Patterns of adjuvant radiation usage and survival outcomes for stage I endometrial carcinoma in a large hospital-based cohort

Objective

Two randomized trials have demonstrated a local control advantage in the absence of a survival advantage for the addition of adjuvant radiation therapy (RT) to surgery in patients with stage I endometrial adenocarcinoma (EC). This study analyzed the National Cancer Data Base (NCDB) to evaluate the impact of adjuvant RT on overall survival (OS) for patients with stage I EC.

The results of adjuvant radiotherapy in endometrial carcinoma

Aim.?To examine the clinical characteristics and treatment outcomes in patients with endometrial cancer receiving adjuvant radiotherapy.

Methods.?A total of 157 patients who received postoperative radiotherapy (RT) between 1999 and 2008 were evaluated, retrospectively. The mean age was 59 years (34–82). All patients received RT following surgery. Stage distribution was as follows: 92 patients (59%) stage I, 21 patients (13%) stage II, and 44 patients (28%) stage III.

Results.?Overall survival rate was 95% at 2 years and 84% at 5 years. By the end of follow up, 135 patients (86%) were disease-free, and 4 (2%) were alive with disease. Univariate and multivariate analyses identified stage, grade, and serosal involvement as significant predictors for overall survival.

Conclusion.?The results of our study suggests that early stage, low-grade endometrial cancer with no serosal involvement is associated with a better survival and adjuvant radiotherapy is a well tolerated and effective therapeutic option.     

The benefit of adjuvant chemotherapy combined with postoperative radiotherapy for endometrial cancer: a meta-analysis

The objective of our study was to determine whether adjuvant chemotherapy combined with postoperative radiotherapy would have benefits for the disease-free survival and overall survival in patients with high-risk endometrial cancer.     

The importance of chemotherapy and radiation in uterine papillary serous carcinoma

Purpose

To identify prognostic and predictive factors of overall survival (OS), relapse-free survival (RFS) and toxicity for patients with uterine papillary serous carcinoma (UPSC).

Materials and methods

Patient, tumor, treatment and relapse characteristics of 135 women with Stages I-IVA UPSC treated between 1980 and 2006 at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) were analyzed using Cox regression models to determine prognostic and predictive factors for OS, RFS and toxicity.

Results

Mean follow-up was 5.5 years (range, 0.01-25.2). Median 5-year OS was 52%, and RFS was 42% for all patients. On Cox regression analysis, increasing age, stage, and myometrial invasion were prognostic factors associated with shorter OS and RFS. A paclitaxel-platinum chemotherapy regimen was significantly associated with longer OS (hazard ratio [HR] = 0.34, 95% confidence interval [CI] 0.15-0.74, p = 0.007) and RFS (HR = 0.45, 95% CI 0.22-0.92, p = 0.03). RFS was improved for patients treated with RT (HR = 0.44, 95% CI 0.25-0.77, p = 0.004). The 5-year grade 3+ toxicity rate was 3.5% for those who received RT and was 2.9% for those who did not (p = NS).

Conclusion

Uterine papillary serous cancer can be an aggressive tumor type with a poor prognosis. RFS was improved by radiation and chemotherapy with few grade 3 or higher complications. Using radiation and paclitaxel-platinum chemotherapy should be attempted whenever feasible for patients with UPSC who do not have distant metastases at diagnosis.     

术后化疗对有高危因素的早期子宫内膜癌患者预后的影响

目的 探讨术后化疗对有高危因素的早期(Ⅰ、Ⅱ期)子宫内膜癌患者预后的影响.方法 选择1994年1月-2007年6月间,北京大学第一医院妇产科收治的66例有高危因素的早期子宫内膜癌且术后均辅以化疗的患者(化疗组),40例相同期别及相同高危因素但术后未予化疗者作为对照组,Kaplan-Meier法计算两组患者的5年累积生存率,并进行比较;对有高危因素的早期子宫内膜癌患者的预后影响因素进行单因素及多因素分析.结果化疗组患者的5年累积生存率为94%,对照组为81%,化疗组明显高于对照组(P<0.05).单因素分析显示,化疗组中≥4个疗程患者的5年累积生存率为100%,<4个疗程患者的5年累积生存率为86%,两者比较,差异有统计学意义(P<0.05);而不同年龄、手术病理分期、病理类型、病理分化程度及术后有无放疗、术后化疗后是否联合放疗、有无孕激素治疗患者间比较,差异均无统计学意义(P>0.05).多因素分析显示,术后化疗是影响有高危因素的早期子宫内膜癌患者预后的独立因素(P<0.05).结论术后化疗可改善有高危因素的早期子宫内膜癌患者的预后,且疗程数应≥4个,但因例数较少,需通过前瞻性随机对照研究的进一步证实.     

Pelvic lymphadenectomy as alternative to postoperative radiotherapy in high risk early stage endometrial cancer

Objective: The purpose of the study is to evaluate whether surgery followed by radiotherapy in high-risk patients of early stage endometrial cancer can be replaced by formal surgical staging. Cancer-related survival and recurrence-free survival (RFS) were the endpoints of the analysis. Study design: One hundred and eighteen patients with endometrioid endometrial adenocarcinoma between 1996–2003 were reviewed. Patients with incomplete follow-up and extrauterine spread excluded, leaving 78 women in the final analysis. Low-risk patients (n=37) (Grade 1, myometrial infiltration <1/2 or Grade2, <1/3), treated by standard surgical procedure including total abdominal hysterectomy, bilateral salpingo-oophorectomy and peritoneal washing, while staging lymphadenectomy (n=24) or postoperative irradiation (n=17) was added in the high-risk group (Grade 1, >1/2 or Grade 2, >1/3 or Grade3). Results: The median age of patients was 65 years (range, 35–80 years) and the median follow-up 38 months (range, 9–98 months). The recurrence rate in low-risk patients was 2.7%, the cancer-related survival 97.5% and RFS 97%, while in the high-risk patients 12%, 93% and 88%, respectively. Comparing the therapeutic modalities (staging lymphadenectomy vs. postoperative irradiation) in the high-risk group the cancer-related survival and RFS was not differed (P=0.70, P=0.90, respectively). The high grade of the tumor was significantly correlated with RFS, while age, stage and myometrial infiltration were not. No moderate or severe complications developed after lymphadenectomy, while two moderate gastrointestinal complications occurred after adjuvant radiotherapy. Conclusion: According our results the low-risk patients of early stage endometrial adenocarcinoma had excellent survival with minimal intervention. The cancer-related survival and RFS in high-risk patients concerning the therapeutic modalities were comparable. Poor tumor differentiation was the most unfavorable prognostic factor related with RFS. Moderate complications developed only after postoperative radiotherapy.     

淋巴结清扫术在Ⅰ期子宫内膜癌中的意义

目的　探讨盆腔淋巴结清扫术在Ⅰ期子宫内膜癌中的临床意义。方法　回顾性分析 1990年 1月～ 2 0 0 0年 12月 ,在我院住院治疗的Ⅰ期子宫内膜癌 112例 ,其中广泛或次广泛子宫切除术加盆腔淋巴结清扫术 6 6例 ,单纯广泛或次广泛子宫切除术 4 6例。结果　在 6 6例Ⅰ期子宫内膜癌中 ,发现 7例淋巴结转移 ,转移率为 10 6 %。Ⅰa期中无淋巴结转移 ;Ⅰb期转移率为 5 9% (2 34) ;Ⅰc期转移率为 2 5 % (5 2 0 )。Ⅰ期子宫内膜癌随着肌层浸润的加深其淋巴结转移率亦增加 ,P <0 0 5。而且特殊类型的子宫内膜癌其淋巴结转移率明显高于腺癌。但是行淋巴结清扫术与未行淋巴结清扫术的 5年生存率无差异。结论　Ⅰa期可以不做淋巴结清扫术 ,Ⅰc期和合并高危因素的Ⅰb期必须行盆腹腔淋巴结清扫术。且加强术前术中对肌层浸润程度的判断 ,以指导Ⅰ期亚分期的确定。淋巴结清扫术本身能否改善Ⅰ期患者的预后有待进一步研究。     

Predictive factors of recurrence following adjuvant vaginal cuff brachytherapy alone for stage I endometrial cancer

Purpose

The purpose of this study is to identify risk factors for recurrence in a cohort of stage I endometrial cancer patients treated with vaginal cuff brachytherapy at a single academic institution.

Methods and materials

From 1989 to 2011, 424 patients with stage I endometrial cancer underwent total hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy (LND), followed by high-dose-rate vaginal cuff brachytherapy (VCB) to patients felt to be high or intermediate risk FIGO stage IA and IB disease. Covariates included: 2009 FIGO stage, age, grade, histology, presence of lymphovascular space invasion, LND, and receipt of chemotherapy.

Results

With a median follow-up of 3.7 years, the 5 and 10-year disease free survival were 98.4% and 95.9%, respectively. A total of 30 patients developed recurrence, with the predominant pattern of isolated distant recurrence (57.0%). On multivariate analysis, grade 3 (p = 0.039) and LND (p = 0.048) independently predicted of increased recurrence risk. χ² analysis suggested that higher-risk patients were selected for LND, with significant differences in age, stage, and grade noted between cohorts. Distant metastatic rate was significantly higher for patients who qualified for GOG 0249 at 23.1% (95% CI 10.7–35.5%) compared to those who did not at 6.8% (95% CI 1.8–11.8%, p < 0.001).

Conclusion

Overall disease-free survival for this cohort of patients was > 95% at 10 years. Univariate analysis confirmed previously identified risk factors as predictors for recurrence. Multivariate analysis found that grade 3 and LND correlated with risk for recurrence. Of those that did recur, the initial site of relapse included distant metastasis in most cases.     

Evaluation of complete surgical staging with pelvic and para-aortic lymphadenectomy and paclitaxel plus carboplatin chemotherapy for improvement of survival in stage I ovarian clear cell carcinoma

OBJECTIVE: The aim was to determine the benefits of lymphadenectomy and paclitaxel plus carboplatin chemotherapy for stage I ovarian clear cell carcinoma (defined as intra-abdominal disease confined to the ovaries). METHODS: Twenty patients with stage I pure clear cell carcinoma of the ovary diagnosed between 1991 and 2001 were divided into two groups: Group A (12 patients, 1997-2001) underwent complete surgical staging including bilateral salpingo-oophorectomy, hysterectomy, omentectomy, and pelvic and para-aortic lymphadenectomy, followed by paclitaxel and carboplatin chemotherapy. Group B (8 patients, 1991-1996) underwent bilateral salpingo-oophorectomy, hysterectomy, and omentectomy without lymphadenectomy, followed by cisplatin-based chemotherapy. The survival of the two groups was compared. The clinical characteristics of the two groups were evaluated for age distribution, grade, substage, preoperative CA-125, presence or absence of endometriosis, and maximal tumor diameter. RESULTS: The estimated 4-year survival rate was 76.9%. The clinical characteristics of the two groups were similar, except for lymphadenectomy and regimen of chemotherapy. With a median follow-up of 36 months (range: 11-130 months), one of 12 patients in Group A had recurrence in comparison with 6 of 8 patients in Group B (P = 0.004). The estimated 3-year recurrence-free survival and 4-year overall survival for Group A was significantly greater than that for Group B (91.7 vs 33.3%, P = 0.014; 100 vs 50%, P = 0.014). Median time to recurrence was 8 months. CONCLUSIONS: Complete surgical staging, including pelvic and para-aortic lymphadenectomy and paclitaxel plus carboplatin chemotherapy, appeared to be capable of improving survival of patients with stage I ovarian clear cell carcinoma.     

Ⅰ期子宫内膜癌盆腔淋巴清扫术的意义

目的:探讨Ⅰ期子宫内膜癌患者预后的相关因素及盆腔淋巴清扫术对其预后可能的影响。方法:收集1997年8月至2005年3月浙江大学医学院附属妇产科医院临床Ⅰ期子宫内膜癌患者202例,分析影响预后的各项临床病理指标,寿命表法计算生存率,比较盆腔淋巴清扫组与平行淋巴结清扫组的复发率,并发症。结果:Ⅰ期子宫内膜癌盆腔淋巴转移率1·53%。病理类型、腹腔细胞学、盆腔淋巴转移、手术-病理分期、肌层浸润及CA125值是影响预后的独立因素。Ⅰ期低危患者,盆腔淋巴清扫术无助于提高生存率(P>0.05),其复发率也无明显差异(P>0.05),手术并发症率明显增高(P<0.05);Ⅰ期高危患者,盆腔淋巴清扫术未能延长其生存期(P>0·05),但可减少复发的例数,并发症率无明显增多(P>0.05)。结论:特殊病理类型,腹腔细胞学阳性,手术-病理分期高,盆腔淋巴转移,深肌层浸润及CA125>100U/ml的患者预后较差(P<0.05)。Ⅰ期高危子宫内膜癌患者盆腔淋巴清扫术具有一定的临床意义。     

Adjuvant treatment for stage IIIC endometrial cancer: options and controversies

Endometrial cancer is the most common gynecologic malignancy. Locally advanced and high risk endometrial cancer encompasses a heterogeneous group of patients and optimal treatment for various sub-groups of these patients remains controversial. Stage IIIC is the most common sub-stage of patients with locally advanced endometrial carcinoma. This article reviews retrospective and prospective data of various adjuvant treatment approaches involving chemotherapy, radiation therapy, or combined modality therapy, including the recently proposed “sandwich” regimens that have yielded encouraging results. Areas of controversy are also discussed to assist clinicians in identifying the most effective adjuvant treatment regimens for patients with locally advanced disease. On-going randomized trials are briefly discussed.     

Risk factors for early and late postoperative complications of patients with endometrial cancer

OBJECTIVE: We have routinely performed staging with pelvic and/or paraaortic lymphadenectomy in patients with endometrial cancer having moderate to high risk for lymph node metastasis. The aim of this study was to investigate the risk factors for the occurrence of early and late postoperative complications in patients managed primarily by surgery in our institution. STUDY DESIGN: Two-hundred and fifty-nine consecutive cases of endometrial cancer were enrolled in the study. Past history, body mass index, type of surgery, intraoperative findings, and follow-up information were collected from patient charts. Of these, 200, 127, and 30 patients underwent systematic pelvic lymphadenectomy, systematic paraaortic lymphadenectomy, and radical hysterectomy, respectively. The median numbers of dissected pelvic and paraaortic lymph nodes were 32 and 14, respectively. RESULTS: None of the complications resulted in death. Of the study population, 36 early complications and 34 late complications occurred. Overall 65 patients (25.1%) had at least one complication. Multivariate analysis revealed that a longer operative time and paraaortic lymphadenectomy were independent predictors for the occurrence of early and late postoperative complications, respectively. CONCLUSIONS: Since the therapeutic value of lymphadenectomy is still under evaluation, the indications for systematic pelvic and paraaortic lymphadenectomy should be carefully considered.     

Adjuvant therapy in stage III endometrial cancer confined to the pelvis

Objective

To review outcomes of patients with stage III endometrial cancer confined to the pelvis treated with adjuvant pelvic radiotherapy (RT) or sequential chemoradiotherapy (CRT).

Primary radiation therapy for medically inoperable patients with clinical stage I and II endometrial carcinoma

Objective

To determine the outcomes associated with primary radiation therapy for medically inoperable, clinical stage I and II, endometrial adenocarcinoma (EAC).

Methods

A multi-institution, retrospective chart review from January 1997 to January 2009 was performed. Overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS) and time to progression (TTP) were assessed using the Kaplan-Meier method. Disease-specific survival was analyzed using a competing risks approach.

Results

Seventy-four patients were evaluable. The median age and BMI were 65 years (range 36-92 years) and 46 kg/m² (range 23-111 kg/m²), respectively. 85.1% had severe systemic disease, most frequently cardiopulmonary risk and morbid obesity. With a mean follow-up of 31 months, 13 patients (17.6%) experienced a recurrence. The median PFS and OS were 43.5 months and 47.2 months, respectively. Overall, 35 women died, including 4 women who died of unknown cause. Of the remaining 31 women, 7 patients (9.5%) died of disease, while 24 died of other causes (32.4%). The hazard ratio comparing the risk of death due to other causes to the risk of death due to disease was 3.4 (95% CI 1.4-9.4, p = 0.003). Among patients who are alive three years after diagnosis, 14% recurred and the conditional recurrence estimate did not exceed 16%.

Conclusions

Primary radiation therapy for clinical stage I and II EAC is a feasible option for medically inoperable patients and provides disease control, with fewer than 16% of surviving patients experiencing recurrence.     

Phase I trial of concomitant vinorelbine, cisplatin, and pelvic irradiation in cervical carcinoma and other advanced pelvic malignancies

OBJECTIVE: To determine the maximum tolerated dose (MTD) of vinorelbine in combination with weekly cisplatin and pelvic radiation therapy (RT). METHODS: Eligible patients included those with bulky or locally advanced cervical cancer. Women with other advanced gynecologic malignancies were also eligible. All patients received cisplatin 40 mg/m(-2)/week (maximum dose, 70 mg) during pelvic RT. Vinorelbine was administered on the same day as cisplatin at a starting dose of 10 mg/m(-2)/week and escalated in 5 mg/m(-2)/week increments. Dose-limiting toxicity (DLT) was defined as: grade 3-4 non-hematologic toxicity, grade 4 hematologic toxicity, or any toxicity which required > or =1 week delay in RT or an omission of >1 dose of chemotherapy. RESULTS: Between April 2001 and September 2002, 12 women with pelvic malignancies (11 cervical, 1 recurrent ovarian) were enrolled. Cohorts of 3, 6, and 3 patients were treated at 10, 15, and 20 mg/m(-2)/week dose levels of vinorelbine. At the 20 mg/m2 level, DLT was observed. Two of three patients missed >1 cycle of chemotherapy secondary to predominantly hematologic toxicity. One patient at the 20 mg level developed a creatinine clearance <50 ml/min and missed 1 dose of cisplatin. Another developed transient grade 3 diarrhea. No grade 4 toxicities were observed. CONCLUSIONS: The MTD of vinorelbine in combination with cisplatin and pelvic RT in patients with cervical cancer is 15 mg/m(-2)/week.     

I期子宫内膜癌盆腔淋巴清扫术的意义

目的：探讨I期子宫内膜癌患者预后的相关因素及盆腔淋巴清扫术对其预后可能的影响。方法：收集1997年8月至2005年3月浙江大学医学院附属妇产科医院临床I期子宫内膜癌患者202例，分析影响预后的各项临床病理指标，寿命表法计算生存率，比较盆腔淋巴清扫组与平行淋巴结清扫组的复发率，并发症。结果：I期子宫内膜癌盆腔淋巴转移率1．53％。病理类型、腹腔细胞学、盆腔淋巴转移、手术-病理分期、肌层浸润及CA125，值是影响预后的独立因素。I期低危患者，盆腔淋巴清扫术无助于提高生存率（P〉0．05），其复发率也无明显差异（P〉0．05），手术并发症率明显增高（P〈0．05）；I期高危患者，盆腔淋巴清扫术未能延长其生存期（P〉0．05），但可减少复发的例数。并发症率无明显增多（P〉0．05）。结论：特殊病理类型，腹腔细胞学阳性，手术-病理分期高，盆腔淋巴转移，深肌层浸润及CA125〉100U／ml的患者预后较差（P〈0．05）。I期高危子宫内膜癌患者盆腔淋巴清扫术具有一定的临床意义。     

A novel low dose fractionation regimen for adjuvant vaginal brachytherapy in early stage endometrioid endometrial cancer

Purpose

To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen.

Methods

We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan-Meier method.

Results

All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8 months (range, 1.5-76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%, locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient.

Conclusion

Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity.     

Phase II trial of vaginal cuff brachytherapy followed by chemotherapy in early stage endometrial cancer patients with high-intermediate risk factors

Objective

To determine the progression free survival (PFS), toxicity, and patterns of failure for early stage, high-intermediate risk (H-IR) patients in a phase II trial with adjuvant vaginal cuff brachytherapy (VCB) and three cycles of carboplatin and paclitaxel.

Methods

Surgically staged patients with stage I-IIb endometrial cancer with H-IR factors were treated with VCB (2100 cGy) followed by three cycles of carboplatin (AUC 6) and paclitaxel (175 mg/m²). The primary endpoint was PFS at 2 years, with toxicity and sites of failure as secondary endpoints. Toxicity was assessed by patient report (CTCAE v. 3) as well as by delays or dose modifications in treatment.

Results

All patients completed VCB and 19/23 (83%) completed both VCB and 3 cycles of chemotherapy. Mean time to complete VCB was 14.5 days with minimal acute toxicity noted. At 6 months, all toxicity related to VCB had resolved. In total 60 cycles of chemotherapy were given, with one dose reduction (1.6%) for grade 2 neuropathy and seven delays (11.6%) in treatment due to hematologic toxicity. At a median follow-up of 44.5 months, 91% of patients remained progression free at 2 years. Four patients experienced a recurrence; they recurred both locally and distant.

Conclusions

Adjuvant therapy with VCB and chemotherapy is well tolerated in a population of patients with H-IR endometrial carcinoma and provides 2 year PFS of 91%. A randomized trial is currently underway to assess whether combined VCB and chemotherapy reduces the rate of recurrence compared to external beam radiation therapy (EBRT) in this patient population.