INTRODUCTION:

Cancer is a frequent cause of death in both developing and developed country including Malaysia. It was proven as the third principle cause of death in Malaysia government hospital¹. Even though bone cancer would not become the most diagnosed cancer in Malaysia like breast cancer or lung cancer, the number of cases is still increases per year².

According to World Health Organization (WHO) (2002), the estimated annual incidence of osteosarcoma was approximately 4–5 per million, occurring most commonly in the second decade of life (ages 11–20)³. Stiller et al. (2006) reported in European population that of 5572 cases, osteosarcoma was the most frequent subgroup, accounting for 52.0% of all registrations, while Ewing’s sarcoma was second most frequent, accounting for 34.0% of cases ⁴. Chondrosarcoma and other specified tumors accounted for 6.0% and 4.0%, respectively, and 4.0% of registrations were for tumors of unspecified type. Osteosarcoma was slightly more common than Ewing’s sarcoma, as shown by the ratio of numbers of cases⁵.

According to Second National Cancer Registry 2003, only 176 cases of bone cancer in Peninsular Malaysia had been reported at National Cancer Registry². The incidence was higher in male than female (55.1% versus 44.9%). Most of the cases in both gender groups were in the age range of 10-19 years old. However, not much information of bone cancer in Malaysia had been reported especially for osteosarcoma.

According to Ajiki (2003), survival rates for total period from 1975 to 1994 of malignant bone tumor in childhood patients in Osaka, Japan was 52.8%⁶. When compared a five-years relative survival rate from 1985 to 1994 in Osaka, England and Wales, and SEER, USA, their survival rate were 57.0% (95% CI:45.6, 68.4), 51.0% and 66.9%. Survival rates for these three places are not much different. Five-year survival rate for European osteosarcoma patients were higher (58.0%) than survival rate for Ewing’s sarcoma (42.0%)⁷.

Survival rate for all bone tumors combined in European was significantly higher among children (n=554, 5-year survival 58.0%, 95% CI 53, 62) than among adolescents (n=483, 5-year survival 47.0%, 95% CI 43, 52)⁴. Survival rate for European osteosarcoma patients at the period of 1990-1994 varied with age: 65.0% in 10–14 year olds, 55.0% in 15–19 year olds and 64.0% in 20–24 year olds⁸. A study by Gurney et al., (1999) in the USA also reported that survival was worse at age 15-19 than at age 10-14years for osteosarcoma⁹.

Over the past three decades, effective induction (neoadjuvant/preoperative) and adjuvant (postoperative) chemotherapy protocols had improved the ability to perform safe limb-sparing resections, and disease-free and overall survival rates had risen. Today, 90.0 to 95.0% of patients with osteosarcoma could be treated with limb-sparing surgery, and 60.0 to 80.0% of patients with localized disease were long-term survivors¹⁰.

An advent of adjuvant chemotherapy, patient survival improved from 40.0% to 50.0%¹¹. Because chemotherapy had significantly improved the survival for osteosarcoma, patients who had tumors that were resistant to chemotherapy would be expected to have a poorer outcome¹². The outcome of osteosarcoma continues to improve with better treatment.

A study in European osteosarcoma patients’ age over 40 years, survival was found to be significantly better in patients having limb salvage surgery, an observation made in other studies and it was probably a reflection not only of the size and resectability of the tumor, but also of the response to neoadjuvant chemotherapy¹³.

The aim of this study was to determine the five-year survival rate of osteosarcoma patients treated at HUSM. Differences in demography, culture and belief may give different result in survival rate for Malaysian compared to other country.

MATERIAL AND METHODS:

A retrospective record review study was done where the recruitment phase of the subjects began from 1^st August 1995 till 31^st July 2006. Additional follow up period of twelve months, after the recruitment of subjects from 1^st August 2006 till 31^st July 2007, was included. The reference population was all patients diagnosed with osteosarcoma in Peninsular Malaysia. Source population was all patients diagnosed with osteosarcoma treated at Hospital Universiti Sains Malaysia (HUSM) during the study period.

The participants were all patients diagnosed with osteosarcoma with confirmed histological and clinical diagnosis. Coding used was as ICD-9-CM code (170) by International Classification of Disease Clinical Modification 9^th editions (before 2000) and as ICD-10 (C40.0-C41.9, C76.0-C76.8, C80.9) by International Classification of Disease for Oncology 10^th editions (from 2000)¹⁴. These participants should have undergone a treatment at least once in HUSM. All patients who refused to be treated or took all treatment from other hospitals were excluded because no data was found according to their treatment. Patient from places other than Peninsular Malaysia and with more than 30% missing data were also excluded.

The calculation of sample size was performed using Power and Sample Size Calculation (PS) software with requirements for level of significance (α) 0.05 and power (1-β) 0.80¹⁵. The median survival time on control treatment (m₁) was 60months and ratio of control to experimental patients (m) was 1.63¹⁶. The detectable hazard ratio (R) was 2.35 was decided by the researcher and expert opinion by clinicians. The accrual time during which patients were recruited (A) was 11 years (132 months) and the additional follow up time after the end of recruitment was 12 months. An estimated 10% was added for the anticipation of non-response. Total sample size that was obtained was 128. There was no probability sampling done since available patients’ medical records obtained were less than predetermined sample size calculated.

About 127 patients were diagnosed as osteosarcoma at recruitment. All important information in the record liked socio-demographic status, clinical characteristics and treatment modalities were collected by using data collection sheet from medical record unit. Before collecting, all registration numbers (RN) from medical record unit for all patients who had been diagnosed as osteosarcoma treated in HUSM were gathered. Patient’s status was obtained from the medical record and contacting their residence through house phone number or home visit with their consent. A single researcher retrieved the required information.

In sociodemographic characteristics, age at diagnosis defined as the difference of the year of diagnosis by the doctor as having osteosarcoma and the year the patient was born. Since most patients treated in HUSM were Malay, ethnicity was divided into Malay and non-Malay. In clinical characteristics, duration of symptoms was defined as onset of pain and swelling report by patients in their first admission. It’s divided into<70 days and≥70 days. 70 days had been chosen because from expert opinion, it was the best time where the symptoms shown. Tumor site was divided into femur, tibia, humerus, fibula and others. ALP and LDH were obtained from laboratory test sheet. Stage at diagnosis was obtained by using Enneking staging documented in patient’s record. Primary metastasis was assumed whenever it occurs at lung, brain or others bone at the time they had been diagnose as osteosarcoma. For treatment modalities, delay of treatment was difference of the date of first treatment patients had received and the date of diagnosis as osteosarcoma. Types of chemotherapy were divided into neoadjuvant, adjuvant and neoadjuvant with adjuvant. Types of surgery were divided into limb salvage and amputation. If the patients received amputation due to infection after doing limb salvage, it considered as limb salvage treatment.

Ethical issue was considered since medical records were explored to obtain information about the patient. Consent form was posted to patients who were still alive or given when patients came to the hospital during follow-up. A permission to look into patients’ medical record in medical record unit was obtained from the Director of Hospital Universiti Sains Malaysia. Instead of using the patient’s RN in the data collection sheet, a confidentiality code was used by researcher and was kept at a separate location with a confidential safe guard. Ethical clearance was obtained from research and ethics committee of Universiti Sains Malaysia on 19^th August 2007 (reference number: USMKK/PPP/JEPeM [194.4(3.1)]).

Statistical Analysis:

Mean and standard deviation (SD) for numerical variable was obtained. Meanwhile, for categorical variable, frequency and percentage for the observations were obtained. Statistical analysis that was used in this study was survival analysis. The outcome variable was survival time which was the time to an event of interest. In this study, survival time refers to the time from diagnosis to death of patients. A death was considered as a terminal event, if the death was due to osteosarcoma or complications of its treatment.

The survival probability was obtained by using the Kaplan-Meier (KM) survival analysis. Median survival time was defined as first observed time at which cumulative survival was 50% or less (time when half of the patients die). Five-year survival rate in this study was defined as the number of osteosarcoma patients treated in HUSM survived within five years after diagnosis over the total number of osteosarcoma patients treated in HUSM within the period of the study (in percentage). The comparison of survival times in all categorical independent variables groups was done by using log-rank test.

SPSS, version 12.0.1¹⁷ was used to perform data entry and STATA/SE software, version 9.2¹⁸for analyzing the data. Data from SPSS was transferred to STATA/SE by using STATA Transfer software, version 6.0.

RESULTS:

Mean (SD) age for osteosarcoma patients were 18.48 years (8.77 years). According to age group, about 37 (29.1%) of the patients were younger than 14 years, 54 (42.5%) were between 14 years to 19 years and 36 (28.3%) of them were aged more than 19 years. More than half of the patients with osteosarcoma were male (81 [63.8%]) and majority of them were Malay race (108 [85.0%]). Clinical characteristics of 127 patients with osteosarcoma showed that 75 (59.1%) of the patients had a duration of symptoms less than 70 days. Most of the tumor was at femur (53[41.7%]) and in stage II (77[60.6%]). It was also revealed that 96 (75.6%) of the patients did not present with metastases at diagnosis. 88 (69.3%) of the patients with osteosarcoma had a treatment less than three weeks and only 39 (30.7%) had a treatment more than three weeks. Most of the patients are having neoadjuvant with adjuvant chemotherapy (66[52.0%]) compare to 39 (30.7%) having neoadjuvant chemotherapy alone and 17 (13.4%) having adjuvant chemotherapy alone. Only 5 (3.9%) of these patients did not get chemotherapy. About 62 (48.8%) of the patients had limb salvage for surgery and 32 (25.2%) had amputations. The remaining (33 [26%]) did not get surgery (Table 1).

Table (1) Descriptive of patients with osteosarcoma treated in HUSM (n=127)

Characteristics

Mean (SD)

Frequency (%)

Died [n (%)]

Censored [n (%)]

Sociodemographic:

Age (year)

≤14 years

14–19 years

≥19 years

18.48 (8.77)

37 (29.1)

54 (42.5)

36 (28.3)

13 (10.2)

28 (22.0)

21 (16.5)

24 (18.9)

26 (20.5)

15 (11.8)

Gender

Female

Male

46 (36.2)

81 (63.8)

20 (15.7)

42 (33.1)

26 (20.5)

39 (30.7)

Ethnicity

Non-Malay

Malay

19 (15.0)

108 (85.0)

7 (5.5)

55 (43.3)

12 (9.4)

53 (41.7)

Clinical Characteristic:

Duration of symptoms

<70 days

≥70 days

75 (59.1)

52 (40.9)

38 (29.9)

24 (18.9)

37 (29.1)

28 (22.0)

Tumor site

Femur

Tibia

Humerus

Others

53 (41.7)

38 (29.9)

19 (15.0)

17 (13.4)

28 (22.0)

15 (11.8)

10 (7.9)

9 (7.1)

25 (19.7)

23 (18.1)

9 (7.1)

8 (6.3)

Alkaline Phosphatase:

Normal

Elevated

586.74 (931.34)

23 (18.1)

102 (80.3)

8 (6.4)

54 (43.2)

15 (12.0)

48 (38.4)

Lactate Dehydrogenase :

Normal

Elevated

809.85 (685.97)

1 (0.8)

106 (83.5)

0 (0.0)

51 (47.7)

1 (0.9)

55 (51.4)

Stage at diagnosis

Stage I

Stage II

Stage III

13 (10.2)

77 (60.6)

37 (29.1)

6 (4.7)

34 (26.8)

22 (17.3)

7 (5.5)

43 (33.9)

15 (11.8)

Metastases at diagnosis

Yes

96 (75.6)

31 (24.4)

44 (34.6)

18 (14.2)

52 (40.9)

13 (10.2)

Treatment modality:

Delay of treatment :

≤3 weeks

>3 weeks

24.51 (41.84)

88 (69.3)

39 (30.7)

46 (36.2)

16 (12.6)

42 (33.1)

23 (18.1)

Type of chemotherapy

No chemotherapy

Neoadjuvant

Adjuvant

Neoadjuvant and

Adjuvant

5 (3.9)

39 (30.7)

17 (13.4)

66 (52.0)

3 (2.4)

28 (22.0)

12 (9.4)

19 (15.0)

2 (1.6)

11 (8.7)

5 (3.9)

47 (37.0)

Type of surgery

No surgery

Limb salvage

Amputation

33 (26.0)

62 (48.8)

32 (25.2)

27 (21.3)

12 (9.4)

23 (18.1)

6 (4.7)

50 (39.4)

9 (7.1)

The overall median survival time for 127 patients with osteosarcoma treated in HUSM was 47.77 months. Table 2 showed the median survival time for other independent variables.

Table (2) Median survival time of patients with osteosarcoma treated in HUSM (n=127)

Variable	Median survival time (95% CI) (months)	Log rank statistics (df)	P-value
Age (year) ≤14 years 14–19 years ≥19 years	- 47.77 (14.83,80.70) 23.90 (5.80,42.00)	3.28 (2)	0.194
Sex Female Male	- 38.03 (9.21,66.86)	0.36 (1)	0.548
Ethnicity Non-Malay Malay	- 38.03 (7.30,68.77)	1.14 (1)	0.286
Duration of symptoms <70 days ≥70 days	40.00 (0.05,79.95) 47.77*	0.40 (1)	0.528
Tumor site Femur Tibia Humerus Others	38.03 (3.56,72.50) - 31.73* 31.53 (0.00,64.59)	2.54 (3)	0.469
Stage at diagnosis Stage I Stage II Stage III	- 65.93* 16.27 (6.38,26.15)	4.47 (2)	0.107
Metastases at diagnosis No Yes	65.93* 16.27 (7.13,25.40)	3.02 (1)	0.082
Delay of treatment ≤3 weeks >3 weeks	37.10 (15.48,58.72) -	1.33 (1)	0.249
Type of chemotherapy No chemotherapy Neoadjuvant Adjuvant Neoadjuvant and adjuvant	14.47 (0.00,44.74) 8.57 (6.12,11.01) 31.73 (8.95,54.52) -	31.64 (3)	<0.001^a
Type of surgery No surgery Limb salvage Amputation	7.03 (4.71,9.36) - 19.17 (7.89,30.44)	71.05	<0.001^a

*cannot be determined

Table (3) Five-year survival rate from Kaplan-Meier estimate of osteosarcoma patients according to characteristics (n=127)

Characteristics

Survival Rate (%)

95% CI

Lower limit

Upper limit

Socio-demographics

Age (year)

≤14 years

14–19 years

≥19 years

59.3

47.3

40.6

39.1

32.8

24.4

74.8

60.5

56.1

Sex

Male

Female

45.8

54.8

33.9

38.9

56.9

68.2

Ethnicity

Non-Malay

Malay

62.7

46.5

37.3

36.2

80.2

56.2

Clinical

Duration of symptoms

<70 days

≥70 days

48.9

49.2

36.7

33.9

60.0

62.9

Tumor site

Femur

Tibia

Humerus

Others

46.0

57.2

45.6

44.8

31.6

38.8

22.5

20.3

59.3

72.0

66.1

66.8

Stage at diagnosis

Stage I

Stage II

Stage III

51.9

52.3

39.6

22.5

39.3

23.9

75.0

63.8

55.0

Metastases at diagnosis

Yes

51.3

40.8

40.0

23.5

61.5

57.5

Treatment modalities

Delay of treatment :

≤3 weeks

>3 weeks

44.4

59.4

33.2

41.6

55.1

73.3

Type of chemotherapy:

No chemotherapy

Neoadjuvant

Adjuvant

Neoadjuvant and adjuvant

40.0

25.9

21.9

70.6

5.2

12.9

5.5

57.2

75.3

41.0

45.0

80.4

Type of surgery

No surgery

Limb salvage

Amputation

16.2

80.5

21.6

5.7

67.3

8.7

31.4

88.7

38.4

^aAfter doing Bonferroni correction which compare with α=0.017, it showed that there were a significant difference between no surgery and amputation (p=0.004), no surgery and limb salvage (P<0.001) and amputation and limb salvage (P<0.001). For type of chemotherapy, after doing Bonferroni correction with α=0.008, it showed that there were a significant difference between neoadjuvant and neoadjuvant with adjuvant chemotherapy (P<0.001) and adjuvant and neoadjuvant with adjuvant chemotherapy (P<0.001).

Table 3 showed the five-year survival rate for osteosarcoma patients treated at HUSM for other variables. The overall five-year survival rate was 48.9% (95% CI: 39.4, 57.8)

There were only two variables showed significant differences of median survival between groups in log-rank statistics, which were type of chemotherapy P<0.001) and type of surgery (P<0.001) (Fig. 1). After doing Bonferroni correction which compare with α=0.017, it showed that there were a significant difference between no surgery and amputation (P=0.004), no surgery and limb salvage (P<0.001) and amputation and limb salvage (P<0.001). For type of chemotherapy, after doing Bonferroni correction with α=0.008, it showed that there were a significant difference between neoadjuvant and neoadjuvant with adjuvant chemotherapy (P<0.001) and adjuvant and neoadjuvant with adjuvant chemotherapy (P<0.001).

(a) Type of chemotherapy

(b) Type of surgery

Fig. 1: Kaplan-Meier survival curves (a) type of chemotherapy (b) type of surgery

DISCUSSION:

The profile of the patients described in the present study was not different from that were observed in other studies. The study by Bielack et al. (2002) from German, Stiller et al. (2006b) from Britain, Bacci et al. (2005a) from Italy and Settakorn et al. (2007) from Thailand showed that a number of male patients in their study were higher compared to female patients, which was similar in the present study ^19,20,21,22. A review by Picci (2007) from Rizzoli Orthopaedic Institute, Scientific Institution for Research Hospitalization and Health Care, Bologna, Italy also showed that males were more frequently affected than females (ratio 1.5:1)²³.

Mean age in continuous variable was 18.48 (8.77) years in the present study which was similar with study from South Korean by Kim et al. (2007) (mean age 18.50 years) ²⁴. While age in categorical showed that most of the patients were at age 14 to 19 years (42.5%) compared to 29.1% in age less than 14 and 28.3% in age more than 19 years. It was supported by Bacci et al. (2005) where they categorized age into two groups, which were less than or equal to 14 and more than 14. They showed that 60% of patients were age more than 14 and 40% patients were age less than or equal to 14²¹. It means that osteosarcoma occurred mostly among adolescents and adult age groups.

Ethnicity had been categorized into two groups which were Malay and non-Malay. A percentage of patients showed that 63.8% of the osteosarcoma patients in HUSM were Malays and only 36.2% was non-Malays. It contrasts with a study by Silva & Subramanian (1975 cited from Yip et al., 1996) where they found that incidence of osteosarcoma in Malaysia was higher in Chinese subpopulations (0.23 cases per 100,000 populations per year) compared to Malay subpopulations (0.11 cases per 100,000 populations per year)^25,26. The difference might have been noted because the previous study was an epidemiological study of osteosarcoma patients in Malaysian populations. For the present study, it was a study conducted in Kelantan population and 95% of population in Kelantan was Malays²⁷.

In the present study, tumor site was occurred more in femur (41.7%) than tibia (29.9%), humerus (15.0%) and others (13.4%). This result supported by study from Brazil by Rech et al. (2004) and Bacci et al. (2005) from Italy where they also showed that femur was the most favorable site compared to the other sites [16,21]. It might have been noted because nearly 80.0% of osteosarcoma cases occurred in the long bones of the lower limbs and only about 5.0% in the central axis and 30.0% in the lower limbs^28,29. In the present study, 62 (48.8%) of osteosarcoma patients were treated with limb salvage for surgery treatment compared to 32 (25.2%) treated with amputation. It was similar to the South Korean study where 376 patients were treated with limb salvage compared to only 44 patients having amputation²⁴. This situation occurred with possible reason being limb salvage had become an alternative surgery treatment compared to amputation. It made patients confident to have a surgery since they might have less likely to become handicapped.

In this study, an overall five-year survival rate for osteosarcoma patients treated in HUSM was 48.9% (95% CI: 39.4, 57.8). It was higher compared to study in Brazil by Rech et al. (2004), where the overall five-year survival rate was 33.2%. The difference might have been noted as the patients included in the previous study were specified into patients with histological diagnosis of high-grade osteosarcoma and age less than 22 years. The smaller samples which were 50 participants may have influenced overall survival rate. In contrast, a study in German by Bielack et al. (2002) and a study by Bacci et al. (2005a) in Italy have shown higher overall five-year survival rate, which were 65.3% and 66.0% respectively compared to the present study^19,21. The difference might have been noted because these studies were based on the bigger sample from population data which were 1702 and 1148 participants. Both studies also included all participants who started their treatment at the beginning of the study and most of the participants had completed the treatment. This situation may have increased the survival rate of the patients.

Present study showed that five-year survival rate for females was higher (54.8%) compared to males (45.8%). But the difference was not significant in log-rank test. This result was similar to the study by Bielack et al. (2002) where five-year survival rate for females was 67.4% compared to males (63.9%) and it was not statistically significant in log-rank test¹⁹. The survival in previous study was higher compared to present study which might have been because the sample size was bigger (1702 patients) and about 1160 patients survived at the end of the study. A bigger sample size and a higher number of osteosarcoma patients survived within five year would increase the five-year survival rate of the osteosarcoma patients.

Five-year survival rate for duration of symptoms more than 70 days was higher (49.2%) compared to duration of symptoms less than 70 days (48.9%) in the present study. The results were not much different and log-rank test was not significant. It might have been noted because within five year, death had occurred more at duration of symptoms less than 70 days compared to duration of symptoms more than and equal to 70 days. It was in a contrast to the results from study by Bielack et al. (2002) where five-year survival rate for duration of symptoms less than 70 days was higher (64.4%) compared to duration of symptoms more than 70 days (61.2%). But it was not significant for log-rank test ¹⁹. The reason might have been because of poor tumor response which was higher (218 patients) for duration of symptoms more than 70 days than duration of symptoms less than 70 days (193 patients). Maybe within five year, a number of deaths were higher for duration of symptoms more than and equal to 70 days compared to duration of symptoms less than 70 days. So, it would have affected survival rate of the patients.

In the present study, five-year survival rate of tumor site at tibia (57.2%) was higher compared to femur (46.0%) and humerus (45.6%). This result was similar with results from UK’s study where they found that five-year survival rate at tibia (61.0%) was higher compared to femur (54.0%) and humerus (51.0%)³⁰. But five-year survival rate results from previous study showed higher than present study. Possible reason being survival time for previous study was calculated from date of surgery compare to present study where they calculated from time at diagnosis. Because of that, might be more patients would survive in the previous study compared to present study within five year and it affected the survival rate.

Five-year survival rate for metastases at diagnosis in the present study was higher for absence of metastases (51.3%) compared to presence of metastases (40.8%). This result was similar with the study from Germany which showed that five-year survival rate for absence of metastases was higher (72.1%) than presence of metastases (31.6%)¹⁹. But log-rank test for previous study showed significant result compared to present study. It was because five-year survival rate for previous study showed a great difference for that category compared to the present study. It also showed that in the previous study, the presence of metastases had 46.6% of poor tumor response compared to the absence of metastases (44.1%). Within five year, it might be more patients were death in presence of metastases group compared to absence metastases which would affect patient’s survival.

In this study, result for delay of treatment showed that delay of treatment more than three weeks had higher (59.4%) five-year survival rate compared to delay of treatment less than or equal to three weeks (44.4%). In contrast, result for five-year survival rate by Bielack et al. (2002) showed that delay of treatment less than or equal to three weeks was higher (65.4%) than delay of treatment more than three weeks (64.4%)¹⁹. The difference might have occurred because in the present study, patients who had died when delay of treatment was less than or equal to three weeks within five year was higher compared to delay of treatment more than three weeks. However in previous study, patients for delay of treatment more than three weeks had higher poor tumor response compared to delay of treatment less than or equal to three weeks within five year. It would have affected patient’s survival.

Five-year survival rate for limb salvage was higher (80.5%) compared to amputation (21.6%) in the present study. This result was similar with study in the UK and South Korean where they showed that five-year survival rate for limb salvage was higher (61.0% and 63.6%, respectively) compared to amputation (42.0% and 40.8%, respectively)^24,30. Results from present study were larger in percentage than previous study because within five year, a number of patients was higher in limb salvage group but had lower number of died patients. It contrast with amputation group where a number of patients was lower but higher in a number of died patients. It was a possible reason why present study had larger percentage than previous study.

There was a limitation of the study that needed to be considered before interpreting the finding of the study. The data for each variable was obtained from medical records. Some of the records were not completed due to missing of records and some of the records were lost especially for non active folders. Besides, the investigator sometime could not get the information before diagnosis like biochemical test (ALP and LDH). So, the baseline data for this information that was important as a prognostic factor could not be determined. Tumor volume or size also could not be determined. Even though it could be found in MRI sheet, however some clinicians did not note down the volume of the patients in MRI sheets and sometimes the sheets were lost. So these variables had been excluded to avoid bias due to large missing data.

HUSM was one of the reference centers for osteosarcoma patients in Malaysia. If other study for osteosarcoma was conducted, it would have been better if the data was taken from all centers in Malaysia. The result for variables such as ethnicity or age was more valuable since the sample was referred to Malaysian population.

As the conclusion, majority of osteosarcoma patients treated in HUSM in this study were in age 14 to 19 years, males and Malays. More than half of these patients had duration of symptoms less than 70 days, tumor site at femur, in stage II at diagnosis and absence of metastasis at diagnosis. Most of the patients were neoadjuvant with adjuvant chemotherapy and limb salvage as their favorable treatment. Delay of treatment mostly occurred less than three weeks.

Overall median survival time reported in this study was 47.77 months. The highest median survival time could be seen in stage II and absence of metastases at diagnosis, while the lowest median survival time was for no cases of surgical treatment. Overall five-year survival rate was 48.9%. Majority five-year survival rate of each variable was more than 40.0%. But neoadjuvant, adjuvant and amputation alone showed a five-year survival rate less than 30.0%. Combination of these treatments increased survival rate since neoadjuvant with adjuvant chemotherapy showed highest five-year survival rate.

ACKNOWLEDGEMENT:

We thank "Institute for Community Development and Quality of Life" at Universiti Sultan Zainal Abidin for assistance us, for comments that greatly improved the manuscript and for publish the manuscript.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 24.11.2017 Modified on 11.01.2018

Research J. Pharm. and Tech 2018; 11(8): 3534-3542.

DOI: 10.5958/0974-360X.2018.00653.4