Influences on pathologic complete response in breast cancer patients after neoadjuvant chemotherapy

Purpose Pathologic complete response is associated with longer disease-free survival and better overall survival after neoadjuvant chemotherapy in breast cancer patients. We, therefore, evaluated factors influencing pathologic complete response. Methods Patients receiving neoadjuvant chemotherapy from 2015 to 2018 at the Saarland University Hospital were included. Patients’ age, tumor stage, tumor biology, genetic mutation, recurrent cancer, discontinuation of chemotherapy, and participation in clinical trials were extracted from electronic medical records. Binary logistic regression was performed to evaluate the influence of these factors on pathologic complete response. Results Data of 183 patients were included. The median patient’s age was 54 years (22–78). The median interval between diagnosis and onset of chemotherapy was 28 days (14–91); between end of chemotherapy and surgery 28 days (9–57). Sixty-two patients (34%) participated in clinical trials for chemotherapy. A total of 86 patients (47%) achieved pathologic complete response. Patient’s age, genetic mutation, recurrent cancers, or discontinuation of chemotherapy (due to side effects) and time intervals (between diagnosis and onset of chemotherapy, as well as between end of chemotherapy and surgery) did not influence pathologic complete response. Patients with high Ki67, high grading, Her2 positive tumors, as well as patients participating in clinical trials for chemotherapy had a higher chance of having pathologic complete response. Patients with Luminal B tumors had a lower chance for pathologic complete response. Conclusion Particularly patients with high risk cancer and patients, participating in clinical trials benefit most from chemotherapy. Therefore, breast cancer patients can be encouraged to participate in clinical trials for chemotherapy

Factors influencing the time to surgery after neoadjuvant chemotherapy in breast cancer patients

Purpose It is suspected that delayed surgery after neoadjuvant chemotherapy (NACT) leads to a worse outcome in breast cancer patients. We therefore evaluated possible influencing factors of the time interval between the end of NACT and surgery. Methods All patients receiving NACT due to newly diagnosed breast cancer from 2015 to 2017 at the Department of Gynecology, Saarland University Medical Center, were included. The time interval between end of NACT and surgery was defined as primary endpoint. Possible delaying factors were investigated: age, study participation, outpatient and inpatient presentations, implants/expander, MRI preoperatively, discontinuation of chemotherapy, and genetic mutations. Results Data of 139 patients was analyzed. Median age was 53 years (22–78). The time interval between end of NACT and surgery was 28 days (9–57). Additional clinical presentations on outpatient basis added 2 days (p = 0.002) and on inpatient basis added 7 days to time to surgery (p < 0.001). Discontinuation of NACT due to chemotherapy side effects prolonged time to surgery by 8 days (p < 0.001), whereas discontinuation due to disease progress did not delay surgery (p = 0.6). In contrast, a proven genetic mutation shortened time to surgery by 7 days (p < 0.001). Patient’s age, participation in clinical studies, oncoplastic surgery, and preoperative MRI scans did not delay surgery. Conclusion Breast care centers should emphasize a reduction of clinical presentations and a good control of chemotherapy side effects for breast cancer patients to avoid delays of surgery after NACT

Uterine Leiomyosarcoma

Uterine leiomyosarcoma (uLMS) is a rare entity among malignant gynecologic tumors with a very unfavorable prognosis and the highest prevalence in the pre- and peri-menopause. Only early-stage tumors have an acceptable prognosis, provided the patient has been treated without injuring the uterus. uLMS is often diagnosed accidentally and the correct diagnosis ishampered by equivocal features similar to the far more frequent benign uterine fibroids. Surgery is the basis of therapy, and it should be done in order to remove the uterus intact. As vaginal, abdominal, and endoscopic surgery – possibly including morcellation – are the methods of choice for the treatment of uterine fibroids, pre-operatively undiagnosed leiomyosarcoma detected by pathologic examination will have a worsened prognosis. Systemic treatment and radiotherapy are of no proven value in the adjuvant setting. Thus, there is strong need for a reliable pre-operative risk score for leiomyosarcoma in order to justify diagnostic means beyond clinical routine and to choose the correct surgical pathway. The clinical problems in the diagnosis of leiomyosarcoma and treatment are exemplified by a case report of a 30-year-old childless patient. Diagnostic tools as well as treatment options in adjuvant and palliative situations are reviewed

Neurologic Consultations and Headache during Pregnancy and in Puerperium : A Retrospective Chart Review

Headache is a common symptom during pregnancy and in puerperium that requires careful consideration, as it may be caused by a life-threatening condition. Headaches in pregnant women and women in puerperium are classified as primary or secondary; acute, severe and newly diagnosed headaches should prompt further investigation. We aimed to further characterise the demographic features, symptoms, examination findings, and neuroimaging results of cases of headache during pregnancy and in puerperium. All pregnant women or women in postpartum conditions who attended neurological consultations at the emergency department of the clinic for Gynaecology, Obstetrics and Reproductive Medicine of Saarland University/Germany between 2001/2015 and 2012/2019 were enrolled in this retrospective chart review. Data collected from the charts included demographic/pregnancy characteristics, clinical features and imaging findings. Descriptive statistics as well as binary logistic regression were performed. More than 50% of 97 patients had abnormal findings in their neurological examination. Magnetic resonance imaging findings were pathological for almost 20% of patients—indicating conditions such as cerebral venous thrombosis, reversible posterior leukoencephalopathy, brain tumour and intracranial bleeding. The odds of abnormal neuroimaging results were 2.2-times greater among women with abnormal neurological examination findings than among those with normal examination results. In cases of headache during pregnancy and in puerperium, neuroimaging should be indicated early on. Further research is needed to determine which conditions indicate a need for immediate neuroimaging

Comparison of intraoperative radiotherapy as a boost vs. simultaneously integrated boosts after breast-conserving therapy for breast cancer

BackgroundCurrently, there are no data from randomized trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost in women at high risk of local recurrence. The aim of this retrospective analysis was to compare the toxicity and oncological outcome of IORT or simultaneous integrated boost (SIB) with conventional external beam radiotherapy (WBI) after breast conserving surgery (BCS).MethodsBetween 2009 and 2019, patients were treated with a single dose of 20 Gy IORT with 50 kV photons, followed by WBI 50 Gy in 25 or 40.05 in 15 fractions or WBI 50 Gy with SIB up to 58.80–61.60 Gy in 25–28 fractions. Toxicity was compared after propensity score matching. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan–Meier method.ResultsA 1:1 propensity-score matching resulted in an IORT + WBI and SIB + WBI cohort of 60 patients, respectively. The median follow-up for IORT + WBI was 43.5 vs. 32 months in the SIB + WBI cohort. Most women had a pT1c tumor: IORT group 33 (55%) vs. 31 (51.7%) SIB group (p = 0.972). The luminal-B immunophenotype was most frequently diagnosed in the IORT group 43 (71.6%) vs. 35 (58.3%) in the SIB group (p = 0.283). The most reported acute adverse event in both groups was radiodermatitis. In the IORT cohort, radiodermatitis was grade 1: 23 (38.3%), grade 2: 26 (43.3%), and grade 3: 6 (10%) vs. SIB cohort grade 1: 3 (5.1%), grade 2: 21 (35%), and grade 3: 7 (11.6%) without a meaningful difference (p = 0.309). Fatigue occurred more frequently in the IORT group (grade 1: 21.7% vs. 6.7%; p = 0.041). In addition, intramammary lymphedema grade 1 occurred significantly more often in the IORT group (11.7% vs. 1.7%; p = 0.026). Both groups showed comparable late toxicity. The 3- and 5-year local control (LC) rates were each 98% in the SIB group vs. 98% and 93% in the IORT group (LS: log rank p = 0.717).ConclusionTumor bed boost using IORT and SIB techniques after BCS shows excellent local control and comparable late toxicity, while IORT application exhibits a moderate increase in acute toxicity. These data should be validated by the expected publication of the prospective randomized TARGIT-B study

H2BFWT Variations in Sperm DNA and Its Correlation to Pregnancy

Abnormalities in sperm nuclei and chromatin can interfere with normal fertilization, embryonic development, implantation, and pregnancy. We aimed to study the impact of H2BFWT gene variants in sperm DNA on ICSI outcomes in couples undergoing ART treatment. One hundred and nineteen partners were divided into pregnant (G1) and non-pregnant (G2) groups. After semen analysis, complete DNA was extracted from purified sperm samples. The sequence of the H2BFWT gene was amplified by PCR and then subjected to Sanger sequencing. The results showed that there are three mutations in this gene: rs7885967, rs553509, and rs578953. Significant differences were shown in the distribution of alternative and reference alleles between G1 and G2 (p = 0.0004 and p = 0.0020, respectively) for rs553509 and rs578953. However, there was no association between these SNPs and the studied parameters. This study is the first to shed light on the connection between H2BFWT gene variants in sperm DNA and pregnancy after ICSI therapy. This is a pilot study, so further investigations about these gene variants at the transcriptional and translational levels will help to determine its functional consequences and to clarify the mechanism of how pregnancy can be affected by sperm DNA

<i>H2BFWT</i> Variations in Sperm DNA and Its Correlation to Pregnancy

Abnormalities in sperm nuclei and chromatin can interfere with normal fertilization, embryonic development, implantation, and pregnancy. We aimed to study the impact of H2BFWT gene variants in sperm DNA on ICSI outcomes in couples undergoing ART treatment. One hundred and nineteen partners were divided into pregnant (G1) and non-pregnant (G2) groups. After semen analysis, complete DNA was extracted from purified sperm samples. The sequence of the H2BFWT gene was amplified by PCR and then subjected to Sanger sequencing. The results showed that there are three mutations in this gene: rs7885967, rs553509, and rs578953. Significant differences were shown in the distribution of alternative and reference alleles between G1 and G2 (p = 0.0004 and p = 0.0020, respectively) for rs553509 and rs578953. However, there was no association between these SNPs and the studied parameters. This study is the first to shed light on the connection between H2BFWT gene variants in sperm DNA and pregnancy after ICSI therapy. This is a pilot study, so further investigations about these gene variants at the transcriptional and translational levels will help to determine its functional consequences and to clarify the mechanism of how pregnancy can be affected by sperm DNA

Uterine Leiomyosarcoma

Uterine leiomyosarcoma (uLMS) is a rare entity among malignant gynecologic tumors with a very unfavorable prognosis and the highest prevalence in the pre- and peri-menopause. Only early-stage tumors have an acceptable prognosis, provided the patient has been treated without injuring the uterus. uLMS is often diagnosed accidentally and the correct diagnosis ishampered by equivocal features similar to the far more frequent benign uterine fibroids. Surgery is the basis of therapy, and it should be done in order to remove the uterus intact. As vaginal, abdominal, and endoscopic surgery – possibly including morcellation – are the methods of choice for the treatment of uterine fibroids, pre-operatively undiagnosed leiomyosarcoma detected by pathologic examination will have a worsened prognosis. Systemic treatment and radiotherapy are of no proven value in the adjuvant setting. Thus, there is strong need for a reliable pre-operative risk score for leiomyosarcoma in order to justify diagnostic means beyond clinical routine and to choose the correct surgical pathway. The clinical problems in the diagnosis of leiomyosarcoma and treatment are exemplified by a case report of a 30-year-old childless patient. Diagnostic tools as well as treatment options in adjuvant and palliative situations are reviewed