Clinical Investigation
Dose–Volume Histogram Parameters and Late Side Effects in Magnetic Resonance Image–Guided Adaptive Cervical Cancer Brachytherapy

https://doi.org/10.1016/j.ijrobp.2009.11.002Get rights and content

Purpose

To evaluate the predictive value of dose–volume histogram (DVH) parameters for late side effects of the rectum, sigmoid colon, and bladder in image-guided brachytherapy for cervix cancer patients.

Methods and Materials

A total of 141 patients received external-beam radiotherapy and image-guided brachytherapy with or without chemotherapy. The DVH parameters for the most exposed 2, 1, and 0.1 cm3 (D2cc, D1cc, and D0.1cc) of the rectum, sigmoid, and bladder, as well as International Commission on Radiation Units and Measurements point doses (DICRU) were computed. Total doses were converted to equivalent doses in 2 Gy by applying the linear-quadratic model (α/β = 3 Gy). Late side effects were prospectively assessed using the Late Effects in Normal Tissues–Subjective, Objective, Management and Analytic score. The following patient groups were defined: Group 1: no side effects (Grade 0); Group 2: side effects (Grade 1–4); Group 3: minor side effects (Grade 0–1); and Group 4: major side effects (Grade 2–4).

Results

The median follow-up was 51 months. The overall 5-year actuarial side effect rates were 12% for rectum, 3% for sigmoid, and 23% for bladder. The mean total D2cc were 65 ± 12 Gy for rectum, 62 ± 12 Gy for sigmoid, and 95 ± 22 Gy for bladder. For rectum, statistically significant differences were observed between Groups 1 and 2 in all DVH parameters and DICRU. Between Groups 3 and 4, no difference was observed for D0.1cc. For sigmoid, significant differences were observed for D2cc and D1cc, but not for D0.1cc in all groups. For bladder, significant differences were observed for all DVH parameters only comparing Groups 3 and 4. No differences were observed for DICRU.

Conclusions

The parameters D2cc and D1cc have a good predictive value for rectal toxicity. For sigmoid, no prediction could be postulated because of limited data. In bladder, DVH parameters were predictive only for major toxicity.

Introduction

Magnetic resonance imaging (MRI)-guided brachytherapy (IGBT) has been implemented in some institutions worldwide for patients with locally advanced cervix cancer. In parallel, with the introduction of dose–volume histogram (DVH) parameters for target volumes and for rectum, sigmoid colon, and urinary bladder, new concepts and terms for treatment planning have been developed 1, 2. Image-guided BT enables appropriate target coverage while better sparing organs at risk (3). The recommendations of the working group for gynecologic brachytherapy of the Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology (GYN GEC ESTRO) have been validated in some clinical studies 4, 5, 6, 7, 8, 9, 10, 11, 12.

When assessing late adverse side effects after combined external-beam radiotherapy (EBRT) and IGBT, relatively small organ or organ wall volumes irradiated to a high dose seem to be of major interest. It is known from classic series based on two-dimensional radiotherapy in cervix cancer that the most significant factor affecting the incidence of late adverse side effects is the total radiation dose to the pelvic organs by both whole-pelvic irradiation and intracavitary insertions 13, 14, 15, 16, 17. In addition, the size of the 60-Gy volume and the dose rate have a significant impact (17).

At our department, the parameters D2cc, D1cc, and D0.1cc (most exposed 2, 1, and 0.1 cm3) for rectum, sigmoid colon, and urinary bladder have been systematically recorded since 1998 and have been integrated into clinical practice 4, 5. First reports on the correlation of the dose–volume parameters for rectum with changes of the rectal mucosa were published in 2007 and 2009 18, 19. The aim of the present study was to evaluate the predictive value of the dose–volume parameters for late rectal, sigmoid, and bladder morbidity for cervix cancer patients treated with three-dimensional (3D) conformal EBRT and IGBT.

Section snippets

Patients and treatment

Our study population consisted of 141 cervix cancer patients from the population of 145 treated at the Medical University of Vienna between 1998 and 2003 (5). The exclusion of 4 patients was based on the unavailability of their complete BT treatment plans.

All patients were treated with definitive radiotherapy, applying EBRT with 45–50.4 Gy in 25–28 fractions of 1.8 Gy with or without cisplatin (40 mg/m2 of body surface per week for 5 weeks) plus 4 × 7 Gy IGBT. Brachytherapy was performed by

Results

The median age of patients at treatment was 60 years (range, 26–92 years). The International Federation of Obstetrics and Gynecology stage distribution was as follows: Stage I, 12 patients; Stage II, 87; Stage III, 35; and Stage IVA, 7. Eighty-two patients (58%) received chemotherapy. Median follow-up was 51 months. The mean (± standard deviation) D2cc, D1cc, and D0.1cc values for rectum were 65 ± 12 Gy, 69 ± 14 Gy, and 86 ± 27 Gy and for sigmoid colon were 62 ± 12 Gy, 67 ± 14 Gy, and 84 ± 32

Discussion

After the introduction of the DVH parameters by the GEC ESTRO recommendations, D2cc, D1cc, and D0.1cc were systematically used in clinical practice in centers where IGBT for cervical cancer was implemented. However, there are still limited published data available correlating these DVH parameters with clinical outcome. In this study we aimed to correlate the DVH parameters for late effects of the rectum, sigmoid colon, and urinary bladder with observed late side effects.

Conclusion

The DVH parameters for OAR (rectum, sigmoid colon, and urinary bladder) as recommend by the GYN GEC ESTRO working group are essential for treatment planning and optimization of IGBT. In our study we could demonstrate a correlation of these DVH parameters with late side effects, but with some uncertainties. The parameters D1cc and D2cc have a good predictive value for rectal toxicity. For sigmoid colon, no dose effect can be postulated owing to the lack of sufficient data (only three adverse

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  • Cited by (0)

    The Department of Radiotherapy at the Medical University of Vienna receives financial and/or equipment support for research and educational purposes from Nucletron, Varian Medical Systems, and Isodose Control. This study was supported in part by Jubilaeumsfonds der Oesterreichischen Nationalbank Grant 10937.

    Conflict of interest: none.

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