Operating procedures for electrochemotherapy in bone metastases: Results from a multicenter prospective study on 102 patients.

INTRODUCTION: Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease (MBD). The purposes of this multicentre study are to confirm the safety and efficacy of ECT, and to identify appropriate operating procedures in different MBD conditions. MATERIALS AND METHODS: 102 patients were treated in 11 Centres and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators and duration of follow-up were registered. RESULTS: 105 ECT sessions were performed (one ECT session in 99 patients, two ECT sessions in 3 patients). 24 patients (23.5%) received a programmed intramedullary nail after ECT, during the same surgical procedure. Mean follow-up was 5.9 ± 5.1 months (range 1.5-52). The response to treatment by RECIST criteria was 40.4% objective responses, 50.6% stable disease and 9% progressive disease. According to PERCIST criteria the response was: 31.4% OR; 51.7% SD, 16.9% PD with no significant differences between the 2 criteria. Diagnosis of breast cancer and ECOG values 0-1 were significantly associated to objective response. A significant decrease in pain intensity and significant better quality of life was observed after ECT session at follow-up. CONCLUSION: The results are encouraging on pain and tumour local control. ECT proved to be an effective and safe treatment for MBD and it should be considered as an alternative treatment as well as in combination with radiation therapy.

Three-year prospective study on fracture risk in postmenopausal women by quantitative ultrasound at the phalanges.

The purpose of this study was the calculation of fracture risk in a prospective study on postmenopausal women by quantitative ultrasound (QUS) at the phalanges. A total of 2341 postmenopausal women were recruited in 5 centers in Italy during 2006 and 2007 for QUS measurement during a screening program for osteoporosis. Two ultrasound parameters were collected: amplitude-dependent speed of sound (AD-SoS) and ultrasound bone profile index (UBPI). Women were then recontacted in 2010 and were asked about fracture occurrence during the period since previous QUS measurement. Data about new fracture occurred in this period, site and cause of fracture were requested. Two thousand two hundred eleven women were successfully recontacted. Mean age of the recruited women was 60.9 ± 10.0 yr, mean age at menopause was 49.3 ± 4.4 yr, mean body mass index (BMI) was 26.5 ± 4.6 kg/m². A total number of 108 new major osteoporotic fractures occurred during the 3-yr period, of which 23 are hip fractures, 51 are vertebral fractures. Relative risk (RR) per standard deviation (SD) decrease for major fractures was 1.77 (confidence interval [CI]: 1.59-1.97) for AD-SoS and 2.06 (CI: 1.78-2.37) for UBPI. When corrected for age, BMI, age at menopause, the RRs are still significant and equal to 1.44 (CI: 1.26-1.65) for AD-SoS and 1.67 (CI: 1.39-2.00) for UBPI. RR for vertebral fractures was 1.63 (CI: 1.41-1.88) for AD-SoS and 1.73 (CI: 1.44-2.08) for UBPI. RR for hip fractures was 1.92 (CI: 1.55-2.37) for AD-SoS and 2.68 (CI: 1.86-3.86) for UBPI. Ultrasound parameters AD-SoS and UBPI are able to significantly predict future major fractures in a prospective cohort of more than 2000 postmenopausal women.

Prospective bone ultrasound patterns during childhood acute lymphoblastic leukemia treatment.

OBJECTIVE: Bone impairment is a well-known complication in childhood acute lymphoblastic leukemia (ALL) survivors but less is known about bone dynamics during ALL therapy. We longitudinally assessed by Quantitative Ultrasound (QUS) skeletal modifications during this treatment. MATERIALS AND METHODS: Forty-four newly diagnosed ALL children underwent bone measurement by QUS parameters BTT (Bone Transmission Time) and AD-SoS (Amplitude-Dependent Speed of Sound), mainly reliant on bone density and cortical thickness, respectively. Measurements were performed at diagnosis, and 6, 12, and 24 months thereafter. The occurrence of skeletal complications such as fractures, vertebral collapse, osteonecrosis, and osteopenia was related to measurement outcome. RESULTS: A rapid deterioration of bone properties measured by BTT and AD-SoS was evident in the first semester of therapy (p<0.001). Subsequently, the next measurements were characterized by progressive uncoupling of the two QUS parameters (p<0.001). These were both significantly reduced at the end of therapy (p<0.001). Twelve subjects with in-treatment skeletal complications displayed an almost two-fold decrease of both parameters (p<0.001). BTT decreasing more than 1 Standard Deviation (SD) over 6 months of therapy was able to predict skeletal complication occurrence (p<0.001). CONCLUSION: This report represents the largest longitudinal cohort systematically submitted to bone condition assessment from the beginning to the end of therapy for childhood ALL. Bone deterioration occurs early and persists throughout therapy, consistent with bone properties uncoupling. This pattern possibly reflects an initial impairment of both mineral density and cortical thickness with a subsequent recovery of this latter. QUS permits an early detection of bone deterioration and related skeletal complications in childhood ALL.

Quantitative ultrasound at the phalanges in monitoring alendronate therapy.

This study evaluated the efficacy of quantitative ultrasound (QUS) at the phalanges in monitoring alendronate treatment. Seventy-nine postmenopausal women were enrolled: 46 subjects entered therapy with alendronate, the remaining 33 did not follow any therapeutic regimen. All subjects underwent phalangeal ultrasound measurement before starting treatment and after 12 mo. Two QUS parameters were measured: AD-SoS (Amplitude Dependent Speed of Sound) in m/s, and BTT (Bone Transmission Time) in micros. Mean age of subjects at the beginning of the study was 58.7 +/- 6.5 y, mean BMI was 26.6 +/- 4.4 kg/m(2), mean time since menopause was 6.7 +/- 5.0 y; no significant differences could be observed between the groups (p > 0.05). At 12-mo follow-up a significant increase of both QUS parameters was observed: +18.8 +/- 24.4 m/s for AD-SoS, p < 0.0001; +0.05 +/- 0.08 micros for BTT, p < 0.001. In the nontreated group AD-SoS was stable (+1.0 +/- 33.7 m/s), as well as BTT (-0.07 +/- 0.25 micros), p = n.s. for both. In the treated group the percentage of responders was 65.2% for AD-SoS and 50.0% for BTT. The percentage of non responders was 13% for AD-SoS and 15.2% for BTT. The results confirm that the effect of alendronate treatment may be suggested by QUS at the phalanges after 12 mo of treatment.

Bone alterations in children and young adults with renal transplant assessed by phalangeal quantitative ultrasound.

BACKGROUND: Bone alterations in young renal transplant recipients were investigated in several studies with conflicting results. Quantitative ultrasound of the phalanges is a recently developed noninvasive procedure to assess skeletal status. STUDY DESIGN: Cross-sectional study at a single transplant center with values compared with previously studied healthy controls. SETTINGS & PARTICIPANTS: 40 children and young adult recipients of renal grafts (15 females, 25 males; age, 20.0 +/- 8.4 years) studied 7.1 +/- 3.8 years after kidney transplantation. PREDICTOR: Clinical, biochemical, and therapeutic features, including calcium, phosphate, and intact parathormone levels; and cumulative dosages of glucocorticoids and cyclosporine administered since transplantation. OUTCOME & MEASUREMENT: Phalangeal quantitative ultrasound, including amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT), mainly dependent on mineral density and cortical thickness, respectively. Age- and sex-matched healthy controls were used to provide age-related z scores; sex- and height-matched healthy subjects, to provide z scores related to statural age. RESULTS: Mean z scores of AD-SoS and BTT were -0.05 +/- 1.59 and -0.54 +/- 1.17, respectively (P > 0.05 and P < 0.001, respectively). Multivariate analysis showed that AD-SoS z score was associated significantly with body mass index, intact parathormone level, cumulative glucocorticoids administered in the first posttransplantation year, and cyclosporine administered since transplantation (model r(2) = 0.79; P < 0.001); BTT z score was associated significantly with glucocorticoid dosage in the first posttransplantation year and age (model r(2) = 0.55; P < 0.001). LIMITATIONS: Absence of other measures of bone structure and longitudinal measures and comparison to a noncurrent control group. CONCLUSIONS: Children and young adults may have decreased cortical thickness with maintained overall mineral density after renal transplantation. The findings of phalangeal quantitative ultrasound parallel observations using other imaging techniques. Phalangeal quantitative ultrasound may be a useful method to assess bone alternations after renal transplantation.