br L range L in patients undergoing EFRT One patient
1.80/μL (range, 0.27–4.40/μL) in patients undergoing EFRT. One patient treated with chemotherapy after hysterectomy and prior to radiother-apy developed grade 4 thrombocytopenia. There were no other chemotherapy-related grade 3 or 4 toxicities reported.
Adjuvant therapy recommendations for node-positive endometrial cancer remain a subject of debate. In this large single institutional series, we found that patients who received adjuvant radiotherapy had consis-tently better outcomes than patients who received chemotherapy alone, particularly for patients with higher risk histologies. Our results are consistent with other retrospective studies demonstrating that combined-modality treatment is superior to single-modality treatment [14,15].
On the surface, our results and others similar studies may appear to conflict with the initial reports of GOG 258 which reported equivalent survival among patients treated with chemoradiotherapy or with che-motherapy alone. GOG-258 enrolled patients with optimally debulked stage III and IV endometrial cancer treated with tumor-directed radio-therapy and concurrent cisplatin followed by 4 cycles of carboplatin and paclitaxel versus 6 cycles of carboplatin and paclitaxel (HR, 0.9; 95% CI, 0.74–1.1) . This study differs from our analysis in that it BMS-936558 in-cluded stage IIIA, IIIB and IVA patients as well as patients with stage IIIC disease. Areas of residual gross disease were boosted only at the ra-diation oncologists' discretion and post-operative imaging was not rou-tinely obtained, potentially causing residual disease to be unappreciated and, therefore, treated to an insufficient dose of radiation. These factors may have contributed to the 10% rate of in-field recurrence already de-scribed in preliminary reports of the trial—a rate N3 times higher than the in-field failure rate seen in our study. In our practice patients are routinely imaged before radiotherapy in the absence of prior imaging or if pre-operative imaging demonstrated gross disease. Because in-
field failures are almost always fatal, these recurrences may have con-tributed to the lack of benefit of radiotherapy observed in this random-ized trial.
In our study, the 36 patients who were treated with RT alone for grade 1/2 endometrioid cancers had an excellent 5-year DSS rate of 78%. As reported in our previous publication, RT alone appears to be an effective treatment for grade 1/2 disease but may not be sufficient for higher grade cancers . The excellent outcome achieved with RT alone leaves a small margin for improvement and the number of pa-tients in our series was insufficient to draw firm conclusions about the benefit of combined modality adjuvant treatment in this group—the 85% 5-year DSS achieved in patients who had CT + RT was not signifi-cantly better than that observed after RT alone. Only 8 patients with grade 1/2 tumors were treated with chemotherapy alone; there were also several long-term survivors in this treatment subgroup and their DSS of 75% was not significantly different from patients who received radiotherapy with or without chemotherapy. Although it is difficult to comment on the relative benefit chemotherapy in this subset of pa-tients, it is apparent that either radiotherapy alone or combined modal-ity adjuvant treatment yield high survival rates for node-positive, low-grade endometrioid endometrial cancer.
The use of combined-modality adjuvant treatment is supported by the NSGO/MaNGO and PORTEC-3 studies, which included patients with positive lymph nodes. The NSGO/MaNGO study demonstrated that the addition of chemotherapy to radiotherapy in patients with high-risk stage I-III endometrial cancer improved cancer-specific sur-vival and reduced the rate of recurrence by 36% (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.35–0.88, P = 0.01) . PORTEC-3, which studied a heterogeneous population of high-risk patients includ-ing patients with positive nodes compared treatment with concurrent chemoradiotherapy followed by adjuvant chemotherapy versus radio-therapy alone reported a significant difference in the co-primary end-point of failure-free survival. Within the subset of patients with stage