Improvements in general health care and oncologic advances have resulted in strongly increasing numbers of geriatric cancer patients [1]. However, due to restrictions in the performance status, prevalent comorbidities or poor treatment tolerance, general therapy guidelines often do not apply to these elderly patients, requiring dedicated trials [2].

Spinal bone metastases (SBM) from solid tumors affect a considerable number of patients and are of particular concern for geriatric patients, as they may more easily result in immobilization and dependence on full-time care [3]. Additionally, relevant comorbidities such as osteoporosis are more prevalent in the elderly and may increase the risk of SBM-related impairments such as pathological fractures [4].

Palliative radiotherapy (RT) constitutes a mainstay in the treatment of SBM and aims at reducing pain and supporting recalcification, resulting in improved bone stability [5, 6]. RT dose and fractionation are commonly adjusted depending on the extent of metastatic disease, comorbidities, performance status, and estimated life expectancy [7, 8, 9, 10, 11, 12, 13]. The influence of palliative RT on the analgesic effects and improvements in neurological deficits have already been subject to previous investigations [9, 10, 12]. However, the benefit of RT for the recalcification and stabilization of initially unstable SBM in geriatric patients is still largely unknown. A deeper understanding of these treatment effects of RT will be relevant to choose appropriate treatment algorithms with regard to treatment time and dose.

Therefore, this retrospective study aimed to assess osteolytic SBM in a large multicenter cohort of elderly patients over 70 years regarding stability, fracture rates before and after RT, survival, and prognostic factors for stability and survival.

The median survival time of the study population after palliative RT of SBM was 5.4 months (95% confidence interval [CI] 4.4–7.2 months). In total, 322 patients presented with a total of 935 osteolytic SBM (range, 1–13 metastases per patient). The baseline characteristics of the study patients are summarized in Table 1.

Survival analysis

For the complete patient cohort, relatively poor survival was evident after palliative RT. Overall survival rates 3, 6 and 12 months after RT amounted to 66% (95% CI 61–72%), 48% (95% CI 43–54%) and 29% (95% CI 24–34%); the median survival following RT was 5.4 months (95% CI 4.4–7.2 months).

To analyze the association of age with overall survival, we stratified the study patients into 3 age groups (i.e., 70–74 years, 75–79 years and ≥80 years) and found a strong tendency towards worse survival after RT for patients ≥80 years, albeit not reaching statistical significance (p = 0.06; Fig. 2). The corresponding median overall survival was 7.6 months (95% CI 4.8–9.0 months) for patients aged 70–74 years, 5.0 months (95% CI 3.6–9.2 months) for patients aged 75–79 years and 4.3 months (95% CI 3.2–6.3 months) for patients aged 80 years or older.

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In comparing overall survival for patients with the 4 most common primary tumor histologies (i.e., breast, renal, colorectal and lung cancer) accounting for 81% of the study population (261/322 patients), we found significantly better survival rates for breast cancer patients and a significantly worse prognosis for lung and colorectal cancer patients (p = 0.003; Fig. 3).

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Using multivariate analyses, KPS was found to be the strongest predictive factor for overall survival after RT (p < 0.001, multivariate Cox regression analysis; Table 6). In patients with KPS <70%, median overall survival was only 1.8 months (95% CI 1.6–2.3 months) compared to 9.1 months (95% CI 7.6–10.5 months) for patients with KPS ≥70% (p < 0.001; Fig. 4). Furthermore, the number of SBM, the application of chemotherapy and a tumor histology from the pooled group of poorly represented entities were significant prognostic factors in the multivariate analysis (Table 6). In patients with only 1 SBM, median overall survival reached 7.4 months (95% CI 5.4–9.2 months) compared to 3.9 months (95% CI 3.3–6.3 months) in those patients with more than 1 SBM (p = 0.029; Fig. 5). Administration of chemotherapy extended median overall survival from 4.9 months (95% CI 3.9–7.2 months) to 5.8 months (95% CI 4.4–8.7 months; p = 0.046).

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Table 6

Analysis of prognostic factors related to overall survival after palliative RT

	Univariate testing			Multivariate testing
Predictor	p-value	HR	CI	p-value	HR	CI
Age	0.197	1.017	0.991–1.043	0.507	1.009	0.982–1.038
Poorly represented cancersa (vs. breast cancer)	0.029	1.529	1.044–2.240	0.016	1.663	1.103–2.509
Colorectal cancer (vs. breast cancer)	0.007	1.858	1.188–2.907	NA	1.548	0.879–2.725
Renal cancer (vs. breast cancer)	0.737	1.071	0.718–1.598	NA	1.116	0.665–1.872
Lung cancer (vs. breast cancer)	0.008	1.576	1.127–2.206	NA	1.602	1.133–2.265
KPS (<70% vs. ≥70%)	<0.001	0.954	0.944–0.964	<0.001	0.953	0.942–0.964
Chemotherapy (yes vs. no)	0.151	1.177	0.943–1.469	0.036	1.295	1.018–1.647
Location (thoracic vs. lumbar spine)	0.523	1.077	0.858–1.351	0.664	1.054	0.832–1.335
Number of SBM (1 vs. >1)	0.004	1.066	1.021–1.112	0.031	1.055	1.006–1.107
Extraskeletal metastases (yes vs. no)	0.276	1.134	0.904–1.423	0.711	0.953	0.740–1.228
Bisphosphonates (yes vs. no)	0.381	0.905	0.724–1.131	0.295	0.834	0.596–1.167
Fractures before RT (yes vs. no)	0.098	1.258	0.958–1.651	0.383	1.138	0.853–1.518

KPS Karnofsky performance score, HR Hazard Ratio, CI Confidence limits of the results for a confidence level of 95%, SBM Spinal bone metastases, RT Radiotherapy, NA not analyzable

^a Included SBM of following tumor entities: Malignant melanoma, adenoid cystic carcinoma (ACC), hepatic cell cancer (HCC), head and neck squamous cell cancer (HNSCC), ovarian cancer, uterine cancer, vulvar cancer, urothelial cancer, prostate cancer

In the univariate analysis, the only further predictive factor associated with a poor overall survival was tumor histology, with lung and colorectal cancer histologies correlating with a reduced survival (Table 6). Patients’ age, the prevalence of additional extraskeletal metastases, the location of SBM, the concurrent administration of bisphosphonates and the presence of pathological fractures prior to RT were not statistically significant predictors of overall survival (Table 6).

While the analgesic effect of RT on bone metastases has already been well investigated, there is a lack of study data concerning the stabilizing effect of RT on unstable osteolytic metastases [12]. In recent years, we and other groups focused on assessment of the remineralization process of osteolytic SBM after RT [16]. As a result, we found substantial differences of recalcification and stabilization rates of initially unstable SBM depending on the histology [5, 6, 15, 17, 18, 19]. Also in this dataset, tumor histology was found strongly associated with differing stabilization rates after palliative RT, and stabilization rates may correspond to individual radiation sensitivities of various tumor cell types, although the exact underlying mechanism regulating radiation-induced recalcification of osteolytic skeletal metastases remains to be elucidated. Recalcification may also depend on the individual tumor micromilieu and the influence of concurrent systemic treatments. In this context, the patients’ age may be an important factor for recalcification of unstable vertebral metastases of various solid tumors. Elderly patients exhibit an increased level of comorbidities that have the potential to influence bone stability and recalcification in the context of bone metastases, among them diabetes mellitus, renal insufficiencies or osteoporosis. Several publications have indicated an influence of bone mineral density and especially osteoporosis on the stability of bone metastases, although no clear evidence is available regarding the stabilization rates following palliative RT in these patients [20, 21]. To the best of our knowledge, no scientific data concerning the stabilization rates have been reported from an explicitly elderly patient cohort, a primary impetus for conducting this retrospective pooled analysis.

Prior to irradiation, 57% of our study patients exhibited unstable SBM in the thoracic or lumbar spinal column. Within 3 and 6 months after palliative RT, significant recalcification and stabilization were observed in up to 40% of the analyzed patients still alive at the time of follow-up; a deterioration of stability was measured in only one patient during the follow-up period. The highest stabilization rates in our study population were found in elderly breast cancer patients, while elderly patients with SBM from lung cancer, colorectal cancer, renal cancer or further poorly represented tumor entities such as malignant melanoma, prostate and urothelial cancers showed minor or negligible recalcification following palliative RT. These findings are largely in line with previous published data reporting histology-dependent recalcification in younger patients [6, 15, 18, 19, 22]. Regarding the observed minor stabilization rates in elderly patients with these histologies, alternate approaches for improving the stability of the metastatic vertebral column may need to be considered. Stereotactic ablative radiotherapy (SBRT) may hold the potential to increase the stabilization rates in unstable SBM, particularly for geriatric patients with a good performance score and SBM from tumor entities with a relatively low chance of bone stability after 6 months. However, evidence remains to be provided regarding the effectiveness of SBRT for the stabilization of vertebral metastases in elderly patients. Also, surgical stabilization options may become more relevant for the respective patients; however surgery may interrupt necessary systemic treatments for a considerable time compared to SBRT. Additionally, perioperative morbidity and mortality is likely increased in affected geriatric patients.

When interpreting the stabilization rates of our study, it is important to consider the histology-dependent differing prognoses of patients with bone metastases, as significant recalcification after RT requires at least 3 to 6 months. Thus, the relevance of stabilization of unstable SBM is higher for patients with an average survival exceeding 6 months. In our dataset, patients aged 80 years or older showed a strong trend towards reduced survival rates compared to elderly patients below 80 years (i.e., 39% vs. 51% at 6 months after RT; p = 0.06). This may not only be due to the patients’ oncologic outcome, but may also reflect the influence of other age-prevalent causes such as cardiovascular diseases. As reported by many studies before, we also found that the performance status was a strong prognostic factor for predicting the residual life expectancy after palliative RT of SBM in elderly patients [23, 24, 25, 26, 27]. Here, patients with a KPS below 70% had an extremely poor overall survival of less than 2 months compared to 9 months for those patients with a KPS of at least 70%. Based on these results, single fraction RT should be the preferred treatment option for elderly patients with a poor general condition and advanced tumor disease, as it has shown equivalent pain control rates compared to more protracted RT schedules [12, 28].

Moreover, our analysis showed that patients with a solitary/singular SBM exhibited an almost doubled median overall survival as compared to patients with 2 or more SBM (7.4 vs. 3.9 months; p = 0.031), while the additional survival benefit by administration of chemotherapy was less than 1 month in these elderly patients (5.8 vs. 4.9 months at the median; p = 0.036). The effect of oligometastatic cancers and consecutive ablative treatments in elderly metastatic patients has not yet been elucidated and will likely be subject to further research in the future.

Our study has some limitations, especially the retrospective character of this patient cohort. For instance, comorbidities (including age- and cancer therapy-related osteoporosis), the patients’ smoking status, medications and lifestyle factors such as physical exercises could not be routinely assessed in our elderly patient cohort, although it is conceivable that these factors might have an impact on the stabilization and fracture rates after palliative RT as well as overall survival. Second, the used Taneichi score is restricted to score the stability of osteolytic thoracic and lumbar metastases. As a consequence, prostate cancer patients are considerably underrepresented in this elderly cohort, as the majority of SBM from prostate cancer has an osteoplastic phenotype. Since the majority of SBM spread to the thoracic and lumbar spine, we believe that the non-consideration of the cervical and sacral spine represents only a minor limitation. A third limitation is due to the long inclusion time period, many patients in our study were treated before modern systemic therapies such as targeted therapies and checkpoint inhibitors became routinely used in the clinic. While these agents substantially contributed to improved survival times in many metastatic tumor diseases in recent years, their routine use in geriatric patients remains subject to some debate [29, 30, 31, 32, 33]. On the other hand, the stabilization effect of palliative radiotherapy in unstable SBM might become better than reported in this study with improved overall survival rates. Nevertheless, results from this large multicenter cohort of patients with an advanced age help to generate hypotheses that may direct further assessment of palliative radiation effects through prospective clinical trials in elderly patients, and these trials are urgently required to address the palliative needs of an increasingly aging population.

The treatment of elderly patients with unstable SBM is complex and requires a multidisciplinary approach whereby palliative RT has a pivotal role in the treatment concept. Histology and performance status seem to dominate prognosis of elderly patients with SBM and should be considered to determine radiation fractionation in order to reduce hospitalization times in the remaining lifespan.