Staging for Breast Cancer: A Comparison Between Old and New Approaches.

Background/Aim: Staging for breast cancer in advanced stages or prior to neoadjuvant chemotherapy is recommended to be performed with CT scan of the chest and abdomen and a bone scan. This recommendation is valid since 2012, when conventional staging with chest x-ray and ultrasound of the abdomen was replaced by the more sensitive CT scan. However, it remains unclear if this approach improves patient outcome and prognosis. Patients and Methods: We identified patients who were treated for breast cancer at the breast center of the St. Elisabeth Hospital, Cologne, in 2012 and 2014. Clinical information such as age at diagnosis, stage, tumor biology, grading, and the applied method for staging was abstracted from the patient chart. We also looked for local or distant recurrence and data of survival. Results: A total of 1,122 patients were identified. Of those, 104 patients developed local or distant recurrence and 54 died. Conventional staging with chest x-ray, abdominal ultrasound and a bone scan was more often in 2012 (482 cases) than in 2014 (135), but CT-staging was more often in 2014 (180 vs. 29 cases). In general, less patients were staged in 2014 than in 2012. There were no significant survival differences between the two groups. Conclusion: Staging habits changed in 2012 compared to 2014 according to the changes in guidelines. This change did not affect disease-free survival.

Staging for Breast Cancer: A Nationwide Survey about Adherence to Guidelines in German Breast Centers.

Introduction: The risk for metastasis at primary diagnosis of breast cancer is about 4%. The German guidelines give clear indications on when, who, and how to stage breast cancer patients. Ideally, this should be done via computerized axial tomography (CAT) scan of the thorax and abdomen and an additional bone scan. But daily practice shows that the way health-care providers handle staging recommendations can vary. To objectify adherence to guidelines we started a nation-wide survey. Methods: Between July and September 2020, we sent out a survey via email to all certified and noncertified breast centers and in addition to all Departments of Obstetrics and Gynecology in Germany. We asked for timing of staging, conditions that cause staging, and the applied method. In case we did not get any reply, we sent out a reminder. Results: A total of 220 certified breast centers, 28 noncertified breast centers, and 48 Departments of Obstetrics and Gynecology who care for breast cancer patients took part in our survey. A general pretherapeutic staging was performed in 16.4%, 39.3%, and 66.7% of all institutions and a general postoperative staging was performed in 4.1%, 0%, and 6.3% of each institutional type, respectively. In terms of the applied method, 75% of all certified breast centers used a CAT scan and bone scan, while 23.3% primarily used chest X-ray, ultrasound of the abdomen (27.7%), or MRI. As a potential reason for using X-ray and ultrasound, the presence of a "low-risk" breast cancer was mentioned. Summary: Although certified breast centers show the highest adherence to current guidelines, some still perform a general staging or do not use the recommended staging method. The low probability of primary metastatic breast cancer and the use of a reasonable exposure to radiation warrant a critical discussion.

Morbidity and quality of life in patients with vulvar cancer after inguinal sentinel lymphadenectomy compared to radical inguinofemoral lymphadenectomy.

AIM: Probability of survival of patients with vulvar cancer directly depends on the lymph node status. Surgery of lymph nodes can be performed as radical inguinofemoral lymphadenectomy or in cases with certain conditions as sentinel lymph node surgery. The aim of this study is to obtain an overview of the intervention-related morbidity and quality of life in patients with vulvar carcinoma after lymphadenectomy. METHODS: Quality of life and morbidity was compared between patients who underwent radical inguinofemoral lymphadenectomy with those who underwent sentinel lymph node surgery. RESULTS: All recorded postoperative complications occur more frequently in the non-sentinel group, Significant difference was shown for the occurrence of lymphedema (p-value = 0.024) and sensitivity loss (p-value = 0.024). Recurrence of disease was more frequent in the non-sentinel group (38 % vs. 20 %, p = 0.621, n.s.) and satisfaction with groin surgery is slightly higher in the sentinel group (94 % vs. 89 %, p = 1.000, n.s.). CONCLUSION: We could demonstrate a significantly lower morbidity of sentinel lymphadenectomy compared to conventional inguinofemoral lymphadenectomy while maintaining the same oncological safety. The low morbidity of sentinel- lymphadenectomy does not seem to influence the postoperative quality of life significantly. However, recording of the individual burden of lymphadenectomy by questionnaires should be optimized.

Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Antiangiogenic therapy has known activity in ovarian cancer. The investigator-initiated randomised phase 2 TRIAS trial assessed the multi-kinase inhibitor sorafenib combined with topotecan and continued as maintenance therapy for platinum-resistant or platinum-refractory ovarian cancer. METHODS: We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial at 20 sites in Germany. Patients (≥18 years) with platinum-resistant ovarian cancer previously treated with two or fewer chemotherapy lines for recurrent disease were stratified (first vs later relapse) in block sizes of four and randomly assigned (1:1) using a web-generated response system to topotecan (1·25 mg/m2 on days 1-5) plus either oral sorafenib 400 mg or placebo twice daily on days 6-15, repeated every 21 days for six cycles, followed by daily maintenance sorafenib or placebo for up to 1 year in patients without progression. Investigators and patients were masked to allocation of sorafenib or placebo; topotecan treatment was open label. The primary endpoint was investigator-assessed progression-free survival, analysed in all patients who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, number NCT01047891. FINDINGS: Between Jan 18, 2010, and Sept 19, 2013, 185 patients were enrolled, 174 of whom were randomly assigned: 85 to sorafenib and 89 to placebo. Two patients in the sorafenib group had serious adverse events before treatment and were excluded from analyses. 83 patients in the sorafenib group and 89 in the placebo group started treatment. Progression-free survival was significantly improved with sorafenib versus placebo (hazard ratio 0·60, 95% CI 0·43-0·83; p=0·0018). Median progression-free survival was 6·7 months (95% CI 5·8-7·6) with sorafenib versus 4·4 months (3·7-5·0) with placebo. The most common grade 3-4 adverse events were leucopenia (57 [69%] of 83 patients in the sorafenib group vs 47 [53%] of 89 in the placebo group), neutropenia (46 [55%] vs 48 [54%]), and thrombocytopenia (23 [28%] vs 20 [22%]). Serious adverse events occurred in 49 (59%) of 83 sorafenib-treated patients and 45 (51%) of 89 placebo-treated patients. Of these, events were fatal in four patients (5%) in the sorafenib group (dyspnoea and poor general condition, septic shock, ascites and dyspnoea, and sigma perforation) and seven (8%) in the placebo group (pulmonary embolism in two patients, disease progression in two patients, and one case each of sepsis with fever, pleural effusion, and tumour cachexia). Sorafenib was associated with increased incidences of grade 3 hand-foot skin reaction (three [13%] vs 0 patients) and grade 2 alopecia (24 [29%] vs 12 [13%]). INTERPRETATION: Sorafenib, when given orally in combination with topotecan and continued as maintenance therapy, showed a statistically and clinically significant improvement in progression-free survival in women with platinum-resistant ovarian cancer. These encouraging results support the crucial role of antiangiogenesis as the treatment backbone in combination with chemotherapy, making this approach attractive for further assessment with other targeted strategies. FUNDING: Bayer, Amgen, and GlaxoSmithKline.

The number of removed lymph nodes by inguinofemoral lymphadenectomy: impact on recurrence rates in patients with vulva carcinoma.

OBJECTIVE: Inguinal lymph node (LN) metastasis is a crucial prognostic factor in vulva carcinoma. The aim of this study was to determine the prognostic value of the number of resected LNs in patients with vulvar carcinoma on recurrence rates. METHODS: This retrospective study includes patients with vulvar squamous cell carcinoma who underwent inguinofemoral lymphadenectomy (IFL) between 1998 and 2011. Dissected groins were stratified by the number of removed lymph nodes (<6 LNs versus ≥6 LNs) or inguinal LN metastasis (pN- versus pN+) and analyzed according to groin, local and distance recurrence rates. RESULTS: In total 45 patients were identified and 79 groins were eligible for this analysis. 11 patients underwent ipsilateral IFL and 34 bilateral IFL. The median age was 58 years (range 31-80). The median tumor size was 2 cm (range 0.1-7.9). A median of 8 (range 0-19) LNs were resected per groin. Overall in 11 groins LN metastases were found. Groin recurrences occurred in four patients, local recurrence in six patients and distant metastasis in one patient. We did not observe any significant improvement in groin recurrence rates, local recurrence rates and distant recurrence rates if more than six LNs were removed per groin. Notably, patients with LN metastasis did not show higher recurrence rates compared to unaffected LNs. CONCLUSION: In this cohort we demonstrated that resection of more than six LNs per groin does not improve the recurrence rates in patients with carcinoma of the vulva. Further prospective studies with more individuals are needed to evaluate the role of resected LNs in vulvar carcinoma.

Estrogen receptor promoter methylation predicts survival in low-grade ovarian carcinoma patients.

PURPOSE: Ovarian carcinoma is the third most common gynecological cancer and only short recurrence-free survival and overall survival times are achieved. The role of the estrogen receptor expression is well studied in breast cancer and breast cancer cell lines. Patients with positive estrogen receptor expression have a lower risk for recurrence and a better overall survival. Previous studies have shown that ESR1 methylation influences ovarian cancer development and might thus play a role regarding prognosis of ovarian carcinoma. METHODS: A total of 75 patients were identified that were treated for ovarian carcinoma by debulking surgery and adjuvant standard chemotherapy. Isolation and bisulfite treatment of genomic DNA from serial sections of surgically resected ovarian carcinoma tissue was performed using commercially available kits. For the detection of methylated ESR1 promoter sequences, real-time methylation-specific PCR was used. RESULTS: Promoter methylation did not show a correlation between clinical-pathological data for all patients. However, within the subgroup of low-grade ovarian carcinoma patients and patients with an ovarian tumor of low malignant potential methylation of the ESR1 promoter inversely correlated with survival (p = 0.031). CONCLUSIONS: Although small numbers of ovarian carcinoma patients were analyzed, methylation status might be useful as a prognostic marker within the subgroup of low-grade ovarian carcinoma patients. Further studies should investigate a larger cohort and also address the use of demethylation agents with respect to improve patient's prognosis in this subgroup of ovarian carcinoma patients.

Intraoperative Boost Radiotherapy during Targeted Oncoplastic Breast Surgery: Overview and Single Center Experiences.

Breast-conserving surgery followed by whole-breast irradiation is the standard local therapy for early breast cancer. The international discussion of reduced importance of wider tumor-free resection margins than "tumor not touching ink" leads to the development of five principles in targeted oncoplastic breast surgery. IORT improves local recurrence risk and diminishes toxicity since there is less irradiation of healthy tissue. Intraoperative radiotherapy (IORT) can be delivered in two settings: an IORT boost followed by a conventional regimen of external beam radiotherapy or a single IORT dose. The data from TARGIT-A and ELIOT reinforce the conviction that intraoperative radiotherapy during breast-conserving surgery is a reliable alternative to conventional postoperative fractionated irradiation, but only in a carefully selected population at low risk of local recurrence. We describe our experiences with IORT boost (50 kV energy X-rays; 20 Gy) in combination with targeted oncoplastic breast surgery in a routine clinical setting. Our experiences demonstrate the applicability and reliability of combining IORT boost with targeted oncoplastic breast surgery in breast-conserving therapy of early breast cancer.

Detection of c-kit point mutation Asp-816 --> Val in microdissected pooled single mast cells and leukemic cells in a patient with systemic mastocytosis and concomitant chronic myelomonocytic leukemia.

The c-kit mutation Asp-816-->Val is detectable not only in neoplastic mast cells (MCs) in patients with systemic mastocytosis (SM) but also in most associated hematologic non-MC lineage disease (AHNMD). In order to prove a monoclonal disease evolution we investigated DNA of pooled microdissected single cells for the presence of the mutation in a patient with SM and concomitant chronic myelomonocytic leukemia (CMML). LightCycler melting curve analysis and direct sequencing of nested polymerase chain reaction (PCR) products revealed the c-kit mutation in tryptase-positive MC and in leukemic CD15-positive cells in bone marrow infiltrates, but not in colonic epithelial cells, thus, suggesting a monoclonal evolution of SM and concurrent CMML on the basis of a somatic mutation in a common hematologic progenitor.