Beyhan Ataseven

Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery

OBJECTIVE Describing the pattern of and reasons for post-operative tumor residuals in patients with advanced epithelial ovarian cancer (AOC) operated in a specialized gynecologic cancer center following a strategy of maximum upfront debulking followed by systemic chemotherapy. METHODS All consecutive AOC-patients treated between 2005 and 2015 due to stages FIGO IIIB/IV were included in this single-center analysis. RESULTS 739 patients were included in this analysis. In 81 (11.0%) patients, chemotherapy had already started before referral. Of the remaining 658 patients, upfront debulking was indicated in 578 patients (87.8%), while 80 patients (12.8%) were classified ineligible for upfront debulking; mostly due to comorbidities. A complete tumor resection was achieved in 66.1% of the 578 patients with upfront surgery, 25.4% had residuals 1-10mm and 8.5% had residuals exceeding 10mm, and 12.5% of patients had multifocal residual disease. Most common localization was small bowel mesentery and serosa (79.8%), porta hepatis/hepatoduodenal ligament (10.1%), liver parenchyma (4.3%), pancreas (8.0%), gastric serosa (3.2%), and tumor surrounding/infiltrating the truncus coeliacus (2.7%); 14.9% of the patients had non-resectable supra diaphragmatic lesions. Size of residual tumor was significantly associated with progression-free and overall survival. CONCLUSIONS Upfront debulking for AOC followed by systemic chemotherapy was our main treatment strategy in almost 90% of all patients. The majority experienced a benefit by this approach; while 11.7% of patients probably did not. Understanding sites and reason for residual disease may help to develop adequate surgical training programs but also to identify patients that would better benefit from alternative treatment strategies.

FIGO stage IV epithelial ovarian, fallopian tube and peritoneal cancer revisited

Epithelial ovarian, fallopian tube and peritoneal cancer (EOC) is the seventh most common cancer diagnosis among women worldwide and shows the highest mortality rate of all gynecologic tumors. Different histological and anatomic spread patterns as well as multiple gene-expression based studies have demonstrated that EOC is indeed a heterogeneous disease. The prognostic factors that best predict the survival in this disease include: age, performance status and patients comorbidities at the time of diagnosis; tumor biology, histological type, amount of residual tumor after surgery and finally tumor stage as surrogate for pre-operative tumor burden and growth pattern. In the majority of patients, the disease is diagnosed in advanced stage, disseminated intra- and/or extra-abdominally. It is unclear whether this is a consequence of distinct tumor biology, absence of anatomic barriers between ovary and the abdominal cavity, delay of diagnosis and/or the lack of sufficient early detection methods. FIGO stage IV disease, defined as tumor spread outside the abdominal cavity (including malignant pleural effusion) and/or visceral metastases, will be present in 12-33% of the patients at initial diagnosis. Overall, median survival for patients with stage IV disease ranges from 15 to 29months, with an estimated 5-year survival of approximately 20%. Unfortunately, over the past decades the overall survival gain compared to stage III remains disappointing. The current review aims to summarize the current data published in the international literature concerning FIGO stage IV EOC and discusses the published evidence for the clinical management of these patients.

Serous Tubal Intraepithelial Carcinoma Associated With Extraovarian Metastases.

Objective The evolving knowledge of ovarian carcinogenesis sets the stage for our understanding of high-grade serous pelvic carcinoma (HGSC). Findings in prophylactic surgery introduced serous tubal intraepithelial carcinoma (STIC) as potential precursor of HGSC. The present study explores whether STIC instead should already be considered as an early stage of HGSC with a need for comprehensive staging and therapy. Patients and Methods We identified all consecutive patients with HGSC who received first-line therapy in our referral center for gynecologic oncology from January 2011 to April 2016. All chemo-naive patients with upfront debulking surgery in whom an association of STIC and tumor lesions could be analyzed were included. Patients with previous removal of the adnexa or overgrown of the fallopian tube by the tumor were excluded. Pathological workup of the fallopian tubes according to the SEE-FIM protocol was conducted. Results We analyzed a series of 231 consecutive patients with HGSC of whom 121 (52.4%) had ovarian cancer, 74 (32.0%) had cancer of the fallopian tubes and 36 patients (15.6%) had primary peritoneal cancer. Serous tubal intraepithelial carcinoma could be identified in 158 (68.4%) of 231 patients; of 22 patients, 28.1% is ovarian cancer, 30.8% cancer of the fallopian tubes, and 9.5% peritoneal cancer. Four patients without any further intra-abdominal disease were identified of whom 2 patients had stage FIGO IA and 2 patients had lymph node metastases only. Conclusions Our data suggest that STIC should be regarded as a malignant lesion with metastatic potential. Therefore, we recommend a comprehensive surgical staging including lymphadenectomy.

Impact of Abdominal Wall Metastases on Prognosis in Epithelial Ovarian Cancer.

Objective Epithelial ovarian cancer (EOC) patients with the presence of abdominal wall metastasis (AWM) are categorized as stage International Federation of Gynecology and Obstetrics (FIGO) IVB, irrespective of other biologic factors or preceding invasive intervention before final surgery. We evaluated the impact of AWM on patients’ overall survival (OS). Patients and Methods In this exploratory study, 634 consecutive patients with advanced EOC treated in our center from 2000 to 2014 were included. Patients were categorized into FIGO IIIC (n = 308), FIGO IVB AWM only (n = 86), and FIGO IV others (metastases other than AWM, n = 240). Clinicopathological parameters and survival data were extracted from our prospectively maintained tumor registry. Survival analyses were calculated using Kaplan-Meier method and Cox regression models. Results In 75 (87.2%) of 86 cases, AWM was seen after a preceding intervention, and only in 12.7%, the deposits were spontaneously established. The median OS in patients with stage FIGO IIIC, FIGO IVB AWM only, and FIGO IV others was 37, 58, and 25 months (P < 0.001), respectively. Patients with FIGO IVB AWM only had a significantly better OS than patients with FIGO IV others (P < 0.001). The numeric longer OS of patients with FIGO IVB AWM only compared with patients with FIGO IIIC was not statistically significant (P = 0.151). In multivariate analysis considering all confounding factors including residual disease, OS of patients with FIGO IIIC did not differ from patients with FIGO AWM only (hazard ratio, 0.84; 95% confidence interval, 0.56–12.26; P = 0.398). Conclusions Most AWM are acquired after preceding intervention (puncture or laparoscopy). Prognosis of patients with AWM as the only site of distant metastasis is superior compared with other stage FIGO IV patients. Therefore, up-staging of patients only because of AWM to FIGO IVB may be questioned. A revision/clarification of the FIGO classification system should be considered to avoid unnecessary stigmatization of patients and to classify these patients more appropriately according to prognosis.

The revised 2014 FIGO staging system for epithelial ovarian cancer: Is a subclassification into FIGO stage IVA and IVB justified?

OBJECTIVE The revised 2014 FIGO staging system for epithelial ovarian cancer (EOC) included many changes of the previous system, particularly dividing FIGO stage IV in two subgroups. We evaluated if classifying patients with EOC in FIGO stage IVA and IVB has any prognostic implication.

The Impact of Neoadjuvant Treatment on Surgical Options and Outcomes

Neoadjuvant systemic therapy (NST) has become a well-established treatment method for patients with breast cancer, not only for those with large tumors, but also for patients with early high-risk cancers. In earlier times, the clinical advantage of NST was seen in improvement of tumor shrinkage for better operability, conversion of mastectomy candidates to breast conservation, and optimization of cosmetic results. Over the decades, therapy regimens were optimized, resulting in significantly higher response rates. Rates for breast conservation and for conversion from mastectomy to breast conservation, especially for patients with advanced breast cancers, rose significantly for patients undergoing NST. A multidisciplinary approach with close and accurate diagnostic assessment of the breast, axillary tumor, or both during NST and individual-response-guided surgery is mandatory. To reduce unnecessary surgery and prevent mastectomies, more conclusive prediction models and minimally invasive methods for selection of patients with pathologic complete remission after NST are needed. Furthermore, prospective studies demonstrate that sentinel node biopsy for patients with initial clinically node-positive axillary nodes converting to clinically node-negative axillary nodes is oncologically safe and offers less morbidity, avoiding complete axillary node dissection. Initial concerns regarding surgical complications and morbidity due to potential immune frailty of patients with NST were not observed.

PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs.

Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27–87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier findings that PTK7 may be a prognostic and predictive marker associated with resistance to anthracycline-based chemotherapy. Further investigations are needed to validate these findings in breast cancer.

Intake of selective beta blockers has no impact on survival in patients with epithelial ovarian cancer

BACKGROUND AND OBJECTIVE Some authors have claimed a significant impact of β-blocking agents on outcome in epithelial ovarian cancer (EOC). This study investigated the impact of concurrent medication with selective beta blockers (SBB) in patients undergoing primary treatment for EOC. METHODS The study included all consecutive patients with primary EOC treated in two tertiary gynecological-oncologic units between 1999 and 2014. Medication was retrospectively analyzed by chart review. RESULTS The study cohort comprised 801 patients, of whom 141 (17.6%) had received SBB. Median age of patients without SBB medication was 56years (range: 19-90years) and 64years (range: 41-84years) in patients taking SBB (p<0.001). The main prognostic factor FIGO stage did not differ between both cohorts. 63.8% of patients taking SBB underwent complete tumor resection compared to 74.2% of patients without SBB (p=0.012). Patients without SBB experienced less severe post-operative complications according to the Clavien-Dindo classification (18.8% vs 29.0%; p=0.003). Between the both groups without and with SBB intake, PFS and OS did not differ significantly (PFS: 27months and 24months, p=0.40; OS: 56months and 44, p=0.15). Multivariate analyses did not yield any association between SBB intake and prognosis but confirmed well-known prognostic factors. CONCLUSIONS Intake of selective β-blockers did not influence the prognosis of patients with EOC.

The impact of type and number of bowel resections on anastomotic leakage risk in advanced ovarian cancer surgery

OBJECTIVE To identify risk factors for anastomotic leakage (AL) in patients undergoing primary advanced ovarian cancer surgery and to evaluate the prognostic implication of AL on overall survival in these patients. METHODS We analyzed our institutional database for primary EOC and included all consecutive patients treated by debulking surgery including any type of full circumferential bowel resection beyond appendectomy between 1999 and 2015. We performed logistic regression models to identify risk factors for AL and log-rank tests and Cox proportional hazards models to evaluate the association between AL and survival. RESULTS AL occurred in 36/800 (4.5%; 95% confidence interval [3%-6%]) of all patients with advanced ovarian cancer and 36/518 (6.9% [5%-9%]) patients undergoing bowel resection during debulking surgery. One hundred fifty-six (30.1%) patients had multiple bowel resections. In these patients, AL rate per patient was only slightly higher (9.0% [5%-13%]) than in patients with rectosigmoid resection only (6.9% [4%-10%]), despite the higher number of anastomosis. No independent predictive factors for AL were identified. AL was independently associated with shortened overall survival (HR 1.9 [1.2-3.4], p=0.01). CONCLUSION In the present study, no predictive pre- and/or intraoperative risk factors for AL were identified. AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections.

Update on Female Cancer in Africa: The AORTIC Conference 2015, Morocco

It was shown in all 3 studies that trained nurses (South African clinics) or volunteers (Sudanese and Tanzanian villages) were able to detect suspicious breast lumps in undiagnosed women. These women were referred and treated to a certain extent, however, some women decided not to be treated. This screening strategy may possibly be used to detect early breast cancers in low resource settings like Africa.