Definitive intensity-modulated radiation therapy with concurrent chemotherapy for patients with locally advanced cervical cancer

Objective

Cervical cancer is one of the most common cancers diagnosed in women worldwide. Concurrent chemoradiotherapy (CCRT) is the mainstay treatment for locally advanced cervical cancer. The purpose of this study was to investigate the treatment outcomes and toxicity of definitive intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy for patients with locally advanced carcinoma of the cervix in a single institution.

Methods

Between January 2004 and November 2008, 109 patients with stage IB2-IVA cervical carcinoma treated with IMRT and concurrent cisplatin-based chemotherapy were evaluated retrospectively. All patients received external irradiation of 45-54 Gy with an IMRT technique. High dose rate brachytherapy of 20-33.5 Gy was prescribed to point A as a local boost. Each patient received concurrent cisplatin-based chemotherapy monthly or weekly. The endpoints were overall survival (OS), local failure-free survival (LFFS) and disease-free survival (DFS). Patients were assessed for acute toxicity weekly according to the Common Toxicity Criteria for Adverse Events (CTCAE), version 3.0. Late toxicity was evaluated according to RTOG-EORTC Late Radiation Morbidity Scoring Schema.

Results

The median follow up time for all surviving patients was 32.5 months, with a range from 5 to 75 months. The 3-year OS, LFFS and DFS were 78.2%, 78.1% and 67.6%, respectively. Three (2.7%) patients developed grade 3 or greater acute gastrointestinal (GI) toxicity and 26 (23.9%) patients developed grade 3 or greater hematological toxicity. Five (4.6%) patients developed grade 3 or greater chronic GI toxicity and 7 (6.4%) patients developed grade 3 or greater genitourinary system toxicity.

Conclusions

Good outcomes were achieved with definitive IMRT and concurrent chemotherapy for patients with locally advanced cervical cancer and the combined treatment was well tolerated with favorable acute and late toxicity.     

ERCC1 (excision repair cross-complementation group 1) expression as a predictor for response of neoadjuvant chemotherapy for FIGO stage 2B uterine cervix cancer

Objective

Platinum-based neoadjuvant chemotherapy for locally advanced cervical cancer has some benefits for patients responding to chemotherapy. However, no validated clinical or biologic predictor of response to this chemotherapy has been identified to date.

Methods

We employ immunohistochemical analysis to determine the expression patterns of the excision repair cross-complementation group1 (ERCC1) protein in pre-treatment cervical biopsy tissue. In total, 43 stage IIB patients had been enrolled in a previous etoposide and cisplatin neoadjuvant phase II clinical trial, allowing comparison of the effects of cisplatin-based neoadjuvant chemotherapy on response in relation to ERCC1 expression.

Results

Among the 43 patients studied, 34 (79.1%) were positive and 9 (20.9%) were negative for ERCC1. Response to chemotherapy (according to RECIST criteria) was observed in all patients with negative ERCC1 expression. In logistic regression analysis, ERCC1 negativity continued to be an independent predictor for responsiveness to neoadjuvant chemotherapy (p = 0.021). Among the pretreatment factors, low ERCC1 expression was a significant prognostic factor of disease-free survival in multivariate analysis (p = 0.046).

Conclusions

The ERCC1 expression patterns in pretreatment specimens may thus facilitate the prediction of responses to cisplatin-based NAC. We propose that patients expressing low levels of ERCC1 derive the most benefit from cisplatin-based NAC.     

Delivery delay with neoadjuvant chemotherapy for cervical cancer patients during pregnancy: a series of nine cases and literature review

Objective

Treatment of locally invasive cervical cancer diagnosed during pregnancy in women who desire to retain their pregnancy is a major challenge to physicians. Neoadjuvant chemotherapy followed by radical hysterectomy has been reported to be an attractive option to delay delivery until fetal viability has been reached.

Methods

Between 1994 and 2009 9 patients were treated at San Gerardo Hospital (Monza, Italy) for cervical cancer during pregnancy.

Results

FIGO stage was IB1 in four patients and IB2 in five. Tumor diameter ranged between 20 and 70 mm. After neoadjuvant platinum-based chemotherapy partial response was achieved in 5 patients, while 4 had a stable disease. One patient received a second-line chemotherapy during pregnancy due to progressive disease, achieving a partial response. Median duration of therapy delay until cesarean section was 16 weeks. Between 30 and 36 weeks of gestation all patients underwent cesarean section. Piver II radical hysterectomy with pelvic lymphadenectomy was performed. Two children had mild perinatal morbidities and were discharged in good conditions after 14 and 40 days. Three patients received adjuvant therapy for pathological risk factors. Four patients relapsed (44%) and two of them (23%) died because of tumor progression.

Conclusion

During pregnancy, the oncological outcome of cervical cancer patients is similar to non-pregnant ones. Chemotherapy does not seem to affect fetal health and development, even if longer follow-up is required. Therefore, neoadjuvant chemotherapy for the treatment of locally invasive cervical cancer during pregnancy seems to be a reasonable option for delay definitive treatment until fetal viability is obtained.     

Chemoradiation and adjuvant chemotherapy in advanced cervical adenocarcinoma

Purpose

The optimal treatment of women with advanced adenocarcinoma of uterine cervix is still undefined. We compared concurrent chemoradiation (CCRT) and adjuvant cisplatin-based chemotherapy with CCRT alone for advanced cervical adenocarcinoma in a randomized trial at the Hunan Provincial Tumor Hospital in China.

Methods

From 1998 to 2007, 880 patients with clinical FIGO stages IIB-IVA cervical adenocarcinoma were randomized to receive either CCRT or chemoradiation with one cycle of neo-adjuvant chemotherapy with Paclitaxel (135 mg/m²) + Cisplatin (75 mg/m²) before receiving radiation and two cycles of consolidation chemotherapy with the same drugs after radiotherapy in 3-week intervals. The disease control and survival rates were calculated using the Kaplan-Meier method.

Results

All patients completed the treatment plan. 340 patients have relapsed, with a median follow-up duration of 60 months. Patients who received chemoradiation with adjuvant chemotherapy showed a significantly longer disease-free (P < .05), cumulative survival (P < .05) and long-term local tumor control (P < .05). Patients who received CCRT alone had significantly more distant metastasis and pelvic failure than those who received chemoradiation with adjuvant chemotherapy (P < .05).

Conclusion

Incorporating neo-adjuvant and consolidation chemotherapy with Paclitaxel and Cisplatin into concomitant chemoradiation is highly effective, safe and may be a very promising treatment protocol for advanced cervical adenocarcinoma.     

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.     

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.     

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.     

20 year experience of postoperative radiotherapy in IB-IIA cervical cancer patients with intermediate risk factors: impact of treatment period and concurrent chemotherapy

Objective

To compare the long-term clinical outcomes of adjuvant radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT) in cervical cancer patients with intermediate risk factors.

Methods

Between 1990 and 2010, 110 cervical cancer patients with 2 or more intermediate risk factors (deep stromal invasion, lymphovascular space invasion, and large tumor size) underwent adjuvant RT (n = 56) or CCRT (n = 54) following radical surgery. Because CCRT had been performed since 2000, patients were divided into 3 groups regarding treatment period and the addition of chemotherapy, RT 1990-1999 (n = 39), RT 2000-2010 (n = 17) and CCRT 2000-2010 (n = 54). Majority of concurrent chemotherapeutic regimens were carboplatin and paclitaxel (n = 48).

Results

Five-year relapse-free survival (RFS) rates for RT 1990-1999, RT 2000-2010 and CCRT 2000-2010 were 83.5%, 85.6% and 93.8%, respectively. CCRT 2000-2010 had a significant decrease in pelvic recurrence (p = 0.012) and distant metastasis (p = 0.027). There were no significant differences in overall survival and RFS between RT 1990-1999 and RT 2000-2010. Acute grade 3 and 4 hematologic toxicities were more frequently observed in CCRT 2000-2010 (p < 0.001). However, acute grade 3 and 4 gastrointestinal (GI) and chronic toxicities did not differ between the groups.

Conclusions

This study shows that the addition of concurrent chemotherapy to postoperative RT in cervical cancer patients with intermediate risk factors may improve RFS without increasing acute GI and chronic toxicities, although hematologic toxicities increased significantly.     

Patterns of recurrence in advanced epithelial ovarian, fallopian tube and peritoneal cancers treated with intraperitoneal chemotherapy

Objectives

To examine the distribution and outcomes of recurrent disease in patients with ovarian, fallopian tube and peritoneal cancers after optimal cytoreduction and adjuvant intraperitoneal (IP) chemotherapy.

Methods

All patients diagnosed with ovarian, fallopian tube, or peritoneal cancer between 2004 and 2009 who underwent optimal cytoreductive surgery and received adjuvant intravenous (IV) and IP chemotherapy with paclitaxel and a platinum-based agent were eligible. Age, performance status, tumor origin, stage, and grade were recorded. First recurrences were identified using CA125 values, radiographic studies, operative notes, and pathology reports. Sites of recurrence were classified as intraperitoneal (IP), extraperitoneal (EP) or distant. Kaplan-Meier estimates and Cox multivariate regression models were used to assess the associations between recurrent disease distribution and progression-free survival (PFS) and overall survival (OS).

Results

One hundred forty-three patients met the criteria for inclusion. The majority were Stage III (86%) and serous histology (77%). Eighty-four (58.7%) received IV/IP paclitaxel/cisplatin per GOG-172 and 59 (41.3%) received IV/IP paclitaxel/carboplatin. Seventy-two percent completed 6 cycles. Ninety (62.9%) patients manifested a recurrence. One-hundred twelve sites of recurrence were identified with 70 (62.5%) IP and 42 (37.5%) EP and distant sites. Nineteen (21%) recurred in more than one site, i.e. both IP and EP locations. Site of recurrence did not impact OS, however, patients who recurred in multiples sites had significantly worse OS (p < 0.001).

Conclusion

Approximately 40% of patients treated with IP chemotherapy have a first recurrence outside the peritoneal cavity. Though site of recurrence did not affect OS those with multi-focal recurrence demonstrate worse survival.     

Outcome of stage IVA cervical cancer patients with disease limited to the pelvis in the era of chemoradiation: a Gynecologic Oncology Group study

Objectives

To evaluate the outcome of stage IVA cervical cancer treated with radiation and concurrent cisplatin-based chemotherapy.

Methods

We conducted a retrospective study of stage IVA cervical cancer patients from four trials (Gynecologic Oncology Group protocols 56, 85, 120, and 165) treated with radiotherapy with or without concurrent cisplatin-based chemotherapy. Patient records were reviewed for demographic and tumor features, treatment, and progression-free survival (PFS) and overall survival (OS). Stage IVA patients were compared to stage IIIB patients from these same studies.

Results

Among the 51 stage IVA patients studied, 92% were stage IVA on the basis of bladder involvement. The median PFS was 10.1 months (95% CI = 6.3-14.5 months) and median OS was 21.2 months (95% CI = 13.3-30.5 months). The 3 year survival was 32%. On univariate analysis, only advanced age was associated with OS (p = 0.0115) but age had only marginal effect on PFS (p = 0.083). Pathologic proven pelvic nodal metastasis was of marginal significance for both PFS and OS, p = 0.059 and 0.064, respectively. Despite similar patient characteristics, the use of cisplatin-based chemotherapy had no impact on PFS or OS but was underpowered to address this question. When compared to stage IIIB patients, stage IVA patients had a poorer performance status (p = 0.0231), larger tumor size (p = 0.0302), and more frequent bilateral parametrial involvement (0.0063).

Conclusion

Patients with stage IVA disease had poor median survival of only 21 months with only 32% 3 year survival. Stage IVA patients have larger tumor size, more bilateral parametrial involvement, and poorer survival when compared to stage IIIB patients.     

A prospective phase II study of topotecan (Hycamtin®) and cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer

Objectives

To evaluate the feasibility, toxicity and activity of neoadjuvant chemotherapy (NACT) using cisplatin and topotecan in patients affected by locally advanced cervical cancer (IB2-IIIB).

Methods

Patients with histologically confirmed FIGO stage IB2-IIIB uterine cervical cancer were treated with topotecan 0.75 mg/m²/day (days 1-3) followed by cisplatin 75 mg/m² (day 1), every 21 days for three consecutive cycles. After the last cycle of chemotherapy, within 3 or 4 weeks, patients underwent radical surgery with lymph node dissection.

Results

In the years 2007-2010, 46 women were enrolled into the study. Hematologic toxicity was the most relevant side effect. Thirty-eight patients (82.6%) underwent radical surgery after neoadjuvant chemotherapy (NACT) and were assessable for pathologic responses; surgery was not performed in 8 (17.4%) non-responder patients or with progression disease. Objective pathological response was recorded in 34 patients (89.5%); 6 patients (15.8%) achieved a complete response (CR), 28 (73.7%) patients achieved a partial response (PR); stable disease (SD) occurred in 2 patients (5.3%) with IIA initial disease and progression disease (PD) was registered in 2 patients (5.3%) with IIIB initial disease. The cumulative 2-year progression free survival (PFS) and overall survival (OS) of the 46 enrolled patients in the study were 70% and 81%, respectively; the 2-year PFS and OS of the 38 operated patients were respectively 79% and 95%.

Conclusions

The cisplatin-topotecan combination seems to be feasible and with an acceptable toxicity profile and a promising response rate for the treatment of locally advanced cervical cancer (LACC). Phase II and III studies are needed to compare this combination with other platinum-based chemotherapeutic associations.     

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.     

The impact of pretreatment thrombocytosis and persistent thrombocytosis after adjuvant chemotherapy in patients with advanced epithelial ovarian cancer

Objective

To evaluate the impact of both pretreatment thrombocytosis, and platelet count reduction post-adjuvant chemotherapy, on survival in patients with advanced epithelial ovarian cancer.

Methods

Records of 179 women who underwent cytoreductive surgery for FIGO stage III or IV epithelial ovarian cancer and received six cycles of platinum/paclitaxel-based chemotherapy between July1998 and March 2009 were retrospectively reviewed. Platelet ratio was defined as the preoperative platelet count divided by the platelet count after chemotherapy. The prognostic significance of thrombocytosis and platelet ratio, together with various clinicopathological factors, were evaluated by multivariate analysis.

Results

Sixty-two of 179 (34.6%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis had greater elevations of CA-125 (p < 0.0001) and a greater volume of ascites (p = 0.007). On multivariate analysis, thrombocytosis and CA-125 elevation retained significance as indicators of poor prognosis in patients with stage III or IV disease. In patients with normal CA-125 after chemotherapy, a high platelet ratio was an independent risk factor for reduced survival (p = 0.05).

Conclusions

Preoperative thrombocytosis and a high platelet ratio appear to be poor prognostic factors of survival in patients with advanced epithelial ovarian cancer who were treated with cytoreductive surgery and adjuvant platinum/paclitaxel-based chemotherapy.     

The role of cytoreductive surgery for newly diagnosed advanced-stage uterine carcinosarcoma

Objectives

Uterine carcinosarcoma (CS) is a rare but aggressive malignancy frequently associated with extrauterine metastasis at the time of diagnosis. The objective of this study was to assess the role of cytoreductive surgery in patients with stage IIIC-IVB uterine CS.

Methods

We conducted a retrospective review of all patients with uterine CS treated at our institution from 1990 to 2009. Clinicopathologic factors, surgical procedures, adjuvant therapy, and survival outcomes were collected for all patients. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Factors predictive of survival outcomes were compared using the log-rank test and Cox regression analysis.

Results

An analysis of 44 patients was performed (stage IIIC, n = 14; stage IVB, n = 30). Complete gross resection was achieved in 57% of patients. PFS and OS for the entire cohort were 8.6 months and 18.5 months, respectively. Complete gross resection was associated with a median OS of 52.3 months versus 8.6 months in patients with gross residual disease (P < 0.0001). Stage IIIC disease was associated with a median OS of 52.3 months versus 17.5 months for patients with stage IVB disease. In patients who received adjuvant therapy, OS was 30.1 months versus 4.7 months in patients who did not receive adjuvant therapy (P < 0.001). On multivariate analysis, only complete gross resection and the ability to receive adjuvant therapy were independently associated with OS.

Conclusions

Cytoreductive surgery, with a goal of achieving a complete gross resection, is associated with an improvement in OS among patients with advanced uterine CS.     

Neoadjuvant chemotherapy and vaginal radical trachelectomy for fertility-sparing treatment in women affected by cervical cancer (FIGO stage IB-IIA1)

Objectives

The aim of the present report is to support the feasibility and the safety of a new fertility-sparing treatment in young women affected by bulky cervical cancer.

Methods

Between February 2007 and October 2010, seven patients presenting large IB-IIA1 tumors (30-45 mm) were scheduled for conservative treatment. All patients underwent neoadjuvant chemotherapy (NACT) followed by laparoscopic pelvic lymphadenectomy and vaginal radical trachelectomy (VRT).

Results

One patient presented hematological toxicity during NACT (grade 3). All patients showed complete disappearance of tumor (n = 4/7) or partial response (a 50% or more decrease in total tumor size, n = 3/7) to neoadjuvant treatment, and they were all treated with pelvic lymphadenectomy and VRT. Additional treatment (interstitial brachytherapy) was offered to only one woman because of a persistent parametrial tumoral lesion.After a mean follow up of 22 months (range 5-49), no relapse was observed. To date, only one woman in our study attempted to conceive and she is currently pregnant.

Conclusions

Neoadjuvant chemotherapy for fertility sparing treatment is an innovative approach which is potentially quite interesting for many young women affected by bulky cervical cancer. These women, i.e. those with tumors larger than 2 cm (2-5 cm), are traditionally not offered fertility sparing treatment, thus the preliminary data we report here might have a promising impact. Nevertheless, for these patients it may be suitable to use the more radical, and time-tested, conservative surgical approach to allow for a complete and conservative excision of the residual tumor after neoadjuvant treatment.Studies with a larger number of patients and adequate follow-up are required to validate this conservative approach and to define clearly the good indications for this treatment.     

Surgical staging and adjuvant chemotherapy in the management of patients with adult granulosa cell tumors of the ovary

Objective

To analyze the role of surgical staging and adjuvant chemotherapy in patients with adult type granulosa cell tumor (GCT) of the ovary.

Methods

Patients were divided into those with early-stage (stages I-II, n = 93) and advanced-stage (stages III-IV, n = 13) GCT and analyzed separately in this retrospective study.

Results

Of the 93 patients with early-stage GCT, 30 were completely staged and 25 underwent lymph node dissection. After surgery, 17 patients received adjuvant chemotherapy with bleomycin/etoposide/cisplatin (BEP). None had lymph node metastasis. Completely staged patients had no recurrence or deaths. However, recurrences were observed in 9 of 63 patients (14.3%) who did not undergo complete staging, with four (6.3%) dying due to disease. The 5-year disease-free survival (DFS) rates of groups with and without complete staging were 100% and 84%, respectively (P = 0.037). Adjuvant chemotherapy was not significantly associated with DFS (P = 0.193). All patients with advanced-stage GCT underwent optimal cytoreduction and received adjuvant chemotherapy with BEP. None of the 6 patients who completed 6 cycles of BEP had recurrence, whereas 5 of the 7 patients (71.4%) who received fewer than 6 cycles of BEP had recurrences and 3 (42.9%) died due to disease. The 5-year DFS rates of these two groups were 100% and 50%, respectively (P = 0.022), with cycles of chemotherapy being the only significant factor for DFS in patients with advanced-stage GCT.

Conclusions

Complete surgical staging is recommended, but lymph node removal is not recommended for early-stage GCT. Optimal debulking followed by six cycles of BEP chemotherapy is recommended for advanced-stage GCT.     

Effect of chemotherapy delays and dose reductions on progression free and overall survival in the treatment of epithelial ovarian cancer

Introduction

Hematologic, gastrointestinal, and neurologic complications are common side effects of the platinum and taxane-based chemotherapy used in the primary treatment of epithelial ovarian cancer (EOC). These side effects and the impact of the resultant chemotherapy dose modification on disease free interval have not been extensively studied. The goal of this study was to determine the effect of chemotherapy delays and dose reductions on progression free survival (PFS) and overall survival (OS).

Methods

A review of patients with primary epithelial ovarian, peritoneal, and fallopian tube carcinoma treated between 1/2000 and 12/2007 was performed. Inclusion criteria were advanced stage disease and first line chemotherapy with a platinum and taxane regimen. Cox proportional hazard models were used to determine the effect of chemotherapy reductions and delays on PFS and OS.

Results

One hundred and fifty seven patients met the inclusion criteria. Patients were divided into four groups: no delays or reductions (48%), delay only (27%), reduction only (8%), and both delay and reduction (18%). The mean number of delays/reductions per patient was 1.1 (range = 0-5) and therapy was delayed a mean of 8 days. The most common reasons for delays/reductions were neutropenia (n = 51), thrombocytopenia (n = 45), and neuropathy (n = 18). There were no differences detected in PFS or OS between groups.

Conclusions

There were no differences detected in survival between patients who required dose adjustments and treatment delays and those who did not. The lack of association between survival and chemotherapy alterations suggests that in specific circumstances patients with advanced ovarian cancer should have individualized treatment plans.     

The association between quality of life domains and overall survival in ovarian cancer patients during adjuvant chemotherapy: a Gynecologic Oncology Group Study

Purpose

To explore the association between baseline quality of life (QOL) scores and overall survival (OS) in ovarian cancer patients receiving adjuvant chemotherapy.

Methods

Patients with stage III ovarian cancer on Gynecologic Oncology Group protocol #172 completed the Functional Assessment of Cancer Therapy-General (FACT-G) and were then randomly assigned to either intravenous (IV) or intraperitoneal (IP) chemotherapy. The FACT scale includes physical, functional, social, and emotional well-being domains (PWB, FWB, SWB, EWB). The PWB item, lack of energy, was used to assess the presence of fatigue.

Results

After adjusting for patient age, treatment assignment, and the presence of gross disease, PWB was associated with OS. Patients who reported baseline PWB scores in the lowest 25% (PWB score < 15 points) relative to those who scored in the highest 25% (PWB score > 24 points) had decreased OS (HR: 1.81; 95% CI: 1.2-2.72; p = 0.005). Patients experienced death rates 20% lower for every mean item point increase in PWB (Hazard Ratio [HR]: 0.80; 95% CI: 0.68-0.93; p = 0.005). Patients complaining of fatigue did not have an increased risk of death compared with those not feeling fatigued (HR: 1.21; 95% CI: 0.91-1.61; p = 0.19).

Conclusions

Poor physical well-being reported at baseline is associated with risk of death in patients undergoing adjuvant chemotherapy for advanced ovarian cancer. Identifying modifiable characteristics that are associated with survival offers the potential for providing support that may improve outcomes.     

An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT)

Objective

The recent EORTC-NCIC randomized trial comparing primary debulking surgery (PDS) to neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian carcinoma (EOC) reported a median progression-free survival (PFS) of 12 months and overall survival (OS) of 30 months for both arms. Due to the equivalent survival and decreased morbidity with NACT, many now consider it the preferred approach. We analyzed the outcomes of patients treated with PDS at our institution during the same time period in which the EORTC-NCIC trial was conducted, using identical inclusion criteria.

Methods

We identified all patients undergoing primary treatment for advanced EOC at our institution from 9/98-12/06. Study inclusion and exclusion criteria were identical to those of the EORTC-NCIC trial. Standard statistical tests were used.

Results

Of 316 eligible patients, 285 (90%) underwent PDS and 31 (10%) received NACT due to extra-abdominal disease, medical comorbidities, and/or advanced age (> 85 years). Of the 285 patients who underwent PDS, most had carcinoma of ovarian origin (248, 87%); stage IIIC disease (249, 87%); grade 3 tumors (237, 83%); and serous histology (249, 87%). Optimal cytoreduction (≤ 1 cm residual) was achieved in 203 patients (71%). Postoperative platinum-based chemotherapy was given to 281 of 285 patients (99%). The median PFS and OS were 17 and 50 months, respectively.

Conclusion

PDS should continue to be the preferred initial management for patients with bulky stages IIIC-IV ovarian carcinoma. NACT should be reserved for those who cannot tolerate PDS and/or for whom optimal cytoreduction is not feasible.     

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.