Sigmoid Colon is an Unexpected Organ at Risk in Brachytherapy for Cervix Cancer

Size: px

Start display at page:

Download "Sigmoid Colon is an Unexpected Organ at Risk in Brachytherapy for Cervix Cancer"

Bethanie Little
6 years ago
Views:

1 Journal of the Egyptian Nat. Cancer Inst., Vol. 18, No. 2, June: , 2006 Sigmoid Colon is an Unexpected Organ at Risk in Brachytherapy for Cervix Cancer HODA AL-BOOZ, FRCR FFRRCSI M.D.*; ION BOIANGIU, MRCP FRCR*; HELEN APPLEBY, Ph.D.**; CHRIS FRENCH, Ph.D.**; HELEN COOMBER, Ph.D.**; PAULINE HUMPHERY, Ph.D.** and PAUL CORNES, MRCP FRCR, M.D.* The Departments of Clinical Oncology* and Medical Physics**, Bristol Haematology and Oncology Centre, Bristol, United Kingdom. ABSTRACT Purpose: To identify organs at risk (OAR) and analyze the dose volume histograms (DVHs) for intracavitary brachytherapy in cancer of the cervix. Late toxicities are our concern in treatment of cancer cervix especially as it is presenting in younger age population. Material and Methods: Patients with cancer of the cervix were treated using CT and MRI compatible, high dose rate, (HDR) applicators. CT images were acquired with the intra-uterine tube and colpostats in place and subsequently imported into Varian Brachyvision planning software. We identified the gross tumour volume (GTV) and organs at risk (OARs) and analyzed the dose distribution using dose volume histograms (DVHs). Doses were calculated according to ICRU 8. Critical tissue DVHs were analysed following the American Brachytherapy Society rules. Dose points are recorded as the dose encompassed by the greatest contiguous 1 cm, 2 cm, and 5 cm volumes in the plan. Results: We found the sigmoid colon to be a relatively immobile structure that repeatedly received doses in excess of 70% of the intended. The only solution in order to bring sigmoid DVHs within 5% toxicity limits was to reduce the dose to point A. Planning images and DVHs for the OARs are shown as an example of our work. Conclusion: The recto-sigmoid colon is identified as an unexpected OAR in a majority of cervix brachytherapy plans. A new consensus on the DVH limit of this structure will be needed in the era of CT planned brachytherapy, if arbitrary dose reductions to point A are to be the solution to the problem of sigmoid DVHs that exceed conventional tolerance limits. Key Words: Brachytherapy - Cervix cancer - Sigmoid colon. INTRODUCTION Radiotherapy is a very effective treatment for patients with carcinoma of the uterine cervix. Correspondence: Dr Hoda Al-Booz, Consultant in Clinical Oncology Bristol Haematology and Oncology Centre, hodabooz@doctors,org.uk It is also an alternative to surgery in Stages I and IIA, comparable survival and tumour control with either modality have been reported [1]. The national audit of cervical carcinoma radiotherapy in the United Kingdom [2] reported that overall survival was lower than that for equivalent stage patients treated in the rest of Europe. The crude rate of late severe complications was 6.1% (actuarial rate 8%) at 5 years. Radiotherapy techniques are consistently under improvement. External beam radiotherapy is moving from conventional to conformal planning. Brachytherapy also, according to the ICRU 8 [], is recommended to stop using point A, due to high dose gradient, and the use of tissue volume encompassed by a reference isodose surface, 60 Gy; this will enable us to compare institutions, regardless variable systems. Image-based brachytherapy is essential in defining target volume coverage and the dose distribution in adjacent dose limiting organs. Proper imaging is central to the development of these techniques. The use of CT-based treatment planning for intracavitary insertions for gynaecologic malignancies is still not routinely implemented at most institutions [4-7]. Recently, there has been a proposal for image based intracavitary brachytherapy guidelines for cervical carcinoma. This proposal was by the image-guided brachytherapy working group; GOG, RPC, ABS, ACR, ACRIN, AAPM, RTOG, and ASTRO [8]. A technique to be more widely used as it will conform the target volume hence will reduce normal tissue dose. This will also make dose escalation possible enabling us to achieve a greater rate of local control. 156

2 Sigmoid Colon an Unexpected Organ at Risk The main complications following treatment of cervical carcinoma involve bowel and urinary tract. The overall actuarial 5-year severe complications rate ranges between 8 and 10% [9]. Late complications mainly occur during the first to 5 years following treatment, these decreases later on. Bowel-related complications usually occur earlier than urinary complications (0 months Vs 48 months). There is continuous risk with an estimated rate of 0.4% per year post treatment. The rectal complications increase by 1% during the first 2 years with a decrease to 0.6% per year after treatment [9]. Aim of work: We are aiming to identify organs at risk (OAR) in intracavitary brachytherapy by analyzing the dose volume histogram (DVHs) using CT-based treatment planning software for intracavitary brachytherapy. If the received dose is in excess of the recommended tolerance level, we intend to investigate potential solutions to optimise dose modelling. PATIENTS AND METHODS A total of 1 patients received full intra-uterine insertion; an intrauterine tube and two vaginal colpostats. This was following a radical course of whole pelvis external beam radiotherapy, at the Bristol Haematology and Oncology Centre between January 2005 and April 2006, were included in this audit. Patient characteristics are shown in table (1). Patients were staged according to the International Federation of Gynecologists and Oncologists (FIGO) staging system [10]. Thirty one patients with cervix cancer received an external beam whole pelvis radiation therapy total dose of 50.4 Gy in 28 fractions over a period of 5 and a half weeks, concomitant with a weekly dose of Cisplatin (40mg/m 2 ); a total dose of 200mg/m 2. This was followed with three fractions of intrauterine HDR insertions (4.5 Gy), days apart. However, if the external beam radiotherapy was 45 Gy in 25 fractions, the Intracavitary dose is increased to 5.4 Gy per fraction. A total of 81 insertions were included in this study; as not all patients have completed their three fractions at the time of this analysis. We were more interested in the individual fraction rather than the total number, as we aimed at analyzing doses to organs at risk with the use of -D imaging and planning. 157 All brachytherapy insertions were delivered using CT and MRI compatible, high dose rate (HDR) applicators. With the intrauterine tube and colpostats in place, CT images were acquired. Images imported into Varian Brachyvision planning software (Fig. 1-A,B). Organs at risk (OARs) were identified; rectum, rectosigmoid and bladder. The dose distribution was analysed using dose volume histograms (DVHs). Conventional orthogonal simulator films were also done, with bladder and rectal contrast. Doses were calculated according to ICRU 8 (Fig. 2). Critical tissue DVHs (Fig. ), were analysed following the American Brachytherapy Society rules [11]; dose points were recorded as the dose encompassed by the greatest contiguous 1 cm, 2 cm, and 5 cm volumes in the plan (Table 2). Where these exceeded 70% of the intended point A dose, we modelled dosimetry solutions in order to maintain the intended dose at point A. If this could not be achieved, we reduced the dose to point A, respecting a maximum dose of 65 Gy to the rectum and 70 Gy to the bladder. Table (1): Patient profile. Table (2-A,B,C): Recordings of doses to the examined organs at risk. A) Rectum B) Rectosigmoid C) Bladder. Age: Range Median Stage: I IIA IIB IIIA IIIB Histology: Squamous Adeno Adenosquamous years 48 years 5 (1.6%) 8 (25.8%) 10 (22.9%) 6 (2.25%) 2 (6.45%) 25 (80.6%) (0.9%) (0.9%) * The sum is higher than the "Total tested" as there was repeated overdose in parts, within the same fraction; e.g. doses to 1cc and doses to 2cc both >70%.

(1-B): D image of the organs defined after marking on all CT slices. ---------- Rectum, ---------- Rectosigmoid, ---------- Small Bowel, ---------- Bladder. Fig.

3 158 Hoda Al-Booz, et al. Fig. (1-A): organ defenition on brachyvision software Rectum, Rectosigmoid, Small Bowel, Bladder. balloon 7 cm bladder reference point intrauterine sources intravaginal souyrces vaginal posterior wall 0.5 cm rectal reference point Fig. (1-B): D image of the organs defined after marking on all CT slices Rectum, Rectosigmoid, Small Bowel, Bladder. Fig. (2): ICRU 8 dosimetry points based on a lateral Xray. Relative dose Fig. (): Example of a recorded DVH after CT volume marking Rectum, Rectosigmoid, Small Bowel, Bladder Volurng (Cm2) Dose (Gy)

4 Sigmoid Colon an Unexpected Organ at Risk RESULTS Thirty one patients were enrolled in this study. A total of 81 insertions were done and analyzed; as some patients received only 2 fractions by the time of this analysis. The sigmoid organ was found to have a dose >70% of dose to point A in 6 out of 81 insertions (44.4%). In 2 out of 81 insertions (28%), the recto- sigmoid dose was >70% of while the rectal dose was <70% of. Although inter-fraction bowel mobility is suggested to limit the OAR dose, we found the sigmoid colon to be a relatively immobile structure that repeatedly received doses in excess of 70% of the intended (8/1 patients). To reduce the dose to the rectosigmoid colon, we have investigated the decrease in the weighting of the dose distribution in the superior intrauterine tube, altering colpostat dwell positions or weighting and altering the intrauterine applicator angles. All options did not significantly alter the sigmoid colon DVH. The only solution in order to bring the sigmoid DVHs within 5% toxicity limits was to reduce the dose to point A. Such reduction varied from one plan to the other with a range of 15-20%, according to the extent of dose exceeded to the sigmoid colon. DISCUSSION Currently, point A is the prescription point for intracavitary brachytherapy. However, orthogonal film-based dose distribution analysis has proven to be inadequate for gynaecologic brachytherapy. Single tumour reference points, such as point A chosen from localization films, do not give sufficient information about the 159 dose distribution throughout the tumour volume, nor do the reference points for the bladder and rectum accurately reflect the dose distribution within these organs [4-5]. Additionally, there is no recognition of the volume of tumour and normal tissues receiving these doses. Schoeppel and associates [12] used three dimensional (-D) computerized tomography based dose distributions and demonstrated that maximum doses to the rectum and bladder were sometimes two to three times higher than doses calculated from standard reference points. This explains the unexpected high rate of reported late toxicities in some series. Extensive work was done by several brachytherapy groups reported the late toxicities after radical radiotherapy in carcinoma of the cervix [1-18]. The Late toxicities documented were proctitis, cystitis, enteritis, vaginal toxicity and subcutaneous fibrosis (Table ). In our dose/ volume analysis, we have attempted to document the dose to the rectum separating it from that of the rectosigmoid. Most previous studies summed the proctitis and enteritis symptoms together (Table ). We have shown that the risk is higher to the rectosigmoid part of the the colon, and this, not uncommonly, passes unnoticed. We have always been concerned about the dose to the rectum, and have been using the rectal retractors, or extra packing posteriorly to reduce the rectal dose. It is the dose to the rectosigmoid, which is sinking in the pelvis and lying very close to the vaginal and intrauterine tubes, that s causing the high risk of overdosing. This explains the unexpected late enteritis, perforation, and subsequent colostomy. Table (): Comparison of severe late toxicities (>grade ) within various series. Trials Barillot et al. [1] Perez et al. [14] Eifel et al. [15] Lanciano et al. [16] Ferrigno et al. [17] Sabiskumar et al. [18] Number of patients Series type Median follow-up 11 years (crude) Median follow-up 70 months (crude) Rectum Included in small bowel toxicity Bladder Small bowel Subcutaneous fibrosis Vaginal stenosis/necrosis stenosis only

5 160 Prior to 1991 no routine individual dosimetry was carried out mainly due to manpower restrictions, such dosimetry is now our standard technique with modifications as outlined. Given the increasing evidence that cancer survival outcomes are poorer in health systems with fewer resources, it is not unexpected that complications may also be higher. We feel that there is no role for cervix brachytherapy without individualized dosimetry in the modern management of cervix carcinoma. Conclusion: The recto-sigmoid colon is identified as an unexpected OAR in a majority of cervix brachytherapy plans. This may help to explain reported cases of unexpected sigmoid perforation following brachytherapy in the literature. A new consensus on the DVH limit of this structure will be needed in the era of CT planned brachytherapy if arbitrary dose reductions to point A are to be the solution to the problem of sigmoid DVHs that exceed conventional tolerance limits. REFERENCES 1- Landoni F, Maneo A, Colombo A, Place F, Milani R, Perego P, et al. Randomised study of radical surgery versus radiotherapy for stage IB-IIA cervical cancer. Lancet. 1997; 50: Denton AS, Bond SJ, Matthews S, Bentzen SM, Maher EJ. National audit of the management and outcome of carcinoma of the cervix treated with radiotherapy in 199. Clin Oncol. 2000; 12: ICRU Report 8. Dose and volume specification for reporting intracavitary therapy in gynaecology, international Commission on Radiation Units and Measurements, Bethesda, Maryland, Stuecklschweiger GF, Arian-schad KS, Poir E, Poier E, Poschauko J, Hackl A. Bladder and rectal dose of gynaecologic high-dose-rate implants: Comparison of orthogonal radiographic measurements with in Vivo and CT-assisted measurements. Radiology. 1991; 181 (): Kapp KS, Stuecklschweiger GF, Kapp DS, Hackl AG. Dosimetry of intracavitary placements for uterine and cervical carcinoma: results of orthogonal film, TLD, and CT-assisted techniques. Radiother Oncol. 1992; 24: Kuipers T, Visser AG. Technical aspects of bladder dosimetry in itracavitary irradiation of cervix carcinoma. Radioth Oncol. 1986; 7: Ling CC, Schell MC, Working KR, Jentzsch K, Harisiadis L, Carabell S, et al. CT-assisted assessment Hoda Al-Booz, et al. of bladder and rectum dose in gynaecological implants. Int J Radiation Oncology Biol Phys. 1987; 1 (10): Report from image-guided brachytherapy working group. GOG, RPC, ABS, ACR, ACRIN, AAPM, RTOG, and ASTRO. Int. J. Radiat. Oncol. Biolo. Phys Vol 60, No Longsdon MD, Eifel PJ. Figo IIIB squamous cell carcinoma of the cervix: an analysis of prognostic factors emphasizing the balance between external beam and intracavitary radiation therapy. Int J Radiat Oncol Bio Phys. 1999; 4: International Federation of Gynaecology and Obstetrics Classification and staging of malignant tumours in the female pelvis. Int J Gynaecol Obstet. 1989; 28: Nag S, Erickson B, Thomadsen B, Orton G, Demanes JD, Peteriet D. The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Bio Phys, 2000; 48: Schoeppel SL, Fraass BA, Hopkins MP, Lavigne ML, Lichter AS, Mcshan DL, et al. A CT-compatible version of the Fletcher system intracavitary applicator: Clinical application and -dimensional treatment planning. Int J Radiat Oncol Biol Phys. 1989; 17: Barillot I, Horiot JC, Maingon P, Truc G, Chaplain G, Comte J, et al. Impact on treatment outcome and late effects of customized treatment planning in cervix carcinoma: baseline results to compare new strategies, Int J Radiat Oncol Biol Phys. 2000; 4, Perez CA, Grigsby PW, Lockett MA, Chao KSC, Williamson J. Radiation therapy morbidity in carcinoma of the uterine cervix: dosimetric and clinical correlation, Int J Radiat Oncol Biol Phys. 1999; 44: Eifel PJ, Levenback C, Wharton JT, Oswald MJ. Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix, Int J Radiat Oncol Biol Phys. 1995; 2: Lanciano RM, Martz K, Montana GS, Hanks GE. Influence of age, prior abdominal surgery, fraction size, and dose on complications after radiation therapy for squamous cell cancer of the uterine cervix. A patterns of care study, Cancer. 69 (1992), pp Ferrigno R, Campos De Oliveira Faria SL, Weltman E, Salvajoli JV, Serqreto RA, Pastore A, et al. Radiotherapy alone in the treatment of uterine cervix cancer with telecobalt and low-dose-rate brachytherapy: retrospective analysis of results and variables. Int J Radiat Oncol Biol Phys. 200; 55: Saibishkumar EP, Patel FD, Sharma SC. Evaluation of late toxicities of patients with carcinoma of the cervix treated with radical radiotherapy: an audit from India. Clinical Oncology. 2006; 18: 0-7.

3D ANATOMY-BASED PLANNING OPTIMIZATION FOR HDR BRACHYTHERAPY OF CERVIX CANCER

SAUDI JOURNAL OF OBSTETRICS AND GYNECOLOGY VOLUME 11 NO. 2 1430 H - 2009 G 3D ANATOMY-BASED PLANNING OPTIMIZATION FOR HDR BRACHYTHERAPY OF CERVIX CANCER DR YASIR BAHADUR 1, DR CAMELIA CONSTANTINESCU 2,