Cervical cancer is the second most common cancer in incidence and mortality in Thai women. In Thailand, the age-standardized rates were 24.5 and 12.8 in incidence and mortality, respectively [1]. Concurrent chemotherapy and radiotherapy is the treatment of choice for locally advanced cancers because combination of these two modalities improves tumor control, overall survival, and progression-free survival [2,3,4,5,6]. In radiotherapy part, combination of whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) has become a standard treatment modality for cervical cancer. Initial WPRT is performed to obtain tumor shrinkage to permit optical ICBT placement [7]. According to the American Brachytherapy Society recommendations for high-dose-rate (HDR) ICBT for carcinoma of the cervix, the whole pelvic external beam radiotherapy (EBRT) dose varies from institution to institution. The HDR fraction size and number depends on the EBRT dose [8]. HDR brachytherapy has been used for more than 30 years in Japan and Europe, and its applications have been increasing in the United States [9,10]. ICBT has been used to increase the dose to cervix to ≥80 Gy. However organs in the proximity of the cervix, such as urinary bladder, small bowel and rectum, can receive rather high doses and adverse side effects can occur. The risk of late effects (i.e., obstruction, fibrosis/necrosis, or fistula) is related to the volume, total dose, dose per fraction, and specific intrinsic radiosensitivity of the normal tissue irradiated. Biologically effective dose (BED) had been used to evaluate the dose to target and organs at risk [11,12]. Because numerical values of BED (in Gy₁₀ or Gy₃) are not familiar to many medical professionals, it is a common practice to convert these BEDs to the biologic equivalent of a total dose in 2 Gy fractions (BED of 2 Gy). These simplified biologically equivalent doses are called either EQD2, denoting equivalent total doses in 2-Gy fractions [13]. Rectal bleeding is a common late toxicity of pelvic radiation. Late toxicity to the rectum includes radiation proctitis, ulceration, stricture, and fistula. Some symptoms may resolve in a few months, whereas others will have a longer course that may involve 1 to 2 years of rectal bleeding. For severe cases, surgical intervention may be needed [14,15].

To evaluate the rectal toxicity, many scores in objective and subjective approaches were used to evaluate. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) toxicity scale were used in objective aspect only while Vienna Rectoscopy Score (VRS) was used in subjective aspect [16,17]. Moreover, there were the combinations of subjective and objective evaluations as late effects of normal tissues (LENT-SOMA) scales [16]. For this study, we retrospectively evaluated the endoscopic findings in cervical cancer patients who were treated by radical radiotherapy and also accumulative dose using EQD2 to rectum is associated with gastrointestinal toxicity ≥grade 2.

This study designed as retrospective study in 336 patients who were treated by radical radio-chemotherapy for locally advanced cervical cancer in the Division of Therapeutic Radiology and Oncology, Faculty of Medicine, Chiang Mai University during 2004-2009. We enrolled 39 patients of them who were evaluated the rectal toxicity by rectosigmoidoscopy during the follow-up period according to symptomatic indications or patient preferences. Treatment schedules for these patients were shown as the followings.

The mean cumulative dose in term of EQD2 to Point As and rectum were 76.4 and 64.2 Gy, respectively. All Characteristic data of these patients were shown in Table 1.

During the past decade, BED was used to evaluate the cumulative dose to tumor and organs-at-risk. For cervical cancer, the cumulative dose to rectum and bladder in terms of BED correlated to rectal toxicity [21,22].

Rectal toxicity is the most common toxicity after radical radiotherapy for cervical cancer. The combined dose of EBRT and brachytherapy to rectum predicted the toxicity in terms of BED. Toita et al. [23] suggested that cumulative BED at the rectal point should be kept below 100-120 Gy3 to prevent late rectal complication. The supported study from Huang et al. [24] and Suzuki et al. [25] reported significant higher rectal toxicity in patients that cumulative rectal BED ≥ 100 Gy₃. Moreover, Ogino et al. [26] also showed that the time-dose factor and the BED at rectal point values were significant correlated with the incidence of late rectal complication.

In terms of EQD2, Sakata et al. [27] found that rectal radiation tolerance dose using EQD2, 5% and 50% complication probability, was about 64 and 79 Gy, respectively, and the probability of rectal complications increased drastically after the maximal rectal dose was >60 Gy.

From our study, only association between cumulative rectal dose in EQD2 >65 Gy and LENT-SOMA ≥2 were observed (p = 0.022). No statistical significance was found between rectal dose and toxicity in terms of RTOG/EORTC scale (p = 0.137) and VRS (p = 0.497). The possible explanation is that LENT-SOMA scale covered both objective and subjective evaluations while RTOG/EORTC and VRS were purely objective and subjective approaches, respectively. So LENT-SOMA scale should be more appropriate to evaluate the rectal toxicity. Moreover, in this study, the association of cumulative rectal toxicity in EQD2 to toxicity ≥1 was not found statistical significance in all toxicity score. This correlates to the clinical aspects that the decision to treat toxicity starts practically when patients developed ≥grade 2 toxicity [28].

However, there are some limitations in this study. The accuracy of the rectal dose calculation is affected by several factors. First, to calculate the rectal dose from EBRT, It assumed that the rectum was completely shielded after central shielding. However, the rectum might be irradiated with some doses according to anatomic variations. Secondly, using orthogonal films for calculation might cause problem to evaluate the really maximal dose to rectum due to anatomy. Volume-based planning brachytherapy could be more accurate on delineating organs-at-risk including rectum and assessing doses through dose volume histograms [29]. The study from Kato et al. [30] reported the dose evaluation of 48 patients who were treated by combination of WPRT plus HDR-ICBT. Computed tomography-based three dimensional (3D) dose-volume parameters of the rectum may be effective for predicting late rectal complications while no correlation between rectal dose in ICRU point and toxicity was found [30]. The using of 3D-based approach will be reported in the future. Thirdly, the number of patients who performed endoscopic exam in our study was small because rectosigmoidoscopy was not routine evaluation after treatment in our country.

Our findings showed correlation between cumulative EQD2 to rectal point >65 Gy and rectal toxicity in term of LENT-SOMA scale at least grade 2. The volume-based planning in both WPRT and ICBT improve the accuracy in dosimetry and toxicity evaluation.