Postoperative pelvic intensity-modulated radiotherapy and concurrent chemotherapy in intermediate- and high-risk cervical cancer

ObjectiveAccording to national surveys, the use of intensity-modulated radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of this study is to report a single-institution experience using postoperative pelvic IMRT with concurrent chemotherapy in intermediate- and high-risk early stage cervical cancer.MethodsFrom 1/2004 to 12/2009, 34 patients underwent radical hysterectomy and pelvic lymph node dissection (28 median nodes were removed) for early stage cervical cancer. Median dose of postoperative pelvic IMRT was 50.4 Gy (range, 45–50.4). All patients received concurrent cisplatin.ResultsWith a median follow-up of 44 months, 3 patients have recurred; 1 vaginal recurrence, 1 regional and distant, and 1 distant. The 3- and 5-year disease-free survival (DFS) was 91.2% (95% CI, 81.4–100%) and overall survival (OS) was 91.1% (95% CI, 81.3–100%). All failures and all deaths were in the high-risk group (n = 3/26). There was 32.3% G3–4 hematologic toxicity, 2.9% acute G3 gastrointestinal toxicity, and no acute G3 or higher genitourinary toxicity. There were no chronic G3 or higher toxicities.ConclusionsOncologic outcomes with postoperative IMRT were very good, with DFS and OS rates of > 90% at median follow-up of 44 months, despite a preponderance (76.5%) of high-risk features. Toxicity was minimal even in the setting of an aggressive trimodality approach. Data from this study and emerging data from the Phase II RTOG study (0418) demonstrate the advantages of postoperative IMRT in early stage cervical cancer.     

Postoperative radiotherapy in endometrial adenocarcinoma

We present the results of the association of surgery and radiotherapy in endometrial adenocarcinoma. We have 151 cases of which we know FIGO classification, pTNM, histological grading and myometrium infiltration. Follow-up is considered between 6 months and 10 years. We report the survival graphic lines for a five year period relative to every single prognostic factor.     

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.     

Pelvic lymphadenectomy in high risk endometrial cancer

Two hundred and thirty-eight out of a total of 1012 patients with 'high risk' endometrial cancer underwent a complete pelvic lymphadenectomy. When the disease was confined to the corpus, the rate of node positivity was 7%, when the cervix was involved it was 22% and with adnexal involvement was 52%. The recurrence rate with negative nodes was 14% compared to 45% with positive nodes. Age, menopausal status, histology and depth of invasion were predictors of survival after stratification by node status. Node status had no significant influence on site of recurrence. Women who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy (TAH-BSO) and pelvic lymphadenectomy followed by vaginal vault brachytherapy had a similar cancer-free survival to those treated by TAH-BSO alone, followed by adjuvant megavoltage therapy and vaginal vault brachytherapy.     

Cost-effectiveness of adjuvant radiotherapy in intermediate risk endometrial cancer

OBJECTIVES: Endometrial cancer is the most common gynecologic malignancy in the United States. Adjuvant radiotherapy in patients with intermediate risk disease (stage IB, IC, and occult stage II) is controversial. Despite no proven survival advantage, a significant number of women undergo this treatment annually. The purpose of this study was to compare the estimated health and economic outcomes for adjuvant whole pelvic radiotherapy to no treatment with salvage therapy for recurrence. METHODS: A decision analytic model was created to estimate the costs of adjuvant pelvic radiotherapy versus no adjuvant radiotherapy in patients with intermediate risk endometrial cancer. Data used was gathered from published literature and institutional data on costs. The model incorporates complications, recurrence rates, treatment of recurrence, and survival in each group. RESULTS: In the base case analysis, adjuvant pelvic radiation reduced the recurrence rate by 50%. Cost-effectiveness as measured by cost per recurrence prevented was highly sensitive to the probability of recurrence and the efficacy of adjuvant therapy. In our model the mean costs of Strategy 1 with observation and treatment reserved until the time of recurrence would be $5016. In contrast the mean cost of Strategy 2 which incorporated adjuvant radiotherapy would be $21,159. Cost per recurrence prevented based on the incremental cost-effectiveness is thus $225,215. In the highest risk subgroup, using the upper limit of the 90% confidence limit of efficacy seen in GOG Protocol 99, cost/recurrence prevented was approximately $50,000. Results did not differ when using parameters solely from GOG 99 or PORTEC. CONCLUSIONS: Although adjuvant pelvic radiation does not appear to improve survival for intermediate risk endometrial cancer patients, it does prevent recurrences, at a net positive cost compared to no therapy. Data are not currently available to incorporate quality of life information into cost-effectiveness analyses. Obtaining such data would allow cost/quality-adjusted life year gained to be estimated. This information is necessary to determine if the extra costs of adjuvant radiotherapy in patients with intermediate risk endometrial cancer are acceptable by current health care policy standards.     

Postoperative radiotherapy in stage I endometrial adenocarcinoma

OBJECTIVE: To evaluate postoperative whole pelvic radiation for high-risk patients with Stage I endometrial adenocarcinoma. METHODS: One hunderd and twenty-two patients with irregular premenopausal or postmenopausal haemorrhage were included into the study. Fractional curettage was performed in all cases. When the pathohistological report confirmed endometrial adenocarcinoma, abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Low-risk patients include women with Stage IA tumours and Stage IB grade 1 or 2 histology. High-risk group include patients with Stage IB grade 3 tumours and Stage IC carcinomas. High-risk patients received whole pelvic radiotherapy between two and four weeks after surgery. RESULTS: Eighty-two patients (67.21%) were low-risk and forty patients (32.79%) were high-risk. In the low-risk group of patients, CA-125 was negative in ten cases and positive in 72 patients with a mean value of 30.12 +/- 12.42 U/ml serum. In the high-risk group of the patients, CA-125 was negative in two cases and positive in 38 patients with a mean value of 60, 48 +/- 20, 14 U/ml serum. Locoregional recurrences were diagnosed in four patients (4.87%) in the surgery group and in two patients (5.00%) assigned to radiotherapy. The incidence of distant metastases was 2.43% in the surgery group and 2.50% in the radiotherapy group. Overall survival at five years was 90.25% in the low-risk group and 87.50% in the high-risk group of patients. CONCLUSION: Five-year overall survival, locoregional and distant metastasis were similar in the low-risk and high-risk groups of patients. That emphasizes the value of whole pelvic radiation in patients with unfavourable prognostic factors in Stage I endometrial cancer.     

Postoperative pelvic radiotherapy for cervical cancer patients with positive parametrial invasion

OBJECTIVE: To evaluate patterns of failure in cervical cancer patients with histopathologic parametrial invasion treated with postoperative pelvic radiation therapy. METHODS: Records of 117 stages IB-IIB cervical cancer patients with parametrial invasion treated with postoperative radiation therapy from 1985 to 2002 were retrospectively reviewed. Patients were divided into two groups based on status of pelvic lymph nodes. Patterns of recurrence and prognosis by status of pelvic lymph nodes were statistically analyzed. RESULTS: Status of pelvic lymph nodes had significant impact on both recurrence and survival. Extrapelvic recurrence was observed in 23 of 66 node-positive patients compared with 6 of 51 node-negative patients (P = 0.005). Of 66 patients with a positive pelvic lymph node, 18 developed visceral metastases, whereas only three visceral metastases were noted in the 51 node-negative patients (P = 0.003). Five-year overall survival in node-positive and -negative patients was 52% and 89%, respectively (P = 0.0005). Corresponding rates for recurrence-free survival were 44% and 83%, respectively (P = 0.0002). The correlation between nodal metastasis and prognosis was enhanced when node-positive patients were stratified into two groups based on number of positive nodes (n = 1 and n > or = 2). Five-year recurrence-free survival rates for patients with negative, one positive, and two or more positive nodes were 83%, 61%, and 31%, respectively (P = 0.0001). CONCLUSIONS: Extrapelvic recurrence was uncommon in node-negative patients with parametrial invasion. These findings do not support use of systemic therapy for cervical cancer patients with parametrial invasion if pelvic lymph node metastasis is negative.     

Impact of para-aortic recurrence risk-guided intensity-modulated radiotherapy in locally advanced cervical cancer with positive pelvic lymph nodes

Objectives

A previous study has suggested the benefit of sub-renal vein radiotherapy (SRVRT) for pelvic lymph node (PLN)-positive cervical cancer. In order to better select patients for SRVRT, this study aimed to evaluate the value of a risk-based radiation field based on PLN location and number in PLN-positive cervical cancer.

Identification of high risk patients with endometrial carcinoma. Prognostic assessment of endometrial cancer

OBJECTIVES: To verify the importance of DNA ploidy on clinical outcome in endometrial carcinoma and to investigate whether the prognostic information obtained by this variable is independent from other clinical-pathologic features. MATERIALS AND METHODS: Univariate and multivariate analysis of clinical and pathologic prognostic factors obtained from 203 consecutive cases of endometrial cancer, that had been surgically treated in our hospital, were performed. RESULTS: Significant prognostic factors according to the Kaplan-Meier method were age at the time of diagnosis, grade of differentiation, peritoneal cytology, node involvement, vascular invasion, myometrial infiltration and ploidy. At multivariate analysis only DNA ploidy resulted to be an independent variable. CONCLUSIONS: In our analysis DNA content is the only parameter which preserved prognostic significance in multivariate analysis.     

宫颈癌术后辅助放疗

早期宫颈癌可选择手术或放疗。同时采用多种治疗手段如手术和放疗合用并不能提高患者的存活率。而且，治疗手段越多，并发症越常见。所以，若选择手术治疗，多数情况下手术后并不需要加用放射治疗。只有对有复发危险因素的患者才考虑进行辅助治疗。宫颈癌术后放疗的有效率可达66．0％，目前被广泛应用于具有高危因素的患者。     

Small bowel displacement system-assisted intensity-modulated radiotherapy for cervical cancer

OBJECTIVE: To evaluate the small bowel displacement system (SBDS)-assisted intensity-modulated radiation therapy (IMRT) for cervical cancer patients. METHODS: Ten consecutive patients that received radiation therapy for uterine cervical cancer, with the SBDS, between January and May 2003, were included in this study. The SBDS consists of a customized Styrofoam compression device, which displaces the small bowel out of the radiation fields and an individualized immobilization abdominal board. Computed tomography (CT) scans were taken in the prone position, both with and without the SBDS. IMRT planning was performed for both CT sets using 15 MV photon beams. The dose distributions in the target volumes and the organs at risk, with and without the SBDS, were compared. The complexity of both the IMRT plans was evaluated by comparing the monitor units (MUs) and multi-leaf collimator (MLC) segment numbers of the plans. RESULTS: The SBDS significantly reduced the small bowel volume within the pelvic radiation field. The mean irradiated small bowel volume, with the SBDS, was 61.46 +/- 4.97% (53.4-97.1%) smaller than the conventional IMRT. The SBDS-assisted IMRT plan was superior to the conventional one in terms of the dose homogeneity in the planning target volume (PTV) but not significantly different in the rectum and bladder. The mean MUs and MLC segment numbers, with the SBDS, were 26.2% and 31.65% lower than the values without the SBDS, respectively (P < 0.0001 for MUs and MLCs). CONCLUSIONS: The SBDS-assisted IMRT is superior to conventional IMRT in terms of the dose homogeneity of PTV and in sparing of the small bowel, which potentially allows dose escalation by further reducing the small bowel complications.     

Postoperative whole pelvic radiotherapy plus concurrent chemotherapy versus extended-field irradiation for early-stage cervical cancer patients with multiple pelvic lymph node metastases

Objectives

The aim of this study was to compare the efficacy of postoperative pelvic radiotherapy plus concurrent chemotherapy with that of extended-field irradiation (EFRT) in patients with FIGO Stage IA2-IIb cervical cancer with multiple pelvic lymph node metastases.

Methods

We retrospectively reviewed the medical records of patients with FIGO Stage IA2-IIb cervical cancer who had undergone radical surgery between April 1997 and March 2008. Of these, 55 patients who demonstrated multiple pelvic lymph node metastases were treated postoperatively with pelvic radiotherapy plus concurrent chemotherapy (n = 29) or EFRT (n = 26). Thirty-six patients with single pelvic node metastasis were also treated postoperatively with pelvic radiotherapy plus concurrent chemotherapy. The recurrence rate, progression free survival (PFS), and overall survival (OS) were compared between the treatment groups.

Results

Pelvic radiotherapy plus concurrent chemotherapy was significantly superior to EFRT with regard to recurrence rate (37.9% vs 69.2%, p = 0.0306), PFS (log-rank, p = 0.0236), and OS (log-rank, p = 0.0279). When the patients were treated with pelvic radiotherapy plus concurrent chemotherapy, there was no significant difference in PFS or OS between the patients with multiple lymph node metastases and those with single node metastases. With regards to grade 3-4 acute or late toxicities, no statistically significant difference was observed between the two treatment groups.

Conclusions

Postoperative pelvic radiotherapy plus concurrent chemotherapy is superior to EFRT for treating patients with FIGO Stage IA2-IIb cervical cancer displaying multiple pelvic lymph node metastases.