7 Gy x 2 – An Effective Brachytherapy Regimen for Stage I-II Uterine Papillary Serous Carcinoma

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International Journal of Radiation Oncology  Biology  Physics

with pelvic radiation therapy) were excluded. The clinical endpoints were calculated from the date of surgery using Kaplan-Meier analysis. Results: The study sample consisted of 152 patients: 62 leiomyosarcoma (LMS), 61 carcinosarcoma (CS) and 29 endometrial stromal sarcomas (ESS). The median follow-up was 3.8 years. Lymph node dissection was completed in 29% of patients. Adjuvant therapy consisted of RT alone in 45%, chemotherapy (CT) alone in 14% and RT + CT in 6%. Thirty-five percent of patients were observed. For the entire cohort, the 5-year OS, CSS, DFS and LC was 58%, 62%, 47% and 72%, respectively. Adjuvant pelvic RT significantly improved pelvic control with a five-year control rate of 78% for the RT group vs 65% for the non-RT group (p Z 0.02). On subgroup analysis, adjuvant RT improved pelvic control for CS (70% vs 57%, p Z 0.14) and LMS (83% vs 72%, p Z 0.17), though only ESS reached statistical significance (100% vs 72%, p Z 0.04). In the entire cohort, and on subgroup analysis, adjuvant RT did not have a statistically significant impact on OS, CSS or DFS. Distant metastases developed in 45% of patients. Late grade 3-4 toxicities developed in 9% of patients. Conclusions: The addition of adjuvant pelvic radiation therapy significantly improved pelvic control for patients with stage I uterine sarcoma with no significant impact on OS, CSS or DFS. As the development of metastatic disease is high in this patient population, investigation and use of systemic therapy should be considered. Author Disclosure: W.J. Magnuson: None. D.G. Petereit: None. B.M. Anderson: None. H.M. Geye: None. K.A. Bradley: None.

Purpose/Objective(s): The adjuvant management of stage III Endometrial Cancer continues to evolve in a multidisciplinary fashion. There remains controversy and practice pattern variation regarding the patient selection, rationale, and benefit of a vaginal brachytherapy boost after consolidative adjuvant pelvic radiation therapy. We evaluated clinical prognostic factors and the impact of a vaginal brachytherapy boost on vaginal and pelvic control of stage III patients treated at our institution. Materials/Methods: We examined medical records of patients treated consecutively from 1998 to 2011 with stage 3A-3C endometrial cancer. Patients were treated with TAH/BSO and adjuvant therapy consisting of chemotherapy and/or pelvic external beam radiation therapy with or without a vaginal brachytherapy boost. Assessed variables include performance status, tumor grade, pathologic T stage, N stage, lymphovascular space invasion (LVSI), vaginal involvement (VI), lower uterine segment invasion, cervical stromal involvement (CSI), myometrial invasion (MI) and use of vaginal brachytherapy (VB). Failure was scored as vaginal, pelvic, abdominal or distant. Fisher’s Exact test was used to assess the impact of these variables on disease control. Results: There were 100 patients identified with a median follow-up of 43 months, average age of 61 years old with a median KPS of 90%. Thirtyone percent of patients had pathologically identified CSI and average depth of MI was 68%. Seventy-eight patients had adenocarcinoma, 11 had papillary serous carcinoma, 7 had carcinosarcoma and 4 had clear cell carcinoma. Thirty-one percent were stage 3A, 6% stage 3B, and 63% stage 3C with an average of 3 positive lymph nodes and 57% with LVSI. Thirtyeight percent received pelvic radiation therapy alone, 62% received adjuvant chemotherapy and consolidative pelvic radiation and 89% were treated with VB. Of the 82 patients who received VB, a total of 5 failed in the vagina with vaginal and pelvic control rates of 94% and 92%. In patients not boosted, the vaginal and pelvic control rates were 90% and 70%. The impact of VB reached borderline significance with its impact on pelvic control, 92% vs 70% (p Z 0.055). Vaginal control with and without VB was 94% and 90% (p Z 0.50). Tumor grade (p Z 0.76), LVSI (p Z 1.00), CSI (p Z 0.37), stage (p Z 0.76), lower uterine segment invasion (p Z 0.39) nor VI (p Z 0.40) was found to have a statistical impact on vaginal control. Conclusions: Stage III endometrial cancer patients treated with consolidative pelvic radiation and a vaginal brachytherapy boost had excellent pelvic and vaginal control. The presence of high grade, vaginal, lymphovascular or cervical involvement did not adversely affect outcomes in our patient cohort suggesting a beneficial role of brachytherapy in this population. Author Disclosure: A.J. Huddleston: None. S. Zhen: None. L. Qi: None. D.L. Rash: None. S. Scudder: None. G. Leiserowitz: None. J.S. Mayadev: None.

2565 The Role of Adjuvant Therapy in Uterine Sarcomas After Definitive Surgery T. Yu, H. Kim, H. Wu, and S. Ha; Seoul National University College of Medicine, Seoul, Korea, Republic of Korea Purpose/Objective(s): To analyze prognostic factors for survivals and evaluate the impact of postoperative whole pelvic radiation therapy (WPRT) on pelvic failure in uterine sarcoma treated with radical surgery. Materials/Methods: We retrospectively analyzed 78 patients with uterine sarcoma who underwent radical surgery with (n Z 24) or without (n Z 54) radiation therapy between 1990 and 2010. Carcinosarcoma and noncarcinosarcoma (leiomyosarcoma: 23, endometrial stromal sarcoma: 25, undifferentiated sarcoma: 6) patients were 24 and 54, respectively. Age, histologic type, stage, mitotic count, tumor size, and postoperative WPRT were defined as prognostic factors for survivals. The median follow-up period was 84 months (range, 15w236 months). Results: Five-year overall (OS) and pelvic failure-free survival (PFFS) of total patients were 71% and 83%, respectively. Multivariate analysis revealed that histologic type (p Z 0.047) and stage (p Z 0.006) were significant predictors of OS. However, any factors were not found to be associated with PFFS. Analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in carcinosarcoma (9.1% vs 53.7%, p Z 0.032), but not in non-carcinosarcoma (11.1% vs 9.8%, p Z 0.935). Patients with carcinosarcoma were found to be at increased risk of pelvic failure (25%, 6/24), whereas those with noncarcinosarcoma had increased risks of distant metastasis (24%, 13/54). Conclusions: Reflected by improved PFFS after postoperative WPRT only in carcinosarcoma and difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns. Author Disclosure: T. Yu: None. H. Kim: None. H. Wu: None. S. Ha: None.

2566 Stage III Endometrial Cancer Treated With Consolidative Pelvic Radiation: The Impact of Additional Dose With Vaginal Brachytherapy A.J. Huddleston,1 S. Zhen,1 L. Qi,2 D.L. Rash,1 S. Scudder,1 G. Leiserowitz,1 and J.S. Mayadev1; 1University of California Davis Comprehensive Cancer Center, Sacramento, CA, 2University of California Davis Medical Center, Sacramento, CA

2567 7 Gy x 2 e An Effective Brachytherapy Regimen for Stage I-II Uterine Papillary Serous Carcinoma S. Damast, S.A. Higgins, E. Ratner, M.C.B. de Leon, S. Mani, D. Silasi, M. Azodi, A. Santin, T. Rutherford, and P. Schwartz; Yale School of Medicine, New Haven, CT Purpose/Objective(s): When prescribing adjuvant high-dose-rate intravaginal brachytherapy (IVB) for endometrial cancer, in terms of equivalent dose in 2 Gy fractions (EQD2), there is growing data to support surface doses as low as 30-40 Gy as compared to more traditional surface doses of 50-55 Gy. Such lower dose regimens may be especially advantageous when IVB is combined with chemotherapy. Since 2000, patients with stage I-II uterine papillary serous carcinoma (UPSC) at our institution have been treated with 6 cycles of adjuvant carboplatin-paclitaxel chemotherapy along with 2 fractions of IVB (7 Gy each), with the first fraction typically delivered one week prior to and the second fraction one week following the second cycle of chemotherapy. IVB is delivered via an Ir-192 source. Prescription depth is 5mm from the cylinder surface, and the estimated total EQD2 surface dose is approximately 36 Gy. We performed a retrospective chart review in order to evaluate the effectiveness of this regimen.

Volume 87  Number 2S  Supplement 2013

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Materials/Methods: We identified 56 patients with FIGO 2009 stage I-II UPSC treated with this regimen between 2000 and 2010. Patients who had received single modality therapy, external beam radiation therapy, or other brachytherapy fractionation were excluded. All patients underwent total hysterectomy and the majority had undergone comprehensive surgical staging including pelvic dissection (96%, median nodes removed Z 18, range, 6-47) and para-aortic dissection (80%, median nodes removed Z 3, range, 1-37). Patients were followed by routine clinical examination, Pap smears, and tumor markers. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS) and overall survival (OS). Results: All 56 patients completed 2 IVB fractions, and 53 patients (95%) completed all 6 cycles of chemotherapy. The median time from surgery to first IVB fraction was 50 days (range, 30-113 days). There were no delays in administering subsequent cycles of chemotherapy due to IVB. The median follow-up time was 49 months (range, 9-145 months). The 5-yr RFS and OS were 85% and 93%, respectively. In all cases of recurrence (n Z 8), the first site of failure was extra-pelvic. The para-aortic region was an isolated failure site in 1 patient. There were no pelvic recurrences. There were no isolated vaginal recurrences, however, there was one vaginal apex recurrence recorded at 19 months in a patient with simultaneous lung metastases. Thus, the 2-year vaginal RFS was 98%. Conclusions: For stage I-II UPSC, 2 fractions of adjuvant IVB to a total dose of 14 Gy with 6 cycles of carboplatin-paclitaxel chemotherapy resulted in excellent disease control and very low rates of vaginal/pelvic failure. Whether this lower dose regimen translates into improvements in patient-centered outcomes compared to more traditional higher dose fractionation schemes is a subject on ongoing prospective investigation. Author Disclosure: S. Damast: None. S.A. Higgins: None. E. Ratner: None. M.C.B. de Leon: None. S. Mani: None. D. Silasi: None. M. Azodi: None. A. Santin: None. T. Rutherford: None. P. Schwartz: None.

(S) for each CT scan. Re-optimization of plans was not performed between fractions. OAR doses from the treatment planning CT (CT[p]) were compared to the average of OAR doses calculated at each treatment (CT [t]). Results: One hundred seventy-eight fractions were delivered with a median dose per fraction of 6 Gy. Patients were treated with a median of 3 fractions to an average vaginal length of 4 cm and median prescription depth of 2 mm (range, 0 - 5 mm). Mean OAR doses for each applicator are shown in the Table. No significant difference was noted between OAR doses calculated at CT(p) and CT(t) for any applicator. Multivariate analysis was carried out adjusting for age, number of fractions, treatment length and prescription depth, assessing OAR doses for the CET MC cylinder versus the others. Rectal D0.1, 1 and 2 cc doses determined from the CT(t) scan dosimetry were 9.7%, 9.7%, and 9.3% (p < 0.05) less, respectively, for the CET MC cylinder compared with the other applicators. Differences in bladder and sigmoid doses between applicators were not observed. Conclusions: OAR doses did not significantly vary between planning and treatment delivery for any of the applicators. This suggests that after verifying a reproducible insertion, re-planning is not required between fractions for MC cylinders. Comparison of OAR doses between applicators revealed that the CET MC cylinder was associated with the lowest dose to the rectum. Author Disclosure: R.N. Banerjee: None. S.J. Park: None. J. Wang: None. O. Kayode: None. D.J. Demanes: None. M. Kamrava: None.

2569 Predictors of Outcome in Early-Stage Papillary Serous and Clear Cell Endometrial Cancer M.M. Dominello,1 P. Paximadis,1 I. Kaufman,1 S. Munns,1 G. Dyson,2 A. Konski,1 R. Morris,1 and S. Miller1; 1Wayne State University, Detroit, MI, 2Karmanos Cancer Institute, Detroit, MI

2568 An Assessment of Organ-at-Risk Dose and Interfraction Variability Using 4 Different Applicators for Intracavitary Gynecologic HDR Brachytherapy R.N. Banerjee, S.J. Park, J. Wang, O. Kayode, D.J. Demanes, and M. Kamrava; Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA

Purpose/Objective(s): Papillary serous (PS) and clear cell (CC) histologies have been poorly represented or excluded from clinical trials for endometrial cancer. Two large trials (MRC-ASTEC and Italian) recently examined the benefit of pelvic lymph node dissection and adjuvant therapy for early stage disease, though were not powered to detect differences for this subgroup. Our objective is to report predictors of outcome and patterns of recurrence for early stage PS and CC endometrial cancer as well as to analyze extent of nodal dissection on progression free survival (PFS). Materials/Methods: Patient records and the social security death index were reviewed for 281 patients with early stage (AJCC 7th Ed/FIGO IA, IB, and II) endometrial cancer from 2000-2012, of whom 53 had PS or CC features and were used in this analysis. A competing risks model was used to determine influence of race, age, stage, lymphovascular invasion (LVSI), type of adjuvant therapy, and extent of nodal dissection on disease recurrence, while a Cox regression model was used for PFS. Recursive partitioning was used to identify extent of nodal dissection predicting PFS. Results: Median patient age was 65 years (range, 38-91 years). Median OS was 7.4 years, 95% CI (3.4, NR) with median follow-up of 4.3 years (2.5, 6.2). Median PFS was 3.4 years (2.3, NR) with median follow-up of 3.4 years (2.8, 4.9). All underwent hysterectomy and 41/53 patients had a lymph node dissection (25 pelvic and periaortic, 15 pelvic). Twenty-five received adjuvant chemotherapy alone, 10 adjuvant radiation (4 vaginal cuff only and 6

Purpose/Objective(s): There are dosimetric advantages associated with the use of multi-channel (MC) cylinders for intracavitary gynecologic brachytherapy, including reduced dose to organs at risk (OAR) and the ability to shape target coverage. Single-channel (SC) cylinders have been shown to have reproducible doses to OAR between fractions (i.e., interfraction variability), but this has not been shown for MC cylinders. This study aimed to assess doses to OAR and inter-fraction variability amongst three different MC cylinders and one SC cylinder for HDR brachytherapy. Materials/Methods: Forty-eight women (38 endometrial cancer, 10 cervical cancer) were included. MC vaginal cylinders were used in 27 (7 13-channel applicator, 11 CET MC Cylinder [CET], 9 Ovoid and Cylinder [O&C]) and one SC cylinder (electronic applicator) was used in 21 patients. The CET cylinder is an MC cylinder designed in-house with 4 outer channels and 1 central channel. CT scans were obtained at treatment planning and prior to each fraction. D0.1 cc, D1 cc and D2 cc doses were recorded for the OAR including the rectum (R), bladder (B) and sigmoid Poster Viewing Abstract 2568; Table 13-channel applicator (CT[p]) RD0.1 cc RD1.0 cc RD2.0 cc BD0.1 cc BD1.0 cc BD2.0 cc SD0.1 cc SD1.0 cc SD2.0 cc

85.9 72.8 66.2 80.8 70.6 65.9 53.6 46.2 45.0

(+/-6.2) (+/-5.0) (+/-4.7) (+/-7.4) (+/-6.2) (+/-5.8) (+/-12.8) (+/-8.4) (+/-7.2)

Mean OAR D0.1, 1, and 2 cc doses as % of prescription dose (with standard error) at CT(t) and CT(p)

13-channel applicator (CT[t]) 83.2 71.7 65.5 77.0 67.2 62.7 59.6 48.8 45.0

(+/-6.0) (+/-4.5) (+/-4.2) (+/-8.7) (+/-6.2) (+/-5.5) (+/-11.9) (+/-8.1) (+/-6.9)

CET (CT[p])

CET (CT[t])

O&C (CT[p])

O&C (CT[t])

69.7 57.6 51.7 66.8 57.0 53.9 63.5 45.5 39.4

71.9 59.6 53.6 68.2 57.3 52.5 57.2 43.5 38.2

81.8 70.0 63.5 85.6 74.8 69.0 38.9 30.8 27.5

82.1 69.7 63.3 79.7 68.9 63.6 39.3 30.7 27.5

(+/-4.9) (+/-4.0) (+/-3.8) (+/-5.9) (+/-5.0) (+/-4.6) (+/-10.4) (+/-6.8) (+/-5.9)

(+/-4.8) (+/-3.6) (+/-3.3) (+/-7.0) (+/-5.0) (+/-4.4) (+/-9.5) (+/-6.5) (+/-5.5)

(+/-5.5) (+/-4.4) (+/-4.2) (+/-6.5) (+/-5.4) (+/-5.1) (+/-13.2) (+/-8.7) (+/-7.4)

(+/-5.3) (+/-4.0) (+/-3.7) (+/-7.7) (+/-5.4) (+/-4.8) (+/-11.9) (+/-8.1) (+/-6.9)

Electronic Applicator (CT[p]) 91.6 72.7 64.2 87.6 69.9 62.1 47.6 34.0 26.4

(+/-3.6) (+/-2.9) (+/-2.7) (+/-4.3) (+/-3.6) (+/-3.4) (+/-12.3) (+/-8.3) (+/-7.2)

Electronic Applicator (CT[t]) 98.2 77.9 69.0 81.9 64.4 56.9 60.0 38.5 31.2

(+/-3.4) (+/-2.6) (+/-2.4) (+/-5.0) (+/-3.6) (+/-3.2) (+/-11.1) (+/-7.6) (+/-6.4)