Consensus on treatment of endometrium carcinoma ... - Springer Link

Clin Transl Oncol (2012) 14:263-270 DOI 10.1007/s12094-012-0794-2

S P E C I A L A RT I C L E

Consensus on treatment of endometrium carcinoma with brachytherapy José Luis Guinot* · José Pérez-Calatayud** · José María Azcoaga* · Ismael Herruzo* · Coral Bodineau** · Angels Rovirosa* · Vicente Crispín** · Pedro Galán** · Ezequiel González-Patiño* · José Pérez-Regadera* · Alfredo Polo*, on behalf of the SEOR and the SEFM Brachytherapy Groups

Received: 15 June 2011 / Accepted: 4 August 2011

Abstract Radiotherapy (RT) is commonly used as adjuvant treatment following hysterectomy and double oophorectomy in endometrial carcinoma. Prophylactic vaginal brachytherapy (BT) is the most common treatment in BT

*Radiation Oncologist **Radiation Physicist J.L. Guinot (쾷) · V. Crispín Fundación Instituto Valenciano de Oncología (IVO) C/ Profesor Beltrán Báguena, 8 ES-46009 Valencia, Spain e-mail: [email protected] J. Pérez-Calatayud Hospital Universitario La Fe Valencia, Spain J. Pérez-Calatayud Clínica Benidorm Benidorm, Alicante, Spain J.M. Azcoaga · I. Herruzo · C. Bodineau · P. Galán Hospital Regional Universitario Carlos Haya Málaga, Spain A. Rovirosa Hospital Clínic de Barcelona Barcelona, Spain E. González-Patiño Hospital Clínico Universitario Santiago de Compostela, La Coruña, Spain J. Pérez-Regadera Hospital 12 de Octubre Madrid, Spain A. Polo Hospital Ramón y Cajal Madrid, Spain

units. The PORTEC and GOG 99 studies have attempted to clarify the indications of BT and postoperative external RT, changing treatment standards. However, prophylactic BT regimens are very varied and there is currently no consensus on how to treat patients in terms of dose per fraction and number of fractions. Moreover, unoperated cases of endometrium are uncommon and there is limited experience in their treatment with BT. The 9th Consensus Meeting of the SEOR and SEFM Brachytherapy Group, held in Malaga on 11 March 2011, was therefore dedicated to “Brachytherapy in Endometrial Carcinoma”. This article presents the consensus on treatment of endometrial carcinoma in operated (prophylactic vaginal BT) and unoperated (endouterine BT) patients. Keywords Endometrial carcinoma · Postoperative radiation therapy · Brachytherapy · Vaginal brachytherapy · Endouterine brachytherapy · Clinical dosimetry

Introduction Endometrial cancer is the most common gynaecological malignancy in women. Its prognosis is good as it is detected in early stages, and surgery is the primary treatment. Hysterectomy with dual oophorectomy removes gross disease in most cases. Lymphadenectomy, while always indicated in histological types of poor prognosis, can be avoided in low-risk forms and it is currently unclear if it should be performed systematically in intermediate-risk cases. Since there is a percentage of patients who experience locoregional failures, some patients may benefit from adjuvant radiation therapy. Pelvic external radiotherapy (RT) has been used for years to prevent nodal and surgical bed recurrence. Considering all stages globally, vaginal

264

prophylactic brachytherapy (BT) has been shown to reduce the incidence of vaginal recurrence from 15% to 2%. Highdose-rate (HDR) BT allows for treatments with minimal side effects and no need for patient admission or isolation. Currently, postoperative prophylactic vaginal BT in endometrial carcinoma, with or without RT, is the most common treatment in BT units [1]. In recent years, three phase III randomised studies have attempted to establish the value of postoperative radiation therapy in endometrial carcinoma. The PORTEC-1 [2, 3] and GOG 99 [4] studies have shown that pelvic RT reduces the risk of relapses but does not increase survival. Lymphadenectomy was not mandatory in the first study but was in the second, and vaginal BT was not performed after pelvic RT in either study. The PORTEC-1 study showed that relapses in the group of patients without postoperative irradiation were most frequently in the vaginal vault. The PORTEC-2 [5] study was conducted to compare the results of pelvic RT vs. vaginal BT only in high–intermediate risk endometrial carcinoma. Patients with elective lymph node dissection were not included. The conclusion was that BT was as effective as RT for vaginal control with fewer gastrointestinal toxic effects. Based on this study, it is considered that BT should be the complementary treatment of choice for intermediate-risk tumours. In low-risk patients, BT has also been shown to be useful to reduce relapses to a minimum [6], although the percentage of vaginal recurrence rate without BT is very low. Conversely, in high-risk patients radiation therapy is always recommended and there is a large percentage of metastasis [7], which has led to several studies in adding chemotherapy (CT) to RT and BT, among others the PORTEC-3 study, the results of which are still pending. Therefore, the indications of RT and BT are gradually being adapted to more individualised treatments based on the needs of each patient. Although there are recommendations, such as those by the American Brachytherapy Society [8], prophylactic BT regimens are varied and there is currently no clear consensus regarding dose, where to prescribe and when to use BT [9]. This is what led the respective Brachytherapy Groups of the Spanish Oncological Radiotherapy Society (SEOR) and the Spanish Medical Physics Society (SEFM) to select this topic for the annual consensus meeting. On 11 March 2011, the 9th Consensus Meeting was held in Malaga, bringing together over 80 experts in radiation physics and radiation oncologists, under the title of “Brachytherapy in Endometrial Carcinoma”. A current review of the mentioned studies and the indications for BT according to the new 2009 International Federation of Gynecology and Obstetrics (FIGO) classification of gynaecological tumours were presented. Two main topics were reviewed: BT in operated endometrium after hysterectomy (prophylactic vaginal BT) and BT in unoperated endometrium (endouterine BT). The former was the main topic of debate, as all hospitals that have a BT unit, over 50

Clin Transl Oncol (2012) 14:263-270 Table 1 Risk factors in endometrial carcinoma Major factors

Minor factors

Tumour differentiation grade Myometrial invasion depth Type 2 histology Carcinosarcomas

Age over 60 years Vascular and/or lymphatic invasion Tumour size greater than 2 cm Involvement of lower third of uterus

in Spain, use it, but with very different regimens. The second topic was patients who cannot be operated for medical reasons or anaesthetics, in many cases due to obesity; since although this treatment is less controversial, there is less experience in it. Therefore, the technique and dosimetric aspects were presented for these patients. In the afternoon, the results of a survey were presented in which a total of 20 hospitals all over Spain responded on how treatment was delivered at each centre. A debate was then held among all participants in an attempt to reach a consensus, which is presented below. The topic of relapses was not addressed and was left for subsequent meetings.

Consensus A. Operated endometrium: prophylactic vaginal brachytherapy 1. Indications and risk groups Different studies on radiation therapy in endometrial cancer [2–5, 10–16] have established a number of risk factors for recurrence following hysterectomy, local, nodal and distant, that need to be considered to establish the indications for treatment (Table 1). We can divide them into major and minor risk factors, although all can be taken into account. Three factors are considered to be major: histological grade, depth of myometrial invasion and histological type. Histological factors of worse prognosis are type 2 histology (serous-papillary carcinoma and clear cell carcinoma, frequently having extrauterine involvement at diagnosis, with a similar behaviour pattern to ovarian carcinoma) and carcinosarcomas. Four factors are considered to be minor: age over 60 years, vascular and/or lymphatic invasion, tumour size greater than 2 cm and involvement of lower third of uterus. Based on these factors, patients are classified according to the risk of relapse into low, intermediate and high risk. The staging for endometrial carcinoma was modified in 2009 [17] and the information available regarding prognostic groups will be based in the current stage but taking into account the old classification. In stage I, considering the new FIGO classification and taking into account the depth of invasion of uterine wall and tumour differentiation grade, we can establish the risk groups for relapse as shown in Table 2.

Clin Transl Oncol (2012) 14:263-270

265

Table 2 Risk groups in stage I endometrial carcinoma

Stage IA Stage IB

GI

GII

GIII

Low Intermediate

Low Intermediate

Intermediate High

The current trend is to conduct observation of low-risk patients, BT only in intermediate-risk patients and external RT plus BT in high-risk patients, sometimes combined with CT. However, in certain circumstances, BT may be indicated in the low-risk group and may be combined with external RT in the intermediate-risk group. 2. Indications by stages (Tables 3, 4) a. Stage IA (without myometrial infiltration): In grades G-I and G-II, it is not necessary to add any radiation therapy after surgery, monitoring of the patient being sufficient. In G-III, BT in the presence of limited surgery (no node sampling) is optional. BT is also recommended in the case of histologies with poor prognosis. b. Stage IA (with myometrial infiltration): In G-I and G-II, it is not necessary to add radiation therapy. BT is optional only in the case of poor prognostic factors or limited surgery. In G-III, pelvic RT may be added in the presence of other risk factors, especially if surgery was limited. c. Stage IB: In G-I and G-II, BT alone is indicated, and if there are risk factors or limited surgery, pelvic external RT may be added. In G-III, both pelvic external radiation therapy and BT are recommended. In the presence of risk factors or limited surgery, it is also required to assess whether to add CT.

d. Stage II: In G-I and G-II, both with and without risk factors, pelvic external radiation therapy and BT are recommended. In G-III, it is also recommended to assess CT. e. Stage III-A: The recommendation is external RT, BT and optional CT. Positive peritoneal fluid alone has no impact on prognosis and so does not change the stage in the new classification, but may be considered as a risk factor. f. Stage III-B: Pelvic and vaginal external RT plus BT is the treatment of choice and CT is optional. g. Stage III-C: Pelvic and paraaortic external RT with BT is the treatment of choice and CT is optional. h. Stage IV: If there are no remote metastases, cytoreductive surgery is attempted if possible and external RT and CT are optional based on patient characteristics. We should remark that RT has been the standard approach for many years but at the present time strong consideration needs to be given to the addition of CT to stage III and IV disease. Whether it should be concurrent or, more commonly, sequential is still under investigation.

3. Type of brachytherapy a. The low-dose-rate (LDR), HDR or pulsed-dose-rate (PDR) modalities of BT are equally effective for treatment of endometrial carcinoma [1, 18]. b. HDR and PDR BT offer the possibility to optimise the dose. c. As HDR BT is given in short sessions, it avoids bed confinement of patients and so is less uncomfortable and better tolerated.

Table 3 Adjuvant treatment in endometrial carcinoma stage I–II Stage FIGO 1988

Stage FIGO 2009

Without myometrial infiltration IA 1988

IA

With myometrial infiltration IB 1988

Grade

Risk factors Without factors

With risk factors

Limited surgery (no node sampling)

G1–2 G3

Observation Observation or brachytherapy

Observation Observation or brachytherapy

Observation Brachytherapy

IA

G1–2 G3

Observation Brachytherapy

Observation or brachytherapy Brachytherapy±pelvic RT

Observation or brachytherapy Pelvic RT+brachytherapy

IC 1988

IB

G1–2 G3

Brachytherapy Pelvic RT+brachytherapy

Brachytherapy±pelvic RT Pelvic RT+brachytherapy± chemotherapy

Brachytherapy±pelvic RT Pelvic RT+brachytherapy±chemotherapy

IIB

II

G1–2 G3

Pelvic RT+brachytherapy Pelvic RT+brachytherapy± chemotherapy



266


Table 4 Adjuvant treatment in endometrial carcinoma stage III–IV Stage FIGO 1988 IIIA

Stage FIGO 2009 Positive peritoneal fluid alone

Adnexial or serosa involvement More than one localisation

IA G1–2 IA G3, IB G1–2 IB G3, II IIIA IIIA

Observation or brachytherapy Brachytherapy±pelvic RT Pelvic RT+brachytherapy±chemotherapy Pelvic RT+brachytherapy±chemotherapy Pelvic RT+brachytherapy±chemotherapy

IIIB

Vaginal involvement

IIIB

Pelvic RT+brachytherapy±chemotherapy

IIIC

Pelvic nodes

III C1

Pelvic±paraaortic RT+brachytherapy±chemotherapy

Paraaortic nodes

III C2

Pelvic and paraaortic RT+brachytherapy±chemotherapy

IVA

Bladder or rectal involvement

IVA

Cytoreductive surgery+chemotherapy±pelvic RT

IVB

Intraabdominal metastasis Groin nodes

IVB

Cytoreductive surgery+chemotherapy±pelvic/groin RT

4. Type of applicators a. There are different types of applicators such as vaginal cylinders or dome type applicators, colpostats, vaginal moulds and Miami type multicatheter cylinders, among others. All are considered appropriate as long as they allow contact of the applicator with the surface of the vaginal mucosa. b. Vaginal cylinders are the most widely used because of their rapidity of placement, the reduction in the total time of the procedure and the greater convenience for the patient. c. In cases of vaginal morphology with extensive vault and narrow introitus, colpostats or vaginal ovoids are considered more appropriate. When the scar of the vaginal vault is not homogeneous (“dog ear”shaped vaginal cuff), vaginal ovoids and vaginal moulds may fit better. d. Cylinders with shielded angles are designed to provide a higher dose in a vaginal wall in cases of vaginal relapse or tumour, so they are not appropriate for prophylactic vaginal BT. e. The Fletcher-type colpostats with rectal and bladder shieldings are not suitable for prophylactic BT as they reduce dosage in portions of the mucosa of the vaginal vault. f. Interstitial implant systems with metallic needles, MUPIT or plastic needles are not indicated in prophylactic BT.

– 5 fractions of 5 Gy daily. c. When BT is used as a boost after external RT, the pelvic RT dose is homogeneous, from 45 to 50 Gy. However for BT, varied regimens are used (2–5 sessions of 3.8–6 Gy or 1–3 sessions of 7 Gy), usually between 2 sessions of 5 Gy and 4 sessions of 4–4.5 Gy, with no regimen being more recommendable than another. d. The recommended time for starting radiation therapy after surgery is less than 8 weeks. If only BT is to be performed, it is advisable to leave sufficient time for complete healing of the vaginal vault. e. Whenever pelvic RT is indicated, it is advisable to add vaginal BT as a boost, usually on concluding external RT. If it is used during external RT, the day on which the session of BT is delivered, RT should not be given. In the survey conducted, BT was performed concomitantly with RT in 35% of the centres and sequentially in 65%. f. The recommended maximum total treatment time adding RT and BT should not exceed 7 weeks. Some studies have shown that vaginal BT after RT may be given in five days and BT alone in 10 days without increasing complications, thus shortening the total treatment time [19, 20]. g. In high-risk cases where external CT concomitant with RT is indicated, it has been recommended not to perform BT sessions on the same day as CT. 6. Technical aspects of applicator placement

5. Fractioning and dose per fraction a. We will refer only to HDR since it is the most widely used type of BT. There are numerous vaginal prophylactic HDR BT regimens (Table 5). b. When only prophylactic BT is used, there are several more common regimens: – 6 fractions of 4 or 4.5 Gy administered two or three sessions per week, – 3 fractions of 7 Gy administered one session per week or

a. Due to the simplicity of application, prophylactic vaginal BT is an outpatient treatment and does not require hospital admission. b. Sedation, analgesia or local anaesthesia may be administered at the discretion of each site, but it is usually unnecessary with vaginal cylinders. c. In the cylinder technique, the longest diameter that is comfortable for the patient should be used, to ensure good contact between the applicator and the surface of the vagina. When colpostats are used,


267

Table 5 Most common regimens for prophylactic vaginal brachytherapy EBRT

Dose per fraction (Gy)

Number of fractions

Prescription point

Fractions per week Recommended total dose in EQD2

Exclusive brachytherapy

0 0 0

4–4.5 7 5

6 3 5

0.5 cm from surface 0.5 cm from surface 0.5 cm from surface

2–3 1 5

60–70 Gy to vaginal surface

Brachytherapy as a boost

45–50 Gy 45–50 Gy

5 4–4.5

2 3-4

0.5 cm from surface 0.5 cm from surface

2–3 2–3

75–85 Gy to vaginal surface

EBRT, external beam radiation therapy; EQD2, equivalent dosage at 2 Gy

they should be joined together to avoid underdosing in the space between them, although in some cases a separation of 5 mm may be acceptable. In one way or another, the dose in the scar should be ensured by appropriate optimisation. d. There are rigid fastening systems to help maintain the applicator in a fixed position if the patient does not move. Experience has shown that fastening systems with bandages around the waist and tied to the applicator are also adequate. To stabilise the cylinders horizontally, it is very useful to place a rolled towel under the metallic bar in the extravaginal portion and between the patient’s legs. e. With cylinders, it is recommended to maintain the applicator in a horizontal position to decrease the dose to the rectum or bladder, and it should press on the vaginal vault to distend it and prevent the applicator from separating from the surface. With colpostats, vaginal packing with a bandage is used. f. Some centres use marking with silver seeds in the vaginal vault to control the position of the applicator in each fraction, particularly when vaginal cylinders are used.

e.

f.

g.

7. Planning a. The current trend is to use 3D planning in BT when it is required to optimise the dose to a tumour in any location. However, there is debate on the need to perform personalised dosimetry in cases in which no tumour is visible. In postoperative treatment of endometrial cancer, whenever the dose administered is prophylactic, there are doubts about the need to perform CT-based planning or planning based on standard dosimetric calculation. b. A library plan can be used, that is, the same theoretical standard dosimetry can be used for all patients without the need to make any personalised calculations, both for CTV and organs at risk (OAR). c. X-rays can be made in a simulator with orthogonal films, which allows for planning based on the applicator and prescribed to points but not volumes, so the dose to OAR cannot be calculated by volume. d. Planning may be based on CT or MRI for which the conditions recommended in the consensus for

h.

i.

3D planning in gynaecological BT are followed [21]. Personalised calculations may be made or a library plan can be used and applied to CT or MRI images. In practice, it is very difficult to estimate the millimetres of prescription in the CTV with CT. Therefore, a standard plan is usually maintained for prescription and the CT information is used to evaluate D2cc for OAR. If X-ray, CT or MRI are performed, moving and immobilisation of the patient for imaging acquisition must be rigorously controlled. In these cases, it is recommended to clean the rectum, and empty the bladder and instil a fixed amount of contrast for the CT scan; in any case, all fractions for treatment of the bladder should always be under the same conditions as the day of calculation to ensure reproducibility of dosimetric calculation. It has been shown that the dose to the bladder is similar in each application; however, the dose to the rectum is highly variable, and particularly the dose to the sigma. This is why some suggest that all applications should be calculated. Prophylactic vaginal BT is the most common treatment of all and if performed with a HDR leads to an increase in the number of applications. 3D planning for each treatment results in increased work and time expenditure to obtain little or no therapeutic benefit, so many specialists consider it unnecessary. There was a consensus that 3D calculation does not imply a change in the treatment decision since the doses in OAR in prophylactic vaginal BT never exceed the acceptable maximum doses. It was agreed that 3D planning should be performed in a centre when BT treatment is started to determine its own data and to verify that the doses administered are within the range accepted in the consensus. From a certain number of cases, it is left to the discretion of each centre to perform standard nonpersonalised treatments with a library plan without having to calculate each case.

8. Dose prescription a. Considering the publications on the subject, LDR, HDR and PDR BT is prescribed either on the sur-

268


face or 5 mm from the surface of the applicator. At this meeting consensus was reached that normalisation, prescription and optimisation of the absorbed dose should be made 5 mm from the applicator. b. Many authors prescribe a fixed dose 5 mm from the applicator regardless of the surface dose, but it is recommended to always consider this dose, since depending on optimisation, particularly with very small diameter (2 cm) cylinders, could cause the delivery of unacceptable mucosal surface doses. c. The CTV is equal to the PTV and should include the proximal third of the vagina, covering a length from at least 2.5 cm up to 4 cm. d. It is considered that the whole length of the vagina should not be included since the incidence of metastasis in the lower third is low, and the risk of complications and particularly of vaginal stenosis increases with the irradiated length.

9. Dosimetry a. The active length depends on the type of applicator. Cylinders should be longer than the length of vagina that it is desired to irradiate to prevent a fall in dose in the lower third of the CTV. b. When the diameter of the cylinder or dome changes, the surface dose is different for each diameter if a fixed dose at 5 mm is maintained due to the dose gradient. It was thus agreed that the total dose to administer adding all applications refers to the EQD2 or isoeffective dose in the vaginal surface. c. The EQD2 or isoeffective dose is the equivalent dosage to that which would be received if standard fractionation of 2 Gy per session with external RT was used. d. According to the recommendations of the GEC-ESTRO, an alpha/beta of 10 Gy is considered when we refer to the tumour or target volume, and an alpha/ beta of 3 Gy when we seek the equivalent in OAR. e. The recommended total dose in EQD2 in prophylactic BT should be between 60 and 70 Gy to the vaginal surface when the BT is used alone, and between 75 and 85 Gy when combined with external RT, adding RT and BT. f. The doses per fraction and number of fractions will comply with these total doses, while any regime keeping within these limits is acceptable. g. The dose in OAR should be assessed in volumes, not points, and the most significant dose is the dose to 2 cc of the organ, using an alpha/beta of 3. The same dose limits are accepted as in all other gynaecological BT: 90 Gy in bladder (BD2cc), 70–75 in rectum (RD2cc) and 75 Gy in sigma (SD2cc). These doses are recommended for definitive treatment of cervical cancer, therefore in prophylactic vaginal BT lower doses should be achieved.

h. Some studies show that in prophylactic vaginal BT the total doses in OAR do not exceed 65 Gy in combination treatments with RT and BT, or approximately 45 Gy when BT alone is used. It is thus considered useful to know the dose to OAR, but not significant to decide on a change in dose, and therefore its calculation is not essential.

10. Treatment a. It is recommended to treat with an empty bladder. Prophylaxis of cystitis can be performed with intravesical hyaluronic acid (according to the survey, this is done in 21% of centres). b. The applicator should be placed in the same position as that used when CT or MRI was done. If vaginal cylinders (domes) are used and imaging is not performed for planning but a standard library plan is used, the applicator should be placed horizontally and exerting pressure on the fundus, and this should be verified in each implant. c. On concluding the treatment, it is recommended to use some type of vaginal dilator to prevent vaginal stenosis, which is the main complication that can be prevented. d. The recommendations for care of BT patients are usually carried out by nursing staff. According to the survey, 79% of centres reported having a nursing clinic.

11. Treatment report a. The discharge report should specify type of BT, applicator type and diameter, clinical examination, and number and date of applications, and indicate whether an imaging method (CT/MRI) or standardised calculation was used for planning treatment. b. It should also specify dose per fraction and the total dose 5 mm from the vaginal surface, and report the equivalent doses of BT to the surface in EQD2. Since the values vary in the surface over the length of the entire CTV, a range of doses may be considered. c. It is not necessary to report the dose to OAR.

B. Unoperated endometrium: endouterine brachytherapy 1. Indications a. BT should be part of treatment in endometrial carcinoma provided that hysterectomy is not performed. b. Endouterine BT is usually used as a boost after external RT when possible.


c. In early cases, BT alone may be considered if a distribution of dose adapted to the shape of the uterus is obtained.

2. Type of brachytherapy a. The LDR, HDR or PDR modalities of BT are equally effective for treatment of endometrial carcinoma [22, 23]. b. HDR and PDR BT offer the possibility to optimise the dose. c. As HDR BT is given in short sessions, it avoids bed confinement of patients and so is less uncomfortable and better tolerated.

3. Type of applicators a. For normal or large uteruses, there are double endouterine rigid metallic probes, appropriate for CT. There are endouterine probes for MRI that are thicker than the CT ones. b. For small uterus, a single endouterine catheter may be used to which vaginal cylinders, colpostats or moulds can be attached. c. More than two endouterine probes may sometimes be placed to improve dose distribution. d. “Packing”, or placement of multiple low-rate loads or multiple high-rate catheters to fill the entire uterine cavity, is rarely used in daily practice.

269

b.

c.

d.

e.

f.

centres treating unoperated patients stated that they used anaesthesia in some applications. It is very useful to use ultrasound as a method to perform image-guided implantation or image-guided brachytherapy (IGBT). It is also useful in some cases to perform a hysteroscopy as it allows de visu to determine the geographical location of the tumour in the uterine cavity, to measure treatment response with external RT and sometimes to help placement of endouterine probes. For CT-based planning, diluted contrast (1 cc) is placed in the Foley balloon in a total amount of 7 cc. When MRI is used, only air or bidistilled water are placed. The bladder can be filled with 200–300 ml of physiological saline to perform a pelvic ultrasound. Vaginal packing is performed with a bandage and if external fixation is required, it may be made with bandages or any rigid fastening system. The position of the applicator must be checked in each fraction.

6. Imaging techniques for planning a. Although planning with X-rays taken in a simulator with orthogonal films can be used, the only way to visualise the dimensions of the uterus is by CT or MRI. b. The conclusions of the consensus on 3D planning in gynaecological BT are applied [21]. c. It is recommended to calculate all applications taking into account the difficulty in placing the endouterine probes in the same position. d. A system to move and immobilise the patient until imaging should be used.

4. Fractioning and dose per fraction a. The uterine cavity is a difficult volume to cover with BT, so whenever possible it is recommended to perform a combined treatment with external RT and BT. BT must be made on concluding external RT so that endouterine tumour volume is reduced and insertion of the applicators is easier. b. The dose per fraction with HDR is from 5 to 6 Gy, between 4–5 fractions after 40–50 Gy of external RT and 2–3 fractions after 60–66 Gy (45 50 Gy on pelvis and rest of the uterine volume). c. When BT is used alone, dose and number of fractions is between 8.5 Gy×5 fractions once weekly and 5–6 Gy×6–8 fractions.

5. Implant a. The first application is performed with sedation and/ or anaesthesia and analgesia, which may require admission. The following applications can be performed on an outpatient basis. In the survey, 41% of

7. Volume contouring, organs at risk a. The recommendations of the ABS and GEC-ESTRO are followed. b. The clinical target volume (CTV) or target volume is the uterus, including the cervix and 2–4 cm of the vagina. c. The OAR in gynaecological BT are the bladder, rectum and sigma. 8. Dose prescription a. Typical dosimetry of the uterine body corresponds to an “inverted pear” shaped dose curve, wider at the fundus and narrower at the cervix. b. The dose can be prescribed to points or to a volume. It has traditionally been prescribed to points related to the applicator that does not take into account the shape of the uterus. The uterine points of prescription are 1 cm below the tip of the applicator and 2 cm lateral to the source when a single probe is used

270


or 2 cm lateral when two probes are used [8]. Another mode of prescription is considering the thicknesses of uterine wall defined by ultrasound. c. Currently, the dose should be prescribed for the uterine volume based on the 3D image, which is usually conspicuous on the CT, covering all the uterine wall to the serosa and 2–4 cm of the vagina. 9. Dosimetry a. The length of the load is the complete extent of the uterus including the cervix. If there is a second probe, it is loaded only from the tip to where the two merge. b. The recommendations of the GEC-ESTRO propose, for the isoeffective dose, EQD2, an alpha/beta of 10 Gy when we refer to the tumour or target volume, and an alpha/beta of 3 Gy when we seek the equivalent in OAR. c. The dose to the uterine volume is from 75 to 85 Gy in total adding RT to BT. The dose to OAR should be calculated by volumes instead of points: 90 Gy in bladder (DV2cc), 70–75 Gy in rectum (DR2cc) and 75 Gy in sigma (DS2cc). 10. Treatment report a. It should specify the type of BT, type of applicators and hysterometry, clinical examination, number and date of applications, and imaging method used for treatment planning (CT/MRI). References 1. González E, Lobato R (2008) Cáncer de endometrio operado. BT con HDR, cilindro vaginal. In: Guinot JL, Lanzós E, Muñoz V et al (eds) Guía de Braquiterapia. SEOR and Nucletron, Madrid 2. Creutzberg CL, van Putten WLJ, Koper PCM et al; PORTEC Study Group (2000) Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomized trial. Lancet 355:1404–1411 3. Scholten AN, van Putten WL, Beerman H et al (2005) Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys 63:834–838 4. Keys HM, Roberts JA, Brunetto VL et al (2004) A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 92:744–751 5. Nout RA, Smit VT, Putter H et al (2010) Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an openlabel, non-inferiority, randomized trial. Lancet 375:816–823 6. Eltabbakh GH, Piver MS, Hempling RE, Shin KH (1997) Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial. Int J Radiat Oncol Biol Phys 38:373–380 7. Creutzberg CL, van Putten WL, Warlam-Rodenhuis CC et al (2004) Outcome of high-risk stage

8.

9.

10.

11.

12.

13.

14.

15.

b. It should specify dose per fraction to the CTV and the total dose adding RT and all fractions of BT in EQD2, and report the dose to 2cc volume of OAR DV2cc, DR2cc and DS2cc.

Conclusion BT plays a key role in therapy in endometrial carcinoma, and it is essential to reach an agreement to offer the best technique in the most appropriate indications according to the latest studies and the new FIGO classification. This consensus aims to create a common language to be able to share experiences and contribute to better clinical practice in our setting. Each centre should follow their regimens based on their judgement but under the direction of these guidelines to offer patients a greater expectation of cure with a lower complication rate. Conflict of interest The authors declare that they have no conflict of interest relating to the publication of this manuscript. Acknowledgements We thank all attendees at the meeting, physicians and physicists, both members and nonmembers of the SEOR, and members of the SEFM, for their participation and their contributions to the debate with the aim of reaching a consensus beyond divergent opinions. We thank Dr J. Romero of H. Puerta Hierro (Madrid) for his contribution on radiobiology and the hospitals that presented their results, Dr F. Casquero of H. Cruces (Baracaldo), Dr R. del Moral of Hospital Virgen de las Nieves (Granada), Dr R. Correa and C. Jódar of H. Virgen de la Victoria (Málaga), Dr P. Samper of H. Central de la Defensa (Madrid) and Dr C. Gutiérrez of I. Català d’Oncologia (Barcelona). We also thank Dr Laura García Sánchez and Dr Rocío Pérez for preparation of the summary of the meeting.

IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol 22:1234–1241 Nag S, Erickson B, Parikh S et al (2000) The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the endometrium. Int J Radiat Oncol Biol Phys 48:779–790 Small W Jr, Erickson B, Kwakwa F (2005) American Brachytherapy Society survey regarding practice patterns of postoperative irradiation for endometrial cancer: current status of vaginal brachytherapy. Int J Radiat Oncol Biol Phys 63:1502–1507 Creasman WT, Morrow CP, Bundy BN et al (1987) Surgical pathologic spread patterns of endometrial cancer: a Gynecologic Oncology Group Study. Cancer 60:2035–2041 ASTEC/EN.5 Study Group (2009) Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet 373:137–146 Johnson N, Cornes P (2007) Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis. BJOG 114:1313–1320 Lee CM, Szabo A, Shrieve DC et al (2006) Frequency and effect of adjuvant radiation therapy among women with stage I endometrial adenocarcinoma. JAMA 295:389–397 Kong A, Johnson N, Cornes P et al (2007) Adjuvant radiotherapy for stage I endometrial cancer. Cochrane Database Syst Rev (2):CD003916 Fanning J (2001) Long-term survival in intermediate risk endometrial cancer (stage IG3,

16.

17.

18.

19.

20.

21.

22.

23.

IC, II) treated with fully lymphadenectomy and brachytherapy without teletherapy. Gynecol Oncol 82:371–374 Nag TY, Niclin JL, Perrin LC et al (2001) Postoperative vaginal vault brachytherapy for node negative stage II (occult) endometrial carcinoma. Gynecol Oncol 81:193–195 Mutch DG (2009) The new FIGO staging system for cancers of the vulva, cervix, endometrium and sarcomas. Gynecol Oncol 115:325–328 Pera J, Gutiérrez C, Polo A (2008) Cáncer de endometrio operado. BT con LDR. In: Guinot JL, Lanzós E, Muñoz V et al (eds) Guía de Braquiterapia. SEOR and Nucletron, Madrid Martinez-Monge R, Nagore G, Cambeiro M et al (2007) Intravaginal 1-week high-dose-rate brachytherapy alone for stages I-II endometrial cancer. Brachytherapy 6:195–200 Rovirosa A, Ascaso C, Sánchez-Reyes A et al (2011) Three or four fractions of 4-5 Gy per week in postoperative high dose rate brachytherapy for endometrial carcinoma. Int J Radiat Oncol Biol Phys 81:418–423 Guinot JL, Pérez-Calatayud J, Rodríguez S et al (2010) Consensus on 3D treatment planning in gynaecologic brachytherapy of the Radiation Oncology Spanish Society (SEOR) Brachytherapy Group. Clin Transl Oncol 12:181–187 Rovirosa A, Biete A (2008) Cáncer de endometrio no operado. BT con LDR. In: Guinot JL, Lanzós E, Muñoz V et al (eds) Guía de Braquiterapia. SEOR and Nucletron, Madrid Pinar B, Martín de Vidales MC (2008) Cáncer de endometrio no operado. BT con HDR. In: Guinot JL, Lanzós E, Muñoz V et al (eds) Guía de Braquiterapia. SEOR and Nucletron, Madrid