Background
The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph node micrometastases on survival ...remains unclear. There are no consistent recommendations for adjuvant chemotherapy (CHT). In this context, we aimed to investigate the impact of micrometastases on the clinical outcome of breast cancer patients according to the adjuvant CHT performed.
Patients and methods
We conducted a retrospective population-based registry study of 26,465 patients aged between 24 and 97 years with primary breast cancer diagnosed between 2003 and 2017. Of these patients, 8856 with early breast cancer were eligible for analysis: 8316 (93.9%) were node negative and 540 (6.1%) had lymph node micrometastases.
Results
The median follow-up was 7.2 years, with a confidence interval (CI) of 7.1–7.3 years. Patients with lymph node micrometastases (pN1mi) without adjuvant CHT have reduced 10-year overall survival (OS) and recurrence-free survival (RFS) compared to patients who had axillary lymph node micrometastases and received an adjuvant CHT. However, this effect disappeared after adjustment for age, tumor size and tumor grading. Furthermore, in the group of patients with lymph node micrometastases, the administration of adjuvant CHT did not improve OS or RFS, compared to patients with lymph node micrometastases without adjuvant CHT: hazard ratio for treated patients was 1.51 (95% CI 0.80–2.85,
p
= 0.208) for OS and 1.12 (95% CI 0.63–1.97,
p
= 0.705) for RFS.
Conclusion
Patients with axillary lymph node micrometastases showed a comparable outcome to node negative patients and their outcome was not significantly improved with CHT. Thus, axillary lymph node micrometastases should not be considered in the treatment decision.
Thromboembolism is a common adverse event in women treated with tamoxifen (TAM) for breast cancer. The risk in male breast cancer patients is poorly investigated. We aimed to examine the risk of ...thrombotic events after TAM in male breast cancer patients.
In this prospective cohort study, 448 patients treated between May 2009 and July 2017 for male breast cancer (BC) were assessed for eligibility. Patients with follow-up shorter than 6 months were excluded. The cumulative risk of thromboembolism was evaluated.
The median follow-up was 47 months (range 6-101 months) with a median age of 69.4 years (range 27-89 years). Oestrogen receptor and progesterone receptor expression levels were observed in 98.3 and 94.9% of cases, respectively. During the follow-up period, thrombotic events were documented in 21 (11.9%) of 177 patients receiving TAM and in 1 (2.5%) of 41 patients who did not receive tamoxifen. The estimated incidence was 51.9 per 1000 person-years and 21.5 per 1000 person-years, respectively. Notably, the highest risk was identified in the first 18 months, where 81% of the observed thrombotic events occurred. Patients aged older than 71 years had a significantly increased risk of thrombotic event under TAM treatment than their younger counterparts (p = 0.033). History of thrombotic event, cardiovascular and liver disease, as well as additional adjuvant treatment were not associated with increased thrombotic risk.
The risk of thrombotic event in men treated with TAM for breast cancer is markedly increased in the first 18 months of treatment, and should be considered during treatment decisions.
Background
The positive effect of systematic lymphadenectomy on survival of patients with endometrial cancer is a topic of ongoing debate.
Methods
We aimed to investigate whether systemic ...lymphadenectomy is beneficial for patients with early endometrial cancer. For this purpose, we analyzed a population-based registry with of 2392 women with endometrioid endometrial cancer, stage I and II at intermediate and high risk of recurrence. The primary outcome measure was overall survival.
Results
After exclusions, 868 women were eligible for analysis. Of those, 511 and 357 were categorized as intermediate (pT1A G3 and pT1B G1-2) and high risk (pT1B G3 and pT2 G1-3) early stage endometrial cancer, respectively. Lymphadenectomy was performed in 527 (60.7%) of the cases. Patients in the lymphadenectomy group were significantly younger, presented with more tumors of intermediate or undifferentiated grade and exhibited significantly lower co-morbidity rates and Eastern Cooperative of Oncology Group (ECOG) performance status. Median follow-up was 6.7 years. Recurrence-free survival was not improved by lymphadenectomy in the intermediate and high-risk group of patients. During the follow-up period, 111 (12.8%) women had disease recurrence and 302 (34.8%) died. Systematic lymphadenectomy was associated with significant improvement of overall survival in the pT1A G3 and pT1B G3 patient subgroups. Notably, adjustment for patient age and ECOG status abolished the improvement of overall survival by systematic lymphadenectomy in all groups. Thus, lymphadenectomy did not improve recurrence-free survival in the intermediate risk or the high-risk group of patients
Conclusions
Systematic pelvic and para-aortic lymphadenectomy did not improve the survival of patients with early stage I and II endometrioid endometrial cancer at intermediate and high risk of recurrence.
Purpose
The usage of radioactive Technetium
99m
(Tc
99m
) 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 Technetium
99m
(Tc
99m
) 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 Technetium
99m
(Tc
99m
) 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 Tc
99m
. The conventional Technetium
99m
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 Tc
99m
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.
The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed ...and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.
Purpose
Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients and relevant for therapeutic strategies. We evaluated the clinical ...value of indocyanine green (ICG) by measuring the sensitivity and negative predictive value of sentinel lymph node mapping compared with the gold standard of complete lymphadenectomy in detecting lymph node metastases for cervical cancer.
Methods
We utilized the near-infrared imaging agent ICG to detect tumor-infested lymph nodes in the pelvis analogue to a classical sentinel lymph node procedure by analyzing data from 20 patients who had undergone surgery for cervical cancer at our institution. A laparoscopic lymph node mapping procedure by means of ICG, followed by a complete pelvic lymphadenectomy with or without paraaortic lymphadenectomy was done in all patients.
Results
Histological examination identified seven patients with tumor-positive pelvic nodes, whereas mapping with ICG identified only five of these patients. Detection rate of positive nodes by ICG mapping and false negative rate was 71.4% and 28.6%, respectively; bilateral detection rate was 83.3%. One of the two false negative patients additionally suffered from deep infiltrating endometriosis.
Conclusions
Our results indicate that ICG can identify the relevant pelvic nodes independent of tumor size, provided bilateral detection is achieved and additional, related diseases are excluded.
Trial Registration
This trial is registered within the German Clinical Trial Register (DRKS-ID: DRKS00014692).
Background
As the population at risk for pelvic nodal involvement remains poorly described, the role of pelvic lymphadenectomy (LAE) in vulvar squamous cell cancer (VSCC) has been a matter of ...discussion for decades.
Methods
In the AGO-CaRE-1 study, 1618 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB or higher primary VSCC treated at 29 centers in Germany between 1998 and 2008 were documented. In this analysis, only patients with pelvic LAE (
n
= 70) were analyzed with regard to prognosis and correlation between inguinal and pelvic lymph node involvement.
Results
The majority of patients had T1b/T2 tumors (
n
= 47; 67.1%), with a median diameter of 40 mm (2–240 mm); 54/70 patients (77.1%) who received pelvic LAE had positive groin nodes. For 42 of these 54 patients, the number of affected groin nodes had been documented as a median of 3; 14/42 (33.3%) of these patients had histologically confirmed pelvic nodal metastases (median number of affected pelvic nodes 3 1–12). In these 14 patients, the median number of affected groin nodes was 7 (1–30), with a groin metastases median maximum diameter of 42.5 mm (12–50). Receiver operating characteristic analysis showed an area under the curve of 0.85, with 83.3% sensitivity and 92.6% specificity for the prediction of pelvic involvement in cases of six or more positive groin nodes. No cases of pelvic nodal involvement without groin metastases were observed. Prognosis in cases of pelvic metastasis was poor, with a median progression-free survival of only 12.5 months.
Conclusion
For the majority of node-positive patients with VSCC, pelvic nodal staging appears unnecessary since a relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease.
The aim of the current study was to investigate the role of promoter methylation of adenomatous polyposis coli (APC) and epithelial cadherin (E‐cadherin) genes in endometrial tumorigenesis. The ...methylation status of both genes was investigated in 43 cases of normal endometrium, 21 simple hyperplasia, 17 atypical hyperplasia, and 86 endometrial carcinoma (EC). Additionally, the methylation pattern of both genes was analyzed in 24 primary ECs and their corresponding metastases. DNA methylation of the APC gene increased from atypical hyperplasia (23.5%) to endometrial carcinoma, reaching its highest level of 77.4% in early stage cancer (FIGO I and II) and decreasing stepwise to 24.2% in advanced stage carcinomas (FIGO III and IV). No methylation of APC was found in normal endometrium or simple hyperplasia. Methylation of E‐cadherin was found only in EC (22.1%). The mean age of the patients with aberrant APC methylation was 68.8 years and was significantly higher compared to the mean age (60.9 years) of the patients without methylation of APC promoter (P = 0.02). APC promoter methylation significantly correlated with decreased protein expression of APC (P = 0.039), with increased expression of the Ki‐67 proliferative marker (P = 0.006) and decreased metastatic potential (P = 0.002). There was no correlation between APC and E‐cadherin methylation patterns and the other clinicopathologic features, nor with patient outcome. Our results suggest that hypermethylation of APC promoter region is an early event in endometrial tumorigenesis. (Cancer Sci 2009)
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.
Purpose
Due to insufficient and conflicting prospective evidence, the recommendations on when to apply adjuvant radiochemotherapy in early-stage cervical cancer vary between international guidelines. ...In this population-based study, we evaluated the outcome of patients with early-stage cervical cancer based on risk factors and the adjuvant therapy they received.
Methods
The effect of primary therapy (surgery and radiochemotherapy RCT, surgery and radiotherapy RT, and surgery alone) on overall survival (OS) and recurrence-free survival (RFS) was evaluated in the complete cohort of 442 patients and in subgroups according to risk profile and nodal status.
Results
In low-risk patients, there was no difference in OS (
p
= 0.276) depending on whether patients received adjuvant therapy or not. Concerning RFS, patients with RT (including one patient with RCT) exhibited a significantly worse outcome compared to the group with surgery alone (
p
= 0.015). In intermediate-risk patients, the administration of adjuvant RT significantly benefited RFS when compared to surgery only in multivariate analysis (
p
= 0.031). Concerning OS, no significant influence for adjuvant treatment could be seen (
p
= 0.354). Though trends towards better OS and RFS could be observed in patients of the high-risk group—both in RCT and RT groups compared to surgery alone—the effects did not prove to be significant.
Conclusion
Our study reaffirms the evidence against the use of adjuvant radio(chemo)therapy in low-risk early-stage cervical cancer. In intermediate-, and less pronounced in high-risk patients, however, it seems to be beneficial. The role of adjuvant radio(chemo)therapy in early cervical cancer should be further investigated in prospective randomized trials.