Clinicopathologic Predictors of Abdominal Recurrence Following Treatment with High-Dose Whole Abdominopelvic Irradiation for High-Risk Endometrial Cancer

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I. J. Radiation Oncology

● Biology ● Physics

Volume 63, Number 2, Supplement, 2005

last implants (p⫽.008). The dose to 2cm3 and 5 cm3 of both the bladder and rectum were not significantly different in the plans with and without optimization. Conclusions: FDG-PET based treatment planning allowed for improved dose coverage of the tumor without significantly increasing the dose to the bladder and rectum. The increased coverage was most pronounced for the mid and last implants when the tumor volume was smaller.

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Outcome of Cervical Cancer Patients Treated with Intensity Modulated Radiation Therapy

J.D. Kochanski, N. Mehta, L.K. Mell, J.C. Roeske, H. Sutton, A.J. Mundt Radiation and Cellular Oncology, University of Chicago, Chicago, IL Purpose/Objective: Intensity modulated radiation therapy (IMRT) is receiving increasing attention in gynecologic malignancies. Numerous investigators have shown that IMRT planning reduces the volume of normal tissues irradiated compared to conventional RT. Less acute and chronic gastrointestinal (GI) toxicities have also been reported in patients treated with IMRT. To date, however, limited data exist regarding tumor control in gynecology patients treated with IMRT. We present here the outcome of cervical cancer patients undergoing IMRT at our institution. Materials/Methods: Between 2/00 and 6/04, 62 cervical cancer patients underwent IMRT. Forty four patients (71%) (Group 1) were treated with an intact uterus (stages: 4 IB1, 16 IB2, 4 IIA, 12 IIB and 8 IIIB) and underwent intensity modulated pelvic RT (IM-PRT) (median dose 45 Gy) followed, in 40, by intracavitary brachytherapy (ICB) and, in 5 IB2 patients, simple hysterectomy. Median Point A doses in patients treated with and without hysterectomy were 75 and 85 Gy, respectively. Four women unable to undergo ICB received an IMRT boost (median dose 24.3 Gy). Forty patients also received concomitant chemotherapy, primarily cisplatin. Eighteen clinical stage I-II patients (Group 2) underwent primary surgery, postoperative IM-PRT (due to adverse pathologic features) and, in 4 with positive nodes, concomitant chemotherapy. The clinical target volume (CTV) in both groups consisted of the upper vagina, parametria, uterus (if present), presacral and pelvic lymph nodes, and was expanded by 1 cm creating a planning target volume (PTV). One patient also underwent paraortic IMRT (39.6 Gy) with a 5.4 Gy boost to an involved lymph node. In the ICB unable patients, the gross tumor and parametria were defined as the CTV for the boost treatment. Normal tissues delineated included the small bowel, bladder, rectum, iliac crest bone marrow (in recent patients) and kidneys (in the paraortic IMRT patient). Inverse planning software were used to generate IMRT plans comprised of 7–9 equally-spaced, 6 MV coplanar fields. Patients were followed with physical exams, cytology, and CT scans. Late toxicity was graded using the RTOG/EORTC scale. Median follow-up was 23 months (range, 4.3– 60.6), with 30% of patients followed for ⬎ 3 years. Results: All IMRT plans were highly conformal, with excellent PTV coverage and considerable sparing of the small bowel, bladder and rectum. Overall, 12 women (19%) recurred (8 Group 1, 4 Group 2), for a 3-year actuarial disease-free survival (DFS) of 72.7%. The 3-yr DFS of Group 1 and 2 patients were 67.8% and 78.9%, respectively. Group 1 patients with early stage (IB1-IIA) disease had a superior 3-yr DFS (80.9 vs 52.7%, p ⫽ 0.049) than those with advanced stage (IIB-IIIB) disease. Recurrences were more common in Group 2 patients with node positive (3 of 4) than node negative (1 of 14) disease. Overall, 5 women (8%) failed in the pelvis (4 Group 1, 1 Group 2), for a 3-yr pelvic control (PC) of 87.5%. The 3-yr PC of Group 1 was 82.8% (93.3% in early stage, 67.4% in advanced stage patients). In Group 2, the 3-yr PC was 93.9%. Overall, 12 women (19%) relapsed in extra-pelvic sites, primarily lung, liver, bone and paraortic nodes. Treatment was well tolerated with 3 women (5%) developing grade 2 or higher late toxicity (1 grade 2 GI, 1 grade 4 GI [rectovaginal fistula] and 1 vaginal pain). Nine (14.5%) developed grade 1 late GI toxicity, predominantly mild diarrhea and cramping with select foods. Conclusions: Our series represents the first outcome report of cervical cancer patients treated with IMRT focusing on tumor control. Albeit promising (particularly in early stage disease), more patients with longer follow-up are needed to fully evaluate the impact of IMRT on the outcome of cervical cancer patients.

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Clinicopathologic Predictors of Abdominal Recurrence Following Treatment with High-Dose Whole Abdominopelvic Irradiation for High-Risk Endometrial Cancer

D. Krauss,1 C. Vargas,1 S. Jolly,1 D. Brabbins,1 S. Weiner,2 A. Martinez1 Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 2Obstetrics and Gynecology, William Beaumont Hospital, Royal Oak, MI 1

Purpose/Objective: Abdominal failure remains a problem for patients treated for high-risk endometrial cancer. This analysis examines clinicopathologic factors predicting for such an outcome despite adjuvant treatment with high-dose whole abdominopelvic irradiation (WAPI). Materials/Methods: From 1982 to 2001, 146 patients with high-risk, FIGO I-IVA endometrial cancer underwent adjuvant high-dose WAPI including para-aortic, pelvic, and vaginal boost to a median total dose of 5700 cGy. This analysis includes 126 patients in whom peritoneal washings were sampled and recorded. All patients underwent TAH/BSO and 98 (78%) underwent surgical nodal staging. Ninety-one patients (72%) had FIGO III-IVA disease, and 48 (38%) had serous papillary (SP, n⫽41)/clear cell (CC, n⫽7) histology. All patients included with FIGO I-II disease had both deeply invasive (⬎50%), high-grade endometrioid tumors or SP/CC histology. Results: Median follow-up for all patients was 4.8 (range 0.2–16.1) years. Median patient age was 67 (range 39 –90) years. For all patients, the 5-year abdominal failure rate was 17.2%. On univariate analysis, 3 clinicopathologic factors were associated with increased abdominal failure rates: age ⬎ 65 (p⫽0.02), malignant peritoneal cytology (p⫽0.01), and tumor grade 3 (including SP/CC) (p⫽0.05). Depth of invasion, histology (endometrioid vs. SP/CC), LVSI, and pathologic lymph node status were not associated with an increased incidence of abdominal failure. With respect to the three significant risk factors, Kaplan-Meier estimates yielded 5-year abdominal failure rates of 0% for ten patients with 0 risk factors; 7.2% for forty-five patients with a single risk factor; 19.6% for fifty patients with 2 risk factors; and 52.8% for twenty-one patients harboring all three (p⬍0.001). Increasing number of risk factors was found to be an independent predictor of cause-specific survival on

Proceedings of the 47th Annual ASTRO Meeting

multivariate analysis. Five- and 10-year cause-specific survival was 84% and 78% for patients without abdominal failure compared to 17% and 0%, respectively, for those patients with abdominal recurrence (p⬍0.001). Conclusions: Abdominal failure following treatment for endometrial cancer is an ominous prognostic sign. Age ⬎ 65, malignant peritoneal cytology, and grade 3 tumors were independently associated with increased rates of abdominal failure. Subgroups of patients harboring all three of these features are at high risk for abdominal failure and subsequent cancer-related death. These patients should be considered for alternative or additional therapeutic options such as systemic chemotherapy. 5-Year Abdominal Failure Rates by Risk Factor

*Risk of abdominal failure increases ⬃3.2 ⫻ per risk factor harbored.

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Primary Adenocarcinoma of the Vagina 1

S.J. Frank, M.T. Deavers,2 A. Jhingran,1 D.C. Bodurka,3 P.J. Eifel1 Radiation Oncology, U.T M.D. Anderson Cancer Center, Houston, TX, 2Pathology, MD Anderson Cancer Center, Houston, TX, 3Gynecologic Oncology, MD Anderson Cancer Center, Houston, TX

1

Purpose/Objective: Primary non-DES related adenocarcinomas of the vagina (NDVAs) are rare gynecologic malignancies. Our purpose was to describe the clinical characteristics and outcome of these cancers and to compare the results of radiation therapy (RT) with those of squamous carcinomas of the vagina. Materials/Methods: We reviewed the records of all patients who received definitive RT for vaginal cancer at UT M. D. Anderson Cancer Center between 1970 and 2000. Patients who had a prior gynecologic malignancy, previous pelvic RT, sarcoma, melanoma, or metastatic (Stage IVB) disease were excluded. Of the remaining 230 patients, 193 (84%) had squamous carcinomas and 37 (13%) had NDVAs. Of these 37, 9 were excluded from our study because we were unable to obtain histologic slides or paraffin blocks. Initial biopsy material from the remaining 28 cases was reviewed using H&E and immunohistochemical stains. Survival rates were calculated using the Kaplan-Meier method with differences assessed using log-rank tests. Results: Two patients who had initial diagnoses of NDVA were excluded after pathology review; one patient with a tumor in the recto-vaginal septum had moderately differentiated adenocarcinoma with villous features suggestive of an intestinal primary, and the second was reclassified as squamous cell carcinoma. Additional analysis focused on the remaining 26 patients with confirmed NDVA. At 5 years, the overall survival rate of patients with NDVA was 34%; this was significantly poorer than the 58% 5-year survival rate of patients treated for squamous carcinomas of the vagina during the same period (p⬍0.01). The FIGO stages of the 26 NDVAs were stage I (5 pts), II (13 pts), III (7 pts), and IVA (1 pt). At 5 years, the overall survival rates of patients with stage I-II and III-IV NDVA were 41% and 23%, respectively (p ⫽ 0.01). Disease specific survival (DSS) rates for patients with early and late stage disease were 50% and 23%, respectively (p ⬍ 0.01). The overall rate of pelvic disease control was 39% at 5 years; this was also significantly poorer than that of patients with squamous carcinoma (81%, p⬍0.01). At 5 years, the rates of pelvic disease recurrence were 50% for patients with Stage I-II disease and 100% for patients with more advanced NDVAs; in comparison, the pelvic recurrence rates for patients with early or late stage squamous carcinomas were 15% and 28%, respectively. Although all of the patients who developed recurrences of NDVA eventually died of their disease, several patients survived with active disease for more than 5 years. While the dominant mode of failure was local-regional, 38% of patients developed distant metastasis in 5 years, also significantly higher than the 14% rate for patients with squamous lesions (p⬍0.01). Conclusions: Primary adenocarcinoma of the vagina is a rare disease that has a high rate of pelvic and distant recurrence and a significantly poorer prognosis than squamous cell carcinoma of the vagina. Attempts to cure this aggressive disease with definitive radiation therapy may require the addition of chemotherapy or novel systemic biologic agents.

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The 4th Dimension of Tumor Volume: Dynamic Volumetric Tumor Regression Analysis in Cervical Cancer and Radiation Therapy Outcome

W.T. Yuh,1 N.A. Mayr,2 J.Z. Wang,2 J.F. Montebello,2 J.C. Grecula,2 D.H. Wu,3 S.M. Edwards,3 S. Nag,2 N. Gupta,2 M.V. Knopp1 1 Department of Radiology, Ohio State University, Columbus, OH, 2Department of Radiation Medicine, Ohio State University, Columbus, OH, 3Department of Radiological Sciences, Oklahoma University Health Sciences Center, Oklahoma City, OK Purpose/Objective: To study individual tumor regression patterns of cervical cancers during therapy by MRI and to correlate volumetric regression parameters with local control and disease-free survival.

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