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Preoperative neoadjuvant chemotherapy (NAC) can significantly reduce tumour burden in patients with primarily unresectable chemosensitive tumours, allowing a more complete cytoreduction during debulking surgery and facilitating evaluation of tumour chemosensitivity, identification of appropriate treatment options and improvement of intervention protocols. In this study, we investigate, using immunohistochemistry, the impact of platinum/taxane-based NAC (NAC) on tumour-infiltrating lymphocytes (TILs) in advanced epithelial ovarian cancer (EOC) and their relationship with clinical outcome. All patients had clinical response, as shown by ascites volume and CA125 levels compared to pre-treatment findings. NAC intervention significantly increased CD4(+), CD8(+) and granzyme B(+) infiltration while Foxp3(+) accumulation remained unaffected. TILs were prognostically neutral for both progression-free survival (PFS) and overall survival (OS) before NAC. In contrast, after NAC, elevated granzyme B(+) infiltration displayed a tendency for improved PFS (log-rank 0.064). Further, low Foxp3(+) cell density was associated with longer PFS, as compared with strong Foxp3(+) infiltration (median 20.94 vs. 11.24 months; log-rank 0.0001) and with improved OS (median 30.75 vs. 16.04 months, respectively; log-rank 0.056), demonstrating clear prognostic significance for PFS. In addition, high granzyme B(+)/Foxp3(+) ratio post-NAC strongly correlated with improved PFS compared to low granzyme B(+)/Foxp3(+) cell ratio (median 17.88 vs. 11.24 months, respectively), and showed to be a favourable prognostic factor for PFS (log-rank 0.014). Our findings indicate that NAC elicited an immunologic profile in which low immunosuppressive Foxp3(+) infiltration and elevated numbers of activated granzyme B(+) cells were significantly associated with EOC-specific PFS, suggesting a contribution of immunologic effects to improved clinical outcome.

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This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.

Vulvar cancer is rare but incidence rates are increasing due to an aging population and higher frequencies of young women being affected. In locally advanced, metastatic or recurrent disease prognosis is poor and new treatment modalities are needed. Immune checkpoint blockade of the PD-1/PD-L1 pathway is one of the most important advancements in cancer therapy in the last years. The clinical relevance of PD-L1 expression in vulvar cancer, however, has not been studied so far. We determined PD-L1 expression, numbers of CD3+ T cells, CD20+ B cells, CD68+ monocytes/macrophages, Foxp3+ regulatory T cells and CD163+ tumor-associated macrophages by immunohistochemistry in 103 patients. Correlation analysis with clinicopathological parameters was undertaken; the cause-specific outcome was modeled with competing risk analysis; multivariate Cox regression was used to determine independent predictors of survival. Membranous PD-L1 was expressed in a minority of tumors, defined by HPV-negativity. Its presence geographically correlated with immunocyte-rich regions of cancer islets and was an independent prognostic factor for poor outcome. Our data support the notion that vulvar cancer is an immunomodulatory tumor that harnesses the PD-1/PD-L1 pathway to induce tolerance. Accordingly, immunotherapeutic approaches might have the potential to improve outcome in patients with vulvar cancer and could complement conventional cancer treatment.

Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes.

Several authors question the potential benefit of preoperative magnetic resonance imaging (MRI) against the background of possible overdiagnosis, false-positive findings, and unnecessary resections in patients with newly diagnosed breast cancer. In order to reveal a better selection of patients who should undergo preoperative MRI after histological confirmed breast cancer, the present analysis was implemented. We aimed to evaluate the influence of preoperative breast MRI in patients with newly diagnosed breast cancer to find subgroups of patients that are most likely to benefit from preoperative MRI by the detection of occult malignant foci. A total of 1102 consecutive patients who underwent treatment for primary breast cancer between 2002 and 2013 were retrospectively analyzed. All patients underwent triple assessment by breast ultrasound, mammography, and bilateral breast MRI. MRI findings not seen on conventional imaging that suggested additional malignant disease was found in 344 cases (31.2 %). Histological confirmed malignant foci were found in 223 patients (20.2 %) within the index breast and in 28 patients (2.5 %) in the contralateral breast. The rate of false-negative biopsies was 31 (2.8 %) and 62 (5.6 %), respectively. Premenopausal women (p = 0.024), lobular invasive breast cancer (p = 0.02) as well as patients with high breast density [American College of Radiology (ACR) 3 + 4; p = 0.01] were significantly associated with additional malignant foci in the index breast. Multivariate analysis confirmed lobular histology (p = 0.041) as well as the co-factors "premenopausal stage" and "high breast density (ACR 3+4)" (p = 0.044) to be independently significant. Previous studies revealed that breast MRI is a reliable tool for predicting tumor extension as well as for the detection of additional ipsilateral and contralateral tumor foci in histological confirmed breast cancer. In the present study, we demonstrate that especially premenopausal patients with high breast density as well as patients with lobular histology seem to profit from preoperative MRI.

PurposeThe management of cervical cancer in pregnancy persists to be challenging. Therefore, identification of factors that influence the choice of therapeutic management is pivotal for an adequate patient counseling.MethodsWe present a literature review of 26 studies reporting 121 pregnancies affected by cervical cancer. Additionally, we add a retrospective case series of five patients with pregnancy-associated cervical cancer diagnosed and treated in our clinic between 2006 and 2013.ResultsThe literature review revealed that the therapeutic management during pregnancy varies according to the gestational age at diagnosis, while in the postpartum period no influence on the treatment choice could be detected. Also in our case series the choice of oncologic therapy was influenced by the gestational age, the wish to continue the pregnancy and the risks of delaying definitive treatment.ConclusionsThere are no standardized procedures concerning the treatment of cervical cancer in pregnancy. Therefore, in consultation with the patient and a multidisciplinary team, an adequate individualized treatment plan should be determined.Electronic supplementary materialThe online version of this article (doi:10.1007/s00404-015-3980-y) contains supplementary material, which is available to authorized users.