Prognostic and predictive value of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score in surgery for recurrent ovarian cancer.

OBJECTIVES: The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score was developed as selection criteria and validated as predictor of a high probability for complete resection in recurrent ovarian cancer. It is not defined whether the predictive value is independent from underlying tumor biology or is solely based on a selection of good prognostic risks. METHODS: We performed an exploratory analysis of all consecutive patients with cytoreductive surgery in recurrent ovarian cancer in a tertiary referral center 1999-2013, before and after introduction of the AGO score. RESULTS: 217 consecutive patients were included of whom 112 patients were AGO score positive and 105 patients were score negative. Corresponding complete resection rates were 89.3% and 66.7%, respectively, and confirm the score's predictive value. However, a positive AGO score was also associated with better outcome after adjustment for surgical outcome. Patients with complete resection and a positive AGO score showed a median overall survival of 63.9 months (95% CI 48.1-79.6) compared to 48.4 months (95% CI 30.3-66.5) after complete resection and negative score (log-rank p=0.10). However, in multivariate analysis the only independent prognostic factor was complete resection (HR 2.450; 95% CI: 1.542-3.891). CONCLUSIONS: The AGO score could identify suitable candidates for secondary cytoreductive surgery but failed to prove an independent prognostic value thus suggesting an effect of successful surgery on its own. However, the latter has to be proven prospectively. In addition, further studies should evaluate the predictive and prognostic impact of a negative score.

Outcome of early breast cancer treated in an urban and a rural breast cancer unit in Germany.

BACKGROUND: Conflicting evidence has been published concerning survival disadvantages in the outcome of breast cancer patients in relationship to their residency in urban or rural communities. METHODS: The primary aim of this study was to evaluate differences in patients and treatment characteristics between an urban and a rural breast cancer unit. Therefore, all early breast cancer patients treated consecutively between 1999 and 2007 in a rural and an urban breast cancer unit were included. Patient and tumor characteristics, treatment strategies, and guideline adherence were included to evaluate the prognoses of both populations. RESULTS: Overall, data from 2,566 patients were included in this analysis. The 610 patients treated in the rural unit showed significantly more negative prognostic criteria than the 1,956 patients treated in the urban center. No differences were observed with respect to surgical and systemic treatment after adjustment for prognostic parameters. Adherence to national guidelines did not differ significantly between both settings and ranged between 78.0 and 95.6%. Furthermore, no differences regarding recurrence-free and overall survival were observed. CONCLUSIONS: The stage-adjusted pattern of care was similar in 2 German breast care units in a rural region and an urban area. Nevertheless, an earlier diagnosis of breast cancer should be enforced in rural areas to avoid extended treatment burden.

Differences in the receptor status between primary and recurrent breast cancer--the frequency of and the reasons for discordance.

OBJECTIVE: Receptor discordances between primary and recurrent breast cancer have been described for years, but only a few analyses have elucidated the factors that influence receptor changes. METHODS: Explorative analyses of prospective data from a breast cancer database of a tertiary breast cancer unit. RESULTS: Recurrent tumours that had expressed oestrogen (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) as primary tumours were negative for the respective receptor in 22.8, 41.4 and 40.8% of cases. ER, PR and HER2 expression was found in 19.8, 16.7 and 11.5% of recurrent tumours, although no expression had been observed in primary tumours. Receptor discordances in recurrent disease leading to different therapeutic approaches were noted in 126 of 411 patients (30.7%). In patients with tumours expressing primary ER and HER2, independent factors associated with discordance were endocrine therapy and treatment with trastuzumab. CONCLUSION: High rates of receptor discordance were found. The impact of factors that influence receptor changes is small so that no subgroup of patients with recurrent breast cancer should be excluded from biopsy. Whenever possible, a biopsy should be taken to confirm the diagnosis of a possible relapse as well as the receptor status of patients with breast cancer.

Outcome of immediate re-operation or interval debulking after chemotherapy at a gynecologic oncology center after initially incomplete cytoreduction of advanced ovarian cancer.

BACKGROUND: Prognosis in advanced ovarian cancer is largely determined by completeness of tumor resection achieved during primary surgery. Incomplete initial debulking occurs frequently in non-specialized centers and there is an ongoing discussion about the best time for re-surgery after referral to tertiary centers. METHODS: Patients with advanced epithelial ovarian cancer (FIGO IIIB-IV) admitted between 1999 and 2007 who had primary incomplete surgery including those with initiated chemotherapy at an outside institution were included. Surgical results, morbidity and prognosis were evaluated in patients with immediate re-operation before chemotherapy and those with interval debulking. RESULTS: 48 eligible patients were identified in our tumor registry. Self-referral by patient was the most frequent mode of admission (n=21, 43.8%). 22 patients (45.8%) underwent immediate re-surgery and 26 patients (54.2%) had an interval debulking after chemotherapy. In 12 patients (54.5%), macroscopically complete tumor removal could be achieved by immediate re-operation and in 17 patients (65.4%) after chemotherapy. Major complications were observed more frequently in patients with interval debulking (26.9 vs. 9.1%, p=0.324). Median overall survival time was 53 and 34 months (p=0.110) after immediate and delayed re-operation, respectively. CONCLUSIONS: Upfront re-operation before start of chemotherapy is feasible and successful in an expertise referral center in more than half of patients with incomplete primary surgery elsewhere. Complete resection even after initial incomplete debulking could improve outcome. Therefore, referral to expertise centers in those patients should be considered. Progression-free survival and overall survival showed a non-significant trend and complication rate is a remarkable advantage in favor of upfront re-operation.

Requirements to assess feasibility of phase 0 trials during major abdominal surgery: variability of PARP activity.

PURPOSE: The aim of this study was to evaluate the feasibility of phase 0 trials in the setting of a routine surgical procedure. Logistic considerations, tissue sampling and tissue handling, and variability of a biomarker during surgery, in here PARP, were evaluated. EXPERIMENTAL DESIGN: Patients with highly suspicious or proven diagnosis of advanced ovarian cancer, planned for debulking surgery were asked to allow sequential tumor biopsies during surgery. Biopsies were frozen immediately and PARP activity was measured subsequently. RESULTS: Baseline biopsies were obtained from eight patients after a median time of 88 minutes (minimum of 50 to maximum of 123 minutes). Second and third biopsies were obtained after a median of 60 (32-96) and 101 (79-130) minutes, respectively. Mean tumor load was 44% (5%-100%), with a cellular viability of 98% (85%-100%). Median baseline PARP activity was 1035 pg/mL (range, 429-2663 pg/mL). The observed interpatient variability at baseline was large: SD was 0.59 after natural logarithm transformation. CONCLUSIONS: Conducting phase 0 trials during surgery seems to be feasible in terms of logistic considerations. In preparation of a phase 0 trial during surgery, a feasibility study like this should be conducted to rule out major interactions of the surgical intervention with respect to the targeted biomarker.

Borderline tumors of the ovary: clinical course and prognostic factors.

BACKGROUND: The prognosis in borderline tumors of the ovary (BOT) is generally favorable. However, some patients experience recurrence, and mortalities occur. There is a need to better characterize prognostic factors to be considered for individualized treatment planning. PATIENTS AND METHODS: The data of 158 consecutive patients who underwent surgery for BOT at a tertiary referral center for gynecologic oncology between 1997 and 2008 were retrospectively analyzed. RESULTS: Most patients had early stage disease, and advanced stages FIGO II/III only occurred in 23.4%. Serous histology was most frequent (68%), followed by mucinous histology (22%). All patients received surgery as initial treatment with no adjuvant systemic therapy. 37 patients (40.7% of the patients under the age of 50) had fertility-sparing surgery (FSS). Recurrent disease occurred in 18 (11.4%) patients, and 4 (2.5%) patients died. Independent risk factors for recurrence were FIGO stages > I (hazard ratio (HR) 37.1; 95% confidence interval (CI) 4.5-155.5), tumor rupture (HR 12.4; 95% CI 1.5-61.5), incomplete staging (HR 5.9; 95% CI 1.6-21.3), and FSS in patients < 50 years (HR 8.0; 95% CI 2.0-31.6). CONCLUSION: Intraoperative tumor rupture, incomplete staging, and FSS - all influenced by the surgeon - may impose a substantial recurrence risk. Therefore, careful counseling and balancing of risk and benefit are mandatory before therapy is applied, especially if FSS is planned.

Impact of a structured quality management program on surgical outcome in primary advanced ovarian cancer.

OBJECTIVE: Surgical outcome in advanced ovarian cancer (AOC) is an important prognostic factor and the only factor amendable to improvement by optimization. Therefore, introduction of quality management programs (QM) regarding the surgical therapy in ovarian cancer may help to improve outcome. METHODS: We introduced a specific ovarian cancer quality management program in 2001 in our gynecologic oncology center. Analysis of 396 consecutive patients with primary surgery for advanced ovarian cancer FIGO stages IIB-IV operated before the introduction of the quality management program 1997-2000, or during the introduction years 2001-2003, or after establishing 2004-2008. RESULTS: Thirty-three percent had complete debulking to no macroscopic residual disease from 1997 to 2000. This rate increased to 47% in 2001-2003 (n = 86) and 62% in 2004-2008 (n = 259). The utilization of extended surgical procedures increased over time. Patients with complete resection had 5-YSR of 55% compared to 16% in patients with residuals 1-10 mm, and 13% in patients with residuals >1 cm (p < 0.001). The median OS increased from 26 months 1997-2000 to 37 months 2001-2003 and 45 months in 2004-2008 (p < 0.003). CONCLUSIONS: Optimizing surgical skills, infrastructure, and introduction of quality management programs may improve both surgical and overall outcome in advanced ovarian cancer.