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Purpose: Data from randomized controlled trials in high-grade endometrial cancer are scarce due to its low prevalence. Therefore, guideline recommendations in this cancer subtype rely on relatively few randomized trials and data from retrospective studies. The aim of this study was to evaluate the benefits from guideline-concordant therapy in high-grade endometrial cancer in a real-world patient group. Methods: The effect of treatment according to German S3 guidelines and the former S2k guideline on overall survival (OS) and recurrence-free survival (RFS) was evaluated in a cohort of 293 high-grade endometrial cancer patients. Results: Treatment concordant with the S3 guideline significantly improved OS (HR 0.623, CI 0.420–0.923, p = 0.018) and RFS (HR 0.578, CI 0.387–0.863, p = 0.007). Treatment concordant with the S2k guideline did not result in a significantly higher OS (HR 0.783, CI 0.465–1.316, p = 0.335) or RFS (HR 0.741, CI 0.347–1.740, p = 0.242). Conclusion: Therapy according to the German S3 guideline improved OS and RFS in univariate as well as multivariate analysis in this cohort of high-grade endometrial cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: The usage of radioactive Technetium99m (Tc99m) colloid for the purpose of sentinel lymph node biopsy (SLNB) in early breast cancer is considered the gold standard in Germany. However, new tracers, such as near-infrared (NIR) imaging agents like indocyanine green (ICG) could offer an alternative in future, as they overcome drawbacks associated with radioactive Technetium99m (Tc99m) like limited availability, high costs and radioactivity exposure for both patients and surgeons. Methods: In this double-arm retrospective study, we sought to establish the usefulness of indocyanine green as an alternative or an addition to the conventional Technetium99m (Tc99m) in the identification of the SLN in early breast cancer. Results: Among the 161 patients who underwent primary SLNB, 34 patients had at least 1 SLN with metastasis. Among these patients with SLN metastasis, 33 had the SLN detected by ICG; while 31 had the SLN detected by Tc99m. The conventional Technetium99m radiotracer failed to detect 2 patients with metastasis in this Arm of the study. Among the 87 patients who underwent SLNB after NACT, 13 patients had at least 1 SLN with metastasis. Among these 13 patients with SLN metastasis, ICG and Tc99m had detected the SLN among 12 patients, while 1 patient had been detected by ICG alone. Conclusions: Our results show that ICG is as effective as the radioisotope for SLNB even among patients who have undergone NACT. This trial is registered with the German Clinical Trial Register, ID: DRKS00013606. [ABSTRACT FROM AUTHOR]

Objective: The primary therapy for intermediate- and high-risk endometrial cancer includes pelvic and paraaortic lymph node evaluation. Laparoscopic surgery is an increasingly popular intervention due to decreased risk and better short-term morbidity; however, a recent study casts doubt on the benefit of this approach in terms of oncological safety. In this cancer registry study, we sought to evaluate the benefit of laparoscopy versus laparotomy and retrospectively compared overall survival, recurrence rates, and recurrence-free survival among patients with intermediate- and high-risk endometrial cancer who underwent either laparoscopic or open surgery. Methods: This observational study included 419 patients who have been treated from 2011 to 2017. We employed Kaplan–Meier method, and univariable and multivariable Cox-regression to compare overall survival, recurrence rates, and recurrence-free survival in 110 patients, who underwent laparoscopic, with 309 patients, who underwent open surgery. To address the confounding bias in this retrospective study, we also performed a propensity score matching (PSM) analysis including 357 patients (laparoscopy: n = 107; open surgery: n = 250). Results: We found a benefit for laparoscopic over open surgery in patients with intermediate- and high-risk endometrial cancer for overall survival in both univariable (p = 0.002; PSM: p = 0.016) and multivariable analyses (p = 0.019; PSM: p = 0.007). In contrast, there was no statistically significant difference between both patient groups regarding the cumulative recurrence rates. A univariable analysis identified a significant benefit for laparoscopy regarding recurrence-free survival (p = 0.003; PSM: p = 0.029) but a multivariable analysis failed to confirm this finding (p = 0.108; PSM: p = 0.118). Conclusions: Our study provides evidence that laparoscopic systematic lymphadenectomy does not present a lower oncological efficacy than open surgery in the treatment of patients with endometrial cancer. [ABSTRACT FROM AUTHOR]

Purpose: The lack of prognostic data impedes implementation of optimal therapy for cervical cancer. For instance, recommended therapy for FIGO IIB cervical cancer is radical hysterectomy or radiochemotherapy. To enlighten different therapeutic approaches, we investigated the benefit of individual therapies or combination thereof in patients with or without infested lymph nodes. Methods: The German Tumor Centre Regensburg registered 389 patients with FIGO IIB, IIIA, IIIB, and IVA cervical cancer between 2002 and 2015. We estimated hazard ratios (HR) for overall survival against different therapies using univariable and multivariable cox regression. After risk adjustment with respect to clinicopathological parameters, we performed model selection using conditional stepwise reverse selection. Results: We demonstrated the need for thorough assessment of the nodal status to obtain reliable data for treatment strategy. Our analysis showed significant differences for overall survival in FIGO IIB depending on therapy and nodal status. Outcome was inferior with radiochemotherapy without surgery for patients with N0 compared to surgery and radiochemotherapy combined (HR 3.012; 95% CI 1.075–8.441; p = 0.036); however, for N1, radiochemotherapy without surgery resulted in comparable outcome (HR 0.808; 95% CI 0.189–3.403; p = 0.765), whereas surgery alone yielded in poor outcome (HR 2.889; 95% CI 1.356–6.156; p = 0.006). Regardless of the nodal status, chemotherapy was superior in advanced stage cervical cancer FIGO III to IVA. Conclusions: Our study suggests that in terms of oncological outcome FIGO IIB cervical cancer patients benefit from a combination of surgery and radiochemotherapy. However, in the presence of lymph node infestation, surgery does not add substantial benefit to the patient. [ABSTRACT FROM AUTHOR]

Purpose: The recommended therapy for type I FIGO IB endometrial cancer (EC) is hysterectomy and adnexectomy, but the therapeutic benefits of additional pelvic and paraaortic lymph node dissection (LND) are still under discussion. In this study, we retrospectively evaluated overall survival (OAS) and recurrence-free survival (RFS) among patients with type I FIGO IB EC who did undergo systematic or elective lymphadenectomy or none at all.Methods: We selected 299 individuals from the database of the German Tumor Centre Regensburg who were diagnosed between 1998 and 2015 with endometrial adenocarcinoma of the uterus type I FIGO IB. We applied multivariable Cox regression to the selected patient data and estimated hazard ratios for OAS and RFS against the performed intervention. Further, we carried out risk adjustments with respect to clinicopathological parameters, and performed model selection using conditional stepwise forward selection.Results: We observed significant benefits of LND in the unadjusted survival analysis; however, we did not confirm this effect in multivariable regression analysis upon risk adjustment. In this case, hazard ratio (HR) for OAS in patients without LND versus patients with LND is reduced to 1.214 (95% CI 0.771-1.911; p = 0.402), HR for RFS is 1.059 (95% CI 0.689-1.626; p = 0.795). Similarly, we were also able to eliminate the statistical benefit of systematic versus elective LND by risk adjustment.Conclusions: In contrast to previous observations in high-grade EC, our study provides compelling evidence that LND, in particular systematic lymphadenectomy, is not beneficial for patients with type I FIGO IB EC in terms of long-term OAS and RFS. [ABSTRACT FROM AUTHOR]

Strategies for diagnosis and therapy in which sex steroid receptor ligands serve as carriers for radionuclides are attractive because a high incidence of carcinomas of the female genital tract and the breast that are seen clinically have an abundant expression of one or more of the receptor proteins. A radiohalogenated estrogen receptor (ER) ligand, 16α-[I]iodo-17β-estradiol [I]E, has met clinical criteria for receptor-mediated diagnostic imaging. Its []I-labeled sister nuclide derivative [I]E decays by orbital electron capture with emission of very-low-energy (Auger) electrons, which gives this latter radiohalogen the potential to serve in pharmaceuticals for radiotherapy; as examples, [I]deoxyuridine, when incorporated into the DNA molecule, or [I]E, when bound to the receptor within ER-rich tumor cells, are both cytotoxic in vitro. Whereas the mechanisms and subcellular changes that accompany the cytotoxicity from [I]deoxyuridine are well documented in the form of aberrations and breaks in the cellular DNA, the effects at the subcellular level causing the cytotoxicity of the sex steroid receptor ligand [I]E have not been characterized and are the focus of our study. We found that in a standard colonyforming assay the addition of [I]E to the cultures decreased the survival rate of ER-positive MCF-7 cells in a dose-dependent manner. The decreased survival rate was prevented by the addition of competing excess radioinert ER ligand (diethylstilbestrol); [I]E did not reduce survival in ER-negative MCF-7 cells. The [I]E-induced and ER-mediated cytotoxicity was accompanied by aberrations in the DNA components of the nuclei of the cells. These included chromatid and chromosome breaks, gaps, and tri-radial chromosome formation. Our findings add plausibility and credence to the notion that the cytotoxicity imparted by Auger-electron-emitting radioligands for sex steroid receptors is in part attributable to radiodecay that causes double-stranded breakage of DNA. [ABSTRACT FROM AUTHOR]