Ultrasoundguided tandem placement for ... - Wiley Online Library

Ultrasound Obstet Gynecol 2011; 37: 241–244 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.8805

Ultrasound-guided tandem placement for low-dose-rate brachytherapy in advanced cervical cancer minimizes risk of intraoperative uterine perforation J. M. WATKINS*, P. L. KEARNEY*, K. J. OPFERMANN*, S. J. ACKERMAN†, J. M. JENRETTE* and M. F. KOHLER‡ *Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA; †Department of Radiology, Medical University of South Carolina, Charleston, SC, USA; ‡Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, USA

K E Y W O R D S: brachytherapy; cervix neoplasms; ultrasonography; uterine perforation

ABSTRACT Objectives Tandem placement as part of low-dose-rate (LDR) brachytherapy boost for cervical cancer may be complicated by uterine perforation. The objective of this study was to describe a 10-year experience of using intraoperative ultrasound guidance in an attempt to minimize the risk of uterine perforation. Methods Operative and inpatient records were reviewed to identify cases in which intraoperative ultrasound guidance was employed in order to assist tandem placement, and to determine whether clinical or radiographic findings subsequently suggested uterine perforation. Demographic factors were collected in order to determine the baseline risk of perforation within this population. Results Between 1998 and 2008, 71 patients underwent 110 ultrasound-guided placements of tandem applicators. The median age was 48 (range, 26–88) years, and 20% were older than 60 years. Disease stage was FIGO IB1 (n = 10), IB2 (n = 13), IIA (n = 4), IIB (n = 19), IIIA (n = 2), IIIB (n = 16), IVA (n = 5) and IVB (n = 2). The median gravidity was 3 (range 1–10) and median parity was 3 (range 0–10). Seven patients had a preimplant history of pelvic infection, four had a history of intrauterine contraceptive device use, and 10 had a prior history of Cesarean section delivery. Only one patient experienced infection that may have been attributable to tandem placement-associated uterine perforation. At median survivor follow-up of 34 months, 19 patients had died. The estimated 3-year disease-free and overall survival rates for the entire population were 60% and 66%, respectively. Conclusions Within the present population, intraoperative ultrasound guidance of tandem placement was

associated with no confirmed cases of uterine perforation. Copyright  2011 ISUOG. Published by John Wiley & Sons, Ltd.

INTRODUCTION Cervical cancers confined to the uterus and locally advanced cervical cancers may be optimally managed with definitive radiotherapy (or radiochemotherapy)1 – 3 . Major randomized trials have employed external beam radiotherapy followed by a brachytherapy boost, typically low dose rate (LDR) with 137 Cs1 – 5 . LDR brachytherapy requires the placement of a tandem applicator into the uterine cavity through the cervical os; this is often done ‘blindly’, by advancing the tandem until the brachytherapist senses slight resistance to indicate that the tandem tip has approximated the uterine fundus6 . The risk of uterine perforation using this technique has been described at rates of 2–14%6 – 10 , and may adversely affect patient outcomes7 . One technique for ‘real-time’ verification of tandem position is intraoperative ultrasonography9,11 . The present investigation reviews our 10-year institutional experience employing real-time ultrasonography for tandem placement.

METHODS Following Institutional Review Board approval at Medical University of South Carolina, a research database was created with study-specific patient, treatment and outcome data fields. Eligible cases were identified by a review of the departmental quality-assurance database, medical records and office management software. Selection criteria for the present study included all cervical

Correspondence to: Dr M. F. Kohler, Department of Obstetrics and Gynecology, Medical University of South Carolina, 169 Ashley Avenue, Charleston, SC 29425, USA (e-mail: [email protected]) Accepted: 9 August 2010

Copyright  2011 ISUOG. Published by John Wiley & Sons, Ltd.

ORIGINAL PAPER

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cancer patients who had undergone intrauterine tandem placement under real-time intraoperative ultrasound guidance. Perforation was documented using real-time intraoperative imaging as well as review of hospital records and patient charts for post-procedural clinical and/or radiographic evidence of perforation. Within our institution, early-stage non-bulky cases of cancer of the cervix (FIGO Stages IA2–IB1) are treated with radiotherapy alone, while early-stage bulky and loco-regionally advanced (and selected oligometastatic) cases (IB2–IVB) are treated with concurrent radiochemotherapy. Patients are generally treated with external beam pelvic radiotherapy (45 Gy in 25 oncedaily fractions over the course of 5 weeks), followed by LDR brachytherapy boost to 80–85 Gy (to point A) using a 137 Cs source placement in tandem and ovoid applicators placed on weeks 6 and 8 (Point A being defined bilaterally at 2 cm cranial and 2 cm lateral to the cervical os, along the axis of the tandem bisection of the ovoids (ICRU, Bethesda, MD, USA, 1985)). Ultrasound guidance is employed at the discretion of the gynecologist, and was used in all the present cases by the corresponding author (M.F.K.), who performed nearly all LDR brachytherapy implants during the study period. Our institutional intraoperative ultrasound technique includes pelvic examination under anesthesia for evaluation of the primary tumor residuum and identification of the cervical os. (General anesthesia was employed in all cases in the present series.) Placement of a Foley catheter and drainage of urine is then performed, followed by retrograde instillation of 150–300 mL of normal saline by gravity into the bladder. The catheter is then clamped and, with the patient’s bladder full, an ultrasound technician proceeds with real-time transabdominal pelvic ultrasound scanning. The skin of the low abdomen just above the pubic symphysis is prepared with Aquasonic Ultrasound Transmission Gel (Parker Laboratories, Inc., Fairfield, NJ, USA). During the present series, a GE LOGIQ 7 or 9 portable ultrasound machine was employed, with a curved 4.0-MHz ultrasound transducer (GE Healthcare Ultrasound, Milwaukee, WI, USA). The uterus is grasped with a single-toothed tenaculum and dilated under ultrasound guidance. The tandem curvature and depth of placement are selected based upon the uterine flexion and height from the external cervical os to the fundus, after which the tandem is carefully placed under real-time ultrasound guidance (Figures 1 and 2). The bladder is then drained, and ultrasound terminated. Placement of vaginal ovoids, as indicated by clinical situation and permitted by patient anatomy, is then performed, followed by vaginal packing using lubricated sterile gauze. Overall survival and progression-free survival were measured from the date of initiation of treatment (external beam radiotherapy) to the date of death or recurrence (earliest sign of clinical, radiographic or pathologic disease), respectively, or last follow-up if the patient was alive without evidence of disease recurrence. Diseasefree and overall survival rates were estimated using the Kaplan–Meier method. All survival figure construction


Figure 1 Photograph of standard Fletcher–Suit intracavitary tandem applicator set.

Figure 2 Ultrasound image of tandem placement in the cervix of a cervical cancer patient, with anatomic labels.

and analyses were performed using SPSS version 16.0 (SPSS, Inc., Chicago, IL, USA).

RESULTS Between 1998 and 2008, 71 patients underwent 110 ultrasound-guided placements of tandem and ovoid applicators. Nineteen patients underwent real-time ultrasonography during only one of the two implants performed because two different physicians performed the procedures. An additional 13 patients did not undergo a second LDR implant after ultrasound-guided placement of the first for the following reasons: patient non-compliance (n = 10); pulmonary embolism (n = 1); genital herpes (n = 1); and deep venous thrombosis following combined LDR implant and mastectomy for synchronous diagnosis of breast cancer (n = 1). Patient demographics are outlined in Table 1. The median external beam pelvic radiotherapy dose was 4500 (range, 4500–5040) cGy, and 58 patients received concurrent chemotherapy (54 platinum-based). During intraoperative assessment of tandem placement, no patient was noted to have experienced perforation of the uterine cavity. Perforation was considered but not verified (no pelvic or abdominal free air noted) in one patient who developed abdominal discomfort and fever during her first implant; she was found to have pyometra, which subsequently resolved with antibiotics. Three

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Table 1 Demographic data of patients included in the study (n = 71) Characteristic

1.0

Median (range) or n (%)

38 (54) 10 (14) 13 (18) 4 (6) 19 (27) 2 (3) 16 (23) 5 (7) 2 (3) 3 (1–10) 0 (0) 7 (10) 13 (19) 19 (28) 29 (43) 3 (0–10) 3 (4) 6 (9) 21 (30) 18 (26) 21 (30) 7 (10) 4 (6) 5 (7) 10 (14) 0 (0) 72.6 (41.3–119.7) 65 (92) 6 (8)

*Data available for only 68 patients. †Data available for only 69 patients. IUCD, intrauterine contraceptive device.

0.6

0.4

0.2

0

10

20 30 40 Disease-free survival (months)

50

60

Figure 3 Kaplan–Meier plot of disease-free survival from date of , censored). initiation of treatment (

1.0

0.8 Cumulative survival

48 (26–88) 14 (20)

Cumulative survival

0.8

Age (years) Age ≥ 60 years Ethnicity Non-White FIGO stage IB1 IB2 IIA IIB IIIA IIIB IVA IVB Gravidity* 0 1 2 3 ≥4 Parity† 0 1 2 3 ≥4 Prior pelvic infection Prior use of IUCD Prior hysteroscopic surgery Prior Cesarean section Prior uterine perforation Weight (kg) Pathology Squamous-cell Adenocarcinoma

0.6

0.4

0.2

patients required (or experienced) early removal of the device, one prior to loading (vaginal laceration) and two following loading (incontinence without fistula, emesisassociated Valsalva ejection of tandem/ovoid apparatus). It is notable that no uterine perforations were suspected or detected in the 19 patients who underwent tandem placement without ultrasound guidance. At a median survivor follow-up of 34 months, 19 patients had died and 28 patients experienced disease recurrence (10 loco-regional, 13 distant, five loco-regional and distant). The estimated 3-year disease-free and overall survival rates were 60% (95% confidence interval (CI), 49–71%; Figure 3) and 66% (95% CI, 55–77%; Figure 4), respectively.

DISCUSSION Uterine perforation during tandem placement for LDR brachytherapy has been described as occurring at rates of 2–14%6 – 10 . Avoidance of this complication is important, as perforations lead to increased patient morbidity and have even been associated with decreased cause-specific


0

10

20 30 40 Overall survival (months)

50

60

Figure 4 Kaplan–Meier plot of overall survival from date of , censored). initiation of treatment (

survival in advanced disease7 . The present investigation represents the largest published experience using this technique. Only one patient experienced infection that may have been attributable to tandem placement, resulting in a rate of < 1%. Established risk factors for tandemassociated uterine perforation include age > 60 years6,7,9 , a history of prior conization7,8 , physician inexperience9 , scarring or distortion of the cervical os6,7,11 and increasing tumor size6 . Interestingly, series of high-risk patients have demonstrated perforation rates of up to 30% despite the use of intraoperative ultrasound9,11 ; however, these series specifically employed ultrasonography in high-risk situations. Further, following a ‘learning curve’ period, no further perforations were noted in one of these series9 .


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The present study population represents an appropriately heterogeneous population, with many patients having one or more of the above-described high-risk factors. We feel that this is representative of a general practice experience, and thus the present investigation demonstrates low perforation rates associated with intraoperative ultrasound guidance of tandem placement by an experienced user and team. Limitations of the study include its retrospective design and the absence of a matched control group. A randomized trial would address this; however, introduction of routine post-implant surveillance may falsely elevate the perforation rate beyond that seen in routine clinical practice. Thus, despite these limitations, we feel that the present study is relevant and important to current clinical practice. The importance of optimal LDR system placement is clinically relevant, as investigators from Fox Chase Cancer Center have demonstrated12 . In reviewing their singleinstitution experience of treating patients with locally advanced cervical cancer, patients whose LDR implants were considered ‘ideal’ or ‘adequate’ (defined by implant symmetry and distance from tandem to ovoids) experienced significantly higher 5-year local control (68 vs. 32%) and suggestion of improved survival (60 vs. 40%) when compared with suboptimal implants12 . In fact, on multivariate analysis, technical adequacy of the implant was best correlated with local control. We believe that ultrasound-guided placement of the tandem allows for optimal distance between tandem and ovoids, such that visual confirmation of the tandem placement within the uterine fundus can be verified in real time. Alternative means of radiotherapy dose escalation have also been described, including high-dose-rate (HDR) brachytherapy13,14 and external beam radiotherapy approaches15 . HDR boost has been prospectively compared with the standard LDR technique, without evidence of compromised disease control or survival13 . HDR tandems also require placement through the cervical os, and ultrasound-guidance techniques have been described in an effort to minimize the risk of perforation in this setting14 . The difficulty with external beam radiotherapy approaches has been the inter- and intratreatment variability of target (cervix/parametrium) position, requiring pretreatment localization and either target immobilization or real-time position tracking and modification. The resultant uncertainty of dose deposition between the target and surrounding sensitive structures (e.g. rectum, bladder) limits the safe integration of definitive external beam techniques as a replacement for brachytherapy boost. In conclusion, ultrasound-guided tandem placement was associated with minimal risk of uterine perforation in the present series. Considering the anatomic distortion often encountered in patients with cervical cancer, intraoperative ultrasound guidance during intrauterine tandem insertion offers an effective technique for minimizing patient morbidity.


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