Purpose
This randomized phase II study was conducted to investigate the efficacy of cryotherapy in preventing peripheral neuropathy and dermatological adverse events in breast cancer patients treated ...with weekly paclitaxel.
Methods
Patients treated with 12 weekly doses of paclitaxel for breast cancer were randomized (1:1) into a cryotherapy or control group. The primary endpoint was the percentage of patients with a marked decrease in the Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-NTX) score. The secondary endpoints were Patient Neurotoxicity Questionnaire (PNQ), Common Terminology Criteria for Adverse Event (CTCAE) for peripheral neuropathy, and FACT-Taxane score.
Results
Forty-four patients were randomly assigned to the cryotherapy (
n
= 22) or control groups (
n
= 22). The percentage of patients with a marked decrease in FACT-NTX scores was significantly lower in the cryotherapy group than in the control group (41 vs. 73%,
p
= 0.03). The incidence of CTCAE grade ≥ 2 sensory (
p
= 0.001) and motor peripheral neuropathy (
p
= 0.01), and PNQ grade D or higher for sensory peripheral neuropathy (
p
= 0.02), and decrease in the FACT-Taxane score (
p
= 0.02) were also significantly lower in the cryotherapy group than in the control group. There were no serious side effects associated with cryotherapy.
Conclusion
Cryotherapy is an effective approach for prevention of peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel.
Abstract
Breast cancer is highly sensitive to systemic therapy. High probability of pathological complete response suggests a clinical question that omitting surgery is an effective alternative to ...surgery in breast cancer showing clinical complete response to primary systemic therapy. However, the validity of omitting surgery for early breast cancer after primary systemic therapy has not been sufficiently established; thus, even if pathological complete response is expected in patients showing clinical complete response, excision of the primary tumor site remains the standard treatment of breast cancer. Inappropriate omitting surgery increases the incidence of local recurrence, which can be the risk of a subsequent distant metastasis and reduced overall survival. To achieve acceptable local control rate, omitting surgery should be investigated in patients with early breast cancer where a high percentage of pathological complete response, a high concordance rate between clinical complete response and pathological complete response and an acceptable local control rate are expected. This review presents concept and ongoing clinical trials for omitting surgery for patients with breast cancer showing clinical complete response to primary systemic therapy.
High rates of clinical complete response and pathological complete response suggest that omitting surgery is an effective alternative to surgery in breast cancer showing remarkable response to primary systemic therapy.
Summary
Objective
This study attempted to clarify the long‐term course of Dravet syndrome (DS).
Methods
Sixty‐four patients diagnosed with DS (44 with typical DS, and 20 with atypical DS) were ...studied. The long‐term outcomes of clinical seizures, electroencephalographic findings, neuropsychological findings, and social situation were analyzed. The follow‐up period ranged from 11 to 34 years 5 months (median 24 years).
Results
At the last visit, the ages ranged from 19 years to 45 years (median 30 years). Fifty‐nine patients continued to have generalized tonic–clonic seizures (GTCS). Status epilepticus and unilateral seizures were not observed and myoclonic seizures, atypical absence seizures, and photosensitive seizures were resolved in most patients. The frequency of complex partial seizures was equally low, with five patients at presentation and six patients at the last visit, respectively. Five patients achieved seizure remission (seizure‐free for 1 year or longer). Only 1 of 44 patients with typical DS had seizure remission, whereas 4 of 20 patients with atypical DS remitted, with a statistically significant difference between the two phenotypes (p = 0.03). Intellectual disability was found in all patients; especially, severe intellectual disability was prevalent. Patients with atypical DS tended to have milder intellectual disability compared to those with typical DS (p = 0.0283). Occipital alpha rhythm in the basic activity was associated with milder intellectual disability (p = 0.0085). The freedom from seizures correlated with appearance of occipital alpha rhythms (p = 0.0008) and disappearance of epileptic discharges (p = 0.0004). Two patients with GTCS died. Mutations of the neuronal voltage‐gated sodium channel alpha subunit type 1 gene were detected at a high frequency (33 of 36 patients examined). Seizure remission was found only in the missense mutation group.
Significance
The long‐term seizure and intellectual outcomes are extremely poor in patients with typical DS compared to those with atypical DS. Epilepsy phenotype may influence long‐term course of DS.
We aimed to determine whether contrast-enhanced ultrasonography can predict the effects of neoadjuvant chemotherapy on breast cancer.
The clinical responses of 63 consecutive patients with breast ...cancer (T1-4, N0-1, M0) to neoadjuvant chemotherapy between October 2012 and May 2015 were assessed using contrast-enhanced magnetic resonance imaging, positron emission tomography/computed tomography and contrast-enhanced ultrasonography. Perfusion parameters for contrast-enhanced ultrasonography were created from time-intensity curves based on enhancement intensity and temporal changes to objectively evaluate contrast-enhanced ultrasonography findings. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography, magnetic resonance imaging and positron emission tomography/computed tomography to predict a pathological complete response were compared after confirming the pathological findings of surgical specimens.
Twenty-three (36.5%) of the 63 patients achieved pathological complete response. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography for predicting pathological complete response were 95.7% (82.5-99.2%), 77.5% (69.9-79.5%) and 84.1% (74.5-86.7%). The sensitivity of contrast-enhanced ultrasonography was significantly greater than that of magnetic resonance imaging (95.7 vs. 69.6%, P = 0.047). The specificity and accuracy were significantly greater and tended to be greater, respectively, for contrast-enhanced ultrasonography than positron emission tomography/computed tomography (specificity, 77.5 vs. 52.5%, P = 0.02; accuracy, 84.1 vs. 69.8%, P = 0.057).
Contrast-enhanced ultrasonography might serve as a new diagnostic modality when planning therapeutic strategies for patients with breast cancer after neoadjuvant chemotherapy.
The prognostic value of sentinel lymph node (SLN) metastases may be minimized by the limited disease burden of lymph node metastases and tailoring adjuvant therapy based on breast cancer biology. The ...aim of this study is to assess the prognostic significance of SLN metastasis in patients with cT1-2N0M0 breast cancer.
Between January 2006 and December 2015, 582 patients underwent SLN biopsy for cT1-2N0M0 breast cancers. cN0 was essentially diagnosed by ultrasound sonography. The prognostic values of SLN metastases were retrospectively evaluated.
Among 582 patients with cT1-2N0M0 breast cancer, 111 patients (19.1%) were positive for SLN metastasis, including 39 cases (6.7%) of micrometastasis and 72 cases (12.4%) of macrometastases. The median size of SLN metastasis was 3.0 mm (range 0.2-16 mm, mean 4.1 mm). In log-rank test, presence of SLN metastasis was not associated with breast cancer recurrence (p = 0.21); 5-year and 10-year recurrence-free survival (RFS) were 93.0% and 96.5%, and 93.0% and 90.4% in the SLN-positive and SLN-negative groups, respectively. In the propensity score matching cohort (n = 178), there was no significant difference in RFS between the SLN-positive and SLN-negative groups (p = 0.90). In Cox regression analysis, a continuous value of Ki67 expression was a significant prognostic factor (HR 1.03; 95% CI 1.01-1.05, p = 0.017).
SLN metastasis has a minimal impact on RFS for patients with cT1-2N0M0 breast cancer in the modern medical era. A proliferation marker is a better factor for poor prognosis than the presence of SLN metastases in this population.
1q41q42 microdeletion syndrome has been established in 2007. Since then, more than 17 patients have been reported so far. The reported deletions showed random breakpoints and deletion regions are ...aligned as roof tiles. Patients with 1q41q42 microdeletion syndrome show intellectual disability, seizures, and distinctive features. Many genotype-phenotype correlation studies have been performed and some genes included in this region have been suggested as potential candidate genes. Recently, de novo variants in WDR26 and FBXO28 were identified in patients who showed consistent phenotypes with 1q41q42 microdeletion syndrome. Thus, both genes are now considered as the genes possibly responsible for 1q41q42 microdeletion syndrome. Here, the first case of a Japanese patient with a de novo 1q41q42 microdeletion is reported. Owing to the distinctive features, this syndrome would be clinically recognizable.
Purpose
FOXP3 + and CD8 + are recognized markers of tumor-infiltrating lymphocytes (TILs) for breast cancer. FOXP3 + TILs are composed of effector Tregs (eTregs) and other subpopulations that are ...classified by their differences in suppressive function. In this prospective study, we evaluated Treg subpopulations and CD8 + TILs in breast cancer.
Methods
84 patients with breast cancer were enrolled. Fresh TILs were extracted andTregs were classified into eTregs (CD4
+
FOXP3
high
CD45RA
−
), other FOXP3
+
Treg subsets (naïve and non-Tregs), and total CD8
+
CD4
−
TILs using flow cytometry. The suppression strength of each Treg subpopulation was analyzed. The association between TIL subpopulations, clinicopathological characteristics, and response to chemotherapy was evaluated.
Results
The mean CD8/eTreg ratio value was 7.86 (interquartile range: 4.08–12.80). The proliferation function of eTregs was significantly suppressed compared with that of the other subpopulations (proliferation rates: control: 89.3%, + naiiveTreg: 64.2%, + non-Treg: 78.2% vs eTreg 1.93%; all P < 0.05). The patients with high with a high CD8 + /eTreg ratio achieved excellent pathological complete response (pCR) rate of neoadjuvant chemotherapy (90.2%) and the CD8/eTreg ratio were independent predictive factors for pCR (odds ratio:18.7(confidence interval 1.25–279) P < 0.05). A detailed assessment of the CD8/eTreg ratio for each patient who underwent NAC revealed that high CD8/eTreg ratio showed a significantly higher pCR rate compared to patients with a low CD8/FOXP3 ratio (39.6% vs 13.3, P < 0.05) in triple negative subtype patients with stromal TILs < 50%.
Conclusions
A high CD8/eTreg ratio enhances pCR rate in patients with invasive breast cancer.
Objective
Gaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme‐replacement and substrate‐reduction therapies are available, their ...efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothesized to offer a new strategy for treating the neurological manifestations of this disease. Specifically, ambroxol, a commonly used expectorant, has been proposed as a candidate pharmacological chaperone. The purpose of this study was to evaluate the safety, tolerability, and neurological efficacy of ambroxol in patients with neuronopathic GD.
Methods
This open‐label pilot study included five patients who received high‐dose oral ambroxol in combination with enzyme replacement therapy. Safety was assessed by adverse event query, physical examination, electrocardiography, laboratory studies, and drug concentration. Biochemical efficacy was assessed through evidence of glucocerebrosidase activity in the lymphocytes and glucosylsphingosine levels in the cerebrospinal fluid. Neurological efficacy was evaluated using the Unified Myoclonus Rating Scale, Gross Motor Function Measure, Functional Independence Measure, seizure frequency, pupillary light reflex, horizontal saccadic latency, and electrophysiologic studies.
Results
High‐dose oral ambroxol had good safety and tolerability, significantly increased lymphocyte glucocerebrosidase activity, permeated the blood–brain barrier, and decreased glucosylsphingosine levels in the cerebrospinal fluid. Myoclonus, seizures, and pupillary light reflex dysfunction markedly improved in all patients. Relief from myoclonus led to impressive recovery of gross motor function in two patients, allowing them to walk again.
Interpretation
Pharmacological chaperone therapy with high‐dose oral ambroxol shows promise in treating neuronopathic GD, necessitating further clinical trials.
The purpose of this study was to identify the risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia (FCD).
77 patients with histopathologically confirmed ...FCD were studied. The statistical relationship between cognition levels and clinical factors at presurgical evaluation was analyzed. Cognitive function was evaluated by development quotient or intelligence quotient (DQ-IQ).
Ages at seizure onset were younger than 15 years (mean ± SD; 5.0 ± 4.2 years). Mean disease duration was 14.5 ± 8.5 years. Mean age at pre-surgical DQ-IQ evaluation was 34.8 ± 10.7 years. Mean DQ-IQ was 60.5 ± 20.5, and 41 of 77 (53.2%) patients had mental retardation (DQ-IQ < 70). Younger seizure onset and seizure clustering were significantly associated with lower DQ-IQ (p < 0.001). A multiple regression study identified higher seizure frequency pattern, a history of epileptic spasm and status epilepticus as aggravating factors of DQ-IQ decline (R2 = 0.63, p < 0.001). On the other hand, the risk was decreased in patients with habitual focal aware seizure and transient seizure-free periods up to 6 months in the course of epilepsy. FCD location (FCD site, extent of radiological lesion and laterality) and histopathology of FCD did not affect DQ-IQ.
Our study suggests that seizure characteristics including higher seizure frequency pattern, a history of epileptic spasm, status epilepticus, seizure clustering and early onset of seizure are risk factors of cognitive impairment in FCD patients.
Background
Intraoperative evaluations of sentinel lymph node (SLN) metastases are performed for providing appropriate and immediate axillary treatments in breast cancer patients who do not meet Z0011 ...criteria; however, standard intraoperative procedure has not yet been established.
Methods
We consecutively performed intraoperative evaluation for SLN metastases using both a cytokeratin immunohistochemistry (CK-IHC) assay on serial frozen sections and a one-step nucleic acid amplification (OSNA) assay of the remaining whole node in patients with invasive breast cancer. In this article, we compared the intraoperative diagnostic ability of CK-IHC assay, the OSNA assay, and in combination.
Results
Between August 2009 and May 2017, 1,103 SLNs from 499 consecutive clinically node-negative invasive breast cancers were intraoperatively evaluated for SLN metastases using an OSNA and CK-IHC assay. The detection rates of SLN metastases by the OSNA and CK-IHC assays and in combination were 11.8, 12.1, and 14.5%, respectively. The concordance rate between the intraoperative SLN findings of the OSNA and CK-IHC assays was 94.9% (95% confidence interval 93.6–96.2%). The false negative rate for the OSNA assay was 3.1% (30/973), including 3 (0.3%) macrometastases and 27 (2.8%) micrometastases, and for the CK-IHC assay was 2.7% (26/969), including 1 (0.1%) OSNA ++ and 25 (2.6%) OSNA +.
Conclusions
The CK-IHC assay and the OSNA assay have compatible diagnostic abilities in intraoperative evaluations for SLN metastases. The low incidence of false negative results with limited disease burden suggests that both assays can be reliable techniques for intraoperative diagnoses of SLN metastases in breast cancer patients.
PDF
