Figure 1
Schematic illustration of the DP model. Contrast agent (CA) concentration within the vessel decreases with position (x) along the vessel length (L), producing concentration gradients between the arterial (x = 0) and venous (x = L) capillary ends. During the CA passage, a portion of the CA molecules diffuses between the plasma and extracellular, extravascular space (EES) at a controlled permeability surface area product (PS) rate, so that the plasma, Cp(x, t), and EES, Ce(x, t), concentrations show both spatial and temporal dependence.
Table 1
Inclusion and exclusion criteria
| Inclusion criteria | Exclusion criteria | ||
|---|---|---|---|
| 1. | Age ≥ 21 years | 1. | Metastatic haematological and germ cell neoplasms |
| 2. | Proven metastatic disease | 2. | Inability to undergo MRI or receive gadolinium contrast |
| 3. | Life expectancy > 3 months | 3. | Prior radiotherapy to region of interest |
| 4. | Eastern Cooperative Oncology group (ECOG) 0–2 | 4. | Recent immediate surgery surgical to affected intervention spinal levels, or patients requiring |
| 5. | ≤ 3 contiguous vertebral body segments, including para-spinal disease | 5. | Spinal instability score (SINS) > 12 |
| 6. | Able to lie supine for ≥ 60 minutes | 6. | Symptomatic cord compression (Bilksy grade 2 or 3), or worsening neurological deficits |
Table 2
Patient characteristics
| Dose (Gy) | Fractions | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 69 | M | RCC | C1 | Lung | Non-opioid | No | No | Yes | 1 | 8 | 6 | Radioresistant histology, pain control | 24 | 3 |
| 2 | 60 | M | RCC | S1 | Nil | Nil | No | No | No | 0 | 3 | 3 | Oligometatasis | 27 | 3 |
| 3 | 60 | M | NSCLC-EGFR - | T5 | Brain, lung bone. | Nil | Yes | No | No | 1 | 5 | 6 | Oligometastasis | 24 | 3 |
| 4 | 62 | F | NSCLC-EGFR - | C5 | Brain, bone nodal, | Opioid | No | No | No | 1 | 8 | 7 | Oligometastasis, pain control | 24 | 2 |
| 5 | 75 | M | adenocarcinoma Prostate | T1 | Bone | Nil | No | No | No | 1 | 6 | 5 | Oligometastasis | 24 | 3 |
| 6 | 62 | M | adenocarcinoma Colon | L1 | LN, lung | Nil | Yes | No | No | 1 | 3 | 9 | Oligometastasis | 27 | 3 |
| 7a | 52 | M | RCC | L1 | Bone | Opioid | No | No | Yes | 1 | 7 | 7 | Radioresistant histology, pain control | 27* | 3* |
| 7b | 52 | M | RCC | L2 | Bone | Opioid | No | No | Yes | 1 | 7 | 7 | Radioresistant histology, pain control | 27* | 3* |
| 8a | 69 | F | NSCLC-EGFR + | T1 | Brain, lung bone. | Non-Opioid | No | No | Yes | 1 | 3 | 5 | Oligometastasis | 24 | 3 |
| 8b | 69 | F | NSCLC-EGFR + | T10 | Brain, lung bone. | Non-Opioid | No | No | Yes | 1 | 3 | 4 | Oligometastasis | 27* | 3* |
| 8c | 69 | F | NSCLC-EGFR + | T12 | Brain, lung bone. | Non-Opioid | No | No | Yes | 1 | 3 | 6 | Oligometastasis | 27 | 3 |
| 9 | 51 | F | ductal Breast carcinoma Invasive | T4 | Nil | Nil | Yes | No | No | 1 | 0 | 2 | Oligometastasis | 27 | 3 |
| 10 | 72 | M | adenocarcinoma Prostate | L3 | Nil | Nil | No | No | No | 2 | 3 | 2 | Oligometastasis | 24 | 2 |
[i] ECOG = Eastern Cooperative Oncology Group; F = female; LN = lymph nodes; M = male; Nil = nihil; NSCLC-EGFR - = non-small cell lung cancer without epidermal growth factor receptor mutation; NSCLC-EGFR + = non-small cell lung cancer with epidermal growth factor receptor mutation; RCC = renal cell carcinoma; SINS = spinal instability neoplastic score; VAS = visual analogue score
*Patient only completed 2 out of 3 fractions
Figure 2
Normalized values of dynamic contrast enhanced (DCE) parameters (A) time-dependent leakage (Ktrans); (B) permeability surface product (PS); (C) fractional plasma volume (Vp); (D) extracellular volume (Ve); and (E) perfusion.
Figure 3
(A) Representative images for Patient 7a showing at L1 with reduction in dynamic contrast enhanced (DCE) parameters [i] time-dependent leakage (Ktrans); [ii] permeability surface product (PS); [iii] fractional plasma volume (Vp); [iv] extracellular volume (Ve); and [v] perfusion (F) across the 3 time points.
Figure 3
(B) [i] Metastatic deposit in L1 vertebral body (yellow arrow), as shown on T1 Axial MR (with gadolinium contrast); [ii] stereotactic body radiotherapy (SBRT) planning image (CT, MRI fused). SBRT 27 Gy in 3 fractions, delivered using volumetric modulated arc therapy. Clinical target volume (CTV) (blue outline), planning organ at risk volume (PRV)_cord (red outline), 95% isodose (orange colourwash).
Figure 4
Correlative plasma markers (A) acid sphingomyelinase (ASM); and (B) sphingosine-1-phosphate (S1P).
Table 3
Clinical outcomes
| Patient ID | (Change Post-SBRT from VAS pre- SBRT baseline) | Acute toxicity | Late toxicity | Response at 3 months assessment (MD Anderson criteria) | Follow-up duration (months) | Local recurrence at last follow-up | Status of patient at last follow-up |
|---|---|---|---|---|---|---|---|
| 1 | 0 (-8) | G1 esophagitis | Nil | PR | 39 | No | Dead |
| 2 | 0 (-3) | Nil | Nil | PR | 54 | Yes | Alive |
| 3 | 0 (-5) | Nil | G1 compression fracture | PR | 50 | No | Alive |
| 4 | 0 (-8) | G1 esophagitis | Nil | SD | 15 | No | Dead |
| 5 | 3 (-3) | G1 esophagitis | Nil | PR | 22 | No | Dead |
| 6 | 0 (-3) | Nil | Nil | SD | 13 | No | Dead |
| 7a | 2 (-5) | Nil | G1 compression fracture | PR | 42 | No | Alive |
| 7b | 2 (-5) | Nil | Nil | PR | 42 | No | Alive |
| 8a | - | Nil | N/A | - | N/A | N/A | Dead |
| 8b | - | Nil | N/A | - | N/A | N/A | Dead |
| 8c | - | Nil | N/A | - | N/A | N/A | Dead |
| 9 | 0 | Nil | G3 compression fracture | SD | 37 | No | Alive |
| 10 | 0 (-3) | Nil | Nil | PR | 22 | No | Alive |