Folia Medica Indonesiana Vol. 44 No. 2 April – June 2008 :
TREATMENT RESPONSE AND ACUTE TOXICITY EVALUATION OF 70 GRAY RADIATION
IN NASOPHARYNGEAL CARCINOMAPATIENTSINDRSOETOMOHOSPITAL, SURABAYA
H. Sugiarto Suwitodihardjo2
1Department of Radiology, NegaraHospital, Jembrana, Bali
2Department of Radiology, AirlanggaUniversitySchool of Medicine, Dr Soetomo Teaching Hospital, Surabaya
Nasopharyngeal carcinoma (NPC) is the most common malignancy of head and neck cancer in Indonesia. Radiotherapy is the mainstay of treatment for NPC. Usually external beam radiation treatment is performed with dose of 60-70 Gy. Result of irradiation treatment is influenced by some prognostic factors including gender, age, tumor stage, histopathologic and hemoglobin level. In addition to eradicate tumor cell, irradiation treatment also influences acute effect (acute toxicity) of normal tissue surrounding tumor as well as late effect. This study was performed with an observational cohort retrospective analysis, which analyzed 54 patients of NPC who had underwent irradiation with cumulative dose of 70 Gy for evaluating the correlation between some prognostic factors and treatment response, and for evaluating acute toxicity. There was positive correlation between tumor stage and irradiation treatment response, proven by Kruskal-Wallis statistic analysis (p = 0.021). Meanwhile, by using Fisher Exact one-tail method there were statistically significant association of irradiation treatment response between patient with stage III and stage IV (p = 0.035 and Odds Ratio = 10.8). The patient with stage III shows predominant risk to have complete response comparing with partial response which 10.8 times higher than those in stage IV. It indicated that dose given of 70 Gy for NPC patients in the early stage had a better treatment response. There were no significant correlation between sex, age, histopathologic and hemoglobin level with irradiation treatment response (p > 0.05). Radiation toxicity was calculated by LENT SOMA scale. Most radiation toxicity was acute with moderate toxicity (grade II).
Keywords: NPC, prognostic factor, treatment response, radiation toxicity.
Correspondence: Nyoman Satya, Department of Radiology, NegaraHospital, Jl. Wijaya Kusuma 17, Negara, Jembrana, Bali, phone: 62-365-41006, email:
Folia Medica Indonesiana Vol. 44 No. 2 April – June 2008 :
Nasopharyngeal carcinoma (NPC) is a malignant tumor in head and neck area that is still widely found worldwide, particularly in Southeast Asia, including Indonesia. The incidence rate in south Chinese population is ranging between 30-50 per 100,000 (Chong 1997; Christophorus 2003; Moorhead 1994; Perez 1998). In Indonesia, the incidence rate of NPC reaches 4.7 per 100,000 populations (Asroel 2002). In Dr Soetomo Hospital, Surabaya, and in Dr Cipto Hospital, Jakarta, NPC holds the third rank among all other malignancies after uterine cervical carcinoma and breast cancer (Christophorus 2003).
Radiotherapy is a therapy of choice in NPC, which is generally given as external radiation. Radiotherapy treats cancer by using high-energy rays (60-70 Gy) to destroy cancer cells, while doing as little harm as possible to normal tissue. The radiotherapy is usually given to the lymph glands in the neck as well as the nasopharyngeal area.
Treatment response against radiation is varied among individuals. It is influenced by several prognostic factors, such as sex, age, stage of disease, the type of tumor histopathology, and hemoglobin level (Ma 2001; Oksuz 2004; Perez 1998; Stevens 1998). In addition to eradicating tumor, radiotherapy may also result in varied side effects (toxicity) to adjacent normal tissues, either acute or chronic. The presence of varied radiotherapy response in NPC, different correlation between radiation prognostic factors and radiation treatment response in several studies both in Indonesia and other countries, and the absence of publication on radiation toxicity among NPC patients in Radiotherapy Installation, Dr Soetomo Hospital, Surabaya, have driven the author to perform this study. The objective of this study was to determine correlation between several prognostic factors, such as sex, age, stage of the disease, tumor histopathological type, and Hb level of NPC patients with radiation treatment response, and to determine the degree of acute radiation toxic effect in patients with NPC.
MATERIALS AND METHODS
This study used retrospective cohort observational analysis method by observing the result of CT scan pre- and post-radiation in 54 NPC patients referred to Radiotherapy Installation, Dr Soetomo Hospital, Surabaya, from October 2005 to March 2006. To find the strength of correlation between independent and dependent variables, we performed bivariate analysis of Kruskal-Wallis method with significance level of p < 0.05. The risk of exposure to radiation treatment response was estimated with odd ratio (OR). We also assessed radiation acute toxicity using LENT SOMA scale.
In this study, there were 78 NPC patients between October 2005 and March 2006 who had conducted radiotherapy in a cumulative dose of 70 Gy, ranging between 1 - 2 months earlier. From those 78 patients, only 54 met the inclusion criteria and were included as the object of study. The distribution of NPC patients based on several prognostic factors, such as sex, age, stage of disease, the type of tumor histopathology, and hemoglobin level, can be seen in the following table.
Table 1. Characteristics of NPC patients based on five independent variables in Radiotherapy Installation, Dr Soetomo Hospital, Surabaya, October 2005 - March 2006Variables / Frequency / Percentage (%)
Female / 39
15 / 72.2
< 50 years
50 years / 33
21 / 61.1
WHO type 2
WHO type 3 / 0
48 / 0
IV / 0
31 / 0
< 13 g/dl
13 g/dl / 32
22 / 59.3
The assessment of the rate of NPC response rate on radiation was based on the result of CT scan evaluation pre- and post-radiotherapy. From all NPC patients, 13% had complete response (CR), 75% had partial response (PR), and 13% were progressive (P). There were no NPC patients who showed no response (NR). Radiation toxicity measured with LENT SOMA scale in this study indicated that 64.8% of toxicity occurred in grade II (moderate), 29.6% grade I (mild), 5.6% grade III (severe). There was no toxicity grade IV. Severe toxicity was found in three patients whose hemoglobin level reduced after receiving several radiation fractions and the patient required transfusion prior to the continuation of radiation.
The result of Kruskal-Wallis test showed significant difference in treatment response between disease stages, or the presence of significant correlation between disease stages and radiation therapy response in NPC patients, with Kruskal-Wallis Test values of 7.704 and significance level (p) of 0.021. However, this study did not find correlation between age (p = 0.940), sex (p = 0.349), tumor histopathology (p = 0.910), and hemoglobin level (p = 0.916) with radiation treatment response. Using one-tail Fisher's Exact test, it was found that there was significant correlation between treatment response between stage III and IV with p = 0.035 and OR = 10.8. This indicated that stage III had a risk of having complete response (CR) 10.8 times higher than that in stage IV. Thus, in radiation of 70 Gy dose NPC cancer with earlier stage had better treatment response. The summary of bivariate analysis among the variables in this study was presented in Table 2.
From the result of observation, it was found that NPC was mostly present in those of more than 50 years (61.1%), with average age of 43.8 years. In China the highest incidence was in those between 40-49 years (Chong 1997), while in the USA the incidence peak was found in age 50-59 years (Perez 1998). Most of NPC patients were male (72.2%) with male : female ratio 2.6 : 1. Compared to the incidence in most countries in the world, the male : female ratio was 2.5-3 : 1 (Chong 1997; Lo 2005; Moorhead 1994; Paulino 2004; Perez 1998). Based on its histopathology, most (88.9%) of NPC patients had type 3 WHO, there were no NPC patients with WHO histopathology type 1. This study was similar to that in the study of Shanmugaratman in Singapore, as quoted by Chong (1997) and the study by Prathap in Malaysia found that NPC patients with WHO type 1 were only about 0.9% - 2%. However, in the Unites States, Low (2005) found that NPC patients with histopathology of WHO types 1, 2, and 3 were respectively 20%, 10%, and 70%. At the time of diagnosis establishment, most of the patients (90.7%) in this study came in advanced stage and only 9.3% were in early stage. Almost similar to the condition of NPC patients in southern China and Hong Kong, about 70% of the patients came in stage III or IV (Ma 2001). According to Chong (1997), based on his screening in China, the proportion of diagnosed NPC patients in stage I was less than 10%.
Table 2. Results of bivariate analysis between the variables of age, sex, histopathology, disease stage, and Hb level with radiation treatment response in NPC patients at Radiotherapy Installation, Dr Soetomo Hospital, Surabaya, between October 2005 and March 2006.
ResponseCR (%) / PR (%) / P (%)
Age< 50 years
≥ 50 years / 12
14 / 76
72 / 12
p Value p = 0.940
Female / 10
20 / 80
60 / 10
p value p = 0.349
HistopathologyWHO type 1
WHO type 2
WHO type 3 / 0
12 / 0
76 / 0
p value p = 0.910
IV / 0
3 / 0
87 / 0
p value p = 0.021
Hb level< 13 g/dl
13 g/dl / 15
6 / 70
80 / 12
p value p = 0.916
Among the five independent variables in this study, it was only the disease stage that had significant prognosis on radiation therapy. The variables of sex, age, tumor histopathology, and Hb level did not have significant correlation to radiation therapy response, probably due to insufficient sample size and the data characteristic of those four variables were almost homogeneous.
The result of this study was different from the result of several studies in a number of hospitals, local or abroad, in which there were only 13% of the patients had complete response, while most (74%) of the radiation therapy response was partial response, and 13% of them had progressive response. Affandi (1992), as cited by Kentjono (2001), in HasanSadikinHospital, Bandung, found that the complete response rate was 65.9%, without mentioning the cumulative radiation dose. Suwitodihardjo (1993-1995) in Adi Husada Hospital, Surabaya, who performed external radiation to CNP patients in cumulative dose of 60 Gy - 70 Gy, found complete response 61% and partial response 39%. A study by Kentjono (2001) in Dr Soetomo Hospital, Surabaya, found high response (CR) as much as 23.68%, while the lower response (CR, NR, P) was as much as 76.31%. The low complete response in this study was due to several factors. First, many of the patients came in advanced stage (III and IV). Second, time required from NPC diagnosis to radiotherapy was averagely 3 months, due to which the patient's condition became more severe along with the course of the disease. It was different from the study of Suwitodihardjo (1995) in AdiHusadaHospital, Surabaya, in which most of the patients were in early stage (stage I and II) and they directly received radiotherapy right after the diagnosis was established.
The result of observation to the radiation toxicity measured based on LENT SOMA scale in this study indicated that most (64.8%) of the toxicity was acute, with moderate grade (grade II). Suwitodihardjo (1997) studied radiation complication in 62 NPC patients in AdiHusadaHospital, Surabaya, and only found mild toxicity, no moderate or severe toxicity. This study only observed NPC radiation treatment response related with its prognostic factor and radiation complication, which presented as acute toxic effect in a short period (approximately 1-2 months post-radiation). Either survival rate or chronic (advanced) toxic effects could not be evaluated as the studies in other countries.
Significant correlation exists between disease stage and radiation treatment response among NPC patients in Dr Soetomo Hospital, Surabaya. There is also significant correlation in the risk of treatment response exposure between stage III and IV. Stage III had the risk of complete response, as compared to partial response, 10.8 times higher than that in stage IV. Thus, the administration of 70 Gy radiation to NPC patients in earlier stages will have a better response therapy. No significant correlation is present between age, sex, tumor histopathology, and Hb level with radiation treatment response among NPC patients in Dr Soetomo Hospital, Surabaya. Most of the radiation toxicities are acute with moderate gradation (grade II). Management evaluation of patients receiving radiation should be performed since most of the treatment response among NPC patients are partial response and many patients remain having grade II acute toxicity. Socialization (health education) should be provided on the early detection of malignant diseases, including NPC, in the community through radio, television, newspapers, internet, or other mass media, or also through direct counseling to the community. Thereby, the management of the patients can be provided as early as possible. To be more representative, further study involving larger sample to obtain results in certain level of confidence should be undertaken.
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