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Palliative radiotherapy in the spine
An estimated 40% of cancer patients are diagnosed with spinal bone metastases (SBM), which can result in significant morbidity including pain, neurologic compromise, fracture, and spinal cord compression. Metastatic spinal cord compression (MSCC) develops in approximately 5% of cancer patients , ; however, the incidence varies with tumor histology and the most common primary histologies are lung cancer, prostate cancer, and multiple myeloma. For patients in their final year of life, those with MSCC are hospitalized twice as long as patients without. The management of SBM and MSCC depends on the clinical situation and may involve observation for simple asymptomatic metastases, radiation alone or surgical intervention followed by postoperative radiotherapy.
Indications for palliative radiotherapy
Palliative radiotherapy for metastatic spinal disease is delivered for a variety of indications, including painful bone metastases, upfront or postoperative for metastatic impending or established spinal cord compression, and retreatment of recurrent/persistent pain. The goals of treatment may include pain relief, preservation and/or restoration of neurologic function and ambulation, local tumor control and maintenance and/or improvement of quality of life (QoL). Palliative spine radiotherapy is most commonly delivered using conventional 3D-conformal field-based approaches, such as an opposed pair of anterior and posterior fields or a direct posterior field. For select cases, a more conformal technique using intensity-modulated radiotherapy (IMRT) may be preferred if additional sparing of nearby organs at risk (OARs) is desired and the treatment urgency allows sufficient time for planning. Collectively these techniques are considered conventional external beam radiotherapy (cEBRT), and typical dose fractionation schedules include 8 Gy/1, 20 Gy/5, 24 Gy/6, and 30 Gy/10. More recently, the usage of stereotactic body radiotherapy (SBRT) for palliative spine treatments has been increasing with an international survey indicating that 68% of respondents deliver spine SBRT. Key features of SBRT include the delivery of high doses in few fractions, the use of simulation MR imaging for target and OAR delineation, increased dose heterogeneity (i.e., intra-target hotspots of 120% to 130% of the prescription dose), image-guided treatment delivery, and treatment precision within a few millimeters of accuracy. , The rapid dose fall-off achievable with SBRT allows for the delivery of ablative doses to tumor while respecting spinal cord dose constraints ( Fig. 22.1 ), making it ideal for spine radiotherapy when indicated. Common spine SBRT dose fractionation schedules include 18 to 24 Gy/1, 24 to 28 Gy/2, 24 to 30 Gy/3, and 30 to 40 Gy/5 ( Table 22.1 ).
TABLE 22.1
Summary of Spine SBRT Dose Fractionations in the Published Literature With Local Control and Vertebral Compression Fracture (VCF) Rates
| Total Dose (Gy) | Number of Fractions | BED (alpha-beta 10) (Gy) | VCF risk |
|---|---|---|---|
| 18–24 | 1 | 50.4 | 39% (median 13 months) |
| 24 | 1 | 81.6 | 27.8% (6 months) |
| 36% (median 25.7 months) | |||
| 24 | 2 | 52.8 | 11% (6 months) |
| 8.5% (1 year) | |||
| 13.8% (2 years) | |||
| 24–30 | 3 | 43.2–60 | Limited data |
| 20.8% (median 13.6 months) | |||
| 5% (reirradiation) | |||
| 30–40 | 5 | 48–72 | Limited data |
| 20.8% (median 13.6 months) | |||
| 9.8% (reirradiation) |
BED , Biological effective dose; SBRT , stereotactic body radiotherapy.
Common histologies
Certain tumor histologies have a predilection for developing bone metastases. In a large cohort of 1880 patients with bone metastases (45% of whom had spinal metastases), the most common histologies were lung cancer (25%), prostate cancer (20%), and breast cancer (20%). For the subgroup of patients who developed MSCC, the distribution of histologies was similar. A review of the Nationwide Inpatient Sample (NIS) identified 75,876 patient hospitalizations due to MSCC. Overall, the most common histologies were lung cancer (25%), prostate cancer (16%), multiple myeloma (11%), non-Hodgkin lymphoma (NHL) (8%), and breast cancer (7%).
When selecting a radiotherapy approach, tumor histology should be considered given the relative differences in radiosensitivity between tumor types. Renal cell carcinoma (RCC), melanoma, sarcoma, gastrointestinal cancers, and thyroid cancers are generally regarded to be more radioresistant and less likely to respond to cEBRT dose schedules. In these cases, there is evidence that SBRT can overcome tumor radioresistance and provide excellent and durable local control rates. For example, in a retrospective series of 811 spinal lesions treated with single-fraction SBRT, tumor histology (radioresistant vs. radiosensitive) was not predictive of local control, suggesting that the higher doses achieved with SBRT may overcome the radioresistant nature of specific histologies ( Fig. 22.2 ). Furthermore, in another cohort of 279 spinal metastases treated with an SBRT dose of 24 Gy/2, the 1-year and 2-year local control (LC) rates for radioresistant histologies was 91.5% and 85.3%, respectively.
Tools for prognostication
Patient assessment tools
Several assessment tools have been developed to help guide practitioners in the management of patients with spinal metastases. The American Spinal Injury Association (ASIA) impairment grade is a validated metric that characterizes neurologic deficits and is predictive of functional outcomes. The scale assigns a letter grade for varying degrees of neurologic dysfunction and ranges from grade A (a complete loss of sensory and motor function) to grade E (normal function). This tool is useful in providing a global assessment of a patient’s neurological status and is important in standardizing reporting on clinical trials and data collection for registries. Grade E refers to normal neurologic function in a patient who has recovered function after previous neurologic deficit. The ASIA grade is not applicable to patients who are neurologically intact from the onset.
Spinal instability is an independent indication for surgical intervention, thus comprehensive evaluation of spinal stability is critical. The Spine Oncology Study Group (SOSG), an international group of 30 spine oncology experts, underwent a modified Delphi approach to develop the Spinal Instability Neoplastic Score (SINS) scale which has become the standard for assessing spine stability. The final scale comprises six components: spine location, mechanical pain, bone lesion quality, vertebral body collapse, spinal alignment, and involvement of posterolateral spinal elements ( Table 22.2 ). The SINS score is determined by summing the individual scores for each component. Factors that were associated with instability included junctional spine locations, the presence of mechanical pain, lytic lesions, the presence of subluxation or translation of spine segments, involvement of bilateral posterior elements and greater than 50% vertebral body collapse. Among these factors, the presence of subluxation or translation on assessment of spinal alignment has the greatest impact on spinal instability. A total score of 0 to 6 is considered “stable”, while scores of 7 to 12 and 13 to 18 refer to “indeterminate and possible impending instability” and “unstable”, respectively. It is recommended that any patient with a SINS score of ≥7 be referred for surgical consultation.
TABLE 22.2
Spine Instability Neoplastic Score (SINS) Classification System
Data from Fisher CG, DiPaola CP, Ryken TC, et al. A novel classification system for spinal instability in neoplastic disease. Spine (Phila Pa 1976) . 2010;35(22):E1221–E1229.
| SINS Component | Score | |
|---|---|---|
| LOCATION | ||
| Junctional spine (occiput-C2, C7–T2, T11–L1, L5–S1) | 3 | |
| Mobile spine (C3–C6, L2–L4) | 2 | |
| Semi-rigid spine (T3–T10) | 1 | |
| Rigid spine (S2–S5) | 0 | |
| PAIN AT TARGET LESION | ||
| Mechanical pain | 3 | |
| Occasional, non-mechanical pain | 1 | |
| Pain-free | 0 | |
| TARGET LESION QUALITY | ||
| Osteolytic | 2 | |
| Mixed | 1 | |
| Osteoblastic | 0 | |
| RADIOGRAPHIC SPINAL ALIGNMENT | ||
| Subluxation/Translation | 4 | |
| Kyphosis/Scoliosis | 2 | |
| Normal alignment | 0 | |
| VERTEBRAL BODY COMPRESSION FRACTURE | ||
| >50% Compression | 3 | |
| <50% Compression | 2 | |
| No compression but >50% vertebral body involved | 1 | |
| None of the above | 0 | |
| FRACTURE OR TUMOR INVOLVEMENT OF POSTEROLATERAL SPINAL ELEMENTS | ||
| Bilateral | 3 | |
| Unilateral | 1 | |
| None of the above | 0 | |
| Total Score | Spinal Stability | Recommendation |
| 0–6 | Stable | No surgical stabilization |
| 7–12 | Indeterminate | Assessment from spine surgeon |
| 13–18 | Unstable | Surgical stabilization |
In patients with MSCC, the degree of spinal cord compression can be described using the epidural spinal cord compression (ESCC) grading system, which has been validated by the SOSG. Using this system, six grades may be assigned ( Fig. 22.3 ). Grade 0 indicates bone-only disease. Grade 1 indicates tumor extension into the epidural space without spinal cord deformation. Grade 1 is further divided into 1a (epidural abutment but no deformation of thecal sac), 1b (deformation of the thecal sac without spinal cord abutment), and 1c (spinal cord abutment without spinal cord deformation). Grades 2 to 3 are considered high grade compression with deformation of the spinal cord present in both cases. With grade 2, cerebrospinal fluid (CSF) remains visible on axial imaging, while CSF is obliterated in grade 3 compression.
Prognostic scoring systems for survival
While precise survival predictions are not possible for patients with spinal metastases, a well-informed estimation of prognosis is critical for selecting treatments that are appropriate for patients. A number of scoring systems examining survival or functional outcomes have been developed for patients with bone metastases (including the spine) and spinal cord compression.
In 2019, Rades et al. developed a scoring system to estimate survival in a patient cohort receiving radiotherapy for painful bone metastases. The model was based on a retrospective analysis of 445 patients treated in Germany between 2009 and 2017 for symptomatic bone metastases from a solid tumor without spinal cord compression. On multivariate analysis performed using the Cox proportional hazards model, there was a statistically significant association between survival and the following factors: Karnofsky Performance Status (KPS) (hazard ratio [HR] 1.91, P < .001) and primary tumor histology (HR 1.12, P < .001). There was borderline statistical significance between survival and age (HR 1.14; P = .054). The scoring system was developed using these three prognostic variables. Favorable factors included age ≤60, KPS 80 to 100 and patients with breast cancer, prostate cancer or RCC. Three prognostic groups were developed based on total scores, with a higher score associated with better survival. Patients with 8 to 9 points, 10 to 14 points and 15 to 17 points had associated 12-month survival rates of 9%, 38% and 72%, respectively ( Table 22.3 ).
TABLE 22.3
Rades et al. Scoring System for Predicting Survival After Radiotherapy for Bone Metastases
Data from Rades D, Haus R, Schild SE, et al.. Prognostic factors and a new scoring system for survival of patients irradiated for bone metastases. BMC Cancer . 2019;19(1):1–8.
| Prognostic Factor | Score | |
|---|---|---|
| AGE | ||
| ≤60 years | 5 | |
| 61–70 years | 4 | |
| >70 years | 4 | |
| KARNOFSKY PERFORMANCE STATUS | ||
| 80–100 | 6 | |
| ≤70 | 2 | |
| PRIMARY TUMOR HISTOLOGY | ||
| Breast | 6 | |
| Renal cell carcinoma | 6 | |
| Prostate | 5 | |
| Lung | 3 | |
| Colorectal | 3 | |
| Other | 2 | |
| Group | Total Score | 1-Year Overall Survival Rate |
| A | 8–9 | 9% |
| B | 10–14 | 38% |
| C | 15–17 | 72% |
Another prognostic model created by Van der Linden et al. used a subset of 342 patients with spinal metastases from a large Dutch randomized trial comparing patients who received 8 Gy in 1 fraction compared with 24 Gy in 6 fractions. The majority of patients had metastatic disease from breast cancer (42%) or prostate cancer (24%) and the mean KPS was 70. On multivariate analysis, patients with a higher KPS (80 to 100), breast or prostate cancer histology, or an absence of visceral metastases had a statistically significant improvement in survival. These factors comprised the scoring system, which stratified patients into three prognostic groups based on their cumulative score. Scores of 0 to 3 (Group A), 4 to 5 (Group B) and 6 (Group C) corresponded to median survival lengths of 3 months, 9 months and 18.7 months, respectively ( Table 22.4 ).
TABLE 22.4
Van der Linden et al. Scoring System for Predicting Survival After Radiotherapy for Bone Metastases
Data from Van Der Linden YM, Dijkstra SPDS, Vonk EJA, et al. Prediction of survival in patients with metastases in the spinal column: results based on a randomized trial of radiotherapy. Cancer . 2005;103(2):320–328.
| Prognostic Factor | Score | |
|---|---|---|
| KARNOFSKY PERFORMANCE STATUS | ||
| 80–100 | 2 | |
| 50–70 | 1 | |
| 20–40 | 0 | |
| PRIMARY TUMOR HISTOLOGY | ||
| Breast | 3 | |
| Prostate | 2 | |
| Lung | 1 | |
| Other | 0 | |
| PRESENCE OF VISCERAL METASTASES | ||
| No | 1 | |
| Yes | 0 | |
| Group | Total Score | Median Survival |
| A | 0–3 | 3 months |
| B | 4–5 | 9 months |
| C | 6 | 18.7 months |
Rades et al. developed a second scoring system specific to patients with MSCC ( Table 22.5 ). This model, based on a multivariate analysis of 1852 patients, found six factors to be predictive of survival: primary tumor histology, other bone metastases at the time of radiotherapy, visceral metastases at the time of radiotherapy, interval from primary cancer diagnosis to the diagnosis of MSCC, ambulatory status before radiotherapy and the time to develop motor deficits before radiotherapy. Strengths of this system include that it is based on a large patient cohort treated with radiotherapy, that its parameters include measures of patient functional status and that the patients were treated in a more recent time period than other systems. It is worth noting that while the patient cohort was large, patients predominantly had advanced disease with present or impending paralysis. Patients were stratified into five prognostic groups based on their cumulative score. Groups A and B included patients with scores between 20 and 30, which were associated with a 1-year survival less than 10%. Patients in group C had scores between 31 and 35 and a 1-year survival of less than 25%. For groups A to C, short-course radiotherapy (e.g., 8 Gy in 1 fraction or 20 Gy in 5 fractions) was recommended given the poor prognosis. Groups D and E included patients with a total score of 36 to 45 and a 1-year survival of 70% to 89%. For these patients, long-course radiotherapy was recommended (e.g., 30 Gy in 10 fractions). The Rades scoring system has also been adapted to predict for death within 2 months after radiotherapy, which can help select patients most appropriate for best supportive care. Finally, there are published survival scoring systems for patients with MSCC based on individual primary tumor histologies, including breast, gynecological, genitourinary, gastrointestinal, head and neck, lung and hematologic malignancies.
TABLE 22.5
Rades et al. Scoring System for Predicting Survival After Radiotherapy for Metastatic Spinal Cord Compression
Data from Rades D, Dunst J, Schild SE. The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer . 2008;112(1):157–161.
| Prognostic Factor | Score | |
|---|---|---|
| PRIMARY TUMOR HISTOLOGY | ||
| Myeloma/Lymphoma | 9 | |
| Breast | 8 | |
| Prostate | 7 | |
| Other | 4 | |
| Lung | 3 | |
| OTHER BONE METASTASES PRESENT | ||
| No | 7 | |
| Yes | 5 | |
| VISCERAL METASTASES PRESENT | ||
| No | 8 | |
| Yes | 2 | |
| TIME FROM PRIMARY DIAGNOSIS TO MSCC | ||
| >15 months | 7 | |
| < 15 months | 4 | |
| AMBULATORY STATUS BEFORE RADIOTHERAPY | ||
| Ambulatory | 7 | |
| Non-ambulatory | 3 | |
| TIME TO DEVELOP MOTOR DEFICITS PRIOR TO RADIOTHERAPY | ||
| >14 days | 8 | |
| 8–14 days | 6 | |
| 1–7 days | 3 | |
| Group | Total Score | 1-Year Survival |
| A | 20–25 | 0% |
| B | 26–30 | 6% |
| C | 31–35 | 23% |
| D | 36–40 | 70% |
| E | 41–45 | 89% |
MSCC, Metastatic spinal cord compression.
Prognostic scoring systems for ambulation
Scoring systems that predict for ambulatory status after treatment are also available. One model was based on a multivariate analysis of 2096 patients treated with cEBRT for MSCC. Five prognostic factors were included: primary tumor histology, interval from primary tumor diagnosis, visceral metastases at the time of cEBRT, motor function before cEBRT and time from development of motor deficits to cEBRT. Patients were stratified into five prognostic groups (A to E) based on cumulative scores. Postradiotherapy ambulatory rates for group A (≤28 points), group B (29 to 31 points), group C (32 to 34 points), group D (35 to 37 points), and group E (≥38 points) were 6%, 44%, 70%, 86%, and 99%, respectively ( Table 22.6 ).
TABLE 22.6
Rades et al. Prognostic Factors for Ambulatory Status After Radiotherapy for Metastatic Spinal cord Compression
Data from Rades D, Rudat V, Veninga T, et al. A score predicting posttreatment ambulatory status in patients irradiated for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys . 2008;72(3): 905–908.
| Prognostic Factor | Score | |
|---|---|---|
| TIME FROM PRIMARY TUMOR DIAGNOSIS TO MSCC | ||
| >15 months | 8 | |
| ≤15 months | 6 | |
| VISCERAL METASTASES AT THE TIME OF RADIOTHERAPY | ||
| No | 8 | |
| Yes | 5 | |
| MOTOR FUNCTION BEFORE RADIOTHERAPY | ||
| Walking without aids | 10 | |
| Walking with aids | 9 | |
| Not walking | 3 | |
| Paraplegic | 1 | |
| TIME TO DEVELOP DEFICITS PRIOR TO RADIOTHERAPY | ||
| >14 days | 9 | |
| 8–14 days | 7 | |
| 1–7 days | 4 | |
| PRIMARY TUMOR HISTOLOGY | ||
| Myeloma/Lymphoma | 9 | |
| Breast | 8 | |
| Prostate | 7 | |
| Small cell lung cancer | 6 | |
| Renal cell carcinoma | 6 | |
| Colorectal cancer | 6 | |
| Other | 6 | |
| Non-small cell lung cancer | 5 | |
| Primary unknown | 5 | |
| Group | Total Score | Post-radiotherapy Ambulatory Rates |
| A | ≤28 | 6% |
| B | 29–31 | 44% |
| C | 32–34 | 70% |
| D | 35–37 | 86% |
| E | ≥38 | 99% |
MSCC , Metastatic spinal cord compression.
Review of studies
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