Journal of Clinical Neuroscience xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database Pamela S. Jones a, Manish K. Aghi b, Alona Muzikansky c, Helen A. Shih d, Fred G. Barker II a, William T. Curry Jr. a,⇑ a
Department of Neurosurgery, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 9E-9026, Boston, MA 02114, USA Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, USA Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA d Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA b c
a r t i c l e
i n f o
Article history: Received 3 February 2014 Accepted 11 February 2014 Available online xxxx Keywords: Chondrosarcoma Population study Radiation therapy Skull base tumors
a b s t r a c t This study aims to demonstrate survival rates and treatment patterns among patients with chondrosarcomas of the skull base using a large population database. Patients with skull base chondrosarcomas between 1973 and 2009 were identified from the USA Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier survival analysis was used to examine the effect of surgery and radiation on overall survival. We identified 226 patients with skull base chondrosarcomas. Median follow-up was 5.4 years. Median overall survival was 22 years, and 10 year survival was 68.2%. Most patients underwent surgery (92.5%). Few received radiation after diagnosis (38.1%). Ten year survival for all patients treated with surgery was significantly increased compared to those without surgery (69.3% versus 53.9%, p = 0.02). There was a significant difference in survival amongst treatment groups (p = 0.02), with median overall survival not yet reached for patients who received surgery and radiation (median follow-up 5.3 years), compared to 22 years for non-irradiated surgical patients. Surgery predicted better overall survival by univariate analysis (hazard ratio [HR] 0.420, p = 0.03). Female sex (HR 0.470, p = 0.011), younger age at diagnosis (HR 1.046, p < 0.0001), and later year of diagnosis (HR 0.949, p = 0.0006) were prognostic of improved survival in a multivariate model. In subgroup analysis of patients with documented tumor size, smaller tumor size (HR 1.054, p = 0.0003) and younger age (HR 1.021, p = 0.0067) predicted improved survival. This population based study further reaffirms the role of surgery as an effective treatment for skull base chondrosarcoma as previously reported in small case series. Adjuvant radiation may also confer survival benefit. Optimal treatment strategy has yet to be defined in the literature. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction Chondrosarcomas are rare tumors, and account for only 6% of all tumors occurring in the skull base [1]. They often arise from the lateral aspects of the skull base that house cartilage, including the temporo-occipital synchondrosis, the spheno-occiput, and the sphenoethmoid complex [2]. Because of this, they typically involve the cavernous sinus, the petrous bone, the sphenoid bone, and the clivus [3]. While en bloc or gross total resection of chondrosarcomas remains the therapeutic ideal, the proximity of skull base tumors to critical neurovascular structures and possible bony invasion often limits extent of safe surgical resection [4]. Therefore, ⇑ Corresponding author. Tel.: +1 617 726 3779; fax: +1 617 726 3365. E-mail address: [email protected] (W.T. Curry Jr.).
treatment may also include the use of adjuvant radiation for patients with unresectable, subtotally resected, or even gross totally resected tumors to limit tumor growth and recurrence. While the use of adjuvant postoperative radiotherapy, particularly proton beam radiotherapy, has been shown in single institution retrospective series to prolong the survival of patients with skull base chondrosarcomas, there have been no prospective or large population studies analyzing the outcomes of adjuvant radiotherapy specifically for these tumors to our knowledge [5,6]. Given the overall low incidence of this disease, single institution series are often subject to selection biases associated with referral and treatment patterns and contain too few patients to provide definitive understanding of the prognoses and role of radiotherapy in treating these diseases. To clarify the epidemiologic patterns, treatment, and prognosis of skull base chondrosarcoma in the general USA population, we evaluated patients reported to the
http://dx.doi.org/10.1016/j.jocn.2014.02.005 0967-5868/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Jones PS et al. Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.02.005
2
P.S. Jones et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
population based registries within the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2009. We paid particular attention to outcomes and trends in radiation utilization.
(p < 0.05) were included in the multivariate model. Treatment strategies were compared using chi-squared analysis. Calculations were performed using SAS version 9.3 (SAS Institute, Cary, NC, USA).
2. Methods 3. Results 2.1. The SEER program 3.1. Demographics The SEER registry, a database maintained by the USA National Cancer Institute, collects incidence and survival data from population based cancer registries. Data on chondrosarcoma patients diagnosed between 1973 and 2009 were available from 18 population based cancer registries across the USA that together represent approximately 25% of the USA population. The 18 registries included nine entire states and nine metropolitan regions. These registry populations are comparable to the overall USA population on a variety of socioeconomic indices, including poverty indices, high school graduation rate, percentage in rural areas, and percentage foreign-born. The database contains information on patient demographics, primary cancer site, histology, methods of diagnostic confirmation, treatment regimens including surgery and radiation therapy, and year of death. Institutional Review Board approval was not required for this study, as the SEER database is free of any sensitive patient information or identifiers. An overview of the SEER database is available at http://seer.cancer.gov/about/.
Between 1973 and 2009, 226 patients were diagnosed with skull base chondrosarcoma. The median age at diagnosis was 43 years, with age range of 1 to 82, and a fairly equivalent sex distribution (50.9% female). A slightly greater proportion of patients (123 patients, 54.4%) were diagnosed before the median diagnosis year of 2002. Cases occurred across 16 registries, of which nine were considered low-volume (66 patients) and seven were considered high-volume (160 patients). The results are summarized in Table 1. 3.2. Tumor characteristics Information regarding tumor size was available in 111 of 226 patients. The mean diameter was 3.7 cm (range 1.0 to 10.7 cm). Information regarding histologic subtype of chondrosarcoma was not available.
2.2. Chondrosarcoma definition
3.3. Treatment
We compiled chondrosarcoma patients diagnosed between 1973 and 2009. Patients were identified through the World Health Organization’s International Classification of Diseases for Oncology, Version 3 (ICD-O-3) morphology code for chondrosarcoma (9220–9239). Primary sites of disease presentation were compiled according to ICD-O-3 topography codes and were limited to skull and face bones (410); meninges (700); any structure in the brain (710–9, 751, 753); connective and soft tissue of head, face and neck (490); or any head structure (760). We restricted our analysis to patients with histologic confirmation of chondrosarcoma.
Most patients (209 of 226, 92.5%) underwent some type of surgical resection beyond biopsy. The SEER data only specified whether surgery was performed, and did not reliably specify extent of skull base tumor resection. Ultimately, 128 patients were treated with surgery alone (56.6%), 81 patients were treated with surgery and radiation (35.8%), and five patients treated with radiation alone (2.2%). Twelve patients received no treatment (5.3%). Radiation utilization did not increase over time (chi-squared analysis, p = 0.9), and there were no significant differences in the rates of radiation use among small and large registries (p = 0.23).
2.3. Treatment Treatment types were limited to surgery and radiation. The SEER surgery code of 0 was used to indicate that surgery was performed. For the purpose of our analysis, all surgical cases were considered to include some type of tumor resection. All other codes were considered cases where only a diagnostic biopsy had been performed. Adequate information on extent of resection was not available from the database. The SEER radiation codes 0, 6, 7, 8, 9 represented no radiation treatment. We sub-categorized registries according to number of skull base patients in order to assess for potential volume-outcome effect. This is an effect whereby better outcomes are observed at treatment centers with higher volume. We looked at numbers of both skull base chordomas (ICD-O-3 code 9370–9373) and chondrosarcomas treated by each registry to assess for volume of skull base cases from 1973 to 2009. A registry was considered to contain a high-volume treatment center if it contained 40 or more histologically-confirmed skull base chordomas and chondrosarcomas over the study period. 2.4. Statistical analysis The primary outcome of interest was overall survival. Survival analysis was performed using Kaplan–Meier product limit estimators and Cox univariate and multivariate proportional hazards models. Predictors of overall survival in univariate analysis
Table 1 Characteristics of 226 patients with chondrosarcoma tumors of the skull base registered in the SEER database (1973–2009) Patient characteristics Patients, n Mean age, years (± SD) Median age, years Females
226 44.3 (± 17.7) 43 115 (50.9)
Race White African American Asian Unknown
192 (85.0) 15 (6.6) 16 (7.1) 3 (1.3)
Registry Low volume (2002
2002 median year (1999 mean) 123 (54.4) 103 (45.6)
Surgical data available No resection Resection
17 (7.5) 209 (92.5)
Radiation therapy Median survival, years (months) 5 year survival, % 10 year survival, %
86 (38.1) 22 (264) 86.9 68.2
Data presented as number of patients (%) unless otherwise indicated.
Please cite this article in press as: Jones PS et al. Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.02.005
P.S. Jones et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
4. Outcomes 4.1. All patients Median follow-up time was 5.4 years (65 months). The 5 and 10 year overall survival rate for all patients by Kaplan–Meier analysis were 86.9% and 68.2%, respectively, and median overall survival was 22 years (264 months). The Wilcoxon test demonstrated significant survival differences between the four treatment groups (p = 0.02). Median overall survival was 264 months for patients treated with surgery only, 42 months for radiation only, and 162 months for no treatment. The longest survival was for patients treated with surgery and adjuvant radiation. This group’s median survival was not reached at time of last data collection, and median follow-up time for this group was 5.3 years (63 months). Ten year survival for all patients treated with surgery was significantly increased compared to those without surgery, other than biopsy (69.3% versus 53.9%, p = 0.02). Figure 1 shows that, by logrank comparison, there was a slight trend towards improved 10 year survival with use of adjuvant radiation compared to patients treated with surgery alone (71.9% versus 68.2% 10 year survival, p = 0.32). By univariate analysis, factors predicting better overall survival included patients who underwent surgical resection (hazard ratio [HR] 0.420 95%, p = 0.0247), were female (HR 0.414, p = 0.0023), had younger age at diagnosis (HR 1.044, p < 0.0001), and had later year of diagnosis (HR 0.959, p = 0.0037) (Table 2). In a multivariate model, female sex (HR 0.47, p = 0.01), younger age (HR 1.05, p < 0.001), and more recent year of diagnosis (HR 0.95, p = 0.0006) were significantly associated with improved survival (Table 3). 4.2. Tumor size subgroup We separately analyzed 111 patients with a tumor size recorded at the time of diagnosis (median age was 43 years [range 6 to 82]). Table 4 shows the breakdown of mean tumor size 100 90 80 70 60 50 40 30 20 10 0 0
50
100
150
200
250
300
350
400
450
Fig. 1. Kaplan–Meier survival plot for patients with skull base chondrosarcomas treated with surgery (dashed line) versus surgery and radiation (solid line) (p = 0.32).
3
according to the four different treatment strategies. The largest mean tumor size, 3.9 cm, was that of the patient group who received surgery only; however, there was no statistical significance to this or the difference between mean sizes of tumors for any other treatment group (p = 0.36). The 10 year overall survival rate for this subgroup population by Kaplan–Meier analysis was 68.0%. By log-rank comparison, there was no significant difference in 10 year survival for patients treated with surgery and radiation compared to those treated with surgery alone (63.6% versus 72.6% months, p = 0.80). By univariate analysis, variables predicting improved overall survival were smaller tumor size (HR 1.024, p = 0.0354), and younger age at diagnosis (HR 0.551, p = 0.0009) (Table 5). The multivariate model demonstrated the same predictors for better overall survival (Table 6). For this subgroup, we again observed no increasing trend of radiation use over time on chi-squared analysis (p = 0.9). Large-volume registries showed higher rates of radiation, although not significantly so (p = 0.06). 5. Discussion Due to the rarity of skull base chondrosarcomas, treatment strategy has largely been addressed in small, single-institution studies. Our study represents a population based analysis looking primarily at practice patterns and outcomes for skull base chondrosarcomas, and we identified 226 patients from the SEER database from 1973 to 2009. Consistent with previous studies, skull base chondrosarcomas occurred at all age groups, with a median age in the fifth decade [3,4]. By univariate analysis, undergoing surgical resection was a significant predictor of survival for all patients with skull base chondrosarcomas. Wilcoxon comparison of survival rates demonstrated significant survival difference according to treatment strategy, with patients treated with surgery and adjuvant radiation having the longest survival times. The group who did not undergo any treatment – neither surgery nor radiation – had a longer median survival than the radiation-only group, however this is of limited interpretation due to the small sample sizes of each group (n = 12 and n = 5, respectively). One theory for this difference, however, is that patients treated only with radiation may have had recurrent tumor or large, unresectable tumors, in which case, radiation would be with palliative intent. Similarly, untreated tumors may have been incidental findings and small asymptomatic lesions. The SEER registry does not allow for deeper analyses of these details. Multivariate analysis showed that female sex, younger age, and more recent year of diagnosis were significant predictors of survival in a multivariate model. The findings of improved survival for people with more recent diagnoses supports the idea that technological advancements have aided in earlier diagnosis and improved treatment. The use of MRI did not become commonplace until the 1980s, and likely has helped visualize tumors at earlier, and therefore more treatable, stages. Additionally, improvements in surgical approach to the skull base, including lateral skull base and endonasal endoscopic technique, and intraoperative advances, such as neuromonitoring and image guidance, have likely helped surgeons reduce morbidity and improve outcomes [7,8]. Within the tumor size subgroup, patients with smaller tumors and younger age were found to have significantly improved survival. It is possible that these smaller tumors may have been more fully resectable and the younger population perceived as better able to tolerate more significant surgeries. Surgical resection of chondrosarcomas has widely been considered the primary treatment option, and our study supported a significant survival benefit among patients receiving surgery compared to those that did not. Adjuvant radiation also modestly
Please cite this article in press as: Jones PS et al. Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.02.005
4
P.S. Jones et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
Table 2 Univariate analysis of all variables with respect to survival Variable
Parameter estimate
SE
Hazard ratio (95% Cl)
p value
Radiation Yes No
0.36961 Reference
0.30138 –
0.691 (0.383–1.247) –
0.2201 –
Surgery Yes No
0.86728 Reference
0.38618 –
0.420 (0.197–0.895) –
0.0247 –
Registry Small Large
Reference 0.19359
– 0.31980
– 0.824 (0.440–1.542)
– 0.5449
Sex Male Female
Reference 0.88177
– 0.28894
– 0.414 (0.235–0.729)
0.0023
Age By year
0.04282
0.00849
1.044 (1.027–1.061)
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database Pamela S. Jones a, Manish K. Aghi b, Alona Muzikansky c, Helen A. Shih d, Fred G. Barker II a, William T. Curry Jr. a,⇑ a
Department of Neurosurgery, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 9E-9026, Boston, MA 02114, USA Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, USA Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA d Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA b c
a r t i c l e
i n f o
Article history: Received 3 February 2014 Accepted 11 February 2014 Available online xxxx Keywords: Chondrosarcoma Population study Radiation therapy Skull base tumors
a b s t r a c t This study aims to demonstrate survival rates and treatment patterns among patients with chondrosarcomas of the skull base using a large population database. Patients with skull base chondrosarcomas between 1973 and 2009 were identified from the USA Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier survival analysis was used to examine the effect of surgery and radiation on overall survival. We identified 226 patients with skull base chondrosarcomas. Median follow-up was 5.4 years. Median overall survival was 22 years, and 10 year survival was 68.2%. Most patients underwent surgery (92.5%). Few received radiation after diagnosis (38.1%). Ten year survival for all patients treated with surgery was significantly increased compared to those without surgery (69.3% versus 53.9%, p = 0.02). There was a significant difference in survival amongst treatment groups (p = 0.02), with median overall survival not yet reached for patients who received surgery and radiation (median follow-up 5.3 years), compared to 22 years for non-irradiated surgical patients. Surgery predicted better overall survival by univariate analysis (hazard ratio [HR] 0.420, p = 0.03). Female sex (HR 0.470, p = 0.011), younger age at diagnosis (HR 1.046, p < 0.0001), and later year of diagnosis (HR 0.949, p = 0.0006) were prognostic of improved survival in a multivariate model. In subgroup analysis of patients with documented tumor size, smaller tumor size (HR 1.054, p = 0.0003) and younger age (HR 1.021, p = 0.0067) predicted improved survival. This population based study further reaffirms the role of surgery as an effective treatment for skull base chondrosarcoma as previously reported in small case series. Adjuvant radiation may also confer survival benefit. Optimal treatment strategy has yet to be defined in the literature. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction Chondrosarcomas are rare tumors, and account for only 6% of all tumors occurring in the skull base [1]. They often arise from the lateral aspects of the skull base that house cartilage, including the temporo-occipital synchondrosis, the spheno-occiput, and the sphenoethmoid complex [2]. Because of this, they typically involve the cavernous sinus, the petrous bone, the sphenoid bone, and the clivus [3]. While en bloc or gross total resection of chondrosarcomas remains the therapeutic ideal, the proximity of skull base tumors to critical neurovascular structures and possible bony invasion often limits extent of safe surgical resection [4]. Therefore, ⇑ Corresponding author. Tel.: +1 617 726 3779; fax: +1 617 726 3365. E-mail address: [email protected] (W.T. Curry Jr.).
treatment may also include the use of adjuvant radiation for patients with unresectable, subtotally resected, or even gross totally resected tumors to limit tumor growth and recurrence. While the use of adjuvant postoperative radiotherapy, particularly proton beam radiotherapy, has been shown in single institution retrospective series to prolong the survival of patients with skull base chondrosarcomas, there have been no prospective or large population studies analyzing the outcomes of adjuvant radiotherapy specifically for these tumors to our knowledge [5,6]. Given the overall low incidence of this disease, single institution series are often subject to selection biases associated with referral and treatment patterns and contain too few patients to provide definitive understanding of the prognoses and role of radiotherapy in treating these diseases. To clarify the epidemiologic patterns, treatment, and prognosis of skull base chondrosarcoma in the general USA population, we evaluated patients reported to the
http://dx.doi.org/10.1016/j.jocn.2014.02.005 0967-5868/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Jones PS et al. Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.02.005
2
P.S. Jones et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
population based registries within the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2009. We paid particular attention to outcomes and trends in radiation utilization.
(p < 0.05) were included in the multivariate model. Treatment strategies were compared using chi-squared analysis. Calculations were performed using SAS version 9.3 (SAS Institute, Cary, NC, USA).
2. Methods 3. Results 2.1. The SEER program 3.1. Demographics The SEER registry, a database maintained by the USA National Cancer Institute, collects incidence and survival data from population based cancer registries. Data on chondrosarcoma patients diagnosed between 1973 and 2009 were available from 18 population based cancer registries across the USA that together represent approximately 25% of the USA population. The 18 registries included nine entire states and nine metropolitan regions. These registry populations are comparable to the overall USA population on a variety of socioeconomic indices, including poverty indices, high school graduation rate, percentage in rural areas, and percentage foreign-born. The database contains information on patient demographics, primary cancer site, histology, methods of diagnostic confirmation, treatment regimens including surgery and radiation therapy, and year of death. Institutional Review Board approval was not required for this study, as the SEER database is free of any sensitive patient information or identifiers. An overview of the SEER database is available at http://seer.cancer.gov/about/.
Between 1973 and 2009, 226 patients were diagnosed with skull base chondrosarcoma. The median age at diagnosis was 43 years, with age range of 1 to 82, and a fairly equivalent sex distribution (50.9% female). A slightly greater proportion of patients (123 patients, 54.4%) were diagnosed before the median diagnosis year of 2002. Cases occurred across 16 registries, of which nine were considered low-volume (66 patients) and seven were considered high-volume (160 patients). The results are summarized in Table 1. 3.2. Tumor characteristics Information regarding tumor size was available in 111 of 226 patients. The mean diameter was 3.7 cm (range 1.0 to 10.7 cm). Information regarding histologic subtype of chondrosarcoma was not available.
2.2. Chondrosarcoma definition
3.3. Treatment
We compiled chondrosarcoma patients diagnosed between 1973 and 2009. Patients were identified through the World Health Organization’s International Classification of Diseases for Oncology, Version 3 (ICD-O-3) morphology code for chondrosarcoma (9220–9239). Primary sites of disease presentation were compiled according to ICD-O-3 topography codes and were limited to skull and face bones (410); meninges (700); any structure in the brain (710–9, 751, 753); connective and soft tissue of head, face and neck (490); or any head structure (760). We restricted our analysis to patients with histologic confirmation of chondrosarcoma.
Most patients (209 of 226, 92.5%) underwent some type of surgical resection beyond biopsy. The SEER data only specified whether surgery was performed, and did not reliably specify extent of skull base tumor resection. Ultimately, 128 patients were treated with surgery alone (56.6%), 81 patients were treated with surgery and radiation (35.8%), and five patients treated with radiation alone (2.2%). Twelve patients received no treatment (5.3%). Radiation utilization did not increase over time (chi-squared analysis, p = 0.9), and there were no significant differences in the rates of radiation use among small and large registries (p = 0.23).
2.3. Treatment Treatment types were limited to surgery and radiation. The SEER surgery code of 0 was used to indicate that surgery was performed. For the purpose of our analysis, all surgical cases were considered to include some type of tumor resection. All other codes were considered cases where only a diagnostic biopsy had been performed. Adequate information on extent of resection was not available from the database. The SEER radiation codes 0, 6, 7, 8, 9 represented no radiation treatment. We sub-categorized registries according to number of skull base patients in order to assess for potential volume-outcome effect. This is an effect whereby better outcomes are observed at treatment centers with higher volume. We looked at numbers of both skull base chordomas (ICD-O-3 code 9370–9373) and chondrosarcomas treated by each registry to assess for volume of skull base cases from 1973 to 2009. A registry was considered to contain a high-volume treatment center if it contained 40 or more histologically-confirmed skull base chordomas and chondrosarcomas over the study period. 2.4. Statistical analysis The primary outcome of interest was overall survival. Survival analysis was performed using Kaplan–Meier product limit estimators and Cox univariate and multivariate proportional hazards models. Predictors of overall survival in univariate analysis
Table 1 Characteristics of 226 patients with chondrosarcoma tumors of the skull base registered in the SEER database (1973–2009) Patient characteristics Patients, n Mean age, years (± SD) Median age, years Females
226 44.3 (± 17.7) 43 115 (50.9)
Race White African American Asian Unknown
192 (85.0) 15 (6.6) 16 (7.1) 3 (1.3)
Registry Low volume (2002
2002 median year (1999 mean) 123 (54.4) 103 (45.6)
Surgical data available No resection Resection
17 (7.5) 209 (92.5)
Radiation therapy Median survival, years (months) 5 year survival, % 10 year survival, %
86 (38.1) 22 (264) 86.9 68.2
Data presented as number of patients (%) unless otherwise indicated.
Please cite this article in press as: Jones PS et al. Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.02.005
P.S. Jones et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
4. Outcomes 4.1. All patients Median follow-up time was 5.4 years (65 months). The 5 and 10 year overall survival rate for all patients by Kaplan–Meier analysis were 86.9% and 68.2%, respectively, and median overall survival was 22 years (264 months). The Wilcoxon test demonstrated significant survival differences between the four treatment groups (p = 0.02). Median overall survival was 264 months for patients treated with surgery only, 42 months for radiation only, and 162 months for no treatment. The longest survival was for patients treated with surgery and adjuvant radiation. This group’s median survival was not reached at time of last data collection, and median follow-up time for this group was 5.3 years (63 months). Ten year survival for all patients treated with surgery was significantly increased compared to those without surgery, other than biopsy (69.3% versus 53.9%, p = 0.02). Figure 1 shows that, by logrank comparison, there was a slight trend towards improved 10 year survival with use of adjuvant radiation compared to patients treated with surgery alone (71.9% versus 68.2% 10 year survival, p = 0.32). By univariate analysis, factors predicting better overall survival included patients who underwent surgical resection (hazard ratio [HR] 0.420 95%, p = 0.0247), were female (HR 0.414, p = 0.0023), had younger age at diagnosis (HR 1.044, p < 0.0001), and had later year of diagnosis (HR 0.959, p = 0.0037) (Table 2). In a multivariate model, female sex (HR 0.47, p = 0.01), younger age (HR 1.05, p < 0.001), and more recent year of diagnosis (HR 0.95, p = 0.0006) were significantly associated with improved survival (Table 3). 4.2. Tumor size subgroup We separately analyzed 111 patients with a tumor size recorded at the time of diagnosis (median age was 43 years [range 6 to 82]). Table 4 shows the breakdown of mean tumor size 100 90 80 70 60 50 40 30 20 10 0 0
50
100
150
200
250
300
350
400
450
Fig. 1. Kaplan–Meier survival plot for patients with skull base chondrosarcomas treated with surgery (dashed line) versus surgery and radiation (solid line) (p = 0.32).
3
according to the four different treatment strategies. The largest mean tumor size, 3.9 cm, was that of the patient group who received surgery only; however, there was no statistical significance to this or the difference between mean sizes of tumors for any other treatment group (p = 0.36). The 10 year overall survival rate for this subgroup population by Kaplan–Meier analysis was 68.0%. By log-rank comparison, there was no significant difference in 10 year survival for patients treated with surgery and radiation compared to those treated with surgery alone (63.6% versus 72.6% months, p = 0.80). By univariate analysis, variables predicting improved overall survival were smaller tumor size (HR 1.024, p = 0.0354), and younger age at diagnosis (HR 0.551, p = 0.0009) (Table 5). The multivariate model demonstrated the same predictors for better overall survival (Table 6). For this subgroup, we again observed no increasing trend of radiation use over time on chi-squared analysis (p = 0.9). Large-volume registries showed higher rates of radiation, although not significantly so (p = 0.06). 5. Discussion Due to the rarity of skull base chondrosarcomas, treatment strategy has largely been addressed in small, single-institution studies. Our study represents a population based analysis looking primarily at practice patterns and outcomes for skull base chondrosarcomas, and we identified 226 patients from the SEER database from 1973 to 2009. Consistent with previous studies, skull base chondrosarcomas occurred at all age groups, with a median age in the fifth decade [3,4]. By univariate analysis, undergoing surgical resection was a significant predictor of survival for all patients with skull base chondrosarcomas. Wilcoxon comparison of survival rates demonstrated significant survival difference according to treatment strategy, with patients treated with surgery and adjuvant radiation having the longest survival times. The group who did not undergo any treatment – neither surgery nor radiation – had a longer median survival than the radiation-only group, however this is of limited interpretation due to the small sample sizes of each group (n = 12 and n = 5, respectively). One theory for this difference, however, is that patients treated only with radiation may have had recurrent tumor or large, unresectable tumors, in which case, radiation would be with palliative intent. Similarly, untreated tumors may have been incidental findings and small asymptomatic lesions. The SEER registry does not allow for deeper analyses of these details. Multivariate analysis showed that female sex, younger age, and more recent year of diagnosis were significant predictors of survival in a multivariate model. The findings of improved survival for people with more recent diagnoses supports the idea that technological advancements have aided in earlier diagnosis and improved treatment. The use of MRI did not become commonplace until the 1980s, and likely has helped visualize tumors at earlier, and therefore more treatable, stages. Additionally, improvements in surgical approach to the skull base, including lateral skull base and endonasal endoscopic technique, and intraoperative advances, such as neuromonitoring and image guidance, have likely helped surgeons reduce morbidity and improve outcomes [7,8]. Within the tumor size subgroup, patients with smaller tumors and younger age were found to have significantly improved survival. It is possible that these smaller tumors may have been more fully resectable and the younger population perceived as better able to tolerate more significant surgeries. Surgical resection of chondrosarcomas has widely been considered the primary treatment option, and our study supported a significant survival benefit among patients receiving surgery compared to those that did not. Adjuvant radiation also modestly
Please cite this article in press as: Jones PS et al. Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database. J Clin Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.02.005
4
P.S. Jones et al. / Journal of Clinical Neuroscience xxx (2014) xxx–xxx
Table 2 Univariate analysis of all variables with respect to survival Variable
Parameter estimate
SE
Hazard ratio (95% Cl)
p value
Radiation Yes No
0.36961 Reference
0.30138 –
0.691 (0.383–1.247) –
0.2201 –
Surgery Yes No
0.86728 Reference
0.38618 –
0.420 (0.197–0.895) –
0.0247 –
Registry Small Large
Reference 0.19359
– 0.31980
– 0.824 (0.440–1.542)
– 0.5449
Sex Male Female
Reference 0.88177
– 0.28894
– 0.414 (0.235–0.729)
0.0023
Age By year
0.04282
0.00849
1.044 (1.027–1.061)
