uncommon but severe toxicities can occur and eventually lead to denosumab discontinuation, such as atypical fracture of the femur (AFF). The optimal management of treatment-related AFF is a matter of debate, and to date, it is unknown whether reintroduction of denosumab at disease progression is a clinically feasible option, as no reports have been provided so far. Hereinafter, we present a case of a patient with metastatic GCTB who suffered from AFF after several years of denosumab; we describe the clinical features, orthopedic treatment, and oncological outcomes, finally providing the first evidence that denosumab rechallenge after AFF occurrence may be a safe and viable option at GCTB progression.

Weekly cisplatin with or without imatinib in advanced chordoma: A retrospective case-series analysis from the Italian Rare Cancers Network.

BACKGROUND: To report on a retrospective case-series analysis of weekly cisplatin (wCDDP) as a single agent or combined with imatinib (wCDDP/I) in patients with advanced chordoma treated within the Italian Rare Cancer Network. METHODS: Adult patients with a diagnosis of advanced, brachyury-positive chordoma, treated from April 2007 to October 2020 with wCDDP or wCDDP/I were retrospectively identified. Imatinib was withheld at the same time as wCDDP. Response according to Response Evaluation Criteria in Solid Tumors, overall survival (OS), and progression-free survival (PFS) were analyzed. RESULTS: Thirty-three consecutive patients were identified (wCDDP as front-line n = 8 [24.2%]; wCDDP as a further line n = 25 [75.8%]; prior imatinib n = 25 [75.8%]; evidence of progression before starting wCDDP n = 33). Of 32 patients evaluable for response (wCDDP, n = 22 [68.8%]; wCDDP/I, n = 10 [31.3%]), best response was stable disease (SD) in 27 patients (84.3%) and progression in 5 patients (15.6%). At a median follow-up of 54 months, the median OS (m-OS) was 30.3 months (interquartile range [IQR], 18.1-56.6), the m-PFS was 8.0 months (IQR, 5.1-17.0), the 6-month PFS rate was 65.2%, and the 12-month PFS rate was 30.3%. Of 22 patients who received wCDDP, the best response was SD in 18 patients (81.8%) and progression in 4 patients (18.2%), and the m-PFS was 8.0 months (IQR, 5.1-17.0 months). Of 10 patients who received treatment with wCDDP/I, the best response was SD in 9 patients (90%) and progression in 1 patient (10%), and the m-PFS was 9.3 months (IQR, 4.9-26.5 months). CONCLUSIONS: This series suggests that wCDDP, both as a single agent and combined with imatinib, has antitumor activity in chordoma. Although no dimensional responses were observed, 65% and 30% of previously progressive patients were progression-free at 6 and 12 months, respectively. A prospective study is warranted.

Reproducibility of Ablated Volume Measurement Is Higher with Contrast-Enhanced Ultrasound than with B-Mode Ultrasound after Benign Thyroid Nodule Radiofrequency Ablation-A Preliminary Study.

The reproducibility of contrast-enhanced ultrasound (CEUS) and standard B-mode ultrasound in the assessment of radiofrequency-ablated volume of benign thyroid nodules was compared. A preliminary study was conducted on consecutive patients who underwent radiofrequency ablation (RFA) of benign thyroid nodules between 2014 and 2016, with available CEUS and B-mode post-ablation checks. CEUS and B-mode images were retrospectively evaluated by two radiologists to assess inter- and intra-observer agreement in the assessment of ablated volume (Bland-Altman test). For CEUS, the mean inter-observer difference (95% limits of agreement) was 0.219 mL (-0.372-0.809 mL); for B-mode, the mean difference was 0.880 mL (-1.655-3.414 mL). Reproducibility was significantly higher for CEUS (85%) than for B-mode (27%). Mean intra-observer differences (95% limits of agreement) were 0.013 mL (0.803-4.097 mL) for Reader 1 and 0.031 mL (0.763-3.931 mL) for Reader 2 using CEUS, while they were 0.567 mL (-2.180-4.317 mL, Reader 1) and 0.759 mL (-2.584-4.290 mL, Reader 2) for B-mode. Intra-observer reproducibility was significantly higher for CEUS (96% and 95%, for the two readers) than for B-mode (21% and 23%). In conclusion, CEUS had higher reproducibility and inter- and intra-observer agreement compared to conventional B-mode in the assessment of radiofrequency-ablated volume of benign thyroid nodules.

Reproducibility of DXA-based bone strain index and the influence of body mass: an in vivo study.

OBJECTIVES: Bone strain index (BSI) is a dual-energy X-ray absorptiometry (DXA)-derived index of bone strength obtained from lumbar densitometric scan. We estimated the reproducibility of BSI in healthy women with different body mass index. METHODS: We enrolled postmenopausal women (mean age ± SD: 66 ± 10 years) divided into three groups (A, B and C) according to body mass index (BMI: < 25; 25-29.9; ≥ 30 kg/m2) and two groups (D and E) according to waist circumference (WC: ≤ 88; > 88 cm), each of 30 subjects. They underwent two DXA examinations with in-between repositioning, according to the International Society for Clinical Densitometry guidelines for precision estimation. Bone mineral density (BMD) and BSI were expressed as g/cm2 and absolute value, respectively. The coefficient of variation (CoV) was calculated as the ratio between root-mean-square standard deviation and mean; least significant change percentage (LSC%) as 2.77 × CoV; reproducibility as the complement to 100% LSC. RESULTS: BSI increased proportionally to BMI and WC and significantly in group C compared to B and A (p = 0.032 and 0.006, respectively). BSI was significantly higher in E compared to D (p = 0.017), whereas no differences were observed in BMD. Although BSI reproducibility was slightly lower in group C (89%), the differences were not significant between all groups. BMD reproducibility did not significantly differ between all groups. CONCLUSIONS: BSI reproducibility was significantly lower than that of BMD and decreased proportionally to BMI and WC increase. This reduction of BSI reproducibility was more pronounced in patients with BMI ≥ 30 and WC > 88, as expected, being BSI a parameter sensible to weight.

Fat Mass Does Not Increase the Precision Error of Trabecular Bone Score Measurements.

INTRODUCTION: Trabecular bone score (TBS) is an indirect index of trabecular microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry. Previous phantom study showed that an increase in soft tissue thickness does not affect TBS reproducibility. We investigated the effect of increasing body mass index (BMI) and waist circumference on TBS precision error on patients, compared to bone mineral density (BMD). METHODOLOGY: A population of postmenopausal Caucasian women was distributed in 3 different BMI (normal, overweight, and class I obesity), plus 2 further groups based on waist circumference diameter (≤88 cm and >88 cm, respectively). In vivo precision error was calculated on 30 consecutive subjects that were scanned 2 times, with patient repositioning, using the Hologic QDR-Discovery W densitometer. Coefficient of variation, percent least significant change, and reproducibility were calculated according to the International Society for Clinical Densitometry guidelines. RESULTS: Ninety-five women aged 66 ± 10 (mean ± standard deviation) were included. No significant differences were found both for BMD and TBS precision errors, respectively, when comparing BMI groups and waist circumference groups. BMD reproducibility ranged from 95.9% (BMI > 30 kg/m2) to 97.5% (BMI < 25 kg/m2). TBS reproducibility ranged between 95.8% (BMI = 25-29.9 kg/m2, waist circumference > 88 cm) and 96.6% (BMI < 25 kg/m2). With the exception of obese group, a significant difference was found between BMD and TBS reproducibility, being that of TBS slightly lower than BMD. A significant decrease of TBS values was found between normal and obese subjects, as well as between waist circumference groups. CONCLUSIONS: TBS precision error is not affected by BMI and waist circumference differences. TBS reproducibility showed to be slightly lower than that of BMD, but this difference was mitigated in obese patients. A negative association was found between the amount of fat mass and TBS mean values.