Brachytherapy for cervical cancer in septate uterus: Dose-volume differences with tandem implant placement in right vs. left uterine canal: A case report

  • Authors:
    • Naoya Ishibashi
    • Toshiya Maebayashi
    • Takuya Aizawa
    • Masakuni Sakaguchi
    • Takehiro Nakao
    • Masahiro Okada
  • View Affiliations

  • Published online on: March 6, 2018     https://doi.org/10.3892/ol.2018.8179
  • Pages: 7273-7278
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Abstract

Brachytherapy is a standard treatment modality for locally advanced cervical cancer. In patients with uterine anomalies, the radiation dose to the target volume and the organs at risk can vary depending on the positioning of the brachytherapy tandem implant. However, there have been few reports concerning the use of brachytherapy in patients with uterine anomalies. The present study reports the case of a 55‑year‑old woman with locally advanced squamous cell carcinoma of the cervix and complete septate uterus. The patient was treated with external‑beam radiation therapy, cisplatin chemotherapy, and brachytherapy. Computed tomography‑based planning was performed for image‑guided brachytherapy with the tandem implant alternately in the right and left uterine canals and using the right and left point A. A comparison of the resulting dose‑volume histograms revealed wide variations in the projected dose to the clinical target volume and organs at risk. Tandem implant positioning for brachytherapy was chosen to optimize the dose‑volume distribution. At the point of writing, the patient has not experienced local recurrence.

Introduction

The standard treatment for locally advanced cervical cancer is pelvic external beam radiation therapy (EBRT) with concurrent cisplatin chemotherapy and brachytherapy (BT) (13). Recently, 3D image-guided brachytherapy (IGBT), which uses computed tomography (CT) or magnetic resonance imaging (MRI) to obtain images of inserted applicators, has come into widespread use (46). The present study reports the use of BT in a patient with locally advanced cervical cancer involving a complete septate uterus with right and left uterine canals. Prior to treatment, CT images were obtained with a tandem implant inserted alternately into the right and left uterine canals. A treatment-planning system was used to compare the resulting dose volumes; the uterine canal that was associated with optimal distribution of the dose volume was chosen for BT. There have been only a few reports of BT in patients with uterine anomalies. To the best of our knowledge, this is the first case in which the dose-volume difference between tandem implant placement in the right versus left uterine canal was examined.

Case report

Patient presentation and diagnosis

A 55-year-old woman presented with a 1-month history of general malaise. A high creatinine level of 2.26 mg/dl (normal range, 0.46–0.79 mg/dl) was found upon hematological examination; CT revealed that a cervical tumor was causing bilateral hydronephrosis involving the bilateral ureters. Therefore, bilateral ureteral stents were inserted. Tissue biopsy of the cervical tumor led to a diagnosis of squamous cell carcinoma. MRI revealed that the endometrial cavity was separated into right and left canals by a septum on the cranial side of the cervical tumor (Fig. 1A and B). The septum reached the level of the internal cervical os, indicating a complete septate uterus corresponding to class V of the American Society of Reproductive Medicine classification (7) and class U2 of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy classification (8). The patient exhibited hydronephrosis at presentation, indicating disease stage IIIB, according to the uterine cervical cancer staging system of the International Federation of Gynecology and Obstetrics (FIGO) (9). CT and MRI revealed no lymph node metastasis; endoscopy revealed no abnormalities of the mucosa in the rectum or the bladder. Thus, combined EBRT and concurrent chemotherapy with 5 courses of intravenously administered weekly cisplatin (40 mg/m2) and high-dose-rate BT were planned with hospitalization. For EBRT, whole-pelvic irradiation, covering the cervical tumor, uterus, parametrium, vagina, and the pelvic lymph node regions as the clinical target volume, was performed using the box technique (6). Irradiation was applied at 2 Gy per fraction five times per week until 30 Gy was reached. Thereafter, a central shield (3 cm wide) was added and irradiation was administered until a total dose of 50 Gy was reached.

Intracanal brachytherapy

A second MRI performed prior to BT revealed that the cervical tumor had shrunk, allowing the tandem insert to be inserted into the right and left uterine canals separately. The right canal lumen was 7 cm long and the left was 6 cm, according to MRI findings. In the BT room, a standard tandem implant (LAR 04-01; Eckert & Ziegler BEBIG, Berlin, Germany) with a 15° angle was inserted in the left uterine canal to a distance of 6 cm from the external cervical os under X-ray fluoroscopy; ovoid implants were inserted into the right and left vaginal fornices. Following X-ray imaging, the patient was transferred to a CT room, where CT images with a 2-mm slice thickness were obtained and tandem implant insertion in the left uterine canal was confirmed (Fig. 2A). The patient was returned to the BT room, where a standard tandem implant (LAR 06-01; Eckert & Ziegler BEBIG) with a 30° angle was inserted in the right uterine canal at a distance of 7 cm under X-ray fluoroscopy; ovoid implants were placed into the right and left vaginal fornices. After X-ray imaging, CT images were obtained that confirmed tandem implant insertion in the right uterine canal (Fig. 2B). At Nihon University School of Medicine (Tokyo, Japan), high-dose-rate BT was performed with a 60Co remote afterloading system (MultiSource; Eckert & Ziegler BEBIG). The CT images were uploaded to the treatment planning system (HDR plus; Eckert & Ziegler BEBIG), and the high-risk clinical target volume (HR-CTV) and organs at risk (OARs; the rectum and bladder) were contoured according to the Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology guidelines (10,11). The gross tumor volume was determined using pretreatment contrast-enhanced CT images and second MRI images prior to BT for reference. At Nihon University School of Medicine, positional checks for BT are performed with X-ray films alone; Manchester point A (12) was used for treatment planning. On CT, the left and right Manchester point A were set 2 cm superior to the line connecting the superior aspects of the ovoid implants and 2 cm to the right and left of the intrauterine source train. Calculation of the 90% target dose (D90) for HR-CTV, the minimum dose delivered to the highest irradiated 2-cm3 area (D2 cm3) for the rectum, and the D2 cm3 for the bladder per fraction at a dose of 6 Gy to the right and left of point A with the tandem implant inserted into the right and left uterine canals in succession revealed the presence of wide variations in the isodose lines for the OARs (Fig. 3). When the dose-volume histograms of these four treatment plans were compared, there were variations in each item; there was a particularly wide variation in D2 cm3 for the bladder, ranging from 7.49 to 12.41 Gy per fraction (Table I). A total of four irradiations (two irradiations based on the treatment plan at the right point A with the tandem implant inserted into the right uterine canal, which was associated with the lowest dose for OARs, and two irradiations based on the treatment plan at the left point A with the tandem implant inserted into the right uterine canal, which was associated with the highest dose for HR-CTV) were applied at a dose of 6 Gy per fraction. Prior to each BT session, X-ray films were obtained and compared with X-ray images obtained at the time of CT for positional checks, and tandem implant insertion in the right uterine canal was confirmed. To reproduce the treatment plan developed with CT imaging as accurately as possible, the patients legs were extended during BT in the same manner as during CT imaging. The total dose of EBRT and BT was ~61.76 Gy [2 Gy per fraction-equivalent dose; (EQD2)] for D90 for HR-CTV, 61.73 Gy (EQD2) for D2 cm3 for the rectum and 115.5 Gy (EQD2) for D2 cm3 for the bladder, with α/β=10 for HR-CTV and α/β=3 for the OARs. The cisplatin dose was reduced to 30 mg/m2 because of renal function impairment, as was administered once a week for five courses. As acute complications, grade 2 diarrhea and grade 2 cystitis (according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.03 (13) were noted; which resolved spontaneously. No local recurrence has occurred at the time of writing, 1.5 months after the completion of radiation therapy.

Table I.

Dose-volume histogram variations for high-risk clinical target volume and organs at risk at a prescribed dose of 6 Gy per fraction at point A.

Table I.

Dose-volume histogram variations for high-risk clinical target volume and organs at risk at a prescribed dose of 6 Gy per fraction at point A.

GrLocation of tandem implantPoint AHR-CTV D90, GyRectum D2 cm3, GyBladder D2 cm3, Gy
Right canalRight5.014.177.49
Right canalLeft6.855.7010.24
Left canalRight4.925.0610.52
Left canalLeft5.815.9612.41

[i] HR-CTV D90, minimum dose delivered to 90% of the high-risk clinical target volume; D2 cm3, minimum dose delivered to the highest irradiated 2-cm3 area.

Discussion

The standard treatment for locally advanced uterine cervical cancer is EBRT with concurrent cisplatin chemotherapy and BT (14,15). For BT, a prescribed dose of irradiation is traditionally applied to the Manchester point A. However, in the case of a large mass, it is possible for irradiation to this point A, administered with a uniform approach, to result in an insufficient dose to the tumor. In recent years, favorable disease control has been achieved with more efficient irradiation of cervical tumors using 3D image-guided BT (IGBT) with CT or MRI, instead of a point A prescription (46). However, a 2015 nationwide Japanese survey reported that 84% of BT treatment facilities used X-ray films during treatment (16). Until recently, position-checking and treatment-planning at Nihon University School of Medicine were performed using a 2D method that used X-ray film, as CT was not available in the treatment room, and it was therefore difficult to obtain CT images with the patient in a proper position and with the applicators inserted properly. A standard fixed dose of 6 Gy per fraction was prescribed to the point A, according to the Japanese Gynecologic Oncology Group 1066 prospective study (15). However, the present patient had a complete septate uterus with left and right uterine canals. Therefore, it was expected that the dose distribution of the point A prescription would vary widely depending upon whether the tandem implant was inserted into the right or left uterine canal. To overcome this challenge, the tandem implant was inserted into the right and left uterine canal by turns and CT images were used to compare the resulting dose-volume histograms. As expected, the D90 for HR-CTV and the D2 cm3 for the OARs varied according to the point A and the location of the tandem implant. The variation was particularly wide in the D2 cm3 for the bladder. This finding might be explained by changes in the intensity of bladder compression by the uterus according to the position of the tandem implant. This variation in the dose to OARs cannot be assessed with X-ray films alone. The use of CT images in this case allowed us to confirm the optimal uterine canal for tandem implant insertion and the optimal point A.

To the best of our knowledge, there have been only four reported cases (1720) of BT in patients with uterine anomalies (Table II). No dose-volume histogram comparisons with insertion of the tandem implant into the right versus left uterine canals were reported in any of those cases. Two cases of BT in patients with uterus didelphys have been reported (17,20). In one of these cases, tandem implants were inserted into the two uterine canals simultaneously, and the point A was defined according to the midline between the two tandem implants and was 2 cm superior to the mean position of the os cervix (17). In the other case, a mold was inserted vaginally and a dose was prescribed for HR-CTV according to IGBT (20). One reported case involved a bicornuate uterus. In that case, a mold was inserted vaginally, and from there a radiation source was inserted into one uterine canal, whereas a marker was inserted into the other uterine canal and the position of the marker of point A of the other side was calculated; this process was repeated for the opposite canal (18). The fourth patient had a partial septate uterus. In that case, the Rotte Y applicator, which includes two tandem implants, was used; tandem implants were inserted simultaneously into the two uterine canals and were locked together with two ovoid implants. Point A was then defined as 2 cm superior to the line connecting the superior aspect of the ovoid implants and 2 cm lateral to the line running between and parallel to the two channels of the Rotte Y applicator (19).

Table II.

Patients with uterine anomaly treated with brachytherapy.

Table II.

Patients with uterine anomaly treated with brachytherapy.

PatientAge, yearsFIGO stageHistologyUterine anomalyEBRTBT technique and doseChemotherapyRFS, months(Refs.)
145IIA1P/D squamous cell carcinomaUterus didelphysWhole pelvis; 45 Gy2 tandems in the two uterine canals; HDR; 6 Gy × 1, 6.5 Gy × 1; modified point AUnknown~36(17)
258IIAM/D squamous cell carcinomaBicornuate uterusWhole pelvis; 50 GyVaginal mold and catheter alternately in each uterine canal; LDR; 9 Gy × 2; point ACisplatin24(18)
334IIBP/D adenocarcinomaSeptate uterusWhole pelvis; 45 Gy; metastatic iliac node; additional 9 Gy2 tandem implants in the two uterine canals and 2 ovoid implants; HDR; 5.5 Gy × 5; point ACisplatin20(19)
437IIIAAdenocarcinomaUterus didelphysWhole pelvis and para-aorta; 50.4 Gy;Vaginal mold; PDR; 20 Gy × 1; HR-CTV GTV 59.92 GyCisplatin30(20)
555IIIBP/D squamous cell carcinomaSeptate uterusWhole pelvis; 50 GyTandem implants in right uterine canal and 2 ovoid implants; 6 Gy × 4; point ACisplatin1.5Present case

[i] FIGO, International Federation of Gynecology and Obstetrics; EBRT, external beam radiation therapy; BT, brachytherapy; P/D, poorly differentiated; RFS, relapse-free survival; HDR, high dose rate; PDR, pulsed dose rate; GTV, gross tumor volume; HR-CTV, high-risk clinical target volume; M/D, moderately differentiated; LDR, low dose rate.

Uterine anomalies are found in up to 7% of women. A septate uterus is the most common of these, found in 0.9–2% of women and accounting for 55% of all mullerian anomalies (21,22). Detailed examination of CT and MRI images from patients with uterine cervical cancer reveals that a septate uterus may not be uncommon. When BT is performed in patients with a septate uterus, the optimal dose distribution can be determined without the use of special instruments by comparing dose-volume histograms with the standard tandem implant inserted alternately into the right and left uterine canals. In the present case, the approximate total dose of EBRT and BT was 61.76 Gy (EQD2) for the D90 for HR-CTV, 61.73 Gy (EQD2) for the D2 cm3 for the rectum, and 115.5 Gy (EQD2) for the D2 cm3 for the bladder. According to a previous study concerning a patient with uterine cervical cancer treated with BRT and BT with central shielding (6), the D90 for HR-CTV reached the necessary dose, and the patient exhibited no local recurrence. However, the D2 cm3 for the bladder was high, necessitating meticulous ongoing follow-up for the possible development of late complications.

The present study shows that when cervical cancer with uterine anomalies is treated with BT, the projected dose and the clinical target volume may vary, putting organs at risk. Where possible, CT based BT should be the preferred course of action.

Acknowledgements

The authors would like to thank Dr Rebecca Tollefson for editing a draft of this manuscript.

Funding

No funding was received.

Availability of data and materials

Not applicable.

Authors contributions

NI treated the patient and analyzed the patients data, and was a major contributor in writing the manuscript. TN biopsied the cervical tumor and performed chemotherapy. TM, TA, MS and MO treated the patient. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The patient provided written informed consent.

Consent for publication

The patient provided written informed consent.

Competing interests

The authors declare that they have no competing interests.

Glossary

Abbreviations

Abbreviations:

EBRT

external beam radiation therapy

BT

brachytherapy

IGBT

image-guided brachytherapy

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Spandidos Publications style
Ishibashi N, Maebayashi T, Aizawa T, Sakaguchi M, Nakao T and Okada M: Brachytherapy for cervical cancer in septate uterus: Dose-volume differences with tandem implant placement in right vs. left uterine canal: A case report. Oncol Lett 15: 7273-7278, 2018
APA
Ishibashi, N., Maebayashi, T., Aizawa, T., Sakaguchi, M., Nakao, T., & Okada, M. (2018). Brachytherapy for cervical cancer in septate uterus: Dose-volume differences with tandem implant placement in right vs. left uterine canal: A case report. Oncology Letters, 15, 7273-7278. https://doi.org/10.3892/ol.2018.8179
MLA
Ishibashi, N., Maebayashi, T., Aizawa, T., Sakaguchi, M., Nakao, T., Okada, M."Brachytherapy for cervical cancer in septate uterus: Dose-volume differences with tandem implant placement in right vs. left uterine canal: A case report". Oncology Letters 15.5 (2018): 7273-7278.
Chicago
Ishibashi, N., Maebayashi, T., Aizawa, T., Sakaguchi, M., Nakao, T., Okada, M."Brachytherapy for cervical cancer in septate uterus: Dose-volume differences with tandem implant placement in right vs. left uterine canal: A case report". Oncology Letters 15, no. 5 (2018): 7273-7278. https://doi.org/10.3892/ol.2018.8179