间歇性肿瘤细胞减灭术与初始肿瘤细胞减灭术对晚期上皮性卵巢癌的疗效评价

目的探讨间歇性肿瘤细胞减灭术(IDS)与初始肿瘤细胞减灭术(PDS)对晚期上皮性卵巢癌(EOC)的疗效。方法根据手术方法的不同将132例晚期EOC患者分为PDS组(n=87例)和IDS组(n=45)。PDS组患者行PDS手术后接受6~8个疗程的化疗。IDS组患者行PDS手术后接受3个疗程的化疗,然后再行IDS手术后化疗3~5个疗程。观察两组患者的PDS切除范围,比较两组患者的减瘤满意率、疗效、血清CA125水平和不良反应发生情况。结果IDS组患者的PDS切除范围明显小于PDS组(P﹤0.01)。IDS组患者的减瘤满意率高于PDS组(P﹤0.05)。IDS组患者的临床疗效明显优于PDS组(P﹤0.01)。术前和第3次化疗后,两组患者的血清CA125水平比较,差异均无统计学意义(P﹥0.05)。IDS组患者PDS后的血清CA125水平高于PDS组,完成化疗后的血清CA125水平低于PDS组(P﹤0.05)。IDS组患者的不良反应总发生率低于PDS组(P﹤0.05)。结论IDS有助于提高晚期EOC患者的手术减瘤满意率和近期疗效,且不会显著增加不良反应。     

Clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery in advanced ovarian cancer patients

Objective

To investigate the clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery (IDS) in advanced epithelial ovarian cancer (EOC) patients.

Methods

We retrospectively reviewed the medical records of 124 advanced EOC patients and analyzed the details of neoadjuvant chemotherapy (NACT), IDS, postoperative treatment, and prognoses.

Results

Following IDS, 98 patients had no gross residual disease (NGRD), 15 had residual disease sized <1 cm (optimal), and 11 had residual disease sized ≥1 cm (suboptimal). Two-year overall survival (OS) and progression-free survival (PFS) rates were 88.8% and 39.8% in the NGRD group, 40.0% and 13.3% in the optimal group (p<0.001 vs. NGRD for both), and 36.3% and 0% in the suboptimal group, respectively. Five-year OS and 2-year PFS rates were 62% and 56.1% in the lymph node-negative (LN-) group and 26.2% and 24.5% in the lymph node-positive (LN+) group (p=0.0033 and p=0.0024 vs. LN-, respectively). Furthermore, survival in the LN+ group, despite surgical removal of positive nodes, was the same as that in the unknown LN status group, in which lymphadenectomy was not performed (p=0.616 and p=0.895, respectively). Multivariate analysis identified gross residual tumor during IDS (hazard ratio, 3.68; 95% confidence interval, 1.31 to 10.33 vs. NGRD) as the only independent predictor of poor OS.

Conclusion

NGRD after IDS improved prognosis in advanced EOC patients treated with NACT-IDS. However, while systematic retroperitoneal lymphadenectomy during IDS may predict outcome, it does not confer therapeutic benefits.     

Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study

Introduction

Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice.

Patients and methods

We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy.

Results

Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93).

Conclusions

NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

     

Role of histological type on surgical outcome and survival following radical primary tumour debulking of epithelial ovarian, fallopian tube and peritoneal cancers

Background:

To assess the clinical impact of the two histological types as designated in the proposed model for ovarian tumourigenesis in primary epithelial ovarian, fallopian tube or peritoneal cancer (EOC) patients.

Methods:

All consecutive EOC patients (n=632) after primary tumour debulking in our institution (09/2000–08/2010) were classified into one of two groups: type I tumours (n=100; 15.8%) composed of low-grade serous, low-grade endometrioid, clear cell, mucinous and transitional carcinomas; and Type II tumours (n=532; 84.1%) composed of high-grade serous, high-grade endometrioid, undifferentiated and malignant mixed-mesodermal tumours. Kaplan–Meier and logistic/Cox-regression analyses were performed to assess the impact of histological type on surgical outcome and survival.

Results:

Type II patients had a significantly higher incidence of advanced disease (FIGO III/IV) than Type I patients (79.8% vs 38%, respectively; P<0.001). Median CA125 values (438 vs 93 U ml⁻¹; P=0.001); operative time (258 vs 237 min; P=0.001); and incidence of incomplete tumour resection (34.4% vs 15% P<0.001) were significantly higher in patients with Type II. During a mean follow-up time of 23 months (range: 1–106), 17% of patients with type I vs 34.8% of patients with type II tumours relapsed and/or died (P<0.001). Overall survival (P=0.021) and progression-free survival (P=0.003) were also significantly higher in patients with type I tumours. Multivariate analysis, while identifying postoperative tumour residuals, positive lymph nodes and extrapelvic dissemination as independent predictors of survival, failed to demonstrate any prognostic significance of histological type.

Conclusion:

Type I EOC patients appear to present at earlier stages have significantly higher survival and more optimal surgical outcome compared with type II patients. However, in advanced stages, histology loses significance as an independent prognosticator.     

Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian,tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602

BackgroundWe conducted a phase III, non-inferiority trial comparing upfront primary debulking surgery (PDS) and interval debulking surgery (IDS) following neoadjuvant chemotherapy (NAC) for stage III/IV ovarian, tubal, and peritoneal cancers (JCOG0602). Two earlier studies, EORTC55971 and CHORUS, demonstrated non-inferior survival of patients treated with NAC. However, they could not evaluate true treatment invasiveness because of adding diagnostic laparotomy or laparoscopy before treatment in over 30% of both arms of EORTC55971 and in 16% of NAC arm of CHORUS.MethodsPatients were randomised into the standard arm (PDS followed by eight cycles of paclitaxel and carboplatin [TC]) and NAC arm (four cycles of TC, IDS, and four cycles of TC). In the standard arm, IDS was optional for patients who had undergone suboptimal or incomplete PDS. Treatment invasiveness was compared between arms (UMIN000000523).ResultsBetween November 2006 and October 2011, 301 patients were randomised. In the standard arm, 147/149 underwent PDS and 49 underwent IDS. In the NAC arm, 130/152 underwent IDS. The NAC arm required fewer surgeries (mean 0.86 versus 1.32, p < 0.001) and shorter total operation time (median 273 min versus 341 min, p < 0.001) than the standard arm and required a lower frequency of abdominal organ resection (23.7% versus 37.6%, p = 0.012) or distant metastases resection (3.9% versus 10.7%, p = 0.027). In the NAC arm IDS, blood/ascites loss was smaller (median 787 ml versus 3235 ml, p < 0.001) and albumin transfusion and G3/4 adverse events after surgery in total were less frequent (26.2% versus 58.5%, p < 0.001; 4.6% versus 15.0%, p = 0.005, respectively).ConclusionOur findings demonstrated that NAC treatment is less invasive than standard treatment. NAC treatment may become the new standard treatment for advanced ovarian cancer when non-inferior survival is confirmed in the planned primary analysis in 2017.     

Preoperative Serum CA-125 Level As a Predictor for The Extent of Cytoreduction in Patients with Advanced Stage Epithelial Ovarian Cancer

BackgroundOvarian cancer is the seventh most common cancer in women worldwide and the eighth most common cause of cancer death. Due to the lack of effective early detection strategies and the unspecific onset of symptoms, it is diagnosed at an advanced stage in 75% of cases. The cancer antigen (CA) 125 is used as a prognostic marker and its level is elevated in more than 85% of women with advanced stages of epithelial ovarian cancer (EOC). The standard treatment is primary debulking surgery (PDS) followed by adjuvant chemotherapy (ACT), but the later approach is neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Several studies have been conducted to find out whether preoperative CA-125 serum levels influence treatment choice, surgical resection and survival outcome. The aim of our study was to analyse experience of single institution as Cancer comprehensive center with preoperative usefulness of CA-125.Patients and methodsAt the Institute of Oncology Ljubljana a retrospective analysis of 253 women with stage FIGO IIIC and IV ovarian cancer was conducted. Women were divided into two groups based on their primary treatment. The first group was the NACT group (215 women) and the second the PDS group (38 women). The differences in patient characteristics were compared using the Chi-square test and ANOVA and the Kaplan-Meier method was used for calculating progression-free survival (PFS) and overall survival (OS).ResultsThe median serum CA-125 level was higher in the NACT group than in the PDS group, 972 IU/ml and 499 IU/ ml, respectively. The PFS in the NACT group was 8 months (95% CI 6.4–9.5) and 18 months (95% CI 12.5–23.4) in the PDS group. The median OS was lower in the NACT group than in the PDS group, 25 months (95% CI 20.6–29.5) and 46 months (95% CI 32.9–62.1), respectively.ConclusionsPreoperative CA-125 cut off value of 500 IU/ml is a promising threshold to predict a successful PDS.Key words: ovarian cancer, tumour marker, CA-125, primary debulking surgery, neoadjuvant chemotherapy     

Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

Background:

It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis.

Methods:

We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC.

Results:

BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HR_mult) 1.47; 95% confidence interval (CI) 1.03–2.08 and HR_mult 1.43; 95% CI 1.01–2.03), and a non-significantly worse OS (HR_mult 1.15; 95% CI 0.84–1.57) and OCSS (HR_mult 1.18; 95% CI 0.85–1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HR_mult 1.99; 95% CI 1.21–3.31).

Conclusions:

Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy.     

Elderly and very elderly advanced ovarian cancer patients: Does the age influence the surgical management?

Background

To examine the surgical treatment and clinical outcome of elderly and very elderly advanced epithelial ovarian cancer patients.

Methods

We retrospectively analyzed FIGO stage IIIC–IV ovarian cancer patients, divided in elderly (Group A, >65 and <75 years) and very elderly patients (Group B, ≥75 years) treated by primary debulking surgery (PDS) or by interval debulking surgery (IDS) at the Catholic University at Rome and Campobasso, Italy.

Results

164 patients were included: 123 (Group A) and 41 (Group B). Complete cytoreduction was achieved in 60 patients (60.6%) in Group A and in 20 patients (62.5%) in Group B (p = 0.75). In the remaining cases, optimal cytoreduction was performed (39 cases (39.4%) in Group A and 12 (37.5%) in Group B; p = 0.75). In Group A complete/optimal debulking was achieved in 53 patients (53.5%) at PDS and in 46 patients (46.5%) at IDS (p = 0.55). In the Group B a higher rate of patients was debulked at IDS with respect to PDS (10 (31.3%) vs. 22 patients (68.7%); p = 0.02). In Group A patients debulked at PDS showed better DFS (p = 0.007) and OS (p = 0.003) with respect to patients submitted to successful IDS, whereas in group B we did not observed any survival difference according to time of cytoreduction.

Conclusions

Our data suggest that elderly and very elderly patients may tolerate radical and ultra-radical surgery. These patients should be managed in a gynecologic oncology unit, with prudent but complete approach.     

Efficacy of weekly administration of paclitaxel and carboplatin for advanced ovarian cancer patients with poor performance status

Objective

The aim of this study was to reveal the efficacy of weekly administration of paclitaxel and carboplatin for advanced ovarian cancer patients with poor performance status (PS).

Methods

FIGO stage III/IV ovarian cancer or fallopian tube cancer patients who underwent interval debulking surgery (IDS) followed by neoadjuvant chemotherapy (NAC) were analyzed retrospectively. Patients were divided into two groups based on NAC: weekly paclitaxel and carboplatin (W-TC) and 3 weeks of paclitaxel and carboplatin (TW-TC). Toxicity, efficacy of NAC, surgery outcome, and prognosis were assessed by comparing the two groups.

Results

Twenty patients treated with W-TC and 18 patients treated with TW-TC were analyzed. All of the W-TC patients were poor PS (PS ≥ 2), and all of the TW-TC patients were good PS (PS ≤ 1). The overall clinical response rates were 70% in W-TC and 83.4% in TW-TC. In the W-TC group, Grade 3/4 anemia and thrombocytopenia and greater than grade 2 neuropathy were significantly reduced compared to TW-TC patients. A frequency of treatment delay greater than 7 and 14 days, G-CSF support, blood transfusion, and dose reduction or regimen change were also significantly reduced in the W-TC group. The rate of IDS, optimal debulking surgery, complications during operation, and blood transfusion were similar between the W-TC and TW-TC groups. Progression-free survival and overall survival were also similar between the two groups.

Conclusion

Our study suggested that NAC with W-TC for poor PS patients with non-treated ovarian cancer reduced the toxicity of chemotherapy and had the same efficacy as TW-TC.

     

Clinical impact of systematic pelvic and para-aortic lymphadenectomy for pT1 and pT2 ovarian cancer: a retrospective survey by the Sankai Gynecology Study Group

Background

The therapeutic value of systematic lymphadenectomy for early-stage epithelial ovarian cancer (EOC) is controversial. This study evaluates the survival impact and adverse events of systematic pelvic and para-aortic lymphadenectomy in patients with pT1 and pT2 EOC.

Methods

A retrospective investigation was performed using data from patients with pT1 and pT2 EOC at multi-institutions belonging to the Sankai Gynecologic Study Group (SGSG). We selected patients who had undergone systematic pelvic and para-aortic lymphadenectomy (Group LA) (n = 284) and patients who had not undergone lymph node resection (Group no-LA) (n = 138). Outcomes for patients and peri-operative adverse events were compared between the two groups.

Results

The median operation time was significantly longer in Group LA (288 min) than in Group no-LA (128 min) (P < 0.0001). Total blood loss was significantly higher in Group LA, 43.7 % of patients receiving blood transfusions. There were no significant differences between the treatment groups for progression-free survival (PFS) or overall survival (OS). However, for patients with pT2, PFS was significantly longer in Group LA than in Group no-LA (P = 0.0150). Lymph node metastases were detected in 23 cases (8.1 %) and these patients had significantly shorter PFS than those without metastasis (P = 0.0409). The outcome for patients who underwent chemotherapy after surgery was significantly improved in the Group no-LA, but no improvement was observed in Group LA.

Conclusions

Systematic lymphadenectomy may improve outcomes only in pT2 EOC patients with acceptable peri-operative events. Furthermore, accurate surgical staging may avoid unnecessary adjuvant chemotherapy in selected early-stage cases.     

BRCA1 expression and improved survival in ovarian cancer patients treated with intraperitoneal cisplatin and paclitaxel: a Gynecologic Oncology Group Study

Background:

Breast cancer 1, early onset (BRCA1) is a tumour-suppressor gene associated with familial epithelial ovarian cancer (EOC). Reduced BRCA1 expression is associated with enhanced sensitivity to platinum-based chemotherapy. We sought to examine the prognostic relevance of BRCA1 expression in EOC patients treated with intraperitoneal platinum/taxane.

Methods:

The GOG-172 was a phase III, multi-institutional randomised trial of intravenous paclitaxel and cisplatin (IV therapy) vs intravenous paclitaxel, intraperitoneal cisplatin plus paclitaxel (IP therapy) in patients with optimally resected stage III EOC. The BRCA1 expression was assessed with immunohistochemistry (IHC) staining blinded to clinical outcome in archival tumour specimens. Slides with ⩽10% staining were defined as aberrant and >10% as normal. Correlations between BRCA1 expression and progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan–Meier method and Cox regression analysis.

Results:

Of the 393 patients, 189 tumours had aberrant expression, and 204 had normal BRCA1 expression. There was an interaction between BRCA1 expression and route of administration on OS (P=0.014) but not PFS (P=0.054). In tumours with normal BRCA1 expression, the median OS was 58 months for IP group vs 50 months for IV group (P=0.818). In tumours with aberrant BRCA1 expression, the median OS was 84 vs 47 months in the IP vs IV group, respectively (P=0.0002). Aberrant BRCA1 expression was an independent prognostic factor for better survival in women randomised to IP therapy (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.47–0.97, P=0.032). Similar survival was observed in the IV and IP patients with normal BRCA1 expression. Multivariate but not univariate modelling demonstrated that IV patients with aberrant vs normal BRCA1 expression had worse survival.

Conclusion:

Decreased BRCA1 expression is associated with a 36-month survival improvement in patients with EOC treated with IP chemotherapy. Although these results merit validation in future studies, the results suggest that decreased BRCA1 expression predicts for improved response to cisplatin-based IP chemotherapy with cisplatin and paclitaxel.     

Results of interval debulking surgery in advanced stage ovarian cancer: an exposed-non-exposed study.

BACKGROUND: To study the results of interval debulking surgery (IDS) in patients treated for 'unresectable' advanced stage ovarian cancer compared with primary debulking surgery (PDS) followed by chemotherapy. PATIENTS AND METHODS: An exposed-non-exposed study including a group of 34 patients who underwent an IDS and were matched to an historic control group of 34 patients treated with PDS. RESULTS: Optimal cytoreductive surgery was achieved in 94% (32 out of 34) of patients in both groups. The rates of post-operative morbidity, blood transfusion and median length of hospitalisation were significantly reduced in the study (IDS) group, but survival did not differ in both groups. CONCLUSIONS: IDS in patients with advanced stage ovarian cancer offers the same chance of survival as PDS, but it is better tolerated.     

Asian perspective on debulking surgery for advanced ovarian cancer: An E-survey

PurposeWe performed an E-survey to evaluate the practice patterns in debulking surgery for advanced ovarian cancer in Asia.MethodsWe designed a questionnaire, including 50 questions related to debulking surgery for advanced ovarian cancer. The questionnaire was sent to Gynecologic Oncologic Groups in Asia from December 2016 to February 2017.ResultsA total of 253 gynecologic oncologists from Japan (58.9%), the Republic of Korea (19%), Taiwan (12.6%), and the other counties including China (7.5%), Malaysia (0.8%), Indonesia (0.8%), and Thailand (0.4%) participated in this E-survey. The median number of debulking surgeries per year was 20, and 46.8% of the respondents preferred <1 cm as the criterion for optimal debulking surgery (ODS). The most common barrier and surgical finding precluding ODS were performance status (74.3%) and disease involving the porta hepatis (71.5%). Moreover, 63.2% had a fellowship program, and only 15% or less had opportunities to receive additional training courses in general, thoracic, or urologic surgery. The median percentage of patients receiving neoadjuvant chemotherapy (NAC) was 30%, and the achieved rate of ODS in primary debulking surgery (PDS) and interval debulking surgery (IDS) was 65% and 80%, respectively. Most of the respondents required three to 6 h for PDS (48.6%) and IDS (58.9%). Moreover, more than 50% depended on ultra-radical surgery conducted by specialists.ConclusionsThe ODS criteria are relatively lenient with a preference for NAC in 30% of the respondents in Asia. This trend might be associated with the dependence on aggressive surgery performed by specialists.     

Effect of tumor burden and radical surgery on survival difference between upfront,early interval or delayed cytoreductive surgery in ovarian cancer

ObjectiveWe sought to evaluate the impact on survival of tumor burden and surgical complexity in relation to the number of cycles of neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer (OC) with minimal (CC-1) or no residual disease (CC-0).MethodsThis retrospective study included patients with International Federation of Gynaecology and Obstetrics IIIC–IV stage OC who underwent debulking surgery at 4 high-volume institutions between January 2008 and December 2015. We assessed the overall survival (OS) of primary debulking surgery (PDS group), early interval debulking surgery after 3–4 cycles of NACT (early IDS group) and delayed debulking surgery after 6 cycles (DDS group) with CC-0 or CC-1 according to peritoneal cancer index (PCI) and Aletti score.ResultsFive hundred forty-nine women were included: 175 (31.9%) had PDS, 224 (40.8%) early IDS and 150 (27.3%) DDS. Regardless of Aletti score, median OS after PDS was significantly higher than after early IDS or DDS, but the survival difference was higher in women with an Aletti score <8. Among patients with PCI ≤10, median OS after PDS was significantly higher than after early IDS or DDS. In women with PCI >10, there were no differences between PDS and early IDS, but DDS was associated with decreased OS.ConclusionThe benefit of complete PDS compared with NACT was maximal in patients with a low complexity score. In patients with low tumor burden, there was a survival benefit of PDS over early IDS or DDS. In women with high tumor load, DDS impaired the oncological outcome.     

Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter,Retrospective Analysis by the MITO Group (MITO 24)

Background

The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking.

Objective

The MITO group conducted a multicenter, retrospective study (MITO 24) to investigate the role of inflammatory indexes as prognostic factors and predictors of treatment efficacy in FIGO stage III–IV EOC patients treated with first-line chemotherapy alone or in combination with bevacizumab.

Patients and Methods

Of the 375 patients recruited, 301 received chemotherapy alone and 74 received chemotherapy with bevacizumab. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were evaluated to identify a potential correlation with PFS and OS in both the overall population and the two treatment arms.

Results

In the overall population, the PFS and OS were significantly longer in patients with low inflammatory indexes (p?<?0.0001). In multivariate analyses, the NLR was significantly associated with OS (p?=?0.016), and the PLR was significantly associated with PFS (p?=?0.024). Inflammatory indexes were significantly correlated with patient prognosis in the chemotherapy-alone group (p?<?0.0001). Patients in the chemotherapy with bevacizumab group with a high NLR had a higher PFS and OS (p?=?0.026 and p?=?0.029, respectively) than those in the chemotherapy-alone group. Conversely, PFS and OS were significantly poorer in patients with a high SII (p?=?0.024 and p?=?0.017, respectively).

Conclusion

Our results suggest that bevacizumab improves clinical outcome in patients with a high NLR but may be detrimental in those with a high SII.

     

Increased serum level of epidermal growth factor receptor (EGFR) is associated with poor progression-free survival in patients with epithelial ovarian cancer

Purpose

Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of multiple malignancies, and its expression also strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of EGFR in epithelial ovarian cancer (EOC) patients.

Materials and methods

A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum EGFR levels were determined by the solid-phase sandwich ELISA method. Age and sex matched 20 healthy controls were included in the analysis.

Results

Median age of patients was 56.5 years old, range 22–83 years. Majority of the patients had advanced disease (FIGO stage III-IV) (90 %). No significant difference in baseline serum EGFR levels between EOC patients and controls (65.9 vs. 65.4 ng/mL, p = 0.86). Patients with normal CA 125 had higher serum EGFR level compared with the higher CA 125 level (p = 0.02). No other clinical variables including histology, stage of disease, and response to chemotherapy were found to be correlated with serum EGFR assay (p > 0.05). The patients with increased serum EGFR levels had poor progression-free survival than those with lower levels (median survival 4 vs. 12 months, respectively, p = 0.01). However, serum EGFR level was found no prognostic role for overall survival (p = 0.15).

Conclusion

Increased serum level of EGFR is associated with poor progression-free survival in EOC patients.     

Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei

Background

The aim of this study was to compare debulking surgery and cytoreductive surgery (CRS) in patients with Pseudomyxoma peritonei (PMP) regarding efficacy and safety.

Patients and methods

Data were extracted from medical records and treatment outcomes were analyzed for all 152 patients with PMP who were scheduled for debulking surgery and intraperitoneal chemotherapy (IPC) or CRS and IPC at Uppsala University Hospital, Uppsala, Sweden, between September 1993 and December 2008.

Results

One hundred and ten patients (73%) were treated with CRS and IPC and 40 (27%) with debulking surgery and IPC. In two patients (1%), surgery was defined as open and close. Patients with CRS and IPC had a 74% 5-year overall survival (OS) rate compared with 40% for those treated with debulking surgery (P < 0.001). Patients with no residual macroscopic tumour (R1 resection) had a better 5-year OS rate of 94% compared with 28% for patients with macroscopic residual tumour (R2) (P < 0.001). Grades II–IV adverse events were seen in 29% of debulked patients and in 47% of CRS/IPC patients (P = 0.053).

Conclusions

CRS and IPC seems more efficient than debulking surgery and IPC but with numerically higher morbidity. Therefore, if surgically possible, CRS should be the treatment of choice for PMP patients. However, debulking surgery may still be of benefit to selected patients for palliative purposes.     

Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma

Background:

Prognostic factors for progression-free survival (PFS), overall survival (OS), and long-term OS (⩾30 months) were investigated in sunitinib-treated patients with metastatic renal cell carcinoma (RCC).

Methods:

Data were pooled from 1059 patients in six trials. Baseline variables, including ethnicity, were analysed for prognostic significance by Cox proportional-hazards model.

Results:

Median PFS and OS were 9.7 and 23.4 months, respectively. Multivariate analysis of PFS and OS identified independent predictors, including ethnic origin, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, prior cytokine use, haemoglobin, lactate dehydrogenase, corrected calcium, neutrophils, platelets, and bone metastases (OS only). Characteristics of long-term survivors (n=215, 20%) differed from those of non-long-term survivors; independent predictors of long-term OS included ethnic origin, bone metastases, and corrected calcium. There were no differences in PFS (10.5 vs 7.2 months; P=0.1006) or OS (23.8 vs 21.4 months; P=0.2135) in white vs Asian patients; however, there were significant differences in PFS (10.5 vs 5.7 months; P<0.001) and OS (23.8 vs 17.4 months; P=0.0319) in white vs non-white, non-Asian patients.

Conclusion:

These analyses identified risk factors to survival with sunitinib, including potential ethnic-based differences, and validated risk factors previously reported in advanced RCC.     

Phase II study of ifosfamide and cisplatin for the treatment of recurrent ovarian cancer

Purpose

The aim of this phase II study was to investigate the efficacy and toxicity of combined ifosfamide and cisplatin chemotherapy in patients with recurrent epithelial ovarian cancer (EOC).

Experimental design

Forty-seven patients with recurrent EOC were treated with ifosfamide 5 g/m² and cisplatin 50 mg/m² on day 1, every 3 weeks for 6 cycles. The primary outcomes were response rate (RR) and toxicity. Other measurements were duration of response, time to progression (TTP), and overall survival (OS).

Results

All 47 patients with 160 cycles were assessed for response and toxicity. The overall RR was 31.9 %; there were 3 complete responses (6.4 %) and 12 partial responses (25.5 %). Grade 3 and 4 hematologic toxicities included neutropenia (23.6 %), anemia (12.8 %), and thrombocytopenia (10.7 %). Non-hematologic toxicities were mild, and no drug-related toxic deaths occurred. The median duration of response, TTP, and OS was 5.1, 4.8, and 17.0 months, respectively. In the initially platinum-sensitive group, RR and OS were 44.4 % and 20.4 months, while in the initially platinum-resistant group, these values were 15.0 and 8.7 months, respectively (P = 0.027 and P = 0.002, respectively).

Conclusion

Ifosfamide combined with cisplatin is a well-tolerated regimen with modest activity in recurrent EOC. In addition, this regimen was especially effective in patients whose disease was initially platinum-sensitive.