The revolving door: hospital readmissions of gynecologic oncology patients

Objective

Rehospitalization within 30 days of discharge was identified by the Obama Administration as a target for reducing health care spending. We examined readmissions to our gynecologic oncology service to determine: 1) rates of readmission, 2) indication for readmissions, 3) whether the admission was planned, and 4) costs.

Methods

IRB approval was obtained for this 5-year retrospective review (2004-2008). Gynecologic oncology patients were included if they were readmitted within 30 days of discharge at a single academic hospital. Abstracted data included: demographics, dates of hospitalizations, cancer history, indication for admission, and cost. A series of admissions was any number of admissions that occurred within 30 days of discharge. An index admission was the first admission in a series.

Results

In the study period, 2455 unique patients were admitted to Gynecologic Oncology. 324 unique patients (13.2%) were readmitted within 30 days, with 37 experiencing > 1 series of admission. 87.3% were readmitted to Gynecologic Oncology. Within a series of admissions, patients were admitted on average 1.5 times following the index admission, up to 9 admissions. The median cost of index admission was $9820; for readmissions, $8059. The total cost of readmissions over 5 years was $6,421,733. Unplanned readmissions accounted for the majority of this cost.

Conclusions

Hospital readmissions affect the cost of care, but also the quality of care delivered to our patients. When extrapolated across institutions and across the country, unplanned readmissions are a costly expenditure to patients and the health system, deserving of attention.     

Location of aortic node metastases in locally advanced cervical cancer

Background

To assess the location of aortic node metastasis in patients with locally advanced cervical cancer undergoing extraperitoneal aortic lymphadenectomy to define the extent of the aortic lymphadenectomy.

Material and methods

Between August 2001 and December 2010, 100 consecutive patients with primary locally advanced cervical cancer underwent extraperitoneal laparoscopic aortic and common iliac lymphadenectomy. The location of aortic node metastases, inframesenteric or infrarenal was noted.

Results

The mean number ± standard deviation (SD) of aortic nodes removed was 15.9 ± 7.8 (range 4-62). The mean number ± SD of inframesenteric (including common iliac) nodes removed was 8.8 ± 4.5 (range 2-41) and the mean number ± SD of infrarenal nodes removed was 7.8 ± 4.1 (range 2-21). Positive aortic nodes were observed in 16 patients, and in 5 (31.2%) of them the infrarenal nodes were the only nodes involved, with negative inframesenteric nodes.

Conclusion

Inframesenteric aortic nodes are negative in the presence of positive infrarenal nodes in about one third of patients with locally advanced cervical cancer and aortic metastases.     

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.     

Metabolic risk factors and cervical cancer in the metabolic syndrome and cancer project (Me-Can)

Background

Little is known about the association between metabolic risk factors and cervical cancer carcinogenesis.

Material and methods

During mean follow-up of 11 years of the Me-Can cohort (N = 288,834) 425 invasive cervical cancer cases were diagnosed. Hazard ratios (HRs) were estimated by the use of Cox proportional hazards regression models for quintiles and standardized z-scores (with a mean of 0 and a SD of 1) of BMI, blood pressure, glucose, cholesterol, triglycerides and MetS score. Risk estimates were corrected for random error in the measurements.

Results

BMI (per 1SD increment) was associated with 12%, increase of cervical cancer risk, blood pressure with 25% and triglycerides with 39%, respectively. In models including all metabolic factors, the associations for blood pressure and triglycerides persisted. The metabolic syndrome (MetS) score was associated with 26% increased corrected risk of cervical cancer. Triglycerides were stronger associated with squamous cell carcinoma (HR 1.48; 95% CI, 1.20-1.83) than with adenocarcinoma (0.92, 0.54-1.56). Among older women cholesterol (50-70 years 1.34; 1.00-1.81), triglycerides (50-70 years 1.49, 1.03-2.16 and ≥ 70 years 1.54, 1.09-2.19) and glucose (≥ 70 years 1.87, 1.13-3.11) were associated with increased cervical cancer risk.

Conclusion

The presence of obesity, elevated blood pressure and triglycerides were associated with increased risk of cervical cancer.     

Para-aortic lymphadenectomy for primary fallopian tube cancer

Objective

To investigate the topography of lymph node spread and the need for para-aortic lymphadenectomy in primary fallopian tube cancer (PFTC).

Methods

Twenty-six women were diagnosed with PFTC at Cheil General Hospital and Women's Healthcare Center, Seoul, Korea, between March 1992 and November 2009. Of the 26 patients, we retrospectively analyzed 15 patients who underwent complete staging surgery, including bilateral pelvic and para-aortic lymphadenectomy.

Results

The median follow-up period was 57.9 months (range, 3-185 months) and the 5-year survival rate was 86.3%. Five (33.3%) patients were diagnosed with FIGO stage I, 1 (6.7%) with stage II, and 9 (60%) with stage III cancer. The median number of lymph nodes removed was 53.8 (range, 18-106 nodes). Four (26.7%) patients had nodal involvement: 2 patients with para-aortic lymph node involvement and 2 patients with both pelvic and para-aortic lymph node involvement. None of the patients was positive for pelvic lymph nodes alone.

Conclusion

A comprehensive para-aortic lymphadenectomy was necessary for accurate staging in PFTC.     

Endometrial cancer in the oldest old: Tumor characteristics, patterns of care, and outcome

Objective

Despite the fact that endometrial cancer commonly occurs in elderly women, little is known about the outcome of the oldest old, those > 80 years of age. We examined the patterns of care and outcome of the oldest old women with endometrial cancer.

Methods

An analysis of women > 65 years of age with endometrioid adenocarcinoma of the uterus diagnosed between 1988 and 2006 and registered in the Surveillance, Epidemiology, and End Results database was performed. Patients were stratified by age into the following groups: 65-69, 70-74, 75-79, 80-84, and ≥ 85 years of age. Multivariable logistic regression models were constructed to examine treatment while adjusting for other confounders. Cancer-specific survival was examined using Cox proportional hazards models.

Results

A total of 37,718 women including 5289 aged 80-84 and 3446 ≥ 85 years of age were identified. Older women had higher grade tumors (p < 0.0001) and more advanced stage disease (p < 0.0001). After adjusting for tumor characteristics, patients ≥ 85 years of age were less likely to undergo hysterectomy (OR = 0.14; 95% CI = 0.12-0.16) and lymphadenectomy (OR = 0.48; 95% CI = 0.44-0.54) and less likely to receive radiation (OR = 0.41; 95% CI = 0.36-0.46). After adjustment for treatment and prognostic factors, cancer-specific mortality was 53% (HR = 1.53; 95% CI = 1.39-1.67) greater in women 80-84 and 89% (HR = 1.89; 95% CI = 1.71-2.08) greater in those ≥ 85 years of age than in women 65-69 years old.

Conclusion

Women > 80 years of age receive less aggressive care than younger women. Even after adjusting for treatment differences, cancer-specific mortality is higher in the oldest old women.     

Vaginal intraepithelial neoplasia (VAIN) after radiation therapy for gynecologic malignancies: a clinically recalcitrant entity

Objectives

Vaginal dysplasia is associated with prior radiation therapy (RT) for gynecologic malignancies. We reviewed our institution's experience with VAIN in patients who were treated with radiation therapy for a gynecologic malignancy.

Methods

A retrospective review of patients treated for VAIN was performed. All cases of patients followed and treated for VAIN after radiation therapy were identified (n = 10), along with a cohort of patients with VAIN who did not have radiation therapy (n = 23).

Results

Mean follow-up after initial diagnosis of VAIN was 37.6 months (range: 12 to 72). Cytologic screening events after diagnosis of VAIN (n = 105) showed that patients with prior RT were more than twice as likely to have recurrent dysplasia (OR 3.625, 95% CI = from 1.454 to 9.0376) after treatment. Of patients who recurred, the mean time to first recurrence was 12.3 months in cases and 15.3 months in controls, which was not statistically significant (p = 0.31). Screening practices at our institution ranged from 3 month to 12 month intervals. 3 patients in the RT group and 1 patient in the control group developed invasive squamous cell cancer of the vagina.

Conclusions

Vaginal dysplasia after radiation therapy is more refractory to treatment than dysplasia not associated with radiation therapy, more likely to recur after surgical and ablative therapy, and may also be more likely to progress to invasive cancer. These data support the need for further study to determine the optimal follow-up screening interval and whether aggressive surgical or ablative treatment stems disease progression in this clinical scenario.     

Incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes in intermediate- and high-risk endometrial cancer

Objective

The aim of this study was to elucidate the incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes (CINDEIN), which are also called suprainguinal nodes, in intermediate- and high-risk endometrial cancer. Removal of these nodes needs to be discussed from the viewpoint of patient's quality of life because removal of CINDEIN is strongly related to lower extremity lymphedema.

Methods

A retrospective chart review was carried out for 508 patients with intermediate- and high-risk endometrial cancer who were included in this study. We identified patients with lymph node metastasis. Lymph node sites were classified into four groups: (1) CINDEIN, (2) external iliac nodes, (3) Group A consisting of circumflex iliac nodes to the distal obturator nodes, internal iliac nodes, obturator nodes, cardinal ligament nodes (including deep obturator nodes), and sacral nodes, and (4) Group B consisting of common iliac nodes and para-aortic nodes. Logistic regression analysis was used to select risk factors for CINDEIN metastasis.

Results

In an analysis of 508 patients with intermediate- and high-risk disease, CINDEIN metastasis was found in fourteen (2.8%) of the patients. Multivariate analysis confirmed that high-risk histology (OR = 5.7, 95% CI = 1.2-16.1) and Group A node metastasis (OR = 9.7, 95% CI = 2.9-31.4) were independent risk factors for CINDEIN metastasis. None of the patients with G1 endometrioid adenocarcinoma had CINDEIN metastasis. Three (2.5%) of the patients with G2 endometrioid adenocarcinoma had CINDEIN metastasis and all of these three patients had other pelvic node metastasis.

Conclusion

Removal of CINDEIN can be eliminated in patients with G1 endometrial cancer and patients with G2 endometrial cancer who have no pelvic node metastasis.     

Initial experience with repetitive transarterial chemoembolization (TACE) as a third line treatment of ovarian cancer metastasis to the liver: indications, outcomes and role in patient's management

Objective

To evaluate local tumor control and survival data after transarterial chemoembolization (TACE) with different drug combinations in the palliative third-line treatment of patients with ovarian cancer liver metastases.

Methods

Sixty-five patients (mean age: 51.5 year) with unresectable hematogenous hepatic metastases of ovarian cancer who did not respond to systemic chemotherapy were repeatedly treated with TACE in 4-week intervals. The local chemotherapy protocol consisted of Mitomycin (group 1) (n = 14; 21.5%), Mitomycin with Gemcitabine (group 2) (n = 26; 40%), or Mitomycin with Gemcitabine and Cisplatin (group 3) (n = 25; 38.5%). Embolization was performed with Lipiodol and starch microspheres. Local tumor response was evaluated by MRI according to RECIST criteria. Survival data were calculated according to the Kaplan-Meier method.

Results

The local tumor control was: partial response (PR) in 16.9% (n = 11), stable disease (SD) in 58.5% (n = 38) and progressive disease (PD) in 24.6% (n = 16) of patients. In group 1, we observed SD in 78.6% (11/14), and PD in 21.4% (3/14) of patients. In group 2, PR in 7.7% (2/26), SD in 57.7% (15/26), and PD in 34.6% (9/26) of patients. In group 3, PR in 36% (9/25), SD in 48% (12/25), and PD in 16% (4/25) of patients. Survival rate from the start of TACE was 58% after 1-year, 19% after 2-years, and 13% after 3-years. The median and mean survival times were 14 and 18.5 months without statistically significant difference for the 3 groups of patients (p = 0.502).

Conclusion

Transarterial chemoembolization is effective palliative treatment in achieving local control in selected patients with liver metastases from ovarian cancer.     

Survivors of uterine cancer empowered by exercise and healthy diet (SUCCEED): a randomized controlled trial

Objective

The majority of endometrial cancer survivors (ECS) are obese and at risk for premature death. The purpose of this study was to evaluate an intervention for ECS to promote weight loss and a healthy lifestyle.

Methods

Early stage overweight and obese (body mass index ≥ 25) ECS (N = 75) were randomized to a 6-month lifestyle intervention (LI) or usual care (UC). The LI group received education and counseling for six months (10 weekly followed by 6 bi-weekly sessions). Weight change at 12 months was the primary endpoint. Secondary outcomes included fruit/vegetable servings/day and physical activity (PA). Multiple imputations were used for missing data and mixed models were used to analyze changes from baseline.

Results

Adherence was 84% and follow-up data were available from 92% of participants at 6 months and 79% at 12 months. Mean [95% CI] difference in weight change between LI and UC groups at 6 months was − 4.4 kg [− 5.3, − 3.5], p < 0.001 and at 12 months was − 4.6 kg [− 5.8, − 3.5], p < 0.001. Mean [95% CI] difference in PA minutes between groups at 6 months was 100 [6, 194], p = 0.038 and at 12 months was 89 [14, 163], p = 0.020. Mean difference in kilocalories consumed was − 217.8 (p < 0.001) at 6 months and − 187.2 (p < 0.001) at 12 months. Mean [95% CI] difference in fruit and vegetable servings was 0.91 servings/day at 6 months and 0.92 at 12 months (p < 0.001).

Conclusions

Behavior change and weight loss are achievable in overweight and obese ECS, however, the clinical implications of these changes are unknown and require a larger trial with longer follow-up.     

Risk assessment and clinical impact of liquid-based cytology, oncogenic human papillomavirus (HPV) DNA and mRNA testing in primary cervical cancer screening (the FASE study)

Objective

New commercial HPV RNA assays require further validation studies in population-based cervical cancer screening settings.To assess the performance of (FDA-approved) APTIMA® HPV Assay (AHPV), Hybrid Capture 2 (HC2), in-house PCR genotyping, and ThinPrep LBC in population-based screening, stratified by three histological gold standards.

Study design

A multi-center trial in 5006 women undergoing routine screening in France was designed to compare the absolute and relative risks of diagnosing CIN3 + and CIN2 + lesions by different diagnostic tests.

Results

Reproducibility between the primary and second pathology reading was excellent for CIN3 + and CIN2 + endpoints (Cohen's kappa 0.948 and 0.854). Absolute risks (PPV) of different tests (AHPV, HC2, PCR genotyping, LBC) in diagnosing CIN2 + (15-20%) and CIN3 + (4-6%) were similar for the first, second, and consensus pathology readings. The relative risks of diagnosing these lesions by the four tests were also similar when the first, second or third pathology readings were employed. AHPV had the highest absolute risk of both histological endpoints, and detects 5% to 15% more CIN3 + and CIN2 + lesions, respectively, than LBC. Compared with HC2 assay, the relative risk of AHPV is 24% to 29% higher, with a significant difference in CIN2 + detection. With LBC as reference, AHPV had the best sensitivity/specificity balance measured by AUC (area under ROC curve) comparison test (significant for CIN2 +), and the colposcopy referral rate (9.2%) comparable to that of LBC (8.7%).

Conclusions

These data corroborate the suitability of AHPV for the primary cervical cancer screening.     

Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC)

Objective

To describe the outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC) so as to define the criteria for patient selection for palliative surgery.

Methods

90 women with relapsed EOC underwent palliative surgery for bowel obstruction between 1992 and 2008.

Results

Median age at time of surgery for bowel obstruction was 57 years (range, 26 to 85 years). All patients had received at least one line of platinum-based chemotherapy. Median time from diagnosis of primary disease to documented bowel obstruction requiring surgery was 19.5 months (range, 29 days-14 years). Median interval from date of completed course of chemotherapy preceding surgery for bowel obstruction was 3.8 months (range, 5 days-14 years). Ascites was present in 38/90(42%). 49/90(54%) underwent emergency surgery for bowel obstruction. The operative mortality and morbidity rates were 18% and 27%, respectively. Successful palliation, defined as adequate oral intake at least 60 days postoperative, was achieved in 59/90(66%). Only the absence of ascites was identified as a predictor for successful palliation (p = 0.049). The median overall survival (OS) was 90.5 days (range, < 1 day-6 years). Optimal debulking, treatment-free interval (TFI) and elective versus emergency surgery did not predict survival or successful palliation from surgery for bowel obstruction (p > 0.05).

Conclusion

Surgery for bowel obstruction in relapsed EOC is associated with a high morbidity and mortality rate especially in emergency cases when compared to other gynaecological oncological procedures. Palliation can be achieved in almost two thirds of cases, is equally likely in elective and emergency cases but is less likely in those with ascites.     

Clinical and pathologic features of young endometrial cancer patients with loss of mismatch repair expression

Objective

This study examines premenopausal and early menopause patients in a unique population with endometrial cancer and loss of mismatch repair (MMR) gene expression. The purpose is to compare clinical and pathologic differences in patients with loss of expression (LOE) to those with normal expression (NE).

Methods

Endometrial cancer patients under age 60 in-between 1998 and 2008 were identified from a single tumor registry. Clinical and pathologic data were abstracted from records. Staining for expression of MSH6, MSH2, MLH1, and PMS2 were performed on archived tissue blocks. Statistical analysis was performed.

Results

158 patients were analyzed; 58% Asian, 34% Pacific Islander, and 8% Caucasian. 31 demonstrated LOE of at least one MMR gene; 127 retained NE. 50% Caucasian, 21.9% Asian, and 12.5% Pacific Island populations had LOE of one or more MMR genes. LOE was found to have a higher incidence of Grade III (p = 0.0013) and stage 3-4 tumors (p = 0.0079), mean depth of myometrial invasion (p = 0.0019), lymphovascular space invasion (p = 0.0020), nodal metastases (p = 0.0157), and a lower incidence of Grade I (p = 0.0020) and stage 1A tumors (p = 0.0085). LOE had a significantly lower mean BMI (p = 0.0001). 35% of patients in the NE vs zero in the LOE group had a BMI greater than 40.

Conclusion

Younger patients with LOE endometrial cancer appear to represent a clinically significant subgroup of patients without features characteristically found in classic type 1 endometrial cancer generally demonstrating lower BMI and tumors associated with poor prognostic characteristics. It is unclear if the distinctive ethnicity found in Hawaii has a significant impact on outcome. Further investigation is necessary to identify appropriate treatment strategies.     

Changing demographics of cervical cancer in the United States (1973-2008)

Objective

To describe changes in the cervical cancer population.

Methods

The SEER database 9 registries from 1973 to 2008 were queried to perform a retrospective cohort study of women with invasive cervical cancer. Estimated annual percent change (EAPC) in incidence rates and 95% confidence intervals (CI) over the entire study period were compared according to age, stage, race, and cell type (squamous [SCC] and adenocarcinoma [ACA]). Proportions and odds ratios (OR) were calculated for patients diagnosed during the second half (1990-2008) compared to first half (1973-89) of the study period.

Results

40,363 women with cervical cancer were entered into SEER. The EAPC are falling fastest among those with localized disease (− 2.5%; 95% CI − 2.8 to − 2.1), age ≥ 50 (− 3.0%; 95% CI = − 3.2 to − 2.8), and black women (− 3.8%; 95% CI = − 4.1 to − 3.6). The odds of a newly diagnosed cervical cancer patient having advanced disease are 10% higher, being less than age 50 are 37% higher, and being Asian or Pacific Islander are 68% higher in the second time period as compared to the first.

Conclusions

In the US, the population with cervical cancer is changing. Patients are presently significantly more likely to be pre-menopausal, Asian or Pacific Islander, and more frequently have non-squamous histology than previously. These progressive and cumulative changes could be due to the disparate impact of current population based screening and prevention strategies. Understanding the implications of these evolving population characteristics may facilitate planning targeted studies and interventions for cervical cancer prevention, screening and treatment in the future.     

The significance of perineural invasion in early-stage cervical cancer

Introduction

Cervical cancer spreads directly and through lymphatic and vascular channels. Perineural invasion is an alternative method of spread. Several risk factors portend poor prognosis and inform management decisions regarding adjuvant therapy.

Objective

To evaluate the incidence and significance of PNI in early cervical cancer.

Methods

Retrospective chart review of early-stage cervical cancer patients (IA-IIA) from 1994 to 2009.

Results

One hundred ninety two patients were included, 24 with perineural invasion in the cervical stroma (cases) and 168 without (controls). The mean age of the cases was 53 years, versus 45.9 in the controls (P = 0.01). PNI was associated with more adjuvant therapy (P = 0.0001), a higher stage (P = 0.005), a larger tumor size (≥ 4 cm) (P < 0.0001), lymphovascular space invasion (P = 0.002), parametrial invasion (P < 0.0001) and more tumor extension to the uterus (P = 0.015). On multivariate analysis using an adjusted hazard ratio, risk factors for recurrence included grade (HR, 95% CI; 3.61, 1.38-9.41) and histopathology (HR, 95% CI; 2.85, 100-8.09). Similarly, risk factors for death included grade (HR, 95% CI; 3.43, 1.24-9.49) and histopathology (HR, 95% CI; 3.71, 1.03-13.33). Perineural invasion was not identified as an independent risk factor for either recurrence or death. The mean follow up time was 56 months. There was no significant difference in recurrence (P = 0.601) or over-all survival (P = 0.529) between cases and controls.

Conclusion

While perineural invasion was found to be associated with multiple high-risk factors, it was not found to be associated with a worse prognosis in early cervical cancer.     

Experimental endometriosis reduction in rats treated with Uncaria tomentosa (cat's claw) extract

Objective

The aim of this study was to analyze the macroscopic and histological changes that occur in experimental endometriosis after treatment with Uncaria tomentosa.

Study design

Experimental endometriosis was induced in twenty-five female Wistar rats. After three weeks, 24 animals developed grade III experimental endometriosis and were divided into two groups. Group “U” received U. tomentosa extract orally (32 mg/day), and group “C” (control group) received a 0.9% sodium chloride solution orally (1 ml/100 g of body weight/day). Both groups were treated with gavage for 14 days. At the surgical intervention and after the animal was euthanized, the implant volume was calculated with the following formula: [4π (length/2) × (width/2) × (height/2)/3]. The autotransplants were removed, dyed with hematoxylin-eosin, and analyzed by light microscopy. The Mann-Whitney test was used for the independent samples, and the Wilcoxon test analyzed the related samples, with a significance level of 5%.

Results

The difference between the initial average volumes of the autotransplants was not significant between the groups (p = 0.18). However, the final average volumes were significantly different between the groups (p = 0.001). There was a significant increase (p = 0.01) between the initial and final average volumes in the control group, and treatment with the U. tomentosa caused a marked reduction in the growth over time (p = 0.009). Histologically, in the experimental group (n = 10) six rats had a well-preserved epithelial layer, three had mildly preserved epithelium, and one had poorly preserved epithelium. The epithelial layer occasionally presented sporadic epithelial cells. The control group (n = 12) presented seven cases (58.3%) of well-preserved epithelial cells and five cases (41.7%) of mildly preserved epithelial cells.

Conclusions

Cat's claw extract appears to be a promising alternative for treating endometriosis.     

Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: a Gynecologic Oncology Group study

Objective

To examine whether clinical outcomes varied with intraperitoneal (IP) and/or retroperitoneal (RP) involvement in stage IIIC epithelial ovarian cancer (EOC) patients with microscopic residual disease after cytoreduction.

Methods

Retrospective review was performed for EOC patients enrolled in Gynecologic Oncology Group (GOG)-182 who underwent primary cytoreduction to microscopic residual disease. Patients were divided into 3 groups: stage IIIC by lymphadenopathy with < 2 cm IP spread (RP); > 2 cm IP spread and negative nodes (IP/RP−); and > 2 cm IP dissemination and positive lymphadenopathy (IP/RP+). Product-limit and multivariate proportional hazards modeling were used.

Results

Analyses included 417 stage IIIC women who underwent primary cytoreduction with lymphadenectomy to microscopic residual. There were 203, 123, and 91 in the RP, IP/RP−, and IP/RP+ groups, respectively. IP/RP+ and IP/RP− were associated with worse progression-free survival (PFS) (Hazard Ratio (HR) 1.68, 95% confidence interval (CI) 1.23-2.30; HR 1.38, 95% CI 1.04-1.84) vs. RP only. IP/RP+ was associated with worse overall survival (OS) (HR 1.79, 95% CI 1.24-2.57) while IP/RP− trended towards worse OS (HR 1.21, 95% CI 0.85-1.73) vs. RP only. Median PFS for IP/RP+ and IP/RP− groups was 21 and 29 months, respectively, vs. 48 months in the RP group (p = 0.0007) and median OS of 63 and 79 months vs. “not reached,” respectively (p = 0.0038).

Conclusions

Among EOC patients surgically cytoreduced to microscopic residual disease, those upstaged to IIIC by retroperitoneal involvement demonstrated significant improvement in PFS and OS compared to patients with intraperitoneal tumor, suggesting that these women may represent a unique subset of FIGO stage IIIC patients.     

A phase II trial of radiation therapy and weekly cisplatin chemotherapy for the treatment of locally-advanced squamous cell carcinoma of the vulva: a gynecologic oncology group study

Objectives

To determine the efficacy and toxicity of radiation therapy and concurrent weekly cisplatin chemotherapy in achieving a complete clinical and pathologic response when used for the primary treatment of locally-advanced vulvar carcinoma.

Methods

Patients with locally-advanced (T3 or T4 tumors not amenable to surgical resection via radical vulvectomy), previously untreated squamous cell carcinoma of the vulva were treated with radiation (1.8 Gy daily × 32 fractions = 57.6 Gy) plus weekly cisplatin (40 mg/m²) followed by surgical resection of residual tumor (or biopsy to confirm complete clinical response). Management of the groin lymph nodes was standardized and was not a statistical endpoint. Primary endpoints were complete clinical and pathologic response rates of the primary vulvar tumor.

Results

A planned interim analysis indicated sufficient activity to reopen the study to a second stage of accrual. Among 58 evaluable patients, there were 40 (69%) who completed study treatment. Reasons for prematurely discontinuing treatment included: patient refusal (N = 4), toxicity (N = 9), death (N = 2), other (N = 3). There were 37 patients with a complete clinical response (37/58; 64%). Among these women there were 34 who underwent surgical biopsy and 29 (78%) who also had a complete pathological response. Common adverse effects included leukopenia, pain, radiation dermatitis, pain, or metabolic changes.

Conclusions

This combination of radiation therapy plus weekly cisplatin successfully yielded high complete clinical and pathologic response rates with acceptable toxicity.     

Clinicopathological prognostic factors and the role of cytoreduction in surgical stage IVb endometrial cancer: A retrospective multi-institutional analysis of 248 patients in Japan

Objective

To evaluate clinicopathological prognostic factors and the impact of cytoreduction in patients with surgical stage IVb endometrial cancer (EMCA).

Methods

The records of 248 patients with stage IVb EMCA who underwent primary surgery including hysterectomy at multiple institutions from 1996 to 2005 were retrospectively analyzed. Data regarding disease distribution, surgical procedures, adjuvant therapy, and survival times were collected. Univariate and multivariate analyses were performed to identify factors associated with overall survival (OS).

Results

The median OS was 24 months. The most common histological types were endometrioid (grade 1: 15%, grade 2: 20%, grade 3: 24%) and serous (17%). The most common sites of intra-abdominal metastases were pelvis (65%), ovaries (58%), omentum (58%), retroperitoneal lymph nodes (52%), and upper abdominal peritoneum (44%). In 93 patients with extra-abdominal metastases, the most common site was the lung (n = 49). Complete resection of extra-abdominal metastases was achieved in only 13 patients. Complete resection of intra-abdominal metastases was achieved in 101 patients, 52 had ≤ 1 cm residual disease, and 95 had > 1 cm residual disease; the median OS times in these groups were 48, 23, and 14 months, respectively (p < 0.0001). Multivariate analysis showed that performance status, histology/grade, adjuvant treatment, and intra-abdominal residual disease were independent prognostic factors. Intra-abdominal residual disease was an independent prognostic factor in patients with and without extra-abdominal metastases.

Conclusions

Cytoreductive surgery and adjuvant therapy may improve survival in stage IVb EMCA, particularly in patients with favorable prognostic factors, even in the presence of extra-abdominal metastases.