MOTION multicentre study overview
Cryoablation for palliation of painful bone metastases
Radiology: Imaging Cancer 2021; 3(2):e200101 Jack W. Jennings, MD, PhD • J. David Prologo, MD • Julien Garnon, MD • Afshin Gangi, MD, PhD • Xavier Buy, MD • Jean Palussière, MD • A. Nicholas Kurup, MD • Matthew Callstrom, MD, PhD • Scott Genshaft, MD • Fereidoun Abtin, MD • Ambrose J. Huang, MD • Jason Iannuccilli, MD • Frank Pilleul, MD, PhD • Charles Mastier, MD • Peter J. Littrup, MD • Thierry de Baère, MD • Frédéric Deschamps, MD.
This multicenter, prospective, single arm, phase II study examined the impact of the treatment of a painful bone metastatic lesion in each patient.
Study objective and design
- The primary objective was to evaluate the efficacy of cryoablation for pain palliation of bone metastases from baseline to 8 weeks after cryoablation in worst pain in the last 24 hours.
- Separate evaluations of ancillary efficacy endpoints were also made through 24 weeks.
Study design
- Multicentre, prospective, single arm, phase II study
- 11 centres: 4 in EU and 7 in US;
- Conducted from February 2016 to March 2018;
- N= 66 patients with painful bone metastases treated, 65 available for follow-up;
- Patient follow-up at 1, 4, 8, 12, 16, 20, and 24 weeks after the cryoablation procedure;
- Treatment of 1 painful bone metastatic lesion for each patient;
- Primary efficacy objective: change from baseline to 8 weeks after cryoablation in worst pain in the last 24 hours as measured by the BPI-SF scale;
- Complications were monitored for 30 days post procedure;
- Hospital stay: median of 26.6 hours (range 19.4 – 45.8 hours).
Patient and tumour characteristics
| Characteristics | Participants (n = 66) |
| Primary cancer diagnosis | |
| Lung cancer | 19 (28.8%) |
| Breast cancer | 9 (13.6%) |
| Other* | 13 (19.7%) |
| Kidney cancer | 8 (12.1%) |
| Colon cancer | 5 (7.6%) |
| Prostate cancer | 4 (6.1%) |
| Sarcoma | 3 (4.5%) |
| Thyroid cancer | 3 (4.5%) |
| Stomach cancer | 2 (3.0%) |
| Prior cancer treatments | |
| No prior cancer treatment | 7 (10.6%) |
| Prior systemic chemotherapy | 50 (75.8%) |
| Prior radiation for bone metastases (index tumour) | 28 (42.4%) |
| Prior hormonal treatment (not restricted to bone metastases) | 12 (18.2%) |
| Prior targeted molecular therapy for bone metastases | 9 (13.6%) |
| Prior ablation therapy for non-index bone tumour(s) | 6 (9.1%) |
| Prior bisphosphonate treatment for bone metastases | 5 (7.6%) |
| Index tumour location | |
| Rib | 16 (24.2%) |
| Illium | 13 (19.7%) |
| Pelvis | 8 (12.1%) |
| Other | 6 (9.1%) |
| Chest wall (rib with non-rib soft tissue) | 4 (6.1%) |
| Acetabulum | 3 (4.5%) |
| Sacrum | 3 (4.5%) |
| Scapula | 3 (4.5%) |
| Ischium | 3 (4.5%) |
| Sternum | 3 (4.5%) |
| Humerus | 2 (3.0%) |
| Femur | 1 (1.5%) |
| Vertebra | 1 (1.5%) |
| Index tumour composition | |
| Predominantly lytic (osteolytic) disease | 48 (72.7%) |
| Mixed | 11 (16.7%) |
| Predominantly sclerotic (osteoblastic) disease | 6. (9.1%) |
Method
Study sites used a standard cryoablation protocol including two freeze-thaw cycles.
If the operator felt that another cycle would improve coverage and local control, it was performed in select cases.
Participants were not denied needed therapy for pain; however, those who received additional targeted therapies to the index tumour were excluded. Pain improvement was evaluated using a single item from the BPI-SF questionnaire completed by participants which asked participants to evaluate the level of the “worst pain in the last 24 hours.”
The primary effectiveness endpoint was the change from pre-treatment baseline rating of worst pain in the last 24 hours to post treatment week 8 rating. A clinically meaningful change for this item was defined as a reduction of at least 2 points.
Results
Sixty-six patients were included in the intention-to-treat (ITT) population in which cryoablation was attempted.
Baseline patient and tumour characteristics are shown in Table 1 with a mean patient age of 60.8 years and predominant primary cancers of lung (28/8%), breast (13.6%), and kidney (12.1%) cancer of targeted bone metastases.
The majority of patients had received previous systemic therapies (75.8%) with 42.4% of patients previously receiving radiation therapy, and only 10.6% of patients with no prior cancer treatments.
Change in worst pain in last 24 hours in 24 weeks
Figure 1
*The primary efficacy endpoint of mean change in worst pain in last 24 hours from baseline to week 8 was -2.61 ± 0.43 points (93% CI: - 3.45, -1.78) as shown in Figure 1. Clinically meaningful changes from baseline were observed at all time points after week 8.
Change in quality of life through 24 weeks
Figure 2
*Quality of life consistently improved over 6 months (Fig. 2). The overall treatment effect was rated “better than at the last visit” by 60.9% (39 of 64) and 30% (11 of 37) of participants at weeks 1 and 24, respectively; treatment effect was rated “worse than at the last visit” by 13% (8 of 64) and 11% (4 of 37) participants at weeks 1 and 24, respectively.
Conclusions
- The mean pain scores improved by 2 points at 1 weeks and reached meaningful clinically relevant levels after 8 weeks and scores continued to improve throughout follow-up;
- 92% (59 of 64) patients achieved pain palliation;
- Opioid doses were stabilised, and functional status was maintained over 6 months;
- Quality of life improved over the course of the study period.
Overall, the data shows a rapid and durable pain relief along with a decrease in MEDD* and a corresponding increase in the quality of life for patients with bone metastases.
Cryoablation offered an alternative to opioids for pain control.
*MEDD = Morphine Equivalent Daily Dose
Most participants achieved their maximum palliation by
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