Progression-free and overall survival of a modified outpatient regimen of primary intravenous/intraperitoneal paclitaxel and intraperitoneal cisplatin in ovarian, fallopian tube, and primary peritoneal cancer

Objective

GOG study 172 demonstrated improved progression-free (PFS) and overall (OS) survival for patients with stage III optimally debulked ovarian and peritoneal carcinoma treated with IV/IP paclitaxel and IP cisplatin compared to standard IV therapy. The inpatient administration, toxicity profile, and limited completion rate have been blamed for the lack of acceptance and widespread use of this regimen. We sought to evaluate the PFS, OS, toxicity, and completion rate of a modified outpatient IP regimen.

Methods

Using a prospectively maintained database, we evaluated the outcomes of patients who underwent primary optimal cytoreduction for stage III ovarian, tubal, or peritoneal carcinoma followed by IV/IP chemotherapy from 1/05-3/09. Our modified regimen was as follows: IV paclitaxel (135 mg/m²) over 3 h on day 1, IP cisplatin (75 mg/m²) on day 2, and IP paclitaxel (60 mg/m²) on day 8, given every 21 days for 6 cycles.

Results

We identified 102 patients who initiated the modified IV/IP regimen and completed chemotherapy. The median follow-up was 43 months. The median age at diagnosis was 57 years (range, 23-76). Primary disease site was: ovary, 77 (75%); fallopian tube, 13 (13%); peritoneum, 12 (12%). FIGO stage was: IIIA, 8 (8%); IIIB, 4 (4%); IIIC, 90 (88%). Residual disease after cytoreduction was: none, 58 (57%); ≤ 1 cm, 44 (43%). The most frequent grade 3/4 toxicities were: neutropenia, 12 (12%); gastrointestinal, 8 (8%); neurologic, 6 (6%). Eighty-two (80%) of 102 patients completed 4 or more cycles of IV/IP therapy; 56 (55%) completed all 6 cycles. The median PFS and OS were 29 and 67 months, respectively.

Conclusions

By modifying the GOG 172 treatment regimen, convenience, toxicity, and tolerability appear improved, with survival outcomes similar to those of GOG 172. This modified IV/IP regimen warrants further study.     

Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum

Objective

To determine whether hormonal therapies have efficacy in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum.

Methods

We searched departmental databases for patients with histologically-confirmed, evaluable, recurrent low-grade serous ovarian or peritoneal carcinoma who received hormonal therapy at our institution between 1989 and 2009. We retrospectively reviewed patients' medical records for demographic, disease, hormonal therapy, and estrogen receptor and progesterone receptor expression data. We used the Response Evaluation Criteria in Solid Tumors version 1.1 to determine patients' responses to hormonal therapy. Because patients could have received more than one evaluable hormonal therapy regimen, we chose to define the outcome metric as “patient-regimens.” Median time to disease progression (TTP) and overall survival (OS) were also calculated. Regression analysis was also performed.

Results

We identified 64 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Patients' median TTP and median OS were 7.4 and 78.2 months, respectively. Patients received 89 separate hormonal patient-regimens, which produced an overall response rate of 9% (6 complete responses and 2 partial responses). Sixty-one percent of the patient-regimens resulted in a progression-free survival duration of at least 6 months. Patient-regimens involving ER +/PR + disease produced a longer median TTP (8.9 months) than patient-regimens involving ER +/PR − disease did (6.2 months; p = 0.053). This difference approached but did not reach statistical significance.

Conclusions

Hormonal therapies have moderate anti-tumor activity in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Further study to determine whether ER/PR expression status is a predictive biomarker for this rare cancer subtype is warranted.     

Five-year outcomes of adjuvant carboplatin/paclitaxel chemotherapy and intravaginal radiation for stage I-II papillary serous endometrial cancer

Objective

The purpose of this study is to report our single-institution experience with concurrent adjuvant intravaginal radiation (IVRT) and carboplatin/paclitaxel chemotherapy for early stage uterine papillary serous carcinoma (UPSC).

Methods

From 10/2000 to 12/2009, 41 women with stage I-II UPSC underwent surgery followed by IVRT (median dose of 21 Gy in 3 fractions) and concurrent carboplatin (AUC = 5-6) and paclitaxel (175 mg/m²) for six planned cycles. IVRT was administered on non-chemotherapy weeks. The Kaplan-Meier method was used to estimate survival, and the log-rank test was used for comparisons.

Results

Median patient age was 67 years (51-80 years). Surgery included hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and paraaortic lymph node sampling. FIGO 2009 stage was IA in 73%, IB in 10%, and II in 17%. Histology was pure serous in 71% of cases. Thirty-five patients (85%) completed all planned treatment. With a median follow-up time of 58 months, the 5-year disease-free (DFS) and overall survival (OS) rates were 85% (95%CI, 73-96%) and 90% (95%CI, 80-100%). The 5-year pelvic, para-aortic, and distant recurrence rates were 9%, 5%, and 10%, respectively. There were no vaginal recurrences. Of the 4 pelvic recurrences, 2 were isolated and were successfully salvaged. Patients with stage II disease had lower DFS (71% vs. 88%; p = 0.017) and OS (71% vs. 93%; p = 0.001) than patients with stage I disease.

Conclusions

Concurrent adjuvant carboplatin/paclitaxel chemotherapy and IVRT provide excellent outcomes for early stage UPSC. Whether this regimen is superior to pelvic radiation will require confirmation from the ongoing randomized trial.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial

Objective.

The primary end-point of this multi-institutional phase-II trial was to assess results in terms of overall survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment-naive epithelial ovarian cancer (EOC) with advanced peritoneal involvement. Secondary end-points were treatment morbi-mortality and outcome effects of time to subsequent adjuvant systemic chemotherapy (TTC).

Methods.

Twenty-six women with stage III-IV EOC were prospectively enrolled in 4 Italian centers to undergo CRS and closed-abdomen HIPEC with cisplatin and doxorubicin. Then they received systemic chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m²) for 6 cycles.

Results.

Macroscopically complete cytoreduction was achieved in 15 patients; only minimal residual disease (≤ 2.5 mm) remained in 11. Major complications occurred in four patients and postoperative death in one. After a median follow-up of 25 months, 5-year overall survival was 60.7% and 5-year progression-free survival 15.2% (median 30 months). Excluding operative death, all the patients underwent systemic chemotherapy at a median of 46 days from combined treatment (range: 29-75). The median number of cycles per patient was 6 (range: 1-8). The time to chemotherapy did not affect the OS or PFS.

Conclusions.

In selected patients with advanced stage EOC, upfront CRS and HIPEC provided promising results in terms of outcome. Morbidity was comparable to aggressive cytoreduction without HIPEC. Postoperative recovery delayed the initiation of adjuvant systemic chemotherapy but not sufficiently to impact negatively on survival. These data warrant further evaluation in a randomized clinical trial.     

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.     

A phase I study with an expanded cohort to assess the feasibility of intraperitoneal carboplatin and intravenous paclitaxel in untreated ovarian, fallopian tube, and primary peritoneal carcinoma: A Gynecologic Oncology Group study

Objective

This study aimed to determine the first-cycle maximum tolerated dose (MTD) of intraperitoneal carboplatin in combination with intravenous paclitaxel and then assess the feasibility of this dose over multiple cycles.

Methods

Beginning at an intraperitoneal (IP) carboplatin dose area under the curve (AUC) of 5 and a fixed intravenous dose of 175 mg/m² paclitaxel, patients were entered on a dose-escalating phase evaluating first-cycle dose-limiting toxicity (DLT). After estimating the MTD, cohorts of 20 patients were then entered in an expanded phase to evaluate DLT over four cycles.

Results

Twenty-one patients were entered on the dose-escalating phase. A first-cycle MTD of carboplatin at AUC 8 was tolerated although thrombocytopenia was dose-limiting over multiple cycles. An additional 69 patients were treated in expanded cohorts. Only 5/90 (5.6%) patients discontinued treatment because of a port problem. Four-cycle DLT required de-escalation to a carboplatin AUC of 6, and even at that dose, there were 14 dose-limiting toxic effects in 40 patients (35%). Seven dose-limiting toxicities were due to neutropenia, and 6 were due to grade 3/4 thrombocytopenia. Six cycles of therapy were completed in 75% of eligible patients, but dose adjustments were required.

Conclusions

The first-cycle MTD did not predict the tolerability of this regimen over multiple cycles. Using an IP carboplatin dose of AUC 6 in combination with paclitaxel, the regimen can be administered with a high completion rate over multiple cycles. Because neutropenia is a frequent DLT, the addition of hematopoietic growth factors may permit a high completion rate while maintaining this dose.     

Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer

Objective

Weekly paclitaxel has been shown to be an effective cytotoxic regimen for recurrent epithelial ovarian cancer (EOC), and may act through inhibition of angiogenesis. Bevacizumab, a potent angiogenesis inhibitor, has also been shown to have activity in patients with EOC. Therefore, we sought to determine if the addition of bevacizumab to weekly paclitaxel led to an increased survival compared to weekly paclitaxel alone.

Methods

A single institutional review was conducted for patients with recurrent EOC treated with weekly paclitaxel (60-70 mg/m²) on days 1, 8, 15, and 22 of a 28 day cycle and those treated with weekly paclitaxel and bevacizumab (10-15 mg/kg on day 1 and 15). Response rates (RR) were calculated, and progression-free survival (PFS), and overall survival (OS) were compared using Kaplan-Meier survival analysis.

Results

Twenty-nine patients treated with weekly paclitaxel and 41 patients treated with paclitaxel/bevacizumab were identified. The groups were similar in demographics, initial optimal cytoreduction, stage, histology, grade, platinum sensitivity, and median number of previous regimens (4 vs. 4, p = 0.69).The overall response rate (ORR) was 63% (complete response (CR) 34% and partial response (PR) 29%) for paclitaxel/bevacizumab and 48% (CR 17% and PR 31%) for weekly paclitaxel (p = 0.23). Improvement in PFS was seen in those treated with paclitaxel/bevacizumab in comparison to weekly paclitaxel alone (median PFS 13.2 vs. 6.2 months, p < .01). There was a trend towards improved OS for paclitaxel/bevacizumab (median OS 20.6 vs. 9.1 months; p = 0.12). Toxicities were similar between the two regimens although more bowel perforations (2 vs. 0) were seen in the paclitaxel/bevacizumab group.

Conclusion

A significant increase in PFS with a trend towards improved OS was demonstrated in this heavily pretreated population treated with paclitaxel/bevacizumab as compared to weekly paclitaxel alone. This data should be helpful in guiding future trials to determine the optimal care for women with recurrent EOC.     

Synuclein-γ (SNCG) protein expression is associated with poor outcome in endometrial adenocarcinoma

Objective

Synuclein-γ (SNCG) is a marker for adverse and aggressive disease in breast cancer. In previous study, we found SNCG mRNA to be overexpressed in uterine serous carcinoma compared to uterine endometrioid adenocarcinoma. The aim of this study is to explore the prognostic value of SNCG in patients with endometrial cancer.

Methods

279 endometrial cancer patients were retrieved from the archives. The tissue paraffin blocks were stained for SNCG antibody and its expression was correlated with clinicopathological prognostic factors.

Results

There was a positive association between SNCG⁺ immunoexpression and tumor grade, tumor stage, type II carcinomas, deep myometrial invasion and lymphovascular invasion. A correlation between SNCG⁺ and adverse outcomes, such as shorter overall survival (OS) and disease free survival (DFS), was also detected. Following adjuvant therapy (radiation and chemotherapy or chemotherapy alone), we observed a difference in 5 years DFS rate between SNCG⁺ (41.6%) and SNCG⁻ patients (59.5%).

Conclusion

Overexpression of SNCG seemed to be a predictor biomarker for aggressive tumor behavior and adverse outcome in patients with endometrial cancer. Future exploration of SNCG as a potential therapeutic target for selected patients could be of interest.     

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Objective

To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II-IV ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods

Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60 mg/m² on day 8. A standard 3 + 3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.

Results

Patients were treated with paclitaxel 175 mg/m² IV and carboplatin IP from AUC 5-7 on day 1 and paclitaxel 60 mg/m² IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4 cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), > 2 week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135 mg/m² IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4 cycles with one DLT (grade 3 hyponatremia).

Conclusions

Paclitaxel at 175 mg/m² IV, carboplatin AUC 6 IP day 1 and paclitaxel 60 mg/m² IP day 8 yield 18-56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.     

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.     

Patterns of first recurrence following adjuvant intraperitoneal chemotherapy for stage IIIC ovarian cancer

Objective

Adjuvant intraperitoneal (IP) platinum-based chemotherapy has been shown to improve outcome for patients with advanced ovarian cancer. We hypothesize that patients who have received adjuvant IP chemotherapy more commonly recur first at extraperitoneal sites than patients who have received adjuvant intravenous (IV) chemotherapy.

Methods

Patients with newly diagnosed stage IIIC optimally debulked serous ovarian cancer were identified from institutional databases. Patterns of recurrence were compared between patients who received IV and IP chemotherapy using standard two-sided statistical tests.

Results

Of the 104 patients who met inclusion criteria, 60 received IV chemotherapy and 44 received IP chemotherapy. Patients in the IV group had a first recurrence more commonly in the lower abdomen or pelvis than the IP group. Patients in the IP group more commonly recurred in the upper abdomen and extra-abdominal lymph nodes. More patients in the IP group than the IV group recurred at extra-abdominal sites (45.5% versus 23.3%, P = 0.018).

Conclusions

Patients receiving adjuvant IP chemotherapy are less likely to first recur in the lower abdomen or pelvis and more likely to recur outside of the abdominal cavity. The data suggest that IP chemotherapy is highly effective in the anatomic areas of peritoneal distribution.     

Sequential bevacizumab and oral cyclophosphamide for recurrent ovarian cancer

Objective

Test the safety and efficacy of sequentially blocking angiogenesis by adding oral cyclophosphamide to bevacizumab following cancer progression on bevacizumab in patients with recurrent ovarian cancer.

Methods

Eligibility included ≤ 2 lines of treatment for recurrence and measurable cancer by RECIST 1.0. Patients received bevacizumab (15 mg/kg every 3 weeks IV) and upon RECIST progression, oral cyclophosphamide (50 mg orally daily) was added. Objectives included safety, toxicities, 3- and 6-month PFS rates, response rate, PFS, and OS.

Results

20 patients were enrolled. Overall response rate was 10%, and 65% of patients had confirmed stable disease (SD). Thirteen of 20 patients received oral cyclophosphamide added to bevacizumab upon bevacizumab progression. Of these 13 patients, 1 patient subsequently achieved a PR (this patient had SD as best response during bevacizumab) and 3 patients had a confirmed SD. For all patients, median PFS was 8.41 months, 6 month PFS rate was 65%, duration of response (DOR) was 7.3 months, and median OS was 22.72 months. Median DOR for patients receiving both bevacizumab and cyclophosphamide was 8.4 months. Most toxicities were grades 1 and 2 and manageable. Grades 3 and grade 4 toxicities included 1 myocardial infarction, 1 gastrointestinal perforation (GIP), and 12/20 patients (60%) developed grade 3 HTN.

Conclusions

Addition of oral cyclophosphamide to bevacizumab at the time of cancer progression on bevacizumab appears to have continued anti-cancer effects in a subgroup of patients and appears to be safe. Randomized trials testing combination versus sequential anti-angiogenic therapy for recurrent ovarian cancer are warranted.     

Is time to recurrence after hysterectomy predictive of survival in patients with early stage endometrial carcinoma?

Purpose/objective(s)

To determine the prognostic significance of time to recurrence (TTR) on overall survival (OS) and disease-specific survival (DSS) following recurrence in patients with stage I-II uterine endometrioid carcinoma.

Materials/methods

After IRB approval, we retrospectively identified 57 patients with recurrent endometrioid carcinoma who were initially treated for FIGO 1988 stages I-II between 1987 and 2009. The Kaplan-Meier approach and Cox regression analysis were used to estimate OS and DSS following recurrence and identify factors impacting outcomes.

Results

Median follow-up times were 54.8 months from hysterectomy and 19.8 months after recurrence. Median time to recurrence was 20.2 months. Twenty-eight (47%) patients had a recurrence < 18 months after hysterectomy and 29 (53%) had a recurrence ≥ 18 months. Both groups were evenly matched regarding initial pathological features and adjuvant treatments. The median OS and DSS in patients with TTR < 18 months was shorter than those with TTR ≥ 18 months, but not statistically significant (p = 0.216). TTR did not impact outcomes after loco-regional recurrence, but for extrapelvic recurrence, a shorter TTR resulted in worse OS and DSS (p = 0.03). On multivariate analysis, isolated loco-regional recurrence (HR 0.28, p = 0.001) and salvage radiation therapy (HR 0.47, p = 0.045) were statistically significant independent predictors of longer OS following recurrence. TTR as a continuous variable or dichotomized was not predictive of OS or DSS.

Conclusions

In our study, the prognostic impact of time to recurrence was less important than the site of recurrence. While not prognostic for the entire cohort or for patients with loco-regional recurrence, TTR < 18 months was associated with shorter OS and DSS after extrapelvic recurrence.     

Surgical cytoreduction in patients with metastatic uterine leiomyosarcoma at the time of initial diagnosis

Objective

To determine whether cytoreduction is associated with improved outcome in patients newly diagnosed with metastatic uterine leiomyosarcoma (LMS).

Methods

We retrospectively identified all patients treated at our institution for high-grade uterine LMS with extrauterine disease at the time of initial diagnosis from 7/1/82 to 7/31/07. Pattern of disease spread was classified as intraperitoneal (IP) or extraperitoneal (EP). Progression-free survival (PFS) and overall survival (OS) were determined from date of initial surgery using Kaplan-Meier estimates.

Results

We identified 96 cases. Median age was 54 years (range, 23-81). IP disease was seen in 48 (50%) and EP in 48 (50%). A complete gross resection of all tumor was achieved in 41/84 (49%). Recurrence or progression was noted in 93 (97%); 81 (84%) have died. Median PFS and OS for the entire cohort was 9.7 months (range, 6.7-10.9) and 20.2 months (range, 15.5-24.8), respectively. All 8 non-surgical cases died within 30 months of diagnosis. Median PFS was 14.2 months (range, 11.4-16.9) for those with a complete gross resection versus 6.8 months (range, 4.1-9.5) for those with any residual disease (P = 0.002). Median OS was 31.9 months (range, 3.3-60.4) versus 20.2 months (range, 11.8-28.6), respectively (P = 0.04). On multivariate analysis, no residual disease was independently associated with PFS when adjusting for disease distribution (IP vs EP) and the use of chemotherapy but not OS.

Conclusions

Surgical cytoreduction of metastatic uterine LMS was independently associated with PFS but not OS in cases selected for surgery. The improvement in PFS must be weighed against the morbidity of surgery.     

CA125 regression in ovarian cancer patients treated with intravenous versus intraperitoneal platinum-based chemotherapy: a gynecologic oncology group study

Objective

CA125 is a non-specific marker of peritoneal irritation which has the potential for false elevation during intraperitoneal treatment. The purpose of this study is to identify the rate of CA125 regression during intraperitoneal (IP) versus intravenous (IV) chemotherapy for ovarian cancer.

Methods

GOG 114, a randomized control trial evaluating IP and IV treatment, includes an intensive CA125 measurement schema with weekly CA125 levels until ≤ 35 units/ml for both IP- and IV-treated patients. Rate of CA125 normalization, median CA125 values for each treatment cycle, as well as clinical and pathologic features were compared between the treatment groups. Baseline CA125 levels and rate of CA125 decline were evaluated with respect to overall survival.

Results

CA125 data were available for 223 patients who received IV cisplatin/paclitaxel and for 231 patients who received IV carboplatin followed by IP cisplatin/paclitaxel. Standard prognostic criteria and baseline CA125 values were similar between the treatment groups. For treatment cycles in which IP-treatment was administered, there was no statistically significant difference in CA125 levels between IV- and IP-treated patients. The rate of CA125 normalization was similar between IV- and IP-treated patients (p = 0.55). Patients with low pre-chemotherapy CA125 levels which rapidly declined during treatment demonstrated a survival advantage (p < 0.0001).

Conclusions

No difference in CA125 decline was identified between IP- and IV-treated patients undergoing a weekly CA125 monitoring schedule. This data supports the utilization of standard CA125 response criteria in the therapeutic monitoring for patients receiving IP treatment.     

Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer

Objectives

To evaluate the efficacy, in terms of safety, overall survival and progression free survival of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemotherapy in patients affected by locally advanced cervical cancer (stage IB2-IIB) with or without node metastases.

Methods

Between June 2000 and February 2007, all patients with diagnosis of locally advanced cervical cancer referred to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome were eligible for this protocol. All enrolled patients received 3 cycles of platinum-based chemotherapy every 3 weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq. After neoadjuvant chemotherapy all patients with stable or progressive disease were excluded from the protocol, the others were submitted to classical radical hysterectomy, bilateral salpingo-oophorectomy and bilateral systematic pelvic lymphadenectomy and 4 cycles of adjuvant treatment with platinum based chemotherapy were executed.

Results

Concerning intention to treat basis analysis, 5 year overall survival (OS) and disease-free survival (DFS) are 77% and 61%, respectively. The 5-year OS of patients with positive pelvic nodes and those with negative nodes metastases was respectively 60% and 87%. Concerning the according to protocol analysis, the 5-year OS and DFS are 81% and 70% respectively. The 5-year OS in patient with positive and negative lymph nodes is 75% and 88% respectively.

Conclusions

The adjuvant chemotherapy regimen after neoadjuvant chemotherapy and radical surgery represents a valid treatment for patients with locally advanced cervical cancer.     

Serous and mucinous borderline ovarian tumors: are there real differences between these two entities?

Objective

To evaluate the clinical outcome and pathological features of patients with borderline ovarian tumors (BOT) with special emphasis on serous and mucinous histology.

Study design

Medical and anatomopathological records were reviewed in the Gynecological Oncology Department of the Canarian University Hospital between 1990 and 2005. Survival rates were analyzed by using the Kaplan-Meier technique.

Results

The study included 163 patients. Serous tumors corresponded to 68 cases and mucinous tumors to 91 cases. Eighty-nine percent of patients were at FIGO stage I, 1.2% at stage II and 9.8% at stage III. Serous histology was significantly related to the presence of peritoneal implants (22.4% vs 3.6%; p = 0.001), positive peritoneal cytology (35.7% vs 8.5%; p = 0.001) and bilaterality (27.9% vs 1.1%, p < 0.0001). Event-free survival (EFS) rates at 2, 5 and 10 years were 96.7%, 92.7% and 90.5%, respectively, with a mean survival time of 183 months (CI 95% 172-193). Thirteen recurrence cases were found (7.9%) with a mean time to recurrence of 39.6 months (range 4-140). Overall survival (OS) rates at 2, 5 and 10 years were 100%, 96.4% and 93.6%, respectively, with a mean time of 189 months (CI 95% 179-198). Mucinous BOT were associated with significantly lower OS rates than serous BOT (10 years OS: 88.5% vs 98.2%; p = 0.01).

Conclusions

Serous tumors present more unfavorable anatomopathological characteristics but are associated with better prognosis than mucinous tumors. If mucinous BOT diagnosis is retained physicians should be aware that their aggressive potential is not negligible.     

Hospital costs associated with adverse events in gynecological oncology

Background and objective

Treatment for gynecological malignancies is complex and may cause unintended or accidental adverse events (AE). We evaluated the costs of hospitalization associated with those AEs among patients who had an abdominal or laparoscopic procedure for proven or suspected gynecological cancer at a tertiary gynecological cancer center in Australia.

Methods

Data on AEs were prospectively collected and matched with cost data (AU$ 2008) from the hospital's clinical costing unit and linked to demographical, clinical and histopathological data. Total costs were adjusted for various clinical factors and estimated using log-transformed ordinary least squared regression. Back-transformation was achieved using smearing factors. From epidemiological data, we also estimated the costs of AEs Australia-wide and undertook scenario and probabilistic sensitivity analyses to investigate the potential cost impact of reducing AEs.

Results

A total of 369 patients had surgical procedures of which 95 patients (26%) had at least one AE. Patients with AEs incurred an extra AU$12,780 on average, adjusted for age, co-morbidities, ovarian cancer, major or minor complications, surgical complexity, presence of malignancy and abdominal surgery. Mean adjusted costs (95% CI) for patients with intra-operative, minor post-operative and major post-operative AEs were AU$40,746 (11,582-71,859) AU$18,459 (17,270-19,713) and AU$67,656 (5324-131,761), respectively. Up to an estimated AU$20.6 million/year could be saved if the AEs were reduced by 40%.

Conclusion

Adverse events are associated with significantly increased hospitalization costs and appropriate evidence-based interventions are justified to minimize AEs.     

Initial failure site according to primary treatment with or without para-aortic lymphadenectomy in endometrial cancer

Objective

The objective of this study was to compare the initial failure sites in patients with endometrial cancer who underwent surgical treatment including pelvic lymphadenectomy with or without para-aortic lymphadenectomy.

Methods

A retrospective chart review was carried out for 657 endometrial cancer patients with no residual disease after initial treatments including lymphadenectomy at two tertiary centers between 1987 and 2004. Surgical treatment at one institute included pelvic lymphadenectomy (PLX) without para-aortic lymphadenectomy (PALX), while surgical treatment including PLX + PALX was routinely performed at the other institute. We identified patients with recurrence and evaluated initial failure sites. Rates of recurrence in the respective sites were compared according to the type of lymphadenectomy.

Results

Of the 657 patients, 103 (15.7%) suffered recurrence. There was no significant difference between the rate of intrapelvic recurrence in the PLX alone group and that in the PLX + PALX group (4.7% vs. 2.9%, p = 0.22). The rate of extrapelvic recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (16.1% vs. 6.2%, p < 0.0001), and the rate of para-aortic node (PAN) recurrence in the PLX alone group was also significantly higher than that in the PLX + PALX group (5.1% vs. 0.6%, p = 0.0004). In the analysis of patients who received adjuvant chemotherapy, the rate of PAN recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (9.5% vs. 1.3%, p = 0.0036).

Conclusion

PAN recurrence was a failure pattern peculiar to the PLX alone group. Adjuvant chemotherapy might not be able to replace surgical removal as a treatment for metastatic lymph nodes.     

Increase in the incidence of gestational trophoblastic disease in The Netherlands

Objectives

The purpose of this study was to clarify the clinical outcome of patients with stage IA mucinous epithelial ovarian cancer (mEOC) treated with fertility-sparing surgery (FSS).

Methods

After a central pathological review and search of the medical records from multiple institutions, a total of 148 stage I mEOC patients were retrospectively evaluated in the current study. All mEOC patients were divided into three groups: group A (FSS; age, 40≥); groups B and C {radical surgery; age, 40≥ (B); 40< (C)}. Survival analysis was performed among these three groups using Kaplan-Meier methods.

Results

The median follow-up time of all mEOC patients was 71.6 (4.8-448.3) months. Among the 41 patients in group A, 27 patients (65.9%) had IA disease, and 14 (34.1%) had IC disease. Five-year overall survival (OS) and disease-free survival (DFS) rates of patients in the groups were as follows: group A, 97.3% (OS)/90.5% (DFS); group B, 94.4% (OS)/94.4% (DFS); group C; 97.3% (OS)/89.3% (DFS). Collectively, there was no significant difference in OS or DFS among these groups even though they were stratified to each substage (IA/IC) (OS, P = 0.180; DFS, P = 0.445, respectively). Furthermore, in multivariate analyses, the surgical procedure was not an independent prognostic factor for either OS or DFS (OS, HR: 0.340, 95% CI: 0.034-3.775, P = 0.352; DFS, HR: 0.660, 95% CI: 0.142-3.070, P = 0.596).

Conclusions

Patients with stage I mEOC treated with FSS did not necessarily show a poorer prognosis than those receiving radical surgery.