Contralateral lymph node metastases in patients with vulvar cancer and unilateral sentinel lymph node metastases

Introduction The risk of contralateral lymph node metastases following unilateral sentinel lymph node (SLN) metastases in patients with vulvar cancer(s) remains to be systematically assessed. Material and methods We performed a multicenter, retrospective registry-based study of 476 patients with vulvar cancer. The primary outcome measure was the rate of contralateral non-SLN metastases in the case of positive unilateral SLN. Results Out of 476 patients with primary vulvar cancer, 202 received SLN biopsy: 58 unilateral and 144 bilateral. Out of 66 patients with unilateral metastatic SLN, 62 (93.9%) received contralateral lymphadenectomy—18 after unilateral and 44 after bilateral SLN biopsy. In the study group, 132 SLN were assessed with a median number of 2 (range 1–4) per patient and 76 of these were positive. Lymph node-positivity was associated with advanced tumor stage, as well as lymph and vascular space invasion. In the group of patients with bilateral inguino-femoral lymphadenectomy, 1004 lymph nodes were resected with a median number of 15 (range 10–29) per patient. After full dissection of the inguino-femoral lymph nodes, no contralateral non-SLN metastases were found. Conclusions The risk of contralateral non-SLN metastases in patients with unilateral SLN metastases was low. Therefore, the impact of contralateral lymphadenectomy on patient survival should be investigated in further studies

Clinical feasibility of (neo)adjuvant taxane-based chemotherapy in older patients: analysis of >4,500 patients from four German randomized breast cancer trials

Introduction Despite the fact that people older than 65 years of age have the highest incidence of developing breast cancer, these patients are excluded from clinical trials in most cases. Furthermore, most physicians tend towards therapy regimens without the use of dose-dense, highly active taxane-based treatments because of a lack of data regarding toxicities of these compounds in older patients. Methods Pooled side-effect data were analyzed from four prospective, randomized clinical trials in which patients of different age groups (60 years, between 60 and 64 years, and 64 years) with primary breast cancer received taxane-based chemotherapy. Results Dose delays, dose reductions, hospitalization, and therapy discontinuation increased with age. Hematologic toxicities and some nonhematologic toxicities were generally more common in older patients. Leucopenia increased from 55.3% in patients aged 60 years to 65.5% in patients aged 64 years (P<0.001), and neutropenia increased from 46.9% to 57.4% (P<0.001). There was no difference, however, in clinically more relevant febrile neutropenia between the different age groups. Thrombopenia shows a similar age-dependent increase, whereas there is no difference between the age groups concerning anemia. Hot flushes and elevated liver enzymes decreased with increasing age. Conclusions The present pooled analysis of a substantial cohort of older primary breast cancer patients demonstrates that taxane-containing (neo) adjuvant chemotherapy is feasible in older patients and that toxicity can be reduced by sequential therapy regimens

Loss of HER2 after HER2-targeted treatment

PurposeHER2 expression has been reported to be discordant between primary tumor and metastatic tissue.Patients and methodsHER2 discordance and relation to HER2-targeted treatment was investigated in 227 patients with primary breast cancer.ResultsHER2 discordance between primary biopsy and second biopsy after neoadjuvant or adjuvant treatment was observed in 20.7%. This discordance was related only to the use of HER2-targeted treatment: 30 of 33 (90.9%) women with downgraded HER2 expression underwent a HER2-targeted therapy, whereas in the group of patients with concordant HER2 expression, only 32 of 180 (17.8%) received HER2-targeted treatment (p<0.0001). HER2 discordance was associated with reduced disease-free survival but not overall survival. In a second cohort, including patients with HER2 overexpressing tumors, trastuzumab treatment was associated with change of HER2 expression from positive to negative in 47.3% of cases. Addition of pertuzumab increased the rate of HER2 loss up to 63.2%. Notably, the interval between last HER2-targeted treatment and the time of surgical excision of the tumor after neoadjuvant chemotherapy (NACT) or the biopsy of the metachronous metastasis was associated with a significant change in HER2 expression. The median time between NACT and the time of surgical excision was 23 days (range 5-81 days) for tumors with decreased HER2 expression and 51 days (range 10-179 days) for tumors with concordant HER2 expression. Furthermore, median time between the end of adjuvant treatment and second histology of the metachronous metastases accounted for 15 days (range 2-165 days) and 478 days (range 7-2739 days) was observed in the group of patients with decreased or unchanged HER2 expression, respectively.ConclusionThe interval between anti-HER2 treatment and the determination of HER2 in second histology is strongly associated with HER2 expression

Management of elderly women with cervical cancer

Background Elderly women with cervical cancer receive less therapy in comparison with their younger counterparts. The exact reason(s) for this treatment strategy remains unclear. Patients and methods We performed a multicenter, retrospective registry-based study of 1559 patients with cervical cancer. The primary outcome was the reason for not performing the indicated treatment. Results Median follow-up was 67.8 months. A total of 956 women were eligible for analysis: 693 (64.2%) were younger than 60 years and 387 (35.8%) were aged 61 years old and older. Elderly women were more likely to have undifferentiated cervical cancer at an advanced stage. For early stage (stage IA1-IIA), tumors patients 61 years old and older were less likely to receive surgery [odds ratio (OR) 0.39; 95% CI 0.20-0.77] and radiochemotherapy (OR 0.37; 95% CI 0.21-0.66) compared with the group of patients aged < 60 years. The rate of lymphadenectomy was similar in both age groups. Patients 61 years old and older with advanced stage (IIB-IV) cervical cancer were also less likely to receive surgery [odds ratio (OR) 0.42; 95% CI 0.27-0.66], lymphadenectomy (OR 0.30; 95% CI 0.12-0.51) and radiochemotherapy (OR 0.31; 95% CI 0.20-0.48) compared with patients aged < 60 years. Notably, the rate of indicated but not performed therapies proportionally increased with an increase in patient age and the most important reason for this phenomenon was the failing of recommendation. Conclusions Elderly women with cervical cancer are undertreated and this is more likely because the therapy was not recommended

Vaginal brachytherapy for endometrial cancer

There is limited information about survival effect of vaginal brachytherapy (VBT) and its comparison to external beam pelvic radiotherapy (EBRT) and no radiotherapy (no-RT) of endometrial cancer patients. We performed a multicenter retrospective registry study of 1550 patients with endometrial cancer treated by no-RT (n = 702), VBT (n = 430) and EBRT +/- VBT (n = 418). The outcome measure was overall survival. RT did not improve the overall survival of patients with a low risk of recurrence. In univariate analysis, the survival effect of VBT was significant in patients with intermediate and high risk of recurrence (HR 0.42, CI 0.29-0.60, p < 0.0001). EBRT +/- VBT demonstrated no survival effect in these groups. Multivariate analysis showed that VBT (HR 0.50, CI 0.36-0.71) significantly reduced the mortality risk in patients with an intermediate and high risk compared with no-RT after adjustment for age, tumor grading, tumor stage, lymphadenectomy, adjuvant therapy and comorbidities. Matching for age, histological type, tumor stage, tumor grade, and performance status between patients treated with no-RT and VBT was performed. The matching analysis again demonstrated the favorable survival effect of VBT compared to no-RT on overall survival with an absolute risk reduction of 17.7%. Notably, in a further 106 matched pairs, EBRT +/- VBT did not demonstrate any survival effect over VBT among patients at intermediate and high risk of recurrence. VBT should be performed in patients at intermediate and high risk of recurrence of endometrial cancer, after operative determination of lymph node status

Endometrial cancer subtypes are associated with different patterns of recurrence

To evaluate the pattern of endometrial cancer recurrence according to its biological subtype in a large cohort of patients. Patients were stage eligible if they had a description of registry risk of recurrence status and were not primary metastatic. Data were prospectively collected. The primary endpoints were the subtype-dependent pattern and time of recurrence. The median follow-up time was 84 months. The highest 10-year recurrence-free and overall survival were seen in the group of patients at low risk of recurrence, 83.1 and 94.1%, respectively. The 10-year recurrence-free survival for intermediate and high risk group was 65.7 and 56.2%, respectively, whereas the estimated 10-year overall survival for both groups was 84.5 and 79.3%, respectively. Patients at high risk demonstrated the highest levels of disease recurrence in the first 3-4 years after diagnosis and the most common site of metastasis was the lung. In contrast, the rate of recurrence for patients at intermediate and low risk of recurrence in the first 5 years was relatively low but remained continuous up to 10 years of follow-up. Overall, the most common site of relapse was local recurrence. Endometrial cancer subtypes are associated with different times and patterns of recurrence and this should be considered when determining the treatment strategy

Comparison of survival of patients with endometrial cancer undergoing sentinel node biopsy alone or systematic lymphadenectomy

Background Recently, sentinel lymph node mapping was introduced in the surgical staging of endometrial cancer as alternative to systematic lymphadenectomy. However, the survival impact of sentinel node mapping is not well characterized yet. Methods We performed retrospective study of 104 patients with endometrial cancer treated with sentinel lymph node alone (n = 52) or with pelvic and para-aortic lymphadenectomy (n = 52). For sentinel node mapping, indocyanine green was used. The outcome measure was disease-free survival. Results Median follow-up was 42 months. Fifty-two patients staged by sentinel lymph node mapping were matched in 1:1 ratio with 52 patients staged by lymphadenectomy using patient age, histological type, tumor stage, tumor grade and lymph and vascular space invasion as matching criteria. The median number of removed lymph node was 3 (range 1-6) and 36 (13-63) in the sentinel and lymphadenectomy group, respectively. The rate of lymph node metastases was not significantly higher in the sentinel group (19.2%) in comparison with the lymphadenectomy group (14.3%). The overall detection rate of sentinel lymph nodes was 100% with a bilateral mapping of 98.1%. Most of the 152 lymph nodes identified and removed were localized in upper paracervical pathway (n = 143, 94.1%). During the follow-up period, overall 21 (20.2%) events were observed, 8 (15.4%) in the sentinel group and 13 (25.0%) in the lymphadenectomy group. The estimated disease-free survival was 84.6% and 75.0% for patients in the sentinel and lymphadenectomy groups, respectively. The survival curves demonstrated similar disease-free survival in two groups (p = 0.774). Conclusion Sentinel lymph node mapping did not compromise the outcome of patients with endometrial cancer

Systematic lymphadenectomy in early stage endometrial cancer

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