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Review
Life expectancy following orbital exenteration James Chiun Lon Wong,1 Reshma Thampy,2 Anne Cook2 1
Manchester Medical School, Manchester, UK 2 Manchester Royal Eye Hospital, Manchester, UK Correspondence to Dr James Chiun Lon Wong, Accommodation Office, Blackpool Victoria Hospital, Blackpool FY38NR, UK; [email protected] Received 7 October 2013 Revised 6 March 2014 Accepted 16 April 2014 Published Online First 30 May 2014
ABSTRACT Orbital exenteration is a physically debilitating procedure that may be a necessity in the management of orbital malignancy. It requires a sensitive multidisciplinary approach, both preoperatively and postoperatively. Providing life expectancy information for patients during preoperative counselling is pertinent to informed consent and in addressing patients’ expectations. A retrospective review from one tertiary care centre was undertaken for a cohort of patients who were exenterated for orbital malignancy between 1998 and 2010. The cases were identified using an International Classification of Diseases 10th Revision (ICD-10)-derived database and were analysed using Prism statistical software (V.5.04). Cause of death was ascertained by liaising with the general practitioner and the National Registrar Office for Births, Deaths, and Marriages, Southport, UK. In total, 41 men and 32 women were identified. Mean age was 72 years with 47 cases living and 26 deceased at the time of review. The overall 5-year survival rate in this study was 64%. Kaplan–Meier analysis for basal cell carcinoma (BCC) against non-BCC returned a p value of 0.0199, with an HR of 0.3927 (CI 0.1788 to 0.8626). Kaplan–Meier analysis for cleared against non-cleared margins returned a p value of 0.2890, with an HR of 0.6571(CI 0.3024 to 1.428). Our results represent the highest 5-year survival data to date. However, the overall prognosis for patients who undergo orbital exenteration for malignancy remains poor. We hypothesise that the causes are multi-factorial. We recommend a multidisciplinary approach to the care of these patients, involving head and neck teams, oncology and other appropriate specialties, to optimise outcomes for this vulnerable patient group. Orbital exenteration is an extensive procedure that is challenging for both the patient and the surgeon. Relatively few studies have investigated life expectancy and its influencing factors. This study provides statistical information that may be of value to patients and clinicians during counselling.1–3 We hypothesise that tumour characteristics (basal cell carcinomas (BCCs) vs non-BCCs) and their surgical margins (cleared vs non-cleared) play a significant role in life expectancy. Our results refute previous conclusions drawn from data from our unit, which showed non-significance for both parameters.4 Furthermore, at the time of writing, our study reported the highest overall 5-year survival rate reported to date.4–8
BACKGROUND
To cite: Wong JCL, Thampy R, Cook A. Br J Ophthalmol 2015;99:1–4.
Orbital exenteration is reserved for the management of serious orbital disease when other less disfiguring methods are deemed inadequate. It may be indicated for both malignant and non-malignant diseases. Examples of malignant diseases that may require this procedure are BCC, squamous cell carcinoma
(SCC), melanoma, sebaceous cell carcinoma and lacrimal gland carcinoma.9–11 Non-malignant diseases —such as necrotising fasciitis, sino-orbital mucormycosis, neurofibromatosis, end-stage and severe non-specific orbital inflammatory disease with intractable pain and blindness—may occasionally also require such radical surgery. Orbital exenteration is categorised as total, subtotal and extensive. In total exenteration, the entire orbital content is removed together with the eyelid, which is in contrast to subtotal or lid-sparing exenteration, where the lids are preserved for better cosmesis. Certain disease processes can be so damaging to the nearby structures that an extensive exenteration is required; for example, paranasal sinuses may be removed at the same time. A formal multidisciplinary team is recommended in all instances. This team typically includes head and neck, oncology, pathology and other appropriate specialties.
METHODS This study is a retrospective review from one tertiary care centre. This 13-year historical cohort of exenterated patients was identified through theatre operation notes using an International Classification of Diseases 10th Revision (ICD-10) clinical code database. The identified cases were reviewed using the local trust database, PAS (Patient Administration System) and MediSec (electronic patient letter system), the local ophthalmic histopathology database, Sunquest, and the central patient notes library. Inclusion and exclusion criteria were as follows. All exenterated cases for orbital neoplasm from 1 January 1998 to 31 December 2010 were included. All types of exenteration techniques were included. Exclusion criteria were non-neoplastic pathology or surgery to allow the fitting of an orbital prosthesis following previous extensive orbital surgery. Patient demographics and surgical and ophthalmic histopathology details were recorded and analysed. The following were recorded: gender, date of birth, age at death (if applicable), age at exenteration, longevity following orbital exenteration to date of study, histological diagnosis and surgical margins. Cause of death for deceased patients was ascertained by liaising with their general practitioners and the health authority, the National Registrar Office for Births, Deaths, and Marriages in Southport, UK. Data were analysed using Prism, statistical software (V.5.04, available from GraphPad Software Inc., San Diego, California, USA). Life expectancy and survival rates following orbital exenteration were calculated using Kaplan– Meier analysis, whereas categorical variables were contrasted using the log-rank (Mantel–Cox) test and were further supported with the Gehan– Breslow–Wilcoxon test.
Wong JCL, et al. Br J Ophthalmol 2015;99:1–4. doi:10.1136/bjophthalmol-2013-304436
1
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Review This paper received no ethical approval, as the data were completely anonymised, were part of a service evaluation project and did not involve any vulnerable groups. Nonetheless, all of the authors strictly adhered to appropriate local disciplinary, ethical and data protection guidelines.
RESULTS A total of 73 orbits of 73 patients were identified within the 13-year time period. The number of cases analysed was lower than we originally anticipated (97 cases) due to inaccurate coding of clinical episodes. The mean age of our historical cohort was 72 years with an SD of 4–100 years of age. At the time of study, 47 patients were living and 26 were deceased. There were a total of 41 men and 32 women. There was no change in the incidence of exenteration over the 13-year period. However, the 3, 5 and 10-year survival rates improved, as compared with previous outcomes in our unit.4 12
Overall life expectancy This cohort had an overall 1-year life expectancy of 88%. This value was reduced to 68% at 3 years, 64% at 5 years and 38% at 10 years (figure 1). To the best of our knowledge, these values are higher than previous reports on 5-year life expectancy.4–8 Table 1 outlines the details of the 26 deceased cases during the study period.
Histology This cohort consisted of 14 different types of neoplasms. Table 2 shows the proportion of cases according to each histological diagnosis. The histological diagnoses were similar to other studies, where the majority of the cases made up the four groupings of BCC, SCC, sebaceous cell carcinoma and melanoma.4–6 9 12 This fact is relevant when comparing life expectancies across studies. The most common cause for exenteration was BCC. BCCs accounted for 27 cases; the remaining 46 were non-BCCs. In order of frequency, these remaining 46 cases consisted of SCC, sebaceous cell carcinoma, malignant melanoma and others. Of all cases used in the study, histological evaluation indicated that 31 had cleared surgical margins and the remaining 42 had non-cleared surgical margins. Table 3 shows the histological breakdown in between the alive and deceased cases for comparison. It is natural to assume that tumour characteristics should influence life expectancy following orbital exenteration.
Therefore, our patients were divided into two groups based on histological diagnosis. Group 1 included cases with histological diagnoses of BCC. Group 2 included cases with histological diagnoses of non-BCC. The rationale behind this grouping was based on the fact that BCCs are considered to be less aggressive neoplasms.13 This assumption was further confirmed with a Kaplan–Meier survival analysis, as shown in figure 2. When these two categorical variables were compared, the log-rank (Mantel–Cox) test returned a p value of 0.0199, indicating that the survival rate difference between the two groups is statistically significant (table 3).
DISCUSSION The current findings differ from those of Rahman et al4 both in terms of survival rates and the significance of the histological diagnosis. HR analysis between the histological groups revealed that deaths in the BCC group occurred at almost half the rate of those in the non-BCC disease group. The analysis returned an HR of 0.4391 with a 95% CI of 0.2006 to 0.9610. Gehan– Breslow–Wilcoxon analysis of the Kaplan–Meier survival curve comparing histological diagnoses returned a significant p value of 0.0494. This statistical test gives more weight to deaths at early time point. Consistent with this result, table 4 shows that the non-BCC group has a higher risk of dying following exenteration. The median survival for non-BCC patients is 81 months (6.8 years), whereas the median survival for BCC patients is undefined, as fractional survival exceeded 50% at the time of analysis. As figure 2 illustrates, the BCC group maintained a percentage survival greater than 50% through the end of our study. From table 4, it may be extrapolated that the BCC group has a 75% probability of surviving 120 months. We urge that these results be interpreted with caution when they are presented to patients, as dividing our cases into BCC and non-BCC diagnoses is an oversimplification of the problem. The non-BCC group is very heterogeneous, with different metastatic potentials. We chose such a categorisation for easier direct comparison with studies that have been previously performed and published in our unit. Our data confirm our hypothesis that BCC is less aggressive than the non-BCC disorders. Therefore, we would expect the life expectancy of a patient with BCC to be higher than that of a patient with a non-BCC diagnosis undergoing orbital exenteration. Based on our results, the chance of dying from the histological disease is much higher in non-BCC case (table 4). In our cohort of patients who died, the percentage of exenterated BCC patients who died of BCC was 33%, whereas that of non-BCC patients who died of their histological diagnosis was 85%. However, this should be interpreted with caution, as patients often present with multiple comorbidities and different baseline functions at different stages of presentation. Additionally, there is a possibility for error or bias during death certification.
Cleared versus non-cleared surgical margins
Figure 1 Survival rate in 73 cases of orbital exenteration. 2
Surgical margins have always been thought to play an important role in any surgical procedure involving neoplasm. Figure 3 is a Kaplan–Meier survival graph contrasting between the two margin clearance groupings. A log-rank (Mantel–Cox) test revealed that having cleared versus non-cleared surgical margins had no statistical significance on life expectancy (p value of 0.2890). This outcome is further supported by the Gehan– Breslow–Wilcoxon test, which returned a p value of 0.2578. The HR for this category was 0.6571 with a 95% CI of 0.3024 to 1.428. Although the p value is not significant, it is important to note the HR. This value indicates that the non-cleared group Wong JCL, et al. Br J Ophthalmol 2015;99:1–4. doi:10.1136/bjophthalmol-2013-304436
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Review Table 1 Details of the 26 deceased cases in our study Surgical margins and histological diagnosis in the 26 deceased patients from ophthalmic histopathology report
Age/sex
Time from exenteration to death (months)
Surgical margins Y=clear margins N=non-clear margins
Histological diagnosis
Cause of death
Cause of death related to reason for exenteration Y=yes N=no
63/M 52/M 61/M 95/M 66/F 76/M 86/F 62/M 54/F 65/F 76/M 67/M 51/M 93/F 72/F 83/F 65/F 84/M 14/F 92/M 83/F 85/F 77/M 91/M 70/M 83/M
3 17 20 22 119 43 9 2 27 84 15 15 15 28 81 67 11 2 31 3 13 31 35 5 14 9
N Y Y Y Y Y Y Y Y Y Y N N N N N N N N N N N N N N N
Merkel cell carcinoma Malignant melanoma Malignant melanoma Malignant melanoma Sebaceous cell carcinoma BCC SCC BCC Sebaceous cell carcinoma BCC Malignant melanoma Sebaceous cell carcinoma BCC BCC SCC Adenocarcinoma Mucoepidermoid carcinoma Merkel cell carcinoma Rhabdomyosarcoma Mucoepidermoid carcinoma SCC BCC Sebaceous cell carcinoma Malignant melanoma SCC SCC
Heart failure Carcinomatosis Liver metastasis Hepatic metastasis Lung cancer Lung cancer SCC Lung cancer Metastatic carcinoma Metastatic carcinoma of the maxillary atrium Metastatic melanoma Cerebral and lung metastasis from eye Gorlin syndrome Pneumonia Pulmonary embolus Brain tumour Carcinoma Chronic lymphoid Leukaemia Rhabdomyosarcoma Pneumonia Acute cardiac failure COPD and acute renal failure Carcinoma Fall Metastatic carcinoma Multi-organ failure
N Y Y Y Y N Y N Y Y Y Y Y N Y Y Y Y Y Y N N Y N Y Y
BCC, basal cell carcinoma; COPD, chronic obstructive pulmonary disease; SCC, squamous cell carcinoma.
has a 65.71% higher probability of dying by the next time point compared with the cleared group. However, one must note that the lines on the Kaplan–Meier curve eventually crossed so that the cleared margins dropped below the non-cleared margins in terms of survival. Cleared surgical margins have a median
Table 2 Ophthalmic histopathological diagnosis of 73 exenterated cases Histological diagnosis
Exenterated cases, n=73
Basal cell carcinoma Squamous cell carcinoma Sebaceous cell carcinoma Malignant melanoma Adenocarcinoma Meningioma Adenocystic carcinoma (lacrimal gland) Rhabdomyosarcoma Merkell cell carcinoma Mucoepidermoid carcinoma Liposarcoma Fibrous histiocytoma Angiosarcoma Neurofibromatosis
27 14 7 7 3 3 2 2 2 2 1 1 1 1
Wong JCL, et al. Br J Ophthalmol 2015;99:1–4. doi:10.1136/bjophthalmol-2013-304436
survival of 119 months, whereas non-cleared surgical margins have a median survival of 81 months. Our study challenges the presumed influence of marginal clearance on survival by demonstrating that there is no statistically significant difference in survival rates when cleared margin cases are compared with non-cleared cases. This finding confirms those of Rahman et al4 and Mouriaux et al.7 One explanation for this finding is that despite having prevented local recurrence, micro-metastasis may have occurred prior to surgery. Additionally, there are many variables that are involved in providing a cure.12 14 15 In our experience in this study, ascertaining the surgical margins’ status from the histopathological report was not always straightforward, as the status was not always clearly concluded in a single sentence. Therefore, interpretation of the reports therefore may be a potential source of error in some cases.
Table 3 Breakdown of the histological diagnoses between the alive and deceased cases Histology (n/%)
Surgical margins (n/%)
Case status
BCCs
Non-BCCs
Cleared
Non-cleared
Alive Deceased
21/29 6/8
26/36 20/27
21/29 10/14
26/36 16/22
BCC, basal cell carcinoma.
3
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Review
Figure 2 Kaplan–Meier survival graphs comparing basal cell carcinoma (BCC) and non-BCC patients.
Figure 3 Kaplan–Meier survival graphs comparing patients with cleared surgical margins and those with non-cleared surgical margins.
CONCLUSIONS
counselling requires a sensitive balance between the honest sharing of statistical information and the effect this information may have on hope and coping. Support frameworks, including both psychosocial strategies and professional networks, should be available to those who may benefit from them. We hope that our data will enable and adequately support more informed patient consent and counselling processes.
Our findings show that our unit had an improved life expectancy and in fact had the highest overall 5-year life expectancy to date. Additionally, our findings indicate that histological diagnosis is significantly more relevant to prognosis than surgical margins. However, the aforementioned uncertainty and limitations in our surgical margins report may have an impact on our results. Nonetheless, these findings support our hypothesis that tumour characteristics play a significant role in life expectancy for patients undergoing orbital exenteration. Enhanced multidisciplinary networking and incremental improvements in the recognition of the roles of other aspects, such as psychology, surgical recovery, wound care, surgical method relative to postoperative cosmesis and postoperative surveillance, are likely to have contributed to an overall improvement in life expectancy. For every malignancy case, it is important use a multidisciplinary head and neck team; additionally, individual prognosis should be tailored after discussions with oncologists, keeping in mind these results. The information on life expectancy may prove valuable to clinicians involved in patient counselling. Once the patient is fully informed of what orbital exenteration involves and the options for postoperative cosmesis, these results should be presented along with a choice of conservative and surgical management plans. However, we would urge caution regarding how and when this information is delivered. Life expectancy
Contributors All authors contributed substantially to conception and design, data acquisition and analysis, manuscript drafting and revision, and final submission. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
2 3 4 5 6 7
8
Table 4 The risk of death (in percentages) for different categorical variables
10
Risk of dying, % Time in months
BCC
Non-BCC
Cleared surgical margins
Non-cleared surgical margins
12 36 60 120
4 16 25 25
16 42 42 77
7 23 31 66
15 39 39 53
BCC, basal cell carcinoma.
4
9
11 12 13 14 15
Clayton JM, Butow PN, Arnold RM, et al. Fostering coping and nurturing hope when discussing the future with terminally ill cancer patients and their caregivers. Cancer 2005;103:1965–75. Buckley J, Herth K. Fostering hope in terminally ill patients. Nurs Stand 2004;19:33–41. Undurraga FJ, Gonzalez M, Calderon J. Counseling: a comprehensive method to support the terminally ill. Rev Med Chi 2006;134:1448–54. Rahman I, Maino A, Cook AE, et al. Mortality following exenteration for malignant tumours of the orbit. Br J Ophthalmol 2005;89:1445–8. Bartley GB, Garrity JA, Waller RR, et al. Orbital exenteration at the Mayo Clinic 1967–1986. Ophthalmology 1989;96:468–73. Mohr C, Esser J. Orbital exenteration: surgical and reconstructive strategies. Graefes Arch Clin Exp Ophthalmol 1997;235:288–95. Mouriaux F, Martinot V, Pellerin P, et al. Survival after malignant tumors of the orbit and periorbit treated by exenteration. Acta Ophthalmol Scand 1999;77:326–30. Nemet AY, Martin P, Benger R, et al. Orbital exenteration: a 15-year study of 38 cases. Ophthal Plast Reconstr Surg 2007;23:468–72. Soysal HG. Orbital exenteration: a 10-year experience of a general oncology hospital. Orbit 2010;29:135–9. Songu M, Unlu HH, Gunhan K, et al. Orbital exenteration: a dilemma in mucormycosis presented with orbital apex syndrome. Am J Rhinol 2008;22:98–103. Kaur A, Khattri M, Jaiswal V. Pattern of orbital exenteration at a tertiary eye care centre in North India. Nepal J Ophthalmol 2012;4:64–7. Rahman I, Cook AE, Leatherbarrow B. Orbital exenteration: a 13 year Manchester experience. Br J Ophthalmol 2005;89:1335–40. Iuliano A, Strianese D, Uccello G, et al. Risk factors for orbital exenteration in periocular Basal cell carcinoma. Am J Ophthalmol 2012;153:238–41.e1. Taylor A, Roberts F, Kemp EG. Orbital exenteration—a retrospective study over an 11 year period analyzing all cases from a single unit. Orbit 2006;25:185–93. Ben Simon GJ, Schwarcz RM, Douglas R, et al. Orbital exenteration: one size does not fit all. Am J Ophthalmol 2005;139:11–17.
Wong JCL, et al. Br J Ophthalmol 2015;99:1–4. doi:10.1136/bjophthalmol-2013-304436
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Life expectancy following orbital exenteration James Chiun Lon Wong, Reshma Thampy and Anne Cook Br J Ophthalmol 2015 99: 1-4 originally published online May 30, 2014
doi: 10.1136/bjophthalmol-2013-304436 Updated information and services can be found at: http://bjo.bmj.com/content/99/1/1
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Review
Life expectancy following orbital exenteration James Chiun Lon Wong,1 Reshma Thampy,2 Anne Cook2 1
Manchester Medical School, Manchester, UK 2 Manchester Royal Eye Hospital, Manchester, UK Correspondence to Dr James Chiun Lon Wong, Accommodation Office, Blackpool Victoria Hospital, Blackpool FY38NR, UK; [email protected] Received 7 October 2013 Revised 6 March 2014 Accepted 16 April 2014 Published Online First 30 May 2014
ABSTRACT Orbital exenteration is a physically debilitating procedure that may be a necessity in the management of orbital malignancy. It requires a sensitive multidisciplinary approach, both preoperatively and postoperatively. Providing life expectancy information for patients during preoperative counselling is pertinent to informed consent and in addressing patients’ expectations. A retrospective review from one tertiary care centre was undertaken for a cohort of patients who were exenterated for orbital malignancy between 1998 and 2010. The cases were identified using an International Classification of Diseases 10th Revision (ICD-10)-derived database and were analysed using Prism statistical software (V.5.04). Cause of death was ascertained by liaising with the general practitioner and the National Registrar Office for Births, Deaths, and Marriages, Southport, UK. In total, 41 men and 32 women were identified. Mean age was 72 years with 47 cases living and 26 deceased at the time of review. The overall 5-year survival rate in this study was 64%. Kaplan–Meier analysis for basal cell carcinoma (BCC) against non-BCC returned a p value of 0.0199, with an HR of 0.3927 (CI 0.1788 to 0.8626). Kaplan–Meier analysis for cleared against non-cleared margins returned a p value of 0.2890, with an HR of 0.6571(CI 0.3024 to 1.428). Our results represent the highest 5-year survival data to date. However, the overall prognosis for patients who undergo orbital exenteration for malignancy remains poor. We hypothesise that the causes are multi-factorial. We recommend a multidisciplinary approach to the care of these patients, involving head and neck teams, oncology and other appropriate specialties, to optimise outcomes for this vulnerable patient group. Orbital exenteration is an extensive procedure that is challenging for both the patient and the surgeon. Relatively few studies have investigated life expectancy and its influencing factors. This study provides statistical information that may be of value to patients and clinicians during counselling.1–3 We hypothesise that tumour characteristics (basal cell carcinomas (BCCs) vs non-BCCs) and their surgical margins (cleared vs non-cleared) play a significant role in life expectancy. Our results refute previous conclusions drawn from data from our unit, which showed non-significance for both parameters.4 Furthermore, at the time of writing, our study reported the highest overall 5-year survival rate reported to date.4–8
BACKGROUND
To cite: Wong JCL, Thampy R, Cook A. Br J Ophthalmol 2015;99:1–4.
Orbital exenteration is reserved for the management of serious orbital disease when other less disfiguring methods are deemed inadequate. It may be indicated for both malignant and non-malignant diseases. Examples of malignant diseases that may require this procedure are BCC, squamous cell carcinoma
(SCC), melanoma, sebaceous cell carcinoma and lacrimal gland carcinoma.9–11 Non-malignant diseases —such as necrotising fasciitis, sino-orbital mucormycosis, neurofibromatosis, end-stage and severe non-specific orbital inflammatory disease with intractable pain and blindness—may occasionally also require such radical surgery. Orbital exenteration is categorised as total, subtotal and extensive. In total exenteration, the entire orbital content is removed together with the eyelid, which is in contrast to subtotal or lid-sparing exenteration, where the lids are preserved for better cosmesis. Certain disease processes can be so damaging to the nearby structures that an extensive exenteration is required; for example, paranasal sinuses may be removed at the same time. A formal multidisciplinary team is recommended in all instances. This team typically includes head and neck, oncology, pathology and other appropriate specialties.
METHODS This study is a retrospective review from one tertiary care centre. This 13-year historical cohort of exenterated patients was identified through theatre operation notes using an International Classification of Diseases 10th Revision (ICD-10) clinical code database. The identified cases were reviewed using the local trust database, PAS (Patient Administration System) and MediSec (electronic patient letter system), the local ophthalmic histopathology database, Sunquest, and the central patient notes library. Inclusion and exclusion criteria were as follows. All exenterated cases for orbital neoplasm from 1 January 1998 to 31 December 2010 were included. All types of exenteration techniques were included. Exclusion criteria were non-neoplastic pathology or surgery to allow the fitting of an orbital prosthesis following previous extensive orbital surgery. Patient demographics and surgical and ophthalmic histopathology details were recorded and analysed. The following were recorded: gender, date of birth, age at death (if applicable), age at exenteration, longevity following orbital exenteration to date of study, histological diagnosis and surgical margins. Cause of death for deceased patients was ascertained by liaising with their general practitioners and the health authority, the National Registrar Office for Births, Deaths, and Marriages in Southport, UK. Data were analysed using Prism, statistical software (V.5.04, available from GraphPad Software Inc., San Diego, California, USA). Life expectancy and survival rates following orbital exenteration were calculated using Kaplan– Meier analysis, whereas categorical variables were contrasted using the log-rank (Mantel–Cox) test and were further supported with the Gehan– Breslow–Wilcoxon test.
Wong JCL, et al. Br J Ophthalmol 2015;99:1–4. doi:10.1136/bjophthalmol-2013-304436
1
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Review This paper received no ethical approval, as the data were completely anonymised, were part of a service evaluation project and did not involve any vulnerable groups. Nonetheless, all of the authors strictly adhered to appropriate local disciplinary, ethical and data protection guidelines.
RESULTS A total of 73 orbits of 73 patients were identified within the 13-year time period. The number of cases analysed was lower than we originally anticipated (97 cases) due to inaccurate coding of clinical episodes. The mean age of our historical cohort was 72 years with an SD of 4–100 years of age. At the time of study, 47 patients were living and 26 were deceased. There were a total of 41 men and 32 women. There was no change in the incidence of exenteration over the 13-year period. However, the 3, 5 and 10-year survival rates improved, as compared with previous outcomes in our unit.4 12
Overall life expectancy This cohort had an overall 1-year life expectancy of 88%. This value was reduced to 68% at 3 years, 64% at 5 years and 38% at 10 years (figure 1). To the best of our knowledge, these values are higher than previous reports on 5-year life expectancy.4–8 Table 1 outlines the details of the 26 deceased cases during the study period.
Histology This cohort consisted of 14 different types of neoplasms. Table 2 shows the proportion of cases according to each histological diagnosis. The histological diagnoses were similar to other studies, where the majority of the cases made up the four groupings of BCC, SCC, sebaceous cell carcinoma and melanoma.4–6 9 12 This fact is relevant when comparing life expectancies across studies. The most common cause for exenteration was BCC. BCCs accounted for 27 cases; the remaining 46 were non-BCCs. In order of frequency, these remaining 46 cases consisted of SCC, sebaceous cell carcinoma, malignant melanoma and others. Of all cases used in the study, histological evaluation indicated that 31 had cleared surgical margins and the remaining 42 had non-cleared surgical margins. Table 3 shows the histological breakdown in between the alive and deceased cases for comparison. It is natural to assume that tumour characteristics should influence life expectancy following orbital exenteration.
Therefore, our patients were divided into two groups based on histological diagnosis. Group 1 included cases with histological diagnoses of BCC. Group 2 included cases with histological diagnoses of non-BCC. The rationale behind this grouping was based on the fact that BCCs are considered to be less aggressive neoplasms.13 This assumption was further confirmed with a Kaplan–Meier survival analysis, as shown in figure 2. When these two categorical variables were compared, the log-rank (Mantel–Cox) test returned a p value of 0.0199, indicating that the survival rate difference between the two groups is statistically significant (table 3).
DISCUSSION The current findings differ from those of Rahman et al4 both in terms of survival rates and the significance of the histological diagnosis. HR analysis between the histological groups revealed that deaths in the BCC group occurred at almost half the rate of those in the non-BCC disease group. The analysis returned an HR of 0.4391 with a 95% CI of 0.2006 to 0.9610. Gehan– Breslow–Wilcoxon analysis of the Kaplan–Meier survival curve comparing histological diagnoses returned a significant p value of 0.0494. This statistical test gives more weight to deaths at early time point. Consistent with this result, table 4 shows that the non-BCC group has a higher risk of dying following exenteration. The median survival for non-BCC patients is 81 months (6.8 years), whereas the median survival for BCC patients is undefined, as fractional survival exceeded 50% at the time of analysis. As figure 2 illustrates, the BCC group maintained a percentage survival greater than 50% through the end of our study. From table 4, it may be extrapolated that the BCC group has a 75% probability of surviving 120 months. We urge that these results be interpreted with caution when they are presented to patients, as dividing our cases into BCC and non-BCC diagnoses is an oversimplification of the problem. The non-BCC group is very heterogeneous, with different metastatic potentials. We chose such a categorisation for easier direct comparison with studies that have been previously performed and published in our unit. Our data confirm our hypothesis that BCC is less aggressive than the non-BCC disorders. Therefore, we would expect the life expectancy of a patient with BCC to be higher than that of a patient with a non-BCC diagnosis undergoing orbital exenteration. Based on our results, the chance of dying from the histological disease is much higher in non-BCC case (table 4). In our cohort of patients who died, the percentage of exenterated BCC patients who died of BCC was 33%, whereas that of non-BCC patients who died of their histological diagnosis was 85%. However, this should be interpreted with caution, as patients often present with multiple comorbidities and different baseline functions at different stages of presentation. Additionally, there is a possibility for error or bias during death certification.
Cleared versus non-cleared surgical margins
Figure 1 Survival rate in 73 cases of orbital exenteration. 2
Surgical margins have always been thought to play an important role in any surgical procedure involving neoplasm. Figure 3 is a Kaplan–Meier survival graph contrasting between the two margin clearance groupings. A log-rank (Mantel–Cox) test revealed that having cleared versus non-cleared surgical margins had no statistical significance on life expectancy (p value of 0.2890). This outcome is further supported by the Gehan– Breslow–Wilcoxon test, which returned a p value of 0.2578. The HR for this category was 0.6571 with a 95% CI of 0.3024 to 1.428. Although the p value is not significant, it is important to note the HR. This value indicates that the non-cleared group Wong JCL, et al. Br J Ophthalmol 2015;99:1–4. doi:10.1136/bjophthalmol-2013-304436
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Review Table 1 Details of the 26 deceased cases in our study Surgical margins and histological diagnosis in the 26 deceased patients from ophthalmic histopathology report
Age/sex
Time from exenteration to death (months)
Surgical margins Y=clear margins N=non-clear margins
Histological diagnosis
Cause of death
Cause of death related to reason for exenteration Y=yes N=no
63/M 52/M 61/M 95/M 66/F 76/M 86/F 62/M 54/F 65/F 76/M 67/M 51/M 93/F 72/F 83/F 65/F 84/M 14/F 92/M 83/F 85/F 77/M 91/M 70/M 83/M
3 17 20 22 119 43 9 2 27 84 15 15 15 28 81 67 11 2 31 3 13 31 35 5 14 9
N Y Y Y Y Y Y Y Y Y Y N N N N N N N N N N N N N N N
Merkel cell carcinoma Malignant melanoma Malignant melanoma Malignant melanoma Sebaceous cell carcinoma BCC SCC BCC Sebaceous cell carcinoma BCC Malignant melanoma Sebaceous cell carcinoma BCC BCC SCC Adenocarcinoma Mucoepidermoid carcinoma Merkel cell carcinoma Rhabdomyosarcoma Mucoepidermoid carcinoma SCC BCC Sebaceous cell carcinoma Malignant melanoma SCC SCC
Heart failure Carcinomatosis Liver metastasis Hepatic metastasis Lung cancer Lung cancer SCC Lung cancer Metastatic carcinoma Metastatic carcinoma of the maxillary atrium Metastatic melanoma Cerebral and lung metastasis from eye Gorlin syndrome Pneumonia Pulmonary embolus Brain tumour Carcinoma Chronic lymphoid Leukaemia Rhabdomyosarcoma Pneumonia Acute cardiac failure COPD and acute renal failure Carcinoma Fall Metastatic carcinoma Multi-organ failure
N Y Y Y Y N Y N Y Y Y Y Y N Y Y Y Y Y Y N N Y N Y Y
BCC, basal cell carcinoma; COPD, chronic obstructive pulmonary disease; SCC, squamous cell carcinoma.
has a 65.71% higher probability of dying by the next time point compared with the cleared group. However, one must note that the lines on the Kaplan–Meier curve eventually crossed so that the cleared margins dropped below the non-cleared margins in terms of survival. Cleared surgical margins have a median
Table 2 Ophthalmic histopathological diagnosis of 73 exenterated cases Histological diagnosis
Exenterated cases, n=73
Basal cell carcinoma Squamous cell carcinoma Sebaceous cell carcinoma Malignant melanoma Adenocarcinoma Meningioma Adenocystic carcinoma (lacrimal gland) Rhabdomyosarcoma Merkell cell carcinoma Mucoepidermoid carcinoma Liposarcoma Fibrous histiocytoma Angiosarcoma Neurofibromatosis
27 14 7 7 3 3 2 2 2 2 1 1 1 1
Wong JCL, et al. Br J Ophthalmol 2015;99:1–4. doi:10.1136/bjophthalmol-2013-304436
survival of 119 months, whereas non-cleared surgical margins have a median survival of 81 months. Our study challenges the presumed influence of marginal clearance on survival by demonstrating that there is no statistically significant difference in survival rates when cleared margin cases are compared with non-cleared cases. This finding confirms those of Rahman et al4 and Mouriaux et al.7 One explanation for this finding is that despite having prevented local recurrence, micro-metastasis may have occurred prior to surgery. Additionally, there are many variables that are involved in providing a cure.12 14 15 In our experience in this study, ascertaining the surgical margins’ status from the histopathological report was not always straightforward, as the status was not always clearly concluded in a single sentence. Therefore, interpretation of the reports therefore may be a potential source of error in some cases.
Table 3 Breakdown of the histological diagnoses between the alive and deceased cases Histology (n/%)
Surgical margins (n/%)
Case status
BCCs
Non-BCCs
Cleared
Non-cleared
Alive Deceased
21/29 6/8
26/36 20/27
21/29 10/14
26/36 16/22
BCC, basal cell carcinoma.
3
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Review
Figure 2 Kaplan–Meier survival graphs comparing basal cell carcinoma (BCC) and non-BCC patients.
Figure 3 Kaplan–Meier survival graphs comparing patients with cleared surgical margins and those with non-cleared surgical margins.
CONCLUSIONS
counselling requires a sensitive balance between the honest sharing of statistical information and the effect this information may have on hope and coping. Support frameworks, including both psychosocial strategies and professional networks, should be available to those who may benefit from them. We hope that our data will enable and adequately support more informed patient consent and counselling processes.
Our findings show that our unit had an improved life expectancy and in fact had the highest overall 5-year life expectancy to date. Additionally, our findings indicate that histological diagnosis is significantly more relevant to prognosis than surgical margins. However, the aforementioned uncertainty and limitations in our surgical margins report may have an impact on our results. Nonetheless, these findings support our hypothesis that tumour characteristics play a significant role in life expectancy for patients undergoing orbital exenteration. Enhanced multidisciplinary networking and incremental improvements in the recognition of the roles of other aspects, such as psychology, surgical recovery, wound care, surgical method relative to postoperative cosmesis and postoperative surveillance, are likely to have contributed to an overall improvement in life expectancy. For every malignancy case, it is important use a multidisciplinary head and neck team; additionally, individual prognosis should be tailored after discussions with oncologists, keeping in mind these results. The information on life expectancy may prove valuable to clinicians involved in patient counselling. Once the patient is fully informed of what orbital exenteration involves and the options for postoperative cosmesis, these results should be presented along with a choice of conservative and surgical management plans. However, we would urge caution regarding how and when this information is delivered. Life expectancy
Contributors All authors contributed substantially to conception and design, data acquisition and analysis, manuscript drafting and revision, and final submission. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
2 3 4 5 6 7
8
Table 4 The risk of death (in percentages) for different categorical variables
10
Risk of dying, % Time in months
BCC
Non-BCC
Cleared surgical margins
Non-cleared surgical margins
12 36 60 120
4 16 25 25
16 42 42 77
7 23 31 66
15 39 39 53
BCC, basal cell carcinoma.
4
9
11 12 13 14 15
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Wong JCL, et al. Br J Ophthalmol 2015;99:1–4. doi:10.1136/bjophthalmol-2013-304436
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Life expectancy following orbital exenteration James Chiun Lon Wong, Reshma Thampy and Anne Cook Br J Ophthalmol 2015 99: 1-4 originally published online May 30, 2014
doi: 10.1136/bjophthalmol-2013-304436 Updated information and services can be found at: http://bjo.bmj.com/content/99/1/1
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