Journal of Cranio-Maxillo-Facial Surgery xxx (2014) 1e5
Contents lists available at ScienceDirect
Journal of Cranio-Maxillo-Facial Surgery journal homepage: www.jcmfs.com
Survival after curative surgical treatment for primary oral squamous cell carcinoma M. Bloebaum*, L. Poort, R. Böckmann, P. Kessler Department of Cranio-Maxillofacial Surgery (Head: Prof. Dr. Dr. P. Kessler), Maastricht University Medical Center MUMCþ, P Debbyelaan, Postbus 5800, NL6202 Maastricht, The Netherlands
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 4 December 2012 Accepted 9 January 2014
The purpose of this retrospective study was to review recurrence rate and survival of patients with primary oral squamous cell carcinoma (OSCC) that have received surgical treatment and adjuvant radiotherapy with curative intent in our clinic over a 6-year period. A total of 106 patients were included. The 5-year overall survival (OS) was 41%, 5-year disease-specific survival (DSS) was 77%, 5-year disease-free survival (DFS) was 72%. DSS was significantly different between early and advanced stage, 87% and 67% respectively (p ¼ 0.04). Recurrence significantly affected survival: OS with or without recurrence at 20 months was 24% and 87% respectively (p < 0.001). Although a guideline based approach for the treatment of OSCC might provide an advantage, more data are needed for these guidelines to be based on. Ó 2014 Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery.
Keywords: Oral squamous cell carcinoma Survival Cancer therapy
1. Introduction Oral squamous cell carcinoma (OSCC) is known for its unpredictability. Although metastases are more likely to occur with increased size of the primary tumour, small cancers can metastasise early, and some large cancers never metastasise. Besides tumour size and nodal status, other prognostic factors are the tumour site, pathological grade, depth of invasion, biological tumour markers, perineural invasion, distant metastases and patient compliance (Shah, 1990; Ferlito et al., 2009; Shaw et al., 2009). Smoking was recently proved to be a high-risk factor for recurrence (Wang et al., 2012). Technological advances in surgery and concurrent chemoradiation therapy have significantly affected the treatment and outcome for patients with advanced stage OSCC (Andersen et al., 2002; Bernier et al., 2004; Cooper et al., 2004; Shiboski et al., 2005). The use of free flap reconstruction improves the survival of patients with OSCC (de Vicente et al., 2012). Despite this its prognosis remains extremely poor, with 5-year survival rates estimated to be 35%e45% (Kademani et al., 2005; Bell et al., 2007; Rusthoven et al., 2010). The purpose of this retrospective study was to review recurrence rates and survival of patients with primary OSCC who have received adjuvant treatment with curative intent in the
* Corresponding author. Tel.: þ31 43 387 2010; fax: þ31 43 387 2020. E-mail address: [email protected] (M. Bloebaum).
Department of Cranio-Maxillofacial Surgery of the Maastricht University Medical Centre (MUMC).
2. Material and methods Records of all 136 patients with primary OSCC treated in the MUMC between June 2006 and December 2011 were reviewed. Inclusion criteria were: diagnosis with primary OSCC and surgical treatment, with or without microsurgical reconstruction, and adjuvant radiation or radio-chemotherapy as suggested by the guidelines of the Dutch Society of Head and Neck Cancer (NWHHT). Exclusion criteria were oral malignancies other than SCC, pharyngeal lesions and subjects with inadequate follow-up data. Thirty patients were excluded: 27 patients had not undergone surgery, two patients had an intra-oral malignancy other than SCC, one patient had incomplete medical records due to having had followup elsewhere. One hundred and six patients met the inclusion criteria for the study. The 106 included subjects consisted of 58 men (55%) and 48 women (45%) with a mean age at surgery of 64.6 years (SD 11.5 years; range 40e91 years). At the time of surgery, 33 cancers were stage I (31%), 21 were stage II (20%), five were stage III (5%), and 47 were stage IV A (44%). Follow-up ranged from 0 to 65 months in our study population, with a mean of 22.3 months (standard error of mean [SEM], 1.6 months). Forty-four patients received adjuvant radiation therapy,
http://dx.doi.org/10.1016/j.jcms.2014.01.046 1010-5182/Ó 2014 Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery.
Please cite this article in press as: Bloebaum M, et al., Survival after curative surgical treatment for primary oral squamous cell carcinoma, Journal of Cranio-Maxillo-Facial Surgery (2014), http://dx.doi.org/10.1016/j.jcms.2014.01.046
2
M. Bloebaum et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2014) 1e5
two adjuvant radio-chemotherapy, one with methotrexate and one with cisplatin. All patients were operated on by the same team of three head and neck oncologists of the department of Cranio-Maxillofacial Surgery. Prior to surgery all patients were presented and discussed in the multidisciplinary team for head and neck cancer of the oncological centre of the MUMC (head and neck MDT). The data were extracted from the electronic patient records (SAPÔ, Walldorf, Germany). Data were entered into SPSS 18 (IBM, United States). Data and variables recorded and evaluated were age, gender, tumour site, regional and/or distant metastasis, TNM stage, operation performed, adjuvant radiation therapy/radio-chemotherapy, type of reconstruction, time to recurrence, time to death. Outcome measures were overall survival, disease-free survival (¼time to recurrence) and length of survival after recurrence. KaplaneMeier survival curves were created for disease-free survival, as well as survival by tumour stage, and survival after recurrence. 3. Results The overall 5-year survival rate for all stages was 41% (SEM, 17%) with a mean survival of 45 months (95% confidence interval [CI], 39e50 months) (Fig. 1). The disease-specific 5-year survival rate was 77% (SEM, 5%) with a mean survival of 54 months (95% CI, 49e59 months) (Fig. 2). The disease-free 5-year survival rate was 72% (SEM, 5%) with a mean survival of 49 months (95% CI, 44e55 months) (Fig. 3). At 20 months follow-up, the overall survival rate of patients who had developed a recurrence was 24% (SEM, 10%) with a mean survival of 19 months (95% CI, 15e23). The overall survival rate with no recurrence was 87% (SEM, 4%) with a mean survival of 54 months (95% CI, 49e59 months) (Fig. 4). Log-rank (ManteleCox) showed that the curves differed significantly p < 0.001. Stage appeared to effect survival. Those patients who had early stage OSCC’s had a 5-year disease-specific survival of 87% (SEM, 6%), mean ¼ 59 months (95% CI, 54e64), whereas those with advanced stage cancers had a 5-year disease-specific survival of 67% (SEM, 9%), mean ¼ 46 months (95% CI, 39e54) (Fig. 5). Log-rank (Mantele Cox) showed that the difference between survival was significant p ¼ 0.04.
Fig. 1. Overall survival.
Fig. 2. Disease-specific survival.
Out of the 106 subjects, 24 (23%) had a recurrence. Of these subjects 18 (75%) had died before the end of the study. At 17 months after diagnosis of recurrent disease, the survival rate had dropped to 6% (SEM, 5%), with a mean survival of 7 months (95% CI, 4e10). 4. Discussion This study is necessary to support the database to define or strengthen existing guidelines in head neck oncology as the database in literature is lacking large populations with OSCC to support therapy concepts with sufficient statistical power. For example, the therapy concepts as suggested by the Dutch Society of Head and Neck Cancer are based on one prospective randomised multi-centre study that included only 35 patients. The study was terminated prematurely, because survival of patients in the treatment group with surgery and radio-therapy on indication turned out to be more favourable compared to primary radiation therapy alone (Robertson et al., 1998).
Fig. 3. Disease-free survival.
Please cite this article in press as: Bloebaum M, et al., Survival after curative surgical treatment for primary oral squamous cell carcinoma, Journal of Cranio-Maxillo-Facial Surgery (2014), http://dx.doi.org/10.1016/j.jcms.2014.01.046
M. Bloebaum et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2014) 1e5
Fig. 4. Overall survival for patients with or without recurrence.
Fig. 5. Disease-specific survival per stage.
3
Overall 5-year survival rate (OS) for patients with OSCC has been reported 45.7% (Sessions et al., 2000) and 48% (Sklenicka et al., 2010). In our study, the OS of 41% was slightly lower. However, a high disease-specific 5-year survival rate (DSS) of 77% indicates that most patients died due to causes other than OSCC or the related therapy. The fact that patients more often die for various reasons non-correlated to the OSCC corresponds with findings in literature (Sessions et al., 2000). In our population main causes of death were other malignant diseases, heart and vascular diseases as well as pulmonary diseases. An explanation for this might be that most of our patients are subject to high morbidity due to a history of tobacco and/or alcohol abuse. It is known that patients with a primary head and neck cancer have an excess risk of developing a secondary primary cancer when compared to the general population, especially in secondary primary head and neck malignancies and secondary lung lesions (Geurts et al., 2005; Chuang et al., 2008). Besides the risk of a secondary primary cancer, a recent study indicated that the presence of a coexisting disorder correlated with the highest risk for disease recurrence (Vazquez-Mahia et al., 2012). We found that recurrence significantly reduced survival. To prevent a low body mass index due to malnutrition from negatively affecting survival (Chang et al., 2012), all of our patients undergoing adjuvant chemo-radiation received parenteral nutrition to secure their intake. A DSS of 60.9% for all stages in the United States has been described (Horner et al., 2006), with 82.5% for early stage and 54.7 % for advanced stage OSCC. In the period 1995e1999, DSS was 46.2% (95% CI, 44.6e47.8) in Europe, and 57.3% (95% CI, 52.0e53.2) in The Netherlands (Sant et al., 2009). The DSS for all stages of the group evaluated here is better than most results reported in literature in larger populations (Horner et al., 2006; Sant et al., 2009). Only Hicks et al. report a similar DSS of 85% for a population of 79 patients with SCC of the tongue who were treated surgically without adjuvant therapy (Hicks et al., 1998). The DSS of 87% for early stages is comparable to other studies (Horner et al., 2006). Although we found that advanced tumour stage correlated with lower survival compared to early stage, the DSS for advanced diseases of 67% is clearly better than the numbers reported in literature. Also, a 5-year disease-free survival (DFS) of 72% is better than reported by Sklenicka et al., whereby tumour stages and mean age in both studies are comparable (Sklenicka et al., 2010). Thus, although patients with primary OSCC die because of their comorbidities as described above, patients in our study had a better chance of surviving OSCC, and more patients stayed disease-free.
Table 1 Dutch treatment guidelines for malignancies of the oral cavity. Localisation of tumour
Tongue, floor oft he mouth, gingiva (mandibula/maxilla), palatum durum Cheek
Other locations
Therapy of preference T-status
Local
cN0 neck
cNþ neck
T1e4
Surgery Brachytherapy as alternative for tongue with sufficient distance to mandibula Surgery or radiation therapy (RT; (external or brachytherapy) Surgery, postoperative RT Postoperative RT on indication of histopathology
Elective treatment region IeIII either surgical either by RT If risk of occult metastasis
Contents lists available at ScienceDirect
Journal of Cranio-Maxillo-Facial Surgery journal homepage: www.jcmfs.com
Survival after curative surgical treatment for primary oral squamous cell carcinoma M. Bloebaum*, L. Poort, R. Böckmann, P. Kessler Department of Cranio-Maxillofacial Surgery (Head: Prof. Dr. Dr. P. Kessler), Maastricht University Medical Center MUMCþ, P Debbyelaan, Postbus 5800, NL6202 Maastricht, The Netherlands
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 4 December 2012 Accepted 9 January 2014
The purpose of this retrospective study was to review recurrence rate and survival of patients with primary oral squamous cell carcinoma (OSCC) that have received surgical treatment and adjuvant radiotherapy with curative intent in our clinic over a 6-year period. A total of 106 patients were included. The 5-year overall survival (OS) was 41%, 5-year disease-specific survival (DSS) was 77%, 5-year disease-free survival (DFS) was 72%. DSS was significantly different between early and advanced stage, 87% and 67% respectively (p ¼ 0.04). Recurrence significantly affected survival: OS with or without recurrence at 20 months was 24% and 87% respectively (p < 0.001). Although a guideline based approach for the treatment of OSCC might provide an advantage, more data are needed for these guidelines to be based on. Ó 2014 Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery.
Keywords: Oral squamous cell carcinoma Survival Cancer therapy
1. Introduction Oral squamous cell carcinoma (OSCC) is known for its unpredictability. Although metastases are more likely to occur with increased size of the primary tumour, small cancers can metastasise early, and some large cancers never metastasise. Besides tumour size and nodal status, other prognostic factors are the tumour site, pathological grade, depth of invasion, biological tumour markers, perineural invasion, distant metastases and patient compliance (Shah, 1990; Ferlito et al., 2009; Shaw et al., 2009). Smoking was recently proved to be a high-risk factor for recurrence (Wang et al., 2012). Technological advances in surgery and concurrent chemoradiation therapy have significantly affected the treatment and outcome for patients with advanced stage OSCC (Andersen et al., 2002; Bernier et al., 2004; Cooper et al., 2004; Shiboski et al., 2005). The use of free flap reconstruction improves the survival of patients with OSCC (de Vicente et al., 2012). Despite this its prognosis remains extremely poor, with 5-year survival rates estimated to be 35%e45% (Kademani et al., 2005; Bell et al., 2007; Rusthoven et al., 2010). The purpose of this retrospective study was to review recurrence rates and survival of patients with primary OSCC who have received adjuvant treatment with curative intent in the
* Corresponding author. Tel.: þ31 43 387 2010; fax: þ31 43 387 2020. E-mail address: [email protected] (M. Bloebaum).
Department of Cranio-Maxillofacial Surgery of the Maastricht University Medical Centre (MUMC).
2. Material and methods Records of all 136 patients with primary OSCC treated in the MUMC between June 2006 and December 2011 were reviewed. Inclusion criteria were: diagnosis with primary OSCC and surgical treatment, with or without microsurgical reconstruction, and adjuvant radiation or radio-chemotherapy as suggested by the guidelines of the Dutch Society of Head and Neck Cancer (NWHHT). Exclusion criteria were oral malignancies other than SCC, pharyngeal lesions and subjects with inadequate follow-up data. Thirty patients were excluded: 27 patients had not undergone surgery, two patients had an intra-oral malignancy other than SCC, one patient had incomplete medical records due to having had followup elsewhere. One hundred and six patients met the inclusion criteria for the study. The 106 included subjects consisted of 58 men (55%) and 48 women (45%) with a mean age at surgery of 64.6 years (SD 11.5 years; range 40e91 years). At the time of surgery, 33 cancers were stage I (31%), 21 were stage II (20%), five were stage III (5%), and 47 were stage IV A (44%). Follow-up ranged from 0 to 65 months in our study population, with a mean of 22.3 months (standard error of mean [SEM], 1.6 months). Forty-four patients received adjuvant radiation therapy,
http://dx.doi.org/10.1016/j.jcms.2014.01.046 1010-5182/Ó 2014 Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery.
Please cite this article in press as: Bloebaum M, et al., Survival after curative surgical treatment for primary oral squamous cell carcinoma, Journal of Cranio-Maxillo-Facial Surgery (2014), http://dx.doi.org/10.1016/j.jcms.2014.01.046
2
M. Bloebaum et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2014) 1e5
two adjuvant radio-chemotherapy, one with methotrexate and one with cisplatin. All patients were operated on by the same team of three head and neck oncologists of the department of Cranio-Maxillofacial Surgery. Prior to surgery all patients were presented and discussed in the multidisciplinary team for head and neck cancer of the oncological centre of the MUMC (head and neck MDT). The data were extracted from the electronic patient records (SAPÔ, Walldorf, Germany). Data were entered into SPSS 18 (IBM, United States). Data and variables recorded and evaluated were age, gender, tumour site, regional and/or distant metastasis, TNM stage, operation performed, adjuvant radiation therapy/radio-chemotherapy, type of reconstruction, time to recurrence, time to death. Outcome measures were overall survival, disease-free survival (¼time to recurrence) and length of survival after recurrence. KaplaneMeier survival curves were created for disease-free survival, as well as survival by tumour stage, and survival after recurrence. 3. Results The overall 5-year survival rate for all stages was 41% (SEM, 17%) with a mean survival of 45 months (95% confidence interval [CI], 39e50 months) (Fig. 1). The disease-specific 5-year survival rate was 77% (SEM, 5%) with a mean survival of 54 months (95% CI, 49e59 months) (Fig. 2). The disease-free 5-year survival rate was 72% (SEM, 5%) with a mean survival of 49 months (95% CI, 44e55 months) (Fig. 3). At 20 months follow-up, the overall survival rate of patients who had developed a recurrence was 24% (SEM, 10%) with a mean survival of 19 months (95% CI, 15e23). The overall survival rate with no recurrence was 87% (SEM, 4%) with a mean survival of 54 months (95% CI, 49e59 months) (Fig. 4). Log-rank (ManteleCox) showed that the curves differed significantly p < 0.001. Stage appeared to effect survival. Those patients who had early stage OSCC’s had a 5-year disease-specific survival of 87% (SEM, 6%), mean ¼ 59 months (95% CI, 54e64), whereas those with advanced stage cancers had a 5-year disease-specific survival of 67% (SEM, 9%), mean ¼ 46 months (95% CI, 39e54) (Fig. 5). Log-rank (Mantele Cox) showed that the difference between survival was significant p ¼ 0.04.
Fig. 1. Overall survival.
Fig. 2. Disease-specific survival.
Out of the 106 subjects, 24 (23%) had a recurrence. Of these subjects 18 (75%) had died before the end of the study. At 17 months after diagnosis of recurrent disease, the survival rate had dropped to 6% (SEM, 5%), with a mean survival of 7 months (95% CI, 4e10). 4. Discussion This study is necessary to support the database to define or strengthen existing guidelines in head neck oncology as the database in literature is lacking large populations with OSCC to support therapy concepts with sufficient statistical power. For example, the therapy concepts as suggested by the Dutch Society of Head and Neck Cancer are based on one prospective randomised multi-centre study that included only 35 patients. The study was terminated prematurely, because survival of patients in the treatment group with surgery and radio-therapy on indication turned out to be more favourable compared to primary radiation therapy alone (Robertson et al., 1998).
Fig. 3. Disease-free survival.
Please cite this article in press as: Bloebaum M, et al., Survival after curative surgical treatment for primary oral squamous cell carcinoma, Journal of Cranio-Maxillo-Facial Surgery (2014), http://dx.doi.org/10.1016/j.jcms.2014.01.046
M. Bloebaum et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2014) 1e5
Fig. 4. Overall survival for patients with or without recurrence.
Fig. 5. Disease-specific survival per stage.
3
Overall 5-year survival rate (OS) for patients with OSCC has been reported 45.7% (Sessions et al., 2000) and 48% (Sklenicka et al., 2010). In our study, the OS of 41% was slightly lower. However, a high disease-specific 5-year survival rate (DSS) of 77% indicates that most patients died due to causes other than OSCC or the related therapy. The fact that patients more often die for various reasons non-correlated to the OSCC corresponds with findings in literature (Sessions et al., 2000). In our population main causes of death were other malignant diseases, heart and vascular diseases as well as pulmonary diseases. An explanation for this might be that most of our patients are subject to high morbidity due to a history of tobacco and/or alcohol abuse. It is known that patients with a primary head and neck cancer have an excess risk of developing a secondary primary cancer when compared to the general population, especially in secondary primary head and neck malignancies and secondary lung lesions (Geurts et al., 2005; Chuang et al., 2008). Besides the risk of a secondary primary cancer, a recent study indicated that the presence of a coexisting disorder correlated with the highest risk for disease recurrence (Vazquez-Mahia et al., 2012). We found that recurrence significantly reduced survival. To prevent a low body mass index due to malnutrition from negatively affecting survival (Chang et al., 2012), all of our patients undergoing adjuvant chemo-radiation received parenteral nutrition to secure their intake. A DSS of 60.9% for all stages in the United States has been described (Horner et al., 2006), with 82.5% for early stage and 54.7 % for advanced stage OSCC. In the period 1995e1999, DSS was 46.2% (95% CI, 44.6e47.8) in Europe, and 57.3% (95% CI, 52.0e53.2) in The Netherlands (Sant et al., 2009). The DSS for all stages of the group evaluated here is better than most results reported in literature in larger populations (Horner et al., 2006; Sant et al., 2009). Only Hicks et al. report a similar DSS of 85% for a population of 79 patients with SCC of the tongue who were treated surgically without adjuvant therapy (Hicks et al., 1998). The DSS of 87% for early stages is comparable to other studies (Horner et al., 2006). Although we found that advanced tumour stage correlated with lower survival compared to early stage, the DSS for advanced diseases of 67% is clearly better than the numbers reported in literature. Also, a 5-year disease-free survival (DFS) of 72% is better than reported by Sklenicka et al., whereby tumour stages and mean age in both studies are comparable (Sklenicka et al., 2010). Thus, although patients with primary OSCC die because of their comorbidities as described above, patients in our study had a better chance of surviving OSCC, and more patients stayed disease-free.
Table 1 Dutch treatment guidelines for malignancies of the oral cavity. Localisation of tumour
Tongue, floor oft he mouth, gingiva (mandibula/maxilla), palatum durum Cheek
Other locations
Therapy of preference T-status
Local
cN0 neck
cNþ neck
T1e4
Surgery Brachytherapy as alternative for tongue with sufficient distance to mandibula Surgery or radiation therapy (RT; (external or brachytherapy) Surgery, postoperative RT Postoperative RT on indication of histopathology
Elective treatment region IeIII either surgical either by RT If risk of occult metastasis
