In the present study, we investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) treated with ...lapatinib and capecitabine (LC).
Of 81 HER2+ metastatic BC patients treated with LC at two Italian institutions, 30 patients with BMs eligible for the analysis were identified. All patients were pretreated with trastuzumab for metastatic disease. No patients had received prior lapatinib and/or capecitabine.
Median age was 45 years (range 24–75) and 26 of 30 patients (86.7%) had received prior cranial radiotherapy. In the 22 patients with BMs evaluable for response, 7 partial responses (31.8%) and 6 disease stabilizations (27.3%) were observed. Overall, the median brain-specific progression-free survival was 5.6 months (95% confidence interval 4.4–6.8). Patients treated with LC had a median overall survival (from the time of development of BMs) significantly longer compared with 23 patients treated with trastuzumab-based therapies only beyond brain progression (27.9 months versus 16.7 months, respectively, P = 0.01).
LC is active for BMs from HER2+ BC in patients not pretreated with either lapatinib or capecitabine. The introduction of LC after the development of BMs may further improve survival compared with trastuzumab-based therapies only beyond brain progression.
Introduction
The efficacy of immune checkpoint inhibitors in patients with brain metastases (BMs) from non-oncogene addicted non-small cell lung cancer (NSCLC) is under investigation. Here, we sought ...to determine the optimal management of NSCLCs with PD-L1 ≥ 50% and asymptomatic BMs who were treated with first-line pembrolizumab.
Methods
Thirty patients from 15 institutions with PD-L1 ≥ 50% NSCLC had asymptomatic BMs, and met inclusion criteria. Patients were classified based on whether they had undergone upfront local radiotherapy for BMs as well as on the type of brain radiotherapy received.
Results
Nine patients were treated with upfront pembrolizumab alone, 8 patients with whole-brain radiotherapy (WBRT) followed by pembrolizumab and 13 patients with stereotactic radiosurgery (SRS) followed by pembrolizumab. Patients’ characteristics were similar among the three groups of patients except for a higher number of BMs ≥ 3 in the WBRT group. One complete and 4 partial intracranial responses were observed with upfront pembrolizumab alone. The median survival was not reached for the pembrolizumab and WBRT (
n
= 8) groups, and it was 7.6 months for the SRS (
n
= 13) group (
P
= 0.09), with 12-month survival rates being 55.5%, 62.5%, and 23.0%, respectively. Salvage WBRT was delivered in 1 patient in the upfront pembrolizumab group and in 4 patients in the SRS group.
Conclusions
Upfront pembrolizumab showed efficacy in selected patients with PD-L1 ≥ 50% non-oncogene addicted NSCLC and asymptomatic BMs. Prospective studies should address whether pembrolizumab alone, and deferral of radiotherapy, could be pursued in this patient population.
In according to Krop's experience, our case shows that T-DM1 could play a significant role in the treatment of brain metastases even in patients with heavily pretreated HER2-positive metastatic ...breast cancer.
Central nervous system (CNS) metastases from breast cancer (BC) represent an important cause of disease-related morbidity and mortality. For BC patients who develop CNS metastases, local control ...measures (both surgery and radiation) are essentially palliative and usually poorly effective, with systemic therapies often failing to achieve optimal control mainly due to the presence of the blood-brain barrier which hampers adequate penetration of therapeutic agents into the brain. However, recent evidence suggests that the status of the human epidermal growth factor receptor-2 (HER2) strongly influences the incidence of CNS metastases and the survival of BC patients from the time of development of CNS metastases, with HER2-positive (HER2+) patients generally experiencing higher rates of CNS metastases and prolonged overall survival compared to patients with HER2-negative disease. This phenomenon likely reflects the difficult CNS drug-penetration and improved control of extra-CNS disease following the clinical use of the anti-HER2 monoclonal antibody trastuzumab. Importantly, this HER2-based survival difference has important implications when planning the optimal treatment of BC patients with CNS metastases. To date, although no systemic therapy has been specifically approved for the treatment of CNS metastases from BC, several targeted agents are being clinically developed for this purpose. In the present review we will discuss the targeted therapies that are under investigation for the treatment of CNS metastases from BC, highlighting the different implications based on whether a given agent is being developed to target CNS metastases from HER2+ or HER2-negative breast cancer.
Purpose
KRAS
mutation has been associated with enhanced dependency on the folate metabolism in preclinical studies. However, whether
KRAS
mutation correlates to increased sensitivity to pemetrexed in ...patients with advanced NSCLC is unknown.
Methods
Patients with advanced non-squamous NSCLC who had a documented
EGFR
and
ALK
WT genotype with simultaneous
KRAS
mutation assessment were evaluated for clinical outcome to pemetrexed- and non-pemetrexed-based first-line platinum doublet according to
KRAS
mutation status.
Results
Of 356 patients identified, 138 harbored a
KRAS
mutation. Among
KRAS
-mutant NSCLCs, those treated with platinum/pemetrexed (81/138) had significantly lower ORR (30.9% versus 47.4%,
P
= 0.05), DCR (51.8% versus 71.9%,
P
= 0.02) and shorter median progression-free survival mPFS 4.1 versus 7.1 months, HR 1.48 (95% CI 1.03–2.12),
P
= 0.03 and median overall survival mOS 9.7 versus 26.9 months, HR 1.93 (95% CI 1.27–2.94),
P
= 0.002 compared to those who received a non-pemetrexed-based platinum doublet (57/138). No difference in ORR, DCR, mPFS and mOS was observed between
KRAS
WT patients who received a pemetrexed-based (124/218) versus non-pemetrexed base platinum doublets (94/218). After adjusting for performance status, age and the presence of brain metastasis at baseline, treatment with pemetrexed-based platinum doublet was associated with an increased risk of death HR 2.27 (95% CI 1.12–4.63),
P
= 0.02 among
KRAS
-mutant patients in multivariate analysis.
Conclusion
Patients with
KRAS
-mutant lung adenocarcinoma have a poorer outcome on pemetrexed-based first-line chemotherapy. Whether
KRAS
-mutant NSCLCs should be excluded from pemetrexed-containing regimens should be assessed prospectively.
Abstract Study objective The objective was to determine if there is a correlation between resident postgraduate year (PGY) of training and self-evaluation of performance using the Accreditation ...Council for Graduate Medical Education milestones. Design Survey. Setting Residency program at a large academic center. Patients Residents and Faculty Clinical Competency Committee (CCC). Interventions None. Measurements Resident and CCC milestone scores. Main results Correlation coefficients for average score for each milestone vs PGY level ranged from 0.80 for receiving and giving feedback to 0.95 for anesthetic choice and conduct. All milestones showed a relatively linear relationship with PGY of training, and none were found to be consistently reached very late or very early in training. When examining variation across the scores for the individual residents, the distributions for PGY-2 and -3 appeared to be wider than those for PGY-1 and -4. The intraclass correlation coefficients ranged from 0.718 to 0.928. Conclusions There was a remarkable degree of consistency in the relationship between level of training and resident self-assessment score for every milestone, as well as strong agreement between the resident and CCC faculty scores. Examination of the variance in the scores, when interpreted in light of our particular training program’s characteristics, suggests that the milestones accurately reflect the progression in skill across the residency. In addition, given the concordance between the self-evaluation scores and the CCC faculty scores, self-evaluation may be a reasonable starting point as programs begin the daunting task of determining scores for each of the 25 milestones as part of the biannual evaluation process.
Introduction. Transarterial chemoembolization (TACE) is a good choice for hepatocellular carcinoma (HCC) treatment when surgery and liver transplantation are not feasible. Few studies reported the ...value of prognostic factors influencing survival after chemoembolization. In this study, we evaluated whether preoperative inflammatory factors such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio affected our patient survival when affected by hepatocellular carcinoma. Methods. We retrospectively evaluated a total of 72 patients with hepatocellular carcinoma that underwent TACE. We enrolled patients with different etiopathogeneses of hepatitis and histologically proven HCC not suitable for surgery. The overall study population was dichotomized in two groups according to the median NLR value and was analyzed also according to other prognostic factors. Results. The global median overall survival (OS) was 28 months. The OS in patients with high NLR was statistically significantly shorter than that in patients with low NLR. The following pretreatment variables were significantly associated with the OS in univariate analyses: age, Child-Pugh score, BCLC stage, INR, and NLR. Pretreated high NLR was an independently unfavorable factor for OS. Conclusion. NLR could be considered a good prognostic factor of survival useful to stratify patients that could benefit from TACE treatment.
PDF
