Role of adjuvant vaginal brachytherapy in early stage endometroid endometrial cancer

Hintergrund: Das Endometriumkarzinom (EC) ist die häufigste gynäkologische Tumorerkrankung. Nach einer Hysterektomie mit beidseitiger Adnexexstirpation und einer Lymphadenektomie (LNE) folgt eine stadienabhängige adjuvante Therapie. Diese erfolgt nach einer Risikostratifizierung unter Einbeziehung von Tumorausdehnung, histologischem Differenzierungsgrad (G) sowie klinisch-pathologischen Risikofaktoren (RF). Das Spektrum der Adjuvanz beim endometrioiden EC im FIGO-Stadium I umfasst eine Observation, eine intravaginale Brachytherapie (VBT), eine perkutane Beckenbestrahlung (EBRT), eine systemische Therapie oder eine Kombination dieser. Ziel der Studie war es, Überlebensdaten von Patientinnen mit frühem endometrioiden EC im FIGO-Stadium IB mit G2/G3 zu analysieren, die nach einer Hysterektomie mit Adnexexstirpation und einem Lymphknotenstaging eine adjuvante VBT erhielten. Ferner war die Frage, ob eine Subgruppe identifiziert werden kann, die von einer intensivierten Therapie profitieren könnte. Methoden: In die retrospektive Analyse wurden Patientinnen mit einem endometrioiden EC im FIGO-Stadium IB, ≥50% Myometriuminfiltration (MMI) mit G2 oder G3 eingeschlossen, die zwischen 2005 und 2017 behandelt wurden und nach einer Hysterektomie mit Adnexexstirpation und einer systematischen LNE eine alleinige VBT erhielten. Primäre Endpunkte waren das Gesamtüberleben (OS), das krankheitsfreie Überleben (DFS) und das Beckenrezidiv-freie Überleben (PRFS). Die Überlebensanalysen basierten auf Kaplan-Meier-Analysen. Ein Log-Rank-Test und Cox-Regressionsanalysen wurden verwendet, um den Zusammenhang zwischen RF und OS/DFS zu bestimmen. Abhängigkeiten zwischen RF und G wurden mittels Pearson-Chi-Quadrat-Test untersucht. Ergebnisse: 111 Patientinnen im FIGO-Stadium IB mit G2 (n=82) und G3 (n=29) nach VBT wurden eingeschlossen. Das 3-Jahres OS betrug 89,6%, das DFS 90,1% und das PRFS 92,8%. 98,2% der Frauen erhielten eine pelvine LNE, wovon bei 78,9% ≥10 Lymphknoten entfernt wurden. Mit einem statistisch signifikant schlechteren OS assoziiert waren eine größere Tumorausdehnung (p=0,001) und ein höherer nukleärer Atypiegrad (NG) (p=0,005). Ein signifikant schlechteres DFS wiesen Frauen mit einer Tumorinfiltration in das untere Uterinsegment (LUSI) (p=0,031), einer Tumorausdehnung >4cm (p=0,024) und <10 entfernten Lymphknoten (p=0,032) auf. 17 Patientinnen erlitten ein Rezidiv. Bei 94,1% und 76,5% der Frauen mit Rezidiv bestand initial eine LUSI respektive eine MMI von ≥66,6%. Schlussfolgerung: Die VBT als alleinige Adjuvanz zeigte bei Tumoren mit FIGO IB G2-3 exzellente Überlebensdaten mit guter lokoregionärer Kontrolle und kann bei Frauen ohne RF ausreichend sein. RF, die die Wahrscheinlichkeit für ein Rezidiv erhöhen waren ein größerer Primarius, LUSI und <10 entfernte pelvine Lymphknoten. In Kombination mit etablierten RF (G3, ≥50% MMI, lymphovaskuläre Invasion) könnte diese Subgruppe möglichweise von einer intensivierten adjuvanten Therapie profitieren.Objective: Endometrial cancer (EC) is the leading gynecologic malignancy in postmeno- pausal women. With atypical vaginal bleeding, as one of the early and often only symp- toms, this cancer type is frequently detected at an early stage. After a surgical staging with lymph node dissection (LNE) an adjuvant treatment follows. Clinicopathologic risk factors (RF) in the decision for a postoperative therapy are FIGO stage and grade (G). Guidelines for adjuvant treatment of FIGO stage I endometrioid EC are vague, and allow adjuvant treatment ranging from observation to pelvic radiotherapy (EBRT) and/or vaginal brachytherapy (VBT) with or without systemic therapy. An optimal treatment regimen of early stage EC therefore is lacking. The aims of this study were to assess outcomes and patterns of recurrence of a patient population with FIGO stage IB G2 or G3 endometrioid EC following comprehensive surgical staging and VBT as sole adjuvant treatment, and to determine whether there is a subset in this population with the highest risk of relapse, who would benefit from treatment intensification. Methods: FIGO stage IB G2 or G3 endometrioid EC patients treated with VBT following comprehensive surgical staging at an academic institution from January 2005 to Decem- ber 2017 were retrospectively reviewed. Inclusion criteria were endometrioid histology with G2 or G3 differentiation. Kaplan-Meier estimates were calculated for overall survival (OS), disease-free survival (DFS) and pelvic-recurrence free survival (PRFS). Log-rank test and multivariable Cox proportional hazards regression were evaluated for RF and survival outcomes. Results: 111 patients with G2 (n=82) or G3 (n=29) endometrioid EC were included. Pelvic LNE was performed in 98,2% (median of 17 lymph nodes dissected; 78,9% (n=86) ≥10 lymph nodes removed). All patients received VBT as sole adjuvant therapy. The median follow-up was 36 months. The 3-year OS, DFS and PRFS were 89,6%, 90,1% and 92,8%, respectively. A higher G was not associated with a poorer OS or DFS. Lower uterine segment involvement (LUSI) (p=0,031), tumor size >4cm (p=0,024), and <10 lymph nodes removed (p=0,032) were significantly associated with reduced DFS. A poorer OS was observed with a larger tumor size (p=0,001) and higher nuclear grade (p=0,005). Of 17 total recurrences, three were isolated locoregional (vaginal or pelvic), and 14 had dis- tant disease with (n=9) or without (n=5) a locoregional component. Conclusion: Surgically staged FIGO stage IB G2 and G3 endometrioid EC patients who were treated with adjuvant VBT only, showed excellent outcomes in terms of OS and DFS. Nevertheless, particularly in patients with additional RF for recurrence (larger tumor size, LUSI, ≥10 lymph nodes dissected) combined with already acknowledged RF (G3, ≥50% myometrial invasion (MMI) and lymphovascular invasion), we might have identified a subset of women in favor of an intensified treatment regimen i.e. EBRT

68Ga-PSMA-PET/CT-based radiosurgery and stereotactic body radiotherapy for oligometastatic prostate cancer

Background: Androgen deprivation therapy (ADT) remains the standard therapy for patients with oligometastatic prostate cancer (OMPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT)-based stereotactic body radiotherapy (SBRT) is emerging as an alternative option to postpone starting ADT and its associated side effects including the development of drug resistance. The aim of this study was to determine progression free-survival (PFS) and treatment failure free-survival (TFFS) after PSMA-PET/CT-based SBRT in OMPC patients. The efficacy and safety of single fraction radiosurgery (SFRS) and ADT delay were investigated. Methods: Patients with ≤ 5 metastases from OMPC, with/without ADT treated with PSMA-PET/CT-based SBRT were retrospectively analyzed. PFS and TFFS were primary endpoints. Secondary endpoints were local control (LC), overall survival (OS) and ADT-free survival (ADTFS). Results: Fifty patients with a total of 75 metastases detected by PSMA-PET/CT were analyzed. At the time of SBRT, 70% of patients were castration-sensitive. Overall, 80% of metastases were treated with SFRS (median dose 20 Gy, range: 16-25). After median follow-up of 34 months (range: 5-70) median PFS and TFFS were 12 months (range: 2-63) and 14 months (range: 2-70), respectively. Thirty-two (64%) patients had repeat oligometastatic disease. Twenty-four (48%) patients with progression underwent second SBRT course. Two-year LC after SFRS was 96%. Grade 1 and 2 toxicity occurred in 3 (6%) and 1 (2%) patients, respectively. ADTFS and OS rates at 2-years were 60.5% and 100%, respectively. In multivariate analysis, TFFS significantly improved in patients with time to first metastasis (TTM) >36 months (p = 0.01) and PSA before SBRT ≤ 1 ng/ml (p = 0.03). Conclusion: For patients with OMPC, SBRT might be used as an alternative to ADT. This way, the start/escalation of palliative ADT and its side effects can be deferred. Metastases treated with PSMA-PET/CT-based SFRS reached excellent LC with minimal toxicity. Low PSA levels and longer TTM predict elongated TFFS

Prolonged antibiotic prophylaxis after thoracoabdominal esophagectomy does not reduce the risk of pneumonia in the first 30days: a retrospective before-and-after analysis

PurposeThoracoabdominal esophageal resection for malignant disease is frequently associated with pulmonary infection. Whether prolonged antibiotic prophylaxis beyond a single perioperative dose is advantageous in preventing pulmonary infection after thoracoabdominal esophagectomy remains unclear.MethodsIn this retrospective before-and-after analysis, 173 patients between January 2009 and December 2014 from a prospectively maintained database were included. We evaluated the effect of a 5-day postoperative course of moxifloxacin, which is a frequently used antimicrobial agent for pneumonia, on the incidence of pulmonary infection and mortality after thoracoabdominal esophagectomy.Results104 patients received only perioperative antimicrobial prophylaxis (control group) and 69 additionally received a 5-day postoperative antibiotic therapy with moxifloxacin (prolonged-course). 22 (12.7%) of all patients developed pneumonia within the first 30days after surgery. No statistically significant differences were seen between the prolonged group and control group in terms of pneumonia after 7 (p=0.169) or 30days (p=0.133), detected bacterial species (all p>0.291) and 30-day mortality (5.8 vs 10.6%, p=0.274).ConclusionA preemptive 5-day postoperative course of moxifloxacin does not reduce the incidence of pulmonary infection and does not improve mortality after thoracoabdominal esophagectomy

A long short‐term memory based Schaeffer gesture recognition system

In this work, a Schaeffer language recognition system is proposed in order to help autistic children overcome communicative disorders. Using Schaeffer language as a speech and language therapy, improves children communication skills and at the same time the understanding of language productions. Nevertheless, the teaching process of children in performing gestures properly is not straightforward. For this purpose, this system will teach children with autism disorder the correct way to communicate using gestures in combination with speech reproduction. The main purpose is to accelerate the learning process and increase children interest by using a technological approach. Several recurrent neural network‐based approaches have been tested, such as vanilla recurrent neural networks, long short‐term memory networks,and gated recurrent unit‐based models. In order to select the most suitable model, an extensive comparison has been conducted reporting a 93.13% classification success rate over a subset of 25 Schaeffer gestures by using an long short‐term memory‐based approach. Our dataset consists on pose‐based features such as angles and euclidean distances extracted from the raw skeletal data provided by a Kinect v2 sensor.This work has been funded by the Spanish Government TIN2016-76515-R grant for the COMBAHO project, supported with Feder funds. This work has also been supported by a Spanish national grant for PhD studies FPU15/04516 and the grant "Ayudas para Estudios de Máster e Iniciación a la Investigación" from the University of Alicante. Experiments were made possible by a generous hardware donation from NVIDIA (Tesla K40)