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Objective: The Gynecologic Oncology Group (GOG) study 240 demonstrated a 3.5-month improvement in overall survival when bevacizumab (bev) was added to a combination chemotherapy regimen. This study established a bev-containing regimen as standard therapy for women with recurrent, persistent, or metastatic cervical cancer (CC). Gastrointestinal fistula (GIF) formation is a known complication of bev, and the long-term data of GOG 240 reported that a GIF rate of 15% in women who were treated with bev compared to 1% in the control group women. We sought to evaluate our experience with women treated with bev for CC and to identify associated risk factors for GIF formation.
Method(s): All patients who have received bev for CC from 2012 to 2018 at two academic institutions were identified, and their records were reviewed. Standard two-sided statistical analyses were performed.
Result(s): A total of 43 women were treated with a bev-containing chemotherapy regimen; among them, 34 (79.1%) were treated for CC recurrence, and the remaining were treated for metastatic disease at initial presentation or persistent disease following primary treatment. Thirty-three women (76.6%) received prior radiation therapy (RT); of these, 10 (32.3%) received external beam radiation therapy (EBRT), and 21 (67.7%) had prior EBRT and brachytherapy (BT). The median dose of bev was 15 mg/kg for both EBRT only and EBRT and BT groups. Eleven women developed GIF after bev treatment (11/43, 25.6%). All 11 (100%) had been previously treated with RT, and six (54.5%) had received EBRT plus BT. This resulted in rates of 33.3% (11/33) for GIF formation among women who received EBRT, and 28.6% (6/21) for GIF formation among women who received EBRT plus BT. The median number of bev cycles prior to GIF development was 8 (1-29), and 7 (7/11, 63.6%) received the dose of bev (15 mg/kg) as prescribed in GOG 240. See Table 1.
Conclusion(s): In our cohort of women with CC who were treated with bev, over 25% developed GIF. This is more than expected based on the 15% seen in GOG 240. Notably almost all who developed GIF had recurrent disease and were treated with prior RT. A third of women treated with RT followed by bev formed GIF, representing a considerable proportion of the cohort. GIF development and the possibility of requiring a colostomy should be a part of counseling prior to bev initiation especially in those who have had prior RT. [Figure presented]
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Purpose: Recurrent or primary vaginal disease located in the rectovaginal septum presents a challenging clinical location for interstitial brachytherapy given reported complications of rectovaginal fistulas posttreatment. This study evaluates the dosimetry of conformal boost to persistent gross recurrent disease in the vagina with a non-invasive, balloon based, multi-channel (MC) CapriTM vaginal brachytherapy applicator in patients with rectovaginal gynecologic cancer following whole pelvis radiation. Materials and Methods: All patients had fiducial markers placed at the site of gross disease, and were treated with whole pelvis radiation to a dose of 45 Gy in 25 fractions. Following whole pelvis radiation, patients were treated with Ir-192 HDR vaginal brachytherapy. Patients underwent sizing using the balloon-based, MC CapriTM applicator (Varian Medical Systems, Palo Alto, CA, USA) expanded to maximum capacity with saline to a median maximum horizontal cross sectional diameter of 4.50 cm. A CT scan was performed with the applicator in place. Target volume was defined as the gross tumor volume delineated by fiducial markers and expanded by 3 mm to create the planning target volume (PTV). Using Brachytherapy Planning in the Eclipse treatment planning system (Varian, Palo Alto, CA, USA), dosimetry of the conformal boost plan was manually optimized to achieve 100% coverage of PTV coverage using a prescription of 4 Gy per fraction using the minimum number of catheters and dwell positions closest to the target volume. Maximum dose to 2 cm³ (D2cm³) to bladder and rectum, as well as vaginal mucosal surface points ipsilateral and contralateral to PTV 400 cGy and biologically equivalent dose in 2Gy equivalents (EQD2) for bladder and rectum were calculated using a prescription of 4Gy x 6 fractions with alpha/beta of 3. Results: Five plans were evaluated from 5 patients with vaginal cancer (2) and endometrial cancer (3) with gross vaginal cuff recurrences. Each patient was planned with separate plans representing each individual insertion. The average GTV and PTV taken from the 14 plans was 5.00 cm³ and 6.30 cm³, respectively with a PTV average depth of 1.1 cm. The median number of loaded catheters used in each optimized plan was 3 (range, 2-4 catheters). The average D99, D95 to PTV for all plans was 3.89 Gy and 3.92 Gy, respectively. Average D2cm³ to bladder was 3.02 Gy (range 1.01- 4.36 Gy), and average D2cm³ to rectum was 3.22 Gy (range 2.23-5.08 Gy). The average maximum dose to ipsilateral vaginal mucosa was 12.79 Gy (range 2.04- 33.0 Gy,) while the average maximum dose to the contralateral vaginal mucosa was 9.8 Gy (range 0.99 Gy- 7.46 Gy.) Average EQD2 total for 45 Gy external beam and 6 fractions of 4 Gy for bladder and rectum was 67.5 Gy and 69.5 Gy, respectively. Conclusions: Although ABS Consensus Guidelines for vaginal cancer suggest that lesions with a thickness exceeding 5 mm cannot be adequately treated with a vaginal cylinder, we demonstrate that with the Multichannel Balloon CapriTM applicator, PTV depths averaging 1cm from vaginal surface were able to be prescribed using a multicatheter approach with clinically acceptable bladder, rectal and vaginal doses. Preliminary data suggests that the use of the Multicatheter CapriTM applicator may be an alternative approach to using an interstitial implant for selected patients with small vaginal recurrences located at the rectovaginal septum, however, a larger cohort of patients with long-term follow-up is required to assess long-term clinical outcomes using this technical approach. (Figure Presented)