Utility of radiation therapy for early-stage uterine papillary serous carcinoma.

OBJECTIVE: Early-stage uterine papillary serous carcinoma (UPSC) has a poor prognosis and high recurrence rate. While adjuvant chemotherapy is generally recommended, the role of radiation is uncertain. We examined the association between vaginal brachytherapy and whole pelvic radiation and survival in women treated with and without adjuvant chemotherapy. METHODS: The National Cancer Data Base was used to identify women with stage I-II UPSC treated between 1998 and 2012. Trends in use of chemotherapy, brachytherapy, and external beam radiation over time were examined. The association between these treatments and mortality were examined using multivariable Cox proportional hazards models. RESULTS: A total of 7325 patients were identified. Overall, 2779 (37.9%) received chemotherapy. The use of vaginal brachytherapy increased from 7.2% in 1998 to 29.1% in 2012 (P<0.0001), while use of external beam radiation decreased from 18.2% to 11.7% over the same period (P<0.0001). Use of chemotherapy was associated with a 22% reduction in mortality (HR=0.78; 95% CI, 0.69-0.88). While brachytherapy was associated with decreased mortality (HR=0.67; 95% CI, 0.57-0.78), use of external beam radiation was not associated with survival (HR=1.03; 95% CI, 0.92-1.17). Stratified by stage, use of chemotherapy was associated with decreased mortality for women with stage IB and II tumors, but not for stage IA neoplasms. Vaginal brachytherapy was associated with reduced mortality for stage IA and II neoplasms. CONCLUSION: For women with early-stage UPSC, chemotherapy is associated with improved survival. Vaginal brachytherapy was also associated with improved survival, however, there was little benefit to use of external beam radiation.

Impact of adjuvant chemotherapy and pelvic radiation on pattern of recurrence and outcome in stage I non-invasive uterine papillary serous carcinoma. A multi-institution study.

OBJECTIVES: To determine the impact of adjuvant chemotherapy or pelvic radiation on risk of recurrence and outcome in stage IA non-invasive uterine papillary serous carcinoma (UPSC). METHODS: This is a multi-institutional retrospective study for 115 patients with stage IA non-invasive UPSC (confined to endometrium) treated between 2000 and 2012. Kaplan-Meier and multivariable Cox proportional hazards regression modeling were used. RESULTS: Staging lymphadenectomy and omentectomy were performed in 84% and 57% respectively. Recurrence was seen in 26% (30/115). Sites of recurrences were vaginal in 7.8% (9/115), pelvic in 3.5% (4/115) and extra-pelvic in 14.7% (17/115). Adjuvant chemotherapy did not impact risk of recurrence (25.5% vs. 26.9%, p=0.85) even in subset of patients who underwent lymphadenectomy (20% vs. 23.5%, p=0.80). These findings were consistent for pattern of recurrence. Among those who underwent lymphadenectomy, adjuvant chemotherapy did not impact progression-free survival (p=0.34) and overall survival (p=0.12). However among patients who did not have lymphadenectomy, adjuvant chemotherapy or pelvic radiation was associated with longer progression-free survival (p=0.04) and overall survival (p=0.025). In multivariable analysis, only staging lymphadenectomy was associated with improved progression-free survival (HR 0.34, 95% CI 0.12-0.95, p=0.04) and overall survival (HR 0.35, 95% CI 0.12-1.0, p=0.05). Neither adjuvant chemotherapy nor pelvic radiation were predictors of progression-free or overall survivals. CONCLUSION: In stage IA non-invasive UPSC, staging lymphadenectomy was significantly associated with recurrence and outcome and therefore, should be performed in all patients. Adjuvant chemotherapy or pelvic radiation had no impact on outcome in surgically staged patients but was associated with improved outcome in unstaged patients.

The survival outcome and patterns of failure in node positive endometrial cancer patients treated with surgery and adjuvant radiotherapy with curative intent.

OBJECTIVE: The purpose of this study was to evaluate the patterns of failure, overall survival (OS), disease-free survival (DFS) and factors influencing outcome in endometrial cancer patients who presented with metastatic lymph nodes and were treated with curative intent. METHODS: One hundred and twenty-six patients treated between January 1996 to December 2008 with surgery and adjuvant radiotherapy were identified from our service's prospective database. Radiotherapy consisted of 45 Gy in 1.8 Gy fractions to the whole pelvis. The involved nodal sites were boosted to a total dose of 50.4 to 54 Gy. RESULTS: The 5-year OS rate was 61% and the 5-year DFS rate was 59%. Grade 3 endometrioid, serous, and clear cell histologies and involvement of upper para-aortic nodes had lower OS and DFS. The number of positive nodes did not influence survival. Among the histological groups, serous histology had the worst survival. Among the 54 patients relapsed, only three (6%) failed exclusively in the pelvis and the rest of the 94% failed in extrapelvic nodal or distant sites. Patients with grade 3 endometrioid, serous and clear cell histologies did not influence pelvic failure but had significant extrapelvic failures (p<0.001). CONCLUSION: Majority of node positive endometrial cancer patients fail at extrapelvic sites. The most important factors influencing survival and extrapelvic failure are grade 3 endometrioid, clear cell and serous histologies and involvement of upper para-aortic nodes.

The role of vaginal brachytherapy in the treatment of surgical stage I papillary serous or clear cell endometrial cancer.

OBJECTIVES: The optimal adjuvant therapy for International Federation of Gynecology and Obstetrics (FIGO) stage I papillary serous (UPSC) or clear cell (CC) endometrial cancer is unknown. We report on the largest single-institution experience using adjuvant high-dose-rate vaginal brachytherapy (VBT) for surgically staged women with FIGO stage I UPSC or CC endometrial cancer. METHODS AND MATERIALS: From 1998-2011, 103 women with FIGO 2009 stage I UPSC (n=74), CC (n=21), or mixed UPSC/CC (n=8) endometrial cancer underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant high-dose-rate VBT. Nearly all patients (n=98, 95%) also underwent extended lymph node dissection of pelvic and paraortic lymph nodes. All VBT was performed with a vaginal cylinder, treating to a dose of 2100 cGy in 3 fractions. Thirty-five patients (34%) also received adjuvant chemotherapy. RESULTS: At a median follow-up time of 36 months (range, 1-146 months), 2 patients had experienced vaginal recurrence, and the 5-year Kaplan Meier estimate of vaginal recurrence was 3%. The rates of isolated pelvic recurrence, locoregional recurrence (vaginal+pelvic), and extrapelvic recurrence (including intraabdominal) were similarly low, with 5-year Kaplan-Meier estimates of 4%, 7%, and 10%, respectively. The estimated 5-year overall survival was 84%. On univariate analysis, delivery of chemotherapy did not affect recurrence or survival. CONCLUSIONS: VBT is effective at preventing vaginal relapse in women with surgical stage I UPSC or CC endometrial cancer. In this cohort of patients who underwent comprehensive surgical staging, the risk of isolated pelvic or extrapelvic relapse was low, implying that more extensive adjuvant radiation therapy is likely unnecessary.

Vaginal brachytherapy for early stage uterine papillary serous and clear cell endometrial cancer.

OBJECTIVE: To report clinical outcomes following adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) for early-stage uterine papillary serous (UPSC) and clear cell (CC) endometrial cancer. METHODS: A retrospective study of Stage I and II papillary serous and clear cell endometrial cancer treated with post-operative HDR VB between October 2005 and May 2012 was performed. A total of 37 patients were identified, 26 with UPSC, 9 with CC and 2 with mixed UPSC/CC. After total hysterectomy and bilateral salpingo-oophorectomy, VB was administered without external-beam radiation with a dose of 24 Gy in 6 fractions prescribed to the vaginal surface. Chemotherapy was given to 30 patients (75%). RESULTS: The median follow up time was 24.8 months (range, 2.0 to 71.5 months). Four patients relapsed, 2 with UPSC and 2 with CC. The initial site of relapse was concurrent vagina, pelvic/para-aortic nodes and abdominal wall (1), pelvic/para-aortic nodes (1) and para-aortic nodes alone (2). The 2-year vaginal-control rate was 96.8%. The pelvic-control rate including vaginal and nodal relapse was 93.5%. The 2-year disease-free and overall survival rates were 89.3% and 100%, respectively. CONCLUSION: HDR VB as the sole adjuvant treatment modality for early-stage UPSC/CC is associated with a low rate of vaginal relapse and excellent survival outcomes. This novel low-dose regimen for VB is safe and effective.

Impact of adjuvant external-beam radiation therapy in early-stage uterine papillary serous and clear cell carcinoma.

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.

Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma.

OBJECTIVE: Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach. METHODS: This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators. RESULTS: Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1-3 disease (44.8%) recurred (average follow-up 28.1 months, range 8-60 months). CONCLUSION: This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.

Palliative radiotherapy for the skin metastasis of ovarian cancer: a case report and review of the literature.

Ovarian cancer which is the most common cause of death among all gynecological malignancies tends to metastasize through peritoneal cavity. Skin metastasis, however, is a very rare clinical entity and related with poor prognosis. We report a 43-year-old patient with recurrent ovarian cancer presented with extensive abdominal skin metastasis approximately 6 years after the initial diagnosis. Patient was treated with radiotherapy with electrons to a total dose of 37.5 Gy given in 2.5 Gy per fraction per day. Skin metastasis showed good response to radiotherapy, and the patient has been alive for 7 months after radiotherapy with no recurrences on abdominal skin. Radiotherapy might be considered as an efficient palliative treatment option for the skin metastasis of ovarian cancer.

Patterns of failure for conservatively managed surgical stage I uterine carcinosarcoma: implications for adjuvant therapy.

To evaluate patterns of failure and overall survival for patients with surgical stage I uterine carcinosarcoma managed conservatively without adjuvant therapy. A computerized database identified 27 patients whose conditions have been diagnosed with surgical stage I uterine carcinosarcoma from 1993 to 2002. Charts were abstracted for patient demographics, tumor characteristics, recurrence, and survival. Of 27 patients, 23(85%) did not receive adjuvant therapy after undergoing total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy. Five patients were stage IA, 14 were stage IB, and 4 were stage IC. Fourteen patients had either poorly differentiated endometrioid carcinoma alone or in combination with papillary serous carcinoma (61%) as their epithelial tumor component. The median nodal count was 9 (range, 3-21). Eleven patients are alive without evidence of disease with a median follow-up of 63 months (range, 12-164 months). Eleven patients had recurrence with a median time to recurrence of 13 months (range, 6-39 months), and all are dead of disease. Univariate analysis demonstrated that poorly differentiated epithelial or papillary serous histologic diagnosis was the only predictor variable associated with recurrence and, consequently, death (P = 0.04). Approximately 50% of patients with surgical stage I carcinosarcoma who are observed without adjuvant therapy will experience a recurrence. Because most patients will recur distantly, systemic chemotherapy should be considered for patients with early stage uterine carcinosarcoma.

Platinum/taxane-based chemotherapy with or without radiation therapy favorably impacts survival outcomes in stage I uterine papillary serous carcinoma.

BACKGROUND: A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients. METHODS: A retrospective, multi-institutional study of stage I UPSC patients diagnosed from 1993 to 2006 was performed. Patients underwent comprehensive surgical staging; postoperative treatment included observation (OBS); radiotherapy alone (RT); or platinum/taxane-based chemotherapy (CT) +/- RT. RESULTS: The authors identified 142 patients with a median follow-up of 37 months (range, 7-144 months). Thirty-three patients were observed, 20 received RT alone, and 89 received CT +/- RT. Twenty-five recurrences (17.6%) were diagnosed, and 60% were extrapelvic. Chemotherapy-treated patients experienced significantly fewer recurrences than those treated without chemotherapy (P = .013). Specifically, CT +/- RT patients had a lower risk of recurrence (11.2%) compared with patients who received RT alone (25%, P = .146) or OBS (30.3%, P = .016). This effect was most pronounced in stage IB/IC (P = .007). CT- and CT + RT-treated patients experienced similar recurrence. After multivariate analysis, treatment with chemotherapy was associated with a decreased risk of recurrence (P = .047). The majority of recurrences (88%) were not salvageable. Progression-free survival (PFS) and cause-specific survival (CSS) for chemotherapy-treated patients were more favorable than for those who did not receive chemotherapy (P = .013 and .081). Five-year PFS and CSS rates were 81.5% and 87.6% in CT +/- RT, 64.1% and 59.5% in RT alone, and 64.7% and 70.2% for OBS. CONCLUSIONS: Stage I UPSC patients have significant risk for extrapelvic recurrence and poor survival. Recurrence and survival outcomes are improved in well-staged patients treated with platinum/taxane-based chemotherapy. This multi-institutional study is the largest to support systemic therapy for early stage UPSC patients.

Boron neutron capture therapy for papillary cystadenocarcinoma in the upper lip: a case report.

Boron neutron capture therapy (BNCT) is a tumor-selective radiation therapy using alpha and (7)Li particles, which are produced by the reaction of neutron with boron ((10)B), and taken up by the tumor. The authors report their first experience of BNCT on a patient with no history of surgery, chemotherapy or conventional radiotherapy for papillary cystadenocarcinoma in the upper lip.

The role of radiotherapy in the management of resected uterine papillary serous and clear cell carcinoma.

OBJECTIVE: Primary uterine papillary serous (PS) and clear cell (CC) carcinoma are aggressive histologies characterized by elevated risk of loco-regional recurrence and disease-specific mortality following hysterectomy. The impact of adjuvant radiotherapy remains to be elucidated. The present study is a single institution, retrospective cohort comparison to determine whether post-hysterectomy radiotherapy improves loco-regional control and/or disease-specific survival outcomes in a population of women with PS and/or CC. STUDY DESIGN: Between June 1992 and November 2006, 50 women underwent hysterectomy alone (H) or hysterectomy with adjuvant radiotherapy (H+RT) for primary uterine PS and/or CC. RT involved either high dose-rate (HDR) brachytherapy, external beam RT, or both. RESULTS: At a median survivor follow-up of 27 months (range 2.7-137.3) for the H+RT group and 61 months (range 11.9-114.6) for the H group (range 3-137), patients in the H+RT group demonstrated a trend toward superior disease-free survival (not yet attained at 26 months versus 25 months; p=0.0625). For patients with > or =24 months of follow-up, disease recurrence was significantly higher in H patients over H+RT patients (45% versus 12.5%; p<0.05). Additionally, the H+RT group demonstrated significant improvement in loco-regional control (0% versus 37.5%; p<0.001), most pronounced within FIGO stages I-II H+RT patients (0% versus 70%; p<0.001). Overall survival was not significantly different between the two cohorts (H=32 months, H+RT=not yet attained at 26 months; p=non-significant). CONCLUSIONS: Hysterectomy with adjuvant radiotherapy significantly improves disease-free survival within 2 years post-hysterectomy and significantly reduces loco-regional failures over hysterectomy alone.

Is adjuvant therapy necessary for stage IA and IB uterine papillary serous carcinoma and clear cell carcinoma after surgical staging?

Adjuvant therapy of early-stage uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC) is controversial. We conducted a prospective cohort study to evaluate outcomes of patients with early-stage UPSC or CCC who were followed without adjuvant therapy after complete surgical staging. From 2000 to 2006, we evaluated all consecutive patients with stage IA/IB UPSC or CCC who had surgical staging by a gynecological oncologist at the London Health Sciences Centre, Canada. Follow-up consisted of history and physical examination every 3 months for 2 years, then every 6 months for the next 3 years. Primary outcome measure was 2-year disease-free survival. There were 22 evaluable patients. Mean patient age was 63.4 years. Median number of pelvic and para-aortic lymph nodes resected was 15 (range 2-39) and 4 (range 0-12), respectively. Thirteen had UPSC, seven had CCC, and two had both UPSC and CCC. Nine had stage IA and 13 had stage IB disease. Median follow-up was 25 months (range 6-72). Only one patient has recurred (stage IB UPSC, isolated vault recurrence 10 months after surgery), but she is well 9 months after receiving pelvic radiotherapy and vault brachytherapy. Two-year disease-free survival was 95%. These results suggest that adjuvant therapy may not be necessary for stage IA and IB UPSC and CCC after surgical staging. Further prospective evaluation of different adjuvant therapy practices is required for early-stage UPSC and CCC, which may be useful in the design of future clinical trials.

Pilot phase II trial of radiation "sandwiched" between combination paclitaxel/platinum chemotherapy in patients with uterine papillary serous carcinoma (UPSC).

OBJECTIVES: To evaluate disease-free survival (DFS) and overall survival (OS) in patients treated with pelvic radiation "sandwiched" between six cycles of paclitaxel(T)/platinum(P) chemotherapy with optimally reduced uterine papillary serous carcinoma (UPSC). METHODS: Surgically staged patients with UPSC and no visible residual disease were enrolled. Treatment involved T (175 mg/m2) and either cisplatin (75 mg/m2) or carboplatin (AUC=6.0, 6.5, 7.5) every 21 days x 3 doses, followed by pelvic RT (45 Gy). Fields were extended for >2 positive pelvic or confirmed para-aortic node disease. Three additional cycles of T/P were administered after RT. Toxicity was graded by NCI CTC Version 3.0. Kaplan-Meier survival statistics were used for DFS/OS. RESULTS: 30 women were enrolled between 1999 and 2004. Median age was 69 years (45-82 years). 60% (18/30) of patients had disease confined to the uterus (Stage I/II) and 40% (12/30) had extra-uterine disease (Stage III/IV). 29 patients completed protocol treatment. One patient was discontinued due to non-compliance and recurred at 7 months. All 30 patients are included in survival analysis. Three-year DFS and OS with Stage I/II disease was 69% and 75% and Stage III/IV disease was 54% and 52%, respectively. Of 177 chemotherapy cycles administered, grade 3 or 4 neutropenia, thrombocytopenia or anemia occurred in 42%, 1% and 3% of cycles, respectively. Six cycles were delayed 1 week for neutropenia. 43% of all neutropenic episodes occurred after RT. CONCLUSION: Radiation "sandwiched" between T/P chemotherapy is a well-tolerated and efficacious regimen for patients with completely resected UPSC. A larger multi-institutional clinical trial should be considered to confirm these pilot data.

Role of systematic lymphadenectomy and adjuvant therapy in stage I uterine papillary serous carcinoma.

OBJECTIVE: To assess surgical staging with systematic lymphadenectomy (LND) and adjuvant therapy in patients with stage I uterine papillary serous carcinoma (UPSC). METHODS: A single-institution, retrospective review was conducted of all surgically treated patients with primary UPSC between 1982 and 2005. RESULTS: 42 patients (IA=15, IB=21, IC=6) were stage I. 81% (n=34) underwent LND (median 40 nodes), 69% omentectomy, and 45% peritoneal biopsies. Median follow-up was 39 months. The 5-year overall survival (OS) and progression free survival (PFS) rates were 85% and 78%. The substage 5-year OS was: IA 100%, IB 89%, IC 60%. No lymphatic recurrences (LR) were observed in 34 patients who had LND compared to 1 LR in 8 who did not undergo LND (p=NS). No recurrences were detected among the 15 patients with stage IA UPSC, irrespective of post-operative therapy. None of the 20 IB and IC patients who received radiation therapy (RT) had vaginal recurrences (VR) compared to 2 of the 7 (29%) who did not receive RT (p=0.02). A systematic LND (>20 lymph nodes) was performed in 19 stage IB and IC patients. No hematological or peritoneal recurrence (HPR) was detected in the 6 patients who received chemotherapy. In contrast, HPR were observed in 3 (23%) of 13 patients who did not receive chemotherapy. DISCUSSION: Observation is an option for patients with stage IA UPSC confirmed by systematic LND. Patients with comprehensively staged IB and IC UPSC are candidates for chemotherapy and vaginal brachytherapy to prevent HPR and VR.

The effect of adjuvant chemotherapy versus whole abdominopelvic radiation on the survival of patients with advanced stage uterine papillary serous carcinoma.

OBJECTIVES: To compare the outcomes of stage III and IV uterine papillary serous carcinoma (UPSC) patients treated with platinum-based chemotherapy (PC) versus whole abdominopelvic irradiation (WAPI) after optimal cytoreductive surgery. METHODS: Surgically staged patients with advanced stage UPSC diagnosed between 1981 and 2002 were identified from tumor registry databases at four hospitals. Survival analyses and predictors of outcome were analyzed using Kaplan-Meier methods. RESULTS: Of the 40 patients with advanced UPSC (median age: 64.5), 84% were Caucasian, 8% were African American, and 8% were Asian. The majority of patients (85%) presented with vaginal bleeding. Twenty-seven had stage III and 13 had stage IV disease. All patients were optimally debulked; 21 patients received adjuvant PC while 19 underwent WAPI. The median follow-up was 27 months (range: 5-209). The 3-year overall survival (OS) and progression-free survival (PFS) for the patients with stage III disease were 49% and 37% compared to 37% and 31% in those with stage IV disease (P = 0.23 for OS; P = 0.41 for PFS). Women who received PC had a 3-year OS and PFS of 43% and 31% compared to 45% and 41% in those receiving WAPI, respectively (P = 0.40 for OS; P = 0.84 for PFS). CONCLUSION: Platinum-based chemotherapy or whole abdominopelvic irradiation resulted in similar survival in this series of women with optimally cytoreduced UPSC. Given the overall poor prognosis of these patients, new treatment modalities are warranted.

Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma.

PURPOSE: To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma. METHODS AND MATERIALS: Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p = 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival. CONCLUSION: Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma.

Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer.

PURPOSE: To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. METHODS AND MATERIALS: Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic +/- paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. RESULTS: With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. CONCLUSION: Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer.

Whole abdominal radiotherapy in the adjuvant treatment of patients with stage III and IV endometrial cancer: a gynecologic oncology group study.

OBJECTIVE: To evaluate toxicity, survival, and recurrence-free interval in women with loco-regionally advanced endometrial carcinoma treated with postoperative whole abdominal radiation therapy. METHODS: Whole abdominal irradiation with pelvic plus or minus para-aortic boost was initiated within 8 weeks of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, and selective pelvic and para-aortic node sampling in eligible, consenting patients. RESULTS: Of 180 evaluable patients entered on the study with surgically staged III and IV endometrial carcinoma maximally debulked to less than 2 cm, 77 had typical endometrial adenocarcinoma and 103 had high-risk histology, either papillary serous or clear cell carcinoma. Patients with typical endometrial adenocarcinoma were significantly younger and had significantly fewer poorly differentiated cancers. Proportionally, there were twice as many non-Whites with high-risk histologies as non-Whites with typical endometrial adenocarcinoma. Forty-five percent of patients with typical endometrial adenocarcinomas had positive pelvic nodes compared to 51% of those with high-risk histologies. Both histologic groups had similar distribution for performance status, para-aortic node positivity, site and extent of disease, and International Federation of Gynecology and Obstetrics (FIGO) stage. The frequency of severe or life-threatening adverse effects among 174 patients evaluable for radiation toxicity included 12.6% with bone marrow depression, 15% GI, and 2.2% hepatic toxicity. The recurrence-free survival rates were 29% and 27% (at 3 years) for the typical endometrial adenocarcinoma and high-risk histologies, respectively. The survival rates were 31% and 35%, respectively. No patient with gross residual disease survived. CONCLUSION: Whole abdominal irradiation in maximally resected advanced endometrial carcinoma has tolerable toxicity, and it is suggested that the outcome may be improved by this adjunctive treatment in patients with completely resected disease.