Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

Int. J. Radiation Oncology Biol. Phys., Vol. 81, No. 4, pp. e639–e644, 2011 Copyright Ó 2011 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/$ - see front matter

doi:10.1016/j.ijrobp.2011.01.053

CLINICAL INVESTIGATION

Endometrium

IMPACT OF ADJUVANT EXTERNAL-BEAM RADIATION THERAPY IN EARLY-STAGE UTERINE PAPILLARY SEROUS AND CLEAR CELL CARCINOMA ANNE KIM, M.D.,* DAVID SCHREIBER, M.D.,y JUSTIN RINEER, M.D.,z KWANG CHOI, M.D.,x x AND MARVIN ROTMAN, M.D. *Department of Radiation Oncology, Vassar Brothers Medical Center, Poughkeepsie, NY; yDepartment of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, NY; zDepartment of Radiation Oncology, MD Anderson Cancer Center Orlando, Orlando, FL; and xDepartment of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn, NY Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA–IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: We identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I–IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB–C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651–1.002, p = 0.052) Conclusion: In FIGO Stage IB–C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival. Ó 2011 Elsevier Inc. Endometrial cancer, Radiotherapy, Papillary serous, Clear cell, Survival.

survival rates of 90–100% for patients with Stage I USPC and clear cell carcinoma who receive adjuvant radiation therapy (RT) (23, 24). Although randomized trials have shown that adjuvant RT can improve locoregional control in early-stage high- to intermediate-risk endometrioid adenocarcinoma (25–28), there is no consensus on the optimum adjuvant therapy for early-stage UPSC and clear cell carcinoma. On account of the rarity of these cancers, small retrospective studies have been published that offer conflicting results regarding the role of RT. We chose to analyze the Surveillance, Epidemiologic, and End Results (SEER) program of the National Cancer Institute, Bethesda, MD, to determine the role of adjuvant RT in a large cohort of patients.

INTRODUCTION Uterine papillary serous carcinoma (UPSC) and clear cell carcinoma constitute <10% of new cases of endometrial cancer (1–4). These variants are typically more aggressive than others and often present with advanced-stage disease. The poor prognosis associated with these variants is often attributed to their high risk of distant failure (1, 2, 5). Up to 75% of patients with UPSC or clear cell carcinoma have advanced-stage disease, and studies have demonstrated that up to 40% of these patients will have extrauterine disease even without myometrial invasion, underscoring the importance of adequate surgical staging (3, 5, 6). Although older data suggest that 5-year overall survival (OS) rates for early-stage disease range from 30% to 50% (5, 7–9), in many of these cases surgical staging was not used. Contemporary series with strict surgical staging have demonstrated 5-year OS rates of roughly 60–80% (10–22). A few small retrospective series have even suggested 5-year

METHODS AND MATERIALS The SEER database gathers information from 17 cancer registries that cover 26% of the United States population, resulting in

Reprint requests to: Anne Kim, M.D., Department of Radiation Oncology, Vassar Brothers Medical Center, 45 Reade Place, Poughkeepsie, NY 12601. Tel: (845) 431-5645; Fax: (845) 4373123; E-mail: [email protected]

Conflict of interest: none. Received Sept 12, 2010, and in revised form Jan 13, 2011. Accepted for publication Jan 26, 2011. e639

e640

I. J. Radiation Oncology d Biology d Physics

a fairly representative sample. The case ascertainment rate is reportedly 97.5%. The patient information available on this registry is first deidentified and then submitted semiannually to the National Cancer Institute before becoming publicly available for research purposes. We identified women in the SEER-17 registry who were coded with American Joint Committee on Cancer Stage Sixth Edition Stage IA–IIB UPSC or clear cell carcinoma and were treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy between 1988 and 2003. We obtained information regarding their age, race, histology, whether they received RT, type of RT, extent of lymph node dissection, and survival. No chemotherapy data were available. The number of patients who received brachytherapy alone was too small to allow for any separate analysis. Therefore, patients who received external-beam RT or brachytherapy were grouped together as having received adjuvant RT. We compared the groups receiving surgery only and surgery followed by adjuvant RT using Pearson’s chi-square test. The variables included in this analysis were age (<70 years vs. $70), race (white vs. nonwhite), stage (IA, IB, IC, IIA, IIB), histology (clear cell carcinoma vs. UPSC), and extent of lymph node dissection (continuous variable). We used Kaplan-Meier analysis with the log-rank test to compare OS across the two groups. We also used univariate and multivariate Cox regression to examine possible confounding and interactive effects of RT with the following factors associated with improved survival: age (continuous) , race (white vs. black), stage (IA, IB, IC vs. IIA–B), and histology (UPSC vs. clear cell carcinoma). We used a p value of 0.05 or less as the threshold for statistical significance. SPSS Version 15.0 (Chicago, IL) was used for the statistical analysis.

RESULTS We identified 1,333 women who fit the selection criteria. Of those, 451 patients had clear cell histology and 882 patients had papillary serous histology. In the complete pool, 775 patients had surgery alone, and 558 also received adjuvant RT. For the patients who received RT, 85 had brachytherapy alone, 329 had external-beam RT alone, and 144 received a combination of the two. The median age of the patients was 69. The median follow-up time for living patients was 53 months. A comparative analysis of the pooled patients showed that patients who received RT were on average younger and had a larger number of lymph nodes removed (Table 1). Impact of RT on survival The impact of RT on survival by stage and histology is shown in Table 2. For patients with Stage I–IIB disease, the median OS improved from 106 months with surgery alone to 151 months with the addition of adjuvant RT (p = 0.006). The corresponding 5-year OS rates were 66% and 71% (Fig. 1). In the patients with Stage IA disease, there was no statistically significant difference in median survival between the two groups (p = 0.224). The median survival for surgery alone was 132 months vs. a median survival of 134 months with the addition of adjuvant RT. The 5-year OS rate was 74% with no RT vs. 78% with RT. Stratifying by histology did not reveal any statistically significant differences, either.

Volume 81, Number 4, 2011

Table 1. Comparative analysis of surgery alone vs. surgery plus radiation therapy Variable Age (y) <70 $70 Race White Nonwhite Stage IA IB IC IIA IIB Histology Clear cell carcinoma Papillary serous carcinoma Lymph node dissection None 1–9 lymph nodes $10 lymph nodes

Surgery alone n (%)

Radiation n (%)

Pearson chi–square

365 (54.2) 410 (52.9)

308 (55.2) 250 (44.8)

0.004

638 (82) 137 (18)

458 (82) 100 (18)

0.513

352 (45.4) 302 (39) 66 (8.5) 27 (3.5) 28 (3.6)

100 (18.6) 245 (45.5) 106 (19.7) 28 (5.2) 59 (11)

265 (34)

186 (33)

510 (66)

372 (67)

267 (36) 180 (25) 282 (39)

127 (25.5) 163 (31.5) 228 (44)

<0.001

0.743

<0.001

Patients with Stage IA clear cell carcinoma had a median survival of 146 months with no RT vs. 105 months with RT (p = 0.224). For those with UPSC, the median survival was 102 months without RT vs. 134 months with RT (p = 0.192). In patients with Stages IB and IC disease, the addition of RT seemed to have a positive impact on median survival. In the patients with Stage IB disease, the group undergoing surgery alone had a median survival of 117 months, and median survival was not reached with adjuvant RT (p = 0.006, Fig. 2). The corresponding 5-year OS rate was 66% with no RT vs. 76% with RT. In the subset of patients with clear cell histology, the group undergoing surgery alone had a median OS of 138 months vs. median survival not reached with RT (p = 0.078). In the UPSC patients, the median survival was 92 months without RT vs. 151 months with adjuvant RT (p = 0.024). Table 2. 5-year survival outcomes by stage and histology 5–year overall survival Stage and histology

No RT (%)

RT (%)

p value

Stage IA Stage IB Stage IC Stage IIA–B Overall Clear cell histology UPSC histology

74.1 66.4 33.9 44.5 66 72.3 62.3

78.5 76.3 60.7 61.4 71.1 76.8 68.1

0.224 0.006 0.001 0.122 0.006 0.281 0.005

Abbreviations: UPSC = uterine papillary serous carcinoma; RT = radiation.

Adjuvant EBRT in uterine carcinoma d A. KIM et al.

e641

Fig. 1. Kaplan-Meier curves showing improvement in overall survival with the use of adjuvant radiation (RT) for Stages I–IIB clear cell or uterine papillary serous carcinoma. The median overall survival improved from 106 months with surgery alone to 151 months with adjuvant radiation therapy (p = 0.006). The corresponding 5-year overall survival rates were 66% and 71.1%.

Fig. 2. Kaplan-Meier curves showing improvement in overall survival with the use of adjuvant radiation (RT) for Stage IB clear cell or uterine papillary serous carcinoma. The median overall survival improved from 117 months with surgery alone to not reached with adjuvant radiation therapy (p = 0.006). The corresponding 5-year overall survival rates were 66.4% and 73.3%.

For patients with Stage IC disease, the group undergoing surgery alone had a median survival of 35 months vs. 120 months with the addition of adjuvant RT (p = 0.001, Fig. 3) The 5-year OS rate was 34% with no RT vs. 61% with RT (p = 0.001). When we stratified the patients with FIGO Stage IC disease by histology, the median OS for clear cell carcinoma patients without RT was 35 months vs. 154 months for those with RT (p = 0.083). Similarly, in UPSC patients, the median OS was higher with the addition of RT: 101 months vs. 33 months without RT (p = 0.010). For patients with Stage IIA–B disease, there was no statistically significant difference in median survival between the group undergoing surgery alone and the group that also received adjuvant RT (p = 0.112). The 5-year OS rate was 44% with no RT vs. 61% with RT (p = 0.112). When patients were stratified by histology, there was no difference in OS between clear cell carcinoma and UPSC (p = 0.369 and 0.141, respectively).

Multivariate analysis demonstrated a significant association of younger age at diagnosis and increased number of nodes with improved survival. Although the benefit of RT fell by comparison with the result of our univariate analysis, the benefit was still close to statistical significance (p = 0.052, Table 4).

Univariate analysis and multivariate analysis In univariate analysis, younger age at diagnosis, increasing number of nodes examined, use of RT, clear cell histology, and earlier stage were associated with improved survival. When patients were stratified by stage, the confidence intervals of the univariate analysis for several stages became quite wide, reflecting in some cases the small number of patients in the cohort and, more specifically, the small number of patients undergoing RT (Table 3).

DISCUSSION This study using the SEER database is one of the largest to date suggesting a positive effect of RTon OS in a select subset of patients with early-stage UPSC and clear cell carcinoma. Earlier studies tended to be smaller and suggested only a reduction in local recurrence as a benefit of RT for this cohort. Because of a lack of power in preceding smaller single-institution studies, the benefit of RT for this cohort has been limited to local recurrence effects, and only a few larger series have suggested that RT can also affect survival(18, 29). Because of the large number of the patients analyzed with SEER, we were also able to identify important characteristics integral to a patient’s survival such as stage, adequacy of lymph node evaluation, and use of RT. By stratifying the 1,333 patients, we determined whether there was any apparent benefit from RT at each stage of the disease. In patients with Stage IA disease, we did not find a statistically significant survival benefit associated with RT, in line with other studies (12, 23, 24). However, for very superficially invasive tumors with high-risk histology,

I. J. Radiation Oncology d Biology d Physics

e642

Volume 81, Number 4, 2011

Table 4. Multivariate analysis for overall survival Multivariate analysis Age at diagnosis (continuous variable) Nodes examined (continuous variable) Radiation therapy (neg vs. pos) Histology (UPSC vs. clear cell) Stage IA IB IC IIA IIB

Risk ratio

95% confidence interval

p value

1.061

1.050–1.072

0.000

0.989

0.980–0.998

0.014

0.808

0.651–1.002

0.052

1.167

0.952–1.432

0.138

1 1.106 1.901 1.387 2.893

0.877–1.396 1.404–2.574 0.842–2.285 1.962–4.265

0.394 <0.001 0.199 <0.001

Abbreviations: Neg = negative; Pos = positive; UPSC = uterine papillary serous carcinoma; FIGO = International Federation of Gynecology and Obstetrics.

Fig. 3. Kaplan-Meier curves showing improvement in overall survival with the use of adjuvant radiation (RT) for FIGO Stage IC clear cell or uterine papillary serous carcinoma. The median overall survival improved from 35 months with surgery alone to 120 months with adjuvant radiation therapy (p = 0.001). The corresponding 5-year overall survival rates were 33.9% and 60.7%.

the risk of regional and distant failure is probably quite low. Therefore, for these superficially invasive tumors, adjuvant RT may not be useful. We also investigated the impact of RT on Stage IB and IC UPSC and clear cell carcinoma. In these cases, the data suggested a significant improvement in OS associated with the use of RT. A few smaller retrospective studies echo this finding. One of the largest, a single-institution series of 68 patients from Stanford, similarly investigated the impact of adjuvant therapy and showed that RT and/or chemotherapy Table 3. Univariate analysis for overall survival Univariate analysis

Risk ratio

95% confidence interval

p value

Age at diagnosis (continuous variable) Nodes examined (continuous variable) Radiation therapy (neg vs. pos) Histology (UPSC vs. clear cell) Stage IA IB IC IIA IIB

1.065

1.054–1.075

<0.001

0.981

0.972–0.990

<0.001

0.769

0.636–0.929

0.007

1.270

1.047–1.539

0.015

1 1.004 1.776 1.183 2.247

0.809–1.245 1.363–2.315 0.740–1.890 1.574–3.208

0.973 <0.001 0.483 <0.001

Abbreviations: Neg = negative; Pos = positive; UPSC = uterine papillary serous carcinoma.

improved survival in these patients with early-stage, highrisk disease; patients receiving adjuvant therapy demonstrated 5-year OS rates of 85% vs. 54% without adjuvant therapy (p = 0.002, 29). Indeed, for these patients there is typically a high rate of local recurrence without RT. Another study by Mehta et al. included a retrospective analysis of outcome and failure patterns in 23 patients with Stage I–II papillary serous carcinomas. Patients who received adjuvant RT had a 5-year pelvic-recurrence–free survival rate of 100%, compared with 57% for those who did not (p = 0.06, 30). In a parallel study of 38 women with Stage IA– IIB clear cell carcinoma, the pelvic failure rate without RT was 83% vs. 0% for those who received RT (p < 0.001, 16). The small size of the samples in the preceding studies limited their ability to detect a difference in survival with the use of RT. With 1,333 patients, this study using the SEER does not suffer from that weakness, but we cannot offer a complete comparison because the SEER does not report local recurrence. Nevertheless, it seems likely that the dramatic improvements in local control found in these small institutional data series would translate into an OS benefit that could be detected in this larger study. Although our data suggested a survival benefit with RT in patients with Stage IB and IC disease, undergoing RT was not associated with a statistically significant difference in survival for patients with Stage IIA–B disease. This may stand to reason, especially if one considers the possibility that the risk of distant failure increases in these patients with higher-stage disease. In these cases, systemic therapy probably plays a more crucial role. One could hypothesize that RT in more advanced early-stage disease might have a locoregional effect, but multimodality therapy is needed to affect survival. In part because of the local failure patterns in these patients with early-stage high-risk disease, several smaller series have investigated whether vaginal brachytherapy can be offered alone as opposed to whole pelvic RT (23, 31).

Adjuvant EBRT in uterine carcinoma d A. KIM et al.

We were unable to address this question because the number of patients in the SEER database with Stage I–II UPSC or clear cell carcinoma who were treated with brachytherapy alone was too small for analysis as a subset. We also studied the importance of lymph node dissection on treatment and survival. Earlier retrospective and contemporary studies of surgical data have demonstrated that the adequacy of surgical staging plays an integral role in the evaluation and management of UPSC and clear cell carcinoma. Historically, the outcomes in patients with earlystage high-risk uterine carcinoma were extremely poor, most likely because of inadequate staging; many of these patients with presumed early-stage disease actually had extrauterine metastases. In fact, surgical lymph node evaluation and omentectomy can upstage up to 40% of early-stage uterine cancer (10–12, 19, 22, 29). As an explanatory variable, the total number of lymph nodes sampled can reflect the adequacy of sampling or the pathologist’s thoroughness in assessing the gross specimen. We found that that the number of lymph nodes sampled was correlated with survival (hazard ratio 0.989, 95% confidence interval 0.989–0.998, p = 0.014). Because of the limitations of using a population-based database, however, we could obtain information regarding only the number and not the specific level of the nodes sampled. There are several further limitations to this study. We did not have information regarding specific patient characteristics, such as performance status, that can influence a clinician’s treatment recommendations. In addition, we did not have data on chemotherapy, which is commonly integrated in the management of these patients. (Because of the high rate of distant failures, chemotherapy has been readily used in the treatment of these high-risk patients.) Indeed, a few small retrospective data series have suggested improvements in recurrence rates and progression-free survival with the use of systemic therapy in comparison with outcomes seen in historical series (6, 24, 32). One of the larger contemporary

e643

studies, by Fader et al., demonstrated that patients with Stage I UPSC treated with carboplatin and paclitaxel, plus or minus RT, had improved 5-year progression-free survival by comparison with patients treated with RTalone. There was a significant difference in recurrence rates: 11% in those who received chemotherapy vs. 28% in those who did not (p = 0.013, 32). Because as the SEER database does not provide information about chemotherapy, we were unable to measure the effect of chemotherapy on survival and how it might confound our results. Moreover, although the SEER database enabled us to ascertain whether patients received external-beam RT and/or brachytherapy, the specifics of the RT were not available for review. As a result, we did not know the radiation dose, field size, or whether there were breaks in treatment—all factors that could have affected outcomes. In addition, SEER has no central pathology review, nor does it contain information that could be used to judge the impact of lymphovascular invasion, the extent of myometrial invasion, or the true adequacy of lymph node sampling. Previous retrospective studies have suggested that these factors may also be correlated with outcome (10, 11, 13, 14, 22, 29). Papillary serous carcinoma and clear cell carcinoma of the endometrium are biologically aggressive variants that typically present with more advanced–stage disease. In this large population-based database, the addition of adjuvant RT was associated with improved survival for patients with FIGO Stage IB–C UPSC and clear cell carcinoma. Despite its limitations, the findings of this study will, it is hoped, raise awareness of the importance of local therapy in patients with early-stage, high-risk UPSC and clear cell uterine carcinoma. A randomized trial in such patients would help to determine whether RT did, in fact, affect survival and not just local control, with obvious and broad implications for the paradigm we use to treat these patients. Local therapy for these patients with early-stage disease may be justified as an integral part of the treatment algorithm.

REFERENCES 1. Carcangiu M, Chambers J. Early pathologic stage clear cell carcinoma and uterine papillary serous carcinoma of the endometrium: Comparison of clinicopathologic features and survival. Int J Gynecol Pathol 1995;14:30–38. 2. Carcangiu M, Chambers J. Uterine papillary serous carcinoma: A study of 108 cases with emphasis on the prognostic significance of associated endometrioid carcinoma, absence of invasion and concomitant ovarian carcinoma. Gynecol Oncol 1992;47:298–305. 3. Abeler V, Khorstad K. Serous papillary carcinoma of the endometrium: A histopathologic study of 22 cases. Gynecol Oncol 1990;39:266–271. 4. Gitsch G, Friedlander M, Wain G, et al. Uterine papillary serous carcinoma: A clinical study. Cancer 1995;75:2239– 2243. 5. Rosenberg P, Blom R, Hogbert T, et al. Death rate and recurrence pattern among 841 clinical stage I endometrial cancer patients with special reference to uterine papillary serous carcinoma. Int J Radiat Oncol Biol Phys 2003;57: 208–216.

6. Sood B, Jones J, Gupta S, et al. Patterns of failure after multimodality treatment of uterine papillary serous carcinoma. Int J Radiat Oncol Biol Phys 2003;57:208–216. 7. Gallion H, Van Nagell J Jr., Powell D, et al. Stage I serous papillary carcinoma of the endometrium. Cancer 1989;63: 2224–2228. 8. Dunton C, Balsara G, McFarland M, et al. Uterine papillary serous carcinoma: A review. Obstet Gynecol Surv 1991;46: 97–102. 9. Jeffrey J, Krepart G, Loctoki R. Papillary serous adenocarcinoma of the endometrium. Obstet Gynecol 1986;67:670–674. 10. Grice J, Marit E, Greer B, et al. Uterine papillary serous carcinoma: Evaluation of long-term survival in surgically staged patients. Gynecol Oncol 1998;69:69–73. 11. Chan J, Loizzi V, Youssef M, et al. Significance of comprehensive surgical staging in noninvasive papillary serous carcinoma of the endometrium. Gynecol Oncol 2003;90:181–185. 12. Havrilskey L, Alvarez Secord A, Bae-Jump V, et al. Outcomes in surgical stage I uterine papillary serous carcinoma. Gynecol Oncol 2007;105:677–682.

e644

I. J. Radiation Oncology d Biology d Physics

13. Bristow R, Asrari F, Trimble E, et al. Extended surgical staging for uterine papillary serous carcinoma: Survival outcomes of locoregional disease (stage I-III) disease. Gynecol Oncol 2001;81:279–286. 14. Thomas M, Mariani A, Cliby W, et al. Role of systematic lymphadenectomy and adjuvant therapy in stage I uterine papillary serous carcinoma. Gynecol Oncol 2007;107:186–189. 15. Martinez A, Weiner S, Podratz K, et al. Improved outcomes at 10 years for serous-papillary/clear cell or high risk endometrial cancer patients treated by adjuvant high dose whole abdominopelvic irradiation. Gynecol Oncol 2003;90:537–546. 16. Murphy K, Rotmensch J, Yamada S, et al. Outcomes and patterns of failure in pathologic stages I-IV clear cell carcinoma of the endometrium: Implications for adjuvant radiation therapy. Int J Radiat Biol Oncol Phys 2003;55:1272–1276. 17. DuBeschter B, Estler K, Altobelli K, et al. High dose rate brachytherapy for stage I/II papillary serous or clear cell endometrial cancer. Gynecol Oncol 2004;94:383–386. 18. Lim P, Al Kushi A, Gilks B, et al. Early stage uterine papillary serous carcinoma of the endometrium. Cancer 2001;91:752– 757. 19. Thomas M, Mariani A, Wright J, et al. Surgical management and adjuvant therapy for patients with uterine clear cell carcinoma: A multi-institutional review. Gynecol Oncol 2008;108: 293–297. 20. Low J, Wong E, Tan H, et al. Adjuvant sequential chemotherapy and radiotherapy in uterine papillary serous carcinoma. Gynecol Oncol 2005;97:171–177. 21. Goldberg H, Miller R, Abdah-Bortnyak R, et al. Outcome after combined modality treatment for uterine papillary serous carcinoma: A study by the Rare Cancer Network (RCN). Gynecol Oncol 2008;108:298–305. 22. Slomovitz B, Burke T, Eifel P, et al. Uterine papillary serous carcinoma: A single institution review of 129 cases. Gynecol Oncol 2003;91:463–469. 23. Turner B, Knisley J, Kacinski B, et al. Effective treatment for stage I uterine papillary serous carcinoma with high dose rate

Volume 81, Number 4, 2011

24.

25.

26.

27.

28. 29. 30.

31. 32.

vaginal apex radiation and chemotherapy. Int J Radiat Oncol Biol Phys 1998;40:77–84. Kelly M, O’Malley D, Hui P, et al. Improved survival in surgical stage I with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum based chemotherapy. Gynecol Oncol 2005;98:353–359. Aalders J, Abeler V, Kolstad P, et al. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol 1980;56:419–427. Creutzberg C, Van Putten W, Koper P, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage I endometrial carcinoma: Multicentre randomized trial: PORTEC Study Group: Post operative radiation therapy in endometrial carcinoma. Lancet 2000;355:1404–1411. Keys H, Roberts J, Brunetto V, et al. A phase III trial of surgery with or without adjuvant external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: A Gynecologic Oncologic Group study. Gynecol Oncol 2004; 92:744–751. Lee C, Szabo A, Shrieve D, et al. Frequency and effect of adjuvant radiation therapy among women with stage I endometrial adenocarcinoma. JAMA 2006;295. 389–297. Hamilton C, Liou W, Osann K, et al. Impact of adjuvant therapy on survival with early stage papillary serous carcinoma. Int J Radiol Oncol Biol Phys 2005;63:839–844. Mehta N, Yamada D, Rotmensch J, et al. Outcome and patterns of failure in pathologic stage I-II papillary serous carcinoma of the endometrium: Implications for adjuvant radiation therapy. Int J Radiol Oncol Biol Phys 2003;57:1004–1009. DuBeshter B, Estler K, Altobelli K, et al. High dose rate brachytherapy for stage I/II papillary serous or clear cell endometrial cancer. Gynecol Oncol 2004;94:383–386. Fader A, Drake R, O’Malley D, et al. Taxane/platinum based chemotherapy with or without radiation therapy favorably impacts survival in stage I uterine papillary serous carcinoma. Cancer 2009;115:2119–2127.